Complications of povidone-iodine absorption in topically treated burn patients. One of the dangers of topical therapy in thermal injuries is absorption of the therapeutic agent with subsequent metabolic and toxic complications. Two patients, one 30 years old with a 75% burn, the second 72 years old with a 35% burn, were treated topically with povidone-iodine ("Betadine", pH 2.43). In both patients severe metabolic acidosis developed which could not be attributed to sepsis, hypovolaemia, renal failure, diabetes, lactic acidaemia, &c. The acidosis associated with the 75% burn required large amounts of sodium bicarbonate to maintain pH at 7.35 and a serum-bicarbonate concentration of 15 mmol/l (meq/l); serum-iodine was 48000 mug/dl (normal 4-8.5mug/dl). Acidosis in the second patient was not as severe, and serum-iodine concentration reached 17600 mug/dl. The rate of urinary excretion of iodine was 50.8 +/- 7.4 mg/dl and seemed to be fixed. Haemodialysis was very effective in reducing serum-iodine concentration. Povidone was also systemically absorbed. The persistent acidosis could be caused by absorption of the iodine or the acidic povidone-iodine. Until the aetiology of the acidosis and renal damage is more clear, iodophors should not be used topically for burns greater than 20% of the body surface or in the presence of renal failure.


Impairment of human polymorphonuclear leucocyte function by influenza virus. The effects of an influenza virus on polymorphonuclear leucocyte function were examined in vitro with a view to explaining why bacterial pneumonia often accompanies influenza in man. The ability of human polymorphonuclear leucocytes to show chemotaxis and to phagocytose staphylococci was inhibited when they were incubated with influenza viruses. Hexose-monophosphate-shunt activation was unaffected. The inhibitory effects were apparently specific to the virus.


Distribution of skin petechiae in fat embolism rash. When patients in whom a fat embolism rash developed were nursed on their left side fresh petechiae appeared on the right side and vice versa. The appearance of petechiae on the least dependent site is consistent with the skimming off of floating fat emboli in the blood and their selective distribution by the branches arising from the top of the aortic arch.


"On-off" effects in patients with Parkinson's disease on chronic levodopa therapy. Fluctuations in performance in patients with Parkinson's disease on chronic levodopa therapy (the "on-off" effect) are due to several factors. The increasing severity during treatment of early morning akinesia, "freezing" episodes, and end-of-dose deterioration are probably due to progression of the underlying disease. Peak-dose dyskinesia and peak-dose akinesia are due to levodopa over dosage. "Yo-yo-ing", which is the severest form of such fluctuation in mobility and dyskinesias, may represent the sum of these disorders.


Cytology in the diagnosis of oesophageal cancer. The value of brush cytology under direct vision in the diagnosis of oesophageal cancer was evaluated and compared with other diagnostic procedures in a prospective study of 33 patients suspected of having an oesophageal lesion. Barium swallow correctly diagnosed cancer in 19 out of 20 patients, the remaining patient was diagnosed by both histology and cytology. In all, cytology was correct in 18 cases (90%), whereas histology confirmed the diagnosis in 10 (50%). In the 13 patients with benign lesions, barium swallow was correct in 12; cytology was benign in all 13; biopsy was only possible in 9, although the results of this procedure were always correct. Thus barium swallow is still the ideal screening procedure for patients with oesophageal symptoms, but per-endoscopic brush cytology seems to be the method of choice for confirmation of the diagnosis.


Regional immunotherapy of lung cancer with intrapleural B.C.G. 60 patients have been entered into a randomised prospective study to answer the question-does a single postoperative injection of B.C.G. into the pleural space improve survival after surgery for lung cancer? 40 patients have been followed up for more than a year. B.C.G. improved survival in patients with a limited tumour burden: there were no recurrences and no deaths in 17 stage-I patients treated with intrapleural B.C.G. whereas 9 of 22 comparable control patients developed recurrent cancer and 5 died in the same interval (p=0.003). Intrapleural B.C.G. treatment did not seem to be beneficial in patients with more advanced disease. The hazards associated with injecting these living organisms into the pleural space have been reduced by preclinical laboratory testing in animals, use of a single limited dose of microorganisms, administration of isoniazid, and careful patient monitoring.


A 5-year controlled study of B.C.G. and radiotherapy inoperable lung cancer. Forty-eight patients with advanced squamous-cell lung cancer were treated with radical radiotherapy. Thereafter twenty-five received B.C.G. regularly and twenty-three did not. Differences in survival during the first year of observation and absence of peripheral metastases were significantly in favour of the patients treated with B.C.G. There was no response to B.C.G. in patients receiving palliative radiotherapy or cyclophosphamide nor in those with undifferentiated carcinoma.


Levamisole in prevention of recurrent upper-respiratory-tract infections in children. 70 children with chronically relapsing mild-to-severe upper-respiratory-tract infections during autumn and winter participated in a six month double-blind placebo-controlled trial: 38 of them received about 1-25 mg/kg of levamisole twice daily for two consecutive days every week, the others were given placebo. During each of the three trial periods, levamisole proved superior to placebo in that it significantly reduced the number, the duration, and the severity of the infections. Moreover, in the group treated with the higher dose (i.e. greater than 2-5 mg/kg/day), the superiority of levamisole to placebo was much more clear-cut. No drug-related side-effects were reported.


Cigarette smoking in pregnancy: Associations with maternal weight gain and fetal growth. 1159 mother-infant "pairs" have been studied to examine the inter-relationship of cigarette smoking in the latter half of pregnancy, maternal weight gain, and fetal growth. Non-smokers gained significantly more weight than heavy smokers (greater than 15 cigarettes per day) while light-to-moderate smokers (1-14 cigarettes a day) were intermediate. Birth-weight, length, and head circumference of the infants showed a similar gradient with infants born to non-smokers being heavier, longer, and with larger head circumferences than those born to heavy smokers. Co-variance analysis showed that a large part of the effect of maternal smoking is mediated through maternal weight gain with only a very small additional direct effect on the fetus. This suggests that increasing weight gain in smoking mothers might prevent some of the harmful effects of smoking on fetal growth. A randomised controlled trial of diet supplementation of smoking mothers would seem justified.


Menstrual blood-loss with intrauterine devices. The effect of three intrauterine contraceptive devices (I.U.D.)-Lippes D, Dalkon Shield, and Copper 7-on menstrual blood-loss has been studied serially by objective methods in 279 women. All the women had a minimum of two cycles following delivery, abortion, cessation of lactation, or previous pill or I.U.D. use. All pads and tampons used for two further menstrual cycles before and for 12 cycles after I.U.D. insertion were collected, and the blood-loss was measured by extracting the haemoglobin by conversion to alkaline haematin. Mean menstrual blood-loss increased with all three devices. The amount of loss, the percentage of women losing more than 80 ml, the decline in haemoglobin concentration, and the incidence of anaemia during the 12 cycles following insertion were all greater among users of the Lippes Loop than of the Copper 7 with generally intermediate values for Dalkon Shield users. The mean increases in blood-loss were: for parous women fitted with the Lippes Loop, 48 ml, with the Dalkon Shield, 34 ml, and with the Copper 7, 18 ml; for nulliparae fitted with the small size of Dalkon Shield, 27 ml, and, with the Copper 7, 19 ml.


Non-invasive quantitation of corneal copper in hepatolenticular degeneration (Wilson's disease). The corneal copper content was measured by X-ray excitation spectrometry in two controls and in seven patients with Wilson's disease. Patients who were treated irregularly or not treated at all showed a high corneal copper content. Those who were adequately treated had low levels, comparable to the controls. In one case the corneal copper content declined 45%, after a course of dimercaprol. The corneal copper measured showed no correlation with the slit-lamp appearance of the Kayser-Fleischer ring. It is suggested that non-invasive X-ray excitation spectrometry can provide a fast and reliable method for the early diagnosis of Wilson's disease and for the objective evaluation of the efficacy of the treatment of this disease.


Immunostimulant therapy with levamisole for rheumatoid arthritis. In a controlled study involving thirty-four patients levamisole was shown to be as effective as D-penicillamine and more effective than placebo in the treatment of rheumatoid arthritis. Its action was slow and was accompanied by a reduction in erythrocyte sedimentation-rate, rheumatoid factor, and technetium index. These properties indicate that it has a specific action like that of D-penicillamine. Stimulation of cell-mediated immunity was evident in patients treated with levamisole, and there was a correlation between such changes and pain relief. Animal models confirmed the absence of anti-inflammatory effect and provided some evidence of enhancement of cell-mediated immunity and macrophage stimulation.


Refined carbohydrate, smooth-muscle spasm and disease of the colon. A diet high in refined carbohydrate is implicated in the aetiology of some diseases of the colon-i.e., diverticular disease, irritable bowel syndrome, ulcerative colitis, non-occlusive ischaemic colitis, and pseudomembranous colitis. It is suggested that spasm of the smooth muscle is the common pathogenetic mechanism in these colonic diseases. The strength of the spasm producing increased pressure in the colonic lumen or wall and the length of time for which the colon has been affected are believed to determine the type of disease resulting. A diet high in refined carbohydrate allows the intense muscle spasm to occur because the physical buffering effect of faecal bulk is considerably reduced.


An alternative theory of herpes-simplex recurrence and a possible role for prostaglandins. Reactivation of herpes-simplex is thought to require stimulation of latent virus in the sensory ganglion before the virus travels to the skin and causes a lesion. An alternative theory is proposed whereby virus is often released from the ganglion to form microfoci of infection in the skin but these are usually eliminated. Physiological changes in the skin, perhaps induced by prostaglandins, occasionally allow lesions to develop.


Alternative explanations of the differing behaviour of ovarian and testicular teratomas. There are several aspects of the biology of teratomas which may be important in the aetiology of malignant versus non-malignant forms. Firstly, the ages when malignant teratomas form in the ovary (children) and testis (adult) follow by a similar span of years the time of oogenesis (fetus) and spermatogenesis (onset at puberty) and, specifically, follow by less than a decade the periods of active mitosis and meiosis during which interconnection of germ cells by intercellular bridges occurs. Secondly, ovarian teratomas may be viewed as parthenogenically activated oocytes, while testicular teratocarcinomas may represent post-meiotic fusion events more comparable to fertilisation; the malignant potential in the latter case could relate to fundamental differences in male and femal germ plasm. Thirdly,, the fact that malignant teratomas are easily produced by transplanting early embryos to extrauterine sites, while there is loss of malignancy with differentiation within a tumour or when malignant cells are injected into pre-implantation embryos and contribute cells to a variety of normal tissues, suggests that the malignant potential of teratomas has to do with gene control rather than mutational events.


Multifactorial regulation of prolactin secretion. The hypothalamus exerts an inhibitory influence on prolactin release from the anterior pituitary. Whether or not peptide hypothalamic prolactin-regulating factors, analogous to those for other pituitary hormones, exist, remains to be confirmed. There is evidence that catecholamines and indolamines directly affect prolactin release. This concept may explain the pathogenesis of galactorrhoea-amenorrhoea and other endocrine diseases produced by hypothalamic-pituitary disorders.


Doctors and administrators. A joint experiment. A course is described in which doctors in the training grades and health-service administration undertook a joint educational exercise to learn more about health care and the roles and interrelationships of the various professional groups. By sharing an educational enviroment, two professions which are frequently in conflict may realise each other's purpose and difficulties and perhaps work more harmoniously to a common aim.


Preoperative or postoperative deep-vein thrombosis? The incidence of deep-vein thrombosis as detected by the 125I-fibrinogen test and confirmed by phlebography was 32% in a high-risk group of patients admitted to hospital more than 4 days before operation. 62% of these thrombi were established before operation. Patients with malignant disease and those receiving preoperative intravenous nutrition were particularly prone to this complication. Recognition that asymptomatic thrombosis may be present before operation helps to clarify many of the enigmatic aspects of this condition, and has important implications for the interpretation of the results of clinical trials of prophylaxis. The condition should be suspected in patients transferred for surgery from medical wards, and prophylactic measures should be commenced at the time of admission in high-risk patients.


Treatment of ulcerative colitis with oral disodium cromoglycate. A double-blind controlled trial. Twelve patients with ulcerative protocolitis were treated for six months with each of oral disodium cromoglycate (2 g/day) and placebo in a double-blind cross-over trial. The active drug significantly improved the patients' sense of well-being and the signoidoscopic and rectal biopsy appearances. Orally administered disodium cromoglycate may have a place in the long-term management of colitis.


Antibody-dependent cell-mediated (K cell) cytotoxicity against isolated hepatocytes in chronic active hepatitis. Lymphocytes from 12 of 17 patients with chronic active hepatitis were cytotoxic towards isolated hepatocytes in a microcytotoxicity assay. Enriched fractions of B cells, prepared by removal of E-rosetted cells, were cytotoxic in all 12 cases, whereas T-cell fractions, prepared by removal of erythrocyte-antibody-complement-rosetted cells, were cytotoxic in only 1 case (P less than 0-0005). HBsAg positive and negative cases reacted similarly. In 6 patients the addition of 5 mug aggregated IgG significantly reduced cytotoxicity from 54% +/- 15 to 13% +/- 15 (mean +/- 1S.D.) suggesting that K cells may be the effector cell in an antibody-dependent, cell-mediated reaction directed against a liver-specific membrane lipoprotein.


Improvement in insulin secretion in diabetes after diazoxide. Diazoxide 5 mg/kg/day was administered to four normal subjects for five days and, together with insulin, to ten diabetic subjects for seven days. In every case there was a substantial increase in the insulin response to combined stimulation of the pancreatic beta cells with 1 mg of glucagon and 2 g of tolbutamide given intravenously. Similar increases were not seen in four diabetics who received placebo with insulin. It is likely that the observed improvements reflected increased insulin stores which resulted from diazoxide inhibition of insulin release. These findings suggest that poor insulin responses in diabetics may be due, at least in part, to chronic overstimulation of the beta cells. Pharmacological agents such as diazoxide, which inhibit glucose-induced insulin release, may have a place in preserving and restoring insulin secretion in diabetes.


Diminished effect of gentamicin under anaerobic or hypercapnic conditions. The in-vitro activity of gentamicin, judged by M.I.C. determinations, was much reduced when a normal aerobic atmosphere was replaced either by air +4% CO2 or by anaerobic conditions. The phenomenon was greatest for Staphylococcus aureus, where a decrease in activity of up to 20-fold was found. For Escherichia coli, Klebsiella aerogenes, Enterobacter spp., and Proteus spp. the factor of decrease was between 15-fold and 2-5-fold. Changes in medium pH, as a result of bacterial growth, can explain these findings for some, but not all, the species tested.


Circulating immune complexes and symptoms in Hodgkin's disease. Increased quantities of the third component of complement (C3) were found in the macromolecular fractions of plasma from patients with untreated Hodgkin's disease (H.D.) These changes provide indirect evidence that immune complexes are present in the plasma of patients with this disease; their presence is closely correlated with the symptoms of night sweats and fever which are associated with a poor prognosis. It is suggested that the detection of circulating complexes may help in assessing the severity of H.D.


Essential fatty acids and fetal brain growth. The fetal brain accumulates long-chain (C20 and 22) polyunsaturated fatty acids--arachidonic and docosahexaenoic--during cell division. De-novo synthesis of these acids does not occur and they are thought to be either directly derived from food or by metabolism from linoleic and linolenic acids, respectively. Administration of isotopically labelled linoleic and linolenic acids to pregnant guineapigs showed that only a small proportion of the label was converted to their respective long-chain polyunsaturated derivatives in the maternal liver. The proportion was increased within the phospholipids (structural lipids) by what appeared to be amultiple processing system which increased chain length and degree of polyunsaturation from maternal liver to placenta, fetal liver, and to fetal brain. Observations in man suggest a similar trend. The porportion of long-chain polyunsaturated acids increased in the phospholipids from maternal blood, cord blood, fetal liver, and fetal brain. These data show that the placenta and fetus are radically modifying the maternal phospholipids so as to achieve the high proportions of the C20 and C22 polyunsaturated fatty acids in the structural lipids of the developing brain.


Woodpeckers and head injury.

Woodpeckers and head injury. The woodpecker is an experiment in Nature, a model for the investigation of mechanisms of basic importance for head injury and its prevention. A preliminary anatomical study of the woodpecker's head suggests that it may be fruitful to explore impact protective systems which are radically different from those in common use.


Is multiple sclerosis an age-dependent host response to measles? Several lines of evidence support the possibility that multiple sclerosis (M.S.) may be an age-dependent host response to measles. In animals, measles evokes different responses depending upon age at inoculation. In man, measles is already known to produce at least two age-dependent responses: risk of subacute sclerosing panencephalitis is increased among those who have had measles before 2 years of age and risk of measles encephalitis increases with age, at least during adolescence. Studies of immigrant populations indicate that an event at or before adolescence but not infancy affects risk of M.S. In the tropics where M.S. is rare, measles tends to be acquired very early in life, usually before the age of 3, whereas in temperate areas, measles tends to be acquired later, after the age of 5. A retrospective study has shown that M.S. patients tend to have had measles later than controls. Mechanisms which might underlie an age-dependent host response to measles include maturation of an immune system (k.g., number of available B cells) or change in the metabolic state of a target cell (e.g., oligocytes which change from laying down myelin to maintaining it). If the hypothesis that M.S. is a host response to later measles infection is valid, then mass measles vaccination programmes should produce a decline in the rate of M.S., but the effect may not be discernible before 1980.


Epidemic infection by a gentamicin-resistant Staphylococcus aureus in three hospitals. A Staphylococcus aureus strain, resistant to aminoglycosides, including gentamicin and tobramycin, and to penicillin, lincomycin, and other antibiotics, caused an outbreak of hospital infection in a surgical ward which spread to the intensive-therapy unit and to two other hospitals. 21 patients were colonised and 9 of these had overt clinical infection. Administration of antibiotics to which the staphylococcus was resistant was associated with colonisation. The use of gentamicin, tobramycin, and lincomycin in these hospitals has increased as has the occurrence of bacterial resistance to these agents. An antibiotic policy to control their use is essential to preserve their value in life-threatening infections by bacteria resistant to other agents.


Epidemiological evaluation of immunisation and other factors in the control of whooping-cough. The general incidence of whooping-cough is lower in fully immunised children, but present immunisation schedules do not adequately protect the infant below 1 year of age either from contracting infection or from its complications. In a recent outbreak in Glasgow, nearly one-third of notified cases were fully immunised. In Glasgow and probably in the U.K. as a whole, the persistance of whooping-cough in some areas is more strongly correlated with adverse socio-economic conditions that with lack of immunisation. The decline in recent years could be attributable to improvement in these conditions at least as much as to immunisation. There is no epidemiological justification for continuing mass immunisation, but there is a strong case for an intensified eradication policy which might include selective immunisation in high-risk groups and areas.


Computer-assisted learning in undergraduate medical teaching. A programme of computer-assisted learning has been introduced for fifth-year medical students at Glasgow University during the teaching course in general practice. The programme allows students to make decisions on all aspects of patient care, and has the potential for combining a learning situation with an objective evaluation of skills and attitudes. The programme is popular with students and could have considerable potential in medical education.


Serum-high-density-lipoprotein and atherosclerotic heart-disease. Serum-high-density-lipoprotein (H.D.L.) concentrations were determined in 49 men who had had a myocardial infarction and in 102 healthy, middle-aged men, all from Northern Sweden. A quantitative immunological assay based on a monospecific antiserum to the main polypeptide (apoprotein A-I) of H.D.L. was used. The mean H.D.L. concentration was significantly lower in the men with coronary heart-disease than in the controls. The results accord with the hypothesis that high levels of H.D.L. to some extent protect against ischaemic heart-disease.


Acute traumatic intracranial haematoma without skull fracture. 307 cases of acute traumatic intracranial haematoma in patients admitted to the Institute of Neurological Sciences in Glasgow have been analysed for various presenting features. 57 (19%) had no fracture, and 14 had neither a fracture nor neurological symptoms and signs immediately after the injury. Apart from the children, immediate admission and observation of these 14 cases for a period of 24 hours rarely led to the early detection of a haematoma.


Comparison of oxprenolol and methyldopa in hypertension. A within-patient double-blind trial. Oxprenolol or methyldopa were administered in double-blind fashion to 29 patients shown to be persistently hypertensive. After a dose-finding, assessment, and washout period, the second drug was given. 24 patients completed a period of treatment with each drug. Blood-pressure falls were similar with each drug in the supine, standing, and post-exercise state. Half the patients responded will to low dosage (oxprenolol less than or equal to 320 mg, methyldopa less than or equal to 1 g, a day) and 9 of 11 such patients responded satisfactorily to each drug. In those whose response was inadequate, oxprenolol was increased to 960 mg or methyldopa to 3 g a day. Increasing dosage had no consistent pressure-lowering effect. Side-effects were assessed by questionnaire and no clear preference emerged. It is recommended that an inadequate response to modest dosage of either drug should lead to the use of an additional agent rather than heavier dosage.


HLA-DW3 associated with coeliac disease. 28 patients with coeliac disease (C.D.) were typed for the HLA-A, -B, and -D loci by several techniques. It was found that C.D. is primarily associated with the DW3 determinant and only secondarily with HLA-B8. The previously described association with HLA-B8 is explained by linkage disequilibrium between HLA-B8 and DW3.


Terminal transferase in human bone-marrow lymphocytes. Activity of the enzyme terminal transferase (TdT) has been localised in normal human bone-marrow lymphocytes. These cells may represent a prothymocyte population, which, on malignant transformation, may give rise to acute lymphoblastic leukaemia, and to some cases of chronic granulocytic leukaemia in the blastic phase.


Oral contraceptives, antithrombin- III activity, and postoperative deep-vein thrombosis. Deep-vein thrombosis (D.V.T.) was detected by the fibrinogen-uptake test in six out of a total of thirty-one young women undergoing emergency abdominal surgery who gave a history of recent oral contraceptive intake. In contrast, no D.V.T. developed in nineteen similar patients who were not on oral contraceptives (P less than 0-01). Plasma-antithrombin-III activity was significantly lower preoperatively in patients taking oral contraceptives; postoperative D.V.T. subsequently developed in three out of five patients with preoperative antithrombin-III activity below 50%. In seventy-eight dental patients undergoing molar extraction, antithrombin-III activity was measured before, during, and after operation. Activity fell in all patients during operation, but the fall was significantly greater in women taking oral contraceptives (P less than 0-01). The intra-operative fall in antithrombin-III activity was prevented by a small preoperative dose of subcutaneous heparin.


Transient hydrocephalus in premature infants: Treatment by lumbar punctures. Three premature infants with post-haemorrhagic hydrocephalus were treated by removing large volumes of cerebrospinal fluid with repeated lumbar punctures. After this treatment, a computerised tomographic brain scan showed that ventricle size had decreased, and subsequent head growth was normal in all three patients. The results suggest that acquired hydrocephalus in premature infants may be transient and that ventricular shunts may not be necessary in all cases.


Absence of ristocetin aggregation factor from the skin of a patient with von Willebrand's disease. Samples of apparently normal skin from one patient with von Willebrand's disease (vWD) and five patients without vWD were examined with fluorescein-tagged antiserum to the component of factor VIII required for aggregation of platelets by ristocetin (VIII-R.A.F.). No evidence of VIII-R.A.F. was found in the vWD skin, while bright granules were seen on and/or in the endothelial cells of dermal capillaries in all patients without vWD. VIII-R.A.F. granules were also found in the interstitial vasculature of all of twelve renal-biopsy specimens from patients without vWD. These observations support the concept that an abnormality of the vascular endothelium is involved in the pathogenesis of vWD.


Efficacy of antihypertensive drugs.

Efficacy of antihypertensive drugs. The magnitude of the fall in blood-pressure in response to an antihypertensive drug depends on the level of the pretreatment pressure, and there is a direct relationship between the two in that the higher the pretreatment pressure the greater the fall in pressure in response to treatment. This simple relationship is inherent in the practical situation of titrating the diastolic blood-pressures of a group of hypertensive patients to a predetermined level. It is assumed that notionally the dose of an antihypertensive drug can be increased in all patients until the diastolic pressure is reduced to the predetermined level. When the fall in diastolic pressure (deltaD.P.) is plotted against pretreatment diastolic pressure (P.T.D.P.), the points for all patients lie on a straight line of slope unity and negative deltaD.P.-intercept numerically equal to the predetermined diastolic-pressure level. This straight-line relationship is termed the predetermined ideal response line. Analysis of data from clinical trials shows that, despite the variability inherent in the practical situation, the data appear to conform to this straight-line relationship. The method of assessing the efficacy of antihypertensive agents is essentially a comparison of each experimental point with the theoretical predetermined response line. In its simplest form the method consists in constructing a scatter diagram of deltaD.P. against P.T.D.P. for all patients. Patients can then be classified as responders or non-responders according to their position on the diagram relative to the predetermined response line. This method of assessing the efficacy of antihypertensive agents has several advantages, the most important of which is that it provides a simple method for displaying all the relevant information in a readily comparable form.


The eupeptide system: A general theory of gastrointestinal hormones. Increasing knowledge of gastrointestinal "hormones" suggests a system which differs in many, if not most, respects from other endocrine systems. The established model of endocrine function, derived from studies of the hormones regulating growth, metabolism, and sexual function, is inappropriate; attempts to apply concepts such as the importance of plasma-hormone concentrations to the digestive tract have met with limited success. A new model of the gastrointestinal polypeptide system is proposed in which local "paracrine" action may be no less important, or more important, than distant "endocrine" action, and in which modulation of integrated neural control is a major function. The application of the word "hormone" to this polypeptide system is a devaluation of the term and an obstacle to the design of relevant physiological studies; an alternative nomenclature is proposed.


HLA matching and corneal grafting.

HLA matching and corneal grafting. A series of 200 cases of full-thickness corneal allografts have been followed to determine whether HLA and ABO incompatibility influence prognosis of the grafts. 85% of patients with avascular corneas had clear, functioning grafts one year after transplantation. Only 33% of patients with severely vascularised corneas had successful grafts one year after transplantation. A significant association was found between severe vascularisation of the patient's cornea and irreversible graft rejection. In this group of patients, the proportion of grafts functioning was found to be ranked according to the number of HLA antigens shared by graft donor and recipient. Patients receiving grafts matching for 2 HLA antigens showed a failure-rate due to irreversible rejection of 26% at one year, in comparison with 57% and 62% of grafts matching for 1 or 0 HLA antigens respectively. ABO incompatibility or ABO phenotype of the recipient did not influence graft prognosis. The results indicate that patients with severely vascularised corneas should receive HLA-matched corneal grafts. The institution of HLA-typed cornea "banks" for treatment of such patients is advocated.


Enhanced preservation of the ischaemic kidney with inosine. The function of rat kidneys subjected to 60 minutes of warm ischaemia at body-temperature was notably protected by the prior administration of the purine nucleoside inosine as a 40 mg/ml solution maintained at 37 degrees C. With direct intrarenal arterial perfusion of the kidney at the onset of ischaemia or with intraperitoneal (i.p.) injection 40 minutes before ischaemia, the plasma-creatinine at 24 hours was significantly lower (P less than 0-001) than that of untreated 60-minute-ischaemia controls and not significantly different from that of non-ischaemic unilateral-nephrectomy controls. Intravenous inosine 20 minutes beforehand also afforded significant (P less than 0-01) protection. 7-day survival was 100% in 30 inosine-pretreated rats and 65% in 45 rats with all other types of pre-treatment (P less than 0-001). Although i.p. adenosine was better (P less than 0-05) than no treatment, i.p. inosine was better (P less than 0-02) than i.p. adenosine. Allopurinol, phenoxybenzamine, A.T.P., or cyclic A.M.P. caused no improvement over controls. Kidneys perfused with inosine maintained higher purine-nucleotide levels during ischaemia and rapidly resynthesised A.T.P. when blood-flow was restored in vivo.


Efficacy of prophylactic gamma-globulin in preventing non-A, non-B post-transfusion hepatitis. Of 279 cardiac-surgery patients receiving a mean of twelve transfusions, 47 had significantly increased transaminase concentrations 14 to 180 days postoperatively and 10 were icteric. Preoperatively, each patient randomly received high-titre HbsAb gamma-globulin, normal gamma-globulin, or placebo and was followed at intervals for 9 months. Only 3 patients had serological evidence of hepatitis-B infection. 3 additional patients had serological evidence of cytomegalovirus infection, while none had evidence of hepatitis-A or Epstein-Barr infection. Less icteric hepatitis occurred in patients receiving the gamma-globulin preparations (P = 0-003), and the overall frequency of hepatitis was significantly reduced when compared with recipients of placebo. The protective effects of the two gamma-globulin preparations were not significantly different. Most post-transfusion hepatitis tody is neither viral hepatitis type B nor type A, and its severity and transmission are reduced by pre-transfusion gamma-globulin.


Mussel-associated viral hepatitis, type A: serological confirmation. 7 members of a family of 14 developed acute viral hepatitis approximately one month after a family outing. Epidemiological investigation incriminated incompletely cooked mussels (Mytilus edulis) as the vehicle of infection and revealed a statistically significant difference in attack-rates between mussel-ingesters (70%) and non-ingesters (0%) (P=0-035). The aetiological role of hepatitis-A virus, suspected on epidemiological grounds, was serologically confirmed by the demonstration of rises in titres of serum-antibody to hepatitis-A antigen (serologically related to the MS-1 strain of hepatitis-A virus), determined by immune adherence haemagglutination.


Deterioration of glucose tolerance in hypertensive patients on prolonged diuretic treatment. Glucose tolerance was investigated in 51 hypertensive patients before and after 1 and 6 years of treatment with oral diuretics. Glucose tolerance was unchanged after 1 year but had deteriorated significantly after 6 years' therapy. In a comparable group of 16 patients tested at similar intervals in which diuretic therapy had been given only for 3 of the 6 years there was no change in glucose tolerance, suggesting that prolonged oral treatment with thiazide diuretics is diabetogenic.


Do "anorectic" drugs produce weight loss by appetite suppression? A peripheral action on glucose metabolism may play an improtant part in the weight loss associated with treatment with some antiobesity drugs such as fenfluramine and mazindol. In therapeutic concentrations these agents increase glucose uptake into animal and human skeletal muscle. This action is distinct from their effects on central transmitters and from the reduction in food intake in animals.


An alternative mechanism for gluten toxicity in coeliac disease. The pathogenesis of gluten-sensitive enteropathies is unknown, although a peptidase deficiency and an immune defect have been postulated. The effect of plant-derived lectins on cells has led to an alternative concept in which a defect of the cell surface membrane allows gluten to act as a lectin and this reaction initiates cell toxicity. The proposed abnormality is viewed as a structural change produced by incomplete oligosaccharide chains in surface-membrane glycoproteins.


The hunt for renal hypertension.

The hunt for renal hypertension. The proportion of cases of hypertension with a renal cause which can be corrected by surgery is very small. Radiological diagnosis of such a cause is expensive and time-consuming; hence the rewards of intensive investigation are small compared with the cost. Measurement of plasma-renin offers a good method of selecting those patients who require further investigation, if the cut-off point is carefully considered in the light of the acceptable incidence of false-positive and false-negative results.


Gentamicin-resistant Pseudomonas aeruginosa and Serratia marcescens in a general hospital. From Aug. 1, 1974, to July 31, 1975, inclusive, 19-1% of Pseudomonas aeruginosa and 50-0% of Serratia marcescens isolates from a general hospital were gentamicin resistant as determined by standardised disc testing; 80% of 118 different clinical isolates showed minimum inhibitory concentrations larger than or equal to 16 mug/ml of gentamicin in agar-dilution testing. All gentamicin-resistant S. marcescens and 79% of Ps. aeruginosa isolates were susceptible to amikacin, while tobramycin and sisomicin were shown to have little advantage over gentamicin. A wide variety of immunotypes was found for Ps. aeruginosa, but only two predominant types were found for S. marcescens. Most isolates originated from the urinary tract, but nine which came from urine or wounds were also isolated from blood. Resistant strains seemed to be as virulent as sensitive strains. A common source was not found. Clinical improvement was noted in 13 of 17 patients treated with amikacin. The high frequency of gentamicin resistance is a continuing problem in this hospital and soon may be in others.


Mortality in diabetic autonomic neuropathy. Thirty-seven diabetics with symptoms and clinical features suggestive of autonomic neuropathy were followed up for 33 months. Of the twenty with abnormal Valsalva or handgrip tests initially, ten (50%) died. There were no other features at presentation that differentiated those who subsequently died from those who survived. The causes of death were renal failure (six patients), cerebrovascular accident (two patients), hypoglycaemic coma (one patient), and "sudden death" (one patient). Of the survivors whose autonomic-function tests were repeated 18 months to 2 years later, five had new or worsening symptoms of autonomic neuropathy with corresponding deterioration of their autonomic-function tests; while two, with initially normal tests, had improved symptomatically. It is concluded that in diabetics with the clinical features of autonomic neuropathy simple autonomic-function tests give a good guide to prognosis, and that abnormal tests are associated with a high mortality.


Lithium carbonate in the treatment of thyrotoxicosis. A controlled trial. Of 24 patients with newly diagnosed thyrotoxicosis, 13 were randomly selected for treatment with methimazole 40 mg per day, and 11 for treatment with lithium carbonate in such doses that the serum lithium lay between 0-5 and 1-3 meq. per litre. The lithium treatment brought about a fall in serum-thyroxine iodine (T4I) of 27.0%, and in the free-thyroxine index (F.T.I.) of 38.1% after 10 days. A comparison of the two patient groups with regard to the fall in F.T.I. after 3 and 10 days showed no statistically significant difference; similarly the calculated confidence limits appeared to exclude any difference of clinical importance. 8 of the 11 patients subjected to lithium treatment had side-effects, so that the general condition, which was already affected by the hyperthyroidism, was worsened. It is concluded that lithium cannot be considered superior to thiocarbamides for the rapid control of thyrotoxicosis.


Psychiatric screening in general practice. A controlled trial. This study reports the efficacy of the General Health Questionnaire (G.H.Q.) in the secondary prevention of minor psychiatric illness in a primary-care setting. 1093 consecutive attenders at a general practitioner's surgery were screened for minor psychiatric disorder using the G.H.Q. 32% were found to have a conspicuous psychiatric disorder and a further 11% had a hidden psychiatric disorder. The group with hidden disorders were randomly assigned to a treated index group and an untreated control group. The effects of case detection and treatment were beneficial and immediate, with the duration of episode of the disorder being much shorter for patients whose disorder was recognised by the general practitioner. For patients with more severe disorders there are significant differences still demonstrable between the groups one year later; but patients with mild disorders do equally well, some recovering spontaneously but others becoming manifest to the general practitioner over the next year and so receiving treatment. The "detected" group of patients increased their consultations for emotional complaints over the next year, but their total consultation-rate was not increased.


Breast-cancer osteolysis, bone metastases, and anti-osteolytic effect of aspirin. 23 (60%) of 38 human breast carcinomas had significant in-vitro osteolytic activity. All patients presenting with bone metastases or hypercalcaemia had active tumours. Over a subsequent three-year follow-up period, bone metastases did not develop in any of the 15 patients with inactive tumours, and metastases at other sites developed in only 2. Of the 23 patients with active tumours, 7 either had, or have since developed bone metastases; in 4 of these hypercalcaemia also developed. 14 tumours, chosen at random, were tested for in-vitro osteolytic activity in the presence and absence of aspirin, which inhibits prostaglandin synthetase. The activity of 8 of the 9 osteolytically active tumours was significantly, though not completely inhibited by aspirin. Although the number of patients is limited, these results indicate that the in-vitro osteolysis assay may detect substances, perhaps including prostaglandins, produced by breast tumours which affect prognosis and contribute to the subsequent formation of bone metastases.


Hypothalamic/pituitary/adrenal function in patients treated with intermittent high-dose prednisolone and cytotoxic chemotherapy. Hypothalamic/pituitary/adrenal (H.P.A.) function was assessed in ten patients receiving intermittent high-dose prednisolone and cytotoxic chemotherapy for myeloma of lymphoma in order to predict their possible requirement for additional steroid therapy between and at the end of treatment courses. Standard insulin hypoglycaemia tests performed 36 hours after the last dose of prednisolone often demonstrated impairment of corticotrophin (adrenocorticotrophic hormone, A.C.T.H.) and growth-hormone responses, indicating hypothalamic/pituitary suppression; plasma-corticosteroid responses to endogenous A.C.T.H. and tetracosactrin were abnormal in two patients, indicating secondary adrenal suppression. Such hypothalamic/pituitary and adrenal suppression may make these patients susceptible to acute adrenal insufficiency in times of stress. H.P.A. function should be fully assessed on completion of chemotherapy.


Laparoscopy in liver disease.

Laparoscopy in liver disease. Laparoscopy was technically successful in 73 of 75 patients in whom liver disease was suspected but not accurately diagnosed after medical investigation. In 46 patients (63%) the final histological diagnosis was either diffuse parenchymatous disease (cirrhosis/hepatitis) or metastatic malignant disease; 2 had a curable medical disease (tuberculous ascites); and 6 had a curable surgical disease (5 with gallstones and 1 with an ectopic adrenal tumour). There were no deaths and no serious complications. With increasingly accurate non-invasive techniques for localising lesions in the liver, laparoscopy, with directed biopsy, should help to provide correspondingly accurate histological confirmation.


Lithium as an adjunct to radioiodine therapy for thyrotoxicosis. 16 patients with diffuse thyroid hyperplasia were given lithium carbonate (400 mg daily) for 1 week before and 1 week after a standardised 5 mCi therapy dose of 131I. A comparable control group of 16 patients were treated with 5 mCi of 131I without lithium therapy. The % retention of the therapy dose was measured in all patients at 7 days (168-hour 131I uptake). In the lithium-treated group the 24-hour 131I uptake showed no significant change after the first week of lithium therapy. The mean 48-hour protein-bound 131I, however, fell considerably from 1-21 to 0.55%/dose/1. The mean 24-168 hour % thyroidal 131I uptake drop was significantly less in the lithium group. These results show that low-dosage lithium therapy increases the retention of a standard-therapy dose of 131I. Lithium promises to be a useful adjunct to 131I therapy in patients with a rapid thyroidal iodine turnover and particularly in young patients where the total body-radiation dose must be kept to a minimum.


Paget's bone disease treated with diphosphonate and calcitonin. Patients with biochemically active Paget's disease were treated with a combination of disodium ethane-1-hydroxy-1, 1-diphosphonate (E.H.D.P.) and synthetic human calcitonin in low doses. The effect on biochemistry was greater and more consistent than that of even higher doses of human calcitonin. Bone biopsy showed decrease or even disappearance of abnormal osteoblasts and osteoclasts from pagetic lesions, and the addition of calcitonin to E.H.D.P. prevented the development of mineralisation defects.


Whole-person medicine and psychiatry for medical students. Doctors predominantly going to work in the community are taught technologically advanced medicine in specialised hospitals. The subject-matter has to be fragmented in order to be teachable, but somebody has to put the whole person together again. The task is taken on by university departments of psychiatry and mental health. A teaching programme has been evolved in Bristol to meet these needs and to teach clinical psychiatry.


Muscle weakness in osteomalacia.

Muscle weakness in osteomalacia. The muscle weakness that frequently accompanies osteomalacia and rickets may arise from a variety of causes. Particularly in patients with muscle weakness, identification of the metabolic disorder is important, since effective treatment is often possible.


Enterotoxin testing of Escherichia coli causing epidemic infantile enteritis in the U.K. Three test systems were used to study enterotoxin production by epidemic strains of Escherichia coli from cases of infantile enteritis in well-documented outbreaks in the U.K. The tests used were the Y1-mouse-adrenal-cell test and the Chinese-hamster-ovary-cell (C.H.O.) test for the detection of heat-labile enterotoxin and the infant-mouse test for the detection of heat-stable enterotoxin. All 6 outbreaks had been studied using full serotyping techniques and the results had been published. In each outbreak the epidemiological studies clearly implicated a particular serotype of E. Coli as the epidemic strain and cultures of that serotype were tested for enterotoxin production. Although a control strain validated by other workers was positive in all three systems, the epidemic strains from infantile enteritis were negative. It seems that the three enterotoxin tests used in this study are of little value in recognising strains of E. coli causing epidemics of infantile enteritis in the U.K.


[Studies on the patency of the reuniting duct (author's transl)]. Using human temporal bone specimens the patency of the reuniting duct was studied. The endolymph was marked by various dyes and fluorescent substance, during the application the cochlea remained closed. It is shown that the substances in the endolymph flow from the first turn of the cochlear duct via the reuniting duct into the saccule. The patency of the reuniting duct is confirmed by histological serial sections, and the clinical significance of these findings is discussed.


[Antigenic properties of the cells of 4 variants of Bacillus brevis var. G.-B]. The antigenic composition was studied among the cells of four variants of Bacillus brevis var. G.-B. (R, S, P+, P-). The variants have a common antigen. Each variant has also an additional antigen. These data confirm that the variants of Bac. brevis var. G.-B. are related.


[The antiarrhythmic effect of digitalis in acute myocardial infarction with cardiac failure (author's transl)]. In 59 digitalized and 3 non digitalized patients the effect of digitalis during the 1st to 4th days after transmural myocardial infarction was controlled. Rhythm disturbances in acute myocardial infarction may arise secondary to a complicating cardiac failure and may be influenced by digitalis. In 9 of 17 cases (53 p.c.) with ventricular or supraventricular extrasystoles daily doses of 0,4 mg beta-Methyldigoxin or 0,4 mg Digoxin i.v. resulted in undisturbed sinus rhythm. In two cases supraventricular tachycardia and extrasystoles with rapid ventricular rate were abolished by 1,2 mg beta-Methyldigoxin within 12 hours, in three other cases an improvement was recorded. Dysrhythmias or other complications did not occur in previously non digitalized patients. When the antiarrhythmic effect of digitalis cannot be obtained cardiodepressive complications by treatment with typical antiarrhythmic agents are diminished. In patients on digitalis and in cardiogenic shock, digitalization should be performed carefully. Intoxication leads to a diminution of cardiac output and to cardiac dysrhythmias.


Vibrio cholerae flagellar antigens: a serodiagnostic test, functional implications of H-reactivity and taxonomic importance of cross-reactions within the Vibrio genus. Serodiagnostic tests for all serotypes of Vibrio cholerae using H-antisera were investigated. Activity motile cell lines of 155 stock and international reference cultures of human, animal, fish, and halophilic Vibrios, Aeromonas, Comomonas, Pseudomonas, Salmonella, and Escherichia were investigated. Without exception, all cholera vibrios (including the NAG serotypes) reacted with H sera. Positive reactions were obtained specifically (a) within 2 hrs at 52 degrees C in the tube test using thick formalized suspensions and H antisera at optimal proportion titre and (b) within 30 sec by slide agglutination of fresh cultures. The other vibrios investigated reacted similarly with their homologous H antisera. 2. The rapid diagnostic techniques of fluorescent antibody labeling or immobilization were unsuccessful, V. cholerae flagella being refractive to H sera in these tests. V. cholerae was, however, sensitive in a type-specific manner to O antisera. These and related observations suggest that O antigen has a functional role in Vibrio motility. 3. Interspecies H cross-reactions between V. cholerae and fish and animal vibrios which correlated with bacteriologic similarity, were demonstrated. O antigens of these vibrios were strain specific. Cross-absorption analysis indicated that the H antigens of vibrios were characteristic and homogenous within the species, and therefore a potentially important taxonomic criterion of Vibrio species.


Humoral and cellular immune response to uveal and joint tissue antigens. The antigens of uveal and joint tissues were investigated in view of the close association between anterior non-granulomatous uveitis and ankylosing spondylitis. Numerous antigenic determinants common to the uvea, the synovail membrane and articular cartilage were demonstrated using soluble and semi-particulate tissue extracts. No circulating auto-anti-uveal or joint tissue antigens could be detected in the sera of patients with anterior non-granulomatous uveitis or ankylosing spondylitis. Cellular hypersensitivity to uvea-retina antigens was present, however, in non-granulomatous uveitis. In ankylosing spondylitis this hypersensitivity was directed against synovial membrane antigens. In rheumatoid arthritis the hypersensitivity was directed against all three tissues (uvea-retina, synovial membrane, articular cartilage). The significance of these findings is discussed.


Quantitation of specific antibodies in the aqueous humor. Six normal rabbits were injected intravitreally with bovine gamma-globulin (BGG). Quantitation of immunoglobulins A, M and G, in the aqueous and in the serum, was performed by the single radial immunodiffusion following the method described by MANCINI et. al. Concentration of anti-BGG antibodies was determined by the reversed Mancini method. The antibody quotient was calculated; it reached to 8 and 5.96 in the aqueous of the injected eyes 10 days after intravitreal injection, 22.69 and 24 days, 22.52 after 28 days and 14.93 after 31 days.


Experimental autoimmune uveo-retinitis and specificity of retinal antigens. Chorio-retinal lesions induced in guinea pigs after one inoculation of bovine rod outer segments (ROS) with complete Freund's adjuvant are described with light and electron microscopy. The auto-antigenic activity of different preparations from bovine retina and uvea is compared for their efficacy to induce the disease. ROS are much more active than total retina homogenate. Pigment epithelium is active, and the effect of choroid is impaired after removal of pigment epithelium from the surface of the choroid. Purification of ROS by several sucrose flotations does not reduce their activity. Almost complete extraction of soluble antigens from pure ROS by buffer washings, controlled with isoelectrofocusing and immunodiffusion, decreases only slightly their pathogenicity. Rhodopsin, extracted using cetyltrimethylammonium bromide from pure washed ROS, induced prominent chorio-retinal damage at the dose of 500 mug. It seems likely that besides soluble retinal auto-antigens, outer segments contain a pathogenic insoluble antigen which seems to be linked to rhodopsin or to be rhodopsin itself.


Behçet's disease and immunosuppressive treatment. Our personal experience. The authors describe the results obtained at the Eye Department of Rome University using immunosuppressive drugs in the treatment of Behcet's disease. Of 31 patients with the disease, 23 were treated with different immunosuppressive drugs. The results obtained suggest that chlorambucil is the best therapeutic agent in this severe disease. As compared with other immunosuppressive agents used, such as azathioprine and ALGG, chlorambucil was the least toxic, the best tolerated and the most effective one.


[Immunogenic properties of DNA from E. coli and T4 phage, containing 5-bromouracil]. 5-BUDR incorporated into E. coli or T4 phage DNAs is an immunogenic determinant. Immunodominance of 5-BUDR is determined by the chemical structure of DNA molecule into which it is incorporated. In E. coli DNA, 5-BUDR inhibits immunogenic activity of all other bases. One can conclude that in this DNA 5-BUDR is the dominant antigenic determinant. In T4 DNA, 5-BUDR acts as an additional antigenic determinant. Anti-5-BUDR-T4-DNA contains antibodies to 5-BUDR and glucosylated 5-HMC.


[DNA synthesis on the heterogeneous nuclear RNA template catalysed by DNA polymerase of avian myeloblastosis virus]. Template activity of nuclear pre-mRNA has been investigated in DNA-polymerase reaction. Active synthesis of DNA was demonstrated on pre-mRNA as a template in the absence of primer. A part of synthetic activity may be attributed to the traces of DNA present in the pre-mRNA preparation. Addition of oligo(dT)10 to the template stimulated the synthesis of DNA product due to transcription of heteropolymeric regions near the poly(A). The rate of DNA synthesis was different depending on the fraction of template used: the RNA extracted by hot phenol at 85 degrees showed higher template activity without adding of primer than the 65 degrees C fraction. On the contrary 65 degrees C pre-mRNA which is known to contain greater quantity of molecules with poly(A) at the 3'-end is more strongly stimulated by addition of oligo(dT). The nuclear RNA corresponding to the precursors of rRNAs extracted at 40 degrees C were not transcribed by the reverse transcriptase. The size of the DNA-product (about 7-8S in alkaline sucrose gradient) did not depend on the size of the template neither on the presence of oligo(dT)10 primer. The inhibition of the second DNA strand synthesis with actinomycin D had also no influence on the size of DNA-product.


[The effect of contrast media containing iodine on selected in vitro thyroid test procedures (author's transl)]. The effect of 6 commonly used contrast media on the results of 3 different methods for determination of thyroid hormone concentration in the serum is examined in vivo. T4 determination by column chromatography proved to be very liable to distortion for contrast media. With some contrast media the Res-O-Mat-ETR test proved unreliable. T4 determination by means of protein binding analysis is not affected by contrast media in the direction of false raised values.


Mutagenicity of actinomycin D in Neurospora crassa. Actinomycin D is known to bind to native DNA and is widely used as an antineoplastic agent and inhibitor of DNA-dependent RNA and protein synthesis. We report here the induction by actinomycin D of purple adenine-requiring mutants (ad-3) in wild-type Neurospora crassa. A significant increase in the frequency of ad-3 mutants was evident when the organism was grown vegetatively in the presence of actinomycin D; the mutation frequency was at least 3.6 per 106 survivors. The actinomycin D-induced ad-3 mutants were 29% ad-3A and 71% ad-3B. The ad-3B mutants were classed by complementation pattern as 25% nonpolarized complementing; 14% polarized complementing; and 61% noncomplementing. The spectrum of complementation types of the actinomycin D-induced mutants most closely parallels that of mutants induced by ICR-170, known to induce base-pair insertions or deletions, or that of X ray-induced or spontaneous mutants. It is significantly different from spectra seen following treatment with nitrous acid or N-methyl-N'-nitro-N-nitrosoguanidine, agents known to induce mainly base-pair substitutions.


Mutagenic effect of epichlorohydrin. I. Testing on human lymphocytes in vitro in comparison with TEPA. The mutagenic effect of the monofunctional alkylating agent epichlorohydrin was tested on human lymphocytes in vitro and compared with the mutagenic effect of the polyfunctional alkylating agent TEPA. The same descending concentrations were used for both mutagens: 10(-4), 10(-5), 10(-6), 10(-7), 10(-8), 10(-9), 10(-10) and 10(-11) M. Similar types of chromosomal aberration were found, but the effect of ECHH was 4-5 times lower than that of TEPA. ECHH was found to be a mild mutagen. Different timing of mutagen application was used in the course of 56 h of cultivation of lymphocytes: 1 h before cultivation, one hour between the 24th and 25th h of cultivation and 24 h before the end of cultivation. From the results presented we conclude that the application of the chemical for the last 24 h of human lymphocyte cultivation should be recommended for routine mutagenicity testing.


Banding technique used for the detection of chromosomal aberrations induced by radiation and alkylating agents TEPA and epichlorohydrin. Blood samples from two healthy donors were exposed, (1) to 200 R of X-rays in G0 and G1S phases of the cell cycle, and (2) to epichlorohydrin 10(-6) M and TEPA 10(-4) M in G0 and/or in G1S and G2 phases. Part of the cells was processed for chromosome studies conventionally and the other part by the trypsinization banding technique. Detailed chromosomal analysis showed that, after irradiation, 38.2% of aberrations in G0 and 18.7% in G1S phases escaped cytogenetic detection when the conventional technique was used. After exposures to TEPA and ECHH, 10.9% of aberrations were undectable in G0 and 3.3% in G1S and G2 phases. The distribution of chromosome breaks was non-random both after irradiation and after exposure to alkylating agents. However, it differed according to the mutagen used. Some chromosomal segments were broken significantly more frequently than the others (e.g. 9q12), some were resistant to breakage (e.g. the whole Y chromsome). The segments represented by G-negative bands were more fragile than the G-positive and G-variable segments.


Cold urticaria: release into the circulation of histamine and eosinophil chemotactic factor of anaphylaxis during cold challenge. Patients with idiopathic acquired cold-induced urticaria were evaluated for the release of the preformed mast-cell mediators of immediate-type hypersensitivity during a study in which one arm was immersed in ice water while the other arm remained as a control. Blood specimens were obtained from each arm serially over a one-hour interval, and serum speciments were assessed for histamine, eosinophil chemotactic factor of anaphylaxis, and complement components. Levels of histamine and eosinophil chemotactic factor rose in the arm subjected to cold immersion for three minutes, with peak values occurring between two and five minutes and returning to base line by 30 minutes. No changes occurred in the control arm or in the immersed arm of normal subjects. Assessment of the classical and alternative complement pathways showed no abnormalities. This initial observation of release of eosinophil chemotactic factor of anaphylaxis in vivo along with histamine assigns the mast cell a central role in cold urticaria.


Mouse MSV transformed cells resistant to 8-azaguanine. Mouse cells transformed by murine sarcoma virus were made resistant to 8-azaguanine. Resistant cells and cell clones isolated from them were deficient in hypoxanthine-guanine phosphoribosyl transferase (HGPRT) activity. They did not grow in HATG medium, did not incorporate labeled hypoxanthine, and had negligible HGPRT activity. The resistance was genetically stable. The resistant cells were hyperdiploid and contained telocentric chromosomes only. The resistant cells as well as the progenitor cells were slightly tumorigenic in mice, the plating efficiency in soft agar was very low. The parental cells and aza-G resistant cells produced C-type viral particles having RNA-dependent DNA polymerase activity. The resistance to aza-G did not influenced the expression of murine sarcoma virus genome in cells. The resistant cells are suitable for preparation of cell hybrids.


Transformation of BHK 21/13 cells by chemical carcinogens and mutagens. In vitro transformation of BHK 21/13 cells by chemical carcinogens is reported. The hamster cells were treated with MCA, BP, 4-NQO and 5-azaCR at various concentration and duration of treatment. The morphological, karyological and growth characteristics of cell lines were investigated. Search for RNA tumor viruses in transformed cells using 3H-uridine labeling, detection of DNA polymerases, electron microscopy investigations failed to detect presence of C-type virus particles.


Immunoglobulin E in renal disease.

Immunoglobulin E in renal disease. Samples of renal tissue from 373 patients were examined for the presence of immunoglobulin E (IgE) by immunofluorescent techniques. Only trace to ++ amounts ( on a scale of ++++) were found in 20 patients: 4/9 with post-streptococcal acute glomerulonephritis (GN), 5/30 with GN associated with systemic lupus erythematosus, 3/20 with membranous GN, 1/4 with Goodpasture's syndrome, 2/18 with recurrent microhematuria and focal GN, 1/5 with hemolytic anemia and uremia, 3/73 with renal homografts, and 1/5 with dermatomyositis. No IgE was found in 18 patients with lipoid nephrosis, 8 of whom were being treated with prednisone, nor in 5 patients with focal glomerular sclerosis and the nephrotic syndrome. Serum IgE was measured in 9 of the 20 patients with glomerular deposits of this globulin. With one exception, levels of IgE were within the range generally considered to be normal. However, they were greater than the mean of this range in all but two and near the highest limits of normal in most. Neither the amounts of serum IgE nor the degree of proteinuria could be related to the intensity of stain for IgE in the glomeruli of these patients.


[Role of chemotherapy in long-term survival of malignant glioma (author's transl)]. Effect of chemotherapy was evaluated from the view point of postoperative survival rate in 102 consecutive cases of histologically verified glioblastomas treated during past 16 years. As a result of the study, the "additive effect" of chemotherapy on the ordinary surgical operation and radiation therapy could not be clarified. However, the effect of chemotherapy was worth to note among 6 cases which survived more than 5 years after operation. Then, combination of various treatment including chemotherapy should be repeatedly applied in individual cases of glioblastoma.


[The effect of bleomycin on brain tumor cells in vitro (author's transl)]. In order to evaluate the efficacy of Bleomycin (BLM) against brain tumor, a study was made on the inhibitory effect of BLM on the proliferation of cells derived from 8 cases of astrocytoma and 2 cases of meningioma and the proliferation of Ehrlich ascitic, HeLa and Mouse-Foot-Pad cells of strained epithelial origin. Morphological changes induced by BLM were also observed with phase contrast microscope and scanning electron microscope. Actively growing monolayer cells were exposed to BLM whose concentration was adjusted to 0.15, 0.6, 2.5, 10, 40, 160 mug/ml in the cultivating medium for 7 days. The inhibitory effect on cellular proliferation was evaluated by calculating the number of cell nuclei. When the concentration of BLM was adjusted to 0.15 mug/ml, the inhibition of Ehrlich ascitic, HeLa and Mouse-Foot-Pad cells was greater than the control by 50%. On the contrary, a higher concentration of BLM, that is 0.6-10 mug/ml, was necessary in the case of brain cells. The latter cells appear to be generally less sensitive to BLM than the foregoing strained cells of epithelial origin. Morphological changes consisted of cytoplasmic vacuolation, shortening and narrowing of cytoplasmic processes, nucleolysis and flattening of the surface structure. These findings, however, were not confirmed to be changes specific to BLM. Lastly, a brief review of the literature and discussion were made on the methods of administration and tissue concentration of BLM.


Amniotic fluid alpha-fetoprotein as a marker in prenatal diagnosis of neural tube defects. The prenatal diagnosis of anencephaly and spina bifida (neural tube defect, NTD) through amniotic fluid analysis for alpha-fetoprotein (AFP) is gradually gaining clinical recognition. AFP concentrations were determined in 237 amniotic fluids from normal pregnancies ranging between 7 and 42 weeks of gestation. A steady decline in AFP from 26 mug/ml at 7-9 weeks to 155 ng/ml at term is observed. AFP concentration was determined in 35 amniotic fluids from 33 confirmed neural tube defective pregnancies. In 14 cases where amniotic fluid was examined prior to the 26th week of gestation. AFP was markedly elevated when compared with the normal range of the same gestational period. In 21 amniotic fluids past the 26th week, 17 cases (85-) had markedly elevated AFP levels; however, 2 cases of anencephaly, 1 of spina bifida, and 1 of hydrocephaly gave levels within the normal range. It is concluded that elevated AFP in the amniotic fluid is a reliable but nonspecific marker for open neural tube defects prior to the 26th week of pregnancy, but may become normal after the 26th week in a small percentage of patients.


Value of screening procedures for the detection of vaginal adenosis. This study describes the use of routine vaginal iodine staining and other screening procedures for the detection of vaginal adenosis in 3871 postpubertal female patients. Iodine staining identified 65 patients with nonstaining areas in the vagina. Colposcopy verified the presence of vaginal adenosis in 11 of the 65 patients. Directed biopsies confirmed the diagnosis in 10 patients. The iodine staining procedure detected vaginal adenosis in only 1 patient who did not have a positive history of DES exposure or coexisting physical findings. Iodine staining of the vagina has little value as a screening procedure for the detection of vaginal adenosis. Based on these findings, a careful medical history and vaginal examination are recommended as the most productive routine screening procedures for vaginal adenosis. Evaluation and followup of those patients with a history of DES exposure in utero or physical findings suggestive of vaginal adenosis should include vaginal Papanicolaou smears supplemented by colposcopy at 6-month to 1-year intervals. Colposcopically directed biopsies of all abnormal areas should be obtained.


[Immunologic parameters in acute lymphatic leukemias in the course of different types of chemotherapy (author's transl)]. In 2 groups of patients under treatment with acute lymphatic leukemia and undifferentiated leukemia, apart from the lymphocyte count, a number of immunologic parameters were examined during the various stages of treatment. These parameters were related to the type of chemotherapy as well as the stages of treatment. This paper deals with the values of lymphocyte counts, of gammaglobulin, IgG, IgM and IgA and the results of the DNCB skin-tests, as a parameter for cellular immunity. The determination of gammaglobulin using the acetate sheet electrophoreses, showed no significant change. However a significant reduction of the IgG was shown during the periods of prophylactic reinduction with Vincristin in the Pinkel VII scheme. IgM quantities were significantly raised in the initial stage before treatment and in all periodes of treatment both in the Pinkel VII group and in an earlier therapeutic group with methotrexate two weekly and Vincristin pulses every 6 weeks. IgA was raised in both groups before treatment but significantly reduced during maintenance and reinduction phases. About 50% of the P VII cases had negative DNCB skintests during maintenance therapy, while all long term survivors in the earlier methotrexate treatment group had positive skintests. The 2 following papers deal with the results of PHA stimulation and the B and T cell determinations.


[Tuberculous meningitis and antibody deficiency disease (author's transl)]. A 13 year old girl not vaccinated with BCG became ill with tuberculous meningitis. After administration of 30 g of Streptomycin, cell counts and protein concentrations of the cerebro-spinal fluid returned to normal values. After continuation of antituberculous therapy without Streptomycin, the patient relapsed, and Streptomycin had to be given for 14 months. Defect in humoral immunity was diagnosed with low IgG and low titers of antiviral antibodies. For this reason the patient was additionally treated with passive administration of antibodies.


Transcription of single base oligonucleotides by ribonucleic acid-directed deoxyribonucleic acid polymerase. The synthesis of DNA products complementary to artificial templates by the enzyme RNA-directed DNA polymerase isolated from avian myeloblastosis virus has been studied. Of the single base polyribonucleotides, poly (rC), poly(rA), and poly(rI) were active while poly (rG) and poly (rU) were almost inactive. The minimum length showing activity for an oligo (rC) template was 9; the minimum primer length of oligo(dG) was 3 or 4. In order to examine the fidelity of transcription, single base oligoribonucleotides of defined length were studied. Using (rC)13 as template and (dG)8as primer, the oligo (dG) product coelectrophoresed with the template. However, using (rA)-20 as template and (dT)10 as primer, a large (10-16s) product was formed. Similarly, using oligo (rI) (2.5S) as template and (dC)10 as primer, a large (greater than 22s) product was formed. No significant activity was obtained with oligo (rU) templates. RNA-directed DNA polymerase transcribes the various oligonucleotides differently: slippage with oligo (rA) and oligo (rI), faithful transcription with oligo (rC), and poor transcription with oligo (rU).


Immunosuppressive properties of mouse amniotic fluid. Previous reports have suggested that the alpha-fetoprotein present in mouse amniotic fluid is a potent nontoxic immunosuppressant. In the present studies mouse amniotic fluid (1:50) from 9- to 20-day gestations markedly inhibited the in vitro responses of mouse spleen cells to SRBC, and spleen cells from nonpregnant females were more affected than were cells from pregnant mice. On the other hand, MAF was less effective in depressing antigen- and mitogen-induced proliferation of human blood cells than were NMS or human serum. Human AF and cord sera did not significantly depress the immune responses of cells from mouse or man when added to cultures at concentrations sufficient to achieve levels of alpha-fetoprotein reported to be immunosuppressive if mouse AFP is used. While these studies do not identify the inhibitory agent(s) present in MAF, they do suggest that mouse AFP either is pharmacologically different from human AFP and/or that the immunosuppressive activity attributed to mouse AFP is actually produced by another agent physically associated with it.


Production of antiserum to human properdin and demonstration of antigenic differences between the native and activated protein. Antisera were raised in rabbits to human properdin in the precursor form (P) and in the activated state (P). On Ouchterlony analysis using the anti-P, reactions of complete identity were obtained between P, P, and properdin in twofold concentrated serum (NHS). However, when anti-P was used, a reaction of identity was obtained only between P and NHS, and a reaction of partial identity was formed between P and P and between properdin in NHS and P, suggestive of the fact that certain antigenic determinants in P may be lacking in P. The results indicate that activation of precursor properdin may involve proteolytic cleavage and/or conformational alterations of the molecule.


Radionuclide imaging of the bones and joints of the hand. A definition of normal and a comparison of sensitivity using 99mTc-pertechnetate and 99mTc-diphosphonate. Normal radionuclide patterns of the hand obtained with 99mTcO4 and 99mTc-Sn-EHDP are described and their validity supported by clinical, radiographic, and laboratory examinations performed to exclude articular disease in the control group. Comparison of the 99mTcO4 and 99mTc-Sn-EHDP images in patients with various articular diseases demonstrated higher sensitivity of 99mTc-Sn-EHDP in detection of involved joints; this was also true when the radionuclide images were compared with fine-detail radiographs in patients with rheumatoid arthritis.


The chemical nature of human atrial specific granules. The nature of human auricular specific granules was assessed by a variety of cytochemical and histochemical methods. The specific granules were found to be argentaphobic when ultrathin sections of Araldite-embedded auricular appendages were stained according to the periodic acid-thiocarbohydrazide-silver proteinate technique of Thiery. The entire core of these granules was moderately positive after ultrathin sections of glutaraldehyde-fixed, glycol methacrylate (GMA)-embedded auricles were stained with phosphotungstic acid (PTA) at a low pH. A similar reaction was shown by the cell coat, residual bodies (C-granules), lysosomes, Z-discs as well as by a very small portion of the Golgi complex. Analogous results were obtained in semithin sections of GMA-embedded auricles stained by the periodic acid-Schiff (PAS) technique. Incubation of ultrathin sections (fixed in glutaraldehyde and embedded in GMA) with proteolytic enzymes (pronase, pepsin, trypsin, or alpha-chymotrypsin) elicited selective digestion of atrial specific granules and Z-bands and, to a much lesser degree, of the cell coat. It is concluded that human auricular specific granules, as in rat atrial cardiocytes, are composed mostly of proteins. In addition, these granules may contain complex carbohydrates.


[Influence of nutrition on hormone secretion. I. Study in Agua Preta (author's transl)]. A positive correlation between the circulating growth hormone levels and the nutritional status was reported in 9 children of both sexes, aged 1 to 6 years, suffering from 2nd degree malnutrition. The mean serum insulin levels, the mean urinary 17-KS and 17-OHCS levels were low before the dietary therapy. No significant correlation between the levels of these hormones and the nutritional status was found. The hormone levels gradually returned to normal after the dietary therapy and the nutritional status of the children improved, according to the observed biochemical, clinical and anthropometric data.


Induced abortion: 1975 factbook.

Induced abortion: 1975 factbook. This report presents an overview of current international data on induced abortion, primarily from the demographic and public health points of view. Statistical tabulations make up the major part of the report, with the text providing background information. Opening sections review definitions, sources of data, and concepts of statistical analysis. Major topics for which data are presented include the legal status of abortion (Table 1); incidence of abortion (Tables 2-20); incidence of repeat abortions (Tables 21-23); period of gestation and abortion procedures (Tables 24-27); incidence of abortion with concurrent sterilization (Table 28); complications (Tables 29-31); and mortality (Table 32). The relationships between abortion and contraception (Tables 33-35) and the effects of changes in abortion policies on trends in the numbers of legal abortions, illegal abortions, total induced abortions, and births are evaluated in the final sections (Table 36). Two technical questions are discussed in the appendix (Tables 37-38).


[Total denervation in painful diseases of the hip]. The authors discuss, on the basis of 16 cases, the results obtained by the total denervation of the hip in the painful affections, of various origins, of this area. The best results have been obtained in painful coxarthroses secondary to luxating dysplasia of the hip, and the least satisfactory in the rheumatic affections.


Antibody-hapten interactions in vivo in mice and sheep. From 5 min to 5 h after an intravenous injection of one of the haptens, elipson-dinitrophenyl-lysine, 2,4-dinitrophenol (DNP), or procaine, mice that were actively immunised against these haptens held more of the hapten in their plasma than did normal mice. Over the same time interval, mice that had been passively immunised with sheep anti-procaine antisera and then treated with procaine held more procaine in their plasma than did mice treated with normal sheep serum. When procaine or DNP was administered orally or intraperitoneally to sheep with circulating antibody to the hapten, the antibody titre was usually reduced 1 h after dosing but returned to the pre-dosing titre by 24 h. Experiments indicated that the reduction in antibody titre was due to in vivo neutralisation of antibody by the hapten.


[Critical evaluation and rational use of nuclear medical techniques in the diagnosis of thyroid function (author's transl)]. The diagnosis of thyroid function has been decisively improved by the in-vitro tests and the radioimmunologic assays of total tri-iodothyronine- and TSH levels before and after stimulation with TRH. The high specificity and value of in-vitro tests lies in the quantitative measurement of peripheral hormoneconcentrations. The radio-iodine test, however, is only a qualitative technique giving information on movements of intrathyreoid radio iodine. The in-vitro tests are not falsified by iodine contamination. Extrathyreoidal protein-changes can be excluded with the ETR test. The radio-iodine test will now have to be done only in rare special cases. As a rule thyroid metabolism can be assessed safely by combining clinical examination with an in-vitro testblock adapted to the individual diagnostic problem with additional technetium scintigraphy.


Effect of bilateral nephrectomy on serum gastrin concentration, gastric histamine content, histidine decarboxylase activity, and acid secretion in the rat. Nephrectomy caused a marked increase in the concentration of circulating gastrin immunoreactivity but did not increase basal acid secretion. In normal rats, both histamine and pentagastrin stimulated gastric acid output, but after nephrectomy only histamine was effective. Histidine decarboxylase in the oxyntic mucosa was greatly activated following nephrectomy. Thus, in the nephrectomized rat gastrin (and pentagastrin) no longer evoked acid secretion, whereas it retained its ability to activate gastric histidine decarboxylase. The results suggest that the kidney is important for metabolism and excretion not only of gastrin but of humoral antagonists of gastrin-induced acid secretion as well.


In vitro target cell lysis mediated by normal human lymphocytes (K cells) or monocytes. Guinea pig IgG1 or IgG2 anti-dinitrophenyl (DNP) Antibody preparations were used for induction of target cell lysis by normal human lymphocytes (K cells) or monocytes. Target cells were DNP-coated 51Cr-labeled chicken erythrocytes. Antibody concentrations were assayed by an ammonium sulphate precipitation technique. When antiserum was obtained by immunization with the antigen in Freund's complete adjuvant (FCA), IgG2 antibodies predominated and were significantly more efficient inducers of K-cell-mediated lysis than IgG1 antibodies. The lowest activity in K-cell-mediated lysis was seen with IgG1 from antiserum obtained by immunization with antigen in Freund's incomplete adjuvant. When these antibody fractions were tested in monocyte-mediated erythrolysis, the two IgG1 fractions were as active as the IgG2 antibodies raised with antigen incorporated in FCA. The results suggest that the Fc receptors of mature human blood monocytes are different from those on the effector cells in the K-cell preparations.


Induction of histamine release and desensitization in human leukocytes. Histamine release from normal human leukocytes can be induced by anti-IgE or protein A from Staphylococcus aureus. After incubation in buffer at 37 degrees C for various time intervals or repeated washings with buffer, or both procedures, the leukocytes lose most of their reactivity to protein A, whereas the reactivity to anti-IgE is unaltered. Cells deprived of their protein A reactivity can be induced to release histamine by IgG complexed with protein A. Maximal release (23%-81%) from 0.6-1.0 times 10(7) leukocytes per ml is obtained if the mixture contains 1-2 mug protein A and 8-16 mug IgG per ml. The ratio between protein A and IgG in the most active mixtures is 1:8 or 1:16 on a weight basis, which corresponds to 2-4 IgG molecules per protein A molecule. Heat treatment does not destroy the capacity of IgG to mediate histamine release. Mixtures of protein A and the Fc part of IgG can also initiate the release. Futhermore, it is shown that the protein A-IgG mixture and anti-IgE induce cross-desensitization to each other. This indicates that, like cell-bound IgG, IgG in complex with protein A triggers partially the same reaction sequence as IgE.


[Clinical-hematological demonstrations: aplastic anemia, acute leukemias, polyneuropathy in Waldenstrom's disease, acute porphyria]. Some cases are reviewed involving hematological diseases caused by exogenously or endogenously induced toxicity. First, 3 cases of aplastic anemia (chlorpromazine, chloramphenicol and probably autoantibodytypes) are discussed. The known aplastic anemia inducing agents are the chloro-hydrocarbon rings (chloramphenicol, hexachlorcyclohexane, chlorpromazine, chlorpropamide and aliphatic potassium perchlorate) as well as phenylbutazone, sulfonamides, benzol, gold, certain antiepileptic drugs and compounds which contain arsenic or bismuth. Isolated erythroblastophthisis is an autoimmune disease and is mainly observed in young people. It is stressed that cases with aplastic anemia generally exhibit considerable immunosuppression. Therefore, gamma-globulins should be given when infection is observed in these cases. In cases refractory to 2-3 years of conventional treatment (steroids, especially androgens), splenectomy is a useful alternative. Five cases of acute leukemia (4 AML and one ALL) point up the considerable advances in the treatment of this group of diseases. Caution should be exercised in interpreting a remission as a cure, since in one of our cases a remission of 12 1/2 years was followed by a lethal relapse.-A case of Waldenström's disease with severe polyneuropathy is described which was associated with severe "neuritic defects" related to inclusions of paramyloid material in the nervous tissue.-In a case of acute porphyria complicated by paraplegia an impressive remission was achieved by forced diuresis with furosemide and sorbitol combined with intensive i.v. glucose therapy (reduction of delta-aminolevulic acid production.


[Immunological diagnosis of cancer].

[Immunological diagnosis of cancer]. Two different types of immunological reaction are of assistance in the diagnosis of cancer: The first is detection of a weak immunological response of the patient toward his own tumor cells. Unfortunately the currently available techniques for the demonstration of humoral or cellular immunological reaction against autologous tumor cells are not reproducible enough to be recommended as routine clinical tests. Secondly, it is possible to use antisera, obtained by immunization of animals with human tumor extracts, for the detection of substances released into the blood by the tumor cells. The two major antigens associated with human cancer that can be measured in the blood by very sensitive immunological methods are the alphafetoprotein (AFP) and the carcinoembryonic antigen (CEA). It is very important for the physician to be fully alive to the usefulness and limitations of such tests in order to interpret them correctly. Clinical situations in which the measurement of AFP and CEA can provide useful information are reviewed.


[Chemotaxis of human polymorphonuclear cells in vitro. Study of inflammatory rheumatic diseases]. Sixty-eight determinations of leukocyte chemotaxis were performed in 42 patients suffering from systemic lupus erythematodes (17 cases), rheumatoid arthritis (15 cases) and scleroderma (10 cases). In contrast to the results of others, this study showed a deficiency in only 15 of 42 cases (35.7%). Impairment of chemotaxis was always transitory and demonstrable only during acute phases of disease. Intrinsic deficiency of PMN leukocytes as well as deficiency of plasma factors were related to the clinical and biological course of the disease and to the treatment.


[The treatment of prostatic adenoma].

[The treatment of prostatic adenoma]. Prostatic hyperplasia is a benign disease of elderly men. In 30-40% of the men the prostatic adenoma causes obstruction which requires operative treatment. 75% of these patients consult the general practitioner. Stage I is treated conservatively. Early surgery is indicated only in those undergoing surgery for hernia and in cases of intermittent obstruction. Operation is definitely indicated in stage II. Stage III should be treated initially with an indwelling catheter for 3-4 months. Treatment with lifelong indwelling catheter is rarely indicated today.


The lead, copper and zinc content of tree rings and bark. A measurement of local metallic pollution. Analysis of samples of wood taken from different tree rings for lead by atomic absorption spectrometry showed that there was little correlation between the sample site or ring age and air borne lead concentrations. However, the concentration of lead in tree bark at several sites was particularly sensitive to traffic flow at that site. The concentration of lead, zinc and copper in the tree bark decreased with increased distance from the road and with height above the ground. The method offers a simple technique for effectively tracing atmospheric metal concentrations.


Cocaine: plasma concentrations after intranasal application in man. Cocaine (1.5 milligrams per kilogram) was applied to the nasal mucosa of human subjects. The cocaine persisted in the plasma for 4 to 6 hours and reached peak concentrations of 120 to 474 nanograms per milliliter at 15 to 60 minutes. In that residual cocaine was detectable on the nasal mucosa for 3 hours, continuous absorption secondary to its vasoconstrictive action might explain its persistence in the plasma.


A serum protein associated with chromatin of cultured fibroblasts. Antibodies to chromatin proteins from human and mouse fibroblasts which have been cultured for more than 25 generations with heterologous serum show specificity for a homologous alpha-serum protein. These results indicate that among the chromatin-associated proteins there is one (or more) which has extensive structural similarity to a serum protein. This is the first direct evidence that a serumlike protein or proteins could be chromatin associated in vivo, as has been suggested by experiments showing in vitro interaction between DNA and certain serum proteins.


[Lupus syndrome during treatment with isoniazid]. In a young girl, aged 17 years, there occurred, 9 months after starting treatment with isoniazid and rifampicin, clinical signs of rheumatoid arthritis with facial erythema of vespertilio type. The presence of L.E. cells and antinuclear antibodies with a high titer, the rapid disappearance of all the clinical signs on stopping isoniazid, and the transient exacerbation of the syndrome on giving a single dose of isoniazid, gave the diagnosis of systemic lupus erythematosus induced by isoniazid. 18 months after stopping the drug, the patient is apparently cured, but there persists in the serum antinuclear antibodies in low concentration (1/200). A study of acetylation of isoniazid in this patient and her 3 sisters, showed that they were all of the slow acetylating phenotype. The late prognosis of this disease and the physiopathological value of the slow acetyl phenotype are worth discussion.


Blood transfusion practice: facts and fallacies. Practical problems and potential dangers associated with blood transfusion have led to the introduction of modifications in transfusion practice and the search for blood substitutes. Many of these changes, promoted by the pharmaceutical industry, have been of questionable value.


[Transportation of great arteries: possibilities and problems of surgical treatment (author's transl)]. The principle of atrial inversion clinically introduced by Senning in 1958 remains the method of choice for total correction of isolated transposition. Simplifactions and refinement of the original technique resulted in a lower operative mortality and in significant reduction of late complications such as life threatening arrhythmias and venous inflow stenoses especially found after the original Mustard operation. Transposition complicated by ventricular septum defect with or without pulmonic stenosis remains a surgical challenge. In these cases the anatomic and hemodynamic corection with the Rastelli procedure may be of advantage. Palliative operations have a high operative risk (17% in the present series). Today, their indication is restricted to patients who are not improved after balloon-septostomy or to patients with inadequate pulmonary flow urging for pulmonary artery banding and aorto-pulmonary shunt, respectively. In isolated transposition of the great arteries primary balloon-septostomy followed by early total correction in infancy after the age of six months seems to be the most appropriate treatment today.


Phenotypic variations with time of some HL-A antigens. In order to study the HL-A antigen turnover in vivo, the HL-A reactivities of the lymphocytes of eight blood donors were tested every week for six weeks with antisera HL-A1, 2, 3, 5, 7, 8 and 11. The analysis of variance showed that the "time" effect and the "time times donors" interaction were statistically significant for the HL-2, 3, 5 and 11 specificities. This supports the hypothesis that phenotypic expression of such antigens on the lymphocyte membrane of some of the blood donors examined varied with time. From a practical point of view, the HL-A antigenic fluctuation with time should be taken into consideration when lymphocyte typing is required for tissue transplantation.


The detection of Ia antibodies in polyspecific H-2 alloantisera absorbed with erythrocytes. H-2 alloantisera contain Ia antibodies whose detection is obscured by the presence of serodominant K,D specificities. A method is described whereby Ia antisera can be prepared by absorbing conventional H-2 sera with donor-strain erythrocytes. The analysis of such absorbed antisera has led to the identification of the new specificity Ia.16, and the redefinition of the specificities H-2.34 and H-2.46 as complex Ia specificities which map in the I-A region of the H-2 complex. A number of other so-called H-2 specificities also appear to have Ia-like properties.


Second locus HL-A antigens and 4a or 4b. A panel of over 100 individuals was tested against several 4a and 4b antisera. A 4a/4b type was assigned to each individual on the basis of overall reactions with each group of sera. It was felt that because 4a and 4b antisera rarely give identical reaction patterns the use of several sera in each group gave a better definition of the specificities. The relationship between each second locus HL-A specificity and 4a or 4b was assessed. Most of the "narrower" antigens showed complete inclusion within one group but there were some anomalies. Associations of these specificities were analysed further by absorption experiments. 4a and 4b antisera were able to define differences in some second locus specificities which were not picked up by the narrower antisera. It seems likely that 4a and 4b represent a separate public site on the HL-A gene product which is multifactorial. For a full description of the antigens all factors should be stated as there is not an invariant association between components.


HL-A8 and LD-8a in patients with myasthenia gravis. The frequency of HL-A8 in myasthenia gravis is markedly increased in women (60-80%) but not in men. The MLC determinant, LD-8a, is frequently associated with HL-A8. Of the 37 female MS patients, 15 were LD-8a positive (41%), whereas of the males only one of seven was LD-8a positive. The frequency of HL-A8 was 68% in women and 29% in men with the disease. We therefore conclude that the gene which is responsible for the increased susceptibility to myasthenia gravis in women and which is present in the MHS region, is more closely linked to the SD-2 than to the LD-1 locus.


[Experience in the treatment of malignant obstructions of the vena cava superior by means of chemotherapeutic decompression and subsequent irradiation]. The clinical picture, pathogenesis and etiology of malignant vena cava obstruction are described. The importance of using modern methods to treat this critical condition is emphasized. Furthermore, the authors examine the principles of chemotherapeutic decompression followed by irradiation. A single dose of nitrogen mustard was applied intravenously, followed by irradiation, on 24 patients with malignant vena caval obstruction. The results of this treatment are presented. The effect of this treatment was controlled by measuring the venous blood pressure and with chest X-rays. The authors conclude, that this method of decompression is successful in the palliative treatment of this syndrom.


Active enhancement of rat kidney allografts. Effect of pretreatment with prednisolone and donor-specific antigen. (Lewis x Brown Norway) F1 hybrid rat kidney allografts were transplanted to bilaterally nephrectomized Lewis recipients pretreated in various ways. The mean survival time of untreated controls was 16.1 +/- 1.7 days. All rats pretreated with 1.67 g/kg of semi-soluble Brown Norway spleen extract and 5 mg/kg of prednisolone on days 15, 8, and 1 before transplantation survived indefinitely. Pretreatment with semi-soluble or soluble extract alone prolonged survival modestly (36.5 +/- 13.6 and 30.8 +/- 5.6 days, respectively), but the former induced indefinite survival in two of eight animals. Prednisolone on its own failed to bring about prolongation of survival and the combined use of soluble extract and prednisolone did not reveal a synergistic effect. Cytotoxic antibody titres in animals showing indefinite survival were very low, and there was no correlation between antibody titres and prolonged survival. It is assumed that the pretreatment with semi-soluble extract and prednisolone inhibited the formation of cytotoxic antibodies as well as cell-mediated immunity, and encouraged the formation of enhancing antibodies. To study the cellular and humoral reactivity of five prolonged survived kidney recipients, 1st and 2nd donor-specific skin grafts were carried out. The humoral and cell-mediated responses were somewhat delayed in these recipients but otherwise normal except for the absence of the second-set phenomenon.