Antigenic changes associated with liver carcinogenesis. Carcinogen-induced experimental hepatomas are often characterized by new individually distinct antigens capable of inducing tumor immunity in syngeneic hosts. These antigens arise as a consequence of cell-carcinogen interaction and may result from modification or replacement of normal cell-surface components. Their role in immunosurveillance is not established, but they offer a target for tumor immunotherapy. Reexpressed fetal antigens have also been detected, either as secretory products (alpha 1-fetoprotein) or as common cell-surface components on hepatoma cells. The role of fetal antigens in therapy is doubtful, but they may be important diagnostic indicators of neoplastic change. Possibly associated with these are common antigens initiated early after carcinogen treatment, before malignant cells are detected. Together, the antigens associated with liver carcinogenesis may prove to be powerful tools in understanding the process of liver neoplasia.


Elongation of DNA complementary to the 5' end of the avian sarcoma virus genome by the virion-associated RNA-dependent DNA polymerase. RNA-dependent DNA synthesis in a virion-associated reaction has been described as being dependent upon the detergent concentration used for disruption of the virion. In this study, the Triton X-100 concentration was found to affect the elongation of the initially synthesized DNA complementary to the last approximately 100 nucleotides at the 5' end of the RNA (cDNA100). Whereas elongation of cDNA100 increased with time of incubation at the optimal detergent concentration, this process was retarded at higher detergent concentrations. At the optimal detergent concentration, elongated DNA was of low chemical complexity, indicating that extension of cDNA100 occurred at a unique site on the RNA. Higher than optimal detergent concentrations resulted in nonspecific elongation and in DNA of high chemical complexity. This was shown by oligopyrimidine tract analysis. Furthermore, actinomycin D was observed to inhibit the elongation of cDNA100 at the optimal detergent concentration. The nature of the elongation process was elucidated by analysis of DNA synthesized in a virion-associated reaction in the presence of bacteriophage Qbeta RNA. At the optimal detergent concentration DNA complementary only to avian sarcoma virus RNA was synthesized, whereas at higher concentrations DNA was copied from both avian sarcoma virus and Qbeta RNA. We conclude that the elongation mechanism of cDNA100 is affected by the detergent concentration and elongation is unspecific at higher than optimal detergent concentrations. The mechanism by which the nonionic detergent stimulates DNA synthesis has not yet been resolve. We assume that other factors in addition to DNA polymerase are involved in elongation of cDNA100.


Avian reticuloendotheliosis viruses: evolutionary linkage with mammalian type C retroviruses. Reticuloendotheliosis viruses have been shown to be causative of tumors in a variety of avian species. The major structural protein of these non-genetically transmitted viruses is demonstrated to possess antigenic determinants common to those of all known mammalian type C viruses. These findings establish a mammalian origin for this oncogenic avian retrovirus group. None of the known mammalian type C virus groups demonstrated a closer immunological relationship to avian reticuloendotheliosis viruses. These results suggest that reticuloendotheliosis viruses have been non-genetically transmitted for a long period of evolution or that these viruses may have arisen by relatively recent infection of birds with an as yet undiscovered mammalian type C retrovirus.


Urinary diversion for ureteral obstruction in the presence of recurrent colon carcinoma. Selection of patients who might benefit from urinary diversion when recurrent colorectal cancer obstructs both ureters is difficult. Combinations of chemotherapy and radiation therapy will prolong a useful, comfortable and dignified life in some patients. Radiation therapy seems to be more effective than chemotherapy and, therefore, patients most likely to benefit are those with localized pelvic recurrences without carcinomatosis and those who are well nourished, active and highly motivated. Herein we discuss 6 patients who were diverted and the methods of selection.


Half and total body radiation for carcinoma of the prostate. Despite recent advances in the treatment of stage D carcinoma of the prostate many patients become refractory to all therapeutic modalities. Progressive and incapacitating pain is one of the most difficult symptoms to manage. Ten patients with severely symptomatic metastatic adenocarcinoma of the prostate have been treated with either single or sequential doses of half body radiation using 800 rad delivered by a Linac 10 mV linear accelerator. There were 15 courses of half body radiation delivered and a good to excellent response was noted in 11 instances. Results often were immediate and the duration of the response was variable. Treatment was well tolerated with no fatal complications. Half and total body radiation appears to offer significant palliation and its use with other forms of therapy warrants further investigation.


Antigenic analysis of human heart tissue--characterization of cardiac antigens. The human heart antigens demonstrated in citric acid extracts by immunodiffusion were submitted to further analysis. Heart antigens were precipitated at 30% to 70% saturated ammonium sulphate. These fractions contained antigens reactive with rabbit antisera to human heart. The third fraction out of four proteins which were separated by Sephadex G-150 gel filtration, was reactive against rabbit antisera to human heart. The intensely stained proteins of both heart antigens were located at the nineth protein band out of proteins separated by polyacrylamide gel electrophoresis. This protein exhibited precipitin line against rabbit antisera to human heart by two-dimensional electrophoresis, and had mobility between that of serum alpha2 and beta1 globulin in immunoelectrophoresis.


DNA polymerase from Gross murine leukemia. DNA polymerase (reverse transcriptase) from Gross virus was characterized with regard to template specificity. Changes in pH in the reaction medium in vitro exert a varying influence on this enzyme's activity depending on the template used.


Inhibition of spontaneous transformation of rat embryo cells releasing endogenous type C virus by virus-specific antiserum. Noninbred Sprague-Dawley rat embryo cell clones predictably undergo transformation after 20-30 in vitro passages following spontaneous release of endogenous rat leukemia virus (RaLV). In the presence of RaLV-specific antiserum, virus production and infectivity were reduced and transformation was delayed from 6 to 25 weeks. Transformation was not associated with an increased expression of Kirsten murine sarcoma virus-related src gene RNA.


[State of the heart conduction system in the sick sinus syndrome (according to the recording of the bundle of His potentials and the atrial stimulation test)]. It was established that the presence of Samoilov-Wenckebach's periods and prolongation of the H--V interval at low frequency of the imposed rhythm as well as periods of asystolia of more than 1,200 msec are most typical for these patients. An attempt was made to determine the type of cardiac stimulation indicated for such patients from the character of the disorders of rhythm observed in them and the initial frequency of their own cardiac contractions.


[Treatment of severe ventricular arrhythmia by means of repeated cardiac stimulation]. The overdrive pacing method is widely used now in clinical practice for prevention and treatment of severe ventricular disorders of the cardiac rhythm. The mechanisms of arrhythmia suppression by means of this stimulation is analysed. Indications are determined for the choice of the site of stimulation and optimal impulce frequency in ischemic heart disease, and overdosage with digitalis drugs, as well as in myocardiopathy.


[Possibility of using trimecaine for the treatment of cardiac rhythm disorders in myocardial infarct]. The antiarrhythmic effect of triamecain (mesocain) was studied in 104 patients with acute or chronic form of ischemic heart disease during 169 episodes of disorder of cardiac activity rhythm. It is shown that trimecain possesses marked antiarrhythmic activity manifested in disorders of automaticity and excitability as well as in cardiac fibrillation. Intolerance to the drug was a relatively rare occurrence.


[Chaotic atrial rhythm (problems of diagnosis and treatment)]. The article gives a clinical and electrocardiographic analysis of 16 cases with chaotic atrial rhythm in ischemic heart disease and in diseases which cause overexertion, dilatation, and changes of the atrial myocardium. The significance of such diagnostic criteria of chaotic atrial rhythm as the presence of three or more different P waves in each ECG lead, the absence of a dominative atrial pacemaker, differnt P--P, P--R, and R--R periods, and the isoelectrical PP segment is confirmed. Symptoms are pointed out for differentiating chaotic atrial rhythm from polytopic atrial extrasystole, cardiac fibrillation, and supraventricular pacemaker migration. The expediency of separating chaotic atrial rhythm as an independent form of atrial arrhythmias is emphasized. The use of isoptin, agents bloking beta-adrenergic receptors, lidocaine, and cardiac glycosides in chaotic atrial rhythm is recommended.


[2 variants of the anti-arrhythmic effect of atropine in extrasystole]. The antiarrhythmic effect of a single intravenous atropine injection (0.02 mg/kg body mass) was studied in 202 patients with extrasystole of various origin by rhythmography. Record of the chronotropic reaction and dynamics of the extrasystole interval suggests that there are two variations of the antiarrhythmic effect of atropine: frequency suppression of extrasystole and a "pure" antiarrhythmic effect. The data obtained are evidence that the mechanism of the antiarrhythmic effect of atropine is heterogeneous and complex.


[Study of ectopic cardiac activity under the effect of psychological stress]. Mental and emotional load consisting of several psychological tests was used in 35 patients with ischemic heart disease to disclose hazardous and latent forms of disorders of cardiac rhythm as possible forewarning of sudden death and to study the role of the psychological factor and stress situation in their origin. The reaction of extopic myocardial activity to the load proved different. In distinction to patients with functional cardiovascular disorders, patients with organic affections of the myocardium responded to the load by the appearance of extrasystoles during the load or by their greated frequency. In patients with functional cardiovascular disorders there was mostly a decrease in the number of initial extrasystoles and in some cases their total disappearance.


[Electrocardiography with the use of the orthoclinostatic test in the diagnosis of extrasystolic arrhythmia in childhood]. The differential-diagnostic importance of some ECG criteria and results of orthoclinostatic test in distinguishing functional form organic extrasystolic arrhythmias in childhood is appraised. Among the electrocardiographic indices the coupling interval is of great importance in differential diagnosis. Left-ventricular extrasystole is mostly encountered in rhythm disorders of functional origin. The data of the orthoclinostatic test are highly reliable in distinguishing functional disorders of rhythm from organic disorders.


[Change in the thresholds of development of ventricular arrhythmias after stimulation of negative emotiogenic hypothalamic centers]. The dynamics of changes in the thresholds of the origin of ventricular extrasystole, paroxysmal ventricular tachysystole and ventricular fibrillation in long-term stimulation of the ventromedial hypothalamic nucleus were studied in experiments on rabbits. It was found that myocardial resistance to the development of arrhythmias depended on the manifestation of the sympathetico-parasympathic interaction on the heart. In predominance of parasympathetic effects on the heart during hypothalamic stimulation, the threshold of the origin of arrhythmia increased by 40% for ventricular extrasystole, by 38% for paroxysmal ventricular tachysystole and by more than 36% for ventricular fibrillation. In predominance of sympathetic effects during stimulation of negative emotiogenic hypothalamic centers, the threshold of arrhythmia origin decreased by 45% for ventricular extrasystole, by 32% for paroxysmal ventricular tachysystole and by 24% for ventricular fibrillation.


[Lymphocyte membrane receptors mediating recognition of antigens (author's transl)]. The present article summarizes briefly our knowledge of antigen-specific B- and T-lymphocyte receptors. Antigen-specific receptors on mammalian B-lymphocytes are mainly monomeric IgM and IgD consisting of conventional immunoglobulin heavy and light chains. The nature of the T-lymphocyte receptors which can specifically recognize antigens is not yet fully defined but it seems that conventional light chains do not participate in the build up of this receptor. However, T-lymphocytes express two polypeptide chains which bear variable domains sharing idiotypic determinants with the corresponding B-lymphocytes. These Tau chains can bind the corresponding antigen.


[The antigenic e system in carriers of the surface antigen of viral hepatitis B (author's transl)]. In 1972, Magnius and Espmark on confronting different sera containing the surface antigen of hepatitis B with each other, demonstrated a new antigenic item which they called e. In later works the presence of this new antigenic specificity was associated with a greater rate of incidence of chronic hepatic lesion and a greater contagiousness of B virus. In the present study the e system was determined in a group of HBsAG positive blood donors and in a group of patients carrying HBeAG who had been admitted to the hospital for different reasons. The results showed an elevated rate of anti-e antibodies in the asymptomatic donors, and this could be correlated with clinical and biochemical indemnity of the liver function. HBsAg carriers mainly presented renal insufficiency or hematologic disorders, probably related to a deficient immune response. Determination of the e system shows its usefulness in enabling HBsAg positive carriers to be classified according to whether they present or not present hepatic lesion. The presence of HBeAg could be correlated with hepatic lesion, while HBeAc seems to determine some type of protection on those patients who have it in their sera.


Prolonged breast-feeding as prophylaxis for atopic disease. 54 babies who had been solely breast-fed for more than 6 months, 77 babies who had been breast-fed for 2--6 months, and 105 babies who had been weaned to cow's-milk-based formulas at less than 2 months were followed for the first 3 years of life. All the babies had the same pattern of solid food intake until 1 year of age. Compared with formula feeding, prolonged breast-feeding resulted in a lower incidence of severe or obvious atopic disease particularly in babies with family history of atopy.


Increase in leg blood-flow by normovolaemic haemodilution in intermittent claudication. Normovolaemic haemodilution down to a packed-cell volume of 35% was done in 10 patients with stable intermittent claudication. For a mean reducation in the packed-cell volume of 21.5% there was a 170% increase in peak calf blood-flow and a 111% increase in haemoglobin delivery. 7 of the 10 patients reported an increased walking distance. Normovolaemic haemodilution may be of use in the management of some patients with peripheral vascular disease.


Preoperative haemoglobin as predictor of outcome of diabetic amputations. Simple factors which may serve as predictors of the success or failure of amputations in the feet were examined in 59 consecutive diabetics. Age, sex, method of diabetic control, smoling, presence of neuropathy or peripheral pulses, preoperative blood-urea, and temperature did not correlate with success of amuptations. The average preoperative white-cell count and blood-sugar were higher in the failure group (p less than 0.01 and p less than 0.05 respectively), but there was considerable overlap between the groups. By contrast, the preoperative haemoglobin level was significantly lower (p less than 0.001) in patients whose amputations healed than in those with failure of healing, both at the digital and metatarsal or transmetatarsal levels; also, there was very little overlap in haemoglobin levels between the success and failure groups. All 18 amputations done in patients with a preoperative haemoglobin less than 12.0 g/dl were successful, whilst all 30 amputations in those with a preoperative level greater than 13.0 g/dl failed.


"Incessant ovulation" and ovarian cancer. A case-control study of 150 ovarian cancer patients under the age of 50 and individually matched controls was done to study the influence of fertility and oral contraceptive use on the risk of ovarian cancer. The risk decreased with increasing numbers of live births, with increasing numbers of incomplete pregnancies, and with the use of oral contraceptives. These three factors can be amalgamated into a single index of protection--"protected time"--by considering them all as periods of anovulation. The complement of protected time--viz., "ovulatory age", the period between menarche and diagnosis of ovarian cancer (or cessation of menses) minus "protected time"--was strongly related to risk of ovarian cancer. Other factors found to be associated with increased ovarian cancer risk were obesity, cervical polyps, and gallbladder disease. Women who had an "immediate" intolerance to oral contraceptive use had a fourfold increased risk of ovarian cancer. 7 patients, but no controls, could recall a family history of ovarian cancer.


Evidence for raised K-cell levels in type-I diabetes. The proportion of blood mononuclear cells forming low-affinity rosettes with sheep erythrocytes (K cells) was abnormally high in 13 (57%) of 23 children with classical type-1 diabetes at diagnosis but normal in children who had had diabetes for more than a year. A raised proportion of K cells was also found in 5 out of 10 unaffected siblings with islet-cell antibodies and at least one HLA haplotype in common with the diabetic proband; and in 10 (45%) of 22 subjects with type-1 diabetes and co-existent autoimmune thyroid disease irrespective of the duration of diabetes or the presence of islet-cell antibodies. These findings may be new evidence for lymphocyte-mediated beta-cell destruction and support the idea of immunogenetic heterogeneity within type-1 diabetes.


Familial pseudohyperkalaemia. A new syndrome. Inherited pseudohyperkalaemia due to an abnormal red-blood-cell potassium leak was discovered in 16 of 28 relatives of a woman with pseudohyperkalaemia. Autosomal dominance seemed to account for inheritance of this abnormality. Affected subjects were not anaemic and had normal in-vivo plasma-potassium concentrations.


Central-nervous-system defects in children born to mothers exposed to organic solvents during pregnancy. In a two-year study of mothers of children with congenital central-nervous-system defects and their matched-pair controls, exposure to noxious influences during pregnancy was analysed. Information on exposure was gained by interviews with all the mothers, sometimes supplemented by visits to their places of work. Significantly more case-mothers than control-mothers had been exposed to organic solvents during the first trimester of pregnancy (p less than 0.01).


Rehabilitation of the coronary patient.

Rehabilitation of the coronary patient. 52 out of 56 patients with myocardial infarction completed a 6-week rehabilitation programme. The exercise programme started on the second day of admission and continued during the patient's stay in hospital and for 6 weeks thereafter, with weekly attendances at the hospital. All the patients were assessed monthly by a coronary rehabilitation team. 77% of the patients went back to work in an average time of 9.5 weeks after onset of the infarction; 61% went to their original jobs and 16% had to modify their jobs. The approximate hospital cost per patient for the complete course was 11.33 pounds.


Evidence of whooping-cough-vaccine efficacy from the 1978 whooping-cough epidemic in Hertfordshire. The question of the efficacy of whooping-cough immunisation was central to the controversy that started in 1974. Definitive answers were not possible at the time because of the very low levels of whooping-cough in the preceding years and the absence of up-to-date information. The widespread abandonment of whooping-cough immunisation and the subsequent epidemic of whooping-cough have provided a natural epidemiological experiment. Figures from Hertfordshire in 1978 show that for children aged 4 years and under whooping-cough immunisation conferred 92% protection.


Intranasal gonadotropin-releasing hormone agonist as a contraceptive agent. The stimulatory luteinising hormone-releasing hormone (LRH) analogue D-Ser(TBU)6-EA10-LRH was administered intranasally once daily to twenty-seven regularly menstruating women to determine its efficacy as a contraceptive agent. Ovulation was inhibited during all but 2 of the 89 treatment months. The failures were due to initial technical problems with the nasal spray. Twenty-one of the twenty-seven women had slight menstrual-like anovulatory bleeds during the 3--6 month trial. The remaining six women were amenorrhoeic. Ovulatory menstrual cycles rapidly returned after discontinuation of treatment. There were no serious side-effects.


Oesophageal lesions in northern Iran: a premalignant condition? An endoscopic survey was undertaken in northern Iran to identify and determine the prevalence of possible precancerous lesions of the oesophagus. 218 men and 212 women, aged between 15 and 70 years, were included in the study. Oesophagoscopies were done on all 430 subjects and biopsies on 418. A chronic oesophagitis, involving mainly the middle and lower thirds of the oesophagus, was found in 80% of the subjects, and the frequency was very high even in the younger age-groups. Clinically and histologically the oesophagitis in this rural population was different from that observed in the low-risk areas of Europe and the United States, where oesophagitis is often associated with reflux. Dysplasia was diagnosed in 16 subjects and invasive carcinoma in 11. The very high prevalence of chronic oesophagitis in northern Iran, where a high incidence of oesophageal cancer has also been reported, suggests that these two lesions are associated.


Antigen-antibody system associated with non-A, non-B hepatitis detected by indirect immunofluorescence. Ten chimpanzees were infected with non-A, non-B hepatitis by inoculation of patient serum or serum from a chimpanzee previously inoculated with patient serum. Convalescent serum from one of them reacted, in indirect immunofluorescent tests, with some of the hepatocyte nuclei in sections of autologous liver biopsy specimens and specimens from eight of the other chimpanzees. Serum from a convalescent patient reacted in the same way. These positive sera did not react with liver sections from uninfected chimpanzees. No reaction with positive liver sections was given by serum from chimpanzees which were uninfected or had antibodies to hepatitis A or B antigens. These control results suggest that the antigen-antibody system detected has specificity for non-A, non-B hepatitis.


Antithyroid-antibody activity in the snyovial fluid of patients with various arthritides. Microsomal and thyroglobulin autoantibody activity has been detected in synovial fluid from 34 of 50 patients with various arthritides (rheumatoid arthritis, ankylosing spondylitis, osteoarthrosis, and gout). Serum from only 4 of these patients showed thyroid-autoantibody activity, and the serum titres were considerably lower than the synovial-fluid titres. This suggests that thyroid autoantibody is produced locally in the joints of these patients.


Sequestration of staphylococci at an inaccessible focus. The persistence of staphylococcal arthritis in a patient treated with nafcillin was attributed to intracellular sequestration of staphylococci. These intraphagocytic organisms were protected against bactericidal activity. The infection was cleared by rifampin--an agent which can penetrate leucocyte membranes. When clinical infections do not respond to seemingly adequate antimicrobial treatment, intracellular persistence of bacteria should be considered.


Fatal aspiration (Mendelson's) syndrome despite antacids and cricoid pressure. Two patients died after inhalation of gastric contents during general anaesthesia for caesarean section. Both had received antacid therapy before surgery and their stomachs contained large volumes of fluid. Failure to empty the stomach preoperatively may have been a major contributory cause of these deaths.


Rapid-turnover transport proteins: an index of subclinical protein-energy malnutrition. The effect of protein and energy restriction on the plasma proteins, albumin, transferrin, prealbumin, retinol-binding protein, haptoglobulins, and immunoglobulins, was studied in obese subjects. Plasma albumin and transferrins failed to respond to short-term restriction of either protein or energy. Prealbumin and retinol-binding protein, however, were very sensitive to changes in both dietary protein and energy and responded rapidly to refeeding. Prealbumin and retinol-binding protein could be used to detect subclinical malnutrition and monitor the effectiveness of dietary treatment.


Observations on the adequacy of breast-feeding. The faltering of growth which frequently occurs in babies at the age of about 3 months in developing countries is sometimes attributed to insufficient food or to increased exposure to infection. The adequacy of breast-milk as a sole source of food for the young infant is examined in relation to the calculated average requirements for protein and energy. It is concluded that breast milk will fail to cover the energy needs of many infants after about 3 months unless a regulatory mechanism permits infants with higher than average requirements to obtain larger amounts of milk.


Changing pattern of schistosomiasis in Egypt 1935--79. A village in the Nile surveyed for schistosomiasis by J. A. Scott in 1935 was surveyed again in 1979. The same number of people as in the 1935 survey were randomly selected for investigation by the same parasitological techniques as those used by Scott. The prevalence of Schistosoma mansoni infection had increased from 3.2% to 73%, whereas S. haematobium infection, which had been very common in 1935 (74%), had almost disappeared (2.2%). In the local district hospital since 1972 the percentage of urine specimens found to contain S. haematobium ova has dropped from 30 to 9%, while the percentage of stool specimens containing S. mansoni ova has increased from 2 to 22%. In the local irrigation canals snail intermediate hosts for S. mansoni have outnumbered those for S. haematobium by a factor of 5--40 in the past 7 years. Changes in the proportions of snail vectors appear to be related to construction of the Aswan High Dam and to changes in the water-flow patterns of the Nile. The change in the relative frequencies of the two infections had important public-health implications, since the hepatosplenic schistosomiasis caused by S. mansoni is more difficult to treat and is associated with more morbidity and mortality than the urinary schistosomiasis caused by S. haematobium.


Cimetidine: interaction with oral anticoagulants in man. In 6 patients anticoagulated with warfarin, nicoumalone, or phenindione the addition of cimetidine prolonged the prothrombin-time (PT) by a mean of 12.6 s (range 5--23 s). In 7 volunteers taking daily subtherapeutic doses of warfarin the addition of cimetidine increased the PT from 19.4 to 22.9 s and the plasma-warfarin concentration from 0.96 to 1.76 microgram/ml. Cimetidine reduced the single-dose clearance of warfarin and antipyrine. The basis of the interaction between cimetidine and oral anticoagulants is probably inhibition of drug metabolism. Care should be exercised in concomitant therapy.


Cold pressor test in detection of coronary heart-disease and cardiomyopathy using technetium-99m gated blood-pool imaging. 50 normotensive subjects (22 controls with no cardiac disease, 24 patients with coronary heart-disease, and 4 with early cardiomyopathy) were investigated with gated cardiac blood-pool scintigraphy before and during cold pressor stimulation. The controls had no change or a significant rise (p less than 0.005) in left ventricular ejection fraction and preserved normal myocardial-wall motion, whereas patients with coronary-artery disease or cardiomyopathy had a significant fall (p less than 0.001) in left ventricular ejection fraction and many developed abnormal regional wall motion despite the absence of angina pectoris. Cold pressor gated cardiac blood-pool studies were more sensitive than single-lead exercise electrocardiography (p = 0.03) in the detection of patients with severe coronary-artery disease without previous myocardial infarction.


Identification of a clinical isolate as Legionella pneumophila by gas chromatography and mass spectrometry of cellular fatty acids. Culture of a bronchial aspirate from an immunosuppressed patient with severe pneumonia yielded a growth of filamentous poorly staining gram-negative rods. Fluorescence with Legionella pneumophila direct fluorescein-isothiocyanate conjugate was equivocal. Gas-liquid chromatography (GLC) and GLC/mass-spectrometry (GLC-MS) of the cellular fatty acids of the isolate confirmed that the organism was L. pneumophila. GLC and GLC-MS constitute a rapid and definitive method for identification of L. pneumophila isolates.


Tolfenamic acid is as effective as ergotamine during migraine attacks. Tolfenamic acid (a potent inhibitor of prostaglandin biosynthesis), ergotamine tartrate, acetylsalicylic acid, or placebo was administered during 160 migraine attacks in twenty women in a double-blind, cross-over study. Tolfenamic acid and ergotamine were equally effective in reducing the duration and intensity of attacks, but side-effects, especially nausea, were less common with tolfenamic acid. This probably accounted for the patients' preference for tolfenamic acid. The effectiveness of tolfenamic acid in acute migraine attacks accords with the postulated role of prostaglandins in migraine.


Pulmonary haemorrhage and haemolytic anaemia due to trimellitic anhydride. Two young men who had been exposed at work to epoxy resin powder containing trimellitic anhydride (TMA) presented with haemolytic anaemia and repeated haemoptyses. They did not return to work at the factory and the symptoms and the anaemia resolved spontaneously. Seven similar cases have lately been presented at meetings, so it seems that TMA, already known to cause respiratory syndromes such as asthma, can also lead to several extrapulmonary toxic effects, including haemoptyses and haemolytic anaemia. Studies on these patients' sera with TMA haptenised protein and cells pointed to an immunological mechanism.


Paraquat poisoning: significance of plasma-paraquat concentrations. Plasma-paraquat concentrations were measured in 79 patients who had ingested liquid or granular weedkillers containing paraquat. At any given time after ingestion, the plasma-paraquat concentrations in the patients who died usually exceeded those in the survivors. It is suggested that measurement of plasma-paraquat concentrations is useful in assessing the severity and predicting the outcome of poisoning. Patients whose plasma concentrations do not exceed 2.0, 0.6, 0.3, 0.16, and 0.1 mg/l at 4, 6, 10, 16, and 24 h respectively are likely to survive.


Acromegaly and narcolepsy.

Acromegaly and narcolepsy. 7 of 372 acromegalic patients had troublesome episodes of paroxysmal daytime sleep. Although 3 patients had complete remission of symptoms within a few days of pituitary implantation of isotopes, the cause of this increased frequency of narcolepsy among acromegalic patients is not known.


Identification of some infants at immediate risk of dying unexpectedly and justifying intensive study. Children who die unexpectedly in infancy often have symptoms of illness before death. Survey data are used to evaluate risks associated with symptoms. There is a 1 in 50 chance of unexpected infant death occurring in the next 9 days when two or more symptoms occur in infants defined to be at high risk by a discriminant score. The score is based on data collected on all infants at birth and by health visitors at 1 month. This system would identify 50% of cot deaths and provides a basis for prospective physiological studies.


Huntington's chorea. The basis for long-term prevention. A long-term programme to reduce the incidence of Huntington's Chorea has been established in South Wales, based on a study of all individuals known to be affected or at high risk in a defined population of 1.7 million people. Systematic but non-directive genetic counselling is being given to all adults at risk, accompanied by regular follow-up to provide both further information and practical support where required. The number of observed and projected new cases of the disorder born between 1900 and 1970 has remained almost constant, despite a progressive reduction in birth-rate in the general population during this period. Prospective monitoring of all births in the high-risk population will allow an estimate to be made of future trends and will show whether preventive measures are having any significant effect on the future incidence of the disorder in the population.


Prospective study of chlamydial infection in neonates. Chlamydia trachomatis was recovered from the cervices of 4% (36/900) of pregnant women tested. 20 infants born through chlamydia-infected cervices were followed up for a year, as were 18 infants born to chlamydia-negative mothers. A statistically significant excess of conjunctivitis and pneumonia was found in infants exposed to chlamydia. The attack-rate for inclusion conjunctivitis was 35% (7/20) and for chlamydial pneumonia it was 20% (4/20). Chlamydiae were recovered from 10 of the 20 (50%) exposed infants, and seroconversion was demonstrated in 14 (70%). None of the 18 unexposed infants showed evidence of chlamydial infection. Thus in our clinic 2.8% of all newborns acquired chlamydial infection, with incidence-rates of 14 cases of conjunctivitis and 8 cases of pneumonia per 1000 live births. Neonatal chlamydial infection is thus a major public-health problem warranting a preventive programme based on the fuller provision of diagnostic services and the treatment of infected pregnant women.


Acupuncture in heroin addicts; changes in Met-enkephalin and beta-endorphin in blood and cerebrospinal fluid. In heroin addicts showing features of heroin withdrawal basal beta-endorphin levels were elevated in both blood and cerebrospinal fluid (CSF) and did not change during electroacupuncture, although this therapy suppressed the clinical features of withdrawal. Met-enkephalin levels were not elevated in blood or CSF before treatment. However, successful electroacupuncture was associated with a rise in CSF met-enkephalin levels in all patients studied, although concentrations in blood did not alter.


Mitral-annulus calcification and cerebral or retinal ischaemia. Radiological and echocardiographic evidence of extensive mitral-annulus calcification was present in 8 patients (aged 64 to 78) from a series of 151 consecutive patients presenting with symptoms of retinal or cerebral ischaemia but in none of 188 controls matched for age and sex. The mitral-annulus calcification syndrome appears to be significantly associated with cerebral emboli, particularly in the elderly. Echocardiography is a valuable noninvasive means of making the diagnosis and distinguishing the condition from others with similar physical signs.


Value of new diagnostic aids in relation to the disease process in pancreatic cancer. An assessment was made of the diagnostic value of six tests done on 28 patients who proved to have resectable and 45 patients who had non-resectable pancreatic cancer. Ultrasonography and endoscopic retrograde cholangiopancreatography (ERCP) were the most sensitive tests for the diagnosis of resectable tumours. Ultrasonography was slightly, and cytology definitely, better for the diagnosis of resectable tumours than for the diagnosis of non-resectable tumours. Computerised tomography, angiography, and scintigraphy were not effective means of diagnosing resectable tumours. The differences in diagnostic sensitivities of the tests for resectable and non-resectable disease are probably due to variations in pathological features which influence not only the stage of presentation, but also the detectability of the tumour. As long as investigation is limited to patients with symptoms, a large proportion of tumours will not be diagnosed at a resectable stage. However, the results of this study suggest that the resectability rate may be maximised by the early use of ultrasonography in patients with symptoms suggesting cancer in the region of the head of the pancreas, and in patients with vague, non-specific complaints. A combination of ERCP and direct ductal aspiration for cytology is the best means of diagnosing resectable tumours.


A new look at HLA genetics with particular reference to type-1 diabetes. HLA genotypes were ascertained in 150 families with a diabetic child from the same geographical area. There was preferential zygotic assortment of the paternal HLA A1-B8 haplotype (63--65% compared with the expected 50%) in 69 diabetic families and 33 control families (pooled from elsewhere) who were informative for this haplotype. In diabetic families, the offspring also had an increased incidence of the maternal HLA A2-B15-Cw3 haplotype. Irrespective of which parent contributed the HLA A1-B8 haplotype, there was a significantly increased incidence of male children (63%) who inherited this particular haplotype. This probably explains the known excess of male diabetic children.


Thymidine sensitivity of cultured leukaemic lymphocytes. Cultured leukaemic lymphocytes from patients with T, null, or pre-B acute lymphoblastic leukaemia are shown to be highly sensitive to growth inhibition by thymidine. Thymidine sensitivity was correlated with reduced activity of the catabolic enzyme thymidine phosphorylase and sustained elevation of the deoxythymidine triphosphate pool after exposure to thymidine. It is suggested that thymidine may have a role in the management of certain acute lymphoblastic leukaemias of lymphomas.


Vitiligo patterns simulating autoimmune and rheumatic diseases. Several variants of generalised vitiligo can be recognised by their cutaneous distribution. In some, certain anatomical regions--e.g., hands--are predominantly affected while the cutaneous depigmentation in other variants shows a similar anatomical distribution to that of the internal structures affected in some of the autoimmune and rheumatic diseases. Five patients have been seen, and three described by others, with vitiligo affecting skin of eyelids and lower front of neck, reminiscent of the anatomical distribution of lesions in thyrotoxicosis with exophthalmos: two of these patients have thyrotoxicosis. Another variant of vitiligo mimicks the anatomical distribution of lesions in ankylosing spondylitis, Reiter's syndrome, and ulcerative colitis and there are cases simulating lupus erythematosus, rheumatoid arthritis, and psoriasis. It is suggested that the parts of the body affected in each vitiligo variant and its corresponding internal disease constitute a set os mosiac patches with distinctive shared characters. These may have morphogenetic functions during embryonic development and be potentially autoantigenic later in life.


Drinking problems: putting the Third World on the map. The extent of alcohol-related problems in developing countries is reviewed, and it shows that alcoholism has a serious impact in these countries. Moreover, the impact has special features, which are discussed. Suggestions for controlling alcoholism in the Third World are made.


Oral glucose-tolerance tests and the diagnosis of diabetes: results of a prospective study based on the Whitehall survey. Men who participated in the Whitehall survey and were found to be glucose intolerant have been studied 6--8 years later, together with a control group of men with normal screening blood-sugar levels. Ophthalmoscopically visible microvascular retinal disease was confined to men diagnosed as probably diabetic after the survey because their 2 h blood-sugar level (after a 50 g oral glucose load) in the survey examination or during a subsequent standard oral glucose-tolerance test was greater than or equal to 200 mg/dl (11.1 mmol/l). The lowest blood-sugar in a "diabetic" subsequently found to have retinopathy was 229 mg/dl. Men with lesser degrees of glucose intolerance, including 34 who had "worsened to diabetes", did not have visible retinovascular disease at follow-up. If diabetes implies a risk of specific microvascular complications in the medium term, then the findings in this study support proposals for the revision of diagnostic criteria based on glucose-tolerance tests.


Haemostatic function and platelet polyunsaturated fatty acids in Eskimos. Death from cardiovascular disease is rare among Eskimos. Haemostasis was investigated in twenty-one Greeland Eskimos and twenty-one age and sex matched Danish controls. Platelet lipid analysis demonstrated that a high consumption of omega-3 polyunsaturated fatty acids (such as cis 5, 8, 11, 14, 17-eicosapentaenoic acid [C20:5]) by Eskimos increased the proportion of omega-3 polyunsaturated fatty acids in the platelets. The Eskimos had a significantly longer bleeding-time due to a reduction in platelet aggregation. It is suggested that C20:5 in the platelets is converted by the vascular-wall tissue to an anti-aggregatory prostacyclin. Partial dietary substitution of arachidonic acid by eicosapentaenoic acid may reduce the incidence of thrombotic disorders, including myocardial infarction.


Prevention of chronic HBsAg carrier state in infants of HBsAg-positive mothers by hepatitis B immunoglobulin. 21 children of HBsAg-carrier mothers were given 0.5 ml/kg hepatitis B immunoglobulin (HBIg) within 48 h after birth and subsequently 0.16 ml/kg every month for 6 months; 20 children were not treated. None of the HBIg-treated children became HBsAg positive, compared with 5 of the untreated children (p less than 0.02). 2 of 3 children who were not started on HBIg until the fourth or fifth day after birth also became HBsAg positive. 4 children of mothers who had acute hepatitis B in the third trimester of pregnancy were treated with HBIg and remained HBsAg negative, whereas another, untreated, child became HBsAg positive.


Plasma-exchange combined with immunosuppressive therapy in myasthenia gravis. Twenty-one patients with myasthenia gravis underwent a course of plasma exchange combined with immunosuppressive therapy. In fifteen there was dramatic clinical improvement which has been maintained for periods up to 19 months. Nine of these patients now take no anticholinesterase drugs. Six patients had a recurrence 3--9 months after the first course but in the three given a second course remissions were again obtained.


HLA-DRW4 in 91% of Jewish pemphigus vulgaris patients. HLA-DRW4 was found in all 11 female and 10 out of 12 male Jewish patients with pemphigus vulgaris, a frequency of 91% in all, which was significantly higher than the 25% frequency among normal Jewish controls. The relative risk was 31.5. The BW38-DRW4 haplotype occurred in 12 out of 22 patients (55%) but in only 2% of White non-Jews and 11% of normal Jewish people.


Effect of irradiation on thyroid-autoantibody production. Irradiated lymphocytes have been found to stimulate thyroid-autoantibody synthesis by lymphocyte cultures. It is proposed that a similar effect is involved in the increased autoimmune response which follows radioiodine treatment for Graves' disease.


New pathways of nitrogen excretion in inborn errors of urea synthesis. The defect in nitrogen excretion in patients with inborn errors of urea synthesis can be controlled by exploiting the biosynthetic pathways of readily excretable non-urea metabolites which contain nitrogen derived from ammonium, alanine, glutamate, and glutamine. Two classes of such metabolites are the urea-cycle intermediates--including citrulline, argininosuccinic acid, and arginine--and the aminoacid acylation products--hippuric acid (the glycine conjugate of benzoic acid) and phenylactylglutamine (the glutamine conjugate of phenylactic acid). Thus the urea cycle may serve as a model for the development of excretion pathways of toxic precursors which accumulate in inborn errors of metabolism.


Prevention and treatment of endometrial disease in climacteric women receiving oestrogen therapy. The treatment regimens are described in 74 patients with endometrial disease among 850 climacteric women receiving oestrogen therapy. Cystic hyperplasia was associated with unopposed oestrogen therapy without progestagen. Two courses of 21 days of 5 mg norethisterone daily caused reversion to normal in all 57 cases of cystic hyperplasia and 6 of the 8 cases of atypical hyperplasia. 4 cases of endometrial carcinoma referred from elsewhere demonstrated the problems of inappropriate and unsupervised unopposed oestrogen therapy and the difficulty in distinguishing severe hyperplasia from malignancy. Cyclical low-dose oestrogen therapy with 7--13 days of progestagen does not seem to increase the risk of endometrial hyperplasia or carcinoma.


Anticonvulsant drugs and cancer. A cohort study in patients with severe epilepsy. Over 2000 epileptic patients admitted to the Chalfont Centre for Epilepsy between 1931 and 1971 and taking anticonvulsants were followed up to the end of 1977. Mortality between 1951 and 1977 was greatly in excess of that in the general population of England and Wales in that period allowing for age and sex. Some of the excess was directly attributable to epilepsy, but there were also more deaths from suicide and circulatory, respiratory, and malignant disease than would be expected. Apart from the brain and central nervous system, no particular site had a significant excess of tumours. In particular, there were no liver tumours (and only one gallbladder carcinoma). This makes it unlikely that the liver tumours produced on feeding phenobarbitone to mice are indicators of major human risk.


Biochemical prediction of gallstones early in an attack of acute pancreatitis. Plasma concentrations of bilirubin, alkaline phosphatase (AP), and glutamic oxaloacetic transaminase (GOT) were measured during 122 attacks of acute pancreatitis in 114 patients, on the day of admission to hospital and 2 days after admission. Concentrations in 74 attacks associated with gallstones were compared with concentrations in 31 attacks in which no stones were found. 24 attacks were severe by clinical criteria. On the day of admission plasma GOT concentrations of more than 60 IU/l were found in 88% of attacks associated with gallstones, but in no attacks without gallstones. Plasma concentrations of more than 25 mumol/l bilirubin and more than 14 King-Armstrong units AP were found in 62% and 66% respectively, of attacks associated with gallstones, and 5% and 10%, respectively, of attacks without stones. In attacks associated with gallstones plasma concentrations of GOT and bilirubin usually fell over the first 48 h of admission. No correlation was observed between these biochemical values and the severity of the attack. In the absence of a history of excessive alcohol consumption, increases in plasma GOT on the day of admission to hospital suggest that gallstones are responsible for the pancreatitis.


Detection of cystic fibrosis homozygotes and heterozygotes with plasma. Evidence is accumulating which indicates that the basic defect in cystic fibrosis interferes with the formation of recognition markers on hydrolytic enzymes. As a result these hydrolases leak into the extracellular space and some of them display abnormal thermolabilities. By heat inactivation of plasma alpha-mannosidase at 41 degrees C and plasma phosphatase at 36.5 degrees C, both enzymes being assayed at pH 5.4, it is possible to differentiate normal people from cystic fibrosis carriers and patients.


Plasma 25-hydroxyvitamin D in pregnant Asian women and their babies. Plasma 25-hydroxyvitamin D (25-OHD) was measured in cord blood taken at delivery and in fasting blood taken from 44 Asian mothers in the first day of the puerperium. Blood was taken from the baby 48 h after delivery. Cord-blood samples were also taken at 43 non-Asian deliveries. Plasma 25-OHD concentrations in Asians were low at delivery; in 81% of the mothers and 36% of the babies plasma 25-OHD was in the osteomalacic range. Asian lower than concentrations in non-Asian controls. 4 Asian babies had vraniotabes and 1 had neonatal tetany. 1 non-Asian baby had craniotabes. A review of 3327 deliveries in 1978 confirmed that neonatal tetany was significantly more common in Asian babies (2.3%) than in non-Asian babies (0.3%). In 44 other Asian mothers supplements of 1000 units of vitamin D daily during pregnancy significantly increased plasma-25-OHD concentrations at delivery.


Incidence of myeloid leukaemia in Lancashire. Identification of a "cluster" of cases of acute myeloid leukaemia and chronic myeloproliferative disorders in Lytham St. Annes, Lancashire, prompted an analysis of the incidence of myeloid leukaemias in Lancashire (excluding Ormskirk Health District), as recorded by the Manchester Cancer Registry. Although statistically there was no significant difference in the trend of incidence between the whole former borough of Lytham St. Annes and the other districts studied, the reported incidence of these diseases in the area as a whole had almost doubled, and in two districts nearly trebled, between two consecutive 6 year periods, beginning in 1965. This represents a substantially larger increase than mortality data suggests has occurred nationally in the same period, and is unlikely to be due solely to more accurate diagnosis or reporting.


Clonidine in Tourette's syndrome.

Clonidine in Tourette's syndrome. Tourette's syndrome (TS) is a neuropsychiatric disorder characterised by changing motor and phonic tics, compulsive actions, and other behavioural symptoms. Small doses of clonidine, an alpha-adrenergic agonist, improves the condition in some children unresponsive to haloperidol. Clonidine presumably acts by inhibiting central noradrenergic function. Metabolic and clinical findings suggest the involvement of monoamines, including noradrenaline, dopamine, and serotonin, in TS.


Blindness and paraplegia in severe childhood hypertension. 3 children with severe renal hypertension and bilateral infarction of the optic nerves are described. 1 patient also had a transverse myelopathy. Such complications may perhaps be prevented by earlier detection of hypertension and gradual reduction of blood-pressure.


Duct obstruction with an acrylate glue for treatment of chronic alcoholic pancreatitis. Six patients have been treated for chronic alcoholic pancreatitis by total obstruction of the pancreatic duct. In each instance the pancreatic duct was of near normal calibre, and any other procedure would have involved pancreatic resection. There has been little morbidity, and three of six cases have had complete pain relief.


Improving the long-term outlook in bacterial meningitis. In bacterial and tuberculous meningitis the supply of glucose to the brain seems to be inadequate for its demands which are increased as a consequence of increased cerebral glycolysis. Treatment of patients with glucose infusions to restore cerebrospinal-fluid glucose to normal is therefore indicated.


Anorexia nervosa in males.

Anorexia nervosa in males. Five cases of anorexia nervosa in males aged 13--23 years are described. Four patients presented to a general medical outpatient clinic with emaciation, and the fifth was diagnosed retrospectively. Sinus bradycardia was a useful pointer to the diagnosis, which was confirmed by the finding of characteristic psychopathological features of a relentless "pursuit of thinness", along with a fear of becoming obese.


Shelf-life of citric acid-toluidine blue O-SO2 and its influence on Feulgen staining. The paper reports on the preparation of a dye-SO2 reagent employing a Schiff-type dye, toluidine blue O. The method is to replace 5 ml of N HCl per 100 ml of the dye solution by citric acid. The usual potassium metabisulphite is then added. The pH of this new modified dye-SO2 reagent is 2.5 as against 1.6 for the hydrochloric acid-toluidine blue O-SO2. The shelf-life of this newly developed dye-SO2 reagent is four weeks with appreciable reduction of staining intensity after this period as compared with that of a freshly prepared dye-reagent with N HCl. A possible interpretation for the observed phenomenon has been suggested.


Detection of DNA in mammalian tissues following removal of RNA with cold phosphoric acid. The paper deals with the staining of nuclei in mammalian tissue sections with night blue, belonging to diphenylnaphthylmethane group and is devoid of any primary amino group in its molecules but is provided with a secondary amino group and tertiary amino groups. Staining of the DNA-phosphate groups with an aqueous solution of night blue depends upon selective removal of RNA from formalin-fixed mammalian tissues by the use of cold concentrated phosphoric acid for 20 min or 75% phosphoric acid in the cold for 2 h. Moreover, sections from which RNA has been extracted can be hydrolysed in 6N HCl at room temperature for 15 min and then can be stained with the aqueous solution of the dye. Sections of tissues after only acid hydrolysis and staining also reveal very satisfactory staining of the nuclei. Possible mechanism of staining has been suggested.


Fixation of mammalian tissues in different fixatives and its influence on the staining with methyl green-pyronin. This investigation is a study on the role of fixation of different mammalian tissues in different fixatives as well as in 10% neutral formalin containing different metal cations and its effect on the staining with the dye-mixture, methyl green-pyronin. The results indicate variation in the colour of the nuclei in tissues fixed in the different fixatives. The possible role of the fixatives on nuclear colouration has been discussed.


Independent learning packages (audio tape/pamphlet) for a course in cell excitation: evidence that they can be at least as effective as conventional lectures. Three tape/pamphlet independent learning packages have been constructed to serve the same learning objectives as three conventional lectures on the physiology of the nerve axon. The learning efficacy of each package was compared with that of its companion lecture with the co-operation of fifty first-year medical students in a controlled experiment. The packages were at least as effective as the lectures in generating both short- and long-term attainment of their intrinsic learning objectives. The findings are discussed in relation to learning efficacy, student study time, student acceptability, package preparation time and costing.


[Studies on human immunoglobulin preparations: I. Viral antibody profiles (author's transl)]. A study was undertaken to assess the viral antibody spectrum in human immunoglobulin preparations from four different manufacturers for intravenous and/or intramuscular application. Studies of the kind seem to be reasonable for calculating the expected therapeutic effect of the administered immunoglobulin. The investigated 16 gammaglobulin batches showed almost the same variety of viral antibodies and only slightly differring antibody titers. It is interesting to note, that antibodies to vaccinia virus could not be demonstrated. Quantitative determination of viral antibody titers in immunoglobulin preparations for standardization purposes should include the testing of antibodies to viruses against which a therapy with gammaglobulins is reasonable.


[Studies on human immunoglobulin preparations: II. Purity and composition (author's transl)]. 16 human immunoglobulin preparations for intravenous and/or intramuscular use of 4 different manufacturers were tested with regard to their purity and composition. Anticomplementary activity was detected in preparations for i.m. application, but surprisingly also in some preparations for intravenous use, a fact which may possibly cause allergic or anaphylactic reactions. Besides IgG, which accounted for the main part of the protein content, small amounts of IgA, IgD, and IgM were found. IgE was detected in every batch studied. Some contained IgE-concentrations, usually seen in atopic persons.


Simulation and prevention of retrovirus--specific reactions by mycoplasmas. From human mycosis fungoides tumor-derived cell lines, Mycoplasma hyorhinis was isolated. This mycoplasma shared the following characteristics with retroviruses: uptake of 3H-uridine, but not of 3H-thymidine in cell culture; banding at 1.16 g/ml sucrose density and partial shift to retrovirus core density position (approximately equal to 1.24 g/ml) after detergent treatment; incorporation of 3H-TMP into high molecular weight material in standard reverse transcriptase assays with the template-primer poly (A) . (dT)12. On the other hand, the specific reverse transcriptase reaction of retroviruses with poly(A) . (dT)12 and poly(C) . (dG) approximately 16 was almost completely abolished in the presence of the mycoplasma. Thus, M. hyorhinis may interfere with identification and isolation procedures for retroviruses.


Cisplatin, bleomycin, and vinblastine combination therapy of testicular tumors: an analysis. A combination regimen consisting of cisplatin, bleomycin, and vinblastine was evaluated in 86 patients with metastatic testicular tumors. Prior therapy included surgical resection of primary tumor (84 patients), radiotheapy (21 patients), chemotherapy (33 patients). Thirteen patients received prior bleomycin and vincristine or vinblastine. Of 80 evaluable patients 51 achieved complete response (CR) and 26 achieved partial response (PR), for an overall response rate 96.5%. There was no significant difference in response rates or survival with respect to prior therapy, sites of metastatic lesions, and tumor histology. The median survival time was not reached in an observation period of 44+ months. Sixty patients were alive 11+--44+ months, and 57 of these were free of disease. Thirty-two of the 60 patients (53%) had a survival time greater than 20 months. Toxicities included nephrotoxicity (18 patients) leukopenia, (69 patients), thrombocytopenia (nine patients), and anemia (56 patients). Bleomycin-induced pulmonary toxicity was fatal in one patient. Other toxicities included nausea and vomiting, stomatitis, fever, alopecia, and neurological effects.


[Congenital analgesia. Third communication: the onset of pain sensitivity (author's transl)]. Congenital analgesia in a girl is reported for the third time. The most prominent symptom in the prepubertal child is that pain is now perceived over the entire body. Training normal perception of pain proceeded by stages. It can be established subjectively and by objective investigations. The physiology of analgesia and its probable pathomechanism are discussed.


[Methodological hints on the gas chromatographic determination of kelevan and kepone in potatoes, potato foliage and soil]. The gas chromatographic determination of Kelevan, an ethyllaevulinic acid derivative of Kepone, requires its conversion to Kepone. Thermal decomposition in the injection block of the gas chromatograph at 45 degrees C. has proved to be well suited for routine work. The sample is extracted with acetonitrile; the extract is purified and concentrated under reduced pressure. The separation of Kelevan from Kepone already metabolically produced is possible by column chromatography (silica gel; elution with benzene and 5% acetone in benzene). The determination of pre-existent Kepone and of Kelevan (after thermal conversion to Kepone) was achieved by means of a Pye-Unicam gas chromatograph. The limits of detection are 0.002 p.p.m. for Kepone, and 0.003 p.p.m. for Kelevan. The recovery of Kelevan and Kepone added to control samples (for every 10 determinations with different amounts added to potatoes, potato foliage and soil samples) ranges from 63 to 88%; the standard derivation, from +/- 1.7 to 7.3%.


CEA-like antigens in different histologic types of human lung carcinoma. Comparative studies on the presence and immunological reactivity of CEA and CEA-like antigens in lung and digestive tract cancers were performed. Specific goat and rabbit anti-CEA immune sera were used. Immunofluorescence studies revealed in histologically different types of the lung carcinomas the presence of the cross reacting antigen with classical CEA. Absorption procedures, and double diffusion tests have shown the existence of two at least antigenic determinants in CEA molecule: 1. the determinant specific for the lower parts of the digestive tract cancers not found in the lung carcinomas, and 2. the determinant common for the lung, and the digestive tract cancers.


Carcinomas of the liver in rats ingesting kepone. Young male and female albino rats ingested 0, 1, 5, 10 or 25 ppm Kepone, an organochlorine pesticide, in the diet for two years. Carcinomas of the liver, as well as hyperplastic nodules and moderate and severe diffuse hyperplasia were observed in Kepone-treated rats. Such hepatic lesions were not seen in control rats. Female rats ingesting Kepone were more susceptible than male rats to hepatic carcinogenesis. Rats ingesting 50 or 80 ppm Kepone developed severe diffuse hepatic hyperplasia and did not survive beyond 26 weeks.


[Prognostic elements in bronchial carcinoma]. In spite of improvements in diagnosis and treatment, the fatal prognosis of lung cancer has persisted over the course of 25 years in a series of nearly 4000 patients. Only 30% (1149 cases) were operable, and on 23% of those resected (i.e. 7% of the total) survived for 5 years. An assessment is made of the relationship between survival and sex, age, tumour size and site, radiological picture, stage of invasiveness, type of surgery and degree of radicality, histological picture, and number of circulating lymphocytes. Age, sex and the type of resection (lobectomy or pneumonectomy) had no relation to prognosis. Palliative surgery was always associated with a fatal prognosis, as were cases with invasion of the chest wall, or, more particularly, with oat cell cancers. The outlook was more favourable in cases where radical treatment was given, in cases of squamous cancer, as opposed to other histological types, in those in stage 1 (Am. Joint Committee classification), and those with greater than 2000/mm3 lymphocytes--especially in adenocarcinomas.


Characterization of murine hepatoma BW7756. I. Selected biochemical properties of liver and hepatoma. Selected biochemical properties, based on hepatocellular function, were assessed in the mouse hepatoma BW7756 and host and/or normal mouse liver. These biochemical properties included (a) alpha-fetoprotein (AFP) production, (b) lipid composition, (c) isozyme patterns and enzyme activities, and (d) cyclic AMP levels. The tumor evidenced an exponential growth phase and vigorous production of AFP in the first 3 weeks following transplant. The concentration of AFP in the sera of tumor-bearing mice increases roughly with the growth of the hepatoma. The percentage of total lipid in the hepatoma was greater than in either normal or host liver; however, the liver displayed more phospholipid than the tumor, while more triglyceride was demonstrable in the hepatoma. Of the 17 isozyme patterns analyzed, seven--acid phosphatase, malate dehydrogenase, aspartate amino-transferase, glucose-6-phosphate dehydrogenase, esterase, lactate dehydrogenase, and xanthine dehydrogenase--were different in the liver and the tumor. The cyclic AMP levels decreased in the tumor and the host spleen from day 10 to day 21; however, slight increases were noted in the tumor and host spleen and liver at day 28. These studies suggested 2--3 weeks posttransplantation as the optimal time for investigational use of this hepatoma.


Endodermal sinus tumor of the ovary. Clinicopathologic study of 6 cases. 6 cases of endodermal sinus tumor of the ovary are presented. In 4 patients pure endodermal sinus tumor was found microscopically. 1 patient had endodermal sinus tumor in one ovary and gonadoblastoma in the contralateral one. In another case endodermal sinus tumor was accompanied by an embryonal teratoma. Histologically, the tumor had characteristic features with meshwork of spaces and channels lined by embryonal cells, glomerulus-like structures known as Schiller-Duval bodies, solid aggregates of epithelial cells, hyaline basement membranes and round, PAS-positive small globules found both intra- and extracellulary. In 1 patient the elevated serum alpha-fetoprotein was stated. All patients were treated surgically with adjunctive radiation and/or with chemical agents. None of them were cured. The median duration of survival amounted to 8.5 months. Discussing the value of the more recent approach to diagnostic and therapeutic methods found in the literature, it must be emphasized that the demonstration of elevated serum alpha-fetoprotein in patient with that tumor lend not only further support to its yolk sac origin but also might be useful to monitor response to the therapy applied. It is also of prognostic significance by indicating the presence of residual or recurrent disease, even in its subclinical stage. Combined postoperative irradiation and triple chemotherapy according to the VAC regimen of patients can prevent recurrence and in some cases even may cause permanent remission of the neoplasm.


Molluscum contagiosum of the palpebral conjunctiva. Report of a case. A molluscum contagiosum nodule, situated at the palpebral conjunctiva of the left lower eyelid at the level of the marginal and tarsal conjunctiva, was observed in a 53-year-old male. A mild follicular conjunctivitis was present, except in a zone immediately below the molluscum. On the corresponding site of this molluscum at the bulbar conjunctiva, the limbus and the cornea, no follicles, epithelial keratitis nor erosions were seen. Clinical diagnosis in atypically situated mollusca can be difficult. Cytological studies in these cases are very helpful. Alcohol-carbowax fixated and Papanicolau stained preparations proved to be very satisfactory for cytological examination. It has never been reported that a molluscum, situated in the palpebral conjunctiva, disappeared spontaneously.


Neurologic sequelae in the survivors of neonatal intraventricular hemorrhage. We report our experience with the neurologic sequelae (at a mean follow-up of 24 months) among the 15 surviving infants who have had neonatal intraventricular hemorrhage (IVH) documented by computerized tomographic (CT) brain scan. Neurologically six infants (40%) are normal, six infants (40%) mildly impaired, and three infants (20%) moderate to severely impaired. The neurologic outcome correlated to the degree of hemorrhage seen in the CT scans when IVH was classified into four grades. None of the other neonatal factors examined showed significant correlation with the outcome.


[Progressive acquisition of resistance to chlorpyrifos in Culex pipiens (L.) larvae in the South of France]. A high resistance level has been detected in certain Culex pipiens populations after seven years of chlorpyrifos larval treatments in the Montpellier area (Southern France). The highest rate recorded in 1973 was x 15, in 1974 x 33,3, in 1975 x 47 and in 1976 x 73. The resistance level depends on the application frequency of this larvicide and the various biotope types. "Closed populations" are subjected to a higher selection pressure than "open populations". It is now necessary to find a replacement compound for chlorpyrifos as there is a quick reinfestation and thus the treatment frequency had to be increased these last two years.


[Comparative action of 31 insecticides on chlorpyrifos-sensitive and resistant Culex pipiens (L.) larvae in the South of France]. In urban and sub-urban areas larval populations of Culex pipiens are now resistant to chlorpyrifos. A replacement compound must be found so 31 pesticides were tested against 3 strains: 2 of them were bred in the laboratory (on sensitive and one resistant) and the third one collected in an area treated with agricultural pesticides and chlorpyrifos. The results show that this last compound induces a cross-resistance only to organophosphorus compounds especially to parathion, chlorpyrifos-methyl, pyrimiphos-methyl, diazinon and Abate. Agricultural pesticides made this species resistant to chlorinated hydrocarbon and organophosphorus compounds. Among the latest, trichlorfon, azinphos-methyl, methidathion and malathion are still efficient as are propoxur, Decis (pyrethroid), methoprene and Dimilin.


Scabies, a current pandemic.

Scabies, a current pandemic. Scabies, caused by the itch mite and transmitted by skin-to-skin contact, is being seen in pandemic proportion. In the United States this infestation is seen in patients of all ages and socioeconomic levels. Scabies is often misdiagnosed, and the classic form occurs less frequently in the current cycle. Differential diagnosis includes most pruritic dermatoses. Diagnosis should be made with certainity, preferably by identification of the mite, before therapy is begun. Modern scabicides are high effective.


[Isotopic indicators in the diagnosis of malignant pleurisies (author's transl)]. The tracers that are used in thoracic pathology have an elective tumoural affinity, present such a special reaction towards pleural effusions that we were led to study Bleomycin labelled with Cobalt 57 in 34 cases of pleurisy of various etiologies. The hyperfixation, circumscribed to the effusion in all these cases, presented a double problem : of radiobiological risk and of diagnostic significance. We tried to solve the last problem by means of a precise protocol applied to 16 cases, quantifying comparatively the specific radio-activity of pleural fluid and serum and studying the evolution of the pleural serous gradient, after injection of 2 mCi of labelled Bleomycin in 16 patients with suspected malignant pleurisy. From this limited study, it appeared that the sero-pleural gradient of the tracer, 24 hours after injection, was very high, above 5 and up to 15 in 7 malignant pleurisies out of 8; between 2 and 4 in others. It was sometimes below 5 and less in effusions, non malignant or doubtful. This gradient decreased very rapidly to reach 0 on the fourth day, except in recurring chronic effusions. Pending the confirmation of results, after a prolonged experiment, this protocol appeared valuable for diagnostic and physiopathological reasons.


Effect of a teaching program on knowledge and compliance of cardiac patients. This study was designed to look at the effect of a comprehensive teaching program on patient knowledge and compliance. Thirty patients who had had valve replacement surgery and 18 patients who had had coronary artery bypass surgery were included in the study. Twenty-five of these patients were taught by masters-prepared clinical specialists and 23 by nurses with less than masters preparation. Measurements of knowledge and compliance were obtained preoperatively, at discharge, and during the first two postoperative visits. Findings included significant changes in knowledge scores from the preoperative test to the discharge test and stability in most scores from discharge to both postoperative visits. Compliance percentages were significantly higher than those reported for cardiac patients in a previous study. Patients taught by masters-prepared nurses had significantly higher test scores at discharge than did patients taught by nurses with less than masters preparation.


Effect of positioning of postoperative fractured-hip patients as related to comfort. Twenty-three elderly patients, who had experienced repair of a fractured hip with Richards' compression nail and plate,were surveyed in a midwestern general hospital over a four and one-half month period. This study, which measured which position best maintained comfort postoperatively for these patients, demonstrated that the best way of positioning patients was not always as perceived by nurses. The study also correlated positioning with body weight and with sleeping side habit. Findings verified previous research on pain and nursing comfort measures. The quality of nursing care can be demonstratively improved when the diagnosis of these elderly patients is not allowed to preclude the provision of appropriate therapy and nursing care.


[Demonstration and semi-automatic assay of gelatin in serum]. We suggest a semi-automatic method for the determination of gelatin. The measured concentration of gelatin is not dependant for the amino-acid composition of that plasma substitute preparation. Plasmatic proteins are separated previously from gelatin by precipitation using trichloracetic acid (5 p. cent; vol/vol). Modified gelatin lower in molecular weight than proteins can be found in the supernatant. It is determined by Lowry method with an automatic continuous flow system. Standardization must be realized using gelatin's solution since the developped coloration intensity with proteins is stronger. At electrophoresis, gelatin migrates essentially towards beta-globulins. beta-globulins increased with the gelatin level in serum. Percentage of variation for beta globulins and other fractions must be determinated in function of the protein level before perfusion. So it is possible to study the percentage of variation of these electrophoretic fractions independantly of the altered protein level.


Cost effectiveness of screening children in health centers. Aides from poor neighborhoods in Denver, Colo., screened children in four health centers for problems in hearing, vision, articulation, and development, and children with abnormal test results were referred to specialists for evaluation. In 3 months, paraprofessional aides did 3,183 tests, of which 302 yielded abnormal results. In 146 instances, these abnormal results led to the evaluation of the children by a specialist, who recommended treatment in 95 instances. The total annual cost of maintaining one paraprofessional aide was $10,937. The average cost per test performed by such an aide was $2.87, $30 per abnormal test result, and $96 per test resulting in a decision to treat. The results show the importance of considering the later stages of followup in evaluating a screening program.


Presence of alloreactive Ia antigens on murine intestine epithelial cells. Purified intestine epithelial cells express Ia antigens as determined by immunoprecipitation and sodium dodecyl sulphate polyacrylamide-gel electrophoresis. The intestinal Ia antigens react at least with alloantisera directed against the H-2 I-A subregion.


Heterologous B-cell antisera may detect non-Ig, non-HLA-DR antigens. A heterologous antiserum (antiserum 7420) against B-lymphocyte antigen(s) was raised in a rabbit by immunization with peripheral blood lymphocytes from a patient with chronic lymphocytic leukaemia (CLL). After absorptions with pooled normal human serum, IgA, IgD, and IgM M-components, the fluorescein isothiocyanate-conjugated F(ab')2 fragments were prepared and further absorbed with normal peripheral blood leucocytes. The F(ab')2 fragments, studied in direct immunofluorescence, reacted with both normal and CLL B lymphocytes but not with T lymphocytes. Comparative studies with an HLA-DR antiserum showed that the antigen(s) detected by 7420 antiserum did not redistribute together with HLA-DR antigens in cocapping experiments, nor did the HLA-DR antiserum block the reaction of 7420 F(ab')2 fragments with B lymphocytes. The 7420 F(ab')2 fragments prcipitated detergent-solubilized B-cell membrane material with a molecular weight of around 40,000 and 150,000 daltons. The conclusion drawn is that the 7420 and HLA-DR antigens are different. The 7420 antigen was also shown to be different from classical HLA antigens, beta 2-microglobulin, surface immunoglobulin, the Fc receptor, and HC protein.


[Isoelectrofocusing on polyacrilamide gel in the study of gamma-globulin changes during neurological illnesses (author's transl)]. Isoelectrofocusing on polyacrilamide gel in the analysis of cerebrospinal fluid proteins is particularly suitable for investigations of gamma-globuline changes in the course of various neurological conditions. This technique makes it possible to recognise three patterns besides the normal one. The first is characterized by a diffuse increase in gamma-globulines with a great number of high density fractions showing uniform distribution in the alkaline pH area. It was observed in a case of Guillain-Barrè syndrome and in two cases of intramedullary tumours. It seems to be due to an alteration in the permeability of the blood-brain barrier. The second pattern shows a diffuse increase in the number of fractions and appears uneven owing to a certain amount of higher density bands which stand out clearly. This was observed in one case of tubercolous meningo-encephalytis, in one case of chickenpox encephalytis and one case of cryptococcal meningitis in a patient affected by lymphogranuloma. This pattern is probably due to an alteration of blood-brain as well as of immunological systems. The third pattern presents a clear fractionation of gamma-globulins gathered in a certain number of highly coloured bands, mainly in the most alkaline area of gel. This was observed in all the ten cases of multiple sclerosis and in the only case of subacute sclerosing panencephalitis. This may be attributed to the intrathecal production of oligoclonal gamma-globulines (Ig.G.).


Idiotypic determinants in alloantigen receptors. I. Role in a leucocyte migration inhibition reaction. An anti-idiotypic serum was prepared by injecting BALB anti-AKR serum into (BALB X AKR)F1 mice. Pretreatment of BALB anti-AKR immune cells with this anti-idiotypic serum plus complement abrogated a leucocyte migration inhibition reaction (LMIR) against AKR extracts but not against purified protein derivative By itself, the serum induced LMIR in immune cells but not in normal cells. The reaction was strain-specific and anti-Thy 1,2 plus complement sensitive. These results indicate that alloantigen receptors, able to trigger in LMIR in immune cells, have idiotypic determinants similar to those of circulating antibodies of the same specificity. Thus the LMIR is a good model for the study of receptors cell-mediated immune reactions of primed cells.


Evidence for the expression of Thy-l-analogous structures on human thymic epithelial cells. Cultured human thymic tissue was examined electron microscopically and analysed for the expression of the Thy-l-analogous antigen. It was found that almost all cultured cells were of epithelial appearance, exhibiting both tonofibrils and well-developed demosomes. Absorption of an anti-human brain serum highly purified for antibodies directed against the non-species-specific determinant of the Thy-l-analogous antigen with these cultured cells revealed its presence on thymic epithelial cells. Using the indirect peroxidase-labelled antibody technique, this molecule could be localized on the non-attached cell surface of human thymic epithelial cells with the preference of their cell processes. The biological significance of the expression of this antigen on the thymic epithelial cells of various species for cellular interaction within the thymus is discussed.


CSF -- oligoclonal bands in multiple sclerosis. The present paper is concerned with a correlation between clinical parameters of multiple sclerosis and different agar gel electrophoretical patterns in CSF. The agar gel electrophoresis represents clearly the most sensitive method for the demonstration of oligoclonal bands in CSF.


[Contraceptive hormones, vascular risk and abnormal precipitation of serum gamma-globulins (author's transl)]. The monoclonal anti-ethinyl-estradiol antibody previously found in the serum of a woman on oral contraceptives, was precipitated by 25% saturated ammonium sulfate à 22 degrees C. This simple test has been used to investigate the possible relationship between abnormally precipitating gamma-globulins (GAP) and the vascular risk of the pill. Four groups of women were studied: --50 women who had never used the pill; --100 women on oral contraceptives; --30 women who had stopped the pill; --17 women who had experienced venous or arterial thrombosis during oral contraception. The results obtained indicate: 1) that a GAP increase is nearly always associated with the thrombotic events (90% of the cases in group 4); 2) that the presence of GAP is seen only in part of the women population on oral contraceptives representing approximately 30% of the total population investigated as indicated by a bimodal distribution; 3) that the GAP remain increased for months and even years after the pill was discontinued. The significance of this test is discussed. It is proposed that the presence of GAP in the serum appears to be related to the presence of ethinyl-estradiol binding antibodies. This hypothesis is verified by experiments in progress.


[Allergy and histamine release (author's transl)]. Histamine is released from mastocytes and basophils polymorphonuclears. This occurs particularly in reaginic type of allergy. The different phases of the reaginic process has been studied: IgE bridgings with antigens, cell membrane activation, cytoplasmic biochemical reactions involving cyclic AMP and GMP leading to microtubules activities, contraction of microfibrils and degranulation. Calcium and magnesium contribute to the regulation of histamine release. Histamine releases could also be seen in non reaginic type of immuns allergic reactions by way of direct or indirect activation of complements, by stimulation of PAF, etc...Finally, quite a few substances could also provoke histamine release of non immunologic type (physical agents, snake and bee venoms chemical substances in micro or macromollecular forms used in therapeutics...). Their mechanisms of action are various; yet in a way, they present similaritis with immunoallergic reactions. In practice, it is often difficult to assert the allergic nature of a histaminic reaction. Immunologic evidences should be cautioniously searched before any conclusion.


Rhabdomyosarcoma presenting as carcinocythemia. A case of rhabdomyosarcoma presenting with circulating tumour cells (carcinocythemia) is discussed. Tumor cells must be differentiated from leukemic cells or a leukemoid reaction. If the abnormal cells appear as syncytia, tumor should be strongly suspected. Cytochemical and/or histochemical stains should also be employed to differentiate tumor cells from hematopoietic cells.


[The fate of children who have undergone correction of Fallot's tetralogy. Report of fifty long term assessments (author's transl)]. 50 children who had beneficied of repair of Fallot's tetralogy with a follow up of 2 to 11 years, were psychologicaly and physicaly evaluated. Work capacity tests were performed in 12 cases. Children with early repair (before 5 years of age) have a very better result. Preliminary palliative treatment cause worse results. Physical capacities are normal in the majority of children. Work capacity is not different from normal children. Repair before school age is the best way for a normal life.


The influence of non-steroidal anti-inflammatory and antithyroid agents on myeloperoxidase-catalysed activities of human leucocytes. Viable leucocytes obtained fresh from normal human subjects were shown to be able to catalyse the in vitro iodination of bovine serum albumin (BSA) in a H2O2-generating system. The rate and degree of iodination were greatly improved by sonication of the cells. A balanced salt solution was a more favourable medium than phosphate buffer for the myeloperoxidase (MPO)-catalysed iodination of whole cells and sonicated cells. Reactions known to be catalysed by other peroxidases (e.g. thyroid peroxidase (TPO) and lactoperoxidase), such as inorganic iodide exchange for organic iodine in di-iodotyrosine (DIT) and the de-iodination of thyroxine (T4), were also catalysed by the sonicated leucocyte suspension in the system used. The non-steroidal anti-inflammatory drugs indomethacin, flufenamic acid and naproxen were far less effective inhibitors of MPO-catalysed BSA iodination of sonicated leucocytes at concentrations expected in blood with therapeutic dose levels than was observed earlier with TPO-catalysed in vitro iodination of BSA. The antithyroid drug methylmercapto-imidazole (MMI) inhibited in vitro MPO-catalysed 131I delabelling of 131I-DIT at all concentrations between 10(-7) and 10(-2)M, whereas 131I-T4 delabelling was markedly stimulated at the same drug concentrations. On the other hand, 125I incorporation into 131I-DIT was not affected by increased concentrations of MMI up to 10(-5)M. At higher drug concentrations the drug caused inhibition of MPO-catalysed exchange of inorganic iodide for organic iodine in DIT.


Light microscopic and ultrastructural observations in advanced stages of induced exencephaly and spinal bifida. This investigation was performed to demonstrate the morphologic basis of the elevation of fetal proteins in the amniotic fluid of fetuses with neural tube defects. Pregnant rats were treated with hypervitaminosis. A to induce exencephaly or with trypan blue to produce spina bifida aperta. The malformations were studied on days 15-20. On day 15 of gestation, edema developed in the primitive nervous tissue. This was followed by the appearance of quickly expanding hemorrhages throughout the ventricular and intermediate zones. Some capillaries did not rupture but collapsed and showed degenerative changes of the endothelium, probably due to lack of blood perfusion. The ventricular layer in exencephaly and spina bifida aperta was exposed to the amniotic cavity due to non closure of the neural tube. On day 17, this superficial lining of the primitive nervous tissue was disrupted by the expanding hemorrhages and subsequent necrosis. As a result vast amounts of fetal blood and cell debris were extruded into the amniotic fluid. During days 18 to 20, the degeneration of the nervous tissue proceeded rapidly. This process showed the same features in the ventricular cells, the primitive neurons and the neurons. Initially it was characterized by condensation of the nuclear chromatin and the cytoplasm, irregular outlines and breakdown of the plasma membrane. Only part of the cell debris was phagocytozed by macrophages. It is concluded that the leakage of fetal serum and cell debris causes the elevation of fetal protein levels in the amniotic fluid of fetuses with open neural tube defects.


Behavioral consequences of interference with CNS development in the early fetal period. As a part of a series of investigations into the structural and functional consequences of interference with cell proliferation, mice were treated with 5-azacytidine during two stages of early fetal life. Treatment on either the twelfth or fourteenth day of gestation led to permanent significant reductions in body weight and brain weight. Behaviorally, the earlier treatment was associated with a delay in development of the righting reflex, permanent deficits in locomotor coordination, and hypoactivity. Treatment on the fourteenth day of gestation led to decreased passive avoidance, increased active avoidance, and hyperactivity--the same syndrome observed after treatment on the eighteenth day. Both treatments led to abnormal behavior on a spatial maze task. The developmental outcome of injuries induced in the early fetal period appears similar to the outcome of injuries at later stages of development.


The effects of compound 48/80 on the fibrinolytic activity of dogs. It has been demonstrated that histamine by itself, did play some role in the activation mechanism of fibrinolysis. In this particular work, it was demonstrated that histamine at doses not affecting blood pressure levels, did not exert any direct immediate effect on fibrinolytic activity. Compount 48/80, a powerful mast cell depleter and histamine liberator, by itself, has no direct molecular effect on fibrinolytic activity, but rather, through the release of activators and/or inhibitors form mast cells, will exert either an activating or inhibiting action, according to the dose used. Low doses, such as 0.2 mg/kg i.v. will achieve a higher degree of activator release, while doses of 1.0 mg/kg will result in higher inhibitors release from mast cells.


Fluorochrome staining of multilamellar liposomes. Multilamellar liposomes can be stained with such fluorochromes as acridine orange, eosin Y, neutral red, and thiazine red. The liposomes are brought into a 1% solution of the fluorochrome; 5-10 minutes later they are centrifuged and washed by resuspending in water or phosphate buffered saline three times. The last pellet is resuspended and a drop studied with the fluorescence microscope (1000 x magnification). The fluorochrome is seen to be accumulated in the liposomal membranes. Acridine orange could also be trapped in the aqueous compartments of the liposomes but the trapped fluorochrome was gradually lost from the liposomes. Part of the fluorochrome, however, remained associated with the liposomal membranes for a long time. Additional experiments justify the conclusion that an equilibrium is maintained between fluorochromes in the aqueous and lipid phases.


Gallocyanin-chromalum for improved scanning electron microscopy of whole nuclei without critical point drying. Bone marrow nuclei fixed with modified Carnoy's, then stained with gallocyanin chromalum followed by air drying showed no difference in morphology when compared by means of scanning electron microscopy with similar nuclei prepared by critical point drying. Glutaraldehyde at pH 4.0 and 7.1, mercury-containing Zenker's fluid, and chromalum alone, all of which are considered to be nuclear protein cross-linking fixatives, failed to preserve the nuclear morphology as well as gallocyanin-chromalum or critical point prepared bone marro nuclei.


Differential dichrome staining of tissue culture monolayers: alternate dyes and possible mechanism. A polyacid-dependent dichrome has been devised which will differentiate epithelial from mesenchymal cells in young dividing primary cultures. Epithelial cells and colonies and nuclei are stained with metanil yellow, the stain is fixed and differentiated with phosphotungstic acid, and the mesenchymal elements are stained with toluidine blue. Several other dyes are tested for substitution in this method. Biebrich scarlet and aniline blue could be substituted for the metanil yellow; Bismarck brown T, Janus green B, crystal violet, and neutral red could be substituted for the basic dye.


A comparison of methods using diaminobenzidine (DAB) to localize peroxidases in erythrocytes, neutrophils, and peroxidase-antiperoxidase complex. Reactions using diaminobenzidine (DAB) to localize the enzyme peroxidase in neutrophils and peroxidase-antiperoxidase (PAP) complex during immunological staining are usually performed in Tris-HCl or phosphate buffer at pH 7.2-7.6. However, DAB solutions at pH 7.2-7.6 often demonstrate erythrocyte pseudoperoxidase as well. By lowering the pH of the DAB solutions, it is possible to selectively suppress the reactivity of pseudoperoxidase while maintaining optimal reactions in neutrophils and PAP complex. For this purpose we recommend ammonium acetate-citric acid buffer at pH 5.5 (pH 5.0-6.0) containing 44 mg DAB per 100 ml buffer and 0.003%-0.03% with respect to H2O2.


Double fluorescent staining for the separate demonstration of chromosomes and microtubules in mitotic cells in vitro. A simple fluorescent method for double staining of mitotic cells using a rhodamine B indirect immunofluorescent method for tubulin and the DNA-specific fluorescent dye Hoechst 33258 for nuclei and chromosomes is described. This procedure enables one through the use of appropriate excitation filters to view at will either chromosomes and nuclei or tubulin within the same cell.


Regulation of collagenase. Therapeutic considerations. Why the cornea ulcerates, in the sense of what goes awry, may be related to the trapping of wound healing in a phase of proteolytic debridement related to a persistent epithelial defect. The initial avascularity of the cornea makes it particularly vulnerable to proteolytic damage. Studies on the biochemistry and cell biology of corneal ulceration have indicated that sequential interactions occur which result in the generation of collagenase activity and the development of ulceration. It is likely that the interactions are susceptible to intervention; and it is thought that eventual, successful treatment of corneal ulceration will require a complex therapy, with interventions at multiple sites of regulation.


Detection of multiple variable antigen types in metacyclic populations of Trypanosoma brucei. The identification of antigen types in tsetse salivary gland metacyclic populations of Trypanosoma brucei requires the production of monospecific antisera to the corresponding bloodstream variable antigen types. Monospecific antisera against clones from cyclically transmitted populations are difficult to prepare, however, owing to the antigenic lability of such clones. This problem has been overcome by isolating an antigenically stable clone from a syringe-infected rabbit at a time when its serum showed incipient activity towards metacyclic trypanosomes. Monospecific antisera raised against this clone reacted with up to 20% metacyclics in trypanolysis and immunofluorescence tests, confirming that a clone-derived metacyclic population of T. brucei is heterogeneous with respect to variable antigen type.


Induction of human antibody responses in vitro with emphasis on allogeneic helper factors. Systems have been developed for the reproducible production of antigen-specific plaque forming cells for both tonsillar and peripheral blood B cells. Allogeneic helper activity was an essential supplement and monocyte removal was important, especially in the peripheral blood situation. Highly active allogeneic helper factors could be obtained from undirectional MLC supernatants which aided the proeuction of antigen-driven plaques. These factors also caused a polyclonal activation of B lymphocytes. A number of clinical applications of the above system were described. A defect in the T cells of patients with chronic lymphocytic leukemia with respect to the generation of helper activities was delineated.


Human B cell function in a polyclonally induced plaque forming cell system. Cell triggering and immunoregulation. The use of a sensitive PFC assay against a specific antigenic determinant (SRBC) following polyclonal triggering of human lymphocytes has provided a unique insight into the complex mechanisms of triggering of human B cells. The system is under the strict regulation of a delicate balance between helper and suppressor influences reflecting in certain circumstances the activity of distinct subsets of immunoregulatory cells. Lymphoid cells in certain diseases characterized by disordered immunoregulation, when as system, may in effect be manifesting an abnormal expression of immunoregulatory mechanisms operable in normal immune responses. In vivo activation of lymphoid cells by PBAs may have an important role in disease states as well as in the subsequent in vitro expression of B cell function. Furthermore, it is quite possible that under certain circumstances some B cell responses which appear to be purely antigen-specific may be reflections of synergy between PBA substances and specific antigen. The use of PBAs as probes and sensitive PVC systems as assays has already proven fruitful in the dissection of the complex mechanisms of nonspecific B cell triggering in man and may indeed ultimately lead to an understanding of the mechanisms of specificity of immune reactivity.


[Bromocriptine for palliation of advanced prostatic carcinoma. Experimental and clinical profile of a drug (author's' transl)]. Since prolactin has several modes of action on prostatic growth and physiology, the effect of the antiprolactin bromocriptine on plasma kinetics and intraprostatic metabolism of testosterone was studied in patients with untreated prostatic cancer; a therapy protocol was deduced which was controlled in 27 patients with advanced inoperable prostatic adenocarcinoma. Bromocriptine resulted in a significant suppression of prolactin and testosterone as well and favored testosterone elimination from the plasma pool. Prostatic androgen uptake was enhanced and the intraprostatic metabolism altered in relation to tumor grade. Adjunctive administration of bromocriptine to 27 patients, mostly in the state of hormone resistance, resulted in an overall objective regression of 22.2% and in stable disease in 55.6% of the patients. In half of the individuals a prompt relief of bone pain from osseous metastases was observed as well as improvement of micturition and decline of phosphatase activity. This preliminary data justify further investigations under controlled and randomized conditions.