Fate of thymine-containing dimers in the deoxyribonucleic acid of ultraviolet-irradiated mutator T1 Escherichia coli transductants. In order to determine whether a relationship generally exists between the mutator property (mutT1) and repair of ultraviolet (UV) irradiation damaged DNA, we performed spontaneous mutation rate and UV-survival determinations without and with acriflavin (4 mug/ml) in P1 phage mediated mut T1 Escherichia coli transductants. The strains constructed were assumed to be coisogenic except for the mutator factor. The mutT1 uvrA, uvrB or exrA transductants had mutation rates similar to the donor strain. Double mutants containing mutT1 and uvrB or exrA had the same level of UV survival as the parent with the same mutator phenotype. Mutator strains were normal for host-cell reactivation of UV-irradiated phage T1, and phage lambda was UV-inducible. The fate of UV-induced thymine-containing dimers in the deoxyribonucleic acid (DNA) of mutT1 transductants was investigated. Dark repair of pyrimidine dimers is equally acriflavin sensitive in the nonmutator and mutator Hcr+ strains. During incubation in the dark, dimers were excised to the same extent from the DNA of the HCR+ mutator and nonmutator transductants, but remained in the DNA of the HCR- MUTANT. A preliminary report of these studies was presented at the 70th Annual Meeting of the American Scoeity of Microbiology, Boston, 1970.


Analaysis of photoenzymatic repair of UV lesions in DNA by single light flashes. XI. Light-induced activation of the yeast photoreactivating enzyme. Photoreactivating enzyme (PRE) from yeast (as semi-crude extract, or in highly purified form) shows increased activity if it is illuminated with near UV or short wavelength visible light prior to its use for photoenzymatic repair of UV-induced pyrimidine dimers in transforming DNA in vitro. This effect results from an alternation in PRE molecules changing those with low activity in the light-dependent step of the reaction to a higher activity. Light-induced activation of PRE preparations is slowly lost by dark storage for several hours to 1 day (faster at 23 degrees C than at 5 degrees C), but can be recovered repeatedly by renewed preillumination. The action spectrum for these preillumination effects generally resembles that for the photoenzymatic repair reaction itself, having its maximum in the same 355-385 nm region as the latter, but light of somewhat longer wavelengths (546 nm) is still effective. Preilluminated PRE is also more stable to thermal inactivation (65 degrees  C) than untreated enzyme.


The effects of temperature on genetic instability in Aspergillus nidulans. Previous work has shown that strains of Aspergillus nidulans with a chromosome segment in duplicate (one in normal position, one translocated to another chromosome) are unstable. Deletions occur from either duplicate segment. The present work has shown that most deletions occur from the translocated duplicate segment. Furthermore, it has been found that the overall frequency of deletions from a duplication is dependent upon the temperature of growth. The overall frequency of deletions from a chromosome III duplication is greatly enhanced by low temperatures, while the overall frequency of deletions from a chromosome I duplication is markedly enhanced by high temperatures. A temperature of 39.5 degrees C appears to enhance to overall frequency of deletions from the I duplication to the greatest extent. With regard to the non-translocated duplicate I segment, an increase in temperature progressively enhances the frequency of those deletions to which it is subject to far more deletions during a particular period of growth than during any other period, and at 42 degrees C, a section of the III duplication is subject to far more deletions during a given period of growth than during  any other period. Comparisons with other cases of genetic instability are made and common underlying connections are proposed.


The resistance of Micrococcus radiodurans to killing and mutation by agents which damage DNA. The resistance of Micrococcus radiodurans to the lethal and mutagenic action of ultraviolet (UV) light, ionising (gamma) radiation, mitomycin C (MTC), nitrous acid (NA), hydroxylamine (HA), N-methyl-N'-nitro-N-nitrosoguanidine (NG), ethylmethanesulphonate (EMS) and beta-propiolactone (betaPL) has been compared with that of Escherichia coli B/r. M. radiodurans was much more resistant than E. coli B/r to the lethal effects of UV light (by a factor of 33), gamma-radiation (55), NG (15) and NA (62), showed intermediate resistance to MTC (4) and HA (7), but was sensitive to EMS (1) and betaPL (2). M. radiodurans was very resistant to mutagens producing damage which can be repaired by a recombination system, indicating that it possesses an extremely efficient recombination repair mechanism. Both species were equally sensitive to mutation to trimethoprim resistance by NG, but M. radiodurans was more resistant than E. coli B/R to the other mutagens tests, being non-mutable by UV light, gamma-radiation, MTC and HA, and only slightly sensitive to mutation by NA, EMS and betaPL. The resistance of M. radiodurans to mutation by UV-light, gamma-radiation and MTC is consistent with an hypothesis that recombination repair in M. radiodurans is accurate since these mutagens may depend on an "error-prone" recombination system for their mutagenic effect in E. coli B/r. However, because M. radiodurans is also resistant to mutagens such as HA and EMS, which are mutagenic in E. coli in the absence of an "error-prone" system, we propose that all the mutagens tested may have a common mode of action in E. coli B/r, but that this mutagenic pathway is missing in M. radiodurans.


A protective effect of caffeine on the ethidium induced petite mutation in yeast. A prerequisite for petite induction by ethidium bromide (EB) is an initial covalent attachment of the drug to cytoplasmic DNA. This DNA modification is thought to initiate repair processes. The repair inhibitor, caffeine, provided a protective effect against the ethidium induced petite mutation at caffeine concentrations known to inhibit the repair of UV damage in cytoplasmic DNA (Fig. 1). Mitochondrial DNA isolated from yeast exposed to EB in vivo was not as degraded in the presence of both drugs as with EB alone (Fig. 2).


Induction of mitotic recombination with N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) in Saccharomyces cerevisiae. A comparison between treatment in vitro and in the host-mediated assay. Two methods, treatment in vitro and the host-mediated assay method, were compared in their ability to demonstrate the induction of MNNG of nitotic recombination in a diploid strain of Saccharomyces cerevisiae. MNNG had a strong activity in vitro but not in the host-mediated assay at the concentrations tested. When the genetic effects of MNNG have been tested in different test systems, sometimes negative, sometimes positive results have been obtained. The relevance of different tests for risk evaluation is discussed, and it is concluded from the data on MNNG that tests on whole mammals may sometimes give false negative results because the cells tested are, in parts of the body, less accessible to the mutagen. Increasing doses of MNNG by treatment in vitro gave decreasing frequencies of mitotic recombination, indicating damage to the recombinational system in the cells. Dose-response relationships for recombination and mutation are discussed.


Mutagenicities of nitrofuran derivatives on a bacterial tester strain with an R factor plasmid. Many nitrofuran derivatives are known to be mutagenic on Escherichia coli WP2 but not on Salmonella typhimurium TA1535, TA1536, TA1537 or TA1538. Ames and coworkers recently obtained a new tester strain of S. typhimurium, TA100, by putting an R factor plasmid, pKM101, into TA1535. We found that all mutagenic nitrofuran derivatives previously found to be mutagenic on E. coli WP2 were mutagenic on this new strain (TA100).


Steroid therapy in severe viral hepatitis. A double-blind, randomized trial of methyl-prednisolone versus placebo. The efficacy of corticosteroid therapy in severe viral hepatitis has never been demonstrated in a controlled clinical trial. For this reason, patients with severe viral hepatitis were randomly assigned to methyl-prednisolone or placebo treatment groups. The two groups were comparable in clinical findings, laboratory results and the presence of bridging necrosis on liver biopsy. Seven of the 14 patients assigned to methyl-prednisolone and two of the 15 assigned to placebo died during the 16-week study period. Although the apparent excess mortality in the steroid-treated patients is not quite statistically significant (P = 0.08), the trend persists when only patients positive for hepatitis B surface antigen (P = 0.04) are analyzed separately. Methyl-prednisolone does not enhance survival in patients with severe viral hepatitis, and it may be detrimental.


Replication control in a composite plasmid constructed by in vitro linkage of two distinct replicons. Although it carries two competent replication systems, a composite plasmid formed in vitro by linkage of the complete ColE1 and pSC101 plasmid replicons at their unique EcoRI endonuclease cleavage sites normally uses only the replication origin and functions of the ColE1 component. Restriction of ColE1 replication functions by DNA polymerase I deprivation results, however, in exclusive use of the pSC101 replication origin. When using the ColE1 replication system the composite plasmid is nevertheless incompatible with both the parent replicons. This suggests that a trans-dominant gene product is involved in plasmid incompatibility and supports negative control rather than positive control models for regulation of the initiation of DNA replication.


Hazards of plutonium with special reference to the skeleton. In the past attempts have been made to deduce plutonium toxicity in man from studies based on animal experimentation. An alternative method is to use the comparative dosimetry of plutonium and radium in man, with results broadly in agreement with maximum permissible levels set by the International Commission of Radiological Protection.


Induction of chronic progressive glomerulonephritis with immunofluorescent "mesangial pattern" in rats. Morphologic changes of extracapillary and chronic progressive glomerulonephritis with contracted kidneys, resembling those of adult human chronic glomerulonephritis, were induced in rats by a single injection of the purified glycopeptide and Freund's incomplete adjuvant into the hind footpads. The purified glycopeptide was prepared by TCA treatment or DEAE-cellulose chromatography from the nephritogenic glycopeptide which is known to have the ability to induce typical morphologic changes of membranous glomerulonephritis. As demonstrated in this report, the purification procedures result in complete elimination of contaminating free amino acids from the nephritogenic glycopeptide. The basic pathogenesis of the new experimental model of proliferative glomerulonephritis (including typical chronic glomerulonephritis) appears to have other than immune complex mechanisms.


High intravenous doses of methylprednisolone for acute cadaveric renal allograft rejection. In a group of 48 patients with a renal cadaveric allograft 38 acute rejection episodes were treated by increasing the daily prednisolone doses to 300 mg the first day, 200 mg the second day and 100 mg the third day, gradually tapering down over a matter of weeks. In a second group of 48 patients 39 acute rejections were treated by 1 g of methylprednisolone intravenously on alternate days with a maximum of four injections. Rejection treatment was successful in 26 of 38 in the first group (68%) and in 30 of 38 in the second group (76%). Complications such as gastrointestinal bleeding, aseptic necrosis and diabetes were more frequent in the first series.


Role of heparin therapy in the outcome of adult hemolytic uremic syndrome. Intravenous heparin therapy was associated with complete recovery of renal function in a young woman who developed adult hemolytic uremic syndrome while taking oral contraceptive agents. No controlled study is yet available but a review of an additional 36 reported patients who fulfill adequate criteria for the diagnosis of adult hemolytic uremic syndrome suggests that consideration should be given to a trial of heparin therapy in patients with this syndrome in whom renal biopsy shows recoverable glomeruli in the presence of persistent severe impairment of renal function.


Relationship between proteinuria and epithelial cell changes in minimal lesion glomerulopathy. The degree of fusion of glomerular epithelial cell foot processes was quantitated by determining the mean number of inter-process slip pores along 10 mum of basement membrane of peripheral capillary walls in 45 children with steroid-responsive nephrotic syndrome and minimal lesion glomerulopathy. Fusion was present in all biopsies performed when the child had proteinuria, but after remission the number of slit pores increased progressively towards normal over the next 4 weeks. There was a close correlation between the degree of fusion and the amount of proteinuria in those biopsied before remission.


A simplified method of percutaneous allograft biopsy. Although the renal allograft represents only a single-functioning kidney, it lends itself readily to biopsy from a percutaneous approach. Previous contraindications to percutaneous biopsy of a single normally situated kidney do not apply to the renal allograft because of its altered extraperitoneal and superficial location. The transplant operative note and palpation serve to adequately localize the kidney without the need of fluoroscopy, metal tagging or other X-ray techniques. The cortex may be safely approached through a perpendicular plane directed toward the lower pole or a tangential plane directed toward the lateral curvature of the allograft. The fibrous capsule's resistance to the neddle passage helps localize the periphery of the kidney. Hemostasis is augmented through manual pressure and subsequent pressure dressing. The technique was used in 62 renal biopsies in 62 different patients. Adequate material for microscopic and bacteriologic evaluation was obtained in all cases. There were three episodes of gross hematuria, but no prolonged bleeding, significant perirenal hematoma formation, infection or decreasing renal function after the biopsy procedure.


Intrasellar abscess.

Intrasellar abscess. A case of intrasellar abscess in a 31-year-old male, with pituitary insufficiency, visual field and acuity disturbances, is reported. In the pus extracted at surgery E. coli and Staphylococcus haemolyticus were identified. The patient died 20 days after the operation. Necropsy revealed the fibrous capsule of an abscess in the hypophyseal region and putriform tissue at the level of the hypothalamus, with three small tumours one of which proved to be a craniopharyngioma.


[Differential diagnosis of stroke in computer tomography]. Computertomography permits an early diagnosis of acute intracerebral hemorrhage a few hours after onset of symptoms. Embolic or thrombotic infarcts may be detected only after 2 to 3 days. Late manifestations of ischemic infarcts are unequivocal when confined to the circulation area of a cerebral artery. They must, however, be differentiated from small gliomas with edema, while in cerebral hemorrhage the differential diagnosis must consider bleeding from tumors and vascular malformations.


Review and new proposals for immunotherapy of brain tumors. The authors give a review of the possibilities and new approaches of therapy of malignant brain tumors.


[A case of primary reticulum cell sarcoma of the brain with uveitis (author's transl)]. In 1972, Neault and his co-workers reported seven cases of uveitis associated with intracranial reticulum cell sarcoma. Recently we have experienced a similar case for the first time in Japan. A 32-year-old woman registered on March 10, 1971, complaining of blurred vision in the left eye for about two weeks. By ophthalmic examination, left posterior uveitis was diagnosed but the etiology was unknown. Treatment with corticosteroids was begun, but her left eye continued to fail in spite of the treatment. In August, 1971, she complained of weakness of left arm and leg, and in October, she suffered from severe headache and vomiting. At that time, uveitis appeared in the right eye too. Neurological findings and carotid angiogram indicated a right cerebral lesion. On November 5, 1971, a right frontoparietal craniotomy was performed but no tumor was found. Since then her neurological and eye symptoms had been progressively worse. The patient died on July 12, 1972. Postmortem examination revealed the tumor infiltrating in the bilateral diencephalon, left internal capsule, left lenticular nucleus, left temporal lobe, midbrain, pons, left dentate nucleus, optic chiasma and intracranial portion of the optic nerves. But no tumor was found at any other parts of the body. Histologically the tumor was a reticulum cell sarcoma. The eyeballs were not examined histologically, but the uveitis in this case was thought to be closely related to the intracranial reticulum cell sarcoma. If the uveitis is resistant to the treatment, we must consider a possibility of reticulum cell sarcoma of the brain.


Immunofluorescence study of LRF-producing neurons in the cat and the dog. A fluorescent antibody study of LRF-producing neurons was made with antisera to synthetic LRF in normal male and female cats and dogs. Specific immunoreactive perikarya have been found in the rostral hypothalamus of both species. In the dog, specific immunoreactive perikarya have also been found in the pars oralis tuberi, the infundibular nucleus, the premammillary region, and even the dorsomedial and ventromedial areas and the rostral mesencephalon.


Evidence for a cholinergic component in the neuroendocrine control of luteinizing hormone (LH) secretion. The possible participation of cholinergic mechanisms in the control of LH and LH-RH secretion has been studied using an in vitro procedure. Halved anterior pituitaries (AP) of normal adult male rats were incubated for 6 h either alone or in the presence of hypothalamic fragments (HF). At the end of the incubation period, LH was evaluated in the media using a biological assay. AP halves, when incubated alone, released small amounts of LH. The addition of HF to the media containing AP tissue did not change LH release. Acetylcholine (Ach) added to the incubation flasks containing only AP tissue did not increase LH output of AP incubated without Ach. On the contraty, Ach significantly enhanced LH release when added to the incubation media of flasks simultaneously containing AP tissue and HF. Atropine had no effect on the release of LH from AP incubated alone. However the addition of atropine to the incubation media containing the halved AP, HF and Ach totally prevented the effects of Ach on LH release. Prostigmine enhanced the release of LH in the media containing AP plus HF. The LH-releasing effect of Ach in the AP plus HF coincubates was not influenced by the alpha-adrenergic blocking agent, phentolamine. These data indicate: (1) that from HFs incubated in vitro, Ach is able to release a factor (most probably LH-RH) which increases the secretion of LH from AP tissue; (2) that this effect of Ach follows the general rules of cholinergic systems (blockade by atropine, potentiation by prostigmine, etc.); and (3) that the LH-RH releasing activity of Ach is not linked to the liberation of catecholamines (dopamine, norepinephrine, etc.). These results suggest that cholinergic mechanisms play a role in the control of LH-RH release.


Studies on the site(s) of blockade by actinomycin-D of estrogen-induced LH release. Ovariectomized rats were injected with estradiol benzoate (EB) on day 1. The rats received propylene glycol alone (control) or with Actinomycin-D (Act-D) at 08.00 h, followed by EB at 12.00 h on day 3. Plasma LH levels were markedly elevated at 18.00 h on days 3 and 4 in control rats; Act-D treatment failed to modify the surge of LH on day 3, but abolished it on day 4. The site of Act-D's blockade of estrogen-induced LH release was investigated. Act-D treatment suppressed serum levels of LRF while it failed to modify either hypothalamic LRF content or noon levels of pituitary and serum LH on day 4. Act-D treatment consistently reduced the weight and the ribonucleic acid (RNA) content of the pituitary; a similar effect on RNA in the medial basal hypothalamus was not detected on day 4. On the other hand, electrochemical stimulation of the medial preoptic area of Act-D-treated rats on day 4 raised plasma LH significantly. However, the elevations at 45 min after stimulation were less in Act-D-treated than in control rats. Similarly, a significantly smaller response of LH release was observed at 15 min following intravenous injections of LRF in Act-D rats than in controls. These studies suggest that Act-D-sensitive steps exist at more than one site on the preopticotuberal pituitary axis involved in the stimulatory feedback action of estrogen on LH release.


Locked-in syndrome caused by a tumor.

Locked-in syndrome caused by a tumor. A case of locked-in syndrome is described. Clinical and radiologic evidence suggested the presence of a brain-stem tumor. Autopsy showed that the patient had a reticulum cell sarcoma. This is the first reported case of locked-in syndrome caused by a tumor.


Equal treatment and unequal benefits: the Medicare program. This paper analyzes the distribution of Medicare benefits among elderly persons on the basis of income, race, and geographical location. It first presents available statistical evidence from Medicare on the distribution of benefits and the magnitude of differentials among these elderly. It then sorts out the contribution to differentials arising from differences in the availability of medical resources. prices of medical services, and other demographic factors. The importance of various Medicare program features on remaining differentials--such as the cost-sharing provisions of Medicare, reimbursement policies, and nondiscrimination enforcement procedures--are then investigated. The effect of health status on utilization of medical services by the elderly is also analyzed, and the distribution of Medicare benefits by income for elderly persons of similar health status is presented. The paper concludes with recommendations for reducing differentials in Medicare benefits and indicates those policy changes which would result in a distribution of benefits more closely related to health care needs of the elderly.


The contributions of Henry E. Sigerist to health service organization. Henry E. Sigerist made profound and strikingly original contributions to health service organization. Not only did he expand greatly our concepts of the functions of medicine, but he redefined health in a manner which was later to be paraphrased by the World Health Organization. Sigerist's account of the evolution of the physician and his discussion of the role of the people in the fight for health provide important new insights into current realities, while his remarkable analysis of the genesis of national health insurance makes it possible to understand its continued absence in the United States. Although he was in the forefront of the campaign for national health insurance, Sigbrist always considered it inferior to a national health service. His thorough studies of the Soviet national health service opened new vistas in the promotion of health and prevention of disease and the development of team practice in health centers. Sigerist's impact was world-wide, and was particularly important in Chile, Cuba, China, and Great Britain.


FSH and LH response to LHRF in Kallman's syndrome. The olfacto-genital syndrome (Kallman's syndrome) is believed to be primarily an hypothalamic disorder resulting in hypogonadotropic hypogonadism or hypo-ovarianism and anosmia. The pituitary response in 2 patients was measured on dialy subcutaneous injections of 100 mug of LHRF. One of the patients was also studied in a similar fashion by administration of LHRF intravenously for 4 consecutive days. A greater response occurred with the subcutaneous route.


Gonadotropin release in patients with androgen insensitivity. Testicular feminization syndrome. Two siblings are presented, both with classic androgen-insensitivity syndrome (AIS). Endocrine testing was carried out and then gonadectomy was performed. Studies in these patients with AIS revealed low control serum FSH. In these patients serum FSH was not significantly suppressed by intravenous estrogen nor adequately stimulated by FSH-LH-releasing hormone but rose normally after castration. The various studies are interpreted in the light of the known kinetics of pituitary gonadotorpins and their modulation by gonadal steroids. A third sibling is also presented.


Treatment of urinary stress incontinence. Use of dermal graft in the sling procedure. Use of dermal graft for a urethral sling in treating urinary stress incontinence is described. This tissue has potential advantages of availability, strength, and freedom from side effects.


[A method of measuring cell orientation]. A method is described for measuring cell nuclei orientation in culture. The nuclear orientation in the experiment was compared with that obtained in the model experiment with electronic computer. The method developed allows to compare nuclear orientation in parts of culture which differ both by area and number of nuclei. The method can be modified for measuring cell nuclei orientation with reference to the substrate relief. Examples are given of the method's application for comparing orientation of mouse embryonic fibroblasts and cells of the strain L.


[Hormonal regulation of gonadal function and reproduction in fish]. On the basis of contemporary data about neurohormonal control of gonadal function in fishes, the hormonal control of reproduction during the normal sexual cycle in sturgeons is considered. The data are given on the state of hypophysis in sturgeons in cases of gonadal function disturbances and the problem is discussed of functional interaction between different components of the system of interrelated organs which takes part in the control of reproduction. Methods of hormonal stimulation for obtaining mature eggs and sperm in sturgeons are considered and a new variant of hormonal influence is suggested.


[A radioautographic study of the turnover and differentiation of mast cells in normal mice and mouse radiation chimeras]. The patterns of renewal of the previously labeled by 35S-sulphate mast cells of peritoneal liquor and loose connective tissue were investigated in normal mice, after their irradiation and transplantation of singenic and xenogenic bone marrow (radiation mouse chimaeras). The renewal of labeled mast cells in the peritoneal liquor proceeds markedly (ca. 10 times) more intensively than in the loose connective tissue. A stage of lymphocyte-like cells-precursors actively synthesizing sulphomucopolysaccharides is established in the series of differentiation of mast cells during postnatal ontogenesis. The duration of this stage amounts to 10-15 days. The patterns of renewal of the previously labeled by 35S-sulphate mast cells do not differ markedly in normal animals and radiation chimaeras.


[Participation of transplanted xenogenic bone marrow cells in an inflammatory reaction]. The course of inflammation reaction was studied both in the lethally irradiated mice just after the implantation of the great number of rat bone marrow cells and the xenogenic radiation chimaeras. The transplanted donor cells did not participate in the inflammation reaction in the lethally irradiated animals just after the implantation of xenogenic bone marrow. The cells of donor type were found in the inflammation focus only after the repopulation of radiation-devastated blood-forming organs of the recipient by the transplanted xenogenic bone marrow cells.


Treatment of external ocular Candida infections with 5-fluorocytosine. 15 patients who suffered from severe and prolonged external Candida ocular infections and who had not responded to Mycostatin and/or Amphotericin B treatment, were successfully treated with 5-Fluorocytosine administered topically or combined topical-orally. In all patients, a cure was achieved after a treatment period of approximately 6 months. No side effects were observed and no resistance to the drug developed.


[Symmetrical shortening of both humeri (author's transl)]. In a Chinese boy from Taiwan shortening of both upper arms were seen. No evidence of exogenous causation was found in this case nor in simular cases reported in the literature.


[Alport's-syndrome: diagnosis, light- and electronmicroscopic findings (author's transl)]. Alport's syndrome is a hereditary nephropathy with grave prognostic consequences. The occurrence of this disease is probably more frequent than was assumed until now - many cases are not immediately recognized as such. It is possible to make a clinical diagnosis from detailed family histories and through careful examinations of family members including audiometric tests. In the early stages of the disease children merely have recurrent macro- or microhematuria. Renal functional tests are normal and there is general well-being of the patient. Whereas the biopsy specimens examined by light microscopy show non-specific alterations, those examined under the electronmicroscope already show specific defects of the basement membrane. Our studies lead us to believe that these morphologic findings correspond with changes of the basement membrane, detectable by immunochemical investigations. 6 of 12 patients have been biopsied in recent time and the above cited typical changes of the basement membrane could be demonstrated. Therefore these investigations are recommended in Alport's syndrome.


The measurement of muscle mass in children using [15N]creatine. In eight infants and children who had recovered from protein-energy malnutrition (PEM), muscle mass was estimated by measuring creatine turnover by an isotope dilution technique using [15N]creatine, creatine concentration, and urinary creatinine output. Creatine turnover varied from 1.5 to 2.6% of the muscle creatine pool per day and muscle creatine concentration ranged from 1.7 to 3.9 mug/mug muscle mass was between 15% and 37% of total body weight. The results indicate that daily creatinine output is not a reliable indicator of muscle mass in children who have recently recovered from severe PEM.


Central nervous system infection with Eikenella corrodens: report of two cases. Two cases of central nervous system infections from which E. corrodens has been isolated are reported. The portals of entry, clinical course, and antimicrobial responses conform to other reports in the literature. The importance of obtaining careful anaerobic cultures is emphasized.


Early perceptual development in humans and animals: a bibliography of English language papers, 1967-1974. 482 articles and books are presented in alphabetical order. The bibliographaphy surveys the English language literature on early perceptual development in animals and humans during the period 1967-1974, inclusive.


Analysis of general anxiety scale for children and draw-a-person measures of general anxiety level of elementary school children. Sarason's (1960) General Anxiety Scale for Children was used as the criterion measure of trait anxiety in a study investigating fifth- and sixth-graders' (ns equals 15) human figure-drawing performance. Figures drawn were man, woman, and self. Significant differentiation by the figure-drawing scores on the sex criterion was obtained for some indices; however, no significant relationships were found between subjects' human figure-drawing scores and their anxiety level as measured by the General Anxiety Scale for Children.


Inherited biochemical defects affecting the kidney. The identification of a disease entity as one that is the result of a heritable defect offers the physician an opportunity to intervene in a variety of ways. As emphasized, knowledge of the heritable pattern of a particular disease allows the physician an opportunity to counsel family members in personal disease risk and the offspring. Such genetic counseling results in a reduction of affected cases for many inherited diseases. There is every expectation that similar approaches would be effective for inherited renal diseases. The heritable diseases are a favored group for investigative purposes since these diseases result from a single gene defect no matter how plieotropic the effects of that defect. Thus the investigator is capable of constant probing with tools available for identifying that one event or component that lies at the basis of the disease. The emphasis of this chapter is on those inherited renal diseases for which we have reached a high level of understanding of this single defect. In many of these diseases a single enzyme is identified as deficient and is the presumed genetic defect. In others (cystinuria, RTA, and cystinosis) the precise biochemical answers appear close at hand. Thus a variety of therapeutic approaches to overcome either the gene defect or ill effects of the gene defect emerge for diseases involving the kidney and are listed in Table 7. For some of these diseases the new diagnostic technique of prenatal diagnosis can be used (Table 8). This genetic option provides couples at risk for bearing affected offspring with reduced risk. For a number of other diseases that are not identified by amniocentesis, this risk can be effectively lowered to acceptable levels by use of artificial insemination. Thus the inherited diseases of the kidney are amenable to medical intervention at a variety of levels. Such intervention can predictably lead to a lowering of both the incidence and consequences of these gene defects.


Comparative evaluation of fractional excretion of sodium following saline infusion in transplanted kidneys and in isolated perfused kidneys in conditions of previous high or low dietary sodium intake. The increase of fractional excretion of sodium following the infusion of isotonic saline solution is quantitatively the same in dog kidneys perfused by a whole animal or by a pump-oxygenator machine at identical arterial and venous pressures. The equal response found in both experimental conditions demonstrates that the dilution of the blood, and primarily the decrease of post-glomerular plasma oncotic pressure, represents the only extrarenal humoral factor of significant importance in the reduction of fractional reabsorption of sodium following large saline infusion. The renal response to hemodilution is reduced similarly in both types of experiments when the dogs have been previously submitted to a dietary deprivation of sodium. The decreased sensitivity of the kidney to the stimulus of hemodilution appears as a major determinant of the poor natriuretic response to saline loading of sodium-deprived animals.


Comparison of vasoactive intestinal peptide (VIP) and secretin in gastric secretion and mucosal blood flow. VIP and secretin were compared in regard to their effects on gastric acid and pepsin secretion induced by pentagastrin histamine or a peptone meal as well as on gastric mucosal blood flow and meal induced serum gastrin level in conscious dogs provided with gastric fistulas and denervated fundic pouches. Both VIP and secretin caused a dose-related stimulation of basal pepsin outputs and inhibition of pentagastrin-induced acid secretion. VIP, like secretin, inhibited pentagastrin and meal-induced gastric acid secretion but in contrast to secretin it caused inhibition of acid response to histamine. Inhibition of acid secretion by VIP or secretin was accompanied by secondary reduction in gastric mucosal blood flow in tests with pentagastrin or histamine and by depression of the serum gastrin level in tests with a peptone meal. This study indicates that in comparison with secretin, VIP  has a wider spectrum of inhibition of stimulated gastric secretion and may be considered as one of the enterogastrones released in the small intestine.


[The K antigens of Escherichia coli (author's transl)]. The development of the serology of Escherichia coli, especially the present division of the antigen into L, B, and A antigens is described. Only the A antigen should be regarded as a capsular antigen whereas L and B antigens are to be considered as envelope antigens. Immunoelectrophoretic studies by Orskov & Orskov (1972) on the K antigens and O antigens of Escherichia coli revealed that the strains could be placed into a few well defined groups according to migration patterns of the O antigens and of the thermostable polysaccharide K antigens. Orskov's et al proposed new criteria for K antigens and studies on the importance of K antigens as determinants of virulence in Escherichia coli are presented


[Treatment of hyaline membrane disease by a new method of continuous positive pressure, 1st results]. In this article the authors report their experience with regard to the use of continuous positive pressure by means of a nasal appliance in the treatement of hyaline membrane disease. In addition to mechanical respiratory assistance and economy in the administration of oxygen procured by continuous positive pressure, its use in conjunction with the nasal appliance has led to some progress being made in comparison with the so-called "bag" technique of Martin-Bouyer. In particular, the positive pressure method can be used without undue risk with children weighing less than 2000 grams at birth whereas the "bag" technique has shown itself to be too dangerous for them.


Interactions between 30s ribosomal proteins and 50s subunits of Escherichia coli. The interaction between ribosomal proteins of the 30s subunit with intact 50s subunits was investigated. Experiments with mixtures of total 30s proteins indicated that several 30s proteins including protein s4 would form a stable complex with 50s subunits. Further work with pure s4 indicates that this protein binds stoichiometrically to the 50s subunits, probably through protein-nucleic acid interaction. The possible significance of this interaction is discussed.


Terminal labeling and addition of homopolymer tracts to duplex DNA fragments by terminal deoxynucleotidyl transferase. Terminal deoxynucleotidyl transferase, which requires a single-stranded DNA primer under the usual assay conditions, can be made to accept double-stranded DNA as primer for the addition of either rNMP or dNMP, if Mg+2 ion is replaced by Co+2 ion. The priming efficiency in the presence of (C leads to) CO+2 ion with respect to initial rate tested with 2 single-stranded primer, is 5-6 fols higher than that observed with Mg+2 ion. In the presence of Co+2 ion, the primer specificity is altered so that all forms of duplex DNA molecules can be labeled at their unique 3' -ends regardless of whether such ends are staggered or even. Thus, using ribonucleotide incorporation, we have for the first time employed this reaction for sequence analysis of duplex DNA fragments generated by restriction endonuclease cleavages. Furthermore, by using Co+2 ion, it is possible to add a long homopolymer tract of deoxyribonucleotides to the 3'-terminus of double-stranded DNA. Therefore, without prior treatment with lambda exonuclease to expose the 3' terminus as single-stranded primer, this reaction now permits insertion of homopolymer tails at the 3'-ends of all types of DNA molecules for the purpose of in vitro construction of recombinant DNA.


DNA replication in eukaryotes: a model for the specific involvement of chromatin subunits. A model is proposed whereby eukaryotic DNA replication is specifically directed by the 200 base pair repeat structure of the DNA-histone complex. The model proposes a mechanism for the sequential, bidirectional replication of DNA from initial origin points on the chromatin fibre and is consistent with the known properties of eukaryotic DNA replication. Several predictions can be made from the model which are amenable to testing.


The surgical management of extracranial cerebrovascular occlusive disease: a review of 200 consecutive surgical cases. The role of surgery in the treatment of extracranial cerebrovascular disease is essentially a prophylactic one but it should be borne in mind that apart from preventing stroke, such procedures will or should eliminate symptoms. The authors believe that every patient suffering from cerebrovascular insufficiency should be thoroughly evaluated for extracranial cerebrovascular occlusive disease and that arteriograms should be performed on all patients who could be expected to be candidates for surgery. The various indications for surgery have been discussed. The authors believe that people who have severe bilateral disease and who are of an advanced age are probably in a higher risk group. They also believe that surgery should not be offered to people who have a complete stroke and who are in semi-coma or coma, no matter how rapidly they may be transferred to the operating theatre. The authors firmly believe that intra-operative E.E.G. monitoring is an important adjunct to the safe surgical treatment of lesions of the carotid bifurcation, not only to indicate when shunting is necessary but also to indicate how well that shunt is functioning. In spite of the frequent presence of associated heart disease, hypertension and other vascular lesions, operation can be offered with confidence to suitable candidates. Elimination of symptoms can be expected in over 90% of cases. Only one patient has suffered a stroke since leaving hospital and this occurred because of occlusion in his internal carotid artery which was not operated on. Apart from patient selection, the factors which have contributed to the authors' low morbidity and mortality have been the use of intra-operative E.E.G. monitoring, intra-operative heparinisation and the availability of excellent angiographic studies.


In vitro and in vivo activity of 2,4-diamino-6-(2-(3,4-dichlorophenyl)acetamido) quinazoline against Cryptococcus neoformans. The minimum inhibitory concentration of quinazoline derivative was determined by the tube dilution method for Cryptococcus neoformans, strain 184. The effect of this chemical agent on macromolecular metabolism indicated an inhibition of incorporations of labeled precursors into RNA and protein of C. neoformans. A mouse model infection with C. neoformans was established. Following this, the animals were given ip or oral doses of different concentrations of the experimental drug. Infected mice responded to ip administration of the drug in that the percentage of surviving mice increased progressively with increasing drug dosage. The curing dose 50 (CD50) was determined, based on the isolation of C. neoformans from organs of animals during or at the termination of the experiments.


Gonadotropin releasing hormone induced luteinizing hormone release after prostaglandin F2alpha in heifers. Twenty Holstein heifers in diestrus were given 30 mg of PGF2alpha Tham salt (im). Thereafter each of five heifers received no further treatment of 40 mug of GnRH (im) at 10, 30, or 50 hr after PGF2alpha. Serum progesterone decreased to less than 1 ng/ml at 24 hr after PGF2alpha and remained low throughout the remainder of the sampling period. Following PGF2alpha, estradiol concentrations increased gradually in serum but GnRH given at 30 hr after PGF2alpha abruptly decreased estradiol concentration. The magnitude of LH release induced by GnRH given at 30 or 50 hr after PGF2alpha was greater than that at 10 hr. All heifers exhibited behavioral estrus except those in group GnRH-50. Spontaneous LH peaks, which usually occur after PGF2alpha were observed in 5/5 (control), 4/5 (GnRH-10), 0/5 (GnRH-30), and 2/5 (GnRH-50) heifers. We conclude that pituitary responsiveness to GnRH increases with time after PGF2alpha and GnRH given at 30 hr completely inhibits and at 50 hr partially inhibits endogenous LH release.


Inhibition by nalidixic acid of post-uv survival of Escherichia coli. Nalidixate inhibited the post-uv survival of E. coli B. TAU-bar and Ts-7, but not Bs-1 or B/r when included in the plating medium. Removal of the drug sensitivity by photoreactivation was consistent with pyrimidine dimers as the target for the effect. Nalidixate did not inhibit liquid-holding recovery from uv when included in the holding medium, but survival was inhibited if the drug was in the subsequent plating medium. In fact, there was an actual increase in the number of nonsurvivors due to the drug following a period of holding.


Endotoxin toxicity in rats is enhanced by tilorone. The relatively nontoxic drug, tilorone, greatly enhanced the susceptibility of rats to lethal effects of endotoxin. The magnitude of the synergy was similar to that produced by adrenalectomy, but the effect of tilorone was not mediated by the adrenal glands. The histopathologic effects of endotoxin plus tilorone resembled those produced by much larger doses of endotoxin alone, including instances of the generalized Shwartzman reaction.


Intracolonic tensions of oxygen and carbon dioxide in germfree, conventional, and gnotobiotic rats. The relation of intracolonic gaseous tension to fecal microflora was investigated by mass spectrometric measurements of intracolonic O2 and CO2 in unanesthetized germfree, conventional, and gnotobiotic rats; ip measurements were obtained in rats whose colons became perforated accidentally; fecal bacterial flora and cecal size were also determined. Gnotobiotes were monoassociated with Escherichia coli, Bacteroides fragilis and Staphylococcus epidermidis, and were diassociated with E. coli plus B. fragilis and with Bacillus macerans plus an aerobic diphtheroid. Mean intracolonic Po2 in conventional rats (11.1 mmHg) was significantly lower than in germfree rats (12.8 mmHg); mean intracolonic Pco2 in conventionals (83.4 mmHg) was greater than in germfree rats (54.6 mmHg). Differences of Po2 values among all rats were slight. However, intracolonic Pco2 values were directly related to CO2 production by the normal intestinal flora, and were thus significantly lower in both germfree and gnotobiotic rats. Intraperitoneal tensions were independent of the status of rats, and the mean ip Po2 and Pco2 (38.9 and 49.1 mmHg, respectively) agreed with values in the literature. The enlarged cecum, characteristic of germfree rats, was also present in gnotobiotic rats. Counts of each bacterial species in feces of monoassociated rats were 10(8) to 10(10)/g; counts were progressively smaller in feces of diassociated rats and conventional rats (10(8) to 10(9)/g and 10(5) to 10(8)/g, respectively). Intracolonic gaseous tensions of CO2 clearly reflected the presence of a normal flora inconventional rats, and were inversely proportional to cecal size.


The use of healed superficial burns as a donor site for split-skin grafts. We compared 30 skin grafts obtained from healed burn areas to 30 skin grafts obtained from normal uninjured skin. The rates and characteristics of healing were studied and compared, both clinically and histologically; in general they were quite similar.


Repair of forehead defects by rotation of local flaps. A simple rotation of the remaining forehead as a flap may permit closure of major defects in the forehead, with relative ease and a good cosmetic result.


[Psychodiagnosis of brain damage and brain damage sequelae in adults]. The author examines methodical problems of construction and validation, and the local value of psychological methods within the framework of neuropsychological diagnostics. He bases this examination on a characterization of the wide field of problems of psychological diagnostics when proving, bjectivizing, quantifying and describing psychic consequences of cerebro-organic conditioned functional lesions and their differential diagnostic delimitation with regard to other symptom images. He goes on to describe diagnostic aims, statement possibilities and the limitations of psychopathometric and psychopathognostic testing devices. Finally, more from pragmatic than from strictly theoretical aspects of neuropsychology, he gives an outline of a number of major psychodiagnostic processes commonly used in practice with a view to objecting and quantifying forms of performance and behavior resulting from cerebro-organic alterations, i.e. processes which definately occupy an equal place in the arsenal of methods employed by the neuropsychiatrist.


Self-inhibiting action of nortriptylin's antidepressive effect at high plasma levels: a randomized double-blind study controlled by plasma concentrations in patients with endogenous depression. Below the toxic plasma level of nortriptyline (NT) an upper therapeutic limit has been postulated in patients with endogenous depression. If so the clinical significance is obvious and a double-blind, randomized study was performed in order to solve this problem. Two groups of patients were controlled at different plasma levels (less than 150 ng/ml and less than 180 ng/ml). The degree of depression was rated weekly. Only about one third (n equals 24) of the patients originally included, were carried through the full protocol, the most prominent reason for drop out beeing spontaneous remission during an initial placebo period. After 4 weeks of NT treatment the majority in the high level group was still depressed, but the difference barely significant (P equals 5.5%). However, a randomized reduction of the plasma level among the patients at the high level resulted in a significant correlation to remission. Evaluation of the total material after 6 weeks of NT treatment demonstrated a strong correlation of high plasma level to poor antidepressive effect of NT. No correlation could be obtained between side-effects, which were few, and plasma level. The non-proteinbound fraction in plasma was found to 7% (SD 1.83) by simultaneous determinations of NT in plasma and CSF in 13 patients. The variation in the proteinbinding was not likely to invalidate the over all results based on total NT determination. A therapeutic plasma range of 50-150 ng/ml is recommended.


The wind of the cannon ball: an informative anecdote from medical history. When Cartesian dualism became a determining philosophical basis of medical theory, psychosomatic events became logical impossibilities. In the nineteenth century, physicians confronted with a class of such events - battle casualties without externally inflicted injuries - sought mechanistic interpretations in the 'wind' of the cannon ball. Those who rejected these ineffective hypotheses were forced to deny the existence of such casualties. Today we acknowledge the existence of psychosomatic events. The logical barrier to understanding them, however, remains at the basis of medical theory and must be eradicated.


Rapid onset of pulmonary infiltration due to histiocytic lymphoma. Five cases demonstrating the rapid onset of pulmonary infiltrates due to hystiocytic lymphoma are presented. In four cases the pulmonary infiltrate occurred at the time of initial presentation and the fifth case occurred 2 1/2 months after the original diagnosis. The radiographic manifestations are nonspecific. Lung biopsy, open or closed, is needed to confirm the diagnosis before initating appropriate therapy.


A computer assisted radiological reporting system. The authors report their experience with a commercially available computerized diagnostic reporting system. The system has been in operation more than 36 months and processes more than 95,000 cases annually. Dictation is needed for only 13% of emergency room cases and 23% of in-patient cases. Savings in overtime and increased efficiency have resulted. The system can be adapted to other computerized systems within the x-ray department. Acceptance by staff and residents has been good.


Computed tomography in the detection of juxtasellar lesions. One thousand consecutive computed tomograms were reviewed to determine the accuracy of the procedure in the detection of juxtasellar lesions. The detection rate was compared to those of plain skull films, radionuclide studies, angiography, and pneumoencephalography. Computed tomography was slightly superior to angiography and was surpassed only by pneumoencephalography, both of which are invasive procedures which carry a definite risk. The data indicate that computed tomography is the screening method of choice in the detection of juxtasellar masses.


"Watershed" infarction in sickle cell disease. A classical "watershed" infarction pattern on brain scintigraphy was demonstrated in a seven-year-old black girl with sickle cell disease. Computed tomography (CT) showed minimal abnormalities compared to the characteristic findings on the radionuclide image.


Positional shift of intraventricular blood clots demonstrated by computed tomography. Computed tomography with the patient in the prone position was employed to obtain information in a case of intraventricular hematoma secondary to arteriovenous maliformation. A gravitational shift in the position of the intraventricular blood clots was demonstrated by a scan obtained with the patient in the brow-down position. Consideration is given to the possible use of the "prone EMI scan" for other intracranial problems of differential diagnosis.


Asymmetric lung involvement in bronchopulmonary dysplasia. The radiographic distribution of pulmonary abnormalities in bronchopulmonary dysplasia (BPD) in all previously reported cases has been bilateral and generalized. The authors studied 11 premature infants who had BPD that was primarily unilateral. The striking feature in each of these patients was the occurrence of an episode of prolonged unilateral atelectasis or tension pneumathorax. Few, if any, radiographic manifestations of BPD developed. Results of a detailed analysis of oxygen exposure and respirator therapy during the periods of unequal lung ventilation further characterizes the protective effect of atelectasis and tension pneumothorax in the development of BPD.


Radiological findings in group B streptococcal Sepsis. Analysis of the radiographs of 9 infants who died of proved Group B streptococcal sepsis revealed a typical pattern of hyaline membrane disease despite birth weights of over 2,000 g in most cases. Pleural effusions subsequently developed in 6 infants; the rest had pleural fluid at postmortem examination. This is an unusual finding for either hyaline membrane disease or non-group B streptococcal sepsis in the neonate, and may have implications for the early diagnosis and treatment of this usually lethal infection.


Evaluation of renal transplants with ultrasound. Ultrasound scanning is useful in evaluating renal transplants: it is atraumatic, independent of renal function, and well suited for analyzing such common complications as lymphocele, abscess, hydronephrosis, and hematoma. When there is uncertainty as to the nature of a paranephric mass, ultrasonically guided percutaneous aspiration is definitive. Ultrasound can also detect the acute increase in renal volume associated with rejection and may prove to be a valuable adjunct in the early diagnosis of this problem.


Hypotonic duodenography with glucagon. A clinical comparison study. This clinical double-blind study shows that glucagon (2 mg) is a valuable agent for hypotonic duodenography. Pro-Banthine (45 mg) is slightly more effective as a hypotonic agent, but there is no doubt that its use is associated with more side effects and subsequent patient discomfort; contraindications to its use are more commonly encountered in a general hospital population.


Radiosensitization of Serratia marcescens by cetylpyridinium chloride. Evidence for membrane-associated events. Cetylpyridinium chloride has been shown to be an effective radiosensitizer of both oxic and anoxic suspensions of Serratia marcescens in buffer. The related compounds ethylpyridinium bromide and cetyltrimethylammonium chloride exhibited no such radiosensitizing properties at comparable concentrations. It is suggested that the efficiency of cetylpyridinium chloride is due to the combination of lipid-soluble (cetyl) and electron-affinic (pyridinium) moieties within the same molecule, and that these may provide for interaction with a membrane-associated target. Cetylpyridinium chloride did not radiosensitize bacteria suspended in nutrient broth.


The impact of computerized radiological reporting systems on the radiologist. Although the advantages of automated reporting systems in diagnostic radiology far outweigh the disadvantages, radiologists have been slow to accept them because of their reluctance to work with the systems, i.e., assume a secretarial function, or to abandon ad lib. dictation. To realize the benefits of automated reporting, it is necessary for the radiologist to change his reporting style from one of "dictating while reading" to one of "reporting" only after searching the films and drawing a conclusion, and to appreciate that in this era of information overload, rapid delivery of a crisp, pertinent summary of his findings to the referring physician maximizes his influence on patient care.


Interactions of prostaglandin E1 (PGE1) and LRH on anterior pituitary function. Numerous biochemical pathways influence the synthesis and release of anterior pituitary hormones. Releasing factors extracted from the hypothalamus and prostaglandins (PGs) appear to alter a common biochemical activity, adenyl cyclase, in pituitary cells. Luteinizing hormone releasing hormone (LRH), prostaglandin (PGE1), 7 oxa-13-prostynoic acid and cycloheximide were tested for individual and interacting effects on the in vitro release of FSH, LH and prolactin from hemipituitaries of 15 day old female rats. LRH (10 ng/ml) consistently released both LH and FSH in all in vitro experiments and inhibited prolactin release in 1 of 2 experiments. Lower concentrations (5 and 1 ng/ml) also stimulated LH and FSH release but did not influence prolactin release. Concurrent depletion of stored LH and FSH in the gland was observed. PGE1 in a 6.5 hour incubation increased the storage of LH within the gland in the absence of LRH. In a 1.5 hour incubation in the presence of LRH, storage of LH was also increased. PGE1 had no effect on LH and FSH release; however, in 1 of 2 experiments it stimulted prolactin release in the absence of LRH. Prostynoic acid stimulted LH and FSH release but did not synergize with LRH action in the same tissue. Cycloheximide did not affect LH release during the first 30 minutes of incubation; however, the release during the subsequent 1 hour was significantly inhibited. Similar tissue also exposed to cycloheximide was still responsive to LRH during the latter 1 hour incubation period. Cycloheximide had no effect on prolactin storage and release from the same tissue.


A new beta adrenergic blocking agent, sotalol, in the treatment of angina pectoris. A double blind-crossed treatment study. The present therapy for coronary insufficiency includes the use of drugs which decrease the cardiac work, thus reducing the needs for oxygen (beta adrenergic blocking agents). The 4- (2-isopropylamino-1-hydroxyethil) methane sulfonamylide (Sotalol (R)) is considered the most active of the alkylsulfonamide phethenolamines group. 69 patients with angina pectoris were selected for treatment with Sotalol. The administration was preceded by a five weeks period during which the patients received placebo. Afterwards they received for three weeks a dose of Sotalol (titration period), set the optimal effective dose. At the end of this period all patients began a double blind-crossed treatment which continued for 12 weeks. Two schedules were followed: group 1, Sotalol-placebo; group 2, placebo-Sotalol. No statistically significant variations were shown in the number of anginose attacks during the initial placebo period. The decline in the number of anginose attacks during the titration period (Group 1: weeks 5 to 8, p less than 0.0001; Group 2: weeks 5 to 8, p less than 0.0002) is statistically significant. In the first group the continued administration of Sotalol decreased the number of painful attacks even further, which describe a slope which is abruptly interrupted at the end of the six weeks, coinciding with the initiation of the placebo treatment (Group 1: weeks 8 to 14, p less than 0.001, significant). In group 2 (drug-placebo-drug) the administration of the placebo in the six weeks following the titration period was followed by a recrudescence of the symptomatology, whose intensity, however remained far below that recorded during the initial period (Group 2: weeks 8 to 14, p less than 0,0783, not significant). Then, in the final six weeks, the administration of Sotalol produced a sustained and considerable improvement in the weekly number of anginose attacks (Group 2: weeks 14 to 20, p less than 0.0011, significant). All the differences produced by the ingestion of Sotalol are statistically significant. These facts, together with the absence of clinical or humoral side effects incontestably bear out the efficacy of the drug in controlling the number and the intensity of painful attacks of coronary origin.


Preponderance of postsystolic period in the positive inotropic effects of increases in (Ca++). If the frequency of stimulation of isolated kitten right ventricular papillary muscles is progressively reduced, the size of contractions decreases until a frequency is reached (rested state rate) where further reduction produces no change (rested state contraction, Koch-Weser and Blinks, 1963). At 30 degrees C and 2.25 mM Ca++, the rested state rate was about one per 2-5 min, the peak tension of 0.2-0.6 g/mm2 was about 5-15% of the tension of 20/min beats, and times to peak tension and 80% repolarization about doubled. Sudden calcium increases in the perfusion fluid, [Ca++]p, from 2.25 to 6.75 mM were produced at random during intervals between rested state contractions, and time and amplitude of peak isometric tension, max +/- dT/dt of subsequent beats were studied. The greatest positive inotropic response of the initial beats following increments in [Ca++]p resulted when [Ca++]p was increased immediately after a rested state contraction: as the postsystolic interval before the [Ca++]p increment was increased, the positive inotropic effects decreased approximately exponentially, attaining a plateau level in about 30 sec. This plateau was then maintained until the period prior to the initial test beat in high calcium was less than the approximately 2-min diffusion equilibrium time between [Ca++]p and the interior of the fiber.


Comparison of energetic patterns of skeletal and cardiac muscles. The shape of the basic oxygen uptake to load relationship for afterloaded contractions by in situ mammalian skeletal muscle was found to be altered significantly when the initial length of the muscles was changed from values of initial length which were less than optimal length to values of initial length which were greater than optimal length. When initial length was greater than optimal length, the relationship was like that reported for isolated amphibian muscles. When initial length was less than optimal length, the relationship was like that reported for heart muscle which is usually studied with initial length less than optimal length. If the effect of initial length is found to be the same for isolated amphibian muscles and heart muscles as it is for mammalian muscles, then the basic energetic pattern for these striated muscles will be similar.


Effects of chronic hypoxia on myocardial metabolism. Chronic hypoxia had widespread effects on myocardial metabolism. In understanding these effects, it is necessary to take account of the indirect ways in which hypoxia may act on the heart. Two such important indirect actions are those which follow the development of pulmonary hypertension and anorexia. The experimental design reported here enables one largely to distinguish the effects of pulmonary hypertension and anorexia from the rest. Using such a design, we have presented a number of diverse aspects of myocardial metabolism under conditions of chronic alveolar hypoxia induced by a low atmospheric pressure.


Myofilament flexibility: a possible role in Hill's model for cardiac and skeletal muscle. The sarcomeric unit ("sark") is an elastic structure (cf. hard rubber). The sark stretch under load is the sum of the deflections of: (a) the naked thick filament, (b) the joined thick-thin filaments, (c) the naked thin filaments, (d) the parallel array of S1 moieties (bending deflection), (e) the parallel array of S2 rods, and (f) the Z-filaments. Hill's model can be revalidated at the molecular level, if the contractile element is identified as the instantaneous array of contract points between each S1 moiety and the thin filament, such that sark stretch accounts for series elasticity. A matrix array of variously activated and test-rig-damaged sarks can account for large quick-release compliances in cardiac muscles.


Failure of increased brain gamma-aminobutyric acid levels to influence amphetamine-induced stereotyped behavior. Increased brain gamma-aminobutyric acid (GABA) levels secondary to the administration of sodium valproate failed to inhibit amphetamine-induced stereotyped behavior. This observation raises some doubt as to whether GABA plays a role in the physiology of the striatum and suggests that GABA does not play a role in the pathophysiology of chorea. If this is true, pharmacologic attempts to increase brain GABA may not improve human choreatic disorders.


[Pulmonary function tests following single lung homotransplantation in emphysematous dogs (author's transl)]. Experimental emphysema was induced by multiple intratracheal instillation of Papain in a dose of 2 mg/kg body weight in 4 bastard dogs. Development of emphysema was objectivated by pulmonary function tests. Increase of static lung compliance, decrease of lung elastance, and increase of air-way resistance were observed. In  addition arterial pO2 decreased while pCO2 remained constant. Following single lung homotransplantation there was an increase of respiratory rate and minute ventilation, the transpulmonary pressure rose in the first postoperative days, static lung compliance was diminished. Four weeks after transplantation typical functional changes of emphysema could be demonstrated concerning the slope and appearance of the compliance loops. Arterial pO2 however remained within the normal range. This functional behaviour does not support the concept of a ventialtion perfusion imbalance after lung transplantation in emphysema patients. Respiratory insufficiency therefore is probably caused by an alveolar type of rejection.


Passive immunity to contagious bovine pleuropneumonia. A significant passive protection against contagious bovine pleuropneumonia (CBPP) was demonstrated in cattle. One group of cattle was inoculated with serum from CBPP-recovered cattle, while another group was inoculated with serum from susceptible cattle. The two groups, along with an untreated control group, were challenged with the virulent Gladysdale strain of Mycoplasma mycoides, using the in-contact method. Four out of the five cattle inoculated with serum from animals which had recovered from CBPP were protected, whereas three of five cattle inoculated with serum from susceptible animals and all the untreated animals died of CBPP.


[Neurophysiopathological hypothesis on startle epilepsy in man]. Clinical observation and S.E.E.G. recordings performed with a surgical purpose in a typical case of startle-epilepsy has led to a reassessment of the relationship of this form of epilepsy and "Startle reaction". It is confirmed that the critical discharges take origin in the primary motor cortex. The authors discuss, in the light of experimental data already published, the physiopathological hypotheses likely to lead to a better understanding of startle epilepsy. On the one hand it is suggested that the startle reaction may be responsible through a feed-back mechanism for triggering the epileptogenic focus. On the other hand it is assumed that afferent pathways, central organization and efferent systems involved in startle reaction and actual fits are different.


[Subacute spongiform encephalopathy and Creutzfeldt-Jakob disease. Apropos of 1 case]. The authors describe a case of sub-acute spongiform encephalopathy with an ultrastructural study in a man of 65 with associated dementia, extra-pyramidal syndrome, myoclonia, optical disorders, pyramidal syndrome and speech disorders, rapidly leading to death one and a half months later. Electroencephalograms were at first disorganized with persistent delta and theta activity and only in the last record did short runs of repetitive activity appear. Histologically, there was severe status spongiosus, a moderate degree of neuronal depopulation with a noticeable astrocytary gliosis. Under the electron microscope, the neuropile in the astrocytes was found to be pitted with numerous cavities and so were, to a lesser extent, the axonal projections. The vessels were normal. Nothing was found to indicate viral structures. Attention is drawn to the nosological connection between this type of observation and Creutzfeldt-Jakob disease.


The effect of low doses of prednisolone compared with placebo on function and on the hypothalamic pituitary adrenal axis in patients with rheumatoid arthritis. A double-blind trial of prednisolone in patients with rheumatoid arthritis using doses of zero, 3 mg and 5 mg is reported. Patients on a dose of 3 mg derived little sustained benefit but subjects on the higher dose showed some improvement which did not last more than two years. Mild suppression of the hypothalamo-pituitary-adrenal axis occurred in both steroid-treated groups.


[Clinical test of the Delcomat miniaturisation system (author's transl)]. A series of 1720 roentgen examinations consisting of 5178 roentgen films were copied with the Delcomat (de Oude Delft) copying apparatus. The copies were re-examined after some months, and the diagnoses were compared with the original ones made of normal size films. The diagnostic accuracy was in most examinations not significantly reduced. There was some extraneous variation not depending on the copying method in complicated pulmonary and cardiologic problem cases, and the lack of immediate screening information also caused some reduction in the diagnostic accuracy. The presumption that there would be some information loss in the miniaturized copies led to false positive statements in some cases. The diagnoses were made by a group of radiologists consisting of one specialist (staff member) and two registrars (residents).


[Radiographic differential diagnosis of tumors of jejunum and ileum (author's transl)]. Tumors of the small intestine form only 1.5-8% of intestinal tumors. After a survey of localization, type of growth and tendency towards degeneration the most important clinical findings are described. The most common sign is high ileus. Barium swallow is recommended which, when all radiologic criteria are taken into account, may even permit identification of the type of tumor. Typical individual tumors are illustrated and described and differential diagnostic data are given. The potential and limits of angiography are discussed.


A method for studying adherence of oral streptococci to solid surfaces. The adherence of different streptococci to test pieces of glass, human enamel and whale dentin carried in the mouth or immersed in saliva or bacterial suspensions was studied by examining the number and frequency of microorganisms which were selectively desorbed by a standardized washing technique. The results obtained from in vivo and in vitro experiments were similar in principle. The proportion of streptococci obtained in the first washing resembled that found in the saliva, but with more vigorous washing the proportion of S. sanguis increased while that of S. salivarius decreased. This illustrates that different microorganisms can attach to solid surfaces with different strengths. The applicability of the method was tested by treating dentin surfaces with fluoride solutions and by incorporating sucrose in the test solution. The fluoride treatment reduced while the sucrose addition increased the number of streptococci which could be removed from the surfaces.


Adult coeliac disease. A case with ulceration, dermatitis herpetiformis and reticulosarcoma. A 64-year-old woman with adult coeliac disease developed recurrent ulceration and perforation of the small intestine, dermatitis herpetiformis and a reticulosarcoma of the small intestine. She died following the third perforation. The possible importance of strict adherence to a gluten-free diet in the hope of preventing these complications in patients with adult coeliac disease is discussed.


A secretory and histological study of the stomach before and after truncal vagotomy and pyloroplasty in duodenal ulcer patients. In 10 patients with duodenal ulcer gastric secretion was studied after graded doses of pentagastrin before and 3 months after truncal vagotomy and pyloroplasty. In 6 patients carbacholine was also infused simultaneously with the greatest dose of pentagastrin after vagotomy. The histology of the gastric mucosa was studied in suction biopsies obtained from the corpus of the stomach before and 3 months after the operation. After truncal vagotomy with pyloroplasty the maximal pentagastrin-stimulated acid and pepsin secretion and the sensitivity of the parietal cells to pentagastrin were all reduced significantly. There was no significant increase in maximal pentagastrin-stimulated acid and pepsin secretion when carbacholine was added to pentagastrin. The average thickness of the gastric mucosa and the mean number of parietal cells per unit area of the stomach did not show any significant change, while the number of patients with deep gastritis increased  significantly after vagotomy.


Effect of azathioprine on the cell cycle of haemopoietic cells. The megaloblastic erythropoiesis encountered in 3 azathioprine-treated patients with renal transplants was found to be associated with a marked increase in the proportion of early polychromatic erythroblasts in the G2 phase of the cell cycle. By contrast, there was only a slight increase in the proportion of G2 cells in the neutrophil promyelocyte-myelocyte pool of these patients.


A plaque technique for assay and characterization of antibody-dependent cytotoxic effector (K) cells. Using monolayers of erythrocytes as target cells, a plaque assay was developed by which individual antibody-dependent cytolytic lymphoid cells (K cells) could be identified at the cellular level. The extent of plaque formation depended on the concentration of sensitizing antibody, time of incubation, and number of lymphocytes added. Most of the plaque-forming cells (50% to 70%) were shown to possess receptors for activated complements, a small but variable fraction (5% to 25%) had surface Ig detectable by indirect immunofluorescence, and 5% to 10% bound sheep erythrocytes at 5 degrees C. The plaque-forming cells appeared as villous, small to medium-sized lymphocytes when studied by transmission or scanning electron microscopy. Under standardized experimental conditions the minimal number of active, plaque-forming K cells in purified lymphocyte preparations could be estimated.


Oxyphenbutazone in the treatment of acute ureteral stone disease. A comparative study between the effect of oxyphenbutazone and placebo in acute ureteral disease was carried out in 45 patients. The results are statistically significant in favour of the group treated with oxyphenbutazone with respect to the rapidity and the incidence of spontaneous passage of ureteral stones.


Femoral head necrosis in renal transplanted patients. Evidence of a haemodynamic etiological factor. In a material of 197 consecutive renal allotransplanted patients, 15 patients developed femoral head necrosis on X-ray examination. Eleven of these patients developed the femoral head necrosis ipsilateral to the renal allograft. It is therefore suggested that the altered haemodynamics caused by the transplantation may be of pathogenic importance in the development of the femoral head necrosis.


Preanastomotic arterial stenosis in renal transplant recipients. A report of four cases. Four cases of arterial stenosis proximal to the renal artery anastomosis in renal transplant recipients are described. In three of the cases infarcts also occurred in the transplanted kidney. The stenoses were probably caused by injury from a vascular clamp. Embolisation from the injured area of the vessel was probably responsible for the infarcts. The radiological findings were characteristic in the three cases thus examined. The importance of special care in handling the blood vessels is stressed. Detailed angiographic studies are required to ensure diagnosis.


Renal transplantation in the rat. III. The effect of colloidal and non-colloidal perfusates on the clearing of blood from the in vitro perfused rat kidney. Rat kidneys were perfused in vitro with Perfadex (Gelin's solution) and a modified Collins' C3-solution with or without colloids. When the same flow rate was used the presence of 5% dextran 40, 5% albumin, or 10% albumin did not alter the clearing of 51Cr-tagged red blood cells. The main difference between the experimental groups was a significant increase in perfusion pressure when colloids were excluded from the perfusate. Results concerning the regional distribution of 51Cr-activity within the kidney are discussed.


Pyelocystostomy used as a treatment of ureteric necrosis after kidney transplantation. A 32-year-old male had chronic glomerulonephritis and terminal renal failure. He was treated with intermittent haemodialysis, and transplantation of a cadaveric kidney. Urine extravasation occurred due to ureteric necrosis. He was treated with temporary diversionary ureterostomy, and 9 weeks later a direct anastomosis between the pelvis of the transplanted kidney and the recipient bladder was performed. Thirty-three months after this operation the transplanted kidney is functioning well.


[Pneumocystis carinii infections following kidney transplantation]. Four adult recipients of cadaveric renal homografts acquired Pneumocystis carinii infections from which they subsequently died. The disease in adults under immunosuppressive therapy runs a course different from the disease observed in newborns. The clinical course is rapidly progressive and early diagnosis by means of aggressive diagnostic procedures is mandatory. To prevent a fatal outcome, treatment even on suspicion is suggested. Epidemiologically, a person-to-person spread seems possible and isolation of the patient is necessary.


[Induction of ovulation by means of synthetic LH-RH following unsuccessful stimulation with clomide]. Synthetic LH-RH was used to induce ovulation and pregnancy in 6 women with suspected hypothalamic anovulation. The women had been previously treated with Clomid, but according to indirect evidence this drug either failed to induce ovulation or the women had insufficient luteal phase. After treatment with LH-RH one pregnancy occurred and in 3 more cases indirect evidence indicated that ovulation had occurred.


[Treatment of arthrosis with a new non-steroid anti-rheumatic agent (Voltaren). A double blind comparison with indomethacin]. The new antirheumatic agent diclofenac sodium (Voltaren) has been compared with indometacin with respect to tolerance and effect on osteoarthritic symptoms. In a double blind trial two groups of 30 arthritic patients each received Voltaren and indometacin respectively for 12 weeks. The initial dose for both drugs was 75 mg per day. Where the effect was inadequate the dose could be raised to 125 mg daily. The outcome revealed no significant differences of the effect and tolerance between the two drugs. An earlier onset of effect, however, was observed in the Voltaren group.


[Comparison of Tyloxapol (Tacholiquin, Alevaire) with physiological saline as inhalation carrier solutions]. By means of a double-blind crossover study the effects of tyloxapol (Tacholiquin, Alevaire) and saline as carrier solutions for the inhalation of beta-agonists have been compared in 24 paitents with bronchial asthma. Specific airway conductance was measured repeatedly over a 2-hour period in order to assess changes of airway caliber due to the inhalation. The results reveal a significant bronchoconstrictive effect of tyloxapol as compared with saline. The bronchodilator activity of solutions with tyloxapol and beta-agonists (orciprenaline, salbutamol) was no better than those with saline and the same beta-agonists. However, side effects (symptoms of airway irritation, increase of pulse rate) were more pronounced with tyloxapol. In view of the direct effects of inhalation with a beta-agonist, no advantage of the expensive carrier solution tyloxapol over saline could be shown.


[Perinatal transmission of Plasmodium falciparum malaria]. Two weeks after leaving Nigeria for temperate zones and a few hours after giving birth to twins, a nigerian mother suffered an acute attack of malaria due to Plasmodium falciparum accompanied by cerebral, renal and hematolgical complications. Both infants were apparently healthy at birth, and no parasites were found on peripheral blood smears. Both placentas were macroscopically normal. At two months of age the second infant,  a boy, developed non-febrile hemolytic anemia due to Plasmodium falciparum. The clinical picture and pathogenic mechanisms of perinatal malaria are discussed. Possible protection of the twin sister by partial glucose-6-phosphate dehydrogenase deficiency is considered.


[Dialysis and kidney transplantation in Switzerland in 1973]. A separate computer print-out for Switzerland of the EDTA registry concerning all patients on dialysis or carrying a renal transplant has been analysed. Of a total number of 857 registered patients, 584 or 91 per million inhabitants were alive on 31 December 1973; 306 patients were on hospital hemodialysis, 68 on home hemodialysis and 2 on peritoneal dialysis. 353 patients had received 385 renal transplants, 208 of which were still functioning at the end of 1973. No major change was noted in cumulative survival rates of Swiss patients, who, as expected, showed lower survival with increasing age. Graft survival in a group of 148 first cadaver transplants with poor tissue match (2 or fewer HL-A identities) was better with 66+/-4% at one year than the 53+/-7% survival in the 63 grafts with at least 3 HL-A identities. The number of patients alive on home dialysis increased by 74% through 1973; one year survival equalled the European average at 93+/-4%. Rehabilitation was rather poor in dialysed patients, 21% of whom were reported to be working full time in the hospital-dialysed group and 42% in the home-dialysed group. Patients with functioning transplants, on the other hand, showed very satisfactory rehabilitation (75% working full time). Hepatitis among staff appeared be on the decrease, with only 9 cases in 1973 despite the fact that some 20% of dialysed and transplanted patients were still reported as hepatitis B antigen carriers. The number of new patients accepted for treatment in Switzerland has stabilized at 25-27 per million population per year since 1971. Average mortality was 15.3% in 1973. At the beginning of 1980 we can thus expect to be treating some 135 patients per million population with dialysis and renal transplantation.


[Testing of granulocyte function].

[Testing of granulocyte function]. Recent work on the in-vitro analysis of granulocyte functions is reviewed. Various forms of granulocyte functions defect have been observed in association with increased susceptibility to infectious diseases. Intrinsic cellular defects can be distinguished from secondary impairment of granulocyte functions due to other diseases, iatrogenic causes or humoral defects. In such cases the in-vitro methods for evaluation of granulocyte functions have become an indispensable diagnostic aid.


[The value of cooperative studies for the evaluation of new forms of therapy]. The principles of clinical therapeutic research that have evolved over the last few years are presented and illustrated with examples. The basis remains prospectively planned, controlled studies using standardized criteria for evaluation and documentation. Such studies are usually carried out cooperatively by several hospitals using a standard protocol. The principles underlying such studies are presented in detail, taking malignant lymphoma and acute leukemia as concrete examples.


[Bone marrow transplantation in leukemia: possibilities and problems]. At present, clinical bone marrow transplantation has reached such an advanced stage that it offers a chance of permanent cure to some patients with acute refractory leukemias. Prerequisites for successful marrow grafts are: careful histocompatibility typing of donor and host, favourable timing of the graft, which should not be performed in the absolutely terminal stages of the disease; optimum conditioning of the recipient, which should aim not only at immunosuppression to allow a marrow take but at maximum reduction of the tumor load; a well-trained team in supportive care and wide experimental and clinical experience in marrow grafting. For the time being only HL-A-identical, MLC-negative siblings or identical twins should be used as marrow donors.


[Viewpoints on the pharmacological suppression of immunologic reactivity]. The pharmacological alteration of immunological reactivity is considered. The immunosuppressive drugs may be classified according to their chemical class and their antigen- or cycle-dependency. A relative specificity towards the lymphoid system is cyclophosphamide. New vistas are opened by the modulation of immunological reactivity by cyclic nucleotides. The possibilities afforded by the combined use of immunosuppressive drugs have not been fully exploited. A short therapeutic program including donor antigen, procarbazine and antilymphocyte serum induces immunological tolerance to allogeneic skin grafts in mice and bone marrow allografts in dogs. Immunosuppressive properties of microorganisms are exemplified.


[Proceedings: Experimental endocarditis. Experimental basis and prophylaxis]. A simple model has been developed for the production of bacterial endocarditis in rabbits. The principle depends on the insertion of a polyethylene catheter into the venous or arterial system so that the tip rests in the heart cavity in which endocarditis is to be established. After catheter placement, intravenous injection of any one of a variety of microorganisms regularly produces infective endocarditis. The characteristics of the infection in rabbits are similar to those observed in infective endocarditis in man. The production of streptococcus viridans infections in previously immunized animals leads to the development of diffuse glomerulonephritis. Translating antibiotic doses on a weight basis, prophylactic antibiotic treatment programs recommended in man have been shown to be ineffective in rabbits. If the activity of antibiotics in this model infection in rabbits can be assumed to be comparable to that in man, it is necessary that we reconsider the currently accepted recommendation for prophylaxis and treatment of infective endocarditis in man.


[Proceedings: Microbiology of endocarditis]. The classical paper published by Schottmüller in 1903 has shown beyond doubt that blood cultures are a crucial diagnostic procedure for the diagnosis of endocarditis. Positive blood cultures also make it possible to distinguish between bacteremia and endocarditis: in the latter condition the number of organisms per ml of blood is relatively constant and all blood cultures are usually positive. Gram positive cocci are still the commonest organisms found in classical endocarditis. Gram negative organisms, yeasts and fungi are cultured with increasing frequency in cases of endocarditis secondary to valve replacement. Sensitivity testing by the disc diffusion method determines the minimal inhibitory concentration of the antibiotic towards the isolated organism. However, minimal bactericidal concentrations are of much greater prognostic value in endocarditis and should be performed routinely on the isolated organism.


[Urinary infections following bladder catheterization]. The incidence and the prophylaxis of urinary tract infection following bladder catheterization have been studied in 142 patients admitted for voiding cystourethrography (VCU). 71 children received a prophylactic treatment of 2 mg/kg nitrofurantoin daily for 4 days, while 71 received no treatment following bladder catheterization. Bacteriologic examination of the urine 4-9 days after catheterization showed significant bacteriuria in 5 untreated children. The germs responsible were E. coli, Proteus, and Klebsiella. None of the treated patients presented with significant bacteriuria. It is concluded that the incidence of significant bacteriuria after a VCU is not inconsiderable, that this urinary tract infection is often asymptomatic, and that the prophylactic administration of a disinfectant is justified.


[The value of dextran 70 in the prevention of thromboembolism in general surgery, orthopedics, urology and gynecology. A review of the literature]. 28 prospective, controlled, randomised studies on the incidence of deep vein thrombosis (DVT) and pulmonary embolism (PE) in surgical patients on dextran 70 prophylaxis are analysed. In all patients the diagnosis had been established by objective methods (fibrinogen test, phlebography, autopsy). In patients undergoing hip surgery (11 studies, mainly fractures of the upper end of the femur) the reduction in the number of DVT under dextran prophylaxis is the more evident the longer after operation phlebography is carried out. Coumarin and dextran prevention are equally effective. In 3 studies where diagnosis by the fibrinogen test was established during the first postoperative week only, no significant effect of dextran can be shown; there is no difference between the effect of dextran, coumarin or small doses of subcutaneous heparin. The effectiveness of dextran prophylaxis in reducing the DVT rate in general surgery (4 papers) is not clear, though 7 studies show that the number of fatal PE is reduced more than fivefold (p less than 0.0005). In patients on dextran prophylaxis, the incidence of DVT is equal to that in patients on coumarin prophylaxis before major gynecological surgery (4 papers). On postoperative initiation coumarin is significantly less effective than dextran. 2 further studies show that dextran is significantly effective as compared to controls and that there is no difference between dextran and heparin prophylaxis. Out of 1932 control patients 36 died of fatal PE verified at autopsy. Only 8 PE were seen in the group of 2011 patients receiving dextran prophylaxis (p less than 0.005). The effectiveness of dextran 70 corresponds to that of small doses of subcutaneous heparin. Dextran prevention is more effective in women than in men. Dextran prophylaxis is simple to carry out, has few contraindications, only rarely causes complications and is already effective during operation.


[Initial reduction of the lung volume and capillary escape syndrome in gram negative peritonitis]. Report on a female patient aged 29 with gramnegative bacterial peritonitis due to perforation of a postpyloric ulcer. A reduction of lung volume was observed, followed after 24 h by non cardiogenic interstitial and alveolar edema resulting in severe hypoxemia and hypercapnia with metabolic acidosis for 4 days. Return of gas exchange to physiological values was established prior to the restoration of normal lung volume. The pathophysiological mechanism of these phenomena is discussed.


[Proceedings: Hypercoagulability and compensated intravascular coagulation in chronic kidney insufficiency and after kidney transplantation]. Seven blood coagulation tests which may indicate a state of hypercoagulability or of chronic intravascular coagulation were assayed in 106 blood samples from 50 patients with chronic renal insufficiency or after renal transplantation. The following abnormal results were obtained: increased titer of fibrin(ogen) degradation products in 60%, abnormal fibrinogen immunoelectrophoresis in 49%, shortened partial thromboplastin time and whole blood clotting time in 45 and 37% respectively, prolonged thrombin time in 34%, increased cryofibrinogen level in 21% and positive protamine sulfate gelation test in 11%. The greatest number of abnormalities was found during the first week after transplantation and during transplant rejection, and the smallest in patients with stable transplant who were anticoagulated with warfarin. Partial thromboplastin times of less than 19 sec were associated in 3/4 patients with thrombosis of the renal artery or vein or with rejection. Rejections could be identified with high probability (p less than 0.001).


[Proceedings: Transfer factor--a preliminary report]. Experience with the production, physicochemical analysis and clinical application of transfer factor (TF) from 1971 to 1975 is briefly reviewed. Standardized TF preparations were given to over 100 patients in controlled studies. Clinical results are discussed and the present position of TF therapy is evaluated.


[Yersinioses].

[Yersinioses]. The principal clinical syndromes caused by Yersinia (Y. pseudotuberculosis and Y. enterocolitica) are described. It is likely that they are zoonoses transmitted to man by ingestion. Fever, abdominal pain and diarrhea are the commonest symptoms, and patients are often operated upon for suspected appendicitis. The symptoms associated with these infections include arthralgia and erythema nodosum, particularly in adults. Most cases are benign, but some may be severe. Fortunately, however, many antibiotics are active against Yersinia. At present these diseases are uncommon in Switzerland but appear to be endemic in Scandinavia. Their relative incidence may increase if physicians become more aware of this possible etiology.


[Lymphangiomyomatosis. Presentation of a case and review of the literature]. Diffuse lymphangiomyomatosis is a rare disorder of the mediastinal and retroperitoneal lymph nodes due to chronic benign proliferation of the smooth muscle cells in the lymphatics. This process leads to chylothorax and chylascites and eventually to cystic lung disease. The pulmonary complications are usually result in respiratory failure and death. The disease is only observed in females. A typical lethal course in a young woman is described and the literature is reviewed. The possible etiologic and therapeutic implications are discussed.


[A false historic representation of the martyrdom of St. Apollonia: decapitation]. The author quotes the only known historical witness on the life and death of Santa Apollonia: the description given by the historian Eusebius. According to his description of the martyrdom of the Saint, her teeth were extracted and her jawbones broken. An extensive iconography exists in museums, churches and private collections. According to statues and images of the Saint, the martyrdom took place by stoning or else by the use of instruments of torture such as pincers, gouge and gammer, and dentists' forceps. Although it is most probable that recourse was taken to lapidation, it is also likely that the above instruments were used, because it agrees with the technic then in use in dental surgery and does not disagree in any way with the historical facts. Such is not the case regarding the beheading. However, the author quotes three groups of iconographic documents displaying that kind of torture. One of them, shown for the first time, appears in a Book of hours of French origin, dating from the 15th century, which exists in the Calouste Gulbenkian Museum, in Lisbon, Portugal.


Review of the chemical elements and environmental chemistry--strategies and tactics. Inspite of advanced technology and the availability of adequate basic analytical instrumentation there is a need to improve the quality of data obtained in many programmes of environmental monitoring. Really new approaches are required based upon interdisciplinary, as distinct from pluridisciplinary cooperation; during the early stages individual disciplines need to extend some degree of charity. Scientists have to acknowledge the social implications of many of their studies and face up to controversial issues particularly in relation to pollution of the environment. Today we do not know the significance of levels of most contaminants and pollutants found in the environment, and many have not even been identified. Besides large releases of pollutants, a fundamental problem concerns man's biological response to low doses of various substances over long periods of time; the interval between an initial insult and the detection of detrimental effects for many physical and chemical agents can amount to between 10-30 years. In the absence of an objective interdisciplinary approach the expertise developed in an individual discipline is not available to others in which it may be of value. Many types of instrumentation and techniques developed in one discipline are unknown, or untried, in another; centralised facilities provide an adequate spectrum of tools and skills which are essential in tackling current problems. This approach has been shown to be rewarding in industry and in several private research organisations. In this paper the versatility of some types of modern instrumentation is illustrated in several fields of environmental chemistry and some of the substantial problems are discussed.


Detection of mutagenic activity of metronidazole and niridazole in body fluids of humans and mice. After humans were treated at therapeutic doses with the trichomonacide metronidazole (Flagyl) and the antischistosomal agent niridazole mutagenic activity was demonstrable in their urines when tested with the histidine auxotroph of Salmonella typhimurium. Both compounds were active in the host-mediated assay in mice, and evidence of activity was found in the blood and urine of mice treated with niridazole but not with metronidazole.


Mutagenicity of malonaldehyde, a decomposition product of peroxidized polyunsaturated fatty acids. Incubation of histidine requiring auxotrophs of the bacterium Salmonella typhimurium with malonaldehyde, a three-carbon dialdehyde, produced an increased number of revertants in specific strains. Mutagenesis was only observed in frameshift mutants with normal excision repair and did not occur in those base-pair substitution mutants tested. The results are consistent with the cross-linking of bacterial DNA by malonaldehyde leading to mutagenesis expressed through the error-prone repair system.