IS2-61 and IS2-611 arise by illegitimate recombination from IS2-6. A more stable derivative of IS2-6 has been isolated, which had lost 54 bp of the 108 bp long insert characteristic of IS2-6. This new allele of IS2, IS2-61, segregates the remaining 54 bp to yield allele IS2-611. DNA sequence analysis shows that the segregation products of IS2-6 arise by recA-independent, illegitimate recombination at 9 bp long direct sequence repetitions.


DNA repair in Proteus mirabilis. VI. Plasmid (R46-) mediated recovery and UV mutagenesis. The expression of plasmid R46-mediated recovery and mutagenic function (s) was studied in P. mirabilis, which is normally either weakly or non-mutable after UV exposure. The plasmid was found to confer on P. mirabilis enhanced UV resistance as well as UV-induced mutability for various types of forward mutations and reversion of the thr273 mutation. The plasmid enhanced survival of UV-irradiated phages in P. mirabilis both in unirradiated host cells and with increased efficiency after UV-exposure of host cells, as is characteristic of UV-inducible phage reactivation. Spontaneous mutability of P. mirabilis harboring R46 was about 2 to 7 times higher than that of cells without plasmid, depending on the marker, repair type, and plating density of the cells used. All of these R46-mediated rescue and mutagenic functions require the rec672 + gene function. It is assumed that the plasmid R46 adds functions to P. mirabilis comparable to those deficient in umuC and uvm mutants of E. coli (Kato and Shinoura, 1977; Steinborn, 1978) and that P. mirabilis possesses functions homologous to those controlled in E. coli by the recA + and lexA + genes. The significance of plasmid-mediated rescue and mutagenic functions for bacteria which lack the misrepair branch of mutagenesis, is discussed.


Lipid composition and polyene antibiotic sensitivity in isolates of Candida albicans. When Candida albicans cells were grown on hydroquinone (Hy cells) or ascorbic acid (As cells) supplemented media, they exhibited a 26% rise and 16% drop in ergosterol content, respectively. C. albicans cells manifested a gradual increase in total lipid levels, when they were grown on n-alkanes of different chain lengths. The magnitude of the nystatin effect (in terms of proline uptake and K+ efflux) was more pronounced in cells having more ergosterol (Hy cells) compared with the cells having low levels of ergosterol (As cells), suggesting a correlation between nystatin sensitivity and ergosterol content of the C. albicans cells. However, such correlation could not be demonstrated in alkane grown cells where levels of different lipids were variable. Results demonstrated that several other lipids besides sterol may also influence the polyene antibiotic sensitivity in C. albicans cells.


Environmental factors influencing nitrate respiration in Escherichia coli K12 and Rhizobium trifolii. The nitrate respiratory systems of both the facultative anaerobe Escherichia coli K12 strain W3350 and the aerobe Rhizobium trifolii strain T1 are regulated in a similar manner by a complex set of interactions involving H2, N2, CO2, glucose and nitrate. In addition, the nitrate respiratory system of strain T1 can be regulated by chlorate. A possible mechanism is presented to illustrate how these complex interactions might take place.


A modification of the polyethylene glycol technique for the purification of small quantities of tobacco mosaic virus. An adaptation of the polyethylene glycol method for the purification of tobacco mosaic virus (sunnhemp strain) from small (2 g) samples of French bean lamina is described. The virus can be precipitated from 1-2 ml of clarified sap by the addition of an equal volume of 8% polyethylene glycol 6000 (w/v) (PEG), and pelleted by centrifugation for 10 min at 1,8000 x g. Details are given of tests which establish that the purity and quality of the virus obtained by the small-scale method are as good as those achieved by the established large-scale method. Even with very low virus titres, the small-scale method effectively precipitates total tobacco mosaic virus nucleoprotein without substantial loss of infectivity. The results are reproducible and in a relatively short time it is possible to purify the virus from large numbers of replicate samples.


Growth and survival studies of psychrophilic and mesophilic yeasts. The effect of temperature on the growth of members of five genera of yeasts was studied in one glucose-containing and two glucose-free media. The maximum growth rate was seen in the glucose-containing medium, and the minimum growth was in either of the two glucose-free media depending upon the organism. Data obtained by optical density measurements was supported by total cell counts. The highest survival at the restrictive temperatures was within 5 degrees C of the optimum temperature for a particular organism. Among the temperatures other than the optimum, the highest growth rate and cell yield was obtained at a temperature 5 degrees C below or above the optimum.


Purification and properties of a protein surface antigen of Streptococcus mutants. A protein, designated antigen III, was extracted from cells and culture supernatant of Streptococcus mutans serotype c, and purified by ammonium sulphate precipitation followed by chromatography on anion-exchanged and gel filtration columns. Monospecific antisera were raised by injecting purified antigen III in rabbits. Antigen III prepared from cells and supernatants appeared identical by reaction with antisera and were of similar chemical composition and physico-chemical properties. Antigen III was resistant to most proteolytic enzymes, but pepsin digestion decreased its molecular weight from 44,000 to 24,000 without destroying antigenic activity. Immunofluorescence showed that antigen III was located at or near the cell surface of S. mutans serotypes b, c, e and f.


[A modification of microglia impregnation (author's transl)]. A modification of the Weil and Davenport (1933) silver carbonate method for microglia impregnation is described. Formalin-dextran-CaCl2 solution was used as a fixation solution. The technique is simple, reproducible and improved. The staining method includes the demonstration of as well resting as progressive microglia.


Identification of beta-hemolytic streptococci isolated from hospitalized children in Baghdad. Two hundred and twenty four hospitalized children in Baghdad aged between 1 month and 10 years were examined for Streptococcal infections. Thirty-four percent of the throat and saliva specimens were positive for beta-hemolytic streptococci. Males were more susceptible to infection with group A streptococci than females. Streptococcus of group A was isolated from 39.5% of the positive cases while group G was 47.4%. The etiological significance of the latter group in tonsillitis and otitis media is to be further investigated. Ninety six percent of the isolated streptococci were T typable and 13.3% of the strains were M typable. A high frequency of type T-11 was found in streptococcal infections. T type 3875 was found to be a new provisional type. All isolates were M untypable, and antiopacity factor negative except for two isolates of T type 4 which were positive in both typings.


"Pseudolysogenization" by RNA phage Q beta. We isolated fairly stable lysogenic-like bacteria from a lysogenic state established between an amber mutant for the maturation protein gene of RNA phage Q beta (Q beta am 205) and its nonpermissive host BE110. These bacteria contained few mature phages intracellularly (less than 10(-3) plaque forming unit per cell), continued to grow with a potentiality to produce Q beta am 205 spontaneously, and showed an immunity-like response against homologous phage infection. These characteristics were maintained by growth in liquid medium containing anti-Q beta serum. We designated these cells as pseudolysogenic bacteria. The relative amounts of RNA genomes in these pseudolysogenic cells (about 10(2) infectious RNA strands per cell) indicated that the RNA genomes could replicate in nonpermissive cells and be distributed in daughter cells synchronizing well with cell division.


Local production of antisperm antibodies in infertile women. The presence and significance of locally produced antisperm antibody in 20 well-documented infertile patients has been investigated. Sera and vaginal washings both from patients and from fertile controls were examined for antisperm antibody by means of four methods. Antisperm antibody was detected in 25% of the washings taken from infertile patients, but in none of those from fertile women. Detection of antibody by the microimmobilization technique discriminated best between infertile and fertile women both in serum (P=0.0166) and in washings (P=0.0166). The results of this study support the concept that locally produced antisperm antibody contributes to conception failure in a subgroup of infertile women, and that the routine study both of sera and of vaginal washings of infertile patients has practical value.


[Isolation of the intracellular lipase of Serratia marcescens]. Various methods have been tested in order to isolate endolipase from the cells of Serratia marcescens 345: cell disintegration by ultrasound and French press as well as incubation of the cellular suspension with sodium salts of bile acids. The combined effect of ultrasound and these salts on the cellular suspension of S. marcescens 345 was also studied. The highest lipolytic activity was found in the supernatant obtained upon incubation of the cells with sodium cholate at a concentration of 0.8% for 30 min.


[Search for life on Mars].

[Search for life on Mars]. The paper presents the data about the catalytic activity of several minerals from the Martian ground and of some laboratory analogues of the planet ground. It has been shown that it is possible to obtain unambigious data about life on Mars by using such methodological approaches which are based on biological principles of the determination of living matter. Microbiological methods for detection of extraterrestrial life should be preferred in future over biogeochemical methods which were used by the Viking stations.


Evaluation of three serological tests for the diagnosis of hydatid disease. A number of techniques is used for the serological diagnosis of hydatid disease; however previous investigations suggest variable degrees or reliability for each test. This study reports an evaluation of the sensitivity and specificity of three commonly used serological tests for hydatid disease; complement fixation (CF), haemagglutination (HA) and the fluorescent antibody (FA) techniques. The results of these serological tests are compared in a series of specimens from 116 hospital patients, 21 of whom were confirmed surgically as having hydatid disease. A similar high degree of sensitivity was found for each of the three serological tests examined. The CF and HA tests gave negative results in two patients with confirmed hydatid disease, and the result of the FA test was negative in only one patient. The HA test was the most specific with no false positive reactions, but only two false positive reactions occurred with the FA test. The CF test was the least specific as the reaction was positive in nine patients without hydatid disease. When the results of both FA and HA tests were considered together, all 21 cases of hydatid disease were detected and false positive reactions occurred in only two patients.


The biochemistry and in vitro activity of soluble factors of activated lymphocytes. Activated lymphocytes release numerous products which are either synthesized de novo or in increased amounts; some of these products play a role in the regulation of the immune response and are designated as mediators of cellular immune reactions or lymphokines. The first lymphokine described was the macrophage migration inhibitory factor (MIF) which has been studied most extensively with regard to its chemical and biological properties. Using sensitive radiolabelling techniques and an antiserum against highly purified fractions of MIF we were able to identify several products of activated guinea pig lymphocytes with different molecular weights of 15.000, 30.000, 45.000, 60.000 which all had an isoelectric point of 5.2 and were all inhibitory to macrophage migration. It is suggested, that these molecules are oligomers of a common subunit of molecular weight 15.000. It was further shown, that molecules of the same physical-chemical and serological characteristics are produced by activated B-cells, L2C leukemia cells and growing fibroblasts, thus further substantiating earlier reports on the production of MIF by lymphoid and non-lymphoid cells. The described molecules were also shown not to contain determinants of the major histocompatibility complex and to be distinct from lymphotoxin, another lymphocyte activation product. It is concluded, that MIF is not a single molecule but rather a system of structurally related molecules. Their interaction with macrophages and possible relationships to macrophage activating factor is discussed.


Fatty acid alpha-hydroxylation and its relation to myelination. alpha-Hydroxylation is an enzymatic reaction by which long-chain fatty acids are converted to their alpha-hydroxy derivatives. This reaction, in animals, can be detected only in developing brain and is the rate-determining step in the synthesis of hydroxycerebroside, which is an indispensable and abundant myelin lipid. In addition to a particulate fraction from brain, two cytoplasmic factors, one heat-stable and the other heat-labile, are required for alpha-hydroxylation. During the past eight years we have been investigating alpha-hydroxylation. Our progress is summarized and discussed here.


[Nuclear antigens in tumorous and non-tumorous tissues]. The observations suggest that the cells of the human malignomas contain such protein or proteins which keep their specific antigenic characteristics even under isolation techniques. These characteristics have been directly due to the nucleus of the malignant cell, and had remained also under the cell-culture process. The nuclear antigen and specific antibody technique described in this paper seem to be suitable as an immunofluorescent method in the immunodiagnostics of the human tumors, furthermore provide valuable data in the clarification of the problem of human tumors.


Immunization of mice with an avirulent pseudohyphal form of Cryptococcus neoformans. Mice were immunized with a viable, avirulent strain of Cryptococcus neoformans. Lymphocyte blastogenic assays showed a 10-fold increase in reactivity of sensitized spleen cells, and histopathologic examination revealed marked splenic hyperplasia. Thirty-two days after intravenous inoculation with a virulent strain of C. neoformans, none of the control animals survived whereas 60 percent of the immunized mice were alive with no clinical evidence of disease. This animal model shows that protective immunity can be established, and once developed, provide a better model for the study of important aspects of immunity in fungal disease.


Cytochemical and biochemical identification of lysosomes in Cryptococcus neoformans. Normaski optics, fluorescence and electron microscopy were employed to demonstrate the occurrence of lysosomes in capsulated, enztmatically decapsulated, and dewalled cells of a human isolate of Cryptococcus neoformans. Fluorescent studies, using acridine orange as a lysosomal indicator, revealed the presence of variously sized, spherical, reddish-orange fluorescing bodies. Electron microscopy studies demonstrated the presence of acid phosphatase (AP), a lysosome marker enzyme, in single-membrane bound organelles. Lysosomes were removed from dewalled cells and separated by differential centrifugation on ficoll gradients. That fraction indicating the highest assay for AP was centrifuged at high speed, and the resulting pellet was fixed for electron microscopy and stained by the Gomori procedure for AP. Sections of the pellets revealed AP stained vesicles of the same size range as those within intact cells.


[Daily and weekly variations in the yeast-digestive flora of a female of giant panda (author's transl)]. Since its arrival at the Paris's zoological Park, the yeasts of the flora digestive tract of a young female of Giant Panda, Ailuropoda melanoleuca, was daily, then weekly studied. Were noted: the diet in captivity, the number of isolates in primary-cultures, the morpho-physiological differences between strains of a same species and the maximal temperature for growth of all the fungi. Were also approached, for the analysis, some data on the yeast-flora of other captive mammals and on the yeast species of the habitat. Short time colonization recorded seems the result of a difficulty of adaptation, even for C. albicans, to the digestive tract of that animal. The majority of the yeasts identified are transient microorganisms of alimentary, aquatic or aerial origin.


Correlation of extracts obtained by high efficiency gel chromatography of lactic dehydrogenase virus infected mouse serum and cytosol from human tumors using leukocyte adherence inhibition assay. Immunochemically active fractions were obtained using Separon Hema-300-glc(R) from serum of lactic dehydrogenase virus (LDV) infected mice and from homogenates of human tumors. The mixture of proteins of tumorous origin from the cytosol giving a positive reaction in the leukocyte adherence inhibition (LAI) test was found in the same fractions showing maximum of absorbance at 340 nm in the spectrophotometer and a corresponding peak in the refractometer. Analogous peaks were not proved in material obtained from healthy controls, but they were found in some human placentas and fetal organs. The LDV fraction obtained from mouse serum served as a "control" antigen in LAI test for human tumor testing, and results corresponded with those obtained using cytosol specific for the tumor under study.


Peripheral blood lymphocyte nucleoi of rats with Yoshida ascitic sarcoma and the effect of endotoxin. Nucleoli of lymphocytes were studied in the peripheral blood of male Wistar rats bearing Yoshida ascitic tumor untreated and treated with Escherichia coli endotoxin. Both the neoplastic process and the endotoxin produced an increase of peripheral lymphocytes with "active" nucleoli in number. The treatment of experimental animals bearing the tumor with the endotoxin decreased their mortality and enhanced the increase of the lymphocytes with "active" nucleoli in their peripheral blood.


Detection of specific immunoreactivity by LAI assay in patients with malignant melanoma of uveal tissue. To monitor the specific antitumor immunity to patients with malignant melanoma of the uveal tissue, use was made of the 20-hr modification of the leukocyte adherence inhibition (LAI) test. Simultaneously, changes in the proportionally of T (total and active) and B lymphocytes in peripheral blood were followed in the same patients by the E and EAC rosette formation test. Peripheral blood leukocytes from patients with malignant melanoma of the uvea, cultured in vitro for 20 hr with syngeneic and allogeneic tumor extract showed a significantly lower adhering capacity than the same cell population cultured without the specific tumor extract (21/22). A retest 3 months after tumor removal showed the percentage of positive cases to have declined (11/19). Leukocyte adherence of control donors, cultured with and without the tumor extract remained unchanged. A follow-up of immunocompetence in patients with malignant melanoma of the uvea, based on proportionally changes of total T, "active" T and B lymphocytes yielded information of an orienting value only. The results of investigation of the various cases proved to be considerably divergent and failed to present a reliable picture of the patient's immunological status.


T and B lymphocytes in lymph nodes and spleen of patients with Hodgkin's disease. Lymphocyte surface markers of 100 tissue specimens (67 lymph nodes and 33 spleens) of 40 patients with Hodgkin's disease were studied by means of spontaneous E-rosette formation and direct immunofluorescence method. The occurrence of active and total T cells was signigicantly higher (p less than 0.001) in the tumor-involved lymph nodes and spleens, while the frequency of B cells was practically the same in the histologically negative lymph nodes and spleens. In the tumorous spleen of 6 untreated patients the frequency of active and total T cells was higher in the tumorous tissue specimens than in the surrounding histologically negative tissue specimens. No correlation has been found between the simultaneously investigated peripheral T and B cell counts, clinical stage and the histological type of the tumor.


Mitotic activity in adult rat brain induced by implantation of pieces of fetal rat brain and liver. By implantation of pieces of fetal CNS into adult host brains it was found that the fetal brain tissue induced a very high mitotic activity in the adult brain at 2-4 days after implantation. The dividing cells were found within a 3-mm zone from the transplant in occipital cortex, hippocampus and brain-stem. Sham operated control animals exhibited only very few mitotic figures close to the lesion. Neither local injection of amniotic fluid nor implantation of other fetal tissues induced mitotic activity with the exception of fetal liver. Possibly, the mitogenic factor(s) released from the transplanted fetal brain is hepatic in origin.


Hypotensive response in spontaneously hypertensive rats following microinjection of alpha-methylnoradrenaline in the caudal brain-stem. Local microinjection of 1.25 nmol (-)-alpha-methylnoradrenaline in the A2-region of the nucleus tractus solitarii (NTS) caused a decrease of blood pressure and heart rate in both spontaneous hypertensive rats (SHR) and Wistar-Kyoto (W/K) rats. Although the maximal responses in both strains did not differ, the decrease in blood pressure lasted longer in the SHR. These results do not support the concept of a diminished sensitivity of catecholaminergic receptors in the NTS of SHR to alpha-methylnoradrenaline.


Degradation of luteinizing hormone-releasing hormone (LHRH) by brain prolyl endopeptidase with release of des-glycinamide LHRH and glycinamide. A highly purified preparation of rabbit brain prolyl endopeptidase cleaved the decapeptide luteinizing hormone-releasing hormone (LHRH) at the ProGly . NH2 bond leading to the release within 1-3 h incubation at 37 degrees C of des-glycinamide LHRH and glycinamide. Evidence for this site of cleavage was obtained by the detection of glycinamide or glycine and groups by a microdanyslation procedure, and by separation of the breakdown products by high performance liquid chromatography (HPLC) on a revers phase C-18 column. Incubation led to the appearance of two new peaks as detected by HPLC one of which was collected and shown to have the composition consistent with des-glycinamide LHRH. The other peak ran in the position identical to that of authentic glycinamide. Results suggest that prolyl endopeptidase could play a role in the inactivation of LHRH in vivo.


Quantitative analysis of dendritic branching. I. Simple formulae for the quantitative analysis of dendritic branching. Dendritic branching of neurons may be quantitatively studied using applications of graph theory. Dendritic ramifications may be considered as 'forests' of planted, stemmed, binary 'trees' with simple mathematical properties. Two fundamental numbers, that of dendritic tips and that of dendritic stems, usually suffice to quantify the dendritic branching of one neuron as, in most cases, they allow the computation of all other numbers of dendritic points and segments.


Relationships between the catecholaminergic and enkephalinergic systems demonstrated by a combined technique of formaldehyde-induced fluorescence and immunocytochemistry. A technique for the localization of catecholamines and enkephalin in the same tissue section is described. Sections from rat brains prepared according to the Falck-Hillarp technique were examined by dark field fluorescence microscopy and then processed for immunocytochemistry for leucine-enkephalin (leu-enk) using the unlabeled antibody technique. In the medial hypothalamus the distribution of the catecholamines and enkephalin is complementary, while in the lateral hypothalamus the patterns are similar but not identical. Enkephalin terminals are also observed in and around the locus coeruleus, while enkephalin cell bodies are adjacent to the nucleus.


Met-enkephaline-like immunoreactivity in a cephalopod neurohemal organ. Using a highly specific antibody we found Met-enkephalin-like immunoreactivity in large granules of numerous distinct cells that are embedded in a layer of secretory terminals inside the octopus vena cava. Application of antibodies against fragments of the mammalian pro-opiocortin precursor -- alpha-MSH, ACTH, beta-endorphin and 16k-fragment -- and against growth hormone did not produce immunostaining in the octopus enkephalin cells. The vena cava neuropil may represent a favourable system for the examination of the physiological role of the opioid peptide enkephalin.


Brain extracellular space fixed for electron microscopy. Adult mammalian brain contains 17--20% extracellular space, but fixatives cause the cellular elements to ingest the extracellular fluid so that the space is reduced to less than 5% with all conventional methods of fixation. This can be prevented by washing out the extracellular fluid with isotonic sucrose, which does not penetrate cells. Subsequent fixation with aldehydes and osmium and conventional processing leads to the preservation of extracellular space in electron micrographs. Extracellular space was found to be unevenly distributed, widely separating some cellular processes while leaving other groups of processes contiguous.


Malaria in Tonga: an imported case.

Malaria in Tonga: an imported case. A case of falciparum malaria in Tonga occurring in a tourist is reported and discussed with the emphasis on awareness of imported diseases to the Pacific.


Noncorticosteroidal anti-inflammatory agents in Ophthalmology. Efforts have been made to develop noncorticosteroidal anti-inflammatory therapy. The goals of such therapy have been to eradicate the primary cause, prevent the initial tissue injury, moderate inflammatory response, and enhance tissue repair while minimizing and eliminating the undesirable aspects of the therapy.


Timolol therapy in secondary angle-closure glaucoma post penetrating keratoplasty. Timolol maleate (o.25% or 0.5% twice a day) was used in 13 eyes of 13 patients with secondary angle-closure glaucoma post penetrating keratoplasty uncontrolled on miotics, carbonic anhydrase inhibitors, or both. When added to each patient's current regimen, tomolol controlled 9 of the 13 eyes that no longer required cyclocryotherapy, and it was well tolerated locally and systemically. Its ocular hypotensive effect appears to supplement miotics and carbonic anhydrase inhibitors.


Interaction of topical and oral timolol in glaucoma. The interaction of oral and topical timolol maleate was studied in patients with open-angle glaucoma. The oral and topical preparations given separately produced a significant and comparable reduction of the intraocular pressure, but no additive effect was observed when both preparations were given together. Pulse- and blood pressure-lowering effects of oral timolol were not enhanced by the application of topical timolol. These systemic effects were not found in those patients using topical timolol alone.


Dislocation of Binkhorst four-loop lens implant. A consecutive series of 1,093 Binkhorst four-loop lens implantations was used to examine the problem of dislocation of implants used in intracapsular cataract extractions; emphasis of the study was on the need for suture fixation. Transiridectomy suture fixation was used in 497 procedures, no suture was used in 403 procedures, and a simple iris suture technique was used in 193 procedures. Although the transiridectomy suture fixation procedure had the lowest percentage of dislocations, the iris suture technique is considered safer. Suture fixation is recommended for Binkhorst four-loop implants used in intracapsular cataract extractions.


Keratoplasty and intraocular lenses: current status. Present methods of treating combined corneal disease and cataracts in elderly patients are unsatisfactory, and multiple operative procedures may be required. From 1975 through 1978, 60 attempts were made to restore relatively normal optics and achieve rapid visual recovery with a single operative procedure consisting of keratoplasty, cataract extraction, and intraocular lens insertion in various combinations. As of this writing, there have been few complications, and 82% of the grafts are clear.


Hard contact lens corrections in aphakia. Hard contact lens correction of aphakia is best performed with a single cut lens by a trial lens fitting. Lenticular design may be necessary. Continuous wear over age 70 may be necessary to achieve success and acceptance in more than 30% of aphakic wearers. Soft lenses are usually not practical in the author's experience. The increased use of intraocular lenses is decreasing the need for aphakic contact lenses. Merits of the hard contact lens in aphakia are discussed as a practical approach to the correction of vision by the ophthalmologist, and indications for single cut lenses and lenticular design are outlined.


[Tracheal compression by the innominate artery (author's transl)]. A five week old male infant is treated under suspicion of whooping cough because of pertussis like cough, cyanosis, and attacks of reflex apnea. These attacks are seen up to 40 times per day. After exclusion of a cerebral genesis there was found a ventral indentation of the trachea. It was also seen by tracheoscopy, but this part of the trachea was not pulsating. In the angiography the compriming structure was identified as the innominate artery. The genesis of this anatomic variant, the often threatening symptoms in this case without inspiratoric stridor, and the diagnostic and therapeutic steps are discussed.


Biofeedback therapy for headache and other pain: an evaluative review. A survey of the literature is presented in two areas of biofeedback treatment for headache--muscle contraction and migraine--and a variety of miscellaneous pain syndromes. The studies done to date are characterized largely by lack of proper no-treatment or placebo control groups, by confounding biofeedback with a variety of other strategies, or by sample sizes too small to afford any reasonable conclusions about efficacy. There is some evidence that biofeedback works better for muscle contraction headache than false feedback, but it also appears that biofeedback is no more effective than relaxation training. The application of biofeedback to migraine or other pain syndromes remains of unproven value. Investigators seldom attempt to relate empirically their interventions to hypothetical models of pain mechanisms. The potential influence of extraneous factors linked to the therapeutic situation is pervasive in these studies, but examination of their specific roles in symptom reduction is largely missing. Some variables are listed which need to be examined and which may contribute to the alleviation of pain with much less expenditure of clinical resources than that demanded by biofeedback. Perhaps the main contribution of biofeedback has been to highlight such extraneous variables in the pain treatment setting.


The lateralisation of pain.

The lateralisation of pain. Pain is more often lateralised on the left, except in the case of trigeminal neuralgia. The factors which promote lateralisation of pain are reviewed and it is noted that hysterical conversion symptoms are also more common on the left. Experimental evidence implies that the right hemisphere is less efficient than the left in processing cutaneous sensory input. Neurological and psychiatric data support the view that the right hemisphere is dominant for emotional experience and this may help to determine the left-sided preponderance of pain.


The pyridine scale for clinical measurement of olfactory threshold: a quantitative reevaluation. Serial dilutions of pyridine in water are employed for measuring the olfactory detection thresholds of patients. Experimental precautions are described that improve the precision and accuracy of the method. Existing data on the sensitivities of hyposmic patients are confirmed, but the sensitivities of normal subjects and of hyperosmic patients are believed to have been substantially overestimated in some earlier publications. Routine clinical applications of the revised pyridine odor threshold test are discussed. In the author's experience, the average cystic fibrosis patient is slightly hyposmic, and some cases of pituitary tumor are accompanied by a 100,000-fold hyperosmia.


An enzyme-immunoassay for myoglobin in human serum and urine. Method development, normal values and application to acute myocardial infarction. An enzyme-immunoassay has been developed for the detection of myoglobin in human serum and urine which is specific, accurate, precise, and has a sensitivity of 3 ng/ml. When compared with radioimmunoassay, the enzyme-immunoassay gives markedly similar results. Sera from normal adults had a myoglobin concentration in the range 3-65 ng/ml, and 64% of the same group had detectable myoglobinuria (range 3-11.5 ng/ml). All of 8 patients with definite acute myocardial infarction had raised serum myoglobin levels (range 200-1125 ng/ml) either at admission or 4 h later. Myoglobin concentration returned to normal in 6 patients, and in the remaining 2 patients there was evidence of infarct extension. Urinary myoglobin excretion was variable. One patient with possible acute myocardial infarction had elevated serum myoglobin (413 ng/ml 4 h post admission) and 5 patients with no evidence of infarction had normal levels (15-53 ng/ml). The results suggest that detection of serum myoglobin by enzyme-immunoassay may be a valuable test in the early diagnosis of acute myocardial infarction.


Further observations on the fate of pedicle osteocutaneous grafts. Recent work has shown that pedicle osteocutaneous grafts retain their viability and participate actively in the restructuring of transferred bone. The present study investigates two aspects of this process: (1) whether or not healthy recipient bone is needed for the survival of these grafts and (2) the degree of periosteal involvement in osteogenesis. Six adult dogs were used. Pedicle osteocutaneous grafts were constructed using the anterior table of the frontal sinus. Rotation of these flaps allowed implantation of the bone transplant into the ipsilateral parietal muscle. Free bone grafts were used as controls and were implanted in the contralateral muscle. Specimens were removed at variable intervals between 8 and 40 weeks after operation. All free grafts were reabsorbed. Pedicle-assisted bone grafts retained their volume and exhibited marked periosteal osteogenesis that eventually produced enough new bone to replace the graft. These experiments provide strong evidence that bone restructuring in osteocutaneous grafts may be independent of recipient bone and that it depends almost exclusively on periosteal activity.


Behavioral science in medical education: a bibliography. Since 1956, there have appeared 125 studies which focus on the issue of integrating behavioral science into undergraduate and graduate medical education.


Effects of active and passive EMG biofeedback training on performance of motor and cognitive tasks. The goal of this study was to compare the effects of general relaxation (passive group) and neuromuscular tension control (active group), both using EMG biofeedback techniques, on the performance of memorization, simple reaction time, and rotary pursuit. 18 subjects were given five consecutive daily sessions of training or were placed under control conditions, after which their performance on these various tasks was evaluated. Results indicate that control of neuromuscular tension seemed to facilitate performance on all tasks over that of the control group. Except for simple reaction time, there was no difference between the "active" and "passive" groups. The results are interpreted in terms of factors in selection of subjects and experimental conditions.


Locus of control and biofeedback: a review of the literature. This paper first reviews studies which have investigated the efficacy of using locus of control orientation to predict performance in various modes of biofeedback. However, contradictory evidence and methodological problems make it impossible to draw any conclusions regarding the connection between internality-externality and biofeedback performance. Second, various attempts to modify externality through biofeedback treatment are reviewed. Although EMG feedback can apparently be used to shift locus of control in an internal direction, there are some major issues that need to be resolved. Of primary importance is the fact that the rationale for modifying externality is based on an unproven assumption that externality has a role in the causation of various undesirable behaviors. Also, as no follow-up testing has been done, there is no evidence that the EMG biofeedback causes relatively permanent, stable locus of control changes. If the shifts are only temporary, then its use as a modifier of externality is questionable.


[Eosinophilic fasciitis (Shulman syndrome) associated with insulin-dependent diabete. 1 case (author's transl)]. A patient with eosinophilic fasciitis and insulin-dependent diabete mellitus is recorded. Diabete and blood hypereosinophilia occurred four months before acute onset of severe proximal sclerodermic features. The deep seated level of fibrosis, mainly localized in subcutaneous fat and fascia was documented by histologic examination. Prednisone therapy (0,75 mg/kg/day) resulted in cutaneous improvement and disparition of eosinophilia. Survey of pertinent literature lead us to consider Shulman's syndrome as a distinct entity amid the broad scleroderma spectrum. Features of esosinophilic fasciitis are very close to, and sometimes undistinguable from generalized morphea. Simultaneous occurence of diabete mellitus in this case is not fortuitous. The same association has already been recoreded with various sclerodermic syndromes.


Blood coagulation and shock.

Blood coagulation and shock. This report describes how a finding at the autopsy table led to the observation of a clinical syndrome. A synthesis of autopsy experience, clinical investigations, and experimental and biochemical studies were able to shed light on one factor in the pathogenesis of this syndrome, namely blood coagulation with pulmonary microemboli and release and delayed elimination of peptides from fibrin degradation extravascularly in the lungs. These peptides may both induce increased permeability in the microcirculation and stimulate fibroblast proliferation. Knowledge about the pathogenesis has led to improved prophylaxis and therapy and a reduction of the number of deaths.


Shock in pregnancy: pathophysiology and morphologic findings. Sepsis and non-septic shock in pregnancy show characteristic modifications which are caused a) by physiologic changes in hemostasis primarily in the third trimester of pregnancy, b) by etiologic distinctions of shock regarded as pregnancy-specific, c) by hemodynamic changes in the circulation during pregnancy, d) by the ability of the healthy, young organism to compensate adequately. In the dead fetus syndrome and in non-septic shock, i.e., in amnionic fluid embolism and in abruptio placentae, the clinical picture is often governed by marked secundary fibrinolysis. Retroplacental hematoma, the characteristic feature of premature placental separation, remains controversial as either the cause or sequela of the hemostatic disorder. Etiologic, pathogenetic, and morphologic similarities exist between septic abortion, chorioamnionitis, and puerperal sepsis, but the varying response of the maternal organism during the course of pregnancy leads to different clinical and morphologic pictures. Due to a decrease in fibrinolytic activity as a consequence of pregnancy, the hypercoagulability state in a septic endotoxic shock predisposes the kidneys to bilateral renal cortical necrosis, principally in the amnion infection syndrome.


Morphologic development of human shock lung. In the initial phase of shock, edema spreads throughout the alveolar interstitium even before injury occurs in the alveolar epithelium and endothelium. The endothelium and the epithelium are damaged only subsequently, causing reduction in the average barrier thickness of the epithelium and the endothelium. A point of irreversibility is reached by the end of the first week. While early cell regeneration may be observed within the alveolar endothelium and epithelium, proliferation of fibroblasts and fibrosis of the alveolar wall occur in addition to edema which spreads within the interstitium. This widening of the gas exchange barrier may be considered as the anatomic substrate of respiratory insufficiency induced by shock. This enlargement continues up to the moment when thickening of the alveoli impedes satisfactory functioning of the lung, and, as consequence, threatens the life of the patient.


[The effects of acebutolol on endocrine and metabolic reactions induced by acute hypoglycaemia. Study in normal subjects and in insulin-dependent diabetics (author's transl)]. Six normal subjects and six normotensive insulin-dependent diabetics underwent two insulin hypoglycaemia tests after administration for three days of either a placebo or of acebutolol--a cardioselective beta-blocker--at a dose of 400 mg per day. The order in which the tests were performed was decided by random selection. Acebutolol suppressed the tachycardia which occurred as a reaction to hypoglycaemia but did not interfere with other warning symptoms and signs. In both normal subjects and diabetics, acebutolol neither worsened the initial hypoglycaemia nor did it delay a return to normal values. The increase in lactate levels following hypoglycaemia was not reduced by acebutolol but free fatty acid rebound was suppressed. Hormonal responses (glucagon, cortisol, growth hormone) were unaffected by the beta-blocker. If they are confirmed by long term studies, these results would suggest that acebutolol is safer to use than non-cardioselective beta-blockers in the treatment of coronary insufficiency and of hypertension in diabetics exposed to the risk of hypoglycaemia.


The dietary management of diabetes in adults. The ultimate object of all types of dietary management before the introduction of insulin was to prevent emaciation and death: the consequences of metabolic derangements due to lack of insulin. Now, while dietary therapy continues to be important in minimizing the requirement for endogenous insulin or in balancing administered insulin, the major objects are changing to prevention of large vessel and microvascular disease. The next decade will probably see a more widespread introduction of diets containing a lower proportion of energy derived from fat. The increased carbohydrate intake will almost inevitably result in increased dietary fibre intake. Whether David Jenkins' Lente carbohydrate foods (those containing viscous unabsorbable polysaccharides) will prove to be of lasting value is not yet known. Since galactomannans occur in legumes perhaps we should consider the possibility of diets containing large proportions of legumes: a twentieth century 'Legume cure'? If this should prove of value it would not have excited ancient Indian physicians who wrote (in the Caraka-Samita) of their use of legumes in the treatment of glycosuria, at least as early as the first century AD, before Aretaeus had applied the term diabetes.


Proteolytic fragmentation of spectrin:effect of removal of terminal phosphopeptides on spectrin binding to human erythrocyte membranes. The involvement of phosphorylated regions of spectrin, from human erythrocytes, in membrane binding has been investigated. Spectrin is phosphorylated at several sites, all near a terminal of the band 2 polypeptide. This region can be removed from the bulk of the molecule by brief trypsinization. Membrane binding of the bulk of the protein is unaffected by brief proteolysis, whereas phosphofragments generated by this treatment exhibit no membrane binding.


Growth hormone control of glucose oxidation pathways in hypophysectomized rats. An in vivo response of glucose oxidation to growth hormone has been demonstrated. Hypophysectomized rats were found to oxidize glucose at rates significantly higher than normal rats. Treatment with growth hormone 1 h before injection of 14C-U-glucose, 14C-6-glucose, or 14C-1-glucose caused a return to a normal oxidation pattern. This acute response was independent of insulin action but clearly time-dependent since no change from untreated hypophysectomized rats appeared when growth hormone was given at various times prior to administration of labeled glucose. The response observed for 14C-6-glucose was comparable to that observed for 14C-1-glucose with regard to dynamics but differed with respect to total 14C recovered as 14CO2. The cumulative percent 14CO2 recovered from oxidation of 14C-6-glucose 1 h after growth hormone injection exceeded that recovered from oxidation of 14C-1-glucose. These results suggest a change in glucose oxidation by a route that cannot be explained solely by changes in either the hexose monophosphate or Embden-Meyerhof pathways.


Prostacyclin and human foetal circulation. Tissues from human umbilical cord arteries and placental veins generated much greater prostacyclin activity than vessels from normal adults. High prostacyclin generation could contribute to maintaining the low peripheral vascular resistance typical of foetal circulation in which blood pressure is low despite very high cardiac output.


Prostacyclin (PGI2) effects on anterior pituitary hormones in the rat in vivo. Intravenous injection of 600 microgram PGE2 or PGI2 significantly increased serum LH and prolactin levels in estradiol treated ovariectomized rats. There was no effect on serum FSH concentration. PGE2 and PGI2 stimulated LH release in a non-dose dependent manner, while prolactin levels were positively correlated with the dose administered following PGI2 treatment. 6-keto-PGF1 alpha at a comparable dose had no effect on pituitary hormone levels. Subcutaneous administration of 1 mg/kg or 60 mg/kg PGI2 for seven days significantly depressed serum LH level both in male and female rats. These doses had no effect on serum FSH or prolactin levels.


Prostaglandin formation in bacteria.

Prostaglandin formation in bacteria. We report here that intact Gram positive and Gram negative bacteria, in the presence of exogenous arachidonic acid, produce and release PGE2 and PGF2 alpha into the medium as measured by radioimmunoassay. The seven bacterial strains so far studied release 6.5-50.9 ng PGE2 and less than 0.02-0.51 ng PGF2 alpha per mg bacterial protein during a 1 hour incubation, quantities of the same order of magnitude as those observed in mammalian systems. PGE2 and PGF2 alpha formation in bacteria are inhibited by indomethacin.


Differential effects of prostacyclin and prostaglandin E1 on bronchoconstriction and thrombocytopenia during collagen and arachidonate infusions and anaphylactic shock in the guinea-pig. The antagonism by prostacyclin (PG12) and prostaglandin E1 (PGE1) of bronchoconstriction  induced by serotonin (5HT), collagen, arachidonic acid (AA) and anaphylaxis, as well as of thrombocytopenia was studied in the guinea-pig. Under conditions where PGE1 prevented bronchoconstriction by 5HT, by collagen or by AA better than the accompanying thrombocytopenia, PG12 was a selective antagonist of bronchoconstriction due to collagen, but failed to interfere with that due to 5HT or to AA. Collagen-induced bronchoconstriction in the guinea-pig is platelet-dependent. PG12 blocks bronchoconstriction by collagen, because it prevents the platelet activation, and fails to interfere with bronchoconstriction  by AA, even though it reduces the accompanying thrombocytopenia, because the role of platelets is negligible. PGE1 and PG12 failed to interfere with thrombocytopenia or with bronchoconstriction of anaphylactic shock, and were inactive even when the acute bronchial effect was suppressed by anti-histamine treatment. Anaphylactic thrombocytopenia is beyond the control of agents which stimulate the cyclic AMP system, and involves specific mechanism which are not stimulated in platelet-rich plasma.


Effects of prostaglandin synthesis inhibitors on human insulin secretion and carbohydrates tolerance. Prostaglandin E (PGE) has been hypothesized to be an endogenous regulator of carbohydrate metabolism because it decreases human insulin secretion and carbohydrate tolerance. This report compares the effects of four inhibitors of PGE synthesis on the acute insulin response to glucose and subsequent glucose disappearance rates. Ibuprofen, acetylsalicylic acid and sodium salicylate treatments in normal volunteers were associated with augmented insulin secretion and improved glucose tolerance while indomethacin had the opposite effects. In view of these findings and the known effects of PGE on carbohydrate metabolism, we suggest that the effects of indomethacin may have been due to an action of the drug other than inhibiting PGE synthesis.


Comparative immunogenicity of BCG substrains for mice. Immunogenicity of four substrains of BCG was studied in mice vaccinated by the intravenous route and evaluated through pulmonary density and through splenic, hepatic and pulmonary indexes (weight of the organ/weight of the animalx100). In addition, tuberculin sensitivity was determined by measuring the thickness of the inoculated leg. All four strains (BCG Brazil, BCG Prague, BCG Russia and BCG Glaxo) showed intermediary virulence (0.78 -- 0.85) between pathogenic mycobacteria, i.e., M. tuberculosis and non-pathogenic mycobacteria, such as M. fortuitum, without however revealing differences among themselves in regard to pulmonary density. Reinoculation of vaccinated animals by the intravenous route, contrary to the subcutaneous route, resulted in significant increase (P less than 0.05) in the organs, except for the spleen. The tuberculin hypersensitivity induced by the four strains was significant and it was possible to distinguish BCG Brazil from BCG Glaxo. The substrain BCG Brazil proved to be the most immunogenic, followed by BCG Prague, whereas BCG-Glaxo proved to be the weakest vaccine.


[Utilization of the Kato-Katz-method (thick-smear technique) the diagnosis of Isospora (author's transl)]. Performing 10475 stool examination using the KATO-KATZ, HOFFMAN-PONS-JANER and direct examination (after agitation) methods, the author showed the best results with KATO-KATZ method for the diagnosis of Isospora hominis and Isospora belli. Among the 10475 stools examined 392 (3.74%) were positive for I. hominis and 55 (0.52%) for I. belli with the KATO-KATZ method; with the use of the others methods only 28 (0.26%) were positive for I. hominis and 6 (0.06% for I. belli.


[Myasthenia and pernicious anemia or Biermer's (author's transl)]. The association of myasthenia and Biermer's anemia is very rarely reported. In a series of 138 cases of myasthenia, this association was found in only one patient, in whom the anemia developed 19 years after the discovery of a calcified thymoma and 13 years after the appearance of the first signs of myasthenia. This led the authors to conduct a prospective study for the presence of intrinsic antifactor antibodies. A total of 81 patients (20 men and 61 women) with myasthenia were studied. The myasthenia had appeared after 35 years of age in 40 patients and 19 had a thymoma. The results of the study for the antibodies was positive in 3 women, as was the test of inhibition of leucocyte migration, but none of them had anemia, vitamin B12 malabsorption, achlorhydria, or gastric atrophy. The discovery of these immunological disorders raises the problem of their significance ; two hypotheses can be discussed : pre-Biermer state or immunological disturbance without pathogenetic significance. The problem can probably only be resolved by studying these antibody levels in a very much larger number of patients with myasthenia.


The value and results of long-term studies with diclofenac sodium (Voltarol). The results of 940 patients treated with diclofenac for 3 to 24 months in comparative and non-comparative trials are presented. Maximal improvement tended to occur in the first 3 to 6 months of treatment and was generally maintained. Diclofenac was at least as effective as equivalent doses of indomethacin and naproxen and, when treatment lasts more than 3 months, may be more effective. The majority of patients reporting unwanted effects or discontinuing treatment did so in the first 6 months. Unwanted effects (similar to those in short-term trials) were mainly gastrointestinal. Central nervous system, cardiovascular and dermatological side-effects were reported in 1% or less of patients. The long-term laboratory tolerability of diclofenac was good, with no changes in the nature, frequency or severity of abnormal tests with increasing duration of treatment. During the development of diclofenac sodium (Voltarol) various types of long-term investigation were conducted (Table I). This paper presents the results, covering a total of 940 patients treated for 3-24 months, and discusses their significance.


Diclofenac sodium (Voltarol) and indomethacin: a multicentre comparative study in rheumatoid arthritis and osteoarthritis. A five-centre double-blind crossover trial of two two-week periods using diclofenac and indomethacin showed that both drug groups (51 patients) with rheumatoid arthritis responded similarly in relation to pain scores and morning stiffness. It was noted that the response was better in inpatients than in outpatients, despite differences in disease severity. In the osteoarthritis trial (58 patients) it was shown that neither drug significantly reduced resting pain, although both drugs were significantly better in reducing pain on movement; however, patient preference was for diclofenac. Three patients treated with indomethacin withdrew owing to side-effects, compared with one on diclofenac. A slight but significant decrease in haemoglobin levels was observed in both treatment groups with osteoarthritis, but this did not appear to be symptom-related.


Diclofenac sodium (Voltarol): drug interactions and special studies. Diclofenac (Voltarol) has no effect on carbohydrate metabolism, insulin levels or tolbutamide metabolism, nor does it enhance the effect of tolbutamide, biguanide or glibenclamide. Although it produces minimal increases in prothrombin and partial thromboplastin times in healthy volunteers, it does not significantly affect the individual clotting factors, nor does it, in patients, enhance the effect of acenocoumarol or phenprocoumon. Like many other other non-steroidal anti-inflammatory drugs, it increases platelet aggregation time. There is a pharmacokinetic interaction between aspirin and diclofenac. Two independent studies have shown that aspirin markedly reduces the bioavailability of diclofenac, as measured by "area under the curve". Furthermore, patients exhibiting aspirin sensitivity as bronchospasm are likely to react to diclofenac in the same manner. Finally, diclofenac, as tested using excretion of 51Cr labelled red cells, induces minimal gastrointestinal blood loss, significantly less so than aspirin or naproxen.


Comparative clinical trials with diclofenac sodium (Voltarol) and naproxen in rheumatic conditions: investigation of possible changes in diclofenac dose and dose interval. In an open, comparative multicentre trial, 96 patients with arthritis of the large joints were treated with 75 mg diclofenac in one single dose in the morning, 50 mg diclofenac given twice daily, or 250 mg naproxen administered twice a day. It was noted that the length of history of pain was significantly longer in this naproxen group. Duration of the study was 14 days. Clinical parameters showed that the best degree of improvement was obtained with the diclofenac 50 mg twice-daily dosage regime. Diclofenac, in this study, showed better tolerability than naproxen.


A double-blind comparison of diclofenac sodium (Voltarol) and placebo in inpatients with rheumatoid arthritis. This preliminary study compared placebo with diclofenac (50 mg, rising to 150 mg per day) in a crossover study for seven days in thirteen inpatients. Regardless of the marked overall effect of hospitalization, an additional effect of diclofenac on grip strength and p.i.p. joint swelling was demonstrated, as well as a significant reduction in pain and in analgesic requirements. In addition, an improved technique for assessing the effect of NSAI drugs on p.i.p. joint swelling is described.


Diclofenac (Voltarol) in rheumatoid arthritis: a report of a double-blind trial. A double-blind trial compared diclofenac with placebo in 44 outpatients. On from each group dropped out with dyspepsia, and one (placebo group) with ineffective treatment. Twenty completers received diclofenac. Dosage was one tablet (25 mg diclofenac) three times daily during the first week. In the second (final) week, most patients had four or six tablets. Diclofenac had significantly greater effect on pain, grip, morning stiffness, joint tenderness and swelling, and in comparison to previous treatments, even though the placebo group required significantly more rescue anaglesic. A few patients in each group had slight dyspepsia. One in the active and six in the placebo group complained of minor central nervous system symptoms. There were no serious side-effects. Haematological, biochemical and urinary analyses showed no clinically important changes. It is concluded that, in the short term, diclofenac (Voltarol) is effective in relieving the symptoms of inflammatory polyarthritis. It is well tolerated as placebo medication, and had no detrimental haematological or biochemical effects.


An open assessment of the efficacy and tolerability of diclofenac sodium (Voltarol) in patients with rheumatic disease and a comparative study of diclofenac sodium (Voltarol) with indomethacin in patients with osteoarthritis and rheumatoid arthritis. The efficacy and tolerability of diclofenac was studied in an initial two-week assessment study in 24 patients with rheumatic disease. During the first week patients received 1 x 25 mg diclofenac t.d.s., with subsequent dosage adjustments according to response. Most completers showed improvement in joint pain and functional grade, and patients' rating of their condition indicated a significant improvement. Nine patients were withdrawn because of poor symptom control or side-effects, and there were a number of other minor side-effects not necessitating withdrawal. However, there were no persistent or lasting side-effects, and laboratory tests revealed no significant abnormalities. In a two-week double-blind study, diclofenac was compared with indomethacin in 43 outpatients with osteoarthritis or rheumatoid arthritis. Dosage in the first week was 1 x 25 mg tablet of either diclofenac or indomethacin (random allocation) t.d.s., with further adjustments as necessary. There were no significant differences in the effectiveness of the two drugs, and no differences in dosage requirements. Three patients were withdrawn from each treatment group. Gastrointestinal side-effects predominated in the diclofenac-treated group, with central nervous system unwanted effects more frequent in the indomethacin group.


Diclofenac sodium (Voltarol): a double-blind comparative study with ibuprofen in patients with rheumatoid arthritis. A double-blind comparative trial in 60 patients, using diclofenac (Voltarol) and ibuprofen (Brufen), showed a considerable improvement in morning stiffness amongst females in the diclofenac group. However, no significant differences was noted between these two drugs in relation to pain score, articular index or proximal interphalangeal joint size. Analysis of withdrawals and side-effects suggests that while ibuprofen may be slightly better tolerated, it is also associated with significantly more withdrawals due to lack of effect. No significant change in laboratory studies was noted, except for a slight decrease in mean haemoglobin levels. The trialist noted that all of the drop-outs and side-effects reported came from one hospital out of the four participating; this was possibly due to differences in pre-trial drug therapy and to the hospital being in an urban, rather a rural, situation.


[Evaluation of the use of caerulein (ceruletide) in the postoperative of abdominal surgery]. In order to evaluate the efficacy of Caerulein in the postoperative stage of abdominal surgery, 25 patients received 0.3 mcg/kg intravenously every 4 hours. Bowel Movements, passage of gases, first evacuation and general improvement were compared to 25 patients in similar conditions who didn't receive the drug. The study group showed an earlier appearance of intestinal motility as compared to the control group. This contributed in a relevant matter to an earlier discharge from the hospital. The differences with the control group were statistically significative. The benefits of the drug in the management of the postoperative stage of abdominal surgery are discussed.


[Studies concerning dysenteric infections in a closed children's community before and after antidysenteric vaccination. I. Epidemiological considerations on acute intestinal infections]. In the closed children's community studied between 1 Jan. 1976 and 13 June 1977, a high proportion (54%) of the total number of acute intestinal infections was of dysenteric etiology, i.e. 46,9% in the 0--1 year age-group and 21,1% in the 1--3 years age-group, the dominant Shigella subtype being represented by Shigella flexneri 2a (25.1%). As only 37.2% of the total number of dysentery cases were manifested by enterocolitis and a high proportion (33.3%) ran a chronic course, the disease was not immediately diagnosed, an inadequate treatment was applied and a great number of carriers appeared. This, together with the high receptivity of such communities, accounts for the endemoepidemic character of the infection. Antidysenteric vaccination with the VADIZEN Dr. Istrati live bacillus vaccine, followed by a period of postvaccinal protection, with diminution in the number of dysentery, carriage and enteritis cases, both among the vaccinated and the non-vaccinated children, proves the utility of this vaccine in closed children's communities.


[History of smallpox vaccination in Romania and source of the IC strains of vaccinia virus]. Smallpox existed in Romania since the 17th century, when both variolation and vaccinia were used for preventing the disease. Jenner's vaccination was performed in 1801 in Cluj and Tirgu Mures and extended to the entire country during the following 31 years. The vaccinia virus strain used for preparing the smallpox vaccine was received in 1893 from the Vaccine Institute of Berlin by Prof. Riegler of the Faculty of Veterinary Medicine, Bucharest. In 1949, it was taken over by the Cantacuzino Institute and has been carried through at most 27 passages in buffalo calves ; it is now designated as strain ICn+m27.


[Characteristics of the outbreak and control of an epidemic of bacillary dysentery of hydric origin]. In December 1978, an unexpected outbreak of acute gastroenteritis occurred in a shoe factory. The clinical, epidemiological and laboratory investigations established the hydric origin of the dysentery due to Shigella flexneri 3 a, caused by the illicit communication of the drinking water and industrial water mains. The antiepidemic measures promptly taken arrested the outbreak in three days ; there were no secondary, contact cases.


[Gastric secretion after vagotomy at different levels]. It is well known that all the different procedures of vagotomy have a great variability in the clinical results and a high incidence of positivity in the Hollander's tests, this probably due to the arrangement of the vagus nerves in the low third of the esophagus and its connection with the mienteric plexus. In a group of ten dogs with a gastric fistula we obtained first a sufficient number of assays with vagal stimulation, later on vagotomy was done at the level of the esophago-gastric union (EGU), getting a decrease in the gastric secretion of hydrochloric acid of 64%, afterwards a second section of the vagus nerves was practiced, five centimeters above the EGU having an inhibition of 90% and finally 95% was attained when the vagotomy was done 15 centimeters above the EGU. It is concluded that it is needed a long vagal resection of the last ten centimeters, instead of the classic section of the nerve at the gastroesophagic union; it is the same case with a parietal cell mass vagotomy.


[Evaluation of the safety and effectiveness of WHR-1142A in the treatment of non-specific acute diarrhea]. A randomized double-blind placebo controlled trial of the safety and efficacy of lidamidine hydrochloride (WHR-1142A) in thirty patients with acute nonspecific diarrhea was conducted. During their 29-hour hospital treatment period, the average number of bowel movements for each ten patient treatment group was: placebo, 5.1: lidamidine hydrochloride (10 mg), 2.4; lidamidine hydrochloride (18 mg), 2.5. The average weight of the feces of the patients in each treatment group was: placebo, 576 grams; lidamidine hydrochloride (10 mg), 364 grams; lidamidine hydrochloride (18 mg), 435 grams. Time intervals between each of the first two doses were greater for those patients in the active treatment groups (lidamidine hydrochloride) when compared to the placebo group. Overall evaluation of therapy was rated by physician and patient at end of study: placebo, 10 of 10, not effective; lidamidine hydrochloride (10 mg), 10 of 10 (100%) effective; lidamidine hydrochloride (18 mg), 10 of 10 (100%) effective. Vital signs and laboratory values remained within normal ranges throughout the duration of study, and no clinically significant adverse effects were reported.


[Emphysematous cholecystitis (author's transl)]. A case of emphysematous cholecystitis is reported. The gallblader size in this case was 25 x 12 cms. The patient underwent successful cholecystectomy and responded adequately to cloramphenicol, peniciline and metronidazol. The late antibiotics are usually recommended due to the prevalence of Clostridia and Escherinchia bacterial infections in the gallbladder of patients with this illness.


[Demonstration of a parotid salivary immunity reaction during chronic oral candidiasis (author's transl)]. The study of specific salivary anti-candida immunoglobulins during chronic candidiasis of the oral mucosa demonstrates the existence of a local parotid immunity reaction, the total IgA level is not altered.


[Treatment of Binder's maxillonasal dysostosis (author's transl)]. The treatment of Binder's maxillonasal dysostosis raises many problems and difficulties of both orthodontic and surgical natures. Orthodontic therapy should be conducted as early as possible and include, principally, an advancement of the maxilla by heavy extra-oral postero-anterior traction on an orthodontic mask. If good occlusion is obtained the patient can then be treated to improve the anatomical conditions of the muscles of the nose and upper lip. Maxillary, and more rarely mandibular osteotomies are indicated in cases with poor occlusion. When occlusion is reasonably good the hypoplasia has to be compensated for by using large portions of ilac bone to reconstruct the ridge and point of the nose. A preseptal graft on the ridge and secondarily, revisions of the point of the nose are often essential to ensure the best results.


A comparison between the transthoracic electrical impedance method and the direct Fick and the dye dilution methods for cardiac output measurements in man. In fourteen patients referred for preoperative evaluation of heart disease we compared the transthoracic electrical impedance method to the direct Fick (four patients) and dye dilution methods (ten patients) for estimation of cardiac output. On statistical analysis of paired differences we found no reliable agreement between the absolute impedance values and the reference methods. The reproducibility was, however, acceptable, and the coefficient of variation for impedance cardiac output was 7.8%, and for impedance stroke volume 7.6%. Our conclusion is that in patients with advanced heart disease cardiac output cannot be determined with accuracy with the impedance cardiographic method. In clinical practice this must be considered so important, that we hesitate to use the method for monitoring cardiac output in critically ill patients even if the reproducibility for individual changes is acceptable.


Acetate production and substrate availability in the dog. Arterial plasma acetate, glucose and NEFA concentrations were measured during loading with glucose/insulin and fat emulsion/heparin, and during epinephrine and norepinephrine stimulation in dogs. The expected alterations in glucose and NEFA concentrations were found. Acetate concentrations were not influenced, and remained constant in all experiments. Since acetate removal from the body pool is mainly concentration dependent, it may be concluded that acetate production was constant under the conditions described. "Overflow disposal" of AcSCoA to yield free acetate in cases of high rates of AcSoA-production does not occur as long as the Krebs cycle is intact.


A modified [125I]fibrinogen technique for thrombus detection in the whole leg. The [125I]fibrinogen uptake test was modified to give a quick result, and improve sensitivity and specificity in the diagnosis of deep venous thrombosis (DVT). At least 800 counts were recorded at each measuring point. The leg veins were emptied more effectively. Thus the proximal thigh could be evaluated and the influence of varicose veins reduced. The feet and the leg points were measured in a zig-zag order (from side to side) to avoid systematic errors in early diagnosis. The modified test detected 62% of the thrombi 1 h after injection, 82% after 1 day and 95% after 2 days. The method still lacks in specificity; this is unavoidable since fibrin accumulates in various other conditions than DVT. The combination of high sensitivity and low specificity makes the modified test reliable as a screening procedure, but not as an independent method.


Effect of aggregates on albumin standardization. In order to investigate the consequences of presence of aggregates in human albumin standards, pools of monomer, dimer and polymer albumin were prepared and quantitated by three total-protein methods (biuret, Folin-Lowry and spectrophotometry at 279 nm) and by four different albumin methods (dye-binding by bromcresol green, electroimmunoassay, radial immunodiffusion and automated immunoprecipitation). Biuret was chosen as the reference method and the monomer was used as the standard in all methods. Both the total-protein and albumin methods gave values for aggregated albumin different from the biuret values. The maximal bias occurred in radial immunodiffusion where quantitation of the dimer and polymer pools gave only 67% and 48% of the biuret values, respectively. In five commercial albumin preparations investigated, the content of di- and polymer varied from 3 to 34%. Uncritical use of albumin preparations in standardization may thus introduce bias in the measurements.


Erythrocyte superoxide dismutase deficiency in Fanconi's anaemia established by two independent methods of assay. Erythrocyte superoxide dismutase (SOD; E.C.1.15.1.1) levels were quantitated in human haemolysates, both by an immunological technique and by an activity assay. The erythrocyte SOD activity level in a group of seven Fanconi's anaemia patients was significantly decreased (27%, on the average) compared to a control group of nineteen healthy individuals. The fact that both the activity per antigenic unit and the electrophoretic mobility of the erythrocyte SOD was normal indicates that the deficiency in these Fanconi's anaemia patients is most probably not due to a mutation in the structural gene for the enzyme but more likely due to a disturbed mechanism regulating the SOD level in the erythrocyte.


Pre-endoscopic medication. A randomized double-blind trial of atropine and meperidine as a supplement to diazepam. The effects of an intramuscular injection of atropine (0.6 mg) and meperidine (1 mg/kg body weight) 30 min before topical benzocaine and intravenous diazepam administration were compared with those of a control group that received only benzocaine and intravenous diazepam in a randomized double-blind controlled trial of premedication for upper gastrointestinal endoscopy in 100 consecutive patients. Atropine and meperidine decreased the amount of salivation and gastric secretion (p less than 0.001 and p less than 0.001, respectively) and increased the period of sedation (p less than 0.001). The patients' and examiners' evaluation of the procedure was the same with either premedication regimen. Neither regimen affected the success rate of the endoscopy. Regardless of the regimen used, every patient who underwent endoscopy stated that they would consent to another examination, if necessary. Patients judged before endoscopy to be most apprehensive tolerated the procedure least, and those judged to be least apprehensive tolerated the procedure best, irrespective of premedication. The addition of meperidine and atropine to a premedication regimen of diazepam and topical benzocaine does not appear to be beneficial.


The release of enterokinase following secretin and cholecystokinin-pancreozymin in man. The release of enterokinase into human duodenal fluid was studied after intravenous injections of secretin and cholecystokinin-pancreozymin (CCK-PZ). In five control subjects there was a significant release of the enzyme after stimulation with either hormone. A similar release of enterokinase was observed after hormonal stimulation in three patients with total biliary obstruction and in four patients with pancreatic exocrine insufficiency. These results suggest that the hormone-mediated release of enterokinase is independent of bile salts and trypsin in man. This release of enterokinase into duodenal fluid may be physiologically important in protein digestion.


Gastric ulcer therapy with a pepsin-inactivating peptide, pepstatin: a double-blind randomized clinical trial. Sixty consecutive patients with gastric ulcer were studied at random after treatment with 100 mg pepstatin or 100 mg placebo seven times a day at fixed hours and controlled 2, 4, 8, and 12 weeks after initial diagnosis. Examinations comprised clinical symptoms and endoscopic evaluation of ulcer healing. Eight patients were withdrawn from the study. Ulcer healing and symptoms were better with placebo than with pepstatin, but a type-2 error of a 10% effect in favour of pepstatin may be overlooked. In gastric ulcer treatment, pepstatin seems to be of only fringe benefit, if of any benefit at all.


Premedication for gastroscopy. A comparative study of diazepam, dixyrazine, and placebo. In a study of 52 consecutive out-patients the effects of diazepam and dixyrazine were compared with each other and with placebo as premedication for elective gastroscopy. All patients also received topical lidocaine and intravenous administration of propantheline bromide immediately before the examination. No difference was found between diazepam and dixyrazine, but they were both significantly superior to placebo in relieving anxiety, retching, and eructations.


Phytohaemagglutinin responsiveness of non-adherent nude spleen cells. Non-adherent spleen cells from athymic nude mice showed incorporation of tritiated thymidine (3H-TdR) at a level comparable to that of non-adherent cells of normal mice when stimulated with the T-cell mitogen phytohaemagglutinin (PHA). The optimal dose of PHA was 50 microliter/ml for nude cells, a concentration that does not stimulate normal cells. In comparison, 2.5 microliter/ml PHA was optimal for cells of normal mice. Anti-theta serum plus complement treatment of the non-adherent nude spleen cells reduced 3H-TdR incorporation by approximately 50%, suggesting that some of the responding cells carried the theta antigen. Direct immunofluorescence showed that the non-adherent nude spleen cells contained 6-9% theta-positive cells. In comparison, more than 80% of the PHA-induced nude blast cells were theta-positive. PHA-induced DNA synthesis of normal mouse spleen cells was inhibited by adherent nude spleen cells. No theta-antigen or surface immunoglobulin could be demonstrated on these inhibitory cells, suggesting that they belong to the macrophage system of the nude mouse spleen.


Plaque assay with protein A-coated erythrocytes for the evaluation of human immunoglobulin-secreting cells induced by pokeweed mitogen. Cells secreting IgM, IgG and IgA were evaluated in cultures of human peripheral blood lymphocytes stimulated in vitro with pokeweed mitogen by a haemolytic plaque assay using protein A-coated erythrocytes in the presence of class-specific antisera. Kinetic study revealed that immunoglobulin-secreting cells appeared after 3 days of culture and peaked between days 5 and 7. IgM-secreting cells predominated throughout the culture period. This plaque assay is a useful and sensitive in vitro test for the evaluation of polyclonal B-cell activation in humans and may provide a good approach to the study of disturbances in the synthesis of the various classes of immunoglobulins.


Diagnostic specificity of immunoglobulin M (IgM) response in differentiation Legionnaires' disease from psittacosis. Specific IgM and IgG antibody responses to Legionella pneumophila (LDB) and Chlamydia psittaci (PSI) in serum specimens from 22 cases of Legionnaires' Disease (LD) were examined by micro-immunofluorescence (IF) tests to explore the diagnostic significance of the IgM antibody response. Serial samples from 5 patients with LD showed greater than or equal to 4-fold changes in IgG antibody against LDB and PSI. All 5 patients possessed IgM antibodies against LDB but not against PSI. In single convalescent serum samples from 17 additional cases, 16 exhibited IgG and 15 showed IgM antibodies against LDB; all 17 exhibited IgG but not IgM antibodies against PSI. The IgM antibody response appears more specific than the corresponding IgG response in the serodiagnosis of LD, and may be valuable in differentiating LDB infections from those due to PSI.


Urography and isotope renography following renal transplantation. The clinical yield from routine urography following renal transplantation was compared with that from isotope renography. In 50 recipients of renal transplants, 59 urograms and 55 renograms were studied. The most common pathologic finding at urography was renal papillary necrosis (in 6 patients). This condition had no obvious correlation with the further fate of the transplant. There were no other significant pathologic changes. It is concluded that isotope renography can be regarded as sufficient for routine follow-up. One baseline urogram is useful, but additional urographies should be carried out only when clinically indicated.


Renovascular hypertension after kidney transplantation. The development of hypertension after kidney transplantation was examined in a consecutive series of 83 transplantations (79 patients) with a graft survival of more than 30 days. After transplantation, 50% of the normotensive recipients developed mild or severe hypertension, while 74% of the hypertensive recipients remained hypertensive. Stenosis of the graft artery with a narrowing of the diameter of more than 50% was found in 13 patients and in 3 patients a minor or peripheral stenosis was found. Significantly more stenoses were seen in the presence of two donor arteries, whereas no other etiological factors could be shown. In arterial stenosis, severe hypertension was established within a few months after transplantation, but in spite of satisfactory controlled blood pressure and good graft function, hypertensive crises could arise. It is therefore concluded that arteriography and renin analysis should be considered in all cases of severe hypertension, and surgical correction should be considered when arterial stenosis is present.


Comparison of a new parallel-flow, plate dialyser and a hollow fibre dialyser. A new, low-price, parallel-flow, plate dialyser--the LPP dialyser--has been compared with a hollow fibre dialyser--the C-DAK dialyser. At dialysate flows of 510-680 ml/min and blood flows 140-200 ml/min the clearances of urea, creatinine and uric acid were 30-40 ml/min greater in the C-DAK dialyser. In the patients the mean creatinine at end of dialysis increased 1.7 mg% during treatment with the LPP dialyser. The ultrafiltration rate was found to be greater in the LPP dialyser than in the C-DAK dialyser. No membrane ruptures were observed in 200 LPP dialysers compared to 2 of 1200 C-DAK dialysers. The mean residual blood volume was 6.4 ml in the LPP dialyser + blood lines and 5.3 ml in the C-DAK dialyser + blood lines. The difference is insignificant. The LPP dialyser may be useful when dialysis is carried out frequency and when overhydration is a major problem.


Continuous blood glucose monitoring and characteristics of diabetes in patients on maintenance haemodialysis treatment. The glucose metabolism of diabetes mellitus during maintenance haemodialysis treatment was studied in four patients with endstage renal failure. There was a large day-to-day variation in the predialysis blood glucose levels, which it was difficult to control by adjusting the insulin dose. In spite of very high blood glucose levels, blood lactate and beta-hydroxybutyrate were not elevated. Triglycerides were markedly and constantly elevated, in no apparent association with the predialysis blood glucose level. The patients were shown to release moderate amounts of glucose, beta-hydroxybutyrate and lactate into the dialysate during the dialysis period. A technique of continuous blood glucose monitoring during the haemodialysis period was applied. With this technique blood sugar levels were accurately determined during the whole dialysis period. A rapid drop in the blood glucose level was found in apparent association with an aggravation of symptoms. A very marked tendency to hypoglycaemia was also revealed. It is concluded that the technique is a valuable aid in the proper management of diabetes in these cases.


The placebo effect.

The placebo effect. The most important factors influencing the effects drugs and other therapeutic measures are discussed. i.e. 1) variations between different patients--"individual factors", 2) variations in the environment--"occupational factors", 3) variations in compliance, 4) variations in the spontaneous course of the disease, and 5) variations in the effect of placebo. It is pointed out that "the placebo effect" must always be allowed for when evaluating different methods of treatment.


Immunoprofile studies in patients with pulmonary tuberculosis. I. Correlation of pretherapy cellular tests with characteristics of the disease. Cell immunity profiles were determined in 46 patients with previously untreated pulmonary tuberculosis, confirmed bacteriologically, and in 21 blood donors. Evaluations were made of T-lymphocytes, blastic transformation of lymphocytes after stimulation with phytohaemagglutinin or tuberculoprotein, and migration inhibition of blood leukocytes stimulated by tuberculo-protein. The average proportion of T-lymphocytes in the peripheral blood was significantly diminished in the group of tuberculous patients, and the intensity of the decline correlated both with age and extent of the disease. Similarly, migration of leukocytes in tuberculous patients was, in the presence of tuberculoprotein, markedly inhibited. The inhibition was correlated to the extent of the disease, expressed as the number of bacilli excreted. It can be concluded that, despite the depression of immunocompetent cells, active daughter clones under the influence of a specific antigen are capable of producing a factor conditioning migration inhibition.


Lung compliance and lung morphology following artificial ventilation in the premature and full-term rabbit neonate. Rabbit neonates delivered on day 27--30 of gestation were subjected to intermittent positive pressure ventilation (IPPV) for 60 min. Tidal volume was standardized to  10 ml/kg, and the insufflation pressure required to maintain this tidal volume was recorded. The quasistatic compliance of the lung-thorax system, corrected for variations in body weight, was significantly lower in animals delivered on day 27--28 than in those delivered on day 29--30. Immature animals with low lung-thorax compliance (less than 0.40 ml/cm H2O.kg) regularly developed widespread necrosis of bronchiolar epithelium following IPPV, whereas no such lesions were observed in mature animals. It seems probable that these lesions are secondary to overdistension of bronchioles during IPPV and that this abnormal expansion pattern is related to a deficiency of surfactant in the lungs of immature newborn animals.


[Absorption and hematologic effect of streptokinase-streptodornase (varidase) after intracavital or oral administration]. A series of patients who received intracavitary streptokinase/streptodornase after thoracotomy or laparotomy were compared with a control group. They showed a highly significant increase in plasma streptokinase tolerance, indicating absorption of the streptokinase from the cavity. Changes in blood coagulation, plasma cell count and immunoglobulins were not observed. In a series of patients with leg ulcers treated with streptokinase/streptodornase by mouth, no increase in plasma streptokinase tolerance was observed, indicating that orally administered streptokinase is not absorbed from the gastro-intestinal tract.


[Nuclear medical methods for the detection of coronary disease]. Three developments in recent years have speeded the advance of nuclear cardiology: gamma cameras have become available, computers have been introduced into nuclear medicine, and radionuclides such as Tc99m and Tl201 have become easily obtainable for imaging purposes. The imaging of the myocard with Tl201 has its established place in cardiology. Sensitivities of about 90% and specificities of about 80-90% make Tl201 exercise tests a powerful tool for detection of coronary artery disease (CAD) in a preselected population. Ejection fraction can be measured at rest and during exercise where an absent increase during physical stress is clearly abnormal (and also not necessarily specific for CAD). Sensitivities of 80-90% and specificities around 90% for detection of CAD seem possible. Wall motion abnormalities again can be brought out during exercise and serve to localize impaired ventricle function. Tc99m-pyrophosphate studies seem to have some implications to prognosis if myocardial accumulation persists. Only preliminary reports are thus far available for these two studies.


[Myasthenia gravis and visceral lupus erythematosus]. The patient described in this clinical demonstration suffered from severe myasthenia gravis shortly before the detection and for 3 years after surgical removal of a cystic thymoma. At the end of this period, when the myasthenia subsided, she developed systemic lupus erythematosus simultaneously with pleural implantation metastases of the thymoma. After local radiation therapy and under systemic immunosuppression she has remained asymptomatic since the spring of 1978. The pathogenetic and immunogenetic basis of myasthenia gravis and autoimmune diseases associated with thymoma and thymus hyperplasia is reviewed, and a plea is entered for more comprehensive and integrative internal medicine.


[Granulocyte defence against bacterial infection in diabetes mellitus with special reference to bactericidal activity]. Granulocytic defence against bacterial infection has been studied in a group of diabetic patients. With the skin chamber method markedly reduced leukocyte mobilization in vivo which was independent of metabolic compensation was found in all diabetic patients. Investigation of phagocytic function of Latex particles and bacterial killing of E. coli revealed firm dependence on metabolic regulation: in decompensated diabetes mellitus the two function tests were clearly pathological, whereas in the compensated metabolism there was no difference between normal individuals and diabetics. Thus, on granulocytic defence pathway analysis, this appears to confirm that reduction of infection depends on how diabetes is controlled.


[Discontinuation of chronic hemodialysis due to improved kidney function caused by the control of arterial hypertension]. Following effective long-term antihypertensive therapy, hemodialysis could be discontinued in 4 patients with malignant hypertension in view of improved renal function. Diagnoses included nephroangiosclerosis (2 cases), scleroderma and chronic glomerulonephritis. All patients had symptoms of hypertension or renal disease for at least one year prior to initiation of hemodialysis treatment. At the outset, blood pressure averaged 249 +/- 43/150 +/- 22 mm Hg (mean +/- SD) and all patients had grade IV hypertensive retinopathy. After 1 to 20 months strict blood pressure control, renal function had improved to such a degree that hemodialysis could be discontinued. One year later, blood pressure averaged 138 +/- 20/89 +/- 6 mm Hg and serum creatinine 3,2 +/- 1,2 mg/100 ml. These data suggest that in hypertensive patients with chronic renal failure, strict control of blood pressure is of the utmost importance whatever the severity and nature of the underlying renal disease.


[Hypertension in unilateral (non-vascular) nephrosclerosis: renin activity in the venous kidney blood and effect of nephrectomy]. 13 patients (9 females, 4 males) with hypertension and unilateral (non-vascular) small kidney underwent nephrectomy. Before surgery, renin activity (PRA) was measured in renal vein blood before and/or 15 and 30 minutes after intravenous stimulation with 40 mg furosemide. From these PRA values renin rations (PRA affected side/PRA unaffected side) were calculated. A ratio of greater than or equal to 1.5 was considered to be significant. After a mean postoperative observation period of 3.9 +/- 1.3 years 6 patients (46%) were cured and 6 were improved. In only 1 patient (8%) did hypertension remain unchanged. No differences could be observed between the renin ratios of cured and improved cases. Furthermore, in no patient was a correlation found between preoperative renin ratios and the degree of postoperative blood pressure reduction. Finally, both patients with renin ratios less than or equal to 1.4 were cured by surgery. Marked differences between cured and improved patients were seen in preoperative blood pressure values, age, duration of hypertension and renal function. Cured patients were younger and had much lower mean systolic and diastolic blood pressure values, shorter duration of hypertension and better renal function than improved patients. These results show that the diagnostic and prognostic validity of renal venous renin ratios is very limited in patients with a unilateral (non-vascular) small kidney. In these patients the effect of nephrectomy can already be predicted by analyzing simple anamnestic, clinical and chemical data.


Sprengel's deformity. Radiology of the pathologic deformation. A unique specimen of unilateral Sprengel's deformity, and contralateral normal pectoral girdle, were studied morphologically and roentgenographically. The cervical spine exhibited multiple abnormalities involving both the vertebral centra as well as the posterior elements (Klippel-Feil abnormality). A small spina bifida involving C5 and C6 was present. Abnormalities of the spinous processes included an articulation with a well-formed omovertebral bone that also articulated with the vertebral (infraspinatus) margin of the scapula. Secondary (presumed epiphyseal) ossification was present in the omovertebral bone at the distal end. The scapula was deformed, especially in the supraspinatus portion. The clavicle was shorter and had a different contour.


Rapid identification of yeasts by serological methods: a combined serological and biological method. A total of 387 yeasts from the contents of the digestive tracts of domestic animals and poultry were identified by slide agglutination tests using factor antisera and urease tests. The results of this serological test were very satisfactory with respect to accuracy and rapidity, particularly when performed in combination with concomitant physiological tests only for assimilation of inositol and potassium nitrate. It may be concluded that such a combination of serological and biological tests is very useful for identifying yeast strains from various sources.


Overwhelming opportunistic histoplasmosis. A patient with chronic granulocytic leukemia developed overwhelming histoplasmosis. During massive fungemia, 59% of peripheral blood neutrophils contained yeast forms. Disseminated intravascular coagulation occurred. Histoplasma capsulatum was isolated not only from the patient's tissues and urine, but also from a serum sample submitted to a reference laboratory for serological testing. The microorganism was demonstrated by specific immunofluorescent staining of peripheral blood films. We suggest that histoplasmosis deserves a definite place on the roster of "opportunistic fungi".


Opportunistic fungal infection by Fusarium oxysporum in a renal transplant patient. A white female with chronic glomerular nephritis received a renal transplant in 1971. After 1 year, Livido Reticularis (LR) developed and in 1976 erythematous, painful nodules formed on the LR and ulcerated. The patient also suffered diffuse calcification of the major blood vessels and small arterioles of the extremities with progressive necrosis and gangrene of the fingers. Hyperparathyroidism was evident. The necrotic ulcers yielded Candida albicans and Fusarium oxysporum; both organisms were seen in histological preparations. The ulcers were excised and grafted; no specific antifungal therapy was given.


Cryptococcus neoformans: gastronomic delight of a soil ameba. During 7 days of incubation in vitro the trophozoite stage of the free-living soil amoeba, Acanthamoeba polyphaga, phagocytized and killed 78-97% of the cells of three strains of Cryptococcus neoformans. With one strain, incubation time was increased to nine days and 99% of the yeast cells were killed. It was calculated that during 4-9 days of incubation a single trophozoite phagocytized and killed a daily average of 84 yeast cells. The lethal effect of A. polyphaga on C. neoformans may represent a biological control mechanism in nature. Some of the surviving cells of C. neoformans developed into colonies containing pseudohyphae; these pseudolhyphal forms may be a biological 'escape hatch'.


Requirement of heat-labile opsonins for maximal phagocytosis of Candida albicans. The requirement for heat-labile opsonins for phagocytosis of 2 serologically distinct strains and a number of clinical isolates of Candida albicans was examined by a previously described radiometric technique. The results indicated that both strains and all 10 isolates of C. albicans examined required heat-labile opsonins for maximal phagocytosis. The data suggest that heat-labile opsonins play an important role in immunity to C. albicans. However, the possibility that some strains of C. albicans may not utilize heat-labile opsonins cannot be excluded.


Comparative study of the effect of thiabendazole and fungizone on Histoplasma capsulatum in macrophages. The antifungal properties of Fungizone (amphotericin B intravenous solution) and thiabendazole on Histoplasma capsulatum within guinea pig macrophages were compared using the staining method and a newly developed plating method to determine the viability of intracellular H. capsulatum. The two methods were compared to determine the effectiveness of Fungizone and thiabendazole on H. capsulatum within macrophages. Fungizone was fungicidal for intracellular H. capsulatum, killing 99.9% of the yeasts at a concentration of 0.5 microgram/ml. There was some indication that non-viable intracellular yeasts were stained which could result in misinterpretation of the effectiveness of Fungizone using the staining method unless the yeasts are very closely examined for staining abnormalities. There was a good correlation between the two methods to demonstrate suppression of the multiplication of intracellular H. capsulatum in macrophages treated with 50 microgram/ml of thiabendazole. Thiabendazole was lethal for some intracellular H. capsulatum.


Vagotomy as a treatment for morbid obesity. Based on animal experiments, on the original clinical observations of Dragstedt, and on similarities with appetitive behavior after jejunoileostomy, truncal vagotomy has been attempted as a treatment for morbid obesity in 13 patients with a mean weight of 123 kg. Weight decreases of 20 to 30 kg (range, 2 to 64 kg) have been observed so far. Impaired gastric emptying alone does not seem to account for the decreases. Possibly, improved glucose tolerance with reduction of hyperinsulinemia and other hormonal and/or neural effects are responsible for weight loss and lack of "hunger." The period of observation is short, yet 2 of the 13 patients seem to be failures, of whom one had gastric hyposecretion before operation. It is too early to consider the procedure for general clinical use, which must await further research efforts.