2,3,7,8-Tetrachlorodibenzo-p-dioxin: environmental contaminant and molecular probe.

The chlorinated dibenzo-p-dioxins and dibenzofurans are formed as trace contaminants during the synthesis of a number of commercially important chemicals. The prototype compound of this group, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), is one of the most potent low molecular weight toxins and teratogens known, and its inadvertent dispersion in the environment has caused concern about the potential hazard to human health. In studying the biochemical effects of TCDD, it was found to be extraordinarily potent as an inducer of two hepatic enzymes: 1) delta-aminolevulinic acid synthetase, the initial and rate-limiting enzyme in heme synthesis, and 2) aryl hydrocarbon hydroxylase, a cytochrome P-450-mediated microsomal monooxygenase. Among a series of halogenated dibenzo-p-dioxins there is an excellent correlation between their toxic potency and their potency as inducers of these two enzymes. The administration of polycyclic aromatic hydrocarbons (e.g., 3-methylcholanthrene (MC)) to certain inbred strains of mice induces aryl hydrocarbon hydroxylase, while other inbred strains fail to respond; and the trait of aryl hydrocarbon responsiveness is inherited as an autosomal dominant. TCDD, about 30,000 times as potent as MC, induces all strains whether responsive or nonresponsive to MC; however, the responsive strains are more sensitive (ED 50 approximately 1 X 10(-9) mole/kg) to TCDD than are the nonresponsive strains (ED50 larger than or equal to 1 X 10(-8) mole/kg). The results suggest that the mutation in the nonresponsive strains results in a ligand binding site (an induction receptor) that has a diminished affinity for MC and TCDD. The correlation among the halogenated dibenzo-p-dioxins, between their potency as toxins and their potency as inducers of aryl hydrocarbon hydroxylase, is discussed in relationship to various proposed mechanisms of toxicity.


A clip applicator for laparoscopic sterilization.

Laparoscopic sterilization using spring-loaded clips promises to reduce complications encountered with other sterilization techniques. A second-puncture clip applicator for laparoscopic sterilization has been developed which has several advantages over the single-puncture method, allowing a full visual field and more accurate placement of the clips. A description of the applicator, its assembly, operative procedure, and preliminary results are reported.


Laparoscopic recovery of sperm from peritoneal fluid, in patients with negative or poor Sims-Huhner test.

Several opinions about the importance of the Sims-Huhner test (SHT) are reported in the literature. Paradoxical are the results relative to conception following a positive or negative SHT. Pregnancy frequently occurs in women with a negative or poor SHT. This observation prompted the author to look for the presence of sperm in peritoneal fluid during laparoscopy in eight patients with a negative SHT and in three with a poor SHT. Complete evaluation was performed to rule out other infertility causes. The peritoneal fluid was aspirated from the cul-de-sac and again after washing the Douglas space and fimbriated portion of the fallopian tubes with 5 to 10 ml of normal saline solution, using a Verres needle. Samples were processed with the Sayk unit, by a special cytosedimentation technique developed for study of the cerebrospinal fluid. In six of the eight patients with a negative SHT and in the three with a poor SHT, sperm were found in the aspirate. No immature or morphologically abnormal sperm were recovered. This procedure illustrates the limitation of the long-accepted SHT in the prognosis for infertile couples. Investigations to eliminate the fixed stage in the processing are being studied to standardize the test.


[Human chorionic somatomammotropin: hCS (human placental lactogen : hPL) and estriol secretion in abnormal pregnancy (author's transl)].

In regard to its biological and immunological characteristics, human chorionic somatomammotropin, otherwise known as human placental lactogen, can be found in its activity as a metabolism regulating hormone during pregnancy.....


[Electronmicroscopic studies on allergic vasculitis].

Electron microscopic investigations were carried out on cutaneous lesions of different morphological appearances in 8 cases of vasculitis allergica Ruiter. The endothelial damages observed (defoliating, vacuolisation, forming of microvilli and bizarre membrane structures within the lumen, interruption of the endothelial continuity) put the question for participating of a Shwartzman phenomenon. The multilayered formation of the basement membrane or their homogeneous spreading may be a sequence of damage and a compensation phenomenon. It is quite possible that filamentous structures, being within the basal cytoplasm of the endothelial cells, represent immune-complexes. During the necrobiotic phase, the perivascular infiltrates partly consists of leucocytes, fibrin, and debris, and during the later phagocytotic phase, the infiltrates partly consists of lymphocytes and histiocytes (macrophages). The findings are explained as morphological substratum of the Arthus-reaction.


[Etiology and morbidity of drug exanthemas from a clinical viewpoint].

After a brief discussion of the potential errors and uncertainies of statistics about etiology and epidemiology of drug eruptions the 144 cases, seen from 1968 to 1974 in our dermatological clinic, are analysed and compared with the data from the years 1957 to 1965 respectively the quantities of special drugs, consumed during one year in Dresden city. The results are: significant increase of drugs eruptions (from 0,9% in 1957 to 1965 to 1,9% in 1968 to 1974) among the hospitalised patients; absolute and relative increase of penicillin- (36,7%) and chloramphenicolreactions (21,6%) combined with a decreasing importance of sulfonamides and barbiturates among the causes of drug rashes; increase of urticarial - and decrease of fixed exanthemas: a yearly frequency of 3 to 4 clinically treated ore diagnosticated drug eruptions/100 000 inhabitants respectively 1 to 2 chloramphenicol and 1--5 penicillin-rashes/10 000 treatments. Even if only 10% of the drug eruptions are diagnosticated by us and 90% in other clinics or ambulances the frequency of penicillin-rashes merely amounts to 1 to 5%.


The importance of PAPS in determining sulfation in gastrointestinal mucosa.

The in vitro sulfation of glycoproteins, mucopolysaccharides and lipids was studied with rat stomach, duodenum and colon mucosal scrapings. In the presence of Na2 35SO4, the incorporation of label was colon greater than stomach greater than or equal to duodenum. In the presence of [35S] 3'-phosphoadenosine 5'-phosphosulfate (PAP35S), the incorporation of label was colon = stomach greater than duodenum. The 35S was incorporated into glycoprotein, mucopolysaccharide and sulfatide. It is suggested that the availability of PAPS may be an important factor in determining the differences in sulfation previously observed histochemically in several species, namely that in vivo colonic mucosa far exceeds stomach mucosa in synthesis of sulfated polyanions.


Dynamics of sulfonylurea-induced insulin release from the isolated perfused rat pancreas.

In the isolated perfused rat pancreas various sulfonylurea drugs were tested with a basal glucose level of 1 mg/ml in the perfusion buffer and were found to cause a biphasic insulin response. NOVOCS 476, a new and potent sulfonylurea, and glibenclamide qualitatively differed from tolbutamide, glibornuride, glipizide, and glisoxepide, which were all alike in terms of the relationship between first and second phases of insulin release.


The development of retinopathy in sucrose-fed and streptozotocin-diabetic rats.

Normal and streptozotocin-diabetic rats have been maintained for 6--11 months on completely balanced, reconstituted diets in which the sole source of carbohydrate was either 68% corn starch or 68% sucrose. The retinal vascular system was isolated by trypsin digestion and examined histologically for the presence of tortuosity and irregularity of capillary diameter, increased PAS-positive deposits, microaneurysms, loss of pericytes, endothelial proliferation, acellularity and strand formation. None of these pathological changes occurred in normal rats fed a starch-rich diet, but all developed to a similar extent in the sucrose-fed normal rats and the starch-fed diabetic group. The changes were more severe in sucrose-fed diabetic rats after 6 months. In all groups the retinopathy progressed with time. The possibility that a factor common to both the ingestion of a sucrose-rich diet and streptozotocin diabetes in rats has been considered since, histologically, the retinopathy observed was identical both with respect to severity and rate of development in normoglycaemia, sucrose-fed and hyperglycaemia, starch-fed diabetic rats.


Cell division and cytodifferentiation of odontoblasts.

The chronological delay of overt cytodifferentiation of odontoblasts in isochronal and heterochronal associations between inner dental epithelium and preameloblasts was analysed. The in vitro action of FUdR of tooth germs was summarised. The respective role of cell interaction and specific cell cycle was discussed.


Plasma precursors of estrogen. III. Conversion of plasma dehydroisoandrosterone to estrogen in young nonpregnant women.

The utilization of plasma dehydroisoandrosterone for estrogen production was studied in 4 normal young nonpregnant women and in one young surgical castrate woman. The mean transfer constant for total conversion to estrogen, [sigma] DE-BU' was 0.0016 of which about one third (0.0005) could be accounted for by conversion of dehydroisoandrosterone first to plasma androstenedione which in turn was converted to estrone. The remaining fractional conversion appeared to result principally in estradiol formation via a pathway probably not involving plasma androstenedione. The conversion of plasma dehydroisoandrosterone to estrogen was similar in the surgical castrate to that observed in the ovulating women. It is concluded that plasma dehydroisoandrosterone is converted to estrogen at extraglandular site(s) but this contribution represents only a minor fraction of total estrogen production in normal young women.


[Effects of divalent cations on the muscle spindle of frogs].

Afferent discharges were recorded in the nerve from the isolated muscle spindle of the m. extensor longus digiti IV of the bullfrog. Discharges of about 10 Hz generated by a sustained stretch were reduced concentration-dependently when Ca2+, Mg2+ or Mn2+ (1.0 approximately 8.0 mM) was added to normal Ringer's solution containing 2.0 mM Ca2+. In terms of the decrease of discharges following the addition of Ca2+ or Mn2+ (4.0 mM), abortive spikes were observed. With an excess of Mg2+ (4.0 mM), abortive spikes were not apparent. Removal of Ca2+ from the Ringer's solution caused an increase in the rate of discharges, and normal levels were restored by the addition of Ca2+ (2.0 mM), Mg2+ (2.3 mM) or Mn2+ (1.8 mM). Application of much higher concentrations of these ions to the nerve trunk produced no alterations in the conduction of afferent discharges. It appears that Ca2+ in the external medium contributes to the inhibition of the mechanism responsible for generating afferent discharges in the muscle spindle and that Ca2+ action is not specific since Mg2+ and Mn2+ can act as substitutes for Ca2+ to regulate afferent discharges.


[Effect of drugs affecting sodium permeability on the muscle spindle of frogs].

Afferent discharges of about 10 Hz were recorded in the nerve from the isolated muscle spindle of the m. extensor longus digiti IV of the bullfrog subjected to a sustained stretch. When grayanotoxin-I, ventridine or aconitine was added to the Ringer's solution, the rate of discharges markedly increased and thereafter decreased. In these terms of decrease of discharges, abortive spikes were observed. The rate of discharges was markedly decreased by the application of procaine, diphenylhydantoin, chlorpromazine or tetrodotoxin. With the latter three drugs, abortive spikes were observed in the course of decrease of discharges. Increase of the discharge rate induced by grayanotoxin-I, veratridine and aconitine was antagonized by procain. No alteration was evident in the conduction of afferent discharges, when test drugs were applied to the nerve trunk in concentrations sufficient to change the rate of discharges when applied to the muscle spindle. These results suggest that the rate of the muscle spindle discharges is closely related to sodium permeability of the membrane.


Influence of cholinergic drugs on the lateral geniculate phasic waves.

The lateral geniculate phasic wave (GL wave, GLW) was studied at awaking, during the REM period of sleep (REMP) and after administration of reserpine (RSP) and parachlorophenylalanine (PCPA). The GLWs were classified by the time relation to the eye movements (EMs) into three groups of the GL-preceding GLW (GLWs precede EMs or concur with EMs), the EM-preceding GLW (EMs precede GLWs) and the EM-discording GLW (GLWs not associated with EMs). Changes in occurrence of thus classified GLWs and in the EM-GLW time (time delay between EM and GLW) were examined with supplementary administration of eserine and atropine. The results were as follows: 1. During the REMP, the EM-GLW time of the GL-preceding GLW showed shortening by eserine and prolongation by atropine. On the other hand, the EM-GLW time of the EM-preceding GLW was recognized no definite affection. 2. After the administration of RSP and PCPA, the GL-preceding GLWs increased soon after the eserine injection whereas markedly decreased after atropine. In the atropine-pretreated cats, the occurrence of the GL-preceding GLWs by RSP was inhibited. These drugs exerted little influence on the occurrence of the EM-preceding GLWs. 3. These results suggest that cholinergic mechanisms underlie the production of the GL-preceding GLWs but don't play an important role in the production of the EM-preceding GLWs.


An analysis of the first one thousand cerebral ACTA scans.

The first 1000 ACTA Scans of the brain are analyzed. ACTA Scanning is ideal for evaluating the ventricular system and other CSF containing spaces. High density lesions, such as intracerebral hematomas are depicted with great consistency. The method is less reliable for detecting subdural hematomas. For brain tumor screening, intravenously applied contrast agents are mandatory, so that tumors with subtle density changes can be identified more positively.


[Super-selective cerebral angiography. III. Diagnostic use and therapeutic possibilities of the telescopic catheterization technic in the circulation area of the external carotid artery in man].

The diagnostic value and technical versatility of the previously described telescopic catheter system was demonstrated in 15 patients by super-selective angiography of the external carotid artery. It was possible in all patients to catheterise the individual branches with the F-catheter; the polyethylene-S-catheter could then be passed 3 to 5 cm, beyond the tip of the F-catheter. In almost half the patients, spasm of the injected artery was observed, particularly of the superficial temporal and external occipital arteries; this was reversed by intravenous papaverine and did not interfere with detailed diagnosis. It was usually possible to obtain filling of peripheral vessels, thereby demonstrating the territory of the middle meningeal artery, the scalp, sub-mandibular gland and the pinna. There were no complications as a result of the catheterisation. The usefulness and advantages of the telescopic catheter system for therapeutic neuro-radiological procedures, with embolisation of external branches in man, are discussed.


[Determination of skull volume (author's transl)].

Various means for indirect skull volume determination were investigated. For this purpose--the procedure of direct measurement of skull volume was improved first, using a latex method. The examinations were carried out on 20 macerated skulls, which were x-rayed in the usual manner and stereoscopically also. Various distances and planes were then determined from the radiographs and varied calculations carried out. From these calculations it appears that skull volume can be simply determined most accurately from the product of transverse diameter (greatest width) and the area of median plane.


[Cervical myelography with water-soluble contrast medium (Metrizamide). Technique and preliminary results (author's transl)].

Use of a water-soluble contrast medium for cervical spinal diagnosis has become possible with the introduction of Metrizamide (Amipaqque). Injection of contrast at the C.1/2 level by a lateral approach results in excellent visualisation of the cervical theca with previously unobtainable detail. This technique, which is so far not well known, allows a rapid examination and when used with the new, well tolerated contrast media provides optimal diagnostic results.


[Radiological aspects of cervical chordomas (author's transl)].

The radiological findings in two patients with histologically verified cervical chordomas are described and compared with 40 others described in the literature. There is no typical radiographic picture. Our cases showed benign-looking, extensive bone erosions of vertebral bodies and neural arches. In addition, there was destruction of the related discs and a soft tissue mass at the level of the bony lesions.


[Pharmaco-angiography with Priscolin in progressive scleroderma (author's transl)].

The morphological and haemodynamic findings in the vessels of the forearm and hand in 21 patients with progressive scleroderma are described. In these patients, brachial arteriograms have been carried out before instituting fibrinolytic therapy. Injections were carried out before and after intra-arterial Priscolin and the results were compared. Obliterative changes in the digital arteries are already present during the oedematous stage. Between the oedematous and advanced stages, there are vascular changes of progressive severity. In the sclerotic stage, the changes may be less marked, but more often consist of advanced obliterative vascular disease; this cannot be distinguished from the atrophic stage. The haemodynamics of the digital arteries can be influenced by Priscolin and this provides some information regarding the arterial side of the dermal micro-circulation. Even during the oedematous stage one can observe contrast stasis which is irreversible and not influenced by Priscolin.


[The topography of the hepatic vein orifices (author's transl)].

The termination of the hepatic veins in the inferior vena cava was studied in 157 bodies. Two types of termination were observed: a cranial group close to the diaphragm with orifices varying between 4 and 25 mm., and a caudal group with orifices between 0.5 and 7 mm. In the first group, three types can be distinguished. In type I (45%) there are two, in type II (40%) there are three and in type III(15%) four hepatic veins which terminate in the vena cava. The caudal group showed no regular pattern. In performing selective angiography of the hepatic veins and during pressure measurements via hepatic vein catheters, it should be remembered that in 55% more than two ostia are present in the inferior vena cava.


[Hepatic vein angiography for the demonstration of intrahepatic tumours (author's transl)].

Fifteen patients with suspicion of metastases of the liver were examined in order to demonstrate the angiographic signs and the diagnostic possibilities of retrograde hepatic vein angiography. By this method, in all of our patients a scintigraphically doubtful or suspicious finding could be cleared up. Since hepatic vein angiography is superior to arteriography, sonography and scintigraphy with regard to identification of minor metastases, but is technically a complicated special examination, it should be applied as an extended diagnostic measure additionally to the other examinations.


[Embolisation of malignant renal tumours (author's transl)].

We have carried out embolisation of malignant renal tumours using homogenised muscle in a number of patients. Since October 1974, this has been done 22 times; in six cases the tumour was inoperable. Pre-operative embolisation of resectable renal tumours makes the operative procedures easier and reduces operative risks in older patients. Haematuria, which can cause bladder obstruction, is considered a particular indication in the presence of an inoperable tumour. Tumour growth can be reduced or there may even be regression. There were no significant complications as a result of embolisation of renal tumours with autologous homogenised muscle.


[Urographic effects of different states of diuresis (author's transl)].

In 35 patients with normal renal function antidiuretic hormone (DDAVP) effected a significant contraction of renal pelvis and calices, while in 10 other cases an enlargement of the roentgenological size of the kidneys was caused by the administration of the diuretic furosemide (Lasix). These results suggest a dependence of urographic findings from the state of diuresis.


[Renal toxicity of contrast media. Experimental study on dogs (author's transl)].

Experiments injecting Indian ink have confirmed the theory that postangiographic renal damage is due primarily to ischaemia. Cortical ischaemia is due to vascular spasm and sludging caused by contrast medium. Current and previous experimental findings suggest the following course in the pathomechanism: vasospasm reduced blood velocity--aggregation of erythrocytes--further deterioration in the circulation--microemboli--irreversible sludge formation--arterial and venous thromboses--ischaemic foci--necrosis or infarction. It is not possible to prevent this damage by alpha blocking sympathicolytic drugs.


Waldenströms macroglobulinaemia and intravenous contrast media.

In vivo and in vitro studies have been performed in a group of patients with immunoproliferative diseases to evaluate the risk of serious reactions due to serum jelling after intravenous injection of iodinated contrast media. Sol-jell convertion and/or turbidimetric variations have not been observed when either sera or plasmas have been mixed with variable amounts of a methylglucamine salt of ioglycamic acid (MGI) and other compounds. In addition, no side-effects have been clinically recorded in three patients with Waldenströms macroglobulinaemia (WM) whose sera and/or plasmas had been studied in vitro, when they have been submitted to intravenous contrast examinations. The results suggest that there is not an evidence of a relationship between iodinated contrast media and fatal reactions due to sol-jell alterations in patients with WM and therefore a radiological examination using contrast media may be carried out in those patients.


[Roentgenmorphologic findings in single homotransplantation of non immunosuppressive treated canine lungs (author's transl)].

According to plain chest roentgenography correlated to needle biopsies the following grades in the course of rejection after single lungtransplantation could be evaluated. 1) Begin of rejection: perihilar alveolar infiltrate. 2) Increase of the infiltrates (positive Airbronchogram). 3) Almost total consolidation of the graft. 4) Complete consolidation of the graft, mediastinal hernia caused by the own lung.


[Painless phlebography (author's transl)].

The routine employment and wide indications for ascending phlebography for evaluating the deep and superficial systems prior to specific therapy makes it desirable that the patient should feel as little pain as possible. By using suitable measures before and after the examination, optimal position of the patient and appropriate choice of instruments, as well as local anaesthesia with a Dermo-Jet pressure injector, it is possible to render the examination almost completely painless.


[Picture quality and film mammography. I. The physical parameters of the filming system (gradation, sensitivity, definition and granularity) and the effect of exposure geometry (author's transl)].

The physical parameters of three radiographic filming systems used for mammography were analysed (industrial film without screens, lo dose system (Dupont), industrial film with lo dose screens). Their effect on image quality was studied and the influence of the exposure geometry on sharpness and detail was investigated experimentally. Geometrical unsharpness so reduces the difference in definition between screenless industrial film and a film-screen combination that the total unsharpness at the centre of the breast parenchyma of an average breast becomes approximately the same. In particular, recognition of fine detail (microcalcification) is reduced by geometric unsharpness. Final grading of the three film systems is only possible after development of a concept of film quality which takes account of the parameters of the filming system and of exposlre geometry, together with physiological and practical requirements (paper II).


[New intensifying screens in clinical radiology. II. Examinations in clinical practice].

A clinically applicable procedure for testing new intensifying rare earth screens, as well as the special Siemens' screen is described. The results are related to universal screens. The film-screen combination alpha 4XD (gadolinium oxysulphide with normal, green sensitive film) results in a reduction of radiation dose to half with detail comparable with universal screens. The Siemens' special screen has similar advantages. Screens with a higher intensification factor and reduction of the mAs to one sixth results in loss of detail. This does not necessarily reduce their clinical use if they are used for appropriate purposes. The results of this clinically orientated technique agreed well with physically objective methods using lead grids. The advantages of the new screens are discussed in terms of their practical application.


[Diarrhea in immunopathies].

The main symptom in immunologic diseases of the gut is diarrhea. This is true for heterosensitization as well as for autosensitization, for local as well as for generalized diseases. Since the immunopathogenetic mechanism is connected with the presence of the antigen, the manifestation is depending on its local and temporal persistence. Elimination of the antigenic factor terminates the diarrhea. In autosensitization this is not possible; therefore an antiphlogistic and immunosuppressive therapy is necessary.


[Amyloidosis as a manifestation and origin of presenile and senile degeneration].

1. All essential attributes of the amyloidosis in aged persons ("senile amyloidosis") correspond to the condition which in younger individuals develops after infections, particularly following tuberculosis and lymphogranulomatosis, as so-called secondary amyloid degeneration, and also manifests many features of the so-called primary amyloidosis, not connected with infections. 2. Amyloid depositions in the brain, cardiac muscle, and in pancreatic islets (the "senile amyloidotic triad") dominate the morbid anatomic aspect. However, we know no organ or tissue which necessarily remains spared. The number of involved organs and tissues, in general, increases with the progressive aging of the patients. In those persons living long enough, amyloidosis affects every individual and probably all organs and tissues. 3. Contrary to the so-called secondary amyloidosis, in many cases of senile amyloidosis the spleen, liver and kidney remain intact. 4. In the so-called Alzheimers disease, in which both clinically and pathoanatomically a particularly destructive cerebral amyloidosis in relatively young persons prevails, just as in the common senile dementia of aged persons, the brain condition is associated with a systemic amyloid degeneration of many other organs. 5. Several cerebral and cardiac lesions due to amyloid accumulations can probably be diagnosed electrographically. Thus, through these already known morbid anatomical observations we have the promise of an essential enrichment of diagnostic perspectives. 6. In general, the etiologic manifoldness of amyloidosis presently seems to be incomparable. Infections, ionizing radiation, traumatic lesions in human pathology, the introduction of chemically definable substances, infections, and stress consequent to social burdening, proved effective in spontaneous and experimental amyloid degeneration of animals. 7. The demonstration of a tuberculous infection with the help of postmortem radiographs, as well as with the employment of histologic and microbiologic procedures to provide the evidence of acid fast bacilli in calcified remnants of pulmonary foci, proved to be eminently successful methods in the exploration of causes of senile tuberculosis and amyloidosis: Tuberculosis, after its invasion of the organism in early childhood, with its toxic and immunobiologic influences, holds it under its spell for an entire, even very long life and can be considered the most frequent cause of senile amyloidosis. 8. Chromosomal disturbances, with their hereditary manifestations, or, as in cases of mongoloid idiocy, associated with individual deformations, may present as amyloidoses. 9. Amyloid deposits in human pathology may develop by the transformation of normal structures, like cartilage, osteoid tissue, vascular elastic fibers, and also from scar hyalin and from fibrin. 10. We observed the disappearance of cerebral and cardiac amyloid accumulations producing typical defects. 11. Amyloidosis represents one of the most frequent spontaneous diseases of animals...


[Treatment of the climacteric symptom complex with a new combined hormone preparation].

A total of 387 women with severe climacteric complaints were treated for a period of 4 years with a new combined hormone preparation containing 200 mg DHEAO (dehydroepiandrosterone oenanthate) and 4 mg oestradiol valerate in 1 ml oily solution. As a depot preparation it has a duration of action of about 6 weeks when administered parenterally. The therapeutic effect is as good as that of the known androgen-oestrogen combinations. There were no observations of voice changes or hirsutism as signs of virilisation. Hormone-cytological studies in all cases showed that proliferation of the endometrium in the sense of hyperplasia cannot be induced by the administered hormones. Cytologically, there is no evidence at all for an androgenic effect. With the exception of transient mastodynia, no mammary changes were observed. Curettage must be performed in existing or suddenly occurring bleeding disturbances, and continuous cytological and hormone-cytological studies are advisable.


[Application of the immunofluorescente (fluorescent antibody technique) in clinical immunology.--II. Application and significance (author's transl)].

The fluorescent antibody technique is nowadays mainly a technique, which is routinely carried out in all clinical-immunological laboratories. The main fields of application in clinical immunology are the determination of autoantibodies (e.g. ANA, AMA, smooth muscle antibodies, parietal cell antibodies), detection of B-lymphocytes as well as bacterial antigens (e.g. Treponema pallidum). Furthermore the demonstration of deposits of immune complexes in tissues (e.g. glomerulonephritis, periarteriitis nodosa). The presented paper shows the different fields of application of the fluorescent antibody technique. It is pointed out that the FAT could be only one out of the variety of methods in clinical-immunological investigations.


Experimental measurement of microcirculation in myocardial infarction by using radioactive microspheres.

Changes in regional blood flow in myocardial infarction experimentally induced in adult dogs have been assessed before and after treatment with normal saline, heparin and a thrombolytic agent. The technic used to measure the local blood flow and its distribution is based on the sequential injection of radioactive microspheres labeled with different isotopes. The resulting data showed that an average of 2.6% of the dose given is distributed in the normal left ventricular wall. Following infarct formation, this value drops to a mean of 0.45%. No appreciable increase was noticed after six hours of normal saline administration. After six hours of heparin infusion, the regional blood flow doubled, provided that the time elapsed between obstruction and the beginning of treatment did not exceed three hours. Fibrinolytic treatment resulted in a remarkable increase of regional blood flow (up to three times that of the postinfarction state). The shorter the time between the beginning of obstruction and commencement of treatment the better the restoration in the regional blood flow.


Etiology of postobstructive diuresis: ouabain-sensitive adenosine triphosphatase deficit and elevated solute excretion in the postobstructed dog kidney.

A selective deficit in ouabain-sensitive adenosine triphosphatase has been shown in unilaterally obstructed dog kidneys; the deficit correlates inversely with Na+ and K+ excretion following relief of obstruction. It is postulated that the enzymatic defect may play a role in the etiology of postobstructive diuresis.


Biochemical variations in the matrix of human tendons in relation to age and pathological conditions.

With increasing age, the human tendon shows an increase of collagen and a diminution of mucopolysaccharides and glycoproteins. Similar findings have recently been reported by other authors in the tendons of mammals. Fragments of tendon affected by tendinosis, obtained dlring suture and tenoplasty operations, were also examined. Marked diminution of collagen and an increase of acid mucopolysaccharides and structural glycoproteins were found as compared with the control tendon.


Dysplasia of the tricuspid valve in the dog and cat.

Dysplasia of the tricuspid valve in 14 dogs and 13 cats was studied. The clinical, electrocardiographic, radiographic, hemodynamic, angiocardiographic, and pathologic findings were reviewed in each species. Alterations of the tricuspid valve complex included long, thick septal leaflets adhered to the septum; absent or short, stout fused chordae tendineae; hypertrophic fused papillary muscles; insertion of papillary muscles directly into the lateral leaflets; incomplete development of the valvular tissue; and enlargement of the right atrium and ventricle. Additional intracardiac anomalies included malformation of the mitral valve complex (5 dogs and 3 cats), ventricular septal defect (3 dogs and 3 cats), pulmonary stenosis (1 dog and 1 cat), aortic stenosis (1 dog and 1 cat), and persistent left cranial vena cava (1 dog).


Vagal afferents essential for abdominal muscle activity during lung inflation in cats.

Maintained inflation of the lung evokes abdominal muscle activity in anesthetized cats only if the vagus nerves are intact, indicating the importance of vagal receptors. The location of these receptors was determined in 14 anesthetized cats by comparing prevagotomy inflation responses of the abdominal muscles and diaphragm to the responses obtained after section of the thoracic vagi at one of three different levels. The abdominal muscle and diaphragm responses to maintained lung inflation persisted following vagotomy below the roots of the lung or denervation of the heart and great vessels. Denervation at the root of the lung, however, abolished the abdominal muscle response and the Hering-Breuer inflation reflex of the diaphragm. It is concluded that pulmonary receptors are essential for the abdominal expiratory activity, but vagal receptors in the abdomen, esophagus, trachea, heart and great vessels are not.


Short-term and serial memory in autistic, retarded, and normal children.

Experimental data on memory ability of autistic children is scarce and contradictory. It is suggested that this may in part be the result of failure to control for acquisition of the correct response before memory is tested. In the first experiment reported, acquisition was controlled in a delayed-response visual discrimination task. The performance of autistic children was compared with MA matched normal and retarded controls. Recall deteriorated with increasing delay interval in each group. There were no significant group differences. The second experiment was designed to measure the effects of interference on memory using a serial memory task. No differences were found among groups in rate of learning, although the autistic children improved significantly on the second and longer series. There was no relationship between performance on the STM and the serial memory tasks over the same time intervals for any group. The results are interpreted as supporting the view that when MA and response acquisition level are equated with normal and retarded children in a memory task, autistic children do not show any specific memory deficits.


Proton translocating ATPase of a thermophilic bacterium. Morphology, subunits, and chemical composition.

1. A stable membrane-bound ATPase [EC 3.6.1.3] (TF0-F1) capable of proton translocation in reconstituted vesicles was purified from the thermophilic bacterium PS3 cultured in medium containing L-[U-14C]amino acids. 2. TF0-F1 was composed of a catalytic moiety (TF1) and a hydrophobic moiety (TF0). TF1 contained 3 polypeptide chains with molecular weights of 56,000, 3 of 53,000, 1 of 32,000, 1 of 15,500, and 1 of 11,000. TF0 contained 1 chain of 19,000, 2 of 13,500, and 5 of 5,400 daltons. TF1 was dissociated into subunits much less readily than F1. 3. TF1 consisted of 95A particles arrayed in hexagonal microcrystals. TF0-F1 consisted of a sphere (TF1) and a stalk plus base (TF0) which was buried in the membrane of the proton translocating vesicles. 4. Vesicles capable of energy transformation were formed when TF1 came in contact with the surface of liposomes containing TF0. On addition of phospholipids, the helix content of TF0 increased 3-fold. The role of F0 in forming channels for protons is discussed. 5. The amino acid compositions of TF0, TF1, and TF0-F1 were compared. TF0 was not hydrophobic, despite its interaction with phospholipids. The phospholipid composition and other properties of the proton translocating vesicles were examined. Vesicles reconstituted from a mixture of phosphatidylethanolamine, phosphatidylgly-cerol, and cardiolipin in the same ratio as in the membranes had the highest activity.


Calcium sensitivity of abalone, Haliotis discus, myosin.

Superprecipitation was observed with abalone myosin and purified rabbit actin in the presence of calcium ions, but was not observed in the absence of calcium. The Mg-ATPase [EC 3.6.1.3] activity of abalone myosin and rabbit actin in the absence of calcium ions (EGTA present) showed about 60% inhibition as compared with values in the presence of calcium ions. The calcium sensitivity may be attributable to abalone myosin, as in the case of scallop myosin.


Dynein 2. A new adenosine triphosphatase from sea urchin sperm flagella.

A new ATPase electrophoretically and immunologically distinct from the dynein ATPase studied previously has been solublized and purified from sea urchin sperm flagella. This ATPase has properties similar to those of dynein ATPase. Therefore, we propose that the two ATPases be considered as dynein isoenzymes, with previously studied dynein being known as dynein 1, and the newly discovered ATPase as dynein 2. Some physicochemical and enzymatic properties of dynein 2 have been determined. The molecular weight calculated from the sedimentation coefficient (12.3 "/- 1 S) and Stokes radius (12.8 "/- 0.4 nm) is 690,000 +/- 70,000. The molecular weight of the high molecular weight subunit of dynein 2 has been determined to be 325,000 +/- 40,000 by Na dodecyl-SO4-polyacrylamide gel electrophoresis. The enzymatic properties of dynein 1 and dynein 2 are similar in substrate specificity, pH optimum, and Mg2+ requirement for ATPase activity, but they differ in their Michaelis constant and in their dependence of ATPase activity upon salt concentration. Digestion of dynein 2 with trypsin yields an ATPase-containing protein fragment, similar to Fragment A obtained from dynein 1. An antiserum prepared against Fragment A from dynein 1 did not precipitate dynein 2 or inhibit its ATPase activity.


Isolation of a human plasmin-derived, functionally active, light (B) chain capable of forming with streptokinase an equimolar light (B) chain-streptokinase complex with plasminogen activator activity.

A functionally active human plasmin light (B) chain derivative, stabilized by the streptomyces plasmin inhibitor leupeptin, was isolated from a partially reduced and alkylated enzyme preparation by an affinity chromatography method with a L-lysine-substituted Sepharose column. This light (B) chain derivative was found to be relatively homogeneous by electrophoretic analysis in both an acrylamide gel/dodecyl sulfate system and on cellulose acetate. It possessed approximately 3% of the proteolytic activity (casein substrate) of the original enzyme, and it incorporated 0.09 mol of [3H]diisopropyl phosphorofluoridate per mol of protein. It contained 3.1 +/- 0.3 carboxymethylated cysteines per mol of protein and can be designated as a CmCys5-light (B) chain (CmCys)3. When this isolated light (B) chain derivative was mixed in equal molar amounts with streptokinase, the mixture developed both human and bovine plasminogen activator activities; the bovine activator activity was approximately 66% of the bovine activator activity of the equimolar human plasmin-streptokinase complex. Although this complex now incorporated 0.50 mol of [3H]diisopropyl phosphorofluoridate per mol of protein, its proteolytic activity, on a molar basis, was the same as the proteolytic activity of the isolated light (B) chain derivative. It was shown by electrophoretic analysis in both an acrylamide gel/epsilon-aminocaproic acid system and on cellulose acetate that the light (B) chain derivative and streptokinase forms an equimolar light (B) chain-streptokinase complex, indicating that the binding site for streptokinase is located on the light (B) chain of the enzyme. A functionally active equimolar light (B) chain-streptokinase complex was also isolated from a partially reduced and alkylated equimolar human plasmin-streptokinase complex by the affinity chromatography method. The plasminogen activator activities (human and bovine) of this light (B) chain-streptokinase complex were similar to those of the plasmin-streptokinase complex from which it was derived. Although this complex incorporated 0.70 mol of [3H]diisopropyl phosphorofluoridate per mol of protein, its proteolytic activity, on a molar basis, was only 14% of proteolytic activity of the plasmin-streptokinase complex.


Isolation and characterization of alpha2-plasmin inhibitor from human plasma. A novel proteinase inhibitor which inhibits activator-induced clot lysis.

A procedure is presented for purifying a novel proteinase inhibitor in human plasma whose apparent unique biological property is to inhibit efficiently the lysis of fibrin clots induced by plasminogen activator. The final product is homogeneous as judged by disc gel electrophoresis, and immunoelectrophoresis. Its molecular weight estimated by sodium dodecyl sulfate gel electrophoresis or sedimentation equilibrium is 67,000 and 63,000, respectively. The inhibitor is a glycoprotein consisting polypeptide chain containing 11.7% carbohyrate. It migrates in the alpha2-globulin region in immunoelectrophoresis. The inhibitor is chemically and immunologically different from all the other known inhibitors in plasma. Inhibition of plasmin by the inhibitor is almost instantaneous even at 0 degrees, in contrast to the slow inhibition of urokinase (plasminogen activator in urine). Plasminogen activation by urokinase-induced clot lysis is inhibited by the inhibitor mainly through a mechanism of instantaneous inhibition of plasmin formed and not through the inhibition of urokinase. The inhibitor also inhibits trypsin. Consequently, it is suggested that this newly identified inhibitor is named alpha2-plasmin inhibitor or alpha2-proteinase inhibitor. A specific antibody directed against the inhibitor neutralizes virtually all inhibitory activity of plasma to activator-induced clot lysis. Immunochemical quantitation of the inhibitor was specific antiserum to the inhibitor and the purified inhibitor as a standard indicates that the concentration of the inhibitory in the serum of a healthy man is in or near the range of 5 to 7 mg/100 ml, which is the lowest concentration among the concentration of the proteinase inhibitors in plasma. The inhibitor and plasmin, trypsin, or urokinase form a complex which cannot be dissociated with denaturing and reducing agents. The formation of the enzyme-inhibitor complex occurs on a 1:1 molar basis and is associated with the cleavage of a unique peptide bone, which is most clearly demonstrated in the interaction of the inhibitor and beta-trypsin. In the complex formation between the inhibitor and plasmin, the inhibitor is cross-linked with the light chain which contains the active site of plasmin. It is suggested that, in a fashion analogous to complex formation between alpha1-antitrypsin and trypsin, the cross-links are formed between the active site serine of the enzyme and the newly formed COOH-terminal residue of the inhibitor, with cleavage of a peptide bond.


Action of ATP-dependent DNase from Hemophilus influenzae on cross-linked DNA molecules.

The ATP-dependent DNase from Hemophilus influenzae digests double-stranded linear DNA molecules exonucleolytically while hydrolyzing large amounts of ATP to ADP. Various cross-linked linear duplex DNA molecules are partially resistant to the exonuclease action. Vaccinia DNA, containing natural terminal cross-links (probably in the form of terminal single-stranded loops), is much more slowly degraded than comparable "open-ended" DNA molecules, and ATP is consumed at a proportionately lower rate. It is postulated that the vaccinia DNA molecules undergo slow terminal cleavage by the single strand specific endonuclease activity of the enzyme, and are then rapidly degraded by the double strand exonuclease activity. Phage T7 DNA, containing an average of 100 4',5'8-trimethylpsoralen cross-links/molecule at random internal sites, is digested only to the extent of 2 to 3%. However, ATP hydrolysis continues at a linear rate long after DNA digestion has ceased. A stable enzyme-DNA complex is formed as demonstrated by co-sedimentation of DNA and ATPase activity in sucrose gradients. The hypothesis is advanced that the enzyme digests exonucleolytically to the first cross-link at each end of the DNA molecules where further movement is prevented. The enzyme then remains bound at the cross-links and functions continuously as an ATPase.


Long term effects of radiation of T and B lymphocytes in peripheral blood of patients with Hodgkin's disease.

Total lymphocyte counts, and the percentage of T and B lymphocytes and monocytes in untreated patients with Hodgkin's disease were not significantly different from those observed in normal donors. At the completion of radiotherapy, the mean total lymphocyte count of 503/mm3 was 4 SD below the mean for normal controls. Although a group of 26 patients in continuous complete remission from 12 to 111 mo after radiation treatment regained normal total numbers of lymphocytes and monocytes, they exhibited a striking T lymphocytopenia and B lymphocytosis. Concomitantly, there was a significant increase of null (neither T nor B) lymphocytes. The response of peripheral blood lymphocytes to phytohemagglutinin, concanavalin A, and tetanus toxoid before treatment was significantly impaired. 1-10 yr after completion of treatment there seemed to be little or no recovery of these responses. The capacity of peripheral blood lymphocytes to respond to allo-antigens on foreign lymphocytes in vitro (mixed lymphocyte reaction) was normal in nine untreated patients. However, the mixed lymphocyte reaction was markedly impaired during the first 2 yr after treatment. There was a partial and progressive restoration of the mixed lymphocyte reaction during the next 3 yr, and normal responses were observed in patients in continuous complete remission for 5 yr or more. The in vivo response to dinitrochlorobenzene was also examined. 88% (15/17) of patients initially sensitive to dinitrochlorobenzene were anergic to the allergen at the completion of a course of radiotherapy, but nine of these regained their hypersensitivity response during the 1st yr after treatment. This data suggests that there is a sustained alteration in both the number and function of circulating T cells after radiation therapy in patients with Hodgkin's disease which may persist for as long as 10 yr after treatment. The restoration of cell mediated immune functions after radiotherapy is time dependent and its kinetics may differ for various T-cell functions. The implications of these findings with respect to the state of immunological competence after radiotherapy are discussed.


Glomerular basement membrane: biosynthesis and chemical composition in the streptozotocin diabetic rat.

To study the effect of streptozotocin induced diabetes on glomerular basement membrane (GBM) synthesis, an isolated rat glomerular preparation has been developed, and its metabolic properties have been defined. The chemical composition of normal rat GBM isolated from this preparation closely resembles human GBM. Incubation with [U-14C] lysine leads to prompt incorporation of label into GBM and the subsequent appearance of labeled hydroxylysine. A 1-h lag before detection of labeled hydroxylysine in GBM suggests a delay in the release of GBM precursors. Significantly lower counts appeared in the nondialyzable fraction of the medium than in insoluble GBM during pulse-chase experiments, and labeled hydroxylysine accounted for a lower portion of the total counts in the medium (0.85%) than in the GBM (1.98%). Isolated glomeruli were prepared from streptozotocin diabetic rats of 4-6 wks duration. After incubation with [ U-14C] lysine recovery of label in diabetic GBM (88.98+/-8.26 nmol/g GBM) did not differ from age matched controls (82.52 +/- 8.26 nmol/g GBM). In pulse-chase experiments recovery of label in hydroxylysine of diabetic GBM (o.473 +/- 0.082 nmol/g GBM) did not differ from age matched controls (0567+/-0.065 nmol/g GBM). These findings indicate normal rates of GBM synthesis and hydroxylation of lysine residues in animals with streptozotocin diabetes.


Screening for fetal chromosome aberrations in early pregnancy.

Seven years' experience in prenatal screening for fetal chromosome aberrations in the west of Scotland is reviewed. Fetal chromosome analysis was undertaken in 716 pregnancies, 49% of which were judged to be at substantial risk of a fetal chromosome aberration. A chromosome aberration was found in 26 pregnancies, 14 of which were sufficiently severe to justify termination: the latter included nine cases of trisomic Down's syndrome, two cases of translocation, two cases of XXY Klinefelter's syndrome and one case of the triple-X syndrome. Ten pregnancies with balanced fetal chromosomal translocations and two with extra, small metacentric chromosomes of no clinical significance continued normally in pregnancy. Prenatal diagnosis permitted many mothers at risk the opportunity of having a family which otherwise they would not have attempted, and saved a number of pregnancies which would have been terminated solely on the risk, rather than the diagnosis, of fetal abnormality. An unexpectedly high frequency (6-6%) of severe fetal chromosome aberrations was found in pregnancies of mothers aged 40 years and over. In the maternal age groups 35-39 years the frequency was 1-4%. It is concluded that specialized cytogenetic facilities are urgently required to allow older mothers the option of prenatal screening. This is also required for younger mothers who have previously had a child with Down's syndrome, and for families at risk of chromosomal translocation and X-linked disease. Prenatal screening is best provided on a regional basis by a department of medical genetics experienced in genetic counselling, human cytogenetics, and cell culture techniques, working in close collaboration with obstetrical colleagues and the ultrasound department.


Similarities in the physiological bases of an abnormal grooming behavior in thyroidectomized cats and in cats with lesions of the central nervous system.

Thyroidectomized cats display a dissociation of the appetitive and consummatory components of grooming behavior when the body surface is tactually stimulated, an abnormal behavior that also occurs in cats with pontile or frontal neocortical lesions. Systemic administration of 5-hydroxytryptophan (5-HTP) abolishes the abnormal behavior, whereas dihydroxyphenylalanine administration does not, and p-chlorophenylalanine (PCPA) administration induces the abnormal grooming behavior in thyroidectomized cats that are not displaying the abnormal behavior because of spontaneous seasonal reversions. Microinjections of 5-HTP or serotonin into the superior colliculi also abolish the abnormal grooming behavior in thyroidectomized cats. Lesions of the superior colliculi prevent the development of the abnormal behavior after thyroidectomy, even with PCPA treatment. These pharmacological results in thyroidectomized cats parallel the behavioral effects observed in cats with pontile or frontal neocortical lesions.


Water fluoridation and congenital malformations: no association.

The incidence of selected congenital malformations in areas with fluoride supplementation of public water supplies was compared with the incidence in areas where the water supply is deficient in fluoride. Comparison of the incidences of several common birth defects (including Down's syndrome) in fluoridated and nonfluoridated areas revealed no substantial or significant differences in which there was a consistent pattern for both sets of data.


A review of controlled surveys of dental disease in handicapped persons.

The need is demonstrated for large scale, definitive, standardized epidemiologic investigations of dental disease in those handicapped groups for whom this information is unavailable. Treatment needs of all groups should also be assessed, because this is not readily deduced from the indices of dental disease reviewed in this article. While a preventive orientation in dental care for the handicapped is most desirable, it must be emphasized that priorities in prevention and treatment should focus as much on periodontal disease as on caries, and due consideration must also be given to malocclusion. Current methods of preventing periodontal disease in the handicapped are quite inadequate.


Intact humoral and cell-mediated immunity in chronic marijuana smoking.

The immune system of 12 healthy chronic marijuana-smoking adults was evaluated while they smoked marijuana daily for 64 consecutive days under controlled hospitalized conditions. Studies included enumeration of B and T cell subpopulations, lymphocyte proliferative responses to PHA and to allogeneic cells, and serum immunoglobulin levels. Percent B cells, initially low in 2 patients, became normal. Baseline total B cells, determined either by surface immunoglobulins (338 cells/mm3 +/- 60 SEM) or complement receptors (162 cells/mms +/- 27) were significantly (p less than 0.05) less than control but increased to normal (485 +/- 97 and 239 +/- 47) over time. Percent T cells, initially low (less than 40%) in 4 patients, became normal. Baseline T cells (951 cells/mm3 +/- 70 SEM), significantly lower than controls (2,010 +/- 210, p less than 0.05), increased to normal by day 63 (1,875 +/- 281). In vitro lymphocyte response to graded doses of PHA and to allogeneic cells was normal initially and did not change over time. Serum IgG (1,064 +/- 33), IgA (166 +/- 13), and IgM (96 +/- 6) were normal. Serum IgE levels increased in 4 subjects without evidence of allergy. Short-term chronic marijuana use does not have a substantial adverse effect on B or T cells of young healthy adults.


Periodontal disease among children with Down's syndrome and their siblings.

The prevalence and severity of periodontal disease were determined in a group of individuals with Down's syndrome and a group of their selected siblings. Prevalence and severity of the disease were measured by the PI of Russell and were greatest in the children with Down's syndrome--more than threefold greater. The siblings demonstrated an experience not unlike that of the US population.


Developmental changes of calcium-stimulated adenosine triphosphatase in rat submandibular gland.

Developmental changes in Ca2-+ ATPase activity were determined in submandibular glands of the rat from the fetus to the 300-day-old rat. Ca2+-ATPase in the homogenate fraction showed a rapid increase from the fetus to the 5-day-old rat, and from the 20- to 30-day-old rat. In the microsomal fraction, enzyme activity increased from the fetus to the 10-day-old rat, and after that is remained at almost the same level. Oscillatory phenomena of Ca2+-ATPase were observed in zymogen and mitochondrial fractions.


The bionomics of the free-living larvae and the transmission of Dictyocaulus filaria between lambs in North-East England.

The bionomics of the free-living larvae of Dictyocaulus filaria on pasture, and the transmission of infection between lambs, were studied during different seasons of the year in North-East England. The rate of development of first-stage larvae to the third stage took 4-9 days in late spring and summer, 1 1/2-4 weeks in autumn and 5 1/2-7 weeks in winter. The proportion of first-stage larvae developing to the third stage ranged from 10-28% in autumn and winter, and 2-25% in spring and summer. The rate of mortality of the third-stage larvae was approximately logarithmic in nature, although the survival time was shorter in spring and summer than in autumn and winter. Third stage larvae were able to survive from autumn until the spring of the following year in sufficient numbers to perpetuate transmission but not to cause clinical disease. In a transmission study, the survival of the infective larvae on the experimental plot was poor in summer, but the larval population increased in the autumn and then declined slowly throughout the winter. Infection in the susceptible lambs was related to the level of infection on the herbage increasing in severity from early summer to late autumn. However, those lambs infected in the summer were resistant to the heavy autumn challenge of larvae on pasture.


Broader investigation into the external environment of the specific antigen of the infectious agent in epizootiological observation and study of the structure of natural foci of plague.

The possibilities of detection of the infectious agent in natural foci of plague can be expanded to some extent by using the method of search for the specific FI capsular antigen of the plague microbe in such objects of the external environment which have not yet been subjected to laboratory analysis and serological analysis in particular. Such objects include soil from the burrow and the substrate of the nest of the rodent as well as the fleas of rodents and regurgitations of birds of prey. The effectivity and suitability of examination of these objects using immuno-adsorption reactions with standard erythrocyte diagnostics (passive haemagglutination reaction, antibody neutralization reaction) were demonstrated experimentally and confirmed under field conditions in various geographical and ecological zones of the Caucasus. Thus in 1971, an earlier unknown natural focus of plague was found in the Mount Elbrus massif by means of serological analysis of the substrate of the nest and of the soil from the burrows of rodents. It can be expected that broadened serological search for the FI antigen of plague will prove useful in the study of the structure of natural foci of plague, in the reconnaissance or retrospective investigation of poorly explored territories and in the solution of some questions concerning the epizootiology of plague, such as the survival of the infectious agent in the inter-epizootic period, telluric plague, etc.


Results of virological and serological studies of three influenza A Hong-Kong epidemics in Leningrad.

An analysis of morbidity of the population in the course of 3 influenza A/Hong-Kong epidemics showed a pronounced decrease in influenza affection of adult population in the last epidemic in 1971--1972. Comparative studies of the diagnostic value of CFR and HIT demonstrated identical sensitivity of CFR as a method of influenza diagnostics in both the epidemic and interepidemic periods. HIT was suitable for the detection of influenza only in the epidemic period. In the interepidemic period, the percentage of influenza infection diagnosed by means of HIT ammounted to only 23--24 of all serologically confirmed cases of influenza. The highest percentage of virus isolation was observed when material from patients with serologically confirmed influenza was used. All strains of influenza A virus isolated in 1969 and 1970 were similar in their sensitivity to inhibitors of animal sera. During the last influenza epidemic, 2 of the 136 isolated strains were found to be resistant to gamma inhibitors and highly sensitive to the inhibitors showed their close relationship to gamma inhibitors. Antigenic analysis of the influenza A strains isolated during the 3 influenza epidemics revealed changes in the antigenic structure of the agents of the influenza epidemic in Leningrad in comparison with the standard strain A/Hong-Kong/I/68 (H3N2).


Culture conditions for induction of suppressor cells in vitro.

Culture conditions have been established for optimal generation of cytotoxic T lymphocytes (CTL) in one-way mixed lymphocyte cultures (MLC). The responder cell concentration was found to be most critical. In general the more active the proliferation was, the lower was the optimum for CTL generation. Optimal proliferation was usually found to occur at lower cell concentrations than optimal CTL generation. Above the optimal CTL generation proliferation also decreased, most likely due to overcrowding. These observations were made on both unpurified and nylon wool-passaged spleen cells, though the latter generally produced higher levels of cytotoxic activity per equal number of harvested cells. Cells prestimulated for 2 or 4 days in the absence or presence of antigen (M-locus differences) were unable to mount an effective response when restimulated with another antigen presenting an H-2 difference. This hyporesponsiveness was not due to the exhaustion of the culture medium or the presence of dead cells (since these were removed before restimulation). A high degree of hyporesponsiveness was also induced in the absence of antigen during prestimulation which rendered antigenic competition highly unlikely. Overcrowding could be excluded since the observed inhibition could not be diluted out by lowering the responder cell concentrations. A carry-over of CTL destroying newly added antigen (Fitch et al., 1975) could not account for our observations since in the system utilized (M-locus stimulation) there was no generation of CTL (Festerstein, 1973; Röllinghoff et al., 1975). The development of suppressor cells would seem the most likley explanation of the data.


Sarcoid.

Patients with sarcoidosis were separated into those treated or not treated with prednisone. Skin test reactivity of both groups was clearly diminished but a significant decrease in T-cells was seen only in the steroid-treated group and this was not sufficient to explain the profound energy. Lymphocyte stimulation studies generally revealed elevated baseline incorporation of [3H]thymidine and reduced stimulation. Factors were present in the plasmsa of 1/4 to 1/3 of the patients which suppressed normal lymphocyte stimulation. When cells from 3 sarcoid patients were precultured in vitro, recovery towards normal occurred with a drop of the elevated baseline and rise in peak response.


Hepatitis A and Down's syndrome: lack of an association.

The occurrence of hepatitis A early in pregnancy has been reported to result in increased births of children with Down's syndrome. Eleven sets of paired sera were obtained before conception and during pregnancy from women who delivered infants with Down's syndrome. These sera were tested for antibody to hepatitis A virus with use of immune electron microscopy. None of the women had seroconversions or increases in levels of antibody to hepatitis A virus. No evidence of an association between hepatitis A and Down's syndrome was found in the women studied.


Studies of subcellular control factors in hearts of uremic rats.

Subcellular fractions in hearts from rats with severe acute uremia (24 hours after total nephrectomy) and moderate chronic uremia (2 weeks after five sixths nephrectomy) were studied and compared with preparations from acute and chronic sham-operated rats, respectively. Calcium- and magnesium-sensitive actomyosin adenosine triphosphatase (ATPase) activities were normal in both groups. Acute uremia was associated with a significant depression of sarcolemmal Na+,K+ ATPase activity. Calcium transport by fragmented sarcoplasmic reticulum was also depressed in the presence and absence of oxalate in acute uremia. Mitochondrial calcium transport and adenosine triphosphate (ATP) and creatine phosphate (CP) concentrations were normal in these animals. Chronic uremic animals showed no abnormal subcellular mechanisms. These data suggest a direct effect of acute uremia on some membrane functions in myocardial cells. The discrepancies observed between acute and chronic uremic groups may be due to a different degree of uremic state. The observation of depressed calcium transport by fragmented sarcoplasmic reticulum (FSR) in acute uremic hearts which were previously shown to have increased contractile reserve suggests that studies of calcium transport in FSR may not always truly reflect the contractile capacity of the heart.


Mineralocorticoid activity of 16beta-hydroxydehydroepiandrosterone and related steroids.

16beta-Hydroxydehydroepiandrosterone (16beta-OH-DHEA) and related C19-steroids have recently been reported to be etiologic in low-renin essential hypertension. The mineralocorticoid potency of 16beta-OH-DHEA and several C19-steroids (16-oxo-A-diol, 16-oxo-testosterone, 16beta-OH-epiandrosterone, 5-androstene-3beta, 16beta,17beta-triol, 19beta-OH-testosterone, 18-OH-DHEA, and 16alpha-OH-DHEA) were investigated in two different rat bioassay systems under a variety of experimental conditions. In all but one instance, only negligible mineralocorticoid activity was observed, usually less than 0.1 per cent that of aldosterone. Since 16beta-OH-DHEA has negligible mineralocorticoid activity in the rat bioassay and the toad bladder assay (as reported by others), does not cause hypertension when injected chronically into the rat, and does not displace aldosterone from its renal receptors, it appears unlikely to be etiologic in low-renin essential hypertension. On the other hand, when 16-oxo-testosterone was injected intraperitoneally instead of subcutaneously, it demonstrated a slight increase in mineralocorticoid activity (from less than 0.1 per cent to 0.2 per cent) which equaled that of 18-hydroxydeoxycorticosterone (18-OH-DOC) injected subcutaneously. Thus, the possibility remains that 16-oxo-testosterone or a closely related metabolite may have sufficient mineralocorticoid activity to be involved in certain forms of hypertension in man.


Correlation of enzymatic activity, muscle myoglobin concentration and lung morphology with activity metabolism in snakes.

In vitro activity of the anaerobic enzymes phosphofructokinase and lactic dehydrogenase from axial muscle tissue of Coluber constrictor, Crotalus viridis and Lichanura roseofusca was shown to correlate with levels of lactate production during activity by these snakes. Additionally, gross and histological lung structure and axial muscle myoglobin concentration were investigated in these species. Coluber was shown to have the most complex lung structure and highest muscle myoglobin content. These are interpreted to be correlated with high aerobic scope in Coluber. Finally, the ophidian saccular lung is postulated to assist in maintenance of high tidal volume.


Studies on niacin biosynthesis from 3-hydroxyanthranilic acid in streptozotocin diabetic rats in vivo and in vitro.

Biosynthesis of niacin from 3-hydroxyanthranilic acid (3-OHAA) in normal and streptozotocin diabetic rats was studied in vivo and in vitro. Streptozotocin (SZ) diabetic rats were found to excrete lesser quantities of 3-OHAA, quinolinic acid, niacin and N1-methylnicotinamide (nmn) in their urines following 3-OHAA administration than corresponding normal rats. In vitro studies indicated that SZ diabetic livers form less quinolinic acid from 3-OHAA than normal livers. It appears that this may be due to elevated picolinic carboxylase activity in the livers of SZ diabetic rats.


Biological basis for vestibuloplasty procedures.

There may be two distinct processes in the healing of open wounds, particularly of vestibuloplasty wounds. The first is the active process of contraction which is limited by grafting. The second is remodeling and includes the subgraft, graft, and changes in peripheral tissue (maturation). The perioral musculature may have an influence on the vestibuloplasty wound and this may explain loss in the vestibular depth. The biology of open wounds is discussed in terms of vestibuloplasty wounds.


Changes in surface ATPase of rat spermatozoa in transit from the caput to the cauda epididymidis.

Rat spermatozoa from the cauda epididymidis were found to have a lower activity of the surface ATPase than the spermatozoa from the caput region. The enzyme from spermatozoa of both regions had the same Michaelis constant (Km) for ATP of 5 X 10(-4) M. It was partly inhibited by ouabain and fluoride, but strongly inhibited by Cu2+, Zn2+,p-chloromercuribenzoate, 8-anilino-1-naphthalenesulphonate Triton X-100, Lubrol-PX, urea, guanidine hydrochloride, sodium dodecyl sulphate and glycerylphosphorylcholine. The enzyme of the spermatozoa from the cauda epididymidis was more sensitive to inhibition by ouabain and fluoride but less sensitive to inhibition by Cu2+ than that of the cells form the caput region. The Arrhenius plot of the temperature dependence of enzymatic activity varied for the cells from the caput and cauda epididymidis. The differences in the enzyme properties of spermatozoa from the two regions of the epididymis suggested that the decline in the activity during epididymal maturation may reflect changes in the lipids and sulphydryl groups of the sperm membrane.


Control of synthesis of mRNA's for T4 bacteriophage-specific dihydrofolate reductase and deoxycytidylate hydroxymethylase.

A 30 degrees C, functional messengers for dCMP hydroxymethylase first appeared 3 to 6 min postinfection and reached their maximum levels at 12 min. Chloramphenicol, added before the phage, reduced the rate of mRNA accumulation. When the antibiotic was added 6 min postinfection, mRNA levels increased at their normal rate but there was no obvious repression of messenger accumulation. Delaying the addition of drug until 8 or 12 min had progressively less effect on the pattern of hydroxymethylase mRNA metabolism. When chloramphenicol was present from preinfection times or from 6 min postinfection, all hydroxymethylase mRNA's synthesized were stable; at later times, however, the ability of the drug to stabilize mRNA decreased with its ability to delay the turnoff of mRNA production. An overaccumulation of hydroxymethylase mRNA was also seen when phage-specific DNA synthesis was inhibited either by mutational lesion in an essential viral gene or by 5-fluorodeoxyuridine. By min 20 of a DNA-negative program, hydroxymethylase mRNA synthesis was repressed to the point where it no longer compensated for decay. However, a finite level of hydroxymethylase mRNA synthesis was maintained at later times of a DNA-negative infection. Such results indicate that replication of the phage chromosome is necessary but not sufficient for a complete turnoff of hydroxymethylase mRNA production. Functions controlled by the maturation-defective proteins (the products of genes 55 and 33) played only a minor role in the regulation of hydroxymethylase mRNA, metabolism. Thus, we favor the hypothesis that a complete turnoff of hydroxymethylase messenger production requires one or more new proteins as well as an interval of DNA replication. The absence of DNA synthesis had no particular effect upon dihydrofolate reductase messenger production. The preinfection addition of chloramphenicol likewise had little effect on dihydrofolate reductase messenger metabolism. These latter data imply that prior synthesis of a phage-coded protein synthesis may not be required for the turnoff of reductase messenger production.


[Ototoxicity of spectinomycin (author's transl)].

Spectinomycin is an aminocyclitol antibiotic, but different in chemical structure from other aminocyclitol antibiotics such as streptomycin, kanamycin and gentamicin. Spectinomycin clinically has been proven to be highly effective in the intramuscular single-dose treatment of gonorrhea. According to NOVAK et al. (1974), all evidence from pharmacological and clinical efficacy studies to date indicates that spectinomycin is free from ototoxic effects at the dose levels recommended for single-dose treatment of gonorrhea (2 or 4 g) or repeated i.m. or i.v. doses, 8g/day. The present experimental study has been made to evaluate the ontoxocic effects of spectinomycin in Hartley strain guinea pigs given i.m. a single-high dose (800 mg/kg or 1,600 mg/kg) and repeated-slightly higher dose (80 mg/kg or 160 mg/kg daily for 4 weeks) respectively. Differential frequency pinna reflex test in frequency range from 20 KHz to 500 Hz revealed that no animals showed disappearance of pinna reflex in the frequencies tested. Histologic examination in serial celloidin sections of the cochlea and vestibulum disclosed that a few animals given a single-high dose of spectinomycin (800 mg/kg or 1,600 mg/kg) and repeated-slightly higher dose or spectinomycin (80 mg/kg daily for 4 weeks) respectively showed limited mild damage of outer hair cells in the spiral organ and of hair cells in the vestibular organ. There were histologically a few focal necrosis in the liver and scattered interstitial cell infiltration around the proximal convoluted tubules which are lined with regenerated epithelial cells in some animals given the single-high dose (800 mg/kg or 1,600 mg/kg) or repeated-slightly higher dose (80 mg/kg or 160 mg/kg daily for 4 weeks) of spectinomycin. Positive correlation between the extent of the hair cell damage and the injury of the liver and kidney was not confirmed. The present study suggests that administration of spectinomycin at the dose levels recommended for single-dose treatment of gonorrhea (2 or 4 g) most probably is free from ototoxic effect.


[Experimental restoration of the renal artery. Comparative study of 3 procedures (author's transl)].

Presentation of theee procedures of experimental revascularization of the renal artery under microscopically controlled surgered (study of 19 dogs): --10 dacron velvet grafts, --6 hypogastric autografts, --3 spleno-renal autografts. Results obtained by three means of investigation: selective angiography, measurement of renal flow using radioactive xenon, microscopic study of the anastomoses and the grafts: --10 dacron 10 failures, --6 hypogastric autografts, 4 successes 2 failures, --3 spleno-renal autografts, 3 successes. Comparative study of the different experimental and clinical works on these subjects. Dacron grafts must be banned for calibers less than 4 mm in diameter. Hypogastric autografts give good congruence of the anastomoses, poses no problems with preservstion, but necessitates two sutures which spoil the results. Spleno-renal autografts, when possible, seem to be an ideal means connnection. A single suture, no nutritional problems and rapidity of execution.


Vectorcardiographic findings in Friedreich's ataxia.

Cardiac manifestations in Friedreich's ataxia occur frequently. We have studied 17 cases of Friedreich's ataxia, of which 94% showed a disturbance of the repolarization in the scalar ECG, 29% showed evidence of left ventricular hypertrophy. These changes are not specific but typical of Friedreich's ataxia. Vectorcardiograms were taken with the Frank-system. The vectorcardiographic findings showed not only the same changes as seen in the sclar ECG, but furthermore an atypical configuration of the QRS-loop was evident, which was not recognized in the scalar ECG. According to our experience compared with the scalar ECT, the vectorcardiographic investigations can be considered a more useful method in the diagnosis of Friedreich's ataxia.


Coronary artery fistula draining into left ventricle: case report and review.

A 6-year-old boy with coronary artery fistula emptying into the left ventricle was reported. An attempt was made to outline clinical manifestations of this disease which have not yet been fully described, based on the experience of the present case and a review of 14 previously reported cases. It is concluded that clinical signs and symptoms are not specific for this anomaly and retrograde aortography is required to establish the definite diagnosis of the lesion. Authors' views are expounded as to the location of maximal intensity of the murmur, genesis of the systolic murmur and electrocardiographic features.


[Accuracy and variability of medical interpretation of the electrocardiogram].

The accuracy of medical interpretation of the ECG, the variability of electrocardiographic conclusions drawn by different physicians and by a specialist when re-analyzing the same ECG were considered. Three experienced physicians analyzed 700 ECG independently from one another. The electrocardiographic inferences were contrasted against the autopsy, roentgenographic and clinical findings. A paired comparison of electrocardiographic conclusions made by the physicians with respect to the principal groups of these conclusions was undertaken. The mean frequency of complete concurrence of the conclusions varied from 26 to 89 per cent, depending upon the type of the electrocardiographic conclusion. Subject to comparison were also conclusions drawn by a single physician with a two-fold analysis of the same ECG. In this case the frequency of divergent inferences amounted to 43 per cent.


[Thrombocyte aggregation in depression and activation of the anticoagulation system of blood in animals].

It was demonstrated in rat experiments that function inhibition of the anticoagulation system by means of intravenous injections of high doses of antiplasmin and aminasine resulted not only in certain changes in the blood coagulation parameters, but also in increased platelets aggregation. The appearance of increased quantities of free thrombin in the circulating blood may be one of the mechanisms favouring increased aggregation of platelets. The activation of the function of the anticoagulation system induced in experimental animals by intravenous injections of low doses of adrenalin, antiplasmin (12 U/200 g of body weight) and tissue thromboplastin results, along with hypocoagulation and enhanced enzymatic and non-enzymatic fibrinolysis, in a decreased platelets aggregation.


Multiple pumps for sodium reabsorption by the perfused kidney.

Several distinct transport mechanisms responsible for sodium reabsorption by the rat kidney can be identified by studying the function of isolated perfused kidneys. Approximately one-half of the fractional sodium reabsorption by the isolated perfused rat kidney appears to depend on Na-K-adenosine triphosphatase (AT-Pase) and is inhibited by ouabain. About 10 to 20% is associated with the reabsorption of bicarbonate and is blocked by acetazolamide. This fraction of transported sodium is unaffected by ouabain and therefore does not involve Na-K-ATPase. Neither furosemide nor ethacrynic acid produce further inhibition of sodium reabsorption in a kidney already exposed to ouabain and acetazolamide. Most of the residual transport of sodium is inhibited by cooling the perfused kidney, suggesting that it is powered by metabolic rather than physical sources of energy.


Soluble immune complexes in sera of patients with nephritis.

Binding of radioactively labeled C1q was used to detect soluble antigen-antibody complexes in sera collected at the time of renal biopsy from 104 patients with immunofluorescent findings consistent with immune-complex disease. In comparison with data obtained with sera from 85 healthy donors, significantly elevated C1q binding activity was demonstrated in sera from 22 patients. C1q binding was elevated in all four patients whose dominant histologic finding on bright field microscopy was an intense interstitial mononuclear cell infiltrate. High C1q binding activity was found preferentially in sera from patients who had diffuse rather than focal histologic abnormalities by light microscopy, heavy glomerular deposits of C4 and C3 by immunofluorescence and elevated serum creatinine concentrations. However, there were many patients with similar immunofluorescent and bright field microscopic changes in whom circulating complexes were not detected and there was no correlation between the pattern of glomerular localization of immune complexes and the C1q binding activity of the sera. Serial measurements of C1q binding activity in the sera from three patients over a 90-day interval emphasized that immune complexes may be demonstrated by this technique only intermittently in the sera of some patients with renal biopsy evidence of immune-complex disease. Nevertheless, these observations suggest that the C1q binding test may be a useful tool to monitor disease activity in patients with immunologically mediated renal disease.


[The fluorescein angiographic picture of hereditary colloid bodies (author's transl)].

The authors present five patients with dominant hereditary colloid bodies of the retinal centre from two family trees. Their fluoroangiographical pictures confirm the variable clinical manifestations and ophthalmological findings which because of the special colloid bodies arrangement show a resemblance to the Hutchinson-Tay, Holthouse-Batton, Doyne and Klaingutti cases, also within the framework of a single family tree. With the help of the angiogram the type and development stage can be followed, while this disease passes from functionally and ophthalmologically unimportant lesions into the final stage of atrophy and the fibrous conversion of the whole rear eye pole.


[Electron-microscopic delineation of acid mucopolysaccharides in the trabecular meshwork (author's transl)].

The presence of acid mucopolysaccharides in the trabecular meshwork was repeatedly investigated histochemically. The electron microscopical demonstration of glycosaminoglycanes with Ruthenium red was to be emphasized. In the material gained by trabeculectomy in 13 patients, a Ruthenium-positive, up to 30 nm thick film of varying degree could be demonstrated on the endothelium of the trabecular meshwork.


Malignant hyperthermia syndrome--evidence for denervation changes in human skeletal muscle.

The presence of denervation-like changes and abnormal mitochondria in the muscle of carriers of the malignant hyperthermia syndrome suggest a neuropathic basis for the human syndrome. A defect in mitochondrial ATP synthesis resulting from denervation, and potentiated by some general anaesthetics, may be the primary muscle fibre lesion in the human malignant hyperthermic syndrome.


Some parasites and other organisms of wild rodents in the vicinity of an SPF unit.

80 Rattus norvegicus and 63 Mus musculus caught near the Laboratory Animals Centre, were examined for parasites and other organisms: 32 parasite species were found and 2 species of Mycoplasma. A small number of individuals were tested and found positive serologically for species of Leptospira.


The establishment of a breeding nucleus of category 4 Dutch rabbits.

A method is described for establishing a breeding nucleus of Category 4 Dutch rabbits. The problems of hand-rearing, causes of mortality and the failure of the does to lactate normally are discussed.


[Tryptophan-load in progressive scleroderma (author's transl)].

This presentation describes effects of oral tryptophan loading (5.0 g DL) on tryptophan metabolism in healthy subjects (n = 10) and persons with progressive scleroderma. N1-methylnicotinamide (N1MN), 3-hydroxyanthranilic acid (3 HAA), kynurine (KN), tryptamin (TA), xantheurenic acid (XA) were determinated. Alterations of tryptophan metabolism were evaluated by 24 h urinary excretions of the following metabolites: 5-hydroxy indolacetic acid (5 HAA) and indole-3-acetic acid (IAA). The pathological pathways were discussed, especially the way and influence of serotonine.


Transaortic repair of double-outlet right ventricle with situs versus, l-loop, l-malposition (I,L,L), subaortic ventricular septal defect, and associated anomalies.

Successful total correction of a rare form of double-outlet right ventricle (I.L.L.) is reported wherein transaortic construction of the ventricular baffle was used. Surgical approach to the defect was unsatisfactory through a right ventriculotomy. Excellent exposure was achieved through the aortic valve. Correction of partial anomalous venous return from the left lung, pulmonary debanding, and repair of the pulmonary artery were also done. Double superior venae cavae made special venous cannulation necessary. Cardiac catheterization at one year documented successful repair. This case illustrates the usefulness of the transaortic approach to a ventricular septal defect when repair through a ventriculotomy is difficult or impossible.


Aortic homograft obstruction.

At the Mayo Clinic from September 1967, to November 1972, 128 patients underwent operations in which an aortic homograft was used to establish right ventricle-to-pulmonary artery continuity. Recently, we studied 18 of these patients who had calcified, obstructed aortic homografts. Seven patients had histories of significant dysrhythmias, all of which required medication and two of which were life threatening. Seventeen of the patients had systemic or suprasystemic pressure in the right ventricle before replacement of the calcified homografts. After placement of the homograft with a Hancock prosthesis, the pressure in the right ventricle of 12 patients was one half the systemic pressure or less. There were no operative deaths, and only 2 patients developed any significant postoperative problems.


Aortic valve replacement with the De Bakey valve.

De Bakey prostheses were inserted in 29 patients with aortic valve disease between October, 1970, and May, 1972. Ten patients have died, but all but one of the remaining 19 have beel followed for a minimum of 19 months. Evaluation of the results in these subjects indicates that the function of the De Bakey valve compares favorably with that of other aortic valve prostheses.


Gluconeogenesis in isolated rat hepatic parenchymal cells. IX. Differential effects of glucagon and epinephrine on phosphofructokinase and pyruvate kinase.

The isolated hepatocyte preparation (from 24-hour fasted rats) comprised a homogeneous population of intact cells as shown by electron microscopy. Homogenates of hepatocytes were incubated for 10 minutes in an ionic buffer solution containing 1.5% gelatin with and without hormones and centrifuged at 27,500 X g for 30 minutes, and the supernatant fractions were assayed for enzyme activities. Hexokinase activity was absent, although it was easily detectable in the same fraction of intact liver. The activity of glucokinase was uninfluenced by any of the hormones. The assayable activity of fructose diphosphatase was not increased by glucagon, monobutyryl cyclic adenosine-3',5'-monophosphate (mb-cAMP), or epinephrine, nor was it inhibited by insulin. The activities of phosphofructokinase and pyruvate kinase were not increased by insulin; however, glucagon and mb-cAMP inhibited the assayable activity of phosphofructokinase and pyruvate kinase to 20 to 25% of control values. Epinephrine did not influence the assayable activity of either enzyme, although it stimulated gluconeogenesis as markedly as did glucagon and mb-cAMP. When liver cell homogenates were subjected to centrifugation at higher forces (37,400 X g for 60 minutes or greater), the assayable activity of phosphofructokinase in supernatant fractions began to diminish. Additional loss of phosphofructokinase activity was observed in supernates prepared from cells that had been incubated with epinephrine; however, in these supernatant fractions, pyruvate kinase activity did not differ from control values. The results reported here demonstrate (1) a behavior of phosphofructokinase which is not predictable on the basis of its known solubility properties, and (2) differential effects of glucagon and epinephrine on the activity of phosphofructokinase which suggest that separate mechanisms are operative in stimulation of glucoeogenesis by glucagon and epinephrine.


[Details of a denounced physician (E.N.T.) suspected of bodily injury, and the following expert judgement (author's transl)].

An otologist was denounced and the patient's case history was confiscated because after tonsillectomy an absecess and a thrombosis of the vena jugularis interna had developed. The procedure and the medical aspect how at first being judged by the lawyer and the public prosecutor are described. On the base of the given medical opinion the court quashed proceedings. Because of the growing number of denouncements this casuistic paper ends with four guiding principles to protect against unjustified medicolegal blame.


[Comparative clinical, histomorphological and immunological investigations into etiological aspects of polyposis nasi et sinuum (author's transl)].

43 patients with polyps affecting the nose and the sinuses were examined for immunological deficiencies on the basis of clinical, histomorphological and immunological findings. Constant histological findings were a chronic non-specific inflammation of varying intensity; immune-histologically a varyingly dense collection of Ig-producing cells with intracellular and extracellular immunoglobulins was observed. A determination of the immunoglobulins in the serum allowed no conclusion to be drawn as to the local condition of the mucosa. Hypertensitivity reactions played no role as a causal pathogenetic factor in the development of polyposis. In a third of the cases, however, polypi led to a secondary bronchial asthma. After the surgical removal of the polypi from the nose and paranasal sinuses, not only an improvement in nasal breathing and in the aeration of the sinuses was regularly achieved, but obstructive disorders of ventilation also disappeared.


[Influence of reserpine on the nasal mucous membrane (author's transl)].

The influence of reserpine on the nasal mucous membrane in the various conditions of its autonomic denervation was investigated in the rabbits. Histochemical analysis of a acetylcholine esterase and quantitative measurements of acetylcholine were performed. The results point out that reserpine influence is found only on the vascular elements in the mucous membrane and not on the subepithelial glands. Analogically it was concluded that in some patients with arterial hypertension who were treated with reserpine, its side effect, nasal obstruction, was caused only by vasodilatation. In rhinitis vasomotorica, in the addition to the vasodilatation the abounding secretion of subepithelial mucous glands is present. The performed experiments also point out that resection of the vidian nerve in resistant cases of vasomotor rhinitis with aboundant secretion is reasonable.


[Complications using imidazolin derivates and neomycin containing substances in irrigation therapy of the maxillary sinus (author's transl)].

A 5-year-old boy, who suffered from a chronical maxillary sinusitis was treated by daily irrigations with an imidazolin derivate, followed by neomycin-containing solutions via drainage plastic tubes. 2 hours after the irrigation the boy showed signs of a generalized hyperergic reaction with unconciousness, bradycardy and hypertonus. After 18 hours the boy had recovered completely without incidents of nephrotoxic, ototoxic or neuronal damage. The toxic effects of Privin and Nebacetin are discussed.


[Report on clinical positive evidence of the nerve excitability test in facial palsy (author's transl)].

Comparative studies of case controls of Bell's palsy, posttraumatic and postoperative palsies in relation to the clinical positive evidence of the nerve excitability test are demonstrated. While an absolutely parallel reaction of clinical function restitution and electrical excitability is observed in Bell's palsy and in posttraumatic late palsy, on the other hand this congruence will not be observed in postoperative palsies (in intact anatomical conduction of the nerve) in most of the investigated cases. In these cases the clinical restitution of isolated movements of the mimetic muscles has further improved than the excitability test demonstrates. The exact developmental mechanism remains still open.


[Determination of the latency for the prognosis of Bell's palsy (author's transl)].

In a previous study the authors discussed the value of the determination of the compound action potential amplitude of the m. orbicularis oris following supramaximal stimuli of the facial nerve for the prognosis of facial paresis. In this study they investigate the suitability of the determination of the latency periods for an early prognosis. The latency periods in 20 normal subjects and 26 patients with idiopathic facial paresis were messured and continuously checked. The study reveals that a difference of more than 0.5 msec. between the latency periods of normal and paretic patients does not even permit the proof of peripheral lesions in patients with partial denervation or absent or insufficient recovery. Ocassionally, even shorter latency were observed in paretic patients, which are probably due to a local increase of the threshold for supramaximal stimuli around the stimulation electrode. The necessary increase of the stimulus intensity probably leads to a nervous excitation further distally. Contrary to the observations of other authors these studies indicate that the determination of the latency does not constitute a useful prognostic criterion for idiopathic facial paresis; for an early prognosis the measurement of latency is less reliable than the determination of the compound action potential amplitude.


[Methods for oscillography on the temporal bone preparation (author's transl)].

Oscillography of the middle ear structure on the temporal bone preparation are of essential importance for the expansion of our knowledge concerning physiological process and thus also for the further development of operation techniques that improve hearing. With the increased technical possibilities we are now able to make processes in the range of only few A measurable and visible. Accordingly, the methods employed for this purpose are complicated and manifold. The goal of this paper is to summarize these techniques as far as possible, to describe them in an understandable way, and to briefly point out their pros and cons. Optical methods, nearly all of which are in use today, as well as new methods such as laser interferometry and the Moessbauer technique, which can be performed only in few laboratories, are discussed.


[Experimental studies on the question of the enzymatic destruction of the ossicular bones during middle ear inflammations (author's transl)].

The proteolytic activity of purulent middle ear secretions from patients with cholesteatoma, chronic otitis media, acute otitis media and radical mastoid cavities were investigated. The proteolytic activity in the secretions from cases with cholesteatoma is higher than from patients with other chronic otitis media. The collagenolytic effect of the matrix of cholesteatoma combined with the high level of the bacterial and leukocytic proteinases in the middle ear secretions is undoubtedly one of the main factors in the destruction of the ossicular bones.


[Morphology and clinical significance of syringomas of the external auditory canal (author's transl)].

Syringomas of the external auditory canal ("ceruminomas"), are very rare their morphology is varied and their clinical course hardly predictable. Their nomenclature is controversial and easily misunderstood. Two cases of syringomas of the external auditory canal are reported (one adenoma and one adenoid-cystic carcinoma) which were also studied by means of electron microscopy. The morphology and clinical significance of these tumors is discussed.


[Late results of stapedectomy after 15 years (author's transl)].

Stapedectomy in Otosclerosis in using polyethylene struts or stainless-steel wire protheses results in permanent correction of the postoperative gap. The use of stainless-steel wire protheses however is successful with 94% of the patients regarding the postoperative gap, compared to 89% of the patients in using the polyethylene struts. The postoperative decrement of bone conduction is statistically significantly lower in the stainless-steel wire protheses than in polyethylene struts.


[Pantopaque cisternography in diagnosis of acustic neuromas (author's transl)].

In 6 out of 37 patients, examined by pantopaque cisternography the suspect of a acustic neuroma could be strengthened. All of these tumors showed growth beyond the internal auditory meatus. Smaller intrameatal tumors were not found. The indication for cisternography were made almost according to the demands from Fisch and Wegmüller, therefore it is asked, wether it should not be better to follow the methods of Valvassori who sometimes performes cisternography based on audiometric findings alone. As results of our own experience and similar cases reported elsewhere, this seems justified. Because of the small amount of contrast medium used the side-effects of Pantopaque-cisternography are practically nil.