[Double-blind polycentric study of the action of S-adenosylmethionine in hepatic cirrhosis]. Two comparable groups of patients with hepatic cirrhosis of different genesis in a compensation phase have been treated for 30 days with S-adenosylmethionine and vitamine B-12 (28 cases) or with vitamine B-12 alone (25 cases). The drugs were given by slow intravenous route at the daily dose of 150 mg of SAMe and 2000 gamma of vit. B-12 or of 2000 gamma of vit. B-12 alone, in two adminstrations. An evaluation of the results was carried out mostly on the laboratory data testing the liver function. Only the group of patients who had received SAMe showed significant modifications of all the parameters considered. This is confirming SAMe ability to restore hepatocyte activity bringing also to normal the protein synthesis.


[Double-blind studies of the therapeutic action of S-Adenosylmethionine (SAMe) in oral administration, in liver cirrhosis and other chronic hepatitides]. Six oral administrations per day of 30 mg S-adenosylmethionine (SAMe) for 30 days, in addition to 6000 gamma/day of Vitamine B12 induced marked improvements of biochemical parameters in 20 patients with hepatic cirrhosis or various chronic hepatites. Particularly, the protidemia, bilirubinemia and radial immunodiffusion have shown the highest favorable drug responses. These improvements were still lasting and even further increasing 30 days after the end of therapy. In another group of patients with similar diagnosis and under clinical conditions comparable to the previous group of twenty, the administration of Vitamine B12 alone, in the same doses as above, has not induced any alteration in the biochemical parameters.


Diarrhoea: a traveller's tale.

Diarrhoea: a traveller's tale. Travellers' diarrhoea is a result of travelling overseas. Proper diagnosis can only be made when a full microbiological investigation is carried. A case due to Shigella flexneri is described.


Perinatal aspects of bilirubin metabolism. Study of bilirubin metabolism in the fetus and newborn continues to reveal new insights into fetal physiology and maternal-fetal-neonatal relationships. Therapeutic advances directed toward prevention as well as treatment of hyperbilirubinemia continue to expand our understanding of both the basic metabolic pathways and previously unsuspected interplay between host and environment. Seemingly insignificant alterations in temperature, oxygen, carbohydrate, or light itself have been shown to affect the delicate balances in bilirubin metabolism. Similar impact upon other developing systems undoubtedly occur. Those who accept responsibility for the care of the fetus and newborn must recognize that all we do and all we fail to do in their care has a much greater potential for affecting the quality of life than at any other time.


Principles of adolescent gynecology.

Principles of adolescent gynecology. Most of the gynecologic problems presented by adolescent girls are dysfunctional. They include, in order of frequency: dysfunctional uterine bleeding, dysmenorrhea, and amenorrhea. Leukorrhea is also very likely to be dysfunctional, in that in many cases it is not a true vaginal discharge but an increase in vaginal secretion. For the most part, gynecologic disorders in adolescent girls are diagnosed and treated in the same fashion as similar conditions in adult women. Genital tumors are managed in accordance with accepted gynecologic principles. Inasmuch as the gynecologic disorders encountered in adolescent patients are similar to comparable ones in adult women, these problems properly belong in the realm of the gynecologist, who is best equipped to diagnose and treat them.


Urologic injuries.

Urologic injuries. Urologic injury during pelvic surgery is primarily a matter of prevention; should it occur, however, prompt recognition and appropriate management are essential. Basic principles are applicable, whether the operation has been performed via the abdominal or the vaginal route. Conditions such as endometriosis, infection, previous operation, and tumor distortion increase the likelihood of damage to the urinary tract. Difficult dissection may easily damage the urethra, bladder, or ureters. Preliminary information as to the position of the ureters and bladder will alert the surgeon. Exacting identification of the ureter and bladder is necessary prior to the use of clamps, sutures, or incision. The next most important factor is recognition of such injury. Whenever the possibility exists, it must be promptly and definitively delineated. Injury to the urethra, bladder, or ureters, when recognized and appropriately repaired, is unlikely to cause subsequent complications. Good surgical techniques, adequate and accurate hemostasis, prevention or treatment of infection, drainage of the operative site, and splinting and resting of the organ are necessary. It is the unrecognized and unrepaired urologic injury that increases the chances of immediate and delayed complications. Peritonitis, infection, stricture, fistula, hydronephrosis, and renal damage as well as death may occur even if the patient survives the immediate postoperative complications. It is important in such instances that the error not be compounded by rash attempts at additional surgical procedures at an operative site where there is maximal tissue reaction. General supportive measures with drainage of the urinary tract to preserve renal function are all that should be done. It is likewise important that the surgeon not be rushed into an early attempt to correct the resultant fistula. Adequate time must be allowed for the tissues to heal so that the subsequent repair may be carried out successfully and without further complications.


Effect of LHRH stimulation in anovulatory women. Serum FSH and LH and levels were determined at different time intervals after the subcutaneous administration of 100 mug LHRH to 24 females. Serum FSH levels were of the same order in the oligomenorrhea-amenorrhea  and the Stein-Leventhal group of patients but elevated in gonadal failure. There was a great degree of overlap between serum LH values in the three groups. Gondal failure patients, however, could be distinguished from the other  two groups because these patients had an elevation of both serum FSH and LH, and the response to LHRH was considereably exaggerated in comparison to the other two groups.


Postmenopausal symptomatology, maturation index, and plasma estrogen levels. An attempt to correlate postmenopausal symptoms with the vaginal maturation index and plasma levels of estrogen was made in a group of patients with surgical menopause. The group was followed up monthly for 6 months in a double-blind study during which the patients received equine esterified estrogen and synthetic esterfield estrogens. No statistical difference in plasma levels of estrogen was  found between the group of patients with symptoms and the patients without symptoms, with or without estrogen therapy. There was no correlation of the maturation index with the presence or absence of symptoms or  with the estrogen plasma levels.


Yeasts in banal external ocular inflammations. In 53 out of 313 patients suffering from longstanding inflammations of the outer eye or dacryocanaliculitis, not yielding to the obligate treatment with antibiotics and steroids, yeasts were isolated and regarded as the causative agents. Among the yeasts, different Candida species were prevalent, with C. albicans and C. guillermondii at the top. An obstinate, superificial epithelial and subepithelial punctate keratitis appeared to represent an entity pathognomonic of a yeast infection. Eradication of the yeasts and cure of the inflammation was achieved only by intensive prolonged treatment with Mycostatin or amphotericin B.


Lymphoproliferative disease of the hard palate: a clinicopathologic entity. A study of twenty-one cases. Twenty-one cases of a lymphoproliferative disorder believed to represent a clinico-pathologic entity were studied. These lesions, which appeared on the hard palate, occurred in elderly men and women with an average age of 70 years. The lesions presented as soft, fluctuant swellings which were occasionally bilateral, ulcerated, or discolored. Microscopically, the lesions were classified as lymphocytic lymphomas; eight were diffuse and well differentiated, seven were nodular and well differentiated, and six were diffuse and poorly differentiated. All lesions were characterized by a tendency of the lymphocytes to show nuclear fragility. Accessory salivary gland involvement was common, this being characterized by acinar obliteration to varying degrees and by periductal hyalinization of collagen. Determinate follow-up of fourteen patients disclosed that eight died of disseminated lymphoma, three are alive with disease, and three are free of disease after treatment with radiation and/or chemotherapy. Lymphoproliferative lesions in this location are believed to be malignant or potentially malignant processes.


Induced hypervitaminemia A test and its standards in adults. Oral administration of large doses of vitamin A permits one to study pos-prandial lipemia. Thanks to a new fluorescimetric and automatic method, estimation of vitamin A is now much easier than formerly. The normal results of the oral vitamin A tolerance test are evaluated with this new method and compared with those given by the previous method.


[Origin, nature, role and fate of prostaglandins liberated during the expansion of intravascular space in the anesthetized rat]. In experiments in which blood was cross-circulating in rats, the blood pressure of the recipient dropped while that of the donor rose, following the increase of the circulating blood volume, produced by infusion either of saline or blood. The phenomenon was almost imperceptible when binephrectomized animals were used. In experiments in which the blood-bathed organ technique was used, prostaglandin-like substances were detected, released during the rise of the blood pressure, produced by the same stimulus (the expansion), in anaesthetized rats. A significant difference was found between the prostaglandin-like substances detected using the blood-bathed organ technique, in normal rats (5.387 ng per ml of blood plus or minus 0.288 = SEM) and those detected in binephrectomized rats (3.202 ng per ml of blood plus or minus 0.330, p smaller than 0.025). The biologically active substances detected in 25 ml of blood collected during expansion, while the assay organs showed a prostaglandin-like activity, were found to have the chromatographic behaviour and the bioassay properties of PGA, PGE and PGF series. A great quantity of the biologically active substances, having the chromatographic behaviour and the bioassay properties of PGA, PGS and PGF was detected in the rat renal medulla. Sufficient quantities of the released prostaglandin-like substances could escape the pulmonary vascular bed in this species of animal. It was concluded that a great quantity of the released prostaglandin-like substances came from the kidney and their release by this particular mechanism suggested that they play an important homeostatic role on the blood pressure, blood volume, and sodium and water balance regulation.


[The inhibitory mechanism responsible for antigenic competition in the mouse, upon successive injections of 2 different antigens: the immunosuppressive function of T cells]. Antigenic competition cannot be obtained in congenital athymic Nude mice, whatever the dose of inhibitor Ag used and the free interval between inhibitory Ag injections and the Ag test. On the other hand, competition is normal and even increased, in thymectomised, adult Swiss mice, used 10 to 30 days after thymectomy. In normal mice, the inhibitory mechanism induced by a first thymodependent antigen, may also occur with regard to certain thymo-independent antigens and thus act on the B cells. The antigens may also serve as inhibitory antigens for thymodependent antigens if the free interval between the two injections is small. Injection of hydrocortisone (25 mg/kg) or ALS a short time before the inhibitory antigens, suppresses competition. On the other hand, methotrexate is without effect. Thus the inhibitory TD mechanism does not require mitoses (methotrexate) and depends on corticosensitive T cells which are, no doubt, recirculated (Anti-lymphocyte serum) with a life span greater than 30 days (adult thymectomy). The previous results were obtained when two antigens were administered by intraperitoneal route and the PF cells sought in the spleen. The same experiment was carried out, injecting two antigens subcutaneously, in the same limb, and counting the PF cells in the appropriate lymph node; it shows the adjuvant effect exerted by the first antigen on the response with regard to the second antigen. On the other hand, inhibition is produced if the first antigen is injected intraperitoneally or into another limb. One may thus distinguish an inhibitory effect or an adjuvant effect depending on the experimental conditions. The inhibitory effect seems to be related to the T cells with an immunosuppressive function.


[A histologic study of Ceratophyllus consimilis Wagn. fleas infected by the agent of murine typhus (Salmonella typhimurium)]. Histological studies of C. consimilis infected with S. typhimurium have shown that the microbes are preserves along the whole extent of the alimentary canal, expecially in the midgut and pyloric portion. Bacteria are concentrated in the gastral cavity; in addition, they were found to penetrate the alimentary epithelium cells and pyloric valve tissue. The number of microbes and their distribution in the intestine undergo great variations that depends largely on the insects feeding rhythm. During bloodsucking a "lavenment" of the alimantary canal takes place; as a result, numerous microbes accumulated here are periodically excreted outside. The infection with Salmonella typhimurium is often accompanied by pathological changes in fleas tht is expressed in the destruction of the midgut epithelium and pyloric valve tissue.


[Cerebromeningeal cryptococcosis. Predisposing role of immunosuppressive therapy in patients with kidney transplants]. Disseminated cryptococcal infection is described in eight patients, seven of them with verified meningeal involvement. Six of the eight patients were recipients of a renal homograft and submitted to the classical immunosuppressive treatment. Consideration is given to predisposing factors and to problems in the clinical, biological and mycological diagnosis. Some comments are presented on the often disappointing results of antifungal therapy of cryptococcal meningitis.


[Encephalitis and ornithosis].

[Encephalitis and ornithosis]. Neuropathology of ornithosis encephalitis in an adult man is reported. Lesions were widespread with severe vascular congestion, hyaline thrombi, intense perivascular infiltration by mononucleated cells and microglial reaction in the parenchyma. No specific lesion of the neurons was found.


[Influence of the daily ingestion of a total unsaponifiable extract from avocado and soy bean oils on cholesterol metabolism in the rat]. The effects of ingestion of an unsaponifiable avocado and soya extract (P.I.A.S.) on the rates of cholesterol turnover were studied in the Rat smaller than in toto greater than. The balance is the same as in control rats, but fecal and urinary excretions of cholesterol are well enhanced and transformation into bile acids is consequently reduced. The absorption coefficient of cholesterol is unchanged in spite of the presence of phytosterols in the extract. The extract having been said to have a beneficial effect on scleroderma a special study was undertaken of the skin. The GLC analysis of sterols show the very probable presence of phytosterols and a richer proportion of cholesterol, precursors particularly methostenol in the skin of rats fed on P.I.A.S. than in that of the controls. These modifications do not produce any variations in the rate of cholesterol synthesis as measured in vitro.


[Influence of environmental conditions on human hematologic constants]. A blood investigation was carried out on 3,030 volunteer blood donors and the results treated on a computer by multivariant analysis. The authors noted a depressor effect of the urban environment on the red and white cells, a rise in small lymphocytes and a reduction in monocytes in patients living in industrial areas. This stimulation of the lymphocyte system may be compared with the experimental results obtained by the same authors in animals.


A shadow-casting technique for the examination of the surface topography of cultured cells. Modifications to a technique of shadowing cultured cells for examination by the light microscope are presented. These consist of using a low angle of incidence, rotating the specimen and employing aluminium as the shadowing material.


"Car. factor" deficiency revisited.

"Car. factor" deficiency revisited. Three members of a Virginia family with a bleeding disorder were found to have a serum defect in thromboplastin generation similar to the previously reported "Car. factor" deficiency. Sera from three members of the original Car. family did not correct the defect of affected members of the Virginia family. Partial thromboplastin times of Car. deficient individuals and affected members of the Virginia family were normal. Although correction with normal serum is attained in vitro, the serum defect persisted after infusion of fresh frozen plasma. Platelet function studies of the Virginia family revealed less than 30% aggregation after the addition of exogenous ADP and disaggregation within 2 min. Evaluation of children with Noonan's syndrome, albinism, and "Portsmouth" syndrome showed coexistent platelet aggregation defects and nonspecific serum defects.


Lamb fetal pulmonary fluid. I. Validation and significance of method for determination of volume and volume change. An indicator-dilution method is described for measuring fetal pulmonary fluid, FPF, volume (Ve), and volume change with time (Vs) in the lamb fetus in utero. The indicator, albumin, which is the predominant protein of normal FPF, was administered directly to FPF in the form of radio-iodinated human serum albumin (RISA). We have shown that (1) RISA is distributed homogeneously throughout the FPF compartment, (2) it is not altered within FPF, (3) it does not alter the functional characteristics of FPF, and (4) it remains within the FPF compartment throughout the period of measurement. Ve varies directly with the weight of the fetus so that Ve per kilogram was 31.6-35.6 ml/kg in four of five fetuses. The Ve per kilogram was lower in one fetus at the start of the experiment but increased rapidly to 29.0 ml/kg within 45 min. Thus the relaxation volume of the fetus in utero is in the range of functional residual capacity (FRC) and thoracic gas volume of the air-breathing neonate, which indicates that the pulmonary transformation at birth is, in essence, an isovolumic change in state wherein the fetal liquid-lung becomes the neonatal air-lung. The rate at which FPF is formed (Vs) is about 1.5 ml/hr-kg; however, the rate may change in so far as both rapid increases and rapid decreases of FPF volume were observed. When breathing movements were induced in the fetus by stimulation of the sciatic nerve, FPF volume decreased rapidly (Vs equals -3.0 ml/hr-kg), which indicates that negative intrathoracic pressures promote its resorption. When FPF volume fell transiently or was low initially, there was subsequent rapid restoration of volume to the range of anticipated FRC.


Lamb fetal pulmonary fluid. II. Fate of phosphatidylcholine. Using the radio-iodinated human serum albumin ([131-I]-RISA) dilution method to measure lamb fetal pulmonary fluid (FPF) volume, we followed the disappearance of protein-complexed, 14-C-labeled phosphatidylcholine ([14-C]PC) during the first 90 min after its injection into FPF. The FPF samples were analyzed for total lipid 14-C activity and for distribution of 14-C in PC, other phospholipids (PL), fatty acids (FA), and neutral lipids (NL). For most sampling periods ascending aortic (AAo) and right atrial (RA) blood samples were obtained simultaneously with FPF and serum was analyzed for total lipid 14-C activity and for distribution of 14-C in total PL, FA, and NL. These studies indicate that (1) PC is cleared rapidly from FPF with an estimated half-time of 15-57 min; (2) FPF-PC may be metabolized to lyso-PC and FA within the fluid itself; and (3) FA derived from PFP-PC enter the pulmonary circulation, thus establishing a pulmonary arteriovenous FA gradient. The possible sites at which PC may be cleared from FPF are considered.


Neonatal paroxysmal supraventricular tachycardia with hydrops. A critically ill infant with paroxysmal supraventricular tachycardia and hydrops fetalis responded well to aggressive management. Care must be taken to avoid digitalis toxicity. Procaine amide or quinidine are effective alternate therapies.


[Immunofluorescence technique in diagnosis of trichinellosis in swine. I. Investigations with the tube test (author's transl)]. Experiments have been made with serological demonstration of Trichinella spiralis infections in swine. The technique applied was the indirect immunofluorescence tube test with whole larvae of T. spiralis as antigen. The blood samples tested were taken from groups of SPF swine inoculated with, respectively, 50, 150, 500 and 1500 Trichinella larvae. In animals inoculated with at least 150 larvae, antibodies could be demonstrated 3-5 weeks p.i. until the investigation was finished 6-7 months later. The technique applied thus appears to represent a reasonably sensitive and reliable method for demonstrating infections with T. spiralis in swine.


[Immunofluorescence technique in diagnosis of trichinellosis in swine. II. Comparative investigations with the tube test and the cryostate method (author's transl)]. A series of comparative IF tests have been made on serum samples from 9 SPF pigs experimentally infected with Trichinella spiralis (50-500 larvae per animal). The techniques applied included a tube test (antigen: whole Trichinella larvae), and a cryostat test (antigen: sections of Trichinella larvae). With the cryostat test a positive reaction was recorded in 2 animals already on the 6th day and in 5 animals on the 13th day p.i., while with the tube test such reaction was not demonstrated until the 27th day p.i. (2 animals). A potential risk of cross-reaction of unknown origin seems, however, to limit the application of the cryostat test to SPF- pigs.


[Functional scintigraphy of the right heart]. After intravenous injection of 99m-Tc-labelled HSA-microspheres indicator dilution curves of vena cava superior, total right heart and lungs are recorded, using a Nuclear Chicago Pho Gamma II camera and a Hewlett Packard 5407 A computer system. A method is described, which permits the determination of the distribution of transit times, the mean transit time and the ejection fraction of the right heart on the basis of these three curves. The usefulness of the method for cardiac investigations is discussed.


Enzymic in vitro repair and chemical nature of DNA chain breaks induced by incorporated phosphorus-32P decay. In vitro repair of single strand breaks in T4 and phage DNA caused by 32p decay was studied. Zone centrifugation procedure showed that polynucleotide kinase, ligase enzyme system failed to repair 32P-damages. It was found that damaged DNA contained gaps and could be repaired by DNA-polymerase I, polynucleotide ligase treatment.


The preparation of 5-cyanouracil and 5-cyano-2'-deoxyuridine from the corresponding 5-iodo derivative and cuprous cyanide. 5-Cyanouracil has been prepared in high yield from cuprous cyanide and 5-iodouracil. The deoxynucleoside has been similarly prepared form 5-iodo-2'-deoxyuridine and this has enabled these compounds to be labelled with (14-C) cyanide. Attempts have been made to incorporate 5-cyanouracil into Escherichia coli 15T and into Mycoplasma mycoides var. capri DNA under conditions in which several other 5-substituted uracils have been incorporated, but without success. Similarly 5-cyano-2'-deoxyuridine could not be incorporated into the DNA of T3 phage under conditions in which 5-bromo-2'-deoxyuridine is easily incorporated. These results suggest that the criteria for a 5-substituted uracil to be incorporated into DNA in vivo depends on some factor other than the size of the substituent.


A study of the interaction of histones with DNA using isopycnic centrifugation in metrizamide gradients. Isopycnic sedimentation in metrizamide gradients has shown that mouse-liver histones bind co-operatively to both homologous and bacterial DNA's. However, at low input ratios of histone to DNA, two types of stable complex are formed, depending on the histone concentration. One complex contains half as much histone as DNA while the other contains approximately equal amounts of histone and DNA. At high input ratios of histone to DNA extra histone is bound giving complexes containing up to twice as much histone as DNA. Poly-L-lysine and protamine were also found to bind co-operatively to DNA.


Number of genes and base composition of mitochondrial tRNA from Saccharomyces cerevisiae. Increasing amounts of mitochondrial [32P] tRNA (4S fraction), were hybridized with mitochondrial DNA OF Saccharomyces cerevisiae. At saturation, the calculated number of genes for 4S mitochondrial RNA was 20. Mitochondrial [32P] tRNA eluted from the hydrids obtained either with an excess of tRNA or an excess of DNA showed, after alkaline hydrolysis and chromatography, a G+C content of 28 and 35 p. cent respectively. This last value is similar to that found with the total 4S fraction. The odd nucleotides T (about 1T per sequence), U, hU are present in mitochondrial tRNA. Some sequence may begin with pG.


An improved method for the purification of tRNA by chromatography on dihydroxyboryl substituted cellulose. An improved method for the rapid separation of aminoacyl-tRNA from tRNA by chromatography on dihydroxyboryl-substituted cellulose has been developed. The method relies on the selective binding of unacylated tRNA to the cell cellulose support containing dihydroxyboryl groups. This binding is the result of complex formation between the cis-diol group of the 3'-terminal ribose in tRNA and the dihydroxyboryl groups immobilized on the resin. Aminoacyl-tRNA cannot undergo borate complex formation and is not retained on the resin. The separation is carried out at near neutral pH values ensuring stability of the aminoacyl ester linkage. The aminoacyl-tRNAs are obtained in very high purity. Aminoacyl-tRNA species containing the modified nucleoside Q are also retained on dihydroxyboryl cellulose. Conditions for isolating all Q base containing tRNA species from unfractionated tRNA are described.


Specific cleavage of tRNA by nuclease S1. Nuclease S1 specifically hydrolizes tRNAs in their anticodon loops, forming new 5' phosphate and 3' OH ends. Some single-stranded regions are not cut by nuclease S1. The strong preference of nuclease S1 for the anticodon region can be used for rapid identification of an anticodon-containing oligonucleotide and subsequent identification of the probable amino acid specificity of tRNA.


The characterisation of a fragment of ribosomal protein S4 that is protected against trypsin digestion by 16S ribosomal RNA of Escherichia coli. After mild trypsin treatment of a complex of ribosomal protein S4 and 16S RNA of Escherichia coli, a large homogeneous fragment of the S4 protein was protected against digestion by its RNA binding site. This fragment was isolated and characterised for molecular weight. It was able to rebind specifically to 16S RNA. Preliminary results indicate that protected protein fragments can also be obtained from other proteins that complex specifically with 23S and 5S RNA.


Two transfer RNA (1-methylguanine) methylases from yeast. Two distinct tRNA (m-1G) methylases have been found in the yeast Saccharomyces cerevisiae. They differ in their chromatographic properties on hydroxyapatite, in their response to spermine, and in their site specificity. Only one of the methylases is active against normal tRNA from Escherichia coli.


The influence of anti-inflammatory drugs on the values of xylose test in man. Anti-inflammatory drugs influence intestinal absorption. Acetylsalicylic acid, indomethacin, and PAS decrease significantly the values of xylose test in man. Paracetamol decreases the values of the test in two thirds of the subjects. Salicylamide, phenylbutazone, and sulfadimethoxine do not possess this action.


Antimalarial compounds. XIV. New derivatives of 2-bromo-N,N-bis-(diethylaminoethyl)-4,5-dimethoxyanaline (RC 12). The molecule of RC 12 which was found previously to exhibit antimalarial activity has been modified, by replacing groups in positions 1 and 2 by NHAr, S-Ar, NO2, sulfonamido and other substituents. The new derivatives (Table 1) were tested for toxicity and antimalarial activity agains Plasmodium berghei in mice (Table 2).


Antimalarial compounds. XIII. New derivatives of phenyl chloromethyl sulfone. A series of chloromethylsulfonyl derivatives of amines, biguanides and amidineureas (Scheme 1) has been prepared and their antimalarial properties investigated.


Prazosin in the treatment of hypertension. In two double-blind, randomized cross-over comparison studies undertaken in elderly subjects, a new quinazoline derivative, prazosin, has been shown to be a safe and effective antihypertensive agent to which there is a progressive response over four- to six-week periods of oral administration at fixed dose-levels.


Topical treatment of dermatophytoses and candidoses. In a double-blind trial clotrimazole cream was compared with tolnaftate cream in the treatment of dermatophytoses and with nystatin cream in the treatment of candidoses. Clotrimazole was shown to be effective against both dermatophytoses and candidoses and was as effective and acceptable as tolnaftate and nystatin creams in each condition.


A comparison of intravenous aminophylline and salbutamol in the treatment of severe bronchospasm. Intravenous salbutamool or aminophylline was administered under double-blind conditions to 20 asthmatic patients presenting with severe dyspnoea and needing urgent treatment with bronchodilators. Ten patients received salbutamol and ten patients received aminophylline. Objective measurements showing improvement were recorded in nineteen patients. A greater response was produced by salbutamol although this failed to reach statistical significance. Neither drug affected pulse or blood pressure. It is suggested that intravenous salbutamol is an effective bronchodialtor in the treatment of acute exacerbation of asthma or bronchitis.


[Dwarfism and the Shereshevskiĭ-Turner syndrome in patients with congenital toxoplasmosis]. Fifty five patients with cerebral and hypophyseal nanism and Shereshevsky-Turner syndrome were examined for toxoplasmosis.  The diagnosis of toxoplasmosis was established on the basis of epidemiological and obstetrical anamnesis, clinical and roentgenological data and serological tests (complement fixation test in 2 modifications--by common and droplet method; precipitation test, fluorescent antibody test) and intradermal allergic test with toxoplasmin (ATT).  Of 48 patients with cerebral and hypophyseal nanism ATT proved to be positive in 17 (35.4 per cent); it was positive in 3 of 7 patients with Shereshevsky-Turner syndrome.  In some of the patients and their mothers serological tests for toxoplasmosis were also positive.  Thus, toxoplasmosis infection among the patients examined was 2.5-3 times more incident than the corresponding indices in healthy children.  It is supposed that there is pathology of hypothalamic regulation of hypophyseal functions in toxoplasmosis and nanism.  A possibility of pathology of the generative apparatus in maternal toxoplasmosis leading to development of chromosomal embryopathies could not be excluded.  The authors consider that further studies are necessary for ascertaining (in some of the cases) of the pathogenetic association between toxoplasmosis and growth and developmental disturbances.


[Simplified method of differential diagnosis of dwarfism]. On the basis of analysis (with the aid of the "Minsk-22" computer) of the data on the information character of 485 signs in hypophyseal, hypothalamic, thyrogenic, somatogenic nanism spondylo-epyphyseal dysplasia ans Shereshevsky-Turner's syndrome the authors selected 50 signs with the greatest diagnostic value.  These signs were assessed and graded by marks; a diagnostic table was elaborated with the aid of which a correct diagnosis with the probability of over 0.90 was established in 72 per cent of cases.


Separation of non-sperm components from seminal preparations and effect on the analysis of sperm proteins. The presence of non-sperm components (NSC) in "washed" rabbit epididymal and ejaculated collections and their interference with the analysis of sperm proteins have been demonstrated. NSC were also found in ejaculates from normal and vasectomized humans and from vasectomized rabbits, and in epididymal preparations from guinea pigs. They comprise about 80% of the total number of particles in rabbit ejaculates and 35% in human ejaculates. The dry weight is approximately equally distributed in rabbit ejaculates between NSC and sperm. The majority of the LDH isozyme activity of the "washed particles" in an ejaculate were associated with the NSC and this study shows that "washed particle" preparations are not equivalent to sperm and that NSC must first be separated from the sperm themselves for studies of sperm proteins to be meaningful. A method for the separation of the NSC from the sperm by equilibrium sedimentation in gradients of sucrose-D20 is described.


Factor(s) from Ehrlich Ascites cells responsible for delayed rejection of skin allografts in mice and its assay on lymphocytes in vitro. Cell free Ehrlich ascitic fluid from tumor bearing mice and the nutrient medium from Ehrlich cells maintained in vitro contain a factor(s) which when transferred to normal mice delays rejection of skin allografts and enhances the growth of a syngeneic transplantable tumor. Both types of prepartions inhibit DNA synthesis in lymphocytes stimulated by PHA. These results suggest that Ehrlich tumor cells release a factor which impairs the normal lymphocytic response to allo and tumor antigens.


Inhibitory effect of synthetic polyribonucleotides on the primary in vitro immune response. The synthetic double-stranded polyribonucleotides, poly (rA):poly (rU) and poly (rI):poly (rC), were shown to be potent inhibitors of the in vitro plaque-forming cell (PFC) response to a thymus-dependent (SRBC) and thymus-independent (E. coli 0127 LPS) antigen in mouse C57BL/6 spleen cell cultures. The same polynucleotides had no effect on the PFC response of nude (athymic) mouse spleen cells to E. coli 0127 LPS, suggesting that functional T lymphocytes are necessary for the inhibitory effect. Enhancement effects were modest and inconsistent in the cultures. Poly (rA) and poly (rU) were ineffective as inhibitors. The data indirectly suggest that the inhibition may be due to the early production of interferon by functional T lymphocytes.


Actin in the cytoplasm of adrenocortical cells. Rat or hamster adrenocortical cells contain a network of filaments mostly 40-80 A in diameter, which is particularly evident at the cell periphery. In frozen sections, adrenocortical cells fix (particularly at their periphery) anti-actin autoantibodies present in sera of patients with chronic aggressive hepatitis. It is concluded that the peripheral network of adrenocortical cells contains contractile proteins (at least actin) and the implication of such proteins in steroid secretion is discussed.


Blood pressure changes in mice after lethal staphylococcal infection and endotoxin challenge. A radioisotope technique has been used to determine blood pressure changes in mice after lethal staphylococcal infection and after lethal endotoxin challenge. The method was verified by making simultaneous direct measurements in rats. Mice in both groups became hypotensive to a similar level (a fall 20-30 mm Hg). This tailcuff technique is simple and reliable but is dependent upon normal tail blood flow. Spurious low pressure readings are obtained in hypothermic or chilled mice because the tail is a major thermoregulator organ. These difficulties can be overcome by warming chilled or hypothermic mice.


Inhibitors of dopamine-beta-hydroxylase in human plasma. There are two types of endogenous inhibitors of DBH in human plasma. One is sensitive to copper, or N-ethyl-maleimide, and is dialyzable. The other is not sensitive to copper, maleimide, or dialysis. Both types can be counteracted by diluting the plasma, thus eliminating the need for inactivators during the assay of plasma.


Decrease in ribosomal density of Proteus mirabilis exposed to subinhibitory concentrations of ampicillin or cephalothin. The finding of reduced ribosomal densities at lower concentrations than those required to stop growth or cause visible defects in the cell wall is in contrast to the current view that the initial lesion produced by penicillins or cephalosporins is a defect in murein synthesis (11). This reduction in ribosomal density could be a primary or secondary effect and might be due to a decreased rate of growth, which has been shown to be associated with a lower ribosome frequency (12, 13) or to less stable ribosomes which disintegrated either spontaneously or as a result of the fixation procedures. The possibility that the decrease in ribosomal frequency was due to dilution (influx of liquid through a defective cell wall and/or cytoplasmic membrane, or efflux of ribosomes) remains, but no gross defect in cell wall was seen in more than 50 sections of cells showing reductions in ribosomal frequency. These findings suggest that an effect on ribosomes may antecede an effect on the cell wall.


Endotoxin binding by charged and uncharged resins. Cholestyramine (Dowex 1-X2), a strongly basic anion-exchange resin, has previously been shown to bind bacterial endotoxin, preventing both its toxicity and intestinal absorption. Because hemoperfusion through charged and uncharged resins is practical, a study was undertaken to test the endotoxin-binding characteristics of a number of resins. The resin to be tested was washed and swelled overnight, and 1 mg/ml of 51Cr-labeled endotoxin was added and the mixture, agitated and incubated at 37 degrees for a specific time period. In the Dowex 1 series, the 1-X2 was superior to the 1-X4 and 1-X8 in its ability to bind E. coli endotoxin, removing about 90% from solution in 15 min. Increasing mesh size seemed to offer more binding sites for each Dowex 1 resin. Activated charcoal adsorbed about 90% of the endotoxin also, but Amberlite XAD-2 showed little binding capacity. Injection of filtrate from unlabeled E. coli and S. typhosa resin-treated solution into rats, demonstrated that both Dowex 1-X2 and activated charcoal prevented the transaminase rise noted in animals injected with solutions not so treated. It is concluded that Dowex 1-X2 resin and activated charcoal efficiently remove endotoxin in vitro, and may offer a unique method for removing circulating endotoxin in vivo.


Luteinizing hormone and androgens in the bovine fetus after gonadotropin-releasing hormone. After an intra-arterial injection of 10 mug GnRH into four bovine male fetuses, serum LH increased (P less than 0.01) 2-fold by 15 min and plateaued at approximately 11 ng/ml from 60 to 180 min. After GnRH in six female fetuses, LH increased (P less than 0.01) 7-fold by 15 min and plateaued at approximately 17 ng/ml from 60 to 180 min. Maternal serum LH was not significantly influenced (P greater than 0.05) by sex of fetus or administration of GnRH to the fetus. After GnRH in male fetuses, serum testosterone increased (P less than 0.05) and remained 2-fold greater than basal levels through 180 min. In contrast, serum testosterone from female fetuses averaged 370 +/- 60 pg/ml at injection and was unchanged after GnRH. Androgen synthesis was significantly increased during in vitro incubation of fetal testicular explants by the addition of LH. We conclude that GnRH causes release of LH from the bovine fetal pituitary as early as 120 days of age and that the testes respond with testosterone secretion after LH stimulation.


Marijuana influenced changes in GSR activation peaking during paired-associate learning. Activation Peaking (AP) refers to a patterned physiological response occurring during learning. Marijuana has been found to interfere with both paired-associate learning and phasic GSR activity. Therefore, a study was performed to assess the effects of marijuana intoxication on paired-associate learning and concomitant GSR AP. Two marijuana usage categories were employed--light and heavy usage Ss. Within each category four groups were run in a design to test state-dependent effects. Each S was seen twice with a seven-day inter-session interval. The groups were P-P, P-M, M-M and P-M with P equals placebo and M equals 14 mg delta-9 THC. At each sessions S learned a nine-word paired-associate list to a criterion of one correct recitation, and then received 100 percent overlearning. No usage or group differences were found in level of basal conductance, except lights showed habituation over sessions and heavies did not. Magnitude of phasic GSR activation, aligned for AP, was significantly reduced for both heavy usage and marijuana intoxicated Ss. Also, only on placebo days was an AP effect evident. The results were discussed in terms of marijuana's effects on learning and physiology with emphasis on possible mechanisms of action.


Intracranial injection of drugs: comparison of diffusion of 6-OHDA and guanethidine. Marked differences in extent of diffusion have been shown with the fluorescence histochemical method between guanethidine and 6-OHDA(64 mug in 2 mul) when injected acutely or chronically into the lateral hypothalamus, the substantia nigra or the amygdala of the rat brain. Cannulation damage up to 1 mm in diameter and attributed to the implantation of cannulae and placebo injection was observed. A further area of generalized damage occurred following the injection of drugs and was far greater for 6-OHDA (2 mm) than for guanethidien (0.3 mm). Guanethidine, but not 6-OHDA, caused specific damage to catecholamine-containing nerurons up to a distance of at least 3 mm and more from the cannula tip. These striking differences between the effects of intracranial injection of 6-OHDA and guanethidine are discussed in terms of the uptake and degradation of the two drugs and the anatomical features of the injection site; they are not explicable in terms of experimental conditions such as concentration, volume of injection, molecular weight or lipid solubility. The different patterns of damage would not easily be distinguished by biochemical analyses and the catecholamine specificity of 6-OHDA in studies of the central nervous system must be seriously questioned. Vascularization of chronically implanted cannula tracks and the presence of anatomical diffusion barriers are also discussed in relation to the diffusion of drugs injected intracranially.


Pulmonary problems in Duchenne muscular dystrophy. Diagnosis, prophylaxis, and treatment. A number of pulmonary problems may complicate muscular dystrophy. Respiratory function, however, can be increased by instruction in diaphragmatic breathing. When patients effectively use their diaphragms during respiration, less muscular work is required for adequate ventilation. Additionally, assistive techniques such as postural drainage, chest percussion and vibration, and IPPB contribute to an ongoing program of respiratory care. Ten children with Duchenne muscular dystrophy underwent pulmonary function studies before, during, and after a three-month period of such respiratory therapy. Comparison of respiratory function before and after treatment indicates that such treatment is useful in increasing pulmonary function. The major goal of pulmonary care in the treatment of the patient with muscular dystrophy is the maintenance of respiratory homeostasis through  beathing exercises and training in the use of various breathing aids, thus enabling the patient to lead as active and comfortable a life as possible within the limits imposed by his evolving respiratory problem.


Effects of chronic intracranial injection of low and high concentrations of guanethidine in the rat. Low (64 mug in 2 mul) or high 320-1280 mug in 2 mul) doses of guanethidine sulphate were injected daily for up to 19 days into the lateral hypothalamus, substantia nigra, locus coeruleus, dorsal raphe nucleus, or amygdala region of the rat brain. Effects on monoamine-containing neurons were determined using fluorescence histochemistry. The noradrenergic terminals of the hypothalamus were depleted over a diameter of 7 mm by both low and high doses of guanethidine whereas, even with high doses, the dopaminergic terminals of the median eminence, amygdala and acudate nucleus were only partially depleted. Fluorescence levels of dopaminergic cell bodies of the sub stantis nigra and 5HT-containing cell bodies of the dorsal raphe nucleus were unaltered by low doses of guanethidine. Low doses of guanethidine did not affect the fluorescence of the noradrenergic cell bodies of the locus coeruleus, however high doses caused a substantial reduction in fluorescence levels. Normal levels of fluorescence were observed in all catecholamine-containing neurons within 14 days from cessation of injections. Thus, the xon retraction and eventual degeneration of peripheral sympathetic adrenergic neurons, which occurs as a result of chronic intraperitoneal injections of guanethidine does not occur with the catecholamine-containing neurons in the central nervous system. The rapid recovery of centrat catecholamine-containing neurons is remarkable in view of the extensive areas of brain damage produced by chronic injection of such high concentrations of drug. Fluorescence in peripheral adrenergic nerves was unaffected by chronic injection of guanethidine into the lateral hypothalamus but adhesions of some internal organs were observed. Blood vessels in the vicinity of the cannula were heavily reinnervated by fluorescent fibres probably arising from intracranial catecholamine-containing neurons. Some of the advantages of intracranial injection of guanethidine compared to 6-hydroxydopamine for behavioral experiments are discussed.


Atrial receptors and renal function.

Atrial receptors and renal function. The hypothesis that receptors in the heart or pulmonary vasculature initiate a reflex that influences urine flow was derived from experiments designed to evaluate the effect of mechanical ventilation on renal function.  These experiments indicated that urine flow usually decreases during positive-pressure breathing and usually increases during negative-pressure breathing.  It was surmised that impulses from certain cardiopulmonary receptors affect the secretion of ADH, which in turn influences urine flow.  A subsequent investigation appeared to localize the pertinent receptors to the left atrium, but the results of this particular investigation were influenced by several complication factors that have not been widely appreciated.  The apparent localization of volume-regulating recpetors to the left atrium and the accumulating evidence that atrial receptors do respond to changes in atrial pressure or atrial volume triggered a myriad of further studies on the function of left receptors.  Nearly all these studies employed indirect techniques that produced changes in systemic and pulmonary hemodynamics in addition to changes in left atrial pressure.  Nevertheless, it often was assumed that if changes in left pressure were produced, any concomitant changes in circulating ADH or in urine flow were attributable to a reflex elicited from atrial receptors.  Mush of the data obtained were interpreted as being compatible with the elft atrial volume-receptor hypothesis, but very liggle of the data pertained to left atrial receptors specifically.


Neurological and behavioral toxicity of kryptopyrrole in the rat. Ten rats were given 9.1 to 82 mg/kg of 2,4-dimethyl-3-ethylpyrrole (kryptopyrrole) and the behavioral and electroencephalographic effects were studied. Kryptopyrrole was found to decrease EEG voltage, disrupt synchronization and induce abnormal spiking at a variety of cortical sites. Intermittent periods of low frequency hypersynchronous EEG activity was consistently elicited by kryptopyrrole. These waves bear a resemblance to the hypersynchronous EEG patterns associated with hallucinatory agents such as LSD-25. Marked behavioral alterations were observed following the initial injection including ataxia, hyperventilation, locomotor depression and catelepsy. Kryptopyrrole causes major central nervous system dysfunction, and these findings are discussed in the context of a drug-induced model of psychoses.


Discriminated escape learning and response to electric shock after 6-hydroxydopamine lesions of the nigro-neostriatal dopaminergic projection. In an earlier report it was observed that bilateral stereotaxic injections of 6-hydroxydopamine (6-OHDA) into the zone compacta of the substantia nigra deficits in the acquisition of a conditioned avoidance response [8], The present experiments were designed to determine if either a generalized learning impairment or a decreased sensitivity to foot shock might be the basis for the avoidance deficit. It was found that rats subjected to bilateral 6-OHDA lesions of the substantia nigra learned a light discrimination shock escape habit in as few trials as unoperated controls. This observation indicates that the integrity of the dopaminergic nigro-neostriatal system is not essential for the formation of learned associations between sensory cues and motor responses. In a second experiment it was observed that neither the shock-induced flinch nor the jump threshold was elevated after nigral lesions, suggesting that these lesions do not decrease the aversive motivational properties of foot shock. In view of these findings, the nature of the avoidance deficit produced by substantia nigra lesions is discussed with reference to the possibility that they selectively block the initiation of voluntary motor responses. According to this hypothesis, the failure of these lesions to disrupt escape responding may be due to the fact that the unconditioned stimulus generates reflexive motor responses (flinch, jump, etc.) which are sufficient to begin the motor sequences that cannot be initiated voluntarily in response to the conditioned stimulus.


Effects of 3-acetylpyridine on spontaneous alternation in the mouse. When administered to mice, 3-acetylpyridine has been shown to selectively destroy the hippocampa neural fields CA3 and CA4. Adult mice, injected i.p. with150 mg/kg 3-acetylpyridine showed a reduced frequency of spontaneous alteration(48%) in a T-maze, compared with saline injcetd controls (73%). The pattern of latency change in the experimental mice was  consistent with a failure to habitatue normally. these behavioral effects of 3-acetylpyrdine resemble those observed following lesions of the hippocampus induced by stereotaxic surgery.


Construction of the perineal body in the female. A simple, one-stage operation is presented for the construction of a perineal body  in a female who has a common rectovaginal opening, or cloaca. The operation has been performed on 3 teenaged girls, with an excellent result in each. In only one instance has been necessary to perform a secondary operation for correction of the rectal incontinence.


The free vascularized bone graft. A clinical extension of microvascular techniques. For the common problem of lower limb injury with extensive. Loss of skin and bone, a new method of free vascularized bone grafting has been used and integrated with an appropriate soft tissue flap repair. The technique was developed to salvage two legs which would otherwise have been amputated. The preliminary result in Case 2 is encouraging. This case would appear to be the first successful distant transfer of a composite fibular graft by microvascular anastomoses to be reported in man.


Surgical treatment of hidradenitis suppurativa of the axilla. We review our surgical experience with hidradenitis suppurativa of the axilla at Cook County Hospital during the years 1963 to 1972. The operation for this entity described by Pollock et al has (1) reduced the length of hospitalization, (2) increased the rate of primary healing and reduced the period of secondary healing, (3) allowed a great amount of tissue to be excised, (4) permitted both axillae to be operated on at once (without incapacitating the patient), (5) avoided the need for skin grafting, and (6) has had less morbidity for those patients in whom primary healing is not achieved. We believe the method reported by Pollock et al is now the treatment of choice for this disease.


Reconstruction of mandibular defects after radiation, using a free, living bone graft transferred by microvascular anastomose. An experimental study. In a previous publication we described the replacement of a mandibular defect by a free, composite rib graft, transferred by microvascular anastomoses of the posterior intercostal vessels to donor vessels in the neck. We now present data which demonstrate that successful results can be achieved even after radical mandibular radiation. This technique, done in dogs, has obvious implications in the management of oral cancer in man.


Free groin flaps in children.

Free groin flaps in children. We report two successful transfers of free groin flaps to the lower legs of children. We believe this method can be safely applied and can often take the place of distant pedicled flap transfers in children.


Panniculectomy specimens as a convenient and inexpensive of homograft skin. Panniculectomy specimens provide a convenient and inexpensive source of skin homografts when harvested in the operating room under sterile conditions.


Neurovascular free flaps. A preliminary report. An experimental, anatomical, and clinical study has confirmed the feasibility of free neurovascular flaps.  The interrelationship between the cutaneous vascular and neural supply has been defined and demonstrated electrophysiologically, both in man and in experimental animals.  A potential donor site in man has been explored.  Free neurovascular flap transfers by microneurovascular anastomoses are technically feasible.  Clinical success will occur with the identification of suitable donor sites.


Burned hands.

Burned hands. Hand involvement is common in patients with severe burns.  Our experience indicates that almost one-third of the patients admitted to the Shriner's Burns Institute and The University of Texas Medical Branch Hospitals with burns exceeding 30 per cent of the body surface had concomitant burns of the hand.  Our approach in managing the burned hand during the acute phase of unjury, as well as during secondary reconstruction of the deformities, is presented and discussed.


Maxillary arch alignment in the bilateral cleft lip and palate infant, using pinned coaxial screw appliance. An arch alignment appliance, capable of both maxillary expansion and premaxillary retraction, based on a pinned screw mechanism and capable of extraoral activation, is described and illustrated.


Secondary reconstruction of the cervical esophagus. Ten patients have had secondary reconstructions of the cervical esophagus after ablation of the laryngopharyngeal complex for cancer. Our use of deltopectoral flaps for this is described.


Malar implants for improvement of the facial appearance. Esthetic correction of flat malar eminences may contribute to the harmony of facial proportions by making the face more oval and by giving a more youthful appearance. Zygomatic augmentation may also be indicated for the treatment of congenital hypoplasias, asymmetries, or traumatic depressions of the malar region. We have used the procedure in 52 cases since 1964. For augmentation we use a perforated soft, silicone rubber implant. The technique and results are described. The results have been satisfactory, for both the patients and the surgeon.


The nerve gap: suture under tension vs. graft. Conduction velocities and amplitudes of evoked responses were used in experimental models to compare reinnervation through nerve gaps sutured under tension or bridged with nerve grafts. The best results were obtained when end-to-end suture was done without tension. Regeneration through mildly stretched nerve repairs was equivalent to applying a properly tailored graft. Minimal axonal activity was exhibited by severely stretched repair sites.


Stoicism and paranoia.

Stoicism and paranoia. A paranoid strain is manifest in Stoic utterances generally, especially in the Stoic conception of autarky, where the Sage regards himself as distinctly "other" in the midst of society, and indifferent to its values, except as he dissembles his indifference. Now, influential theories of paranoia stress a projective process: for Freudians, the projection of repressed homosexual libido in altered form, for Ovesey, a "pseudohomosexual" anxiety arising out of a maladaptation in the male to the culturally assigned competitive male role, a failure perceived as effeminate. But Stoicism took root in the culture (Classical Greece) where homosexuality, far from being universally regarded as degenerate, was widely extolled as the norm for superior men and the most advantageous frame work for the tutelage of aristocratic boys. It would seem unlikely that paranoia in this context would reflect uneasiness over unconscious homoerotic (or distorted pseudo-erotic) strivings. What light is shed on the purported projection of either homosexual or pseudo-homosexual anxiety by paranoid elements in Stoicism?


Apomorphine-induced rotation in normal rats and interaction with unilateral caudate lesions. Apomorphine (i.p.) induced rotational behavior (i.e. circling) in normal unoperated rats. This rotation increased with increasing dose up to 10.0 mg/kg, after which the dose-response curve appeared to plateau. Although there was large variability among rats, rotation for each rat was consistent in both direction and magnitude from week to week. Rotation was not antagonized by alpha-methyl-para-tyrosine. When rats with unilateral lesions of the caudate nucleus were tested with apomorphine, postoperative rotation was significantly influenced by the direction of preoperative rotation; rats rotated more postoperatively if the lesion was made ipsilateral rather than contralateral to their preoperative direction of rotation. These results suggest that there is a bilateral asymmetry of dopaminergic receptors in the nigro-striatal pathways of normal rats.


The effect of cyproheptadine on hunger, calorie intake and body weight in man. The appetite stimulating action and the weight gaining potential of one month's treatment with the antihistamine and antiserotonergic compound cyproheptadine (Periactin) 4 mg three times daily was compared to placebo in a double-blind crossover trial in sixteen thin but otherwise normal volunteers who wanted to gain weight. Subjects gained significantly more weight on cyproheptadine than on placebo. There was also a corresponding relative increase in subjective hunger ratings and food intake during the period on active drug. Drowsiness was the most frequent side effect observed. These findings are discussed in relation to a possible serotonergic feeding mechanism.


Extrapyramidal reactions and amine metabolites in cerebrospinal fluid during haloperidol and clozapine treatment of schizophrenic patients. 8 male schizophrenic patients participated in a double-blind, cross over study of the extrapyramidal side-effects of haloperidol and clozapine (acute dystonis, Parkinsonism and tardive dyskinesia), together with their effect on homovanillic acid (HVA) and 5-hydroxyindoleacetic acid (5-HIAA) in the cerebrospinal fluid (CSF). Haloperidol (9 mg/day) caused Parkinsonism, reduced tardive dyskinesias and increased the HVA concentration in the CSF. Clozapine (225 mg/day) had no effect on the neurological phenomena but reduced HVA and 5-HIAA concentrations in the CSF. During the discontinuation phase following the administration of haloperidol, tardive dyskinesia occurred or was aggravated; this did not occur after administration of clozapine. Accordingly, it is suggested that clozapine does not induce dopaminergic hypersensibility and, therefore, will not induce tardive dyskinesias.


[Effects of (--)delta-9-trans-tetrahydrocannabinol (delta-9-THC) on tests of psychoticism. A study of Eysenck's drug postulate on the effects of hallucinogens in relation to psychoticism (author's transl)]. In a double-blind study on 36 volunteers the effects of 250 mug/kg (--)delta-9-trans-tetrahydrocannabinol p.o. on objective and performance tests measuring psychoticism according to Eysenck were assessed. The hypothesis was tested that subjects treated with delta-9-THC differ from those receiving placebo in the same way as endogenous psychotics differ from normals. Confirmation was obtained in only 5 out of 19 variables. Four of these 5 variables may be considered as tests of concentration.


The repair of potentially lethal damage; an alternative approach. An alternative approach to the explanation and analysis of post-irradiation effects is presented. The analysis is based on the repair of a radiation-induced lesion and it is shown that the experimental results are compatible with the repair of one type of critical lesion involved in cell reproductive death. The nature of the lesion with respect to potentially lethal damage and sub-lethal damage is discussed.


Osmotic Nephrosis Induced by Water-Soluble Triiodinated Contrast Media in Man. A Retrospective Study of 47 Cases. Renal biopsies were performed in 211 patients which 10 days of excretory urography or renal arteriogrpahy in which diatrizoate, iothalamate or ioxithalamate had been used. In 47 renal specimens, osmotic nephrosis of the proximal tubular cells was found. Previous renal function had been normal in 10 patients, moderately impaired in 19, and severely impaired in 18. Tubular atrophy and/or necrosis was associated with histological features in 29 of 47 patients. Diffuse osmotic nephrosis was more often found in patients biopsied soon after roentgenography and also with severe renal insufficiency, but was not necessarily associated with declining renal function. The mechanism(s) by which contrast media may induce osmotic nephrosis remains unclear.


Computer Diagnosis of Breast Thermograms. A computer-based technique was developed for the automated diagnosis of breast thermogram. Eighty-five thermograms were digitized and analyzed, and 23 parameters computed for each thermogram. A statistical decision program, based on a linear discriminant analysis technique, classified the thermograms into normal and abnormal categories. The accuracy of classification was evaluated by several techniques and found to be comparable to that of trained thermographers.


The Use of Computer Tomography in Ophthalmology. Fifty-three orbital lesions of various types were studied by computer tomography to assess the capabilities and limitations of this technique. Although CT scanning in ophthalmology is in its infancy, results showed that it is useful in the investigation of a number of pathological conditions, including congenital anomalies, arteriovenous malformations, bone lesions, trauma, inflammation, granulomas, pseudotumors, epidermoid cysts, and tumors arising in or near the optic nerve, behind the optic bulb, or in the lacrimal region, as well as changes following eye surgery.


Cultures of pig macrophages.

Cultures of pig macrophages. Freshly collected blood from pigs was defibrinated with glass beads. The white cells were collected on a Ficoll-Hypaque mixture and grown in RPMI 1640 medium containing 20 per cent fetal calf serum. Monocytes adhered to the plastic or glass flasks and the erythrocytes and lymphocytes remained in suspension. The adherent cells assumed the appearance of macrophages and the mean cell size at eight days was 40 mum. Phagocytosis was demonstrated and, in the first few days, incorporation of tritiated thymidine occurred. Cells remained viable in culture for more than eight weeks. Histo-chemical studies and the appearance of the cells under the electron microscope are described.


A double-blind cross-over trail of Prenazone and aspirin in the management of rheumatoid arthritis. A double-blind cross-over trial of Prenazone 600 mg and Aspirin 4 g daily was carried out on 20 patients suffering with rheumatoid arthritis. The analgesic and anti-inflammmatory activity was indistinguishable from that of aspirin under the conditions of the trail. Twelve patients expressed a general preference for Prenazone and six for aspirin. Prenazone appeared to be well tolerated and free from serious side-effects. These results suggest that it will be a useful drug in the management of rheumatoid arthritis.


A double-blind cross-over trial of Prenazone (DA 2370) and phenylbutazone in rheumatoid arthritis. A short-term double-bind cross-over trial of prenazone 600 mg daily and phenylbutazone 300 mg daily was carried out in twenty out-patients with rheumatoid arthritis. Ten patients preferred prenazone, and eight preferred phenylbutazone. No significant difference in analgesic and antiinflammatory potency was demonstrated under the conditions of the trial, and no serious adverse effects, either clinical or laboratory, were encountered. These findings support other claims that prenazone may be a useful alternative in the treatment of rheumatoid arthritis.


[Rheumatoid synovial fluid].

[Rheumatoid synovial fluid]. In making a comparative study of different parameters in the examination of synovial fluid (rheumatoid factors, ragocytes, leucocytes, synovial complement, immunoglobulins) the authors show that rheumatoid fluid has characteristics that make differentiation from other inflammatory arthropathies possible on a statistical basis, thanks to the test for the homogeneity of the means. The presence of these characteristics seems to constitute a diagnostic argument which can be measured by mathematical methods.


[Quantitative histological study of the cartilage of human arthrotic femur head]. A quantitative histological study of the cartilage of the human arthrosic femoral head. In this work, samples of unsplit cartilage taken from 15 arthrosic femoral heads and 26 normal femoral heads from the same topographical areas, and of identical age, were studied by quantitative histological methods. This study was concerned with the thickness of the calcified and non-calcified cartilage, the cellular density, the average number of nuclei per lacuna, and the average surface area of the lacunae in the different layers of the cartilage. Comparison between the two groups of samples showed that the arthrosic cartilage differed from the normal cartilage by a diminution in the size of the superficial lacunae, a reduction in the number of nuclei per lacuna in the middle layer, a diminution in the cellularity of the deep layer and an augmentation in the layer of calcified cartilage. These modifications suggest that arthrosis of the hip is secondary to diffuse cellular alterations associating a diminution in metabolic activity and necrosis of the chondrocytes.


Genetic control of B-cell responses. I. Selective unresponsiveness to lipopolysaccharide. Spleen cells from C3H/HeJ mice fail to develop both proliferative responses and increased polyclonal antibody secretion in the presence of concentrations of the B-cell mitogen lipopolysaccharide that are optimal for the induction of B-cell responses in conventional strains. This unresponsiveness is selective for lipopolysaccharide, since C3H/HeJ spleen cells respond normally to two other polyclonal B-cell activators-dextran-sulphate and purified protein derivative of tuberculin. These findings are interpreted as indicating a selective defect in the B-cell subpopulation that responds to lipopolysaccharides in conventional strains.


Serum factors causing impaired macrophage function in systemic lupus erythematosus. Leukocytes from patients with systemic lupus erythematosus (SLE) and healthy controls were cultured for 4 days in either SLE serum or control serum. The remaining monolayer of monocyte-derived macrophages was allowed to ingest yeast cells. Macrophages (from SLE patients or controls) incubated in SLE sera presented impaired phagocytic activity and glass adherence compared with cells grown in control sera. SLE sera contain one or more factors that impair macrophage function; IgG-containing immune complexes may be one such factor.


Human interferon therapy for herpes zoster in adults. Of 37 patients with herpes zoster 28 were treated with human exogenous interferon and 9 received only culture medium. The interferon was produced in leukocyte cultures and was given intramuscularly in one daily dose of 1 million units for 5-8 days. In the interferon-treated patients interferon was detectable in serum (peak level 1-5 hours after interferon injections) and in vesicle fluid, and in some patients also in urine samples. Anti-interferon antibodies were not found. Of the 28 interferon-treated patients 8 had a slight temperature increase and 4 showed a transient local reaction. In the interferon treated group of patients the duration of pain was shortened and the development of crust formation was enhanced compared with the control group.


Epidemiological aspects of impetigo contagiosa in western Sweden. 200 patients with primary impetigo were studied. Staphylococcus aureus was the only organism isolated in 72.5%, beta-hemolytic streptococci, group A, in 10%, and both pathogens in 15%. 17 of the 50 streptococcal isolates were typed serologically; 11 of these belonged to potentially nephritogenic types. A majority of these cases had identical strains in the nose and throat. Hence, the primary source of skin streptococcal in this study may be the nasopharynx. Uncomplicated cases were treated with topical antibiotics, and oral antibiotics were added in 22 cases with extensive lesions, fever or a concurrent throat infection. None of the 200 patients developed acute glomerulonephritis and urinary analyses were normal at follow-up after 3 weeks.


Effect of circulating norepinephrine on the renin release from the denervated kidney. The effect of renal denervation on the reactivity of the renin release mechanism to circulating norepinephrine was studied in six dogs with renal autografts. The renin release was determined simultaneously in the transplanted and the untouched kidney. Both kidneys showed an increased release of renin when norepinephrine was given. A slight reduction in renal blood flow and increase in arterial blood pressure was recorded. Propranolol blocked the release of renin induced by norepinephrine without affecting either the reduced blood flow thorugh the autograft or the elevated blood pressure. The denervation of the autotransplanted kidney was histochemically verified. The findings indicate that the renin release induced by circulating norepinephrine is independent of the intrarenal adrenergic nerves, and rather suggest that it is the result of an action of norepinephrine directly on the renin-producing juxtaglomerular cells. In this mechanism a beta-adrenergic receptor system appears to be involved.


Condylomata acuminata of the bladder.

Condylomata acuminata of the bladder. A case of invasion of the bladder by condylomata acuminata in a kidney-transplanted patient under immunosuppressive treatment is presented. Conservative treatment with application of podophyllin and transurethral resection was carried out. There were numerous recurrences, but so far it has been possible to control the disease, in contrast to the four cases found in the literature, which have all resulted in total cystectomy.


Immunological aspects of sarcoidosis.

Immunological aspects of sarcoidosis. Circulating immune complexes were found in sera from patients with acute sarcoidosis during the initial phase of the disease. The symptoms of acute sarcoidosis may be explained by the presence of such complexes. The total number of peripheral T cells was lower in most patients with sarcoidosis than in healthy controls. The difference was most marked in cases with long duration of the disease. The composition of peripheral T cells was altered irrespective of the total number of such cells, and a lack of cells responding to PPD and con A was shown. Tis may be related to the impairment of delayed hypersensitivity reactions which may be present in all stages of the disease. The atypical mononuclear cells which have been found in blood from patients with sarcoidosis are lymphocytic cells. Some have B cell properties whereas some seem to have T cell origin. The presence of such cells may indicate a persistent activation of the immune system. Immunological reactivity determined by genes closely linked to the major histocompatibility complex does not seem to be responsible for susceptibility to sarcoidosis.


Live attenuated influenza virus vaccines in patients with chronic broncho-pulmonary diseases. Clinical and immunological evaluation. The safety and potency of two live attenuated influenza A virus vaccines, administered intranasally, were tested in outpatients suffering from chronic obstructive lung disease, during two successive trials performed between 1972 and 1974. The vaccine strains were representative of the prevalent influenza A virus types; the Ann strain was derived from a classical H3N2 (A/Hong-Kong/878/69) isolated and the Alice strain from a recent H3N2 drift (A/England/42/72). The serum and nasal antibody responses were studied in a total of 40 vaccinees. When a sufficient virus dose was administered, the hemagglutination-inhibition (HI) seroconversion rate was, respectively, 86 and 73% for each vaccine trial in patients with low (less than or equal to 32) prevaccination antibody titers. A booster effect was also observed in some subjects with higher prevaccination titers. In the two trials, clear-cut rises in local antibody activity, as tested in nasal washings' samples were found in, respectively, 92 and 75% of the patients devoid of initial titer before vaccination and in 40 and 37%, respectively, of the subjects having low prevaccination titers. Clinical symptoms were observed in 29% of the cases; they were, however, mild and transient and their occurrence was not necessarily related to the vaccination. Two administrations of intranasal attenuated virus appear therefore to be safe and to lead to a satisfactory antibody response in this "high risk" group of patients.


Immunofluorescence of mitotic spindles by using monospecific antibody against bovine brain tubulin. Monospecific antibody directed against bovine brain tubulin has been purified by affinity chromatography and tested against soluble tubulin and intact microtubules of brain and mitotic apparatus. Binding of the tubulin antibody to the mitotic spindle of rat kangaroo cells was demonstrated in all stages of mitosis by indirect immunofluorescence.


Studies on coagulation and fibrinolysis in cases of Falciparum malaria. Coagulation and fibrinolytic studies were conducted in 18 cases of severe falciparum malaria including cases with parasitaemia above 5% and with pernicious manifestations such as coma, jaundice, anuria, pulmonary oedema, bleeding tendency, etc., irrespective of parasitaemia. Marked changes in blood coagulograms and high levels of serum fibrin degradation products appeared only in cases with very severe cerebral involvement and also in cases with very high parasitaemia alone. These investigations indicated that intravascular coagulation occurs only in patients suffering from falciparum malaira who develop cerebral manifestations and in cases with high parasitaemia.


Maintenance haemodialysis and renal transplantation facilities in South Africa-July 1974. A survey of facilities available in South Africa for patients suffering from chronic renal failure was made in July 1974. This showed that 14 maintenance haemodialysis centres had a total of 59 dialysing stations with a capacity for treating 154 patients. Five centres had established programmes for renal transplantation. The total number of renal failure survivors on treatment included 129 patients on maintenance dialysis and 177 with grafts. This represents a 31% increase in the number of patients on treatment since a similar survey was made in July 1973.


History of mental health services in South Africa. Part VII. Services since union. The main task of the mental health service since Union has been to overcome a chronic shortage of accommodation. The main reason for the lack of success was financial. The strain on accommodation was partially relieved by the introduction of modern methods of treatment and by the erection of hospitals for Blacks in the Homelands. The new Mental Health ACT OF 1973 is an improvement on the Mental Disorders Act of 1916.


Penetrating wounds of the heart and great vessels. Experience with 24 cases including 3 with intracardiac defects. Twenty-four cases of penetrating cardiac injuries due to stab wounds, which were seen over a 3-year period, are reviewed. Ten patients were treated by aspiration alone because tamponade was mild, or because they were seen more than 12 hours after injury. One patient with multiple stab wounds in the ventricles and left atrium died during emergency thoracotomy in the admission room. The mortality rate of 4,5% is considerably lower than rates reported in other series. Two cases of traumatic ventricular septal defects, one case of traumatic aortic incompetence and sinus of Valsalva fistulae with rupture into the right ventricle and right atrium, and one case of ascending aorta-innominate vein fistula are discussed. Our present plan of management is outlined.


Clinical experience with a synthetic absorbable surgical suture. The Vicryl suture was assessed in 72 surgical patients who underwent follow-up observation for at least 30 days, and it proved to be an excellent inert absorbable synthetic suture.


Metabolic rate in acute respiratory failure complicating sepsis. A simple, reproducible, and noninvasive method was developed for measuring metabolic rate in patients receiving assisted ventilation and increased concentrations of inspired O2. In nonseptic patients requiring assisted ventilation, metabolic rate was within the predicted normal range, but in septic patients it was increased by an average of 60 percent over the predicted normal. This level of resting hypermetabolism is greater than previously reported in septic patients not requiring assisted ventilation. The explanation of this difference is likely to be related to the greater severity of the illness in the present group. The potential clinical significance of these findings is discussed.


Notes on the handling of ultrafine suture material. For the convenient handling of microsurgical suture materials, suitable forceps are needed and these must be finely adjusted and well cared for. Only a short length of thread should be used on the needle. Difficulties arise in picking up the needle, in making a loop in the thread, in keeping the loop on the forceps while tying, and in picking up the end of the thread. Simple methods of avoiding entanglement and exasperation in these situations are described.


Effect of antithymocyte globulin and other immune reactants on human platelets. Human platelets suspended in autologous plasma do not respond to nonspecific immune complexes as do platelet suspensions from rabbits and dogs. However, platelets of all three species do undergo aggregation and the release reaction when exposed to antibodies directed against platelets. Antithymocyte globulin (ATG) contains such antibodies, apparently because of antigens common to both thymocytes and platelets. ATG-induced platelet aggregation and release is thus a specific reaction which may be responsible for the thrombocytopenia and thrombotic complications occasionally seen following the administration of ATG. However, if ATG is given properly, its effect on platelets should not constitute a contraindication to the use of this immunosuppressive drug. Since nonspecific immune complexes do not affect human platelets in the presence of plasma, it would appear that platelet aggregates seen in hyperacute and acute rejection result from endothelial damage rather than an effect of immune complexes on platelets.


Recognition and treatment of pathologic fractures in the nineteenth century. The spread of cancer to the skeletal system was first clearly recognized in the 19th century, and accounts of pathologic fractures appear in many clinical and pathologic reports published during that period. Noteworthy descriptions included fractures observed in both living patients and in patients who died of cancer. The problems considered by the 19th century physicians included the still timely areas of clinical diagnosis, prevention of fracture, the occurrence of prefracture pain, and treatment by immobilization or operation.


Effect of three proteinaceous foreign materials on infected and subinfected wound models. A model was devised to determine the effects of several foreign bodies (microcrystalline collagen hemostat (MCCH), blood clot, catgut suture) on S. aureus wound contamination and wound infection. In a subinfected wound model, MCCH, when compared with the other foreign bodies, showed an increase in the number of wounds classified as "contaminated," but 84 percent of these wounds yielded bacterial counts below the level accepted for biologically significant wound infection (10 to the 5th power bacteria per gram tissue). The number of "infected" wounds was not significantly greater than the number found in the uninoculated control group. In the infected wound model, all groups of inoculated animals showed significant infections. The severity of the wound infection was unaffected by the presence of catgut suture, clotted blood, or MCCH. Higher levels were not seen for the MCCH animals than for the inoculated control animals. We did not see in these experimental wound studies with MCCH a significant aggravation of wound contamination or wound infection during the 48 hour period following inoculation with varying dose levels of S. aureus. Further studies would be necessary to determine the possible bacteriological response after 48 hours.


Renal autotransplantation and partial resection of the ureter for recurrent benign ureteral tumor. A report of a patient treated by partial resection of the ureter and renal autotransplantation for recurrent benign ureteral tumors and impaired renal function in the contralateral kidney is presented. Autotransplantation of the ipsilateral kidney associated with benign disease of the renal excretory system is recommended even with normal function of the contralateral kidney. Experience with renal homotransplantation has led to excellent technical and functional results from autotransplantation, and use of the procedure is expanding to include treatment of a variety of renal, ureteral, and renovascular pathology. The role of renal autotransplantation in the preservation of functioning renal units is emphasized.


Pyloric reflux gastritis: the offending agent. Tubes of canine gastric corpus were constructed so that the mucosa was exposed chronically to jejunal contents, pancreatic juice, or bile. Biopsies of these mucosae obtained 4 to 24 months later were compared with each other and with the normal stomach for parietal cell numbers, mucus cell numbers, inflammation, glandular disorder, and surface-cell hyperplasia. All three preparations showed marked gastrititis, but whole jejunal contents caused more severe changes than did either pancreatic juice or bile, which were approximately equal.


Computerization of the surgical intensive care unit: improvement of patient care via education. For the past 18 months we have been evaluating and developing a computerized patient-monitoring system in our surgical intensive care unit. Despite the enormous potential for use of such systems, we have been impressed with its underutilization and its failure to yield objective improvement in patient care at our institution and many others. The output of the system was ignored because the decision maker was unable or unwilling to integrate the more sophisticated data presented to him. The computer was relegated to the position of "redundant secretary". In an attempt to reverse this situation, we have developed a multilevel, multigoal educational system employing the computer. We have implemented brief educational programs for use by all unit personnel to explain deviant monitored variables. Given a physiologic subsystem and a particular variable, personnel can: (1) inquire whether or not the variable is deviant; (2) obtain a list of probable causes for the deviation; (3) obtain an explanation of the pathophysiology of particular deviants as well as instruction on how to identify a most probable cause; and (4) inquire how to correct specific deviants. When we monitored the system utilization after implementation of the educational programs, we found all of the system had improved utilization. As a result we have a better educated staff who communicate more effectively, deal with more sophisticated information, and make better decisions with resultant improved patient care. Additionally, the staff is eager to help improve the system. We believe the full potential of such systems can be obtained only through education.


Measurement of cardiac output by thermal dilution in infants and children. The accuracy of the thermal dilution technique for measuring cardiac output in infants and children has been assessed by comparison with the direct Fick technique. Satisfactory correlation between the two methods has been demonstrated, and it is concluded that a commercially available monitor can be used to determine cardiac output by thermal dilution in acutely sick infants and children. The volume of injectate should be selected according to the weight of the child, and the value displayed by the monitor should be adjusted by the appropriate fraction.


Intravenous prednisolone in chronic bronchial asthma. A single injection of 40 mg prednisolone phosphate was given to 10 patients with chronic bronchial asthma. Changes in pulmonary function were followed over a 30-hour period. Statistically significant changes occurred in the tests employed one hour after the injection of prednisolone. The maximum change for the group as a whole was seen to occur after eight hours. This time course of response is very similar to that obtained in previous studies on similar groups of patients with oral prednisolone where the peak effect occurred nine hours after the drug had been given. Intravenous hydrocortisone produces a much earlier peak effect, at five hours, when it is administered to chronic asthmatic patients.


Growth and development of human fetal trachea and lung in immune-deprived mice. Trachea and lung parenchyma from human fetuses were transplanted subcutaneously into immune-deprived mice. After seven to 10 weeks they were removed for histological examination. It was found that the tissues continued to grow and develop along similar lines to those which they would have followed in utero.


[Problems of resistance (author's transl)]. The results of sensitivity tests performed during the period from 1970 up to 1973 inclusive are compared with those obtained in pervious years. This showed that resistance to penicillin had increased in staphylococci causing bovine mastitis. During each single year, however, there was a decrease. S. typhimurium isolated from cattle showed increased resistance to chloramphenicol, neomycin and ampicillin; S. dublin showed an increase in resistance to chloramphenicol. E. coli isolated from calves with coli-bacillosis had become less sensitive to all the antibiotics studied. Pathogenic strains of E. coli isolated from swine also showed increased resistance, among others to tetracycline, neomycin and ampicillin. The danger constituted by this development and the factthat comparison with the results obtained by other presents difficulties in some cases are stressed.


[A case of cutaneous actinomycosis (streptothricosis) in cattle, caused by dermatophilus congolensis (author's transl)]. A skin condition in cattle, associated with crusted lesions on the back, flanks, neck, head and skin of the udder was found to be cutaneous actinomycosis (streptothricosis) caused by D. congolensis, which is common in tropical regions during the rainy season. This actinomycete was isolated for the first time from cattle in the Netherlands in the case reported. Data culled from the literature as well as the diagnosis and treatment of the patient are discussed.


[The femoro-crural venous bypass in chronic arterial block of the leg (author's transl)]. A report on 58 reconstructive vascular operations in chronic blocks of arteries of the leg. 4 different types of block in these arteries can be distinguished. Operation is indicated only in severe disturbances of circulation of stage III and IV. The criterion for reconstruction is not found in the proximal part of the arteries. Angiographic proof of at least one leg-artery down to the periphery being patent and permitting free flow is required. The various techniques applicable to each type of block, early and late results are reported on. Suring a period of up to 3 years block recurred in 26%. Most recurrences (46%) were seen within the first 30 days.


[Successful surgical correction of total anomalous pulmonary venous drainage into the portal vein in a ten days old infant (author's transl)]. An infant, nine days old, with total anomalous pulmonary venous drainage into the portal vein was examined. The exact anatomy was clarified by means of cardiac catheterization and angiocardiography. One day later the operation was performed utilizing circulatory arrest in deep hypothermia. The procedure was successful, and the child, two years old now, is doing well. The problems of examination, treatment and surgery are discussed. There are only a few cases with successful correction in the literature.


Agar-screew specimen carrier for bulk processing of biopsy material for electron microscopy. A specimen carrier for processing large numbers of biopsy materials for epoxy embedding and electron microscopy is described. Commercially available  18-mesh stainless steel or 16-mesh aluminum wire screening is used. The screening is cut into 1 x 3-inch strips. One corner is snipped off for orientation purposes. Four drops of warm 4% agar is placed on a prewarmed standard microscopic glass slide. A thin agar support film is formed on the bottom side of the horizontally held wire screen by lightly running it against the agar. Tissue blocks trimmed to 1 mm-3 are blotted on filter paper and placed in a prearranged order on the top surface of the support film. A thin top coating of agar is applied on the specimen by touching it with the tip of a pasteur pipette containing warm 4% agar. The agar-screen unit with the mounted specimens is stabilized in 4% buffered formalin and rinsed with Sorenson's phosphate buffer, pH 7.4, with 6.8% sucrose. It is then processed as a unit through routine osmium tetroxide postfixation, alcohol dehydration, and Epon 812 filtration. The tissue blocks are plucked off the agar support film with fine-tipped tweezers and embedded in individual capsules. No difficulty in thin sectioning was encountered and examination of the sections under the electron microscope showed good infiltration by the epoxy resin.


Anaemia in mice with concomitant Schistosoma mansoni and Plasmodium berghei yoelii infection. 1. The effect on anaemia in mice given Plasmodium berghei yoelii 3 and 5 weeks after exposure to Schistosoma mansoni cercariae, was investigated. 2. Haematological criteria (PCV and haemoglobin levels), reticulocytosis, parasitaemia and splenomegaly were used as indices. 3. Anaemia was severe in the animals given P. b. yoelii and in those with mixed infection (P. b: yoelii plus S. mansoni). Malaria was found to dominate the picture until the clearance of the parasitaemia. The effect of the interaction between the diseases on the anaemia was nil. 4. Toward the end of the experiment, moderate splenomegaly was observed in the mice with mixed infection.


The rapid isolation from human blood of concentrated, white-cell-free preparations of Plasmodium falciparum. The sucrose gradient centrifugation method has been applied to representative samples of human (Gambian) blood infected with ring, trophozoite, schizont and gametocyte stages of P. falciparum in order to assess quantitatively the efficiency of recovery, white cell removal and the degree of enrichment of the infected cell fraction. Maximal white cell removal was 90%. (a.v.) Average infected cell recoveries varied with the level of white cell contamination, namely 47% (2-5% WBC), 34% (1-2% WBC) and 24% (smaller than 1% WBC); infected cells were enriched 2-9-fold on average, and up to 22-fold in the case of gametocytes. Preliminary attempts to prepare free parasites by nitrogen cavitation of infected cells showed that disruption took place at much lower pressures than those required to break normal red cells. Gel diffusion analyses showed that the most highly purified infected cell preparations retained the full precipitinogenic spectrum of the original crude preparation.


[Ecology of Culex pipiens fatigans larvae in an area of high endemicity of Bancroftian filariasis (author's transl)]. Culex pipiens fatigans in the main vector of bancroftian filariasis in the Mayotte island (Comores) where it imposes an important health problem. The breeding-sites of C. p. fatigans are either man-made (latrines, cesspools, various containers), or natural (polluted water of estuaries of some rivers). The man-made breeding-sites are not similarly distributed in the different localities of the island. Their distribution varies according to the customs of the inhabitants, size and site of the community. They are mainly represented by latrines, where Anjouan ethnic group is predominent; by cesspools in localities inhabited by Sakalava (a Malagasian ethnic group) and by other latrines and cesspools in mahoraises (inhabitants of Mayotte) and cosmopolitan localities. In rural areas, the percentage of habitations with cesspools usually increases with the size of the villages. The various breeding-sites are primarily productive when they are built on a ground with poor permeability. The importance of the present information is further discussed with relation to the population dynamics of C.p. fatigans and to the measures which may be useful for a control program of this mosquito.


[Chemotherapeutic studies on litomosoides carinii infection of mastomys natalensis. 5. Alterations of haematological parameters after the administration of filaricidal compounds (author's transl)]. The peripheral blood picture of multimammate rats (Mastomys natalensis) infected with Litomosoides carinii was studied. Changes were followed in patent infections from 64 to 176 days after infection in animals treated with diethylcarbamazine (5 x 100 mg/kg per os), HOE 258 V (5 X 10 mg/kg subcutaneously), suramin (5 x 40 mg/kg subcutaneously) and with a combined treatment of diethylcarbamazine and suramin. In addition, haematological changes were followed in non-infected animals treated with suramin alone as well as in non-infected and infected animals receiving no treatment. During the course of non-treated L. carinii infection in Mastomys natalensis, animals developed anaemia, an increased sedimentation rate and a leucopenia. In addition there was a relative increase in circulating eosinophils, in large lymphocytes and monocytes and a relative decrease in small lymphocytes. After treatment with the microfilaricidal drugs diethylcarbamazine and HOE 258 V blood changes followed those of infection controls but there was a transient change towards normal in peripheral blood values when the microfilariaemia was reduced by the drugs. After treatment with the macrofilaricide suramin, nearly normal values were reached at the end of the experiment for the red blood cell and leucocytes levels. Combined treatment with suramin and diethylcarbamazine resulted in relatively normal levels for some parameters. Suramin was shown to cause haematological changes in normal animals which became evident several days before use of the drug. Such changes added to the pathological alterations caused by the filarial infection. In both infected and non-infected animals suramin treatment resulted in oedema around the nose and on the front feet approximately three weeks afterwards.


[Cytogenetic characteristics of suckling mouse brain cell cultures, chronically infected with Japanese encephalitis virus]. The brain cells of the suckling mice line MSB-1-K-33 chronically infected by an attenuated variant of the Japanese encephalitis virus and of cell clones isolated from the later, had mainly a neartetraploid keryotype (the modal class 70-71 chromosomes). In metaphases of cloned cell populations, an increase of number of the chromosomes was especially obvious in clones 3 and 4 (modal classes in both cases were 76-77 chromosomes). Cell population of clone 1 differed insignificantly from that of the parental line MSB-1-K-33 in respect of its cytogenetic characteristics. In metaphases of the line MSB-1-K-33 and clones 1, 3, and 4, a high frequency of chromosomal damages was observed. The most frequent type of structural chromosome aberrations were chromatid breaks. The karyotypes of clones 3 and 4 were characterized by presence of a large marker metacentric chromosome in 50-53% of the cells. The data obtained suggest a continuous effect of the Japanese encephalitis virus on the karyotype of cells in infected culture.