Penile carcinoma in renal transplant recipient.

A case of squamous cell carcinoma of the penis occurring in a renal transplant recipient is presented. Despite a markedly increased incidence of epidermoid carcinoma in the transplant population, this is the first reported case of penile carcinoma occurring in a renal transplant recipient. As with other superficial epithelial tumors in this population, conventional therapeutic techniques are recommended. However, excisional biopsy is recommended for penile lesions at the time of initial presentation or if any clinical suspicion exists.


Bilateral renal malakoplakia.

A case of malakoplakia is presented which was confined to the renal parenchyma of both kidneys in a thirty-five-year-old woman in whom fatal renal failure developed in three weeks. Bilateral renal malakoplakia is rare, and unlike malakoplakia of the bladder, it behaves as a progressive, destructive, and fatal disease.


Reversible renal artery stenosis in renal transplantation.

Spontaneous regression of an arterial stenosis in a renal transplant recipient is documented. Implications of this observation and possible pathogenic mechanisms are discussed.


[Peridural anesthesia during mitral commissurotomy on patients in the late stages of the disease].

Peridural anesthesia in T1--T6 regions was used together with general anesthesia in closed mitral commisurotomy in 40 patients with the disease in stages 4 and 5. The study was aimed at the evaluation of the effect of peridural anesthesia upon hemodynamics, gas exchange, adrenal cortex function, energy exchange in the myocardium and the evaluation of its expediency for these patients. The authors studied hemodynamic alterations (HR, AP, CVP, MV, CBV etc.), changes of acid-base equilibrium and in the blood gases, concentration of summary 11-oxycorticosteroids in the blood plasma and of creatinophosphate in the myocardium left auricle. On the grounds of these studies the authors have come to some practically important conlusions.


[Autoalloplasty method in deep defects in the femoral head].

A method of the replacement of the femoral head deep defects, resulting from the removal of pathologic foci, by means of combined auto-allografts, devised by the author, is described in the paper. This method allows for the transplantation of a bone autograft, filling up a greater portion of the defect, together with an osteocartillaginous allograft with a thin (up to 1 cm) spongy base.


[Theoretical basis for and the results of using bone marrow-devoid spongy allografts in the surgery of tuberculous spondylitis in adults].

Experimental studies over 189 animals have proved that spongy allografts, devoid of the bone marrow, possess high plastic properties, get very soon replaced with a newly formed bone tissue and reconstruct. Experimental and clinical findings advocate, the rationality of their use of antero-lateral spondylodesis in tuberculous spondylitis.


[Perforations of the gastrointestinal tract by a fish bone].

A brief of the literature dealing with perforations of the gastrointestinal tract at its different levels with fish bones is set forth. In recent 20 years the author has managed to collect 68 observations published in the home literature. 6 cases of the perforation of the duodenum, the small intestine, the ileum with injuries to the mesenteric vessels, resulting in massive bleeding, the caecum and the colon in the hepatic angle are presented. All the patients were operated upon. 2 patients died.


[Organ-preserving procedure and blood retransfusion in children with splenic ruptures].

An analysis of anesthesiologic and surgical tactics in the treatment of children with spleen traumas proves the reliability and effectiveness of the blood retransfusion and of the principle of the organ-preserving interventions, according to the amount of the blood loss and the character of the spleen ruptures. In authors' opinion splenectomy is indicated in total crush of the spleen and the detachment of its vascular pedicle. There were no fatal outcomes.


[Role of forced detoxication for correcting microcirculatory disorders in suppurative, septic diseases in children].

The author has studied microcirculatory changes in pyo-septic diseases in 112 children, 10 of them--healthy ones (control group). The use of an intense diuresis in complex treatment of severe forms of pyo-septic diseases in children results in a considerable decrease of the blood protheolytic activity and toxicity and allows to interrupt microcirculatory disorders 3 or 4 days earlier than the routine method of detoxication therapy.


[Surgical treatment of fractures of the olecranon].

56 patients with olecranon displaced fractures have been studied. The diastasis exceeding 1 cm and the failure of the closed reposition served as indications for surgical interventions. The olecranon fixation was performed by means of silk and wire sutures (11 cases), with a screw (8), with a rod (4), with a compression fixative, devised by the author (33). The check of the late results in 54 patients has shown the union of the fracture and good results in all the cases, but as to the terms of the functional and working capacity restoration--it was 2 to 3 times shorter with the osteosynthesis with the compression fixative than with the suture or rod osteosynthesis.


Absence of bacterial adherence in the establishment of experimental mastitis in mice.

The possibility of adherence of Staphylococcus aureus, Staphylococcus epidermidis, Escherichia coli or Streptococcus agalactiae to the epithelium of the mammary gland was investigated by inoculating them into this gland of mice. S. aureus, S. epidermidis and E. coli did not adhere to alveolar epithelium in suckling or non-suckling mice. S. agalactiae adhered to alveolar epithelium in non-suckling mice but adhesion was not sufficiently strong to withstand suckling. Bacterial adherence probably does not play a significant role in the establishment of mastitis by these organisms.


Spina bifida in the dog.

Spina bifida was diagnosed in four English Bulldogs and one Collie dog. These cases and the examination of records from the Veterinary Medical Data Program suggested a high incidence of spina bifida in the English Bulldog. Urinary and fecal incontinence was the most common reason for initial examination for the five dogs. Radiographs and myelography confirmed the diagnosis of spina bifida. Blood, cerebrospinal fluid and urine analyses did not aid diagnosis but urocystitis was identified. In addition to spina bifida, clinical signs and morphologic changes in the spinal cords of all five dogs fulfilled the criteria for an additional diagnosis of spinal dysraphism. A common pathogenesis for the two conditions is suggested.


[Cytopathic effect of the Newcastle disease virus on the BHK-21 cell line].

The cytopathic effect (CPE) of the Newcastle disease virus (NDV) in the BNK-21 permenant cell line is studied in a series of experiments. The CPE is assessed as a percentage of hemadsorption and polykaryocytosis, and the dynamics of the viral replication is followed up with the aid of the immunofluorescent method. The effect of the cyclohexamide protein inhibitor of the replication of various NDV strains, on the CPE, respectively, is likewise studied. Five vellogenic, one mesogenic and one lentogenic strains are used in the experiments. It is found that through the immunofluorescent method the viral replication is delayed some three hrs in the case of the La Sota lentogenic strain in comparison with the other strains used. The direct relationship, already established, between the virulence of the NDV and the percentage of haemadsorption and polykaryocytosis is confirmed also in the BNC-21 heterologous cellular tissue. On the basis of this relationship, a rapid typing method of virulent from avirulent field NDV strains is suggested. The blocking effect of the cyclohexamide protein inhibitor on the CPE in NDV is demonstrated in the BNK-21 line, as a result of the blocking of the viral specific protein synthesis.


[Histopathological studies of silworms (Bombyx mori Linn.) spontaneously infected with nuclear polyhedrosis].

Pathohistological changes in silkworms, spontaneously affected by nuclear polyhedry are investigated. The J-124 X C-122 hybrid after the fourth moulting is tested. After being subjected to a low temperature stress the silkworms were killed and material for pathohistological studies were taken from them. It is established that the most suitable tissues for the replication of the polyhedry virus of the silkworm were the cells of the fat bodies, the tracheal matrix and the hypoderm. Not all polyhedra form simultaneously. The virus as polyhedral bodies is detected in the infected tissues, cells respectively, on the 55th day (at the earliest) by the action of the low temperature stress. The histopathological investigation is recommended as a method for reliable and relatively early diagnoses.


[Presence of E. coli bacteria in raw and pasteurized cow's milk].

Investigated for the presence of E. coli-bacteria belonging to the O-groups of dispeptic strains, are 85 samples of raw and 212 pasteurized milk, taken from subsequent departments of the milk-producing industry. Dispeptic E. coli are detected in 11.76 per cent of the samples of raw milk studied, and in 5.18 per cent in those of the pasteurized milk. No coli forms are established in samples, taken directly from the pasteurizing equipment. The secondary infection with E. coli results from the use of vessels and equipment in the course of the technological process. E. coli-bacteria, belonging to the O-groups of dispeptic strains, are demonstrated in samples both with the aid of a coli-titre, in conformity with standard requirements, and in samples that are not standard, according to this indice. The 21 strains of E. coli-bacteria isolated are referred to the following O-groups: 06, 025, 026, 055, 078, 086, 0111, 0119, 0124, 0125 and 0127. Some of the strains isolated manifest an atypical behaviour to lactose and sucrose in comparison with the properties, indicated in the scheme by Kauffmann.


[Antineoplastic action of retinol and its derivatives (retinoids)].

Morphologic alterations in epithelium, caused by imcompetency of retinoids in a diet, were similar to those, obtained after treatment with chemical carcinogens. This suggests to use various derivatives of nature retinoids for treatment of epithelial tumors in skin and other tissues. Cultures of mouse prostatic gland and skin epithelium from metatarsus of chicken embryo were used for study of antitumoral activity of various synthetic retinoids. The most active preparations proved to be cyclopentenyl- and trimethyl methoxyphenyl ethyl ester derivatives of retinolic acid. The antitumoral effect of retinolic acid and its derivatives appears to involve a tight binding of the preparations with specific protein and inhibition of ornithine decarboxylase in tumor. The enzyme is well known to be related to synthesis of DNA, RNA and protein.


[Assessment of the cardiac output by impedance cardiography (differential rheography) to give optimum continuous positive pressure ventilation (author's transl)].

It is very important to know the cardiac output in artificial positive pressure ventilation for the determination of the exact dosage of dopamine and the endexpiratory pressure. Invasive monitoring of the cardiac output is not suitable for routine bedside use. In our study we looked into the question of whether the dosage of dopamine in continuous positive pressure ventilation could be controlled by impedance determination. Differential rheography, as described by Kaindl, Polzer, and Schuhfried, was used in the study. Relative changes in cardiac output after dopamine administration are shown with sufficient accuracy using the above-mentioned method.


[F' transfer from Escherichia coli to Proteus mirabilis].

The task of this work was the establishment of an effective transfer system for F'-plasmids from Escherichia coli to Proteus mirabilis. It is shown that cells of PG VI act as recipients in crosses with E. coli F' strains but with a low transfer rate of the plasmid. The presumption that a restriction -- modification system in P. mirabilis was the only reason for the low transfer could not be confirmed. An indirect selection method was developed to isolate P. mirabilis cells which are better recipients. Conjugation experiments showed that the isolated mutants had a better recipient capacity (increase of about 100). This is true not only for the transfer of a F'-plasmid but also for a R-plasmid. The stability of these plasmids in the mutant cells, however, was much lower than in the wild type.


[Comments on cerclage (author's transl)].

Cerclage was performed by us during the past 5 1/2 years in 71 women (0.68% of all births). In 23 women, cerclage was performed prophylactically and in 48 women as therapy of early maturing of the cervix. Cerclage was applied, mainly according to McDonald, between the 13th and 33rd weeks of pregnancy, maximum incidence of surgery occurring between the 17th and 27th week (63%). Cervical insufficiency is only temporarily removed by cerclage. After the suture has been removed, cervical dilatation should be variable. If this is not the case, the diagnosis of "cervical insufficiency" must be considered doubtful. This criterion was fulfilled in 83% of the therapeutic cases of cerclage compared with 43% in the prophylactic cases. Within 24 hours after removal of this suture, 39 patients (59%) had given birth. The prophylactically indicated cerclages often did not meet the criterion cervical dilatation uteri after removal of suture and rapid birth", whereas the majority of the therapeutic cerclages complied with the criterion. Our results are compared with those published in the literature. Despite the trend noticeable in literature towards a more liberal indication of cerclage, we will continue to perform this operation with discretion.


[The Zinsser-Cole-Engman syndrome. A contribution to congenital poikilodermias as well as a contribution to familial pancytopenias].

The Zinser-Cole-Engman-syndrome (Dyskeratosis congenita), which is characterized by the cardinal symptoms pigmentatio reticularis, onychodystrophia and leukoplakia oris, is discussed as a clinical entity, which is different from Fanconi's anemia and Braun-Falco-Marghescu-syndrome. A review of the literature is given.


[Results of modern syphilis serology in blood donors, at the same time a contribution to spontaneous healing of syphilis].

261 out of 336 845 blood donors have been shown to had undergone a syphilitic infection. About 52 per cent of these donors have had knowledge of their infection and of specific treatment of the disease. In about 43 per cent of the investigated cases the T. pallidum infection has had probably an inapparent course and healed without treatment, that means spontaneously. In times with an increasing number of infections by T. pallidum blood banks have to look intensively for donors which are in the first stage of primary syphilis. For identification of these people and for the differentiation between antibodies against T. pallidum and apathogenic treponemes the use of a TPHA-ABS test is discussed.


[Immunopharmacology of levamisole].

Levamisole, a simple chemical, first introduced as a broad spectrum anthelmintic, is an immunotherapeutic agent with anti-anergic properties. It is the first member of a potential new class of immunologically active, probably thymomimetic compounds. The present knowledge from studies on isolated cells, experimental animals, healthy volunteers and patients with various diseases shows that levamisole behaves physiologically as a thymus hormone and restores to normal the functions of phagocytes and T-lymphocytes in compromised hosts and induces T-cell differentiation. The biochemical mechanism of action remains still unclear. The various mechanisms by which levamisole might act are not mutually exclusive. Levamisole is well tolerated in doses of 2,5 mg/kg. Side-effects are markedly more frequent in patients with rheumatoid arthritis than with other diseases. The only potentially fatal adverse reaction is agranulocytosis.


[Effect on lymphocyte and granulocyte function of levamisole in chronic mucocutaneous candidamycosis].

In 5 patients (3 children, 2 adults) suffering from familial or non-familial chronic muco-cutaneous Candidosis (CMCC) combined with cellular immune deficiencies of different extent, an immunostimulating therapy regimen with levamisole was performed over 6 months. Post-treatment clinical and immunological re-examinations offered a favourable effect on the cellular immune system in all patients. As to the general health condition, in the children all clinical symptoms of CMCC clearly improved or disappeared completely, whereas in both adult patients no satisfactory clinical effect of levamisole therapy could be observed so far.


[Levamisole therapy under different dermatological indications].

More than 180 patients were treated for immunostimulation with levamisole within three and a half years. The results were statistically evaluated in 128 subjects. A highly significant improvement was noted in 44 patients suffering from recurrent herpes simplex labialis, facialis and oralis. 14 patients with recurrent herpes genitalis, lumbalis and glutaealis only experienced a reduction of the recurrence frequency. Aphthae in 16 subjects became less frequent and pain was reduced. Levamisole should be tried in recalcitrant chronic candidoses and bacterial infections not responding to specific antibiotic treatment. Slight side effects are relatively frequent, but severe ones are only rarely observed.


[Traumatic injury to the heart. A clinical study (author's transl)].

Nonpenetrating chest injuries often lead to cardiac traumas. Posttraumatic coronary thrombosis with myocardial infarction is shown in two cases. Large anterior aneurysm occured after total occlusion of the descending anterior in both cases. There was no correlation between the severity of the chest injury and the ensuing cardiac damage. An intramural anterior infarction was seen in a third case; because of a normal coronary angiogram an intramyocardial bleeding without coronary thrombosis can be suspected. A direct connection between chest injury and myocardial infarction can only be assumed if there is an onset of symptoms within 24--48 hours after thoracic trauma. A coronary angiogram should be performed in any case of myocardial infarction following chest injury especially in medico-legal cases.


[Effect of indications and pre-existing conditions on the result of McDonald's cervix-closure surgery].

Authors have performed the McDonald cerclage operation on 172 gravidae because of cervical incompetence. From these pregnancies 80.2 per cent of the infants have survived over the sixth day. While with operations performed on the basis of extended indications for surgery an effect of 56.5 per cent was achieved, it was in cases of classical ones 92.8 per cent. Two complicated cases are reported caused by blastospores or bacteria respectively, isolated also in the vaginal secretion which have ascended into the uterine cavity. Both cases resulted in fetal death and in a septic condition of the mother. It is emphasized that the normal vaginal bioflora is essential condition for the cervical suture.


[Surgical obstetrics in past and presence (author's transl)].

The history of surgical obstetrics is highlighted by discussing the historical development of forceps delivery, vacuum extraction, forceps vectis (application of a single blade only), embryotomy, and caesarean section operations. Finally present status of operative obstetrics is outlined from a modern point of view.


Fosfomycin therapy of experimental infections in mice.

Fosfomycin inhibits the development of severe pyogenic infection by Staphylococcus aureus in kidneys if administered during establishment of infection. It inhibits the development of lethal infection by Escherichia coli. It has a positive therapeutic effect on listeria infection in mice even with a fosfomycin resistant mutant.


The lethal effect and the inhibition of colicin production by leucine on a phenylalanine requiring E. coli strain as a function of age and dilution of culture.

The lethal effect caused by leucine on a phenylalanine requiring strain of Escherichia coli K-12 (7), was found to be strongly affected by the age of the culture. Early log cells were the least sensitive, while older cells became more sensitive to leucine. Another important factor affecting the sensitivity of this strain to leucine in liquid medium was the range of dilution of the culture. The age sensitive culture reacted to leucine only when its dilution was at a certain specific range. The sensitivity to leucine of a culture treated at the "right" age and at the proper dilution was proportional to the concentration of leucine. Colicine production was studied with cultures treated in various ways using a colicinogenic derivative of the leucine sensitive strain. It was found that leucine in a rather high concentration (2 mg/ml) prevented colicine production when given in the absence of phenylalanine, while phenylalanine at a very low dose (0.2 microgram/ml) could reverse this inhibition. The effect of leucine on colicine production, like lethality, operated only under certain conditions of culture dilution, but unlike lethality, was not very sensitive to the age of the culture. Tryptophane was found to resemble leucine in its effects on viability and on colicine production in liquid medium. Its effect was likewise reversed by a small amount of phenylalanine, and like leucine, tryptophane acted best only under very specific conditions of culture dilution.


[Effect of immunization on the radioresistance of mice to the action of 90Sr].

The preliminary immunization with heated Proteus vulgaris culture introduced in a single injection was found to have a positive influence on the resistance of white mice to radiation emitted by incorporated 90Sr. This effect was manifested by an increase in the survival rate and the mean survival time of the animals, as well as by their increased physical endurance, and the stimulation of recovery process in the spleen.


[Biological preparations in the overall therapy of children convalescing after dysentery].

In studying the state of microbial population in the intestine of children after dysentery dysbacteriosis was revealed in 72.7% of cases. Use of biological preparations normalizing microbial population in the intestine (colibacterin) in 859 children reduced the incidence of protracted forms of the disease and of repeated excretion of the causative agent in comparison with the control group (785 children).


[Use of the passive hemagglutination inhibition reaction for the purpose of determining the antigenic activity of anatoxins in vitro].

The work deals with the study of the possibility of using the passive hemagglutination inhibition test (antibody neutralization) for the determination of the antigenic activity of botulinum toxoids, types A, B and E. Erythrocytic diagnostic preparations were shown to allow the determination of up to 0.1 g of antigen. At the same time in vitro determinations were found to satisfactorily correlate with the results of in vivo determinations of the antigenic activity of these toxoids in the antitoxin-fixation test.


[Method of determining the microbial flora of the small intestinal cavity and mucosa in different gastrointestinal tract diseases].

Intestinal microflora in patients with chronic enterocolitis and duodenal ulcer was studied. Both the cavity of the small intestine and the structures of its mucosa were investigated. The method of aspiration biopsy was used, the samples of multiple washings of the intestinal mucosa and its homogenate were used for seeding. The results thus obtained in indicated that the structures of the mucosa contained microorganisms similar to those isolated from the intestinal cavity, but in lesser amounts and with different characteristics. The proposed method of detecting the microflora in the intestinal cavity and mucosa is simple and can be used in clinical practice.


[Use of a computer to predict the development of vertebrogenic lumbosacral radiculitis].

On the basis of a linear discriminant analysis, a special system of automatized prognosis and early diagnosis of vertebrogenic lumbosacral radiculitis was elaborated with the aid of a computer. The system permits to elucidate among the population examined a group of individuals with high risk of the disease. The information file for computer processing included data of the studies on 24 risk factors in 350 patients and 450 individuals in the control group. The prognostical value of different risk-factors is discussed. The results of the system trial in industrial conditions are given.


Aging and the cardiovascular system.

With advancing age blood pressure rises in most populations with the exception of some isolated tribes. In western countries 30 to 40% of the people above the age of 60 years have casual blood pressure levels greater than or equal to 160/95 mm Hg. Advancing age per se produces a number of physiological changes related to blood pressure, such as a decrease in cardiac output, an increase in peripheral vascular resistance and a decrease in plasma renin-angiotensin-aldosterone levels. The mechanism causing the elevation in pressure with age are unknown though increased rigidity of the great vessels contributes to the rise in systolic pressure. There is a decline in the sensitivity of the baroreceptor reflex, but the contribution of this to the elevation of pressure has not be elucidated. Elderly patients with uncomplicated essential hypertension have a low cardiac output and high peripheral vascular resistance. The rise in blood pressure is associated with an increased cardiovascular morbidity and mortality even in the elderly hypertensives. The available data on the efficacy of hypotensive treatment in the elderly is scanty. There are no data proving that hypotensive therapy prolongs life. Controlled studies on the prevention of organ damage especially cerebrovascular accidents are inconclusive, showing either a significant decrease or no effect. Isolated reports illustrate, however, that drastic blood pressure reduction can provoke serious side effects, thus decreasing the quality of life. Hypotensive treatment is indicated in elderly hypertensive patients with hypertensive retinopathy grade III or IV, congestive heart failure or cerebral haemorrhage, in elderly patients with a markedly elevated diastolic blood pressure (greater than or equal to 120 mm Hg) and a trial of hypotensive therapy should be offered in milder forms of hypertension when it is accompanied by certain specific symptoms such as angina, headache and dyspnoe. The management of elderly hypertensive patients is more difficult than in the young. General measures are often not well accepted. The dose adjustment of the hypotensive agent is more critical and volume depletion or orthostatic hypotension are more likely to occur.


Heritability estimates from twin studies. I. Formulae of heritability estimates.

Over the past 50 years a large number of methods have been proposed for estimating heritability from twin studies. The present paper describes the most commonly cited of these estimates as a first step in evaluating their usefulness. A critical review will then follow.


[Neurosurgical anatomy of Forel's field H as applied to campotomy].

Based on a study of 100 specimens of the brain of adult humans, data are presented on the variability of the shape and size of Forel's H field and its position in relation to intercerebral orienting points depending on the length of the intercommissural line and the breadth of the cerebral hemisphere and third ventricle. The stereotaxic coordinates, the shape and size of the foci of destruction for campotomy are given with due consideration for the individual anatomical features of the H field.


The effect of positive end expiratory pressure after three types of open heart surgery.

It has previously been shown that patients who have undergone mitral valve replacement (MVR) tolerate a positive end expiratory pressure (PEEP) of 1.0 kPa better than patients who have had aortic valve replacement (AVR). the difference was explained by the fact that the mitral patients had pre-existing pulmonary vascular disease. In the present study the effect of PEEP up to 2.0 kPa is investigated in three types of operations: aortocoronary bypass graft (ACBG), mitral valve replacement, and aortic valve replacement; there were five patients in each group. We found that our mitral patients tolerated PEEP better than the two other groups, and that tolerance was not correlated to a higher pulmonary vascular resistance, but rather to a higher level of pulmonary capillary wedge pressure. The influence of PEEP varies in different types of patients and the effect is still difficult to predict.


Spontaneous breathing with continuous positive airway pressure in adult respiratory distress syndrome.

The authors describe three systems of spontaneous respiration with positive end expiratory pressure (P.E.E.P.) : the system of continuous positive airway pressure (C.P.A.P.), the bubble and the intermittent mandatory ventilation with C.P.A.P. (I.M.V.-C.P.A.P.) by Servo-Ventilator 900 B. The results are conclusive with the C.P.A.P. unit used for post-traumatic adult patients in acute respiratory distress and for patients who have been anesthetized for more than three hours. The PaO2 significantly increase in subjects whose PaO2 in the ambient air without P.E.E.P. is lower than 70 mm Hg. The bubble is less used due to its drawbacks. The Servo 900 B offers many possibilities, one of which is reported in this paper.


[A stereological study of the angioarchitecture of the cerebral cortex in rabbits].

An attempt is made to describe the vascular architecture of the cortex employing a stereological method. Brains perfused with india ink were sectioned in frontal, sagittal and tangential levels. The course of the vessels was described as a spatial vector from the center to the penetration point of the globe or radius 1. In order to present a two-dimensional image, we projected the penetration point together with the longitudinal and horizontal meridians of the globe in an orthograde fashion into the level of the image. The frontal and sagittal sections were projected in an equatorial image, the tangential level was projected to an axis. Direct observations and stereological imaging demonstrated that, in lamina 4, there is a relatively constant hexagonal vascular net with branching angles of 60 degrees at an edge length of 50--60 microns.


The cell masses in the diencephalon of Amphisbaena darwini heterozonata Burmeister (Amphisbaenia, Squamata, Reptilia).

The cell masses of the diencephalon of Amphisbaena darwini heterozonata are studied and confronted with those of other reptiles, specially with the burrowing ophidian Typhlopidae. The main differences are in the thalamus dorsalis. The amphisbaenids share with the Typhlopidae the absence of the lateral and pretectal geniculate bodies, and share with the squamate reptiles, differing from the typhlopids, the remaining structures of the dorsal thalamus, characterized by the well-developed nucleus rotundus. These features support the idea that the amphisbaenids could be situated within the Squamata at the same level as in Ophidia and Lacertilia. The adaptive processes toward a burrowing behavior have not been the same in amphisbaenids and in the typhlopids. The causes of the dissimilarities of the dorsal thalamus could be related to other sense and non-sense systems apart from the optic. The morphology of the elements of the cell masses has been studied by the Golgi method.


Replica study of plaque formation on human tooth surfaces.

Plaque formation on buccal tooth surfaces was studied by replica technique, consisting of impressions using low viscosity silicone impression materials and positive models produced in epoxy resins. Bacterial accumulation occurred near the cemento-enamel junction in 6-hr specimens, and subsequently expanded in a coronal direction. This development took place partly by extensions of single layers of bacteria, and partly by a pattern where the colonization was mostly restricted to vertical enamel cracks. Plaque accumulations were also frequently located in abrasion grooves and surface pits in the enamel, and prolific plaque areas were consistently surrounded by a monolayer of bacterial cells. Globular and hemispheric structures which occurred, especially on root surfaces immediately after cleaning, were probably artefacts caused by air bubbles or remaining moisture. In separate series of experiments it was demonstrated that improved reproduction of details from the plaque could be achieved by repeating the replicating procedure. The findings indicate that plaque formation starts by adsorption and proliferation of individual bacteria on tooth surfaces, and not by adsorption of aggregates of cells. Special attention should be directed against the problem of artefacts and moisture in replica studies of dental plaque.


Morphologic studies on dental plaque formation.

The present summary and the following papers (I--VII) are submitted in partial fulfillment of the requirements for the degree of Doctor Odontologiae at the University of Bergen. 1: Growth of dental plaque on hydroxyapatite splints. A method of studying early plaque morphology. J. Periodontal Res. 1974, 9, 135--146. II: Pellicle formation on hydroxyapatite splints attached to the human dentition: Morphologic confirmation of the concept of adsorption. Arch. Oral Biol. 1975, 20, 739-742. III: Scanning and transmission electron microscope study of pellicle morphogenesis. Scand. J. Dent. Res. 1977, 85, 217-231. IV: Early dental plaque morphogenesis. A scanning electron microscope study using the hydorxyapatite splint model and a low-sucrose diet. J. Periodontal Res. 1977, 12, 73-89. V:  Ultrastructural study of early dental plaque formation. J. Periodontal Res. 1978, 13, 391-409. VI: Dental plaque morphology as revealed by direct observation and by replicating techniques. Acta Odontol. Scand. 1978, 36, 279-288 Co-author: F. Gusberti. VII: Replica study of plaque formation on human tooth surfaces. Acta Odontol. Scand. 1979, 37, 65-72. Co-author: F. Gusberti. These papers are referred to as I-VII in the present summary. Other papers are referred to in conventional manner.


Oral mycoses and their treatment.

Mycoses of the mouth and nearby areas can be caused by both yeasts and filamentous fungi. They may appear either independently or as part of a systemic infection. It is typical of many mycoses that they occur as a consequence of local factors operating in the mouth, or in patients debilitated by severe diseases. Yeasts that are part of the normal microbial flora of man, among them especially Candida species, are the most frequent causative agents. Some tropical or semitropical infections may occur in Scandinavia and Finland, but they are rare. Local therapy with antimycotics is often effective in acute infections, whereas some chronic ones may make systemic administration necessary. Some of these infections are treated surgically.


Neonatal septicemia and perinatal risk factors.

Many methods for screening and prediction of neonatal septicemia have been tried. In this study a score, related to both perinatal risk factors and neonatal diseases, was tested upon healthy newborn infants, infants with septicemia and infants with other diseases. Statistical differences were found between infants with neonatal septicemia and infants with other neonatal diseases as well as normal newborns. It was also possible to find a relationship between certain predisposing factors and predominance of certain pathogens. Complications during pregnancy and delivery were most often found in the group B streptococcal, combinations of invasive procedures and neonatal diseases in the staphylococcal group and surgical procedures in the gram-negative group.


Dosage of salicylates for children with juvenile rheumatoid arthritis. A prospective clinical trial with three different preparations of acetylsalicylic acid.

41 children with juvenile rheumatoid arthritis (JRA) and 6 with postinfectious arthropathies, aged 3--15 years, were treated with acetylsalicylic acid for 14 days during which time the patients were hospitalized. Three different acetylsalicylic acid preparations were used: a microencapsulated form, an enteric-coated form and standard acetylsalicylic acid tablets. Serum salicylate concentrations were measured by Trinder's photometric method. With doses of 90--120 mg/kg/day symptoms of salicylism appeared in about 50% of the cases. Daily doses of 2 g/m2 (not exceeding 70 mg/kg) proved relatively safe in this study, whereas symptoms and signs of intoxication appeared at doses exceeding 3 g/m2/day. In this respect there were no significant differences between the three acetylsalicylic acid preparations used. The results of this study also suggest that the serum salicylate concentrations should not exceed 2000 mumol/l (about 27 mg/100 ml). The symptoms of salicylism correlated closely with serum salicylate levels, which, in turn, correlated well with the dosage in g/m2. Elevation of serum aspartate aminotransferase was noted in 1/3 of the cases. All of these had a dose exceeding 2 g/m2, and the frequency of elevated enzyme activities increased with increasing dosage. In the group receiving enteric coated form of acetylsalicylic acid, there were fewer positive benzidine tests (12%) than in the two other groups (22--28%).


Genetic transformation in Streptococcus sanguis. Spontaneous and induced competence of selected strains.

Nine strains of Streptococcus sanguis were examined for competence in genetic transformation with streptomycin resistance (str-r) as marker. Eight strains belonged to serogroup H and one to the newly-described serogroup W. Seven of the strains, one of which was the reference strain NCTC 7868 (strain Challis), were competent with str-r DNA from strain Challis. Strains NCTC 9124 (strain Wicky) and 480 were incompetent. The efficiency of transformation was examined in four different media. Use of Todd Hewitt broth gave frequencies of transformants as high as the more complex media. Addition of serum to the transformation media was not essential for the development of competence. The presence of a competence factor (CF) in the culture filtrate of strain Challis was confirmed. The factor transferred strain Wicky to competence with a great variation in the number of transformants and had no influence on strain 480. On the other hand, this spontaneously incompetent strain became competent after addition of culture filtrate from the competent strain 13b, in contrast to Wicky which now remained incompetent. Thus, it is suggested that several factors are involved in the induction of competence of S. sanguis.


The laminar organization of the prospective auditory cortex in the human fetus (11--13.5 weeks of gestation).

The prospective auditory cortex was analysed in human fetuses at 11--13,5 post-ovulatory weeks with Nissl, Golgi and E.M. techniques. At 11--12 weeks, marginal, cortical plate, intermediate, subventricular and ventricular layers were recognized. Post-migratory neurons with developing dendrites were seen in marginal layer, cortical plate and superficial part of the intermediate zone only. At 12--13,5 weeks the superficial part of the intermediate zone is transformed into the true cortical layer--"subplate layer"--characterized by maturing neurons with growing dendrites, fine axonal arborization and low cell density. The neuronal circuitry elements are thus present very early in the prospective auditory cortex and distributed throughout the deep cortical plate of the "subplate layer" corresponding to the synaptic territory of other areas of the human fetal cortex.


Genetic transformation in Streptococcus sanguis. Distribution of competence and competence factors in a collection of strains.

Forty-one strains of Streptococcus sanguis (37 of serogroup H and four of the newly-described serogroup W) were examined semiquantitatively for genetic transformation with streptomycin as marker. The material comprised eight reference laboratory strains and 33 recent isolates. Eighteen strains (16 of serogroup H and two of W) showed spontaneous competence in genetic transformation (without added competence factor, i.e. culture filtrate.). Individual culture filtrates from 19 spontaneously competent and ten incompetent strains were tested for competence-inducing effect on 23 spontaneously incompetent strains. Competence was induced in 16 of the strains, and 20 of the culture filtrates were active. There was considerable variation with respect to the number of recipient strains which were induced to competence by individual filtrates. Furthermore the recipients varied as regards the number of filtrates that were able to induce that particular strain. There was some relationship, but no complete association, between competence, competence-inducing ability and the occurrence of spreading zones around the colonies assumed to correspond generally to fimbriation. Thus, three incompetent strains had an active culture filtrate and one spontaneously competent strain had an inactive filtrate. Most, but not all, strains with spontaneous or inducible competence showed spreading, as did most of the strains from which broadly inducing filtrates could be produced.


Cochlear hearing loss and viral infection.

A group of about 100 consecutive patients admitted to an otorhinolaryngological outpatient department for treatment of cranial nerve affections underwent detailed neurological, audiological and laboratory examinations. Of 34 patients with hearing loss, objective signs of viral infection were found in 12. The hearing loss was sensorineural of the cochlear type, in 7 cases of the high-frequency type, in 5 cases of the low-frequency (Menière) type. Within one year after the onset of the disease the hearing loss had disappeared in all but 2 cases. Reversible dysfunction of two or more cranial nerves was found in 7 of 8 cases examined. In the cerebrospinal fluid the cell count and the total protein and gamma-globulin values were increased in most patients. Our findings indicate a reversible sensorineural hearing loss to be part of a viral-induced meningoencephalitis and cranial polyneuropathy. The mechanism of the reversible low- and high-frequency hearing loss is discussed.


Studies on Yersinia enterocolitica isolated from swine and dogs.

Yersinia enterocolitica serotype 03 was isolated from the colon contents of 27 (4.5%) of 599 bacon pigs on slaughter. Two (1.7%) out of 115 dogs were positive by culture for this human-athogenic serotype of Y. enterocolitica. A number of other serotypes of Y. enterocolitica were also obtained both from porcine and canine enteric contents (4b, 5a, 6, 7, 11, 12, 15, 17, 19, 26b, and non-typeable strains). All these serotypes are supposedly non-pathogenic for man and may possibly originate from the microflora of the environment. Haemolysis on bovine blood agar was observed for strains belonging to O-serotype 3.


Studies on the interaction between different O-serotypes of Yersinia enterocolitica and HeLa cells.

Eighty strains of Yersinia enterocolitica were examined for their ability to invade HeLa cells. The following O-serotypes were found to be invasive: 1, 3, 4a, 4c, 5b, 8, 9, 15a, 18, 20, 21 and 22. Biochemically, these types are either indole-, aesculin-, and salicin-negative, or indole-positive but aesculin- and salicin-negative. Other serotypes of Y. enterocolitica did not invade HeLa cells. Biochemically, these non-invasive strains are indole-, aesculin- and salicin-positive. Also the non-sucrose-fermenting strains of O-serotypes 11 and 12 were non-invasive. The interaction with HeLa cells was not restricted to viable bacteria, since also bacterial cells inactivated by formalin or ultraviolet light could gain entrance to the HeLa cells. Heating of the bacteria to 100 degrees C for 30 min. completely inhibited their invasiveness. Monolayer cultures of porcine kidney cells were also invaded by strains which invaded HeLa cells.


Influence of O and K antigens on the surface properties of Escherichia coli in relation to phagocytosis.

Strains of Escherichia coli with different O and K antigens were investigated with respect to physicochemical surface characteristics and liability to phagocytosis. Using two-phase partitioning analysis for the surface characterization, three main groups of strains emerged: Group I (O1:K1, O2:K1, O3:K2ab) showing both smooth hydrophilic O antigens and negatively-charged K antigen which rendered the strains maximally resistant to phagocytosis. Group II (O55:K59, O111:K58) showed no acidic K antigen but only smooth hydrophilic O antigen properties. However, these strains were as resistant to phagocytosis as the strains in group I. A third group (O14:K7, O24:K +) contained strains with rough, hydrophobic O antigen and negatively-charged K antigen. When the K antigen was removed by heat treatment these strains became more sensitive to phagocytosis. Certain other strains (O28:K-, O56:K + and O118:K-) did not fit into the three groups. These experiments show that the physicochemical surface effects and biological significance of the K antigen must be evaluated in relation to the properties conveyed by the corresponding O antigens.


Surface characteristics of Escherichia coli strains in relation to development of bacteraemia.

Three groups of E. coli bacteria isolated from blood, urine and faeces were analysed with respect to physicochemical surface properties in aqueous polymer two-phase systems. Eighty-eight per cent of the bacteria isolated from blood cultures showed affinity for the dextran-rich bottom phase, whereas 60% and 30% of the bacteria isolated from urine and faeces, respectively, collected to the same phase. Further two-phase analysis indicated that the bacteraemia strains exposed more negative surface than the other groups of bacteria, and that this charge was reduced after heat treatment (70 degrees C, 40 min). These results thus indicate that the strains causing bacteraemia possess similar surface properties, and may have been selected from the more heterogeneous group of bacteria found in urine and faeces. It is further conceivable to propose that bacteria found in the blood expose more heatsensitive, negatively-charged K antigen than the other groups of bacteria.


Human macrophage differentiation in vivo and in vitro. A comparison of human peritoneal macrophages and monocytes.

Human mononuclear phagocytes isolated from venous blood or sterile peritoneal exudate were cultured in an in vitro system known to induce differentiation of monocytes to macrophages. Morphological and functional studies were performed at different stages of in vitro differentiation, in order to compare the two macrophage populations. Freshly-isolated human peritoneal macrophages (PEC), which are presumed to represent monocytes which have differentiated in vivo in the peritoneal exudate for 1--2 days, showed several signs of increased effector cell function, as compared to the relatively immature blood monocytes. Cell adherence after phagocytosis, ability to degrade ingested 125I-labelled Candida albicans, and ability to suppress DNA-synthesis in a target cell line of human origin, were all found to be greater in the peritoneal cells in early culture. During in vitro differentiation in this system, both PEC and monocytes developed remarkable morphological and functional changes. Cell size and granule content increased considerably. Cell function, measured as phagocytic, digestive and cytostatic ability, increased for both macrophage populations. The differences between the two cell populations in early culture suggest that the functional and morphological changes induced by in vivo differentiation in peritoneal exudate involve changes of the same kind as those induced by in vitro differentiation in our system. The lodging of mononuclear phagocytes in sterile peritoneal exudate does not seem to impair the capacity for further differentiation to any great extent.


Uptake of non-opsonized E. coli by unstimulated mouse peritoneal macrophages.

A method is described for the study of phagocytosis of 32P-labelled, non-opsonized, viable E. coli by mouse peritoneal macrophages. Factors influencing the uptake, such as medium, number of bacteria and time of phagocytosis, were standardized. The kinetics of the uptake were studied by visual counting of bacteria and by measuring the distribution of radioactive labelling. The uptake of 32P by the macrophages is well correlated to the number of bacteria phagocytized. The amount of phagocytosis depends on the bacterial density of the medium and the time of phagocytosis. When the medium contains more than 10(9) bacteria per ml, the maximum phagocytic capacity is reached after 90 minutes.


[Lofepramine: a comparative clinical study with amitriptyline].

Lofepramine, a new tricycle antidepressant, is compared with amitriptyline in a double-blind study. A brief pharmacological description of the drug is made emphasizing its low toxicity and anticholinergic peripheral effects, high plasmatic concentration levels and good tolerance and elimination in comparison with some other known  tricycle antidepressants. Sixty depressive outpatients of a Mental Health Service in Lima, 5 male and 55 female, aging 16 to 65, 29 endogenous and 31 neurotic were studied with both drugs in a equimolar dosage. Through the chi square test, no statistical significance was found in maximal therapeutic response, Hamilton Depression Rating Scale scores, type of depression, and side-effects xerostomy which is lesser with lofepramine. A discussion of these results is made and it is concluded that in the present study lofepramine compared with amitriptyline has a similar therapeutic effect. Though not statistically significant, lofepramine seems to be better for neurotic depression and patients sensitive to anticholinergic side-effects.


[Indications for mianserin in relation to its absence of side-effects (author's transl)].

About twenty-five years ago thymoleptics made their first appearance which were soon followed by a great number of pharmacological agents that allied a mood elevating activity to an anxiolytic effect. Mianserin, a novel tetracyclic antidepressant, has an antidepressive effect similar to that of its predecessors but without causing the following side-effects : dry mouth, constipation, intestinal atony, tachycardia, cardiac rhythm disorders, accommodation difficulties, intra-ocular hypertension, dizziness, bladder atony and urinary retention. Consquently, its use is particularly indicated for the treatment of those patients who did not react to other antidepressants of those who stopped treatment on account of side-effects. Mianserin may also be used with those patients suffering from glaucoma, urinary or prostatic disorders and cardiac disorders even when the patient is recovering from a recent heart infarction. Furthermore it is recommended for aged people, for patients in a bad general condition and for those who were in a confusioned state during treatment with tricyclic antidepressants.


Zinc supplementation in alcoholic cirrhosis. A double-blind clinical trial.

A double-blind clinical trial with zinc sulfate, 0.2 g three times daily, and a placebo was performed in 30 patients with biopsy-proven alcoholic liver cirrhosis. The disease was in a stable phase, and none of the patients showed evidence of a decompensated liver function. Parameters of liver function, taste acuity, dark adaptation and of zinc and vitamin A metabolism were followed for six weeks. In the zinc-treated group of 16 patients, serum zinc rose from a normal mean value of 13.3 to 17.4 mumol/l, whereas the mean serum vitamin A level remained practically unaltered within the normal range, 1.89 at the entry and 1.83 mumol/l at the end of the study. Plasma prothrombin and serum alkaline phosphatase levels of the zinc group increased and serum bilirubin and serum carotene decreased significantly. The dark adaptation did not change, but the taste function was significantly improved during zinc treatment. The results indicate that zinc supplementation causes alleviation of certain abnormalities of cirrhotics, which deserves further attention.


Mianserin plasma levels and differential clinical response in endogenous and reactive depression.

Fifty patients with moderate to severe primary depression were treated in equal groups of inpatients and outpatients with a constant dose of 60 mg. of mianserin daily for four weeks in a double blind placebo controlled trial with either a three times daily dosage regime or a single nightly dose. There was no difference in apparent compliance, side effects or therapeutic effect in either day-time or night-time dosage regimes. Patients developing high plasma levels of mianserin (greater than 70 microgram/l) were associated with a highly significantly poorer therapeutic outcome. Patients identified as endogenous depression demonstrated a significant negative correlation between plasma levels of mianserin and therapeutic response measured as an amelioration of either the Hamilton Rating Scale scores (r = --0.48) or on a new depression scale by Montgomery and Asberg (r = --0.51) with high levels associated with poor response. There was a significant correlation (r = 0.66) between mianserin plasma levels and age in endogenous depression. In those patients identified as suffering from reactive depression, no significant relationship could be seen between plasma levels and therapeutic response or with age. These findings support the view that the relationship between mianserin plasma levels and clinical response is more likely to be demonstrated in endogenous depression.


The antidepressant properties of mianserin and its effect on  sleep.

Patients diagnosed as suffering from manic-depressive psychosis-depressed (ICD 296.2) were retained and randomly assigned to two groups, one receiving mianserin, the other placebo. For the pre-trial period and throughout the trial, patients' sleep was estimated by themselves and by nurses. Patients rated themselves on the Beck Self-Rating Inventory (BSRI) before the trial and at weekly intervals thereafter. Nurses rated the patients twice daily on a seven-point global rating scale of depression. A blood sample for estimation of mianserin levels was taken on day 14. Eighteen patients received placebo and 21 mianserin. On the BSRI, the mianserin group improved significantly, whereas the placebo group showed no change. The mean daily nurse ratings showed some improvement in the placebo group, but a greater improvement in the mianserin group, particularly towards the end of the 14 days. Sleep (nurses' observations) improved significantly in the mianserin group from the first night of the trial and over the following 2 weeks. Sleep as assessed by the patients also improved significantly on mianserin. Blood levels of mianserin did not correlate significantly with changes in mood or sleep. This study confirms that mianserin is an antidepressant. The mianserin group showed an improvement in sleep which, since it started from the first night of the trial, was probably due to the hypnotic sedative properties of the drug.


Cardiovascular tolerance of mianserin and interactions of mianserin with other drugs.

The presented data clearly show that mianserin, which is therapeutically equal to other antidepressants, is a drug with a new chemical structure, with a most probably different mechanism of action and with distinct advantages above comparative drugs. Mianserin has not only pronouncedly fewer anticholinergic and central side-effects but: a) apparently has no cardiotoxic effects neither on healthy subjects nor on depressive individuals nor on cardiac patients; b) doses not cause orthostatic hypotension; c) is devoid of adverse drug-drug interactions with coumarin-like anticoagulants, with sympathomimetic amines, with antihypertensive agents and shows but little and short lasting interactions with alcohol.


[A double-blind comparison between mianserin and imipramine (author's transl)].

Fifty-four depressed patients aged 18 to 65 years were treated for 4 weeks with a daily dose of either 60 mg mianserin or 150 mg imipramine in a double-blind controlled trial. The results which were measured on the Hamilton rating scale, on the Beck and on the Overall rating scale, on the brief psychiatric rating scale (BPRS) and on a global rating scale, did not show any significant difference relative to the antidepressive efficiency of both products. The frequency of side-effects however was significantly lower in the mianserin group than in the imipramine group.


Influence of pharmacologic intervention and valvular heart disease on left ventricular ejection phase indices: a review.

Echocardiography represents an established noninvasive technique to evaluate left ventricular (LV) performance. The LV ejection phase indices may be divided into three categories: (1) volume-dependent, (2) circumferential, and (3) wall thickening. Since the latter two are not volume dependent, they are clinically more useful in patients with dilated left ventricles. These parameters have limited clinical value in the presence of left-sided volume overload conditions (e g, mitral regurgitation and aortic regurgitation) since significant LV dysfunction may exist in the presence of normal ejection phase indices by echo. The echocardiogram is also a sensitive procedure to detect subtle alterations in LV function following acute or chronic interventions with various types of vasoactive and inotropic drugs.


[Double blind clinical study of mianserin and nortriptyline (author's transl)].

The present study was done in double blind during 6 weeks on 36 depressed patients having a minimal score of 15 on the Hamilton rating scale. Seventeen received mianserin and nineteen nortriptyline. A comparable therapeutic efficacy was observed for both drugs, without significant differences for the delay of action or the activity during 6 weeks. The number of side-effects was much more elevated for nortriptyline, and a significant difference was particularly observed for the frequency and severity of tachycardia, dry mouth and oedema.


[The place of mianserin among the antidepressants (author's transl)].

The originality of mianserin lies mainly in its chemical formula ; it is a tetracyclic piperazino-azepine compound. Moreover its pharmacological profile differs from that of other antidepressant drugs because it is devoid of central anticholinergic effects, it inhibits 5-hydroxytryptophane (the precursor of serotonine) and contrary to the tricyclics it does not affect the re-uptake of the amine-transmitters but increases the turnover of noradrenaline. It has been shown in a clinical trial that mianserin induces a hypomania in some manic-depressed patients. Regarding the antidepressive effect, mianserin is superior to placebo and as effective as imipramine and amitriptyline. It simultaneously works on anxiety, psychomotoric retardation and suicidal tendency; sleep improves under mianserin's influence. The value of mianserin is proved by its safety in use. It has no cardiotoxic effect and does not interact with coumarin-type anticoagulants. Since there are no anticholinergic effects, mianserin can be given to patients suffering from glaucoma or prostatic hypertrophy. Finally it appears that mianserin lowers  the suicidal risk through its sedative properties.


Office analysis of bacteriuria.

Several techniques for determining significant bacteriuria are convenient, accurate, inexpensive and applicable for office use. The nitrite test, the dehydrated culture media technique, the dip-slide method and the agar tube method are all applicable for screening at-risk populations and for treatment follow-up. In addition, the accuracy, subculturing capabilities and potential for presumptive bacterial diagnosis of the dip-slide and agar tube methods qualify them as excellent office culturing systems.


Anticoagulation in myocardial infarction: modern approach to an old problem.

The role of routine anticogulation in acute myocardial infarction continues to be a source of controversy. There is currently strong evidence to suggest that conventional anticoagulation will prevent the formation of most deep vein thrombi and subsequent pulmonary embolization. Anticoagulant agents also appear to reduce the incidence of emboli from cardiac mural thrombi to peripheral arteries. Patients without a predisposition to bleeding are unlikely to have hemorrhagic complications in the hospital after usual doses of anticoagulant drugs. In patients with severe hypertension, prior gastrointestinal bleeding, carcinoma or advanced age, small dose heparin therapy appears to reduce the incidence of venous thrombosis and probably of pulmonary emboli as well. Its value in preventing peripheral arterial embolization has not been defined. Anticoagulation with standard "large" doses is an effective means of preventing the risks of pulmonary and peripheral emboli during the in-patient phase of acute myocardial infarction. Small dose heparin therapy provides an excellent alternative to conventional anticoagulation when there is more than a negligible risk of hemorrhage. There is little evidence at this time to support the use of long-term anticoagulation beyond the acute phase of myocardial infarction.


Observations on the composition of milk-substitute products for treatment of inborn errors of amino acid metabolism. Comparisons with human milk. A proposal to rationalize nutrient content of treatment products.

We tabulated and compared the stated compositions of four milk-substitute products, now in wide use for the treatment of various inborn errors of amino acid metabolism, and the known composition of human milk. Variations between the treatment products is great not only in the content of amino acids but also in minerals and vitamins, for example. Different source materials and rationales for their manufacture appear to explain these differences. All four products deviate in many ways from the composition of human milk. Although the existing treatment products are quite effective clinically, we propose that a more rational approach to the feeding of young infants whose nutrition is compromised by inborn errors of metabolism would begin with a synthetic product based on the composition of human milk that could be modified specifically to fit the needs and tolerance of the individual patient.


Alcohol, malnutrition, and alcoholic cirrhosis.

The relative importance of malnutrition and alcohol toxicity in the pathogenesis of cirrhosis has been controversial. In epidemiological studies the incidence of cirrhosis can be correlated with the duration and amount of alcohol imbibed. The importance of nutrition has been discounted. In these studies few analyses of dietary intake were included. Diets of patients with alcoholic cirrhosis characteristically are poor. Furthermore, alcohol toxicity impairs nutrition by interfering with absorption, transport, and utilization of essential nutrients. Patients with cirrhosis respond favorably to nutritious diets despite the concurrent intake of alcohol, although in lesser amount than their usual intakes. In long-term studies highly nutritious diets have protected rats against cirrhosis from alcohol. However, in acute experiments with "loading" doses there was evidence of direct hepatotoxicity in animals and man. Recently, cirrhosis has been produced in baboons with alcohol and a diet considered adequate. The findings are important, but there is some question whether dietary factors (imbalance) may have played a role. Also of recent interest has been the occurrence of lesions simulating alcoholic hepatitis and cirrhosis after jejunoileal bypass surgery. The evidence suggests that malnutrition may have been a major factor in this disease. The roles of alcohol toxicity and of malnutrition in the pathogenesis of cirrhosis are not fully understood. Further studies are needed to clarify these relationships.


Current concepts of platelet structure.

The involvement of blood platelets in hemostasis, hemorrhagic disorders, and thrombotic disease is well known. In more recent years it has been appreciated that platelets also participate in host defense against infection, transplantation rejection, would healing, and the pathogenesis of atherosclerosis. As a result, it became essential to develop knowledge of basic relationships between platelet structure, biochemistry, and function in order to define the mechanisms involved in normal hemostatic activity and pathologic behavior. The specialized approach to identify these associations has been termed platelet structural physiology and pathology. This H. P. Smith lecture summarizes relationships between platelet structure, biochemistry, and hemostatic activity and presents some of the new concepts which have resulted from the multidisciplinary approach.


Familial idiopathic pulmonary hemosiderosis.

Two brothers, aged 3 and 6 years, respectively, had their pulmonary conditions diagnosed as idiopathic pulmonary hemosiderosis (IPH). Both boys had severe iron-deficiency anemia, chronic cough, hemoptysis, and exertional dyspnea, and one had recurrent epistaxis. The results of light microscopic lung histopathologic studies in both patients showed numerous hemosiderinladen macrophages and chronic interstitial pneumonitis. No specific patterns of immunofluorescence of the alveolar capillary basement membranes were found. The results of electron microscopic examinations showed intact alveolar and capillary basement membranes and no evidence of electron-dense deposits. The lack of clinical or biochemical evidence for renal disease as well as the absence of serum antinuclear and antibasement membrane antibodies excluded associated autoimmune disorders. Evaluation for milk-protein allergy was negative and neither child demonstrated a clinical response to a milk-free diet. Sequential pulmonary function studies performed over four years showed episodes of acute obstructive airway disease that correlated with pulmonary hemorrhage and mild persistent restrictive lung disease. The results of this family study suggested that some cases of IPH may have a genetic basis.


Sample-size estimation: a sensitivity analysis in the context of a clinical trial for treatment of mild hypertension.

The effectiveness of treatment for mild hypertension (diastolic pressures of 85 to 105 mm Hg) has not been conclusively demonstrated. Both the costs of a carefully designed clinical trial and the likelihood that it will produce definitive answers will depend importantly on the sample size. This paper presents sample-size estimates under a variety of assumptions regarding the characteristics of the population to be studied, the degree of blood pressure control to be achieved, and the health benefits to be expected. Under a central set of assumptions, the estimated sample size per group is 22,700 with death as an endpoint and 14,000 with morbid events (CHD and stroke) as endpoints. As individual assumptions are varied one at a time, required sample sizes range from 10,900 to 101,100 and from 6,800 to 63,100 for the respective endpoints. Results are most sensitive to the degree of blood pressure control actually achieved to the expected health benefits from blood pressure control. They are also highly sensitive to the sex composition of the population and to expected dropout rates. The choice of sample size will depend on the decision maker's assessment of the likelihood that each assumption will be fulfilled and on the degree of willingness to risk an inconclusive study result. By making explicit the effect of variation in each assumption, decision making is rendered more susceptible to critical examination by outside reviewers.


Etiology of gastroenteritis among Americans living in the Philippines.

Between December 1975 and June 1976, American military personnel with diarrhea who were seen at an outpatient clinic at Clark Air Force Base Hospital were investigated to determine the etiology of their disease. Enterotoxigenic Escherichia coli were detected in 16% (18/115), rotavirus in 4% (4/111), salmonellae in 3% (3/115), shigellae in 2% (2/115) and Giardia lamblia in 2% (3/152) of patients with diarrhea. Thus from only 27% of the subjects studied were identifiable potential pathogenic agents found. The incidence of gastroenteritis increased in May and June with the increase in rainfall; however, there was no increase in the proportion of diarrhea caused by any of these identifiable enteric pathogens. Americans experienced a seasonal increase of diarrhea similar to that affecting the Philippine population in Manila. Enterotoxigenic E. coli was the most common identifiable enteric pathogen among Americans with diarrhea at Clark Air Force Base in the Philippines during the study, though even in these cases, it may not have been the agent responsible for their illness.


Mild chronic watery diarrhea-hypokalemia syndrome associated with pancreatic islet cell hyperplasia. Elevated plasma and tissue levels of gastric inhibitory polypeptide and successful management with nicotinic acid.

A 46 year old woman is described who had a 13 half year history of watery diarrhea associated with hypokalemia and hypochlorhydria. The diarrhea was secretory as measured by triple lumen tube perfusion and was associated with an increased concentration of fasting plasma immunoreactive gastric inhibitory polypeptide (GIP) of 750 pg/ml which was stimulated to 4,000 pg/ml after a standard meal. The diarrhea decreased after partial pancreatectomy. Diffuse pancreatic islet cell hyperplasia was present and, although GIP was unmeasureable in the pancreas of normal subjects, it was at least 83 ng/g wet weight in this patient. Postoperatively, the patient's diarrhea responded dramatically to the oral administration of nicotinic acid.


Reproducibility of biotypes using enterotubes.

Using both stock and clinical isolates, the Enterotube system was examined for reproducibility of its biotype identification. Fifty stock strains of Enterobacteriaceae were tested on each of 22 separate days (interrun evaluation), and ten Enterotubes per strain were inoculated from one subculture (intrarun evaluation). It was found that 2 of the 50 strains (4 percent) demonstrated reproducibility of biotypes, defined as no variation in the results of the 22 interrun Enterotubes. Twenty-one of the 50 strains (42 percent) demonstrated reproducibility of biotypes, defined as no variation in the results of the ten intrarun Enterotubes. In addition, 20 replicate Enterotube biotype identifications were performed on each of 114 urine cultures which had greater than 10(5) morphologically identical colonies per milliliter of urine. Forty-two of these 114 clinical urine cultures (34 percent) demonstrated no variation in biochemical test results with the 20 replicate Enterotubes. In 47 (44 percent) of the 20 replicate urine cultures, one biochemical test result varied. Two or more biochemical test results were different in the 20 Enterotubes from 25 (22 percent) of the urine cultures.


Prophylactic antibiotics in cesarean section: a double-blind study of cefazolin.

One hundred twenty-two patients were evaluated prospectively to determine the clinical efficacy of prophylactic cefazolin (Ancef) in cesarean section. The cefazolin was administered intravenously in a high-dose, short perioperative regimen. Postoperatively, each patient was evaluated for morbidity. Over all, the post operative morbidity rate was reduced from 30 per cent in the placebo group to 18 per cent in the cefazolin group. More important, the infection rate associated with primary cesarean section was significantly lessened from 38 per cent in the placebo group to 16 per cent in the drug group (p less than 0.025). In repeat cesarean sections, the postoperative morbidity rate was greater in the antibiotic-treated group (20 per cent) than in the placebo group (14 per cent). Of major importance, a predominant organism, Group D streptococcus, was encountered in the postoperative cultures of the cefazolin group.


Clinical course and diagnosis of genital herpes simplex virus infection and evaluation of topical surfactant therapy.

A prospective study of 37 men and 32 women with culture-proved genital herpes simplex virus (HSV) infection was undertaken to characterize the clinical manifestations of the disease and effects of topical therapy with Nonoxynol 9, a nonionic surfactant active in vitro against HSV. The duration of pain, lesions, and virus shedding was significantly longer in initial than in recurrent genital HSV infection. Cervical HSV shedding occurred in 11 of 13 initial infections versus two of 19 recurrences (p less than 0.001). Type 1 HSV caused seven of 29 initial and none of 40 recurrent infections (p less than 0.01). Clinical recurrences within six weeks were detected more often in men than in women and were unrelated to the menstrual cycle. The influence of coitus on recurrence is unclear. Papanicolaou smears were transiently abnormal (Class II) in four (12.5 per cent) of 32 female patients. Evidence of herpesvirus was detected cytologic smears from only 28 (41 per cent) of 69 culture-proved external lesions and three (23 per cent) of 13 culture-positive cervices. Serology was also of limited diagnostic value except in testing paired sera from initial infections. The topical therapy had no beneficial effect.


Legal and social issues in medical genetics.

This paper was written for the purpose of providing the physician with a perspective of the conflicting scientific, individual, and societal interests which have been evoked by increasing medical and scientific innovation in the area of human genetic disease. In it the following subjects are considered: (1) obtaining genetic information by amniocentesis, by genetic counseling, and by screening; (2) disclosure of genetic data to the patient; (3) inclusion of genetic data on the medical record; (4) courses of action available to the individual after disclosure of genetic information, i.e., abortion, sterilization, etc.; (5) the state and involuntary sterilization; and (6) prohibitions on marriage.


Corneal changes in aniridia.

Nineteen patients with aniridia and one patient with bilateral iris colobomata from eight families were examined for corneal abnormalities. Thirty-six eyes revealed changes that are consistent with a progressive corneal dystrophy. These changes begin in the corneal periphery in the early years of life and progress to the corneal center with increasing age. This dystrophy has been staged into four typical clinical patterns. Central corneal scarring, and in some cases, ulceration may occur, which may be a significant threat to vision.


Marginal corneal ulcers with acute beta streptococcal conjunctivitis and chronic dacryocystitis.

A 73-year-old woman had right dacryocystitis, intense conjunctival hyperemia and chemosis, marginal corneal ulcers, and abscesses and conjunctival cultures that were positive for beta hemolytic streptococci. A distinct lucid interval separated the peripheral corneal ulcers and infiltrates from the corneoscleral limbus. Gram stain of corneal scrapings revealed polymorphonuclear leukocytes but no bacteria, and corneal cultures were negative for bacteria. The peripheral corneal ulcers and abscesses in our patient with the lacrimal conjunctivitis of Morax clinically resembled the catarrhal ulcers found with staphylococcal blepharitis. A hypersensitivity or toxic reaction to streptococci or their products may have played a role in the development of the marginal ulcers in this patient.


Immunologic characterization of ocular adnexal lymphoid neoplasms.

We correlated the light microscopic features of ten ocular adnexal lymphoid neoplasms with the results of selected immunologic and histochemical lymphocyte marker studies. The lesions were divided into three histomorphologic patterns: inflammatory pseudotumor, reactive follicular hyperplasia, and malignant lymphoma. The six inflammatory pseudotumors, and reactive follicular hyperplasia, despite diverse histomorphology, were immunologically polyclonal and consisted of from 45 to 73% T cells and 27 to 60% B cells, the B cells being polyclonal with respect to light chain determinants. The four malignant lymphomas were immunologically monoclonal. Each consisted of a predominant B-cell proliferation, greater than 50% of the cells, which were monoclonal with respect to surface light chain determinants. No T-cell proliferations were observed. Our preliminary data indicate that, as in systemic lymphoid neoplasms, benign reactive lymphoid hyperplasias are immunologically polyclonal whereas malignant lymphomas are immunologically monoclonal. The systematic application of immunologic and histochemical techniques to the study of ocular adnexal lymphoid neoplasms may elucidate the natural history of these lesions.


Laboratory isolation techniques in human and experimental fungal infections.

In laboratory experience with a heterogenous group of 26 human ocular fungal isolates, brain-heart infusion broth proved to be the most useful medium for isolation. Although Candida and Fusarium species grew out within four days of inoculation, one fourth of the cultures did not become positive until 14 to 19 days had elapsed. In an animal model of endophthalmitis due to F. solani infection, brain-heart infusion broth again was the most useful. The highly nutritious media used for fungal isolation are prone to contamination by organisms that are difficult to distinguish from true pathogens. Sham culture studies demonstrated that this contamination can easily occur during the process of sampling the lesion and inoculating the media.


Non-carious interproximal grooves in Arikara Indian dentitions.

The dentitions of adult Arikara Indians from the Larson site (39WW2) were examined to determine the frequency and etiology of noncarious interproximal grooves. The observations included groove morphology, loci and association with dental pathology. Approximately 30% of the individuals exhibit one or more pronounced grooves. The use of dental probes in conjunction with dietary grit is the likely responsible for interproximal grooves in this population sample.


Increase of tooth size in prehistoric coastal Peru, 10,000 B.P.-1,000 B.P.

Teeth increase in size during a 9,000-year period in an archaeologically derived, radiocarbon dated sample of skeletons from a geographically restricted area of coastal Peru. Although cultural change is extensive, including the transition to food production and pottery making, teeth do not reduce as predicted under these conditions by Brace's Probable Mutation Effect. Since most of the dental literature dealing with size change of teeth focuses upon dental reduction, hypotheses explaining why teeth increase through time are not well developed. No obvious selective forces explaining size increase are apparent in the present data. Attrition decreases through time. The increase in tooth size in this collection may be a function of overall cranialfacial size increase, which (pending further data) may be related to a general body size increase.


Calcium mediation of cholinergic-stimulated amylase release from mouse parotid gland.

Amylase release from mouse parotid fragments was stimulated independently by cholinergic and beta-adrenergic agents. The cholinergic agonist, carbachol, significantly increased release of amylase only in Ca2+ containing medium whereas isoproterenol-stimulated amylase release was unaffected by Ca2+ removal. The ionophore, A23187, mimicked the effect of cholinergic stimulation when Ca2+ was present in the medium. Uptake of 45Ca2+ into tissue fragments was enhanced by carbachol and A23187 but not by isoproterenol; atropine blocked the effect of carbachol. Diphenylhydantoin (DPH) and verapamil partially inhibited carbachol-stimulated amylase release and 45Ca2+ uptake, whereas diazoxide potentiated these effects; in all cases there was good parallelism between 45Ca2+ uptake and amylase release. It was concluded that the primary step in the release of amylase from mouse parotid gland in response to cholinergic agents is an increased influx of Ca2+.


Peritubular capillary control of proximal tubule reabsorption in the rat.

Changes in peritubular capillary hydrostatic and oncotic pressures, which probably affect net interstitial pressure and, thus, the force on fluid movement across the tubule basement membrane, can modulate absolute proximal reabsorption rate (APR). To examine the relationship between APR and net interstitial pressure, we measured peritubular capillary hydrostatic and oncotic pressure, single nephron filtration rate, APR, absolute distal reabsorption (ADR), and tubular hydrostatic pressure in hydropenic, saline-loaded, and plasma-loaded rats. Net interstitial pressure in saline loading was estimated from subcapsular hydrostatic pressure and lymph protein concentration measurements. The surface area-hydraulic conductivity product of the peritubular capillary network was estimated from these measurements with a model of capillary fluid exchange in which fluid uptake was defined to be APR plus ADR. The estimated value was assumed to remain constant in all three states, and was then used to estimate net interstitial pressure in hydropenic and plasma-loaded rats. APR and net interstitial pressure correlated strongly, a finding consistent with the hypothesized role for net interstitial pressure in regulating proximal reabsorption.


Role of ligandin in transfer of bilirubin from plasma into liver.

Multiple-indicator dilution studies of labeled bilirubin uptake were carried out on isolated perfused rat livers with variable ligandin concentrations (from normal and thyroidectomized animals with and without phenobarbital pretreatment). Ligandin concentrations, measured immunologically, increased 25% after thyroidectomy and approximately doubled after phenobarbital pretreatment but decreased to normal during perfusion in the thyroidectomized nonpretreated group. A distributed two-compartment model was fitted to the dilution data and estimates of influx, efflux, and sequestration coefficients were obtained. Influx and sequestration coefficients did not vary significantly between the groups. Efflux coefficients were significantly smaller (P less than 0.001), and hepatic ligandin concentrations were significantly larger (p less than 0.001) in phenobarbital-treated rats than in other groups. The efflux coefficient varied inversely with ligandin concentration and the volume of distribution in tissue, as perceived from the plasma space, increased in proportion to the concentration of ligandin. The increased net uptake of tracer bilirubin by the liver of phenobarbital-pretreated animals is due to decreased tracer efflux secondary to the increase in intracellular binding of bilirubin by ligandin.


Secretion of an insulinotropic factor from isolated, perfused rat intestine.

To examine gut-islet interrelationships, we entirely separated the gastrointestinal tract from the rat. When we arterially perfused this preparation with an erythrocyte-free solution for 1 h, it remained histologically intact and took up oxygen and glucose. Feedings were given via a duodenal tube. The gut absorbed glucose when glucose in the feeding was high (9.2 g/dl), but not when glucose in the feeding was low (58 mg/dl). With feeding, the portal venous effluent (PVE) from this preparation (stomach to ileum) enhanced late-phase, glucose-induced insulin secretion from pancreas of another rat. This enhancement occurred when the gut was fed either glucose (9.2 g/dl) in electrolyte solution or electrolyte solution alone. PVE from glucose-fed upper gut (stomach, duodenum) was similarly insulinotropic. In contrast, PVE from unfed gut or from glucose-fed gut of old rats was not insulinotropic. PVE from all gut preparations except upper gut produced a glucagon "spike" during basal pancreatic perfusion. Effects of gastrointestinal peptides (gastric inhibitory polypeptide, cholecystokinin octapeptide, secretin, gastrin) and immunoassays of PVE suggested that the insulinotropic substance is not one of these peptides. Thus, an insulinotropic substance that is not dependent on feeding nutrient material is secreted from the intestine.


Possible role of cytosolic calcium and Na-Ca exchange in regulation of transepithelial sodium transport.

Emerging evidence in a number of different epithelia suggests that changes in cytosolic calcium ion levels play a critical role in the regulation of transepithelial sodium transport. Maneuvers believed to raise cytosolic calcium ion activity lead to an inhibition of net sodium transport in toad urinary bladder, frog skin, and isolated perfused proximal renal tubules. Regulation of the level of ionized calcium in the cytosol of the epithelial cells appears to involve a process of coupled Na-Ca exchange across the basolateral plasma membrane, energized, at least in part, by the sodium gradient. It is suggested that changes in cytosolic calcium ion levels, secondary to changes in Na-Ca exchange, in turn dependent in part on the activity of the sodium pump, constitute a link in a negative feedback mechanism. Through such a feedback mechanism, the rate of entry of sodium into the cell across the apical surface may be kept in step with its rate of extrusion across the basolateral surface.


Cardiac output and mean transit time using the phase plane of dye-dilution curves.

Thirty-five indicator-dilution curves were recorded in dogs following the injection of indocyanine dye into the femoral vein, right atrium, pulmonary artery, or left ventricle. Sampling was from the femoral artery through a dichromatic cuvette densitometer. The exponential decay constant of each dye-dilution curve was calculated by a new method utilizing the phase plane and compared with the value obtained by the Stewart-Hamilton procedure. A high level of correlation was found between the two methods. Mean difference between areas was only 1.04 mg.1(-1).s (r = 0.999) and between mean transit times 0.02 s (r = 0.999). The phase plane method has the additional advantage of demonstrating the portion of exponential decay, enabling the elimination of indicator-dilution curves and abnormal downslopes.


Choline and lecithin in the treatment of tardive dyskinesia: preliminary results from a pilot study.

Tardive dyskinesia is thought to reflect increased dopaminergic activity of the central nervous system. To compensate for this by increasing CNS cholinergic tone, the authors administered oral choline and its natural dietary source, lecithin, to 5 men with mild to severe tardive dyskinesia in a nonblind trial. Both choline and lecithin increased serum choline levels and improved abnormal movements in all patients. Lecithin had fewer adverse effects.


Objective personality changes in residents of a therapeutic community.

The authors tested several groups of drug-abusing young adults who were residents of a drug-free therapeutic community. Three instruments were used: staff ratings, sociometric ratings by members of the community, and MMPI scores. All three measures showed objective evidence of decreasing psychopathology correlated with length of time in treatment, demonstrating the effectiveness of the therapeutic community in the rehabilitation of drug abusers. Individuals who left before completing treatment had MMPI scores indicating inability to develop social relationships; this elucidates a probable cause of the dropout phenomenon.


Dantrolene and suxamethonium. The effect of pre-operative dantrolene on the action of suxamethonium.

A single oral dose of dantrolene (100--150 mg) given at least 2 hr pre-operatively has been found to reduce significantly the strength of muscular fasciculations, the hyperkalaemia and the incidence of muscle pains following suxamethonium (from 56 to 4%) in a series of forty-eight patients compared with controls. The biceps EMG of the fasciculations was unchanged by dantrolene; the incidence of troublesome side effects was low (9%) and there did not appear to be any alteration in the duration of action of suxamethonium.


Computer-assisted learning in the teaching of anaesthesia.

A comparison of computer-assisted learning and small tutorial group teaching was carried out in the instruction of final year medical students in anaesthesia. The scores attained by fifteen of the sixteen students were higher after computer-assisted learning than after small group teaching. Statistical analyses of the results demonstrated that in this study computer-assisted learning was significantly better than small tutorial teaching.


From Clover to computer. Towards programmed anaesthesia?

The control of depth of anaesthesia has been viewed as a control-system problem the solution of which can involve both feedback and feedforward techniques. The nature of the problem in Clover's day and the solutions he found have been examined. A similar analysis has been made in respect of the modern anaesthetist. Finally, the way in which computers may aid the anaesthetist in his task has been illustrated by reference to various attempts reported from around the world and, in particular, by describing the development in Cardiff of a system which should produce, in the brain of the patient, any tension of an inhaled anaesthetic which the anaesthetist chooses to specify.


Fine structural studies of the rat vas deferens.

A fine structural study of the normal rat vas deferens was undertaken utilizing perfusion fixation. Morphological features not previously appreciated were revealed using this technique of fixation, and included the following. The rat vas deferens exhibited a gross morphological and microscopic differentiation along its length: A proximal segment was characterized by a thin muscular wall, an epithelium of low height (comparable to that of the cauda epididymidis) and a distended lumen typically filled with an accumulation of sperm; a distal segment exhibited a thick muscular wall, a convoluted mucosa, and a pseudostratified columnar epithelium with long stereocilia extending into the lumen. The transition from the morphology typical of the proximal segment to that of the distal segment was gradual and progressive, marked by an increase in the mass of the muscular wall and in the height and ultrastructural complexity of the epithelium. Clear or "foamy" cells, characteristic of the cauda epididymidis, were observed in the initial centimeter of the vas deferens. Also, a cell type designated as "mitochondrion-rich" was observed in the distal vas segment. The structure of the small mitochondria in such cells, however, did not conform to the description of mitochondria in similar cells found in the human (Hoffer, '76). Intraepithelial macrophages containing residual accumulations which often resembled spermatozoan remnants in advanced stages of dissolution were present in all segments of the rat vas deferens, confirming in this species a spermiophagic role for such cells.


[Hormones in depressive illness. The role of cortisol and sexual steroids (author's transl)].

It is actually highly probable than depression is linked to a decrease in noradrenergic activity in brain, at least in some areas including hypothalamus. The complexity of relations between dopaminergic and serotoninergic systems lead to multiple possibilities in hypothetical etiologic factors and in therapeutic interventions. A plasmatic drop in testosterone in men and estradiol in women is one of the situation able to induce a decrease in noradrenergic activity. It seems to be of primordial influence on depression at least in patients with predominant clinical hypogonadic symptoms. We still don't know the frequency on hypogonadism in peoples with predominant depressive symptoms. However this incidence may be fairly high because it is now demonstrated than environmental stress could impaired testicular and ovarian function by the means of anxiety hormones, catecholamines and cortisol, and also by a direct effect on hypothalamus. In no case this hormonal reactions are adaptative by means of anti-anxiety or anti-depressive effects. In contrary, they contribute to maintain the psycho-endocrine syndrome.


[Biochemical prospects in treatment of depressive illness (author's transl)].

Biochemistry of the brain has to avoid the dead-end where psychopharmacology is trapped at the present time. First of all it is needed to draw of the lack of efficacy of the antidepressants of today. Brain biochemical research must go beyond the moamine models and take into considerations the afferent and efferent influences. The sutdy of ECT and ions like lithium, rubidium, and cesium may open up new perspectives to the knowledge of new psychotropic drugs and to their mecanisms of action. Starting from clinical observations new indications for already known non psychotropic drugs could appear.


A fiberoptic bronchoscopy technique to obtain uncontaminated lower airway secretions for bacterial culture.

Seven types of brush catheter were studied in vitro to determine the optimal catheter design for obtaining specimens for bacterial culture using fiberoptic bronchoscopy. The various catheters were inserted through the inner channel, which was contaminated with fresh saliva. The specimen was then obtained by inserting the brush into a broth culture of a marker organism at the distal end of the bronchoscope. Relative merits were based on quantitative bacterial counts of salivary "contaminants" and the marker organism. The catheter that proved superior had telescoping cannulas with a distal occlusion. Twenty-six samplings using catheters with this design uniformly showed no contaminants and high counts of the marker organism. The catheter with telescoping cannulas and a distal occlusion composed of polyethlene glycol was then tested with bronchoscopy performed on 8 healthy volunteers and 6 patients with clinical evidence of a lower airway infection. The specimens yielded likely pulmonary pathogens in high concentrations from patients with pneumonia or lung abscess. Possible contaminants were recovered in low concentrations from 2 of 14 subjects. These in vitro studies and the preliminary clinical trial support the use of this type of catheter for obtaining bronchoscopic specimens for bacterial culture.


Age-related changes in elastic fibers and elastin of lung.

The effect of age on the lung elastic tissue of inbred BALB/c mice were studied. Static compliance of excised lungs increased with age. Morphometrically determined total elastic fiber length increased with lung expansion in age- and sex-matched mice (r = 0.83, P smaller than 0.001), indicating an axial extension of elastic fibers. However, total elastic fiber length of aging lungs fixed at a distending pressure of 15 cm H2O showed no significant change despite an age-related increase in lung volume (male, r = 0.96, P smaller than 0.001; female, r = 0.95 P smaller than 0.001). The correlative finding of decreased elastin content (r = -0.87, P smaller than 0.001) indicates that there is a loss of elastic fibers in the aging lung. It is suggested that the absence of pseudoelastin fibers, as demonstrated by histochemical techniques, accounts for the observed differences in elastin content of aging human and mouse lungs.


Clinical trial of six-month and four-month regimens of chemotherapy in the treatment of pulmonary tuberculosis.

In a study in Singapore, Chinese, Malay, and Indian patients with pulmonary tuberculosis received 2 months of daily treatment with streptomycin, isoniazid, rifampin, and pyrazinamide followed either by daily treatment with isoniazid, rifampin, and pyrazinamide (SHRZ/HRZ regimen) or by daily administration of isoniazid and rifampin (SHRZ/HR regimen) allocated at random. Both regimens were given for either 6 or 4 months by random allocation. All 330 patients with drug-sensitive tubercle bacilli before treatment had a favorable bacteriologic response during chemotherapy. During the first 6 months after the end of chemotherapy, there was only a single bacteriologic relapse among 84 SHRZ/HRZ and 80 SHRZ/HR patients treated for 6 months, but 8 (10 per cent) of 80 SHRZ/HRZ and 4 (5 per cent) of 74 SHRZ/HR patients treated for 4 months relapsed. Of a total of 33 patients with bacilli resistant to isoniazid, streptomycin, or both drugs before treatment, only one had an unfavorable response during chemotherapy, and none of 31 patients relapsed during the first 6 months after stopping chemotherapy. The incidence of adverse reactions was low; 11 (3 per cent) of 397 patients had hepatitis, but not all episodes were attributable to drug toxicity, and one patient had thrombocytopenic purpura.


The use of antiepileptic drugs.

The use of antiepileptic drugs has become increasingly effective through several factors: new techniques that allow better diagnosis of the seizure disorder and its underlying cause; the development of new medications and increased knowledge of old ones; and the widespread use of antiepileptic drug-level determinations. The choice of a drug depends heavily on an accurate diagnosis of seizure type, which may determine the response to the medication. Because of better diagnostic criteria and intensive monitoring procedures, the correct seizure disorder can be more easily diagnosed and, therefore, the proper medication selected. Minimal efficacious and toxic blood concentrations have now been identified for most antiepileptic drugs. Several, including primidone, carbamazepine, methsuximide, and mephenytoin, have pharmacologically active metabolites that affect both the toxicity and efficacy of the prescribed drug and can now be measured in the plasma. The most effective use of the antiepileptic drugs depends on a combination of reliable blood level measurements, clinical observation, and knowledge of their pharmacokinetics and biotransformation.