Long-term treatment of parkinsonism with bromocriptine. 92 patients with parkinsonism have been treated with bromocriptine for up to 30 months. 48 continue to receive bromocriptine with benefit; of these, 35 take bromocriptine (mean dose 53 mg daily) in combination with levodopa and 13 take bromocriptine (mean dose 45 mg daily) without levodopa. In those who were originally on levodopa, addition of bromocriptine allowed a mean 41% reduction in the dose of levodopa; the largest group of patients to benefit from bromocriptine entered the study because of excessive dyskinesia or "on-off" phenomena induced by levodopa. In 40 patients bromocriptine was stopped because of adverse reactions, absence of therapeutic response, or non-compliance with the protocol. The main problems were psychiatric disturbance (8 patients) and erythromelalgia (7 patients); these effects tended to occur late (mean 6 months and 10 months, respectively) and with high dosage (mean 66 mg and 115 mg daily). Other frequent adverse effects were dizziness and nausea; these began considerably earlier (at 2 months and 1 month) and with much lower dosage (31 mg and 12 mg daily). 4 patients died, for reasons apparently unrelated to therapy.


Double-blind controlled trail of electroconvulsive therapy (E.C.T.) and simulated E.C.T. in depressive illness. 40 patients prescribed electroconvulsive therapy (E.C.T.) for treatment of a depressive illness were randomly allocated to two groups. One group had the first two E.C.T. treatments replaced by simulated E.C.T. on a double-blind basis. The results show that E.C.T. is significantly superior to simulated E.C.T. in the treatment of depressive illness.


Dexamethasone-responsive hypertension in young women with suppressed renin and aldosterone. Pronounced hypoaldosteronism was found in three young women with hypertension and symptoms of mineralocorticoid overproduction--i.e., hyporeninaemia, hypokalaemia, and a fall in blood-pressure after diuretic therapy. Plasma 11-deoxycorticosterone and 18-hydroxy-11-dooxycorticosterone concentrations were normal Treatment with dexamethasone induced a return to normal of blood-pressure and plasma-potassium and an increase in plasma-renin activity and urinary aldosterone excretion. The data suggest that hypertension in these patients is maintained by overproduction of an unknown adrenocorticotropindependent mineralocortocoid.


Manchester regional breast study. Preliminary results. 1020 patients with early breast cancer were treated between March, 1970, and October, 1975, according to a prospective clinical trial. The results have been recorded after a follow-up of two to seven years. 713 cases of clinical stage-1 cancer were randomly allocated to treatment by simple mastectomy and postoperative radiotherapy, or simple mastectomy alone. There was no statistically significant difference in overall survival or in survival without distant metastases between the two groups. There was a significant reduction in the incidence of local recurrence in those who had received early postoperative radiotherapy compared with those who had not. 307 cases of clinical stage-11 cancer were randomly allocated to treatment by simple mastectomy and postoperative radiotherapy or radical mastectomy alone. There was no statistically significant difference in survival or in the incidence of local recurrence or distant metastases between the two groups.


Protruding auricle: A neuromuscular sign. A protruding auricle is usually associated with a defect in development or function of the posterior auricular muscle, which normally draws the pinna towards the calvarium. Hence, a protruding auricle may be a sign of a neuromuscular disorder, as is ptosis.


Acid-phosphatase reaction in acute lymphoblastic leukaemia. The diagnostic value of the acid-phosphatase reaction was assessed double-blind in 148 cases of acute lymphoblastic leukaemia (A.L.L.) classified by surface-membrane markers and entered into the M.R.C. U.K. A.L.L. trials. 90% of cases of T-A.L.L. showed a positive reaction in the majority of blast cells, while only 2% of common-A.L.L. and 10% of null-A.L.L. were positive. This cytochemical reaction distinguished the more aggressive form of A.L.L. any may aid the choice of therapy.


Increased incidence of malignant melanoma after peaks of sunspot activity. The age-adjusted incidence-rate for malignant melanoma in the State of Connecticut has risen from 1.1 per 100 000 individuals in 1935 to 6.2 per 100 000 individuals in 1975. Superimposed on a steady rise in incidence are 3-5 year periods in which the rate of increase in incidence rises. These periods have a cycle of 8-11 years and follow times of maximum sunspot activity.


Gonorrhoea in women. Diagnostic, clinical, and laboratory aspects. Examination of the case-notes of all women seen at a large metropolitan clinic during 1976 showed 607 episodes of gonorrhoea (92.3% of all such cases seen in the hospital), of which 3 were in prepubertal girls. Gonorrhoea occurred more often and at an earlier age in Negroids than in Caucasians. In about 30% of patients gonococci could be found in only one of the sites tested (cervix 18%, urethra 6%, rectum 4.8%, and throat 1.5%). Microscopical examination of gram-stained cervical and rectal samples was of value, but that of urethral samples made no significant contribution to the diagnosis. 31% of the gonococcal isolates showed diminished sensitiivty to penicillin, but none showed significant resistance to spectinomycin, kanamycin, or sulphamethoxazole. The complication rate was lower than that reported from the United States. Overall, 40% of patients were symptom-free. The presence of other infection significantly increased the probability of a patient with gonorrhoea having symptoms. "Epidemiological" treatment would have led to the unnecessary treatment of 142 females and would have included only 4 of 16 patients with gonorrhoea who defaulted before treatment could be given.


A randomised trial of home-versus-hospital management for patients with suspected myocardial infarction. Home and hospital management of patients with suspected myocardial infarction were compared in a randomised trial in which a hospital-based team responded to calls from general practitioners. 500 calls were received, and 349 patients (70%) were suspected of having myocardial infarction. Of these, 24% were excluded from the trial on predetermined medical and social grounds; for the remainder (76%) there was no significant difference in the 6-week mortality between the home group (13%) and the hospital group (11%). For the majority of patients to whom a general practitioner is called because of suspected infarction, hospital admission confers no clear advantage.


Osteomalacic dialysis osteodystrophy: Evidence for a water-borne aetiological agent, probably aluminium. In patients maintained on regular haemodialysis in Newcastle upon Tyne the development of osteomalacia is substantially reduced when water used to prepare dialysate is deionised. After 1--4 years of dialysis, osteomalacia was evident in 15% of patients on deionised water in 70% of patients on softened water from the same source. The close association of dialysis encephalopathy and osteomalacia suggests a common aetiology. Both diseases occur in centres with a high tap-water aluminium content. Serum-aluminium concentrations were raised in patients undergoing regular haemodialysis in the Northern Region of England. Those using softened water had higher concentrations than those using deionised water. Patients on softened water who had encephalopathy or dementia had serum-aluminium concentrations similar to those of patients using the same water-supplies without symptoms of these diseases, but they had been treated for longer. The evidence that aluminium absorption from dialysate causes osteomalacia and encephalopathy is strong enough to justify the expense of treating water by deionisation, reverse osmosis, or both in centres where tap-water aluminium is high.


Is pancreatic polypeptide a marker for Zollinger-Ellison syndrome? Basal human pancreatic polypeptide (H.P.P.) concentrations have been measured in 41 pateints with Zollinger-Ellison syndrome (Z.E.S.) and in 100 controls. Basal H.P.P. concentrations in controls varied widely from less than 8 pmol/l (assay detection limit) to 313 pmol/l. In controls, but not in the Z.E.S. patients, there was a highly significant positive correlation between basal H.P.P. and age (P less than 0.01). 4 of the Z.E.S. patients (9.8%) and 3 of the controls (3%) had H.P.P. concentrations over 240 pmol/l. These findings indicate that raised basal H.P.P. concentration is an infrequent finding in patients with gastrinomas and therefore it is not a useful tumour marker.


Mechanism of the antipsychotic effect in the treatment of acute schizophrenia. In a double-blind trial in which 45 patients with acute schizophrenia took part the alpha-isomer of flupenthixol (which blocks the dopamine receptor) was found to be significantly more effective than both beta-flupenthixol (which does not) and placebo. The drug effect was confined to the "positive" symptoms--delusions, hallucinations, and though disorder--and appeared only in the 3rd and 4th weeks of the trial. It was as great in patients with evidence of deterioration (Feighner-positive patients) as in patients without deterioration and was less in patients who had affective disturbance in addition to schizophrenia symptoms. The findings are consistent with the hypothesis that dopamine-receptor blockade is the only requirement for antipsychotic activity and suggest that the antipsychotic effect occurs in patients with typically schizophrenic illnesses but may be limited to positive symptoms.


Long-term transfer-factor treatment for multiple sclerosis. In groups of 16 patients with multiple sclerosis, 13 months' double-blind treatment with transfer factor from random normal donors differed from placebo treatment only in producing a temporary restoration of lymphocyte reactivity to measles virus antigen, and did not arrest the degeneration of nerve tissue.


A life-threatening complication of the infusion pump. Serious disturbances in respiration and venous return developed in 2 infants in whom infusion into a central vein was controlled by a peristalic pump. The effects were the result of extravasation which led to build-up of pressure in the medistinum.


Antithrombin-III transfusion in disseminated intravascular coagulation. Three patients with a severe bleeding disorder and disseminated intravascular coagulation were effectively treated with human antithrombin-III concentrates. This treatment, followed by administration of prothrombin complex and platelet suspensions, resulted in a normal haemostasis, which was maintained during clinical investigations and surgery.


Selective deficiency of 3-beta-d-galactosyltransferase (T-transferase) in Tn-polyagglutinable erythrocytes. A single genetic defect in membrane synthesis--namely, a deficiency of 3-beta-D-galactosyltransferase--can account for the serological and physicochemical properties of Tn-polyagglutinable erythrocytes.


Adverse effects of routine procedures on preterm infants. Continuous monitoring of arterial oxygen tension (PaO2) in sick neonates has shown that handling the baby for reason often causes a fall in PaO2. Although the baby usually recovers spontaneously, a series of procedures one following closely upon the other may cause a prolonged fall in PaO2 necessitating respiratory support. This survey showed that infants were being disturbed at hourly or more frequent intervals, often for routine purposes, some of which do not justify the resulting hypoxia. Even simple procedures which are part of neonatal intensive care are hazardous and their routine use should be reconsidered.


Sequelae of covert bacteriuria in schoolgirls. A four-year follow-up study. A trial involving 208 girls aged 5-12 who had bacteriuria on screening was carried out to determine the effects of covert bacteriuria on renal growth and scarring. 98 were observed for 4 years without treatment and 110 were treated. 77% of the treated girls,  but only 26% of the untreated controls, were free of infection for at least half of the 4-year follow-up. However, treatment had no effect on the emergence of symptoms, clearance of vesico-ureteric reflux (V.U.R.), kidney growth, or the progression of kidney scars. New kidney scars did not develop in previously unscarred kidneys. 12 (6%) of the 208 girls had progression of re-existing kidney scars; this high-risk group was characterised by kidney scarring on the initial X-ray, a high prevalence of v.u.r., and persistent or recurrent bacteriuria. Screening for covert bacteriuria cannot therefore be recommended in schoolgirls since kidney damage associated with infection arises before the age of 5.


Repeated adjuvant chemotherapy with phenylalanine mustard or 5-fluorouracil, cyclophosphamide, and prednisone with or without radiation, after mastectomy for breast cancer. 172 patients who had had mastectomy for breast cancer were treated by repeated adjuvant chemotherapy, either with phenylalanine mustard (P.A.M.) or a combination of cyclophosphamide, 5-fluorouracil, and prednisone (C.F.P.) with and without radiotherapy. Tumours recurred significantly more frequently and mortality tended to be higher in P.A.M.-treated patients than in patients on other treatment. The interval between surgery and disease recurrence was significantly shorter for P.A.M.-treated premenopausal but not postmenopausal patients than for patients of equivalent menstrual status treated with C.F.P. with or without radiation. The associations in premenopausal patients between the mode of treatment and both survival and the disease-free interval were significant before and after adjustment for variations between the treatment groups in the number of involved lymph nodes and the size of the primary tumour.


The galactorrhoea-endometriosis syndrome. A new syndrome consisting of galactorrhoea and endometriosis is described. Nine patients with endometriosis, eight of whom had galactorrhoea either at diagnosis or after treatment with danazol are reported. Prolactin concentrations were normal in seven patients. Galactorrhoea in a woman with regular menstrual periods should suggest a possible diagnosis of underlying endometriosis,  especially if there is a history of dysmenorrhoea.


Oxygen-15 brain scanning for detection of cerebral involvement in systemic lupus erythematosus. In 47 patients with systemic lupus erythematosus seen during fifty-one clinical episodes, oxygen-15, a short-lived gamma-emitting isotope, has been employed in a scannng technique to study cerebral oxygen utilisation and blood-flow. Abnormalities in regional distribution of oxygen utilisation and blood-flow were seen in twenty-three out of twenty-four instances of definite central-nervous-system disease, in fourteen out of fifteen instances of suspected C.N.S. lupus, and in ten out of twelve instances in which C.N.S. disease was not clinically apparent. The technique reflected remissions and relapses. It may prove valuable in diagnosis of subclinical cerebral disease, in monitoring of responses to therapy, and in study of the pathophysiology of cerebral lupus.


Brain-aluminium concentration in dialysis encephalopathy. Brain-aluminium concentrations were found to be significantly higher in 7 patients dying with dialysis encephalopathy (mean 15.9 microgram aluminium/g dry weight) than in 11 dialysed controls  (4.4 microgram/g) and in 2 uraemic patients who were not dialysed (2.7 microgram/g). The grey matter from the patients with dialysis encephalopathy contained about three times as much aluminium as white matter. The results suggest that dialysis with untreated and/or softened tap-water (aluminium concentration 0.1-1.2 mg/1) makes the major contribution to brain-aluminium levels; dialysis with deionised water (aluminium concentration normally less than 0.02 mg/1) and intake of phosphate-binding AL(OH)3 gel are less important. Brain aluminium levels remain elevated for up to four years after restoration of good renal function by transplantation. The association of dialysis encephalopathy with high levels of aluminium in the brain and in the dialysis water emphasises the potential neurotoxicity of aluminium in man.


Do thyroid-stimulating immunoglobulins cause non-toxic and toxic multinodular goitre? The prevalence of serum thyroid-stimulating immunoglobulins (T.S.I.) in a variety of thyroid diseases was determined in 96 patients and 35 normal controls. Significantly elevated levels of T.S.I. were found not only in patients with Graves' disease and Hashimoto's thyroiditis but also in those with non-toxic and toxic multinodular goitre, whereas patients with a single autonomously functioning thyroid nodule, with subacute thyroiditis, and with "hyperthyroiditis" had levels which did not differ from those in the controls. We postulate that non-toxic multinodular goitre, like Graves' disease, may result from increased circulating T.S.I., which in some cases may be present in sufficient concentration to cause thyrotoxicosis.


Prostaglandin-synthesis inhibitors in prophylaxis of food intolerance. Prophylactic doses of aspirin, indomethacin, or ibuprofen prevented symptoms of food intolerance in five out of six patients who on several occasions had had acute gastrointestinal symptoms after the ingestion of specific foodstuffs. Blood and stool prostaglandin E2 and F2alpha concentrations during unprotected challenge were consistent with the idea that these symptoms were mediated through prostaglandin release. Prostaglandin-synthetase inhibitors may benefit some patients with specific food intolerance who are unable or unwilling to avoid the offending food.


Passive transfer of diabetes mellitus from man to mouse. Lymphocytes extracted from peripheral-blood samples from each of six patients with newly diagnosed insulin-dependent diabetes mellitus were transplanted into arthymic nude mice. At one or more sampling times (in the thirty-day study) blood sugar was higher in mice which had received lymphocytes from diabetic patients than in the control mice which had received lymphocytes from non-diabetic donors. Blood-sugar concentrations reached 260 mg/dl in some mice in the experimental group. This study demonstrates that lymphocytes may have an aggressive role in diabetogenesis. With this mouse experimental model mechanisms involved in diabetogenesis, and probably also in other disease in which lymphocytes are suspected of being involved in pathogenesis, could be investigated.


Role of IgG4 subclass in childhood allergy. In 38 asthmatic patients (34 children and 4 adults) raised serum concentrations of IgE and the IgG4 subclass were found to correlate with the clinical picture. 5 children with eczema, asthma, and hayfever had grossly increased concentrations of both immunoglobulins, as did 4 adults who had had atopic eczema as children. Raised concentrations of just one of the immunoglobulin classes (i.e., IgE or IgG4) did not seem to be associated with atopic eczema. 75% of the asthmatic children in whom serum-IgG4 was raised had not shown a satisfactory response to disodium cromoglycate and required steroids to control their asthma; but 82% of patients in whom only IgE was raised responded satisfactorily to disodium cromoglycate.


Varicose veins: A comparison of surgery and infection/compression sclerotherapy. Five-year follow-up. A randomised controlled trial was carried out to compare the clinical outcome 5 years after inpatient surgery and outpatient injection/compression sclerotherapy. 91.3% of those originally treated by injection/compression sclerotherapy and 93.9% of those originally treated surgically were seen at follow-up. 40% of patients treated initially by injection/compression sclerotherapy and 24.2% of those treated surgically were given further treatment. The probability of having no further treatment is significantly greater for those treated surgically. The improved outcome after surgery increased with age, being most striking in those aged over 45. The implications of the 5-year follow-up findings for the long-term cost of treatment are discussed.


Self-inflicted bleeding and bruising.

Self-inflicted bleeding and bruising. Of 8 psychiatrically referred patients with bruises and bleeding, self-injury was admitted in 2 cases and the means of self-injury were discovered in 6. All the patients were fairly young, single or unhappily married females, with unresolved emotional problems, most commonly sexual. 22 of 43 female haematology outpatients showed no haemostatic abnormality and were though to be seeking attention.


Clinical application of human-placental-lactogen values in late pregnancy. Human-placental-lactogen (H.P.L.) levels were measured in the blood of 1000 women in the third trimester of pregnancy to see how measurement of H.P.L. could help in the management of an obstetric population in Britain. It was found that in the 93% of the population with a mean H.P.L. level of 4.3 mg/l or above, only 1.1% would have a poor pregnancy and 4.8% a compromised pregnancy. Of the 7% with levels below 4.3 mg/l, 57% woul have a normal outcome and 43% a poor or indifferent outcome. The false-positive rate was considerable, but the results of the study indicate nevertheless that H.P.L. levels are useful in predicting the outcome of pregnancy and that their measurement should be included as part of routine screening in the third trimester.


Cytomegalovirus D.N.A. and adenocarcinoma of the colon: Evidence for latent viral infection. The cause of adenocarcinoma of the colon has not been proven and a viral association has not been reported with this disease. A sensitive biochemical technique for the detection of viral nucleic acid was used to determine whether one type of herpesvirus, namely a human strain of cytomegalovirus, was uniquely present in tumour tissue. 24 specimens of colon, obtained at surgery from 14 patients, were analysed by membrane CR.N.A.-D.N.A. hybridisation. 4 of 7 tumours of the colon were definitely positive for C.M.V. D.N.A. (2greater than or equal to 2 genome-equivalents/cell), or repeatedly showed more than 1 genome-equivalent/cell. Macroscopically normal colon 5 cm from the tumour, as well as histologically normal and abnormal colon from a control population with Crohn's disease were uniformly negative for C.M.V. D.N.A., except for 1 specimen which was macroscopically normal tissue from a patient with carcinoma of the colon. Among patients with conditions that predispose to adenocarcinoma of the colon, 1 of 2 patients with familial polyposis and 1 of 3 with ulcerative colitis harboured in their colon greater than or equal to 2 genome-equivalents of C.M.V. D.N.A. per cell, and another ulcerative colitis patient had 1-2 genome-equivalents/cell.


Relative deficiency of plasma-calcitonin in normal women. A new radioimmunoassay technique was used to measure plasma-calcitonin in normal subjects. Plasma-calcitonin concentrations in women were less than 25% of those in men, and were often undetectable. However, during pregnancy or administration of the oestrogen-progestagen contraceptive pill, plasma-calcitonin equalled or exceeded male concentrations. These findings are consistent with an effect on calcitonin production of normal male testosterone concentrations and concentrations of the sex steroids during pregnancy. Calcitonin may protect the skeleton during calcium stress. Further, although it is unknown whether a deficiency of the hormone plays a role in postmenopausal osteoporosis, this is now a definite possibility which requires urgent investigation.


Penetration of four cephalosporins into tissue fluid in man. The penetration of four cephalosporins into tissue fluid obtained with a skinabrasion technique was studied. Two oral antibiotics, cephalexin and CGP 9000, had similar pharmacology and penetrated the fluid in equivalent amounts. Cefuroxime (33% protein-bound) and cefoxitin (65-79% proteinbound) attained levels in tissue fluid which were very similar to their blood levels. The level of antibiotic in the tissues seems to be closely related to the blood level and is not adversely affected by protein binding.


Transmission of herpes-simplex virus type 1 in a nursery for the newborn. Identification of viral isolates by D.N.A. "fingerprinting". The occurrence of herpes-simplex-virus type-1 infections in two newborn infants in a nursery within a one-month period suggested the possibility of transmission in the nursery. One infant may have been infected by his father, who had active herpes labialis at the time of the child's birth. The source of the second infant's infection was not apparent. Viruses isolated from the two infants were "fingerprinted" by cleaving the virus-specific D.N.A. with several restriction endonucleases and comparing the electrophoretic patterns. Isolates from the two infants were identical and differed from other isolates from epidemiologically unrelated cases. This observation confirmed the possibility of transmission of herpes-simplex virus type 1 in the nursery, but did not define the mode of transmission. Type-1 infections are serious in neonates: one of the infants died and an oesophageal stricture developed in the other. The "fingerprinting" technique provides a useful epidemiological technique for tracing the transmission of herpes virus infections.


Strong association between HLA-DRW2 and antibody-mediated Goodpasture's syndrome. In a study of HLA types in Caucasian patients with nephritis due to antibodies to glomerular basement membrane, antigen frequencies at A, B, or CW loci were normal. However, 15 out of 17 (88%) patients to whom DRW types were definitely assigned had HLA-DRW2 compared with 32 out of 100 Caucasian blood-donors. This difference is highly significant.


Fatal overdosage with disopyramide.

Fatal overdosage with disopyramide. The most common clinical finding in five patients who died after deliberately taking overdoses of disopyramide was an early loss of consciousness after an apnoeic episode. An initial response to resuscitation and antiarrhythmic drugs in four patients was not sustained and these patients deteriorated rapidly with cardiac arrhythmias and loss of spontaneous respiration. At necropsy the appearance of the lungs in four cases was consistent with pulmonary congestion secondary to left ventricular failure.


Paralytic poliomyelitis in England and Wales 1976-7. In 1976-7 26 cases of paralytic poliomyelitis were notified, of which 6 were vaccine-associated. 16 of the 20 non-vaccine-associated cases were due to type-u poliovirus, the type usually associated with outbreaks. The most important factor in the increase was the occurrence of poliomyelitis in unvaccinated persons.


Biochemical and haematological markers of alcohol intake. The serum gamma-glutamyl-transpeptidase (gamma-G.T.), aspartate transaminase (A.T.), urate, and triglyceride levels and the mean cell volume were estimated in 2034 healthy men. In 14.9% gamma-G.T. was elevated, in 8.0% A.T. was raised, and in 4.2% both enzymes were elevated. Findings were almost identical in a subgroup of 146 whose alcohol intake was known. Both enzymes, serum-urate, and mean cell volume showed a progressive rise with increasing alcohol consumption. The sensitivity of these markers is such that elevated levels are present in those whose alcohol intake would be regarded as normal and who are in no sense alcohol-dependent.


Is measurement of placental function and maternal weight worth while? A prospective survey of 1029 women delivered during 1976 at St. Bartholomew's Hospital was undertaken to assess the predictive value of a variety of clinical, ultrasonic, and biochemical variables in the detection of high-risk pregnancies. The best antenatal predictors of fetal risk were severe pre-eclampsia, depressed maternal serum levels of human placental lactogen, low maternal weight at 32 weeks' gestation, and heavy smoking by the mother. 62% of the high-fetal risk group had one or more of these features, but so did 33% of the controls.


Primary hyperparathyroidism in paraneoplastic hypercalcaemia. Hypercalcaemia is often associated with malignant disease. Causes of elevated serum-calcium levels in the absence of bony metastases include parathyroid-hormone production by the tumour, osteolytic factors made by the tumour, and coexistent primary hyperparathyroidism. By measuring nephrogenous cyclic-A.M.P. excretion to assess parathyroid-hormone function, we have determined the mechanism of such hypercalcaemia in 15 patients. Nephrogenous cyclic A.M.P. ranges from 0.05 to 2.40 mumol/g of creatinine in normal subjects, from 2.27 to 8.45 mumol/g in patients with primary hyperparathyroidism, and from 0.50 to 1.30 mumol/g in patients with proven non-hyperparathyroid hypercalcaemia without malignancy. 9 patients (60%) with hypercalcaemia and malignancy had normal levels of nephrogenous cyclic A.M.P. (range 0.35-2.07 mumol/g creatinine). The other 6 (40%) had elevated nephrogenous cyclic A.M.P. (range 2.70-5.55 mumol/g) consistent with increased parathyroid-hormone secretion. Surgical exploration of the neck in these patients showed that the increased parathyroid-hormone secretion was secondary to primary hyperparathyroidism, not ectopic hyperparathyroidism. Thus, the data indicate that coexistent hyperparathyroidism may be common in patients with hypercalcaemia and malignancy and that the measurement of nephrogenous cyclic A.M.P. is very useful in identifying patients at risk for hyperparathyroidism.


Induction of remission in hepatocellular carcinoma with doxorubicin. Doxorubicin (60 mg/m2 at 3-weekly intervals to a maximum total of 550 mg/m2) induced clinical remission in 14 (32%) of 44 patients with hepatocellular carcinoma. In 3 of those who responded, hepatic arteriography showed clearing of the previously extensive tumour circulation, and in a 4th there was disappearance of the tumour on serial ultrasound examinations. A fall in serum-alpha-fetoprotein level after the initial injection of doxorubicin predicted a favourable clinical response, whereas the level continued to rise in patients who did not respond.


Familial medullary thyroid carcinoma.

Familial medullary thyroid carcinoma. Medullary thyroid carcinoma (M.C.T.) is a tumour of the calcitonin-secreting cells of the thyroid gland; it affects both lobes, has a variable malignant potential, and is often familial. Despite the availability of diagnostic plasma-calcitonin immunoassays, the condition is rarely considered in the initial assessment of a patient with a thyroid mass so that the is often disseminated by the time it is diagnosed, inadequate surgery is performed, and family members are not investigated. We studied 22 members of a family with M.C.T. and gave alcohol to provoke calcitonin secretion. 3 (excluding the index case) had raised basal calcitonin levels and the diagnosis of M.C.T. was confirmed at operation; their calcitonin levels became undetectable after total thyroidectomy. 3 others had detectable levels after alcohol stimulation and are being re-screened at regular intervals.


Treatment of idiopathic orthostatic hypotension (Shy-Drager syndrome) with indomethacin. Four patients with idiopathic orthostatic hypotension (I.O.H.) and one with postural hypotension and diabetes were studied. Plasma-renin activity (P.R.A.) was low and did not rise appropriately with salt restriction and diuretic stimulation. Aldosterone levels were normal and rose with diuretic therapy. Plasma-volume, plasma dopamine beta-hydroxylase, urinary catecholamines, metanephrines, and vanillyl mandelic acid (V.M.A) were normal. Treatment with indomethacin (75-150 mg/day) raised the upright blood-pressure (B.P.) by an average of 20-30 mm Hg diastolic and allowed the four patients with I.O.H. to walk about without orthostatic symptoms but it had no effect in the fifth patient. When indomethacin was discontinued in one patient who had been taking it for 9 months with symptomatic relief, the B.P. fell to pretreatment levels within 48 h. When indomethacin was reinstituted the B.P. rose again. Indomethacin was more effective in these patients than either propranolol or fludrocortisone. There may be an absolute or relative excess of certain vasodepressor prostaglandins in the peripheral vessels which results in pooling of blood and orthostatic hypotension. If this is the case indomethacin might improve the orthostatic symptoms of I.O.H. by its inhibitory effect on prostaglandin synthesis, but its mechanism of action remains to be determined.


Hypoimmunoglobulinaemia with deficiency of pre-B cells. No pre-B cells were found in the marrows of two girls with congenital antibody deficiency who lacked B cells. The presence of variable T-lymphocyte defects in these and thymoma patients lacking pre-B cells favours a metabolic aetiology rather than selective failure of a single cell series.


Chronic hepatic inflammation and fibrosis due to low doses of paracetamol. Chronic hepatic necrosis developed in a man who had been taking 4 g of paracetamol daily for about a year (cumulative dose 1700 g). Liver biopsy done 23 days after the drug was stopped showed prominent diffuse central necrosis and portal changes. Repeat biopsy 5 months later showed chronic active hepatitis. This prompted anti-inflammatory treatment, with subsequent improvement in liver histology. Liver concentrations of reduced glutathione and paracetamol metabolism, assessed 1-1 1/2 years after drug was stopped, were normal; the basis for this patient's drug sensitivity is thus unclear. In some patients, chronic ingestion of therapeutic doses of paracetamol may produce hepatic necrosis and hepatitis which persist long after the drug has been discontinued.


Mortality from leukaemia and cancer in shipyard nuclear workers. A review of death certificates in New Hampshire, Maine, and Massachusetts for 1959-77 yielded a total of 1722 deaths among former workers at the Portsmouth Naval Shipyard where nuclear submarines are repaired and refuelled. Next of kin were contacted for 592. All deaths under age 80 were classified as being in former nuclear or non-nuclear workers depending on information supplied by next of kin. With U.S. age-specific proportional cancer mortality for White males as a standard, the observed/expected ratio of leukaemia deaths was 5.62 (6 observed, 1.1 expected) among the 146 former nuclear workers. For all cancer deaths, this ratio was 1.78. Among non-nuclear workers there was no statistically significant increase in proportional mortality from either leukaemia or from all cancers. The excess proportional leukaemia and cancer mortality among nuclear workers exceeds predictions based on previous data of radiation effects in man.


Leucocyte adherence inhibition for detecting specific tumour immunity in early pancreatic cancer. Tumour-specific immunity to pancreatic tumour antigens, assayed by an automated tube leucocyte-adherence inhibition assay (L.A.I.), was detected in 3 of 3 patients with localised pancreatic cancer and 3 of 8 patients with more extensive pancreatic cancer. Leucocytes from pancreatic cancer patients with L.A.I. reactivity did not react to antigens of stomach, colon, or lung tumours; leucocytes from patients with stomach, colon, or lung cancer of inflammatory disease of the pancreas and bowel did not show L.A.I. reactivity to pancreatic tumour antigens.


Uterine cervical cytology and young women. 9000 women aged 20 years and under who had cervical smears taken in the 10-year period 1967-76 were studied. The number of young women with abnormal smears rose, but this increase was in proportion to the number screened. Abnormal smears were found in 145 (1.6%) cases. Follow-up for periods of up to 10 years showed that in over half the cases subsequent smears had reverted to normal without treatment. 19 of the 145 patients progressed to have smears which were suggestive of malignancy: 16 of these were diagnosed histologically as carcinoma-in-situ, and the other 3 were histological dysplasias. At follow-up no cases of carcinoma-in-situ were found in women under 21. No cases of invasive cancer were found on the initial biopsy. One microinvasive cancer was found in a woman aged 26 on a second biopsy 6 1/2 years after the first atypical smear. The preclinical cases were detected from smears taken during pregnancy, or, in the case of the one possibly nulliparous girl, during a gynaecological consultation. These women did not attend family-planning clinics until after a pregnancy.


Effect of thyroid hormone on the levels of erythrocyte carbonic anhydrase isozymes and 2,3-diphosphoglycerate in rabbits. Levels of rabbit erythrocyte carbonic anhydrase B and C isozymes were determined in experimental hyperthyroidism using a quantitative immunologic technique. Levels of erythrocyte 2,3-diphosphoglycerate and protein binding iodine were simultaneously determined. Thyroxine and 3,5,3'-triiodothyronine were administered to rabbits orally for 30 days. A significant decrease in carbonic anhydrase B type was observed after 30 days, although no significant change was observed in carbonic anhydrase C type. These findings suggest that the steady state level of carbonic anhydrase B type in red cells is affected by thyroid hormone more readily than that of carbonic anhydrase C type. The level of red cell 2,3-diphosphoglycerate increased markedly after 10 days of treatment, corresponding to the increase of protein binding iodine. The clinical or pathologic significances were discussed in relation to the changes in the levels of these isozymes and 2,3-diphosphglycerate in red cells.


[Results after resection of left ventricular aneurysm (author's transl)]. This resport concerns 105 left ventricular aneurysmectomies, 44 of which were combined with additional operations. Mortality in hospital was 7.6%, the survival rate after 4 years 84%. Postoperative examinations were carried out in 74 patients after an average interval of 21 months. There was a subjective improvement in 2/3 of the cases, only 1/3 returned to work. Angina pectoris was improved in 2/3, principally in the group with additional revascularization. The functional tolerance test showed that only 57% improved their physiological capacity for work. The effect of aneurysmectomy on preoperative cardiac arrhythmias was unreliable and on the whole disappointing.


Role of complement in the toxicity of dietary legumes. On the basis of in vivo data Jayne-Williams (1) has proposed that the toxicity of dietary legumes is due to their content of lectins which are immunosuppressive. On the basis of in vitro data with cultured lymphocytes (2), it is now proposed that ingested lectins bind to cell surfaces and cause autologous complement components to bind to and destroy immunologically competent cells. The hypothesis throws a possible light on the aetiology of favism and Whipple's disease.


Localization of alpha-fetoprotein by immunofluorescent method during induction of rat liver tumors by 3'-methyl-4-dimethylaminoazobenzene. Localization of alpha-fetoprotein (alpha-FP) has been followed in hepatal tissue and tumors during induction of primary hepatomas with the aid of 0.12% 3'-Me-DAB (3'-methyl-4-dimethylammoazobenzene) in Wistar rats. The indirect immunofluorescence method was used for the localization of alpha-FP positive cells. During the course of carcinogenesis, alpha-FP in serum was detected by means of the crossing over immunoelectrophoresis. This study has yielded the following results: Alpha FP positive cells resembling small hepatocytes occurred dispersed and in groups beginning with the 5th week of a carcinogenic diet until the appearance of tumors. No alpha-FP positive oval cells have been found. Alpha-FP positive cells were always found in rats with alpha-FP positive serum, but they were rarely present in rats with alpha-FP negative serum. From the 10th week, tumors of the cholangiohepatoma type began to be formed in which variously scattered alpha-FP positive cells of the type of small hepatocytes were present, with the serum being negative. Between week 14 and 21 hepatoma nodules began to be formed. At week 21 frequent alpha-FP positive cells close to normal hepatocytes were observed both singly and in groups. These are considered to be the sites of developing tumor nodules. In all the hepatoma nodules, the number of positive tumorous cells and the intensity of fluorescence proved to be directly proportional to alpha-FP concentration in serum.


[Acute and subacute intracranial hepatoma with hemophilia A--two cases report (author's transl)]. Two cases of traumatic intracerebral hemorrhage in hemophiliac are presented. Case 1 was a 3-year-old boy, who had a mild trauma and became semicomatous. The carotid angiogram showed the findings of intracerebral hematoma and extravasation of contrast medium from the temporal branch of the middle cerebral artery. Evacuation of hematoma was successfully performed under human AHF administration. Postoperatively, the human AHF was administrated to maintain 30% of the plasma concentration of the VIII factor for 3 weeks. He discharged without any neurological deficit. Case 2 was a 14-year-old boy who had experienced several episodes of hemorrhage in nose and knee joints. He had a minor head trauma. Then, 12 days later, he became drowsy and the left hemiparesis developed. The right carotid angiogram revealed the presence of thin subdural hematoma and intracerebral hematoma. From clinical state, however, the conservative treatment was selected and human AHF was administered. The concentration of plasma VIII factor was kept in 30% with human AHF for 2 weeks like case 1. He completely recovered. The authors believe that the human AHF is very effective and 30% of plasma VIII factor is enough for treatment of intracerebral hemorrhage in hemophiliac.


Intracellular calcium accumulation in Duchenne dystrophy and other myopathies: a study of 567,000 muscle fibers in 114 biopsies. Ultrastructural studies have shown plasmalemmal defects in a proportion of non-necrotic muscle fibers in Duchenne dystrophy, suggesting that intracellular calcium overloading may be an important mechanism of muscle fiber degeneration. To investigate this assumption, we studied the localization of calcium with the von Kóssa method, with alizarin red, and with glyoxalbis-(o-hydroxyanil) in serial, fresh-frozen sections of 114 biopsy specimens. The biopsy material included Duchenne dystrophy (24 cases), other dystrophies (27 cases), inflammatory myopathies (47 cases), and normal controls (11 cases). Counted in each specimen were every muscle fiber, the so-called large-dark fibers, and all calcium-positive fibers. Separate counts were made of the large-dark, necrotic, and other types of calcium-positive fibers. In Duchenne dystrophy, non-nectotic calcium-positive fibers occurred with a mean frequency of 4.83 percent. For all other groups, the corresponding value was 0.57 percent, with a range of 0.21 percent (normals) to 1.76 percent (scleroderma), p less than 0.001. Large-dark fibers were 12 times more common in Duchenne dystrophy than in all other cases. Forty-three percent of the fibers were calcium-positive in Duchenne dystrophy, whereas calcium-positive large-dark fibers were extremely rare in the other cases.


Vital staining of coronal dentin in monkey teeth. Vital staining of monkey incisor teeth with the incisal dentin exposed to the oral environment by attrition was carried out, with the use of a number of dyes (pH and redox indicators). There was a distinct staining of the coronal dentin, regardless of which dye was introduced into the pulpal cavity. The exposed dentin was stained like the unaffected dentin, with the exception of a narrow centrally located zone that extended from the tip of the original pulp horn to the incisal edge of the tooth. The suggestion is that this zone is not unstained because of exposure of the dentin to the oral environment, but because it coincides with an area of the tissue where the pulpal ends of the dentinal tubules are blocked by atubular hard tissue normally laid down in the pulp horn of incisor teeth.


"Cold" lesion in bone scan of an osteogenic metastasis of Wilms' tumour. Isolated mandibular metastasis in Wilms' tumour resulted in cold lesion on a bone scan.


Enzymatic synthesis of DNA complementary to mitochondrial mRNA via reverse transcription. The poly(A)-containing mitochondrial mRNAs of rat liver were tested for their ability to serve as templates for the DNA synthesis by means of reverse transcription in the presence of the oligo(dT) primer and the RNA-directed DNA-polymerase from avian myeloblastosis virus. The mT-mRNA does not support the DNA synthesis in the standard conditions sufficient for effective reverse transcription of rabbit globin mRNA and of poly(A) in the presence of oligo(dT) primers. After a mild alkaline treatment of the mRNA and subsequent polyadenylation of the 3'-termini of the generated fragments with ATP:RNA adenyltransferase from E.coli the poly(A) (+) polyribonucleotides are able to serve as templates for reverse transcription in the presence of oligo(dT) and the reverse transcriptase. A conclusion is made that a "structural stop" exists in mitochondrial mRNA non-translable regions adjacent to the poly(A) terminal sequence. The "structural stop" is suggested to be caused by post-transcriptional modification of mRNA (methylation, etc.) or by a particularly stable secondary structure in this region of the mRNA molecules.


Choosing a drug regimen for obstructive pulmonary disease. 2. Agents other than bronchodilators. Cromolyn sodium, oral and inhaled corticosteroids, antibiotics, and mucolytic agents all have a place in treatment of the reversible components of obstructive pulmonary disease. Patient education about the particular condition causing airflow obstruction and the chosen treatment program is extremely important in promoting patient acceptance.


Studies on pyrazine derivatives. Part X. Synthesis and tuberculostatic activity of some 6-cyclamino-, 6-imidazolyl--and triazolylpyrazine-2-carboxylic acids derivatives. The 6(2'-methylpiperidine-, 2',6'-dimethylmorpholino-, imidazolyl- and triazolyl)-2-cyanopyrazines were prepared from 2-cyano-6-chloropyrazine. The -CN group was then transformed into COOH, CONH2, CSNH2, CONHNH2, CONHOH and C(NOH)NH2 functions. All compounds obtained were of weak tuberculostatic activity. Comp. 13 was active against isoniazide, capreomycin and ethionamide resistent strains at the concentration range of 31.2--62.5 microgram/cm3.


Early events and mechanisms in the induction of bacterial SOS functions: analysis of the phage repressor inactivation process in vivo. Different inducing agents and treatments produced distinctly different kinetic patterns of inactivation of prophage repressor molecules. The different patterns were related to differences in the initial altered states of DNA that were produced. The timing of appearance of DNA degradation was correlated with the time needed for repressor inactivation. These characteristics suggest that all the inducing treatments lead to the formation of a final predegradative DNA structure(s) (probably involving scissions) that is acted on by specific DNases, including the recBC DNase, to produce the signals for the induction of prophage.


Isolation and characterization of the normal crossreacting antigen: homology of its NH2-terminal amino acid sequence with that of carcinoembryonic antigen. The normal antigen, NCA, which crossreacts with the carcinoembryonic antigen, CEA, was purified from normal spleen tissue by an immunochemical purification method using insolubilized antibodies to either CEA or NCA. The highly purified NCA obtained was extensively characterized by immunological tests. The molecular weight of NCA determined by chromatography on Sephadex G-200 was approximately 100,000. The total amount of carbohydrate in NCA was 30%, compared to 60% in CEA. NCA and CEA also differed in sugar composition. The amino acid composition of NCA was nearly identical to that of CEA, except for the apparent presence of methionine in NCA but not in CEA. The sequence of the first 26 NH2-terminal amino acids in NCA was identical to that of CEA except at position 21, where alanine was found in NCA instead of valine in CEA.


Growth state-dependent phenotypes of adult hepatocytes in primary monolayer culture. A proliferation-competent adult rat liver cell monolayer system has been analyzed for tissue-specific functions during its growth cycle. High levels of the adult (L type) form of pyruvate kinase (EC 2.7.1.40) and glutathione S-transferase B ("ligand," EC 2.5.1.18) are observed during the early lag phase; they decline markedly during the logarithmic phase and reappear during the stationary phase. By contrast, elevated levels of the fetal (K type) form of pyruvate kinase and alpha1-fetoprotein production appear only after proliferation begins; this pattern diminishes slightly during stationary phase as the adult phenotype is restored. Albumin production continues throughout the entire growth cycle. These in vitro findings simulate those observed during hepatoproliferative transitions in the intact animal and, as such, constitute a developmental program for normal epithelial cells in primary culture.


Growth of embryonal carcinoma cells in serum-free medium. Two mouse embryonal carcinoma cell lines, PCC.4 aza-1 and F9, have been grown in serum-free F-12 medium supplemented with Pedersen fetuin, insulin, transferrin, and 2-mercaptoethanol. This medium supports long-term growth of both cell lines. When these cells are transferred from medium containing serum to this serum-free medium, growth continues without any detectable lag. PCC.4 aza-1 grown in this medium for over 20 generations retains the capacity to differentiate in vivo. This medium appears to be a general serum-free medium for the growth of embryonal carcinoma cells.


Immunogenicity of the envelope glycoprotein of avian sarcoma virus. The expression of type E-specific glycoprotein in chick-helper factor-positive [chf(+)] chickens is not restricted to a certain stage of embryogenesis but persists in postembryonic life. This finding prompted an investigation of the immunogenicity of the viral envelope glycoprotein of exogenous avian sarcoma virus in chf(+) and chf(-) chickens. Sensitization of both classes of chickens resulted in the induction of detectable antibody reactivity to determinants of the glycoprotein that were type-specific as well as group-specific. Because group-specific determinants are present on type E-specific glycoprotein, these results link immunity to exogenous viral envelope glycoprotein in chf(+) chickens with autoreactivity. A model is proposed to rationalize the induction of reactivity in this system.


Components in multiple sclerosis cerebrospinal fluid that are detected by radioimmunoassay for myelin basic protein. Components in cerebrospinal fluid that are antigenically related to myelin basic protein have been identified by a technique described recently [Barbarese, E., Braun, P. E. & Carson, J. H. (1977) Proc. Natl. Acad. Sci. USA 74, 3360-3364] involving separating the cerebrospinal fluid proteins by sodium dodecyl sulfate/polyacrylamide gel electrophoresis and measuring the individual components by radioimmunoassay for myelin basic protein. Samples of cerebrospinal fluid from 48 different patients (23 with definite multiple sclerosis, 4 with suspected multiple sclerosis, and 21 with other neurological diseases) were examined by this technique. The results indicate that cerebrospinal fluid can contain at least three separate components that are detected by radioimmunoassay for myelin basic protein. On the basis of their apparent molecular weights, the three components were identified as follows: component I, intact myelin basic protein; component II, proteolytic fragments of myelin basic protein; and component III, a protein of unknown origin with an apparent molecular weight of 50,000. Most samples of cerebrospinal fluid (45 of 48) from patients with multiple sclerosis and from patients with other neurological diseases contained components I and II. Component III was detected in all of the samples from patients with definite multiple sclerosis, in three of four samples from patients with suspected multiple sclerosis, and in none of the samples from patients with other neurological diseases. Some implications of these findings are discussed.


Crossreacting determinants in variant-specific surface antigens of African trypanosomes. A number of variant-specific surface antigens (VSSAs) were purified from clones of Trypanosoma brucei and T. congolense and tested for immunological crossreactivity. Anti-VSSA sera were clone-specific when tested by indirect immunofluorescence of living trypanosomes, but they were not clone-specific when tested by radioimmunoassay with purified 125I-labeled VSSAs. In this double-antibody radioimmunoassay every VSSA tested was precipitated by the homologous and all heterologous anti-VSSA sera. Any unlabeled VSSA could inhibit the heterologous precipitation reactions by 100%. The homologous precipitation reactions were effectively inhibited only by unlabeled homologous VSSA. Crossreactions between different VSSA molecules were also revealed by microcomplement fixation tests. The results confirm the presence, in VSSAs, of variable determinants specific to individual VSSAs and also show crossreacting determinants in all VSSAs tested, including those isolated from different species of trypanosomes. These results contrast with previous studies which failed to find evidence for immunological crossreactivity between different VSSA molecules. We suggest that the crossreacting determinants in VSSAs may represent common structural regions. The existence of such regions would have considerable implication for the development of theories and experiments concerning the mechanism of antigenic variation in African trypanosomes.


Biosynthesis of reverse transcriptase from Rauscher murine leukemia virus by synthesis and cleavage of a gag-pol read-through viral precursor polyprotein. Reverse transcriptase (RT; RNA-dependent DNA nucleotidyltransferase) from Rauscher leukemia virus is synthesized in infected cells by way of a read-through poly- rotein of 200,000 molecular weight. This polyprotein (Pr200(gag-pol)) was precipitated by antiserum to RT; in a previous study all the monospecific antisera to gag proteins recognized Pr200(gag-pol). Pr200(gag-pol) contains both p30 and RT peptide sequences. Intermediate RT-related precursors of 145,000 (Pr145(pol)), 135,000 (Pr135(pol)), and 125,000 (Pr125(pol)) molecular weights were specifically recognized by precipitation from infected cell extracts by antiserum to RT. These proteins shared methionine-containing tryptic peptide sequences with a virion polypeptide of 80,000 molecular weight (p80(pol)) precipitate by antiserum to RT. Purification of active RT enzyme from virions labeled with [(3)H]methionine showed that p80(pol) was the major component, based on analysis by gel electrophoresis and tryptic peptide mapping experiments. A polypeptide (Pr80(pol)), similar in size to mature viral p80(pol), was also precipitated from infected cells by antiserum to RT. Its peptide map was nearly identical to that of virion p80(pol). Pulse-chase studies showed that Pr80(pol), Pr125(pol), and Pr135(pol) were stable polypeptides, whereas Pr200(gag-pol) and Pr145(pol) were unstable precursors. Pulse-chase studies with the protein synthesis inhibitor, cycloheximide, showed that the processing of Pr200(gag-pol) occurred for a short time in the absence of protein synthesis.


Regulation of rat alpha-fetoprotein production by methionine and adenosine 5'-triphosphate. Simultaneous and equimolar injections of methionine and adenosine 5'-triphosphate significantly accelerated the rapid fall of rat serum alpha-fetoprotein (AFP) concentrations after birth. The results were compared with those obtained by administrations of prednisolone and adult tissue extracts. Correlations between a methionine-related metabolic event(s) and the repression of AFP synthesis were discussed.


Standardization of Romanowsky stains. The relationship between stain composition and performance. A panel of 17 eminent haematologists has assessed the performance of 5 Romanowsky stains prepared from pure component dyes, comparing the suitability and acceptability of these stains for the preparation of routine blood and bone-marrow films. It was found that the results obtained using the stain described by Marshall et al (1975) were comparable to those obtained using a modification of the stain described by Wittekind et al (1976). The performance of the 3 other stains was less acceptable. Variations in stain formulation have been correlated with stain performance.


[The treatment of epileptic encephalopathies with gamma globulin in children (author's transl)]. The authors have treated 10 children presenting with severe epilepsy with repeated large doses of gamma-globulin. They noted a marked improvement in 7 of the children with respect to behaviour and a disappearance of seizures in 8 with comparable EEG improvement. Four children have been able to reduce their conventional anticonvulsant therapy considerably and 2 others havers received no other medication at all for 8 months. The possibility of an immune disturbance in some childhood epilepsies is thus suggested.


[Measures in cases of suspected rabies exposure]. Criteria are discussed for evaluating cases in which exposure to rabies is to be suspected. Due to an incubation period generally exceeding 20 days, active immunization can be performed even after exposure. Vaccination programs current in Switzerland and indications for additional passive immune prophylaxis are discussed. In every case, local wound treatment remains essential.


Channel structures of gramicidin: characterization of succinyl derivatives. Succinyl derivatives of gramicidin were tested for their ability to form channels in planar artificial lipid bilayers. Both N-succinyldeformylgramicidin methyl ester and charged O-succinylgramicidin formed channels, but the channels had markedly different sizes and lifetimes. This implies that gramicidin forms channels by end-to-end association. However, the doubly charged N,O-bissuccinyldeformylgramicidin was inactive, which suggests that only end-to-end association of gramicidin may result in channel formation.


Prenatal diagnosis of genetic disorders. Sampling of amniotic fluid, visualization of the fetus, fetal blood sampling, and screening of maternal blood represent successive approaches to the diagnosis of specific genetic disorders in the second trimester of pregnancy. Clinical and ethical concerns about the appropriateness, safety, and efficacy of the techniques have led to multidisciplinary assessments at an early stage. A major growth in demand for medical and educational genetic services can be anticipated.


Defense of the radical perineal prostatectomy. There is sharp disagreement as to what constitutes the proper surgical approach to localized carcinoma of the prostate. We have performed 31 radical perineal prostatectomies in a six-year period with no mortality and minimal morbidity. Thirteen of these patients were understaged preoperatively and had extraprostatic cancer; however, only one has died from his tumor. One patient is incontinent but none has troublesome local symptoms. These patients required an average of 15 postoperative days, none required more than two units of blood, and careful preoperative consultation has minimized the psychologic stress of impotence. These data contrast sharply with the published morbidity and mortality statistics associated with a preliminary staging lymphadenectomy and a definitive radical retropubic prostatectomy. Also, we are convinced that our patients with stage C cancer have been done a real service by removing the prostate gland even though cancer remains in the stumps of the seminal vesicles. Unless the advocates of the staged procedure can demonstrate an improvement in the patients' survival data, we believe the radical perineal prostatectomy remains the procedure of choice for the cure of localized prostatic cancer and we would advocate this operation as an acceptable palliative approach to selected patients with stage C lesions.


Active enhancement of canine liver allografts with polyspecific antigen. Of 34 canine liver allograft recipients, 17 in the control group survived for 6.9 +/- 1.5 days. Six recipients, group 3, were given 780 milligrams per kilogram of body weight polyspecific semisoluble antigen prepared from 20 spleens together with 10 milligrams per kilogram of body weigth prednisolone on days 15, 8 and 1 before transplantation. The mean survival time of this group was 10.1 +/- 2.0 days, p less than 0.01, compared with the control group. Six other recipients, group 4, were similarly treated with antigen from a pool of 70 spleens. Three survived for more than three weeks, and the other three died on days 1, 7 and 8 postoperatively with signs of accelerated rejection. Donors and recipients were not identical for leukocyte defined determinants. The recipients displaying accelerated rejection had markedly higher lymphocytotoxic and hemagglutinating antibodies. In addition, all recipients undergoing progressive rejection showed an inhibition of leukocyte migration. After three antigen dosages, rosette forming lymphocytes were present in increased numbers in peripheral blood and remained unchanged thereafter.


Effects of alpha2-plasmin inhibitor on fibrin clot lysis. Its comparison with alpha2-macroglobulin. The major plasmin inhibitors namely alpha2-plasmin inhibitor and alpha2-macroglobulin were compared for their effects on lysis of fibrin clot. Plasmin fibrinolytic activity was immediately inhibited by alpha2-plasmin inhibitor, whereas alpha2-macroglobulin inhibited plasmin progressively. Urokinase(plasminogen activator)-induced clot lysis was inhibited efficiently by alpha2-plasmin inhibitor present in the clot. Inhibition of urokinase-induced clot lysis by alpha2-macroglobulin was weak and the molar concentration necessary for alpha2-macroglobulin to achieve the same degree of inhibition as that achieved with alpha2-plasmin inhibitor was about 10 times higher than that of alpha2-plasmin inhibitor. Binding of Lys-plasminogen to fibrin was inhibited by alpha2-plasmin inhibitor but not by alpha2-macroglobulin. Molar concentrations of alpha2-plasmin inhibitor which were effective in inhibiting the binding were 30 times less than that of 6-aminohexanoicacid. alpha2-Plasmin inhibitor was found to interact with Lys-plasminogen to form a weakly-bound complex which is dissociable in the presence of 6-aminohexanoic acid, suggesting that inhibition of binding of Lys-plasminogen to fibrin by alpha2-plasmin inhibitor may be due to interaction of alpha2-plasmin inhibitor with a specific site of the plasminogen molecule and that the site may be 6-aminohexanoic acid-binding site. It is suggested that alpha2-plasmin inhibitor is more reactive and efficient inhibitor of fibrinolysis than alpha 2-macroglobulin.


Immunofluorescence study on thrombolysis with special reference to the patterns of distribution and the contents of fibrin, plasminogen, alpha2-macroglobulin and urokinase in artificial thrombi. By the immunofluorescence technique, fibrin, plasminogen and alpha2-macroglobulin demonstrated a similar basic pattern of distribution in the artificial thrombi, rimming the platelet aggregates in the white part and forming a network structure in the red part. The content of plasminogen seemed to be higher in the red part than in the white part. After superfusion with urokinase solution, urokinase was found in a similar pattern of distribution of that of fibrin. The content of urokinase seemed to be higher in the red part, especially in its outer area, than in the white part. It is concluded that urokinase diffused into the artificial thrombi can convert plasminogen, trapped onto fibrin in threads to plasmin. Poor lysibility of the white part might be due to thick strands of fibrin, a low content of plasminogen and a low diffusibility of plasminogen activator, in addition to the antifibrinolytic activity of platelets.


[Strongyloides westeri Ihle, 1917 (Nematoda: Strongyloididae. II. Parasitological and haematological features of experimental infection (author's transl)]. Experimental infections using 600,000 infective larvae of Strongyloides westeri were carried out in seven worm-free Shetland ponies, four foals and thee yearlings. In the foals, the prepatent period varied from ten to fourteen days, the patent period ranging from forty-three to eighty-three days. Within approximately two months after infection, a decrease in the concentration of haemoglobin and an increase in the beta-globulin fraction of the protein pattern of the serum, practically coinciding with the maximum S. westeri faecal egg counts, were recorded. In the yearlings, the prepatent period varied from sixteen to eighteen days, the patent period ranging from fifty-five to seventy-three days. The experimental infection by an identical dose in a yearling which had previously had S. westeri infection as a foal, did not become patent. Unlike the foals, the yearlings did not show any changes in the haematological parameters following experimental infection.


[Effectiveness of coumaphos against chorioptes bovis in a horse with foot-mange (author's transl)]. A horse with foot-mange failed to recover following a number of courses of treatment with coumaphos. Mites isolated from this horse were tested in vitro for their sensitivity to coumaphos and lindane. The mites were resistant to coumaphos and sensitive to lindane. Following treatment with lindane, the horse recovered within four weeks.


Bu--a new antigen at the HLA-B locus.

Bu--a new antigen at the HLA-B locus. Evidence is presented for a new allele at the HLA--B locus defining a new antigen, Bu. Population studies indicate a gene frequency of 0.0043 in English Caucasians. No HLA--B locus triplets involving the Bu antigen have been observed. Inheritance of Bu has been established in three informative families, each of at least three generations. Platelet absorption studies and analysis of a large number of multispecific HLA--B antisera suggest that Bu is "intermediate" between the well-established antigens Bw15 and Bw21.


HLA-A antigens of patients with Wegener's granulomatosis. The frequency of HL-A antigens was determined in 31 patients with biopsy-confirmed Wegener's granulomatosis and compared with their frequency in healthy Caucasian control population. There was no significant difference between the two groups for any of the 24 HL-A antigens tested.


On the mapping of PGM3, GLO and HLA.

On the mapping of PGM3, GLO and HLA. In a combined Danish, American and Icelandic study, the odds for the orientation PGM3 :GLO:HLA-B:HLA-A versus GLO:HLA-B:HLA-A:PGM3 are estimated to be 75:1. The GLO:HLA recombination frequency is estimated at 5% for males and 12% for females. The recombination fraction for PGM3:GLO is 12--13% in males and is significantly higher in females (approximately free recombination). The findings are consistent with the large sex differences in recombination frequency between HLA and PGM3.


HL-A markers in the Vietnamese population. A total of 126 normal, unrelated individuals from northern central and southern Vietnam have been typed for 32 alleles of the A and B loci, including B HS. The gene, haplotype frequencies and delta values obtained are compared with those of four other Mongoloid populations. The gene frequencies were similar to those found in a Chinese (Cantonese) population.


HLA-Dw2 as a marker of resistance against juvenile diabetes mellitus. Juvenile-onset diabetes mellitus (JDM) is one of the human diseases shown to be associated with histocompatibility antigens. The occurrence of serologically defined HLA antigens B8 Bw15, B18 and Cw3 is increased among these patients (Singal & Blajchman 1973, Nerup et al. 1974, Cudworth & Woodrow 1975). However, lymphocyte defined HLA-D antigens Dw3 and Dw4 (LD 8a and LD w15a), positively associated with these serologically defined antigens, seem to be even stronger markers of susceptibility to this disease (Thomsen et al. 1975).


The major histocompatibility complex of Rhesus monkeys IX. Current concepts of serology and genetics of Ia antigens. Eleven Ia or B-cell specificities of rhesus monkeys have been serologically identified. They are probably all controlled by the RhLa complex, but, according to results of a large population and family study, only five or six can be placed in a segregant series, designated as Ia1. Data from recombinant offspring in two rhesus families place the Ia1 locus in the close vicinity of the D or major MLC locus within RhLA. The genetic control of the Ia antigens not defined by the Ia1 locus has not yet been clarified.


Modification of HLA antigens in patients with malignancies following hormone therapy. In 23 out of 39 patients with various malignancies, treated with hormones (Prednison, Agostiben, Agovirin, separately, or combined; Prednison plus another hormone) modification of HLA antigens was established. Out of 51 patients with hitherto untreated malignancies HLA modification was demonstrated in 12 cases. This variation is statistically significant (P  0.0006), and suggests hormonal therapy to be one of the causes of HLA modification in malignant tumors. The serological pattern of HLA modification varied: in five patients lymphocyte polyreactivity; in 10, loss of HLA antigens; in six, weakening of HLA antigens and in two, transformation of HLA--A2 IN HLA--A28. The modification was transient in character. It occurred most frequently following administration of Prednison, or Prednison combined with some other hormone, and was unrelated to drug dosage.


Primary affective disorders and HLA antigens. In 125 patients with various types of primary affective disorders, 27 HLA antigens of the A, B and C loci were examined. Bw40 occurred more frequently in the primarly form (20.83% against 7.64% in controls) and Cw4 in the unipolar form (25%) and, in disease in general, 16%, against 9.58% in controls. Following correction, however, these differences are statistically insignificant.


Primed lymphocyte typing (PLT): dichtomizing responses into "positives" and "negatives". In primed lymphocyte typing (PLT), it will often be useful to divide the test cells for any given reagent into a positive and a negative group. Some general problems in PLT analysis are discussed here. The author describes a model for PLT data, to provide a conceptual framework, and suggests a statistical procedure based on the model.


The genetic control of HLA-A and B antigens in somatic cell hybrids: requirement for beta2 microglobulin. The lymphoblastoid cell line Daudi lacks both HLA-A and B antigens and beta2 microglobulin. Somatic cell hybrids derived from a fusion between this line and D98/AH--2 were shown to express four HLA antigens not detectable on either parent cell, A1, A10(Aw26), Bw16(Bw38, Bw17. The initial definition by direct cytotoxicity assay was confirmed by absorption of reactions against target T lymphocytes, thus avoiding problems due to contaminating Ia antibodies, and by blocking the reactions by pretreatment with a chicken anti-human beta2 microglobulin serum. That the new specificities were due to the Daudi HLA region was confirmed by the finding that interspecific hybrids between Daudi and A9L, containing a single human chromosome 6, expressed A10 and Bw17. This also defined the haplotypes of Daudi as A10(Aw26), Bw17 and A1, Bw16(Bw38). The re-expression of the Daudi HLA-A and B antigens in two independent sets of hybrids indicates that it does not carry a mutation in the HLA region. It has previously been reported that somatic cell hybrids with Daudi, which contain chromosome 15, do not express human beta2 microglobulin. These results suggest that the reason for the lack of HLA-A and B antigens on Daudi is a secondary effect due to the mutation(s) in the beta2 microglobulin gene.


Alphafetoprotein is not a component of the 8 S estradiol receptor from the immature mouse uterus or brain. The hypothesis that alphafetoprotein (AFP) could be a consitituent of the estradiol receptor in the uterus and brain of the immature mouse has been tested. Cytosols prepared from 2 week-old mice were depleted of AFP by immunoadsorption with a Sepharose-coupled anti-mouse AFP anti-serum. Aliquots of these cytosols containing nondetectable levels of AFP by RIA were then brought to 0.4 M KCl to convert 8 S estradiol receptors to the 4-5 S forms, reacted either with anti-AFP or with a control anti-IgG immunoadsorbent, labeled with 3H-estradiol, and centrifuged on glycerol gradients. There was no, or very little, loss of estradiol receptors in the experimental as compared to the control cytosols indicating that AFP is not a constituent of the 8 S estradiol receptor.


Rat and human embryo and post-natal sera contain a potent endogenous competitor of estrogen-rat alpha-fetoprotein interactions. A highly active inhibitor of the binding of estrone and estradiol-17beta to rat alpha-fetoprotein is demonstrated for the first time in embryo, immature and adult rat sera as well as in fetal and adult human sera. The competitive character and the narrow specificity of this inhibition effect is shown. The major compound responsible for this activity is isolated by successive column Sephadex LH20 and thin layer chromatography: it is characterized as a nonpolar, nonphenolic, dialysable and thermostable substance, unreactive towards anti-estrone and anti-estradiol-17beta antibodies. The possible biological role of an endogenous non-estrogen ligand of rodent fetoproteins is discussed.


Clinico-pathological study of heartwater in goats. The clinico-pathological features of heartwater were studied in goats experimentally infected with a Nigerian isolate of Cowdria ruminantium. Significant drop in haemoglobin values and marked leukopaenia caused by lymphopaenia and neutropaenia and a fall in total serum protein were observed during the course of the disease. A significant increase in the alpha-globulins and an apparent fall in the gamma-globulins also occurred. Marked depletion of lymphocytes in the follicles of spleen and lymph nodes was observed in histological sections. A dramatic rise in blood levels of glucose, pyruvate and lactate, and a drop in blood pH occurred terminally and appeared to contribute to the fatal outcome of the disease.


A cytofluorometric method of counting trypanosomes. A rapid automated method of counting trypanosomes was developed using cytofluorometric methods. Organisms were vitally stained with acridine orange, and DEAE cellulose separated T. congolese were accurately counted at all concentrations. T. congolense in heparinized whole bovine blood were also counted accurately at levels greater than 1,000 per microliter. At lower levels, small fluorescent particles in whole blood interfered with the counts.


A system of cancer-related urinary glycoproteins: biochemical properties and clinical applications. Gel-filtration and immunodiffusion reveal most patients with disseminated cancer excrete 100 to 1000 mg/day of urine proteins, mol wt 10,000-60,000, which are distinct from known plasma proteins and cancer-related antigens. By gel-filtration and ion-exchange chromatography, 5 novel urinary glycoproteins have been isolated which are responsible for about 1/2 the mass of the "low molecular weight proteinuria" of patients with advanced cancer: BJC1 and BJC2 (patient B.J., chronic myelocytic leukemia); JBB5 (J.B., metastatic pancreatic carcinoma); EDC1 (E.D., acute myelocytic leukemia); HNC1beta (H.N., acute monocytic leukemia). Mol wts respectively are 29,000, 22,000, 55,000, 27,000 and 33,000, and carbohydrate contents respectively 61%, 23%, 23%, 27% and 40%. Attention to date has focussed on EDC1 and HNC1beta, because their urinary excretion directly reflects the course of the neoplastic disease. EDC1 and HNC1beta possess the same protein but different carbohydrate moieties. They are antigenically related to inter-alpha trypsin inhibitor, mol wt 160,000, which is one of the 6 antiproteolytic proteins in normal human plasma. EDC1 and HNC1beta both possess antitryptic activity. Specific radioimmunoassays (RIA) to these 2 glycoproteins were developed. Normal individuals (n = 210) excreted 0.3 +/- .02 (ave. +/- SE) mg EDC1 per g creatinine. In 18 non-neoplastic diseases (n = 75), urinary EDC1 was .5 +/- .06 mg/g creatinine. In disseminated cancer of 7 types (n = 81) (breast, ovary, colon, squamous of head-neck and lung; melanoma; acute myelocytic leukemia), ave. EDC1 excretion ranged from 10 to 190 mg/g creatinine. A significant increase (P less than .05) was found in the localized stage of squamous cancer of head-neck-lung, but only after regional or distant spread in the other types. Similar results were found with HNC1beta, urinary excretion of which averaged 1/10 that of EDC1. Effective chemotherapy in 5 patients with leukemia or solid tumors caused prompt disappearance of urinary EDC1; the glyco-protein reappeared in the urine several weeks before clinical relapse. (i) EDC1- and HNC1beta-proteinuria is a useful indicator of some types of localized and most types of disseminated cancer; (ii) the degree of this proteinuria reflects the effectiveness of chemotherapy; (iii) the antiproteolytic property of EDC1 and HNC1beta suggests a relation between proteolysis and tumorigenesis.


Fucosidosis and I-cell disease: a fine structural and silver-staining study of abnormal inclusion bodies in small-intestinal cells. Small-intestinal cells of children with fucosidosis or the I-cell type of lysosomal storage disease were investigated with special attention to the fine structure and silver-staining patterns of abnormal inclusion bodies. The results indicate an accumulation of mucopolysaccharide and or glycoprotein, and lipid materials in the greater part of these inclusion bodies. The significantly enlarged lysosome-like bodies in the absorptive cells of these patients showed the same silver-stain affinity as the Golgi apparatus, apical vesicles and tubules, and the cell coat. This might indicate a crinophagic function of the lysosome-like bodies in the transport or secretion of cell coat material. Additional information is given on the storage of material in the significantly enlarged inclusion bodies in cultured fibroblasts and in the abnormal vacuoles of peripheral blood lymphocytes in I-cell disease.


[Study of the antigenic specificity of hemagglutinin of influenza viruses type A by quantitative radioimmunoassay. Comparative study of differences in the specificity of H3 hemagglutinin in epidemiologically active strains]. Comparative radioimmunoassays (RIA) of hemagglutinin of influenza type A viruses were carried out. The RIA was shown to detect definite type differences of influenza A and B virus hemagglutinin and subtype differences (HO and H3), as well as to determine both qualitative and quantitative characteristics of renewal of determinants within the antigenic drift. The A/Victoria/3/75 strain was found to have more renewed determinants than the A/Scotland/870/74 strain but less than the A/Victoria/112/76 strain which could be considered as a next drift variant. The epidemic strains circulating after 1972 had no more than 10% of the antigenic determinants characteristics of the original A/Hong Kong/1/68 strain. One of the advantages of the RIA was demonstrated to be its high sensitivity and economy as the specific antiserum can be used in dilutions 1:20,000 and higher. The test antigens may be both freshly isolated strains and virus-containing fluids showing no hemagglutinating activity (a titer in HA test 1:0).


[Virion precipitation reaction based on determination of reverse transcriptase activity: Method of study of membrane antigens of oncornaviruses]. A method for the study of the envelope antigens of oncornaviruses of C, B, and D types by the virion precipitation test (VPT) based on the measurement of the amount of precipitated virus by its reverse transcriptase activity is described. The method is immunologically specific for titration of antibody to the envelope antigens of oncornaviruses. By means of the VPT it is possible to identify oncornaviruses, to study antigenic relationships between them and to detect some or other antigens in virion coat.


[Treatment of burned children--current therapeutic principles (author's transl)]. This paper deals with the working plan of immediate care, parenteral nutrition and surgery in burned children according to experience gained in the treatment of these children at the specialist Burns Unit of the Department of Dermatology (I) of the University of Vienna. Features peculiar to this age group lie in the appropriate recommendations for shock therapy and prophylaxis as well as parenteral nutrition. The guidelines for surgical treatment of burns are basically similar in adults and children.


[Serum, cord blood and amniotic fluid concentrations of beta2-microglobulin in patients with normal and complicated pregnancies (author's transl)]. Serum, cord blood and amniotic fluid beta2-microglobulin contents were measured from normal pregnancies complicated by EPH gestosis, Rh immunisation and pathological serum levels of HPL and alpha1-fetoprotein. We found no changes in high risk pregnancies from normal serum levels. beta2-microglobulin seems to be no parameter in managing complicated pregnancies and fetal growth retardation.


[Evolution of H3 antigen of influenza viruses isolated during 1968-1976]. Influenza viruses type A isolated in 1968--1976 were found to have changes in the content of the antigenic determinant H3. The experiments showed that while in the viruses isolated in 1968--1972 the H3 antigen was dominating, in the A/Port Chalmers/1/73 virus and some viruses isolated in 1975--1976 this antigen became more and more minor. A correlation was observed between the content of H3 antigen in viruses and the capacity of anti-H3 antiserum to inhibit the infectious activity of viruses. The prepared monospecific serum to H3 antigen contained no antibody to the other two antigenic determinants of virus or to neuraminidase and host cell antigen and was completely free from inhibitors. The serum could be used in HI, CFT, and immunodiffusion tests for the analysis of the antigenic composition of newly isolated influenza viruses.


The anaphylatoxic peptide C3a of guinea pig complement. I. Purification, physicochemical and antigenetic properties. Highly purified guinea pig C3a was obtained after specific cleavage of isolated C3 by the alternative pathway enzyme VF-B in a one step procedure. It turned out to be a low molecular weight peptide with basic character (M.W. 9500; isoelectric point above 9.4). C3a represents an antigenetic determinant of its own in the native C3 molecule, different from the B determinant. Guinea pig C3a resistant to 100 degrees C for 10 minutes. Its smooth muscle contracting activity can be destroyed by trypsin and carboxypeptidase B. These findings indicate that guinea pig C3a is quite similar to human C3a.


[Antigenic properties of influenza virus type A inactivated by ultraviolet irradiation]. The effect of ultraviolet irradiation (UVI) on influenza A virus was studied. UVI of influenza A virus purified by adsorption chromatography on porous glass (PG) was found to result in irreversible inactivation of virus. The rate of inactivation directly depended upon the degree of virus purification. A reduction in the neuraminidase, hemagglutinating and antigenic activity of the virus occurred after a considerably longer UVI (over 7--10 min) than that required for inactivation of the purified virus (1--2 min) with the regimen of inactivation used. No changes in specificity of hemagglutinin and neuraminidase antigens after UVI were observed. The immunogenic activity of hemagglutinin and neuraminidase of the experimental lots of influenza vaccine purified on PG but inactivated by different means (UVI or formalin) was similar.


Antigenic difference between serum amyloid protein SSA and its low molecular weight derivative SAAL revealed by an anti-amyloid A antiserum at different temperatures. Serum amyloid protein SAA and its low molecular weight derivate SAAL have been compared in immunodiffusion with an antiserum to amyloid A at different temperatures. At room temperature or at 37 degree C SAAL and SAA did precipitate with anti-AA forming a line of identity. At 4 degrees C, however, only SAAL did react with anti AA. Experiments are described which show that the SAA-derivative SAAL has AA-related antigenic determinants exposed whereas these determinants are hidden in the parent SAA and are only exhibited as result of an unknown temperature-dependent process. Therefore, SAAL can also be distinguished from SAA by the availability of AA-related antigenic determinants for anti-AA antibodies at 4 degrees C.


[Quantitative analysis of the peripheral arterial blood pressure curve in patients with peripheral obstructive cardiomyopathy after premature beats (author's transl)]. Changes of the brachial artery pressure curves after mechanically released extrasystoles were investigated in 20 patients suffering from hypertrophic obstructive cardiomyopathy. Diagnosis was confirmed by heart catheterisation and laevocardiography. At the average, the postextrasystolic beat showed a more pronounced reduction of the pressure at the systolic dip and the second systolic peak (19.7 +/- 14.2 and 17.2 +/- 13.8) than at the first systolic peak and the incisure due to the aortic valve closure (8.4 +/- 10.5 and 12.8 +/- 9.9). The diastolic pressure decreased of about 11 +/- 4.9%.--The ejection time of the postextrasystolic beat increased of about 0.029 sec (at rest 0.335 +/- 0.047 sec). Compared to the presystolic beats these changes were significant.


Ultrastructure of Babesia major vermicules from the tick Haemaphysalis punctata as demonstrated by negative staining. The ultrastructure of Babesia major vermicules was studied in samples derived from the haemolymph of Haemaphysalis punctata adults and negatively stained with phosphotungstic acid. Most of the organelles observed were typical of those found in apicomplexan parasites. These were the apical complex with the polar ring and the ribs, micronemes and subpellicular microtubules. The number of ribs was 27 or 28. The outer membrane of the pellicle was composed of a large number of fibrils running along the length of the parasite. The inner membrane had large numbers of irregularly scattered holes. A cytoplasmic organelle similar to the granular body described in Theileria annulata ookinetes was seen for the first time in a B. major vermicule.


[A contribution to the early diagnosis and differential diagnosis of bladder neoplasms by means of immunological methods]. According to the present examinations it is pretty probable that already in early histological forms of the carcinoma of the urinary bladder the EM-test is able to indicate immunologically malignity, i.e. that the papillary non-infiltrating carcinoma of the transitional cell as well as the carcinoma in situ of the urinary bladder (23) also immunologically behave like tumors of the bladder. In differential-diagnostic questions concerning the organ localisation of the primary tumor the EM-test seems to give valuable references. Histologically not unequivocally malignant tumors of the bladder with positive results in the EM-test should be submitted to an exacter examination and control.


[Destruction of the colon due to a wrong enema (author's transl)]. By mistake an enema consisting of 10% potash lye was administered to a patient. A resection of the colon and parts of the rectum and the small intestine had to be performed.


[Comparison of methods for the quantitative detection of moulds in foods. I. Communication: selective staining procedures for the directmicroscopic mould count (author's transl)]. The most important proposed direct microscopic method for the detection of moulds were critically compared in 9 different nonfluid foods, of which 7 were naturally and 2 were artifically moulded.--Neither the Rot fragment test, nor the Howard Mould count or the NaOH treatment method proposed by Mossel (1975) were satisfying with non-fluid foods.--A significant improvement of the direct microscopic detection in the Breed-smear could be achieved by selective product specific staining of the fungi elements.--For low protein foods, a modified Pianese staining, and for low polysaccharide foods the Perjod-Schiff reaction proved to be appropriate and easy to carry out.--The slides of the selectively stained Breed-smears also allow a microscopic examination with high magnifications, so that a differenciation of fungus spores and hyphaes is possible.--Fungus spores, yeast cells and hyphal fragments can be counted by the method of Seck (1976). Hyphal fragments can also be recorded according to the prescription of the Howard Mould Count method.


A receptor-immunoassay for the determination of the specificity of anti-HCG-beta sera. In the receptor-immunoassay, the binding of anti-HCG-beta sera to 125I-HCG and 125I-HLH is measured in the presence of bovine corpus luteum "receptor". Anti-sera specific for HCG show little binding with 125I-HLH. The receptor-immunoassay permits an evaluation of specificity, affinity and the ability of anti-HCG-beta sera to compete with the "receptor" for binding to 125I-HCG.


The use of proteolytic enzyme inhibitor (Trasylol) in radioreceptor assay of TSH-its application to measuring thyroid stimulating immunoglobulins (TSI) in thyroid diseases. In order to estimate thyroid stimulating immunoglobulins (TSI) in serum, a stable, reproducible and sensitive radioreceptor assay (RRA) capable of detecting 100 micromicron of thyroid stimulating hormone (TSH) has been developed using a proteolytic enzyme inhibitor (Trasylol), partially purified human TSH and particulate fractions of human thyroid homogenate. The binding of 125-I-labelled TSH to the crude thyroid membranes was significantly increased from 2-3% to 15-20% in the presence of Trasylol (2000 KIU per tube). Further investigations suggested that Trasylol might inhibit the aggregation of 125I-labelled TSH during incubation with these membranes. With this assay system, the serum immunoglobulins from a great majority of untreated patients with Graves' disease were shown to inhibit the binding of 125I-labelled TSH to those membranes more markedly than those from control subjects. Therefore, this RRA for TSH was considered to provide a sensitive and stable method for detecting TSI.


Fluorescence microscopic demonstration of rat mast cells stained with acid dyes. The amphoteric acid dyes acid fuchsin, aniline blue WS, azocarmine G, fast green FCF, light green SF and the wholly acid dye thiazine red R were used for fluorochromy of mast cells in sections of formalin or alcohol-formalin fixed rat tongues. By ordinary light the mast cell granules were barely visible. By UV or blue light exitation, however, a selective, secondary fluorescence of varying intensity and contrast against the tissue background manifested itself. By thin layer chromatography each dye revealed 3--7 components. Except for aniline blue WS, the main component(s) of each dye conferred to the granules the same fluorescence as the corresponding whole dye. These results of fluorochromy, together with the findings of methylation and deamination experiments, allowed the assumption that the anionic groups of the dyes were bound to unoccupied basic groups of the mast cell granules.


The mechanism of histamine release induced by the ionophore X537A from isolated rat mast cells. I. Significance of monovalent cations, calcium, metabolic energy and temperature. Histamine release induced by X537A from isolated rat mast cells was dependent on the presence of sodium or potassium but not on calcium in the incubation medium. The rate of release was faster in potassium than in sodium, but the final release was the same after prolonged incubation. Extracellular calcium as well as metabolic inhibitors depressed the rate or release induced by X537A. Pretreatment of mast cells with either EDTA or the ionophore A23187 in the absence of extracellular calcium did not influence subsequent release induced by X537A. The findings of release at 45 degrees C and lack of release at 0 degrees C distinguish the mechanism of action of X537A from calcium- energy-dependent releasing agents like compound 48/80 and A23187 on the one hand and the simple lytic action of decylamine on the other.


Fulminant hepatic failure associated with methyldopa. A patient with fatal submassive hepatic necrosis after methyldopa is described. Patient had positive L.E. cell preparation. The literature and the two previous cases of submassive hepatic necrosis were briefly reviewed. Methyldopa occasionally produces severe hepatitis, chronic active and rarely submassive necrosis.


Evidence that e-antigen is not transmitted with hepatitis B infection. The correlation between transmission of e-antigen (e-Ag) and hepatitis B antigen (HBsAg) was investigated in primary and secondary cases of type B hepatitis occurring in 15 families. The e-Ag was not consistently transmitted in the familial environment, as were the d and y subtypes of HBsAg, but occurred in erratic fashion among genetically and epidemiologically related cases. It is concluded that e-Ag is probably the non-transmissible product of a specific individual response to hepatitis B infection.


Basophil histamine release by RNA, DNA and aggregated IgG examined in rheumatoid arthritis and systemic lupus erythematosus. Results compared with basophil counts and antinuclear antibodies. Basophils from patients with rheumatoid arthritis (RA) respond to RNA, DNA and immune complexes (aggregated IgG) with histamine release. The RNA response was well correlated to the clinical activity of the disease, since histamine liberation was found in all patients with severe activity, whereas no liberation was observed in patients with moderate or quiescent activity. A less significant correlation was obtained with DNA and aggregated IgG. In contrast, no response was obtained with RNA, DNA and aggregated IgG in patients with systemic lupus erythematosus (SLE) or in controls. In the RA and the SLE groups no significant correlation was found between the response of RNA, DNA and aggregated IgG and the serum titres of anti-DNA and antinuclear antibodies. No difference in basophil cell count in peripheral blood and basophil histamine content was found between RA, SLE and controls. Our results point to an involvement of an autoimmune type I reaction in the pathogenesis of RA directed against the nuclear components RNA and DNA and against immune complexes.


The role of the anaesthetist in chronic pain management. The role of the anaesthetist in the continuing care of patients suffering from chronic pain has been discussed. Many of the techniques, both invasive and non-invasive, which are currently available for the treatment of chronic pain have been reviewed.


Comparative clinical evaluation of two salts of quinidine using 24-hour Holter monitor recordings. In 13 patients admitted to a coronary care unit, antiarrhythmic efficacy and safety of quinidine gluconate in a nonmatrix formulation were compared to placebo and quinidine sulfate. Both quinidine preparations were effective in reducing the number and severity of ventricular and supraventricular extrasystoles when compared to placebo. Except for a few cases in which quinidine gluconate was significantly more effective, both quinidine preparations appear to have similar clinical antiarrhythmic efficacy and duration of action. A 24-hour Holter ECG monitoring device and electrocardioscanner were utilized in this research. No major unexpected adverse effects were observed.


Recent advances in antitumor antibiotics. An effective treatment schedule with bleomycin in combination with mitomycin and a new effective area in treatment with neocarzinostatin was introduced. Studies on more useful derivatives or analogues of bleomycin and anthracycline antitumor antibiotics were described. Bleomycin PEP thus selected may become a useful agent. Aclacinomycin and various other anthracycline glycosides were isolated from beer fermentation and tested. Future progress in microbiol secondary metabolites useful in cancer treatment was discussed.


[Selective action of novobiocin on Act. levoris, the producer of levorin and levoristatin]. The effect of sodium novobiocin on Act. levoris, strain LIA 0868 producing levorin and levoristatin was studied. High lethal effect of the antibiotic on Act. levoris was found. The effect increased with a rise in the antibiotic concentration in the agar from 2 to 6 lambda/ml. The inhibitory effect of novobiocin on Act, levoris was evident from a marked increase in the number of morphologically changed colonies with a low level of levorin production. The selective effect of novobiocin on the organism producing levorin and levoristatin was evident from selection of variants with high levels of levoristatin production on media containing novobiocin.


Selection of treatment in the management of thyrotoxicosis in childhood and adolescence. The management of 105 patients between the ages of three and 18 years, 83 females and 22 males, with thyrotoxicosis was reviewed retrospectively (1952-1976) with the intent of identifying criteria that would help predict response to therapy with antithyroid drugs and thereby permit earlier selection of alternative treatment. All patients were initially treated with antithyroid drugs. Twenty-six per cent (27) achieved remission with thioamides, 68% (72) underwent subtotal thyroidectomy with three patients requiring subsequent therapy with radioiodine, 6% (6) received radioiodine with one patient subsequently requiring subtotal thyroidectomy. Failure of remission after thioamide therapy was related to drug toxicity, persistent disease, noncompliance and recurrence after an initial remission. During the last decade there was earlier selection of subtotal thyroidectomy based on prior experience. The most significant discriminants were sex, age, and regression of thyromegaly. Ninety-one per cent of the males, 89% of children over 11 years of age and all patients who had no regression of their thyromegaly after a sustained period of control of their thyrotoxicosis by thioamide therapy received subtotal thyroidectomy or radioiodine therapy for control of their thyrotoxicosis. Recognition of these factors at the time of diagnosis should permit earlier selection of the most suitable treatment and expedite patient care. Subtotal thyroidectomy has a low morbidity and is effective treatment for thyrotoxicosis in adolescence and childhood.