[Haematological features of anorexia nervosa (author's transl)].

Nine patients with anorexia nervosa were studied, who had varying degrees of bone marrow failure ranging from a slight neutropenia to severe pancytopenia. In addition to routine laboratory work bone marrow biopsies were performed at admission and during the course of disease. In four of those patients erythropoietin excretion per 24 hours was measured by the bioassay in the polycythemic mouse at least twice during the course of treatment. At admission most bone marrow showed a marked although varying hypocellularity with grossly apparant background gelatinous material, which appeared to consist of acid mucopolysaccharides. Leukopenia and the changes of the bone marrow morphology reversed to normal after refeeding. Erythropoietin excretion was only elevated in patients who were anemic and returned to normal when the haematocrit reached normal levels. It seems therefore unlikely that an impaired production of erythropoietin or other postulated humoral factors cause the haemopoietic changes in anorexia nervosa. A direct effect of fat or carbohydrate depletion and/or of the increased mucopolysaccharides upon the proliferation of the haemopoietic cells can be suggested, but is an entirely speculative preposition.


[Erythropoietin in serum and urine in man upon hypoxic stimulation and hypoxic stimulation after pretreatment with fluoxymesterone (author's transl)].

The effect of the androgen fluoxymesterone (Flu) upon the hypoxic stimulus of erythropoietin (ESF) production was studied in 8 male and 3 female normal human subjects. After 4 weeks Flu pretreatment (40 mg/day/m2 body surface in men and 10 mg in women) hypoxic stimulation corresponding a maximum of 4000 m altitude was employed. After Flu pretreatment serum ESF titers increased by 80%, ESF excretion by 490%, and ESF clearance by 200% compared to hypoxic stimulation alone. The increase in serum ESF titers after Flu plus hypoxic stimulation employing only 25% of the Flu dose in females was higher than in males. ESF excretion, however, was lower in females than in males. Whereas Flu causes a marked increase in ESF production, ESF clearance is even more enhanced. As in the case of other serum proteins not only glomerular filtration, but also tubular processes may be involved in the excretion of ESF. Since results are available after a short term experiment of 24 h the double stimulation (androgen + hypoxia) may be recommended for clinical trials in men testing the ESF stimulating effect of androgens and anabolic hormones.


Providing library services in a time of fiscal crisis: alternatives.

The nature of the fiscal crisis in health science libraries in the United States is in part due to the style of management in these libraries, in part due to the lack of user identification, in part due to the lack of economically valid fees for service, and in part due to the success of the Biomedical Communications Network. These issues are discussed in terms of how they might be approached. A pragmatic stance is advocated for practitioners, the MLA, the NLM, and library schools to jointly address the questions raised.


Analysis of interlibrary requests by hospital libraries for photocopied journal articles.

A study of the 1975 borrowing requests made by all hospital libraries in central western Massachusetts showed that there were 4,368 requests for articles contained in 1,071 different periodical titles. The numbers of requests per title ranged from eighty-nine for one title to one for each of 123 titles. A graph of the data showed a geometric progression, and the Bradford constants for this dispersion averaged 1.28. The percentage of total requests related to the age of requested issues varied from 62.48% for items not over five years old and 78.15% for issues not over ten years, to 95.57% for materials not over thirty years old. Bradford constants averaged 2.13. Of the thirty most requested periodical titles, sixteen were published in foreign countries, as follows: England--ten; Netherlands--three; Australia--one; Canada--one; and Sweden--one. The study's significance included its total coverage of a relatively large and isolated region, its focus upon the records of requesting rather than lending libraries, and its analysis of interlibrary rather than in-house activities.


Departmental libraries: why do they exist?

In response to an increasing concern on the part of the library staff over the role of the departmental libraries at The Milton S. Hershey Medical Center of The Pennsylvania State University, a questionnaire was developed by the George T. Harrel Library and sent to departmental libraries. From the analyzed responses, the authors were able to define the role of departmental libraries in a medical school/hospital situation, to analyze the Hershey Medical Center situation in an objective manner, to outline areas of possible cooperation between the main and departmental libraries, and to delineate some trends which appear to result from inadequate finding of a central library. Overall, the library found that departmental libraries at Hershey are currently maintaining collections consistent with the functional role of a departmental library.


Improving library effectiveness through a sociophysical analysis.

A library's environment as an inviting place to study, read, and relax is an important function often overlooked or avoided. A nursing school library was underutilized and had an unacceptable of lost materials. A study undertaken to determine the setting's impact on all the library's intended functions showed that the physical environment seriously hampered many activities. A change in the library's arrangement offered users a more functional area for all types of library activities. Statistics show that the library is now more fully utilized, with an impressive decline in losses. The majority of students and faculty report more positive feelings toward the library and the librarian.


Frontiers for prevention.

Developing a balanced approach to today's health problems means paying greater attention to the strategy of prevention. This strategy should encompass environmental measures, self-care activities, and health education; it should carefully weigh the prospective costs and benefits of proposed preventive measures; and it should see that such measures are tailored to the needs of the various specific groups within the general population.


IUD use effectiveness in an urban Guatemalan clinic.

Contraceptive continuation rates-the rates at which people continue to use a particular contraceptive method-can be a great help in determining whether a family planning program is effective or whether new contraceptive methods should be introduced. Until now, very little systematic work has been done to study contraceptive continuation rates in Latin America. The present article reports the results of one of the few existing studies on this subject, which examined the IUD experiences of women admitted to a large family planning clinic in Guatemala City. The study showed that these experiences compared favorably with the IUD experience of groups previously studied in Costa Rica, Taiwan, and the United States.


Use of the bifurcated needle for BCG vaccination of newborns.

The bifurcated needle vaccination method used successfully against smallpox is a relatively simple technique that can be administered by personnel with only basic preparation and a minimum of training. This fact suggests that it could prove useful in campaigns of BCG vaccination against tuberculosis--especially for vaccination of newborns. With this end in mind, two studies were carried out in Santiago, Chile, to examine previously reported difficulties with the method and to assess its potential as an alternative to the best current method, that of intradermal inoculation. These studies indicated that previously reported variations in the results achieved by different vaccinators could be markedly reduced. However, they also found that the bifurcated needle method did not cause a sufficiently large dose of vaccine to enter the subject--even when fifteen needle strokes and a highly concentrated vaccine (160 mg per ml) were employed. It was thus concluded that although modification of the needle or other changes might ultimately yield satisfactory results, the bifurcated needle technique cannot yet be recommended for BCG vaccination of newborns.


Isolation of serotype hardjo and other leptospirae from armadillos in Argentina.

A serologic, bacteriologic, and histopathologic examination for leptospires was carried out on 89 armadillos (Chaetophractus villosus) from Argentina. Forty-seven per cent of the serum samples yielded positive results when tested by microscopic-agglutination. Predominant agglutination reactions were to the Hebdomadis and Bataviae serogroups. A total of 15 Leptospira isolations (from 16.8 per cent of the animals tested) were obtained from kidney tisse. Nine of the isolates were identified as belonging to the Bataviae group serotypes argentiniensis, paidjan, or bataviae; three other isolates proved to be the Canicola group serotype canicola; two others were Leptospira biflexa strains; and the last isolate was found to be serotype hardjo of the Hebdomadis group. The latter finding represents the first isolation of serotype hardjo from this animal species. Histopathologic examination of kidneys from 11 of the animals yielding pathogenic leptospires permitted a diagnosis of interstitial nephritis. This intersitial nephritis, presenting the characteristic picture of lymphoid infiltration, appeared intense in two animals, moderate in five others, and only slight in the remaining four. These histopathologic findings of chronic nephritis, combined with the high positive serologic and cultural isolation rates, suggest that the armadillo is an important natural reservoir-host for pathogenic leptospirae.


Role of the nurse in primary health care.

One of the principal goals to which the Ministers of Health of the Americas have committed their peoples through the Ten-Year Health Plan adopted at Santiago in 1972 is the extension of health services in some form to every man, woman and child in the Hemisphere by the end of the decade. The nurse is in a unique position to contribute to the attainment of this objective. Recognizing the need to redefine the nurse's role in regard to the delivery of primary health care, PAHO/WHO, in collaboration with the  Government of Costa Rica and the College of Nurses in that country, recently sponsored a Seminar on New Dimensions of the Nurse's Role in the Delivery of Primary Health Care. Held in San José from 27 October to 3 November 1976, this meeting brought together 19 professional nurses and 17 physicians from a total of 13 countries. The final report is transcribed below.


Electron density and atomic number determination by computed tomography. Part I: Methods and limitations. Part II: A study of colloid cysts.

The feasibility of extracting electron density and effective atomic number from measurements of tissue in vitro and in vivo has previously been reported. The method requires scans to be obtained at two different beam energies. Optimization of these energies at 40 keV and 80 keV could enable a variation of 1 part in 400 of effective atomic number to be detected. The method is subject to certain limitations related to accuracy and sensitivity. The effect of varying the concentrations of certain atoms has been modelled demonstrating the limits below which variation in effective atomic number is unlikely to be detectable at acceptable radiation doses. A series of 12 patients with colloid cysts has been considered. All were treated by bilateral ventriculo-cisternostomy from one to 23 years ago. Nine of these patients, and the colloid cyst of one patient who died before treatment could be instituted, have been subjected to double energy scanning. The results suggest that the high attenuation values observed in colloid cysts are due to increased electron density and not to any increase in high atomic number elements. The cysts do not appear to change in size or content over long periods.


Mixed connective tissue disease--clinical and radiological aspects of 20 cases.

The clinical and radiological features of 20 cases of mixed connective tissue disease (MCTD), a newly defined disorder, are described. MCTD shares a number of abnormalities with other collagen diseases, notably diffuse systemic sclerosis and systemic lupus erythematosus. However, patients with MCTD have a specific circulating antibody to extractable nuclear antigen (ENA). Most of the cases described exhibited multi-system involvement with radiological changes in the skeleton, chest, and gastro-intestinal tract. Twelve of the 20 cases had an erosive arthritis. This finding has not been previously noted in the radiological literature.


Verification and recording of radiotherapy treatments using a small computer.

A small computer has been interfaced to a linear accelerator used for routine radiotherapy. The objectives are to assess the rate and magnitude of some of the mistakes which may occur, to prevent these where possible and to assist radiographers with record keeping. In this paper we describe our approach to the problem, the apparatus used, the computer program, and the results of several years of operating experience while the system was continually being developed. On one linear accelerator, we estimate that an error has been prevented roughly once in every 500 field parameters set. The most common error is in setting the diaphragms and a detailed analysis is given of possible reasons. Doses in monitor units are recorded automatically and a running total of cumulative dose is maintained; plans for the printing of the dose in rads at selected points are discussed.


A model for treating post-irradiation nausea and vomiting in man: the action of insulin in abolishing radiation-induced delay in gastric emptying in the rat.

Radiation-induced delay in gastric emptying in rats, which may be comparable to radiation-induced nausea and vomiting in man, can be successfully treated with insulin. Biphasic insulin, given in the appropriate dose for the radiation exposure, restored the rate of emptying to normal and was used instead of soluble insulin which made the stomach empty quicker than normal. Some of the evidence suggests that this effect of insulin is related to its action on carbohydrate metabolism, but there was no simple correlation between the hypoglycaemic action of insulin and its effect on stomach emptying. A complete explanation for this action of insulin cannot be given at this stage but the possible involvement of intestinal hormones, such as enteroglucagon is discussed. It is suggested that the use of insulin to treat radiation-induced nausea and vomiting in man should be considered.


RBE of neutrons generated by 50 MeV deuterons on beryllium for control of artificial pulmonary metastases of a mouse fibrosarcoma.

Artificial pulmonary metastases of a mouse fibrosarcoma were produced by the intravenous injection of 10(4) cells admixed with 2 X 10(6) plastic microspheres into mice preconditioned with 600 rad whole-body irradiation 24 hours earlier. Four days after injection of tumour cells, mice were irradiated with neutrons generated by 50 MeV deuterons on Be at the Texas A & M Variable Energy Cyclotron or with 137Cs gamma rays. One, three or six fractions of radiation were delivered on a three-hour fractionation schedule. Surviving lung metastases were scored macroscopically 16 days after irradiation. The data indicate that: (1) the RBE (n/gamma) was in the range 1.6-2.6 depending on the size of dose per fraction; (2) the slopes of the gamma-ray curves decreased with increasing fraction number (i.e. decreasing fraction size); (3) the slopes of the neutron curves decreased only slightly with increasing fraction number (and decreasing fraction size); (4) no additional sparing was achieved by further fractionating doses of neutrons of 300 rad or less.


Some long-term effects of negative pions in mice exposed to partial body irradiation.

The long-term effects of partial body exposure of one-day-old mice given either 60Co gamma rays or negative pions have been studied. Both radiations produced considerable life-shortening; for pions 6.8 +/- 1.5% of life is lost per 100 rad and for gamma rays the value is 5.7 +/- 0.5% per 100 rad. The RBE of pions for ten weeks of life-shortening is about 1.3 compared with 60Co gamma rays, although at lower doses the RBE may be higher reaching about two for six weeks of life shortening. The incidence rate of tumours at any particular age was greater in mice irradiated with pions at the peak and in those given higher doses of gamma rays than in the controls.


Study of cardiac arrhythmias and other forms of conduction abnormality in newborn infants.

In an unselected population of 2030 newborn infants studied by electrocardiography (ECG) between April 1975 and April 1977, 35 were found to have arrhythmias or other cardiac conduction abnormalities. Further investigation by means of 24-hour ECG monitoring showed that apparently serious tachyarrhythmias, such as ventricular tachycardia and slow heart rates associated with sinoatrial block, may be present without clinical disturbance in some newborn babies. Six infants had both bradycardia and tachycardia in the 24-hour recording, although the screening ECG had shown only one of these abnormalities. The alarming ECG appearance of some of the arrhythmias suggested a possible aetiological link with some unexplained sudden infant deaths: a multicentre study could determine this more readily and is therefore recommended.


Cardiac conduction disorders in six infants with "near-miss" sudden infant deaths.

Cardiac conduction disorders caused sudden serious illnesses in six infants that might have been fatal if diagnosis and treatment had been delayed. These cases provide circumstantial evidence to support a link between cardiac conduction disorders and some sudden infant deaths. A further potential long-term effect of these disorders is illustrated in one child in whom psychomotor retardation seemed to develop after an episode of cerebral hypoxia that was probably by an arrhythmia associated with the Wolff-Parkinson-White syndrome. Cardiac conduction disorders may be detected by routine neonatal ECG screening, and it may therefore be appropriate to start prophylactic antiarrhythmic treatment in certain children before clinical signs develop.


Comparison of the antilipolytic effect of metoprolol, acebutolol, and propranolol in man.

Metoprolol and acebutolol, two supposedly cardioselective beta-adrenoceptor antagonists, were tested in 11 healthy men against propranolol, a non-selective drug, for their effect on plasma free fatty acid concentrations before and after insulin. The fasting concentrations of free fatty acid were significantly reduced after acebutolol and propranolol, and their return to normal after insulin was delayed. Metoprolol had no significant effect on free fatty acid levels either before or after insulin. Although both selective and non-selective beta-blocking drugs should be expected to delay the return of free fatty acid values to normal after insulin, in contrast to propranolol and acebutolol, metoprolol had no such effect. This suggests that metoprolol may not be as effective as the other two drugs in controlling lipid metabolism during long-term treatment with beta-adrenoceptor antagonists.


Staging breast cancer: role of bone scanning.

Bone scans using technetium-99m phosphate complexes and a rectilinear scanner were carried out on 192 women with primary operable breast cancer four to six weeks after operation. The lymph node status of all these patients was assessed histologically from triple node biopsy specimens. Only nine patients had positive scans, although 94 patients had histological evidence that the tumour had already spread beyond the confines of the breast. Bone scanning, although accurate as a prognostic guide, is helpful only in a very few cases, and serves mainly to confirm prognostic information obtained more simply and less extensively by histological examination of lymph node biopsy specimens.


Blood glucose control and glomerular capillary basement membrane thickening in experimental diabetes.

Glomerular capillary basement membrane thickness (BMT) was measured in 23 rats which had had streptozocin-induced diabetes for 14 months and in 12 age-matched controls. Diabetic rats were randomly allocated to different groups, either receiving no treatment or treated with a low carbohydrate diet or insulin, or both. Control rats were randomly allocated to a normal or low carbohydrate diet. Among the diabetic rats mean plasma glucose concentrations for the groups ranged from 27-4 mmol/l (494 mg/100 ml) in the untreated rats to 9-8 mmol/l (177 mg/100 ml) in those receiving both a low carbohydrate diet and insulin. A highly significant positive relation was found between BMT and plasma glucose concentration for individual rats. When BMT was corrected for body weight a similar relation was observed.


Improving drug compliance after hospital discharge.

The effect of counselling on medication errors was assessed in 165 elderly patients after leaving hospital. Counselling was effective, with counselled patients making under one-third of the errors made by uncounselled patients. Three types of memory aid were tried to supplement counselling. The pill wheel increased errors, a tablet identification card was unhelpful, and only a tear-off daily calendar seemed to improve results modestly. Counselling was virtually as effective in improving compliance in poorly orientated patients. A designated member of staff should spend about 15 minutes with each elderly patient before discharge to ensure that the discharge drug regimen is fully understood and remembered, that old tablets are destroyed and that other people's tablets are not taken.


Presentation of rheumatoid arthritis and its relation to prognosis.

A review of published reports in an attempt to relate the way rheumatoid arthritis presents to its manner of progression and prognosis has provided few positive answers. Certain, but not all, studies indicate that cases with an acute explosive onset do better than those of more insidious onset, but the latter have almost certainly lasted longer by the time they come under medical supervision. Cases of monarthritis and palindromic (remittent) arthritis do better than polyarthritic and persistent cases, but true diagnosis of the former is often uncertain. Undoubtedly persistent high-titre seropositivity and nodule formation are bad prognostic pointers. A plea is made for a more intensive study of the early case: if any therapeutic agent now or in the future can reverse the inflammatory process this is surely the time it is most likely to do so. This is the curable end of what is now an incurable disease.


Composition of the domestic water supply and the incidence of fractures and encephalopathy in patients on home dialysis.

Of the 202 patients undergoing home dialysis in the Trent region, 11 developed dialysis encephalopathy, 21 suffered spontaneous fractures, and 36 who had undergone dialysis for over four years had neither of these complications. Because the incidence of complications seemed to be unevenly distributed the water supplies were analysed. Water supplied to the homes of the patients with fractures or encephalopathy contained significantly less calcium and fluorine and significantly more aluminium and manganese than that piped to patients without these complications. The high aluminium concentrations in the bone of patients with encephalopathy was confirmed, but aluminium concentrations in the brains from three patients with encephalopathy were not increased. Patients who undergo dialysis in areas where water contains high aluminium concentrations should be supplied with deionisers.


Fulminant Wilson's disease with haemolysis and renal failure: copper studies and assessment of dialysis regimens.

Two girls, aged 12 and 17 years, presented with hepatocellular dysfunction and severe haemolysis due to Wilson's disease (hepatolenticular degeneration). This was accompanied by acute renal failure. In the absence of renal function sufficient for the urinary excretion of penicillamine, studies were performed to assess the potential of peritoneal dialysis, ascites removal by ultrafiltration-reinfusion, and haemodialysis as alternative excretory pathways for copper. The greatest amount of copper, as judged by rising bath concentrations, seemed to be eliminated with haemodialysis. But this was accompanied by a progressive increase in serum copper concentrations with rapid clinical and biochemical deterioration leading to death within 48 hours. A small amount of copper was lost with ascites removal. Significant amounts of copper were removed during peritoneal dialysis (36 mumol/day (2287 microgram/day)), although a clinical response was not evident before haemodialysis was introduced. The administration of penicillamine orally, intravenously, or intraperitoneally produced no measurable increase in copper excretion into the peritoneal dialysate. Hence peritoneal dialysis alone appears to offer the greatest potential benefit with regard to both eliminating copper and altering the course of this fulminant form of Wilson's disease.


Accidental percutaneous hexachlorophane intoxication in children.

Eighteen children with normal skin were accidentally intoxicated by a talc powder containing 6% hexachlorophane. Four died and two remained paraplegic. The clinical picture was intracranial hypertension, eight patients developing signs of spinal cord damage. The condition seemed to result from massive intramyelinic oedema. In the spinal cord vascular disturbances may occur as mechanical complications of oedema, giving rise to permanent sequelae.


Minoxidil for severe hypertension after failure of other hypotensive drugs.

Forty-four patients with severe hypertension who were resistant to treatment with more conventional hypotensive drugs or could not tolerate the side effects were treated with minoxidil, a potent peripheral vasodilator. A beta-blocking drug and a diuretic were used routinely to control, respectively, the tachycardia and fluid retention caused by minoxidil. During treatment the outpatient supine blood pressure fell from a mean of 221/134 mm Hg to 162/98 mm Hg. Eleven patients required additional or alternative hypotensive agents before blood pressure was adequately controlled. Side effects were minor, although the invariable hirsuties caused by minoxidil was unacceptable to three women. The possibility of cardiotoxic effects, raised by early studies in dogs, has not been excluded, and therefore this drug should be used only in patients with severe hypertension. In such patients minoxidil appears to be most effective.


Arterial embolism in thyrotoxicosis with atrial fibrillation.

In 262 patients with thyrotoxicosis and atrial fibrillation there were 26 episodes of arterial embolism (17 cerebral and nine elsewhere) in 21 patients. Twelve incidents occurred with active thyrotoxicosis, three on reversion to sinus rhythm, and 11 after the patients were euthyroid. This important complication is more common than is realised, and most patients should be put on prophylactic anticoagulants when first seen with atrial fibrillation.


Immunohistochemical studies of Wolfgram proteins in central nervous system of neurological mutant mice.

Immunohistochemical localization of Wolfgram proteins has been studied by the indirect immunoperoxidase technique with Wolfgram protein W1 antibodies in the nervous system of myelin deficient mutant mice: Jimpy, MSD and Quaking. In all these mutants, the myelinated fibers and the oligodendroglial cells (few in number) in the corpus callosum and the white matter of the cerebellum folium show a positive reaction to protein W1. These observations are in accordance with the immunological studies showing that the two major Wolfgram proteins, W1 and W2, of mutant mice have immunological similarities with that of the controls.


Dorsal noradrenergic bundle lesions fail to disrupt self-stimulation from the region of locus coeruleus.

Intracranial self-stimulation (ICSS) from the region of the locus coeruleus (LC) was not attenuated by ipsilateral dorsal noradrenergic bundle (DNB) lesions. Bilateral DNB lesions also failed to affect LC ICSS, whereas the same lesions, in the same animals, resulted in a marked enhancement of lateral hypothalamic (LHA) ICSS responding. Behavioral, neuroanatomical and fluorescent histochemical data confirmed destruction of the DNB, thus suggesting that the dorsal noradrenergic system is not necessary for ICSS from the region of the LC.


Neuronal activity with cardiac rhythm in the nucleus of the solitary tract in cats and dogs. I. Different discharge patterns related to the cardiac cycle.

In anaesthetized, spontaneously breathing cats and dogs, extracellular recordings were made of the spontaneous activities of 28 single neurones with cardiac rhythm. It was confirmed by histological examination that the neurones were situated in the mediodorsal portion of the nucleus of the solitary tract. Different discharge patterns in relation to the heart cycle were demonstrated using R-deflection triggered histograms. Most of the neurones discharged with systolic bursts. In the cat, about half the neurones showed two to three activity peaks in the histograms which could occur at any time of the heart cycle. The height of the various peaks sometimes changed in different ways in the course of the respiratory cycle. It can be concluded that different cardiovascular afferents converge to single neurones. In some neurones it could be shown by elimination of the vagus nerves that the pulse-rhythmical discharge pattern was induced mainly by vagal inputs, mainly by glossopharyngeal inputs or by inputs from both nerves. Two-thirds of the neurones discharging with systolic bursts could be enhanced by increasing the arterial blood pressure. In some of these neurones a proportionality between the number of impulses per heart cycle and the mean arterial blood pressure was found.


Neuronal activity with cardiac rhythm in the nucleus of the solitary tract in cats and dogs. II. Activity modulation in relation to the respiratory cycle.

In anaesthetized, spontaneously breathing cats and dogs extracellular recordings were made of the spontaneous activities of 28 single neurones with cardiac rhythm. Histological exmaination confirmed that the neurones were situated in the mediodorsal portion of the nucleus of the solitary tract. The neurones, which had already been analysed in respect to their pulse-rhythmical pattern27, were investigated by means of inspiration triggered histograms. The neurones could be grouped according to the respiratory modulations of their activities. Increased activities occurred during (a) the rise of the respiratory blood pressure wave, (b) the respiratory rest period, and (c) the inspiration. Three neurones did not exhibit respiratory modulation. The respiratory modulations of groups a and b were most probably caused by changing inputs from cardiovascular receptors in the course of respiration. It could be shown by adequate stimulation and elimination of the vagus nerves that the neurones of group c were influenced by lung inflation receptors as well as by cardiovascular receptors.


Somatotopic and columnar organization in the corticotectal projection of the rat somatic sensory cortex.

Single injections of tritiated amino acids into the first somatic sensory area (SI) of the rat neocortex result in axoplasmically transported labeling of the stratum griseum intermidiale and stratum griseum profundum of the ipsilateral superior colliculus. The terminal labeling in these layers takes the form of multiple, column-like patches. The SI projection is somatotopically organized with the face and head representations projecting to an extensive anterolateral part of the colliculus and the limb representations projecting to a restricted posterolateral part. Injections of horseradish peroxidase into the superior colliculus result in retrograde labelling of corticotectal cells in the superficial part of layer VB of SI and of the second somatic sensory area (SII).


The postnatal development of the caudate nucleus: a Golgi and electron microscopic study of kittens.

This study used light and electron microscopy to describe changes in the synaptic organization of developing caudate nucleus and to quantitate postnatal synaptogenesis in this region. Observation at the light microscopic level focus on the perinatal period and suggest an early maturation of spiny interneurons of the caudate nucleus. Golgi impregnation of these cells at early postnatal ages (birth to 7 days) reveals 3-5 primary dendrites which radiate from the cell body and extend for distances of 8-16 micron before branching. Secondary dendritic branches contain spines and extend, with further branching, for additional distances of 60-160 micron. The dendritic fields of neighboring caudate neurons overlap and the axons which arise from these cells course and branch within the dendritic fields. Examination of perinatal caudate neuropil (birth to 5 days) by electron microscopy reveals an extensive and well-developed axodendritic connectivity. Axonal profiles form multiple synapses en passant along single dendrites and dendritic spines or on several adjacent dendritic branches. At these ages, terminals contain few synaptic vesicles and synaptic junctions are slightly asymmetrical. By the fifteenth postnatal day, boutons are filled with vesicles, junctional complexes are distinctly asymmetrical, and axondendritic connectivity has been modified by the increase of dendritic spines and branchlets. Thus, the basic pattern underlying the organization of synapses  in the mature caudate nucleus, is established within the first week postpartum and subsequent changes are primarily quantitative.


Effects of hippocampal electrical stimulation on longterm memory and on cholinergic mechanisms in three inbred strains of mice.

Two sets of experiments have been carried out in an attempt to determine the role of hippocampal cholinergic mechanisms in a long-term memory storage. Three inbred strains of mice were presented with two different learning tasks in order to estimate their long-term retention abilities as well as changes in this ability after a post-trial hippocampal stimulation. In parallel experiments the enzymes involved in acetylcholine metabolism were studied under different experimental conditions. Our results indicate: (a) The capacity for long-term memory of the BALB/c line is much greater than that of either the C57BL/6 or C57BR strain. (b) Hippocampal post-trial electrical stimulation leads to an improvement of this capacity in the BALB/c strain. This phenomenon is less pronounced in C57BL/6 and non-existent in C57BR mice. (c) Choline acetyltransferase activity in the hippocampus is significantly higher in BALB/c than in the other two strains. In BALB/c this enzyme activity is greatly changed by the post-trial stimulation whereas in the C57BL/L strain only a slight variation of enzyme activity is observed. No modification occurs in C57BR. The results suggest that the more active acetylcholine synthesizing enzyme in the hippocampus of BALB/c may be related to a greater acetylcholine availability, thus favoring the establishment of a long-term memory, perhaps by releasing greater amounts of acetylcholine in the hippocampus immmediately after the learning session. The electrical stimulation of the hippocampus acts to magnify or accelerate this phenomenon. It is suggested that the efficiency of the stimulation would be related to the genetically determined higher cholinergic activity of the hippocampus.


Diazepam blockade of repetitive action potentials in skeletal muscle fibres. A model of its membrane action.

Diazepam inconcentrations of 10(-6) and 10(-5) M effectively blocks trains of action potentials (AP) in individual rat diaphragm muscle fibres 'in vitro'. Single APs, evoked and recorded intracellularly with double microelectrodes, were not affected by diazepam. Trains of APs, evoked in diaphragm fibers in a SO42-- -medium (Cl-- -free), were not affected by diazepam. Diazepam decreased the dependence of the membrane resting potential of muscle cells in chloride media on elevated external potassium whereas no effect was observed in SO42-- --Cl-- -free saline. Similar to in the rat diaphragm, diazepam blocked the trains of AP of individual muscle fibres in the frog sartorius muscle (Cl-- -medium). Diazepam did not affect the spontaneous fibrillatory APs recorded extracellularly from rat gastrocnemius muscles 10 days after denervation. Diazepam apparently increases the resting permeability of the muscle fibre memebrane for chloride ions. In the presence of the drug, the higher permeability for Cl- diminishes the depolarization caused by the potassium released and accumulated in the vicinity of the membrane in the course of AP. The muscle fibre membrane thus does not respond by repetitive activity when partially depolarized and only one AP can be evoked when diazepam is present. It is suggested that similar changes in Cl-- permeability may occur in brain excitable structures after diazepam administration and may account for some of the therapeutic effects of the drug.


Purification of viable ciliated cuboidal ependymal cells from rat brain.

Trypsinization of coronal sections of rat brain, followed by incubation with the chelating agent, ethyleneglycol-bis(beta-aminoethyl ether)-N,N'-tetraacetic acid (EGTA), results in selective release of ciliated cuboidal ependymal cells which may be further purified by centrifugal methods. The isolated cells are motile, viable, and exhibit ultrastructure comparable to that in situ.


Quantitative aspects of the synaptic organization of the superior colliculus in control and dark-reared rabbits.

Fine structural and quantitative aspects of the synaptic organization of the superior colliculus of the rabbit were studied. The synaptic density, the frequency of the distinct types of terminals, the length of the contact zones, the percentage of serial contacts and the number of synaptic vesicles per terminal were estimated in control, dark-reared and dark-reared-recovered animals. The ultrastructure of the synaptic terminals and the complex interconnectivity correspond to that described for other species. The depth distribution of terminals with round synaptic vesicles agrees quite well with the distribution of cortical and retinal afferents found in lesion experiments. Dark-rearing has little effect on the quantitative organization of the synaptic terminals. In contrast with previous observations in the visual cortex of the same animals37 no changes in the density of synaptic vesicles is observed in the superior colliculus after long term dark-rearing.


Development of kitten hippocampal neurons.

Cells in the CA1 region of the hippocampus of kittens were studied using an in vitro slice preparation. Good quality intracellular records were obtained from over 100 cells from kittens 2 days to 4 weeks of age. Cell resistance was high in 2-day-old animals and decreased over the following 4 weeks. Both excitatory and inhibitory synaptic potentials were seen in all animals. EPSPs were only weakly effective in triggering spikes in the youngest kittens, but were greatly potentiated by repetitive stimulation at 3-10/sec; IPSPs caused a potent blockade of cell discharge in even the youngest preparations. Stimulation of the orthodromic input pathway led to a complex series of excitatory and inhibitory synaptic events which was not seen in the adult. In the 2- and 4-week-old kittens, a cell type with physiological properties different from the predominant pyramidal cell began to appear in recordings from the CA1 region. Technical difficulties inherent in in vivo recordings from neonatal animals were considerably less with the in vitro technique. Careful developmental studies may now be pursued in the slice at the single cell synaptic level.


Evaluation of control populations: body weight and rate of gain in Japanese quail.

1. Two control populations of quail of different origin were maintained by cyclical mating, one for 4 and the other for 6 generations. Means, heritabilities, genetic and phenotypic correlations of body weights at 1, 14 and 35 d and rates of gain from 1 to 14 d and from 14 to 35 d did not show any trend of change with generation. 2. The variability between generations was greater in the characters having intermediate and lower values of heritability, genetic and phenotypic correlations than in those with higher values.


The sparing action of inorganic sulphate on sulphur amino acids in practical broiler diets: preliminary trials with young chicks.

1. In three trials marked responses to Na2SO4 were obtained, both in terms of growth rate and of food/gain ratio. In a fourth trial the chicks responded to graded additions of synthetic methionine but not to inorganic sulphate. 2. The response of the chicks to Na2SO4 depended on the amount of sulphur amino acids in the diets, being absent or difficult to demonstrate in severely deficient diets or in those adequately supplemented, respectively. 3. Sodium sulphate cannot replace more than about 0-05% supplementary methionine. 4. Usually the efficacy of Na2SO4 in improving performance appeared to range from 40% to 60% that of synthetic methionine.


The sparing action of inorganic sulphage on sulphur amino acids in practical broiler diets: the capacity of sodium sulphate to replace some of the supplementary methionine in diets of chicks up to 5 weeks of age.

1. Graded responses, in terms of both weight gain and food/gain ratios, were obtained to increasing increments of Na2SO4 added to diets containing suboptimal amounts of sulphur amino acids. 2. In most cases the relative efficiency of Na2SO4 ranged from 25% to 55% of that of synthetic methionine, when the former replaced 0-04 to 0-05 percentage units of the latter. This efficiency tended to be higher during the 3 to 5 than the 1 to 3 weeks of age periods. 3. The addition of either methionine or Na2SO4 decreased relative food consumption, which was apparently increased by suboptimal contentrations of dietary sulphur (as a compensatory response).


The ulstrastructure of the extracellular phase of bone as observed in frozen thin sections.

The fine structure of the extracellular phase of avian medullary bone and embryonic chick femur was examined in thin sections prepared by ultracryotomy and ultramicroincineration. Since contact with solutions was completely avoided, little or no loss or dislocation of mineral constituents could occur. Amorphous bone mineral (ABM) was present in two forms: as 15-30 nm spheres and as a structure-free haze. Removal of all organic material by low temperature ashing left the ABM intact. Crystals were usually associated with the ABM. In newly ossifying regions clusters or nodules of randomly oriented crystals and ABM appeared to coalesce when they reached approximately 1 micron in diameter. In highly calcified regions crystals appeared to be oriented along collagen fibers. ABM did not appear to be associated with collagen. Unmineralized collagen was visible in osteoid after staining with dry OsO4 vapor and it appeared to be diverted around nodules. Structures which resembled matrix vesicles were present. Selected area electron diffraction patterns indicated the presence of hydroxyapatite.


A micromethod for the determination of fluoride in blood plasma and saliva.

A simple and accurate technique for the determination of fluoride (F-) in capillary-sampled blood is presented. The method is based on the known addition-slope determination technique using the fluoride electrode. No calibration curve or calibration of the electrode is required. A standard deviation of 1.3-5.6% in the range 300-10 ng F/ml was given by 259 duplicate determinations on human plasma. Measurements of parotid saliva showed that it was possible to analayze fluoride concentrations as low as 4 ng F/ml with good reproducibility. The results also show that a 150 microliter sample is sufficient for fluoride determination with high accurary. This method can easily be used in clinical laboratory.


Phosphatase content of rat calvaria after in vivo administration of vitamin D3 metabolites.

The effects of acute or chronic administration of small doses (130 pmol) of 25-hydroxycholecalciferol, 24,25-dihydroxycholecalciferol, and 1,25-dihydroxycholecalciferol on rat calvaria acid and alkaline phosphatase activities were investigated in weanling male albino Wistar rats raised on a vitamin D-deficient, low-calcium diet. The results indicate that each of these active metabolites has a different effect on calvarial phosphatase activities. 25-hydroxycholecalciferol causes a significant increase, and 24,25-dihydroxycholecalciferol a decrease in the enzymatic activity. In animals treated with 1,25-dihydroxycholecalciferol these activities are lower after one injection, but after seven daily doses they are not different from those of ethanol-injected control rats. The observed changes do not seem to be related to changes in serum calcium and/or phosphorus concentrations.


Proliferation of osteoclasts in rat bone following bleeding and femoral fractures.

There is a significant transient increase in the number of osteoclasts in intact bone after bleedings and fractures in rats. This rise in the osteoclast population might be due to an increased parathyroid activity released by the trauma, but other factors may be involved. Both bleedings and ractures in rats are followed by hypercalcemia.


The role of synthetic and bone extracted Ca-phospholipid-PO4 complexes in hydroxyapatite formation.

The calcium-phospholipid-phosphate (Ca-PL-PO4) complex isolated from young bone has been shown to initiate hydroxyapatite formation from a metastable calcium phosphate solution. The action of the complex was compared to that of the acidic phospholipids: phosphatidyl serine, phosphatidyl inositol and phosphatidic acid. These phospholipids first remove calcium, and a small amount of phosphate from the metastable solution forming a material similar to the complex isolated from bone, and then form hydroxyapatite. The rate of hydroxyapatite proliferation, once phosphatidyl serine and phosphatidyl inositol are converted to Ca-PL-PO4 complexes, is the same as the rate observed for comparable weights of the complex isolated from bone. It is suggested that the complex isolated from bone was formed in a manner similar to the complexes in our in vitro experiments. Finally, our evidence supports the possibility that a similar complex is responsible for the initial mineralization in matrix vesicles.


Glycosaminoglycans in congenital pseudarthrosis.

Light and electron microscopic studies on cells and matrices of congenital pseudarthrosis of the femur of a 5.5-year-old male revealed three areas with different morphological features; a fibrous area, a cartilaginous area and an osseous area. Glycosaminoglycans were isolated from each of the three areas and characterized by the degradation with chondroitinases. Although chondroitin sulfate was the major component in all regions, a significant amount of dermatan sulfate occurred in the fibrous area. A small amount of hyaluronic acid was found in both fibrous and osseous areas. These suggest that the peculiar composition of glycosaminoglycans in the affected part may account for some clinical aspects of the disease which resists treatment.


Maintenance of a calcemic response to parathyroid hormone in D-deficient rats by the prevention of severe hyperparathyroidism.

Parathyroid gland transplanted rats and hypophysectomized rats were raised from weaning on a diet without vitamin D and low in calcium (0.02%) for 4 weeks. At the enn of this period the animals of both experimental groups, when compared to their respective controls (i.e., sham-operated animals for parathyroid-transplanted ones, and hypophysectomized plus bovine growth hormone-supplemented ones for hypophysectomized rats) were characterized by (a) moderate or absent secondary hyperparathyroidism; (b) near normal bone calcium content; and (c) a maintained responsiveness to the calcemic effect of parathyroid extract (PTE). The PTE action is a bone effect that does not require the presence of the kidneys and is not related to changes in serum calcium and/or phosphorus concentrations. These results indicate that when severe hyperparathyroidism is prevented, the sensitivity of bone to the calcemic action of PTE can be maintained in D-deficient calcium-deprived rats. They also suggest that in these animals the main factor leading to resistance to PTH is the state of severe chronic hyperparathyroidism.


Quantitative analyses of osteoclast changes in resorbing bone organ cultures.

The stimulation of bone resorption, assessed by the release of 45Ca from prelabeled bones, was associated with an increase in number of osteoclasts per bone section in parathyroid hormone (PTH)-treated bones, but not in lipopolysaccharide (LPS)-treated bones. By contrast the number of nuclei per osteoclast increased following LPS treatment, but was not affected by PTH. LPS-treated bones had more multinucleated cells, some having as many as 27 nuclei per osteoclast. More osteoclasts were adjacent to the bone collar in bones treated with LPS or PTH than in control bones. In LPS-treated bones this area also contained the largest osteoclasts, as determined by the greatest number of nuclei per osteoclast. The results suggest that LPS and PTH stimulate osteoclastic resorption by different mechanisms.


Effects of increased earth gravity and estrone treatment on intact and healing avian radii.

Estrone, 0.4 mg administered daily for 7 days to developing chicks at 2 weeks post hatching, increased total mass and accelerated the rate of growth of the diaphyseal and proximal epiphyseal diameters of intact radii. Fractured radii of animals subjected to the same hormonal treatment displayed decreased bone weight but increased rate of growth of the proximal epiphyseal diameters and longer but thinner and lighter calluses. Two-week-old chicks, which had received no estrone, when exposed to a week-long 2g environment showed decreased intact bone weight and, with the exception of length of fracture callus, a reduction of all measured parameters of fractured bones. Estrone treatments of 0.4 mg administered daily to hypergravity-exposed animals over a week-long period resulted in greater length of fracture callus and increased rate of growth of the proximal epiphyseal diameter of both intact and fractured bones. The same treatments decreased weight and linear growth of fractured bones and width and weight of the fracture callus.


Preliminary studies on the binding of plasma albumin to bone tissue.

The extractability of 125I-labelled plasma albumin from bone pieces and from powdered bone has been compared after both in vivo and in vitro incorporation. The results show that albumin is more readily extracted from bone pieces than from bone powder which implies that tissue disruption exposes additional protein adsorption sites. It is suggested that incorporation of plasma albumin into calcified matrix during bone formation occurs mainly as a result of its strong interaction with bone mineral.


Effect of propranolol on renin release in the dog.

Infusion of d,l-propranolol in both anesthetized and conscious dogs caused decreases in heart rate (HR), plasma renin activity (PRA), and plasma aldosterone. There was no consistent change in mean arterial blood pressure, plasma renin substrate concentration, packed cell volume, plasma potassium, or plasma sodium concentration following the infusion of propranolol. In five conscious animals, infusion of propranolol (1 mg/kg followed by 0.47-0.65 mg kg-1 h-1) reduced HR from 117.6 +/- 4.0 beats per minute (mean +/- SE) during control periods of 73.2 +/- 2.0 beats per minute (P less than 0.005) 90 min after the start of infusion. PRA decreased from 9.97 +/- 1.79 ng ml-1 h-1 during control periods to reach 1.50 +/- 0.42 ng ml-1 h-1 (P less than 0.005) at the end of the 90-min infusions. Plasma aldosterone also decreased during this time from 17.60 +/- 1.93 ng% during control periods to reach 6.64 +/- 0.98 ng% (P less than 0.005). The data suggest that propranolol at the dose administered suppresses renin and aldosterone secretion in unstimulated dogs. They suggest also that beta-receptor activity contributes to basal renin release.


Effect of norepinephrine on intramyocardial distribution of blood flow in normal and ischemic myocardium.

Using labelled microspheres, the effect of norepinephrine (NE) infusions (15 microgram and 30 microgram/min) on coronary blood flow and its intramyocardial distribution during ischemia was studied. The results reported here show that in the ischemic myocardium, the ratio of endocardial to epicardial flow was 0.67. This value became 1.0 in dogs receiving NE at a dose of 30 microgram/min. Since an adrenergic discharge is known to accompany angina in man, these data suggest that an imbalance between the endocardial and epicardial blood flow might not be present in this clinical condition.


Effects of acetylcholine mustard aziridinium ion and its choline analogue on choline transport into synaptosomes.

A compound thought to be choline mustard aziridimium ion was found previously in our laboratory to inhibit choline transport into human erythrocytes. Experiments with synaptosomes prepared from brain of rat now show that the aziridinium ion of choline mustard hydrochloride inhibited high- and low-affinity choline transport, with the inhibitory effect being about 10 times less than that of hemicholinium-3. Acetylcholine mustard aziridinium ion also inhibited the transport of choline, but it was less potent than its choline analogue. Studies with choline mustard aziridinium ion may yield important information about the transport of substances into the presynaptic nerve terminal.


A new chronically cannulated carotid artery preparation for determination of drug half-lives in quinea pig.

A reliable procedure for implanting a cannula into the carotid artery of the guinea pig is described. The gaseous anaesthetic used provided excellent control, rapid recovery, and caused no fatalities. There was no evidence of postoperative infection and patency of the cannula could be maintained for 21 days after surgery. There was no indication of postoperative trauma and removal of blood appeared to be painless. Efficacy of the preparation was demonstrated by repeated removal of 3-ml volumes of blood for the determination of the half-life of phenobarbital acutely in five animals and chronically in three guinea pigs treated with the drug for 14 days. Administration of phenobarbital twice daily (20 or 50 mg/kg, ip) for 1 week increased its clearance rate fivefold. Treatment for an additional week produced a further increase in phenobarbital clearance. The cannulated guinea pig preparation described should allow determination of the pharmacokinetics of many drugs in this species.


Reduction of intrinsic sinoatrial frequency and norepinephrine response of the exercised rat.

Physical training is associated with a reduction of intrinsic sinoatrial activity; the present study examined the role of the parasympathetic nervous system in this reduction. Six groups of rats were studied for 10 weeks: inactive control; treadmill exercised; parasympathetic receptor blockade with atropine; exercise plus atropine; parasympathetic receptor stimulation with carbachol; and exercise plus carbachol. In vivo ISF (cardiac frequency 20 min after injection of propranolol and atropine) was measured at 3-week intervals. At the end of 10 weeks the right atrium was excised, in vitro measurements were made of ISF, and chronotropic dose-response curves to acetylcholine and norepinephrine were established. In vivo, ISF was reduced with time, the greatest reduction being found in the exercise plus atropine group; the treadmill-exercised and the atropine-treated groups also had a greater reduction than the control group. In vitro, no differences were observed in acetylcholine responses. The maximum norepinephrine chronotropic response was reduced in the treadmill-exercised and the exercise plus atropine groups. The maximum norepinephrine-induced frequency correlated with the in vitro ISF (r = 0.75). Thus, ISF was reduced with training, but this effect was independent of parasympathetic activity. The properties of the sinoatrial node which set ISF also influenced the maximum norepinephrine response.


Study of reversibility of effects of hypoxia in airway smooth muscle.

We have shown in the past that hypoxia impairs contractile activity in tracheal smooth muscle (TSM). This was associated with partial uncoupling of mitochondria. It remained to be determined whether these changes were reversible. The TSM model was felt to be superior to the isolated mitochondria since it was likely to be free from artefacts inherent in procedures involving homogenisation and extraction. We report here that the oxygen uptake rates of the isolated, mechanically active TSM were increased in the posthypoxia recovery period when compared with the prehypoxia active muscle. Mechanical recovery was complete.


Isometric and isotonic contractions in airway smooth muscle.

Canine tracheal smooth muscle was used as an in vitro model of smooth muscle in intrapulmonary airways to determine whether active tension curves derived from isometric and isotonic muscles are similar, and thus resemble striated muscle in this respect. Isometric, isotonic after-loaded, and isotonic free-loaded contractions elicited at different lengths and loads, were analysed. The data demonstrate that length-tension (L-T) diagrams were different in these various types of contractions for electrically and carbachol driven tracheal smooth muscles strips. In general, at any given length active tension is less in isotonic and free-loaded modes of contraction as compared with isometric. We conclude that the ability to actively develop tension at a given length in airway smooth muscle depends on the mode of contraction.


Epileptiform seizures in domestic fowl. VI. Plasma phenobarbital concentrations and anticonvulsant activity.

The relationship between plasma phenobarbital concentrations and anticonvulsant activity was determined against seizures induced in epileptic chickens by intermittent photic stimulation (IPS). Intraperitoneally administered phenobarbital produced a plasma-concentration-dependent reduction in both the incidence and severity of seizures. Complete protection against IPS-induced seizures was observed for a period of 6 h after acute phenobarbital administration during which the mean plasma phenobarbital concentrations were between 16.2 +/- 0.91 and 13.6 +/- 1.0 microgram/lm. Plasma phenobarbital concentrations below 3.6 +/- 0.06 microgram/ml had no measurable effect.


The effects of glucose and insulin on contraction of the isolated diaphragm.

High glucose concentrations (55 mM) were found to suppress the isometric contraction tension of rat diaphragm. The effect appears to be due to the resulting transmembrane osmotic gradient in spite of the fact that glucose uptake by the diaphragm is fairly rapid. Insulin can reverse the effect of hypertonic glucose to a considerable extent. The problems of estimating intracellular glucose concentration in the isolated muscle are considered. Estimates of intracellular glucose taking into account extracellular space and extracellular diffusion gradients were made using a two-compartment model. Calculations based on the model show that in the presence of insulin, intracellular glucose increases from about 1 to 19 mumol/ml of muscle fibre. The mean transmembrane glucose concentration gradient dcreases from 41 to 18 mumol/ml. With the use of the model it appears possible to relate most of the observed effect of glucose and insulin on isometric contraction to their influence on the osmotic gradient across the muscle fibre membrane. Insulin appears to have some additional effects on muscles suppressed by hypertonic solutions which are not accounted for by this mechanism.


The effect of hypoxia on prostaglandin output and on tone in isolated coronary arteries.

The relationship between bath Po2, intramural prostaglandin synthesis, and vessel tone in isolated coronary arteries of cattle was studied. The basal output of prostaglandin under 95% O2-5% CO2 (580 mmHg) was elevated markedly when the Po2 was decreased to 47 mmHg but extreme hypoxia (9 mmHg) sharply curtailed output. The coronary vessels responded to 47 mmHg with relaxation but they contracted when the Po2 was decreased further to 9 mmHg. Known inhibitors of prostaglandin synthesis attenuated both the hypoxia-induced relaxations and contractions. Analysis of the effects of extreme hypoxia and of inhibitors of prostaglandin synthesis on tone indicated that both suppress prostaglandin production. It is concluded that coronary prostaglandin synthesis is accelerated by hypoxia unless the oxygen deprivation is so severe as to limit the availability of oxygen for synthesis.


A pharmacological study of SRS-A on the bovine cutaneous vasculature.

Bovine slow-reacting substance of anaphylaxis (SRS-A) is capable of producing dose-dependent vascular permeability changes in the skin of calves. The wheals are well-defined indurations, similar to wheals induced by histamine but different from those induced by prostaglandin (PG) E2. Three proposed SRS-A receptor blockers (i.e., FPL 55712, PR-D-92-EA, and sodium meclofenamate) were studied with respect to their antagonism of wheals induced by SRS-A, histamine, and PGE2. PR-D-92-EA and FPL 55712 antagonized SRS-A, and also histamine and PGE2 at high concentrations. Meclofenamate was ineffective against SRS-A but antagonized histamine and PGE2 at higher concentrations. The significance of these results, especially with respect to passive cutaneous anaphylaxis, is discussed.


Muscarinic feedback inhibition of acetylcholine release from the myenteric plexus in the quinea pig ileum and its status after chronic exposure to morphine.

Atropine (10(-8)-10(-6) M) produced a dose-related increase in the release of ACh from the electrically stimulated longitudinal muscle-myenteric plexus preparation. This increase in release was frequency dependent, being greater at low frequencies of stimulation where the pulse release of ACh was greater than at high frequencies. The muscarinic agonist oxotremorine (up to 100 micrometer) did not inhibit ACh release although 100 micrometer oxotremorine did antagonize the ability of atropine to increase release. The effect of chronic exposure to morphine, both in vivo and in vitro, on the reactivity of muscarinic receptors mediating this increase was examined. Neither the control rate of ACh release nor the dose-response curve for atropine were altered by (a) an 8-day morphine injection schedule, and (b) exposure of the tissue to morphine in the bath for 90 min. The results of this study support the existence of a muscarinic feedback mechanism which controls ACh release from the myenteric plexus. Chronic exposure to morphine does not produce specific changes in the muscarinic receptor mediating this inhibition.


Purification of rabbit transcobalamin II by labile ligand affinity chromatography.

Rabbit transcobalamin II has been purified to homogeneity from serum containing 5-30 nmol unsaturated transcobalamin II. The method described consists of labile ligand affinity chromatography and G-200 Sephadex gel filtration. The recovery of pure protein was about 80%.


Calcium-linked changes in myocardial metabolism in the isolated perfused rat heart.

Rat hearts were perfused for 40 min with aerobic medium containing different concentrations of calcium (0-5 mM) and their abilities to take up and oxidize glucose, and to produce lactate and glycerol were examined in addition to measuring glycogen, lipids, cyclic AMP, and high energy phosphate stores. Increasing the concentration of calcium was found to decrease myocardial glycogen but increase glucose uptake, glucose oxidation, and lactate release. A decrease in myocardial triglycerides and an increase in free fatty acid contents as well as glycerol release without any changes in cholesterol and phospholipid contents were observed upon increasing the concentration of external calcium. In comparison with the hearts perfused with Ca2+-free medium, the levels of creatine phosphate and ATP were lower and that of ADP higher in hearts perfused with medium containing 5 mM calcium. No differences in AMP and cyclic AMP contents were seen among hearts perfused with different concentrations of calcium. The contractile activity initially increased upon increasing the concentration of calcium from 1.25 to 5 mM and then declined towards the control level. The hearts were unable to generate contractile force in the absence of calcium, whereas the contractile force decreased and then began to recover upon perfusing the hearts with 0.31 mM calcium. These results indicate that elevated levels of intracellular calcium stimulate glycogenolytic, glycolytic, and lipolytic processes in myocardium directly.


Improved cold tolerance and its mechanism in cold-acclimated rats by high fat diet feeding.

Cold tolerance and metabolic responses to cold were studied in cold-acclimated rats on high fat diet (CAHF). Cold tolerance at-5 degrees C was assessed by fall of colonic temperature of clipped rats after 18 h of fasting. Rate of fall in colonic temperature was greatest in warm-acclimated control rats (WAST), slowest in cold-acclimated rats on standard diet (CAST), and remained unchanged in CAHF during cold exposure for 240 min. Increment in blood free fatty acid (FFA) concentration 80 min after cold exposure was greatest in WAST, less in CAST, and least in CAHF. Blood glucose decreased similarly in WAST and CAST after cold exposure, while it remained unchanged in CAHF. Blood beta-hydroxybutyrate also increased similarly in WAST and CAST, while it did not change in CAHF. Nonshivering thermogenesis tested by noradrenaline was greatest in CAHF, followed by CAST and WAST. Shivering induced by cold exposure was less pronounced in CAST than in WAST and did not develop in CAHF; changes in colonic temperature were inversely related to the extent of shivering during cold exposure for 90 min. These results suggest that an integrating effect of cold and high fat diet could improve cold tolerance much more than cold acclimation itself, possibly through enhanced nonshivering thermogenesis caused by metabolic modifications such as increased lipid use and gluconeogenesis.


Reduced hyperglycemic action of glucagon in cold-acclimated rats, especially in venous drainage from brown adipose tissue.

Glucagon infusion at a rate of 2 microgram/min for 30 min into warm-acclimated rats induced a marked rise of glucose concentration in venous blood both in the external jugular vein and in Sulzer's vein from the interscapular brown adipose tissue. In cold-acclimated rats the increase in the concentration of glucose was significantly reduced in the former vein and abolished in the latter one. These results suggest an enhanced use of glucose in the brown adipose tissue in cold-acclimated animals under the influence of glucagon.


Substance P selectively blocks excitation of Renshaw cell by acetylcholine.

In cats, under Dial anaesthesia, Renshaw cells were excited by microiontophoretic applications of acetylcholine (ACh), aspartate, and glutamate. Substance P, in small doses (10-30 nA), selectively abolished the responses to ACh, leaving the discharges evoked by the amino acids unchanged or enhanced. Higher doses (greater than 50 nA) depressed all responses, but those evoked by amino acids went down last and recovered sooner. By contrast, neither synaptic responses to ventral root stimulation nor spontaneous discharges were affected by substance P, presumably owing to the high efficacy of synaptic transmission and the presence of diffusion barriers around junctional sites.


Actions of microiontophoretically applied ibotenate on cat spinal interneurones.

Microiontophoretic applications of ibotenate, an amino acid analogue of glutamate, evoked biphasic responses from single dorsal horn interneurones of the cat spinal cord, i.e., an initial increase in the firing rate followed by a sustained depression of spontaneous firing. A reduced cell sensitivity to excitatory amino acids or peripheral field stimulation was also found during the ibotenate-induced depression. These effects were not produced by glutamate, quisqualate, or kainate, although occasional transient reductions of spontaneous cell firing were observed after application of glutamate. It is suggested that ibotenate might act on inhibitory as well as excitatory receptors of cat spinal interneurons.


Antagonism of conditioned salivation in conscious dogs by antihypertensive drugs.

Methyldopate (methyldopa (ethyl ester)), carbidopa, clonidine, and ST-91 were evaluated for their effects on conditioned salivation in unanesthetized dogs. Clonidine produced dose-dependent inhibition of salivation 20 min after an intravenous injection. At equivalent and larger doses, ST-91, a clonidine analog which does not penetrate the blood-brain barrier, was ineffective  in inhibiting conditioned salivation, suggesting that central rather than peripheral mechanisms are involved in clonidine-induced inhibition of salivation. Methyldopate also produced a dose-dependent inhibition of salivation in dogs. The mechanism involved in methyldopa-induced inhibition of salivation may involve both central and peripheral mechanisms because carbidopa, an inhibitor (like methyldopa) of peripheral aromatic decarboxylase (EC 4.1.1.28), significantly inhibited salivation.


Simulation of oviductal ovum transport.

The present note describes a Monte Carlo simulation of ovum transport in the rabbit oviduct. Ova execute a random walk through a one-dimensional oviduct and the jump probabilities at each point are obtained from in vitro electrical recordings of smooth muscle activity. Simulated transport are compared with experimental findings at 18 and 66-68 h after human chorionic gonadotropin injection.


Myocardial infarction, hyperthyroidism and normal coronary arteries: report of two cases.

Myocardial infarction is uncommon in persons with hyperthyroidism and also uncommon in the absence of demonstrable coronary artery disease. Cardiac catheterization and selective coronary angiography were performed in two men following apparent myocardial infarctions. Both patients were 33 years of age, thyrotoxic and angiographically free of coronary artery abnormalities.


Hypertension in a family practice.

The performance of an urban Canadian family practice in the detection, evaluation, treatment, control and follow-up of hypertension for a 10-year period 1965-74 was reviewed. Vigorous case-finding and treatment were followed by good control of hypertension in 67% of cases and a significant decrease in mortality from stroke and congestive heart failure. It is strongly suggested that the proper location for dealing with hypertension is the primary-care practice and that the general practitioner deserves greater assistance from clinical specialists, health foundations and ministries of health in attacking this problem.


Athletic aids: fact or fiction?

A major problem facing physicians involved in the daily care of amateur athletes in international competition is that of so-called doping. While there are many substances used that might be considered ineffectual or physiologic, the two main categories of substances considered as doping agents are stimulants and anabolic steroids. No substance is as yet known that will improve an athlete's performance. Often such substances are taken in error rather than in a misguided attempt to improve one's ability. These substances can be dangerous and, because of this, doping rules were established basically to protect the athlete. Anabolic steroids are particularly dangerous; they usually are taken by those engaged in lifting or throwing sports in an attempt to improve performance by increasing muscle bulk. There is as yet no scientific proof that performance is improved. Dope testing for stimulants should be carried out in a quantitative rather than qualitative manner so that the athlete who has taken a small amount of a so-called stimulant (such as an asthma or common cold preparation) would not be excluded from competition. Rigid testing for anabolic steroids should be continued.


Experience of the Canadian medical team at the 21st Olympiad.

The Canadian medical team at the 21st Olympiad--11 therapists, 8 physicians and 2 nurses--was larger than necessary, partly because the Canadian athletes were not affected by the stresses of competition in a foreign land and partly because many used the medical facilities established by le comité organisateur des Jeux olympiques. There were few injuries of a serious nature or of lasting consequence among the Canadian athletes; only 10 of the 475 athletes were withdrawn from competition on the advice of the medical staff. On the average the athletes had two visits to a physician and five treatments by a therapist. Track and field competitors accounted for the largest number of visits to the therapy clinic, and musculoskeletal problems were the most frequent type. Most of the treatment consisted of local supportive measures.


Hemoglobin values: comparative survey of the 1976 Canadian Olympic team.

In view of the role of hemoglobin in oxygen transport, the hemoglobin concentration in whole blood may indicate readiness for maximal physical performance. Hemoglobin concentrations were determined in members of the 1976 Canadian Olympic team and compared with those of the 1975 Canadian general population and with published data for the 1968 Australian and Dutch Olympic teams. The mean hemoglobin concentrations of the 123 male and 64 female Canadian Olympic athletes were 14.7 +/- 1.0 and 12.9 +/- 0.7 g/dL, respectively. Both male and female Canadian Olympic athletes had significantly lower (P less than 0.01) values than the other three groups. The suboptimal hemoglobin concentrations may be related to inadequate dietary intake of protein and iron.


Epiphyseal injuries in the growing athlete.

The epiphyses and epiphyseal plates are vital structures in the bone development of the growing athlete. The epiphyseal plate is two to five times weaker than the surrounding fibrous tissue in children and adolescents; consequently a force causing a ligamentous tear in adults is likely to cause an epiphyseal plate injury in growing children. Two types of epiphyseal injury that are common in the growing athlete are (a) separation across the epiphyseal plate, which is usually produced by a direct blow to the joint area or by a strong muscular contraction, and (b) traumatic epiphysitis, the more common of the two, which is usually caused by strong, repetitive contraction of a muscle attached to a traction epiphysis. Each epiphyseal site has specific anatomic features and the forces causing injury differ slightly at each site. An improperly treated separation of an intra-articular pressure epiphysis can have a disastrous effect on the proper functioning of the normally well-fitted articulation of bone ends in the joint. Consequently, proper diagnosis and treatment are essential. Traumatic epiphysitis can result in chronic inflammation or fragmentation, or both, if the condition is not arrested. Therefore the athlete must discontinue the activities that are causing the trauma until the inflammation is completely arrested. Absolute rest may even be required.


Physiotherapeutic treatment of athletic injuries to the muscle--tendon complex of the leg.

An overview is presented of the most common soft-tissue injuries of the leg in athletes. A simple classification is made on the basis of cause, location of the injury and severity. These injuries can be classified into direct and indirect types. Direct injuries, which are usually the result of one episode of trauma, can be classified further into three grades of severity. Treatment is based on the severity of the injury and its location in the muscle--tendon complex. Indirect muscle--tendon injuries are the result of repetitive subacute microtrauma to the muscle--tendon complex or injury to the structures associated with muscle function (bursa, tendon sheath or fascia). Appropriate treatment regimens are suggested.


[Major hockey injuries: a three-year study].

In a major junior hockey team there were 238 injuries in 257 games during the three seasons of 1973-76 (mean number of injuries per game, 0.926). Incapacity from these injuries resulted in a loss of 345 practices and 299 games (mean number per injury, 1.45 and 1.26, respectively). The site of the game, whether at home or out of town, and the period in which the injury occurred did not seem to be important. Risk of injury seemed to be greatest in the defensive zone. Forwards were the most often injured, their injuries accounting for 45.8% of the total; defensive players were next most often hurt (31.9%). The age of the injured players ranged from 16 to 19 years, those 19 years old predominating (42.0%).There were 91 injuries of the lower limb (38.2% of the total), the knee being the site most frequently injured (31 injuries; 34.1% of the 91), and 74 injuries of the upper limb, the shoulder being the site most frequently injured (25 injuries; 33.8% of the 74). The main causes of injury were a blow by the puck (frequency, 21.0%), a check (18.5%), a blow by a stick (14.7%) and a fight (13.4%).


The general practitioner as sports physician.

General practitioners must become more knowledgeable about sports medicine in order both to treat the injured athlete and to provide better rehabilitative treatment and advice on fitness and exercise to other patients. Close involvement with young amateur athletes also helps to keep the older physician "in tune" with the younger generation. Finances remain a major problem for amateur sporting events and sports medicine groups, as well as for the individual physician volunteering his time.


Diagnostic irradiation of women during the reproductive period.

The date of onset of the last menstrual period should be given on radiographic requisitions for all women of reproductive age. Every effort should be made to avoid unnecessary irradiation of any woman who might be pregnant. Radiation damage in the first 2 weeks of pregnancy, however, should be "all or none", resulting in either a miscarriage or a normal child. Diagnostic radiology procedures are not indications for therapeutic abortion. Ultrasound has now replaced ionizing radiation in most examinations of the fetus and placenta. Pelvimetry should be done only when the decision to do a cesarean section hinges on precise knowledge of measurements of the bony pelvis. On the rare occasion when a radiograph of the fetus is necessary the woman should be prone for the examination. All such examinations are best ordered after consultation with a radiologist. Radiography of distant areas with the beam directed away from the woman's abdomen can be done without concern at any stage of pregnancy.


The effect of photon irradiation on blood-brain barrier permeability to methotrexate in mice.

Methotrexate was administered by intraperitoneal injection (100 mg/kg) to unirradiated mice, and to mice receiving varying doses of cranial irradiation. The animals were sacrificed 24 hours after injection, and methotrexate assays were performed on brain tissue. No methotrexate was detected in the brains of the unirradiated animals. Detectable levels of methotrexate were present after 2000 rad cranial irradiation, but not after 500 rad, 1000 rad, or 1500 rad. The implications of these findings are discussed.


Pathoradiologic correlation of pulmonary candidiasis in immunosuppressed patients.

The diagnosis of pulmonary candidiasis can only be made with certainty when tissue invasion by the organism is demonstrated histologically. In order to ascertain whether characteristic radiographic patterns are seen in patients with pulmonary candidiasis, antemortem radiographic abnormalities were correlated with autopsy findings in 25 immunosuppressed patients who had histoinvasive pulmonary candidiasis. Pathological analysis enabled division of patients by route of infection into hematogenous and endobronchial groups, characterized by disseminated nodules and patchy bronchopneumonia, respectively. However, no specific radiographic patterns emerged in either patient group due to the small size of lesions and the high frequency of other pulmonary infections, edema, and hemorrhage. Since the radiographic patterns described for other opportunistic fungi do not appear to apply to this organism, a decision to institute antifungal therapy should not await evolution of radiographic changes.


Antibody-dependent cell-mediated cytotoxicity in treated and nontreated cancer patients.

Antibody-dependent cell-mediated cytotoxicity (ADCC) exhibited by peripheral blood leukocytes was used as a criterion for assessing immune competence of groups of noncancerous individuals and of treated and untreated cancer patients. The results show that, as a group, leukocytes of nontreated cancer patients exhibited significantly lower ADCC than that exhibited by leukocytes of noncancerous individuals. However, the ADCC of leukocytes from cancer patients under treatment approximated that of normals. Thus, using ADCC as criterion, the results indicate that as a group, cancer patients under treatment tend to exhibit restored immune competence.


High-dose rate intracavitary radiation therapy for advanced head and neck tumors.

Fifty-seven treatments were performed on 27 head and neck pateints with recurrent or residual tumors on a high dose rate, remote controlled afterloading unit: There were 16 cases of maxillary sinus tumors, 6 epipharynx, 3 alveolar ridge, 1 hard palate and 1 floor of mouth. All patients have been followed up more than 2 years except one. Five patients are alive without local recurrence for more than 2 years. In 13 patients local tumors disappeared once and normal mucosa covered the tumor sites. Two patients died from local bleeding. In six patients this method failed to destroy tumors. Our prupose was palliative local control: therefore, in two-thirds of cases treated we were successful with this easy method of nonfractionated acute intracavitary radiation. This result is favorable, considering that all cases treated here were failures following full dose external radiation, although the treatment had to be repeated more than twice in 15 cases. Relief of symptoms is excellent when this therapy is used.


Treatment of lung cancer by radiotherapy, chemotherapy, and methanol extraction residue of BCG (MER): clinical and immunological studies.

Fifty-one patients with advanced lung cancer were divided at random into two groups. One group of 29 patients received the methanol extraction residue (MER) of Bacille-Calmette-Guerin (BCG) in addition to radiotherapy and/or chemotherapy. The other group of 22 patients was treated by radiotherapy and/or chemotherapy alone. The immune status of the patients was evaluated by skin tests to three recall antigens and KLH and by in vitro lymphocyte stimulation to PHA and three recall antigens. The immune status of both groups was similar before and after conventional treatment. The cutaneous reactivity, as well as the in vitro lymphocyte reactivity, became stronger in the MER-treated group, as compared with the control group. The MER-treated patients had less distant metastases. In a comparable clinical stage the survival in the MER treated group was slightly but not significantly better. This study has shown that MER stimulates the immune response, can be well tolerated and has few side effects. Therefore, MER treatment of patients with minimal tumor load can ethically be done with hope of obtaining better results.


Lymphopenia caused by cranial irradiation in children receiving craniospinal radiotherapy.

The peripheral blood changes were studied in 67 children who received craniospinal irradiation for posterior fossa tumors. At the completion of a cranial dose of about 3500 rad to the whole brain port, the lymphocytes were reduced to 858/mm3 rom 3084/mm3 preoperatively. The counts of the remaining leukocytes stayed at a level somewhat higher than preoperatively; the eosinophils rose to 288/mm3 from 125/mm3. With the initiation of the spinal field irradiation, which included a large proportion of the total bone marrow, the numbers of all the leukocytes decreased rapidly; the observed leukopenia was mainly secondary to neutropenia. A mechanism that was operating to restore the number of leukocytes became manifest immediately after the completion of radiotherapy, though the number of lymphocytes had not been totally restored to the preoperative level 6 years later. Irradiation of the lymphocytes that circulate through the vascular bed can explain the lymphopenia observed during cranial radiotherapy. Mild leukopenia observed in patients receiving radiotherapy through a relatively small port may be secondary to lymphopenia, and this does not necessarily indicate impaired bone marrow reserves.


A light and electron microscopic study of a hemangiopericytoma of the prostate with local extension.

A case of primary hemangiopericytoma of the prostate is reported. The patient presented with obstructive uropathy and was diagnosed as "benign prostatic hypertrophy." A transurethral resection was done and was diagnosed as "cellular leiomyoma." Obstructive symptoms recurred and skin and pubic bone involvement appeared 2 months later. Light and electron microscopy of the repeat transurethral resection and biopsy of the perineal mass confirmed the diagnosis of hemangiopericytoma of the prostate.


Chromosomes and causation of human cancer and leukemia. XXII. Karyotypic changes in malignant melanoma.

Detailed karyotypic analysis with G- and C-banding has been performed on cells of four malignant melanomas. The modal number in two cases was in the hypodiploid range, the chromosome numbers varying from 39 to 43. These two tumors had 5 to 13 marker chromosomes. The other two tumors were in the polyploid range, with modal numbers of 63 to 157 chromosomes. The cells had a minimum of 11 and a maximum of 40 marker chromosomes. Chromosome no. 1 was more frequently involved in aberrations than any other chromosome. The most common breakpoints on this chromosome were 1q21, 1q25 and 1q32. Frequent breakpoints were also noticed in the centromeric region in various chromosomes. In chromosome no. 1, however, the centromeric area does not seem to be involved. The more common breakpoints on the various chromosomes were 1q21, 1q25, 1q32, 5p13, 9q13, 11q23, 12q13. No common markers were noticed among these four cases of melanoma, but are noticed in unrelated tumors.


Leukocyte alkaline phosphatase activity in patients with malignant disease.

One hundred patients with malignant disease were screened for leukocyte alkaline phosphate (LAP) activity. The new observation made was that patients with malignant disease demonstrate significantly lower levels of LAP than in normal controls. The low LAP activity is present irrespective of primary tumor category, "activity" of disease, or type of therapy. The pattern of metastases may influence LAP activity, in that patients with liver metastases tended to have higher LAP levels. In spite of low baseline LAP levels in patients with malignant disease, the development of secondary infection is associated with elevated LAP levels.


Flow microfluorometry and transrectal fine-needle biopsy in the classification of human prostatic carcinoma.

Flow microfluorometry (FMF) and transrectal fine-needle biopsy were used for obtaining DNA histograms from 50 patients suffering from various prostatic lesions. Based on the cytomorphological pattern, the material was classified as benign prostatic hyperplasia (29 cases), suspected carcinoma (1 case), well-differentiated carcinoma (6 cases), moderately differentiated carcinoma (12 cases) and poorly differentiated carcinoma (2 cases). The biopsy material was prepared for FMF analysis according to a new detergent technique. It was observed that increasing anaplasia paralleled an increasing occurrence of cell populations in the tetraploid and octoploid DNA region. According to the DNA histograms the moderately differentiated carcinomas could be divided into two groups: one with no or a few tetraploid cells (similar to the well-differentiated carcinomas), and another with a high percentage of tetraploid and octoploid cells (similar to the poorly differentiated carcinomas). FMF analysis in combination with fine-needle biopsy is therefore proposed as a valuable addition to the cytomorphological classification of human prostatic carcinoma.


Clinicopathologic features of unsuspected regional lymph node metastases in prostatic adenocarcinoma.

Histologic features of the primary tumor and their effects on the incidence of unsuspected pelvic lymph node metastases have been studied in a prospective series of 62 patients with clinical stage B1, B2, or C prostatic adenocarcinoma who underwent pelvic lymph node removal. Twenty-one patients (34%) proved to have unsuspected nodal metastases. Differentiation of the primary tumor and extent of involvement of the prostate by carcinoma were the only two features that correlated significantly with the incidence of pelvic nodal metastases, 56% of those with undifferentiated tumors had metastases. Thirty-one of these patients underwent total prostatectomy; an average of only 46% of the sections of prostate contained tumor in the patients without metastases but an average of 65% of the sections were involved by carcinoma in those patients who did have nodal metastases.


Study on the ratio of lymphocytes to epithelial cells in thymoma.

In order to quantify the lymphocyte to epithelial cell ratio (L/E ratio of the thymoma, actual counting was performed. The L/E ratio was investigated in 25 specimens of 22 cases (22 initial tumors and 3 recurrent tumors). L/E ratios ranged from 0.27 to 4.10, and the mean value was 1.93 +/- 0.21. The mean L/E ratio of histologically malignant group was lower than that of the benign group. In the three recurrent cases, L/E ratios of the recurrent tumor decreased in all cases. It was concluded that the epithelial element increases with the adva


Breast cancer incidence according to weight and height in two cities of the Netherlands and in Aichi prefecture, Japan.

A study was made in the cities of Rotterdam and The Hague, the Netherlands, and in Aichi prefecture, Japan, to assess the effect of weight and height (and their combinations) on the age-specific incidence of breast cancer. It is based on a comparison between 1006 cases of breast cancer and 4201 women from the general population, 33-69 years old. The results suggest that about one-half of the differences in incidence between the regions in Holland and Japan can be attributed to differences in body weight and height. In breast cancer patients in Rotterdam and The Hague those with metastases in axillary involvement. A hormonal factor related to body weight and/or height might be responsible for the increased incidence and the more rapid course of breast cancer in women with a large body mass.


Non-epithelial tumors of the nasal cavity, paranasal sinuses and nasopharynx: a clinicopathologyic study. VIII. Adipose tissue tumors (lipoma and liposarcoma).

In a study of 256 non-epithelial neoplasms involving the nasal cavity, paranasal sinuses and nasopharynx, only two lesions were classified as adipose tissue tumors (one lipoma and one liposarcoma). The lipoma was found incidentally when tissue removed from the maxillary sinus was studied histologically, the patient having been treated with a Caldwell-Luc procedure for maxillary sinusitis. The liposarcoma produced a large mass involving the nasal cavity, maxillary sinus, ethmoid area, hard palate and maxillary, temporal and sphenoid bones. The tumor extended into the cranial cavity and eventually led to the patient's death. The problems involved in histologically differentiating liposarcomas from other lesions are discussed. Even though adipose tissue tumors are among the most common soft tissue neoplasms, these lesions rarely occur in the nasal cavity, paranasal sinuses and nasopharynx.


Serum vitamin B12 and transcobalamin abnormalities in patients with cancer.

One hundred and thirty-nine patients with non-hematologic malignancy were studied to define the incidence of vitamin B12-related abnormalities and correlate them with clinical findings. Based on vitamin B12-binding patterns, the following relatively distinct groups were defined: (A) 50% had normal results; (B) 6% had very high transcobalamin (TC) I and vitamin B12 levels as reported in isolated instances previously: most had hepatic metastases and early death, and all had definite metastatic disease; (C) 11% had high vitamin B12 levels with little or no unsaturated TC I elevation: most also had hepatic and other metastases and early death; (D) 23% had high vitamin B12-binding capacity with normal TC I and vitamin B12 levels: there were no distinguishing features for this group other than an increased proportion of black patients; and (E)  10%  had low vitamin B12 levels, in many cases not associated with vitamin B12 deficiency or other known causes of low serum levels. Thus, high serum vitamin B12 level, with or without unsaturated TC I elevation, usually implies a poor prognosis in a patient with cancer. However, while most such patients have hepatic and other metastases, hepatic involvement was not universal nor did most patients with hepatic disease have high vitamin B12 levels. High serum TC I thus is not always due to increased granulocytic proliferation or to hepatic tumor, and alternative mechanisms for TC I accumulation should be sought.


Transthoracic needle biopsy of mediastinal and hilar lesions.

Fifty patients, from 5 weeks to 7) years of age, were subjected to transthoracic thin needle biopsy of their mediastinal or hilar masses from May 1975 to May 1976. The material aspirated was satisfactory for cytological examination in 41 patients (82%). The cytological diagnosis could be made in 36 patients (72%) and could be confirmed by histological examination in 12 patients, and by the clinical course of the disease in 16 patients, while 7 patients are lost to follow-up. A false negative diagnosis was probably made in one patient. The complication rate was low, mainly pneumothorax (in eight patients) and hemoptysis (in six patients) of little clinical significance. The main drawback of the method seems to be its inability to provide enough material for reliable diagnosis of benign lesions.


An experimental study of mummification pertinent to the antiquity of cancer.

The relatively recent description in scientific literature of many types of cancer suggests their infrequency until the relatively recent past, a view supported by the paucity of diagnoses of malignancies in ancient remains. While overall life span was short in antiquity, many individuals did live to the "cancer age," as there is ample evidence of a variety of degenerative disorders. It has been suggested that tumors are not well enough preserved for diagnosis, and tumors experimentally mummified and rehydrated were evaluated as to their preservation. It was found that cancers were actually better preserved than normal tissues. The absence of tumors in ancient tissues must be considered a reflection of a markedly lower incidence than in the modern population of the Lnited States, in which cancer accounts for approximately 17% of all deaths. It is suggested that this increase in cancer is due to factors in the modern industrialized environment.


Selection of chemotherapy for metastatic mammary cancer by effect on cesium-131 uptake.

Cesium-131 was administered intravenously to 39 patients with superficial metastases of mammary carcinoma and the concentration in tumor was compared with that in normal tissue by application of a detector in vivo, before and after 1 to 5 days of chemotherapy with cyclophosphamide (CP), 5-fluorouracil (FU), or diethylstilbestrol. A change of the cesium concentration ratio (tumor/normal tissue) greater than 15% after brief treatment correctly predicted the therapeutic effect after 1 to 39 months on the tumors that were tested in 30 of 33 tests. No reliable correlation could be made in the remaining 21 tests in which the change of ratio was less than 15%. The concentration of cesium-131 in the skin, fat, and skeletal muscle of mice was not appreciably altered by treatment for 5 days with CP or FU.


Adriamycin, 1,3-bis (2-chloroethyl)-1-nitrosourea (BCNU, NSC 409962) and cyclophosphamide therapy of drug-resistant metastatic breast carcinoma.

Thirty-two evaluable patients with metastatic carcinoma of the breast received chemotherapy consisting of BCNU plus cyclophosphamide followed in 18 hours by Adriamycin. Treatments were repeated every 4 weeks. Complete or partial responses were observed in 14 patients (43.7%) and in 12 of 27 drug-resistant patients (44.4%). An additional 26% of patients had objective improvement, for an overall objective response rate of 70.4% in drug-resistant patients. Skin, lymph node, and soft tissue metastases more frequently responded to therapy, while hepatic, peritoneal, and osseous metastases responded with an intermediate frequency. Pulmonary, pleural, and central nervous system metastases did not respond to therapy. The median duration of complete and partial responses was 6.8 months, and the median survival of these patients was 9.6 months. Overall, the median survival of all patients in this study was 6.5 months. The dose-limiting toxicity was myelosuppression, particularly granulocytopenia. Congestive heart failure and stomatitis were rare. This combination of drugs is a reasonably well-tolerated regimen for treating advanced breast carcinoma in an ambulatory setting, and produces a high rate of objective antitumor response of moderate duration.