Heparin-induced decrease in circulating antithrombin-III. Plasma-antithrombin-III (AT-III) concentrations were measured throughout therapy in 24 patients receiving continuous intravenous heparin infusion and in 2 patients treated with repeated intravenous heparin injections. In all patients, including 1 with congenital AT-III deficiency, heparin therapy was associated with a considerable progressive reduction in AT-III-binding capacity and antigenic protein. The net individual decrease in plasma-AT-III was 0-31 +/- 0-05 units/ml (normal plasma-AT-III was 1-00 units/ml) or 9-5 +/- 2-0 mg/dl and the decrease was independent of initial concentration. Plasma-AT-III returned to normal two to three days after heparin was stopped. There was no decrease in plasma-AT-III after a single dose of intravenous heparin. When present in blood for long periods heparin significantly reduced AT-III, the proteinase inhibitor that is responsible for the anticoagulant effect of this drug. The finding is very relevant to the interpretation of clinical data in patients treated with heparin and suggests that AT-III depletion may underly the thromboembolic complications sometimes encountered during heparin therapy.


Polymorphic hydroxylation of Debrisoquine in man. Debrisoquine and its primary metabolite, 4-hydroxydebrisoquine, were measured in the urine of 94 volunteers after a single oral dose of 10 mg debrisoquine. The ratio between excreted debrisoquine and its metabolite was bimorphically distributed in the study population. Family studies supported the view that alicyclic 4-hydroxylation of debrisoquine is controlled by a single autosomal gene and that a defect in this metabolic step is caused by a recessive allele.


Sperm granuloma and reversibility of vasectomy. Ninety-two consecutive patients who had undergone bilateral vasectomy 1 month to 28 years earlier were studied at the time of vasectomy reversal for sperm output, dilatation of the vas-deferens lumen, and sperm granuloma. Thirty-nine men had unilateral or bilateral sperm granuloma. The presence of of a sperm granuloma virtually assured normal sperm in the vas fluid no matter how long ago the vasectomy was performed. In the absence of a sperm granuloma, the interval since vasectomy had an important influence on the quality of vas fluid. The presence of a sperm granuloma was associated with significantly less dilatation of vas-deferens lumen at the testicular end. The site of the vasectomy and the amount of vas deferens removed did not influence sperm quality. A sperm granuloma on only one side resulted in normal spermatozoa in the vas fluid on that side, whereas the side without the sperm granuloma had abnormal spermatozoa or no spermatozoa in the vas fluid. It is concluded that when sperm granuloma follows vasectomy it vents the high pressure otherwise created by vasectomy and prevents disruption of sperm output in the vas fluid.


Weakness in myotonic syndromes.

Weakness in myotonic syndromes. Muscle weakness occurs in a number of myotonic syndromes, including those in which muscle bulk is preserved. The possible causes of muscle weakness may be considered in terms of the different stages of the electromechanical activation process and defects in the contractile machinery. In individual myotonic disorders the ability to identify the origin of the muscle weakness (whether neurogenic or myogenic) and the functional level at which the defect occurs would assist the choice of rational treatment.


Serum-ferritin in diagnosis of haemochromatosis. A study of 43 families. 242 members of 43 families with idiopathic haemochromatosis were investigated for increased body-iron stores in order to assess the value of serum-ferritin determination as a screening-test to detect preclinical disease. The serum-iron concentration was elevated in only 76% of relatives with increased iron stores, and it was also elevated in 10% of relatives with normal iron stores. The percentage saturation of transferrin was elevated in all relatives with increased iron stores but also in 33% of relatives with normal iron stores. Serum-ferritin was raised in 98% of relatives with increased iron stores and in only 3 (1.8%) of those with normal iron stores. These 3 subjects consumed alcohol in excess of 100 g ethanol per day, and their serum-ferritin levels fluctuated widely. Increased iron stores were reflected in increased serum-ferritin concentrations in subjects as young as 14 years in whom the liver-iron concentration was twice the normal upper limit and before there was any evidence of architectural damage to the liver. The serum-ferritin concentration is a useful non-invasive screening test for precirrhotic haemochromatosis.


Prostaglandins and breast cancer.

Prostaglandins and breast cancer. Malignant human breast tumours produced more prostaglandin-like material during homogenisation than did benign tumours or normal breast tissue. Greatest synthesis in vitro occurred with tumours associated with bone metastases, and the highest "basal" amounts tended to occur in tumours showing spread histologically. It is suggested that prostaglandins may play a part in tumour spread and growth in bone and that drugs which inhibit prostaglandin synthesis may be valuable therapeutic agents in cancer.


Correlation between leucocyte-migration inhibition by breast-cancer antigens, mammographic findings, and other breast-cancer risk factors. A double-blind study of 62 normal women was carried out to determine if there was any correlation between the mean score of six weekly leucocyte-migration-inhibition tests (L.M.T.) against breast-cancer antigen, xeromammographic findings, and the presence of other epidemiological risk factors for the development of breast cancer. 36 women had abnormal mammograms, and 11 of these 26 (30.5%) had a mean L.M.T. score greater than or equal to 10%. 26 women had normal mammograms, and only 1 of these (3.8%) had a mean value greater than or equal to 10%. This difference was significant (p less than 0.02). A family history of breast cancer and/or previous surgery for cystic and proliferative disease also correlated significantly with L.M.T. score (p less than 0.05); the combined presence of epidemiological risk factors and an abnormal mammogram correlated most strongly with L.M.T. score (p less than 0.01). Although the results may indicate an "immunological risk factor" towards the development of breast cancer, the biological relevance of this observation remains to be proven.


Vitamin-D metabolism in nephrotic syndrome. Plasma concentrations of 25-hydroxy-cholecalciferol (25-OHD3) and  vitamin-D-binding globulin (V.D.B.G.) were significantly reduced in ten nephrotic subjects. V.D.B.G., which is undetectable in normal urine, was present in substantial amounts in the urine of each nephrotic subject. Administration of 3H-labelled cholecalciferol to three subjects resulted in the rapid appearance of the labelled vitamin in the urine, mainly as the 25-hydroxylated metabolite bound to V.D.B.G. in amounts which could largely account for the low plasma-25-OHD3. The plasma half-life of 25-OHD3 was substantially reduced in the nephrotic syndrome.


Death from acute pancreatitis. M.R.C. multicentre trial of glucagon and aprotinin. The influence of glucagon and aprotinin ('Trasylol') on the death-rate of acute pancreatitis has been studied in a randomised double-blind multicentre trial. The death-rate in 257 patients was 11%. In the doses used neither drug was found to diminish the risk of death.


Alteration in fibrinolytic capacity after operation. The fibrinolytic response to 20 min of forearm venous occlusion was studied in patients undergoing major and minor operations. Fibrinolytic capacity, which is defined as the increase in fibrinolytic activity resulting from a period of venous occlusion, was significantly reduced on the first postoperative day after major operations, but not after minor operations. Since venous occlusion results in the release of plasminogen activator from the vascular endothelium into the blood, these findings suggest that the reduction in the level of spontaneous fibrinolytic activity after major operations is the result either of exhaustion of the vascular endothelium of plasminogen activator or defective synthesis and release of this enzyme from the endothelium.


Isolation of Herpes simplex virus from human trigeminal ganglia, including ganglia from one patient with multiple sclerosis. Herpes-simplex virus (H.S.V.) was isolated from 18 of 39 trigeminal ganglia (T.G.) obtained within 12 h of death. The virus was isolated from ten persons who had died of trauma, from one case of lymphoma, and from one case of multiple sclerosis. In the cadaver with histologically confirmed multiple sclerosis, large bilateral areas of demyelination were present near the points of entry of the nerve root, and the possibility that H.S.V. migration to the root entry zone caused demyelination cannot be excluded.


Micro-ELISA for detecting and assaying snake venom and venom-antibody. Enzyme-linked immunosorbent assay (ELISA) can detect venom levels down to 1-5 ng/ml. The assay is specific; no cross-reaction of clinical importance was found in a range of 14 different types of venom. Both venom and venom-antibody levels were monitored in mice. Specific antibody was detected in human serum more than 2 years after an accidental bite by Echis carinatus. ELISA should clarify many basic problems of envenoming in man.


One hundred kidney transplants in the Belfast city hospital. 100 kidney transplants have been carried out on 91 patients (7 had 2 transplants and 2 had 3 transplants). 4 transplants were from living related donors and 96 from cadavers. 76 patients survive, all but one with functioning kidneys. The cumulative survival of patients was 82% at 2 years and 80-7% at 5 years. 8 patients died with functioning grafts, and 2 of the other deaths took place more than 3 months after removal of a rejected kidney and resumption of haemodialysis. There were no deaths from sepsis in the first 60 days after transplantation. The cumulative survival of all grafts was 82-1% at 2 and 5 years. The cumulative survival of first grafts was 82-5% at 2 and 5 years.


Effect of antilyphocyte-globulin potency on survival of cadaver renal transplants. Prospective randomised double-blind trial. 71 recipients of cadaver primary and secondary renal transplants were investigated in a prospective randomised double-blind study. Patients were given one of two rabbit antilymphocyte globulin (A.L.G.) preparations made by similar techniques but differing in potency as measured by skin-graft prolongation in rhesus monkeys. Patient selection and management were otherwise similar. A statistically significant difference (P less than 0-05) in graft survival (78% vs. 42%) developed between the two groups at a mean follow-up of 18-4 months and patient entry into the study was terminated. After a 3-5 year interval from the start of the trial the double-blind code was broken. It was found that the high-potency-A.L.G. group had better graft survival and fewer rejection episodes (P less than 0-05) than the moderate-potency group. The results suggest that preclinical testing of A.L.G. by the primate skin graft test can be a valid indicator of the potential efficacy of an A.L.G. preparation in renal-transplant recipients. It is suggested that quality-control standards may improve the clinical results of A.L.G. therapy.


Grey-scale ultrasonography of portal vein. The state of the extrahepatic portal venous system was correctly assessed by grey-scale ultrasonography in twenty-one patients with extrahepatic portal-vein obstruction and the results agreed with those obtained by portal venography. In twenty-two age-matched controls a patent portal vein was displayed. The diameter of the portal vein on the ultrasound scan was significantly less in the twenty-two controls than in eighteen patients with chronic liver disease. Grey-scale ultrasonography is a reliable, inexpensive, and non-invasive method for diagnosing extrahepatic portal-vein obstruction.


Urinary oxalate on a high-oxalate diet as a clinical test of malabsorption. 100 g of spinach a day was added to the hospital diet of fifty-four patients with suspected malabsorption. Hyperoxaluria was found in thirty-eight patients; all of them had steatorrhoea. No patient with steatorrhoea had a urinary oxalate excretion of less than 40 mg a day. Ten other patients had hyperoxaluria, but the faecal fat determinations were regarded as unreliable in almost all and malabsorption could not be confirmed. It is suggested that in clinical practice determination of urinary oxalate after an oral load of oxalate could replace faecal fat determination in most patients with suspected malabsorption.


Depletion and disruption of dietary fibre. Effects on satiety, plasma-glucose, and serum-insulin. Ten normal subjects ingested test meals based on apples, each containing 60 g available carbohydrate. Fibre-free juice could be consumed eleven times faster than intact apples and four times faster than fibre-disrupted purée. Satiety was assessed numerically. With the rate of ingestion equalised, juice was significantly less satisfying than purée, and purée than apples. Plasma-glucose rose to similar levels after all three meals. However, there was a striking rebound fall after juice, and to a lesser extent after purée, which was not seen after apples. Serum-insulin rose to higher levels after juice and purée than after apples. The removal of fibre from food, and also its physical disruption, can result in faster and easier ingestion, decreased satiety, and disturbed glucose homoeostasis which is probably due to inappropriate insulin release. These effects favour overnutrition and, if often repeated, might lead to diabetes mellitus.


Corynebacterium bovis as a cause of human disease. Corynebacterium bovis is a gram-positive rod which can cause bovine mastitis and rancidity in cream. On only one occasion has this organism been reported to cause human disease. Six further cases are described in which infections were caused by C. bovis. In two patients the nervous system was involved; two patients had bacterial endocarditis; one had chronic otitis media; and one had a persistent leg ulcer. Five patients recovered completely from the infection; the other died from endocarditis.


Combined electrophysiological technique for assessment of the cellular basis of early ventricular arrhythmias. A new technique has been used in dogs to make combined measurements in vivo of conduction delay, action potentials, and epicardial ST-segment during myocardial ischaemia. These measurements should provide new information about ionic and metabolic cellular changes relating to the onset of ventricular arrhythmias.


Unexplained acute fever after a hot bath. An outbreak of repeated chills, fever, respiratory-tract symptoms, and muscle pain, starting 4 h after a hot bath, involved 56 persons, nearly all of whom lived in an area supplied with water from the same source. The symptoms lasted for 6--15 h. A polymorphonuclear leucocytosis was a feature of the illness. The causal agent, which has not yet been identified, was found to enter the body by inhalation. Bacteriological and chemical studies and investigation of the water for endotoxins and algae revealed nothing unusual.


Is dextran 70 a lymphocyte mitogen?

Is dextran 70 a lymphocyte mitogen? Dextran 70 ('Lomodex') roduced significant increases in thymidine incorporation in a modified whole-blood method of investigating lymphocyte blastogenesis. This blastogenesis occurred at molar concentrations of 7 X 10(-6) and 7  10(-5). At 7 X 10(-7) mol/l dextran alone did not significantly increase thymidine incorporation; however, when this concentration of dextran was added simultaneously with phytohaemagglutinin there was a significant increase in incorporation. Conversely when dextran was added before P.H.A., thymidine incorporation was decreased. These variable effects indicate that dextran 70 may be a B-cell mitogen. Dextran 70 is widely used and these effects on lymphocyte blastogenesis may be clinically relevant.


Head injuries in Scottish hospitals. Scottish Head Injury Management Study. A study was designed to discover how patients with a head injury are managed in Scotland. Preliminary findings based on retrospective examination of hospital records describe and compare the characteristics of 3035 patients arriving at accident and emergency departments, 1181 admitted to primary surgical wards, and 424 treated in neurosurgical units in Scotland, excluding the Lothians. These data are being used for further studies to define the needs of these patients and to explore alternative management policies which could make better use of existing health-service resources.


Enzyme abnormalities in the porphyrias.

Enzyme abnormalities in the porphyrias. Evidence is presented that each of the porphyrias represents a different inborn error of metabolism in haem biosynthesis. Control of the pathway takes place by feedback repression and inhibition by haem of delta-aminolaevulinic-acid synthase. It is suggested that insituations where the activity of this enzyme is derepressed, prophobilinogen deaminase represents a secondary control step.


On the inappropriate in hypertension research. The concept of the "inappropriate" has a well-defined and easily comprehended meaning when applied to tumour secretion of antidiuretic hormone (A.D.H., vasopressin). When applied to high A.D.H. in other situations such as nephrotic syndrome, congestive cardiac failure, or cirrhosis, the use of the term "inappropriate secretion" simply reflects the fact that an easily measured controlling factor (plasma tonicity) is being overridden by a less easily measured one (effective extracellular volume). Similarly, sodium excretion in hypertension is said to be inappropriately low for the raised renal perfusion pressure: in this case inappropriateness results from the antinatriuretic effect of a minor degree of sodium depletion produced by pressure natriuresis. A similar objection can be made to the application of the term to the relations between renin or angiotensin-II concentrations and blood-pressure in some forms of hypertension. Since inappropriateness merely reflects the position and predilections of the observer, the widespread use of the term should be abandoned.


Mortality among oral-contraceptive users. Royal College of General Practitioners' Oral Contraception Study. In a large prospective study carried out in the United Kingdom, the death-rate from diseases of the circulatory system in women who had used oral contraceptives was five times that of controls who had never used them; and the death-rate in those who had taken the pill continuously for 5 years or more was ten times that of the controls. The excess deaths in oral-contraceptive users were due to a wide range of vascular conditions. The total mortality-rate in women who had ever used the pill was increased by 40%, and this was due to an increase in deaths from circulatory diseases of 1 per 5000 ever-users per year. The excess was substantially greater than the death-rate from complications of pregnancy in the controls, and was double the death-rate from accidents. The excess mortality-rate increased with age, cigarette smoking, and duration of oral contraceptive use.


Mortality among women participating in the Oxford/Family Planning Association contraceptive study. 43 deaths are known to have occurred among the 17 032 participants in the Oxford/Family Planning Association contraceptive study up to the end of April, 1977. 9 deaths from cardiovascular causes have been observed among the women in the oral-contraceptive entry group (49 681 woman-years of observation) while no such deaths have been observed among the women who entered the study while using a diaphragm or an intrauterine device (39 146 woman-years of observation). These findings are consistent with the results presented in the accompanying report from the Royal College of General Practitioners Oral Contraception Study.


Haemoglobin A1: An indicator of the metabolic control of diabetic patients. The level of the minor glycosylated haemoglobins (HbA1) in ambulatory diabetic patients correlated closely with their physicians' ratings of the degree of control and their fasting plasma-glucose levels. In patients admitted to hospital for more detailed study, HbA1 correlated significantly with the mean fasting glucose, mean daily glucose, and highest daily glucose values. HbA1 measurement is a simple, rapid, and objective procedure to assess diabetic control and may serve both as a screening test for uncontrolled diabetes and as an indicator of the efficacy of various therapeutic regimens.


Iron absorption in iron-loading anaemias: Effect of subcutaneous desferrioxamine infusions. Absorption of 59Fe ferrous sulphate was measured in patients with a variety of iron-loading anaemias both before and during subcutaneous infusions of desferrioxamine. The infusions were associated with a reduction in absorption (P less than 0-025). This effect was not altered by saturation with ascorbic acid.


Vitamin D and human lactation.

Vitamin D and human lactation. Circulating serum-25-hydroxyvitamin-D concentration was measured in recently delivered mothers who were breast-feeding and in those who were not. 4-6 weeks' lactation produced no significant change. Basal and 4-6-week values in the breast-feeding group were significantly higher than in those who were not breast-feeding. There was no evidence that lactation was an indication for supplementary vitamin D.


Complexed IgE in atopy.

Complexed IgE in atopy. Evidence of circulating high-molecular-weight forms of IgE was found in 16 patients with hayfever and/or atopic eczema. This finding of what appears  to be complexed IgE in the serum of atopic patients may help to elucidate the aetiology of atopy.


Failure of syngeneic bone-marrow graft without preconditioning in post-hepatitis marrow aplasia. A patient with post-hepatitis bone-marrow aplasia had bone-marrow transplants from an identical twin. The first two transplants were only partially and temporarily successful, but after cyclophosphamide treatment bone-marrow function was resotred.


Changing pattern of respiratory distress in newborn. A retrospective study of respiratory distress in a special-care baby unit revealed that transient tachypnoea of the newborn (T.T.N.B.) lasting more than 24 h was as common as the respiratory distress syndrome (R.D.S.). Delivery by caesarean section was associated with T.T.N.B. and the results of measurement of crying vital capacity in caesarean section and vaginally delivered babies indicate that babies delivered by caesarean section are at a considerable disadvantage during the first few days of life.


English law relating to experimentation on children. Children who are capable of understanding and coming to a decision on what is involved in a non-therapeutic experimental procedure are as able as adults to give a legally effective consent to such procedures. There is no "age of consent" in this context, for capacity to consent depends on the child's intellectual capability and the complexity of the procedure in question. Where a child is incapable of consenting on his own behalf a parent may give a legally effective consent to non-therapeutic procedures which are in the public interest and are not in any significant way detrimental to the child's interests. The procedure need not be for the benefit of the child.


Treatment of diabetes with guar gum. Reduction of urinary glucose loss in diabetics. When nine diabetic patients supplemented either their normal home diets (four patients) or metabolic ward diets (five patients) with 25 g guar gum daily for 5 or 7 days their mean urinary glucose excretion fell by 46% (P less than 0-05) and 54% (P less than 0-01), respectively. Gel-forming,, unabsorbable carbohydrate may therefore be a useful adjunct to anti-diabetic therapy, irrespective of the type of treatment or insulin dosage used.


Purified antigen radioimmunoassay in serological diagnosis of schistosomiasis mansoni. A radioimmunoassay has been developed for detecting human schistosomiasis with a highly purified Schistosoma mansoni egg antigen labelled with iodine-125. The antigen, major serologic antigen 1 (M.S.A.1), has striking immunochemical and species specificity and appears to be the principal antigen responsible for the granulomatous response to S. mansoni eggs. This 125I-antigen was tested with 5 microliter of patient serum as a potential serodiagnostic test for schistosomiasis. 92 control sera from uninfected St. Vincentian patients were seronegative. In studies on 135 lightly infected St. Lucians the 5 microliter serum 125I-M.S.A.1 serodiagnostic test was more sensitive than any tests available at the Center for Disease Control, with 64% of infected children, 83% of adolescents, and 98% of adults being positive. 49 heavily infected Kenyans of all age-groups were uniformly (100%) seropositive. Finally, a semiquantitative version of the 125I-M.S.A.1 radioimmunoassay that uses 0-5 microliter of patient sera demonstrated quantitatively significant differences among age-watched and intensity-watched groups of patients with S. mansoni, S. haematobium, and S. japonicum infections.


Plasma renin and "prorenin" in essential hypertension during sodium depletion, beta-blockade, and reduced arterial pressure. An inactive form of renin is activated by incubating human plasma at -5 degrees C. The relative proportions of active renin and this cryoactivatable "prorenin" in plasmas of untreated hypertensive patients varied widely. However, prorenin increased in parallel with active renin after sodium deprivation or diuretic therapy in 36 patients; the increases were similar whether or not blood-pressure fell. In contrast, propranolol administration in 22 patients lowered active renin in all, but it increased prorenin by 98% in 15 in whom systolic pressure fell. In the other 7 blood-pressure did not change, and beta-blockade produced a fall in total renin (active renin plus prorenin) while prorenin was unchanged. For all 22 there was an inverse relationship between propranolol-induced changes in plasma-prorenin and systolic pressure (r=-0-77, P less than 0-001). The fraction of active plasma-renin fell during propranolol administration from 43% to 18%, regardless of the blood-pressure response. Clonidine produced similar changes in 10 patients. Thus, sodium depletion stimulates total renin release, while propranolol and clonidine produce divergent responses of active renin and prorenin, the changes in prorenin depending on the changes induced in blood-pressure. These observations suggest that propranolol may block intrarenal conversion of prorenin to active renin while also suppressing total renin release. But the latter effect may be offset by concurrent baroreceptor-mediated release of total renin (mostly prorenin) when blood-pressure is lowered.


Is hyperviscosity a treatable component of diabetic microcirculatory disease? Blood viscosity at low shear-rates was significantly higher in sixty-four patients with longstanding diabetes than in sixty-one matched non-diabetic controls. This increase was most striking in patients with either proliferative retinopathy or nephropathy, although it was present to a lesser extent in diabetic patients with evidence of myocardial or peripheral ischaemia. Erythrocyte deformability was lower in the fourteen diabetic patients with the most extensive microangiopathy than in twenty-two diabetics with slight or no complications or in controls. Hyperviscosity and reduced erythrocyte deformability may well be important and potentially treatable factors in the aetiology or progression of microcirculatory disease is diabetes.


Deprenyl in Parkinson's disease.

Deprenyl in Parkinson's disease. In a double-blind crossover trial, (-)-deprenyl, a fast-acting selective monoamine-oxidase-B inhibitor without a "cheese effect", was given to 41 patients with idiopathic Parkinson's disease who were receiving maximum tolerated doses of levodopa either alone or combined with carbidopa ("Sinemet"). In a dose of 10 mg, daily or on alternate days, (-)-deprenyl prolonged the therapeutic effect of levodopa and was effective in mild "on-off" disabilities with end-of-dose akinesia; the majority of patients with nocturnal and early-morning akinesia also improved. No statistically significant improvement occurred in diurnal akinesia, and there was no improvement in patients with severe on-off disabilities with freezing and rapid oscillations ("yo-yo" effect). Levodopa-induced dyskinesias were aggravated in 14 patients. In 5 previously untreated patients, (-)-deprenyl alone gave no benefit, but when it was used with levodopa and carbidopa a mean dosage reduction of 200 mg levodopa daily was possible. Depression, present in 15 patients, was unchanged. (-)-Deprenyl in combination with smaller total daily doses of levodopa and a peripheral decarboxylase inhibitor may prove useful in reducing the frequency and severity of some types of on-off effect with overall benefit comparable to that obtained with larger doses of levodopa.


Association of postmedication hypocortisolism with early first relapse of idiopathic nephrotic syndrome. A 2-hour adrenocorticotrophic-hormone (A.C.T.H.) test was given to 23 children in their first attack of idiopathic nephrotic syndrome, after treatment with prednisone according to the schedule of the International Study of Kidney Disease in Children. The length of the first remission was correlated with the response to the postmedication A.C.T.H. test. In 11 children this response was subnormal, and 10 of them had the first relapse within a year. Of the 7 children who stayed in remission for more than a year, 6 had normal responses. The treatment scheme should be adjusted to prevent postmedication adrenocortical suppression.


Intravenous lignocaine in prevention of deep venous thrombosis after elective hip surgery. Intravenous lignocaine is a possible means of preventing deep venous thrombosis (D.V.T.) after elective hip surgery. In 14 control patients the total incidence of D.V.T. was 78%, with a 57% incidence of thigh-vein thrombosis. In 14 patients treated at random with intravenous lignocaine during the first 6 postoperative days, there were only 2 calf-vein thrombi (14%; P less than 0-005). In a further 14 cases treated consecutively there were 4 unilateral calf-vein thrombi. No thrombi originated in the thigh veins (P less than 0-001). After intravenous lignocaine was stopped the total incidence of D.V.T. in the 28 patients rose to 53% with a 21% incidence of thigh-vein thrombi between the 7th and 14th postoperative days. There was no significant difference in postoperative coagulation and fibrinolytic activity between control and treated patients, and blood loss and transfusion requirements were similar. Immediate or delayed hypersensitivity reactions to lignocaine were not observed. The results support the view that damage to the vessel wall may be the initial event in the formation of a venous thrombus.


Low-dose heparin as a prophylaxis against deep-vein thrombosis after acute stroke. A trial of subcutaneous low-dose heparin in the prevention of deep-vein thrombosis was carried out in elderly patients admitted to hospital after an acute stroke. A statistically significant reduction was observed in deep-vein thrombosis as assessed by isotope leg scanning.


Maternal and infant antibody response to meningococcal vaccination in pregnancy. The antigenic capacity of a mixed vaccine prepared with polysaccharides of meningococcus groups A and C, the placental transfer of antibodies, and the persistence of positive titres in the infant were evaluated in 21 pregnant women and their offspring during an epidemic of meningitis in São Paulo, Brazil; and antibody response was assessed in 29 infants vaccinated at less than 6 months of age. Antibodies were detected by passive haemagglutination; the high titres found and the high frequency of positive results are thought to be due to the use of a more sensitive technique. Increased antibody titres were found in most women, and there was evidence for passive transfer to the newborn, especially with regard to antibody type C. However, passive transfer was irregular, and the presence of antibodies in the mother did not guarantee their presence in the child. Passive transfer lasted for only 2-5 months. Vaccination in children under 6 months of age had poor results; only 1 child seroconverted.


The condom and gonorrhoea.

The condom and gonorrhoea. The use of the condom by male patients attending a clinic specialising in sexually transmitted diseases has been assessed over a period of six months. Condom users were divided into those who used them properly and invariably, and those who did not. In the group studied, correct use of the condom was associated with a significantly lower probability of acquiring gonorrhoea (P less than 0-001) and a significantly higher chance of there being no sexually transmitted disease diagnosed (P less than 0-0005). The diagnosis-rate of non-specific urethritis, however, did not differ among the groups.


Induction and properties of DNP-specific T cells in mice sensitized to DNP-coupled mycobacterium. Splenic T lymphocytes from mice sensitized to 100 microgram of DNP-coupled mycobacterium (DNP-Tbc) showed in vitro proliferative response against DNP- or TNP-conjugated protein antigens. The increased uptake of 3H-thymidine induced by DNP-HSA was partially inhibited by the addition of 10(-4)M DNP-EACA. DNP-AECM-Ficoll did not induce any significant proliferative responses in DNP-Tbc-primed T cell population. However, priming with DNP-Tbc augmented anti-DNP IgG antibody response induced with DNP-Ficoll. The augmentation of IgG response was not due to the presence of DNP-primed B cells or anti-DNP antibody. The results showed that the priming with DNP-Tbc induced DNP-reactive T helper cells which could be triggered with DNP-Ficoll. The possible role of mycobacterium in the induction of hapten-specific T helper cells is discussed.


[Treatment of rhythm disorders of ventricular origin with KO 1173 (Mexiletin) (author's transl)]. In 52 patients, KO 1173 (Mexiletin) administered intravenously and/or orally has been used for the treatment of rhythm disorders of ventricular origin. The disturbances of rhythm studied included ventricular extrasystoles, ventricular tachycardia and by DC-cardioversion abolished ventricular fibrillation. By intravenously administered KO 1173, 31 of the 32 patients had a more than 75% reduction of their ventricular extrasystoles or complete abolition of the arrhythmia. In 5 patients with ventricular tachycardia, rhythm disorder was terminated by administration of a total dose of 125 to 250 mg. When used prophylactically in patients with ventricular fibrillation terminated by electrical means, KO 1173 was successful in 10 of the 11 patients. Oral administration was carried out in a total of 32 patients. In 26 of the 32 patients optimum dosage for maximum beneficial effect appeared to be 200 mg 3 times daily. 6 patients responded unsatisfactory to KO 1173. The intravenous administration of KO 1173 induced side-effects, primarily manifested by central nervous system disturbances, which we have partly attributed to the dosage and the time of injection. No noteworthy side-effects have been reported at the oral administration. In 1 patient complaining of gastric irritation KO 1173 was withdrawn.


On the expressivity of aberration hot spots after treatment with mutagens showing delayed or non-delayed effects. The intrachromosomal distribution patterns of chromatid aberrations induced by agents with delayed effects (as exemplified by ethanol and maleic hydrazide) were compared with those produced by agents with non-delayed effects (as exemplified by fast neutrons, X-rays and bleomycin). Despite nonrandomness of aberration distribution in all cases, the mutagens with nondelayed effects generally showed up with much less pronounced aberration hot spots than the mutagens with delayed effects. From the results obtained it is concluded that hot-spot expressivity is a characteristic "group-specific" feature of the two classes of mutagen and that aberration production during DNA replication (S-phase) by agents with delayed effects strongly favours a very pronounced aberration clustering, which is partly mutagen-specific. Possible causes of these differences with respect to hot-spot expressivity after treatment with mutagens showing non-delayed and delayed effects, respectively, are discussed.


In vitro synthesis of infectious DNA of murine leukaemia virus. DNA synthesised in vitro by purified virions of murine leukaemia virus is infectious. Neither RNA nor protein is required for infectivity. Transfection with reverse trancriptase product shows a single-hit dose response and results in the production of complete, infectious virus.


Myelin encephalitogenic protein fragments in cerebrospinal fluid of persons with multiple sclerosis. With a double-antibody radioimmunoassay performed on unconcentrated cerebrospinal fluid, eight of 14 patients in an acute phase of multiple sclerosis had levels of 3.4 to 15.4 ng per milliliter of the P1 fragment (residues 43-88) of myelin encephalitogenic protein. Encephalitogenic protein-P1 was found only in the acute phase and was present in six of seven persons in the first week of an exacerbation and absent in 29 multiple sclerosis patients who were stable or had a gradually progressive course. Six of 117 controls had detectable cerebrospinal fluid encephalitogenic protein-P1. Only in two of these, one with a recent cerebral infarction and one with diabetic nephropathy who was in coma, were the levels in the range encountered in patients in the acute phase of multiple sclerosis. Although not entirely specific for multiple sclerosis, the presence of material in the cerebrospinal fluid of multiple sclerosis patients cross-reacting with encephalitogenic protein-P1 appears to be a characteristic of acute exacerbations.


Plasma estrogens and pregnancy-associated plasma proteins: a study of their variability in late pregnancy. The plasma concentration of several estrogens (unconjugated estradiol and estriol, total estriol, and estriol sulfate) and of the placental proteins hPL and PAPP-C were measured daily for 8 days in 9 subjects. The steroids showed coefficients of variation ranging from 14 to 21%. The proteins were much less variable (PAPP-C 5% and hPL 6%).


Evaluation of postterm pregnancies with maternal serum placental lactogen and alpha-fetoprotein concentrations. Studies of maternal serum placental lactogen (hPL) levels in 70 women delivering beyond 42 weeks of gestation revealed significantly lower levels of hPL when the offspring had one or more of ten signs of postmaturity or distress. A sequential combination of hPL measurements and intrapartum fetal heart rate monitoring (FHRM) (performed in 61 patients) gave a high degree of prognosis (75% of abnormalities detected, 88% with normal tests having no abnormalities). Considered separately, neither maternal serum hPL levels nor FHRM predicted abnormalities in the offspring to the same high degree. On the other hand, hPL could not be correlated with staining, desquamation, and the presence of meconium in the amniotic fluid at delivery, these criteria being considered separately or in combination. Maternal serum alpha-fetoprotein (AFP) levels during late gestation showed considerable variation and did not permit distinction between pregnancies with or without an abnormality in the offspring.


[Dynamics of the regional metabolic differences in the early development of the sea urchin]. The regional differences in Strongylocentrotus intermedius from the stage of 32 blastomeres till the middlelate gastrula stage were studied by the vital and supravital staining (intensity of oxidative-reductive processes), the incorporation of 3H-leucine (intensity of protein synthesis) and 14C-acrilamide (intensity of free radical processes). Two periods of rapid switches of metabolic intensity correlated within the same embryo were established. The beginning of the first period coincides with the onset of blastula epithelization and that of the second one with the onset of gastrulation. The metabolic "patterns" are multivariant up to the second switch although, in the most cases, the metabolic activity of the equatorial area is the lowest. From the onset of gastrulation the metabolic patterns become uniform: the vegetative area dominates by the intensity of precursors' incorporation and by the sensitivity of its respiratory systems to the oxygen deficiency. The relationships between the metabolic and morphological rearrangements are discussed.


Adenoid cystic carcinoma of the salivary gland and its histologic variants. A clinicopathologic study of thirty cases. Thirty adenoid cystic carcinomas were seen among 384 salivary gland tumors during the 24-year period from 1952 to 1975. They caused the most difficulty in diagnosis, as they showed a spectrum of histologic appearances. In addition to tumors with the typical cribriform pattern of uniform dark cells, there were some with a more solid basaloid pattern resembling basal-cell carcinomas of the skin. Others manifested both cribriform and basaloid patterns in juxtaposition. A shorter duration of symptoms in lesions with a basaloid component suggests a more rapid growth rate in such tumors. Ultrastructural examination of a tumor with a typical cribriform pattern showed spaces of two types; the more frequent type was bounded by cells with straight plasma membranes and contained filamentous and basement-membrane-like material, and the less frequent type was surrounded by cells with numerous microvilli and contained nonfilamentous homogeneous material. The filamentous and basement-membrane--like material corresponded to connective tissue mucin and the non-filamentous material to epithelial mucin in the light microscopic sections.


Giant-cell hyalin angiopathy.

Giant-cell hyalin angiopathy. Seven examples of an unusual hyalin degenerative change in the walls of blood vessels are discussed. We believe this is a localized phenomenon, not connected to systemic vascular disease. Inflammation is usually present, and in each case a dental procedure had previously been performed. Dental extraction was the most common procedure. Giant cells of the foreign-body type are present, but particulate foreign material was seen in only one case.


[Efficiency of primary radiotherapy in generally or locally inoperable carcinoma of the endometrium]. The usual method of irradiation in the therapy of the carcinoma corporis uteri is described. It is stressed, that none but inoperable carcinomas were irradiated: this means, of course, a negative selection in disfavor of the radiotherapy. A report is given of 802 cases of carcinoma of the corpus uteri, treated by primary radiotherapy in the 1st University Clinic of Obstetrics and Gynecology in Vienna in the years 1950-1970. The 5-years-survival rate in this period was 50.4%. In the last half decade of this period the 5-years-survival rate of 300 patients went down to 48.6%. The reduction of this survival rate may be caused by the increasing age of the patients, who underwent therapy and is corresponding to world-wide experiences. Additive therapies like the "second-look abrasio" for early diagnosis of a local recidivation and the gestagen therapy for the prevention of metastatic carcinoma of the corpus uteri are discussed.


Motor development of autistic monozygotic twins: a case study. A pair of autistic monozygotic twins were assessed on relevant portions of the Geddes Psychomotor Inventory. Over-all motor development of the 3-yr., 6-mo. old twins was similar and considered a partial consequence of the same genotype and comparable environmental experiences from birth. The twins exhibited poor or unsuccessful performance on tasks requiring abilities in language, communication, and appropriate relationships to objects; superior performance on specific fine manual motor skills, walking balance board, and climbing; at-age performance on tasks which were considered measures of patterned gross movement, balance, postural maintenance, and spatial orientation; and few typical autistic motor characteristics.


Reverse transcription of phage RNA and its fragment directed by synthetic heteropolymeric primers. DNA synthesis catalysed by RNA-directed DNA-polymerase (reverse transcriptase) was found to proceed on the RNA template of an MS2 phage in the presence of heteropolymeric synthetic octa- and nonadeoxyribonucleotide primers complementary to the intercistronic region (coat protein binding site) and the region of the coat protein cistron, respectively. The product of synthesis consists of discrete DNA fractions of different length, including transcripts longer than 1,000 nucleotides. The coat protein inhibits DNA synthesis if it is initiated at its binding site, but has no effect on DNA synthesis initiated at the coat protein cistron. It has been suggested that, in this system, the initiation of DNA synthesis by synthetic primers is topographically specific. The MS2 coat protein binding site (an RNA fragment of 59 nucleotides) serves as a template for polydeoxyribonucleotide synthesis in the presence of octanucleotide primer and reverse transcriptase. The product of synthesis is homogenous and its length corresponds to the length of the template. The effective and complete copying of the fragment having a distinct secondary structure proves that the secondary structure does not interfere, in principle, with RNA being a template in the system of reverse transcription.


[Treatment of diffuse toxic goiter with radioactive iodine in combination with prolonged antithyroid therapy]. The authors analyzed clinically the results of treatment of 237 patients with diffuse toxic goiter with radioactive iodine in combination with prolonged antithyroidal therapy (12--18 months). The advantages of combined therapy consisted in the use of relatively low 131I doses, a great frequensy of clinical remissions of thyrotoxicosis (83%), in the absence of thyrotoxicosis remissions after the administration of a low radioactive iodine dose and a low percentage of stable hypothyroidism development (0.8%) as a complication of radioiodine therapy.


[Hypothalamus-hypophysis-thyroid gland system activity in altered functional state of the sex glands. 2]. The role played by the hypophysis and the hypothalamus in the interrelationship of the gonads and the thyroid gland was studied on female albino rats. Their interaction could be realized only in the presence of the intact hypophysis. The content of the thyrotropin-releasing-hormone (TRH) determined in the hypothalamic extracts altered depending on the blood estrogen level. Ovariectomy decreased the TRH content, whereas the administration of estradiol dipropionate to the operated animals increased the content of this hormone. Besides, ovariectomy caused a disturbance of the reaction of the hypophysis to TRH. Possibly the hypophysis of the castrated animals became refractory (to some extent) to the stimulating action of the TRH.


[Characteristics of the action of excess thyroid hormones in guinea pigs]. A study was made of the action of various doses of thyroidin in its prolonged administration to guinea pigs on the functional and morphological changes of the thyroid gland and the adenohypophysis. A high sensitivity of guinea pigs to the excess of thyroid hormone in comparison with such in dogs was shown. Already with the less thyroidin doses guinea pigs displayed an increased oxygen consumption under conditions of the basic metabolism, a marked increase of the content of protein-bound iodine in the blood serum and of the corticosteroid urinary excretion. There were revealed no significant differences in the thyroidin action depending on the method of its administration, i.e. in case of a gradual increase of the doses or in the administration of high doses from the very beginning. The presence of significant individual differences in guinea pigs in the resistance to the excess of the thyroid hormones was demonstrated.


Crystallographic studies of bovine beta2-microglobulin. Crystals of the bovine milk protein lactollin yield x-ray diffraction data extending to a resolution of 2.8 A. Lactollin is a bovine analogue of beta2-microglobulin, a protein that is homologous in amino acid sequence to the constant domains of immunoglobulins and is the light chain of the human and murine major histocompatability antigens. The protein crystallizes in the orthorhombic space group P2(1)2(1)2(1) with a = 77.4, b = 47.9, and c = 34.3 A. The unit cell parameters and physical chemical solution studies indicate that the molecule exists in the crystal and in solution as a single polypeptide chain of 12,000 daltons.


Identification of prelarge and presmall basic proteins in mouse myelin and their structural relationship to large and small basic proteins. A new technique is described to identify antigenically related proteins by radioimmunoassay after sodium dodecyl sulfate/polyacrylamide gel fractionation. When adult mouse myelin was examined by this technique, four proteins that are antigenically related to the small myelin basic protein were identified. They were designated: prelarge (molecular weight 21,500), large (18,500), presmall (17,000), and small (14,000). The four proteins were isolated by elution from polyacrylamide gels, and each protein migrated as a single band when analyzed by either sodium dodecyl sulfate or acidic polyacrylamide gel electrophoresis. Serial dilutions of the purified proteins were measured by radioimmunoassay. Both the slope of the inhibition curve and the level of maximal inhibition for each protein were the same as for the small myelin basic protein, indicating that each of the four proteins contains all of the antigenic sites present in the small basic protein. Structural relationships among the four proteins were examined by using two-dimensional analysis of tryptic digests. The results showed that: large was similar in amino acid sequence to the major myelin basic protein from other species; small was identical in sequence to large, except for an internal deletion of approximately 40 amino acid residues: prelarge contained the sequence of large plus an additional sequence of 25-35 amino acid residues; and presmall contained the sequence of small plus the same additional sequence as in prelarge. The four proteins were also treated with 2-(2-nitrophenylsulfenyl)-3-methyl-3'-bromoindolienine (BNPS-skatole) which cleaves proteins specifically at tryptophan residues. Analysis of the cleavage products indicated that the additional amino acid sequence in both prelarge and presmall extends from the amino terminus of the molecule. Several implications of these results are discussed.


Multiple antigenic determinants on the major surface glycoprotein of murine mammary tumor viruses. The major external protein of murine mammary tumor viruses (MMTVs) is a glycoprotein of molecular weight 52,000 (gp52). We report here that the gp52s of MMTVs from different mouse strains contain both type-specific and group-specific antigenic determinants. Competitive radioimmunoassays with externally labeled virion preparations were used to demonstrate that MMTV virions from C3H, RIII, and GR mice competed identically in "group-specific" assays but either competed with altered slopes or competed incompletely in the appropriate "type-specific" assays. Similar results were obtained with purified gp52 preparations as competitors. MMTVs of RIII, C3H, and GR mice, grown in feline cells, competed similarly to the corresponding murine-derived MMTVs, thus demonstrating that the observed type-specific and group-specific antigenic reactivities are viral coded. In competitive radioimmunoassays using an antiserum against MMTV of C3H mice that was preabsorbed with MMTV of GR mice, type-specific reactivities were further magnified; MMTV of C3H mice competed completely whereas no competition was observed with MMTV of GR mice as a competitor. These studies are in agreement with previous biological and molecular hybridization studies on the diversity of MMTVs from different mouse strains.


Molecular events and energy changes during the action potential. A novel interpretation of the existing data concerning the energy changes associated with nerve impulse propagation is proposed. The main conclusion is that the negative phrase ofthe initial heat of activity cannot be accounted for without recourse to conformational changes in membrane proteins. It stems from analyzing and computing the energy changes associated with ionic flows, capacitive currents, and structural changes in membrane gateways. A close quantitative agreement with microcalorimetric measurements was achieved.


Relative stability of alpha- and beta-globin messenger RNAs in homozygous beta+ thalassemia. The relative concentrations of alpha-, beta-, and gamma-globin mRNA sequences were measured in bone marrow nuclear and cytoplasmic RNA and in RNA from peripheral blood reticulocytes of three patients with homozygous beta+ thalassemia. Our results suggest that the quantitative deficiency in beta-globin mRNA may arise because of abnormal metabolism of molecules containing beta mRNA sequences. Complementary DNAs specific for each of the globins were synthesized. Variable quantities of RNA were incubated to equilibrium with 3H-labeled alpha- and 32P-labeled beta- or gamma-enriched cDNA. We found for each of the patients that the alpha/beta mRNA sequence ratio was more nearly normal in the nuclear RNA than in either cytoplasmic or reticulocyte RNA. Conversely, gamma mRNA sequences were very low in the nucleus with an increase in the relative concentration in both cytoplasm and reticulocyte RNA. The thermal stability of nucleic acid duplexes formed between beta cDNA and nuclear RNA from one patient with beta+ thalassemia was equivalent to that of duplexes formed with normal nuclear RNA. Approximately equal amounts of thalassemic alpha and beta mRNA were retained by oligo(dT)-cellulose, indicating that the 3' poly(A) segment was present on both. Our results indicate that beta-globin mRNA, although grossly normal in structure, fails to accumulate in beta+ thalassemic erythroid cells in amounts equivalent to the mRNA for alpha-globin.


Key antigenic determinants in regulation of the immune response. The immune response to beta-galactosidase (beta-D-galactoside galactohydrolase; EC 3.2.1.23)is characterized by a wave of early help followed by a wave of suppression to a subsequent in vitro challenge with galactosidase-fluorescein. A cyanogen bromide peptide of beta-galactosidase, CB2, mimics the suppression seen with the enzyme. It is time dependent, carrier specific, and anti-theta sensitive; however, this suppression is not preceded by a wave of help. It is possible that CB2 cannot stimulate helpers, and is only able to activate suppressor cells. These data indicate that one small region of an antigen, capable of activating suppressors, can nullify the positive effect induced in helper T cells reactive with other epitopes on beta-galactosidase. Key determinants on macromolecules may in this way be influential in regulating the immune response to the entire antigen molecule.


A postsynthetic modification of human alpha-fetoprotein controls its immunosuppressive potency. In a previous study, we demonstrated three variants of human alphafetoprotein by crossed immunoelectrophoresis. In addition, we correlated the capacity of alpha-fetoprotein isolates from various hepatoma and fetal sources to suppress human lymphocyte transformation in vitro with the relative proportion of the electronegative variant, HAFP-3, present in each isolate. We have now isolated alpha-fetoprotein from the serum, ascitic fluid, and saline extract of tumor from a single hepatoma patient and from a homogenate of fetal livers. When tested for their capacity to inhibit human lymphocyte transformation in vitro, tumor and fetal liver alphafetoprotein were found to be extremely potent, serum alphafetoprotein had intermediate potency, and ascitic fluid alpha-fetoprotein was the least potent. Analysis of these isolates by crossed immunoelectrophoresis confirmed the correlation between the proportion of HAFP-3 and the immunosuppressive potency of each isolate. In addition, analysis of these isolates by isoelectric focusing in polyacrylamide gels containing 8 M urea revealed further evidence of microheterogeneity; at least six molecular variants were apparent. The proportion of one of these variants, termed HAFP-3a, in each isolate was correlated with the immunosupressive potency of the isolate. The sialic acid content of the various alpha-fetoprotein isolates did not vary significantly. Our data suggest that a postsynthetic modification of alphafetoprotein occurs, probably after secretion, which reduces immunosuppressive potency by converting the active electronegative species to an inactive electropositive form. This modification probably involves a charged moiety other than sialic acid on the molecule.


Expression of Ia-like antigen molecules on human granulocytes during early phases of differentiation. Human B lymphocyte antigens analogous to the murine Ia determinants were found on myeloblasts and promyelocytes but not on more mature granulocytes. This was apparent by fluorescent staining with both human alloantisera and rabbit antisera to the isolated Ia-like proteins. The cells of patients with chronic myelocytic leukemia showed this difference especially clearly. Separation of the myeloblasts and promyelocytes by multistep density gradient fractionation produced a marked enrichment of the positive cells. The remaining cells from higher density fractions were more-mature neutrophils that were essentially negative. In acute myeloid leukemia, in which myeloid cells early in differentiation predominate, the vast majority of cells were strongly positive. Similar results were obtained with normal bone marrow cells. Here also, only the early forms of the myeloid series separated by gradient centrifugation had Ia antigens. Evidence was also obtained for the presence of Ia determinants on cells with the appearance of early erythroid precursors. Support for the presence of the Ia determinants on granulocyte-macrophage committed stem cells was provided by the inhibition of granulocyte colony formation in agar cultures following preincubation of normal bone marrow with antiserum and complement. Cross absorptions with purified preparations of immature cells provided evidence for the close similarity of the antigenic determinants on both myeloblasts and B cells. A 28,000-37,000-dalton bimolecular complex obtained from myeloblast membranes contained the Ia determinants and was similar to that obtained from peripheral blood B cell membranes.


Distribution of HLA-A, B, C and the Merrit B-cell alloantigen specificities in chronic lymphatic leukemia. Based upon reactions with both normal peripheral B-lymphocytes and a CLL panel, an additional 3 new specificities of the Merritt B-cell alloantigenic system have been defined. this brings the number of provisionally designated specificities to 22. The system of antigenic determinants is well represented on normal B-lymphocytes, and has a roughly similar distribution when compared to the CLL panel; however, evidence is presented which suggests that certain speficities may have significantly idfferent distributions on the 2 different panels, but the number of cells tested is low.


Evaluation of anomalous HLA reactivity in the typing of neoplastic lymphoreticular cells. Lymphoblasts from 6 cases of acute lymphocytic leukemia showed a paucity of receptors for T-cells (E-rosettes) and B-cells (surface membrane immunoglobulin). In contrast, neoplastic lymphoid cells from 5 cases of non-Hodgkin's lymphoma demonstrated that 4 cases could be listed as B cell proliferations and 1 case as a T-cell tumor, Anomalous HLA cytotoxic reactions were observed in all 6 cases of acute lymphocytic leukemia and probably in 1 case of non-Hodgkin's lymphoma. When the HLA antisera was absorbed of its HLA specificity, lymphoblast cytotoxicity was still observed, indicating the presence of some contaminating nonHLA antibody in HLA antisera. Severson et al. (3) demonstrated the presence of anti-B-cell activity in 2 of the 4 antisera used in this study. Lymphoblasts failed to stimulate autologous peripheral blood remission lymphocytes and neoplastic lymphoid cells did not stimulate autologous peripheral blood lymphocytes in mixed lymphocyte culture, indicating the lack of a neoantigen as measured by this technique. However lymphoblasts from 4 cases of acute lymphocytic leukemia and neoplastic lymphoid cells from 2 cases of B-cell lymphoma stimulated better than they responded to allogeneic lymphocytes. The data suggest the possibility that lymphoblasts without receptors of E-rosettes and surface membrane immunoglobulin may contain B-cell antigens which crossreact with HLA antisera and vigorously stimulate allogeneic lymphocytes.


Quantitative assay of Schieff and PAS reactivity during nerve degeneration in rats. Quantative histochemical analysis of nerve degeneration in rats from zero to 192 hours was studied utilizing both Schiff reagent and PAS reaction. In addition, amylase digestion prior to PAS staining and aniline blockade of Schiff reactivity were employed. The staining intensity of all the reaction was measured histophotometrically and the mean optical density (OD) was determined for the following time intervals: 0, 24, 48, 96, and 192 hours.


Standardization of rhinomanometry.

Standardization of rhinomanometry. Current methods of rhinomanometry used by various workers from around the world were investigated. The data for this communication were based on the studies of 11 scientists who have an accumulation of approximately 81 years of experience with more than 20,000 rhinometric examinations. The results of this survey provide a consensus of methods, procedures, data collection, and presentation which should be considered so that rhinomanometric uniformity may be achieved. It is fully recognized that standardization of rhinomanometry requires further inquiry and evaluation and that this is not the final communication on the subject but merely a current consensus from a limited few working in the field.


Clinical management of sinusitis.

Clinical management of sinusitis. In the clinical management of sinusitis, consideration should be given to the etiology of the disease, which today can be classified as infection, allergy and vasomotor conditions and local and general immunity deficiency. It is important to mention that infection can be present with an allergy, as well as with immunity deficiency. Knowledge of this differentiation is necessary for providing more effective and longer lasting conservative treatment. Surgical interventions are kept at a minimum and used only for derisation and drainage of sinuses, while preserving the mucosa.


Prevention of plasmin autodigestion by human plasma alpha2-macroglobulin. The autodigestion of plasmin in neutral solution at 37 degrees C and prevention of plasmin autodigestion by methylamine were confirmed by using rho-Tosyl-L-Arginine-Methyl ester as a substrate of plasmin. The autodigestion of plasmin was prevented by human plasma alpha2-macroglobulin which has been reported as an antiplasmin of immediate and reversible type but was not prevented by alpha1-antitrypsin which has been reported as an antiplasmin of slow and irreversible type.


[Chronic myeloid leukemia and periurethral adenoma]. Dysectatic disturbances in leukemia patients can be determined by leukemic infiltration of the prosthate or by the evolution of a co-existing peri-urethral adenoma. Indications and results of physiotherapy and surgery are evaluated in connection with an observation of peri-urethral adenoma in a patient with chronic myeloid leukemia.


Influence of an M-locus difference on the cellular and humoral immunological reactivity against H-2 determined antigens of the mouse. Studies were initiated to determine whether an immune response to the Mls antigen of C3H mice could modify responses of CBA lymphocytes (H-2-compatible) to a foreign H-2 complex. CBA lymphocytes, partially tolerant to the C3H-determined Mls antigen, generated less effector cell activity against C57Bl cells (H-2-incompatible) than lymph node cells from normal CBA donors when infused into irradiated C3H X C57Bl hosts. Effector cell activity was measured as the capacity of the cells in the irradiated spleens to inhibit CBA X C57Bl bone marrow proliferation. In contrast, immunization of CBA mice with C3H X C57Bl cells yielded lower antibody titers against C57Bl cells than immunization with CBA X C57Bl cells. Furthermore, preinjection of CBA mice with C3H X CBA cells strongly reduced the capacity of the animals to produce antibodies against C57Bl cells. Thus, these data support the conclusion that an immune response to a foreign Mls antigen may either enhance or suppress an immune response to H-2-incompatible cells.


Specific suppression of MLC and CML by anti-idiotypic antibodies in the mouse. Rabbit antisera directed against idiotypic determinants of alloreactive mouse CBA anti-C57BL/6 T blasts were raised in the following manner: first, a rabbit serum directed against nonspecific CBA blasts cells was prepared by injecting CBA concanavalin A blasts three times at monthly intervals into a rabbit. Second, specific CBA anti-C57BL/6 T lymphoblasts were induced in a mixed lymphocyte culture (MLC), were purified by gravity sedimentation through a fetal calf serum gradient, and, finally, were incubated with the anti-blast serum from the first step. During this incubation, presumably all epitopes of the blast cell population were blocked by anti-blast antibodies, except for the greatly amplified set of CBA anti-C57BL/6 alloreactive idiotypes. The mixture was then injected into fresh rabbits, which were boosted with similar mixtures after 3 and 6 weeks. Blood samples were removed 10 days after each injection. Such sera, when used together with complement, inhibited specifically the stimulation of CBA cells by C57BL/6 antigens in MLC and the CBA anti-C57BL/6 killer cells.


Double minute chromosomes and the homogeneously staining regions in chromosomes of a human neuroblastoma cell line. Four human neuroblastoma cell lines were studied by chromosome banding techniques. All of the lines contained a marker chromosome with a long nonbanding homogeneously staining region (HSR). The HSR-containing chromosome differed in each line. One line contained two classes of cells: one with an HST marker chromosome and the other with double minute chromosomes. Each cell had one of these abnormalities; no cell had both. The presence of two additional chromosomal markers in all cells of this line indicates a common origin. These observations suggest that the double minute chromosomes are derived from the HSR.


The painful shoulder.

The painful shoulder. The shoulder, a very common site of pain syndromes in medical  practice, lends itself well to precise clinical analysis and identification of the pain-sensitive structure or structures. Once identified, rational and effective management can be applied, associated with predictably good prognosis. Early identification of the emerging specific syndrome is important in decreasing the duration of the clinical disorder and in achieving optimum return of shoulder function. Laboratory and X-ray studies are not commonly required in diagnosis and management. There are a confusing variety of names attached to the many shoulder pain syndromes; however, there are two most common categories. One is associated with severe pain but little or no limitation of shoulder movement (at least passive movement), in which the pain-sensitive structure is tendon or tendon sheath; the other is associated with both pain and limitation of active and passive motion, in which the pain-sensitive structures are capsule, bursa, and synovium as well as muscle and multiple tendons.


Enumerative fluorescent vital staining of live and dead pathogenic yeast cells. A quantitative technique is presented for differentiating live and dead yeast cells grown in culture through the use of the fluorescent dye acridine orange. The method gives results that correlate well with those of other commonly used vital staining techniques and is free of certain interpretative errors inherent in them. Vital staining of yeasts with acridine orange also allows for more precise assessment of the physiological state of individual cells and the culture as a whole. The progressive senescence of yeast cells in culture can be monitored by the changing staining characteristics of several subcellular organelles. The method is simple and reliable.


Procion brilliant orange, a counterstain for decalcified sections vitally labeled with procion brilliant red H-8 bs. Procion brilliant red H-8 BS is a fluorescent dye that stains the organic matrix of bone supravitally. A procedure is described for counterstaining sections of such bone for visible light examination without interfering with the demonstration of sites of bound dye under UV illumination. Sections are brought to water, stained in Delafield's alum hematoxylin for 10 minutes, washed in tap water for 10 minutes, counterstained in 1% Procion brillant orange M-GS for 15 minutes and washed in distilled water for 10 minutes. After dehydration the sections were mounted in Eukitt.


Surface staining of sawed sections of undecalcified bone containing alloplastic implants. A simple new method is described for the histological evaluation of bones containing alloplastic implants of ceramic and/or metallic materials. The undecalcified bone is embedded in acrylic resin and sectioned at 50-200 micrometer using a sawing microtome. One surface of the preparation is stained up to 10 micrometer deep by floating the preparation on Giemsa stain. Other staining procedures are possible. Microscopic detail is satisfactory for histological and morphometric evaluation.


Enzyme clearing of alcian blue stained whole small vertebrates for demonstration of cartilage. Preparation of small vertebrates cleared after alcian blue staining of cartilage is facilitated by trypsin digestion. Specimens are fixed in formation, washed, skinned, and eviscerated. After staining in a solution of alcian blue in acetic acid-alcohol for 24-48 hours, they are transferred to water through graded alcohols. Excess alcian blue is removed over a period of up to three weeks by changes every 2-3 days of 1% trypsin in approximately one-third-saturated sodium borate. Bony tissues may be stained after this in a solution of alizarin red S in 0.5% KOH. Specimens are bleached if necessary and dehydrated through graded KOH-glycerine mixtures for storage in glycerine. Since alcohol treatment in addition to formalin fixation does not affect results with this method, it should be useful to researchers who want to study the cartilage or cartilaginous skeletons in museum specimens, which are routinely fixed in formalin and stored in alcohol.


Methyl green-pyronin with hematoxylin and orange G for the identification of inflammatory cells in tissue sections. Methyl green-pyronin is a notoriously difficult stain to reproduce. Although very useful in detecting cells containing substantial amounts of RNA, it is of limited use in broader problems of cell identification. By careful standardization of the proportions of methyl green to pyronin and combination of these stains with hematoxylin to enhance nuclear contrast and with orange G to improve connective tissue staining, it was possible to produce a consistently reliable staining preparation in which it is possible to identify all the component cells of a mixed inflammatory infiltrate in routine paraffin sections.


A new aspect of voiding dynamics: the relationship between flow rate and the frequency of drops in the external urinary stream. The method of drop spectrometry gives the possibility of registering the instantaneous trend drop frequency and the instantaneous trend flow rate. By plotting the flow rate against the frequency, patterns are obtained which depend on the flow and the elasticity of the external meatus.


Formaldehyde in the pathogenesis of hemodialysis-related anti-N antibodies. The role of formaldehyde (CH2O) in the pathogenesis of anti-N-like antibodies found in patients on chronic hemodialysis was investigated. In vitro studies were performed by incubating MM cells in varying concentrations of CH2O for variable time periods, corresponding to conditions that occur in dialysis. This MM cells acquired reactivity to anti-N antibody. The antigenic shift is felt to occur from the interaction of CH2O with the terminal N-acetylneuraminic acid (sialic acid) groups of M substance, resulting in the exposure to an altered-N antigen that is immunogenically active. Through a similar mechanism, CH2O may also directly modify N substance.


A new look at bladder neck obstruction by the food and drug administration regulators: guide lines for investigation of benign prostatic hypertrophy. A basic assumption of current guide lines to test drug therapy for benign prostatic hypertrophy is that the clinical disease is caused by bladder neck obstruction and its sequelae and complications. Asymptomatic non-prostatic hypertrophy, no matter how large the adenoma, is considered to be a pre-clinical phase of the disease as long as bladder trabeculation, impairment of the flow rate and residual urine are absent. The guide lines recognize that histological changes and gross anatomical enlargement of the prostate are the essence of the disease but objective signs of current therapeutic relief of symptoms lend themselves more practically to measurement of progression or remission, whereas no current drug has a clear enough effect on prostatic histology to predict subsidence of the clinical picture. Since no one criterion or single test serves this purpose a cluster of symptoms, with flow rate and residual urine, provides the hardest data. It would be preferable for each patient to serve as his own control in a prospective double-blind randomized study, since the literature shows no uniformity of approach, methodology, patient population or other useful data for clinical norms. Guide lines have been developed with the aid of clinical pharmacologists, biostatisticians, lawyers and government officials and approved by the Food and Drug Administration. Misconceptions outside of the profession of Urology need to be dispelled and further research in methodology, urodynamics, ultrasonic evaluation of the prostate, definition of symptoms, criteria for efficacy, etiology of the disease, and mode of action of drugs, placebo and surgery were highlighted. The literature does not have an overabundance of data but does contain evidence of definite but weak drug efficacy in the treatment of this condition.


Recent progress in ultrasonography of the bladder and prostate. Gray scale transrectal ultrasonography has proved to be a valuable adjunct in the evaluation of patients with tumors of the prostate and bladder. Its application in patients with prostatic disease is in the detection of early asymptomatic tumors, in the accurate staging of local disease and in the following of patients after the institution of specific treatment. Although it is not being used for the detection of bladder tumors the procedure is a reliable means to evaluate the degree of tumor invasion so that proper therapy can be instituted.


[Comparative electrophoretic study of the molecular forms of alkaline phosphatase in the leukocytes of agricultural animals]. The alkaline phosphatase enzyme, isolated by Morton's method from leukocytes of sheep, goats, and pigs gave after agarose elctrophoresis two isoenzyme fractions moving to the positive pole at the sites of the alpha 1- and alpha 2-globulins of the blood serum. In bovine leukocytes, besides these two fractions there was a third one that moved more slowly in the zone of the beta-globulins. In horses the alkaline phosphatase of leukocytes produced a wide band within the zones of the beta-globulins and the albumins. It was established that the proportion between the individual isoenzyme fractions of the leukocyte alkaline phosphatase in farm animals presents species variation.


[Demonstration of the infectious rhinotracheitis-pustular vuluovaginitis virus (IBR-IPV) in the placenta and aborted fetuses of cows]. A well expressed correlation was found to exist between the immunofluorescence and the histologic methods in the demonstration of IBR-IPV infection of fetuses and placentae in 75 cases of spontaneous undiagnosed abortions. If those that were positive by the immunofluorescence method were 100 per cent as many as 87 per cent of them showed coincidence with the results obtained by the histologic method. The isolation of the virus of IBR-IPV coincided in 44 per cent of the cases only. Clearest specific fluorescence, established most frequently, was demonstrated in the kidneys of the fetuses. It was found that contrast staining with Evans blue effectively inhibited the unspecific fluorescence. Exceptions in this respect were observed with some preparations of liver, lung, and placental tissues, where there were cells of unspecific fluorescence, which, by its character and localization differed essentially from the fluorescence that was specific for IBR-IPV. It is assumed that the immunofluorescence method performed at contrast staining with Evans blue makes possible the fast and precise diagnosis of IBR-IPV.


Distribution of mucosubstances in adenoid cystic carcinoma. The distribution of mucosubstances in adenoid cystic carcinoma was investigated, and an attempt was made to characterize histochemically the various mucosubstances present. For these purposes the high iron diamine technique (HID), as well as the Astra blue, aldehyde fuchsin and Alcian blue staining methods were employed. Alcian blue was further combined with the periodic acid-Schiff (PAS) technique, the Alcian blue being applied at pH levels between 0.5 and 2.5. In addition the effect of neuraminidase and hyaluronidase treatment as well as methylation and acid hydrolysis procedures on the staining qualities were studied. Acidic mucosubstances with varying histochemical properties were present in different structures of the neoplasm. The characteristic pseudocyst, a major structural component of the neoplasm, stained strongly with HID, Astra blue, aldehyde fuchsin and Alcian blue at low pH. These staining reactions were markedly suppressed by hyaluronidase treatment, and are apparently attributable to the presence of chondroitin 4- and/or 6-sulfate. Employing the Alcian blue-critical electrolyte concentration technique, the basophilia of the pseudocysts was suppressed at a concentration of 0.5-0.6 M MgCl2, which might indicate polysaccharides of relatively low degree of sulfation. An additional, non-sulfated acid mucin could also be demonstrated in these structures. In certain duct and gland like structures of the tumours, a change in staining pattern from blue or blue-red to red could be observed after exposure of the sections to neuraminidase and subsequent staining with the Alcian blue (pH 2.5)-PAS sequence. Similar observations were also made when the pH of the Alcian blue was lowered to 1.5-1.0, as well as after acid hydrolysis. These findings afford evidence for the presence of a neuraminidase susceptive sialomucin in certain epithelial secretions of the tumor. At the ultrastructural level the replicated basement lamina of the pseudocysts displayed a strong positive reaction with the PA-CrA-silver staining technique. Furthermore, amorphous material within the lumina of small duct like structures also displayed a positive reaction. The amorphous material of the cystic compartments was less reactive.


[Use of areflux anastomoses in inoperable stomach cancer]. Under consideration is the experience with 64 operations of palliative areflux gastro-enteroanastomoses for inoperable cancer of distal portion of the stomach. The absence of lethal issues and such complications as suture incompetency at the anastomosis site, peritonitis, postoperative reflux-gastritis are felt by the authors to be due to the advantages of this operative technic. In 39 of 64 patients palliative surgery was soon followed by chemotherapy. The longer survival from 4--6 months to 11 months was noted only after palliative operations.


In vitro and in vivo immune response to specific antigens in canine marrow graft recipients. Cellular and humoral immune reactivity to primary and secondary challenge with tetanus toxoid, diphtheria toxoid and keyhole limpet hemocyanin was studied in normal dogs and canine bone marrow chimeras prepared for marrow grafting by lethal doses of cyclophosphamide. Short-term chimeras (less than 100 days postgrafting) showed general impairment of immune function as indicated by marked depression of skin test reactivity, lymphocyte blastogenesis in vitro and antibody formation. Long-term chimeras (more than 100 days post-grafting) demonstrated gradual improvement of immunologic capacity related to the stage of postgrafting. Prolonged immunoincompetence was suggested by decreased lymphocyte proliferation in vitro in response to stimulation with tetanus and diphtheria toxoids and by incomplete conversion from 19S to 7S antibody synthesis. Lymphocyte blastogenesis to specific antigens may prove a useful parameter for the in vitro evaluation of defects in cell-mediated immunity following allogeneic bone marrow transplantation. Our findings of prolonged immunodeficiency in the preclinical canine model point out the necessity for vigilance in early detection and treatment of infection and underline the importance of approaches aimed at accelerating immunologic reconstitution.


[Comparative characteristics of influenza virus A/USSR/02/76 and swine influenza virus]. Comparative studies of the biological properties, antigenic structure and ultrastructure of influenza A viruses isolated in the USSR, A/New Jersey/8/76 and A/swine/31 were carried out. Antigenic differences between A/USSR/02/76 and A/swine/31 strains as well as A/New Jersey/8/76 strain were found in the hemagglutination-inhibition and neuraminidase activity-inhibition tests. These differences were confirmed by serological examination of human sera.


[Interpretation of the trace element content of hairs in criminology, toxicology and environmental protection. Experimental migration of metal ions in keratine (author's transl)]. Metal ions of exogenous origin can penetrate into the hair and can be accumulated. Penetration and distribution of metal ions could be examined by means of electron microprobe-analysis. The dependence of the accumulation of different kations on the concentration of these in the surrounding solutions have been determined by atomic absorption spectroscopy. The dimension of accumulation depends on various factors: the chemical nature of the ion involved, its concentration in the solution and the solutions pH-value, the nature of the anions present as well as the nature and concentration of other kations. The distribution of the kations in the hair can be changed by washing with distilled water. The significance of the present physical-chemical experiments with hairs for criminology, toxicology and to environmental protection were discussed in detail. It was shown that the content of zinc in the hair is of predominantly endogenous origin; moreover, a strong accumulation in the hair root took place. The study of the accumulation mechanism should contribute to clarifying other possible accumulation mechanisms. Further information should be expected from extention of these experiments.


[Modification of immune reactions by antigen-immunosuppressive agent conjugates. V. Studies on antigen-specific activity of 6-mercaptopurine bovine gamma globulin conjugates on the humoral immune response in rabbits]. Rabbits treated daily and for seven consecutive days with 6-mercaptopurine bovine gamma globulin conjugates (MPI--n-BGG; 'I'--characterizes the king of chemical binding and 'n' the number of coupled MP-residues per one mole BGG) show an altered immunological reactivity. A following intradermal immunization with BGG alum adsorbate results in a suppressed anti BGG antibody production on the third day after antigen application (antibody titer 1:320, antibody titer of control animals--pretreated with BGG and uncoupled 6-MP equals 1:5120). Already three days later the antibody titers of the test groups show a significant increase and are two dilution stages higher than the titers of the controls. A suppressive effect on the third day is induced by MPI--13-BGG, MPI--26-BGG, MPI--36-BGG and MPI--46-BGG; the later adjuvant effect can only be seen in the MPI--26-BGG, MPI--36-BGG and MPI--46-BGG but not in the MPI--13-BGG pretreated animal group. While the short time suppression was antigen specific--the humoral immune response against a second unrelated antigen was not reduced--the adjuvans effect was not antigen specific. A pretreatment with the substances mentioned above results in an increased anti BGG and anti HSA serum antibody level. Comparing investigations on the unspecific immunosuppression in rabbits by 6-mercaptopurine shows that application of 10 mg 6-MP/kg/day for seven days at first leads to a suppression but later on to an enhancement of antibody production. Application of 10 mg 6-MP/kg/day for 10 days results in a long lasting suppression without enhancement effect. As a reason for these differences the different catabolism of immunosuppressive agent and antigen is discussed. For the phenomena following antigen specific immunosuppression, similar mechanisms can be responsible.


Analysis of factors affecting limb salvage and mortality after embolectomy. A series of 108 arterial embolectomies in 91 patients performed during 1960-64 and 1970-74 is presented. The Fogarty catheter was introduced in our clinic between these periods. Early mortality was 56 and 29%, respectively. Limb salvage rate according to our definition was 38 and 53%, respectively. We found a significantly higher mortality when embolies were located proximal to the profunda femoral artery compared to more distally located embolies. Amputation frequency was 4% after embolectomies performed within 12 hours, but 27% with longer duration of symptoms. Limb salvage rate was significantly higher in patients treated with anticoagulation. In conclusion it is stressed that local surgical therapy should be combined with adequate measures against cardiac failure and other systemic complications. This therapeutic principle is particularly important in cases with proximal embolies.


Lichen simplex chronicus Vidal: comparative submicroscopic aspects of acanthotic disorders. Electron microscopic analyses of lichen simplex chronicus Vidal (LSC) are reported. The submicroscopic organization is described. The frequent occurrence of collagen fibres directly juxtaposed to and contiguous with the lamina basalis seems to be a distinguishing feature of the LSC. Discontinuations in the lamina basalis are rarely indicated. A ubiquitous fragmentation and a certain paucity of tonofilamentous structure are present in cells preceding parakeratosis. There is an indubitable paucity of tonofilament-keratohyalin association. Mitochondria, endoplasmic reticulum and ribosomes are abundant. Odland bodies of type II are completely dominant. Parakeratosis and observed submicroscopically deficient or incomplete orthokeratosis are related to the numbers of defective Odland bodies. The keratinization of some acanthotic disorders is discussed.


5-S-cysteinyldopa in the urine of melanoma patients. A newly discovered amino acid, 5-S-cysteinyldopa, present in the urine of healthy subjects is excreted in pathological amounts in many patients suffering from melanoma metastases. Increased excretion of 5-S-cysteinyldopa may be observed before metastases become clinically evident. Determination of 5-S-cysteinyldopa is superior to determination of dopa+dopamine in the diagnosis of melanoma metastases.


Analysis of soluble proteins in comedones. The detergent-soluble fraction of purified, concentrated comedo samples was analysed for protein by disc-gel electrophoresis and fluorescamine assay. Spectrophotometer scanning revealed a characteristic pattern of 14 peaks which was essentially uniform in comedones from individuals having acne, Favre-Racouchot syndrome, or prepubertal comedones. The pattern was different in material derived from keratinous cysts and the contents of follicles from the nose. The presence of small amounts of serum proteins, notably globulins, was detected by immunodiffusion.


Epidermal location of beta-2-microglobulin in human skin. Beta-2-microglobulin (beta2-m) is associated with the epidermis in normal and pathological human skin and gives an immunofluorescence pattern similar to that of pemphigus antibodies and concanavalin A (Con-A). Inhibition experiments indicate, however, that the binding site of anti-beta2-m is not identical with that of pemphigus antibodies or Con-A. It is suggested that beta2-m might be an epidermal cell surface marker useful for the study of antigens associated with the epidermal cell surface.


Response of skin to ammonium persulphate. In order to investigate the histamine liberating actions of ammonium persulphate, skin slices from three species (guinea pig, rat and monkey) were incubated in vitro with concentrations of ammonium persulphate ranging from 1 to 1000 microgram/ml. None of these concentrations released significant amounts of histamine in guinea pig or monkey skin. In the rat the highest concentration (1000 microgram/ml) released 20-24% of the histamine content of the skin, but the intensitivity of this response to cooling indicates a non-specific "toxic" action on mast cells. By contrast a known chemical histamine liberator, compound 48/80, released significant amounts of histamine from skin at much lower concentrations in all three species. Ammonium persulphate is clearly not a potent histamine liberator. Ammonium persulphate dermatitis is presumably a result of increased sensitivity of skin mast cells, due to immunological or other factors, in susceptible individuals.


Cytologic diagnosis of echinococcosis.

Cytologic diagnosis of echinococcosis. A case of echinococcus liver cyst is presented in which definitive diagnosis was made by Papanicolaou staining of hooklets and scolices present in cyst fluid.


The role of oxygen in the photodamaging effect on erythrocytes of some photoallergic and phototoxic compounds. Red blood cells irradiated with longwave ultraviolet light in the presence of a number of photoallergic or phototoxic compounds showed a marked loss of K+ ions. This process was strongly restricted by anaerobic conditions. During irradiation, oxygen was consumed. Since pre-irradiated photosensitizers were not toxic to erythrocytes, it is concluded that during irradiation, oxidative processes take place in the erythrocyte. The concentrations of the investigated photoallergic compounds required to induce photohaemolysis, were several times higher than those required for the phototoxic compound protoporphyrin. These findings indicate that photoallergic compounds, like the photodynamic compounds, also have photo-oxidative capacities, but to a much lower degree.


The epidermal cell proliferation in lichen planus. The proliferative activity of epidermal structures was determined in 6 patients suffering from lichen planus (i.p.). By using the in vitro 3H-thymidine labelling technique, semithin Epon sections of lesional and perilesional uninvolved skin were compared autoradiographically with normal controls. The following results were obtained. The labelling index of epidermal cells was significantly increased within the i.p. papules. The mean values ranged from 41% in acanthotic i.p. to 23% in atrophic i.p. whereas in adjacent unaffected skin (15% and 11% respectively) as well as in normal controls (6%) a lower 3H-index was observed. As regards damage to basal cells within i.p. lesions, a factor--the relation between the number of basal cells in involved and uninvolved skin in reference to the epidermal length--was calculated in order to correct the autoradiographic results in involved skin. The differences between i.p. papules, adjacent skin and controls remained statistically significant even after correction. The intradermal eccrine ducts revealed a significantly increased labelling index in i.p. lesions as compared with perilesional and normal skin. In this respect no difference could be observed between the acanthotic and the atrophic variant of i.p. These findings indicate that replacement of damaged basal cells in i.p. is achieved by an increase in actively dividing keratinocytes in both epidermis and skin appendages within the lesion.


Suppressed cell-mediated immunity associated with eczematous inflammation. In order to determine if an eczematous inflammation could have any influence upon already established cell-mediated immune reactivity, a widespread allergic as well as primary irritant, eczematous dermatitis was produced in tuberculin-sensitive guinea pigs. Their tuberculin reactivity was significantly suppressed both by allergic contact dermatitis due to dinitrochlorobenzene and by primary irritant dermatitis due to croton oil. After the dermatitis had subsided, tuberculin reactivity was restored to approximately the same level as before the induction of the dermatitis, which suggests that the suppression is temporary.


On cell-mediated immunity in acne conglobata. In 25 of 35 cases of acne conglobata, a reduction in or lack of delayed reactivity was found by intracutaneous tests with a battery of antigens. On the basis of these findings as well as of normal T-cell function in lymphocyte culture and of negative Kveim-tests (in three cases), the possible immunological mechanisms are discussed.


Nodules on the legs. A clinical, histological and immunohistological study of 82 patients representing different types of nodular panniculitis. Eighty-two cases of nodular panniculitis of the legs were examined clinically, histologically and immunohistologically. Clinically the cases could be divided into four groups: typical erythema nodosum (ENty) (35 cases), erythema nodosum migrans (ENmi) (11 cases), erythema induratum (EI) (11 cases) and the remaining 25 cases not consistent with the others as "non-definite panniculitis" (NDP). The main histological categories were septal panniculitis and lobular panniculitis, the former including erythema nodosum, both typical and migrans, the latter EI and NDP. Lobular panniculitis was divided into three subgroups in which the most prominent histological features were epithelioid cell granuloma, vasculitis and palissading granuloma, respectively. Immunoglobulins in the vessel walls were found in 5 of the 46 cases of erythema nodosum, in 19 of the 36 EI and NDP cases and, in the histological groups in 4 of the 43 cases of septal panniculitis and in 19 of the 35 cases of lobular panniculitis, respectively. Fibrin was found in the walls of the papillary capillaries and deep dermal vessels in the majority of cases of lobular panniculitis. In EI and NDP the follow-up time was 40 months, on average. Twenty-two patients were treated with antituberculous drugs, 15 became symptomless, as did 5 of the 12 patients who were not treated at all.


Acral arteriovenous tumor.

Acral arteriovenous tumor. A unique, superficial, lobulated, benign vascular tumor of the skin, found in the acral areas of adult males, is described. The combination of three different elements--arterial, venous, and transitional vascular channels--make up the predominant histologic features of this tumor. The transition of fibromuscular channels indicates a venous lesion, but the acral location of the lesions and the structure and staining characteristics suggest that the lesion is a hamartomatous proliferation of the Sucquet-Hoyer canal of the true glomus.


Provocation with cow's milk and cereals in atopic dermatitis. Oral provocation test with cow's milk and cereals were performed in 81 children with atopic dermatitis, all below 5 years of age. In 15 of the children exacerbation of the dermatitis occurred on the second or third day after initiation of the tests. These patients, whose mean age was 13 months, underwent repeated provocation during the ensuring 18 months. Eleven children lost their sensitivity to the offending foods and 2 children became more tolerant during this period. Initial levels of serum IgE and specific reagins against the foods tested did not distinguish those patients who were positive to the provocation tests. In this group, however, reagins against egg white were significantly increased. The specific serum reagins were unaltered or increased in the majority of cases during the period of study. The radioallergosorbent test (RAST) was found of limited value as a screening tool in patients with atopic dermatitis in whom exacerbation of the condition appears to be caused by food sensitivity.


Lichen planus and acne provoked by gold. A 58-year-old man with rheumatoid arthritis developed lichen planus during treatment with gold. Four months after cessation of treatment, a severe acne with comedones, papules, pustules, and small cystic elements broke out. No connection could be demonstrated between the eruption and other drugs or chemicals. Acne provoked by gold seems not to have been described elsewhere. The case history confirms that gold treatment, even in the same patient, can give rise to a wide range of skin disturbances, which in many cases do not break out until long after the drug has been withdrawn.


Malignant acanthosis nigricans--a para-endocrine syndrome? A case is reported of acanthosis nigricans associated with a gastric carcinoma. The gastric cancer was of the diffuse, infiltrating type. Many tumour cells were identified by means of histochemistry and electron microscopy as neoplastic enterochromaffin-like cells. It is suggested that cancers associated with acanthosis nigricans might constitute a certain group of carcinomas in which parts of the tumour cells arise from the APUD-series of endocrine cells.