[Surgical approach of retroperitoneal neuroblastoma in infancy (author's transl)].

Rarely retroperitoneal neuroblastoma is a well localized, encapsulated tumor, like it my appear somewhere else, as in the pelvic floor or mediastinum. Even with the same histological findings they are different from de point of view of invasion. Therefore the surgical approach should be different in each case. This is our main conclusion after de study performed in 48 cases operated upon in the last 8 years. We have tried three kinds of operations. 1. The so called curative, total resections. Performing a surgical ablation of the tumor and the organs macroscopically involved, either prior or after radiotherapy or quimiotherapy. At any risk, even of life in the early postoperative period. This kind of surgery has been undertaken in 34 cases with an early mortality of 9. The main aim of this technique is to divide the tumor in two across the supraaortic line well below the renal vessels and up to the diaphragm. In 18 cases the homolateral kidney was resected with the suprarrenal gland. Spleen and pancreas in 5 cases, colon in 4, and the inferior vena cava in 3. The survivors over 2 years are 19 cases. 2. Paliative resection, taking out the main tumor only, has been achieved in 4 cases, with the highest mortality because postoperative hemorrhage. We believed is a dangerous procedure. None of these children survived more than one year. 3. Biopsy and surgical macroscopic diagnosis of invasion plus placing clips at their margin has been carried out in 12 occasions. This had naturally the best early postoperative but not in the long run, none survived more than 2 years. A second look up with resection was undertaken in 3 cases with mortality of one. Most surgeons are puzzled when dealing with retroperitoneal neuroblastoma and some how disappointed before undertaking a long, difficult and highly risk operation, but in many instances still is about the only hope they may have.


[Craneopharyngioma in children (author's transl)].

Clinical findings in the initial and developed stages were studied in 33 cases of craneopharyngiomas in children under sixteen. A predominance of intracraneal hypertension symptoms and sight defects over endocrine symptoms was discovered; the latter appearing later on or only being detected after exhaustive studies.


[Thyroid papillary adenocarcinoma (author's transl)].

A case of papillary adenocarcinoma of thyroid is reported in a 13 years old boy. The clinical and pathological features are discussed and the pertinent literature is reviewed.


[Thyroid cancer in childhood (author's transl)].

The authors present three cases of thyroid cancer in the child with comments on the etiologic, clinical and therapeutic aspects of this rare disease. The authors insist on the danger of local radiotherapy and on the need to suspect thyroid cancer in cases of persistent laterocervical adenopathies whose diagnosis can only be confirmed by means of a biopsy. It is of note that the illness took a favourable course and various therapeutic criteria are discussed.


[Local treatment of angiomas with corticoids (author's transl)].

The angiomas studied at the Clinica Infantil "La Fe" in a four and a half years period are reviewed. The different therapeutic approaches are considered. Thirteen cases selected at random have been treated with local injections of steroids, with a 84% satisfactory results. The technique seems to be simple and without complications. It is recommended in the management of the parotideal, small size, subcutaneous and those angiomas in which the therapy could be followed by sequelae and in those where other therapy has failed.


[Correlation between scanning,  Radiological images and clinical findings in tumoral processes (author'a transl)].

During last years bone scanning has shown a great accuracy in the diagnosis of primitive bone tumors and bone metastasis in adult patients. With the use of short lived tracers this technique has also been used in Pediatrics. The authors present their experience in the evaluation of bone scanning in 31 patients with different tumoral processes doing a correlation between scanning, radiological images and clinical findings. The technique is presented for discussion showing its possibilities, limitations and future of its application in Pediatrics.


[Hemihepatectomy with I.V.C. by-pass. Experience of 11 cases (author's transl)].

22 malignant tumors of the liver in children have been treated so far at the "La Paz" Childrens Hospital. 11 cases underwent hemihepatectomy with intracaval by-pass. This technique is described and its advantages underlined.


[Treatment of one case of severe laryngeal papillomatosis (author's transl)].

One observation of severe laryngeal papillomatosis is reported. After diagnosis by biopsy and tracheostomy the patient was treated with bleomycin and thio-tepa associated with punch extirpation of residual papillomata following Kleinsasser. Results at two and half years were excellent.


[Isolation and intestinal sterilization in prevention of infection in patients with malignant diseases (author's transl)].

Results obtained by isolation and intestinal sterilization in prevention of infections in 42 patients with malignant diseases are shown. A substantial decrease of infection is observed, as compared with a control group of 33 patients with similar disease, treated in normal hospital conditions. The problem of intestinal sterilization is discussed and literature on this subject revised.


[Our experience in pediatric oncology (author's transl)].

An initial statistical study on the incidence of oncologic pathology during infancy carried out in the Pediatric Department of the University of La Laguna, is presented. They study includes 33 tumors which have been collected over a period of 3.5 years.


[Tumor committee and pediatric oncology. Importance for management of infantile neoplasias (author's transl)].

The organization for the diagnosis, treatment and follow-up of the children with malignancies at the Hospital Infantil "Virgen del Rocio", are described. There is a Tumor Committee made up by two pediatrics oncologist, two pediatrics surgeons, one pathologist, one radiotherapist, one pediatric psiquiatrist and one social worker. The Oncology Section of the Hospital is made up by one pediatric oncologist and one registerers nurse (A.T.S.) and several clinical assistants.


[Psychological approach in pediatric oncology (author's transl)].

An attempt to describe the procedures with fatally ill children, from a psychotherapeutic point of view is made. Special attention is paid to selecting nursing staff assigned to those children, requiring highly human and professional qualifications. Children with mild or severe psychopathological reactions, and/or their parents, are referred to Psychiatric Services for individual and/or family therapy. At the same time, group therapy is carried with parents. Finally, parents are followed in order to prevent unwanted psychopathological reactions after death of the child.


Ten-year experience with childhood rhabdomyosarcoma.

The ten-year (1965-1975) experience of the Pediatric Tumor Clinic with 14 cases of proven CRM was reviewed. Seven cases seen prior to 1970 acted as control. They were treated by surgery and X--ray therapy alone (one received one chemotherapeutic agent). Seven other cases seen after 1970 adhered to a strict protocol of therapy. After surgery (resection or biopsy), roentgenological and hematological survey for diagnosis and staging, they received curative radiotherapy locally in doses of 5,200 r to 6,000 r. Concomitantly a regimen of multiple chemotherapeutic agents (vincristine, dactinomycin and cyclophosphamide) was administered according to the protocol followed at the M.D. Anderson Hospital, Houston. Only one of the seven controls is alive and free of disease for 9 years. Only one of the seven cases who adhered to the protocol died. The other six are alive and free of disease for periods of one to two and a half years (one has a 4 months follow-up so far). One of the six cases presenting with a solitary pulmonary metastasis had a lobectomy 2 and a half years after start of treatment, as no new metastasis developed. Another, presenting with a local recurrence after excision is alive and free of disease 2 years after the star of treatment with the protocol. The results of treatment of CRM with the protocol adopted show a significant improvement in terms of local recurrences, distant metastasis and survival rates.


Teratomas in childhood.

Of 109 teratomas in children 86 were benign and 23 malignant. Sacro-coccygeal and pelvic teratomas predominated 52 cases, and these fell into three groups, post-sacral, dumb bell and pre-sacral. The 34 purely posterior tumours were always congenital and benign whilst the incidence of malignancy in dum bell and pre-sacral teratomas increased as the tumour became more internal. Other sites affected in order of frequency were: the gonads, head and neck, retroperitoneal anterior mediastinum and the central nervous system. Malignant teratomas were carcinomas usually containing glandular, capillary and clear cell areas, and metastases were similar. Immature tissues in benign teratomas were usually neural or connective tissue. They did not give rise to neuroblastomas or sarcomas and did not indicate a worse prognosis. Only two originally benign teratomas later developed malignancy.


Medulloblastoma of the cerebellum.

On the base of 77 medulloblastomas of the cerebellum, it is a point out the actual management of children with medulloblastoma which can be summed up as a combination of surgery to relieve pressure and remove as much of the tumor as possible, para-operative vincristine, radical treatment of the whole C.N.S. by radiotherapy followed by maintenance chemotherapy of B.C.N.U. and vincristine.


Investigations of red cell glyoxalase in recombinant families.

The polymorphism of the red cell glyoxalase (GLO), which has recently been found to be linked with the major histocompatibility complex (HLA) in man, was investigated in a number of selected families showing various recombinations between HLA-A, HLA-B and the third locus of the phosphoglucomutase (PGM3). In two families with a recombination between HLA-A and HLA-B, the GLO allele travels with the HLA-B locus fragment of the chromosome, indicating that GLO is located on the side of the HLA-B locus. In other families, recombinations occurred between HLA-A and B on one side and GLO and PGM3 on the other side, demonstrating that GLO and PGM3 are located on the same side of HLA. Other recombinations separated PGM3 from GLO so that it can be assumed that GLO is located between HLA-B and PGM3. Thus the immunogenetic linkage group on human chromosome C6 has been increased by yet another outside marker gene to include now the following genes in this order: HLA-A--HLA-C--HLA-B--Bf--HLA-D--GLO--PGM3.


[Importance of echocardiography in aortic valve disorders].

It would seem that, despite certain limitations, echocardiography may be considered to be an important method of investigation in the diagnosis and prognosis of aortic valve disease. Quantitative measurements may possible study of the progression of the lesions. Nevertheless, echocardiography only appears to be a simple technique and emphasis should be placed on the importance of a complete investigation as well as the quality of the recordings to be studied.


[Anatomo-pathologic forms of lymphoid and lymphoreticular fibrosis of the bone marrow].

The development, within the bone marrow, of reticulo-fibrosis with a lymphoid organ structure forms part of a pathological model common to several lympho- and reticulo-proliferative syndromes. Various cytological types develop within this reticulo-fibrous framework: lymphocytes, lymphoblasts, plasmocytes, "hairy cells" and histiocytes. This cytological variety has led to different names: leukaemic reticulo-endotheliosis, lymphoid myelofibrosis, histio-lymphocytosis, malignant histiocytosis, etc. Similar cell type sequence is seen in non-Hodgkins lymphomas, with the same problems of parent and daughter cells. In fact the architectural metaplasia of the bone marrow prevails over the cellular metaplasia in the definition of the single clinical, haematological nature and course of these syndromes which have been too widely dissociated by classical haematology.


[The role and functions of the lung in equilibrium of the internal milieu. Protein metabolism and enzyme systems].

The different anatomical zones of the lung show a high degree of variation in metabolic function, involving many protein molecules and complex enzyme systems. Recent data in the literature concerning such activity are described with respect to bradykinin, fibrinolysis, haemostasis, angiotensin, serotonin, catecholamines, prostaglandins, vaso-active amines, the protease-antiprotease system and benzopyrene-hydroxylase.


[Insufficiency of secretion from the exocrine pancreas in infants (excluding mucoviscidosis) Diagnosis and consequences].

The diagnosis of insufficiency of exocrine pancreatic secretion was made in two infants after demonstration of a marked decrease in the flow rate of enzyme secretions during the duodenal infusion of milk and after the IV injection of C.C.K.-P.Z. The two infants had a normal sweat test. One had pancreatic lipomatosis with neuropaenia, whilst the other had pancreatic deficiency which did not fall into the context of Shwachman's syndrome. This study suggests that the absence of exocrine pancreatic secretion is accompanied by multiple abnormalitites : decreased absorption of fats and vitamin B12 and, it would appear, variations in certain activities of the jejunal mucosa and decreased insulin stimulation from the intestine. Such a situation reflects the complexity of the relations established between the organs participating in the processes of absorption and digestion.


[A radioisotope test of muscular function (skeletal)].

A new radioisotopic method measuring the alterations in local blood volume of a muscle before, during and after exercise would seem to make possible the detection of frankly pathological muscular irrigation. The latter is characterised by a marked reduction in blood volume during effort, with or without slight secondary hyperhaemia. Given the correlation between flow and volume, the state of the blood flow may be deduced, and probably to follow the spontaneous progression of progress with treatment of the vascular problem and to assess its prognosis.


["Analysis of fate" in psychiatry and psychotherapy. II. Correlations withe the level of general psychopathology].

We demonstrated in a group of 166 psychiatric patients, with disorders of schizophrenic and cyclothymic circle and with neuroses too, significant relations between the results of the projection test of Szondi and between the greatness of total psychopathology, evaluated by means of the Minnesota Multiphasic Inquiry (M.M.P.I.). We could ascertain, that the patients with the higher level of total psychopathology (evaluated by means of M.M.P.I.) have also a greater number of abnormal results according to the projection test of Szondi. At these patients we saw significantly more "valve groups", which witness to the irresolution in the instinctive motivations of behaviour. At these patients we could ascertain further the greater number of those personalities, which according to the projection test of Szondi suffered from a lack of breaking and self-critical elements in their behaviour. Subjects with heightened values of M.M.P.I. have significantly more results with abnormal relations of masculinity and of feminity according to the sexual index of Szondi test. The choices and the selection from the set of 48 fixed photographies, which the patient realises at the Szondi test in teen repeated sessions, form so a significant relation not only to the psychiatric diagnoses, as was ascertained in the first part of this work, but also to the height of total psychopathology, evaluated by means of the M.M.P.I. The familial subconsciousness influences so significantly the consciousness of personality and can participate substantially in the development of psychopathologic symptoms.


[Psychiatric aspects of modern drug addiction].

The author did beforehand a brief historical survey of drug usage, going throught the concepts of what might be called classic drug addiction, until the present stage of the phenomena of what is known as contemporary drug addiction was reached. Accepting the clinical reality of psychiatric accidents, as presented by the classic psychiatric nosological classification as a fact, the author points out the possibility for establishing a relation between the misuse of toxicomanogenic substances and the frequently pre-morbid personality of the user.


[Nitrosamines. Review].

Nitrosamines are an extremely carcinogenic class of compounds. The hasard, bound with the occurrence of this compounds in the food and the possibility to be formed in vivo, during the digestion, justifies the current works. The authors quoting numerous works on different laboratory's animals, remind the toxicity. and carcinogenicity of this compounds. The metabolism is also discussed. The N-nitroso, compounds may be formed in food from the presence of the precursors (nitrite or nitrate, amines and amino-acides). The synthesis takes place during the technological processes, the storage and the house cooking. Today, the marginal effect dose is estimated as 10 mug/kg of daily food. The carcinogenicity has not been demonstrated in human, but is strongly suspected. The amount of N-nitroso compounds in human food is generally low. Many factors can influence the reaction; it is inversely related to the basicity of secondary amine and optimum pH is around pH 4. A lot of compounds such as sodium ascorbate inhibit the synthesis in food. A number of recent reports using reliable methodology have identified nitrosamines at the lower part per billion level. Dimethyl-nitrosamines occurs, very sporadically in a number of cooked meat samples. The nitrosopyrrolidine appears frequently in fried but not in uncooked products. The nitrosopiperidine seems to be bind with the presence of pepper in food. Finally the presence of nitrosamides (nitrososarcosine) and nitrosoaminoacides (nitrosoproline, nitrosohydroxy-proline) is being quested. The N-nitroso compounds may be synthetized in vivo during the digestion at the acide medium of the stomach or by bacterial action during the transit in the gut...


[Influence of a low-protein diet on the acute toxicity of a pesticide: Nabam].

Male rats are fed during twenty eight days from the weaning with semi-synthetic isocaloric diets containing 3,5 p. 100 and 26 p. 100 of proteins under the from of casein and with a standard laboratory diet. At the end of this period the LD50 and the pathological clinical syndrome of a fungicid belonging to the dithiocarbamate series : the Nabame, are determined in each of the groups of rats receiving their respective diet. The LD50 is significantly reduced among the rats with a deficiency in proteins compared with the LD50 determined among the two other groups of animals. A likely explanation is to be looked for, at least for a part, on the level of the production or of the activity of detoxicating microsomal hepatic enzymes which the restrictions of nitrogen supply could reduce. The pathological - clinical syndrome of toxicity : stimulation then depression of the central nervous system, severe inflammation of the gastro-intestinal tract, important renal necrosis, is essentially the same among all the animals and it does not seem to be influenced by the level or nature of the proteinic supply.


[Diminution of activity of liver microsomal oxygenase in a rat fed with a diet with added zineb].

Young Wistar CF male rats were fed with diets containing 6,15,60,600,3600 p.p.m of zineb (a zinc thiocarbamate used as fongicide). Four weeks after the beginning of the treatment, a calcic precipitation method is used for obtaining a preparation of liver microsomes from these animals. The microsomes are then used for measuring the activity of both aminophenazone demethylase and aniline hydroxylase as well as the liver concentration of cyt. P 450 and cyt. b5. The weight growth was reduced by the highest dose of zineb, which corresponds to about a daily intake of twentieth of the LD 50 per os. The fongicide brings down the activity of the microsomal monoxygenases and reduces the P 450 quantity. The lessening of the aminophenazone demethylation is apparent starting from a dose between 60 and 600 p.p.m...


[Nutritional effects in the rat of oxythioquinox (morestan) as a function of its concentration and of the lipid content of the diet].

Of two groups of rats, one received a normal diet and the other a high fat diet for 5 weeks. The effects of oxythioquinox, administred at diet concentration of 200, 400 and 800 mg/kg, of fresh food are studied on weight gain, food and calorie intake and on the weight and composition of various organs. Growth, food and calorie intake are diminished in relation to oxythioquinox concentration in the diet. There exist an interaction between the fat content of the diet and the toxicity of oxythioquinox. The decrease of the efficiency of calorie by oxythioquinox indicates a perturbation of the rats metabolism. An increase in the weight of the liver is observed with a significant interaction between the fat concentration and the oxythioquinox with the results expressed in weight of organ per 100 g body weight. There is an increase in the degree of the water content of the animals liver with normal fat diet. In the case of a high fat diet there is an increase of cholesterol and fatty acid content. In all case, the variations are more strongly marked in relation to the oxythioquinox concentration of the diet and at the same concentration, the high fat diet is more effective that the normal diet. There is an interaction between the lipids in the diet and the oxythioquinox and this interaction indicates, an accentuation of the effects of oxythioquinox by lipids of the diet.


Central retinal vein occlusion: life and sight implications.

Central retinal vein occlusion is an ophthalmic disease with both life and sight threatening implications. Treatment should be aimed at the underlying ophthalmic or systemic disease. Questionable modes of therapy (ie, anticoagulation) may injure the patient as a whole without offering any really better results for the ophthalmic condition.


Fluorescein angioscopy: techniques of partial fluorescence, permanent drawing record and photocoagulation.

Fluorescein angioscopy with the indirect ophthalmoscope might be the preferred technique for evaluating and treating certain lesions, particularly those in the retinal periphery. Three techniques which are helpful in extending the advantages of angioscopy are described. (1) Partial fluorescence is achieved with careful adjustment of the cobalt blue filter which relates the fluorescence to retinal landmarks, ie, color angioscopy. (2) A permanent record of angioscopy in different phases can be made with tracing paper over the retinal drawing. (3) Correct localization of lesions to be coagulated is achieved with blue filters over the coagulator beam following fluorescein injection. The filter is removed during coagulation.


Assay of parathyroid hormone in human serum and its uses.

The assay of parathyroid hormone has contributed greatly to our understanding of calcium metabolism in health and disease. The most important clinical application of the assay is in the differential diagnosis of hypercalcaemia, which is an increasing clinical problem. PTH assays are of little or no value in the absence of other biochemical data, especially accurate determinations of plasma calcium and phosphate.


[Cutaneous manifestations in disseminated intravascular coagulation syndrome].

The principal cutaneous manifestations indicating the need to seek intravascular coagulation are: purpura fulminans, extensive sheets of purpura, acralcyanosis, gangrene in a plaque distribution and perhaps, acute necrosis of the digits. The biological, anatomo-pathological and immunological signs of the conditions should be detected early and precisely by virtue of its nature as a medical emergency. The diversity of its clinical manifestations would seem to be related to the greater or lesser extent of the coagulopathy and resultant thrombosis in the microcirculation. Purpura, though of variable degree, is the constant cutaneous accompaniment of this condition, which is considered to be the equivalent of the experimental phenomenon of Sanarelli-Schwartzman. Heparin, which blocks the tendency to thrombosis in the small vessels in the treatment of choice, associated when possible with treatment of the underlying aetiology.


[Proposed new treatment for excessive statural growth using minimal corticotherapy. A propos of 11 cases treated with prednisone].

Treatment for excessive growth has alway constituted, in the endocrinological field, and particularly in the United States where such problems are frequently encountered, an incompletely solved problem, where the use of oestrogen therapy for girls has given more or less convincing results. We believe we have found a better solution which comes closer to tackling the real problem by using a minima corticotherapy, delayed until a height 1 or 2 cm short of the desired height is reached and bridging the time later required for the conjugation cartilages to fuse, under the influence of physiological puberty which is allowed to occur naturally under this method. 11 adolescents (1 boy, 10 girls) underwent this treatment at ages between 12 1/2 and 16 (average age 14 years 2 months), at a standard dose of 15 mg/day of prednisone in 3 equal doses over a period of between 7 and 25 months with periodical checking of the clinical condition, radiological bone structure and satisfactory biological tolerance. Results on growth were quite clear: growth rhythm was immediately inhibited, falling from 7,2 cm to 0,5 cm/year and there was total arrest of expected growth and a final height of about 1 or 2 cm more than the height at the onset of treatment was reached. The quality of the results obtained by this method seems to be considerably better than those obtained by other methods which have so far been suggested and this is all the more important as, provided specialised clinical and biological checks are carried out very regularly, it is not countered by unfortunate side-effects. Side-effects either do not occur at all with this method or are very minor and always regress when treatment is terminated.


[Histopathology of cutaneous aphtha in Behçet's syndrome].

The authors studied cutaneous biopsies of papulo-pustular lesions in Behçet's syndrome. In biopsies taken early, superficial oedema of the dermis appeared to be the first histological sign, subsequently resulting in a true sub-epidermal bulla, containing neutrophil polynuclear and eosinophil leucocytes. At this stage no major vascular involvement was seen. In later specimens, by contrast, marked vascular changes were seen with the appearances of allergic angiitis. At this stage, there is frank epidermal necrosis with resultant ulceration.


[Dermatomyositis with spinulosis (Wong type dermatomyositis). Histologic study. Attempt at pathogenic interpretation].

The authors present a case of dermatomyositis with generalised spinulosis of pilose pityriasis rubra (lichen ruber acuminatus) type, giving a highly characteristic appearance of linear verruciform spinulosis of the back of the hands. They describe the histological lesions and feel that this spinulosis is probably due to marked degenerative smooth muscle myositis of the erector pili muscles. They recall the earlier cases of O'Leary and Christianson and above all those of Wong. The case reported is the first in a child.


[Influence of the thymus-adrenal interaction on the allograft rejection in rats (author's transl)].

Adrenalectomy was followed in young male Sprague-Dawley rats by a delayed rejection of D-A skin grafts. This could be suppressed by implantation of both corticosterone and DOC pellets only. Thymic hormone injections did not interfere with this action of the corticosteroids.


[Clomiphen-test in anovulatory sterility (author's transl)].

Twenty women with sterility due to an anovulatory cycle, were submitted to a load of hundred milligramms by day of clomiphene citrate during five days. The test was always performed between the 10th and the 14th day of the cycle. Before and after the clomiphene administration, FSH and LH in plasma and total estrogens and pregnanediol in 24 hours urine, were estimated. The results, are compared with those of ten normal women and the observed results may schematically been classified into three groups: A) Normal response. -- B) Week gonadotropic response. -- and C) High LH baseline. This results seem to indicate three main origines for the anovulatory cycle syndrome: hypothalamic, pituitary and ovarian.


[Association of Kaposi's sarcoma and Hodgkin's disease].

The authors report a new case of the association Hodgkin's disease and Kaposi's sarcoma. A woman of North African origin and suffering from mediastinal Hodgkin's disease developed, after the commencement of polychemotherapy with radiotherapy, Kaposi's cutaneous sarcoma, typical, clinically, histologically and by electron microscopy. In the light of this new case, the authors review 41 cases of the Hodgkin-Kaposi association found in the literature and discuss the inter-relations between Kaposi's sarcoma and diseases of the haemoreticular system, in particular carcinomas, immuno-depressive states (notably in association with renal transplants) and virus disorders (essentially herpes). It might be possible to incriminate in the aetiology of Kaposi's disease a carcinogenetic process of viral origin during a state of immuno-depression.


[Recurrent hyperaldosteronism and hypertension post adrenalectomy (author's transl)].

Primary Aldosteronism may be due to adenoma or hyperplastic adrenals. Such a distinction can be obtained from biochemical studies. In our observation, a man with recurrent aldosteronism after right adrenalectomy was studied. Radiological and surgical data might indicate an adenoma. This opinion was modified by pathological studies. This absence of capsule and the presence of microadenomatous hyperplastic lesions indicated pseudo-adenomatous hyperplastic glands. On the other hand, high blood pressure remained after adrenalectomy. A treatment with beta-blocking substances corrected this hypertension.


[Antiandrogenic effect of spirolactones: different mechanisms of action (author's transl)].

The spirolactones decrease the plasma testosterone levels in men. They also inhibit the specific dihydrotestosterone binding to rat prostate, and have no effect on 5 alpha-reductase. The spirolactones are antiandrogenic drugs, acting at several levels.


[Feminishing adrenal tumor with primary hyperaldosteronism. Report of a case (author's transl)].

A case of feminishing adrenal tumor with primary hyperaldosteronism is reported. The aim of this report is to emphasize on the terminal evolution of the disease. This phase was marked by malignant hypertension, severe renal insufficiency, and iatrogenic cellular hyperhydration with hyponatremia secondary to spironolactone therapy.


[Analytical and analogical study of a model of the adrenal-postpituitary function (author's transl)].

After an analyitical study of mathematical models connected with osmotic or volemic regulations, and the mention of its contribution to the therapeutic act, the authors approach the stimulation, by the mean of an analogical computer, of the complete and non-linear model which associates both types of regulation. So it is possible to attempt to determine the level of adrenal and vasopressin actions according to: 1 degree the sum of the agonistic effects and the difference of their antagonistic effects; 2 degrees the perturbations brought to the system; 3 degrees the parametric values of the model. Theoretical and empirical curves seem to be in favour of such a formulation.


A mapping function for human chromosomes.

The available simple mapping functions are surveyed, and a new mapping function that provides for positive interference within chromosome arms and no interference across the centromere is proposed, together with the corresponding formula for centromeric linkage. This new function is derived by assuming that all chromosome arms except the short arms of acrocentric chromosomes hav an obligatory chiasma, and that the remaining chiasmata are distributed at random; assumptions which may correspond reasonably well to reality. A method for the comparison of the goodness of fit of mapping functions with family data is given. Low levels of interference seem to be indicated, although as yet insufficient human data is available to allow interference to the specified. Interference has a considerable effect on the estimation of map distances between loci from 3-point lod scores as is shown by the linkage group Rh, UMPK, PGM1, Amy, 1qh, Fy, on chromosome 1.


Cytogenetics and infertility in man. II. Testicular histology and meiosis.

Within a group of 207 subfertile men, selected for testicular biopsy, histological investigations were made successfully in 194 chromosomally normal and 7 chromosomally abnormal individuals. Fifty-two per cent of men with a normal karyotype showed normal testicular histology, 31% showed a general depression of spermatogenesis and 8% showed deficiency in the late stages. Ten per cent had only Sertoli cells in the testis. The range of testicular conditions seen in the chromosomally abnormal men was similar to that found in the chromosomally normal. Meiotic studies carried out on 118 chromosomally normal individuals gave a mean chiasma count of 48-9 per cell. There was a positive correlation between high numbers of cells at diakinesis/metaphase I showing X and Y univalents and low numbers of cells reaching metaphase II. Meiosis was studied in 3 translocation heterozygotes, one 47, XYY male, one 47, XY+mar individual and one patient with a ring Y chromosome.


The testing of dominants for heterozygoisty.

A simple method of estimating the frequency of heterozygotes among the dominants by test-making has been described; and then a maximum likelihood estimate is obtained by an iterative counting procedure. Eearly results of Haldane have been review and modified. Methods of estimating the gene frequencies, their ratio, and the inbreeding coefficient from test-mating results have also been given.


Estimating distances from the centromere by means of benign ovarian teratomas in man.

Under the assumption that benign ovarian teratomas in man arise parthenogenically from a germ cell by suppression of the second meiotic division, the distance of a gene from its centromere can be estimated from the observed proportion of heterozygous teratomas collected from heterozygous hosts. The frequency of heterozygous teratomas of heterozygous hosts is equivalent to the frequency of second division segregation at the gene locus which has been used for centromere-related mapping in fungal genetics for more than 40 years. Mapping functions useful for teratoma-based mapping in man are presented.


A restriction on the space of genetic relationships.

It was pointed out by Trustrum (1961) that even for non-inbred pairs of relatives it is possible for all four cross-parental kinship coefficients to be non-zero, and hence that the expression often assumed for the correlation between such relatives is not completely general. Van Aarde (1975) has recently made the same comment. We derive a restriction on the space of attainable Cotterman coefficients for a relationship between two arbitrary non-inbred relatives. This restriction implies that the form of the expression for the correlation is in fact general, although the components cannot always be interpreted as parental kinships.


The secondary sex ratio in the United States 1969-71: association with race, parental ages, birth order, paternal education and legitimacy.

The simultaneous effects of several variables on the secondary sex ratio have been examined using data from over 5,000,000 births which occurred in the United States during 1969-71. The previously described negative association of birth order and sex ratio has been confirmed. For legitimate and illegitimate births combined, maternal age and paternal age are unimportant factors once account is made of birth order. This pattern obtains for both blacks and whites. The sex ratio for legitimate and illegitimate births is equivalent but the fact of legitimacy or illegitimacy may affect the association of the ratio with birth order and the parental ages. Paternal education is not significantly related to the ratio, but the highest probability of a male birth is found among fathers with intermediate levels of attainment. Even though the association between sex ratio and order of birth is highly significant in the statistical sense, the proportion of male births changes less than 2% over the extreme values of birth order. Furthermore, it is emphasized that the association accounts for only a very minor (less than 10%) proportion of the total variation in the ratio.


Two-sided assortative mating for a single locus.

Most models previously considered for assortative mating were such that no change in gene frequencies occurred, or that one-sided assortative mating was occurring. Two-sided assortative mating is more realistic for human populations, and in this paper a model of two-sided assortative mating is analysed for two autosomal alleles with dominance, an important case for human genetics. The concept of a relative probability of matin between two phenotypes is used, and this variable can take into account factors such as different propensities for assortment in the various phenotypes and so forth. It is shown that the gene frequency may vary from generation to generation and conditions for the establishment of a stable polymorphism are given. For instance, Stanton (1947) has considered a special case of two-sided assortative mating with two autosomal alleles and a constant correlation between mates, where the value expressed by the heterozygote is numerically exactly half-way between the values exhibited by the two homozygotes. Also he has considered a special form of assortative mating, where the probability of occurrence of matings between the same homozygotes has been increased in each generation by the same constant factor as the probability of occurrence of matings between different homozygotes has been decreased. The probability of occurrence of matings involving heterozygotes remains the same as if mating were random. For this particular model the frequency of the genotypes in those who mate in generation t is the same as for the general population in generation t, but the genotypic frequencies change from generation to generation, reaching an equilibrium value. Stark (1976) has also considered a similar model to Stanton's (1947), the major difference occurring in the construction of the mating frequencies, which in this case occurs according to the canonical decomposition of the 2-way table of mating frequencies. Stark shows the correspondence between the results for this model and those given by Malécot (1939, 1948). The results for all these models depend on the particular values assigned to the genotypes. Also these models could be extended as outlined in this article for the case of two autosomal alleles with dominance.


Limits of the general two-allele single locus model with incomplete penetrance.

A graphical method is presented that allows an investigator to find the mathematical limits of the general one locus two allele genetic model for any trait whose population prevalence is known. It is seen that while the model is quite flexible in its ability to fit family data, there remains a large area where the model cannot be fitted. Specific sub-regions corresponding to particular hypotheses (e.g. underdominant v. intermediate v. overdominant) can be found, thereby limiting the area that needs to be searched by other more complicated techniques. Moreover, knowledge of where a set of observations lies can enable an investigator to frame and test specific subhypotheses.


Asymptotic behaviour of the mean of a phenotypic diffusion process.

Asymptotic genotypic frequencies are evaluated as functions of selection parameters and initial conditions of a phenotypic diffusion process. On the basis of asymptotic relations between genotypic frequencies some analytic results about equilibrium are obtained.


The fitness of human translocation carriers.

A simple method to estimate the mean fitness of human translocation carriers is described. The method is based on information about the inheritance pattern of the translocations. This kind of data can be obtained from the surveys of the chromosome constitutions of new-born babies. The following fitness estimates are obtained: D/D translocation carriers, 0-94; D/G translocation carriers, 0-83; and reciprocal translocation carriers, 0-67. The estimates are rather uncertain due to the scarcity of information, but they are consistent with the expected results. More accurate estimates will be obtained in the future when more data on translocation carriers are available and the cytological classification of the different translocations becomes more exact.


Exercise-induced bronchocontriction, skin sensitivity, and serum IgE in children with eczema.

Forty-two children with eczema were studied for exercise-induced asthma (EIA), skin sensitivity to prick testing, blood eosinophil count, and immunoglobulins. 29 had a fall in peak expiratory flow rate after exercise greater than 20% and of these, 23 had symptoms of wheezing. 13 of the eczematous children showed a fall of less than 20%. The children with EIA showed greater cutaneous sensitivity (p less than 0.001) and a higher total serum IgE (p less than 0.025). 3 of the group with a fall of less than 20% had allergic rhinitis with skin sensitivity to grass pollen. The remaining 10 had no clinical evidence of allergic disease, other than eczema and skin sensitivity, and total IgE fell within the normal range. It is suggested that in a proportion of chilren with eczema there is little evidence of reaginic allergy.


Investigation and management of long-standing chronic constipation in childhood.

The anorectal physiology of 106 children with long-standing chronic constipation, who had failed to response to a trial of medical treatment, was assessed. 10 (9%) were shown to have ultrashort-segment Hischsprung's disease, later confirmed on histology, The remainder showed evidence of hypertrophy of the internal sphicter on anorectal manometry and had a vigorous anal dilatation (to accept 4 fingers) under general anesthesia. After this, 38% were able to be weaned off all medication and most of the remainder improved. Further anal dilatation and internal sphincterotomy allowed a further 10 children to stop laxative, bringing the total to 48%.


Maternal diabetes mellitus and congenital malformation. Survey of 205 cases.

Twenty-five out of 205 (i.e. 12%) babies born to diabetic mothers in the Birmingham Maternity Hospital in the period 1969-1974 were malformed as against 6% in a control group. The incidence was highest in the group where mothers were on insulin at the time of conception (17 out of 117, i.e. 15%). No correlation was observed between major malformation in this group and age of onset or duration of the diabetes, progressive vascular complications, maternal age, or parity. Cardiovascular malformations were over-represented.


Clinical and subclinical vitamin D deficiency in Bradford children.

A survey of the vitamin D status of Bradford schoolchildren was carried out in April 1973, employing conventional biochemistry, radiology, and measurement of 25-hydroxycholecalciferol levels. Biochemical evidence of rickets was present in 45% of the Asians. When re-examined in September, several children showed spontaneous biochemical resolution; nevertheless, radiological abnormalities were present in 12% of the original sample. No evidence of rickets was detected in the smaller White sample. Minor biochemical abnormalities were present in 9 of the 40 West Indian children. A study of admissions of Bradford hospitals in the 4 years 1969-1972 inclusive confirmed that clinical vitamin D deficiency was confined to Asians except for a few cases of infantile rickets in White children. The probability that one Asian child in 40 may require admission during the period from birth to adolescence emphasizes the urgent need for the introduction of prophylactic measures.


Vitamin deficiencies and neural tube defects.

Serum folate, red cell folate, white blood cell vitamin C, riboflavin saturation index, and serum vitamin A were determined during the first trimester of pregnancy in over 900 cases. For each of these there was a social classes I + II showed the highest levels which differed significantly from other classes, except for serum folate. In 6 mothers who gave birth to infants with neural tube defects, first trimester serum folate, red cell folate, white blood cell vitamin C, and riboflavin values were lower than in controls. In spite of small numbers the differences were significant for red cell folate (P less than 0-001) and white blood cell vitamin C (P less than 0-05). These findings are compatible with the hypothesis that nutritional deficiencies are significant in the causation of congenital defects of the neural tube in man.


Analysis of 100 children with severe and persistent hypertension.

In 100 children with persistent hypertension seen over the past 5 1/2 years the commonest causes of hypertension were chronic glomerulonephritis, reflux nephropathy, coarctation of the aorta, and obstructive uropathy, accounting for some 70% of cases. 17 children have died, but in the remainder hypertension has been controlled by surgery, chronic haemodialysis, or by the use of pharmacological agents. Methyldopa was the commonest drug used, and the children appeared relatively resistant to the side effects of this and of other drugs, even when large doses were used. The improvment is the prognosis of severe hypertension in childhood indicated in this survey is largely due to the availability of chronic haemodialysis and transplantation for end-stage renal disease, but the advances in diagnositc methods and surgical techniques and the introduction of new drugs have also contributed.


Measurements of muscle strength and performance in children with normal and diseased muscle.

A study has been made of two simple means of measuring muscle power in children with normal and diseased muscle. In one the length of time that the leg and the head could be held at 45 degrees above the horizontal was measured with the child supine. In the second, measurements were made of the isometric strength of six muscle groups with the newly developed Hammersmith Myometer. In the timed performance tests only 5 (8%) of a group of 61 children known to have muscle disease achieved the minimum expected values for their ages. Myometer readings of the isometric power of the children with muscle disease also have values which were below those of a comparable group of normal children. The reproducibility of muscle strength measurements in young children has been shown to be good, whereas the timed performance tests, though able to differentiate normal children from children with muscle disease, did not show sufficient reporducibility for this test to be recommended for sequential measurements.


Quantitative morphological studies of developing human cerebellar cortex in various disease states.

A quantitative morphological assessment was carried out of the cellularity and staining properties of the cells of the layers of the human cerebellar cortex, both in the normal child and in 41 children suffering from a series of disorders including mental retardation. A computerized image analyser and highly standardized procedures were used. All of the cases of mental retardation and some cases with congenital cardiac anomalies showed abnormal cell concentrations and staining properties. 3 cases of 'cot death' also showed abnormal results. These findings are presented as a new measurable aspect of brain disease, and as a indication for further study.


Motor nerve conduction velocity in spinal muscular atrophy of childhood.

The ulnar and posterior tibial conduction velocities were measured in 29 children with spinal muscular atrophy, 14 of whom had the servere form of the disease. The ulnar nerve velocity was slow in 12 of the 14 severely affected infants, but normal or fast in 11 of 14 children less severely affected. The corresponding results for the posterior tibial nerve were slow velocities in 11 of 12 infants in the severe group and normal or fast in all 11 infants less severely affected. The difficulty in distinguishing infantile spinal muscular atrophy from peripheral neuropathy is emphasized.


Failure to thrive and death in early infancy associated with raised urinary homovanillic and vanillylmandelic acids.

A case of failure to thrive in an infant with persistently raised urinary levels of homovanillic and vanillylmandelic acids is descirbed. No neural crest tumour was discovered at surgical exploration or at necropsy. The relation of this biochemical abnormality and failure to thrive is unclear.


Childhood actinomycosis. Report of 3 recent cases.

Three cases of childhood actinomycosis are reported, 2 with the commonest presentation of cervicofacial abscess and the third with a rarely reported superficial chest wall abscess. The importance of prompt bacteriological diagnosis and adequate treatment with surgical drainage and chemotherapy is stressed. Though in adults males are affected more frequently than females, the sexes are probably equally affected in childhood.


Measurement and prediction of the disappearance rates from soil of 6-chloropicolinic acid.

6-Chloropicolinic acid is the sole detectable metabolite, other than carbon dioxide, arising from decomposition of 2-chloro-6-(trichloromethyl) pyridine in soil. The pyridine compound is a potent inhibitor of nitrification now in use with ammonium fertilizers. The purpose of this study was to evaluate the relative influence of various soil and climatic factors on rates of degradation of 6-chloropicolinic acid in soil. Experiments with a wide range of soil types (23 soils) demonstrate that the most important factor influencing the decomposition rate of 6-chloropicolinic acid is soil temperature. When temperature is not a variable, the quantity of organic matter (0.9 to 6.9% by weight) and pH (4.8 to 8.1) significantly affect the rate of decomposition, but sand, silt, and clay percentages do not. Moisture content was without apparent effect because the range of values investigated was too narrow. A fractional-order rate law (0.7) describes the disappearance rate best. Application of the Arrhenius equation to the data for the decomposition of 6-chloropicolinic acid in soil indicates an activation energy of 6.57 kcal per mole, suggesting that the chemical is biologically rather than chemically degraded. It was not possible to develop a suitably precise equation for prediction of loss rate as affected by the above soil and climatic factors because undefined biological factors in the soils override the effect of measurable properties of soil and climate.


Insecticide and nutrient transport in water, related to agricultural land use of a stream basin in Ontario, Canada.

Transport by stream water of insecticides and nutrients in Big Creek, Norfolk County, Ontario, Canada, was examined by combining concentrations of substrates with flow data. Big Creek has its headwaters in dairy cattle country, its central basin area is mainly devoted to tobacco growing, and its lower reaches contain mixed farming, corn and vegetables, etc., before it flows into Lake Erie. Three sampling sites were chosen to represent these 3 different land uses. Generally concentrations of substrates in the water were quite uniform at the 3 sites resulting in transport of quantities in proportion to stream flow. Certain anomalies occurred and are discussed. The 2 chief insecticides found were DDT and dieldrin. Analyses for potassium, calcium and magnesium indicated that these nutrient losses into the stream were area-rather than usage-dependent. Midseason variations in loss of nitrogen and phosphorus may be the result of agricultural practices in the three areas represented in this study. The largest quantities of all nutrients lost occurred early in the season before crops were established.


Toxic, neurochemical and behavioral effects of dieldrin exposure in mallard ducks.

Toxic, neurochemical and behavioral alterations were evaluated in ducks fed various dietary levels of dieldrin. Increasing amounts of dieldrin in the diet caused an appreciable decrease in the levels of three biogenic amines in whole brain, i.e. serotonin, norepinephrine and dopamine. No effect was noted in whole brain gamma aminobutyric acid contents. Hepatic microsomal enzymes were assayed in these birds using p-nitroanisol and O-ethyl-O-p-nitrophenyl benzenethionophosphate as substrates. Sublethal amounts of dieldrin caused an increase in hepatic drug metabolizing enzymes. Similar alterations were noted in liver protein, deoxyribonucleic acid and ribonucleic acid contents. Studies involving encounters between mallard drakes indicated a decline in the tendency for dieldrin exposed drakes to take the initiative and establish rights of access in approach confrontations. Although many of these changes are compatible with life processes, their significance is not well understood, especially in terms of lifelong exposure to persistent pesticides. The possible relationship between neurochemical alterations and the mechanisms of insecticide neurotoxicity is discussed.


Disappearance of dislodgable residues of five organophosphate pesticides on citrus leaves and fruit during dry and wet weather in Florida.

Citrus leaf discs and fruit taken from trees sprayed at recommended levels and twice recommended levels with ethion, parathion, azinphosmethyl, carbophenothion, and dioxathion were shaken with water and wetting agent for removal of dislodgable residues at 0, 1, 3, 5, 7, 14 and 21 days following treatment. The first portion of the field experiment was performed during a period of no rainfall (April) and the second when there was rainfall (July) in 1973. Four replicates of 50 leaf discs and 4 fruit, respectively, were averaged from each sampling to give data reported. A gas chromatograph equipped with a flame photometric detector was used for analysis. Dislodgable residues found decreased with increasing time following application and samples from the wet period were lower than those from the dry period. Moisture and temperature could account for the differences in the two sampling period.


Alteration of O,O-dimethyl S-[alpha-(carboethoxy)benzyl] phosphorodithioate (phenthoate) in citrus, water, and upon exposure to air and sunlight.

The fate of 32P- and 14C-labeled O,O-dimethyl S-[alpha-(carboethoxy)benzyl] phosphorodithioate (phenthoate) was determined in citrus, water, and upon exposure to air and sunlight. The products recovered from citrus and glass plates exposed to sunlight were unchanged phenthoate, phenthoate oxon, demethyl phenthoate, mandelic acid, bis-[alpha-(carboethoxy)benzyl] disulfide, O,O-dimethyl phosphorothioic and phosphorodithioic acid. Similar products generally were found in citrus leaf and fruit extracts. Phenthoate was fairly stable in phosphate buffered water with a half-life of approximately 12 days at pH 8.0. The major hydrolysis products were phenthoate acid, demethyl phenthoate and demethyl phenthoate oxon.


[Sensitivity tests on bacterial strains from respiratory tract: comparison between direct and on isolated strains antimicrobial disc susceptibility test (author's transl)].

The validity of the direct antimicrobial disc susceptibility test has been compared with the same test carried out on bacterial strains isolated from clinical materials obtained from the respiratory tract. The experimental evidence so far obtained raises some doubts concerning the reiliability of the direct test. The use of the latter seems to be reccomended in urgent cases only considering that either with multimicrobic or monomicrobic material the results obtained are partial and slightly reproducible. The conclusion is that, in order to obtain an accurate picture of the sensitivity to the various antibiotics, the direct test should be followed always with the antimicrobial disc susceptibility test carried out with isolated strains.


[Statistical research into the diagnostic methodology in bacterial infections of the respiratory system as at present practised by various centres (author's transl)].

A research program has been carried out using a questionnaire to survey statistically the diagnostic methods obtaining in the bacteriological examination of sputum. Of the 336 forms sent to: 1. all the regional, 2. most of the provincial, 3. some local, hospital laboratories, only 48 were returned. From these limited numbers we have extracted the data discussed in the present paper.


[Significance of mycoplasma species in the respiratory tract (author's transl)].

After consideration of the tassonomic and biological characteristics of Mycoplasma species, the Author discusses the most significant aspects on M. pneumoniae infections. On the basis of: natural history of respiratory infections; epidemiology; experimental aspects of M. pneumoniae infection; immunology; microbiological and serological diagnosis.


[Contributions to the interpretation of the immunoglobulins's variations in the bronchial secretions (author's transl)].

Study of the relationships between the variations of the connections between the components of the bronchial secretion and the viscosity of the sputum, with particular regard to the role of the IgA IIS and to the secretory piece.


[Mycobacterial infections in man: bacteriological, clinical and epidemiological evaluation (author's transl)].

At present time the direct microscopy of acid-alcohol fast bacteria includes Mycobacteria, Nocardia, "rhodochrous complex". Direct microscopy is suitable to identify visible and not viable bacteria, the debacillization curve and the fall and rise phenomenon. Strains of M. tuberculosis complex are frequently with partial virulence low infectivity, and are modified by drugs. Little or no reaction to PPD is present.


[The secretory IgA. The local secretory immunitary system (author's transl)].

The Authors take into examine the local secretory immunitary system (L.S.I.S.) starting from the presence of antibody-molecules in secretions: they study origin, characteristics, action and excitement procedures of this class of molecules, also compared with the immunitary central system.


[Anaerobic flora of the respiratory tract (author's transl)].

The general outlines for the microbiological study of respiratory tract anaerobic flora are indicated. To day research tend to assign to these bacteria a significant role in sustaining some diseases of lungs pleural space and upper respiratory tract; anaerobes are therefore a subject of outstanding interest for clinical microbiologists. Difficult arise in isolation and identification of respiratory tract anaerobes owing to normal presence of anaerobic flora in the mouth; the difficult can be overcomed by avoiding contamination with normal flora (lung puncture for instance) or by quantitative evaluations of bacteria in sputum.


[Microbiological and cytological aspects of the aspirate bronchoscopy (author's transl)].

The Authors compare by microbiological and cytological aspect the result got by sputum and aspirate at bronchoscopy. They point out that aspirate at bronchoscopy permits a more significant etiological diagnosis by both microbiological or cytological point of view.


[Bidimensional I.E.F. of proteins in the bronchial secretion (author's transl)].

Qualitative and quantitative determination of the proteins in the bronchial secretions (of about 50 patients suffering from chronic bronchitis) after extraction.


[IgE levels in children affected by respiratory allergies (author's transl)].

Radioimmunological technique has been used in order to measure IgE seric levels on 100 children affected by respiratory allergies, on 46 children with non allergic respiratory diseases and on 54 healthy children distributed in different classes of age. In the 58% of cases, allergic subjects presented IgE levels remarkably increased compared with non allergic ones, in the 28% of cases IgE levels had an insignificant increase, and in the remaining 14% the values were comparable with those of the non allergic subjects.


Recurrent hyperparathyroidism.

Recurrent hyperparathyroidism occurred in 11 of 295 patients from 10 months to 34 years after an initially successful operation. Seven patients with recurrent hyperparathyroidism had either multiple endocrine adenomatosis type I (MEA) or familial hyperparathyroidism (FHP), one patient had parathyroid cancer, and two patients had renal failure at the time of recurrence. Four of these patients ahd their initial operations elsewhere. Recurrence developed in 33% of patients with MEA or FHP but in only 0.4% of 242 patients without MEA or FHP. The presence of MEA or FHP was known before parathyroid exploration in 18 (86%) of the 21 patients. In patients with MEA or FHP, subtotal parathyroidectomy should be performed if there is more than one gland involved. Other patients should be treated by selective removal of an adenoma because recurrence is rare. Subtotal parathyroidectomy should be reserved for patients with diffuse hyperplasia.


Pancreatectomy for chronic pancreatitis.

Of one hundred and forty-nine patients (101 male and 48 female) 4-67 years of age, 117 were alcoholics and underwent pancreatectomy because of episodic or continuous abdominal pain or complications or chronic pancreatitis. Nineteen patients underwent pancreaticoduodenectomy, seventy-seven 80-95% distal resection, anf fifty-three 40-80% distal pancreatic resection. There were 3 operative death and 30 late deaths 6 months to 11 years post pancreatectomy. Twenty-one patients were lost to followup, 1 to 11 years post pancreatectomy. Ninety-five patients are known to be alive, 4 of whom are institutionalized. Indications for pancreatectomy in addition to abdominal pain include recurrent or multiple pseudocysts, failure to relieve pain after decompression of a pseudocyst, pseudoaneurysm of the visceral arteries associated with a pseudocyst, recurrent attacks of pancreatitis unrelived by non-resective operations, duodenal stenosis and left side portal hypertension. The choice between pancreaticoduodenectomy or distal resection of 40-80% or 80-95% of the pancreas should be based on the principle site of inflammation whether proximal or distal in the gland, the size of the common bile duct, the ability to rule out carcinoma, and the anticipated deficits in exocrine and endocrine function. The risk of diabetes is very significant after 80-95% distal resection and of steatorrhea after pancreaticoduodenectomy. When the disease process can be encompassed by 40-80% distal pancreatectomy this is the procedure of choice.


Abnormalities in gallbladder morphology and function in patients with cholelithiasis.

Thirty-seven symptomatic cholelithiasis patients who had cholecystectomy were studied to determine the relationships between clinical manifestations, histologic findings and gallbladder absorptive capability. A clinical score was calculated from clinical data which we thought might be predictive of abnormal gallbladder histology. Histologic parameters indicative of gallbladder disease were used to calculate a histologic score. Shortcircuit current measurements, which reflect gallbladder sodium absorption,were used to assess absorptive function. Patients with very high clinical scores, indicative of pronounced clinical score was not predictive of histologic findings or absorptive function of the gallbladder is directly related to the degree of histologic abnormality, and that absorptive capability is not an all-or-none phenomenon. The data also show that visualization on oral cholecystography is an unreliable measure of gallbladder absorptive capability.


The value of thymectomy in myasthenia gravis: a computer-assisted matched study.

In the absence of a prospective randomized study of patients treated conservatively or with thymectomy, a computer-assisted retrospective matches study was devised. Of 563 patients treated for myasthenia gravis without thymoma up to 1965, 104 had thymectomy. With computer assistance, each surgical patient was matched with a medical patient on the basis of age, sex, and severity and duration of disease. On this basis 80 of the 104 surgical patients could be matched satisfactorily. There were 16 males and 64 females in each of the matched surgically treated and medical control groups. A complete remission was experienced by 27 of the 78 patients in the surgical group as compared to 6 of the medical group. Improvement was noted by 26 of 78 surgically treated patients and 13 of 78 receiving medical treatment. Survival for patients having thymectomy. Thirty-four patients in the medical group had died as compared to 11 in the surgical group. Comparison of survival in relation to sex, duration of symptoms, or age (less than 30 or less than 30 years) did not show a significant difference. Until more effective treatment is available for myasthenia gravis, thymectomy deserves consideration for both sexes, and with increased age or long duration of symptoms.


Proximal gastric vagotomy: effects of two operative techniques on clinical and gastric secretory results.

PGV performed in 39 patients by separating the lesser omentum from the stomach beginning 6 or 7 cm proximal to the pylorus and skeletonizing the distal 1 to 2 cm of esophagus was followed by 15.4% of proven and 10.2 of suspected recurrent ulcers. Insulin tests were done during the first 3 months postoperatively on 31 of the patients, including the 6 with proven and the 4 with suspected recurrent ulcers. The peak acid output to insulin minus tha basal acid output (PAOI-BAO) was less than 5 mEq/hr in 16 cases (52%) and from 5 to 25 mEq/hr in the remaining 15 cases. In 6 patients with proven recurrent ulcer, PAOI-BAO averaged 21.9 mEq/hr (range, 11.3 to 41.8); in the 4 patients with suspected recurrence, 9.5 (range, 4.4 to 11.8). The operative technique was changed in one respect; the distal 5 to 7.5 cm of the esophagus was skeletonized. In 14 patients, the mean PAOI-BAO +/- S.E. within 3 months of PGV was 1985 +/- 0.7 mEq/hr, and 13 of 14 values were less than 5 mEq/hr. One patient developed recurrent ulcer and required re-operation; this patient's value for PAO-BAO was 1.8 mEq/hr. The results show quantitatively that great differences in the completeness of PGV result from differences in the periesophageal dissection and emphasize its importance if optimal results are to be obtained and, especially, if the efficacy of the operation is to be judged.


Prognosis of gastric ulcer: twenty-five year followup.

Four hundred twenty-two patients with gastric ulcer treated during 1950-1960 were followed up to 25 years with a mean followup of 9 years. Nonoperative treatment was used in 59% with a hospital mortality of 35%, one-third of these deaths being directly due to gastric ulcer perforation or hemorrhage. Operative treatment was used in 41% of patients. The most common operation (86%) was gastric resection without vagotomy. Overall operative mortality was 16%; 34% for emergency procedures and 6% for elective procedures. Cachexia seemed to be the most important factor related to operative mortality. Nonoperative treatment resulted in more than twice the hospital mortality compared to operative treatment. Approximately one-half of all patients treated non-operatively had a recurrent gastric ulcer at some time during this study. The recurrence rate following definitive gastric resection was 1.3% compared with 16% during nonoperative therapy. Three-fourths of recurrences occurred later than two years and nearly half of recurrences after more than 5 years of followup. Patients with a prior history of overt bleeding from gastric ulcer disease particularly were at risk for further bleeding. There were coincidental duodenal ulcers in 10% of our patients and a 0.8% incidence of gastric cancer during followup. Long term followup demonstrates the superiority of operative treatment of gastric ulcer and also reveals the continuous propensity of such ulcers to recurrence following nonoperative treatment. Earlier elective operation in patients with overt bleeding, recurrence or persisting symptoms should decrease overall mortality and result in a lower overall long-term risk of ulcer complications.


Ultrasonography as an aid in the diagnosis and management of surgical diseases of the pelvis: special emphasis on the genitourinary system.

Technological advances, particularly the advent of the gray scale technique, has greatly extended the application and usefulness of this modality to clinical diagnoses and surgery. The ultrasonic beam uniquely provides anatomical profiles in the transverse (cross-sectional) and sagittal (longitudinal) planes of the body. Intra-rectal and intra-vaginal ultrasonic probes have provided unique definition of both the normal and pathologic anatomy of the pelvic organs. The present report is drawn from a continuing experience with ultrasonography of the genitourinary system with an update of current technological advances. Ultrasonography has proven especially valuable in the following clinical applications: 1) Early diagnosis of cancer (especially of the prostate); 2) Accurate staging of cancer of the bladder and prostate; 3) Monitoring of the response of the pathologic process to therapy.


Parotid neoplasms: a report of 250 cases and review of the literature.

A 25-year experience with parotid tumors was reviewed. From a total of 250 neoplasms, 173 were histologically benign and 77 were malignant. Benign mixed tumors accounted for 59% of all lesions. Clinical parameters used to diagnose parotid neoplasms were found to be unreliable in determining whether a given tumor was benign or malignant. The mean age for malignant lesions was 10 years greater than for benign lesions. The phenomenon of malignant transformation of a benign tumor was considered in four patients. Complete surgical excision is the safest and preferred method for diagnosis. Preoperative needle or incisional biopsy are associated with a high degree of local recurrence. The appropriate management of any parotid tumor is predicated on special histological type. Local excision or enucleation no longer have a place in the surgical management of benign parotid tumors. Postoperative tumor recurrence and morbidity are directly related to awareness of surgical anatomy and pursuit of correct surgical techniques for adequate resection. The five-year recurrence rate for 102 benign mixed tumors was 6%. Recurrence in malignant tumors varied with specific histological types but was generally high. Five-year survival for all malignant parotid tumors was 48%.


Comparison of Payne and Scott operations for morbid obesity.

One hundred five patients were operated upon for morbid obesity using accepted criteria for operation. Forty-five patients with the Payne operation (35 cm of jejunum anastomosed end-to-side to 10 cm of ileum) were compared with 45 patients having the Scott operation (30 cm of jejunum anatomosed end-to-end to 15 cm of ileum with the proximal cut end of ileum vented into the transverse colon). The weight loss in the first two years was similar, although the Scott procedure patients lost slightly more weight. Comparison of the two groups by a new grading system also showed little difference in the two procedures. The Scott procedure takes longer and subjects the patient to an additional anastomosis. Study of a smaller group of patients having the Scott operation with varying lengths of jejunum and ileum indicates that there should not be less than 30 cm of jejunum nor more than 15 cm of ileum left in continuity. The length of jejunum is particularly important in the production of weight loss, and accurate intraoperative measurement of intestinal length is crucial. In the postoperative period the length of functional jejunum and ileum can be determined by upper gastrointestinal barium roentgenograms.


[Comparative study of the most frequently used clinical methods for the analysis of immunoglobulins].

Methods for the quantitation of seric immunoglobulins are compared in this work: euglobulins by the Sia methods vs. IgM by radial immunodiffusion, and gammaglobulins with the zinc reactive vs. IgG by radial immunodiffusion. The results of the analysis of 81 sera of patients from the National Institute of Cardiology indicates that the values obtained with the methods for euglobulins and gammaglobulins are comparable to those obtained for IgM and IgG by radial immunodifussion.


[Molecular mechanism of noradrenaline transport by rat auricles in vitro].

The transport of tritium-labelled noradrenaline (3H-NA) into bisected rat auricular appendages in vitro, has been studied, using 14C-inulin as an extracellular space tracer, thus allowing a precise measurement of the 3H-NA transported into the cells. The NA transport time course is relatively fast, and initial rates lasted 5 min. in 150 mM sodium, 3 min. in 26 mM sodium, and about 1 min. in 50 mM potassium. Intracellular accumulation of 3H-NA by synaptic vesicles, was found not to be important in the first minute of transport. In the presence of 150 mM sodium a transport Km for NA of 0.59 +/- 0.06 muM (mean +/- S.E.M.) and a maximal velocity (Vmax.) of 2.44 +/- 0.43 pmol/mg. protein/min. were estimated. When sodium was lowered to 26 mM, the Km increased to 2.26 +/- 0.7 muM (P less than 0.001), while Vmax. showed no change. With 0 mM sodium (choline substitution) active NA transport is completely suppressed, and only a diffusional component can be discerned. No binding of NA to beta adrenergic receptors was found, and a small but highly significant binding to the non-specific catechol receptors could be detected.


[Single ventricle. II. Clinical study. Special studies and surgical treatment].

A study was made of 29 cases of single ventricle confirmed by autopsy, hemodynamic study, or both. It must be emphasized that the term single ventricle excludes whatever malformation which shows traces of an intraventricular septum. Thus conceived, the malformation has been seen to have different clinical courses, which only permit partial diagnosis that may suggest the possibility of "single ventricle". In live patients this can only be diagnosed with specialized studies. In outline, there exist 4 types of clinical hemodynamic behavior: 1) The type with marked increase of pulmonary flow, in which the single cavity vascular systems, pulmonary and aortic, had similar pressures. This type behaves, in a certain way, like large interventricular communications. 2) The type which behaves hemodynamically like a large hypertensive communication with delayed cyanosis of rapid evolution and with few manifestations of heart failure. 3) The third type also has pulmonary hypertension with delayed cyanosis. This differs from the preceeding in that there is a preferential flow in such a way that the venous blood proceeding from the right atrium empties into the aorta and the arterial blood from the left atrium empties into the pulmonary artery. 4) The fourth type is characterized by rapid cyanosis and from the anatomical point of view has stenosis or atresia of the pulmonary artery. An analysis was made of the varieties which within these four classes actually ocurred or cases which were present as theoretical possibilities: single ventricle with crossed great arteries; single ventricle with transposition of the great arteries; single ventricle with partial distortion of the great arteries; single ventricle with common trunc. A detailed analysis was made of the clinical, hemodynamic, electrocardiographic, and radiological manifestations which are seen in these combinations and an anatomic-embriologic classification is proposed on the basis of the systematization of the 29 cases of the present study. Finally brief considerations are made of the operability of those cases of single ventricle according to their anatomic variety.


[Diagnostic problems in visceral heterotaxia].

Due to the lack of uniformity in the criteria for formulating the diagnosis of the syndrome of heterotaxy, 12 cases with this abnormality were reviewed. The patients were selected on the following basis: symmetrical liver, changeable P waves in consecutive electrocardiograms, bronchial isomerism, hematological disturbances, anomalous relationship of the inferior vena cava and abdominal aorta, anomalous systemic and pulmonary venous drainage and complex cardiac malformations. The most frequent findings were: symmetrical liver, changeable P waves, anomalous systemic venous return, anomalies of the atrio-ventricular valves, particularly atrioventricular canal, aorto-cava juxtaposition, single atrium, anomalous pulmonary venous return, transposition of the great arteries and pulmonary stenosis. Less frequent anomalies were: atrial and ventricular septal defects, atrial isomerism, truncus arteriosus and partial distortion of the great arteries. The hematological disturbances as well as the radioisotope scanning of the liver and the spleen were of little help. Suggestions are given for the diagnosis of the syndrome and for the evaluation of present diagnostic procedures making necessary to use the data gathered with more precision.


[Congenital cardiopathies in the newborn].

Ten years experience in newborn congenital cardiac malformations with severe hemodynamic changes is reported. The anatomic diagnosis was made at necropsy (85%) or by cardiac catheterization and angiocardiography (15%). One hundred and twenty-six cases were found in which aortic valve atresia or stenosis, tricuspid atresia, cardiac anomalies associated to visceral heterotaxy, tetralogy of Fallot, aortic coartation, endocardial cushion defect, ventricular septal defect, total anomalous pulmonary venous return and pulmonary atresia with intact ventricular septum were the most common malformations. They presented with either cardiac insufficiency or hypoxia and acidosis. The principal anatomic features of these cases were discussed and the associated malformations in other systems was noted.


Antihypertensive activity of a propranolol analog (ORF 12,592) in rodents.

Studies were carried out to determine the antihypertensive effects of the 5-hydroxy derivative (ORF 12,592) of propranolol. Acute administration of ORF 12,592 produced a reduction in mean systolic blood pressure in desoxycorticosterone acetate (DOCA) rats and in spontaneously hypertensive rats (SHR). Propranolol was not effective in DOCA rats and produced a significant blood pressure reduction in SHR 48 hr after acute administration. These results demonstrated antihypertensive activity of an analog of propranolol and support the concept that the antihypertensive effects of propranolol may be mediated through a metabolite.


A comparison of skeletal, cardiac, and smooth muscle actions of dantrolene sodium--a skeletal muscle relaxant.

Dantroline sodium, a skeletal muscle relaxant, has been proposed to inhibit the relase of Ca++ from the sarcoplasmic reticulum. Such a mechanism suggests that other muscle contractile systems operating with the same Ca++ denominator should also be affected by the drug. In the present studies dantrolene sodium effects on smooth, cardiac and skeletal muscle have been evaluated with in situ and in vitro techniques. In anesthetized dogs in situ skeletal muscle contractions were inhibitied in a dose-dependent manner, but cardiac muscle contractions were not. Effects on intestinal smooth muscle responses were highly variable and of short duration. In vitro, ED50 values were developed with dantrolene sodium (0.15-120 mg/l) in DMSO for each tissue. Skeletal muscle was the most sensitive (ED50 = 4.1 mg/l), cardiac muscle contractions were not inhibited by the drug and intestinal smooth muscle (ED50 = 59.0 mg/l) was approximately 1/14 as sensitive as skeletal muscle. It is concluded that skeletal muscle is uniquely sensitive to dantrolene sodium. A hypothesis for this specific action is offered.


[Value of the indices of myocardial contraction rate in patients with chronic mitral insufficiency].

Determinations of dp/dt max, Vec and Vmax were made in 20 patients with chronic mitral regurgitation of several degrees. Each of these results was correlated with the corresponding ejection fraction. Only dp/dt max showed adequated correlation and few scattering of individual results, demonstrating its true dependence on the intrinsec contractile state of the left ventricule. Vec. and Vmax. determinations also reflected contractility changes, but their variability and difficult clinical applicability does not allow to recommend its routine utilization in a clinical setting. We could not demonstrate any influence of the valvular lesion on the results of the measured contractility indicators.


[Electrocardiography changes in newborn infants during the 1st 6 weeks of life in Mexico City. Physiological implications].

The electrocardiograms of 150 newborns who were born in Mexico City (2,240 m. above sea level) were obtained in the first 24 hours of life and six weeks later. The electrocardiographic changes were similar to those observed at sea level; AQRS shifted to the left, the T waves became negative in the right precordial leads and the R/S relation increased in the left precordial leads. Mid-altitude does not affect the pulmonary vascular maturation of the normal newborn.


The effect of acetylcholine on biliary excretion of ouabain in the physostigmine pretreated isolated perfused rat liver.

The effect of acetylcholine (ACh) on bile flow and biliary excretion of 3H-ouabain was studied in the physostigmine pretreated isolated perfused rat liver. ACh added into the perfusion medium to give a concentration of 1 X 10(-4)M after the addition of physostigmine (2 X 1 X 10(-5)M) transiently decreased bile flow and biliary concentration of tritium, originated from 3H-ouabain. A deficit of 34 mul of bile during the decreased bile flow could be calculated, compared to the control group. This deficit in bile flow possibly reflects an inhibitory secretory effect of ACh on canalicular bile secretion, or enhanced reabsorption of water in the biliary tree. The decline in the concentration of 3H-oubain in the bile after the addition of ACh indicates that ACh inhibits biliary transport of ouabain by an unknown mechanism, in addition to its effect on bile flow. Physostigmine alone possibly was without an effect on biliary elimination of ouabain. The results show that ACh retards the biliary elimination of ouabain through its influence on bile flow and biliary concentraton of ouabain.


[Effect of intravenous disopyramide on the hemodynamics of patients hospitalized in intensive care units].

A single dosis of disopyramide (100 mg), given intravenously in 10 min to 30 patients admitted in the coronary or respiratory care unit, induces a reduction of cardiac output of 13.4%, which is highly statistically significant, without altering the systemic and pulmonary pressures. The heart rate is also slightly diminished.


[Heart and circulatory effects of quinidine stereoisomers].

Quinidine sulfate shows dose-related activity. On the cardio-vascular system of anaesthetized cats. It reduces heart rate, prolongs QRS and QT of the ECG, lowers peripheral blood pressure and depresses slightly myocardial contractility. Quinidine hydrochloride lowers blood pressure but alters the ECG only in very high doses. Epiquinidine has no blood pressure lowering activity. According to the Easson and Stedman hypothesis this may be the result of stereoselectivity of alpha-adrenergic receptors. Only very high doses of the epimer produce a transient decrease of blood pressure. The ECG-waves are, however, markedly altered. QT is prolonged only with epiquinine-epiquinidine-sulfate. The salts of epiquinidine tested are much better water-soluble than those of quinidine.


[Diagnosis of venous thrombosis by using radioisotopes].

Thromboembolism problem is a grave complication which occurs with great frequency in patients hospitalized in a critical state. The association between periferical venous thrombosis and the thromboembolic accident is plainly demonstrated, although the accurate establishment of the clinical diagnosis of phlebothrombosis is only feasible in 50% of the cases. In the present work, we describe the methodology and the experience which we have acquired with the use of radioisotops in the diagnosis of these problems. We studied 64 patients to whom in the supine position we injected into a vein in both heels, from 3 to 5 millicuries of 99m-Tecnecio, practicing three stages: dynamic venography, a static study, and a pulmonary gammagram. In the normal cases, we clearly identified the tracts of the principal femural, iliac, and the inferior third of the inferior vena cava veins. In the abnormal studies, we observed the obstructive process manifested by the absence of radioactivity in the affected venous tract, with appearence of collateral circulation, definitive data which establishes with certainty the diagnosis. It can be concluded that the method is rapid and easily carried out, meaning that it could be a routine practice in all of those patients who are suspected of having this problem.


[Treatment of supraventricular paroxysmal tachycardia and auricular flutter by auricular stimulation].

Although the management of supraventricular tachycardias (SVT) and atrial flutter (AF1) with drugs or cardioversion is usually effective, their use in the high risk patient commonly digitalized, may be dangerous. Since the availability of an alternate therapeutic method is desirable, the usefulness of atrial pacing was evaluated in 31 episodes of tachyarrhythmia in 31 patients with varied heart conditions. The arrhythmia diagnosis and the stimulation were done through a right atrial electrode. In most cases the rate of stimulation was higher than that of the atria (up to 400 stimuli per min). Of 17 cases with SVT (four with preexcitation syndrome), pacing led to sinus rhythm (SR) in all, even though it was transient in two. SR was obtained in six of eleven cases of AF1, through a short lasting atrial fibrillation (AF) in three of them. Four patients with paroxysmal atrial tachycardia with A-V block changed to AF. SR was achieved shortly after termination of the procedure in two of the latter. It is concluded that atrial pacing is a valuable therapeutic method since it is effective, it has very low risk specially in digitalized patients, its does not require anesthesia and because it may be used repeatedly in case of recurrence. The technique of atrial pacing permits, in some cases, the identification of the mechanism responsible for the arrhythmia.


An increase of liver uptake of thyroxine, an initial step of an increased fecal loss of thyroxine in response to propylthiouracil in rats.

Propylthiouracil augmented fecal loss of thyroxine (T4), but methimazole was without effect in this respect in rats. In vitro uptake of labeled T4 by the liver was significantly enhanced by a small amount of propylthiouracil in the presence of dilute rat plasma. Methimazole was without effect under comparable conditions. In contrast, propylthiouracil and methimazole failed to affect in vitro uptake of labeled T4 by the kidney and diaphragm in the presence of dilute rat plasma. Since deiodination of T4 does not occur in the presence of dilute rat plasma, it is suggested that propylthiouracil specifically stimulates liver uptake of T4 as an initial step of an increase of biliary-fecal excretion of T4 in rats.


[Hemodynamics changes in children and adolescents with mitral valve replacement].

The authors analyze the pre and post-operative hemodynamic picture of 30 children and adolescents with mitral valve replacement, which corresponds to a group of 106 patients operated on from 1964 to 1974. At variable time periods, between 9 days and 48 months (average 28 months) from the valve replacement, a new catheterization was done. The majority of the studies were done in the period between 13 and 36 months. Of the 30 cases, 21 were carriers of the Starr-Edwards valve, and the rest of different types. The Starr-Edwards valves produced a lawering of the CVP from 23.0 to 11.0 mm. Hg (average values) whereas with the other types the average pre-operative figure was 21.0 and in the post-operative period it fell to 11.0 mm. Hg. In the group with SE valves, pre-operative SPP was an average of 64.3 and in the post-operative period it was 32.0 mm. Hg. In the cases of SE valves the pre-operative total pulmonary resistances were 12.3 units and post-operatively they fell to 3.7 units. With the other types of valves the pre-opeative average was 10.9 units and post-operatively it was 5.3 units. The hemodynamic results obtained over a period of time with valvular substitution were similar in the distinct types of valves. However in the SE the benefits resulted more constant. The value of radiological and electrocardiographic study in order to predict the early post-operative hemodynamic changes is discussed. These studies serve essentially for a long range evaluation, whereas the hemodynamic, and clinical improvement maintained a strict relationship. This work shows that, in children and adolescents, the presence of severe venous-capillary and arterial pulmonary hypertension, and the elevated pulmonary resistences, are not contraindications for surgical treatment. It equally proves the eficacy of the valvular replacement, when the surgical indication and the control of the patients are handled in the proper way.


Neurotoxicity of digitoxin in adult and newborn rats: drug distribution.

Electrocardiographic monitoring of adult and 1 week old (newborn) rats during severe acute digitoxin toxicity demonstrated a lack of acrdiotoxicity despite marked neurotoxicity in both age groups. To examine the possibility that drug disposition is a factor in the unusual digitoxin sensitivity of newborn rats, 3H-digitoxin distribution in liver, heart, brain, kidney, adrenal, blood and fat was compared in 1 and 3 week old (weanling) rats at 2, 12 and 24 hr. H3-label was rapidly sequestered by the liver in weanlings but not in newborn rats. Newborns had significantly higher concentrations of 3H-substance in all other organs, particularly in brain (greater than 25% of the administered dose at 24 hr), indicating a cerebrotoxic basis for the newborn's sensitivity to digitoxin. Only trace amounts of 3H-substance were recovered from adult rat brain during severe neurotoxicity (72 hr) suggesting that digitoxin metabolites may be potent cerebrotoxins. Extremely high adrenal concentrations were noted in all animals.


The effects of digitoxin and its metabolites on the transmembrane potential and contractile characteristics of guinea-pig ventricle strips.

The effects of 10(-7) and 10(-6) M digitoxin, and some of its metabolites, digitoxigenin-bis-digitoxoside, digitoxigenin-mono-digitoxoside and digitoxigenin on the transmembrane potential and contractile characteristics of guinea-pig right ventricle strips were studied to define the role of the sugar side-chain in these cleavage products of digitoxin. Digitoxin and digitoxigenin produced their maximum inotropic responses, without induction of arrhythmias, at about 30 min. However, the bis and mono compounds produced arrhythmias within 12 min, so the inotropy recorded may not be the maximum response. Digitoxin with 3 sugar residues and the bis compound with 2 sugar residues produced a prolongation in the action potenital duration. In contrast, the mono compound with one sugar residue and the digitoxigenin with no sugar residue produced a shortening of the action potential duration. There may be a relationship between the number of sugar moieties and the action potential duration; digitoxin and its bis derivative increased the action potential duration and mono- and digitoxigenin decreased the action potential duration. There also appeared to be an unusual relationship between the number of sugar moieties and induction of arrhythmias; arrhythmogenicity occurred at the doses employed with only the bis- and mono-digitoxoside. Finally, there appeared to be no simple relationship between chemical structure and inotropic potency.


Relationships between chronotropic effect, 1-3H-noradrenaline uptake and tissue concentrations of desipramine, protripyline and doxepin in rat isolated atria.

The pharmacological effects of three tricyclic antidepressant agents (desipramine, protriptyline and doxepin) are evaluated in rat isolated atria in relation to their accumulation and efflux kinetics. The pharmacological effects studed are: inhibition of 1-3H-noradrenaline uptake, potentiation of 1-noradrenaline chronotropic response, and changes in spontaneous atrial rate. All drugs inhibit noradrenaline uptake and potentiate noradrenaline chronotropic response (desipramine congruent to protriptyline greater than doxepin). Desipramine and protriptyline, at concentrations of 10(-7) -- 10(-6)M stimulate the spontaneous rate; higher concentrations (greater than 10(-6)M) depress it. Doxepin has only a negative chronotropic effect. When the drugs are removed from the incubation medium, the depressing effect starts to disappear immediately for doxepin and desipramine and after 20 min for protriptyline. On the contrary the stimulating effect persists after repeatedly washing the preparations. Desipramine, protriptyline and doxepin extensively accumulate in the myocardial tissue (desipramine larger than or equal to protriptyline greater than doxepin). In the efflux studies doxepin is washed out more rapidly than desipramine and protriptyline. Although the kinetics of uptake and efflux of the three compounds are not sufficient to interpret their different pharmacological activities in isolated atria, they give useful information on the persistance of the sympathomimetic effect and the rapid disappearing of the negative chronotropic effect after washing.


Calcium-dependent, iproveratril-resistant contractions of aortic strips induced by a convulsant barbiturate.

At 3 X 10(-5) M concentratons, 5-(2-cyclohexylideneëthyl)-5-ethyl barbituric acid (CHEB) causes a contraction of rabbit aortic strips that is equivalent to about half of the maximal response to norepinephrine. If a calcium-free medium is substituted for normal bathing solution and drug is added immediately thereafter, there is no response to the convulsant barbiturate but a nearly normal response to norepinephrine. When calcium is replaced in stepwise increments, the contractor response to CHEB appears in corresponding increments. The prompt influence of changes in external calcium-concentration suggests that CHEB-induced contraction occurs as a result of calcium influx into cells rather than a release of free calcium from previously accumulated intracellular stores. CHEB effect, like that of potassium, is prevented by pretreatment with lanthanum (5 X 10(-3)M). CHEB differs from potassium in that its effects are even more sensitive to changes in extracellular calcium concentration. Nevertheless, CHEB can contract aortic strips in the presence of iproveratril at a concentration (10(-4)M) that blocks all response to potassium (100 mM).


Effect of some antihypertensive drugs and catecholamine depletors on the plasma renin activity in the rat.

The effect of some antihypertensive drugs and catecholamine depletors on the plasma renin activity (PRA) has been investigated in the rat. Diazoxide and CIBA 4416-Go. increased and clonidine decreased the PRA significantly. The increase in PRA following diazoxide was partially blocked by oxprenolol, adrenalectomy and demedullation. Adrenal cortex does not seem to contribute to this increase in PRA following diazoxide. Pretreatment of rats with reserpine, guanethidine or 6-hydroxydopamine alsine, guanethidine and 6-hydroxydopamine when given acutely or repeatedly (for 3 days) did not produce any significant change in PRA. It is concluded that vasodilators like diazoxide and CIBA 4416-Go. increase PRA resulting from sympathetic activation which follows hypotension; this increase is blocked by catecholamine depletors like reserpine, guantethidine and 6-hydroxydopamine.


Role of neuronal and extraneuronal factors in temperature mediated responsiveness of adrenoceptors.

Changes in bath temperature caused changes in the adrenergic responsiveness of rabbit iris dilator muscle as indicated by shifts in dose-response curves along the log axis and changes in maximum responses. Responses of control tissues to an alpha agonist (norepinephrine) were increased at lower temperatures and responses to a beta agonist (isoprenaline) were increased at higher temperatures. Responses of control tissues were compared with responses of tissues pretreated with cocaine or with responses of adrenergically denervated tissues (chemical and surgical). Changes in ED50 values with temperature change are similar in control, cocaine pretreated or denervated muscles. In contrast, changes in maximum response with temperature change are reversed by cocaine pretreatment or denervation. Pretreatment of tissues with an inhibitor of catechol-o-methyl transferase (tropolone) or an inhibitor of monoamine oxidase (iproniazid) did not affect the temperature sensitivity of adrenoceptors. Also, responses to terbutaline, a beta agonist not susceptible to catechol-o-methyl transferase, changed with temperature. These data indicate that for rabbit iris dilator muscle both a neuronal and an extraneuronal component are involved in adrenoceptor response changes induced by temperature change and that changes in rates of activity of metabolizing enzymes are not involved.