Clinical value of pulmonary needle biopsy in diagnosis of pulmonary carcinoma. In 92 consecutive pulmonary needle biopsies, preliminary diagnoses on the basis of radiological and clinical data were compared with cytological reports. Three groups emerged. In the first, of 43 cases with radiological changes typical for primary lung carcinoma and no clinical data making other diagnosis a plausible alternative, the cytologist found carcinoma cells in 37 and malignant lymphoma cells in one. A further 3 cases proved to be carcinomas at the histological examination. Two cases were not carcinomas. In the second group, where 30 patients displayed radiological changes less typical for primary diagnoses, or clinical/anamnestical data also supported alternative diagnoses, the cytologist found malignancies in 8 cases, carcinoid in one and no signs of malignancy in 21 cases. In 19 cases the patients were considered radiologically to have no malignancies. Malignant cells were found in none. It is concluded that in a certain group of patients, the diagnosis of pulmonary carcinoma can be made with reasonable accuracy from radiological and clinical data alone. Needle aspiration biopsy and similar techniques are of questionable value as routine procedures when the probability of this diagnosis is already very high on other grounds. Their use should be reserved for cases where plausible diagnostic alternatives are present.


Giant-cell carcinoma of the lung. Clinical and pathological assessment. Comparison with other large-cell anaplastic bronchogenic carcinomas. Fewer than 40 cases of giant-cell carcinoma of the lung have been described in the world literature. Fourteen new cases are now presented. This is a special type of large-cell anaplastic carcinoma characterized by tumour giant cells with one or more nuclei and by a very pleomorphic appearance. A number of previous authors have emphasized the following special features of this type of tumour. Occurrence in a younger age group, a more rapid course from initial symptoms until death, more extensive metastasization, and a more peripheral location of the primary tumour than in other large-cell anaplastic carcinomas. It has also been stated that the tumour differs from other large-cell anaplastic carcinomas in its shorter duration (average 4 1/2 months) and more peripheral distribution (c/p ratio 1:2.2). In the present material only the survival period was significantly shorter (average 7 months), while in other respects the tumour did not differ from other large-cell anaplastic carcinomas.


[Sodium and magnesium levels in the vitreous body]. The technique of atomic absorption spectrophotometry was employed for the estimation of sodium and magnesium in 50 deceased persons. No dependence on the time elapsed after death was found. Significantly higher average quantities of sodium were proved in subjects who had died as a result of brain contusion; higher quatities of magnesium were found in subjects who had suffered from chronic liver involvement.


[The mechanism of the origin of acute subdural hemorrhage]. Acute subdural haemorrhage was found in 220 persons, i. e. 30.1% of a group of 731 of those who died as a result of blunt impact head injuries. The result of an analysis confirmed the significant effect of the direction and site of the blow on the development of acute subdural bleeding. Subdural haemorrhage was found the most frequently in violent blows coming from the side on the temporal region [43.4%] and in blows coming from behind on the occipital region [40.5%]. Another point proved was that in blows dealt in these directions the highest incidence of subdural haemorrhage was due to significantly more frequent development of bleeding in the group of middle-aged persons over 50, and that at the site of contrecoup. Proceeding from the results of his analysis the author stresses the significance of brain contusion and laceration for the development of acute subdural haemorrhage.


[Changes in the myocardium due to shock in resuscitated persons]. The authors report on myocardial changes in 60 patients who died at resuscitation wards after a clinical diagnosis of shock. A separate section is devoted to complications developing after cardiosurgical operations.


Population, food and nutrition during the remainder of this century: Part I. World prospects. People mainly depend on food that can be produced on arable land. However, the amount of this land is strictly limited and is less than is generally assumed. Particularly in the developing countries it is usually very fully exploited, but the crop yields obtained are poor and all too often the productive capacity is steadily decreasing. Efforts to improve conditions were often successful, but they have been largely arrested by the rapid rise in the cost of energy. These improvements were partly responsible for a slight rise in the standard of living, sufficient to cause a corresponding slight reduction in the awesome rate at which the population was increasing. For the same reason this encouraging tendency can no longer be expected; indeed it will be reversed. Other adverse effects must be expected from this new factor which will increase the gravity of a situation already so very serious. More and more people cannot be nourished by land that is becoming less and less productive. But how can the nations be awakened from their mutual suspicions and fears? From their preoccupation with creating ever more deadly tools of destruction? How can they be made to see the magnitude of the danger which will affect them all? Is there not an urgent need for them to draw on their immense resources and engage in a concerted effort, on an adequate scale, to win what is becoming a war for survival?


Population, food and nutrition during the remainder of this century: Part II. South Africa. Whether South Africa can grow enough food over the next 20 years to meet the needs of a population estimated to be increasing by up to 1 million a year depends primarily on the extent, nature and condition of its natural resources and secondly on how they will be conserved and used. These, together with other relevant matters, are the subjects considered for both White and Black areas, especially as they affect the production of our basic foodstuff--maize. The maize production potential of the homelands is considerable, but at present they are largely dependent on imports obtained from White farms. Possible reasons for this unhealthy state of affairs are discussed. What can be done to enable the homelands to make their contribution to the food supplies of the country?


Diagnosis of pituitary micro-adenomas by computed tomography. Ten cases of pituitary micro-adenomas are reported. Skull radiographs and tomography were negative or questionable in all 10 cases. All patients were scanned because of changes in the endocrine system governed by the pituitary fossa. All patients presented clinically with symptoms which indicated the presence of micro-adenomas. Surgery verified 4 cases which were proved to be adenomas on histological examination.


Retroperitoneal neural tumours obstructing labour: A report of 2 cases. Two cases of dystocia due to retroperitoneal tumours of the nervous system are described, as well as the patients' course, obstetric management and a review of the literature.


Epidemiologic study of dermatophytoses in Salamanca (Spain). An epidemiologic study of the dermatophytoses in Salamanca (Spain) from 1973 to 1976 was performed. Dermatophyte species were identified in 224 patients with clinical tinea infections; 31 bovines, 18 rodents and 70 soil samples. The prevalence of Trichophyton verrucosum and Epidermophyton floccosum was strikingly high in relation to other statistics. The most common clinical forms were tinea corporis and tinea cruris. Tinea capitis by anthropophilic species was uncommon.


Incidence of dermatophytosis in Kuwait.

Incidence of dermatophytosis in Kuwait. Dermatophytosis in Kuwait was found to be associated with poor, over-crowded socioeconomic localities. This infection occurred in all age groups, but patients below 10 years of age were most susceptible. Tinea capitis was observed in 71.1% of 135 patients with dermatophytosis, with a higher incidence (48.2%) in males than in females. Microsporum canis caused 60.7% of all cases of dermatophytosis and 76% of tinea capitis. A high rate of failure to culture from microscopically positive specimens was observed in tinea cruris and onychomycosis.


[Study of yeast phase Histoplasma capsulatum antigens used for skin tests]. The results of skin tests with two antigens of the yeast phase of Histoplasma capsulatum are presented. Both antigens were able to fix complement and form precipitating bands in the presence of sera from patients with active histoplasmosis. Their sensitivity was lower than the metabolic antigen usually employed in serology. Results of skin tests obtained with both yeast phase antigens and a standard histoplasmin coincided in animals infected with H. capsulatum. Only one cross reaction was observed in animals inoculated with Paracoccidioides brasiliensis. Skin tests in humans were conducted on patients with and without mycotic disease. The percentages of positive reactions in patients with histoplasmosis were not significantly different between control histoplasmin and whole cell extracts. In the patients with non mycotic diseases the frequency of positive tests varied between 28.8% and 32%, which agrees with previous statistical data for the general population of the area. Equally the positive percentage of 55% and 68% in patients with paracoccidioidomycosis coincided with the results of previous studies. The histological patterns of these skin tests showed that they were produced by cell mediated hypersensitivity. The sensitivity of a whole yeast cell extract was similar to histoplasmin L48, but its preparation was quicker and easier to perform and it had no foreign substances from the culture medium, so we think that it would be easier to standardize it chemically.


Coccidioidin sensitivity in San Diego schools. San Diego is located within the geographic distribution of known occurrence of Coccidioides immitis contamination of the soil. Forty-five to fifty-five cases are diagnosed in San Diego hospitals each year. Skin tests were administered to one thousand and twenty-seven ninth grade students in five selected San Diego schools. Coccidioidin 1:100 was administered by Mantoux technique, intradermally. Induration was measured at forty-eight hours. Greater than 5 mm of induration was noted in 9.7% of students tested. Among 378 students who had been lifelong residents of San Diego County, 7% had greater than 5 mm of induration. Coccidioidomycosis is endemic in San Diego but the level of endemicity is rather modest.


Cerebellar malformations in prenatally X-irradiated rats: quantitative analysis and detailed description. Pregnant WKA/Hok rats were exposed to 100 R or 200 R X-irradiation on one of gestation days 16 through 21. Offspring were killed at 60 days of age and the cerebellum was examined. The cerebellum of animals exposed to 200 R was slightly reduced in weight but not in width. The observed reduction in the dorsoventral length of the cerebellum was more evident when the X-irradiation was early in gestation. The anteroposterior length of the hemispheres increased following exposure to X-ray on days 16 through 19, and that of the vermis and paravermis decreased following treatment on days 17 through 21. Therefore, the anterior portions of hemispheres were situated anterior to the culmen in every 200 R group. Somewhat anteroposteriorly and horizontally directed lobules, as opposed to the normal transverse arrangement, were seen in the cerebellum of rats treated on day 16 or 17. Lobule contortion and fragmentation and an increased number of sublobules were striking in cases treated later. Histologically, ectopic Purkinje cells in the granule cell layer and white matter appeared following X-irradiation on day 20 or 21, but they were not found following earlier treatment. In the cerebellum of animals exposed to 100 R the reduction in size was mild and the folial abnormalities were rare, but the number of sublobules decreased.


The murine Ah locus: in utero toxicity and teratogenesis associated with genetic differences in benzo[a]pyrene metabolism. Benzo[a]pyrene, at dose between 50 and 300 mg per kg body weight given at Day 7 or 10 of gestation, causes in utero toxicity and teratogenicity more so in genetically "responsive" C57BL/6 than in "nonresponsive" AKR inbred mice. With the use of AKR X (C57BL/6) (AKR)F1 and (C57BL/6) (AKR)F1 X AKR backcrosses, it was shown that allelic differences at the Ah locus in the fetus can be correlated with dysmorphogenesis. If the mother is nonresponsive (Ahd/Ahd), the Ahb/Ahd genotype in the fetus is associated with more stillborns and resorptions, decreased fetal weight, increased congenital anomalies, and enhanced P1-450-mediated covalent binding of BP metabolites to fetal protein and DNA, when compared with the Ahd/Ahd genotype in the fetus from the same uterus. If the mother is responsive (Ahb/Ahd), however, none of these parameters can be distinguished between Ahb/Ahd and Ahd/Ahd individuals in the same uterus, presumably because enhanced BP metabolism in maternal tissues and placenta cancels out these differences between individual fetuses. Of particular interest in our study is the fact that the mother and the father both must be of a particular genotype before differences in teratogenesis among fetuses (due to their genotype) will be expressed. These data might provide an example in attempting to explain clinically why only one child is affected with an apparent "drug-induced syndrome" although the mother has taken the same dose of the particular drug during each of numerous pregnancies.


Teratogenic potential of dichlorvos given by inhalation and gavage to mice and rabbits. Dichlorvos (2,2-dichlorovinyl dimethyl phosphate) is an important organophosphate insecticide and anthelmintic with widespread use. The purpose of this study was to evaluate the teratogenic potential of dichlorvos given orally at the maximum tolerated dose to mice (60 mg/kg/day) and rabbits (5 mg/kg/day) and by inhalation in both species at a concentration of 4 microgram/l seven hours daily. Dichlorvos was not found to be teratogenic in either species by either route of administration.


Amphetamines reduce embryonic size and produce caudal hematomas during early chick morphogenesis. Experiments were designed to study some of the similarities and differences in the effects of amphetamines and trypan blue on early chick morphogenesis. Both dextroamphetamine sulfate (0.5 mg/egg) and methamphetamine hydrochloride (1.0 mg/egg) were capable of inducing, in 3-day chick embryos, caudal hematomas which were similar in appearance and location to those routinely observed following treatment with trypan blue. It was found, too, that both dextroamphetamine and methamphetamine treated embryos frequently exhibited a significant decrease in crown rump length and cross-sectional area of the notochord, neural tube, dorsal aortae and whole body section, when compared with unopened or saline injected controls. Trypan blue treated embryos had only a rare decrease or increase in the size of structures when compared to either control group. These findings suggest that the amphetamines have an ability to decrease or retard embryonic growth in the chick.


The survival and implantation of mouse blastocysts at varying degrees of reduced atmospheric pressure. Pregnant mice were exposed to reduced atmospheric pressures ranging from 630 to 390 mm Hg during the pre-implantation and implantation periods and the numbers of embryos surviving 85 hours post coitum compared with those in litter-mate controls. Even at a pressure of 630 mm Hg (= 1,550 mm Hg) there was a significant fall in numbers of normal blastocysts and rise in abnormal forms before implantation, and implantation sites were reduced in number. The numbers of abnormal forms increased and implantation sites decreased at lower pressures, suggesting strongly that the hypoxia of reduce atmospheric pressure was responsible for the abnormalities observed. The pre-implantation period appears to be one during which the fertilised ovum is at particular risk, both of hypoxic damage and of failure to implant. Implantation may afford a degree of protection against hypoxia.


Chronic unilateral external ocular inflammation. To diagnose the cause of chronic unilateral external ocular inflammation, the physician must take into account many factors usually not considered in bilateral cases. We report on the diagnosis and treatment of ten unilateral cases encompassing a variety of ocular and systemic problems. The purpose of this report is to emphasize the importance of systematic consideration of all diagnostic possibilities and to suggest a diagnostic protocol to aid in the study of patients with chronic unilateral external ocular inflammation.


A teratogenicity study on hydroxyurea and diphenylhydantoin in cats. Hydroxyurea, an antitumor drug and known teratogen in rat, miniature swine and dog, and diphenylhydantoin, a teratogen in mouse and rat, were assessed for teratogenic effects in cat. Pregnancies were induced, by synchronizing gonadotropin-stimulated estrus and ovulation with natural copulations. Hydroxyurea at 50 or 100 mg/kg, and sodium diphenylhydantoin at 1 or 2 mg/kg dosages, were administered orally in single daily doses from gestation days 10-22. Appropriate controls given empty capsules, were included for each drug. Cats were necropsied on gestation day 43. Fetuses were examined for external, visceral and skeletal malformations. Hydroxyurea at 50 mg/kg dose produced a low teratogenic activity and at 100 mg/kg a high incidence of non-pregnancy and resorptions with, consequently, fewer live fetuses. Diphenylhydantoin gave no clear evidence of teratogenicity at any test dose but was embryolethal at the maternally toxic dose of 2 mg/kg. So far, studies conducted suggest that the cat is a useful species for screening drugs and chemicals for their teratogenic potential.


Teratogenic effects of external egg applications of methyl mercury in the mallard, Anas platyrhynchos. The embryotoxic potential of external applications of methyl mercury on mallard eggs was investigated to assess the possible impact of mercury transferred from the plumage of effluent-contaminated aquatic birds to their eggs. Eggs were treated on day 3 of development with microliter applications of methyl mercury that was dissolved with ethyl acetate into an aliphatic hydrocarbon vehicle. Mercury analysis by atomic absorption indicated that almost half of the mercury applied entered the eggs past the shell membranes within several days of treatment. Most mortality occurred within this period at doses of 9 microgram of mercury per egg or higher. Decreased embryonic growth resulted with similar doses. A significant incidence of malformations occurred at a dose of 1 microgram per egg. These malformations were mainly minor skeletal aberrations and incomplete ossification. With higher doses of mercury, defects included gross external ones such as micromella, gastroschisis, and eye and brain defects. Application of the aliphatic hydrocarbon vehicle did not result in any of these defects.


Intersexes in the dog.

Intersexes in the dog. A litter of five salukis was presented in which all of the individuals were intersexes or hermaphrodites. Anatomical abnormalities were observed. The external genitalia resembled a combination of penile sheath and vulva positioned approximately midway between the anus and umbilicus. At birth structures resembling scrotal sacs were present on either side of the genital structure. These were not apparent in older animals. Internal anatomy consisted of two gonads in a position expected for ovaries, oviducts, uterus and cord-like structures lateral to the uterus which extended from gonad to inside of the "scrotal sacs." Histologically, the gonads appeared to be ovaries which contained many dysgenic follicles. Cause of the condition is unknown.


Threatened abortion, hormone therapy and malformed embryos. Causal relations between maternal genital bleeding, supportive hormone therapy and external malformations of the embryos were investigated with special reference to the critical period of organogenesis. This was done using morphological and obstetrical data obtained by Nishimura and his associates from 667 undamaged embryos derived from induced abortions whose mothers had genital bleeding in early pregnancy. In addition, data from 90 embryos with polydactyly and 38 with limb reductions in the Nishimura collection were used for case history studies. Evidence was presented to demonstrate that, for major malformations such as CNS anomalies, cleft lip, polydactyly and limb reductions, maternal genital bleeding was not a cause but a consequence of the conception of an abnormal embryo. No indication was revealed that exogenous female hormones currently used in Japan for preventing miscarraiges could produce major malformations recognizable at the embryonic stage, including limb reductions, nor salvage the severely malformed embryos. This does not however mean to exclude the possible relationship of progestogens/estrogens intake during early pregnancy with an increased incidence at birth of certain internal and/or external malformations. It was suggested that most, if not all, of the minor anomalies observed at certain embryonic stages are kinds of normal variants without any functional impairment of embryonic development.


Estimation of lung volumes from chest radiographs using shape information. The cross-sectional shapes of the chest and its contained structures have been assessed in post-mortem anatomical sections and from computerised tomographic scans in living subjects. These shapes are described by simple equations that can be used to increase the accuracy of measuring lung volumes from chest radiographs. Radiographic estimates of total lung capacity, using the equations, were compared with plethysmographic and single-breath helium dilution measurements in 35 normal subjects. The postures commonly used for taking chest radiographs were found, on average, to decrease total lung capacity (TLC) and to increase residual volume by about 200 ml when compared with the sitting positions used for the other two measurements (studies made in 18 of the subjects). After correction for this effect, the radiographic estimates of TLC, which measure the displacement volume of the lung, exceeded the plethysmographic estimates of contained gas volume by a mean of 720 ml, which was taken as the volume of tissue, blood, and water in the lungs. The single-breath dilution estimates of TLC fell short of the plethysmographic values by a mean of 480 ml, taken as the volume of contained gas that was inaccessible to helium in 10 seconds. The tomographic studies suggested that the radiographic technique of measuring lung displacement volumes has an accuracy of +/- 210 ml. The method is rapid and simple to use and has intra- and inter-observer variabilities of less than 1% and less than 5% respectively.


Post-mortem lung volumes.

Post-mortem lung volumes. The volumes of 78 adult human lungs at necropsy after fixation with intrabronchial 10% formaldehyde at a transpulmonary pressure of 25 cm of water (VL) were similar to their total lung capacity (TLC) as assessed radiologically (VX). Corrected for stature, VL and VX did not increase with age in non-emphsematous lungs, nor did the radio of VL to VX (VL/VX) change with age. VL and VX relative to body length increased with emphysema, and the increase even occurred in lungs from men with trivial or equivocal amounts of emphysema. Thus alteration of the mechanical properties of the lung may precede the appearance of obvious emphysema. VL/VX was not affected by the presence or severity of emphysema. The right lung formed 53% of VL with a range of 49-58% in apparently normal lungs. The amount of air in 13 human lungs at necropsy averaged 61% of TLC with a wide variation, indicating that this is not a useful point at which to measure lung dimensions. It is concluded that the volume of lungs fixed with formaldehyde at a transpulmonary pressure of 25 cmH2O closely approximates to total lung capacity.


Treatment of postpneumonectomy empyema: the case for fenestration. In Mearnskirk Hospital, Glasgow, 29 patients with postpneumonectomy empyema were treated by fenestration in a 12-year-period. Seven of these were not considered fit enough for definitive closure and died of continuing disease or respiratory infection. Twenty-two patients went on to closure of their fenestra, and in 17 (77%) the pneumonectomy space was rendered permanently sterile. If the empyema recurred treatment was repeated but proved less successful. Fenestration is an effective method of dealing with postpneumonectomy empyema, but also has several other advantages, particularly if the empyema is associated with a bronchopleural fistula.


Intravascular haemolysis after valve replacement: comparative study between Starr-Edwards (ball valve) and Björk-Shiley (disc valve) prosthesis. Seventy-four patients with single prosthetic valves (Björk-Shiley or Starr-Edwards) in the mitral or aortic position and 18 controls with rheumatic valvar heart disease were investigated for evidence of intravascular haemolysis. Serum lactate dehydrogenase (LDH) was used as the most sensitive indicator of haemolysis. Raised concentrations were found in a third of 39 patients with Björk-Shiley prostheses (mean 281 IU/l) and in all 35 patients with Starr-Edwards prostheses (mean 859 IU/l. Values were considerably higher in patients with Starr-Edwards prostheses and particularly in those with aortic prostheses (mean 927 IU/l). Eight out of 12 patients with haemosiderinuria had Starr-Edwards valves. Intravascular haemolysis was of little clinical significance in patients with Björk-Shiley prostheses, but some patients with Starr-Edwards prostheses became iron deficient as a result.


Does sleep cause nocturnal asthma?

Does sleep cause nocturnal asthma? The effects of sleep interruption and deprivation were studied in 21 patients with nocturnal asthma. Seven patients were awakened at 0200 on three consecutive night and exercised for 15 minutes. This produced no significant improvement in the overnight fall in peak expiratory flow rate (PEFR) compared with a control night of uninterrupted sleep. In a second study in five patients PEFR was measured at two-hourly intervals to estimate the time of onset of the nocturnal fall in PEFR. On three subsequent nights they were awakened and exercised one hour before this time. This also failed to prevent a fall in PEFR by 0600. Eleven patients, who had followed a similar protocol to the second study, were kept awake until after 0300 or later, and PEFR was observed hourly. Six of them (group A) sustained their usual fall in PEFR while awake, proving that sleep was not responsible for their nocturnal asthma. Five patients (group B) showed little fall in PEFR until they were allowed to sleep, when an appreciable fall was noted on waking at 0600. When sleep deprivation was repeated in two patients in group B, however, they sustained falls in PEFR while still awake. We conclude that the circadian rhythm in PEFR is often in phase with the timing of sleep but sleep does not cause nocturnal asthma. Disruption of sleep therefore has no apparent value in the treatment of nocturnal asthma.


Frequency dependence of dynamic compliance in patients with rheumatoid arthritis. An investigation of lung function was carried out in 99 randomly selected patients with calssic or definite rheumatoid arthritis and in 60 control subjects matched for age, sex, and smoking habits. Mean FEV1 and mean VC were both significantly lower in the rheumatoid patients due to significant differences for women but mean FEV/VC ratio was 73.0% in the rheumatoid group and 72.1% in the control. Steady-state transfer factor was significantly greater in the normal men than in the comparable rheumatoid group, but there was no difference for women. After excluding patients with FEV1 less than 80% predicted normal and patients with low compliance, 72 rheumatoid patients and 45 controls provided series of tracings that could be assessed for a fall in Cdyn of 20% between 20 cycles and 60 cycles a minute. Dynamic compliance was not significantly different in any group at any rate of respiration. Fourteen of 72 rheumatoid patients and three of 45 controls showed frequency dependence (FDC). After the age of 50 the prevalence in the rheumatoid groupwas 11/38 and in the control group 2/27. This difference was significant (P less than 0.05). FDC was not consistently related to other abnormalities of lung function or to the duration, severity, or treatment of the rheumatoid arthritis. In various categories of smoking habits, dust exposure, or allergic tendency, the prevalence was always greater in the rheumatoid group. This provides evidence of patchy involvement of small airways, or alveoli and connective tissue, by the rheumatoid process.


Isocyanate asthma: respiratory symptoms due to 1,5-naphthylene di-isocyanate. Occupationally related asthma developing in three patients due specifically to exposure to 1,5-naphthylene di-isocyanate (NDI), a hot curing agent used in manufacturing rubber, has been confirmed for the first time using bronchial provocation testing. This substance has been thought to be safer than toluene di-isocyanate (TDI) and diphenylmethane di-isocyanate (MDI) because of its relatively high melting point (120 degrees C). Each patient worked in the same factory and the circumstances of exposure were similar. Provocation testing was also performed with TDI in concentrations up to 0.018 parts per million (ppm) and MDI in concentrations up to 0.02 ppm, to which the patients had been exposed in the past, but no reactions were elicited. None of the patients had increased bronchial reactivity judged by histamine lability and exercise testing. Each patient was advised to give up his job, but two of the three could not find alternative employment and remained exposed. Three-year follow-up shows that airways narrowing has persisted in those who have remained exposed.


Hypersensitivity pneumonitis in a technician using Pauli's reagent. A technician working in a medical laboratory used a spray of sodium diazobenzenesulphate (Pauli's reagent) in chromatography. She developed a respiratory illness with both airways obstruction and radiographic and physiological evidence of interstitial pneumonitis. An occupational type of challenge test was followed by both immediate and late bronchial obstructive responses, by a fall in arterial oxygen tension, and by increased radiographic shadowing. Histology of a lung biopsy specimen, a low serum C3, and a postive skin prick test to the reagent suggested that the illness was a hypersensitivity reaction to Pauli's reagent.


A study of plasma proteins in the sol phase of sputum from patients with chronic bronchitis. We have studied the sputum/serum protein concentration ratios from 23 patients with bronchitis both in the stable clinical state and during acute chest infections. During the stable state there was a significant negative correlation (2 P less than 0.005) between the ratio and protein size. The ratios of IgG, IgA, C3, and alpha 1-antichymotrypsin were significantly displaced from this relation suggesting local production in the lung. IgM was found in all samples and alpha 2-macroglobulin in 55% of non-infected samples which may be the result of local production rather than transudation from serum, because of their larger size. During acute chest infections the albumin content of sputum rose from a mean sputum/serum ratio of 0.83 (SE +/- 0.08) X 10(-2) to 13.77 (SE +/- 3.21 X 10(-2) suggesting increased transudation from the blood. In the presence of increased transudation, local production of protein appears to be less significant.


Diet, absorption, and hormone studies in relation to body weight in obstructive airways disease. Sixteen male patients with stable chronic obstructive airways disease were separated into two groups of eight according to arterial carbon dioxide tensions. Hypercapnia was associated with lower arterial oxygen tensions, higher red cell volume, and increased weight, while normocapnic subjects were decidedly thin. The considerable difference in body weight between the two groups could not be explained by variation in caloric intake, and malabsorption was excluded as a cause of weight loss in the underweight subjects. Serum tri-iodothyronine, thyroxine, cortisol, and oestradiol concentrations were similar and normal in each group, but both groups had significantly low testosterone values as compared with controls, values in the hypercapnic being appreciably lower than in the normocapnic group. The adrenal androgen dehydroepiandrosterone was significantly high in the normocapnic group and low in the hypercapnic group compared with controls. Serum pituitary luteinising and follicle stimulating hormones were normal, but three hypercapnic individuals had high serum prolactin values. Early morning urinary aldosterone values were significantly higher in the hypercapnic than in the normocapnic group. Such hormone comparisons have not previously been made in subjects with chronic obstructive airways disease grouped according to arterial blood gas values, and it is concluded that major alterations in adrenal and testicular function may occur, possibly due to pituitary suppression from hypoxia. Such hormonal changes might in part account for the contrasting alterations in body habitus found in this condition.


Prothrombin time standardization: report of the expert panel on oral anticoagulant control. The International Committee on Thrombosis and Haemostasis, The International Committee for Standardization in Hematology. In collaborative experiments in 199 laboratories, nine commercial thromboplastins, four thromboplastins held by the National Institute for Biological Standards and Control (NIBS & C), London and the British Comparative Thromboplastin were tested on fresh normal and coumarin plasmas, and on three series of freeze-dried plasmas. One of these was made from coumarin plasmas and the other two were prepared from normal plasmas; in each series, one plasma was normal and the other two represented different degrees of coumarin defect. Each thromboplastin was calibrated against NIBS & C rabbit brain 70/178, from the slope of the line joining the origin to the point of intersection of the mean ratios of coumarin/normal prothrombin times when the ratios obtained with the two thromboplastins on the same fresh plasmas were plotted against each other. From previous evidence, the slopes were calculated which would have been obtained against the NIBS & C "research standard" thromboplastin 67/40, and termed the "calibration constant" of each thromboplastin. Values obtained from the freeze-dried coumarin plasmas gave generally similar results to those from fresh plasmas for all thromboplastins, whereas values from the artificial plasmas agreed with those from fresh plasmas only when similar thromboplastins were being compared. Taking into account the slopes of the calibration lines and the variation between laboratories, precision in obtaining a patient's prothrombin time was similar for all thromboplastins.


Results of calibration by the Dutch National Reference Laboratory of the thromboplastins included in the ICTH/ICSH collaborative study of prothrombin time standardization. Results obtained with the original calibration procedure of Biggs and Denson obtained by one expert laboratory compare well with those obtained from the ICTH/ICSH collaborative study. The simplified calibration procedure described in 1975 should only be used for the assessment of inter-batch variability of a given brand of thromboplastin; for the calibration of unlike thromboplastins, the simplified procedure should be revised by using more than two abnormal plasmas, e.g. different plasmas representing seven levels of anticoagulation between international calibrated ratios (ICRs) from 1.5 to 4.5. The formula for the calculation for the proposed ICRs based on the calibration constant should be modified to allow for instances where the calibration line for dissimilar thromboplastins, fitted in the therapeutic range, does not pass through the origin of ratio 1,1.


Prothrombin time standardization report of the expert panel on oral anticoagulant control: a minority opinion. The ICTH/ICSH collaborative study failed to achieve its aims because each combination of plasma, thromboplastin and method was tested by too few laboratories in relation to intra and inter laboratory variation, and because the stability of the reference thromboplastin 70/178 is suspect. The evidence of the study does not support the superiority of reference thromboplastins over reference plasmas, but the concept of reference plasma was not adequately explored.


The stability of the WHO reference thromboplastin NIBS & C 67/40. The International Reference Preparation of human brain thromboplastin coded 67/40 has been thought to show evidence of instability. The evidence is discussed and is not thought to be strong; but it is suggested that it would be wise to replace 67/40 with a new preparation of human brain, both for this reason and because 67/40 is in a form (like Thrombotest) in which few workers seem to use human brain. A 'plain' preparation would be more appropriate; and a freeze-dried sample of BCT is recommended as the successor preparation. The opportunity should be taken also to replace the corresponding ox and rabbit preparations. In the collaborative study which would be required it would then be desirable to test in parallel line the three old and the three new preparations. The relative sensitivities of the old preparations could be compared with those found in earlier studies to obtain further evidence on the stability of 67/40; if stability were confirmed, the new preparations should be calibrated against it, but if not, the new human material should receive a calibration constant of 1.0 and the new ox and rabbit materials calibrated against that. The types of evidence available for monitoring the long-term stability of a thromboplastin are discussed.


Inhibition by N-acetyl neuraminic (sialic) acid of platelet aggregation induced by different stimuli. Addition of N-acetyl neuraminic acid (sialic acid, NANA) to citrated rat platelet-rich plasma significantly inhibited aggregation induced by near-threshold concentration of ADP, collagen or thrombin. In heparinized rat platelet-rich plasma aggregation of platelets induced by endotoxin or tumour cells of various origins was also inhibited by sialic acid. It is suggested that exogenous or endogenous sialic acid may act against various aggregating stimuli on the platelet membrane by masking a common factor through which various aggregating agents exert their effect.


Collagen-induced platelet aggregation:--evidence against the essential role of platelet adenosine diphosphate. The hypothesis that platelet ADP is responsible for collagen-induced aggregation has been re-examined. It was found that the concentration of ADP obtaining in human PRP at the onset of aggregation was not sufficient to account for that aggregation. Furthermore, the time-course of collagen-induced release in human PRP was the same as that in sheep PRP where ADP does not cause release. These findings are not consistent with claims that ADP alone perpetuates a collagen-initiated release-aggregation-release sequence. The effects of high doses of collagen, which released 4-5 microM ADP, were not inhibited by 500 microM adenosine, a concentration that greatly reduced the effect of 300 microM ADP. Collagen caused aggregation in ADP-refractory PRP and in platelet suspensions unresponsive to 1 mM ADP. Thus human platelets can aggregate in response to collagen under circumstances in which they cannot respond to ADP. Apyrase inhibited aggregation and ATP release in platelet suspensions but not in human PRP. Evidence is presented that the means currently used to examine the role of ADP in aggregation require investigation.


Interaction of bovine platelets with bovine glomerular basement membrane. The interaction of bovine platelets with bovine glomerular basement membrane has been studied by aggregometry, transmission and scanning electron microscopy and measurement of [3H] serotonin release. In the absence of added calcium platelets adhere to basement membrane but fail to undergo the release reaction or aggregation. In the presence of 0.2-0.5 mM calcium release of serotonin and complete aggregation of the platelets are observed when sufficient basement membrane is present. Platelets were strongly adhered to the basement membrane surface, the platelet surface in the aggregates closely following the surface of the basement membrane. Platelet morphology in aggregates with basement membrane closely resembled that of platelets from collagen-induced aggregates. Basement membrane differed from collagen in its requirement for calcium for the aggregation and release reactions. In addition purified basement membrane was 1.5-3 fold less active on a weight basis than bovine tendon collagen in promoting aggregation.


The released proteins from avian thrombocytes. The effect of aggregating agents on the amounts and nature of released proteins from washed goose and chicken thrombocytes was studied. The released protein material was separated on Sepharose 4B. Protein fractions with low molecular weight were next chromatographed on Sephadex G-200. The released proteins from thrombin aggregated pig platelets were analysed in the same way. It was shown that during aggregation avian thrombocytes release protein material containing a well separated fraction (the major component) which seems to correspond to a platelet specific beta-thromboglobulin.


Spectrophotometric assays of prothrombin in plasma of patients using oral anticoagulants. Two spectrophotometric assays for prothrombin have been developed and compared with a one stage coagulant and an immunological assay. One of these assays (called the XAPC assay) uses a combination of factor Xa, phospholipid, Ca2+ and factor V as activator of prothrombin, and measures only normal prothrombin. The second (the ECAR assay) uses Echis carinatus venom as activator. This assay measures both normal prothrombin and PIVKA II (protein induced by vitamin K antagonists/absence). Combination of the results obtained by the XAPC and ECAR assays provides rapid and reliable information on the degree of "subcarboxylation" of prothrombin (oral anticoagulation, vitamin K deficiency). For patients on long term anticoagulant treatment the prothrombin time (Thrombotest) shows better correlation with the ratio prothrombin/prothrombin plus PIVKA II (XAPC/ECAR) than with the factor II concentration. For patients starting the anticoagulant treatment there is no correlation between the Thrombotest time and the XAPC/ECAR ratio. It seems doubtful that (a) spectrophotometric factor II assay(s) will be as useful as the prothrombin time in the control of oral anticoagulation.


In vitro stability of human fibrinopeptide B. In anticipation of a future clinical application of plasma fibrinopeptide B (FPB) measurement, we studied the stability of FPB in an ultrafiltrate of normal plasma, normal urine and alkaline buffer by measuring the immunoreactivity of the peptide by FPB radioimmunoassay using anti FPB serum (R-29). FPB was unstable in an ultrafiltrate of plasma and urine and demonstrated a temperature dependent loss of activity. In plasma ultrafiltrate the loss of immunoreactivity was not significant during the first 24 hours, however, 92% of the peptide activity was lost at the end of seven days at 25 degrees C and 37 degrees C. The rate of FPB degradation in urine was comparable. The peptide was stable in an alkaline buffer (pH 8.5) at temperatures ranging from -10 degrees C to 37 degrees C or in plasma ultrafiltrate or urine when incubated at -10 degrees C. Treatment with carboxypeptidase B or leucine aminopeptidase for two hours at 37 degrees C (enzyme/substrate molar ratio of up to 1:100) did not cause a loss of FPB immunoreactivity. EDTA (1.0 mM) and Trasylol (500 units/ml) completely stabilized the peptide in a plasma ultrafiltrate.


Role of reduced glutathione on platelet functions. The role of reduced glutathione (GSH) on platelet functions was investigated utilizing thiol oxidizing agent, "diamide". Diamide reacted rapidly with GSH in platelets, but not with protein thiols. Platelets treated with diamide showed inhibition of platelet aggregation induced by ADP, epinephrine and collagen in a concentration dependent manner. Clot retraction was grossly inhibited by diamide. Platelet interaction with polymerizing fibrin was examined by the method of Niewiarowski et al. (1972). There was no interaction obeserved between diamide-treated platelets and polymerizing fibrin. Ultrastructural observation  of clots formed in the presence of diamide also showed no direct contact between platelets and fibrin strands. Platelets retained their granular contents, but showed loss of microtubules and dilatation of open canalicular system. Our findings may further support the idea that GSH plays an important role on platelet functions.


Changes in platelet aggregability after ovariectomy. Changes in platelets in 48 patients with uterine myoma before and after hysterectomy with and without ovariectomy were examined. Bilateral ovariectomy in 25 cases (ovariectomized group) and unilateral or non-ovariectomy in 23 cases (control group) were performed at the hysterectomy. Platelet count and an appearance rate of secondary aggregation decreased at one day after and increased at one week after the operation, similarly in both the ovariectomized and the control group. The appearance rate of secondary aggregation was reflected in an intensity of aggregation at 5 min after the addition of reagent to PRP. At one month after the operation, the appearance rate of secondary aggregation induced by 3 microM ADP showed a statistically significant decrease in comparison with the preoperation value (P less than 0.05) and the enhancement of 5-min aggregation was still observed in the control group, while ceased in the ovariectomized group. The difference between the two groups was significant (P less than 0.05). There was almost no change in the speed and intensity of primary and secondary aggregation during the observation period. No significant differences in collagen-induced aggregation were noted between the two groups. The results suggest that ovarian hormones, mainly estrogen, facilitate platelet activation which is mediated by the so-called secondary aggregation.


The need for surgery in an unselected bronchial carcinoma population. An epidemiological study of bronchial carcinoma was carried out in the county of Uppsala, Sweden, during a five-year period. The number of cases found was 273. Of these, 25% were operated upon. The operation rate was six operations/100,000 inhibitants per year. Including additional patients with a false preoperative diagnosis of carcinoma, the operation rate was seven operations/100,000 inhabitants per yera. This figure is clearly subject to influence by the level of medical ambition. The expected five-year survival rate of the surgically treated carcinoma cases in 29%. Twenty-nine percent of the surgically treated patients and 45% of the expected survivors were detected by mass miniature chest X-ray during a general health survey. Fifty-five percent of the surgically treated patients and 75% of the expected survivors were discovered by chance. In no group comparisons with comparable non-surgically treated patients were the deceased surgically treated patients found to have a longer survival. Among the patients who were operated upon, a small tumor size, a peripheral location, clinico-anatomical stage 1 of the disease, and detection by chance were favorable prognostic indicators. Twenty-eight percent of the surgically treated patients were over 70 years of age. Their expected five-year survival rate is 21%. Active early diagnosis (increasing the need for surgery) and restriction of surgery only to those most likely to benefit from it (decreasing the need for surgery) may be expected to give maximum effectiveness in the surgical treatment in bronchial carcinoma.


Ventilation studies with krypton-81m.

Ventilation studies with krypton-81m. Nuclear medicine offers well-established methods for regional lung function assessment in the preoperative evaluation of patients with lung disease. The perfusion study with Tc-99m macroaggregates is simple and can be performed without special precautions in radiation shielding. The ventilation study with Xe-133, however, requires more elaborate apparatus as well as special procedures to collect the exhaled radioactive rare gas. Nuclear medicine departments with access to short-lived radionuclides from a nearby cyclotron can use the krypton isotope Kr-81m. The physical half-life of Kr-81m is 13 s. Its gamma energy of 190 keV is optimal for gamma cameras. Kr-81m can be used as a medical isotope in spite of its short half-life. It can be eluted with a continuously flowing gas from the generator containing the mother nuclide Rb-81 which has half-life of 4.6 h. This short half-life not only simplifies radiation protection but allows repeated studies in different projections as well. Examples of comparative studies with Xe-133 and Kr-81m are presented. The importance of taking not only anterior and posterior pictures but also lateral oblique views is stressed.


Bronchofiberscopy in the postoperative management of lung surgery patients. A retrospective study of 60 bronchofiberscopic lavage procedures following lung surgery showed an increase of prebronchoscopy oxygen partial pressure from 64.2 mmHg (S.D. +/- 16.2) to 69.9 mmHg (S.D +/- 18.0) after bronchoscopy (P less than 0.01), while carbon dioxide partial pressure did not change significantly. Lobectomied patients tended more often to develop ipsilateral atelactases, invariably responding well to lavage; this group may benefit from prophylactic fiberoptic lavage. Cases are presented to demonstrate this point and to show the need for repeated lavage in some instances. Administration of a standard premedication dosage to patients sedated for other reasons occasionally led to worsened respiratory status; pre-medication should be reduced or eliminated in sedated patients. The effective application of lidocain and salbutamol intrabronchially is discussed. The bronchofiberscope is an important tool in optimal post-operative management of lung surgery patients.


Thymolipoma--a rare, benign tumor of the thymus gland two case reports and review of the literature. Two case reports of thymolipoma are presented. In a review of the literature on the subject, the clinical and etiologic features of this nonmalignant tumor in the anterior mediastinum are discussed. Although rare, thymolipoma should be considered in the differential diagnosis of mediastinal tumors.


Hydatid cyst of the heart.  Clinical and surgical implications. Hydatid cyst of the heart is an uncommon lesion which usually develops in the left ventricle. Diagnosis should be considered in patients coming from an area where hydatid cyst is endemic and who present with an abnormal heart shadow on chest X-ray, frequently associated with T wave changes on the electrocardiogram. The cyst tends to grow and thus compress the neighboring myocardium. It causes displacement of the coronary vessels, rhythm disturbances and mechanical interference with the AV valves and ventricular function. Spontaneous involution of the cyst with calcification of its wall as well as rupture with anaphylactic shock may occur. Early excision with standby cardiopulmonary bypass is advisable. Three patients with hydatid cyst of the left ventricle, 2 of whom were operated on by using cardiopulmonary bypass, are presented. Results of the surgical treatment, both early and late, are rewarding, with relief of symptoms, regression of electrocardiographic abnormalities and very low incidence of recurrence.


Doppler ultrasound studies of subclavian steal hemodynamics in subclavian stenosis. By means of ultrasound Doppler sonography it is shown that a proximal subclavian stenosis does not necessarily influence the blood flow of the vertebral artery in a subclavian steal syndrome (permanent retrograde flow in the vertebral artery) as is characteristic for subclavian occlusion. Depending on the peripheral resistance in the cranial and brachial circulation, the vertebral artery competes with the brachial artery for the poststenotic flow. Thus, a reduction of the vertebral flow during hyperemia within the brachial artery ststem, alternating vertebral flow, or a temporary steal syndrome may result in stenosis. Obviously the relation of the flow resistance may also change within one pulse beat, so that in the vertebral artery a characteristic flow pulse, i.e., an alternating flow, is detected with opposite direction in systole and diastole.


Management of concomitant occlusive disease of the supraaortic and lower-limb arteries. Angiography examinations of the extracranial cerebral arteries in patients with peripheral occlusive disease of the lower limbs indicate cerebro-vascular disease more often than might be assumed from clinical-neurological examinations alone. In total, 61.5% of the patients examined showed lesions of the extracranial cerebral arteries which necessitated an operation. The elimination of risks in an operation requiring extensive peripheral vessel reconstruction necessitates initial supraaortic vessel reconstruction. Of the 48 patients with reconstructions in both vascular systems, none has suffered any postoperative neurological dysfunction. Concomitant occlusive disease of the supraaortic and peripheral arteries should not be treated simultaneously.


Synergistic effects on the toxicity of organotins on cotton leafworms. Piperonyl butoxide, sulfoxide and MGK 264 were found to act as synergists for certain organotin compounds; with respect to their toxicity on the larvae of a susceptible strain of the cotton leafworm, Spodoptera littoralis (Boisd.). High degree of synergism was obtained when either piperonyl butoxide or MGK 264 was combined with Plictran and/or MGK 264 when combined with Duter. The 3 synergists were equivalent in their synergistic action with Brestan. In all cases, the relatively high degree of synergism was brought about when organotins and synergists were mixed at ratio of 10 : 1. On the basis of synergistic ratios, data indicated that detoxification mechanism of Plictran may be more sensitive to synergistic effects than that of Duter and Brestan. Testing organotin compounds against the more tolerable field strain provided probable evidence of negative correlation between different insecticides and organotins, especially Plictran.


On the role of metallothionein in cadmium absorption by rat jejunum in situ. The role of metallothionein (MT) in the mechanism of cadmium absorption from the jejunum was studied in 7--9 week-old-male rats exposed to 50 ppm of cadmium in drinking water for 9 days. Exposed animals contained an average of 144 micrograms MT/g of mucosal tissue, compared to 40 micrograms in control anaimls. During jejunal perfusion in situ with 5 mM glucose-saline containing 10--20 nM CdCl2 the increased MT content of mucosa exerted no effect either on cadmium absorption from the lumen (step I), or on its further transport into the body (step II). Immediately after perfusion, essentially all cadmium removed from the lumen was fully recovered in the intestinal mucosa. About 50% of the mucosal cadmium was found in the sediment after homogenization and centrifugation; a large portion of this cadmium may be assigned to the membrane fraction. The binding of freshly absorbed cadmium in the mucosal cytosol was not restricted to low molecular weight protein, although cadmium binding capacity in the MT fraction of controls as well as of exposed animals greatly exceeded actual binding of newly absorbed cadmium. Our results offer no support for the view that MT in the jejunal mucosa serves as determinant of cadmium absorption.


Potentiation of CCl4 hepatotoxicity in rats by a metabolite of 2-butanone: 2,3-butanediol. The role of ketaone metabolism in 2-butanone-induced potentiaion of carbon tetrachloride (CCl4) hepatotoxicity was studied in rats. The blood concentrations of 2-butanol, 3-hydroxy-2-butanone and 2,3-butanediol detected 4 h after dosing were 3.2 mg/100 ml, 2.4 mg/100 ml and 8.6 mg/100 ml, respectively. Eighteen hours after 2-butanone, the concentration of 2,3-butanediol rose to 25.6 mg/100 ml, while the concentrations of 2-butanol and 3-hydroxy-2-butanone declined to 0.6 mg/100 ml and 1.4 mg/100 ml, respectively. A 16-h pretreatment with either 2-butanone (2.1 ml/kg, p.o.) or 2,3-butanediol (2.12 ml/kg, p.o.) markedly enhanced the hepatotoxic response to CCl4 (0.1 ml/kg, i.p.), as measured by serum glutamic pyruvic transaminase activity and hepatic triglyceride content. In vivo, limited formation of 3-hydroxy-2-butanone occurred after this dose of 2,3-butanediol. These data suggest that the production of 3-hydroxy-2-butanone and 2,3-butanediol via 2-butanone metabolism may participate in the augmented necrogenic effect of CCl4 seen after pretreatment with 2-butanone.


Delayed neurotoxic, late acute and cholinergic effects of S,S,S-tributyl phosphorotrithioate (DEF): subchronic (90 days) administration in hens. Subchdronic administration of S,S,S-tributyl phosphorotrithioate (DEF) caused 3 toxicologic effects in hens, depending upon route of administration. Small delay oral doses (0.5--20 mg/kg) of DEF produced ataxia, which progressed to paralysis and death in some birds. Large daily oral doses (40 and 80 mg/kg) caused a 'late acute' effect 4 days after administration. The clinical signs of the late acute effect were identical to those produced by n-butyl mercaptan (nBM), a hydrolytic product of DEF, and were not relieved by atropine sulfate. The late acute effect of DEF overlapped with the clinical signs of delayed neurotoxicity. These hens died early, and while one hen showed histopathological lesions in peripheral nerves, another showed unequivocal lesions in the central nervous system. Topical application of daily doses of DEF consistently produced delayed neurotoxicity in the absence of late acute poisonining and was characterized by degeneration of the central and peripheral nerve tissues. Orally administered DEF was rapidly metabolized in the gastrointestinal tract to nBM, which apparently caused the late acute toxic effect. Topically administered DEF, which was not subjected to gastrointestinal tract hydrolysis, caused delayed neurotoxicity but did not produce a late acute effect.


Retention of cadmium in the duodenum of the rat following oral administration. The retention of cadmium in selected organs of the rat was studied following oral administration of the metal in the form of a carrier-free tracer and also as cadmium chloride. These 2 contrasting approaches (only the second being toxic) resulted in a similar retention pattern in the tissues. Both the cadmium burden and retention was greatest in the duodenum, followed by the kidney and the liver. This retention of cadmium in the duodenum following oral administration is relevant to the toxic effects of this metal associated with imparied calcium absorption in the intestine.


Nasopharyngeal removal of ozone in rabbits and guinea pigs. In estimating pollutant concentrations responsible for observed pulmonary effects, nasopharyngeal removal of the pollutant plays an important role. The nasopharyngeal removal of ozone (O3) in anesthetized male guinea pigs and male and female rabbits was determined by drawing O3 through the isolated upper airways at a constant flow rate which approximated the animal's respiratory minute volume. The tracheal O3 concentration in rabbits and guinea pigs was markedly similar and was linearly related to the chamber concentration of O3 over a range of 196--3920 micrograms/m3 (0.1--2.0 ppm O3). Regression analyses showed that O3 removal in the nasopharyngeal region is approximately 50% in both species. Both rabbit sexes responded similarly over the concentration range studied. Exposures of guinea pigs to O3 concentrations between 3920 and 5880 micrograms/m3 (2.0 and 3.0 ppm) showed that, at these higher concentrations, relatively more O3 is removed by the upper airways.


Limitations of in vitro short-term tests as prescreening models for carcinogenicity in industry: a theoretical approach. The validity of in vitro short-term tests was investigated using published data from 10 investigations on a total of more than 800 compounds. The predictive value strongly depends on the number of carcinogens investigated in a test and, therefore, is not suited to describe the reliability of a short-term test. The usefulness of short-term tests as prescreening models for possible carcinogenicity to be used as a routine procedure in industry is very limited. If it is assumed that most of the compounds tested are non-carcinogenic, other criteria than results of short-term tests should be used additionally in deciding which compounds require investigation in long-term bioassays for possible tumorigenic hazards.


Inorganic and organic fluoride concentrations in tissues after the oral administration of sodium monofluoroacetate (Compound 1080) to rats. Male rats were used to study the inorganic (ionic) and organic fluoride concentrations in plasma, liver, kidneys and stomach content after oral doses of 0, 2.2, 3.5, 4.0, 5.0 and 7.0 mg sodium monofluoroacetate (SMFA, Compound 1080)/kg body weight. Tissue and plasma ionic fluoride concentrations were observed to be higher in all rats given SMFA as compared to rats in the control group. This observation suggests in vivo defluorination of SMFA. Homogenates of liver obtained from SMFA poisoned rats showed significant increases in ionic fluoride concentration during a 6-day storage period at +4 degrees C, with the total fluoride concentration (ionic and organic) remaining constant. The average percentages of distribution of SMFA (organic fluoride) in plasma, liver, and kidneys were 7.05, 5.07 and 1.68, respectively. Plasma and tissue SMFA concentrations were generally lower than the corresponding stomach fluid SMFA concentrations for all dosage groups. Lethal concentration of SMFA in the liquid stomach content was in the range 84.9--189 micrograms/ml, corresponding to total (ionic and organic) fluoride concentrations in the range of 16.1--36 micrograms/ml.


Repeated exposure to butenolide vapour: subacute study in Syrian golden hamsters. The subacute inhalation toxicity of butenolide was examined in hamsters by repeated exposure of 4 groups of 10 males and 10 females to butenolide vapour at concentrations of 0, 5.4, 25 and 130 ppm respectively (6 h/day, 5 days/week) for a period of 13 weeks. The effects found at 130 ppm included eye irritation, salivation, nasal discharge, growth retardation, decreased number of eosinophils, increased liver weight, and hyper- and metaplastic epithelium in the nasal cavity. At the 5.4 and 25 ppm levels no changes were observed which could be attributed to butenolide; 25 ppm was, therefore, considered the highest no-toxic effect level observed. The actual no-adverse effect level was placed at 75 ppm.


Transmission dynamics of endemic schistosomiasis. Observations on schistosome infections in a human population, on the occurrence of the intermediate host, and on the exposure of man to infested water in an endemic area in Ethiopia, are brought together. It is observed that there is an apparent lack of correlation between the results of the first type of observation and those of the other two. The relative insensitivity of stool examination methods, the low counts of S. mansoni eggs, and the consequent underestimation of infection rates is discussed along with serologic findings. Finally, it is suggested that schistosomiasis in the area could be described as 'hyperendemic', a situation with a surplus of transmission in which the parasite populations do not seem to be regulated any more by transmission factors.


Immunoglobulins in serum and duodenal juice and peripheral blood lymphocyte subpopulations in patients with giardiasis. Forty eight patients with symptomatic giardiasis and 22 apparently healthy matched controls without Giardia lamblia were studied with respect to the following variables--immunoglobulins (Igs) G, A and M in serum, IgA in duodenal juice and T and B in lymphocyte sub-populations. There were no differences observed between the two groups with regard to any of these variables except for serum IgG which was found to be higher in patients. It was concluded that endemic giardiasis has no immunodeficient basis and has nothing in common with the association of giardiasis, mal absorption and immunodeficiency reported from the West. Further, no change in these variables was observed when the tests were repeated after cure.


Prevalence of toxoplasma antibodies in dogs in Chandigarh territory, North India. Sera from 119 dogs examined by the indirect haemagglutination test for Toxoplasma antibodies showed an overall prevalence rate of 29.4 per cent; 10.9 per cent with antibody titre of 1:128 or more. The per cent of positive cases in a dog clinic was not significantly higher than in apparently healthy subjects. Higher titre levels were more frequent in the sera of older animals and in those having concomitant disease.


Enzyme immunoassay of antibodies to influenza A virus in Nigerian children. Although attempts have been made to define the significance of influenza A virus infection serologically in children from developing countries, this has not been done in Nigeria. Based on this study of sera by the method of enzyme-linked immunosorbent assay from 179 healthy Nigerian children aged between 0--5 years of age, a prevalence rate of influenza A virus infection of 40.22% has been demonstrated. This is more significant during 1--4 years of age and particularly between 2--3 years. The clinical significance of this finding is discussed: the high prevalence is probably related to high susceptibility due to genetic factors linked to ABO blood groups.


Forecasting the onset of a scrub typhus epidemic in the Pescadores Islands of Taiwan using daily maximum temperatures. Daily maximum atmospheric temperatures were used to forecast the seasonal onset of scrub typhus in the Pescadores Islands of Taiwan. The day of the year on which the temperature first reached 30 degrees C was selected as the predictive base. Predictions for 1977 closely matched observed events. The model provides an easy and effective means to forecast the start of scrub typhus epidemics in the Pescadores Islands and could be used for such practical purposes as determining when prophylactic antibiotics should be administered to subjects whose risk of infection with Rickettsia tsutsugamushi is high.


Staphylococcal pericarditis with pyopericardium. Seven previously well patients with acute staphylococcal pericarditis and purulent pericardial effusion are described. All had a septicaemic illness in which worsening heart failure with signs of cardiac tamponade became the major problems of management. Tropical pyomyositis was probably the predisposing illness in four patients. This number of proven cases within an 18-month period suggests that staphylococcal pyopericardium is in a tropical environment probably commoner than realised.


Sicklers surviving childhood in Tanzania. Sixty two cases of sickling haemoglobinopathy have been admitted and specially studied between 1973 and 1977 in the Bugando Hospital, Mwanza, Tanzania. Presenting symptoms are described. The problems of recognition in the medical diaspora and of management are considered. It is expected that with improving regional health facilities more cases will survive childhood but also will cause special difficulties in adequate care. It is pleaded that because of the ubiquity of the HbS gene in Tanzania sufficient priority is given to the affected in planning health services in Tanzania.


Epidemiological aspects of neonatal jaundice in Chinese infants. A study of 200 full-term Chinese newborns within a twelve months period has not demonstrated any significant effect of early immunizations on the incidence of neonatal jaundice in the first seven days of life. Study of cord serum immunoglobulin M (IgM) levels has also failed to establish an association between raised IgM levels with more severe degrees of jaundice. The significantly higher serum bilirubin levels seen in normal Chinese neonates cannot be attributed to infection, either natural or attenuated, and further investigations are indicated.


Hiatal hernia in the African.

Hiatal hernia in the African. Eight cases of symptomatic hiatal hernia were investigated; four presented with respiratory symptoms simulating chronic asthmatic bronchitis or bronchopneumonia. Among 27 patients with gastro-oesophageal reflux but without radiologically visible hernia, six presented with fibrous stricture; no stricture was found in association with hiatal hernia. It is suggested that patients with gastro-oesophageal reflux should be offered surgical follow-up or surgery to prevent the development of a stricture before the more easily recognizable symptoms of heart burn and postural acid regurgitation get worse.


Early discharge of low-birthweight babies. Forty-two breastfed low-birthweight infants were followed up from 2 to 12 weeks for postnatal weight gain after an early discharge from hospital. Thirty one (74%) were discharged within 7 days after birth and 10 (24%) in the second week. Twenty seven (64.3%) had a birth weight between 1501 and 2000 g and 4 (9.5%) weighed 1500 g or less. Mean daily weight gain at home was steady and satisfactory when compared with standards. It is suggested that low-birthweight babies may be discharged as soon as they start sucking well on breast irrespective of their weight at birth and on discharge.


Nutrition and nutritional status of rural women in East Java. In the rural parts of nine regencies of the province of East Java Indonesia, in the dry seasons of 1975 and 1976 extensive nutrition surveys were carried out. So designated surplus, marginal and minus areas were included. Social and hygienic features of the household were recorded. The reproductive characteristics of the mother population were noted. Anthropometric data were collected. Their diet, including consumption frequency of staple and secondary foodstuffs, was registered by interview. Of a total of 3,828 mothers of children 0--15 years old 37% were lactating and 6.7% were pregnant. Of the latter some 10% were still nursing a child. The number of live children per family was rather small (2.0--3.4) and the percent of those who had died was high (10--31%). Average height of the mothers was 149 cm and weight 42 kg. A cross-sectional calculation of weight gain during pregnancy resulted in 5.0--7.4 kg. Lactating mothers showed a higher weight-height ratio than non-lactating or pregnant. Taking 90% of the Indonesian standard of weight-for-height as cut-off point for an acceptable nutritional status, 18--24% of the nonpregnant non-lactating, 13--35% of the lactating and 33--57% of the pregnant mothers fell below that standard. Considerable and rather unexpected differences existed between regencies. Low percentages of illiteracy and highest of child survival were found in an area designated as 'minus' for per capita income and food production. Only in Sidoarjo was rice the most frequently consumed staple food. In Trenggalek (south coast) and in Sampang (Madura) it was cassava. In Blitar (south coast) it was rice, maize and cassava mixed or varying according to season. In the remaining six regions a mixture of rice and maize was the common food.


Differences in blood status of three ethnic groups inhabiting the same locality in Northern Nigeria. Anaemia, splenomegaly and associated causes. In a village population in N. Nigeria the Fulani form a heterogeneous group in comparison with the Hausa and Maguzawa people. It was demonstrated that, apart from having a different body build, Fulani men have on the average lower haemoglobin concentrations, more splenomegaly and higher IgM and IgG concentrations. Splenomegaly and higher IgM levels were correlated in the Fulani only, and this probably is a manifestation of their altered immune response to malaria, which is manifested by the prolonged parasitaemia in Fulani men suggesting that their control over malaria parasites is less effective. Very high IgM levels (more than 9.6 g/l) were present in 6/70 (9%) of Fulani and in none of the others. According to the criteria used the Tropical Splenomegaly Syndrome could be diagnosed in 4/70 (6%) of Fulani and in 2/89 (2%) of Hausa and Maguzawa. A nutritional factor, presumably iron intake, and Schistoma haematobium infections appeared to be determinants of haemoglobin concentration in the Hausa and Maguzawa. In Fulani a different pattern emerged characterised by the nutritional factor and a haemolytic factor related to the sickle cell trait. The frequency of the sickle cell trait, however, was similar in all tribes. The significance of the findings is discussed and it is suggested that the heterogeneity of Fulani is possibly due to their less complete adaptation to stable malaria.


Machakos Project Studies: agents affecting health of mother and child in a rural area of Kenya. XVI. The outcome of pregnancy. The outcome of pregnancy of all women belonging to the study population of the Machakos project studies who delivered during 1975 and 1976 is presented. The birth-rate was 43.0 per 1,000 population per year, the fertility rate was 235 per 1,000 women 15--44 years of age per year. Unexpected low mortality rates were found; stillbirths, neonatal and infant death rates were respectively 29.8 per 1,000 total births and 22.5 and 50.0 per 1,000 live births. One maternal death occurred among the 2,223 deliveries. Maternal age of less than 25 and over 34 years, a history of previous perinatal death and breech delivery were associated with higher perinatal mortality. Parity, marital status, birth-interval and maternal height were not associated with a difference in outcome of pregnancy. The stillbirth rate among the children born in hospital (26.4%) was 4.4% compared with 2.4% among the children born at home, neonatal and infant death rates were the same. Half of all perinatal deaths were caused by either prematurity or birth trauma, 75% of all infant deaths after the first week of life were caused by infections.


Developing world. Patients' choice of anaesthetic techniques in a developing country. A study of the choice between general and local anaesthetic techniques among 200 post-operative Nigerian patients was conducted, using a questionnaire. The patients were interviewed between two and seven days after various types of surgery. Most of the patients (59.5%) preferred general anaesthesia. The commonest reason was fear with psychological upset if they are awake during surgery. This appears to be a basic human feeling which does not appear to be related to sophistication or level of development. Adequate pre-operative communication between doctors and patients should minimise this apprehension. 18% preferred local anaesthetic techniques while 21.5% would not mind either.


Experimental bovine trypanosomiasis (Trypanosoma vivax and T. congolense). I. Sumptomatology and clinical pathology. Twenty five cattle were infected with T. vivax, 25 with T. congolense, and 25 served as controls. Pathogenic clinical signs of trypanosomal infection were not observed. Secondary bacterial infections were common. Fever, increased heart and respiratory rates, anorexia, and emaciation developed. Elevations in parasitemai and body temperature were positively correlated in the T. vivax group. Infected groups were affected non-uniformly, with some animals in each group remaining asymptomatic and tending to have lower parasitemias. The T. vivax parasitemia was cyclic and the organisms had a genaration time of 7.9 SD 2.5 hours. The first peak of parasitemia in both infections was closely associated with the development of pancytopenia, i.e. anemia, leukopenia, and thrombocytopenia. The bone marrow erythroid response in the T. congolense group was significantly greater thn that in either the T. vivax or control groups. Leukopenia was due to concomitant neutropenia and lymphopenia.


The complement fixation test and African trypanosomiasis. II. The complement fixation test as an aid for assessing therapy. Complement-fixing antibody titres decline after successful treatment of trypanosoma infected cattle during a fixed period. For investigating the practicability of the resulting double test procedure in the field, cattle under controlled drug regimes were tested at treatment and again 3 weeks later. Alternatively, the results from groups of treated and untreated animals from the same area were compared. Both serological and parasitological test results indicated an insuffieicnt effectiveness of therapy in the area under investibation.


Experiments on the Babesia bigemina carrier state in East African buffalo and eland. Three captive East African buffalo (Syncerus caffer) were injected with 5 x 109 bovine erythrocytes with Babesia bigemina pathogenic for cattle. None of the buffalo showed signs of disease, but Babesia were found in blood smears for four days indicating their multiplication. The carrier state of Babesia bigemina was established in two buffalo for 28 and 147 days respectively by sub-inoculation into splenectomized calves, while no parasites were demonstrated 28 days after injection in the third buffalo. Two buffalo shot in Kenya did not appear to be carriers of Babesia gibemina, as shown by sub-inoculation of blood in splenectomized calves. Two captive eland (Taurotragus oryx) were inoculated and their blood investigated as with the experimental buffalo. Neither eland appeared to harbour Babesia bigemina 28 days after injection, even though one was splenectomized. The experimental data indicate that the East African buffalo can be a carrier of Babesia bigemina for at least 5 months, while this parasite did not survive in eland. Buffalo may play a role in the epidemiology of babesiosis in cattle, while eland most likely do not.


Entomological aspects of the first five years of the Onchocerciasis Control Programme in the Volta River Basin. The history and structure of the WHO Onchocerciasis Control Programme in the Volta River Basin are described. An outline of the vector control operations is given, and the techniques and organisation of the entomological evaluation network are described in detail. During the course of the evaluation and related studies undertaken between November 1974 and October 1978 almost 1.2 million S. damnosum females have been taken in over 52,000 man days of catching, and 674,000 flies were dissected. An assessment based on this effort using Annual Biting Rates and Annual Transmission Potentials shows that the transmission of O. volvulus has been reduced to below a defined maximum permissible level over most of the central part of the Programme Area. The difficulties encountered in the remainder, and at certain problem sites are outlined and relevant data given. The benefits to be expected from extending the area further southwards and the possibilities of later reductions in control activity are discussed.


Chemotherapeutic studies on Litomosoides carinii infection of Mastomys natalensis. 8. The action of furazolidone on adult worms and microfilariae. After oral administration of furazolidone in doses of 5 x 50 mg/kg and 1 x 100 mg/kg body weight to Litomosoides carinii--infected Mastomys natalensis microfilaraemia decreased continuously and was reduced by more than 98% 42 days after start of treatment. After the 5-day treatment all adult female and male worms were found dead and encapsulated within 2 weeks, whereas after the single dose 100% of the female parasites were encapsulated 28 days after treatment. In untreated animals quantiative examinations of the intrauterine stages showed an average number of 500 x 103 embryos per adult female worm. Following the 5-day treatment the number of embryos per female parasite was reduced after 42 days to 12.5 x 103, and after the single treatment to 26.9 x 103. By classification into 5 different stages (2- and 4-cell stages, Morula stage, "Horse-shoe" stage, "Ring" and "Brezel" stages, and intruterine microfilariae) an embryogram showed a continuous increase in pathologically-altered embryos during the whole observation period. The 2- and 4-cell stages suffered the most damaged. By 16 days after the end of the 5-day treatment and by 28 days after the single treatment all embryonic stages in the uteri were found to be pathologically altered. Furazolidone possessess high macrofilaricidal activity together with a considerable adverse effect on embryognesis and some delayed effect on microfilaraemia.


IgE serum levels in urinary schistosomiasis. IgE serum levels were determined by PRIST in 56 patients suffering from urinary schistosomiasis and in 39 healthy subjects living in the Coriolei area, south of Mogadishu. Abnormally high IgE values (as referred to normal values found in European healthy controls) were observed in 87.5% of the patients, the mean average being 1359.58 +/- 721.11 U/ml in schistosomiasis and 430.57 +/- 600.90 U/ml in Somalian healthy controls (P less than 0.01). The possible role of IgE in parasitic infection is discussed.


[Echinococcus multilocularis: superinfections in experimentally infected mice (author's transl)]. The influence of subcutaneous superinfections following an intraperitoneal primary infection after 4 and 14 weeks respectively has been examined in Echinococcus multiolcularis infected NMRI-mice. It could be shown that the growth of subcutaneous echinococci is inhibited in superinfected mice (372 mg) if compared with control mice (903 mg parasite weight). Other differences (composition of serum proteins and white blood cells, hemoglobin content) are exclusively due to the primary intraperitoneal infection.


The effect of praziquantel on Hymenolepis diminuta in vitro. Qualitative observations were made on Hymenolepis diminuta, H. microstoma, H. nana and pre-adult Echinococcus multilocularis in vitro. A dose as low as 0.0001 microgram praziquantel/ml affects the tapeworms, while concentrations of 0.01 - 0.1 and 1-10 microgram/ml cause contraction and paralysis in the contracted state within 10 min and 10-30 s, respectively. The in vitro effects of praziquantel on Hymenolepis diminuta have been studied using anaerobic and aerobic incubations and media containing or lacking glucose. Praziquantel inhibits glucose up-take by half at a concentration of 0.1 microgram/ml, both under anaerobic and aerobic conditions. The stimulation of lactate release was most marked in the absence of glucose. A doubling of the amount of lactate released during anaerobic incubation in the presence of glucose was achieved in 0.1 microgram/ml, while 0.01 microgram/ml had the same effect in the absence of glucose. Under aerobic conditions and in the absence of glucose, 0.1 microgram/ml doubled the amount of lactate released while 3 and 10 microgram/ml were without effect in the presence of glucose. Praziquantel increases the total amount of excreted acidic metabolites only in the absence of glucose. The oxygen consumption of H. diminuta was unaffected by praziquantel at a concentration of 10 microgram/ml. Worms treated in their host and then incubated display the same changes as worms treated in vitro. Praziquantel causes an efflux of glucose and alpha-amino-N from the worm into the medium. This impairment of tegumental integrity and the inhibition of glucose up-take and the stimulation of lactate release are reversible after a 15 min incubation in praziquantel solution. Discussion of pharmacokinetic data indicates, that in the in vivo situation, effective concentrations of praziquantel prevail for much longer. Mechanisms that might explain the observed effects are discussed.


The efficacy of praziquantel against Taenia saginata cysticercosis in naturally infected calves. The effect of Praziquantel on Taenia saginata cysticerci was investigated in a trial involving 80 calves from an endemic area in East Africa. When administered subcutaneously at a dose rate of 100 mg per kg of body weight Praziquantel killed all cysterci in all treated calves. A few cysticerci remained viable after a single subcutaneous infection at 50 mg/kg.


The symptoms of newly diagnosed pulmonary tuberculosis and patients' attitudes to the disease and to its treatment in Hong Kong. A questionnaire was applied by Government Health Visitors in Hong Kong to 201 consecutive patients with smear-positive, and 199 with smear-negative pulmonary tuberculosis who were attending one of the 7 full-time Government chest clinics for the first time on account of their current illness. Information was obtained about the symptoms of the disease and its diagnosis and management outside the Government service, and about patients' knowledge and attitudes towards the Government service. Among the 343 patients who sought treatment because of respiratory symptoms, the first symptom for the great majority (81 %) was cough, 15 % having sputum and 27 % haemoptysis as well. However, treatment was sought by only 15 % because of cough alone, compared with 40 % because of haemoptysis. Most patients (76 %) attended their first source of treatment or investigation within a month of the onset of symptoms, but some allowed long delays, and only 35 % attended a Government chest clinic within a month (whether this was the first source of treatment or not). The first source attended was a private practitioner for 53 % of the patients, another private medical establishment for 4 %, a Government chest clinic for only 11 % and another Government medical establishment for 17 %, 9 % went first to a herbalist and 5 % went to a drug store or treated themselves. The delays between the patients' first attendance at a source of treatment and their first attendance at a Government clinic were important, because outside the Government chest clinics only 49 % were investigated by chest radiograph and only 7 % by sputum bacteriology. Only 33 % were even suspected of having pulmonary tuberculosis, and many were correspondingly inadequately treated. The patients were, in general, ill informed about the Government chest clinic service; 52 % did not know, before their current illness, of the existence of the service, only 9 % knew that it was free, and only 12 % that it specialised in the management of tuberculosis. This study thus revealed a need to educate the public about the symptoms of tuberculosis, and about the possibility of their being investigated and treated, free, in a Government chest clinic.


The protective effect of BCG vaccination as indicated by autopsy studies. In a detailed study of the pathology of tuberculous infection made in Finland in 1961, tuberculous foci were found at autopsy in 61 of 67 non-vaccinated subjects and in 35 of 83 BCG-vaccinated subjects, all of whom had died between the ages of 1 and 45 years (with 2 exceptions from causes other than tuberculosis). In the present note on the same material, national information on tuberculin sensitivity and tuberculosis mortality has been used to calculate the risk of tuberculous infection in Finland at different times and ages during the lifetime of these subjects. From these risks of infection in Finland it was estimated that 63 or 64 of the non-vaccinated subjects had been infected during their lifetime and that between 25 and 31 of the BCG-vaccinated subjects were expected to have been naturally infected (had they not been vaccinated) between the time of vaccination and death. It is concluded that virtually all tuberculous infections in unvaccinated subjects lead to pulmonary foci, which are demonstrable at autopsy. Further, the same appears to be so in vaccinated subjects; there is no evidence to support the suggestion that in man BCG vaccine can prevent the establishment of infection in an exposed subject. The effects of BCG (as demonstrated in the earlier paper) appear to be confined to limiting the multiplication and dissemination of the bacilli and the development of lesions following infection.


The treatment of tuberculous meningitis in children with a combination of isoniazid, rifampicin and streptomycin--preliminary report. Twenty two children with tuberculous meningitis were treated with isoniazid, streptomycin and rifampicin and 19 were treated with isoniazid, PAS and streptomycin for at least 18 months. Both groups received corticosteroids at the beginning of treatment. The 2 groups were compared for clinical and neurological improvement, rate of recovery, the presence of neurological sequelae and for mortality. The drug toxicity of both regimens was also compared. The rate of recovery in the first 2 months of treatment was slightly more rapid in group I than in group II and neurological sequelae were less frequent in group I than in group II, but the differences between the groups were not statistically significant. There was very little difference in the death rate in both groups. A high incidence of jaundice was found amongst the children who received rifampicin.


In vitro and in vivo selection of two Lewis lung carcinoma cell lines. Two tumor cell lines adapted to grow in vitro were originated from an explant of lung metastases of Lewis lung carcinoma. These lines differ in their malignancy when reinoculated into syngeneic animals; nevertheless, they do not show any difference for their in vitro clonogenic ability. From these lines 2 in vivo sublines of 3LL carcinoma were developed. The TD50 of the 2 in vivo sublines are different, and both the values obtained are lower than that of the original line. These results are interpreted as a selection of more malignant tumor cell lines.


Analysis of tumor incidence in BALB/c mice used as controls in carcinogenicity experiments. The tumor incidence was studied in 4 groups of BALB/c mice kept under observation in the same experimental conditions as untreated controls in the course of bioassays of chemical carcinogenesis. Two parameters that reflect the variations of environmental factors were studied: body growth and survival rate. Their possible influence on tumor incidence was also considered. Fluctuations were observed in the incidence of different tumor types among the groups, but the level of significance was reached only when comparing the incidence of hepatomas, adrenal cortex tumors and subcutaneous fibrosarcomas among males and the incidence of angiomas and angiosarcomas among females. No association was found between the variations of tumor incidence and body growth and survival rate, which remained constant among the groups.


Treatment of advanced breast cancer with norethisterone acetate. The medical records of 84 postmenopausal women treated with oral norethisterone acetate (NTA) for advanced breast cancer were retrospectively analyzed. Treatment was devoid of significant toxicity. Twenty-one patients were not evaluable for treatment response either because of insufficient data or inadequate treatment trial. Complete plus partial response was obtained in 21 (33.3%) of the 63 evaluable patients, with a median duration of 10 months. Disease stabilization was observed in 16 (25.4%) patients for a median duration of 5 months, while 26 patients (41.3%) showed progressive disease while on treatment. The best response was observed in women with dominant soft part disease and an age over 70 (CR+PR 48%). The literature on norethisterone acetate is reviewed and compared with present results. The role of progestational agents in the treatment of advanced mammary carcinoma is discussed.


Bone metastases from breast cancer treated with calcitonin. Case report. A case of bone metastases from breast cancer is reported. After 6 months of therapy with calcitonin, the skeletal radiological examination showed an evident change in the roentgenographic pattern of a large metastasis of the left femur. A possible relationship between the calcitonin treatment and the radiological change is discussed.


Hodgkin's disease in children. Pathologic study of 87 cases. From 1963 to 1977 at the Istituto Nazionale Tumori at Milan, 112 patients below the age of 16 years with Hodgkin's disease (HD) were observed, representing 13.2% of all the cases of this disease seen during the stated time interval. Eighty-seven of these cases are the subject of the present study. Fifty-nine patients were males and 28 females (2.1:1 ratio). The age range varied from 2 years 10 months to 15 years 10 months (median 10 years). Forty-three (49.4%) children, of whom 35 were males and 8 females, were below the age of 10 years at the onset of their disease. The clinical staging resulted in 34 patients as stage I, 33 as stage II, 13 as stage III and 7 as stage IV. The histologic type was nodular sclerosis (NS) in 49 cases (56.3%), lymphocytic predominance (LP) in 15 cases (17.2%), mixed cellularity (MC) type in 9 cases (10.3%) and lymphocytic depletion (LD) in 8 cases (9.2%). In the remaining 6 cases the histologic classification was not applicable. LP type in 15/15 (100%) patients was associated with stages I and II, and NS in 38/49 (77%) patients was related to stage I and stage II. The latter was also the istologic type most often encountered in patients with stage II disease (23/33 or 70%). Eleven patients have died, and their survival varied from 6 to 47 months (median 30 months). The histologic type was LD in 4 cases, NS in 3 cases, MC in 1 case, and LP in 1 case. In the other 2 nonsurvivors, the histologic type was not identifiable. Of the 23 patients with more than a 5-year survival, 14 (60.8%) had NS HD. As in adults, LP and NS were associated with early stages of the disease and with long survival.


Feasibility of different combinations of chemotherapy (6 MOPP) plus radiotherapy in Hodgkin's disease. During a preliminary clinical experience (1973-1977) we experimented three different sequences in associating 6 MOPP cycles (CT) with radiotherapy (RT) for the treatment of stage II and III Hodgkin's disease. A total of 55 consecutive previously untreated patients can be estimated to contribute in defining feasibility, immediate results and toxicity of the combined treatment. In this group of patients RT preceded CT in 20 cases (RT-6 MOPP), the opposite sequence (6 MOPP-RT) was preferred in 16 cases, whilst a split-course CT fitting in the RT (3 MOPP-RT-3 MOPP) was employed in 19 cases. Except for the sequence used with respect to irradiation, the CT was carried out in all the cases according to the classical scheme proposed by De Vita et al. (11). RT was effected with 60Co-teletherapy and a wide field or segmental sequential fields, having variable extension depending on the stage ("extended nodal irradiation" for stage II and III cases with lymph node involvement not below L3; "total nodal irradiation" for the remaining cases in stage III). The programmed doses were 45.0 Gy to the involved areas and 40.0 Gy to the clinically uninvolved regions for the RT-6 MOPP and 6 MOPP-RT groups. Doses of 35.0/30.0 Gy were planned for the 3 MOPP-RT-3 MOPP group. The three different groups are not homogeneous with regard to certain important clinical and pathological characteristics; in fact, a higher quota of stage III patients, with systemic symptoms and spleen positivity is present in the 6 MOPP-RT and 3 MOPP-RT-3 MOPP groups. The combined treatment has achieved a complete clinical remission in 18/20 patients in the RT-6 MOPP group (90.0%), in 12/16 patients of the 6 MOPP-RT group (75.0%), and in 17/19 cases in the 3 MOPP-RT-3 MOPP "sandwich" combination (89.5%). The average overall duration of the treatment was 48 weeks for the sandwich combination, 50 weeks for the RT-6 MOPP group, and 56 weeks for the 6 MOPP-RT association. As regards the sandwich combination, both CT and RT took a reasonable length of time to complete. On the contrary, both the medical treatment and irradiation required an excessively long time and were not well tolerated when preceded by either RT or CT in full doses. In particular, myelosuppression was less acute and prolonged in the 3 MOPP-RT-3 MOPP group, whereas the actual doses of CT and RT were higher than those which can be reached with respect to other groups. Three preliminary cycles of CT considerably reduce the target volumes and complications arising from RT. The first CT time gave an objective response greater than 50% in 9/9 cases of the 3 MOPP-RT-3-MOPP group with mediastinal involvement. In this group, rather considerable pulmonary complications were observed in 3/9 patients (33.3%) with respect to the 40% found for the 6 MOPP-RT group (2/5 cases) and the 67.7% for the RT-6 MOPP group (6/9 cases).


Histologic subclassification of nodular sclerosis Hodgkin's disease. Nodular sclerosis (NS) Hodgkin's disease was pathologically subdivided by cellular composition and degree of fibrosis in a series of 49 children admitted to the Istituto Nazionale Tumori of Milan between 1967 and 1977. NS showed lymphocytic predominance (LP) in 26 cases, mixed cellularity (MC) in 16 cases, and lymphocytic depletion (LD) in 7 cases. "Early fibrosis" (EF) and "advanced fibrosis" (AF) subgroups in 28 and 21 cases, respectively, were observed. Of the cases with LP 76.9% (20/26) presented with stages I and II disease, compared with 37.5% (6/16) and 28.6% (2/7) of the MC nad LD subgroups, respectively. LP and EF subgroups coexisted in 12 of 28 (42.9%) patients at stages I and II. Predominance of lymphocytes, rarity of lacunar cells, and a mild degree of fibrosis were asociated with early stages of disease. This data confirms that subclassification of NS is feasible.


[Computerized tomography of lymphomas: a simple method in the control of abdominal localization after treatment]. The authors, according to their experience of repeated controls of abdominal computed tomography (CT) in 10 patients with Hodgkin's and non Hodgkin's lymphomas, obtained a clear demonstration of therapy response and disease evolution. The reduction or enlargement after therapy of periaortic, pericaval, hepatic, splenic and pancreatic lymph nodes not always opacified from lymphographic contrast medium is evaluated. It was possible, during the same examination, to evaluate liver, spleen, kidneys parenchyma and regional bone. CT results were always well correlated with clinical findings.