Techniques and results of ventricular aneurysmectomy with emphasis on anteroseptal repair. We have reviewed an 8 year experience with ventricular aneurysmectomy in 170 patients. Ninety percent had anterior aneurysms and underwent "anteroseptal repair" with exclusion of nonfunctioning septal myocardium. Preoperative left ventriculograms and coronary arteriograms were studied and "scored," and the hospital mortality and long-term survival rates for various subsets of the group were correlated with their radiographic data. A postoperative score for the coronary arteries was developed according to the preoperative anatomy and the vessels bypassed. Both the ventriculogram score and the postoperative coronary score had significant effects on both hospital mortality and long-term survival rates. The severity of preoperative coronary disease had minimal predictive value. Recent myocardial infarction did not preclude a good result. The value of an aggressive surgical approach to patients with ventricular aneurysm was confirmed even for certain subsets with indicators suggestive of poor prognosis. Anteroseptal repair appears to give optimal results for the typical "anterior" aneurysm. All suitable coronary arteries should be bypassed. Attention to the details of preoperative anatomy and function allows the most accurate prediction of prognosis and dictates the optimal therapeutic approach.


A twenty-year analysis of the results of sleeve resection for primary bronchogenic carcinoma. Ninety-six patients with primary bronchogenic carcinoma were treated by lobectomy with sleeve resection of the bronchus, over a 20 year period (1958 through 1977). In 80 resections undertaken prior to 1973, a 5 year survival rate of 34 percent was realized, with an operative mortality rate of 7.5 percent. Survival at 10 and 15 years has been assessed. A review of factors influencing survival has been undertaken and the biologic behavior of these pulmonary neoplasms, modified by sleeve resection, has been outlined. Of interest is the high rate of local recurrence accounting for death within 5 years postoperatively and the late incidence in the survivors of second malignancies and other diseases of surgical interest. Sleeve resection represents a surgical alternative in selected cases of bronchogenic carcinoma in which wider resection may be hazardous, and the indications should be extended to include some lesions commonly managed by pneumonectomy.


Lung transplantation. Hypothermic storage for 24 hours in a colloid hyperosmolar solution. We studied the effects of a colloid hypersomolar solution in perservation of lungs for transplantation in dogs. Fresh allografts were compared to lungs stored (4 to 7 degrees C), in Ringer's lactate for 3 hours and in modified silica gel function (MSGF) for 8, 16, and 24 hours before transplantation. Lungs preserved in Ringer's lactate for 3 hours were significantly damaged, and there were no long-term survivors in recipient dogs (1.2 +/- 0.4) (mean +/- S.E.). In contrast, the recipients of lungs preserved in MSGF for periods of up to 24 hours stored MSGF grafts = 10.5 +/- 3.1 days, survival, mean +/- S.E. Fresh Ringer's lactate grafts = 8.5 +/- 2.3 days, mean +/- S.E.; Fresh MSGF grafts = 13.6 +/- 3.8 days, mean +/- S.E.). Arterial blood gas measurements and chest roentgenograms were good methods of assessting the condition of preserved lung allografts. No significant differences were observed between the fresh and MSGF-preserved grafts. Pneumonia and rejection were the most frequent causes of death for both the fresh and MSGF-preserved allograft recipients. We demonstrate that a calloid hyperosmolar solution (MGSF) is a good method for 24 hours hypothermic storage of lung allografts for transplantation.


Guidelines for the management of transient ischemic attacks. On the basis of a review of the literature on anticoagulant, antiplatelet, and surgical treatment, supplemented by our personal experience, we have developed guidelines for the management of patients with transient ischemic attacks (TIA). 1. The majority of patients with vertebral-basilar TIA are treated medically. 2. If a skilled surgeon and an experienced angiographer are available, patients with typical carotid TIA who are suitable medical risks should have angiography followed by carotid endarterectomy if an appropriate lesion is found. 3. Nonoperated patients with TIA of less than 2 months' duration are treated with 3 months of warfarin therapy (unless contraindicated) before treatment with aspirin is begun. 4. Nonoperated patients with continuing TIA of 2 or more months' duration are treated with aspirin unless there has been a recent increase in the frequency, duration, or severity of TIA. Under these circumstances, warfarin therapy is advised for 3 months before aspirin is started. Aspirin therapy should be continued until the patient has been free of TIA for 1 year. 5. No treatment is advised for nonoperated patients whose last episode of TIA was longer than 12 months ago.


Some aspects of maternal behaviour in mammals. Lactation is the one common factor in the behaviour patterns of maternal care in mammals. A series of behaviour patterns is elicited by the different stages of the developing young and these are related to the way of life of the animals concerned. Infants which are born naked, blind and helpless elicit retrieving and nest building and are cleaned and cared for by the female. Older animals or those born with fur, but with poor locomotion, are still carried and cleaned. When the young can move well other behaviour patterns which keep the young and mother together are important, so signals for communication and recognition of individuals develop. At the end of lactation various behaviour patterns bring about weaning. Sometimes this is the result of dispersal by the young, and sometimes the young are actively rejected or deliberately abandoned. Several examples of maternal behaviour are given in relation to the classes of mammals and some related problems are discussed.


Studies of process--outcome correlations in medical care evaluations: a critique. The validity of process evaluations of medical care has been challenged by a number of studies which purport to show that process and outcome measures are unrelated. However, each of the studies had numerous methodological flaws which biased their results against finding a relationship: either their outcome measures had questionable validity, their research designs were inappropriate, or the statistical analyses were poorly conceived. Better studies have found significant, although modest, correlations between process and outcome measures. Since the  validity of outcome measures has never been determined, there is little reason at present for believing that outcome measures are more valid than process measures.


Reliability of information abstracted from patients' medical records. Two recent studies by the Institute of Medicine on the reliability of hospital discharge data abstracted from patients' medical records raise serious questions about the adequacy of information on diagnoses and procedures. The findings are particularly timely, since increasingly important decisions about the content of medical care and levels of reimbursement may be based on such information. A series of recommendations are offered to guide the use and improvement of abstracted medical record information.


The Frey syndrome: a review and double blind evaluation of the topical use of a new anticholinergic agent. The symptom complex of localized facial gustatory sweating and flushing during mastication (The Frey syndrome) is a common sequela of parotidectomy with facial nerve dissection. A thorough review of the literature concerning the Frey syndrome is reported. The procedure of tympanic neurectomy has received special emphasis with a review of 73 cases of tympanic neurectomy. The treatment modalities available, if tympanic neurectomy fails, are discussed. Important guidelines for the safe use of topical therapy to control gustatory sweating are presented as an alternative to surgical therapy. The author studied 129 post parotidectomy patients in whom 60% noted symptomatic gustatory sweating, and approximately one-fourth fo these symptomatic patients requested topical anticholinergic therapy, with one patient electing tympanic neurectomy. The only form of medical treatment presently available utilizes the topical application of scopolamine, a drug having potentially significant central nervous system side effects if systemically absorbed. In an effort to find an effective drug for topical application with a more favorable therapeutic index than scopolamine, glycopyrrolate was investigated. Glycopyrrolate was compared in varying concentrations to topical scopolamine in a personally conducted double blind clinical trial involving 16 patients. Initial results of this investigation suggest that topical glycopyrrolate in concentrations 0f 0.5% and 1.0% provide complete effective control of gustatory sweating for at least several days duration after a single application. There have been no significant side effects with the use of topical glycopyrrolate to date. Commercial topical antiperspirants were also investigated and found to be of limited benefit.


Alkaloid N-oxides. A review of recent developments. The preparation, characterization and chemistry of alkaloid N-oxides is reviewed. Because the literature on amine N-oxides is more extensive for animals than for plants, a brief resumé of the pharmacology, metabolism, and toxicity of N-oxides is given. Some 64 naturally occuring N-oxides representing pyrrolidine-piperidine-, pyrrolizidine-, quinolizidine-, tropane-, isoquinoline-, morphinane-, indole- and miscellaneous-type alkaloids are reviewed. These alkaloid N-oxides are additional to and, in the main, have been isolated since those described in a 1971 review. The earlier review dealt with some 56 naturally occurring N-oxides which represented mainly pyrrolizidine and indole types. The role of N-oxides in plants is discussed.


Shikimic acid and quinic acid are not mutagenic in the Ames assay. Shikimic acid, reported to cause tumors in mice, and its close structural analog, quinic acid, both ubiquitous constituents of higher plants, were found not be be mutagenic in the Ames assay when tested with and without the rat liver microsomal activation system.


[Device and method for neuro-psychic relaxation]. A pattern model of a device for tranquilization a relaxation--a photo-acoustic relaxator--was constructed and procedures for its application elaborated. Unlike psychotherapy, hypnosis, autogenic training and pharmacological agents in this method natural factors of actions, such as light and sound are used. The relaxation achieved by rhythmic photoacoustic effects with the help of the device pre-supposes the regulation of the patient's respiration. The effect produced by the relaxation sittings is shown to depend on the temperament of the examined. The use of the device is particularly effective in persons displaying a high degree of suggestibility and emotional susceptibility.


Lidocaine prophylaxis in acute myocardial infarction. Primary ventricular fibrillation (PVF) occurs in approximately 3--10% of uncomplicated acute myocardial infarction (AMI) patients. The major reason for this variability in incidence appears to be population diferences in the time from symptom onset to admission. Other risk factors have not been consistently shown to influence the risk of PVF. Warning arrhythmias do not warn of impending PVF in from 20--80% of AMI patients; thus, antiarrhythmic therapy reserved for those with warning arrhythmias may fail to prevent PVF in a significant number of patients. Although a review of 13 controlled trials of lidocaine prophylaxis shows only two suggesting a protective effect from this drug, only one study was free of major defects in trial design. This trial showed a striking decrease in PVF incidence when lidocaine was employed. Lidocaine should probably be administered to all uncomplicated AMI patients during the first 48 hours after infarction. Its utility in preventing ventricular fibrillation in complicated AMI patients and in the very early AMI period is unclear.


Overwhelming strongyloidiasis: an unappreciated opportunistic infection. Strongyloides stercoralis is an intestinal nematode which infects a large portion of the world's population. Individuals with infection confined to the intestinal tract are often asymptomatic but may have abdominal pain, weight loss, diarrhea, and other nonspecific complaints. Enhanced proliferation of the parasite in compromised hosts causes an augmentation of the normal life-cycle. Resultant massive invasion of the gastrointestinal tract and lungs is termed the hyperinfection syndrome. If the worm burden is excessive, parasitic invasion of other tissues occurs and is termed disseminated strongyloidiasis. A variety of underlying conditions appear to predispose to severe infections. These are primarily diseases characterized by immunodeficiency due to defective T-lymphocyte function (Table 1). Individuals with less severe disorders become compromised hosts because of therapeutic regimens consisting of corticosteroids or other immunosuppressive medication. The debilitation of chronic illness or malnutrition also predisposes to systemic stronglyloidiasis. The diagnosis of strongyloidiasis can be readily made by microscopic examination of concentrates of upper small bowel fluid, stool, or sputum. Important clues suggesting this infection include unexplained gram-negative bacillary bacteremia in a compromised host who may have vague abdominal complaints, an ileus pattern on X-ray, and pulmonary infiltrates. Eosinophilia is helpful, if present, but should not be relied upon to exclude the diagnosis. The treatment of systemic infection due to Strongyloides stercoralis with either thiabensazole 25 mg/kg orally twice daily is satisfactory if the diagnosis is made early. Because of several unusual features of this illness in compromised hosts, the standard recommendation for 2 days of therapy should be abandoned in such patients. Immunodeficiency, corticosteroids, and bowel ileus reduce drug efficacy. Thus a longer treatment period of at leuch as blind loops or diverticula necessitate longer treatment. Stool specimens and upper small bowel aspirates should be monitored regularly and treatment continued several days beyond the last evidence of the parasite. In particularly difficult situations where either worm eradication is impossible or reinfection is probable, short monthly courses of antihelminthic therapy seem to be effective in averting recurrent systemic illness. Finally, prevention of hyperinfection or dissemination due to Strongyloides stercoralis can be accomplished by screening immunocompromised hosts with stool and upper small bowel aspirate examinations. These would be especially important prior to initiating chemotherapy, or before giving immunosuppressive medications or corticosteroids to patients with nonneoplastic conditions such as systemic lupus erythematosus, nephrotic syndrome, or renal allografts.


Pulmonary hemorrhage in systemic lupus erythematosus. The clinicopathological features of four patients with systemic lupus erythematosus and pulmonary hemorrhage are described. Our study confirms that pulmonary hemorrhage may be a dominant clinical expression of lung involvement in this disease. Its clinical manifestations are usually quite characteristic. However, hemoptysis may be absent. Radiographically, bilateral alveolar infiltrates resembling pulmonary edema or infection may be seen. Pulmonary hemorrhage was a major contributing factor to the death of three of our patients. The possible pathogenetic mechanisms responsible for pulmonary hemorrhage in our patients and other patients previously recorded in the literature are reviewed. Evidence supporting an immune complex pathogenesis is presented. Our immunopathological and ultrastructural studies demonstrate deposition of immune aggregates in the lungs in the alveolar septa, large blood vessels, and bronchioles in a manner similar to that which has been observed in the experimental serum sickness model of immune complex mediated pulmonary injury. The histological abnormalities, although nonspecific, are consistent with this interpretation, and collectively show diffuse alveolar lining cell and endothelial cell injury. However, an immune complex pathogenesis may not completely explain the occurrence of pulmonary hemorrhage in SLE. Other factors, including bleeding disorders, pulmonary infection, oxygen toxicity, and the "shock lung" syndrome, may also have contributed to lung hemorrhage in some of these patients.


Studies on the modes of action of azaserine in Escherichia coli. Mechanism of resistance to azaserine. Growth of wildtype Escherichia coli was inhibited by azaserine. There was an inverse relationship between the initial rate of uptake of phenylalanine and the azaserine concentration. Moderately azaserine-resistant mutants exhibited an initial rate that was similar to that of an aroP mutant, but highly azaserine-resistant mutants exhibited little, if any, uptake of phenylalanine. All of the azaserine-resistant organisms tested harboured a mutation in the aroP+ gene. However, resistance to the antibiotic was not due solely to this lesion.


Inhibition of some respiration and dehydrogenase enzyme systems in Escherichia coli NCTC 5933 by phenoxyethanol. Low concentrations (less than 0.2% w/v) of phenoxyethanol stimulated both the rate of respiration and total oxygen uptakes of Escherichia coli NCTC 5933 suspensions with glucose and other substrates, whilst higher concentrations (0.2--0.6% w/v) although still below those showing significant bactericidal activity, produced progressive levels of inhibition. The degree of respiratory inhibition varied with different substrates in the order malate less than succinate less than pyruvate less than or equal to glucose less than lactate, and suggested appreciable inhibition at a point after malate in the tricarboxylic acid cycle. This suggestion was supported by the use of tetrazolium salts as alternative electron acceptors, and by cytochrome difference spectra, which together implicated malate dehydrogenase as the most likely site of action. Isolated dehydrogenase enzymes of the tricarboxylic acid cycle in cell-free preparations were unaffected by high concentrations of phenoxyethanol (0.8% w/v) with the exception of malate dehydrogenase which was inhibited in extracts to extents similar to those of malate oxidation by intact bacteria. Lineweaver-Burke plots for malate dehydrogenase activity in the presence of phenoxyethanol suggested a competitive inhibition of the oxaloacetic acid-limited reaction and a non-competitive inhibition of the NADH-limited reaction. Accordingly, Ki values were found to be low when the rate of reaction was limited by oxaloacetic acid concentration yet relatively high when NADH was rate limiting.


Investigations on the outer membrane proteins of Salmonella typhimurium. The number, nature and organization of the outer membrane proteins of Salmonella typhimurium have not yet been resolved. Therefore these proteins were isolated using a concentrated solution of guanidine hydrochloride and studied using different analytical techniques. Upon chromatography on Sephadex G-200 four fractions were obtained. Only the fraction containing a protein of molecular weight 13,000 produced immunoprecipitation reactions with the antisera raised against the whole bacteria. On polyacrylamide gel electrophoresis in the presence of sodium dodecyl sulphate, 7 major proteins were found, with molecular weights between 13,000 and 43,000. Isoelectric focusing on 4.6% polyacrylamide gels resolved the outer membrane proteins into 10 bands with apparent isoelectric points between 5.0 and 8.4. Finally these proteins could be further resolved into as many as 50 spots where a two-dimensional electrophoresis was carried out with isoelectric focusing in the first dimension, and polyacrylamide gel electrophoresis in the presence of sodium dodecyl sulphate in the second dimension. These results demonstrated that the outer membrane proteins of S. typhimurium are extremely heterogeneous. To investigate the mode of organization of lipopolysaccharides in the outer membrane, the membrane proteins were separated by the liquid isoelectric focusing technique. Lipopolysaccharides were primarily found to be associated with a protein of isoelectric point 7.8.


A histochemical method for the detection of metals in tissues, with reference to the use of surgical implants. This report describes a method for the detection of metals in tissues that is suitable for a routine pathology laboratory. The method has been developed specifically for the examination of soft tissues taken at biopsy from the site of surgical implants. It involves the mineralization of organic matter in sections by sodium metasilicate and the conversion of the metals to sulphates by sulphuric acid, which are then stained by appropriate solutions. The method is described with particular reference to titanium and cobalt.


A procedure for obtaining thin sections of undercalcified bone biopsies embedded in methyl methacrylate. A complex of techniques is described, including a specially designed mould and a method for flat mounting of the sections, enabling to obtain well-stretched and undamaged thin sections of undecalcified bone biopsies. Apart from a gain in polymerisation time, a clear advantage of the special mould is a more favorable temperature course in and around the tissue during the polymerisation process.


The 1976 influenza epidemic in Melbourne. Some aspects of the 1976 influenza epidemic are described and compared with findings in previous years. Rapid diagnostic techniques gave encouraging results, but were less sensitive than conventional techniques. A higher rate of virus isolation was obtained from nasopharyngeal aspirates than from pooled nose and throat swabs.


Rubella vaccination in Australia: 2. Experience with the RA27/3 rubella vaccine and results of a double-blind trial in schoolgirls. RA27/3 rubella vaccine (Almevax) was used for the first time in Australia. The seroconversion rate was similar to that seen with Cendehill vaccine (Cedevax), but there were fewer subjects with low antibody titres after Almevax vaccine. Although Almevax vaccine was associated with a significantly higher incidence of sore throat, rash and joint involvement in seronegative adults, the incidence of side effects in a double-blind trial in schoolgirls was similar for the two vaccines, and the morbidity was low in both groups. Almevax vaccination successfully boosted low antibody titres in 11 of 14 women who had previously responded poorly to Cendevax vaccination. It would be difficult to differentiate the better vaccine for the schoolgirl programme. In some clinical situations, however, one vaccine has advantages over the other.


Measurement of critical properties of muslin and nonwoven sterile-wraps. Empirical evaluations closely simulating actual use conditions were employed to compare critical property levels of commonly used muslin (140-thread) and nonwoven sterile-wraps. Critical properties and experimental methods used to measure these properties are: (a) ease of steam penetration determined by time-temperature measurements in large, double-wrapped packs subjected to steam sterilization, (b) bacterial barrierness measured by microbiological assay of initially sterile double- and single-wrapped packs contents after pack storage in hospitals, (c) compatibility with ethylene oxide sterilization measured by inactivation of spore strips and by quantities of ethylene oxide residuals after aeration of packs and (d) generation of lint by counting particles generated by flexing wrap materials. It was concluded that the nonwoven steril-wrap was superior in ease of steam penetration, bacterial barrierness, and linting. No differnece was detected between materials in ethylene oxide sterilization.


Reversion in variants from a duplication strain of Aspergillus nidulans. Strains of Aspergillus nidulans with a chromosome segment in duplicate, one in normal position and one translocated to another chromosome, are unstable at mitosis. In addition to variants which result from deletions in either of the duplicate segments, which usually have improved morphology, they produce variants with deteriorated morphology. Three deteriorated variants reverted frequently to parental type morphology, both spontaneously and after ultra-violet treatment. Of six reversions analysed genetically, five were due to suppressors and one was probably due to back mutation. The suppressors segregated as single genes and were not linked to the mutation which they suppress. The instability of these so-called "deteriorate"variants is discussed in relation to mitotic instability phenomena in A. nidulans.


A DNA segment within the colicin E1 structural gene on ColE1 affecting immunity to colicin. Insertion of DNA at the EcoRI site of ColE1 results in increase of immunity to colicin killing in E. coli harboring such recombinant ColE1 plasmid as compared to E. coli (ColE1). This effect is neither due to cis or trans interactions originating from the inserted foreign DNA fragment, nor to changes in plasmid copy number. This defect in the immunity mechanism is not trans complemented for by wild type ColE1. Increase in immunity can also be obtained by deleting a DNA segment from the ColE1 genome. This segment is approximately 120 bp left to the EcoRI site within the colicin structural gene. It is concluded that the structure of DNA per se, around the EcoRI site, within colcin structural gene, is the structure which affects immunity expression.


Catabolic synergism: a cooperation between the availability of substrate and the need for nitrogen in the regulation of arginine catabolism in Saccharomyces cerevisiae. The simultaneity of the presence of substrate (inducer) and the absence of a better nitrogen nutrient causes a strong cooperative effect (catabolic synergism) on arginase production. This effect is shown to operate by a specific mechanism. carg A+ 0h mutation (Dubois et al., 1978) identifies an element of this process located near the arginase structural gene and acting in cis. This mutation produces constitutivity for synergism in addition to constitutivity for induction (this last effect is produced alone by cargA +0- operator constitutive mutation). The receptor of the signal for the presence of substrate is the same as for induction. cargA + 0h mutation allows to make further distinction between the promotion of arginase synthesis caused by nitrogen limitation and nitrogen starvation.


Genetic control of invertase formation in Saccharomyces cerevisiae. II. Isolation and characterization of mutants conferring invertase hyperproduction in strain EK-6B carrying the SUC3 gene. Invertase formation in the yeast Saccharomyces cerevisiae is subject to repression by hexoses in the growth medium. Mutagen-induced (ethyl methanesulfonate or N-methyl-N-nitro-nitrosoguanidine) invertase hyperproducer mutants have been derived from the SUC3 MAL3 strain EK-6B by selecting for their ability to grow on media containing the sugar raffinose plus 2-deoxy-D-glucose (2DG). Raffinose like sucrose is a betta-fructoside which can be hydrolyzed by yeast invertase (beta-fructoside which can be hydrolyzed by yeast invertase (beta-fructofuranoside fructohydrolase). These mutants, designated dgr, produce higher levels of invertase (pi-glucosidase levels are also elevated but to a lesser extent) under conditions normally repressing invertase biosynthesis in the parent. Invertases of mutants dgr2 and dgr3 are indistinguishable from that of EK-6B with respect to their Km's for sucrose and thermal labilities. Genetic studies revealed that dgr2 and dgr3 are recessive and unlinked to the SUC3 gene.


A mutation defective in the xanthine alternative pathway of Aspergillus nidulans: its use to investigate the specificity of uaY mediated induction. In Aspergillus nidulans uric acid can be produced from xanthine via purine hydroxylase I (xanthine dehydrogenase) or via the xanthine alternative pathway (Darlington and Scazzocchio, Biochem. Biophys. Acta, 166, 569--571; 1968). A mutation defective in the xanthine alternative pathway of Aspergillus nidulans is described. By combining this mutation with hxB-20 which results in complete loss of purine hydroxylase I and II activities, but which conserves cross-reacting material, it is possible to block completely uric acid production and thus investigate which are the effective in vivo inducers of three enzymes under the control of the positive regulatory gene uaY: adenine deaminase, purine hydroxylase I (measured as cross-reacting material) and urate oxidase. It is concluded that uric acid is the only effective physiological inducer, while its 2 and 8 thio-analogues serve as gratuitous inducers.


RNA polymerase mutant with altered sigma factor in Escherichia coli. A structural gene for sigma factor (rpoD) of DNA-dependent RNA polymerase (RNA nucleotidyltransferase; nucleoside-triphosphate: RNA nucleotidyltransferase, E.C. 2.7.7.6) was mapped precisely by a set of F' factors including those already published (Proc. Natl. Acad. Sci. USA. 74, 1831-1835 (1977)). Based on the result that rpoD is located at the dnaG-uxaAC region, a number of mutants containing a temperature-sensitive mutation at or near the uxaA gene were isolated by localized mutagenesis. One of these mutants was found to produce RNA polymerase altered in both thermostability and optimum salt concentration as a result of structural alteration of sigma factor. This mutation, U303, maps at 66 min on the genetic map of E. coli, near the dnaG locus, and affects normal growth of cells.


Polarity of mutations induced by insertion of transposons Tn5, Tn7 and Tn10 into the nif gene cluster of Klebsiella pneumoniae. Three new genes nifM, nifI and nifN have been mapped in the nif gene cluster of Klebsiella pneumoniae and a fourth gene nifJ has been confirmed as being a separate cistron. Polar nif mutations were obtained by transposition of Tn7 to plasmid pRD1, and of Tn5 and Tn10 to plasmid pMF100, a derivative of pRD1. Complementation analysis of the nif::Tn mutants led to the identification of at least six transcriptional units: nifB; nifA; nifJ; nifH, nifD and nifK; nifE and nifI; nifN, nifM and nifF. Biochemical and genetic evidence suggest that the three genes nifH, nifD and nifK, which are probably the structural genes for nitrogenase, belong to the same operon and are transcribed from nifH to nifK. A polypeptide with a molecular weight of approximately 120,000 is presumed to be the nifJ product.


Inhibition of yeast sporulation by ethidium bromide. Ethidium bromide blocks ascus formation in the yeast Saccharomyces cerevisiae. This may mean that the presence of the mitochondrial genome is required for sporulation in this organism.


Mutations affecting the structural genes and the genes coding for modifying enzymes for ribosomal proteins in Escherichia coli. Temperature-sensitive mutants of an Escherichia coli K-12 strain PA3092 have been isolated following mutagenesis with nitrosoguanidine, and their ribosomal proteins analyzed by two-dimensional gel electrophoresis. This method was found to be very efficient in obtaining mutants with various structural alterations in ribosomal proteins. Thus a total of some 160 mutants with alterations in 41 different ribosomal proteins have so far been isolated. By characterizing these mutants, we could isolate not only those mutants with alterations in the structural genes for various ribosomal proteins, but also those with impairments in the modification of proteins S5, S18 and L12. Furthermore, a mutant has been obtained which apparently lacks the protein S20 (L26) with a concomitant reduction to a great extent of the polypeptide synthetic activity of the small subunit. The usefulness of these mutants in establishing the genetic architecture of the genes coding for the ribosomal proteins and their modifiers is discussed.


Correlation between the serine sensitivity and the derepressibility of the ilv genes in Escherichia coli relA- mutants. Upon addition of excess one carbon metabolites (including serine)bacteria stop growing because of isoleucine starvation. After such treatment stringent bacteria rapidly resume normal growth whereas relaxed mutants remain unable for some time to grow. We show here that this is due to a lack of derepressibility of ilv genes after the starvation period. Results are also presented which show that RNA polymerase structural mutants may be selected among the clones resistant to a mixture of serine, methionine and glycine, in relA- strains. Finally circumstancial evidence suggests that the one carbon metabolism may be involved in a process controlling isoleucine metabolism.


Regulation of the int gene of bacteriophage lambda: activation by the cII and cIII gene products and the role of the Pi and Pl promoters. The activation of the int gene by the cII and cIII gene products was studied by analysing int expression following infection of UV-irradiated cells by various phage mutants. Residual expression of int, probably from Pl, takes place in the absence of cII/cIII activation. Activation of the int gene, like that of the cI repressor gene, is poor at low multiplicities of infection. The mutation intC, which allows constitutive int expression in the lysogenic state, partially relieves the requirement for cII and cIII activation. The kinetics of Int synthesis after addition of the inhibitor rifampicin suggest that the activation occurs at the transcriptional level.


Mutational alterations in 50 proteins of the Escherichia coli ribosome. A strain of Escherichia coli, VT, which spontaneously gives rise to mutations in many ribosomal proteins, has been used in conjunction with chemical mutagenesis and varying the subsequent incubation temperature to select mutants which have alterations in every ribosomal protein amenable to analysis of 70 S proteins on two-dimensional polyacrylamide gels under standard conditions. Alterations have been detected in 50 ribosomal proteins, namely in 20 from the small and in 30 from the large subunit. This is the most complete set of mutants with altered ribosomal proteins described so far. The difficulty until recently in obtaining mutations in most ribosomal proteins arises not because they are lethal, as has often been supposed, but because of the lack of a suitable selection heretofore.


Gene expression in Escherichia coli B/r during partial rifampicin-mediated restrictions of transcription initiation. The antibiotic rifampicin inhibits transcription initiation, but not the elongation and completion of nascent RNA transcripts. Addition of low concentrations of rifampicin only partially blocks initiation but at the same time specifically alters the general pattern of transcription in the culture. The transcription of genes specifying the beta and beta' subunits of RNA polymerase, and to a lesser extent of the genes specifying the RNA and protein components of the ribosome, was specifically stimulated relative to total transcription. In contrast, the transcription of the lactose operon was selectively reduced. These results are consistent with the ideas that the level of expression of the genes specifying the beta and beta' subunits is sensitive to the general rate of RNA synthesis in the culture, and that the expression of the beta and beta' RNA polymerase genes is related to the expression of ribosome component genes.


Uvm mutants of Escherichia coli K12 deficient in UV mutagenesis. I. Isolation of uvm mutants and their phenotypical characterization in DNA repair and mutagenesis. Selection for defective reversion induction, after UV treatment of E. coli K 12, yielded uvm mutants. These mutants exhibited highly reduced or no UV mutability for all loci tested although they were moderately and normally mutable by X-rays and EMS, respectively. Uvm mutations confer only a slight sensitivity to killing by UV and X-rays and no clear sensitivity to the lethal effect of HN2, EMS or MMS. Growth and viability of untreated uvm cells were normal. The properties of uvm mutants are discussed in relation to those of other relevant  mutant types and to some actual problems of induced mutagenesis.


Synthesis of tryptophanase in Escherichia coli: isolation and characterization of a structural-gene mutant and two regulatory mutants. A mutant of E. coli has been isolated that is temperature-sensitive in respect of tryptophanase. When incubated at 60 degrees C, cell-free extracts of the mutant suffer inactivation of enzyme activity much more rapidly than similar extracts of the wild type. After lysogeny with a specialized transducing phage carrying the wild-type tryptophanase gene, the mutant is able to synthesize tryptophanase that is wild-type in its response to treatment at 60 degrees C. It is concluded that the mutation lies in the structural gene for the enzyme. Two further mutants have been isolated that synthesize tryptophanase constitutively. One mutation renders synthesis of the enzyme indifferent to the presence of inducer; the other mutation allows synthesis of the enzyme in the absence of inducer at about 35% of the fully induced wild-type rate. Neither mutation alleviates catabolite repression. Genetic mapping shows that the constitutive mutations lie very close to the structural-gene mutation, on the side of the structural gene distant from bglR.


[Methods for the demonstration of the basal membrane of the glomerular capillaries]. Author for the demonstration of the basal membrane of the glomerular capillaries recommends oxidation with periodic-acid followed by treatment with potassium-metabisulfite and staining with resorcin-fuchsin, or impregnation with silver-nitrate solution in sodium borat.


The relationship between carcinogenicity and mutagenicity of some polynuclear hydrocarbons. 25 polynuclear hydrocarbons were tested for mutagenicity using the Ames Assay and the results were compared with existing carcinogenicity data. The assessment of the predictive value of this particular short-term test showed a 58% positive and a 41% negative correlation.


The relationship between mutagenicity and carcinogenicity of some nitrosamines. The carcinogenicity and mutagenicity of 26 nitrosamines were compared to help validate the predictability of a short-term in vitro test. 80% of the compounds showed agreement between the two characteristics, while 20% did not. Of the latter group, 8% were false positives and 12% were false negatives.


Cell-cycle variation in the induction of lethality and mitotic recombination after treatment with UV and nitrous acid in the yeast, Saccharomyces cerevisiae. Exponentially growing yeast cultures separated into discrete periods of the cell cycle by zonal rotor centrifugation show cyclic variation in both UV and nitrous acid induced cell lethality, mitotic gene conversion and mitotic crossing-over. Maximum cell survival after UV treatment was observed in the S and G2 phases of the cell cycle at a time when UV induction of both types of mitotic recombination was at a minimum. In contrast, cell inactivation by the chemical mutagen nitrous acid showed a single discrete period of sensitivity which occurred in S phase cells which are undergoing DNA synthesis. Mitotic gene conversion and mitotic crossing-over were induced by nitrous acid in cells at all stages of the cell cycle with a peak of induction of both events occurring at the time of maximum cell lethality. The lack of correlation observed between maximum cell and the maximum induction of mitotic intragenic recombination suggest that other DNA-repair mechanisms besides DNA-recombination repair are involved in the recovery of inactivated yeast cells during the cell cycle.


Use of human-liver microsomes from kidney-transplant donors for the induction of chromatid aberrations and sister-chromatid exchanges by means of pre-carcinogens in Chinese hamster cells in vitro. Samples of two human livers taken during operation of kidney donor patients were processed for microsome fractions and used for metabolization of cyclophosphamide (CP) and dimethylnitrosamine (DMN) in combination with the NADPH-generating system. Rat-liver microsomes were checked for comparison. Induction of chromatid aberrations and sister-chromatid exchanges in a newly isolated clone of Chinese hamster fibroblasts served as indicators of activity. Human S-9 fractions standardized on protein content showed strong variations of CP and DMN activation. Whereas liver microsomes of one patient (who also suffered from Gaucher's disease) were highly active for both pre-carcinogens and metabolized DMN at the same level as the uninduced rat-liver microsomes, the S-9 fraction from the second patient failed to activate CP, but was distinctly positive for DMN. It is suggested that samples of liver and other organs of renal transplant donors might be a practicable source of freshly prepared human microsome fractions usable in biochemical, genetic and carcinogenetic studies. Problems concerning the extrapolation of results are discussed.


Factors influencing the frequency of mitomycin C-induced sister-chromatid exchanges in 5-bromodeoxyuridine-substituted human lymphocytes in culture. Newly developed techniques for the detection of sister-chromatid exchanges (SCE) require the substitution of 5-bromodeoxyuridine (BrdU) for thymidine in DNA. We investigated the possibility of interactions between BrdU and one mutagen--carcinogen, mitomycin C (MMC) for the induction of both chromosomal aberrations and SCE in human peripheral lymphocytes in culture. No effect on aberration yield was found. Neither comparisons between the yields of SCE by BrdU substitution and differential staining and those detected by tritiated thymidine incorporation and autoradiography nor between the yields of SCE for different levels of BrdU incorporation provided any evidence of synergism. It was found, however, that MMC persists in cultures and continues to increase SCE frequencies for about 30 h. It was also observed that some MMC-induced DNA lesions persist long enough so that some of those present prior to S phase of the first cell cycle cause additional SCE in the third cycle.


A mutagen assay detecting forward mutations in an arabinose-sensitive strain of Salmonella typhimurium. Strain SV3 of Salmonella typhimurium is sensitive to arabinose, that is, unable to grow in a medium containing arabinose plus glycerol as carbon source. Arabinose resistance is the consequence of the mutational inactivation of one of at least three different genes. The selection of arabinose-resistant mutants provides a simple and sensitive assay for the detection of weak mutagens and for refined quantitative studies of strong ones. The assay is not influenced by experimental artifacts derived from physiological or lethal effects or from differences in plating density. Such artifacts are common with other bacterial mutagen assays, including those using strains analogous to SV3. As practical examples, the assay was used with N-methyl-N'-nitro-N-nitrosoguanidine and the fungicide captafol.


A quick method for testing recessive lethal damage with a diploid strain of Aspergillus nidulans. A simple method capable of detecting recessive lethal damage in a diploid strain of Aspergillus nidulans is described. The method scores the recessive lethals on the 1st, the 3rd and the 5th chromosomes, which represent about 40% of the total map of A. nidulans. Two examples of induced lethals, with ultraviolet irradiation and methyl methanesulfonate are shown. The frequency of lethals may reach 36% of the total population with UV irradiation.


Dominant lethal effects of triethylenemelamine in the guppy Poecilia reticulata. The need to screen potential chemical pollutants for mutagenicity has increased with the increasing volume of such materials being introduced into natural water. The present study demonstrates the utility of a fish, the guppy (Poecilia reticulata), as a model test system in which water-borne chemical mutagens may be assayed for dominant lethal effects. Mature male guppies were injected with three doses of triethylenemelamine (0.1, 0.2 and 0.4 mg/kg) in addition to a control sham treatment. Each male was subsequently mated to virgin females. In an alternative test, male fish were allowed to swim in triethylenemelamine solutions of known concentration for a period of 24 h prior to being mated to virgin female guppies. 10 days following matings, females were dissected, and numbers of live and dead embryos were recorded. Significant dose effects were demonstrated by analysis of variance techniques in both the injection and the emersion tests with the results showing higher percentages of dead embryos and lower total number of embryos with increasing doses of TEM.


Granuloma pouch assay. I. Induction of ouabain resistance by MNNG in vivo. Growth of granulation tissue was induced in rats inside a subcutaneous air pouch by injection of croton oil. Granulation tissue, isolated and cultured in vitro, gave satisfactory and reproducible cloning efficiency of fibroblast-like cells. This experimental model system was used to study the induction of autosomal point mutations in vivo leading to ouabain resistance. For this purpose the mutagen MNNG was administered in the granuloma pouch, and the formation of ouabain-resistant clones was determined in vitro. Various application schedules, expression times in vivo and selective conditions in vitro were evaluated. The highest frequencies of ouabain-resistant clones were found when MNNG was injected into the pouch 24--48 h after induction of granulation tissue, followed by an expression time in vivo of 24--48 h. No ouabain-resistant clones were formed by cells isolated from untreated rats or from animals receiving the highest tolerated doses of MNNG per os or by intraperitoneal injection. The potential usefulness of the granuloma pouch assay for the evaluation of mutagenic and carcinogenic substances in vivo is discussed.


Mutagenic properties of ethylidene gyromitrin and its metabolites in microsomal activation tests and in the host-mediated assay. Ethylidene gyromitrin (acetaldehyde-N-methyl-N-formylhydrazone) is the main poisonous hydrazine derivative in the edible mushroom false morel (Gyromitra esculenta Pers. Fr.). The mutagenic properties of this compound, and of its metabolites N-methyl-N-formylhydrazine and N-methylhydrazine, were tested by microsomal activation and host-mediated assay. Histidine auxotroph strains of Salmonella typhimurium were used as indicator organisms. Microsomal preparations had no detectable effect on the biological activity of the compounds tested, but the results of host-mediated assay experiments suggested that a bacteriocidic metabolite is formed from ethylidene gyromitrin.


A sequential screening of the cytogenetic damage induced by triaziquone. A sequence is described of test procedures for a screening in vivo of the clastogenic potential of the alkylating agent triaziquone (Trenimon). Two intraperitoneal injections of 0.125 mg/kg body weight caused a considerable increase in the number of aberrations in both the micronucleus test and the bone-marrow metaphase test, but not in the spermatocyte translocation test or the spermatogonial metaphase test. With the latter test a severe cell-killing effect was detected. An analysis of whole mounts of seminiferous tubules showed that 0.125 mg/kg was a lethal dose for all B- and intermediate-type spermatogonia and partly killed A-type spermatogonia. A single administration of the same dose caused stable chromosomal rearrangements in spermatids that could be demonstrated with the F1 translocation test, and gave rise to dominant lethality of fetuses originating from post-meiotic sperm. The comparative triaziquone study has provided arguments in favor of the micronucleus test as a reliable screening method for chromosomal aberrations. The analysis of seminiferous tubules is a recommendable method for studying lethal effects of a compound on germ cells, whereas the F1 translocation test gives important information about viable aberrations and their effect on the fertility of the progeny.


Screening for the mutagenicity of nitro-group containing hypoxic cell radiosensitizers using Salmonella typhimurium strains TA 100 and TA98. A series of sixteen 2-, 4- and 5-nitroimidazoles, four nitrobenzenes, five nitrofurans, and a nitropyrrole, most of which have been studied previously as hypoxic cell specific radiosensitizers, have been screened for their mutagenicity using the Salmonella typhimurium strains TA 100 and TA 98 developed by Ames and co-workers. Most of these compounds were mutagenic and had a one to two order of magnitude greater mutagenicity towards TA 100 (base-pair substitution sensitive) than TA 98 (frame-shift sensitive). The spectrum of mutagenic efficiencies for the drugs which was observed could be correlated to some extent with the electron affinity of these compounds. Exceptions to this correlation may indicate drugs of interest for further studies both as mutagens and hypoxic cell radiosensitizers.


Mutagenicity of some commercially available nitro compounds for Salmonella typhimurium. Benzoyl chloride and 53 commercially available aromatic heterocyclic and aliphatic nitro compounds were tested for mutagenicity in Salmonella typhimurium TA98 and TA100. 34 of 53 nitro compounds (64%) were mutagenic, 4 in TA100 only, 15 in TA98 only, and 15 in both strains. 13 of the heterocyclic derivatives of pyridine, indole, indazole, quinoline, and benzimidazole were mutagenic. 21 of 34 mutagenic nitro compounds were bactericidal. Nitromethane was the only aliphatic tested and was not mutagenic. Benzoyl chloride, a human carcinogen, was mutagenic for TA98.


Frameshift mutations in bacteria produced in the dark by several furocoumarins; absence of activity of 4,5',8-trimethylpsoralen. 4 furocoumarins, namely psoralen (P), 8-methoxypsoralen (8-MOP), 4,5',8-trimethylpsoralen (TMP) and angelicin (A) were tested for dark mutagenesis in E. coli lac-. Three compounds; P, 8-MOP and A were shown to be weak frame-shift mutagens. TMP, surprisingly in view of its very active photosensitizing action, was found to be non-mutagenic. These results are discussed in relation to the photosensitizing action of the furocoumarins.


Suppression of mutation induction and failure to detect mutagenic activity with athabasca tar sand fractions. 5 different histidine-requiring strains of Salmonella typhimurium were used to test the mutagenic activity of 7 different fractions of Athabasca tar-sand. None of the 7 fractions (bitumen, maltenes, asphaltenes, saturated, monoaromatic, diaromatic and polyaromatic hydrocarbons), showed positive mutagenic response in any of the Salmonella typhimurium strains. We have tested a wide range of concentrations. The results obtained so far are consistent with the lack of mutagenic activity of all investigated fractions in the absence and in the presence of metabolic activation. Assuming that there might be an association between the absence of mutagenic activity and the complexity of the tar-sand fractions, we investigated the effect of the polyaromatic hydrocaron fraction on the mutagenicity of the carcinogenic agent 2-aminoanthracene. The data obtained indicate clearly that the polyaromatic hydrocarbon fraction suppresses the mutagenic activity of 2-aminoanthracene.


Changes in mutagenicity of protein pyrolyzates by reaction with nitrite. Pyrolyzates of protein and related materials were treated with nitrite under acidic conditions, and the mutagenic activity toward Salmonella tester strains was determined. After treatment with nitrite in acidic solution, casein pyrolyzate, an extract of roasted chicken meat, tobacco-smoke condensate and some aromatic amines showed appreciable decreases in their mutagenic activities toward Salmonella typhimurium TA 98. Aromatic amines in the pyrolyzates may be changed by nitrite treatment to other forms having no or lower mutagenic activity toward Salmonella typhimurium TA 98. The contribution by aromatic amines to the total mutagenic activity of the pyrolyzates was as high as 80% in both casein pyrolyzate and extract of roasted chicken meat and 50% in tobacco-smoke condensate. Pyrolyzates of protein and related materials did not show a decrease in the mutagenic activity toward Salmonella typhimurium TA 100 with the same treatment.


The evaluation of sixteen carcinogens in the rat using the micronucleus test. Sixteen carcinogens were evaluated in rats for their ability to induce micronuclei. The direct acting agent, ethyl methanesulfonate and the procarcinogens/promutagens, cyclophosphamide and 4-nitroquinoline-1-oxide, induced dose-related increases in micronucleated polychromatophilic erythrocytes. Aflatoxin B1 also significantly increased the number of micronucleated polychromatophillic erythrocytes for 2 doses although no dose-response could be detected. Dimethylnitrosamine produced variable results. The remaining 11 compounds, 2-acetylaminofluorene, 4-aminobiphenyl, benzidine, diethylnitrosamine, dimethylbenzanthracene, 1,2-dimethylhydrazine, ethionine, ethyl carbamate, hexametapol, metronidazole, and beta-naphthylamine, failed to induce significantly increased numbers of micronuclei. The large number of false negative results obtained in the present investigations using the micronucleus test suggests that in vivo cytogenetic assays utilizing bone marrow may also lack the sensitivity needed to detect clastogenic effects of procarcinogens/promutagens which require tissue specific metabolic activation.


Induction of gene conversion in Saccharomyces cerevisiae by the nitrofuran derivative furylfuramide (AF-2). The nitrofuran derivative furylfuramide (AF-2) is known to be both mutagenic and carcinogenic in a number of test systems. In this report we show that AF-2 can also induce gene conversion in diploid yeast in a manner dependent on both duration and concentration of treatment.


Treatment of chronic oral candidiasis with clotrimazole troches. A controlled clinical trial. Twenty patients with chronic oral candidiasis were assigned by random allocation to a two-week course of either 10-mg clotrimazole buccal troches or placebo taken five times daily in a double-blind clinical trial. Each of the 10 recipients of clotrimazole had marked regression of symptoms and mucosal lesions, and in nine patients potassium hydroxide preparations and cultures of mucosal scrapings gave no evidence of candidiasis. In contrast, only one of the 10 patients receiving placebo showed any improvement. The clinical outcome in the clotrimazole-treated group was significantly more favorable (P less than 0.001) than in the group receiving placebo. No adverse reactions to the drug were observed. After the blind phase of their trial, 15 patients were treated with clotrimazole troches in an open trial. One to three troches per day were found adequate to sustain remissions. We conclude that clotrimazole is highly effective treatment for chronic oral candidiasis.


Clinical relevance of the histopathological subclassification of diffuse "histiocytic" lymphoma. Because diffuse "histiocytic" lymphoma, which is an immunologically heterogeneous disease, responds well to chemotherapy in some but not all patients, we attempted to identify the morphologic features that might correlate with its behavior and prognosis. We identified five histopathological categories in 66 patients: one with an excellent prognosis (large, cleaved cell, six of eight patients surviving for two years); two with an intermediate prognosis (large, noncleaved and mixed follicular-center cell, nine of 18 and eight of 17, respectively, surviving for two years); and two with a poor prognosis (blastic and pleomorphic pyroninophilic, one of 10 and two of 13, respectively, surviving for two years). The differences among categories were significant (P less than 0.02) and not dependent on stage (P greater than 0.20). Tumors of follicular-center origin had a better prognosis than tumors of nonfollicular-center origin (P less than 0.01). Differences in survival were due to differences in complete response rate. Morphologic subclassification of diffuse "histiocytic" lymphoma may be useful in predicting response to chemotherapy and survival.


Effects of inhaled beclomethasone dipropionate and alternate-day prednisone on pituitary-adrenal function in children with chronic asthma. Two corticosteroid regimens, alternate-day prednisone and inhaled beclomethasone dipropionate, have been more acceptable than daily oral corticosteroids for treatment of chronic asthma. To compare the effect of these regimens on hypothalamic-pituitary-adrenal function, 20 children with asthma were evaluated while receiving 20 to 40 mg of prednisone on alternate mornings or 400 to 800 microgram per day of inhaled beclomethasone dipropionate in divided daily doses; seven children requiring only non-corticosteroid medication served as controls. Early-morning serum cortisol concentration, urinary free-cortisol excretion and the 11-desoxycortisol response to metyrapone were decreased to a similar degree among children receiving both corticosteroid regimens in comparison with the control patients and were lowest when alternate-day prednisone and inhaled beclomethasone dipropionate were given together. Thus, inhaled beclomethasone dipropionate appears similar to alternate-day prednisone in its effect on hypothalamic-pituitary-adrenal function when used alone; the effect is additive when the two are used together.


Insulin to inhibit protein catabolism after injury. Using patients with varying degrees of trauma as their own controls we compared three isocaloric regimens in three-day crossover studies; 9.4 g of nitrogen as l-amino acids was also given daily. The urea production rate was used as an index of protein breakdown. We found that in catabolic patients, insulin and glucose produced a strikingly greater inhibition of protein breakdown that glucose alone, and that glucose alone was marginally more protein sparing than a regimen containing mainly fat (intralipid and sorbitol). These differences were not seen in noncatabolic patients (urea production rate less than 15 g daily). In the catabolic patients (urea production rate greater than 15 g daily) the protein-sparing effect of insulin was proportional to the initial urea production rate. We therefore concluded that insulin has important protein-sparing effects in severely ill traumatized patients, but little effect when there is no increased catabolic rate.


Migration inhibition factor study in Histoplasma capsulatum. Mice sublethally infected with viable Histoplasma capsulatum or immunized with merthiolate-killed yeast phase cells showed decreased mortality on subsequent challenge infection as compared to controls. Migration inhibition (MI) assays using peritoneal and spleen cells from immunized but unchallenged mice showed no parallel correlation with percent mortality. MI assay indices fluctuated without concomitant changes in resistance to challenge injection with live yeast phase cells. Viable vaccines induced greater resistance to challenge infection than killed cells, although both were comparable in sensitizing ability as measured by MI assay techniques with this mouse model.


Candida albicans dimorphism and virulence: role of copper. Previously reported observations that Candida albicans grows in the yeast phase at 30C and the mycelial phase at 37 degrees C and that the former phase is more virulent than the latter were confirmed. A novel factor, copper, was discovered to suppress filamentation. Injection of copper into mice permitted the filamentous phase to be as virulent as the yeast phase. In subsequent studies on candidosis, copper assays should be performed on relevant body fluids to determine if there might be a correlation between elevated copper and heightened susceptibility to the fungus.


[Lactate dehydrogenase. An example of the development of modern enzymology]. Lactate dehydrogenase is the prototype of an oligomeric, intracellular enzyme. Its primary, secondary, tertiary, and quaternary structures are now well known. This fact, especially with regard to the occurrence of isoenzymes, has effected a great progress in the understanding of the structure-function relationship of enzymes. The historical development of modern enzymology is described, together with discussions of the various methods and problems of enzymology.


Baclofen for spasticity in multiple sclerosis. Double-blind crossover and three-year study. Baclofen is a safe and effective means for treating spasticity associated with multiple sclerosis. We found no toxic effects on hepatologic, hematopoietic, or renal function, acutely or for over 3 years of follow-up. A statistically significant reduction was noted in frequency of spasms, and clonus, and there was improved range of joint movement, which enabled patients to maintain functional status for prolonged periods. For the more disabled patients, treatment with baclofen gave symptomatic relief of painful spasms and made immobility more tolerable. Optimum effect was achieved when baclofen was administered in the early stages of disease, before major disabilities became permanent.


Some factors influencing the proliferation and differentiation of myelin-forming cells. Fundamental questions arising from study of the multiple sclerosis lesion are: (1) why the myelin-forming oligodendrocyte is adversely affected; and (2) what factors might induce the proliferation and differentiation of replacement oligodendrocytes. This paper discusses factors that influence the number and differentiative capacity of myelin-forming cells both in the central nervous system (CNS) and the peripheral nervous system (PNS). New experiments utilizing cultures of fetal rat sensory and autonomic ganglia are also herein reported. It has been found that in cultures free of fibroblasts, normal Schwann cell proliferation and ensheathment of axons require contact with a collagen substrate and may be facilitated by a medium containing chick embryo extract. This demonstration of a connective tissue requirement for normal Schwann cell function raises the question of whether additional factors are necessary for normal oligodendrocyte activity.


Syndrome of primary transtentorial cerebellar displacement--"inverse Chiari type II syndrome". Transtentorial upward displacement of parts of the cerebellum and the brain stem into the supratentorial space, a condition which has occasionally been described in the literature since 1958 in children with hydrocephalus and spina bifida, is demonstrated in one case together with a discussion of its pathogenesis. A former hypothesis regarding the condition as a result of long standing shunt treatment of the hydrocephalus with supratentorial decompression is opposed. Different findings in the present and in two formerly recorded observations point out that the cerebellar upward displacement must be a prenatally originated malformation complex associated with hydrocephalus. The main criteria of the syndrome, which seems to be very much related to the Arnold-Chiari malformation, are summarized.


[Acupuncture, "vital" drugs and psychotropic agents in psychiatric patients. 50 cases]. A therapeutical trial by means of acupuncture and "vital" drugs (1-glutamine and N-dipropylacetic acid) in 23 out of 50 psychiatric chronic patients basically depressive, and by means of acupuncture, vital drugs and psychodrugs in the remaining 27 similar patients, is carefully reported. 49 of this patients got improvement, 41 of them in a middle degree. The different neurochemical curcuits (GABA-ergic, glutamergic, adrenergic, noradrenergic, serotoninergic and dopaminergic) put in balance by such therapeutical association have been discussed.


[Inhibition of tumor growth and metastases in mice with Lewis lung tumors by vitamin A and BCG]. The anti-tumor effect of vitamin A and/or BCG was investigated in Lewis lung tumor system. Tumor growth and lung metastases were significantly suppressed, when tumor cells were mixed with BCG and inoculated subcutaneously into vitamin A-treated animals. Survival time was also prolonged by the same treatment. Vitamin A alone, without BCG, showed no effect on tumor growth, lung metastases or survival time.


[Localization of Hodgkin's disease and non-Hodgkin lymphoma by means of 67 gallium subtraction scintigraphy]. 67Ga-subtraction scan was found to be useful and a promising new method for the pre-treatment evaluation of the patient with Hodgkin's disease or non-Hodgkin's lymphoma. The scan appeared to be most accurate in the neck, chest, and axillary regions. It appears to offer a means of increasing the accuracy of evaluating the abdomen, the paraaortic and pelvic regions. It may be a useful method for follow-up to detect recurrences. It was an easily performed, safe, non-invasive test, well tolerated and accepted by patients.


[Treatment of relapses in juvenile acute lymphoblastic leukemia]. Recurrence of childhood acute lymphoblastic leukemia occurs in about 30-50% and indicates irresistable progression of the disease. While systemic (= hematologic) relapse is due to drug resistance of leukemic cells, pharmacologic barriers may be responsible for local relapses as meningeal involvement, leukemic ophthalmopathy or testicular infiltration. L-asparginase seems to be an important component of drug combinations for re-induction therapy for systemic relapse. Following reinduction therapy modification of continuation therapy is necessary. Local relapses require local treatment, i.e. radiotherapy and e.g. intrathecal drug application. Local relapse is almost always followed by hematologic relapse. Therefore, intensification of systemic therapy is also recommended. Prevention of these relapses is much more important and probably more successful than treatment. Therefore, initial therapy should include preventive measures for pharmacologic sanctuaries.


[Clinical aspects of the excretion of alkylating cyclophosphamide metabolites in the urine of tumor bearing patients]. The urinary excretion of alkylating CP metabolites was measured in 33 tumor patients by using NPB-test under consideration of different doses, routes of administration (i.v. and i.m.) and function of the liver and the kidney. There was no limit in activation capacity with increased doses of CP. The estimation of the upper activation limit was hindered by the host's subjective toxicity. CP was activated in a comparable manner after i.v. or i.m. administration. It is of interest that liver involvement by the disease or functionally compensated post-nephrectomy state of patients investigated so far did not diminish the excretion of alkylating CP metabolites.


[Optimal care of the oncologic patient: a question of organization]. The rapid development of oncology as a subspecialty in internal medicine presents a dilemma for the specialist and the private practitioner. How can one offer the best technical and scientific care which often requires an institutional setting for its delivery and at the same time maintain a continuous meaningful relationship with a primary care physician? The outpatient clinic of the oncology center of the Basle University clinics as a paragon for the patient care in these changing times may represent one of several possible solutions to this contemporary dilemma.


[Immune stimulation with vitamin A therapy in patients with pulmonary neoplasms]. Based on a clinical trial, in which patients with unresectable bronchogenic cancer were treated with a combination of vitamin A plus chemotherapy, or vitamin A plus radiotherapy, a study was initiated in which vitamin A alone was given for tumor treatment. 9 male patients with metastatic unresectable squamous cell carcinoma of the lung were treated with vitamin A palmitate or 13-cis vitamin A acid. Up to seven treatment courses were given during a period of 60 weeks. Through weekly evaluation of the patients' immune status, an immune potentiating effect of the vitamin A therapy could be demonstrated. An increase of lymphocyte blastogenesis response to PHA which is significant (p less than 0.001) compared with the pretreatment values, was found in all patients at the end of one vitamin A treatment course. Increased delayed cutaneous hypersensitivity reactions were observed also in all patients. The immune potentiating effects of vitamin A therapy, as well as the demonstrated direct effect on the tumor, introduces a wide range of combination therapies.


[HL-A antigens in bronchogenic carcinoma]. A decrease in the frequency of HLA-A2 was noticed in 37 bronchogenic carcinoma patients studied. HLA-B8 was found to be increased in the prolonged survivors of bronchogenic carcinoma.


[Diagnostic measures in various manifestations of bronchial carcinoma]. The mortality of bronchogenic carcinoma is still rising. In the etiology cigarette smoking is the main cause. High risk groups are persons between 45 and 65 years exposed permanently to inhalative noxae. These groups should be observed carefully for early cancer detection. With radiological, endoscopial, cytological methods the possibility for early diagnosis is given. Careful preoperative staging is necessary for differential therapy and prognosis of the cancer patient.


[Efficacy of diagnostic measures in colonic carcinoma]. It has been tried to ascertain the comparative value of the different diagnostic measures with regard to colorectal cancer. On the basis of the results achieved, the addition of the Hämoccult test (if this has not yet been done), of the rectoscopy and of endoscopic polypectomy to the programme of preventive medicine is indicated. Also measures for an early diagnosis of the post-operative recurrence of tumors are advisable.


[Tissue antigens in ovarian carcinoma].

[Tissue antigens in ovarian carcinoma]. Five tissue antigens have been identified which appear in carcinoma arising in the ovary. Antisera to a variety of human tissues were absorbed with a saline extract of normal ovary as well as plasma; five distinct antigens (A1-A4, TA) were detected in ovarian tumor extracts as well as in normal tissues. A1, A2, and A3 were widely distributed in normal tissues while A4 was found principally in buffy coat blood cells and spleen, and TA was mainly associated with normal cervix but was variably detected in liver and lung. Heating the tumor extract to 56 degrees resulted in inactivation of A1, A2, and A3. A4 was inactivated at 80 degrees, whereas TA was stable at 100 degrees. Pronase treatment readily abolished A3 activity, more slowly inactivated A1, A2, and A4, and only very slowly destroyed TA. Partial separation of the antigens was obtained by Sephadex G-200 chromatography. TA from individual benign and malignant tumors as well as normal cervix appears to be the same molecule by criteria of immunodiffusion, immunoelectrophoresis, and gel filtration. The potential use of these antigens as tracers of ovarian carcinoma is indicated.


[Clinical and immunological studies with OK-432 (Streptococcus pyogenes) on immunotherapy in cancer patients]. In a phase I study, the bacterial vaccine OK-432 (streptococcus pyogenes) was investigated in eight patients with advanced malignant tumors. Besides a fever reaction after i.v. application no toxic side effects were observed. Additionally, its therapeutic effectiveness could be demonstrated by i.v. and local therapy. There was also observed an increase of lymphocyte blastogenesis response in patients under treatment with OK-432.


[The prognostic value of lymphocyte transformation by phytohemagglutinin in children with acute lymphatic leukemia]. The response to phytohemagglutinin (PHA) of lymphocytes from 62 children with acute lymphoblastic leukemia (ALL) was tested before and during cytostatic therapy. Nineteen patients were tested as well for reactivity in autologous mixed lymphocyte-blast cell cultures. The prognostic value of the results obtained has been assessed. Children remained longer in their first complete remission 1) if the response to PHA before therapy was normal or only slightly diminished, or 2) if it returned to normal as soon as complete remission was attained, and 3) if periodic intensification therapy was followed by a rebound in spontaneous lymphocyte proliferation. The stimulatory response to PHA during maintenance therapy and the reactivity in mixed lymphocyte- blast cell cultures were not helpful prognostic criteria. In conclusion, determination of the PHA responsiveness at specific times, i.e. before therapy, after remission induction and after periodic intensification therapy, could help identify poor risk patients in ALL.


[Immunologic potency of pregnancy associated alpha 2-glycoprotein (alpha 2-PAG)]. The suggestion that the pregnancy-associated alpha2-glycoprotein could depress the immune response was investigated using the modified electrophoretic mobility test. The presence of the glycoprotein, at physiological levels, significantly reduced the inhibition of the migration velocity of indicator cells in the electric field caused by the MSF. In the contrary alpha2-PAG-free serum had no effect in the test system. Therefore, it can be supposed that alpha2-PAG may have an immunoregulatory function within the immunological mechanism which protects the conceptus and malignant tumor.


[Risk of lung cancer and "smoker's prophylaxis" in Austria]. The smoking habits of the Austrian population and their significance for the development of effective smoking control programmes are reported. An increasing trend in the consumption of cigarettes with a lower content of tar and nicotine can be observed as well as a slight reduction of lung cancer death-rates in Austria. An analysis shows that, at present, only the younger male age groups show a decrease of lung cancer risk. Possible relations of these findings to the improvement in the quality of cigarettes are discussed, namely the reduction in the amount of carcinogens.


[The extent of neoplastic involvement of the regional lymph nodes in cervical neoplasms and its effect on the rate of cures. (A report on 103 cured cases)]. At the 1st University Clinic for Gynaecology in Vienna (Austria) nearly every other woman suffering from cervical carcinoma suitable for operation was cured by abdominal radical hysterectomy with obligatory lymphonodectomy and routine postoperative irradiation between 1951 and 1972 in spite of carcinomatous involvement of their lymph nodes. Cases of the histological stage Ia were excluded of this study. Although the survival rate of the cases with minimal lymph node involvement (61%) exceeds the one of cases with extended involvement (35%) further radicalization of obligatory lymphonodectomy seems to be promising. At the above mentioned Clinic this is aspired by the use of radioisotopes for intraoperative exposition of the lymph nodes.


[Progress in the therapy of medulloblastoma]. The nearly exclusive metastatic spread of the radiosensitive medulloblastoma into the fluid spaces of the liquor system allows a curative therapeutic attempt by a systemic radiation. The actual 5-years survival rate is about 40%. It should be possible to improve it to up to 50% by consequently applicating radiotherapy. A prospective study concerning the possibilities of chemotherapy presently underway, does not yet permit a definite statement. The most essential complication after radiotherapy of children concerns the symmetric reduction of growth.


[Immuno-chemotherapy in patients with disseminated metastasizing stage III melanoma. Randomized study with methyl-CCNU versus C. parvum plus methyl-CCNU]. 34 patients with disseminated malignant melanoma (stage III) were randomized to the following therapy groups: Chemotherapy (MeCCNU, NSC 99441; 200 mg/m2, given orally every 8 weeks), or immuno-chemotherapy (1 mg Corynebacterium parvum i.v., on days 1-4 + MeCCNU 200 mg/m2 on day 8, repeated every 7 weeks). Total therapy response rate was 33%; total and partial remissions were achieved in 26% of the patients receiving chemotherapy, and in 40% under immuno-chemotherapy. Interim life table analysis shows that in the group receiving C. parvum + MeCCNU 50% of the patients survived more than 12 months, whereas in the group with MeCCNU survival of 50% was 6 months. Pretreatment with C. parvum did not only potentiate the therapeutic effect, but also reduce the myelosuppression of MeCCNU.


[The cellular immune status in normal subjects, patients with and without neoplasms]. The distribution of lymphatic subpopulations in the peripheral blood of patients with malignant solid tumors has been studied in two steps. Firstly, it was investigated whether there are changes in the distribution of blood lymphoid cell populations in tumor patients (n = 101) compared to normal individuals (n = 39) and whether there is a correlation between the distribution pattern and the clinical stage of the disease. There was found a significant reduction of T-lymphocytes in patients with cancer, which was marked in the advanced tumor disease (n = 34). In a further step the influence of curative tumor-resection on the lymphatic subpopulations was studied, when 26 operated tumor patients were compared with 23 operated patients without neoplasia. In the group with non-malignant diseases there could not be found a significant pre- and postoperative difference concerning the T- and B-lymphocyte counts. Tumor patients showed after resection of the tumor a significant increase of the absolute and relative number of preoperatively reduced T-lymphocytes. The pathophysiological possibilities for the phenomena of a reversible reduction of T-lymphocytes by the curative resection of the tumor are discussed.


[Premonitory blood count changes in the relapse of juvenile acute lymphatic leukemia]. Investigation was done in 80 children with acute lymphocytic leukemia (ALL) with respect to premonitory changes of peripheral blood cell counts before a hematologica relapse. 38 patients suffered from one or more relapses. Evaluation was done by t-test and Friedmann test. 9 weeks before a relapse there was a significant decrease in thrombocytes numbers demonstrable. Granulocytes numbers and monocytes numbers declined 6 and 3 weeks before the relapse, respectively. The lymphocytes counts had already increased 6 weeks before a relapse. The blood cell counts during intercurrent infections did not interfere with the typical pattern of blood cell counts before a relapse. Also the changes in blood cells found are different from those seen in untreated cases of ALL.


[Juvenile rhabdomyosarcoma. Diagnosis and new therapeutic possibilities]. Seventeen children with rhabdomyosarcoma stage I to III diagnosed since 1973 are presented. The coordinated management utilizing surgical excision, irradiation (5000 rad) and systemic adjuvant multiagent chemotherapy is described. The favorable sites were head and neck sites and genitourinary region. The mean survival is at present 19 months. 14 children are alive and well. 13 children had no tumor recidivation, 1 child had 8 months after beginning of the therapy lung metastases which after irradiation with 2000 rad disappeared. 3 children (stage III) died 9, 14 and 20 months after diagnosis during therapy by metastases. Acute and late effects on normal tissues from radiation and chemotherapy were noted in 12 cases. A review of the literature and therapeutic alternatives in the future are indicated.


[Androgen therapy of incurable breast neoplasms. Controlled clinical study: nandrolone-testololactone-drostanolone]. In 91 patients with advanced breast cancer testololactone, drostanolone, and nandrolone were compared in a controlled clinical trial. Remissions were registered after 4 weeks and after another 12 week period; during this second interval the patients received an additional treatment with cyclophosphamide. There was no difference in the effectivity between the three drugs. Remission rate was in average after 4 weeks 24% and after 16 weeks 46%.


[Immunochemical markers of embryonic lens differentiation in Rana temporaria. I. Composition and properties of water-soluble lens antigens]. Antisera were obtained to the total extract and individual electrophoretic fractions of lens proteins: alpha-, beta-, gamma1- and gamma2-crystallins. The crystallins under study are immunochemically heterogenous: each class of lens proteins contains 2--4 antigens. Using the indirect method of fluorescent antibodies, it was established that the appearance of crystallins during development coincided with the onset of formation of the presumptive lens fibers. No crystallins were found in the lens placode and early lens vesicle. gamma-Crystallins appear later than the other lens proteins and are characteristic, mainly, for the lens fibers; at the advanced stages of organogenesis gamma-crystallins are regularly found in the epithelial cells of the developing lens as well.


[Immunochemical markers of embryonic lens differentiation in Rana temporaria. II. Immunohistochemical analysis of the manifestation and localization of individual classes of lens proteins]. Individual lens proteins were studied during development of Rana temporaria. Antisera to alpha-, beta-crystallins of chicks and gamma-crystallins of Rana ridibunda were used as immunochemical markers. Besides the main crystallins, a new antigen was found in the R. temporaria lens tentatively called alphabeta-crystallin. It appears to be characteristic only for the amphibian lens. Using the indirect method of fluorescent antibodies, it was shown that all the antigens under study appeared in the lens of the R. temporaria tadpoles within 1--2 days (at 20 degrees). The crystallins are found initially only in the developing lens fibers and later in the lens epithelium. It was established that the lens epithelium contained gamma-crystallins which appeared somewhat earlier than alpha- and beta-crystallins, but simultaneously with alphabeta-crystallin.


[Tectonic keratoplasty in the case of infected Elliot's trephination]. A case is reported with respect to the method concerning the treatment of late infection of the filtering blebs after anti-glaucoma surgical procedures. The infected conjunctival flap and the adjoining scleral tissue was excised with the help of a tectonic keratoplasty and the defect was made watertight in the region of the cornea with a running suture and in the region of the sclera with single sutures. In the case reported the tectonic keratoplasty healed up without any complications. The intraocular pressure remained normal. The indication leading to this operation after a late infection of glaucoma filtering blebs is especially reserved for cases in which the conjunctival flap is unmoveable.


[Keratoplasty in children and juveniles]. The morphological and functional results of 42 penetrating keratoplasties performed on 38 eyes of 36 children are reported on. Surgical indications, contraindications and postoperative complications are discussed. Emphasis is placed on the close cooperation between the clinic, the practitioner responsible for the aftercare, and the parents of the child.


Histology of the epithelium of the normal and cataractous lens. Compared with the normal lens, the cataractous lens is characterized by morphological and distribution anomalies of the epithelial cells. At the electron microscope an enlargement of the intercellular spaces and large intercellular, as well as intracellular, vacuoles are seen. An important development of the lysosomal system and of the endoplasmic reticulum is also observed.


Tissue culture of the epithelium of the normal and cataractous adult lens. Tissue culture of cataractous lens epithelium shows deterioration of cellular tropism, anisomorphism, anisometry, and formation of large intracytoplasmic vacuoles with deterioration of the lysosomal system, the vacuolated cells showing no tendency to form fibers.


Autoimmune phenomena of the external eye. The immunologic status of patients with ocular pemphigoid, Mooren's ulcer, chronic herpetic keratitis, and staphylococcal peripheral corneal ulcers was studied. Although tissue-fixed and circulating antibodies to the conjunctival epithelium were found in all groups, patients with Mooren's ulcer demonstrated these findings most consistently. Immunoglobulins bound to the conjunctival basement membrane were found not only in ocular pemphigoid but also in patients with Mooren's and staphylococcal ulcers. Approximately one half of the patients with ocular pemphigoid and Mooren's ulcer demonstrated elevations in serum IgA levels. An increased prevalence of HLA-B12 was found in ocular pemphigoid.


The surgical-orthodontic correction of maxillary deficiency. To date surgeons have primarily emphasized advancement of the retrusive or retodisplaced maxilla. There has been no emphasis on combined surgical-orthodontic treatment sequencing in this deformity. Moreover, the maxilla may be deficient not only anteroposteriorly but also vertically and/or transversely. Frequently, when the maxilla is deficient, two or three of these spatial components of the deformities coexist to various degrees. Thus, the term maxillary deficiency is used here to describe the general nature of the skeletal deformity.


Clinical evaluation of a prototype intraoral source x-ray system. A prototype dental roentgenographic system which incorporates a tightly collimated intraoral x-ray source and an extraoral Polaroid film screen cassette was evaluated both in vitro and in vivo. Findings indicate that the detectability of artificially induced incipient enamel lesions was significantly less than that demonstrable for conventional roentgenograms produced with an extraoral source, long-cone geometry, and Kodak Ultra Speed D film. Larger lesions were found to be reliably detected by either technique. The new intraoral approach reduces the dose to the patient by possibly as much as 98 per cent and yields positive dry prints in 15 seconds. This system was clinically tested and found to be useful in endodontics and presurgical evaluation. Modifications are discussed which could reduce some of the technical problems and many of the shortcomings encountered.


Early detection of pemphigus vulgaris.

Early detection of pemphigus vulgaris. Two cases of pemphigus vulgaris are described. These cases showed that, using the direct method of immunofluorescence, early detection of the disease was possible when repeated blood investigations had failed to show circulating antibodies to the intercellular cement by the indirect method.


Immunopathogenesis of chronic periapical lesions. A review. The pathogenesis of periapical lesions has not been fully elucidated. Currently, the possibility of its being an immunologic phenomenon is receiving much attention. This article presents a review of the literature concerning immunologic reactions which may involve periapical lesions. It appears that antigen-antibody complexes and IgE-mediated reactions can initiate preliminary changes in periapical tissues. It is also likely that delayed hypersensitivity participates in the perpetuation and progression of periapical disease.


[B-streptococci infection in the newborn (author's transl)]. The authors describe their experiences with the treatment of 3 newborns with meningitis due to B-streptococci,, and give a review of the problems of etiology, clinical symptoms, diagnosis and therapy of infections with B-streptococci in newborns. Furthermore, the article deals withthe frequency of the ocurrence of these bacteria in mothers, children and in the medical personal staff as well as with the possible ways of transmission. The relations between infections with B-streptococci and respiratory distress syndrome in newborns are discussed with the problems of differential diagnosis and therapy.


[Fosfomycin, a new antibiotic drug (author's transl)]. After i.v. injection of 25 mg/kh/BW and 50 mg/kg/BW to children age 5--6, no difference in the pharmakokinetic action can be found. The pattern of the plasma concentration allows the assumption of a 2 compartment model. There is a decrease of the plasma concentration in the steady state with a half life of 1,6 and 1,7 hours resp. The total volume of distribution is 30% of the body weight. Fosfomycin is eliminated by glomerular filtration only. The drug is not metabolished, as 98% and 95% of the dosage are recovered in active form in the urine. In premature and newborn babies there was a 1 compartment model assumed after i.v. administration of 25 mg/kg/BW. The distribution volumes with 41% of the body weight considerably greater then in older children. Elimination is again by glomerular filtration only. Plasma levels are decreasing considerably slower so that less of the drug is excreted in the 24-hour-urine. There is a sufficient penetration of the drug into the CSF. Bactericidal levels are reached within 48 hours by cumulation of the drug.


Accessory diaphragm in the left side.

Accessory diaphragm in the left side. A case with accessory diaphragm is presented. She was diagnosed primarily by X-ray and bronchography. The patient also had spina bifida at the T 1-2 level. The accessory diaphragm was on the left side in our patient, contrary to most of the reported cases. Since our patient was clinically in good condition surgical intervention was not considered. Previously reported cases are also reviewed especially in the respect of associated congenital malformations.


Searching for molecular abnormalities in genetic diseases by the use of a double labeling technique. II. Deficiency of a basic protein in fibroblasts of patients with Pompe's disease. We used a double labeling technique to search for molecular defects in two fibroblast strains obtained from patients with Pompe's disease. Analysis of the double labeled subcellular fractions by sodium dodecyl sulfate (SDS) electrophoresis did not reveal any abnormalities except in the "mitochondrial-lysosomal" fraction. In this fraction ratio deviations indicated that in Pompe's disease there was a significant decrease in counts of a protein with molecular weight of about 29,000. After solubilization by freeze-thawing this protein was shown to have an isoelectric point of 7.9 in contrast to the alpha-glucosidase which focused at about pH 4.7. Two-stage gel studies demonstrated an estimated 90% reduction of this protein in Pompe's disease. Two-stage studies of acid alpha-glucosidase did not show any abnormal ratios of leucine incorporation. Similar although quantitatively less pronounced results were obtained in the study of skin fibroblasts from a patient with adult glycogen storage disease type II.


Effects of continuous positive airway pressure after oleic acid-induced lung injury in dogs. The physiologic effects of continuous positive airway pressure (CPAP) of 5,10,15, and 20 cm H2O during spontaneous ventilation were studied in six anesthetized dogs with simulated respiratory distress syndrome (RDS) induced by iv infusion of oleic acid and in three normal controls. After oleic acid, mean PaO2 dropped to 63.6 +/- 3.1 mm Hg while breathing 100% oxygen and mean shunt fraction was 48.3 +/- 3.0%. PaO2 and shunt fraction improved significantly at the two highest levels of CPAP (e.g.,PaO2 271.3 +/- 41.3 mm Hg and shunt fraction 17.8 +/-2.2% at 20 cm H2O CPAP). Mean mixed venous PO2 rose from 37.4 +/- 1.5 mm Hg with no CPAP TO 60.8 +/- 3.1 mm Hg at 20 cm H2O CPAP. Tissue oxygenation appeared to improve during CPAP, since cardiac output, oxygen delivery, and serum lactate were not significantly affected and mixed venous PO2 rose significantly. However, significant hypoventilation occurred at all but the lowest level of CPAP, mean PaCO2 rising from 44.1 +/- 1.8 mm Hg with no CPAP to 77.6 +/-6.8 mm Hg at 20 cm H2O CPAP. The hypoventilation during CPAP is consistent with increased work of breathing due to a combination of decreased lung compliance and increased dead space ventilation due to rapid, shallow breathing.


Maternal ABO blood group type B: a risk factor in the developement of neonatal group B streptococcal disease. In a prospective study of maternal genital colonization with group B streptococci (GBS) at the time of delivery, epidemiological data, including blood type (ABO group), were recorded for the 1,062 patients studied. Blood type B was found in a statistically significant higher proportion of patients colonized with GBS (28%) compared with the total population (16.4%) (P less than .005, X2 = 8.43). Women with blood type B were twice as likely to be colonized as those with types O or A. Hypotheses to explain this observation include the possibilities that GBS possess a B-like antigen, rendering parturients who lack anti-B antibody at increased risk for GBS colonization, or that GBS possess a receptor site for B surface antigens. One may speculate that a mutation toward an affinity for the human ABO blood group type B accounts for the advent of the group B Streptococcus as a significant perinatal pathogen.


Urinary tract infection presenting with jaundice. Jaundice was the presenting feature in an 8-year-old girl suffering from urinary tract infection (UTI) due to Escherichia coli. The jaundice cleared with the cure of the infection. The mechanisms of jaundice complicating UTI are discussed, and the importance of urine culture in infants and children with jaundice is stressed.


Microangiopathic hemolytic anemia and thrombocytopenia in a neonate associated with a large placental chorioangioma. The case of an infant born in association with a large chorioangioma of the placenta is presented. The maternal complications of polyhydramnios, preeclampsia, and premature labor are those described in the "syndrome" of a chorioangioma. The immediate neonatal course was unusually complicated by severe microangiopathic anemia with persistent thrombocytopenia and hemolysis which required three exchange blood transfusions. The relationship between the neonatal complications and the placental tumor is discussed in terms of possible pathophysiologic mechanisms.


American Academy of Pediatrics. Nutrition Committee of the Canadian Paediatric Society and the Committee on Nutrition of the American Academy of Pediatrics. Breast-feeding. A commentary in celebration of the International Year of the Child, 1979. 1. Full-term newborn infants should be breastfed, except if there are specific contraindications or when breast-feeding is unsuccessful. 2. Education about breast-feeding should be provided in schools for all children, and better education about breast-feeding and infant nutrition should be provided in the curriculum of physicians and nurses. Information about breast-feeding should also be presented in public communications media. 3. Prenatal instruction should include both theoretical and practical information about breast-feeding. 4. Attitudes and practices in prenatal clinics and in maternity wards should encourage a climate which favors breast-feeding. The staff should include nurses and other personnel who are not only favorably disposed toward breast-feeding but also knowledgeable and skilled in the art. 5. Consultation between maternity services and agencies committed to breast-feeding should be strengthened. 6. Studies should be conducted on the feasibility of breast-feeding infants at day nurseries adjacent to places of work subsequent to an appropriate leave of absence following the birth of an infant.


[Generalised cortical hyperostosis. One case (author's transl)]. Generalised cortical hyperostosis, a case of which is reported here, was distinguished from other condensing osteopathies by Van Buchem in 1955. It is characterised by a fairly special facial dysmorphia, associated with osteocondensation of the skull, spine, flat bones and the cortex of the long bones of the limbs. There is a form with recessive transmission, which is usually associated with cranial nerve involvement by compression, and alkaline hyperphosphatasemia, whilst in the form with dominant transmission these abnormalities are not usually present. By contrast, there is often a palatal torus. A case appeared to share features of both forms. The prognosis is usually favourable, in contrast to that of osteopetrosis, a condition with which it is often confused.


Relaxation technique to increase comfort level of postoperative patients: a preliminary study. Effectiveness of a relaxation technique to increase the comfort level of patients in their first postoperative attempt at getting out of bed was tested on 42 patients, aged 18 to 65, who were hospitalized for elective surgery. Study group patients were taught the relaxing technique; control group patients were not taught the technique. Each group had an equal distribution of cholecystectomy, herniorrhaphy, and hemorrhoidectomy patients. Blood pressure, pulse, and respiratory rates of subjects in both groups were compared prior to surgery and after the postoperative attempt to get out of bed. Subjects' reports of incisional pain and bodily distress were measured via a pain and distress scale after their attempt at getting out of bed. Amount of analgesics used in the first 24 hours following surgery was examined. Mean differences in report of incisional pain and body distress, analgesic consumption, and respiratory rate changes were statistically significant, supporting the hypothesis that use of a relaxation technique to reduce muscular tension will lead to an increased comfort level of postoperative patients.


Dialysis therapy and transplantation in uremia: which to use when. In the United States, 10,000 to 18,000 new patients require therapy for end-stage renal disease each year. A combination of medical and psychosocial criteria can be used to predict whether renal transplantation or maintenance hemodialysis or peritoneal dialysis may be the most efficacious treatment. In most cases, dialysis therapy should be initiated when signs and symptoms of uremia are only subtle, usually when creatinine clearance is between 3 and 6 ml/min. One mode of therapy can be exchanged for another to suit changing needs, and vascular access should be created even in patients who ultimately will undergo peritoneal dialysis or receive a transplant.


[Anaesthesia and immunology (author's transl)]. There is evidence of immunosuppressive influence of trauma/operation and anesthesia. The human immunological system is outlined as a complex functioning apparatus with humoral and cellular factors. The influence of operation and/or anesthesia on immunocompetence has been demonstrated by animal studies, in vitro examinations and clinical investigations. The analysis of these results and their significance for an impairment of the immunological surveillance of the patient is tried to be elucidated. There should be payed attention to the clinical consequences, especially in patients on high risk.