Occupational asthma in an electronics factory.

Workers in a modern electronics factory were surveyed by questionnaire and lung function testing to see if there was evidence of widespread work-related respiratory symptoms. Of the responding workers exposed to solder flux fumes on the shop floor, 22% had work-related breathlessness or wheeze or both. Exposed workers had a lower FEV1 and FVC than unexposed workers. Work-related rhinitis was also present in 22% of exposed workers. The most likely cause for these results is sensitivity to colophony fumes, released from solder flux during soldering. Levels of solder flux fume were below the threshold limit value in this factory during the survey.


Work-related respiratory disease in employees leaving an electronics factory.

Examination of the records of employees leaving an electronics factory over three-and-a-half years showed that a significantly greater proportion left the shop floor (where soldering took place) because of ill health than left the stores and office areas. This difference was largely due to work-related respiratory disease in those whose job was soldering. Shop floor workers leaving for health reasons also had increased sickness certification due to respiratory illness compared to stores and office workers. These findings suggest that work-related respiratory illness is a significant cause of morbidity and loss of employment in solderers working at the factory and that this has been a longstanding problem with its onset before the first recorded cases of occupational asthma caused by solder flux containing colophony.


Intrathoracic manifestations in non-Hodgkin's lymphoma.

A total of 16 of 86 patients (19%) with non-Hodgkin's lymphoma were found to have intrathoracic disease in this retrospective study. Paratracheal, mediastinal, and hilar lymphadenopathy was the commonest manifestation followed by pulmonary lesions and pleural effusion. The lymphoma was at an advanced clinical stage in all the patients with intrathoracic disease. About one-third of the intrathoracic lesions first developed at the time of relapse after successful initial therapy. There was a better response to therapy when intrathoracic disease was part of the initial presentation than when it was a manifestation of relapse. If it did not respond to therapy it was always indicative of a poor prognosis.


Resectional surgery in the treatment of primary carcinoma of the lung with mediastinal lymph node metastases.

Between 1966 and 1970 we reviewed 46 consecutive patients undergoing resection for primary carcinoma of the lung, in whom mediastinal lymph node metastases were found at operation. There was one operative death. Five of the remaining 45 patients survived five years--one of 10 cases of large cell carcinoma, one of 19 cases of adenocarcinoma, and three of 12 cases of epidermoid carcinoma. We believe that mediastinal lymph node metastases are not per se a contraindication to resection of epidermoid carcinoma of the lung.


"Acute" asthma in adults.

Forty-four adult patients with acute severe asthma were studied on admission to a general hospital to determine the mode of presentation and clinical severity of the acute illness. Most patients described poorly controlled wheezing for a mean period of five weeks before a more rapid deterioration, usually over 24 hours, caused them to seek medical attention. The clinical severity of the acute attach was not related to the duration of acute wheezing before admission to hospital. Recovery, studied in 11 of the patients, was slow, and most had reached only 70% of their predicted spirometric values after seven days' treatment in hospital. The rate of recovery was not influenced by the antecedent history of acute wheezing. Very sudden deterioration from a background of good control appears to be uncommon in adults with asthma who present to hospital as emergencies, and it is likely that improvement in the standard of routine management of asthmatics at home would prevent many such admissions.


Sudden death in asthma.

Two deaths after sudden severe asthma attacks in young people are reported from a clinic set up to identify and manage "at risk" patients. These deaths occurred despite frequent visits at which recommendations made by previous studies were implemented. The risk factors and management of such episodes have been reviewed. Precautions taken proved inadequate due to the severe, abrupt nature of the attacks, failure of the patients' immediate treatment, and delay in reaching hospital. Consideration should be given to the self-administration of subcutaneous adrenaline or specific beta-agonists, the provision of a detailed medical card, and free access to the nearest hospital in such cases.


Lung clearance of soluble radioaerosols of different molecular weights in systemic sclerosis.

Clearance rates of soluble radioaerosols of sodium pertechnetate (99mTcO4; mol wt 163) and diethylenetriaminepenta-acetate (99mTc-DTPA; mol wt 492) were determined in seven normal subjects and ten patients with systemic sclerosis affecting the lungs. Twenty millicuries (mCi) each of 99mTcO4 and 99mTc-DTPA in 5 ml saline were aerosolised and inhaled using a disposable "Blount" nebuliser on two different days. Two regions of interest over each posterior lung field were monitored with scintillation camera, and data were stored on magnetic tape using a Hewlett Packard Data Analyser. Decreasing levels of radioactivity were plotted semilogarithmically and half-time (T 1 1/2) removal rates were calculated. The T 1 1/2) values in normal subjects did not differ significantly from T 142 values of the patients with TcO4. However, the removal rates of the higher molecular weight solute were significantly faster from lower lung zones in patients with systemic sclerosis than in the normal subjects. The faster absorption of DTPA from lower lung zones of the patients could be due to regional abnormalities of alveolar epithelium at the lung bases, presumably as a result of greater retractive forces secondary to fibrosis.


Cell-mediated immunity in operable bronchial carcinoma: the effect of injecting irradiated autologous tumour cells and BCG.

In 52 patients undergoing tests of cell-mediated immunity before surgical resection of bronchial carcinoma a positive tuberculin test result was found in 71% compared with 68% of age- and sex-matched controls. Sensitisation to DNCB occurred in 52% of 37 patients but in 78% of controls. There was depression of lymphocyte transformation by PPD in 19 patients compared with controls (P=0.001), but there was no difference in lymphocyte transformation by PHA or pokeweed mitogen between 34 patients and controls. In a pilot study patients were randomly allocated to autograft (eight) or non-autograft (seven) groups. The autograft group were given an intradermal injection of a suspension of irradiated autologous tumour-cells mixed with intradermal BCG on the day of operation. Tests of cell-mediated immunity were repeated two weeks after operation. Five patients in each group received a course of radiotherapy to the mediastinum three weeks after operation. There was a rise in cutaneous tuberculin reactivity (P=0.08) and total leucocyte count (P=0.09) in the autograft group postoperatively with a fall in total lymphocyte and T lymphocyte counts in the non-autograft group (P less 0.05). These differences, however, were not followed by any difference in the frequency of tumour recurrence or the survival rate two years after operation. The results show that the immunological surveillance mechanism is impaired even in patients with early bronchial carcinoma and that it is possible to overcome postoperative immunological depression with specific immunotherapy combined with BCG. This treatment did not produce any clinical advantage in this small number of patients and the skin lesions caused the patients considerable discomfort.


Pectus excavatum and cardiac dysfunction: a case report with pre- and post-operative haemodynamic studies.

A 48-year-old man with severe pectus excavatum presented with incapacitating supraventricular tachycardia, paroxysmal in nature and invariably provoked by exercise. During mild supine leg exercise on a bicycle ergometer an abnormal increase in right heart pressures, particularly in the right atrium, was observed, followed immediately by supraventricular tachycardia. The latter was also shown during upright exercise on a treadmill. Operative correction of the deformity led to complete relief from the dysrhythmia and a normal haemodynamic response on exercise. The pre- and post-operative studies lend support to the conclusion that the sternal depression was the most likely cause of the cardiac abnormality.


Ultrastructural artefacts in biopsied normal myocardium and their relevance to myocardial biopsy in man.

Biopsy specimens, as a source of myocardial tissue, are being used increasingly in the appraisal of various myocardial diseases. A study of myocardial tissue, biopsied and processed in various ways, and obtained from normal healthy experimental animals, showed that a variety of artefacts may be found. These artefacts develop in reactive, beating myocardium but not in non-reactive hearts. The artefacts are in many instances similar to, or mimic, changes previously described as pathological in origin. This is most unsatisfactory, and if valid pathological appraisals of myocardial biopsies are to be made, a technique allowing the recovery of tissue, free of biopsy artefact, is required. Such a technique is described.


[Some results obtained in artificial insemination on a large rabbit farm (author's transl)].

In commercial rabbit-farming, activities associated with mating take up a great deal of the working hours required. Efforts were made to help to obtain optimum results in rabbit-farming by carrying out artificial insemination. The conception rates following insemination of does which are not prepared to mate naturally, are too low. After preliminary treatment of these animals with 20 I.U. of pregnant mare serum forty-eight hours prior to insemination, the results obtained were more satisfactory. It is concluded that artificial insemination in rabbit farming does not present any technical problems and that satisfactory results should be obtainable on healthy farms.


[The effect of Mycoplasma synoviae infection on the state of health and results of fattening of broiler chickens compared with the effects of various virus infections. A field study (author's transl)].

Field studies in 160 flocks of broiler chickens in two areas in the Netherlands showed that Mycoplasma synoviae infection, the presence of which was detected by serological testing in 17.5 per cent, had only a slight adverse effect on the results of fattening. Mycoplasma synoviae as well as IB infections were found to be more common in flocks affected with colibacillosis and/or in which higher proportions of birds were condemned because of polyserositis. Infectious bursal disease, IB and CELO virus infections are very common particularly in the southern areas of the Netherlands, and have a significantly adverse effect on the results of fattening. The findings suggest that vaccination against IB and Gumboro disease often fails in flocks in areas showing a high incidence of infection.


Recovery of the heart after normothermic ischemia. Part I: Ultrastructural findings during postischemic reperfusion.

The influence of controlled ischemia on myocardial ultrastructure was investigated in isolated, metabolically supported canine hearts. Recovery of functionally normal tissue as indicated by the reversibility of morphological alterations was observed up to 60 minutes of anoxia. It was shown that prolonged reperfusion of the empty beating heart supports the recovery of normal cellular ultrastructure. Severe ischemic damage of mitochondria due to ischemia of 60 minutes was almost completely reversible after a reperfusion period of 50 minutes.


Penetrating wounds of the heart and pericardium.

Fifty-seven patients with penetrating cardiac or pericardial trauma were treated at the Department of Cardio-Thoracic Surgery, University of Stellenbosch at the Tygerberg Hospital during a 6 1/2 year period from June 1971 to January 1978. Eleven patients were treated by aspiration alone because tamponade was mild, or because they were seen between 24 hours and 3 weeks after injury. Six patients underwent late elective surgery. Cardiopulmonary bypass had to be employed in four patients to correct intracardiac lesions. All other patients underwent emergency operations 8 minutes to 2 hours after admission to hospital. The hospital mortality was 4 of 57 patients (7%), lower than rates reported in other series. Some selected cases will be described more fully and our present plan of management is outlined.


Surgical treatment of aneurysms of the ascending aorta: early experience with the sinus-shaped composite dacron graft.

This paper reviews the early and late results of 36 operations for aneurysms of the ascending aorta. Cystic medial necrosis was the predominant cause of aneurysm formation (56%), followed by arteriosclerosis (25%), previous aortotomy (11%) and syphilitic aortitis (8%). Dissection was encountered in 42%. The ascending aorta was replaced by a tubular Darcron graft in 26 patients, whereas 10 underwent aneurysmorrhaphy. Additional procedures were aortic valve replacement (27), resuspension of the aortic commissures (4) and coronary ostial implantation into sinus-shaped composite Dacron graft (4). Hospital mortality (0--18 days) was 8/36 patients (22%), but higher with cystic medial necrosis (30%), dissection (33%), duration of ECC greater than 180 minutes (38%), graft replacement (44%), emergency operation (45%) and heart volume greater than 900 ml/m2 BSA (50%). Late mortality (average 3 years) was 29%, but higher with cystic medial necrosis (33%), following aortic valve replacement (36%) and during anticoagulation (47%). Late cumulative survival (average 3 years) was 47% for the entire series, but only 33% in the presence of cystic medial necrosis. The poor overall prognosis for patients with cystic medial degeneration was closely related to a high incidence of fatal anastomotic complications and late deaths from cerebral haemorrhage during anticoagulation. Radical exclusion of the diseased aortic wall and omission of long-term anticoagulation are therefore desirable in order to lower the mortality rate. Surgery concerns the aneurysm per se, the aortic incompetence and the coronary ostia. The sinus-shaped composite graft with a Björk-Shiley prosthesis at its base appears to be a promising device for such a procedure, which should be performed electively, following early diagnosis in order to prevent dissection and emergency operations.


Long term performance of 580 homograft and autograft valves used for aortic valve replacement.

Homograft valves have been used at the National Heart Hospital since 1964, and autograft valves since 1967. The homografts were treated either by freeze drying, by flash freezing, or by tissue maintenance in a nutrient medium (fresh). In order to compare these three groups of homograft valves with the autograft valves some long term assessment of valve function was required. In the whole group of 580 valves there have been 40 late deaths, which is a probability of only 7% over 6 to 14 years. Homografts and autografts are therefore excellent valves in terms of patient survival. Thromboembolism, haemolysis and bleeding may be regarded as complications which do not occur with homograft and autograft valves. There was one thrombogenic episode in this group, an incidence of one per 11,994 patient years and a probability of only 0.000083 patient years. Potentially fatal hazards of late complications with homoor autograft valves decrease with time and at this time is a negligible factor. The similarity in pattern of onset of late infections and degeneration probably reflects the greater susceptibility to infection of a degenerating valve. All three groups of homografts are very similar and differ only from the excellent performance of the autograft valves.


Mitral annuloplasty--a long term clinical and haemodynamic study.

One hundred and thirteen hospital survivors with mitral annuloplasty have been followed-up from 3--19 years. Actuarially 82.4 +/- 12.1% and 65.1 +/- 18.1% of all patients are expected to be alive at 10 and 19 years respectively. 90.1 +/- 5.9% of patients were predicted to be free from reoperation at 5 years postop, while at 10 and 15 years the figures are 77.2 +/- 13.9% and 53.8 +/- 23.9% respectively. Postoperative haemodynamic investigations, performed in 18 patients at a mean duration of 8.5 (range 4--11) years, showed significant reduction in both mean pulmonary artery and wedge pressures as compared to pre-operative values. 92% of patients were in grade I and II (NYHA) clinically at the latest evaluation as compared to 84% being in grade III and IV pre-operatively. Mitral annuloplasty provides statisfactory long term clinical and haemodynamic improvement in a selected group of patients and should always be considered in the management of mitral regurgitation.


Twelve year results with a caged-ball mitral prosthesis.

Over a 12 year period in 230 patients mitral valve replacement was performed using the model 6120 Starr-Edwards prosthesis. Operative mortality was 6.5%, mean follow-up of the operative survivors was 3.9 years. Estimated late survival rate was 80% at 5 years and 73% at 12 years. 38% of late deaths were considered valve-related. Under routine anticoagulation thromboembolism occurred at a rate of 4.7% per patient-year with a fatal thromboembolic incidence of 1.4% per patient-year. In comparison with data available on other currently used prosthetic valves it appears that the rates of valve-related complications are quite similar, with the 6120 Starr-Edwards model being subject to the longest follow-up.


Rupture of the ventricle following prosthetic replacement of the mitral valve.

40 cases, 36 from the literature and 4 of ours, of rupture of the posterior wall of the left ventricle following prosthetic mitral valve replacement are presented. Twelve of these patients survived. Possible causes of this complication, the therapeutic approach and its prevention are discussed.


Funnel chest correction by use of AO implants and instruments.

A new method for funnel chest correction using AO implants and instruments is described. The method appears to offer certain advantages particularly in the more rigid chest wall of aldolescents and adults.


HLA--A, B haplotype frequencies in 5,202 unrelated Danes by a maximum-likelihood method of gene counting.

A population sample of 5,202 persons comprising normal, healthy individuals from three laboratories in Copenhagen was used for estimating HLA-A, -B antigen, gene, and haplotype frequencies, besides delta-values and their standard errors. The serum panels used allowed the determination of a total of 273 HLA-A, -B haplotypes, and the most significant delta-values were in agreement with those found in other Caucasian populations. The methods used for the calculations of frequencies, delta-values, and standard errors are described.


The distribution of HLA antigens and genes in the Greek population.

200 Greeks were typed by lymphocytotoxicity for 14 HLA-A and 18 HLA-B antigens with 120 sera. A high frequency of Bw35 and B5 antigen was apparent. The most remarkable disequilibria found were those between A2-B5 and A9-B18.


HLA antigens in chronic alcoholic pancreatitis.

HLA typing was performed in 90 unrelated patients with chronic alcohol-associated pancreatitis. Compared with 523 healthy controls, an increased frequency was found for the HLA-B series antigen, B40 (Pless than 0.00041, corrected P less than 0.011). The increase was slightly more pronounced in patients without pancreatic calcifications than in those with calcifications. Factors such as alcohol consumption, age of disease onset and the presence of diabetes did not affect antigen frequency distribution.


Assay for antibody mediated cytotoxicity of mouse spermatozoa by 86rubidium release.

The analysis of the antigenic structure of murine spermatozoa has been hampered by the lack of a convenient objective serological assay. Spermatozoa, in common with other cells, are capable of concentrating 86rubidium. Antibody mediated complement dependent cytotoxicity of murine spermatozoa has been quantitated by measuring release of 86rubidium from pre-labeled spermatozoa. We have used this assay to study the murine T/t locus.


HLA-A and B antigen frequencies in an asbestos exposed population with normal and abnormal chest radiographs.

Previous studies of HLA antigen frequencies in asbestos related pulmonary fibrosis have suggested some weak associations both with susceptibility to the disease (B12 and B27) and protection from the disease (B18 and Bw35). HLA typing was performed on a further series of 64 asbestos workers with no chest abnormality and 166 workers with various radiographic changes, 78 having pulmonary fibrosis. The results fail to give statistical confirmation of these associations although B27 was twice as frequently associated with pulmonary fibrosis and diffuse pleural thickening. Analysis of the combined data from this and four other studies failed to show any consistent associations.


Observations of vincristine-induced paracrystals in human erythroblasts in vitro.

Ultrastructural observations were made on human erythroblasts incubated in a vincristine solution. In certain concentrations and at certain incubation time intervals, paracrystals were observed in the erythroblasts. The fine structure of the paracrystals was similar to that described in platelets, leukemic lymphoblasts or cultured fibroblasts. They showed parallel filaments, amorphous mass or honeycomb-like crystalline structure. One paracrystalline form turned into another form when the sections were tilted by the use of goniometer. These paracrystals were often closely related to other organelles, such as lysosome, Golgi apparatus and nucleus. In the mitotic erythroblasts degraded microtubules coexisted with typical paracrystals.


Arrest reaction in man: motor arrest response by electrical stimulation of the deep structure of the cerebrum.

In spite of many reports of arrest reaction in animals, there are very few reports in man. During a therapeutic stereotactic operation we observed peculiar phenomena caused by electrical stimulation to the deep structure of the cerebrum. The electrical stimulation caused an interruption of counting and other motor actions, which could be resumed following release of stimuli. In almost all cases psychic confusion of memory disturbances were not observed. The head of the caudate nucleus and its adjacent white matter cause arrest reaction with the lowest threshold of 5 V; on the other hand, substantia medullaris lobi frontalis, radiatio corporis callosi and nucl. reticularis oralis of the thalamus caused arrest reaction with the highest threshold of 10--15 V. The arrest reaction that we observed is thought to be due to a direct effect on the head of the caudate nucleus, not due to secondary effects on the internal capsule and the motor fiber in the vicinity of the caudate nucleus. However, the possibility that the current spread to the motor fiber cannot be definitely ruled out.


Contribution of beta-glucuronidase to the degradation of chondroitin 4-sulfate by canine liver lysosomal enzymes.

Oligosaccharides derived from chondroitin 4-sulfate (Ch4-S) and chondroitin were digested by canine liver lysosomes under acidic conditions. The degree of digestion of Ch4-S by hyaluronidase and beta-glucuronidase was examined on the basis of types of the digestion products. Tetradeca- and dodecasaccharides derived from Ch4-S and chondroitin were first digested by hyaluronidase, while the octasaccharide was hydrolyzed by beta-glucuronidase. Decasaccharide was degraded by both hyaluronidase and beta-glucuronidase. The results showed that decasaccharide from Ch4-S served as the largest-molecular-weight substrate for beta-glucuronidase in the degradation of Ch4-S by the enzymes of lysosomes in contrast to the results of the digestion studies of hyaluronic acid (HA). The contribution of beta-glucuronidase to the depolymerization of chondroitin and HA by hyaluronidase was examined in the presence of saccharo-1,4-lactone, a specific inhibitor of beta-glucuronidase, in the reaction mixture. The depolymerization of chondroitin by hyaluronidase was significantly reduced by the addition of saccharo-1,4-lactone. From the results, it is suggested that beta-glucuronidase contributes to the degradation of the even-numbered oligosaccharides which inhibit the action of hyaluronidase in the depolymerization of Ch4-S.


Adriamycin instillation therapy for bladder tumors.

Topical instillation of Adriamycin, 40 mg in 20 ml sterilized distilled water, was performed in 20 cases of bladder tumors every day for two weeks. In 8 cases (40%) the tumors disappeared completely, while in 5 cases (25%) tumors were reduced in size, but in 7 cases (35%) there was no effect. Therefore, the rate of effectiveness was 65%. The local bladder reaction and urethral pain were noted in all cases, as a result of which the therapy was interrupted in 2 cases. Abnormal values of red blood cells, white blood cells and platelets were not observed. In 3 cases the serum level of Adriamycin was only trace 1 or 2 hr after instillation. In conclusion, Mitomycin C was thought to be superior to Adriamycin as far as the effectiveness and irritability on the normal bladder epithelium were concerned.


Immunotherapeutic effect of allogeneic tumor cells on the growth of autochthonous 3-methylcholanthrene-induced sarcomas in rats.

The tumor-inhibitory effect of injections of allogeneic tumor cells was observed. Established autochthonous sarcomas induced in the subcutaneous tissue of rats by 3-methylcholanthrene (MCA) were treated with immunization by using allogeneic Hirosaki sarcoma cells. When MCA-induced sarcomas grew to approximately 1 cm in mean diameter, Hirosaki sarcoma cells were inoculated into various tissues of primary tumor-bearing rats. Immunizing procedures consisted of intraperitoneal and subcutaneous injections in one experimental group, and of intradermal and intraperitoneal injections in another. Significantly inhibitory effect on the growth of autochthonous sarcomas was observed in the initial stage up to 2 cm in diameter as compared with that of control sarcomas. No significant inhibition was seen in the course of the growth of sarcomas larger than 2 cm in diameter. This results may indicate that immunotherapy by using allogeneic tumor cells should be considered to be valuable for the treatment of human cancer.


Evolution of glomerular lesions in rats with spontaneous diabetes.

The development of glomerular lesions associated with ageing was investigated electron microscopically in rats with spontaneous diabetes. In young diabetic rats at eight weeks of age, there was no particular difference in ultrastructure from age-matched control rats showing an even contour of glomerular basement membrane, whereas in the diabetic rats at 12 weeks of age thickening of basement membrane with irregular protrusion of the epithelial side of lamina densa and accumulation of basement membrane-like materials in the mesangial regions could be observed. After 16 to 24 weeks of age in the diabetic rats, hemispherical thickening in addition to diffuse thickening of glomerular basement membrane was noted. The thickening of basement membrane was due to widening of lamina densa consisting of accumulation of basement membrane-materials on the epithelial side of the lamina densa, all the way along the peripheral capillary loops. These features of glomerular lesions in the diabetic rats were progressively accentuated accompanying ageing. The early glomerular ultrastructural alterations in the diabetic rats were very compatible with those seen in the elder control rats. The results indicated that the development of diabetic glomerulopathy might be destined very early in life of the spontaneously diabetic rats supposedly by their diabetic genes.


Isolation and characterization of proteohyaluronic acid from human umbilical cord.

Proteohyaluronic acid was extracted from human umbilical cord with 0.2% NaCl, then purified by cetylpyridinium chloride(CPC)-precipitation, DEAE-cellulose column chromatography, gel-filtration on Sephadex G-200 and on Sepharose 4B, in succession. The purified preparation contained glucosamine (40.1%), glucuronic acid (45.7%) and protein (2.6%). Glutamic acid, glycine, alanine, serine and aspartic acid were the major amino acids of the protein moiety. The result of the gel-filtration suggested that an average molecular weight was more than 1 x 10(6). Although analytical data for the constituent sugars and infrared spectra were similar before and after pronase digestion of this proteohyaluronic acid, the mobilities in electrophoresis and the elution patterns of gel-filtration differed remarkably from one another. Since the protein content decreased from 2.6% to 0.3% by the proteolytic digestion, it is evident that the degraded protein moiety played an important role in maintaining the macromolecular structure of this proteohyaluronic acid.


Ammonia metabolism in the rat liver in biliary obstruction.

Arginine synthetase activity and ammonia removal in liver slices were determined in rats with obstructive jaundice or acute carbon tetrachloride (CCl4)-induced liver dysfunction and the following results were obtained: (1) Urea synthesis and ammonia removal in liver slices progressively decreased with prolonged biliary obstruction. The effects of ATP and/or ornithine addition were also markedly decreased, particularly in the group with 6 weeks of biliary obstruction. (2) Arginine synthetase activity also fell with prolongation of biliary obstruction and the fall was most pronounced in the 6-week group. (3) The CCl4-induced liver dysfunction group showed a significantly higher level of arginine synthetase activity than the group with 6 weeks of biliary obstruction, but ammonia removal was markedly decreased and the effects of ATP and ornithine addition were prominent. From the results, it is concluded that, due to a fall in the enzyme activity of the urea cycle in obstructive jaundice, liver dysfunction can easily occur with prolongation of the obstruction, while hepatic urea cycle dysfunction is brought about by severe metabolic disruption in the liver damaged by CCl4.


Uteroplacental blood flow and uteroplacental shunt rates in normal and prolonged pregnancies in rats.

To reveal the regulatory function in uteroplacental blood flow we measured, using the method of double tracer microspheres, the rates of uteroplacental blood flow (UPBF) and uteroplacental shunt (UP-shunt) in SD-strain rats of normal and prolonged pregnancy. (1) In the group of rats of normal pregnancy, the rate of UPBF attained a peak on the 20th day of gestation, while the UP-shunt rate was highest on the 18th day of gestation. (2) In the progesterone-induced prolonged pregnancy group, the rate of UPBF remained at an 8% level until the the 22nd day, i.e., the first day of prolonged pregnancy, and dropped to 6.6% on the 23rd day. The UP-shunt rate in the progesterone-administered group was about 27% on the 20th day, more favorable than the corresponding rate in the normal group, but thereafter rapidly decreased. The rate of increase in fetal body weight in this group became lower, showing a fetal death rate of 4.6%. (3) The decreases in placental alkaline phosphatase and leucine aminopeptidase examined as markers of placental function lagged behind the fall in the UP-shunt rate. On the 23rd day of gestation when the rates of UPBF and UP-shunt dropped, the decreases in their placental enzyme activities were remarkable.


[Radiotherapy of the medulloblastoma: development of methods and results of the treatment of 30 patients from 1963 to 1976 (author's transl)].

The results of the treatment of 30 patients with medulloblastoma from 1963--1976 are analysed. 20% of all patients had no evidence of disease after five years. Radiation technique and dose were subject to change in these years and the results show, that a 5 year cure rate about 40% or more can only be achieved, if the radiation dose in the fossa posterior is about 5000 rd in 5--6 weeks. The ongoing studies will show, whether the results of an optimized radiotherapy can further be enhanced by chemotherapy.


[Bisectorial small-angle pendulum irradiation alternatively to other methods of 60Co-teletherapy: valence and volume doses (author's transl)].

A comparison is made between five irradiation methods, the dose distribution and volume doses of which had been ascertained by means of two phantoms presupposed differently large. Of the two methods of small-angle pendulum irradiation, the bisectorial monaxial pendulum technique turns out to be a practicalbe alternative to fixed-field and rotation irradiations. Similarly to fixed-field irradiation with two opposed fields, to which, after all, this technique is superior in every respect, it makes possible a relatively simple spatial irradiation planning. In this regard it is also more favorable than the rotation irradiations, though they give security of a more homogeneous load to axially parallel focuses; but an oblique position of the focal axis can be compensated only by an extension of the target volume and consequently augmentation of the volume dose. The necessity of confining to a certain extent the sum of absorbed energy is accentuated.


[Further considerations on the basis of the Ellis-formula and its application (author's transl)].

Computational methods for the determination of normal tissue tolerance under various modes of dose fractionation are applied at many radiation therapy installations. The methods differ in details, but most are based on the Ellis-formula. A survey of the relevant quantities and relations is given in order to facilitate comparison of the various methods. The established equations which are applicable to regular fractionation are related to the generalization of the Ellis-formula which is also applicable to irregular fractionation modes.


[Thermographically visualized cutaneous reactions after irradiation with fast electrons (author's transl)].

A comparison was made between thermographically visualized cutaneous reactions of two groups of patients after a therapy with fast electrons. One group underwent one-series irradiation, the other group received two series with an interval of 21 days. The cutaneous reaction after the interval only appeared following considerably higher doses than with one-series therapy. This difference indicates the recuperative capability of normal tissue after the exposition to subtolerance effects. The data were evaluated using a function derived from the Ellis-formula. A "biological dosimeter" can be developed based on thermic reactions of subcutaneous connective tissue.


[Cellular immune response and concentrations of serum immunoglobulins in patients with Hodgkin's disease (author's transl)].

The cellular immune response was explored by us with the help of tuberculin and DNCB reactions in 73 cases of Hodgkin's disease. Serum immunoglobulins were simultaneously determined. Tuberculin and DNCB reactions had significantly been decreased before treatment. A significant augmentation of the IgA is remarkable in tuberculin and DNCB positive groups. The positivity of the cutaneous tests is only temporarily lowered by radiation therapy, the difference being not significant, while IgM values in patients who had undergone radiation therapy are remaining at a lower level. Patients in remission revealed a positivity in tests that was approximating the values before treatment. Lower values were observed in all the three groups of immunoglobulins; the decrease of the IgM-values was significant. In case of a relapse, a significant decrease of positivity developed, accompanied by significantly increased values of IgA in tuberculin and DNCB negative groups. Only insignificantly positive values of the cutaneous tests were seen in the course of cytostatic treatment, and the values of the IgM were significantly decreased.


Characterization of metronidazole-phosphate, a water-soluble metronidazole derivative, as a radiosensitizer of hypoxic cells.

A water-soluble derivative of metronidazole (Flagyl) was synthetized with the purpose to overcome some practical difficulties in the clinical administration of the drug. The derivative, a phosphate ester of metronidazole, was characterized for different physical-chemical properties. It had a low toxicity both in vitro and in vivo. In vitro, it retained a radiosensitizing effect specific for hypoxic cells which was, however, decreased in comparison with the parent compound. The decreased sensitization was related to a decreased one-electron reduction potential and octanol/water partition coefficient. In mice, metronidazole-phosphate had a prolonged blood life in comparison to metronidazole.


Liver RNA biosynthesis in adrenalectomized rats: effect of whole-body X-irradiation.

Exposure of rats to a single whole-body dose of X-rays led to an enhanced rate of RNA synthesis in the liver during 4 to 18 hours post-irradiation. This increase in RNA synthesis could not be obliterated by protecting the liver during irradiation. On the other hand, if adrenals were surgically removed prior to whole-body radiation exposure, no elevation either in liver RNA synthesis in vivo or liver chromatin template activity in vitro was apparent. Protection of only the head during irradiation could also prevent the stimulation in liver RNA synthesis in vivo. These results are suggestive of the involvement of neuro-endocrine reactions along the hypothalamus-pituitary-adrenal axes to be the underlying factors in whole-body radiation-evoked activation of the transcription machinery in the liver.


Steroid synthesis. The modified Hunsdiecker degradation of bile acids and related compounds.

The modified Hunsdiecker degradation using red mercuric oxide-bromine has been found to be a convenient method for the conversion of bile acids to steroids containing bromo alkyl sidechains.


Differences in steroid specificity for rat androgen binding protein and the cytoplasmic receptor.

Two proteins in the rat, androgen binding protein (ABP) and the cytoplasmic receptor (CR), have high affinity and limited capacity for binding androgens. To determine the structural requirements for binding with high affinity, each protein was partially purified and the ability of over 100 steroids to compete with [3H]dihydrotestosterone (17 beta-hydroxy-5 alpha-androstan-3-one) for binding sites was assessed. The results indicate marked differences in the steroid specificities of the two proteins. Some alterations of dihydrotestosterone at C-2 or C-2 and C-3 increase binding to ABP two to four-fold. Similarly, the affinity of 17 beta-hydroxy-7 alpha-methyl-4-estren-3-one for ABP increases two-fold when a double bond is created at C-14. Addition of a methyl group in the alpha position at C-7 or C-17, or an ethinyl group at C-17 cause little change in affinity; however, modifications at C-11 and C-17 beta, and deletion of the methyl group at C-10 significantly impair binding to ABP. Binding to the CR is maintained or increased by deletion of the methyl group at C-10. Binding is lessened by modifications at C-3 and C-17 beta. Most alterations at C-2, C-7, C-11, and C-17 alpha have only minor effects on binding to the CR. These studies should provide a molecular basis for predicting the effects of specific structural modifications. When some modifications at C-2 or C-2 and C-3 are combined with changes at C-17  beta, the resulting steroids retain very high affinity for ABP and very limited binding to the CR. Such steroids may provide a means for assessing the function of ABP.


Selective inhibition by secosteroids of 5 alpha-reductase activity in human sex skin fibroblasts.

The effects of 5,10-secoestra-4,5-diene-3,10,17-trione (Compound I) and 5,10-seco-19-norpregna-4,5-diene,3,10,20-trione (Compound II) on the 5 alpha-reductase activity and on the androgen receptors of normal human sex skin fibroblasts were investigated. The Vmax and Km of the transformation of testosterone to 5 alpha-reduced products was 387 pg/microgram DNA/30 min and 234 X 10(-9)M, respectively. When the inhibitors were introduced in the assay, the 5 alpha-reductase activity was markedly reduced, Compound I being a less potent inhibitor than Compound II. At 15 min, the inhibition was greater than at 30 and 60 min. The Ki for Compound I was 1.60 x 10(-6)M with a Vmax of 83 to 553 pg/microgram DNA/30 min. For Compound II, the Ki was 0.53 x 10(-6)M with a Vmax of 70 to 340 pg/microgram DNA/30 min. The inhibition was of the noncompetitive type. Studies with androgen receptors showed that Compound I had a lower affinity for the receptors than Compound II. The ID50 for 3H-DHT and 3H-T for Compound I were 42.9 x 10(-7)M and 8.6 x 10(-7)M, respectively, whereas for Compound II, they were 10.6 x 10(-7)M and 4.8 x 10(-7)M.


Lumi-mestranol and epi-lumi-mestranol.

Treatment of lumi-estrone 3-methyl ether (I) with acetylene gave the C-17-epimeric compounds lumi-mestranol (3-methoxy-17 alpha-ethynyl-13 alpha-estra-1,3,5(10)-trien-17 beta-ol, III ) and epi-lumi-mestranol (3-methoxy-17 beta-ethynyl-13 alpha-estra-1,3,5(10)-trien-17 alpha-ol, IV). The structures of the two isomers were assigned on the basis of their molecular rotations and shift-reagent experiments in the NMR. The irradiation of estrone 3-methyl ether (II) to provide compound I was investigated in two solvent systems. Minor products of these reactions were the seco-steroids VII, VIII and X.


The synthesis of methyl 3 alpha, 7 alpha-diacetoxy-11-oxo-5 beta-cholan-24-oate.

Reaction of methyl-3 alpha-7 alpha-diacetoxy-11 alpha-bromo-12-oxo-5 beta-cholan-24-oate with sodium borohydride in pyridine solution containing sodium acetate gave the corresponding 11 beta, 12 beta-epoxide in 65% yield. The epoxy-ring was opened with hydrobromic or hydroiodic acid to give the corresponding 12 alpha-halo-11 beta-alcohols, which were converted to the halo-ketones and finally to methyl 3 alpha,7 alpha-diacetoxy-11-oxo-5 beta-cholan-24-oate.


Significance of various cholesterol, ester hydrolases in aorta.

This study for the first time has simultaneously assayed three cholesteryl ester hydrolase activities located in the various subcellular fractions (lysosomal, microsomal, and soluble) of the aorta and their significance in aortic cholesteryl ester accumulation during genetic and cholesterol-fed atherosclerosis is assessed. When the enzyme activities in the aorta of age-matched atherosclerosis-susceptible White Carneau and atherosclerosis-resistant Show Racer pigeons were compared, a decrease in microsomal cholesteryl ester hydrolase activity was found during the period of cholesteryl ester accumulation. However, under cholesterol-fed conditions (which further increase cholesteryl ester accumulation), an increase in lysosomal cholesteryl ester hydrolase activity and a decrease in soluble cholesteryl ester hydrolase activity was found. These studies have documented differences in response in specific cholesteryl ester hydrosases of the aorta to genetic and cholesterol-fed atherogenesis and warrant further studies to investigate the effect of hormonal and dietary factors on the activities of these enzymes.


Configurational assignment of 5 beta-cholestane-3 alpha, 7 alpha, 12 alpha, 23, 25-pentol excreted by patients with cerebrotendinous xanthomatosis (a circular dichroism study).

The absolute configuration of the C27 pentahydroxy bile alcohol present in bile and feces of two patients with cerebrotendinous xanthomatosis (CTX) was determined by circular dichroism (CD) spectroscopy. Under anhydrous conditions CD spectra of 5 beta-cholestane-3 alpha, 7 alpha, 12 alpha, 23, 25-pentol in the presence of Eu (fod) 3[tris (1, 1, 1, 2, 2, 3, 3-hepta fluoro-7, 7-dimethyl-octane-4, 6-dionato) europium (III)] exhibited a large induced split Cotton effect at ca. 310 nm. From the induced circular dichroism of 5 beta-cholestane-3 alpha, 7 alpha, 12 alpha, 23, 25-pentol with Eu(fod) 3 it was concluded that the CTX bile alcohol has the 1, 3 glycol structure with carbon 23 having the R configuration. This information will be useful in elucidating a structural mechanism for the conversion of 5 beta-cholestranepentols into bile acids in man and rat.


Synthesis of iodine-131 labeled 6 beta-iodomethyl-19-norsitost-5(10)-en-3 beta-ol and 19-iodositost-5-en-3 beta-ol for adrenal imaging.

6 BETA-Iodomethyl-19-norsitost-5(10)-en-3 beta-ol (V) was synthesized by homoallylic rearrangement of 19-iodositost-5-en-3 beta-ol (IV), which was obtained by the hydrolysis of 19-iodositost-5-en-3 beta-ol acetate (III) derived from the displacement of sitost-5-ene-3 beta, 19-diol 3-acetate 19-p-toluenesulfonate (I) with sodium iodide in isopropanol. The radioiodinated IV and V were prepared by isotope exchange with sodium iodide-I-131.


Mass spectrometry and stability of t-butyldimethylsilylethers of some estrogens and androstanes.

In addition to using radioimmunoassays for the determination of estrogens and other steroids, the possibility of using mass fragmentography for analysis was investigated. t-Butyldimethylsilyl chloride was selected as a reagent for derivatisation because it forms rather stable silylethers. In all the mass-spectra obrained from the steroid derivatives, one pronounced peak suitable for mass fragmentography was always present. Some of the spectra of the investigated estrogens, as well as testosterone, 3 alpha-hydroxy-5 alpha-androstan-17-one and 17 alpha-methyl-17 beta-hydroxy-5 alpha-androstan-3-one are discussed. The stability of various t-butyldimethylsilylethers and the rate of enolization of testosterone and progesterone in the presence of the silylation-agent under different conditions were established.


A microassay for the measurement of androgen receptors in human prostatic tissue.

A microassay utilizing R 1881 (methyltrienolone) has been developed for the measurement of androgen receptor sites in the cytosol and nuclear extract of human prostatic tissue. Binding of R 1881 to the progesterone binding molecule in cytosol was eliminated by the addition of triamcinolone acetonide. Utilizing a six tube, single point assay, the number of binding sites estimated in nuclear extract averaged 95% of the number measured by a full 7 point Scatchard analysis; the number estimated by the microassay in cytosol averaged 91%. When the single point assay was applied to needle biopsy specimens (200 mg of tissue), the estimated number of binding sites in nuclei averageed 83% of the number measured in bulk tissue (2 grams) utilizing a 7 point Scatchard analysis; the number in cytosol estimated by the microassay on needle biopsy specimens averaged 73%. It is hoped that this technique may be useful in correlating receptor content with hormonal responsiveness in men with metastatic carcinoma of the prostate.


Binding properties of testosterone receptors in the hypothalamic-preoptic area of the adult male mouse brain.

This study reports the specificity, kinetics and thermodynamics of the binding of tritiated testosterone to specific receptors in the cytosol of the hypothalamic-preoptic area of the adult male mouse brain. Values for the kinetic is parametrs KA, KD, ka, kd and the apparent free energy (delta GOoc) are reported. The specificity of these receptors was investigated by LH-20 chromatography and sucrose-gradient centrifugation. Differences inreceptor specificity between the mouse and that reported for the rat are described. The effects of the antiandrogens, cyproterone acetate and BOMT, and the anti-estrogens MER-25 and clomiphene citrate on the binding of tritiated testosterone to specific 8S receptors are also reported. The effect of these steroid receptor antagonists on testosterone binding is discussed in relation to the current theory on the mechanism by which androgens influence brain function.


Novel epimerization of steroidal allylic alcohols.

Epimerization of 4-pregnene-3 beta,20 alpha-diol into 4-pregnene-3 alpha,20 alpha-diol was achieved under the mild condition of an acidic medium at room temperature. This reaction was favorable for synthesis of 4-pregnene-3 alpha,20 alpha-diol in better yield, after chemical reduction of 20 alpha-hydroxy-4-pregnen-3-one with metal hydrides, which resulted in predominant production of 4-pregnene-3 beta,20 alpha-diol. The by-product which was formed more by raising the temperature was identified as 3,5-pregnadien-20 alpha-ol. This method was also applicable for epimerization of other delta 4-3 beta-hydroxysteroids.


Estradiol 17 beta-dehydrogenase and estradiol binding in human mammary tumors.

The metabolism of estradiol was studied in 31 human breast carcinoma in vitro. All 16 estrogen-receptor-poor tumors transformed estradiol to estrone with percent conversions ranging from 11.4 to 95 except for one poorly differentiated tumor where 0.5% conversion to estrone was observed. On the contrary, only 3 out of 15 estrogen-receptor-rich tumors showed higher than 10% conversion of estradiol to estrone (p = 0.001). There is indication that the enzymatic activity in receptor-poor tumors steadily decreases in premenopausal patients as they approach menopausal age, whereas, the activity steadily increases in post-menopausal patients as the duration of menopause lengthens.


Failure of thiopental to modify global anoxic injury.

To corroborate thiopental protection from cerebral anoxia after cardiopulmonary arrest, 23 sedated, curarized, adult dogs were asphyxiated by plugging the endotracheal tube. Cardiopulmonary resuscitation (CPR) was started 7 minutes after electrocortical silence. Twelve animals received no other treatment (controls), 10 regained consciousness and spontaneous respirations, but remained decerebrate, blind, unable to drink or feed. Two dogs returned to a normal neurologic state. Ten dogs were treated with thiopental after CPR, 7 received 15 mg/kg the first minute, followed by 23 mg/kg over 1 hour; 3 received 60 mg/kg in the first 3 minutes, followed by 30 mg/kg over 1 hour. Except for 1 dog in the low-dose group that recovered neurologically, thiopental-treated dogs showed no neurological or survival improvement over the controls.


Physostigmine-induced cerebral protection against hypoxia.

Physostigmine, at 0.1, 0.2 and 0.3 mg/kg, was tested for effect on the survival of mice exposed to 5% O2-95% N2. Some treated animals survived for one hour under the hypoxic atmosphere (2 out of 14 at 0.1 mg/kg and 8 out of 28 at 0.2 and 0.3 mg/kg), an event never observed in untreated controls. The physostigmine-treated animals that died before the hour showed a dose-related increase in survival time from 4.3 min (untreated controls) to 27.6 min (0.3 mg/kg physostigmine). The effect of physostigmine may be related to its reported ability to increase cerebral blood flow and decrease cerebral oxygen consumption


Cervical carotid aneurysm presenting as recurrent cerebral ischemia with head turning.

Extracranial carotid artery aneurysms are uncommon lesions with protean manifestations. This report describes a patient in whom the presenting symptom of a right carotid aneurysm was recurrent right hemisphere ischemic attacks when he turned his head to the left. The angiographic and operative findings explained the mechanism(s) of his symptoms. The importance of such symptoms is that they should suggest a mechanical etiology and that the probability of a surgically correctable lesion exists. Arteriography is the only reliable means of making a definitive diagnosis and should be considered early in the evaluation.


Protection from cerebral ischemia by a new imidazole derivative (Y-9179) and pentobarbital. A comparative study in chronic middle cerebral artery occlusion in cats.

For the purpose of investigating the protective action against cerebral ischemia by a new imidazole derivative (Y-9179) and pentobarbital, regional cerebral ischemia was produced in 53 cats by permanent occlusion of the middle cerebral artery (MCA) via the transorbital approach. In 20 cats, the clips were applied at the origin of the right MCA whereas in the remaining 33 they were applied laterally. The administration of Y-9179 (6.25 and 12.5 mg/kg/day), pentobarbital (25 mg/kg/day) and saline was started 30 min after MCA occlusion and continued for 3 days. The cats were observed for 7 days and then sacrificed. Since there was a remarkable difference in mortality between the medial (65%) and the lateral occlusion groups (15%), the evaluation of drug effects was based only on the results obtained with the lateral occlusion group. The brains were sliced at 4 fixed coronal planes, in which the ratios of the infarcted area in the 2 hemispheres were obtained by planimetry. A statistically significant decrease in the infarction rate was found both in Y-9179 and pentobarbital-treated groups compared to the control group. Since the CNS depressant action of Y-9179 is far less potent than that of pentobarbital, the present results indicate the potential usefulness of Y-9179 in the management of strokes.


Influences on family planning acceptance: an analysis of background and program factors in Malaysia.

Which factors have the greater influence on family planning performance: fixed background variables such as racial composition, urbanization, and mortality, which are affected by level of development, or program inputs such as assignment of personnel and location of clinics, which are subject to manipulation by administrators? An analysis of differences in family planning acceptance among 70 districts of Malaysia shows that two main program-manipulable variables--level of personnel deployment and accessibility of clinics--have the largest direct effect upon acceptance levels. Variations in background factors explain a smaller proportion.


Underlying family-size preferences and reproductive behavior.

Although about half the married women in a US survey said they wanted one or two children, underlying family-size preferences indicate a potential for many to have larger families. Using a measure of family-size preference that probes beyond single-valued statements, it is found that identical stated family-size desires or intentions may have different meanings for different people. Differences are systematically related to the stage in family building at which contraception begins, to current (or likelihood of future) use of effective methods, to the probability of continued childbearing, and to unwanted pregnancies.


New issues, new options: a management perspective on population and family planning.

As population problems increasingly are seen in the context of socioeconomic development and as programs to reduce fertility become more diversified and multisectoral, issues facing program managers are changing. In addressing today's challenges in the areas of population policy and development planning, family planning program design, and problem-solving mechanisms, a variety of options can be considered. No blanket prescriptions can be made, but familiarity with some of the alternative and an understanding of their political and administrative implications may be helpful to managers, not only of population programs but in related development field as well.


Serum dopamine-beta-hydroxylase activity in acute stroke.

Serum dopamine-beta-hydroxylase (DBH) activity was measured in 34 patients with acute cerebrovascular disease. The serum level of DBH activity showed its highest value soon after the onset of stroke and then gradually decreased over the next few days. After reaching its lowest level, the DBH activity again showed a slight increase. There was no direct relationship between serum DBH activity and total serum protein, or blood pressure. In 8 of 12 patients, DBH activity in the cerebral venous blood was higher than that in the arterial blood. These results suggest that rapid release of DBH into the circulating blood occurred after stroke, presumably from sympathetic nerve endings in the vessels or organs, including the brain.


Platelet thrombi in experimental cerebral infarction.

Cerebral infarction was produced in paralyzed, ventilated rats by a 30 min period of right common carotid artery occlusion combined with systemic hypoxia (Pao2 21-25 mm Hg). After 30 min the arterial clamp was removed and the animals were reoxygenated and allowed to survive for 1 min (6 animals), 30 min (12 animals), or 1 1/2 to 2 h (6 animals). The animals were reanesthetized and sacrificed by perfusion-fixation with paraformaldehyde-glutaraldehyde. Light and electron microscopy revealed ischemic cell change in neurons in the ipsilateral cerebral cortex, striatum and hippocampus. These changes were mild to moderate in the early post-ischemic period and severe in the post-ischemic period. Cerebral infarction was present in one of the 30 min survivors and in all of the 1 1/2 to 2 h survivors. Electron microscopy showed platelet thrombi in the infarcted brain in 3 of the 7 animals with infarcts, and in an area of very severe ischemic cell change in a fourth animal. They were not present in areas of brain showing only mild to moderate ischemic cell change. These findings showed that platelet thrombi form in association with cerebral infarcts and suggested that they are induced by tissue necrosis rather than by neuronal ischemic cell change alone.


Intracranial saccular aneurysm and moyamoya disease.

Moyamoya disease is a rare but well described entity which has been found in the angiographic investigation of subarachnoid hemorrhage, its most common symptom in adults. We present 4 patients in whom moyamoya disease and an intracranial saccular aneurysm were discovered. In 2 of the 3 patients suffering a hemorrhage, the aneurysm was the source of bleeding. Three of the aneurysms were located at the basilar artery bifurcation. We recommend a careful search for a concomitant aneurysm in all patients with subarachnoid hemorrhage in whom moyamoya disease is found. We believe these patients should be treated as though the aneurysm were the source of bleeding.


Influence of sex on cerebral ischemia following bilateral carotid occlusion in spontaneously hypertensive rats: a metabolic study.

Cerebral lactate, pyruvate and adenosine triphosphate (ATP), and acid-base balance were measured in male and female spontaneously hypertensive rats (SHR) before, and 1, 3 and 5 hours after bilateral carotid occlusion. In male SHR, cerebral lactate and the lactate/pyruvate (L/P) ratio progressively increased after occlusion, while cerebral ATP decreased. In female SHR, an increase in lactate and the L/P ratio was less marked than in male SHR. Cerebral ATP remained unchanged 5 hours after occlusion. These data suggest that bilateral carotid artery occlusion may cause more pronounced ischemic changes in the brain in male SHR than in female SHR, resulting in a greater increase in lactate with a concomitant decrease in ATP in male SHR. Results suggest that female SHR are more resistant to cerebral ischemia following bilateral carotid occlusion than male SHR. Blood pressure and gonads in the susceptibility to cerebral ischemia are discussed.


Stroke-associated deaths in Washington county, Maryland, with special reference to water hardness.

Deaths associated with strokes from 1963 to 1975 among 36,860 adult residents of Washington County, Maryland, were studied in relation to the hardness of drinking water at home, assessed on the basis of 1,569 water samples taken during this period. There was no satisfactory evidence that water hardness was related to stroke mortality. Age was a strongly related factor. There was little or no association with sex, marital status, socio-economic status as reflected by education or housing, smoking history, or frequency of church attendance.


Incidence of stroke in an African City: results from the Stroke Registry at Ibadan, Nigeria, 1973-1975.

Studies based on hospital populations reported from negro communities in several countries in Africa suggest that cerebrovascular disease (CBVD) shows increasing mortality and morbidity in Africans although 2 decades ago CBVD was believed to be uncommon. We report the first study in the African to determine the incidence of stroke in an urban area, Ibadan, Nigeria.


The problem of emesis during oral glucose-electrolytes therapy given from the onset of severe cholera.

In an attempt to obviate the need for intravenous fluids by preventing dehydration, 57 adult volunteers who experienced induced clinical cholera during a vaccine development programme were treated from the onset of diarrhoea with oral glucose-electrolytes therapy. 44 individuals with mild to moderately profuse diarrhoea (less than 8 L. total volume) were maintained in normal water and electrolyte balance with oral therapy alone. 13 individuals with severe diarrhoea (greater than 8 L. total volume) could not be maintained in balance with oral therapy alone, due chiefly to emesis during the first day of illness. Emesis occurred in the absence of significant dehydration or acidosis. Since emesis precludes effective early oral therapy in severe cases, domiciliary oral therapy is unlikely to eliminate cholera mortality. Rural diarrhoea treatment centres using oral therapy with limited amounts of intravenous fluids when needed, could reduce case fatality from cholera and related diarrhoeas virtually to zero with least expense.


Dengue in the Caribbean: virus isolation in a mosquito (Aedes pseudoscutellaris) cell line.

During outbreaks of dengue fever in the Caribbean in 1977 and 1978 a continuous cell line derived from Aedes pseudoscutellaris was successfully used for the isolation of dengue virus strains from acute human sera. 238 strains were isolated and culture fluid was successfully used as antigen for the identification of several strains. The isolates all produced a marked syncytial cytopathic effect often visible as early as four days after inoculation. The method was successfully employed in the field where, because of their low optimal incubation temperature, the cells suffered no ill effects under ambient conditions. The isolation method was found to be much more sensitive than conventional mouse inoculation.


Immunoglobulin levels in Nigerian cord blood sera.

We have quantified the levels of IgG, IgA and IgM in Nigerian cord blood samples during the dry and the wet seasons. Almost all the samples collected during both seasons had detectable levels of IgG and IgM, while IgA was detected in 71% of those collected in the rainy season and in only 45% of those collected during the dry season. We observed seasonal variations in the levels of each of these immunoglobulins but the variations were not consistent for all three immunoglobulin classes. This suggests that the levels of each immunoglobulin class in the cord blood is probably controlled by different antigenic factors in our environment. The mean values for all three immunoglobulin classes were raised in all our samples above those of UK cord blood samples. This is consistent with earlier reports for samples collected in the tropics. In the paired cord/maternal immunoglobulin estimations, 75% of cord sera had higher levels of IgG than their corresponding maternal samples, suggesting either active transfer of the immunoglobulin across the placenta or increased rate of synthesis or decreased rate of catabolism in utero.


Immunity of cholera in man: relative role of antibacterial versus antitoxic immunity.

Purified cholera toxoid is antigenic when given enterally and orally. Purified toxoid fails to provide protection against experimental challenge. Clinical cholera confers formidable protection against homologous or heterologous rechallenge. Failure to culture vibrios from intestinal fluid or stool of re-challenge volunteers suggests that the predominant immune mechanism is antibacterial rather than antitoxic.


Factors affecting the acquisition of resistance against Schistosoma mansoni in the mouse: III. The failure of primary infections with cercariae of one sex to induce resistance to reinfection.

Mice which were given a primary infection consisting of male or female Schistosoma mansoni cercariae alone failed to acquire the same degree of resistance against homologous challenge as did mice with a bisexual primary infection. The degree of resistance acquired by "single-sex"-infected mice was not augmented either by increasing the number of cercariae administered in the primary infection, or by increasing the interval between primary infection and challenge, or by injection of S. mansoni eggs. The results are discussed in relation to previous observations on the capacity of "single-sex" schistosome infections to induce resistance.


Sugar absorption by the mouse small intestine following infection with Schistosoma mansoni.

The effect of acute schistosomiasis on the structure and function of the mouse small intestine has been examined. Whole loops of small intestine from normal mice, and mice seven weeks post-infection were incubated in an in vitro perfusion apparatus. The transport of glucose, 3-0-methylglucose, sorbitol and fluid were all markedly impaired in loops from the infected animals. Kinetic analysis of the data for glucose transport indicated that schistosome infection brought about a reduction in the total number, but not the affinity, of the absorptive sites for glucose. Under the scanning electron microscope, villi from normal mice were tall and erect, with intact surfaces devoid of mucus, whereas the villi from the infected animals were partially covered with strands of mucus and appeared swollen and eroded, with lesions around their apices.


Kala-azar in north-western India: a study of 24 patients.

Twenty-four sporadic cases of kala-azar diagnosed over an 11-year period in a referral medical centre in north-western India are reported. Most of the patients were residents of non-endemic areas or where endemicity was low. Certain unusual clinical and laboratory features were seen in some of the cases, namely, lymphadenopathy, nasopharyngeal growth, acute and chronic hepatic involvement and portal hypertension. Awareness of the occurrence of the disease and of its protean modes of presentation was found to be an important factor in early diagnosis.


Severe ulcerative herpes of mouth and eye following measles.

Malnourished children in the north of Nigeria who had had a severe attack of measles were prone to deep ulcers of the mouth and eyes. Herpes simplex virus was isolated from 17 of 25 of the mouth ulcers which were erosive, slow to heal and caused much suffering and loss of weight. Herpes virus was also identified, either by immunofluorescent staining or viral culture, in the corneal scrapings of the eye ulcers from 16 of 34 children. These ulcers healed slowly in two to six weeks leaving damaging scars which impaired vision and caused blindness in some cases. It is suggested that measles leads to profound depression of cell mediated immunity in malnourished children with the consequence that secondary herpes simplex infections become abnormally severe and erosive.


An evaluation of nutrition centre effectiveness by measurement of younger siblings.

Thirty children were measured when they entered nutrition centres. Their younger siblings were later measured at the same age. Over the same period, a matched group of control children and their siblings were measured. The younger siblings of Centre participants showed the same growth patterns as the younger siblings of control children. Centre teaching had evidently not affected the way mothers fed their younger children, and thus it had no effect on their growth.


The significance of proteinuria and haematuria in Schistosoma haematobium infection.

The intensity and prevalence of proteinuria and haematuria were studied with urinanalysis reagent strips in a Gambian community in which the intensity of infection with Schistosoma haematobium was high. The level of proteinuria present was shown to be related to the intensity of infection. Follow-up for 12 months showed that infected subjects with heavy proteinuria had a good prognosis. These findings suggest that the urinary protein in such subjects is likely to originate from lesions in the bladder and ureters and that advanced glomerular pathology is probably rare. The relationship of the levels of proteinuria and haematuria to the egg count suggests they may be parameters which could have value as indications for chemotherapy. Detailed study showed that the effect of treating all the subjects who had both 30 mg/100 ml or more of protein and at least a trace of haematuria would have been very similar to treating all those with an egg count of 200 ova/10 ml or more. Since urinalysis with reagent strips is very simple and rapid it could have a role in mass chemotherapy campaigns, particularly those aimed at the identification and treatment of heavily infected subjects.


Intestinal parameters in acute murine schistosomiasis mansoni.

Intestinal involvement is very important in acute murine schistosomiasis mansoni. Nevertheless intestinal parameters have not previously been used in assessing the severity of intestinal disease. The present observations demonstrate that in Schistosoma mansoni-infected mice, the mean total egg count of the small intestine and the mean number of eggs per g in the small and the large intestine were higher than the corresponding egg counts in the liver. The increase in weight of the small intestines of infected compared with uninfected mice was greater than the increase in weight of the corresponding livers. The small intestines from infected mice were considerably shorter than those from uninfected mice. These findings argue for the small intestine as a valuable organ for pathophysiological studies in acute murine schistosomiasis mansoni and simple parameters such as total egg count of the small intestine, the number of eggs per g tissue in small and large intestine and the weight and length of the small intestine, are recommended.


Infant foods as a potential source of diarrhoeal illness in rural West Africa.

It is common practice in rural areas of The Gambia to prepare infant foods in quantities which are sufficient to meet the needs of the day rather than one meal. These are then stored at ambient temperatures for periods up to 12 hours for feeding to the child on demand. The total viable counts and levels of Bacillus cereus, Clostridium welchii, Staphylococcus aureus and Escherichia coli were determined in 294 infant foods samples from nought to eight hours after preparation. The presence of Salmonella was determined in 10 g samples of food. In the first hour after preparation the proportion of foods dangerously contaminated was high during the rainsy season, significantly more so than during the dry season. Foods not consumed fresh were very often hazardous and almost always so after 8 hours. This problem may be a causal factor in weanling diarrhoea which also shows marked seasonal variation in prevalence.


Functional characteristics of monocytes. II. Further observations on lymphocyte-monocyte collaboration in the response to phytomitogens.

Monocytes play a crucial role in the response of lymphocytes to phytomitogens. This role is evident during the very early events after exposure to the mitogen. Thus, significant lymphocyte transformation does occur when monocytes are removed from the culture within a few hours after exposure to mitogen, and the presence of monocytes after the initial period is no longer necessary. Monocytes appear to be required for the early increase in protein synthesis and burst in RNA synthesis following exposure to the mitogen. Monocytes may help in lymphocyte responses partly by longer range, by way of release of soluble humoral factors into culture supernatant fluids. Temperature dependence of the effect of pulse exposure of lymphocytes to these supernatants raises the possibility that membrane receptors on these cells to humoral factors released by monocytes may exist. Moncytes do not appear to act primarily by preserving the viability of lymphocytes in culture.


Kaposi's sarcoma in organ transplant recipients: report of 20 cases.

There is an increased incidence of Kaposi's sarcoma (KS) in organ transplant recipients in whom it comprises more than 3% of all de novo neoplasms. Any such patient who develops reddish blue macules or plaques in the skin or oropharyngeal mucosa, or has apparently infected granulomas that fail to heal, should be suspected of having KS. In 45% of the patients, the internal viscera are involved. This variety has a bad prognosis. Apart from conventional treatment with surgical excision, radiotherapy or chemotherapy, cessation, reduction, or modification of immunosuppressive therapy produces gratifying results in a significant number of patients.


Adenosine triphosphate regeneration and function in the rat kidney following warm ischaemia.

Tissue levels of adonosine triphosphate (ATP) have been measured in rat kidneys following periods of warm ischaemia: (1) immediately after the ischaemic period and (2) after the kidney had been reperfused with blood for 10 min. ATP levels at the end of the period of ischaemia are similar for ischaemic periods of 10 to 60 min and give no indication of the kidneys subsequent functional ability. The amount of ATP regenerated in 10 min of reperfusion correlates both with the duration of the period of ischaemia and with the subsequent functional ability of the kidney.


Genetics of F1 hybrid susceptibility to myeloma grafts.

The genetics of hybrid susceptibility of parental myeloma transplants in histocompatible F1 hybrids was investigated. Various inbred mouse strains and their descendant congenic lines were crossed with BALB/C mice to produce appropriate F1 hybrids. Genetic inferences were drawn from the comparison of the frequencies of tumor graft takes among congenic combinations. Hybrids containing the C57BL/10 genetic background were less susceptible to myeloma transplants than were hybrids of other genotypes. Both H-2-associated and non-H-2-associated genetic factors played significant roles in determining host susceptibility to the transplants. The D end of the major histocompatibility complex did not play a predominant role in determining hybrid susceptibility in C57BL-derived F1 hybrids.


Electron microscopical studies on onchocerciasis. III. The onchocerca-nodule.

Six onchocerca-nodules from five Liberian patients were examined by electron microscopy. The bulk of cells in the centre of the nodules consists of lymphocytes and macrophages. The lymphocytes can be observed in various stages of differentiation. A major part of the macrophages shows degenerative changes with decrease of lysosomes and increase of fatty vacuoles. Near the worms epithelioid cells and giant cells can be found. Other cells in the nodule include polymorphonuclear neutrophils, eosinophils, plasma cells, and mast cells. Adult Onchocerca volvulus show the basic nematode body plan. The cuticle is subdivided into cortex and two layers with differently arranged fibrillar structures. The characteristics of the hypodermal cells are best seen in the lateral chords, in the interchordal regions the hypodermis is flattened by a muscle layer. The intestine typically contains pigment granules, the cells of the epithelium have folds of their cell membranes forming a basal labyrinth. The uterus consists of two tubes in which the development of the microfilariae from the early embryonic forms to the mature stages is examined.


Some observations on onchocerciasis including sowda in the Yemen Arab Republic.

A pilot study on onchocerciasis and sowda was carried out in the south-western region of the Yemen Arab Republic. Of 61 persons examined in eight villages 35 (= 57%) were found positive for microfilariae by the skin-snip method, 13 had typical manifestations of sowda, 17 had other onchocercal-suggestive skin lesions and five had subcutaneous nodules. A single larva of Simulium damnosum s.I. was collected in Wadi Barakani. Numerous larvae and pupae of S. ruficorne and S. hargreavesi were taken in fast-flowing streams in four localities. The examination of microfilariae and adult worms by scanning electron microscopy as well as the histochemical staining of microfilariae for the demonstration of acid phosphatase activity confirmed that the concerned filaria belongs to the species Onchocerca volvulus. No morphological differences could be detected between the smaller number of the examined worms from the Yemen and the extensive parasite material from Liberia, West Africa.


The complement fixation test and African trypanosomiasis: I. Experimental infection and re-infection in cattle before and after treatment.

The complement fixation test was applied to assess antibody responses in cattle infected with T. brucei, T. congolense, and T. vivax which had been treated and re-infected. After the first infection, the specificity of the results was low in T. congolense, fair in T. brucei, and high in T. vivax infected animals. After re-infection with the same trypanosoma species as used for previous infections, the specificity of CF results was high in all cases. After a foregoing T. vivax infection, specific titres of T. congolense and to a lesser degree of T. brucei infections were frequently masked by residual T. vivax titres. After treatment of trypanosoma-infected cattle the fasted drop of CF antibody titres occurred in T. congolense cases, followed by T. brucei infections. T. vivax titres persisted over prolonged periods.


Immunization against anaplasmosis and babesiosis. Part III. Evaluation of immunization under field conditions in the Cauca River Valley.

Bovine anaplasmosis and babesiosis constitute serious constraints to efficient cattle production in Colombia. Nine commercial ranches located in the Cauca River Valley were used to evaluate the applicability, safety and economics of the newly developed immunization technology to control these diseases under actual field conditions using the minimum infective doses techniques. A total of 432 calves, 6--8 months old, of different breeds were used in this experiment. Calves born and raised in nonendemic areas of Valle, vaccinated against anaplasmosis and babesiosis and then moved to the endemic zone had developed a high degree of resistance. None of them died or required treatment after field challenge. In comparison, non-vaccinated controls suffered severe clinical anaplasmosis and babesiosis. Eighteen percent dies and 85% required chemotherapy to survive. Calves born and raised in the endemic zones of Valle and vaccinated did not suffer clinical disease nor require treatment after field challenge. However, non-vaccinated controls had 2% mortality and 60% of them required treatment to survive under the same field conditions. The weight gains favored vaccinated animals. The results of this study indicate significant reductions in deaths and production losses of cattle and the economic benefits to the livestock producers in controlling tick-borne diseases by vaccination.


Granuloma size in the liver of mice with Schistosoma haematobium infection and Schistosoma mansoni challenge.

Swiss albino mice have been infected with S. haematobium and challenged with S. mansoni. S. haematobium infection in the mouse runs a course more or less parallel to that of S. mansoni infection. Granuloma has reached a maximal size at 135 days post infection and has regressed thereafter. Suppression of S. mansoni granuloma was observed in mice previously infected with S. haematobium. This manifests the presence of cross immunization.


Pentamidine in chemoimmunisation of cattle against Babesia bigemina infection.

A single dose of 0.5 to 1 mg/kg of Pentamidine led to clinical recovery of splenectomised calves infected with Babesia bigemina. On the other hand as much as 5 mg/kg administered during patency did not destroy the carrier state in intact calves. The fact that the sterilising dose was at least five times as great as that needed for clinical recovery makes Pentamidine a promising agent for chemoimmunisation against B. bigemina infection.


An outbreak of tropical theileriosis in cattle in Afghanistan.

An outbreak of tropical theileriosis (T. annulata infection) is reported in artificial insemination Holstein bulls in Kabul (Afghanistan). The diagnostic work at the Central Veterinary Diagnostic Laboratory is described and the treatment given and results obtained by the Kabul Animal Health Clinic are reported. This case report constitutes the first account of the disease in Afghanistan where diagnostic confirmation has been made from material sent to internatinational reference centres.


[Electron microscopic study of experimental allergic encephalomyelitis in dogs. II. Relationship between ultrastructural changes in the central nervous system and the severity of the course. Mechanism of allergic demyelination].

It is determined that in grave forms of experimental allergic encephalomyelitis (EAE) demyelination and inflammatory infiltration are spread widely, whereas in easy forms only demyelination is observed. A conclusion is made that disturbances in the vascular permeability, activation of lysosomes and degeneration of synapses are of pathogenic value. Important role of a glia in phagocytizing myelin is emphasized. Significance of the role of immunological humoral factors and of biologic active substances in the pathogenesis of EAE is discussed.


Bovine brucellosis in the southern regions of the Somali Democratic Republic.

For the first time a survey of the prevalence of bovine brucellosis in three regions of the Democratic Republic of Somalia has been carried out. Blood sera were tested by the SAT and CFT and milk samples by the MRT. An average prevalence rate of 9.5 per cent (SAT) and 12.0 per cent (MRT) was found. There was considerable differences between regions and the reasons for this are discussed.


Newcastle disease in Cyprus: a review.

The first Newcastle disease epidemic in Cyprus was reported in 1949 to 1950 and between 1953 and 1959 there was a second. In November 1977 another Newcastle disease outbreak occurred. Measures implemented immediately were; quarantine of all foci of infection, destruction of diseased and in-contact birds disinfection of premises and island-wide (Government controlled) vaccination. Within a month the epidemic was brought under control. In all 47 outbreaks were recorded with the loss of about 35,000 birds. Only 2 commercial units were affected, the remaining outbreaks occurring in premises of back-yard poultry keepers. The virus was the Asiatic type.


Cutaneous water loss and respiration rates of various breeds of sheep at high ambient temperatures.

The sweating and respiratory rates in rams of Rambouillet (R), Chokla (C), Malpura (M), R x C and R x M breed/breed crosses were recorded when housed in sheds or exposed to 20, 25, 30, 35 and 42 degrees C ambient temperatures in a climatic chamber. The sweating (cutaneous moisture) was higher (P less than 0.05) in Rambouillet and its crosses than the natives, the Malpura sheep producing the least sweat at all temperatures. There was no breed difference in the response of increase in sweating up to 35 degrees C but at 42 degrees C the Chokla showed a considerable increase. Sweating was more pronounced on the shoulder than on the mid-side region. Sweating and respiratory rates increased (P less than 0.05) with the increase in ambient temperature. The Rambouillet exhibited the highest increase in respiration rate at 25 degrees C and the trend continued up to 42 degrees C. The relationship between fleece characteristics, evaporative heat loss tolerance of sheep is dicussed.


A survey of abattoir data in northern Nigeria.

A survey of the abattoirs in 10 selected towne in Nigeria showed that about 41.9 per cent of whole carcasses condemned between 1975 and 1977 were due to tuberculosis and 22.2 per cent to beef cysticercosis. Seventy per cent of organ condemnations, mainly of livers, were due to fascioliasis. Other major causes of organ condemnations were hydatid cysts, tuberculosis and pneumonia of various causes. An estimated 500 tonnes of meat valued at about 1.25 million Naira (US $1.8 million) are condemned each year throughout Nigeria. The use of abattoirs as monitoring stations in national animal disease eradication programmes is highlighted.


VP-16, cyclophosphamide, adriamycin and cis-platinum (V:CAP-I) in patients with metastatic adenocarcinoma of the lung.

In an attempt to improve upon the 42% regression rate of the CAP-I regimen in patients with advanced adenocarcinoma of the lung, VP-16 was added to that regimen. VP-16, as a single agent, had a response rate of 12.5% (3/24) In a similar group of patients. The new regimen, V:CAP-I, had a tumor regression rate of 35% (7/20) and an estimated median survival of 171 days. Hence, we were unable to conclude that the addition of VP-16 to the CAP-I regimen statistically improved the regression rate of the CAP-I regimen.


Basal-cell tumors of the lumbar skin after radiotherapy for arthrosis.

Twenty-three cases of basal-cell tumor of the skin arising in the lumbar-sacral region after repeated irradiations in anti-inflammatory doses for arthrosis are discussed. The involved cutaneous region had been submitted to a number of roentgenotherapy cycles, varying from a minimum of 2 to a maximum of 10. The total dose absorbed at skin level varied between 14.4 and 72.0 Gy, administered over 2 to 6 years. Thirteen to 30 years (median, 19) had elapsed since the end of the irradiations. This observation compels a critical re-evaluation to be made concerning certain radiotherapy indications. The treatment of these lesions involves some problems: radiotherapy is made difficult by the coexistence of often serious dystrophic lesions on the surrounding skin, and surgery is often unsuccessful. The topic application of 5-fluorouracil ointment seems to achieve good results.


Biochemical and cytochemical effects of cytosine arabinoside (ARA C) and hydrocortisone on HeLa cells.

The biochemical and cytochemical effects of cytosine arabinoside (Ara C) and of hydrocortisone on HeLa cell in vitro have been studied. In cultures treated with Ara C, a relationship exists between the cytocidal effects of the drug and an increase in alkaline phosphatase. Although hydrocortisone had no influence on the proliferative rhythm, it induced an increase in alkaline phosphatase. Results obtained with the cytochemical technique were evaluated, particularly in relation to enzyme localization.


Clinical classification and survival in chronic lymphocyte leukemia.

Sixty-one consecutive patients with chronic lymphocytic leukemia (CLL) treated at the Istituto Nazionale Tumori of Milan from September 1962 to August 1976 were classified according to the staging system of Rai et al. (16). Analysis of this series showed the following median survival (in months) from diagnosis: stage 0-I, 73; stage II, 44; stage III-IV, 32. In 11 patients without peripheral palpable adenopathies, the lymphangiogram showed abnormal retroperitoneal lymph nodes. Therefore, the initial stage was changed from 0 to I in 5 cases. The median survival for the entire series was 50 months. Patients with "indolent" disease had a median survival of 52 months, while in patients with "active" CLL, the median survival was 32 months. Both sex and age were shown to be poor predictors of survival. Increased duration of survival was observed in patients with less compared to those with more than 30,000 lymphocytes/mm3 (66 versus 41 months). The method of staging proposed by Rai et al. and utilized to classify this series at the time of diagnosis was confirmed to be a reliable predictor for survival.


Restatement of lymphography in childhood: experience with 413 consecutive patients in ten years.

From January 1969 to June 1978, 413 children under 15 years of age underwent lymphography at the Istituto Nazionale Tumori of Milan. Successful lymphatic cannulation was accomplished in 97.7% (769/787) of the sites where it was attempted. No major or permanent complications were encountered. In those children undergoing biopsy of opacified lymph nodes, the lymphographic-histologic correlation was 94.5% (104/110). This study has shown that lymphography in childhood can be as readily performed as in the adult and that its diagnostic accuracy is acceptable. As in adults, it is useful in treatment planning, evaluating results of therapy, and detecting a recurrent tumor.


Axillary lymph node metastases from occult carcinoma of the breast.

From the case records of the Istituto Nazionale Tumori of Milan from 1956 to 1976, 49 cases of metastases in axillary lymph nodes from an occult carcinoma of the breast were selected. Forty-four patients underwent removal of the suspicious breast. In 11 patients no tumor was found at the pathologic examination. The survival of these patients was no different from the survival of those in whom the tumor was found. The 5-year survival of the total series was 87%, confirming that this type of presentation of breast cancer has a prognosis that is better than that generally reported for stage II carcinoma of the breast.


Concanavalin A and wheat germ agglutinin receptors in the ascitic fluid of rat hepatomas.

The presence of glycopeptide lectin receptors in the ascitic fluid of rats bearing Novikoff or AS-30D hepatoma was investigated. Macrosialoglycopeptides, resistant to pronase digestion, were partially purified from the ascitic fluid of hepatoma-bearing rats by gel filtration on Sephadex G-50. A macrosialoglycopeptide fraction, isolated from the ascitic fluid of rats bearing the Novikoff hepatoma, possessed potent concanavalin A (Con A) receptor activity. This fraction possessed higher Con A receptor activity than did the comparable macrosialoglycopeptide fraction from the ascitic fluid of rats bearing the AS-30D hepatoma; this obeservation is in agreement with the Con A-induced agglutination properties of these 2 hepatoma cell lines and with the Con A receptor activities of the glycopeptides released from the surface of the hepatoma cells by papain digestion. Rat blood serum contained a comparable macrosialoglycopeptide fraction, which possessed weak Con A receptor activity. The macrosialoglycopeptide fractions from the ascitic fluid of hepatoma-bearing rats possessed wheat germ agglutinin receptor activity. However, this activity was also present in normal rat serum. These results suggest that glycopeptides present on the surface of Novikoff hepatoma cells are shed into the ascitic fluid and may be distinguished from components in normal serum by their Con A receptor activity.


Hormonal study in patients developing amenorrhea during adjuvant chemotherapy for breast cancer.

The sera of 15 premenopausal women with operable breast cancer and who had developed amenorrhea during adjuvant chemotherapy with cyclophosphamide + methotrexate + fluorouracil were analyzed for the following hormones: 17-beta-estradiol, luteinizing hormone, thyroid stimulating hormone and prolactin. The blood levels did not differ significantly from those found in patients operated on for breast cancer and in spontaneous menopause (controls). These origins suggest that the amenorrhea induced by CMF chemotherapy is of ovarian origin.


Phase I trial with peptichemio.

Thirty-two patients with tumor progression, even after conventional cytostatic drug treatment, were treated with peptichemio, with increasing doses for groups of 4 patients. The maximum tolerated dose (with minimum hematological toxicity and without any other evident toxicity) with repeated administrations, was 1.2 mg/kg twice weekly. The recommended doses for phase II trials are, as shown by the detailed analysis of the results, 0.9 mg/kg, twice weekly and administered alone, and 1.3 mg/kg, once weekly combined with other cytostatic drugs, in 500 ml of infusion fluid, with 25 mg of heparin and 25 mg of hydrocortisone to minimize the freqent risk of local phlebosclerosis.


Dimensions of postcapillary venules sensitive to bradykinin and histamine-induced leakage of macromolecules.

Microvascular leakage of macromolecules was studied in the hamster cheek pouch preparation using fluorescein labelled dextran (FITC-dextran 145 Mw = 145,000) as a tracer. When the preparation is superfused with 10(-5) M histamine or 10(-7) M bradykinin the permeability to macromolecules increases exclusively at postcapillary venules. Microinjections of 30-200 picolitres (pl) of 0.1 M histamine and 10(-4) M bradykinin close to arterioles and capillaries caused extravasation from several postcapillary venules at a distance from site of injection but not from arterioles or capillaries. The minimal diameter of the postcapillary venules where leakage occurred was (n = 45) 8.6 +/- 2.6 (S.D.) microM and the maximal diameter was 14.0 +/- 5.3 microM. Histamine and bradykinin caused leakage of macromolecules in postcapillary venules but not in arterioles, capillaries or larger venules even when these were exposed to high local concentrations of these agents.


Local traumatization with heat--cutaneous reactions and early effects on serum zinc concentration in rats with alloxan diabetes of very short duration.

Local heat trauma was induced in rats with alloxan diabetes of 3 days' duration. The cutaneous reaction, water content of the skin and serum zinc concentration were estimated. Petechiae within the area of traumatization were observed more often and were more abundant in the controls than in the diabetic animals. There was no difference between diabetic animals and controls with regard to the increase of water content of traumatized skin or to the water content of non-traumatized skin. There was no difference in serum zinc levels between non-traumatized diabetic animals and controls. After traumatization there was a decrease of serum zinc levels in both animal groups, but to a significantly lower level in the diabetic animals compared to the controls.


The effect of short-term high-dose treatment with methenamine hippurate of urinary infection in geriatric patients with indwelling catheters. II. Evaluation by means of a quantified urine sediment.

The urine sediment of 12 geriatric patients with indwelling catheters was quantified by the glutaraldehyde-cytocentrifuge method prior to, during and after a clinical trial of methenamine hippurate (MH), 2 g x 3 daily given for 34 days as the sole therapeutic agent for the urinary tract infection. The median leukocyte concentration in the urine of these patients was 100 cells/microliter (Q1 - Q3 50-350), i.e. tenfold higher than the upper normal limits reported in healthy probands. The median bacteriuria in the control period was 12 x 10(5) bacteria/ml urine, interquartile range 10-60 x 10(5) bacteria/ml and extreme individual values 300-500 x 10(5) bacteria/ml. Hematuria, defined as greater than or equal to 24 erythrocytes/microliter urine, was not prominent and could not be correlated with MH treatment, nor with catheter changes. The reported observations suggest that short-term high-dose treatment with MH as sole therapeutic agent reduced pyruria and bacteriuria in the group of patients studied.


The effect of glucose-, arginine- and leucine-deprivation on mouse blastocyst outgrowth in vitro.

To estimate the degree of trophoblast outgrowth in vitro, mouse blastocysts obtained after delay of implantation were cultured either in a modified Brinster medium or in the same medium with exclusion of various combinations of glucose, arginine and leucine. Trophoblast outgrowth was prevented only in a medium from which all three substances were excluded. In this medium the blastocysts remained expanded for 5 days without signs of trophoblast outgrowth--a growth arrest in vitro. After transfer of blastocysts growth arrested in vitro for 5 days to a complete medium including both glucose and the two amino acids, normal outgrowths occurred within two or three days. The growth-arrested blastocysts also developed normally for at least one week when transplanted into salpingectomized foster mothers. It is concluded that blastocysts activation in vitro can be controlled by a few nutrients in a way reminiscent of the activation prior to implantation in utero. Blastocysts activated in utero by systemic administration of oestrogen for various lengths of time before the start of culture, or in vitro by preincubation in a medium containing glucose and all amino acids, also grew out in the growth arrest medium if they had been activated for a sufficiently long time, 18 h in utero and 1 h in vitro, thus indicating that when a blastocyst has reached a certain degree of activation its growth can not be arrested by exclusion of glucose, arginine and leucine.


[Investigations on formation risk of calcium oxalate stones with special regard to stress (author's transl)].

Concentrations and excretion of ten urine parameters were recorded in defined urine portions of 20 calcium oxalate stone patients and 10 normal subjects; some of these urine constituents show a day-night rhythm thus indicating a daily risk variation. From the analysis of questionnaires on physical strain and psychonervous stress, correlations between stress and urine substances can be established. In this connection, oxalic acid concentration and excretion seem to be of special importance. The obtained results provide the basis for further complex-chemical calculations.


Morphologic effects of metallic copper and cadmium directly implanted into the rat kidney.

The discovery of increasing amounts of copper and cadmium in public drinking water supplies has prompted an exploration of the effects of these elements upon the kidney. Markedly different responses are observed during the 6 months after the surgical implantation of copper and cadmium wires into kidneys of Sprague-Dawley rats. Those organs which contained copper showed only mild fibrosis near the site of injury and some pelvic distortion. The cadmium-containing kidneys revealed striking parenchymal destruction and pyraminal distortion. The coexistence of persistent foci of mononuclear cells in the cadmium kidneys and widespread parenchymal destruction is accepted as evidence for the actuality of a tissue hypersensitivity to this metallic element.