[A case of Jakob-Creutzfeldt's disease (form of Heidenhain) electrophysiological, clinical and anatomical correlations (author's transl)]. We report a case of Jakob-Creutzfeldt's disease (amaurotic form of Heidenmain's disease) showing typical clinical, anatomical, microscopic and electrophysiologic (E.E.G, polygraph sleep recordings, Evoked Potential) signs. Changes in visual Evoked Potentials were quite specific whereas Auditory and Somesthesic E.P'. were not modified. Early elements (O, I, II, and III having a latency of less than 100 ms) were strongly developed, while later elements of the associative type were absent. The precociousness and specificity of the E.P. abnormalities are stressed in the differential diagnosis of J.-C's disease from other insanities, or from cortical blindness of other aetiology. The physiopathologic implications of electrophysiological data is discussed to illustrate the possibility of using Evoked Potentials to help resolve the problems of functional cerebral stratigraphy in man.


[Facial noma and modified deltopectoral flap (author's transl)]. A commonly fatal condition, by virtue of the malignant infectious syndrome which it causes initially, facial noma leaves sequellary mutilitations which may be treated surgically using a panoply of technical procedures from maxillofacial surgery (skin flap, skin and mucosal graft, oestotomy, bone graft, plasty, mechanotherapy by mobilisers, facial massage etc.).


[Cervical and cervicodorsal flaps. Vascularisation. Surgical applications (author's transl)]. The authors used injected anatomical specimens to analyse the cutaneous vascular distribution of the cervical and cervicodorsal regions. The arrangement of the arterial network does not make it possible to define flaps with a vascular pedicle. Only the jugular vein may be used as the axis for such a flap. The most valuable flaps, in everyday practice, are transverse flaps, a vertical flap pediculated on the external jugular and the cervicodorsal flap used without autonomisation. The combined musculocutaneous flap, including the sternocleidomastoid, is used in the treatment of extensive loss of laterofacial substance.


[The correction of traumatic loss of substance from the auricle of the ear (author's transl)]. Simple and reliable repair techniques are described, selected for their simplicity, rapidity and the quality of the results obtained. For losses of substance of the helix, reduction of the pavillion (Antia) or a flat retro-auricular flap suffice for a limited loss, whilst miniature tubular flaps give a good result in cases of total loss. For the concha and the lobule, flat mastoid flaps (Rao-Preaux) are very simple to carry out. Following amputation, a broad, long Crikelair mastoid flap and Converse's tunnelisation procedure may be used to reconstruct the upper 2/3 and mastoid flaps (Preaux-Brent) the lower 1/3.


Clinical applications and technical aspects of parathyroid hormone measurements. A review of human parathyroid hormone measurements is presented. Although parathyroid hormone was among the first hormones to be measured with the radioimmunoassay technique in 1963, there are even now still many pitfalls in both the technical aspects and clinical applicability of this assay. The main reasons for these difficulties are presented: firstly the complex intra- and extraglandular metabolism of parathyroid hormone results in the heterogeneity of the hormone in serum; secondly, the scarceness of pure human parathyroid hormone delays the development of a complete homologous human assay. The existing assays however have, despite their limitations, enormously contributed to our knowledge of parathyroid hormone secretion in both the normal state and in disease. The clinical applicability of these assays is reviewed and future technical improvements are suggested.


Treatment of severe foot ischaemia by defibrination with ancrod: a randomized blind study. Forty-two patients, mean age 68 years, with severe leg ischaemia were randomly treated with placebo or by controlled defibrination with ancrod for 3 weeks. Plasma fibrinogen concentration was kept at about 20% of normal in the ancrod treated group. The two groups proved to be well matched regarding factors which could affect the degree of ischaemia. Objective measurements showed a significant rise in ankle and toe systolic blood pressure in the ancrod group lasting for 3 months. There was no rise in distal blood pressure in the control group. In the ancrod treated group the toe and ankle systolic pressures rose about 8 mmHg, but this was not accompanied by an improvement in the clinical course.


Immune response to haptenated syngeneic and allogeneic lymphocytes. I. Restrictions for B cell activation by haptenated lymphocytes and specificity of the antibodies generated. The B cell immune response to altered self was studied using fluoresceinated syngeneic and allogeneic lymphocytes as antigens. Antibody synthesis could be induced in mice injected with syngeneic or allogeneic haptenated lymphocytes as well as heterologous labelled red cells using one particular hapten density. The response to haptenated syngeneic lymphocytes was thymus-independent since nude mice gave a strong response even when the immunogen was FITC-labelled nude cells. The antibodies induced reacted with a complex between a self structure and the hapten, since the best response was detected using FITC-labelled mouse erythrocytes as targets in the plaque assay. These results indicate that a clear distinction must be made between recognition and activation of the responding B cells. The nature of the structures on the modified lymphocyte required to perform these two functions is discussed. It is pointed out that in a dual recognition model of altered self, the duality involved may concern recognition and activation events, rather than two recognition receptors.


Lymphocyte multiplication in vitro induced by mitogens and antigens. A simple technique requiring only 0.2 ml whole blood for measuring the response of lymphocytes in cultures to each of various mitogens and antigens has been elaborated. The response is quantified by comparing the number of lymphocytes with and without a stimulating agent. The increment of cell numbers is given by a cell multiplication index. In healthy subjects PHA induced almost a doubling of the cell numbers in 3 days, i.e. an index of 1.90 +/- 0.38. After 7 days the indexes for PHA, PWM and Con A were 7.25 +/- 4.12, 2.72 +/- 0.65 and 1.81 +/- 0.31, respectively. PPD and Candida-extract induced cell multiplication in skin positive individuals, with indexes ranging from 1.12 to 3.05. In contrast, patients with various severe immune deficiencies showed decreased responses to at least one mitogen, depending on the type of the deficiency. Likewise, skin test negative individuals had no or faint in vitro response to the antigens. The method, which correlated well with the response by a conventional method for incorporation of tritiated thymidine, has a high degree of precision and sensitivity, and should be applicable for routine use.


Penetration of antibiotics into bile.

Penetration of antibiotics into bile. In experimental cholecystitis in dogs, the eradication of E. coli with ampicillin, chloramphenical and kanamycin, all of which showed nearly the same MICs for this bacterial species, varied according to the differences in the penetration of the antibiotics through the liver into the bile. Antibiotics such as cephalothin and rifampicin, which are partially metabolized in the liver to inactive forms, showed higher biliary levels in CCl4-damaged animals than in the normal ones. The results were considered to be due to a reduction in the inactivating effect of esterases in the liver cells. These esterases were mainly found in the cytosol fraction and their intracellular distribution differed from that of esterases for aspirin and/or phenyl acetate.


A review of experimental models for studying the tissue penetration of antibiotics in man. Measurement of tissue antibiotic levels is of great importance in developing rational treatment for infection, particularly in patients whose host defense systems are compromised. This review outlines some of the main approaches to this problem, giving examples of the application of the new techniques in different clinical situations.


Protection of phagocytosed bacteria against antimicrobial agents. Antibiotic sensitive Staphylococcus aureus phagocytosed by human neutrophil granulocytes were exposed to penicillin G (benzyl penicillin), gentamicin or rifampicin in concentrations from 2.5 U/ml, 2.5 microgram/ml and 0.2 microgram/ml to 250 U/ml, 250 microgram/ml and 20 microgram/ml, respectively. The bacteria were protected from the antibacterial effects of penicillin G and gentamicin. Considerable numbers of phagocytosed bacteria remained viable after 24 hours exposure to antibiotic concentrations that killed more than 99% of extracellular bacteria in less than one hour. Killing of intracellular bacteria was more pronounced with rifampicin, indicating that the penetration of this drug into the phagocytic vacuole is superior to penicillin G and gentamicin.


Penetration of antimicrobials into tissue culture cells and leucocytes. When exposed to HeLa cells in tissue culture for 72 hr., antimicrobials could be categorised into three groups characterised by cell associated concentrations much lower (ampicillin, cephalexin, cloxacillin, flucloxacillin, streptomycin and trimethoprim, all 14% or less), much higher (tetracycline and polymyxins) or approximating to those extracellularly (erythromycin, lincomycin, fusidic acid and gentamicin). For kanamycin, neomycin and sulphonamides, cell associated levels were between 24 and 47% and for penicillin G and cephaloridine were 66% of those extracellularly. With mouse peritoneal macrophages and human peripheral blood leucocytes cell associated levels for representative antibiotics were all lower after 3 hr. exposure than in the tissue culture cells. However, studies on the rate of release of cell associated antibiotic and of the effects of surface active agents indicated that the differences between cell types were due to loss of cell association during washing procedures to remove extracellular antibiotic. The effects of bactericidal antibiotics on survival of bacteria phagocytosed by mouse macrophages suggested that the cell association observed in tissue culture cells represented true intracellular penetration rather than mere binding to the cell surface. Within families of antibiotics, alterations to the molecule change cell penetration and the variations observed can not be explained merely in terms of simple diffusion, molecular size, dissociation constants, lipid solubility or protein binding.


Bacterial persistence in vivo: resistance or tolerance to antibiotics. The in vivo persistence of bacteria in spite of "adequate" therapy may be due to a variety of causes or factors. The most "obvious" cause is the presence of drug resistant strains, missed in conventional testing because of heterogeneity of resistance, special test requirements or emergence during treatment. A second large group of causes is due to atypical forms, whereas a third cause is due to tolerance. A fourth group of causes may be termed invironmental factors, and this includes drug inactivation, bioconversion or antagonism, often a result of the infection itself.


[Malaria introduced into Switzerland from 1974-1976]. In recent years there has been an increase in imported tropical diseases in Switzerland. Travellers to the tropics are often inadequately or not at all informed about the dangers and possible prophylaxis of infection. This is true for malaria, of which 207 cases covering the years 1974 to 1976 are studied. Most involved were people between 21 and 30 years old. The main infections (71%) come from African countries. Plasmodium falciparum was found somewhat more frequently than P. vivax. Only a seventh of those infected took chemoprophylaxis regularly. Very many took irregular prophylaxis, while scarcely a third ever took an antimalarial drug. All the severe cases were in this group. A review is conducted of aspects of malaria in Switzerland, a country where the disease is not endemic. However, as it can be brought in at any time from tropical areas, it must be considered in the diagnosis of various clinical pictures. As the characteristic course of the fever is rare and onset of the disease often follows later than a month after the return from the infection area, malaria is only recognized late. The diagnosis is nevertheless relatively easy if the possibility of malaria is borne in mind.


[Transitory bacteremia in rectoscopy].

[Transitory bacteremia in rectoscopy]. A prospective study was undertaken to determine the frequency of transient bacteremia on recto-sigmoidoscopy. Blood specimens were drawn for aerobic and anaerobic bacterial culture immediately before, and 1, 5, 10, 15, 20, 25 and 30 min after the beginning of recto-sigmoidoscopy. 19 blood cultures were supposed to be contaminated. In 3 patients (6%) a positive blood culture was found with the following types of organisms: enterococci, Escherichia coli and nonhemolytic streptococci. The need for antibiotic prophylaxis in patients with valvular heart diseases or prosthetic valves is discussed. In such cases the authors propose prophylaxis with 1 g streptomycin i.m. and 3 g ampicillin by mouth 30 min before recto-sigmoidoscopy.


[Strongyloidiasis following kidney transplantation]. A 50-year-old Swiss male died from strongyloidiasis 8 weeks after renal allotransplantation. Past history revealed malaria at age 20 years, when the patient had stayed in tropical and subtropical areas, as well as pulmonary tuberculosis. Hypertension, erythrocyturia, proteinuria and unexplained episodes of blood eosinophilia were first noticed age 45, and 4 years later dialysis was started. A mild acute rejection crisis was successfully treated 4 weeks after transplantation. 2 weeks later, however, bilateral pneumonia developed. Despite vigorous antibiotic and tuberculostatic therapy the patient died in septic shock. Autopsy revealed strongyloidiasis with adult females, eggs and rhabditiform larvae of Strongloides stercoralis in the small intestine. Numerous filariform larvae were detected in the lungs, in the walls of bronchi and trachea, in the brain, in the walls of arteries, and in lymphnodes. Massive granulomatous inflammatory reaction and extensive pulmonary hemorrhage were the main pathological findings.


[Transitory early rejection of transplanted kidneys; course and prognosis]. Early acute rejection with oligo-anuria was observed in 9 cases among 103 cadaver kidney allografts transplanted between January 1969 and May 1977. According to our experience this type of rejection crisis occurs between the 6th and 9th day after transplantation. It is characterized by a typical clinical course. The beginning is acute with high fever and swelling of the graft, followed by oligo-anuria demanding treatment with hemodialysis. In all cases except one there was total restoration of graft function after an oligo-anuric period of 4--16 days. The late prognosis was good in 5 cases. The other 4 patients lost their grafts during the first 4 months after transplantation as a consequence of a second irreversible rejection reaction. The pathogenesis of this early acute and reversible failure of the transplant is discussed, together with the histologic findings in one case.


[Principles and indications for prosthetic restorations]. Once it has been explained and defined what a prosthesis and what the masticatory apparatus and its function are, the author defines the three principles of a prosthetic restauration: --Any prosthetic restauration should be conceived and realized only after a complete study of the odontostomatognathic system. --Any prosthetic restauration must reestablish the health of the masticatory apparatus. --Any prosthetic restauration must assist in the conservation of the remaining teeth. Six corollaries are deduced from those principles and are equally defined and analysed. The indication of a prosthetic restauration comes from those principles and their corollaries. A possible fixed restauration is to be studied first, then comes the possibility of a semifixed construction. When both those solutions are impossible, the planning of a removable prosthesis, even simple, must be studied with method. This prosthesis must be composed of a cast metallic framework. If the planned prosthetic restauration can not be beneficial to the whole masticatory apparatus, it is better to renounce to do it.


[Possibilities of orthodontic pretreatment]. Five practical cases are shown where orthodontic pretreatment preceded the rehabilitation. Most important for the success of such a mixed treatment is the teamwork between the 2 dentists and their understanding of the other's problems and limitations. A clear priority list is indispensable. As a general rule, the role of the orthodontist is subordinate to the prosthetic problems. The 5 cases are: a light and a severe anodontia, a distal bite with spaced protrusion of the upper anteriors, and a distal bite with circular and total nonocclusion, finally a lip, jaw and palatal cleft case. All patients are adult. In 3 cases an instrumental functional analysis was made.


[Preparation and impression in crown and bridge prostheses]. The dental profession is asked to increase its efficiency in fighting oral disease. The means to this end are: Improve working quality in every sector and with many small improvements over the minimal effort. Furthermore the service practice, which means an office which offers thorough prophylaxis, teaches oral hygiene to the patients. This is the other efficient means to reduce disease at its root.


[The selection of a concept of occlusion]. The choice of a functionally and morphologically faultless concept of occlusion is of primary importance in crown and bridge prosthodontics. Generally speaking we can choose between two concepts:--the concept of harmonious occlusion--the gnathological concept of organic occlusion. A case study was used to illustrate in depth the range of application of these two concepts.


[Clinical cases casuistic of oral rehabilitation]. To rehabilitate means to give back to the patient the former and initial function of his teeth. Various clinical cases are shown, different in age, sex, health and financial status of the patient. They illustrate the method to apply to each case definite constructive principles dictated by biomechanics. The solutions are diversified, but the principles underlying the decision are identical. Before starting work, 3 questions must be asked: What do to? How to do it? At what fee? Thus we can fulfil the patient's wish to eat with pleasure, to talk agreeably and to smile without inhibitions.


Sickling rates of human AS red cells infected in vitro with Plasmodium falciparum malaria. The kinetics of sickling of malaria-infected red cells from humans with sickle cell trait were studied in vitro in an attempt to obtain direct experimental evidence for a selective advantage of the hemoglobin S heterozygote in a malarious region. The sickling rates of cells infected with Plasmodium falciparum and of non-infected cells were studied both in the total absence of oxygen (by dithionite addition) and at several different concentrations of oxyhemoglobin which might obtain in vivo. In all cases, red cells containing small plasmodium parasite forms (ring forms) sickled approximately eight times as readily as uninfected cells. Cells containing large parasitic forms (trophozoites and schizonts) appeared to sickle less readily than uninfected cells, by light microscopy criteria, but electron micrographs demonstrated the presence of polymerized deoxyhemoglobin S with a high frequency. It is concluded that enhanced sickling of plasmodium-infected AS cells may be one mechanism whereby the hemoglobin S polymorphism is balanced in favor of the heterozygote.


Childhood enuresis: a psychologic perspective. Childhood enuresis has long been an enigmatic clinical entity. The purpose of this paper is to focus current psychologic thinking as it applies to etiology, diagnostic work-up, treatment, and follow-up. A large number of etiologic formulations are briefly mentioned, but our primary thrust is to emphasize the psychologic liabilities of urologic instrumentation and to encourage the early application of nonsurgical therapeutic approaches consisting of behavior modification and imipramine. Follow-up evaluation is suggested for children requiring diagnostic or therapeutic genitourinary instrumentation.


Rhegmatogenous retinal detachment complicating diabetic retinopathy. Retinal detachment complicating proliferative diabetic retinopathy is being recognized with increasing frequency. Although one type of detachment is tractional and requires vitrectomy for hopeful repair, the other variety of detachment is rhegmatogenous. The rhegmatogenous form of retinal detachment does not generally require the radical surgical approach of vitrectomy. However, because of the unusual nature of the retinal detachment , a standard encircling scleral buckling procedure does not suffice to correct the problem. The unusual characteristics of this form of retinal detachment are discussed, and the criteria for types of surgical repair are considered. A modification of scleral buckling procedure which has been successful in anatomically reattaching most rhegmatogenous retinal detachments is described. The complications resulting from surgery are reviewed along with methods to avoid complications.


Amnesia.

Amnesia. Amnesia is a common clinical problem characterized by four features: (1) normal immediate recall, (2) impaired ability to learn, (3) relatively spared ability to retrieve previously learned material, and (4) preserved cognitive and personality characteristics. Amnesia occurs as a distinct mental disorder, and nine variations seen clinically are described here: Korsakoff's psychosis, posttraumatic amnesia, amnesia stroke, postoperative amnesia, postinfectious amnesia, anoxic amnesia, transient global amnesia following ECT, and psychogenic amnesia. The clinical findings which characterize and differentiate these disorders are presented, along with suggestions for management and a discussion of the the outcome of amnesia.


Primary and membranous dysmenorrhea.

Primary and membranous dysmenorrhea. Organic, physiologic, and psychologic causes of dysmenorrhea are presented. Signs and symptoms include pelvic fullness, nausea, vomiting, diarrhea, urinary frequency, nervousness, and headaches. Primary dysmenorrhea has been treated with analgesics, diuretics, and antispasmodics. Androgen therapy was also found to be effective, but it cannot be used for women who have acne or hirsutism. Surgery is rarely indicated for primary dysmenorrhea.


Frustrations in renal donation.

Frustrations in renal donation. Extensive evaluation of a small series of potential renal donors has revealed an alarming rate of previously unsuspected disease precluding acceptability for renal donation. Of 19 patients considered for donation at the Medical University of South Carolina, 15 were unsuitable for medical reasons (diabetes mellitus, multiple sclerosis, sickle cell trait, hypertension, polycystic kidneys, duodenal ulcer, pulmonary disease), psychologic reasons, or changes on renal arteriography consistent with nephrosclerosis. The importance of a thorough donor evaluation including total patient awareness of the risks involved for both himself and the recipient and extensive psychologic testing is stressed. Even with strict criteria for renal donation, this high rejection rate is surprising.


Saturday conference: non-hodgkin's lymphoma. The non-Hodgkin's lymphomas represent an area of rapid medical progress. Recent studies of staging have suggested that with respect to therapy disease is either limited (stage I or II) or advanced (stage III or IV). Bone marrow biopsy is important as an initial staging tool, and retroperitoneal evaluation (lymphangiography, ultrasound) is important when marrow involvement is not present and also as a means of establishing a baseline for clinical evaluation. For patients with nodular lymphoma, combination chemotherapy can produce high rates of complete remission, but relapses occur and survival has not been shown to be improved as compared to patients receiving single-agent therapy; the value of therapy is asymptomatic patients is not established. In contrast, advanced histiocytic lymphoma, which is rapidly fatal when single-agent therapy is used, is cured in half of patients receiving new combination chemotherapy regimens. While clinical discussions must use the Rappaport system of pathologic classification, because most data have been expressed using this terminology, it should be recognized that immunologic approaches to the classification of lymphoma exist, and that their clinical utility is undergoing evaluation.


Human filariae in Indonesia.

Human filariae in Indonesia. The distribution of human filariae in Indonesia has not changed significantly since initial reports of the disease were made in 1928. Wuchereria bancrofti and Brugia malayi are widely distributed but the newly described Brugia timori appears to be restricted to the Lesser Sunda Islands. W. bancrofti and B. timori in Indonesia are nocturnally periodic and B. malayi has nocturnally periodic and B. malayi has nocturnally periodic and nocturnally subperiodic strains.


Nocardiosis. Case report and review of the diagnosis and treatment. Purulent draining skin sinuses are a striking clinical finding when Nocardia organisms infect skin or deeper tissues and the lesion is often mistakenly ascribed to actinomycotic infection. This distinction is important because in contrast to actinomycosis, nocardiosis does not respond to treatment with penicillin or most antibiotics, and a fulminating systemic infection may occur. Smears made from purulent discharges do not always show the organism and microbiological culture may likewise prove fruitless. This article reports a patient suffering from nocardiosis and the pitfalls in diagnosis are illustrated. Successful culture of the organism was obtained by inoculating media with fresh biopsy material and a plea is made for routine use of this method. The need to use sulphadiazine in high doses initially, followed by maintenance treatment for considerable time, is emphasized.


The manifestations, aetiology and assessment of ethanol-induced hangover. The well-known phenomenon of hangover after ingestion of alcoholic beverages is reviewed; it appears to be due to both ethanol and congeners. Detailed studies must be preceded by the development of a system for measurement of hangover symptoms. Hangover scales are described for measurement of intensity in studies of its drug treatment. Attention is drawn to the changes in hormone levels, notably of aldosterone, renin, cortisol and testosterone in males during hangover.


Biochemical differences between serotypes of Cryptococcus neoformans. Prior studies have shown that C. neoformans isolates belonging to serotypes B and C differed from serotype A and D isolates in respect to the morphology of the perfect state, geographic distribution within the U.S.A. and frequency of isolation from avian droppings. The current study found that uptake of radiolabeled l-malic acid was approximately tenfold greater in serotype B and C than in A and D isolates. Assimilation of l-malic, fumaric and succinic acids also distinguished serotypes B and C from A and D. Greening of Guizotia seed agar occurred with 18 of 32 serotype B and C but in none of 91 serotype A or D isolates. The one property not following the same line of division was relatively slow creatinine assimilation, which distinguished type A alone.


[An endemic area of sporotrichosis in Guatemala]. An endemic area of sporotrichosis is described in the Lake of Ayarza District, South Guatemala, where 53 patients have been observed within 3 years. In 45.3% of the cases, the infection appeared after handling fish. The disease was more frequently observed in man (83%) and in patients less than 30 years of age. The most frequent clinical type was the ascending lymphocutaneous sporotrichosis of the limbs. Some cases of ulcerative or verrucous lesions were seen. Almost all the patients cured rapidly either by potassium iodide (46 patients) or spontaneously, or after application of local heat (4 patients). Intradermal tests were performed in healthy population in the endemic area and, for comparison, in Guatemala City. Whole yeast cell antigens of Sporothrix schenckii and Ceratocystis stenoceras were used in these tests. Skin tests to both antigens were more frequently positive in the endemic area; the highest frequency was obtained with the antigen of C. stenoceras. A serological study was performed in 26 patients. The fluorescent antibody staining technique was more sensitive than yeast cell and latex particles agglutinations. C. stenoceras was isolated from bark of some trees, especially Eucalyptus, in the environment, but not S. schenckii.


Rapid germination of Aspergillus fumigatus conidia in mouse kidneys and a kidney extract. Intravenously injected conidia of Aspergillus fumigatus germinated rapidly in the kidneys of untreated and cortisone-treated specific-pathogen-free (SPF) mice and in the livers of cortisone-treated SPF mice. Extracts of kidneys from untreated and cortisone-treated mice stimulated germination of A. fumigatus conidia in vitro. The possible roles of a germination stimulant and host defences in the kidney localisation of A. fumigatus infection are discussed.


Preliminary investigation of the use of the enzyme linked immunosorbent assay (ELISA) in the serodiagnosis of mycetoma. Antibody levels in a small group of Sudanese patients with clinically diagnosed mycetoma, and control groups were measured by countercurrent immunoelectrophoresis (CIE) and enzyme linked immunosorbent assay (ELISA). Antigens were prepared from the following organisms: Streptomyces somaliensis, Actinomadura madurae, A. pelletieri, Nocardia brasiliensis and Madurella mycetomi. Positive reactions were obtained in clinical cases against the homologous antigens in both CIE and ELISA; all heterologous and control sera negative in CIE but produced some reaction particularly against N. brasiliensis and M. mycetomi antigens in ELISA.


The beneficial and harmful effects of positive end expiratory pressure. The effects of increasing levels of positive end expiratory pressure on gas exchange and pulmonary mechanics were determined utilizing an ex vivo ventilated perfused canine pulmonary lobe. When zero positive end expiratory pressure was used, shunting, weight gain and a decrease in compliance occurred over the four and one-half hour experiment. Shunting was eliminated when 5, 10 or 15 centimeters of water of positive end expiratory pressure were used. However, increasing extravascular fluid sequestration and decreasing pulmonary compliance occurred progressively with increasing levels of positive end expiratory pressure above 5 centimeters of water. Pulmonary artery pressure increased immediately along with end inspiratory pressure, an amount approximately equal to the increase in positive end expiratory pressure, and this is thought to be the primary cause of the increased rate of fluid sequestration. These experiments suggest that an optimal level of positive end expiratory pressure exists when the shunt can be reduced and oxygenation improved without increasing the rate of extravascular fluid accumulation to the point where long time deleterious effects could outweigh immediate benefits.


Effect of pretreatment with norepinephrine on survival of cardiac allotransplants in dogs. Two groups of puppies were studied regarding survival of the heart and the animal after epinephrine induced shock. All puppies in the control study died. In each of the eight puppies in the experimental group, the heart was removed and transplanted orthotopically into a healthy recipient. Six of the eight recipients died within hours, and the two which survived 14 days exhibited extensive cardiac structural changes at autopsy. The failure of recipients of hearts from these spinephrine-shock puppies to survive was in sharp contrast to the almost uniform survival of animals receiving orthotopic heart transplants from dogs subjected to irreversible hemorrhagic or endotoxin shock. This diference was due to the fact that the high levels of epinephrine infused were found to have produced extensive structural damage in the donor heart.


Fulminant pulmonary infections in renal transplant recipients. Opportunistic pulmonary infections often appear in patients requiring immunosuppressive therapy following renal transplantation. Fungal protozoal, viral and bacterial infections demand an immediate definitive diagnosis, since the outcome is related to the rapidity in establishing a diagnosis and the institution of appropriate therapy. Of 200 consecutive renal transplants during a seven year period, severe pulmonary infections developed in 21 patients. In 17 patients, a specific infectious agent was identified, using the flexible fiberoptic bronchoscope. Pathogenic specimens were obtained by bronchial washing, brushing or transbronchoscopic biopsy of the lung through the inner channel of the flexible bronchoscope. Bronchoscopy for localized lesions of the lung was aided by fluoroscopic guidance; for diffuse lesions, a roentgenogram of the chest was used to obtain bronchoscopic specimens from areas of maximum infiltration. Specimens were immediately dispatched and processed by the pathology laboratory. Except for one patient, all the others with fungal, protozoal and viral infections survived with functioning kidneys. Three deaths resulted from bacterial infections. Antemortem diagnoses were confirmed in all four patients who died.


Pulmonary sequestration.

Pulmonary sequestration. Pulmonary sequestration is an uncommon congenital abnormality in which nonfunctioning lung tissue is supplied by an anomalous systemic artery. Both the extralobar and intralobar forms probably develop from an accessory lung bud from the primitive foregut. Both forms are situated on the left side in about two-thirds of patients. The anomalous arterial supply usually originates from the descending thoracic aorta, and there may be a large left-to-left or left-to-right shunt through the sequestration. The sequestration may have a fistulous communication with the upper gastrointestinal tract. Congenital anomalies, particularly diaphragmatic hernia, are frequently associated with the extralobar form. Intralobar sequestration occasionally is an incidental finding on roentgenograms of the chest in an asymptomatic patient; however, the disorder is usually symptomatic and the most common presentation is recurrent pulmonary infection. Presentation may be characterized by gastrointestinal symptoms, congestive heart failure, hemoptysis or hemothorax. Extralobar sequestration is usually an incidental finding on routine roentgenograms of the chest or during the management of some other congenital anomaly. Infrequently, extralobar sequestration presents with symptoms similar to those seen with the intralobar form. Roentgenograms of the chest, upper gastrointestinal series and arteriography are the most helpful diagnostic aids. The usual treatment is resection of the sequestration by removal of only the sequestration in patients with the extralobar form and by lobectomy or segmental resection in patients with the intralobar form. The reported results of operation have generally been excellent.


Corneal dystrophies. I. Dystrophies of the epithelium, Bowman's layer and stroma. Most corneal dystrophies are autosomal dominant, bilateral disorders that primarily affect one layer of an otherwise normal cornea, progress slowly after their appearance in the first or second decade, and are not associated with a systemic disease. Epithelial basement membrane dystrophy and Fuchs' endothelial dystrophy are seen commonly by the general ophthalmologist; fleck, posterior polymorphous, granular or lattice dystrophies are seen more rarely, and others may never be seen in general office practice. While the distinctive clinical appearance of most corneal dystrophies allows accurate diagnosis, the integration of slitlamp findings with histopathologic and biochemical findings aids in the understanding of the clinical observations and provides a more rational basis for therapy. Transmission electtron microscopy is the most accurate method of histopathologic diagnosis. Epithelial dystrophies usually manifest intraepithelial cysts and abnormal basement membrane. In stromal dystrophies, an abnormal substance accumulates within the keratocytes or among the collagen fibrils; it may be an excess normal metabolite (like glycosaminoglycans in macular dystrophy), a material not usually present (like amyloid in lattice dystrophy), or a substance of unknown composition (like hyaline in granular dystrophy). Each dystrophy is illustrated with a composite drawing. Endothelial dystrophies will be reviewed separately in a second article.


[Counting colonies of micro-organisms on solid media (author's transl)]. The base of the system consists in a stainless steel cup with a shallow recess into which about 3 ml. of fluid agar medium may be poured, which produces a flat rectangular surface of about 8.65 sq. cm. after solidification. In the majority of cases, inoculation was performed by flooding the medium with a diluted suspension of micro-organisms. The cups were then put upright and carried over into a centrifuge tube which was closed with a rubber stopper. After the required incubation period, the colonies were counted, if necessary, using a specially developed colony counter connected to an electromechanical counting relay. Dilutions were prepared in screw capped bottles of various sizes. Pipettes were used only with connected "Volac" pipette holders. Cleaning and sterilisation could be done in an efficient and reliable way. In addition to the above method, the cups containing media may also be used for: impression counts, examination of fluids by immersion, inoculation by swabs or wire loops, studying air pollution. the system requires a rather large investment, but the daily cost and quantities of material used are small. The underlying study of the literature and the discussion of statistical methods used are available to the interested reader.


Mutagenicity of acrylonitrile.

Mutagenicity of acrylonitrile. Incubation of Salmonella typhimurium strains in an atmosphere of 0.2% gaseous acrylonitrile increased the numbers of his+ revertants/plate only in the presence of a fortified S9 liver fraction. The mutagenic effect was particularly pronounced with strains TA1530, TA1535 and TA1950 and much weaker with strains TA100, TA98 and TA1978. The results of bacterial fluctuation tests confirmed the necessity of the presence of S9 mix and showed the particular sensitivity of TA1530. The reversion rate varied with the S9 mix composition, the animal species utilized and the type of pretreatments applied to the animals. The mutagenicity of acrylonitrile in S. typhimurium is therefore microsome-mediated and is particularly discernable with strains sensitive to base-substitution mutagens.


[Use of synthetic saliva in dryness of the mouth in prosthetic stomatology]. A model experiment has been performed to investigate the possibilities of improving the adhesion of dentures. The best results were obtained with a synthetic saliva which, due to its medicamentous side-effect, might be indicated in case of hyposalivation.


[Gagging as a symptom of induced anxiety reactions]. In the light of personal studies and relevant reports in the literature, the authors deal with gagging during dental treatment and after denture insertion. In this connection, aetiopathologic and therapeutic aspects of the gagging syndrome are analysed. It is postulated that the gagging reaction is a conditioned anxiety reaction.


[Prosthetic treatment of patients with clefts. 3. The edentulous cleft patient]. Whereas the prosthetic treatment of an edentulous cleft patient with timely closure of the cleft promises to yield good results, the rehabilitation of an edentulous cleft patient with open cleft makes special demands on the prosthetist. Separate impressions for the denture and the obturator have proved a success at the Rostock University Clinic. On the basis of personal experience and results from re-examinations, the authors emphasize the value of regular ambulatory supervision.


[Aspects of prosthetic therapy in deep bite]. The authors deal with the peculiar aspects of prosthetic treatment in case of deep bite. The possibilities of bite-raising depend upon the functional conditions. The necessity is determined by secondary changes in jaw relation and by the kind of treatment. Any correction of the occlusal position must consider the relationships of the anterior teeth.


Enzyme immunoassay for cortisol in serum using cortisol 21-amine. Cortisol 21-amine (21-amino-11beta,17-dihydroxy-4-pregnene-3,20-dione) was prepared and an enzyme immunoassay for cortisol in serum was established using cortisol 21-amine conjugated with alkaline phosphatase. The minimal amount of cortisol detected was 1ng/tube and the measurable range was from 1 to 80 microgram/d1, using 10 mu 1 of serum sample. This enzyme immunoassay satisfied the standard criteria of dilution, accuracy and precision. The values correlated well with those obtained by radioimmunoassay. This enzyme immunoassay is applicable to the routine determination of serum cortisol in any clinical laboratory. Cortisol 21-amine was found to be a useful derivative for preparing cortisol-enzyme conjugate in enzyme immunoassay.


Susceptibility to vivax malaria in Ethiopia. Plasmodium vivax prevalence rates for Nilotic and Hamitic-Semitic residents of an Ethiopian town were compared. Over a ten-year period, 8,316 blood films from Nilotes were examined and 59 P. vivax infections (0.7%) were diagnosed. In 1,630 films from Hamito-Semites, 75 probable P. vivax infections (4.6%) were found. The problem of morphological differentiation between P. vivax and P. ovale was evaded by combining the two diagnoses. P. vivax/ovale infection rates for Hamitic-Semitic subjects were higher than for Nilotic subjects in all age groups. It was concluded that the two populations are inately different in susceptibility to patient infection with vivax malaria.


Serological survey of toxoplasmosis in the northern part of Iran, using indirect fluorescent antibody technique. A total of 1,779 persons from the Caspian Sea area, Iran, were serologically examined by the indirect fluorescent antibody technique for Toxoplasma antibodies. 55.7% were positive with titres of 1:20 or higher. No significant difference was demonstrated between the sexes. The highest antibody level as well as a high geometric mean of reciprocal titres were observed in the population between the ages of two and 19 years.


A study of the role of immunological factors in the pathogenesis of the anaemia of acute malaria. Children with acute Plasmodium falciparum malaria and anemia were investigated to see if immunological factors could be implicated in the pathogenesis of their anaemia. Direct Coombs tests using an anti-whole immunoglobulin antiserum were negative in all 12 children tested but two had positive tests with antisera to C3b and C3d. Low plasma levels of C3 and C4 were found but these were not significantly different from values found in a group of children with acute malaria who were not anaemic. Serum levels of immune complexes were normal at the time of their presentation at hospital with anaemia but were elevated one month later. Incubation of group O rhesus-negative red cells in a serum pool obtained from children with acute malaria and anaemia did not cause enhanced haemolysis or reduce their survival time on injection into mice. Splenic uptake of red cells was, however, significantly enhanced. We conclude that the anaemia of acute malaria is due mainly to destruction of red cells by malaria parasites and to enhanced erythrophagocytosis of normal cells.


Intravenous glycerol in cerebral infarction: a controlled 4-month trial. A double-blind, randomized trial was performed with 51 patients suffering from focal ischemic lesions in the territory of the middle cerebral artery. Intravenous infusions of 10% glycerol in 0.9% NaCl--5% glucose solutions were administered twice daily for 6 days to 26 patients, and the same amount of NaCl--glucose solutions to 25 controls. Glycerol did not reduce mortality (9 deaths in each group). The functional recovery was assessed by repeated neurological examinations during the 4 month trial. Glycerol significantly improved global performances and motor and sensory functions in patients with moderate disability, but its effect on global performances was transient. The patients with severe disability were not improved at all.


Rapid testing of ficinized cells in capillary tubes. A technique is described for capillary tube testing using small amounts with cell rapidly treated with a 4% ficin solution. This test aids antibody identification and cell screening.


Stimuli for the production and control of IgE in rats. In Hooded Lister rats IgE responses may be induced by administration of antigen together with one of a number of adjuvants. The primary IgE response may subsequently be enhanced either specifically by a further exposure to antigen (booster response) or non-specifically by infection with helminth parasites (potentiated response). In the latter case the enhanced response is associated with a great increase in total serum IgE. The primary response itself is not significantly influenced by variations in the general theme of conventional immunization, including dose or route of administration of antigen, or the nature of the adjuvant employed. The booster response however is inhibited, a) in rats primed with a 'large' (e.g. greater than 100 microgram EA) dose of antigen and B. pertussis, and b) rats primed with any dose of antigen given in Al(OH)3 or CFA, and c) following repeated booster doses of soluble (i.e. unadjuvanted antigen even at a dosage of a few picogrammes. It is thought that each of the stimuli generate antigen specific suppressor T cells. Live worm parasites selectively, but non-specifically, stimulate heterologous antigen primed IgE responses. The evidence suggests that it may be this non-specific IgE stimulating effect rather than the parasite specific IgE response per se which leads to the great elevation of total serum IgE. Other immunoglobulin classes are not elevated in the same way. The potentiated IgE response is not susceptible to the suppressive influence generated by previous administration of large or repeated doses of the heterologous antigen. On the other hand, a parasite specific regulatory mechanism acts to prevent repotentiation of the heterologous (but not the parasite specific or total IgE) responses following reinfection. These results are discussed in relation to the work of others in rats and other species.


Autologous bone marrow transplantation in patients with adult acute leukemia in relapse. Nine patients with adult acute leukemia were treated in relapse with piperazinedione plus supralethal total body irradiation in conjunction with autologous marrow infusion. Bone marrow cells were collected and stored in first remission. Storage time varied from 3 to 23 months. Before storage, marrow cells were separated using density albumin gradients in order to reduce the number of leukemic cells in the graft. Three patients died before day 14 after transplantation because of complications already present at the time of transplantation. In six patients, hemopoietic recovery started to occur within 14 days after transplantation. In four patients leukemia-free periods were obtained, lasting 60+ days. The three patients with the longest leukemia-free period after transplantation (range 75 to 220+ days) are reported in more detail. One patient is still alive without evidence of leukemia, with full hematological recovery 220+ days after transplantation.


Renal transplantation in a patient with lipoatrophic diabetes. A case report. A patient with congenital generalized lipodystrophy developed nephrotic syndrome with progressive renal glomerulosclerosis attributed to diabetic nephropathy. Renal transplantation was performed and the patient was discharged with normal renal function. Marked hyperlipidemia (17,500 mg/dl) persisted. One month later renal malfunction developed, and an open renal biopsy was performed when there was no response to antirejection therapy. Massive lipid deposition in renal tubular cells with tubular necrosis and hemorrhage was present but only minimal evidence of graft rejection. Rejection therapy was tapered and renal function stabilized. Death occurred 2 months later because of pulmonary sepsis. Patients with generalized lipodystrophy and severe hyperlipidemia may be at an unusually high risk for renal homograft destruction.


A heterophile system in human renal transplantation. VII. The antigen is an intrinsic component of several human tissues. The presence or absence of the heterophile transplantation antigen was sought in renal tissue from stillborn infants, primary cell cultures, and several organs from adult human cadavers. The heterophile transplantation antigen was found in renal tissue at birth, was retained in human renal cell culture, and was present in human organs other than kidney. The most likely explanation for these results is that the heterophile transplantation antigen is an intrinsic component of many human tissues.


Factors which have a significant effect on the survival of human skin grafts. Survival of 436 ABO-compatible skin grafts exchanged in 97 Caucasian families was prolonged if donor and recipient were genotypically, as compared with phenotypically, HLA identical. Among skin grafts between haploidentical family members, a mismatch at the A locus was equivalent to a mismatch at the B locus. Skin grafted from child to mother survived longer than did skin grafted between other family members, other variables being equivalent. A highly significant positive correlation was found between the age of recipient and skin graft survival. In addition, a significant interaction was found between the relationship of donor and recipient and degree of antigen match.


Immunological donor pretreatment in combination with pulsatile preservation in cadaveric renal transplantation. The extended experience on the efficacy of pretreating the cadaveric renal allograft donor by means of large doses of cyclophosphamide and methylprednisolone (group A, 36 kidneys) was compared with the experience regarding untreated renal allografts (group B, 32 kidneys). Kidneys in both groups were perfused by pulsatile means using cryoprecipitated plasma. There was a significant difference in allograft survival (72% in group A versus 36% in group B at 3 years by actuarial means). Also, large doses of cyclophosphamide and methylprednisolone as pretreatment did not cause any detrimental effect to the allograft kidney when used in combination with cryoprecipitated plasma and pulsatile perfusion.


Function of autotransplanted kidneys after 24-hour preservation by hypothermic pulsatile perfusion or simple cord storage. Canine kidneys, flushed with either Collins solution or autologous cryoprecipitated plasma, were then stored for 24 hr by either simple cold storage (submersion) in the flushing solution, or by continuous hypothermic pulsatile perfusion with cryoprecipitated plasma. After autotransplantation without contralateral nephrectomy, detailed split renal function studies were carried out immediately as well as 2 and 7 days later. Measurements were made of inulin clearance, maximal transport of p-aminohippurate, reabsorption of sodium, chloride, and glucose, and the reabsorption of free water. Contralateral nephrectomy was performed 7 days after transplantation, following measurement of renal functions on that day, and plasma urea nitrogen and creatinine were measured periodically over the ensuing 3 weeks. Renal function after transplantation was affected very little by the choice of flushing solution, and the course of azotemia that developed following contralateral nephrectomy was the same in all groups. However, the detailed functional measurements showed that during the 7-day period after transplantation, renal function was depressed to a much greater extent in kidneys treated by simple cold storage than in those that had been perfused.


Studies on skin-reacting transplantation antibodies. Evidence is presented that skin-reacting transplantation antibodies (SRTA) can be elicited not only by skin allografts, but also by injection of dispersed allogeneic lymphoid cells. Two mechanisms of action of SRTA, which are not mutually exclusive, are compatible with the experimental results. (1) SRTA may act as homocytotropic antibodies, producing skin reactions by fixing to the skin of the test animal and combining with circulating antigens brought to the test site. (2) SRTA may produce skin reactions by combining directly with "sessile" antigens in the skin. Genetic studies showed that the antigens combining with SRTA are inherited as simple Mendelian traits. Furthermore, it was shown that these antigens are not related to the major rat histocompatibility antigens, Ag-B, nor are they related to any other described rat alloantigen system. Thus, the antigens responsible for SRTA belong to a new antigenic system.


Effect of prior third-party blood transfusions on canine renal allograft survival. The relationships between immune reactivity after blood transfusions, subsequent kidney allograft survival, and donor selection were studied in dogs. Animals with a high as well as low serological immune reactivity toward antigens contained in blood transfusion were observed. Genetic control of this reactivity or a linkage of this property to DLA, sex, or red blood cell markers inheritance was not apparent in the four beagle families studied. The two recipients with the lowest immune reactivity scores were also found to be the longest survivors after a DLA-mismatched kidney graft. Seven other recipients with higher scores rejected their DLA-mismatched kidneys as rapidly as did untransfused animals. Kidney graft survival was decreased in some recipients of DLA-identical kidneys (n = 5), presumably through sensitization for minor histocompatibility antigens. A normal or an increased survival time of DLA-identical kidneys was found in the remaining animals (n = 6). The majority of these recipients appeared to have a higher than average reactivity in two-stage microcytotoxicity testing. This might have been attributable to the presence of enhancing antibodies. Further studies in preclinical animal models are needed to define the optimal transfusion policy for human patients awaiting a kidney graft.


Prolongation of renal allograft survival in DLA tissue-typed beagles after third-party blood transfusions and immunosuppressive treatment. Significant prolongation of survival of nonrelated DLA-mismatched renal allografts has been obtained in beagle recipients receiving three blood transfusions from nonrelated donors prior to kidney transplantation and immunosuppression after transplantation. Nontransfused DLA-identical or DLA 1 haplotype-different littermates of the transfused dogs were used as controls. Lymphocytotoxic antibodies were formed after the blood transfusions. A quantitative immune reactivity score correlated with graft survival. Low scores prior to transplantation were found in five transfused dogs that did not reject their allografts. High scores prior to transplantation were found in four animals rejecting their graft and in one dog that survived after an abortive rejection episode. The great similarities between the results obtained in this animal model and the observations made in human transplant patients indicate that this model can be utilized for a further analysis of the possibilities of blood transfusions in protecting subsequent renal allografts from immunological rejection.


Reversal of diabetes in rats using fetal pancreases stored at -196 C. Fetal rat pancreases frozen to and stored at -196 C were used for transplantation into streptozotocin-induced diabetic syngeneic adult recipients. Transplantation was carried out either directly after thawing from -196 C, or after a 21-day growth period in a syngeneic, normoglycemic adult carrier. All transplants were placed under the kidney capsule. A single, frozen fetal rudiment was sufficient to restore blood glucose, urine volume, and urine glucose to normal, provided it had first been grown for 21 days in a normal carrier. It vitro perfusion studies showed that fetal pancreases stored at -196 C were equivalent to fresh rudiments in their responses to a glucose stimulus.


Lymphocytotoxic antibodies and bone marrow grafts from HLA-identical siblings. I. HLA antibodies. In a series of 30 bone marrow grafts (in 29 recipients) from HLA-identical siblings for aplastic anemia, no correlation was demonstrated between rejection and pregraft HLA antibodies (P greater than 0.50). However, after grafting, HLA antibodies persisted in nine cases and graft rejection occurred, whereas in all but one of the remaining eight cases the HLA antibodies disappeared and a permanent engraftment was observed (P = 0.0008). These results suggest a relationship between engraftment and persistence or disappearance of HLA antibodies as an indication of the level of immunosuppression obtained with the conditioning regimen.


Evaluation of an indirect fluorescent antibody test, enzyme-linked immunosorbent assay and quantification of immunoglobulins in the diagnosis of bovine trypanosomiasis. An indirect fluorescent antibody test (IFAT), a microscale version of the enzyme-linked immunosorbent assay (microELISA) and determination of IgM levels in serum were assessed for their comparative diagnostic value in the detection of bovine trypanosomiasis. Serum samples from drug-treated N'dama cattle and untreated N'dama and Zebu cattle from Liberia were examined for the presence fo antibodies to trypanosomes. In the untreated Zebu cattle, infections with T. vivax predominated and the prevalence of infection was higher than that found in untreated N'damas in which infections with T. congolense predominated. The proportion of animals which showed serological evidence of trypanosomiasis in the untreated Zebus was slightly higher than that found in the untreated N'damas. The prevalence of infection was low in N'dama cattle which had been treated with diminazene aceturate and homidium chloride but 50% of the animals showed serological evidence of trypanosomiasis. More serologically positive animals were detected by microELISA than IFAT, but both tests were equally sensitive in detecting antibodies in cattle in which trypanosomes were demonstrated by examination of peripheral blood. With both IFAT and microELISA it was necessary to carry out tests using antigens prepared from T. brucei, T. vivax and T. congolense in order to detect all serologically positive animals. Increases in serum IgM occurred in both N'dama and Zebu cattle but the levels were raised in only approximately half of the known infected animals. Overall, more animals gave positive reactions with IFAT and microELISA than showed raised IgM levels.


[Mutagenic activity of antitubercular preparations: isonicotinic acid hydrazide and its derivatives]. Mutagenic activity of anti-tuberculosis drugs: isoniazide, phtivazide, metazide, larusan and saluzide soluble was studied using the semiquantitative plate technique of S. typhimurium tester strains TA 1950 and TA 1538 (after B. N. Ames) within the system of metabolic activation in vitro. No ability to induce gene mutations was found using this modification of the technique. A study of mutagenic activity of isoniazide and saluzide soluble in the experiments with a mammal as intermediate and using the tester strain TA 1950 showed a mutagenic effect of isoniazide and no such effect of saluzide soluble.


The usefulness of 125I-sodium lothalamate as a GFR-indicator in single intravenous injection tests. Clearance of sodium iothalamate was estimated from plasma elimination curves obtained from 90 patients having varying renal function, after a single intravenous injection of 125I-sodium iothalamate. The usefulness of sodium iothalamate as a GFR-indicator with this technique was tested by a strict statistical comparison with conventional inulin clearance as a reference. The regression line, covering the clearance range 2-163 ml min-1, Clinulin = 1.08.Clsodiumiothalamate-3.7, (n = 84, r = 0.85, SEE = 2.3 ml.min-1) was not significantly different from the identity line, which means (i) that extrarenal elimination could not be detected, and (ii) that I125-sodium iothalamate should be regarded as a useful glomerular marker for single intravenous injection studies. An open two-compartment model of mamillary type was found to give an adequate representation of the plasma disappearance curve. The results are not critically dependent on the choice of approximating function. The method by Sapirstein et al., the method by Nosslin and a power-law method were used for comparison and were found to give the same results. However, the present type of curve fitting analyses requires frequent blood sampling or external counting over a long period in order to give reliable estimates of GFR. This circumstance makes these methods less attractive for clinical use.


[Cell cultures as vitality test for preservation of kidneys by deep freezing (author's transl)]. Cytologic examinations of kidneys, which were frozen for preservation in a nitrogen atmosphere below 3 ata, show a considerable damage of the cells. This does not only occur by significant reduction in the amount of isolated cells, but also in the loss of the ability to form cell colonies. DNA measurements show, however, that after 3--4 days the DNA amounts in surviving cells are intact. In one of the cultures we even found DNA values, which stand for a DNA synthesis. Experiments with mechanical perfusion alone show that this procedure results in a severe damage of the cells, only about one-third of these cells being able to form colonies.


[Biochemical parameters for determination of graft viability during the early postoperative period (author's transl)]. In 54 patients with graft failure the changes of urine sodium concentration and of urinary enzyme activities (alanine aminopeptidase, AAP) were investigated. It was found that: (1) the kidneys with irreversible acute tubular necrosis are characterised by high urine sodium level, and low AAP activities. These changes correspond to the end stage of renal insufficiency. (2) Low concentration of sodium and extremely high AAP excretion are characteristic in grafts with severe rejection episodes. (3) If kidneys lost their function due to irreversible rejection, the biochemical variables showed the same changes as in the first group. We concluded that by continuous determination of sodium levels and enzyme activities in urine and by their correlation it is possible to detect the non-functioning grafts in the early posttransplantation period.


Relation between the vaginal introital and perianal flora in recurrent cystitis in women. 15 patients with urinary infection were selected and analyzed in relation to infection in the vaginal and perianal areas. After treatment, 12 patients with urinary infection were cured, but bacterial organisms persisted in their vaginal and perianal areas. In spite of the persistence of the vaginal and perianal infection, those patients remained free of urinary infection. We can conclude that other factors, besides the persistency of bacterial organisms in the vaginal introitus and perianal regions, may be important in the development of ascending urinary infection.


Experiences and critical comments on the temporary intravesical electrostimulation of the neurogenic bladder in spina bifida children. This is a report of a special method of a temporary intravesical electrostimulation of the bladder for the treatment of the urinary incontinence of spina bifida children. The technique with presentation of apparatus and catheter is described in detail. The criterias for the selection of the patients are explained, the most important of which is the response of the detrusor muscle during the stimulation recorded by uromanometry. 26 spina bifida children were treated. There is at least a success in 50% of the patients, if the criteria are fulfilled.


Evaluation of urodynamic studies by computer. In an attempt to simplify urodynamic evaluation, the data obtained from cystometry, urethral profile and flowmetry were analysed using the ICS recommendations for standardization and terminology. All studies were compiled from check lists feasible for computation. The aim was to establish standards and "typical" changes for the normal bladder and pathological states to enable automatic readout of computed data. The results did, in fact, show "typical" changes but failed to establish standard measurements suitable for completely computed diagnoses.


[Experiences with temporary intravesical electro-stimulation of the neurogenic bladder in spina bifida children (author's transl)]. This is a report of a special method of a temporary intravesical electrostimulation of the bladder for the treatment of urinary incontinence of spina bifida children. The technique with presentation of apparatus and catheter is described in details. The criterias for the selection of the patients are explained, the most important of which is the response of the detrusor muscle during the stimulation recorded by uromanometry. 28 spina bifida-children were treated. There is success in 70% of the patients, if the criteria are fulfilled.


Infertility and genitourinary infection. There is a vast amount of evidence linking the presence of genitourinary infection with infertility. Infection in either partner can result in specific effects on sperm function, accessory sexual gland dysfunction, and the induction of immunologic responses in either partner. Careful investigation for infection should be undertaken in every couple with the complaint of infertility. Treatment needs to be individualized in each instance.


Clinical comparison of cefadroxil, new oral cephalosporin, and cephalexin in uncomplicated urinary tract infection. Efficacy and safety of cefadroxil, a new oral cephalosporin, were compared with that of cephalexin in the treatment of 28 women with acute urinary tract infections. According to a randomized double-blind design, each patient received cefadroxil 1,000 mg. twice daily or cephalexin 500 mg. four times a day for ten days. Cures based on urine culture five to nine days post-treatment were obtained for all but 1 patient receiving cefadroxil; reinfection after eradication of the original pathogen was recorded for only 1 patient in each treatment group. No drug-related side effects or significant clinical laboratory abnormalities were observed during the study. Cefadroxil 1,000 mg. given twice daily was as effective and as well tolerated as cephalexin 500 mg. given four times daily. The significance of this dosage schedule advantage is discussed.


[Hyperbaric oxygen therapy and dimexide in the overall treatment of osteomyelitis in children]. In the complex treatment of 25 children with acute osteomyelitis and 7 children with aggravation of chronic osteomyelitis HBO-therapy and dimexide wwere used. This treatment produced a favourable therapeutic effect in all the patients. X-ray investigation proved the decrease of bony destructions and acceleration of reparative process in the bones.


[New suture material for intestinal sutures in children]. In the experiments on puppies the authors studied the possibility for the use of ophthalmologic tendinous threads as a suture material for interintestinal anastomoses after intestinal resection. Ophthalmologic tendinous thread was used in a neonate with atresia of the small bowel. Six months' follow-up revealed a good result.


[Autodermoplasty in the treatment of wound emaciation]. Different types of dermoplasty aimed at the closure of reactive wounds were applied in the treatment of 26 cases with protracted non-healing wounds (up to 30 years) following burns, frostbites, open fractures, outcomes of acute suppurative diseases with sepsis phenomena. The treatment failed only in one patient. The transplantation of free stamp-like skin grafts proved to be the most effective one. Biostimulating effect of the single grafts which fuse has been noted.


[Toxicity of oximes and their effect on acetylcholinesterase activity in the blood and myoneural synapses of animals]. The effect was followed up of 2-PAM and Toxogonin (T), reactivators of choline esterase, at a single muscular application on the activity of acetylcholine esterase (ES 3.1.1.7) (ACE) of whole blood (WB) and the myoneural synapses (MS) of an interrib muscle. It was found that a species-specific effect was produced by T and 2-PAM on ACE of WB and MS in lambs and sheep. Optimal doses of 50 and 80 mg/kg led to a slight drop in the activity of ACE at the 2nd hour following injection, after which it rose gradually up to values that were higher than the initial ones for more than ten days. 100 and 200 mg/kg led to a more sensitive and long-term drop in the activity of ACE (up to 48h--72nd hour), after which it likewise rose above the initial value, and came back to normal on the 13th day. With lambs the reaction was analogous, though weaker. In rats and rabbits there was no change in the activity of ACE of WB and MS following the use of oximes. The optimal nontoxic and inductoenzyme rates of the two oximes for lambs and sheep proved to be about 50 mg/kg. It was established that both for rats and for sheep and lambs T was almost twice as toxic as 2-PAM. Intoxication with T was characterized by severe hemorrhagic and necrotic nephroso-nephritis, acute toxic dystrophy of the liver, and ulcerous, necrotic enteritis. 2-PAM was found to potentiate the toxic effect of T.


[Fractionation and purification of DNA methylation enzymes from Escherichia coli CK cells on phosphocellulose P-11]. Conditions for purification and fractionation of the methylases from E. coli CK cells using phosphocellulose P-11 were studied. A fraction, obtained after ammonium sulphate precipitation, was used as a starting preparation for column chromatography. Elution was carried out with linear gradient of NaCl concentration from O to 0.8 M. The methylase activity was found in effluent fractions, in rinsing solutions and in the gradient zone (G). The fractions, unadsorbed on P-11, contained methylases of adenine and cytosine. In the experiments with the gradient elution the methylase activity was observed in fractions, corresponding to NaCl concentration of 0.12, 0.18, 0.26, 0.33 and 0.68 M. The specific activity was increased 10-4O-fold in the fraftions during the purification. The G1, G2, and G5 fractions contained only the adenine methylase and did not possess the cytosine-methylating activity. A mixture of enzymes, methylating adenine and cytosine, was found in G3 and G4 fractions. The data obtained suggest that several methylases are present in E. coli CK cells; these enzymes exist apparently as isoenzymes.


[Quantitative determination of immunoglobulin A in human serum by an immunoenzyme technic]. A complex of immunoglobulin A (IgA) with peroxidase was obtained as a result of interaction of IgA with the enzyme, modified with sodium periodate. The molar ratio of IgA/peroxidase was equal to 1 in the complex, as shown by gelfiltration and sedimentation analysis. Peroxidase maintained 75% of the initial activity in the complex. The antigenic and enzymatic properties of the complex were retained completely within 5 months, if the preparation was kept at 4 degrees in phosphate buffer, pH 7.4. The complex isolated was used for quantitative estimation of IgA in human blood serum. The method is based on the reaction of competitive binding between free and labelled with peroxidase IgA molecules and antibodies, immobilized on inorganic porous carrier--sylochome. The method enables to estimate quantitatively IgA concentration within the limits of 102=105 ng/ml.


Emergencies in oncology. Current management. Malignant neoplasms may cause life-threatening complications requiring prompt diagnosis and emergency therapy. Whether or not the underlying neoplasm is potentially curable, the physician can often provide worthwhile prolongation of life and dramatic symptomatic relief. Among the serious complications of neoplasia are superior vena cava obstruction, airway obstruction, pericardial tamponade, spinal cord compression, brain metastasis, meningeal involvement by cancer, hyperuricemia, hypercalcemia and hyperkalemia.


The case for control in diabetes mellitus. In all diabetic animal models studied to date, microangiopathic complications develop which can be prevented by tight control and reversed by either islet cell transplantation or transplanting the diabetic kidney into a nondiabetic environment. In humans the prevalence of these complications in secondary diabetes mellitus is similar to the prevalence in genetic diabetes. Furthermore, mesangial basement membrane thickness is normal at the onset of the disease and increases shortly thereafter. These two facts strongly suggest that the microangiopathic complications are not an independent genetic component but rather are secondary to the metabolic derangements of uncontrolled diabetes. Normal kidneys transplanted into diabetic recipients developed the vascular lesions of diabetes. Conversely, two diabetic kidneys inadvertently transplanted into nondiabetic recipients showed clearing of the vascular lesions.Most retrospective studies support the conclusion that control is associated with lessened complications. The three prospective studies published to date also support this hypothesis. Because glucose concentrations cannot be brought to normal levels by present methods, the critical question is whether a major emphasis on restoring metabolism to as nearly normal as possible will help ameliorate the microangiopathic complications in our patients. The accumulated evidence would strongly favor an affirmative answer. Two daily injections of intermediate-acting insulin supplemented with small amounts of short-acting insulin as needed is one method to approach this goal.


[The activated modified smooth muscle cell: morphology, metabolism, distribution and transitory forms]. On human as well as on animal vascular material a characteristic distribution of activated smooth muscle cells is observed which is characteristic for the course of a lesion. In early stages these cells are above all found below the tunica elastica as well as in the marginal parts of the plaques, whereas later on the distribution is increasingly balanced. These cells are metabolically active and also show a higher division rate. The morphological characteristics of the activated smooth muscle cells are a reference to the metabolic and synthetic activity of the cells. Independent on this a characteristic content of activated smooth muscle cells is revealed during ageing. It is still unclarified in as far prognostic conclusions may be derived from the distribution of this cell form on the human vascular material.


[The carotid sinus pressure test--a screening method for the demonstration of latent bradycardial arrhythmias]. 100 patients with peripheral arteriosclerotic obstructive disease were examined for latent bradycardic disturbances of the rhythm by means of the pressure experiment on the carotid sinus under screening conditions. 57% of the arteriosclerotics had sinus-auricular or atrioventricular blockings, 67% of them an asystole over 3 s. In 84% of the cases this asystole was conditioned by a sinus-auricular block. In a comparative group of the same age only a retardation of the sinus rhythm was found. An asystole over 3 s in a pressure experiment on the carotid sinus refers to an endangering by Morgagni-Adams-Stokes-attacks, since the substitution pacemaker in form of the secondary stimulation formation system insufficiency compensatorily steps into the breach. Particularly endangered seem to be patients with additionally bradycardizing medicaments (glycosides, antihypertensive drugs, beta-receptor blockers, antiarrhythmic drugs) which frequently and combined are prescribed in arteriosclerotics with hypertensive cardiac disease. In synopsis with anamnesis, findings of the examinations and the ECG-analysis with and without pressure experiment on the carotid sinus can be decided on the actual therapy up to the pacemaker implantation. The method proved to be suitable as screening and preliminary examination before the prescription of the medicaments mentioned above when performed correctly and the contraindication was taken into consideration. It is to be discussed whether before recommendation of the broad application of the pressure on the carotid sinus without possibility of reanimation a phase of another testing should precede.


[Improvement of healing of pedicled skin flaps and free skin grafts (animal experiments)]. A combined therapy in order to improve the healing of dermatoplasties is presented. Epicutaneous application of oxygen is combined with injection of a vasodilating drug. The results from experiments on 25 rabbits showed accelerated healing, smaller necroting areas, and improved circulation in pedicled skin flaps of well as in free cutaneous grafts. All results are statistically secured and are confirmed by histologic examinations. The method is uncomplicated and very effective.


[Free skin-adipose tissue flap transplantation in rats]. An important precondition for the clinical application of the free flap transplantation with microvascular anastomoses is the training in the animal experiment. With some fundamental anatomical observations concerning the vessels of the skin and types of flaps the suitability of different laboratory animals is demonstrated. The technique of the free composite flap transplantation utilizing the abdominal flap of the rat is described. This flap model is not only suitable for test the success of the microvascular suture, but is also useful in cases of special pharmacological, pathological and physiological problems of the free flap transplantation.


[Effect of portocaval shunt and arterialization of the liver on antibodies to Escherichia coli in patients with cirrhosis of the liver (author's transl)]. The effect of a portocaval shunt with and without portal arterialization of the liver on serum immunoglobulin concentrations and on the incidence of antibodies to 8 different serotypes of Escherichia coli was studied in 29 patients with cirrhosis of the liver. Compared with healthy controls, the serum concentrations of IgG, IgA and IgM were significantly elevated in cirrhotic patients. No difference in immunoglobulin concentrations could be observed between shunted and arterialized cirrhotics. The incidence of E. coli antibodies was significantly higher in patients with cirrhosis of the liver, showing a further increase in patients with portocaval shunt operations. Portal arterialization of the liver after portocaval shunting did prevent this additional increase, presumably by restoring the antigen clearing capacity of the cirrhotic liver, thus avoiding an additional stimulation of the antigen response after the portocaval shunt. The quantitative contribution of E. coli antibodies to the hyperimmunoglobulinemia of patients with cirrhosis of the liver seems to be of little significance. The results of this study underline the significance of the portal hepatic blood flow for the function of the reticulo-endothelial system of the liver.


Extra-amniotic prostaglandin F2alpha in gel for prelabor cervical ripening. In 22 normal term gravidas with unfavorable cervix, 5 mg PGF2alpha in Tylose gel was instilled into the extra-amniotic space. The treatment improved the cervical state so much that the women could be successfully induced by conventional methods. The procedure was well tolerated by the mother and it appeared to be perinatally safe.


[In vitro examinations - a basis of additional cancer therapy (author's transl)]. The necessity of additional cancer therapy by cytostatic agents and hormones tested on human malignant tumour cell cultures is stressed. Randomized correlative findings of in vivo and in vitro tests are reported. Surgical procedures, irradiation, cytostatic treatment, hormone therapy, and immunotherapy should be used successively in efficient combination.


[In vitro lysis of schizophrenic patients' erythrocytes in an autologous system]. Using the Erne method in N.N. Klemparskaya's modification the author studied peripheral blood of 59 schizophrenic patients with different types of the course and 23 normals. It is shown that in the peripheral blood preparations of schizophrenic patients there is a reliably greater number of zones of local hemolysis of erythrocytes. This phenomenon is associated with a general immunological status of the body.


The interaction of uranyl ions with inorganic pyrophosphatase from baker's yeast. The interaction of uranyl ions with inorganic pyrophosphatase from baker's yeast was investigated by measurement of their effect on the protein fluorescence. Fluorescence titrations of the native enzyme with uranyl nitrate show that there is a specific binding of uranyl ions to the enzyme. It was deduced that each subunit of the enzyme binds one uranyl ion. The binding constant was estimated to be in the order of 10(7) M-1. The enzyme which contains a small number of chemically modified carboxyl groups was not able to bind uranyl ions specifically. The modification of carboxyl groups was carried out by use of a water soluble carbodiimide and the nucleophilic reagent N-(2,4-dinitro-phenyl)-hexamethylenediamine. The substrate analogue calcium pyrophosphate displaced the uranyl ions from their binding sites at the enzyme. From the results it is concluded that carboxyl groups of the active site are the ligands for the binding of uranyl ions.


[Absorption of anti-placenta serum by means of immunosorbents]. An anti-placenta serum was absorbed by means of immunosorbents to remove antibodies against human serum proteins. The absorption met with some difficulties, because the anti-placenta serum contained antibodies against several human serum proteins. 12 different methods were compared for their suitability to adsorb these antibodies against human serum proteins. Most suitable is human serum cross-linked by glutardialdehyde. Good results were obtained too with human serum linked to Enzacryl, Polyaminostyrene or CNBr-activated Sephadex.


On the properties of alpha-glucosidase and the binding of glucose to the enzyme. An alpha-glucosidase was purified from baker's yeast. The molecular weight was approximately 44 000 daltons. SDS-disc gel electrophoresis suggested that the enzyme consisted of four subunits. The isoelectric point was at pH 5.4. The Km values for p-nitrophenyl alpha-D-glucopyranoside and maltose were 2.9 X 10(-4) and 2.5 X 10(-2) M, respectively. Binding of 2-(p-toluidino)naphthalene-6-sulfonate to the alpha-glucosidase was associated with a strong increase in fluorescence. The dissociation constant of the enzyme-TNS complex was 8 X 10(-5) M. The fluorescent probe did not interfere with the binding of glucose to the enzyme although the alpha-glucosidase was inhibited by high concentrations of TNS. The formation of an enzyme-glucose complex was indicated by an increase of fluorescence and by a shift in the wavelength for maximal emission which suggests that the binding process is associated with a change in conformation. The dissociation constant of the glucose--alpha-glucosidase complex KD = 0.57 X 10(-3) M, was calculated from the increase in fluorescence as a function of glucose concentration.


Implantation of pacemaker electrode from parasternal mediastinotomy. A review of the literature on the possibilities of myocardial pacemaker electrode implantation is presented. The field of indication of myocardial electrode implantation is restricted to cases of repeated intracardial electrode dislocation and multiple suppuration. In the authors' experience parasternal mediastinotomy offers an appropriate surgical approach for myocardial electrode implantation and has several advantages over other methods of penetration.


Circular crural ulcer; its surgical therapy. Experience with the surgical therapy of two serious cases of crural ulcer is described. The ulcers were widely and deeply excised together with the fascia and covered three weeks later by a split free skin graft. As a technical innovation, a mesh graft was applied in one case and in the other the ulcer was removed in two steps to avoid secondary shrinking. The functional result was in both cases unobjectionable even two years after the operation. In similar, apparently hopeless, cases the method will help to avoid amputation and to achieve complete freedom from symptoms for years.


[Suturing of the resected renal parenchyma]. A historical and technical survey of the indication and application of people resection is presented. A new method is described to ensure rapid haemostasis, reduced parenchymal loss and early mobilization of the patient. The records of 29 patients operated upon in this way are reported.


Experimental heterotopic pancreas segment transplantation. Autologous and allogenic transplantations of the caudal part of the pancreas into the omentum and the spleen were performed in 18 dogs. The fate of the transplants was followed histologically. In the grafts the Langerhans-islands preserved their integrity longer than in the other parts of the organ, but in 4 to 6 weeks they, too, necrotised.


[Reliability of sutures in gastroenterologic surgery]. Four methods have been worked out to improve the reliability of sutures, the seromuscular cuff, the technique of "sterile" closed and semi-closed mechanical anastomoses, the intraoperative emptying of the congested intestine and the transanal (lower) bridging over of the operated area. During three decades of gastrointestinal surgical practice these techniques have ensured satisfactory results and their application can be recommended. The results achieved with the application of these techniques in gastric surgery and in primary colon resection in the presence of ileal-subileal symptoms are discussed.


Influence of digitalis on cardiac function before and after autonomic blockade. The influence of Deslanoside C (D), 1.2 mg intravenously on the systolic time intervals (STI) was assessed in 15 individuals with right ventricular pacemakers, who were studied on two occasions, ten days apart. In the first case D was given under basal conditions, and in the second after autonomic blockade (with practolol 20 mg intravenously and atropine 1.5 and 1.0 mg intravenously) at 1 hour's interval. There were similar changes of the STI with digitalis administration both before and after automic blockade. Autonomic blockade is not necessary for full expression of digitalis action on the human heart, as advocated by some authors to be the case in experimental animals.


Radioactive isotopes in the diagnosis of heart disease. Since the first application of radionuclides in cardiology, fifty years ago, a lot of invasive and noninvasive techniques have been developed. Invasive methods, performed in the catheterization room, have increased our comprehension of physiopathological mechanisms in congestive heart failure and coronary insuffiency. Noninvasive methods have allowed assessment of regional left ventricular wall motion and ejection fraction, of myocardial perfusion at rest and after exercise and of intracardiac shunts, in ambulatory patients. Most of these methods have been developed in the last two decades, and particularly in the last few years. Technical improvements, like scintillation cameras, computers and shortlived tracers, have considerably improved their possibilities. New techniques, like positron imaging with three-dimensional reconstruction, current use of ultra-short life indicators and further refinements in radio-immunoassays, will undoubtly increase our fundamental and clinical knowledge of congenital and acquired heart diseases.


Radioisotopic diagnosis and quantitation of left to right shunts in childhood and adolescence. In 187 patients (141 adults and 46 children) left to right shunts were assessed using quantitative radionuclide angiography. After injection of 99mTc into the femoral vein time activity curves were registered over both lungs and the heart (Ohio Nuclear Camera, ON SIGMA 400, 110, HP 5407 computer). Using a modified gamma function area ratio technique the shunt sizes were calculated. The radioisotopic method allows a precise quantitation of left to right shunts ranging from 15--80%. There was a good agreement between the shunt sizes calculated by the radioisotopic method and oximetry or dye-dilution at cardiac catheterization (adults r = 0,87, children r = 0,85). The shunts sizes assessed with this nontraumatic method appear sufficiently reliable to be a real alternative to conventional techniques in screening for shunts.


Collagen types in early phases of wound healing in children. Small silicone rubber tubes containing a standard size viscose cellulose sponge (Cellstic) were implanted in wounds of ten children at the end of surgery. The Cellstics were drawn out of the wound 24--120 hours after implantation and the cellulose sponges were sectioned and studied for collagen types. Immunologically detectable Type III collagen and procollagen was detected in the sponges 24--48 hours after implantation whereas Type I collagen was not found at that time. From hour 72 onwards a substantial increase in Type I collagen was noted, while the relatively low levels of Type I procollagen remained unchanged. The levels of Type III collagen and procollagen increased only slightly. Primary cultures from 9-day-old granulation tissue synthesized preferentially Type I collagen, on the basis of chromatographic analysis. We conclude that Type III collagen is produced at the earliest phases of wound healing by primitive mesenchymal cells followed by the production of Type I collagen after the appearance of mature wound fibroblasts.


[Surgical treatment of lungcancer five-year survival. Major surgical complications (author's transl)]. In the period 1961--1971, 41 patients with a squamous-cell carcinoma were operated upon. The absolute 5-year survival is 47.6% for the lobectomy and 20% for the pneumonectomy. In the period 1971--1976 (6 years), 211 resections for carcinoma (all types) were performed including 19 cases of squamous cell carcinoma, operated in 1971 and also studied in the first part of the work. They represent only 15.2% of all the hospitalized lungcancer patients. The lobectomy/pneumonectomy ratio is 60/40. The postoperative mortality is respectively 4% and 9.5% and the major surgical complications (bleeding, broncho-pleural fistula, empyema) are 0.8% and 3.6%. The causes of postoperative death are examined. Remarkable is the low incidence of bronchial fistulisation: 1 in 211 resections for malignant tumors, i.e. 0.47%. These results are discussed and compared with the literature.


Response of acromegaly to long term bromocriptine therapy: a biochemical and clinical assessment. The long term effects of bromocriptine in 12 acromegalics treated for a mean duration of 10.2 months are reported. Seven showed a significant (P less than 0.05) and sustained fall in serum immunoreactive growth hormone (GH) levels throughout 24 h, 6 of whom had a 50% or greater reduction in mean circulating GH during glucose tolerance testing. Only one patient had mean serum GH levels throughout the day suppressed to normal (less than 5 mIU/l) but 3 had suppression of mean serum GH during GTT to normal or very near normal (less than 10 mIU/l). The effective dose was 20 mg daily. Only 4 patients reported any improvement in soft tissue swelling and acral features, which was unrelated to the GH response. Possible reasons for the discrepancy between clinical and biochemical responses are discussed. In 9 of the 12 patients bromocriptine was discontinued and pituitary ablative therapy offered. Three out of 4 patients who underwent trans-sphenoidal hypophysectomy had mean GH levels during GTT reduced to less than 7 mIU/l. In the three who continued bromocriptine treatment GH suppression was maintained at less than 10 mIU/l for up to 3 years but with little change in acral features. Although bromocriptine is safe and was well tolerated it is not as effective as existing forms of pituitary ablative therapy and should be reserved for those cases where ablation is contraindicated or unsuccessful.


Glucagon and insulin secretion in potential diabetes. Insulin and glucagon have been studied in 20 subjects (both of the subjects' parents were diabetic or in case of only one diabetic parent, the other showed a first degree familiarity of diabetes): 10 showed normal glucose tolerance ('true prediabetics') and 10 impaired glucose tolerance ('genetic chemical diabetes'). Mean insulin response to oral (100 g) and i.v. glucose load (200 mg/kg followed by 20 mg/kg/min for 60 min) and to arginine infusion (25 g in 30 min) was normal in the prediabetics and delayed and higher in the subjects with chemical diabetes as compared to the control group. Glucagon response to arginine was higher, but not significantly, in prediabetics and in subjects with chemical diabetes. In both of these groups glucagon suppression by glucose was not observed. The insulin/glucagon molar ratio was significantly reduced after glucose infusion in these two groups. No correlation was found between insulin and glucagon secretion after arginine or glucose. A possible alteration in the mechanism controlling glucagon secretion even in the earliest phases of diabetes is suggested.


Influence of the purity of the iodinated tracer on the specificity of the radioimmunoassay of human luteinizing hormone. Human luteinizing hormone (HLH) iodinated with 125I by the use of a lactoperoxidase method, was fractionated by either cellulose adsorption, gel filtration or by the combination of these methods. The products of iodination were characterized by their in vitro biological LH activity and by their binding profiles with antisera to HLH, HLHalpha and HLHbeta subunits. Several radioactive components were obtained after gel filtration with or without an initial cellulose adsorption step. One of these fractions was identified as biologically active HLH and another as the HLHalpha subunit. Radioimmunoassay studies were conducted with different iodinated fractions as tracers, using three well defined and widely available antisera to HLH. The standard used was the HLH International Reference Preparation for immunoassay (68/40). Cross-reactivity was examined with several purified pituitary preparations, such as HFSH, HTSH, HLHalpha and HLHbeta subunit. A significantly higher cross-reactivity with HLHalpha, HFSH and HTSH was obtained with the [125I]HLHalpha fraction as tracer than with biologically active [125I]HLH. Furthermore, in the radioimmunoassay of HLH preparations of varying purity, significantly higher estimates of immunological activity were obtained with the [125I]HLHalpha tracer than with the biologically active [125I]HLH. It is concluded that the presence of [125I]HLHalpha in the [125I]HLH tracer can result in serious overestimates of the immunological activity in the measurement of LH. Therefore [125I]HLHalpha should be separated from [125I]HLH prior to radioimmunoassay. Many of the fractionation methods commonly used (cellulose adsorption and short column gel filtration systems) are inadequate for this purpose. However, an adequate separation can be achieved by the use of high resolution gel filtration systems.


Insulin secretion in patients with myotonic dystrophy and their relatives. Oral glucose, i.v. tolbutamide and i.v. arginine tolerance tests were performed in 11 patients with myotonic dystrophy and 9 of their clinically unaffected relatives. Five of the myotonic patients had glucose intolerance; 7 had exaggerated immunoreactive insulin (IRI) response to glucose. One of the 9 relatives demonstrated glucose intolerance and none had exaggerated insulin response to glucose. Three relatives, all obese, hyperresponded to arginine and one of them also responded excessively to tolbutamide. The results indicate that an exaggerated IRI response to glucose is common in myotonic dystrophy. Enhanced responses to other stimuli are less frequent. Although glucose intolerance occurred in half of the patients, the fact that the highest IRI levels were seen in non-diabetic patients suggests that this excessive response may protect against glucose intolerance. Our studies in relatives do not support the potential usefulness of testing for hyperinsulinemia in the early detection of myotonic dystrophy.


Immunodeficiency in hypophysectomized rats. The response of hypophysectomized, sham-operated and non-operated female Fischer 344 and Wistar-Furth rats was compared to various antigenic stimuli. Antibody production against sheep red blood cells, skin response to dinitrochlorobenzene and the development of adjuvant arthritis after treatment with Freund's complete adjuvant were all markedly suppressed in hypophysectomized animals. Sham-operated rats responded as well as did non-operated controls. Skin graft survival was also prolonged in hypophysectomized rats when compared to controls. These results indicate that the pituitary gland plays an important role in immune reactions.