Maternal effects of regular salicylate ingestion in pregnancy. 6.6% of all Australian patients attending an antenatal clinic were found to be taking salicylate preparations regularly, most commonly in powder form and almost always as self-medication. In this group of salicylate takers there was an increased incidence of anaemia, anti-partum and post-partum haemorrhage, prolonged gestation, complicated deliveries, and perinatal mortality compared with non-takers. These findings suggest that regular salicylate consumption has detrimental effects in pregnancy. Routine antenatal urinary screening for salicylate in pregnancy is recommended.


Fetal effects of regular salicylate ingestion in pregnancy. The babies of 144 mothers who took salicylates regularly in pregnancy are described. These babies had a significantly reduced birth-weight compared with controls; many of them had a raised cord-blood salicylate level but had no clinical evidence of bleeding or hypoglycaemia. Their perinatal mortality was increased, but the incidence of congenital anomalies was not significantly raised.


Humoral antibodies to acetylcholine receptor in patients with myasthenia gravis. Sera from patients with myasthenia gravis (M.G.) were studied by the quantitative micro-scale complement-fixation assay for the presence of humoral antibodies against acetylcholine receptor (AChR). The purified receptor was extracted from the electrogenic tissue of the electric ray, Torpedo californica. A significant difference in the antibody titres was observed between myasthenic and non-myasthenic patients. Out of fifteen patients with myasthenia gravis, at least 12 (80%) had antibodies against AChR. Only one case out of twenty-four controls had an indication of anti-receptor antibodies. In view of observations on the role of AChR as the autoantigen in myasthenia gravis, such antibodies may have significance in producing the neuro-muscular block characteristic of the disease.


Renin-angiotensin system in essential hypertension. In a random sample of normotensive and hypertensive fifty-year-old men plasma-renin-activity (P.R.A.), plasma-renin-concentration (P.R.C.), and renin substrate were measured using radioimmunoassay for angiotensin I. P.R.A. in normotensives and untreated hypertensives were normally distributed with slight skewness to the right. The mean P.R.A. for untreated hypertensives (0.65 ng. per ml. per hour) was slightly, but not significantly, lower than that of the normotensive reference group (0.78 ng. per ml. per hour). Previously untreated hypertensives who had been off treatment for four weeks had either high or low P.R.A. depending on the previous treatment. No differences in the angiotensin-generation rate were noted as judged from the P.R.A./P.R.C. ratio. No differences in the renin-substrate concentration between the groups were found. The findings suggest that renin changes in essential hypertenion are secondary to pressure changes. Thus, the renin-angiotensin system may not be of primary pathogenetic importance in the development of essential hypertension.


Casual blood-ethanol estimations in patients with chronic liver disease. Patients attending a clinic for diseases of the liver were tested for blood-ethanol by a gas chromatographic technique sensitive to about 5 mg/dl (1 mmol/1). Of 172 patients (51 men, 121 women) 36% gave a history of heavy drinking (greater than 80 g ethanol/day; equivalent to 8 fl oz of whisky or 1 litre of wine) and 13% had ethanol in the bloodstream at values of 8-400 mg/dl. 42 patients (24%) had the liver-biopsy changes of alcoholic liver disease, and 17 of these had ethanol in the blood at one time or another. Nearly half (22/49) of all patients admitting heavy drinking also had detectable blood-ethanol. In all cases but 1 where blood-ethanol was found, a drinking history was admitted on first attendance, and alcoholic liver disease was nearly always found on subsequent biopsy. Blood-ethanol and admission of drinking were most constantly found in association with alcoholic steatosis and hepatitis. Both features were less commonly present in cases of alcoholic cirrhosis. Only 1 patient of 22 with "cryptogenic" cirrhosis on biopsy was found to have both ethanol in the blood and an alcoholic history, although 5 had an alcoholic history alone. The value of serial blood-ethanol estimations in the treatment of alcoholics and the detection of relapses is demonstrated. The findings confirm the relatively low frequency of alcoholism as a contributor to cirrhosis in the United Kingdom. Alcohol does not seem a major cause of cryptogenic cirrhosis. Casual blood-ethanol estimation is a useful and objective adjunct to techniques of investigating diseases of the liver.


Dinitrochlorobenzene sensitisation test in women on hormonal contraceptives. Cell-mediated immunity was measured in women on hormonal contraceptives using the 2,4-dinitrochlorobenzene (D.N.C.B.) sensitisation test. Three groups of women were studied: forty-eight women were taking oral contraceptives of combined oestrogen/progestogen (thirty-seven of them had used oral contraceptives for a year or longer); twelve women were using a sequential pill (ethinyloestradiol and megestrolacetate); and sixteen women had received intramuscular injections of medroxyprogesterone acetate. The results were compared with those of a control group of twenty-nine age-matched women not taking contraceptive steroids. In women on the combined contraceptive pill and those who had received intramuscular progesterone, mean D.N.C.B. reactivity was significantly increased. The results were even more striking in women who had used combined contraceptive pills for more than one year. These results do not accord with the previously reported decrease in cell-mediated immunity in women on hormonal contraceptives.


Controversy in the detection of disease. The quality of discussions and debates into the proper roles for screening, case-finding, diagnosis, and epidemiological surveys in the detection of disease will be improved when participants use consistent definitions, understand the different purposes and properties of the manoeuvres, recognise ideological differences between advocates and methodologists, and consider the quantitative and qualitative differences between decision making for the individual patient and decision making for the community. Although attention to these causes need not detract from the colour of the continuing controversy, it should render the exchange more comprehensible to participants and spectators alike.


Patients with head injury who talk and die. Of 66 patients with head injuries who had talked at some time after injury, 25% did not have intracranial haematoma at necropsy. Most of these had raised intracranial pressure (I.C.P.), and the commonest finding was local swelling related to contusions. Almost half of the non-haematoma cases had ischaemic or hypoxic brain damage, usually without contusions; 3 were children who had had status epilepticus. Fatality without raised I.C.P. was most often due to meningitis. In deteriorating patients without haematoma mortality and morbidity might be reduced by more diagnosis and treatment, particularly of raised I.C.P.


Hepatitis-B immunoglobulin in prevention of HBs antigenaemia in haemodialysis patients. In a double-blind study, hepatitis-B immunoglobulin significantly protected patients in a haemodialysis unit against the development of HBs antigenaemia, compared to control patients receiving normal human immunoglobulin (p less than 0-01). Injections were given at the beginning and after 6 months, and observations extended over 16 months. Analysis of antiHBc and anti-HBs antibodies suggested that neutralisation of the virus inoculum, as well as modification of infection, may be implicated in the prevention of HBs antigenaemia.


Decreased premature ventricular contractions through use of the relaxation response in patients with stable ischaemic heart-disease. To determine whether decreased sympathetic-nervous-system activity achieved by the relaxation response could decrease premature ventricular contractions (P.V.C.s), eleven ambulatory patients with proven, stable ischaemic heart-disease and P.V.C.s were investigated. The patients, who were taking no medication for the P.V.C.s, were trained to elicit regularly the relaxation response through a non-cultic psychological technique. The frequency of the P.V.C.s was measured by computer analysis of Holter monitor tapes for 2 complete days before learning the technique, which was learned in approximately 5 minutes after the second day. Patients were instructed to evoke the response for 20 minutes twice daily thereafter. After 4 weeks, a reduced frequency of P.V.C.s was documented in eight of the eleven patients. This effect was especially striking during the sleeping hours and less so during the entire monitoring session. The relaxation response is a simple, no cost, non-pharmacological mechanism without side-effects which seemed to decrease the frequency of P.C.V.s in most patients with ischaemic heart-disease.


Impaired cardiovascular responsiveness in liver disease. Cardiovascular responsiveness to reflex impaired in patients with cirrhosis compared with control subjects. Peripheral vascular responses to exogenous noradrenaline were also impaired in cirrhotic patients, but peripheral vascular responses to infused adrenaline and to angiotensin II were similar in both groups. Impaired cardiovascular reactivity in patients with chronic liver disease could predispose them to circulatory failure after haemorrhage or surgery and should be considered when prescribing drugs which affect autonomic activity.


Hyperuricaemic acute renal failure after epileptic seizures. Seven patients admitted to hospital during or immediately after status epilepticus or recurrent episodes of grand-mal seizures had very high concentrations of uric acid in their blood at a time when the blood-urea was normal in five of them. The blood-lactic-acid was high in the five patients in whom it was measured. All of the patients developed reversible renal failure, and two required haemodialysis. The blood-uric-acid should be measured in patients who have had prolonged seizures, and the measures which might be taken in hyperuricaemic patients to prevent the development of acute renal failure include rehydration, alkalinisation of urine, and, where alkalinisation is impossible, haemodialysis.


Secretory component and sudden-infant-death syndrome. Post-mortem specimens of blood, respiratory-tract washings, bronchopulmonary tissue, spleen, and thymus were examined for respiratory viruses, immunoglobulins, and secretory component (S.C.) in eight infants with sudden-infant-death syndrome (S.I.D.S) and in eight other (control) infants with an identifiable cause of death. Serum-immunoglobulin levels were similar in infants with S.I.D.S. and in control infants. In some S.I.D.S. cases serum-IgM was slightly raised. Respiratory syncytial virus was found in the pulmonary tissues of five S.I.D.S. patients but no viruses were isolated from other subjects. However, in one control subject parainfluenza type-3 viral antigen was detected in the bronchial tissue. In all patients with S.I.D.S., immunological reactions and fluorescent antibody staining for S.C. in the broncho-pulmonary epithelium were absent or grossly reduced. The levels of IgG and IgM in bronchial washings were unremarkable. These observations suggest a possible defect in respiratory mucosal defence in patients with S.I.D.S.


Blood-group precursors and cancer-related antigens. Glycoprotein extracts from colonic tumours were tested for blood-group precursor-like activities using human anti-I and anti-i cold agglutinins as reagents. Substantial activity was detected in the high-molecular-weight fractions of two metastatic tumours. A carcinoembryonic antigen (C.E.A.) fraction from one of these tumours was also active. The C.E.A. and the precursor-like activities were located on separate molecules. These data indicate that the levels of precursor-like antigens in entodermal tumours and their possible diagnostic value warrant detailed investigation.


Hypothalamic peptides: New evidence for "peptidergic" pathways in the C.N.S. Hypothalamic peptides, discovered because of their effects on stimulation or inhibition of anterior-pituitary-hormone release, have now been shown to be distributed in many regions of the central nervous system (C.N.S.). Demonstration of their localisation in nerve terminals, of behavioural effects exclusive of anterior pituitary actions, and of depressant effects in electrophysiological experiments suggests a role in central-nervous-system function. It is postulated that a system of peptidergic neurons exists within the C.N.S. with axon terminations both on the pituitary portal system and on other neurons.


The justification for early radiological investigations of urinary-tract infection in children. 97 children, 67 girls aged 0-13 years and 30 boys aged 0-11 years, with apparent first urinary-tract infections were investigated radiologically. The intravenous pyelogram was abnormal in 15.5% of the girls and 33% of the boys and the micturating cystourethrogram was abnormal in 34% of the girls and 39% of the boys. When both examinations were combined the abnormality-rate rose to 41% in the two sexes. Accordingly, radiological investigation of the renal tract is recommended after the first proven urinary tract infection.


Appendicitis and mimicking conditions. A prospective study. A prospective study of 444 consecutive patients diagnosed as having acute appendicitis was carried out in a district general hospital. The appendix was acutely inflamed, gangrenous, or perforated in 346 patients. Diagnostic error, 22% overall, was twice as common in females as in males. Organisms were isolated from the outer appendix wall in 117 patients, isolation increasing with the severity of inflammation. 12% of children under 11 had mesentric adenitis, 10% of all females had gynaecological lesions, and 14% of patients over 50 had acute diverticulitis. In only 6% of patients was no abnormality found at operation, and in every case the disorder was dealt with through the gridiron incision.


Effect of urogastrone in the Zollinger-Ellison syndrome. The effects of human urogastrone (0-25 mug. per kg. per hour intravenously) in four male patients with proven Zollinger-Ellison syndrome (z.e.s.) and in four healthy control subjects have been studied. After urogastrone in z.e.s. patients gastric acid volume and concentration decreased and basal acid output was reduced by 50-82%; the concentrations of intrinsic factor and pepsin in gastric juice increased by 60-300%; and peak plasma-gastrin concentration increased by 127-164% of basal concentration. A significant negative correlation between increase in plasma-gastrin concentration and decrease in acid output was observed (r=-0-72, P less than 0-01). Ulcer pain was relieved 30-60 minutes after the beginning of urogastrone infusion. These results suggest that urogastrone can inhibit the endogenously stimulated acid hypersecretion in z.e.s.


Serum-albumin as a prognostic indicator in oedematous malnutrition. Examination of the records of 340 children admitted to hospital in Uganda with oedematous malnutrition (kwashiorkor) showed that the serum-albumin concentration at admission was closely related to mortality-rates. Furthermore, in this series, it was not possible to show a simple relation between mortality-rates and the degree of wasting present. The results further emphasise the need to include serum-albumin concentration in international classification systems for the assessment of protein-energy malnutrition, especially that of the kwashiorkor type.


Acute myelocytic leukaemia and leukaemia-associated antigens in sisters. In a sibship of 5 brothers and 7 sisters, 3 sisters died from acute myelocytic leukaemia while a 4th probably had the same disease. Laboratory studies on the close relatives revealed that a 5th sister had persistently high erythrocyte sedimentation-rates and serum-IgM levels and serological evidence of acute leukaemia-associated antigens. These findings suggest a possible preleukaemic state in this patient.


Treatment of severe combined immunodeficiency with bone-marrow from an unrelated, mixed-leucocyte-culture-non-reactive donor. A 7-month-old boy with severe combined immunodeficiency had no relative who was a suitable bone-marrow donor as determined by mixed-leucocyte-culture (M.L.C.) testing. In the general population an M.L.C.-nonreactive, unrelated donor was found among individuals who were identical with our patient at the Four locus. Following a bone-marrow transplant this child showed signs of rapid immunological reconstitution and only a mild graft-versus-host reaction. Unfortunately, the child died 31 days post-transplantation of cytomegalovirus infection. The findings support the hypothesis that matching for lymphocyte-defined antigens among unrelated individuals will permit successful immunological reconstitution.


Manipulation of brain serotonin in the treatment of myoclonus. The response of myoclonus to oral and intravenous L-5-hydroxytryptophan (5-H.T.P.) in combination with a peripheral decarboxylase inhibitor (carbidopa) and to clonazepam has been examined in 9 patients. Moderate improvement or complete cessation of myoclonus followed treatment with one or both of these regimens in 5 patients, 1 of whom also responded to the concurrent administration of L-tryptophan and a monoamineoxidase inhibitor. The remaining 4 patients were at best only slightly improved by either 5-H.T.P. or clonazepam. The responsive group consisted of 3 patients with a history of anoxia, 1 patient with non-history of severe head injury, and 1 patient with non-progressive focal myoclonus and epilepsy. This group had low levels of 5-hydroxyindole acetic acid in the lumbar cerebrospinal fluid. It is suggested that 5-H.T.P. plus carbidopa, L-tryptophan plus a monoamine-oxidase inhibitor, and clonazepam may all act by elevating brain levels of serotonin (5-H.T.) and that some human myoclonic syndromes may be specifically related to a cerebral deficiency of 5-H.T.


Integrator enzyme hypothesis for replication of hepatitis-B virus. A hypothetical model for the replication of hepatitis-B virus is presented. It is suggested that the D.N.A. polymerase associated with Dane particles facilitates integration of viral D.N.A. into the genome of the liver cell. The viral D.N.A. is then replicated with the host genome. The hypothesis accounts for certain curious experimental and clinical observations and makes several predictions which are amenable to laboratory investigation.


Aspiration cytology in breast cancer. Its relevance to diagnosis. Fine-needle aspiration cytology as a routine method in the management of breast disease was assessed in 237 patients presenting with a breast lump. The diagnostic accuracy of the method was 95.5% in both benign and malignant lesions. Fine needle aspiration is a safe procedure with an accuracy exceeding that of other diagnostic methods; it does not replace frozen-section histology but improves the management of breast disease by giving accurate preoperative diagnosis.


Safeguards for healthy volunteers in drug studies. Safeguards for healthy volunteers in drug studies have not been as strict as those involving patients. The shortcomings include the lack of surveillance over the scientific validity of the protocol and its ethical review, and over the financial inducements to volunteers. Recruitment is open to abuse because the volunteers may have some allegiance to the investigators. There is an urgent need to institute checks on these aspects. Most important, however, is the lack of legal safeguards for volunteers taking part in research done outside the pharmaceutical industry. The suggested procedure for obtaining consent, for health checks, and for providing compensation can be equitable to all concerned, and yet not restrict initiative, nor curtail research aims.


Inhaled corticosteroids compared with oral prednisone in patients starting long-term corticosteroid therapy for asthma. A controlled trial by the British Thoracic and Tuberculosis Association. Inhaled beclomethasone dipropionate and inhaled betamethasone valerate have been compared with oral prednisone in the treatment of 75 patients with asthma who were starting long-term corticosteroids for the first time. Both of the inhaled corticosteroids controlled asthma as well as did oral prednisone in those who had responded to therapy in the initial period of the trial. A daily dose of 400 mug of inhaled drug was approximately equivalent to 7-5 mg daily of prednisone. Prednisone suppressed the adrenal response to tetracosactrin, whereas the mean responses in the groups receiving inhaled corticosteroids did not change significantly from pre-trial values. The 30% incidence of other systemic unwanted effects of prednisone contrasted sharply with the low incidence (5%) of symptomatic oropharyngeal candidiasis in the patients receiving inhaled corticosteroids. In a sample of 19 patients no change in exfoliative cytology was detected over the period of the trial nor was there any evidence of fungal colonisation of the bronchial tree. There was no difference between the three treatment groups in the number of antibiotic courses prescribed. The persistent production of sputum made no difference to the response to inhaled corticosteroids. Patients not on sodium cromoglycate did as well in the trial as those receiving sodium cromoglycate. Both inhaled beclomethasone dipropionate and inhaled betamethasone valerate have advantages over oral prednisone in the maintenance treatment of patients with asthma, but in the management of exacerbations systemic corticosteroids will usually be needed as a supplement to inhaled therapy.


Idiopathic parkinsonism treated with bromocriptine. The efficacy and toxicity of bromocriptine, a drug which simulates dopamine, have been studied in twenty-eight patients with idiopathic parkinsonism. A double-blind, within-patient comparison between maximum tolerated doses of bromocriptine (mean 46-9 mg daily) and placebo revealed a substantial and statistically significant therapeutic response to the active drug. Adverse reactions were dose dependent, reversible, and similar to those encountered with levodopa. While taking bromocriptine fourteen patients were able to stop levodopa (with or without carbidopa); in five patients the dose of levodopa was reduced by 54% (mean). Eight patients could not tolerate bromocriptine; one patient failed to comply with prescribed adjustments of dosage.


Hepatitis-B antibody in polymyalgia Rheumatica. Thirteen patients with polymyalgia rheumatica (P.M.R.) were examined for evidence of viral infection. Hepatitis-B surface antibody (HBsAb) was detected in nine out of twelve patients tested prior to therapy. The antibody persisted up to six months in four patients but reverted to negative in the other five. HBsAb was found in only one of twelve age-matched controls. Hepatitis-B surface antigen was not detected in any patient or control. No significant elevation of antibody titre was detected to a panel of twelve other organisms. Immunoglobulin levels were elevated prior to treatment in several patients. With steroid therapy the IgG and IgA levels fell serially but the IgM levels increased in six patients. These results suggest that hepatitis B is an important trigger for P.M.R. In view of the association with giant-cell arteritis, P.M.R. may represent an abnormal immunological response to infection in elderly patients.


Association between cleft lip with or without cleft palate and prenatal exposure to diazepam. From 278 interviews of women who had infants with selected major malformations, a history of diazepam ingestion in the first trimester of pregnancy was found to be four times more frequent among mothers of children with a cleft lip with or without a cleft palate than among mothers of children with other defects. This association was one of many that was examined in the analysis; thus it is quite possible that it is simply due to chance. This report, however, is the second one linking diazepam to cleft lip with or without cleft palate. Until there are more data bearing on this question, this possible risk should be considered when prescribing diazepam for women in their reproductive years.


Antithyroid antibodies in Alport's syndrome. Two families in which more than two members had Alport's syndrome were examined. Serum-antithyroid-antibodies were found in all those with Alport's syndrome and some of their relatives. These included three cases of Alport's syndrome with nephritis and/or nerve deafness and two normal people who can be regarded as carriers of Alport's syndrome from one family, and one case of the syndrome with nephritis and deafness from the other family. One case of Alport's syndrome had symptoms of hypothyroidism, and biopsy specimens from another case were characteristic of chronic thyroiditis. The results indicate that serum-anti-thyroidantibodies, together with nephritis and deafness, are a sign of Alport's syndrome. The results accord with transmission of the syndrome as an autosomal dominant trait and suggest that Alport's syndrome may be caused by an immunological abnormality.


Bilateral Wilms' tumour. Age at diagnosis, associated congenital anormalies, and possible pattern of inheritance. A series of 87 patients with Wilms' tumour seen during the period 1960-73 included 11 (13%) with bilateral tumours. 6 patients presented with simultaneous bilateral tumours, 2 had tumours in each side of a horseshoe kidney, and 3 later developed a tumour in the remaining kidney. There was no reported familial incidence of Wilms' tumour. Maternal age at birth of the patients with simultaneous bilateral tumours was over 30 years in 7/8 cases. The average of patients with bilateral tumours was 15 months, whereas that of patients with unilateral tumours was 31/2 years. All the simultaneously occurring bilateral tumours and those within a horseshoe kidney were multifocal, whilst the sequentially occurring bilateral tumours and the unilateral tumours all developed as a single tumour mass within the affected kidney. Associated congenital anomalies were found in 5 (45%) of 11 patients with bilateral tumours, several of whom had more than one defect. Of 76 patients with a unilateral tumour, only 3 (4%) had congenital anomalies.


Type-IV hyperlipidaemia and weight-gain after maturity. Twenty men with mild to moderate type-IV hypertriglyceridaemia were compared with normal men of the same age in the Busselton population survey. The type-IV men were not heavier but they were 3-2 cm. shorter and relatively hyperuricaemic. When gives a reducing diet, mean weight declined from 76-8 kg. to 68-7 kg. over 4-4 months and was kept steady over the next 10 months at 67-6 kg. Before, immediately after, and in the 10 months after weight reduction serum-triglycerides were 273, 112, and 126 mg. per 100 ml. and serum-cholesterol was 245, 227, and 226 mg. per 100 ml., respectively. On entry the mean daily calorie intake was 3165 and the contribution of the various nutrients were characteristic of the Australian diet. At lower weight, daily caloric intake was 2335. Protein intake was unchanged, but intake of fat and especially carbohydrate declined significantly. The findings support the view that type-IV hyperlipidaemia is the expression of a metabolic defect brought to light by weight-gain after maturity. In susceptible subjects "normal" weight-gain may be sufficient to induce hyperlipidaemia. Since type-IV and type-IIb hypertriglyceridaemias appear to increase the risk of coronary heart-disease, it is concluded that ideally no weight should be gained after reaching maturity. Avoidance of weight-gain should materially reduce the incidence of coronary disease in affluent western communities. Reduction to truly ideal weight gives much more impressive therapeutic results than drug therapy.


Prelusive skin grafts in live-donor kidney transplantation. In recipients receiving oral azathioprine (50 mg. a day) the fate of skin grafts taken from live human prospective kidney donors correlates well with the outcome of kidney transplantation from the same donors. Correlation between the fate of skin grafts and HL-A serotyping is not nearly as good except in the case of complete HL-A identity. There is little or no correlation between the mixed-lymphocyte-culture test and the fate of skin grafts and the outcome of kidney transplantation. When the degree of compatibility does not exceed one haplotype the results of live human-kidney transplantation can be significantly improved if the fate of a preliminary skin graft from the prospective kidney donor is used as an index.


Shedding of infectious virus/antibody complexes from vesicular lesions of patients with recurrent herpes labialis. The concentration of herpes-simplex virus (H.S.V.) in the lesions of adults with recurrent herpes labialis was determined. On the 1st day the vesicle appeared, the fluid within the lesion contained 10(5-3) plaque-forming units (P.F.U.) of H.S.V./mul. By swabbing the surface of the lesions with a sterile pledget, 10(6-2) P.F.U. of virus was isolated from the inflamed labial mucosa. The amount of virus obtained from the labial surface decreased on the 2nd and 3rd day to 10(5-0) and 10(3-0) P.F.U., respectively. In two patients on immunosuppressive drugs, high concentrations of virus (greater than 10(4-0) P.F.U.) were obtained per swab for more than 3 weeks. The presence of infectious virus-antibody (V.A.) complexes in herpetic lesions was demonstrated by examining fifty-two isolates from twenty-eight patients at various times during the course of their disease. 71% of the patients had V.A. complexes in their lesions on the 1st day of the vesicular eruption, and by the 3rd day all of the lesions examined contained complexes. It is concluded that patients with active lesions shed high concentrations of virus and that natural infection may be transmitted by an infectious V.A. complex.


Fulminant hepatic failure in leukaemia and choriocarcinoma related to withdrawal of cytotoxic drug therapy. In three patients with malignant disease HBsAg was detected in the serum at least 6 months before the development of acute hepatitis type B, which in each case followed a fulminant course to death. It is suggested that suppression of the normal immunological responses to hepatitis-B viral antigens by cytotoxic drug therapy permitted widespread infection of hepatocytes. Subsequently, upon withdrawal of these drugs, recovery of immunocompetence resulted in rapid destruction of all infected hepatocytes and massive liver damage. Screening for HBsAg before cytotoxic drug therapy, careful monitoring of liver function during its withdrawal, and prompt treatment with corticosteroids should abnormalities occur may prevent this unfortunate sequence of events.


Mononucleosis-associated subacute sclerosing panencephalitis. Three cases of coincidental infectious mononucleosis (I.M.) and subacute sclerosing panencephalitis (S.S.P.E.) in children are reported. In two of the cases, I.M. preceded the appearance of S.S.P.E. symptoms. The other case of S.S.P.E. was associated with apparent mononucleosis encephalitis. All three patients died within 3 months of S.S.P.E. being diagnosed and had pathological changes characteristic of that disease and raised levels of measles antibody. Two of the patients had apparent T-cell-associated abnormalities which suggested a degree of I.M.-associated immunosuppression. The relation between the two conditions remains obscure.


Use of pertussis vaccine in an epidemic involving hospital staff. An epidemic of pertussis occurred among hospital staff caring for paediatric patients. Eight physicians and five nurses were affected. Pertussis developed in six newborn infants exposed to infected hospital staff in the nursery. Erythromycin prophylaxis was used to control the epidemic. Clinical pertussis developed in five adults infected with Bordetella pertussis before erythromycin was used, whereas symptoms developed in only one of the eight adults who became infected after erythromycin prophylaxis was started. Pertussis vaccine was given to adult volunteers in the hospital, and in 77% of two hundred and eighty-six vaccinees there was a fourfold rise in pertussis agglutinins. Local reactions were common, and in two vaccinees generalised rashes developed. One of these required treatment with corticosteroids. The risk of pertussis occurring in adults providing medical care for children should be recognised, and employees with symptoms should be removed from the hospital environment.


After the hospital episode.

After the hospital episode. A scheme by which clinical students follow, after discharge from hospital, the progress of patients for whom they have had responsibility in the ward supplements students' knowledge of the natural history of disease and emphasises the importance of communication and the use of community resources. By commitment to a patient and his problems for a long period, the student can take an active role in care and, in presenting his patient's progress, finds himself in the role of teacher.


Tubectomy by paraprofessional surgeons in rural Bangladesh. In Bangladesh, social as well as economic factors strongly favour the use of women over men; and of papaprofessionals over qualified physicians, for tubectomy surgery. Of 600 tubectomies carried out in three centres, 366 were performed by female paraprofesional workers with an average of only two months' part-time training in tubectomy surgerymthe rest were performed by qualified physicians. The infection-rate in tubectomies done by paraprofessionals was 5-5%; in those performed by physicians it was 6-4%. Comparison of other factors indicates that the results of paraprofessionals were in no way inferior.


Micrococcal urinary-tract infections in young women. In a prospective study in young women, novobiocin-resistant subgroup-3 micrococci were the second commonest cause, after Escherichia coli; of acute urinary infections. Proteus mirabilis was the only other causative organism. Symptoms, pyuria, or possible aetiological factors were the same in micrococcal and coliform infections. The infecting micrococcus "biotype" was only rarely found among the normal flora of the genitourinary tract of young women, though other micrococci and staphylococci were commonly present. Evidently, the infecting micrococci are selectively pathogenic in the urinary tract. Micrococcal infections, like coliform infections; commonly followed sexual intercourse, but there was no evidence that the micrococci were sexually transmitted. The infecting biotype was rarely found in the male urethra or prepuce.


Association of amyloidosis with erythema nodosum leprosum reactions and recurrent neutrophil leucocytosis in leprosy. Rectal biopsy in 190 inpatients at a leprosy hospital in the Highlands of Papua New Guinea disclosed 16 patients with secondary amyloidosis. This represented 20% of the patients who had had polar lepromatous leprosy (L.L.) for more than 2 years. Patients with amyloidosis characteristically had either a history of recurrent attacks of erythema nodosum leprosum (E.NH) reactions or chronic trophic ulcers. Levels of the serum component (protein SAA) antigenically related to the amyloid fibril protein AA were monitored, at varying intervals for three months, in lepromatous patients with E.N.L. reaction. The SAA levels rose during E.N.L. reactions in parallel with the neutrophil count. SAA occurred with greatest frequency among patients with LH, while most non-lepromatous patients with detectable SAA had chronic trophic ulcers. The correlation between raised neutrophil count and elevated SAA concentration, observed in this and other studies, suggests that neutrophils are associated with the production of SAA.


Thyroid function in the long-term follow-up of patients treated with iodine-131 for thyrotoxicosis. In February, 1972, 58% of patients euthyroid after iodine-131 therapy for thyrotoxicosis between 1954 and 1966 had a raised plasma thyroid-stimulating-hormone (T.S.H.) (greater than 7-4 mU/l) and 42% a normal T.S.H. level. A group of 69 of the euthyroid patients with a raised plasma T.S.H. (25-0 +/- 2-0 mU/l) in 1972 was re-examined annually for three years. There was no apparent change in the mean plasma T.S.H. level between 1972 and 1975 in the patients remaining euthyroid, but overt hypothyroidism developed in 3 patients in 1973, in a further 3 patients in 1974, and in 1 patient in 1975. In contrast, none of a group of 61 patients, euthyroid with a normal plasma T.S.H. (4-0 +/- 0-2 mU/l) in 1972, developed overt hypothyroidism over the next three years, although slightly raised T.S.H. levels were recorded in 3 patients in 1974 and in a further 6 patients in 1975. Both the mean serum T-4 and T-3 in the euthyroid patients with a raised plasma T.S.H. were significantly lower, but still in the respective normal ranges, than those in the euthyroid patients with a normal plasma T.S.H. No significant difference in the fasting serum-cholesterol or triglyceride levels could be demonstrated between the two groups. Since no patient with a normal plasma T.S.H. after iodine-131 treatment for thyrotoxicosis six to eighteen years earlier developed overt hypothyroidism over a three-year period, the follow-up of such patients need not be so frequent as that of similarly treated euthyroid patients with a raised plasma T.S.H. in whom overt hypothyroidism develops at the rate of 2-5% per year.


Liver damage after paracetamol overdose. Comparison of liver-function tests, fasting serum bile acids, and liver histology. 54 patients have been studied after paracetamol (acetaminophen) overdose. Liver-function tests and fasting serum bile-acids were measured daily; liver biopsy was done in all cases, and slides were examined "blind" to assess liver damage. The plasma-paracetamol was measured on one occasion. A histological abnormality was present in the livers of 53 of the 54 patients, and was minor in 23, moderate in 16, and severe in 14. In 6 patients with moderate and 18 with mild histological abnormality liver-function tests were normal. A serum-aspartate-aminotransferase above 400 units/1 was always associated with severe histological liver damage. Fasting serum bile-acids were raised in 51 of the patients with abnormal liver histology; the serum-bile-acid seemed to be a more sensitive indicator of mild liver-cell damage than was the transaminase level. There was, however, little correlation between increase in bile-acid concentration and the degree of histological abnormality. As a result of these investigations empirically determined levels of plasma-paracetamol have been drawn which give a guide to the likelihood of liver damage after paracetamol overdose.


Increased urinary excretion of albumin, light chains, and beta2-microglobulin after intravenous arginine administration in normal man. Infusion of 60 g of arginine in six healthy men over a 40-50 min period caused a 16-fold increase in the excretion-rate of albumin from 8-6 to 142-4 mug/min. After injection of 3, 6, 9, and 12 g of arginine the mean albumin-excretion rate of another six normal subjects rose from 5-8 mug/min to 9-4, 13-2, 21-6, and 33-9 mug/min, respectively. Excretion of light chains of immunoglobulin increased from 5-5 mug/min to 18-0, 30-0, 40-5; and 52-0 mug/min, respectively, and the excretion rate of beta2-microglobulin increased from 0-092 mug/min to 2-97, 9-23, 16-39, and 25-71 mug/min. Thus a clear dose response pattern was found. The results strongly suggest that the mechanism behind the arginine-induced protein excretion is an inhibition of tubular reabsorption.


Treatment of primary melanoma by intralesional vaccinia before excision. The results of treatment of two groups of patients with primary melanoma are compared. 25 patients in group 1 were treated by wide local excision of the primary melanoma, and 23 in group 2 were treated by vaccination with live vaccinia virus 14 days before wide local excision. Vaccination exerts a favourable effect on the course of melanoma both in terms of survival and prolongation of the interval between treatment of the primary lesion and subsequent development of metastases.


Evidence for abnormality of bone-matrix proteins in osteogenesis imperfecta. Immunological and biochemical techniques demonstrated that the non-collagenous proteins of the organic matrix of bone were abnormal in quantity and composition in four children with osteogenesis imperfecta. This represents the main molecular difference found so far between bone in osteogenesis imperfecta and normal bone.


Staphylococcal food poisoning aboard a commercial aircraft. On Feb. 3, 1975, 196 (57%) of 344 passengers and 1 steward aboard a commercial aircraft contracted a gastrointestinal illness characterised by nausea, vomiting, abdominal cramps, and diarrhoea; 142 passengers and the steward were admitted to hospital. Symptoms developed shortly after a ham and omelette breakfast had been served. An investigation strongly incriminated ham as the vehicle of the outbreak, and the source seems to have been a cook with lesions on his fingers. The attack-rate was 86% for passengers who ate the ham handled by this cook and 0% for passengers who ate ham handled exclusively by another food preparer. Before being served, the ham and omelette had been held at room temperature for 14 h and at 10 degrees C (50 degrees F) for 14 1/2 h Specimens of stool and vomitus from ill passengers, left-over food, and the finger lesions of the cook were positive for Staphylococcus aureus of identical phage types and antibiotic sensitivities. Preformed enterotoxin was detected in the left-over ham and omelette. This outbreak re-emphasises that people with infected lesion should not handle food and that foods must be stored at temperatures low enough to inhibit the growth of bacteria. To ensure against a common foodborne illness incapacitating the entire flight crew, cockpit crew members should eat different meals prepared by different cooks.


Clinical aspects of outbreak of staphylococcal food poisoning during air travel. An outbreak of staphylococcal food poisoning among 364 charter-flight passengers and crew members is described. Symptoms appeared just before landing, about an hour after a meal containing contaminated ham had been served. 143 passengers were admitted to hospital. 1 patient developed acute anuria and 1 had hemiplegia and aphasia; both recovered. Fever and bloody stools were recorded with unusual frequency.


M.L.Q.: a supplement to M.C.Q.

M.L.Q.: a supplement to M.C.Q. A method of testing candidates' ability to recall and manipulate factual information is described. It comprises the insertion of a term which forms a logical link between two other, given, terms and probably tests higher cognitive attributes than do multiple-choice questions. This method seems to discriminate quite reliably between good and poor candidates.


Demonstration of cytoplasmic actomyosin fibrils by the freeze-etching technique. Cytoplasmic actomyosin fibrils of Physarum polycephalum were demonstrated by the freeze-etching technique. Within the fibrils the electron micrographs reveal 40-80 A thick filaments presumably representing F-actin. Thicker filaments (myosin) could not be detected. To avoid freezing artefacts, a pretreatment of the living material with 50% sucrose was necessary. The influence of freeze-protecting agents upon the fine structure of cytoplasmic actomyosins and the resulting difficulties in the investigation of constituents of the groundplasm with the freeze-etching technique are discussed.


Anomalous refractivity changes of gramicidin A in ethanol solutions. Studies of the refractive properties of Gramicidin A in absolute ethanol and in ethanol water mixtures showed that this peptide in solution undergoes a conformational transition resulting in species with different refractivity. Accordingly, the folded form of this peptide shows a lower specific refractive index increment than the unfolded form. In addition, the occurrence of a strong pressure dependence of the transition is documented.


[Medical considerations on the treatment of metastasizing mammary carcinoma (author's transl)]. The routine therapy of metastasizing mammary carcinoma at the present time is reported. The course of the treatment is considered in every case in connection with the mental problems of the patient which are partly caused by the often drastic treatment measures carried out. The methods of local radiation therapy, which is combined with ablative hormonal methods or, in cases of progressive metastasization, with added exogenous hormones, estrogens, androgens or anabolics, is explained in detail. The final part of the paper is devoted to the currently used polychemotherapy which replaces the hormonal methods in progressive metastasization.


Integration of viral genomes.

Integration of viral genomes. DNA transcripts of infectious RNA viruses were found to be integrated in the DNA of chronically-infected tissue cultures.  DNA sequences homologous to RNA of measles virus were found in tissues affected with systemic lupus erythemotosus.  These data open up a new class of virus-cell interaction that may be a result of cooperation between infectious and oncogenic viruses.


Biodegradation of alpha-hexachlorocyclohexane. IV. The extent of degradation of single doses in vivo. 1. Urine and stools were collected daily of 4 adult rats kept in single cages and injected once i.p. with alpha-hexachlorocyclohexane (alpha-HCH; dose per animal 126-150 mumoles), labelled uniformly with 14-C (10.8-14.0 X 10(6) dpm per animal). 2. In 4 weeks, 65% of the label was excreted through the kidneys and 16% by way of the intestine, with an estimated 8% being retained in depot fat. 3. GLC-analysis of the pooled urine showed it to contain very little unchanged drug, on average 0.05% of the dose. The time-course of the renal excretion of 14-C-labelled substance corresponded rather closely to the excretion of organically bound 36-Cl seen in earlier experiments with 36-Cl-labelled drug, indicating that the majority of urinary metabolites, presumably, still bear chlorine. 4. All or nearly all of the faecal 14-C was found by GLC to be accounted for by the stool's content of unchanged alpha-HCH. 5. Taken together, the results indicate a mean extent of alpha-HCH-degradation in the rat in the order of 80-85% of a dose. 6. Two rats were given 400 mg/kg of "cold" alpha-HCH by mouth 4 days before i.p. application of 14-C-labelled drug and were found to excrete more label through the kidneys in the first week than did the non-pretreated rats. This indicates that the drug stimulates its own degradation.


Biodegradation of alpha-hexachlorocyclohexane. V. Characterization of the major urinary metabolites. 1. Free 2,4,5- and 2,4,6-trichlorophenol (TCP) have been identified by co-crystallization with authentic carrier as constituents of the urine of rats given 3-H-labelled alpha-hexachlorocyclohexane (alpha-HCH). The two TCP's constituted 7% and 63%, respectively, of the free phenol fraction which was found to account for less than 5% of all urinary metabolites. 2. 75% of the label contained in the urine of rats collected for four weeks after an i.p. dose of 14-C-alpha-HCH could be extracted into an organic solvent after alkaline and acid hydrolysis. The radioactive material thus extracted was examined by TLC and GLC. It is shown to consist mainly of chlorophenols and chlorothiophenols. 3. The extracts' major constituent was 2,4,6-TCP. Its amount was determined by GLC and was found to account for, on average, 45% of the total urinary metabolites. In conjunction with other evidence, this is considered to establish 2,4,6-TCP as the major product of alpha-HCH-biodegradation in the rat. 4. Chromatographic evidence is presented for 2,3,4,5-tetrachlorophenol and 2,4,5-TCP being other components of the chlorophenol fraction isolated from hydrolysed urine. 5. The amount of label associated with the chlorothiophenol fraction suggests a pathway involving endogenous thiol to be of significance in alpha-HCH-biodegradation in rats. Pretreatment with the drug itself increased the proportion of label associated with the fraction.


The utilization of adenosine triphosphate in rat mast cells during histamine release induced by anaphylactic reaction and compound 48/80. The ATP content of rat peritoneal mast cells has been studied in relation to histamine release induced by compound 48/80 and antigen-antibody (anaphylactic) reaction in vitro. When the ATP content of actively sensitized mast cells was reduced to different levels by oligomycin, a good correlation was obtained between the ATP levels and the amounts of histamine released by the anaphylactic reaction. A similar linear relation has previously been demonstrated between the ATP levels of mast cells and histamine release induced by compound 48/80. The ATP content of mast cells was also studied at different intervals after the exposure of the cells to antigen or compound 48/80. No significant change in the ATP content was observed in untreated mast cells during the short period when histamine release occurs. If, however, the mast cells were preincubated with oligomycin or 2-deoxyglucose to reduce the rate of ATP synthesis while a large part of the histamine release remained unaffected-a decrease in the ATP content could be demonstrated in close time relation to both anaphylactic and compound 48/80-induced histamine release. The observations indicate an increased utilization of ATP in mast cells during the release process.


Treatment of hyperthyroidism in pregnancy with propylthiouracil and methimazole. Twenty-one women were studied who had received propylthiouracil or methimazole during 26 pregnancies. Four of the infants had a goiter at birth, and 3 of these had neonatal thyrotoxicosis. In 2 children neonatal thyrotoxicosis was not evident at birth because of maternal antithyroid therapy. Five children had congenital defects. Two mothers were responsible for 4 of the children with abnormalities, and both mothers had been treated with thiourea drugs for long periods, ranging from 7 to 11 years. The majority of children who are exposed to these drugs in utero appear to have no subsequent ill effects. However, prolonged therapy with these agents may be undesirable.


Evaluation of carcinoma of the cervix using 111In-bleomycin. Indium-111 attached to bleomycin is useful in the scintigraphic localization of a variety of tumors. Since it does not normally accumulate in bowel and feces, it is superior to other radiopharmaceuticals, such as gallium-67 citrate, in the demonstration of abnormalities in the abdomen and pelvis. Twenty-eight patients with know carcinoma of the cervix were studied with whole body 111In-belomycin scans. Two "false-positive" scans were produced by local inflammation. Six "false-negative" scans were attributed to small tumors escaping scintigraphic detection. In the remaining 20 patients, scan findings correlated well with site and extent of the tumor as determined by other means. 111In-bleomycin scintiscanning may prove to be a highly useful adjunct in the evaluation of patients with carcinoma of the cervix.


Enhancement by hydrazine sulfate of antitumor effectiveness of cytoxan, mitomycin C, methotrexate and bleomycin, in walker 256 carcinosarcoma in rats. Use of hydrazine sulfate potentiates the antitumor action of Cytoxan (cyclophosphamide), Mitomycin C, methotrexate and bleomycin against Walker 256 intramuscular carcinosarcoma in in vivo short-term studies in rats.  Experimental data suggest this potentiation by hydrazine sulfate to result from a mechanism of action other than direct cytotoxicity, and further, that combination chemotherapy with hydrazine sulfate and a cytotoxic agent may be useful in the treatment of human cancer.


Apocrine mixed tumour of the lid.

Apocrine mixed tumour of the lid. The clinical features and pathological characteristics of a case of apocrine mixed tumour, a rare sweat gland neoplasm located in the lid, are described.


Alpha globulin intracytoplasmic hepatocyte globules in round heart disease in turkeys, visualized by immunofluorescent technique. The intracytoplasmic hepatocyte globules described in round heart disease of turkeys were found by immunofluorescent technique to contain alpha globulins. The diagnostic value of this method is discussed.


Effect of inositol, lecithin, vitamins (B12 with choline and E), and iodinated casein on induced fatty liver-hemorrhagic syndrome in laying chickens. Egg production, liver lipid, and liver hemorrhagic score were not significantly altered by diets that contained inositol (at 1 or 2 g./kg. diet) and fed ad libitum, or force-fed to S.C. White Leghorn hens to produce fatty liver-hemorrhagic syndrome (FLHS). FLHS was not prevented by lecithin, iodinated casein alone or with inositol. The vitamins B12, choline and E appeared to reduce FLHS and liver lipid in the one group tested. The dose-response relationship between feed intake, liver hemorrhagic score and liver lipid content was again demonstrated.


Neoantigens of the membrane attack complex of human complement. The membrane attack complex of complement is a fusion product of five complement proteins: C5b, C6, C7, C8, and C9. The complex causes complement-dependent cell membrane damage. It is assembled following complement activation both on the target cell surface and in the fluid phase. The isolated soluble complex, which has a molecular weight of one million, exhibited reduced expression of the antigenic determinants of the native precursor proteins. Antisera produced to the intact complex contained antibodies to neoantigens which were not detectable on the five precursor proteins. Antisera were rendered neoantigen-specific by adsorption with fresh human serum. Since the adsorbed antisera precipitated the complex, the complex must contain multiple neoantigenic sites. The complex-specific antibodies not only reacted with the soluble complex, but also with the target cell-bound membrane attack complex.


Inhibition of 4,alpha-dimethyl-m-tyramine (H 77/77)-induced hypermotility in rats by single and repeated administration of chloropromazine, haloperidol, clozapine and thioridazine. The effect of H 77/77 (5 mg/kg s.c.) on motility of rats kept in a familiar cage was investigated. H 77/77 produced hypermotility, which was reduced by oral pretreatment with chlorpromazine, haloperidol, clozapine and thioridazine. The 4 neuroleptics were administered acutely and for a 14 day period. H 77/77 was given 30 min after the single or last dose of neuroleptc (chronic treatment) condition. After both single and repeated administration the neuroleptics showed H 77/77-antagonism in doses ranging from 0.1-2.0 mg/kg. The effect on H 77/77 activity did not change significantly after repeated treatment. Clozapine and thioridazine, which clinically produce only minor extrapyramidal side effects, exert a weak effect or none at all in tests commonly used for neuroleptic activity. These 2 neuroleptics were potent H 77/77-antagonists. Inhibition of H 77/77-hypermotility may possibly be used as a test for neuroleptics.


The reflex sympathetic dystrophy syndrome. A comprehensive analysis using fine-detail radiography, photon absorptiometry, and bone and joint scintigraphy. Nine patients with reflex sympathetic dystrophy were examined. Clinical manifestations suggesting arthropathy were supported by radiographic demonstration of juxta-articular and subchondral bone erosions and by radionuclide demonstration of increased activity localized in the joint regions. Aggressive demineralization was demonstrated by fine-detail radiography and consisted of endosteal and intracortical excavation and subperiosteal and trabecular bone resorption. A one-third reduction in bone mineral was confirmed by quantitative analyses. Newer modalities of study have aided in the documentation of arthropathy in reflex sympathetic dystrophy and have helped in defining the patterns of aggressive bone resorption.


More effective devices for teaching undergraduate radiology. Two effective methods of teaching radiology to medical students are described. The Rotating Exhibit and Matching Displays methods allow students to master film facts by themselves and provide contact with the teaching radiologist for discussion of the film findings. Elements of participation, entertainment, variety, and discovery are features of these teaching techniques which supplement self-instructional methods.


[Economical surgery, bronchial or pulmonary, in the treatment of lung cancer]. In the present uncertainty as to the relative importance of maximum radical resection, surgical treatment of bronchial carcinoma should be guided by the state of cardio-pulmonary function and quality of survival.  In borderline cases, therefore, consideration should be given to economic resection, either parenchymal or bronchial.  Surgery was performed for bronchial carcinoma in 369 cases between 1963 and 1974, involving 30 segmental resections and 26 bronchial sleeve resections.  Favourable results are reported for the curative operations, whereas the results of palliative resections show low mortality but unfavourable longterm survival.


Rat and rabbit response (in relation to age) to inhalation of automobile exhaust fumes. Rats of two age groups, of 119 and 163 g mean body weight, were exposed for three and thirty days, respectively, to automobile gases diluted with air. In addition, rabbits, of 1.88 kg mean body weight, were exposed for twenty-four days. The conditions of exposure were kept nearly constant as related to the concentration of CO in the chamber. The following determinations were performed: (1) Body weight measurements as evidence of growth of the animals; (2) The number of alveolar macrophages (AM) in the lung washings; (3) Damage to the integrity of the cytoplasmic membrane of AM; (4) Glucose-6-phosphate dehydrogenase activity (G6PD) in AM; (5) The acid-base balance in the capillary blood of the rabbits. The results of the 30-day exposure show that automobile exhaust gases significantly inhibit the growth of both age groups; with significant body weight losses in the older animals from the 16th day of exposure. The number of AM was elevated in both groups. The activity of G6PD increased in the AM of the younger animals and decreased in the AM of the older as compared with the controls. The number of dead AM was higher in the older than in the younger rats. After the three-day exposure, no significant difference was found in the number of AM washed from the lungs of both exposed groups, compared with the controls. However, G6PD activity and the number of viable AM in the older animals were decreased and the percent of dead phagocytes was significant. The opposite effect was seen in the younger group. Alterations of lung tissue structure in the exposed animals were apparent to the naked eye. Acid-base response showed metabolic and respiratory disturbances as evidenced by the decrease in carbon dioxide tension (PCo2), the rise of hemoglobin by the reduction of pH level and by the base excess (BE). The inhibition of the growth of the rabbits was noted. The intra- and extrapulmonary effect of automobile exhaust gases after inhalation was observed as a complex of disturbances of the fundamental metabolic processes in the organism. The gases affected the cells of lung defence-alveolar macrophages and their biosynthetic activity.


[Regional chemotherapy of stomach cancers]. Fifty patients with a stomach cancer received regional chemotherapy by infusion. Two kinds of cancers were treated with this technique: cancers inaccessible with usual surgical treatment and some limited cancers. In most cases, the catheter was introduced by transcutaneous puncture of axillary artery. According to the site of the cancer, the extremity of the catheter was introduced into the left gastric artery, hepatic artery or coeliac trunk. Efficiency of the infusion was checked by arteriography and by gastric fibroscopic examination with intra-arterial injection of evans blue. The duration of the treatment was two weeks or three weeks. The chemotherapy was made on a sequential method, taking account of the tumoral cellular cycle. The results show an objective response in 80 per cent of the cases, 39 per cent of the non operable cancers were later accessible to surgery. This study shows that chemotherapy should be used in the treatment of any stomach's cancers before surgical treatment.


Cromolyn sodium in the treatment of asthma: its effectiveness and use. Thirty-six asthmatic children received placebo and cromolyn sodium, a new drug, in a double-blind crossover study; the majority were not using corticosteroids. Significant decreases in wheezing, breathlessness at rest, and cough occurred when the active drug was compared to placebo. Marked preference for cromolyn over placebo was expressed at the end of the study. Our results agree with previous reports on the effectiveness of cromolyn sodium. We found this drug to be especially useful as an adjunct to other treatment in the control of asthmatic children.


Cardiovascualr changes with acute subdural hematoma. Of 100 consecutive patients with acute subdural hematoma, 53 survived. Blood pressure and heart rate changes were not reliable indicators of increased intracranial pressure or cerebral disaster. Electrocardiographic changes in these patients were dramatic. Forty-one patients developed a new cardiac arrhythmia. Increased intracranial pressure and brain lesions adversely affect the heart. These effects must be recognized and appropriately treated.


[ Immunoelectrophoretic study of salivary proteins]. The proteins in saliva samples from 60 individuals (subdivided into three age groups) were analysed immuno-electrophoretically to reveal possible relationships with periodontal disease and caries. No such relationship was established with regard to caries. In subjects with periodontal inflammation transferrin and haptoglobin were twice as frequent as in control individuals, which is indicative of a correlation with the inflammatory process. Multiple IgA and IgG bands were detected in saliva samples from elderly subjects. Incidentally, IgM was absent in saliva samples from 10-year-old children, which was in contrast to the results obtained for serum samples.


[Lysosome-like alpha-granules of thrombocytes: detection by acridine orange treatment, properties and transformations during the course of blood coagulation reactions]. Using the ability of lysosome-like alpha-granules of thrombocytes to accumulate flurochrome acridine orange, their transformation kinetics was studied in the course of cell viscous metamorphosis utilizing the fluorometric technique. It turned out that during the thrombin induced cellular viscous metamorphosis lysosomes released their contents: the process is stimulated by the presence of extracellular Ca2+. Competitive relations were revealed between the accumulation within cytoplasmic granules of thrombocytes of acridine orange and serotonin, and that of histamine and novocaine. The process of fluorochrome accumulation was found to be temperature dependent and to be inhibited by monoiodacetate.


[Biochemical and cytospectrophotometric analysis of the extraction of RNA from spinal cord cell structures]. By means of two-wavelength spectrophotometry, according to Tsanev and Markov, a stability of RNA content has been demonstrated in rabbit spinal cord sections treated with cold perchloric acid: it was only after 18 and particularly 48 hr incubation of the section in a 16% perchloric acid solution that the total tissue RNA began to be extracted. Cytospectrophotometrical study of the motoneurons of spinal cord anterior horns and perineuronal glial cells in gallocyanin -- chrome alum stained sections has shown a rapid loss of RNA under effect of the cold perchloric acid: as early as after a 2 hr treatment, about 2/3 of the whole cellular RNA was extracted from the motoneurons, while about 1/2 from their glial satellite cells. Hydrolysis of the rest of RNA was found out in the neurons and in the neuroglia only after a 18 hr extraction with the perchloric acid. Similarities and differences in the features of neuronal and glial RNA are discussed.


Candicidin: physiologic effect on prostate. In a double-blind study, candicidin therapy resulted in over-all clinical improvement of benign prostatic hypertrophy symptoms in 78.1 per cent of treated patients compared with 10 per cent for patients given a placebo. Histologic review of prostates of candicidin-treated patients showed more stroma relative to the epithelium. The epithelium was less active with more cuboidal than columnar cells. There were fewer papillary infoldings, and the epithelium contained more true cysts than did the prostates of patients given a placebo. Urinary testosterone, 17-ketosteroids, 17-hydroxycorticosteroids, and serum androgen, follicle-stimulating hormones, and corticosteroid levels ramained within normal values with candicidin therapy.


Early removal of catheter after transurethral prostatectomy. A prospective study of 100 patients with benign prostatic hypertrophy treated by transurethral prostatectomy with catheter removal as soon as possible after surgery was carried out. The results were compared with a retrospective review of 100 similar cases treated by long-term catheter drainage. Incidence of retention requiring recatheterization was equal (5 per cent versus 6 per cent); incidence of secondary hemorrhage was increased by early catheter removal (6 per cent versus 13 per cent); postoperative hospital stay was decreased by 50 per cent (8.2 versus 4.0 days); and patient comfort and acceptance were improved markedly.


Alpha fetoprotein determinations in germ cell tumors of testis. Alpha fetoprotein was demonstrated in 15 of 115 patients with histologically proved germinal testicular neoplasms. Alpha fetoprotein was detected in patients only with embryonal carcinoma and teratocarcinoma; determinations were negative in all cases of pure seminoma, teratoma, and choriocarcinoma. Of 15 patients having detectable alpha fetoprotein, 14 had Stage III disease and one had Stage II disease. When alpha fetoprotein is present, it usually heralds progression of the disease and therefore may serve as a valuable biologic marker to monitor response to therapy.


The multiple mixed lymphocyte reaction: variables important in the test as a measure of lymphocyte competence in man. In order to utilize the mixed lymphocyte reaction (MLR) as an assay of T-lymphocyte competence, pools of target lymphocytes obtained from different individuals are used to increase the magnitude and decrease the variation of the in vitro response.  We evaluated variations in MLR response due to  variations in target cell populations.  Response increased with an increased target/responder cell ratio.  Peak response occurred with a target/responder cell ratio of between 1:1 and 1:4.  Response to a pool of lymphocytes from different individuals increased as the number of individuals contributing to the pool increased.  Peak stimulation occurred with three to four different donors to the target cell pool.  Stimulation produced by pooled target cells resulted in a higher mean index of stimulation and decreased variation of response as compared to stimulation  produced by target cells from individual donors.  Stimulation produced by pooled target cells was approximately equal to the sum of the stimulation produced by each of the target cell populations acting alone.  These findings indicate a practical method of modifying the MLR as a test of T-lymphocyte function.


[Demonstration of immunoglobulin determinants on lymphocyte surfaces by membrane immunofluorescence]. Isolated lymphocytes from peripheral blood of 22 healthy donors were examined with the help of the indirect membrane immunofluorescence (MIF) for immunoglobulin determinants on the surface of the cells. The quantity of MIF+-cells for IgM was on the average 8.7% (3-18) and for IgG 15.5%(8-18). Five different anti-IgM-sera were characterised with regard to their use in the MIF (precipitation titre, entire protein content, content of anti-IgM-antibodies). Differences in the quantity of the MIF+-lymphocytes were above all based on differing antibody concentrations of the sera. It was referred to further possible causes for these differences. The influence on the results of the examinations by protein addition and trypsination.


[Drug therapy of myocardial infarct in ambulatory practice]. For the practicing physician the medicamentous treatment of the patients with infarction is the main problem of the secondary prevention in the prehospital phase as well as in the after-treatment. In these cases in the acute phase not the myocardial insufficiency is in the centre of the out-patient care, but the therapy of the disturbances of cardiac rhythm, which mainly cause the high lethality in the early phase. Therefore, uncomplicated infarctions, in whch care must be taken only for a sedation of sympathico-adrenergic reactions and a volume reduction of the heart, should be differed from complicated cases. However, an immediate transport to the hospital must be guaranteed. If there appear a contraction insufficiency of the left ventricle or threatening disturbances of the rhythm, additionally glycosides and saluretics must be administered as well as an aimed antiarrhythmic therapy must be initiated. The necessary medicamentous measures are described dependent upon the diagnosis of brady- and tachycardiac disturbances of the rhythm. The author enters briefly the problems of volume substitution, treatment of acidosis as well as the administration of beta-sympathicolytics and gluco-corticoids. - In the after-treatment of infarctions anticoagulants are the only medicaments to be prescribed, when findings completely without complications are present. If, however, there are signs of activity of the coronary heart disease in the post-infarction phase, a basic therapy with a glycoside and anticoagulants as well as an individually to be varied additive therapy with nitro-preparations, beta-sympathicolytics, saluretics, anti-hypertensive agents and antiarrhythmic agents are necessary.


[Accident during local anesthesia in a patient with antiarrhythmic therapy]. A side reaction of antiarrhythmic treatment in a 18-year-old patient with congestive cardiomyopathy is reported. During treatment with high doses of aprindine cerebral convulsions occurred. After ceasing the medication temporarily, a pacemaker revision was done in local anesthesia. Cerebral convulsions reappeared after injection of the local anesthetic. The patient died due to cardiac arrest. It is discussed that some amount of the local anesthetic agent (mepivacaine) was absorbed from the tissue elevating the blood level of local anesthetic drugs (aprindine and mepivacine) into the toxic range, thus producing cerebral convulsions, augmenting the stimulation threshold and depressing the automaticity of the heart. It is urged that antiarrhythmic treatment should be stopped before local anesthesia will be performed.


[A new method of transseptal levocardiography]. Perforations of the left atrial or ventricular wall and extravasations of contrast medium during transseptal left heart catheterization or angiocardiography can be eliminated by replacing the routinely used transseptal catheters with Pigtail-catheters. With 2.8% minor complications without sequelas in 181 successful studies, transseptal angiocardiography of the left heart through Pigtail-catheters is not only less hazardous than injections through the transseptal catheters employed up to now, but bears even less risk than direct retrograde injection into the left ventricle. To show the left atrial cavity and the mitral valve, transseptal left atrial injection is the method of choice. For quantitative angiocardiography to evaluate left ventricular function, transseptal angiocardiography with injection into the left atrium is superior to retrograde direct ventriculography in our experience, as ventricular ectopic beats were absent and supraventricular ectopic beats as rare as 5% of the cases, local disturbances of wall motion during injection could be avoided and 1 or 2 more cycles could be evaluated before the depressant effect of contrast medium started.


[Myelin sheath staining (author's transl)]. In Loyez-Woelcke's myelin sheath staining the author studied the effect of the tanning time, that of the ripening grade of hematoxylin as well as the effect of the staining time.  In case of a determined staining time a certain proportion must be present between the ripening grade (or the quantity of the oxidizing agent added to the solution to enhance ripening) and the quantity of the alkalizing agent. On the other hand the absolute quantity of the two substances has only little influence on staining.  A neutral red staining was found efficacious to demonstrate cell nuclei and Nissl substance.


[Sensitization against the antigens of the brain after experimental vaccinia infection. I. Evidence for cell-mediated immune response to brain-antigens (author's transl)]. Vaccinia virus infection was performed by scarification of the shaved skin (5 times 5 cm2) on the back of Pirbright guinea pigs. The macrophage migration inhibition test was performed with peritonealexudate cells 7, 11, 14 and 21 days after infection. Macrophage migration inhibition occurred after exposure of the cells to whole brain tissue antigen on the 7th, 11th, 14th day after infection (s. table 1). Lymphocyte transformation responses were examined by 14C-2-Thymidin uptake using blood cultures and basic encephalitogenic protein and whole brain tissue extract as antigens. A positive transformation response could be demonstrated from one to 8 weeks after infection (s. table 2). The specificity of the transformation response to brain antigen was established using control cultures stimulated with PHA or PPD. In no case stimulation occured with PPD. Stimulation with PHA was not altered. On the other hand the spontaneous lymphocyte transformation was enhanced at one week after infection and lymphocyte cultures exposed to heat inactivated vaccinia virus showed transformation from the 3th week after infection until the end of the observation period (i.e. 8 weeks) (s. table 2). The reason why cell mediated hypersensitivity to brain antigen is induced following vaccinia infection remains unknown. The most probable among several possible mechanisms seem a) the induction of virus-specific antigens on the surface of infected cells or b) the release of brain specific antigen through virus infection.


[Biochemical differentiation between N. sicca and N. perflava (author's transl)]. Neisseria sicca forms an iodine-positive metabolic product when grown on Trypticase soy agar without the addition of sucrose. This reaction which does not occur with N. perflava may be useful for differentiating between the two species.


[Growth and lipopolysaccharide content of salmonellae grown in submersed cultures according to the batch-method. 2. Communication: influence of growth phases on lipopolysaccharide synthesis (author's transl)]. The paper describes cultivations of 4 Salmonella S-forms and 1 SR mutant, performed in complex medium under constant conditions of temperature, pH and aeration. The experiments show that lipopolysaccharide (LPS) biosynthesis underlies quantitative differences with the growth phases, resulting in changes in the LPS content of the cell masses. During the exponential phase a decline takes place in the percentage of LPS contained by the 4 S-forms. In addition, in the phase of delayed growth acceleration, 3 of these strains exhibit temporary, complete stagnation in LPS formation. When the cultures enter the stationary phase, LPS biosynthesis also discontinues. The SR-mutant differs from the S-forms especially in that the rate of LPS synthesis and with it, the percent lipopolysaccharide content of the cells, increase greatly in the exponential growth phase. The causes and effects of the changes observed are discussed.


[Sensitization against the antigens of the brain after experimental vaccinia infection. II. Humoral anti-brain antibodies and morphological changes in the CNS (author's transl)]. 29 guinea pigs, strain Pirbright, were infected with vaccinia virus, strain Elstree, by the dermal route. The observation period was 14 days. Thereafter, the animals were killed and their central nervous systems (CNS) histologically and immunohistologically, the blood fluorescence-serologically examined. Histological examination revealed meningitis, ependymitis or disseminated meningoencephalitis with slight perivascular cuffing in 72% of the animals. The viral antigen was found in 3 animals (10%). It was present most often in the cytoplasma of the arachnoidal and/or ependymal cells, as well as in the cells of the vessel walls and less often in the glial and/or nerve cells. The infected cells showed no severe degenerative changes. The blood-brain-barrier displayed localized disturbances. The examination of the myelin sheaths revealed disseminated foci of disappearance of myelin fluorescence in the perivascular, paraventricular and subcortical regions. Antibodies directed against myelin sheaths, or nerve cells could be detected in the sera of 48% of the animals. The results give evidence that the vaccinia infection is capable to induce a potentially pathogenic autoimmune reaction directed against brain. Such an immunomechanism can be triggered without any signs of acute lytic infection of the CNS. The mechanism and significance of this reaction are discussed.


[The methylene-blue-reduction-test (MR-test) and the micro-TTC-test for the determination of substances as sole source of carbon in the taxonomy of Pseudomonas species (author's transl)]. Two methods are described for the determination of substances as sole source of carbon for taxonomic tools: the Methylene-Blue-Reduction-Test and the Micro-TTC-Test. Both methods are giving results superior to the technique introduced by STANIER and co-workers and used hitherto in the taxonomic classification of Pseudomonas species. The evaluation of the comparative test results is based on the criterion that a substance is useful for taxonomic purpose provided that at least 90 per cent of the strains of a species are giving homogeneous results. - The MR-Test is superior to the Micro-TTC-Test concerning the reproducibility of the results. The Micro-TTC-Test is useful as a screening technique in the routine work and the primary investigation of numerous strains.


Feulgen-DNA-cytophotometry on mammary tumor cells from aspiration biopsy smears. The nuclear DNA content of cells from 20 cases of mammary aspirates was estimated by microspectrophotometry. Smears stained according to Papanicolaou were destained and Feulgen-reacted. Among the smears there were 14 with doubtless tumor cells, four with a benign cell picture, and two of a doubtful nature. The mammary lesions were in all cases verfied by histology. Measurements showed that smears of benign tumors had a diploid or diploid to tetraploid distribution of DNA. The two doubtful smears also showed the same DNA pattern, although in one case the cells were from a papillary carcinoma and in the second case from a fibroadenoma. Malignomas with a cell picture, monomorphous-atypical in Papanicolaou staining exhibited a DNA histogram with a peak in the diploid to hyperdiploid ranges. Carcinomas showing a polymorphous-atypical cell picture were characterized either by polyploid values, by a large spread, or by aneuploidy. Hence, it is impossible to safely distinguish benign cases from carcinomas by the DNA pattern, since DNA distribution is fairly identical in part of the cases in either group.


Microglioma and/or reticulosarcoma of the nervous system. 49 microgliomas of nervous parenchyma were studied, all of them with aniline techniques in part of the material embedded in paraffin, and the rest with Del Rio Hortega-Polak's technique in frozen sections. It is considered that the microglia is the representative of the R.E.S. in the nervous tissue, and is characterised by its cytoplasmic argentophilia. The existence of a non-argentophilic primitive reticular cell is denied, and it is maintained that microglioma and reticulosarcoma are synonymous thus refuting the concept of the existence of a reticulosarcoma consisting of non-argentophilic cells and a microglioma consisting of argentophilic cells, as different neoplasms.


Cytochemical heterogeneity of human circulating monocytes. Normal human monocytes, based on appearance after Romanowsky-type staining, have been considered to be a homogenous class of mononuclear leukocytes. Cytochemical studies, however, indicate that these cells are markedly heterogenous with respect to certain hydrolytic and oxidative lysosomal enzymes and to a lesser extent show variability in cytoplasmic carbohydrate and ribonucleic acid content. Individual monocytes were found to vary most widely in non-specific esterase activity and least in acid phosphatase activity. Variation in monocyte peroxidase activity was intermediate between these extremes. Using a cytochemical "scoring" technic, younger adults were found to have higher mean monocyte non-specific esterase scores than older adults. No significant age or sex differences were found for peroxidase or acid phosphatase activity. Furthermore, the overall activities of these monocyte enzymes in healthy adults, as estimated by intensity of staining, were unrelated to one another. Using consecutive double staining technics, individual monocytes were also found to vary in their content of these biochemical consituents. A statistically inverse relationship was found in individual monocytes between their nonspecific esterase and acid phosphatase activities (r = -0.68). Analysis of other combinations studied showed only random distribution with no significant correlations. These findings emphasize the biochemical individuality of circulating monocytes and the variations noted probably reflect differences in number and composition of lysosomes.


Alpha-fetoprotein producing clones derived from ascites hepatoma AH70B culture. The establishment of permanent cell line that can produce an alpha-fetoprotein has made tissue culture a powerful tool for the study of alpha-fetoprotein. For this reason, the hepatoma cells of rat ascites hepatoma AH70B were cultured in vitro and some biological characters of the isolated six clones examined. The cultured cells were morphologically epithelial and the mode of chromosome number in hypotetraploid range, and possessed tumorigenicity. The cells secreted alpha-fetoprotein at the high level and a few components of serum proteins in the culture medium for more than one year. Alpha-Fetoprotein was also detected in cytoplasm by fluorescent antibody technique. The examined character was little different among the six colonial clones. From the present cloning procedure, it was suggested that the cultured cells derived from a single cell were secreting alpha-fetoprotein and several components of serum proteins together.


Microheterogeneity of rat alpha-fetoprotein. A purified and homogeneous preparation of rat alpha-fetoprotein (AFP) was separated into two components, AFPa and AFPb, by polyacrylamide gel electrophoresis. These two components had a definite difference in electrostatic net charge and gave only a single band on sodium dodecyl sulfate-electrophoresis. Neuraminidase-treated AFP gave clearly separable, slower moving four to six and finally two components depending on the time of incubation with neuraminidase. The time-dependent conversion of each AFPa and AFPb into slower migrating components upon neuraminidase treatment was confirmed by re-electrophoresis of separated and similarly treated AFPa and AFPb.


[Unusual cis AB phenotype in ABO group system]. The authors present serologic characteristics of the "cis AB" phenotype in the ABO blood system on the basis of investigation of three families in Poland and data from the literature and genetic concepts explaining the mechanism of development of this phenotype.


Menaquinone (vitamin K2) therapy for bronchial asthma. II. Clinical effect of menaquinone on bronchial asthma. A series of 191 patients with bronchial asthma were treated with menaquinone for not less than one year to investigate the clinical effects of the drug. The clinical effect may be summarized as follows: 1) The therapy with menaquinone only gave an effective rate oo 90.9% (a markedly effective rate of 42.4%) in mild patients, an effective rate of 86.7% (a markedly effective rate of 30.0%) in moderate patients, and effective rate of 72.7% (a markedly effective rate of 27.3%) in severe patients; namely, considerably a high effective rate was attained by the therapy in the respective patients. 2) The therapy with menaquinone, in conjunction with hyposensitization therapy, gave an effective rate of 100% (a markedly effective rate of 33.3%). 3) The double blind study of the clinical effects of menaquinone revealed that placebo used in the study was effective on only 16.7% of the patients treated with it, and that the incidence of recurrence due to withdrawal of meaquinone therapy tended to be low in the patients treated with the drug for a long period of time.


About some possible anti-inflammatory properties of various membrane permeant agents. Non steroidal anti-inflammatory drugs uncouple mitochondrial oxidative phosphorylation. They are membrane permeant agents. They also inhibit nucleic acids synthesis in lymphoid cells. Three antibiotics (valinomycin, gramicidin A, alamethicin) and one cyclic polyether (dibenzo-18-crown-6) which are potent membrane permeant agents and good uncouplers are demonstrated to inhibit such a nucleic acids synthesis. This inhibition is largely dependent on the ionic composition of the incubation medium. It is suggested on the basis of some preliminary results that these drugs, which are non-acidic molecules, should be further investigated for potential anti-inflammatory properties.


Substances that increase the cyclic AMP content prevent platelet aggregation and the concurrent release of pharmacologically active substances evoked by arachidonic acid. Arachidonic acid-induced platelet aggregation was inhibited by prostaglandins E1 and F2alpha(PGE1 and PGF2alpha), papaverine and dibutyryl cycle AMP. Prostaglandin E2 displayed a biphasic effect, as concentrations below 2 muM potentiated aggregation, whereas concentrations above it were inhibitory. Isoproterenol (up to 10 mM) failed to block aggregation but inhibition was uncovered in presence of adrenergic alpha-blocking agents. Isoproterenol potentiated aggregation due to sub-threshold amounts of arachidonic acid, and this effect, but not that due to PGE2, was suppressed by the alpha-blocking agents. Isoproterenol and PGE2 appear thus to enhance arachidonic acid-induced platelet aggregation after interacting with different receptor sites. The yield of rabbit aorta contracting activity formed during AA-induced aggregation was markedly reduced by PGE1, dibutyryl cyclic AMP and high concentrations of PGE2, and was increased by low concentrations of the latter. PG-like activity was not significantly reduced when aggregation and generation of rabbit aorta contracting activity were inhibited by bibutyryl cyclic AMP. It is hypothesized that interaction of human platelets and arachidonic acid results in formation of different pharmacologically active materials, possibley bearing similar lipoperoxide structures. Generation of one portion of these materials is controlled by the adenyl cyclase-cyclic AMP system, whereas another portion, that comprises the natural PG, is cyclic AMP-independent. Prostaglandins formed during platelet aggregation have a regulatory role and modulate the platelet response, rather than constitute a trigger stimulus for aggregation.


Ultracytochemistry of the surface coat/pellicle complex in Trypanosoma brucei. Ultracytochemistry of polysaccharides and specific sugar residues reveals differences in the surface staining pattern between developmental forms of Trypanosoma brucei. The techniques used were the PA (periodic acid)-TCH (thiocarbohydrazide)-silver albumose reaction for the polysaccharides, and the Concanavalin A (Con A)-perioxdase-DAB coupling method for specific sugar residues. Blood and metacyclic forms, both possessing a surface coat, stain distinctly for carbohydrates at the level of the pellicular membrane. The external portion of the bloodform coat lacks any positive staining. Pellicles of non-coated culture and vector forms react only faintly for polysaccharides, whereas heavy staining of oxidized peroxidase/DAB reaction product, indicative of sugar bound Con A, occurs. It is suggested that the sugar moieties of the coat glycoproteins are located close to the membrane-coat junction.


Salivary secretion in three species of tsetse flies (Glossinidae). The study of the mechanism and process of salivation in tsetse flies is of paramount importance towards a fuller understanding of the transmission of trypanosomiasis and nagana diseases. Gordon, Crewe and Willett (1956) made direct observations, through a microscope, of the haustellum of G. morsitans as it penetrated into the ear of an anesthetised mouse and found that probing was accompanied by a copious but intermittent ejection of saliva from the hypopharynx. The outpouring of the saliva commenced during penetration of the stratum corneum and was maintained throughout probing of the tissues. During engorgement, blood is taken in through the labium while saliva was discharged from the hypopharynx at the same time. Besides this work, very little else seems to have been done on the salivary secretion by tsetse flies especially in relation to the hunger cycle of the fly and to the species of tsetse. These aspects were studied on three important species of tsetse and are reported upon in this paper.


Correlation of blood pressure with skinfold thickness and protein levels. To plan prospective studies of obesity and hypertension, we measured skinfold thickness, weight, blood pressure, and protein fractions in 920 children who were divided according to age, sex, and race. Correlations between measurements were calculated within each of these groups. Children aged 10, 11, and 12 years had direct correlations between diastolic blood pressure and serum albumin level, but inverse correlations between diastolic blood pressure and alpha-globulin level as well as inverse correlations with alpha-globulin level. These correlations did not occur in similar children aged 8, 9, and 10. Although diastolic blood pressure correlated with skinfold thickness in all groups, there was no correlation between skinfold thickness and serum protein levels.


Functional implications of differential chromosome banding. Information on DNA content and banding patterns has been utilized in the construction of a novel ideogram of the human complement. Correspondence between certain features of this ideogram and the clinical record of human autosomal imbalance supports the idea that banding patterns reflect structural as well as functional heterogeneity of chromosomes.


Amyloidosis associated with dermatomyositis and features of multiple myeloma. The progression of amyloidosis associated with corticosteroid and cytotoxic drug therapy. Described here is a 59 year old man with dermatomyositis and hypogammaglobulinemia. His muscle power improved after corticosteroid therapy, but extensive amyloidosis and repeated infections appeared. Bone marrow morphology suggested multiple myeloma, but treatment with cytotoxic drugs had no beneficial effect on the amyloidosis. Because of rapid progression of the amyloidosis and further infections, cytotoxic drug therapy was stopped, corticosteroid dosage was decreased, and supplementary immunoglobulin therapy was instituted. The infections occurred less frequently and the amyloidosis appeared to regress. This case suggests that immunosuppressive therapy may exacerbate amyloidosis. The literature is reviewed, and the possible role of humoral immunodeficiency in the pathogenesis of amyloidosis is discussed. It is suggested that supplementary immunoglobulin may be beneficial in amyloidosis.


Perivascular and intervascular reticular fibers of the retina. We demonstrated the existence in the retina of an argyrophilic perivascular membrane comparable in all respects to that which exists throughout the vascular system. We compared our findings by light microscopy with those previously reported. We identified, by electron microscopy, the normal general location of the network between the basal laminae of the glial and vessel cells and demonstrated its selective staining with silver methenamine. These perivascular fibers, intercapillary strands, and bridges develop in relation to the process of retinal vascularization and the potential for forming these fibers is reactivated in senility and disease, as in diabetes. We summarized the evidence by concluding that these fibers are most likely composed of reticulin; it appears provable that in the past there may have been some confusion with neural fibers.


Cataracts in bleomycin-treated rats.

Cataracts in bleomycin-treated rats. Bleomycin was administered to 126 normal or human-tumor-bearing baby rats we observed for the development of cataracts. Eighty-four percent of the rats receiving this drug before the age of 10 days developed lens opacities. Bleomycin given to 10-day-old rats or older did not induce cataract formation. The cataracts initially occurred in the nuclear area and later involved most of the lens whether or not bleomycin was later discontinued. The presence of the tunica vasculosa lentis in rats younger than 10 days old may explain why cataracts developed only in these young animals.


Age-related incidence of sclerotic glomeruli in human kidneys. The incidence of sclerotic glomeruli as a function of age in kidneys from 122 patients without clinical evidence of renal disease or hypertension was estimated by histologic quantitation. Based on statistical analysis of data from this sample, 95% of the normal population up to 40 years of age would be expected to have less than 10% sclerotic glomeruli. After the age of 40 years, the upper limit containing 95% of the normal population exceeds 10% sclerosis, and after the age of 50, there is a broad scatter of observed percentage of sclerotic glomeruli. These findings suggest that, in patients 40 years of age and younger, sclerosis of glomeruli at an incidence greater than 10% is disease-related, while in patients older than 40 years (and particularly those older than 50), there is a transition, and the distinction between abiotrophic involutional sclerosis and disease-related sclerosis becomes less clear.


Induced metabolic sequelae of tularemia in the rat: correlation with tissue damage. Serum and liver zinc concentration, amino acid uptake by liver, seromucoid content, and alpha2-macrofetoprotein production were measured in vaccinated as well as nonimmune rats exposed to either virulent (SCHU S4) or attenuated (LVS) strains of Francisella tularensi. It appears that liver damage (pyogranulomatous lesions) must occur before there is any alteration in the above variables. The presence of bacteria in the liver is not of itself sufficient to lead to the onset of systemic, induced metabolic sequelae (IMS). The occurrence of zinc redistribution in all instances of increased serum protein synthesis may imply a necessary relationship between these two sequelae. Amino acid redistribution does not appear to be linked to serum protein synthesis. An endogenous mediator of systemic IMS can be detected in tularemic rats by injection of the serum of these animals into healthy recipients. The occurrence of zinc redistribution and increased serum protein synthesis in some groups of rats in the absence of amino acids uptake by liver, as well as the apparent differential dose responsiveness of these responses, are suggestive of a multiplicity of endogenous mediators.


Carcinoembryonic antigen (CEA) monitoring in the management of radiotherapeutic and chemotherapeutic patients. We have  measured serial carcinoembryonic antigen (CEA) titers in 122 radiotherapy and 52 chemotherapy patients, randomly selected from the patient population of a Radiotherapeutic and a Cancer Chemotherapy Clinic, and correlated with the clinical and follow-up evaluation. Seventy-eight the radiotherapeutic patients had detectable CEA levels which represents the majority of these proven cancer patients. In this group, 57 patients (73 per cent) showed correlation between the curves of CEA response and clinical evaluation diseases activity in the radiotherapy group. Thirty-one of 52, or 60 per cent of patients of the chemotherapy group showed correlation between CEA and clinical response. These data indicate that CEA serum levels parallel, in general, clinical tumor reponse.


[Ductus thoracicus drainage in man. Changes of the lymph cells and protein fractions]. 1. During thoracic duct drainage a significant decrease of serum beta- and gammaglobulins can be found. 2. The withdrawn lymphprotein can be sufficiently substituted by human serum albumin. 3. The number of small lymphocytes decreases significantly during thoracic duct drainage, while the number of large lymphocytes and lymphoid cells increases. 4. The drainage of thoracic duct in humans is a highly immuno-suppressive procedure without major risks.


Mechanism of respiratory injury by TDI (toluene disocyanate). The pharmacological action of TDI (toluene-diisocyanate) has been measured in vitro, using peripheral leukocytes of human blood. In this system TDI does not release histamine but it appears to contribute to the action of histamine and other mediators by moderating the beta-adrenergic function. Like propranolol TDI reduces the CAMP (cyclic AMP) stimulation produced by cathecolamines. However it differs from propranolol through its inhibition of the glucagon effect on CAMP (which propranolol does not possess) and also by inhibiting antigenic release of histamine.


Arrhythmias in dogs associated with epinephrine and thiamylal anesthesia. Sinus tachycardia bigeminy, ventricular rhythm, ventricular tachycardia, and ventricular fibrillation are produced by relatively small intravenous doses of epinephrine in nonanesthetized dogs and in dogs anesthetized with thiamylal sodium. Origin of the abnormal beat in coupled bigeminal rhythms generated from the bundle o of His or above. Increases in arterial blood pressure may predispose to arrhythmia formation during thiamylal anesthesia.