Monovalent inactivated A/New Jersey/8/76 (Hsw1N1) vaccine in healthy children aged three to five years.

Single doses (50, 100, or 200 chick cell-agglutinating [CCA] units) of split-product or whole-virus (50 or 100 CCA units), monovalent inactivated A/New Jersey/8/76 (Hsw1n1) virus vaccine or placebo were given to healthy children aged three to five years in Maryland. Split-product vaccine was nonreactogenic but also virtually nonimmunogenic. Lower doses of whole-virus vaccine (50 CCA units of Merck, Sharp and Dohme [West Point, Pa.] and 50 or 100 CCA units of Merrell-National Laboratories [Cincinnati, Ohio] vaccine) were mildly reactogenic (approximately 25% of the children had low-grade fevers of 100 F-101 F). These dosage levels of whole-virus vaccine stimulated titers of greater than or equal to 1:20 in 68% and titers of greater than or equal to 1:40 in 37% of the children. Two inoculations of whole-virus vaccine (primary immunization followed by a booster one month later) were tolerated and induced titers of greater than or equal to 1:80 in 100% of the children.


Clinical reactions and serologic responses in healthy children aged six to 35 months after two-dose regimens of inactivated A/New Jersey/76 influenza virus vaccines.

In collaborative clinical trials, two-dose regimens of four monovalent A/New Jersey (NJ)/76 influenza virus vaccines were evaluated in 89 children aged six to 35 months. Clinical reactions to vaccination consisted primarily of low-grade fever. Rectal temperatures of between 100 F and 102 F occurred less frequently after inoculation with split-product vaccines (seven [23%] of 31 children) than whole-virus vaccines (19 [33%] of 58). After administration of single doses of vaccines, titers of hemagglutination-inhibiting (HAI) antibody reached greater than or equal to 1:20 in three (13%) of the 23 recipients of split-product vaccines and in 23 (51%) of the 45 recipients of whole-virus vaccines. After administration of two doses, 89%-94% of recipients of Parke, Davis and Company (PD, Detroit, Mich.), Merrell-National Laboratories (Cincinnati, Ohio), and Merck Sharp and Dohme (West Point, Pa.) vaccines, but only 50% of the recipients of Wyeth Laboratories (Philadelphia, Pa.) vaccine, had titers of HAI antibody of greater than or equal to 1:20. Single doses of more reactogenic whole-virus vaccines may be justifiable for rapid immunization of young children during epidemics of influenza. Given in a two-dose regimen, however, PD split-product vaccine was immunogenic and was the most well-tolerated vaccine tested in this age group.


Clinical trials with inactivated monovalent (A/New Jersey/76) and bivalent (A/New Jersey/76-A/Victoria/75) influenza vaccines in Los Angeles children.

Clinical and serologic responses to inactivated influenza virus vaccines were studied in 444 children in Los Angeles under doubld-blind, placebo-controlled protocols. One- and two-dose regimens employing monovalent (A/New Jersey/76) and bivalent (A/New Jersey/76-A/Victoria/75) vaccine were studied in separate trials. In a single dose, whole-virus vaccines were more potent than split-product vaccines as primary inducers of immunity against influenza A/New Jersey/76 virus. Split-product vaccines were better tolerated clinically and, after two-dose regiments, produced rates of seroconversion (greater than 90%) against A/New Jersey/76 virus comparable to those produced by two doses of whole-virus vaccines. Analysis of heterotypic antibody responses induced by monovalent A/New Jersey/76 vaccines revealed only slight increases in antibody against influenza A/Victoria/75 virus. After vaccination with bivalent vaccines, levels of antibody against influenza A/Victoria/75 virus were significantly higher in subjects who received high doses of split-product vaccines than in subjects who received whole-virus vaccines.


IgM and IgG antibody responses after immunization of children with inactivated monovalent (A/New Jersey/76) and bivalent (A/New Jersey/76-A/Victoria/75) influenza virus vaccines.

The character of the immune response to inactivated monovalent influenza A/New Jersey/76 and bivalent influenza A/New Jersey/76-A/Victoria/75 vaccines was studied in children six months to 18 years of age. Titers of hemagglutination-inhibiting antibody in sera taken after vaccination were measured before and after treatment with 2-mercaptoethanol. IgG antibody predominated in responses to the influenza A/Victoria/75 component of bivalent vaccines. In contrast, specific IgM antibody to influenza A/New Jersey/76 virus developed after administration of both monovalent and bivalent vaccines and appeared to characterize the immune response to this antigenic "shift" strain in children. Prevalences of IgM antibody against influenza A/New Jersey/76 virus did not differ significantly by age. This finding implies that type rather than extent of previous experience with influenza determines the IgM antibody response to an antigenic "shifts." Split-product vaccines produced significantly fewer IgM antibody responses to influenza A/New Jersey/76 virus than did whole-virus vaccines, a phenomenon that may correlate with their diminished reactogenicity and immunogenicity in children.


Bacterial flora of the small bowel before and after bypass procedure for morbid obesity.

The contents of the proximal jejunum and distal ileum were cultured quantitatively in eight patients who were undergoing intestinal bypass procedure for obesity. Five jejunal specimens were sterile, and three contained low counts of a predominantly aerobic flora. Ileal contents yielded variable but usually higher counts than in the jejunum, and there were similar numbers of anaerobes and aerobes. In three patients in whom a bypass was established, contents of the functioning small bowel showed counts of 10(5.0)-10(7.6) colony-forming units/ml. These counts exceeded the counts in the normal terminal ileum, and the flora qualitatively resembled that of feces. Four specimens from excluded loops revealed colonization with fecal organisms, and the counts ranged between 10(6.4) and 10(9.7) colony-forming units/ml. In jejunoileal bypass both the functioning small bowel and the excluded loop become colonized with colonic flora, a phenomenon that may contribute to some of the side effects of this procedure.


Phagocytosis of Candida albicans by human leukocytes: opsonic requirements.

The kinetics of phagocytosis of Candida albicans by human polymorphonuclear leukocytes was studied. The basis for these studies was a phagocytic assay with use of C. albicans radiolabeled with [3H]adenine. After incubation of leukocytes with C. albicans, extracellular C. albicans was separated from phagocytes by centrifugation through Ficoll-Hypaque suspensions (specific density, 1.175 g/cm3). Recovery of leukocytes by this technique was greater than or equal to 85%. The initial rate of phagocytosis was more rapid than that previously reported for bacteria. Ethylenediaminetetraacetate, vinblastine, ethylmaleimide, NaF, and ice bath temperature completely inhibited phagocytosis. Colchicine had no effect, and NaN3 was partially inhibitory. Pooled sera possessed low titers (greater than or equal to 1:40) of heat-stable opsonins. The opsonic activity of pooled sera was shown to depend primarily upon complement activated through both the alternative and classical pathways. Decomplemented hyperimmune sera were opsonic at high dilutions (greater than or equal to 1:160), and  complement amplified the initial rate of ingestion seen with hyperimmune sera.


The epidemiology and genetics of antibiotic resistance of Salmonella typhimurium isolated from diseases animals in New York.

Only 12% of 249 strains of Salmonella typhimurium isolated during the period 1973-1976 from diseased animals were sensitive to six commonly used antibiotics. Isolates from calves exhibited the highest frequency of resistance as well as a steadily increasing frequency of resistance to ampicillin and chloramphenicol. The majority of strains from horses, dogs, and cats were also resistant to more than one antibiotic, a finding which was interpreted as primarily an effect of therapeutic rather than of growth-promoting use of antibiotics in these species. Ninety-one percent of resistant strains possessed transferable resistance. In 31% of these strains, the transfer factors were heat-sensitive and did not function at 37 C. The determinant of resistance to ampicillin was usually associated with a non-heat-sensitive transfer factor, whereas resistance to chloramphenicol, kanamycin, and tetracycline was more commonly associated with heat-sensitive transfer factors. Strains of S. typhimurium with similar patterns of resistance often contained different plasmids. There was more genetic homogeneity among determinants of resistance to tetracycline than among other determinants.


Prevention of endotoxin-induced abortion by treatment of mice with antisera.

Small amounts of bacterial lipopolysaccharides (LPS), usually extracted from smooth organisms, have previously been shown to interrupt pregnancy in mice. The findings reported here demonstrate that LPS obtained from rough bacterial strains were also abortifacient. Moreover, lipid A, which represents a common toxic structure of LPS in many species of gram-negative Enterobacteriaceae, had the same activity, whereas the nontoxic polysaccharide moiety did not affect pregnancy. Our data also showed that specific bacterial antisera raised in various animal species protected pregnant mice from the abortifacient effect of smooth or rough LPS, and that this activity disappeared after absorption of the antisera with homologous bacteria. Nevertheless, antibodies to lipid A protected pregnant female mice challenged with lipid A or even with LPS extracted from various organisms. Moreover, pregnant mice treated with both antiserum and an antiserotonin compound were protected more effectively against LPS-induced abortion than mice treated with either substance alone.


Hepatitis B immune globulin: final report of a controlled, multicenter trial of efficacy in prevention of dialysis-associated hepatitis.

In a randomized, double-blind multicenter trial, 284 patients and 282 staff members of renal dialysis units who lacked detectable hepatitis B surface antigen (HBsAg) and antibody to HBsAg (anti-HBs) were randomly assigned to receive two 3-ml injections of immune serum globulin with high, intermediate, or low titers of anti-HBs four months apart. The incidence of infection with hepatitis B and of development of HBsAg was significantly lower in both patients and staff who received the high-titer material than in subjects who received the low-titer preparation eight but not 12 months after randomization (P less than 0.01 for patients and P less than 0.04 for staff, low-titer vs. high-titer at eight months). The high-titer hepatitis B immune globulin preparation did not appear to affect the severity of the cases of hepatitis that did occur, the proportion of subjects who developed persistent antigenemia, or the magnitude or timing of primary anti-HBs responses.


Demonstration of mycoplasmas in tissue by the immunoperoxidase technique.

The immunoperoxidase technique was shown to be a sensitive method for demonstration of the presence of mycoplasmas in tissue and swabs taken from the upper respiratory tract.


Correlation between rate of infection and preexisting titer of serum antibody as determined by single radial hemolysis during and epidemic of influenza A/Victoria/3/75.

During an outbreak of infection with wild-type influenza A/Victoria/3/75 virus, a correlation was established between the rate of infection and the preepidemic titer of serum antibody to that virus as measured by the single radial hemolysis technique. Titers of antibody determined by the hemagglutination inhibition method as well as by the single radial hemolysis technique were directly correlated with the rate of infection. By use of the single radial hemolysis technique, the 50% protective titer of antibody was calculated for a population of recipients of live influenza A/Victoria/3/75 virus vaccine.


A method for specific diagnosis of Rocky Mountain spotted fever on fixed, paraffin-embedded tissue by immunofluorescence.

For specific demonstration of Rickettsia rickettsii in fixed, paraffin-embedded tissues, the technique of trypsin digestion of deparaffinized, rehydrated sections was investigated. It was determined that 3.5 hr of digestion was optimal for achieving discrete, bright, green immunofluorescence of rickettsiae. At autopsy kidneys from seven of 10 cases of probably Rocky Mountain spotted fever contained structures that were specifically stained and that had the size and shape of rickettsiae. These structures were strictly limited to the endothelium and vascular walls of renal capillaries, veins, and arteries. Results from controls indicated that specificity of the immunofluorescence. R. rickettsii may be demonstrated by this method with greater sensitivity and specificity than by current histological methods. The technique allows retrospective analysis of certain organs for pathogenesis of involvement in Rocky Moutain spotted fever and offers a specific diagnostic test.


Antigens in urine of patients with glomerulonephritis and in normal human serum which cross-react with group A streptococci: identification and partial characterization.

Hyperimmune rabbit antisera antisera against group A streptococci precipitate protein antigens present in the urines of patients with poststreptococcal AGN and other glomerulopathies and also present in normal human serum. Over 90% of patients with AGN excrete detectable amounts of cross-reactive antigens in their urines, as do approximately 20% of patients with nonstreptococcal glomerulopathies. The streptococcal antigens are present in culture supernates, and immunodiffusion reactions in agar gel show identity or partial identity of serum, urine, and streptococcal antigens with antisera prepared against either urine proteins or against whole group A streptococci. Cross-reactive antibodies are removed from rabbit antisera by absorption with streptococcal culture supernates but not by absorption with a variety of streptococcal somatic constituents. The cross-reactive antigens have been isolated from streptococcal cultures grown in synthetic medium, thus eliminating the possibility of artefact due to tissue antigens present in Todd-Hewitt broth. The principal antigens have now been purified both from AGN urine and streptococcal supernates by molecular sieve and ion-exchange chromatography. They both have a molecular weight of approximately 360,000 daltons, as estimated on columns of agarose. The urine antigen has been applied to SDS-PAGE, and the migration of the major band was consistent with a molecular weight of 85,000 daltons. Rabbit antiserum to purified urine antigen precipitates both AGN urine and streptococcal supernates. These newly recognized human antigens, which cross-react with group A streptococcal antigens, are of particular interest because of their presence in readily available biologic fluids and their preferential excretion in almost all patients with poststreptococcal AGN.


Facial nerve schwannoma.

The present article gives a brief and complete account of the incidence, pathology, clinical features, diagnosis, management and prognosis of the schwannoma with special reference to facial nerve schwannomas. A case report of a rare schwannoma of the vertical part of the facial nerve found on biopsy of tissue during a postaural modified radical mastoidectomy is included.


Oestradiol receptors in the rat anterior pituitary gland during the oestrous cycle: quantitation of receptor activity in relation to gonadotrophin releasing hormone-mediated luteinizing hormone release.

Specific oestradiol binding to a receptor in nuclear and cytosol fractions of the rat anterior pituitary gland and pituitary responsiveness to gonadotrophin releasing horomone (GnRH) during the oestrous cycle have been studied. To accomplish this, both unoccupied and occupied oestradiol-binding sites in the nucleus and total cell were measured during the oestrous cycle. The concentration of unoccupied and occupied sites and total oestradiol binding in the cytosol fluctuated during the cycle. At pro-oestrus, the concentration of cytosol receptor was diminished by about 40% and replenishment occurred during oestrus. On the other hand, a profound increase is concentrations of cellular and nuclear receptors occurred at pro-oestrus. Administration of GnRH significantly LH release at all stages of the cycle. The maximum stimulation of LH release by GnRH was observed at 13.00 h of pro-oestrus. From these studies, it is concluded that pituitary responsiveness to exogenous GnRH during pro-oestrus parallels the changes in the content of oestrogen receptors in the cytosol and nucleus.


The interaction in vitro of Pneumocystis carinii with macrophages and L-cells.

A model was developed for studying the interaction between Pneumocystis, rat-derived cells, and humoral factors. Pneumocystis were obtained in large quantity by bronchial lavage of steroid-treated rats. The trophozoite was the predominant form obtained, and it could readily be recognized by phase contrast microscopy. Organisms maintained a typical morphology for at least 3 days in culture, and 10-20% took up radiolabeled nucleotides. Pneumocystis readily adhered to cell surfaces in a similar manner in alveolar macrophages from steroid-treated or normal rats, mouse peritoneal macrophages, and L-cells. Adherent organisms were not interiorized to a significant degree in the absence of antipneumocystis serum. After addition of rabbit antipneumocystis serum, rapid interiorization of organisms occurred from the surface of macrophages but not L-cells. Organisms appeared to be promptly destroyed within macrophages after interiorization. Persisting or multiplying intracellular forms were not seen. Antipneumocystis serum did not morphologically alter Pneumocystis. These observations suggest a role for antibody and mononuclear phagocytes during the immune response to Pneumocystis.


Culture of mononuclear phagocytes on a teflon surface to prevent adherence.

A method is described for the culture of mononuclear phagocytes in suspension by incubation on a Teflon film to which the cells do not adhere. The characteristics of peritoneal macrophages, bone marrow mononuclear phagocytes, macrophage cell lines, and fibroblasts cultured in this way are similar to those observed after culture on glass or plastic surfaces. Culture of mononuclear phagocytes in Teflon film dishes has three important advantages: the cells can be easily harvested without damage, recovery is almost complete, and the cells are not functionally impaired. Thus, this method makes it possible to use cultured mononuclear phagocytes for many studied that could previously only be done in freshly collected cells.


Genetic control of endotoxic responses in mice.

A number of altered immunologic responses to lipopolysaccharide (LPS) in C3H/HeJ mice result from the expression in B lymphocytes of a defective genetic locus, termed Lps. Lps has been mapped to chromosome 4 between two loci, Mup-1 and Ps. As it is difficult to type individual mice for LPS responsiveness in more than one type of assay, we have utilized Mup-1 as a genetic marker to correlate LPS responses in mice to the expression of the Lps locus. Three nonlymphoid responses to LPS have been examined in 12 recombinant inbred strains of mice and in a backcross linkage analysis, and are all regulated by the expression of the Lps locus. These responses are hypothermal changes in body temperature, and the elevation in serum levels of a colony stimulating factor and the precursor of the secondary amyloid protein AA. Therefore, the initiation of LPS responses in different cell types in mice involve the expression of a common locus. These linkage studies provide a means for analyzing the genetic control of many of the diverse reactions of the endotoxic response to LPS.


Tissue culture of isolated glomeruli in experimental crescentic glomerulonephritis.

As a means of studying mechanisms of response to injury in glomerulonephritis, glomeruli from normal sheep and rabbits and from sheep and rabbits with experimental crescentic glomerulonephritis have been isolated and grown in tissue culture. The cellular outgrowths from the normal and diseased glomeruli have been compared. The outgrowth of glomeruli from normal animals contained only two cell populations whose microscopic and ultrastructural appearances were of epithelial and mesangial cells. The same cells were also observed in the outgrowths of glomeruli from animals with crescenti nephritis but in addition a third population of cells was present in large numbers. These cells were identified as macrophages by their mobility, ultrastructure, phagocytic capacity, and presence of Fc receptors. Glomerular outgrowth from sheep with crescentic glomerulonephritis contained 170 +/- 20 (SEM) macrophages and outgrowths from rabbits with crescentic nephritis contained 64 +/- 6 (SEM) macrophages per glomerulus. We have previously observed large numbers of macrophages in the outgrowth of isolated glomeruli from humans with rapidly progressive crescentic glomerulonephritis. The predominance of the macrophage in cultures of glomeruli from both human and animal crescentic glomerulonephritis suggests that this is an important cell in the inflammatory reaction occurring in crescentic glomerulonephritis and may comprise a substantial proportion of the cells forming the crescent.


The differential destructive and enhancing effects of anti-H-2K, H-2D, and anti-Ia antisera on murine skin allografts.

Nude (athymic) or anti-lymphocyte serum-treated mice have absent delayed graft rejection due to impaired T-cell responses. Nonetheless, these mice can reject skin grafts, acutely, when treated with anti-H-2 antibody and additional complement. Resolution of the components in the H-2 antisera, by either absorption or by selective production of antisera of restricted specificity has demonstrated that anti-H-2K or H-2D antiser are graft destructive, and as shown elsewhere, are nonenhancing. By contrast, anti-Ia sera are not capable of causing allograft destruction even when used in extremely high doses and were previously noted to be enhancing. The mechanism of such differential effects is not apparent, but the findings are clearly of importance to transplantation in man, where sera reacting specifically with B cells may also be enhancing and nondestructive.


Streptococal throat infections in family practice.

Beta hemolytic streptococcal throat infections occur often enough and cause sufficient morbidity that careful diagnosis and appropriate treatment are matters of concern to the family physician and others involved in primary patient care. Throat cultures aid the precision of diagnosis; a simple, inexpensive, and accurate method of performing cultures in the office is described. The risk of rheumatic fever secondary to untreated streptococcal infections appears to be less than it once was, and further work defining this risk in various population groups is needed. Penicillin remains the drug of choice for treatment, with blood levels maintained for at least ten days either by oral administration or by a single intramuscular dose of benzathine penicillin G. The results of a recent survey of US family practice programs and an equivalent number of practicing family physicians show that most physicians use a selective approach to diagnosis and treatment of throat infections based on symptoms, signs, and age of the patient.


Inhibition of "spontaneous," notochord-induced, and collagen-induced in vitro somite chondrogenesis by the calcium lonophore, A23187.

The present study represents a first step in investigating the possible involvement of calcium (Ca2+) in the stimulation of somite chondrogenesis elicited by extracellular matrix components produced by the embryonic notochord. The ionophore, A23187, a drug that facilitates Ca2+ uptake leading to elevation of cytoplasmic Ca2+ levels, at concentrations of 0.25-1.0 microgram/ml severely impairs "spontaneous" somite chondrogenesis, i.e., inhibits the formation of the small amount of cartilaginous matrix normally formed by embryonic somites in vitro in the absence of inducing tissues. This inhibition is reflected in a considerable reduction in sulfated glycosaminoglycan (GAG) accumulation by A23187-treated somite explants. Furthermore, A23187 inhibits the striking stimulation of cartilaginous matrix formation and sulfated GAG accumulation normally elicited by the embryonic notochord and collagen substrates. In fact, 1.0 microgram/ml of A23187 reduces sulfated GAG accumulation by somites cultured in association with notochord or on collagen to a level even below that accumulated by somites cultured in the absence of these inductive agents. Although these results must be interpreted with caution, they provide incentive for considering a possible regulatory role for Ca2+ in the chondrogenic response of somites to extracellular matrix components produced by the embryonic notochord.


Interaction of immunoglobulin fragments with the mammalian sperm acrosome.

A study was made of the interaction of immunoglobulins and immunoglobulin fragments from sera of rabbits and pigs with the acrosomes of ten species of mammalian spermatozoa to investigate previous reports of an interaction between normal serum and the acrosome. It was shown that this could be predominantly attributed to IgC, although there was weak staining due to IgM. Further, it was shown that IgG interacted through the Fc fragment, the Fab fragment causing only weak staining of homologous spermatozoa.


Ganglioside alterations in guinea pig brains at end stages of experimental Creutzfeldt-Jakob disease.

Gangliosides were isolated from guinea pig brains at the end stages of experimental Creutzfeldt-Jakob disease. Quantitative analyses revealed marked decreases of ganglioside levels in pathologically devastated tissues such as cerebral cortex (-21%), basal ganglia and thalamus (-18%), and brain stem (-23%). The cerebellum revealed only minor pathological abnormalities and its ganglioside level remained unchanged. Thin-layer chromatography of the Creutzfeldt-Jakob brain gangliosides showed aberrant ganglioside patterns in all regions studied, including the cerebellum. With some exceptions, a trend in ganglioside pattern changes was detected which consisted of proliferation of GM3, GD3, GD2 and loss of GM1, GD1a, GD1b and GT1b.


A 3-months' study of enzymes as denture cleansers.

It was the purpose of the study to test the efficacy of dissolvent tablets containing mutanase and protease in removing denture plaque. The study group consisted of forty institutionalized geriatric denture wearers, who were assigned randomly into an enzyme group and a placebo group. Enzyme tablets and placebo for denture soaking were administered by the nurses. The dentures were immersed for 15 min once daily for three months. The amount of denture plaque, the clinical condition of the palatal mucosa, and the concentration of yeasts and bacteria in mucosal and denture smears were recorded before, during, and after the experimental period. The study was designed and carried out as a double-blind study. After denture soaking for six weeks a significant reduction of the amount of denture plaque and improvement of the clinical condition of the palatal mucosa was recorded. After denture soaking for twelve weeks the conditions had improved further when comparing the enzyme group with the placebo group.


Mechanism of adhesion of polymers to acid-etched enamel. Effect of acid concentration and washing on bond strength.

The tensile bond strengths of composites to enamel etched with various concentrations of phosphoric acid have been shown to correlate closely with the phase diagram for the system Ca(OH)2/H3PO4/H2O. Bond strengths were independent of the adhesive used and were a maximum when using approximately 20% phosphoric acid as etchant. High bond strengths were obtained with 2% phosphoric acid etchant without 'tag' formation, after short term water immersion. Washing the enamel for 60 s instead of 15 s after etching significantly increased the bond strengths obtained with 16 and 30% acid but not with 2%. Etching enamel with phosphoric acid results in deposition of calcium phosphates, which must be removed to give optimal bonding.


The status of psychological testing in clinical psychology: relationships between test use and professional activities and orientations.

A survey of clinical psychologists determined that both objective and projective tests were used with high frequency. The two tests clinicians most frequently recommended clinical students learn to administer were projective (the Rorschach and the TAT) and, among the 10 most frequently recommended tests, projective tests were recommended approximately 30% more often than objective tests. Clinicians who were frequent test users recommended both objective and projective tests more often than those not using tests. Clinicians doing substantial teaching and research tended to recommend projective tests less often than clinicians not engaged in those activities. Behavior therapists recommended projective tests less often than eclectic, Freudian, and neo-Freudian therapists.


Differentiation of brain damage among low IQ subjects with three projective techniques.

Using a battery of three projective techniques (Rorschach, Hand Test, Bender-Gestalt) only slight discrimination was found between low IQ subjects classified according to the presence or absence of brain trauma (exogenous vs endogenous), while substantial discrimination was obtained between the same subjects categorized in terms of "lower" (60-74) and "higher" (75-89) FS WAIS IQ. All four groups used in this study had been first equated on sex and age. Results were interpreted as supporting the position that some sort of brain impairment underlies most or all retardation. Question was raised concerning the efficacy of projective techniques for diagnosing organicity in subjects of average or better intelligence.


Piroxicam (CP 16171) in rheumatoid arthritis: a controlled clinical trial with novel assessment techniques.

Piroxicam (CP 16171), a new nonsteroidal anti-inflammatory agent, decreased pain, stiffness, and inflammation and increased the patient's ability to perform tasks in a double-blind study of patients with active, definite rheumatoid arthritis, poorly controlled despite standard therapy. Clinically and statistically significant improvement occurred in grip strength, walking time, and morning stiffness, and in patient and physician evaluation. Seventy-five per cent of the piroxicam-treated patients increased their daily activities. Three patients treated with the tablet form of piroxicam developed gastrointestinal ulcerations. Another patient developed iron deficiency anemia.


Treatment of rheumatoid arthritis with L-histidine: a randomized, placebo-controlled, double-blind trial.

A randomized cooperative double-blind trial of oral L-histidine for the treatment of rheumatoid arthritis was carried out. Patients were treated with either L-histidine 4.5 g daily, or placebo, for 30 weeks. None of the clinical measurements showed an advantage of histidine over placebo. A small decrease in rheumatoid factor titer and a small increase in hematocrit were found only in the histidine group. There was suggestive evidence of a beneficial effect of histidine in patients with more active and prolonged disease, based upon subjective doubld-blind evaluations by physicians and patients. No adverse effects of histidine therapy were noted. Histidine cannot be advocated as a therapeutic agent in rheumatoid arthritis, but further studies in certain groups of patients seem justified.


Branched-chain analogues of luteinizing hormone-releasing hormone.

Benzoyl-, acetylsalicylyl-, indomethacinyl-, pyroglutamylhistidyl-, and pyroglutamyl-D-phenylalanyl-D-tryptophanylseryltyrosyl groups were attached to a moderately active inhibitory analogue of LH-RH, [D-Phe2,D-Trp3-D-Lys6]-LH-RH, via the epsilon-amino group of the lysine residue. The resulting compounds were assayed for anti-LH-RH activity and for their ability to block ovulation in the rat. The decrease in polarity and increase in size of the lysine side chain resulting from addition of the aromatic acyl groups gave almost no increase in inhibitory activity. Addition of the dipeptide, less than Glu-His, also had little effect on potency. However, incorporation of the pentapeptide sequence to give a branched pentadecapeptide with essentially two N termini resulted in antiovulatory activity greater than the parent peptide or any other analogue thus far tested by us. The corresponding agonist peptide, [Nepsilon-(less than Glu-His-Trp-Ser-Tyr)-D-Lys6]-LH-RH, was also synthesized and tested for LH- and FSH-releasing activity. Surprisingly, it was no more active than [D-Lys6]-LH-RH itself, suggesting that an intact C terminus as well as an N terminus is necessary for the full expression of gonadotropin release.


Synthesis of pyrimido[5,4-c]quinolines and related quinolines as potential antimalarials.

3-Ethylaminomethyl-2-methyl-4(1H)-quinolone (1a) and its 6-CH3, 6-OCH3, and 7-Cl derivatives were prepared by means of the Mannich reaction. Conversion to the 4-chloro derivatives and condensation with 3-chloroaniline gave the corresponding 4-(3-chloroanilino) derivatives. Cyclization of 4-(3-chloroanilino)-2,6-dimethyl-3-ethyl-aminomethylquinoline (3a) and its 6-OCH3 derivative with paraformaldehyde gave 1-(3-chlorophenyl)-3,9-dimethyl-3-ethyltetrahydropyrimido[5,4-c]quinoline (4a) and the 9-OCH3 derivative 4b. Treatment of 4b with benzaldehyde gave 1-(3-chlorophenyl)-3-ethyl-9-methoxy-5-styryltetrahydropyrimido[5,4-c]quinoline (5). 3-Benzylaminomethyl-6-methoxy-2-methyl-4(1H)-quinolone (1e) and 3,3'-(1,3-benzyliminodimethylene)di[2-methyl-4(1H)-quinolone] (6b) were also synthesized. The compounds were inactive as antimalarials.


Analysis of family history data for evidence of non-Mendelian inheritance resulting from vertical transmission.

A number of infections of man, as well as of other animal and plant species, are heavily dependent upon 'vertical transmission'--that is direct parent-to-progeny transfer--for their maintenance in host populations. Such vertical transmission may be considered as a form of inheritance. It is usually non-Mendelian. This paper discusses the implications of such inheritance for the distribution of disease in families. A method is described for making quantitative predictions of prevalence rates of infection and of disease within different classes of relatives of either infected or uninfected probands. It is pointed out that, whereas a maternal line excess is to be expected among relatives of positive probands, the opposite should be found in families of negative probands. Expected differences between maternal and paternal line prevalence rates of observable disease decline rapidly with distance of relationship from the proband, and are greatly reduced by diagnostic insensitivity (analogous to penetrance). The implications of this analytic method for the design of family history studies are discussed. Published data on familial breast cancer are reviewed, and found to show no evidence that this condition is associated with a non-integrated vertically transmitted agent.


A 'new' syndrome of mental retardation with characteristic facies and brachyphalangy.

This paper describes 6 individuals, occurring in 3 generations of a single family, who were affected by a distinct syndrome which included: retardation and microcephaly; a small oval face with almond-shaped eyes, droopy eyelids, a small nose, and small downturned mouth; minor acral skeletal anomalies, and short stature. Craniosynostosis, heart defects, and limited elbow extension were seen less frequently. Expression was variable and parents who were in the direct vertical line of transmission of the syndrome showed few, if any, overt signs of the disease. However, the metacarpal/phalangeal profile of the parents showed a similar pattern to that seen in the affected individuals, and it is suggested that this profile may be the most sensitive indicator of carrier status.


Effects of calcium ionophores on the transport and distribution of calcium in isolated cells and in liver and kidney slices.

The effects of calcium ionophores on cellular calcium metabolism were studied in cultured kidney cells, in cells freshly isolated from rat kidney, and in liver and kidney slices. In isolated cells, these ionophores decreased the total cellular Ca content and the mitochondrial Ca. 45Ca efflux from prelabelled cells was also stimulated even in the absence of extracellular Ca. In slices, the ionphore A23187 increased the total slice Ca and the uptake of 45Ca. However, the mitochondria isolated from these slices treated with the ionophore had a lower total Ca and a depressed relative radioactivity. These results suggest that the increased cytosolic Ca produced by Ca ionophores may be due to mobilization of intracellular Ca stores rather than to a net shift of Ca from the extracellular fluids to the cell.


Structural and functional aspects of biological freezing techniques.

The cooling procedures used to prepare samples for ultrastructural examination at low temperatures often differ markedly from those used to recover optimal function of cells on thawing. The implications of these differences are reviewed. Damage and alteration to the structure and function of the cells may be caused by the high concentrations of cryoprotective agents such as glycerol or dimethyl sulphoxide (DMSO) often added to reduce ice crystal artefacts. Under the rapid cooling conditions commonly employed for structural studies, these additives are not cryoprotective; low rates of cooling are necessary for them to be effective. Rapidly cooled cells that contain intracellular ice are only injured during rewarming so their structure may be as yet unaltered by any damaging effects at low temperatures. Most cells able to recover on thawing are grossly shrunken at low temperatures but since they are potentially functional they are of interest structurally. These cryobiological principles are illustrated with freeze-fracture, freeze substitution and functional assays. The cell types chosen were Chlorella sp. and mammalian tissue culture cells.


Calcium antagonists and islet function: VII. Effect of calcium deprivation.

The role of extracellular Ca2+ in the regulation of islet function is investigated. Decreasing extracellular Ca2+ concentrations cause a dose-related inhibition of glucose-induced insulin release. Whereas the efflux of 45Ca from perifused islets is transiently increased on exposure to Ca2+-deprived media, it is unaffected by a partial lowering of the extracellular Ca2+ concentration. Under the latter condition, therefore, the observed reduction in the size of the islets' exchangeable calcium pool(s) appears to be due to reduced Ca2+ entry. The proper effect of glucose on Ca handling by the islets is apparently not affected by a lowering in the extracellular Ca2+ concentration. Nevertheless, in islets exposed to glucose and incubated in Ca2+-deprived media, glucose uptake and oxidation and lactate output are decreased, whereas the islet ATP level is increased, as if extracellular Ca2+ shortage were to affect not only the cellular pool of Ca regulating insulin release, but also energy-consuming processes possibly located at the cell membrane.


Biological freezing and cryofixation.

Freezing and freeze fixation are commonly used to achieve ultrastructural and biological preservation. Freezing in biological materials is complex because of their heterogeneous nature-water is unevenly distributed and the various domains are separated by semi-permeable membranes. Processes to be considered include: (1) osmotic gradients leading to redistribution of water, (2) nucleation and uncontrolled growth of ice crystals, (3) recrystallization of nucleated aqueous substrate. To avoid ultrastructural deformation in biological specimens cryofixatives are commonly employed. These are water soluble molecules, able to penetrate cell membranes (e.g. glycerol and dimethylsulphoxide). Interacting strongly with water, ions and bipolymers, they give rise to metabolic and physiological changes which render them useless for X-ray microprobe analytical studies. However, they can enable tissues to survive low temperature storage. Some plants and animals develop in vivo mechanisms which enable them to avoid or tolerate freezing. Alternative means of cryofixation have recently been developed. They rely on non-penetrating polymers of high and specific water binding capacity. These polymers enable the extracellular spaces to be vitrified rather than frozen. Such suppression of ice nuclei enables the cell contents to be maximally subcooled, resulting in the formation of nm dimension ice crystals. Since the polymers have a low osmotic activity and do not penetrate membranes, the interior of the cell is substantially undisturbed. Also hydrophilic polymers used as cryofixatives are physiologically less active than conventional cryoprotectants at equivalent weight concentrations, and th eir mechanical properties render them useful as matrices for cryosectioning.


Benzene toxicity: a critical evaluation: analytical techniques.

The choice of any procedure for analysis involves consideration of a number of factors and is best resolved by professional judgment. In general, techniques that require the fewest steps for sample preparation give the best results and instrumentation should be selected with this in mind. In recent times, the most successful determinations of benzene have used nonvisible spectrophotometry and gas chromatography. These techniques provide good sensitivity and require minimal sample preparation. Spectrophotometric methods are best used where there are few interfering compounds and therefore they are adequate for determinations of benzene in air, water, some industrial gases, and simple solvent mixtures. The development of Fourier transform interfacing has greatly improved the sensitivity of spectrophotometers and allows for improved accuracy using small samples. This has been especially realized in the direct analysis of gases by infrared spectrophotometry. The usefulness of gas chromatography lies in its ability to separate components in a mixture before analysis. For this reason, gas chromatography is the technique of choice for determining benzene in complex gaseous or liquid mixtures and biological systems. The development of microcircuitry has improved detector response as well as reduced the costs of most instruments. This, combined with the availability of prepacked columns, has made the gas chromatograph a standard instrument in even small laboratories.


Nasoseptal perforation--closure by external septorhinoplasty.

The successful correction of perforations of the nasal septum is still difficult. This treatment has been greatly facilitated by the use of the external septorhinoplasty, without compromising the airway or causing cosmetic deformity. Supportive autogenous graft material is used routinely and bipedicled mucoperichondrial flaps are used when necessary. Seven consecutive patients have been successfully treated by this method.


Camouflaging scars in the head and neck area.

Any break in the continiuty of healthy skin results in the formation of a scar. The way the scar is formed and the factors affecting the final appearance are discussed. Basic surgical principles as they relate to the revision of scars and the different surgical techniques used for revising scars are presented. Surgical adjuncts used following scar revision and hypertrophic scars and keloids and their treatment are also discussed.


Inhibitory effect of fatty acids on the entry of the lipid-containing bacteriophage PR4 into Escherichia coli.

Various unsaturated fatty acids (notably palmitoleic acid and oleic acid) interfered with plaque production by the lipid-containing bacteriophage PR4 on lawns of Escherichia coli. Addition of fatty acid to give 50 mug/ml ( approximately 0.2 mM) at the time of infection prevented phage replication. If, however, the fatty acid was added after infection, normal amounts of phage were produced. If the fatty acid was added (to 50 mug/ml) to the host cell culture a long enough time before infection such that the fatty acid concentration in the growth medium at the time of infection was reduced to less, similar5 mug/ml (due to fatty acid incorporation by the host cells), normal phage replication occurred also. Neither palmitoleic acid nor oleic acid prevented PR4 attachment to E. coli. Several types of experiments indicated that it is the entry process of the virus that is inhibited by these fatty acids. Specifically, if the fatty acid was added at the time of infection, the host cells were not killed by the virus and no detectable amounts of viral protein were synthesized. In addition, experiments using purified radioisotope-labeled virions showed directly that entry is inhibited. Mutants of PR4 that did replicate in the presence of oleic acid arose spontaneously at a frequency of 10(-6). Three of these mutants that have been further characterized have protein and phospholipid compositions indistinguishable from those of wild-type PR4.


Late effect of bacteriophage T4D on the permeability barrier of Escherichia coli.

Cold centrifugation of lysis-inhibited Escherichia coli B infected with wild-type T4D results in extensive lysis beginning around 20 min after infection at 37 degrees C. Infection with an e mutant, which fails to make lysozyme, prevents lysis, but does not prevent a marked loss of K+ and Mg3+. The t gene product, thought to disrupt the cytoplasmic membrane in natural lysis, is not required for this handling-induced cation loss or lysis. Three lines of evidence argue that late protein synthesis is required to develop this potential for cation loss; the potential does not develop in infections by: (i) mutants defective in DNA synthesis, (ii) mutants defective in gene 55, and (iii) wild-type T4 when chloramphenicol is added at 6 min after infection. All late mutants examined, which are blocked in the major pathways of morphogenesis, do not prevent development of the potential. The evidence argues for a new, late effect of T4 infection on the cytoplasmic membrane.


Exclusion of bacteriophage T1 by bacteriophage lambda. I. Early exclusion requires lambda N gene product and host factors involved in N gene expression.

Two modes of exclusion of T1 by lambda are distinguished. "Early" exclusion depends on gene N, but not on gene Q. It is at least partially ineffective against T1am23. "Late" exclusion depends on gene Q and effects T1am23 as well as T1+. Early exclusion is a direct effect of N gene product, rather than N gene being required for the expression of some other lambda gene. Three host mutations, groN, nusA, and nusB, known to interfere with lambda replication by affecting N gene expression, also interfere with the ability of lambda to exclude T1.


Purification and structures of recombining and replicating bacteriophage T7 DNA.

During the infection of Escherichia coli by bacteriophage T7, there is a gradual conversion of host DNA to T7 DNA. Recombination and replication occur during this time. We have devised a new way of examining the physical structures of the intermediates of these processes. It is based on the observation that there are no sites in T7 DNA susceptible to cleavage by the restriction endonuclease EcoRI. E. coli DNA, on the other hand, is susceptible to degradation by EcoRI. Thus, phage and host DNA can be separated by sucrose gradient centrifugation after treatment with EcoRI. Concatemeric T7 DNA contains a high proportion of branched, gapped, and whiskered structures. These appear to be intermediates of replication and recombination. This approach also monitors the conversion process from host to T7 DNA.


Chenotherapy for gallstone dissolution. I. Efficacy and safety.

Clinical experience with chenodeoxycholic acid therapy for dissolving gallstones is reported, with particular attention to determinants of response. Of 12 patients receiving 15 mg/kg/day or more, ten responded (83%); only 15 of 40 patients (38%) receiving less than 15 mg/kg/day responded. Large solitary stones and stones in gallbladders that visualized poorly after oral cholecystography had a lower response rate. Radiopaque stones did not respond in 18 patients. Five of ten patients with stones in the common bile duct responded. Small, dose-related elevations in SGOT were the only biochemical abnormality observed. Liver biopsy specimens showed no notable abnormality. Diarrhea was an infrequent problem. Stones recurred in three of 15 patients during six to 48 months of observation without treatment. Chenodeoxycholic acid, when given in adequate dosage, continues to appear promising as medical therapy for asymptomatic radiolucent gallstones in radiologically visualizing gallbladders.


Influenza vaccination in renal transplant recipients.

Renal transplant recipients receiving immunosuppressive therapy are prone to major pulmonary infections. Development of influenza virus infection may lead to renal allograft damage or rejection. These patients should therefore be protected against influenza viruses by vaccination. A satisfactory antibody response was found in 12 (60%) of 20 renal transplant recipients vaccinated. Among 15 control subjects, the antibody response was satisfactory in all participants (100%). Factors that might play a role in suppression of antibody response include use of immunosuppressive drugs and renal allograft function. Immunization is safe and does not appear to affect renal allograft function.


Single-dose tetracycline therapy for shigellosis in adults.

Forty-two adults who had Shigella isolated from stool (26 symptomatic, 16 asymptomatic) received a single oral dose of tetracycline hydrochloride (2.5 g). Minimal inhibitory concentrations of the 42 isolates demonstrated that 41% were sensitive to tetracycline. Sixteen of 18 patients with diarrhea who had tetracycline-resistant Shigella and all eight patients with diarrhea who had tetracycline-sensitive Shigella were clinical well and had Shigella-negative stools 48 hours after therapy. Fifteen of 16 asymptomatic patients demonstrated clearing of Shigella from stool within 48 hours of therapy. Single-dose tetracycline therapy is effective in the treatment of Shigella regardless of clinical expression of illness or in vitro sensitive of the organism.


Serious group B beta-hemolytic streptococcal infections in adults: report of two cases and review of the literature.

Adult infections with group B beta-hemolytic streptococci have been infrequently reported in the past. Two patients described herein, one with meningitis and the other with suppurative arthritis, emphasize that the organism is a potential pathogen and cause of serious infections in adults. The literature pertinent to these group B streptococcal infections is reviewed.


Nephrotoxicity induced by gentamicin and amikacin.

We evaluated 124 patients for nephrotoxicity associated with gentamicin or amikacin therapy. The incidence of definite nephrotoxicity was 10.5% during therapy, with a mean increase in creatinine of 1.0 mg/100 ml (range, 0.5-3.6 mg/100 ml). Nephrotoxicity developed late in therapy (mean, day 10) and the creatinine continued to increase after cessation of therapy for as long as nine days. Age, initial creatinine, total dose and initial "peak" and "valley" levels did not correlate with nephrotoxicity. Nephrotoxicity developed in 8 of 97 patients treated for less than or equal to 11 days and 5 of 19 treated for greater than 11 days (chi square, p less than .01). "Peak" and "valley" levels rose significantly (t-test, p less than .05) during therapy and increased more in those with nephrotoxicity. A "peak" level of amikacin of greater than or equal to 38.5 micrometer/ml or of gentamicin of greater than or equal to 10 micrometer/ml or a rise in the "valley" levels of amikacin above 10 micrometer/ml was also associated with nephrotoxicity (chi square, p less than .025). These data help define the natural history and the host and drug factors that affect the development of gentamicin- and amikacin-induced nephrotoxicity.


[Combined use of glucagon and strophanthin in myocardial infarct complicated by severe cardiac insufficiency].

The effects of isolated and combined use of strophanthin and glucagon on the values of central hemodynamics and cardiac contractile function were compared. The study was conducted on patients with myocardial infarction complicated by congestive heart failure in the acute period of the disease. It was found that a combination of these drugs had a synergic inotropic effect. A conclusion was drawn on the advantages of the combined use of strophanthin and glucagon in the treatment of severe congestive heart failure in the acute period of myocardial infarction.


[Acid-base state and blood oxygenation in cardiac insufficiency treated by drug agents].

The effect of different drugs on the acid-base condition and gases of arterial blood was studied by Astrup's micromethod in 124 tests in patients with circulatory insufficiency. Cardiac glycosides correct the moderate decrease in blood oxygen tension and respiratory alkalosis in patients with left-ventricular failure. Morphine has a good arresting effect in attacks of cardiac asthma and corrects or reduces the respiratory alkalosis typical of the disease but at the same time reduces the saturation of blood with oxygen. The use of oxygen together with morphine removes this unfavourable effect of the drugs. Euphylline often intensifies respiratory alkalosis, while its effect on oxygen tension in the blood and its saturation with oxygen is poorly pronounced and diversely directed. Lasics causes a favourable correcting effect on the acid-base condition and oxygenation of blood in pulmonary edema marked by metabolic acidosis.


[The medical arrangements of the Westphalian Wilhelms-University in Münster (author's transl)].

The buildings of the clinics and institutions of the medical faculty in Münster which were planned in 1914 and completed in 1925 were enlarged considerably with numerous new buildings in the 1950's because of increasing specialisation in medicine. The university eye clinic built in 1925 was enlarged in 1970 by the addition of a bed wing and in 1975 by the new construction of the out patients department. In 1969 the foundation stone for the new central clinic with the four bed towers was laid. The eye clinic will not move into the new central clinic, because the old part of the present eye clinic was also completely renovated, besides the construction of both the additions. This description is complemented by conclusive data on the number and bed-use of the single clinics and on the cost of the new wing and the number of students.


[On the history of ophthalmology and of the eye clinic in Münster (author's transl)].

The development of ophthalmology in Münster is described from the itinerant oculists and sooth-sayers of the middle ages to the completion of the enlargements to the eye clinic in the year 1977. After the foundation of the university in 1780 Prof. Anton Sentrup, Professor of Anatomy, held the first lecture in the special field of instruction of ophthalmology. But up to the introduction of a chair for ophthalmology more than a century passed by, after the university in Münster was closed in 1818 in favour of the unversity in Bonn following political changes. In the so's of the 19th century private eye clinics were foundet in Münster. In 1924 the new University in Münster received a chair for ophthalmology. The first director of the eye clinic was Prof. Aurel von Szily. He was followed by Oswald Marchesani, Wilhelm Rohrschneider, Wolfgang Riehm and Fritz Hollwich. The increase in the diagnostic and therapeutic possibilities and the continuously increasing numbers of patients made necessary the enlargement of the clinic by the addition of an operation and ward wing and of an outpatients' department. These additions which were begun in 1968 were completed in summer 1977 under the leadership of Prof. Hollwich.


[The history of glaucoma (author's transl)].

In the clinical history of chronic open angle glaucoma one can distinguish four periods concerning the pathogenetic theories. These are: 1. the nervous and vascular theory, 2. the mechanical theory, 3. the mixed theory and 4. the biochemical, enzymatic and molecular theory, which in the future will become more and more important.


[The iridociliary suture (author's transl)].

During a trabeculectomy it is possible to interfere with the boundary between the iris and the ciliary body-that is with the iridociliary suture. The author describes some special features of this region which can be recognized through the operating microscope, with allusions to some aspects of optical microscopy.


[On the normalization of the content of human urine of procoagulant after renal transplantation (author's transl)].

With human urine a very active procoagulant is excreted which converts prothrombin into thrombin in the presence of factor V, phospholipids and calcium chloride. In kidney diseases, its excretion is considerably reduced or totally absent. A negative correlation exists between these diseases and protein excretion. Kidney transplantation results in a normalization, however showing a trend which is not always parallel with the normalization of the blood creatinine levels. During the post-transplantation period, an occasional temporary, but very clear reduction with abnormal values of the kidney function tests can be observed. It is presumed that the procoagulant excretion could represent a hitherto unexplored function of the tubuli.


Ultrastructural evidence, by immunoperoxidase technique, for a tubular reabsoprtion of endogenous albumin in normal rat.

The reabsorption of endogenous albumin in the proximal tubules of the normal Munich-Wistar rat has been studied using immunoperoxidase techniques. The lumina of the superficial proximal tubules were found to remain open after in situ fixation, allowing good penetration of the conjugates. Labeling typical of an endocytotic process was observed only in the proximal tubules. This fact suggests that the glomerular filtration barrier is not an absolute one for denogenous albumin.


Comparative study of skin reactions in leprosy patients to M. leprae-lepromin and to ICRC-in, an antigen from cultivable acid-fast bacilli from M. leprae isolated from lepromatous nodules.

Skin test antigens (Dharmendra type) were prepared from fresh M. leprae (lepromin) and from a culture of strain C-44 ICRC bacilli (ICRCin) grown 'in vitro' from M. leprae isolate from lepromatous nodules. Comparative study of skin reactivity to lepromin and ICRCin--both "early" and "late" reactions in 76 leprosy patients was conducted. In 29 lepromatous (LL) cases, 25 exhibited totally negative reaction at the end of third week. In tuberculoid (TT) 22 and 23 out of 31 were positive (greater than 4.5 mm) at 3 weeks to lepromin and ICRCin respectively. In the 16 BB group, the reactions were comparable in the same patient. The cellular reaction in tuberculoid cases consisted of lymphocytic infiltration, epitheloid giant cells and Langhan type cells and indistinguishable from each other. These data with characteristic total lack of reaction in 25/29 lepromatous leprosy cases and identical cellular reaction in TT patients, provide strong evidence that ICRC bacillus strain C-44 is antigenically identical with M. leprae.


Tissue lipids in leprosy.

A total of 30 cases of leprosy (15 lepromatous and 15 tuberculoid) were studied by histochemical procedures for lipids in the morbid skin. The possible origin and relation of lipids to the presence of lepra bacilli in the lepra cells is discussed.


The chemotherapy of leprosy from a microbiological standpoint.

The increased knowledge concerning microbiology and chemotherapy of leprosy is exposed. Great stress is put on the knowledge of chemotherapy of tuberculosis that has accumulated during the last two decades and the guidelines that are equally valid for the chemotherapy of leprosy. The problems of the chemotherapy of the different forms of the disease are exposed and future lines of research indicated.


Response of neoplastic and non-neoplastic cells to a yeast extract.

PCO, an aqueous-alcoholic extract of the yeast, Saccharomyces cerevisiae, was found to inhibit mitoses of 4 different ascites tumors removed from mice. Carried as established in vitro lines 6 tumors and 4 established lines of non-neoplastic cells could not be inhibited by PCO. Primary cultures (diploid) of mouse embryo tissue cells and granulocytic blast cells from adult mice also could not be mitotically inhibited by PCO.


Internal configuration of saphenous-coronary anastomoses as studied by the cast-injection technique.

A study of the internal configuration of saphenous vein--to--coronary artery anastomoses was undertaken to examine the effect of technical factors. One hundred fifty anastomoses were constructed in isolated swine hearts and epoxy-resin casts were made of the anastomoses by pressure-injection. The effects of interrupted sutures, continuous suture, vein tailoring, vein-to-artery size ratio, and end-to-side and side-to-side anastomoses were evaluated. We made several observations: (1) The external appearance of an anastomosis is not a reliable indicator of internal configuration. (2) Interrupted suturing consistently produces an internal configuration with minimal deformity. (3) Unless special precautions are taken with continuous suturing, severe deformities may occur. Very fine suture spacing and knotting distal corner sutures are recommended. (4) Proper vein-to-artery size ratio and "cobra-head" vein tailoring are desirable. (5) Side-to-side anastomoses are similarly significantly affected by suture techniques, vein graft size, venotomy size, and orientation. The study of the internal configuration of saphenous-coronary anastomoses is a simple and readily available method which should be useful to all coronary surgeons in assessing and perfecting their techniques.


Prevention of pulmonary insufficiency through prophylactic use of PEEP and rapid respiratory rates.

This study evaluated the effectiveness of prophylactic positive end-expiratory pressure (PEEP) rapid respiratory rates (RRR), and high tidal volume (HTV) in prevention of congestive atelectasis. Measurements of pulmonary hemodynamics, mechanics, gas exchange, functional residual capacity (FRC), pathology, and cinemicroscopy were performed in 45 anesthetized dogs subjected to hemorrhagic hypotension. Randomly, the animals received control ventilation, HTV (20 ml. per kilogram), RRR (32 breaths per minute), or PEEP (5 cm. of water). Carbon dioxide was added as needed to maintain normocapnia. Control and HTV animals showed characteristic changes of congestive atelectasis (capillary congestion, stasis, interstitial edema, periarterial hemorrhage, alveolar edema, and hemorrhage). These microscopic and cinemicroscopic changes were prevented by PEEP and RRR and correlated with decreased physiological shunting (PEEP 10 percent, RRR 13 percent, HTV 22 percent; p less than 0.01) in the postshock phase. PEEP increased FRC by 40 percent (p less than 0.02) and reduced the pulmonary artery--small pulmonary vein gradient (PA-SPV), suggesting a direct effect on the capillary bed. RRR did not affect FRC but minimized the SPV-LA gradient. This effect on the pulmonary venules theoretically could be mediated by stimulating lymphatic flow, thereby decreasing interstitial edema. Thus PEEP and RRR are beneficial when used prophylactically but may work by widely differing mechanisms.


Hospital emergency room utilization in Montreal before and after Medicare: the Quebec experience.

The impact of the introduction of Medicare in Quebec on hospital emergency room services was examined in Metropolitan Montreal. After Medicare, the emergency room visit rate increased 14 per cent per year compared to a 7 per cent per year increase in the five years preceding Medicare. The outpatient clinic visit rate continued an upward trend (4 per cent per year). In six of the hospitals selected for more detailed studies, patient interviews revealed that before Medicare 33 per cent of emergency room attenders attempted to contact a physician before reporting to the emergency room and 63 per cent were successful in speaking to the physician. After Medicare, 39 per cent attempted but only 38 per cent were successful. Before Medicare, 47 per cent of patients said that their usual source of care was a private physician, and only 17 per cent usually sought care in the emergency room. After Medicare 58 per cent reported a private physician and 31 per cent the emergency room. These findings together with the increased population density of physicians and increased annual number of physician visits per person suggest that there has been a substantial rise in demand from the public for medical care of which one important early manifestation is an increased reliance on emergency rooms.


[Facial reconstruction (author's transl)].

The radical tumour surgery and an adequate covering of defects in the face area are preferably combined in one operation. On ten examples of a total of 58 cases methods of covering of one, two and three layers of cheeck defects were demonstrated.


[Covering defects after exstirpation of tumours in the ear region (author's transl)].

Some possibilities are shown to cover defects in the ear region. Especially "bi-loped flaps" will be used, and some variations of this type of flap are described.


Primary amoebic meningoencephalitis.

As a serendipitous by-product of polio virus research, a highly fatal amoebic meningoencephalitis was recognized in animals. The causative microorganisms, contaminants of the viral cultures, were identified as small soil amoebae. These organisms, previously considered non-pathogenic, are prevalent throughout the world. Based on animal studies, the original investigators suggested the possibility of a similar disease in humans. Seven years later, human cases of amoebic meningoencephalitis were reported from widely separated areas of the world. Since 1965, a total of 79 cases have been reported. The literature of primary amoebic meningoencephalitis is presented. The history of the discovery and elucidation of this disease is reviewed. The 79 cases reported in the world literature are divided into two groups, those diagnosed retrospectively after reviewing previous deaths from meningoencephalitis, and those diagnosed at the time of the illness. The classification, morphology, pathogenicity, virulence and distribution of pathogenic soil amoebae are reviewed. The presenting clinical findings, diagnostic procedures, pathology, and management of this recently recognized, highly fatal, human disease is presented along with a report of a new case. Otolaryngologists should become familiar with this serious disorder with a transnasal portal of entry.


Levamisole in the treatment of recurrent aphthous stomatitis.

In a pilot study as well as in a double-blind placebo-controlled study, 21 patients suffering from recurrent aphthous stomatitis were treated with the immunotherapeutic agent, levamisole. The results obtained confirm previous studies that levamisole has a beneficial effect on the symptoms of recurrent aphthous stomatitis and is well-tolerated.


Process or product: awareness vs. aesthetics.

A historic perspective on the roles of the patient and psychotherapist relative to creative expression clearly demonstrates an emphasis on content, on the projective interpretation of the product. The author challenges the emphasis on product rather than process, the educational 'shop-window' approach to achievers and the talented, as well as the negative effects of 'labeling', and the validity of some forms of projective psychological testing. Discussed is the influence exerted by the psychotherapist through Rogerian 'leakage'. In addition, techniques are suggested for expanding sensory awareness and synthesizing communication skills as a means of enhancing self-image and creative potential. The contention is that the more ways that a skill is synthesized, the more complete is the learning. The more complete the learning, the greater the sense of security. The more secure the individual, the more willing (s)he is to venture into other areas where risk of failure has been a deterrent.


The use of drawings for psychiatric evaluation of a defendant in a case of homicide.

From an initial spontaneous drawing on the back of a cigarette carton and through a series of subsequent drawings, a defendant, who shot and killed his victim before five witnesses, was granted a complete psychiatric examination on the findings of the drawing analysis. He was evaluated as a paranoid schizophrenic and eventually was acquitted but found insane and committed to a state hospital for treatment. His drawings indicated his threatened sexual identity through a disturbed body image while his movement from reality to disintegration and back is evidenced in corresponding crystalline and fragmentary form productions. The case points out the significance of drawings for psychiatric examination and evidence where they are available. An outline and discussion is appended of the history of the determination of criminal responsibility.


Isolation of labeled triiodothyronine from serum using affinity chromatography: application to the extimation of the peripheral T4 to T3 conversion in rats.

A method for the isolation of small quantities of labeled 3,5,3' -triiodothyronine (T3) from serum or thyroid extracts is described. Conjugates of rabbit anti-T3 antibody to Sepharose 4B are incubated with 0.5 to 1 ml of human or rat serum at pH 8.6 for 1 hr. The tubes are centrifuged and washed with buffer followed by 6 M guanidine to remove nonspecifically bound labeled thyroxine (T4). The fraction of T3 and T4 bound to the Sepharose conjugate varies depending on the concentration of serum in the initial incubation tubes, the T3 and T4 content, and the specificity of the antiserum used. In a system that contains 0.5 ml of normal human serum, 1 ml of glycine-acetate buffer (pH 8.6), and 0.25 ml settled Sepharose-anti-T3 conjugate, the T3 to T4 binding ratio was generally 150-200, with up to as much as 50% of T3 bound to the pellet. The coefficient of variation of the method is less than 5%, and it may be performed in a matter of hours. There is no detectable conversion of T4 to T3 during the separation process. Using this technique, conversion of T4 to T3 was evaluated in euthyroid rats after injection  of 125l-T4. Over the period of 36-72 hr after injection, a ratio of T3 to T4 of 0.74 +- 0.06 x 10-2 (mean +- SE) was present in the plasma. Using the calculated metabolic clearance rates for T3 and T4 in these animals, fractional conversion of T4 to T3 was estimated to be 27%, in good agreement with results obtained by other techniques. This method would appear to be of value for specific isolation of the small quantities of T3 produced from T4 after in vivo or in vitro T4 to T3 conversion.


Immunological properties of Vibrio cholerae lipopolysaccharides.

Immunological effects of wall lipopolysaccharide (LPS) preparations obtained from Vibrio cholerae Inaba 569B, Ogawa NIH 41 and NAG 4715 strains by the hot phenol-water procedure were examined in mice. Although these LPS lack KDO, which are basic components of the core region of most gram-negative LPS, they still have potencies as B-cell mitogens, adjuvants, immunosuppressants, polyclonal B-cell activators and phagocytic stimulants for macrophages. The activities of these V. cholerae LPS on murine immune system seemed to be weaker than those of Salmonella typhimurium LT2-LPS. Among these V. cholerae LPS, NAG 4715-LPS showed the strongest mitogenic activity and phagocytic stimulation, while the potencies of this NAG 4715-LPS for the induction of polyclonal B cell activation, adjuvant effects and immunosuppression did not seem to be greater to those of the other LPS.


Temperature sensitive R plasmids isolated from Proteus strains.

Out of 32 R plasmids isolated from Proteus strains, 17 were found to be temperature sensitive with respect to inheritance in E. coli cells. They were fi- and classified into incompatibility group T or V. Cells carrying T group Rms273 plasmid were temperature sensitive with respect to growth and conjugal transfer in both E. coli and Proteus. The V group YOR-10 plasmid was stable in Proteus even at 42 C. However, the loss frequency of YOR-10 plasmid in E. coli reached 100% after 4 hr of incubation at 42 C, in spite of stable inheritance at 25 C. Conjugal transfer of the YOR-10 plasmid in E. coli was also strongly inhibited at 42 C. It has been concluded that instability of V group R plasmids in E. coli is due to their thermosensitive inheritance in the progeny cells at high temperatures.


An endotoxin induced serum factor that causes enhancement of antibody response to heterologous erythrocytes.

The sera obtained from blood of the mice, which had been intravenously injected with LPS several hours in advance, contained some active substance capable of enhancing anti-sheep red blood cell (SRBC) antibody responses in mice. Activity of the sera was still retained after passage through a rabbit anti-LPS antibody-coated Sepharose 4B column, but greatly reduced by passage through a rabbit anti-mouse thymocyte antibody-coated Sepharose 4B column. The active substance in the sera was eluted through a Sephadex G-200 column at the same position as the serum albumin. The addition of this substance to B cell rich spleen cell cultures in vitro in the presence of SRBC generated tremendous numbers of antibody forming cells 4 days after the incubation, suggesting that this substance was able to take over the helper function of T cells in thymus dependent antibody responses. However, this substance was not capable of stimulating 3H-thymidine-uptake into cultured spleen cells. The possible role of this substance in the adjuvant effect of LPS is discussed.


Attitudes of medical undergraduates in Glasgow to computer-assisted learning.

Computer-assisted learning (CAL) has been introduced as part of the undergraduate teaching course in general practice during the penultimate year of the medical course. The student is given an opportunity to make clinical decisions and to manage a case over a significant time scale. The attitudes of the students are favourable to this method of instruction.


[Effects of the beta-adrenergic blocking agent propranolol on the carbohydrate- and lipometabolism (author's transl)].

Intravenous glucose tolerance tests were performed in 17 patients suffering from hyperthyreosis before and after a week of treatment with propranolol. The blood taken until the 125. minute after the glucose load was used for the determination of serum glucose, the free fatty acids (FFA), the free glycerol and the radioimmunologically measurable insulin (IRI). The following results were received: After the treatment with propranolol the glucose tolerance decreased significantly. The insulin secretion was diminished showing a significant difference for the fifth minute after glucose injection. The concentration of the FFA remained unchanged. The levels of the free glycerol were significantly lower after the propranolol treatment than before. Though an inhibition of lipolysis was possible by the propranolol treatment the glucose tolerance did not improve due to the inhibition of insulin secretion under propranolol. Beta-adrenergic blocking agents do not lead to an essential change in the carbohydrate- and lipometobolism. Therefore, their use in hyperthyroidism is mainly justified because of the cardial symptomatology.


[Fluphenazine dekanoate (Dapotum D minor): onset and duration of the effect. A psychological trial. 1st communication (author's transl)].

36 patients with psychosomatic symptoms were treated in a double blind study versus placebo with fluphenazine dekanoate (Dapotum D minor). They were tested before injection and on the 1st, 7th and 14th day. The patients were selected by the personality questionnaire of Maudsley (MMQ). All showed signs of neurotic reactions and vegetative instability. The therapeutic success was controlled with the mentioned questionnaire, with the self states of v. Zerssen and with a specified questionnaire. The evaluation was done by variance and covariance analysis. The onset of effect was observed after 24 to 48 hours. After one week the optimal effect occured, which was maintained until 2 weeks after the injection. The general behaviour improved significantly.


Serum immunoglobulin E level and search for myelin basic protein specific IgE antibodies in patients with multiple sclerosis.

Circulating levels of immunoglobulin E (IgE) have been determined by solid-phase radioimmunoassay in groups of patients with different clinical courses of multiple sclerosis (MS) and in healthy controls. The geometric mean of the serum IgE level in the MS patients was somewhat less than that in the control group (64 U/ml), but this decrease was not significant. Contrary to the findings of Campbell [1, 2, 3, 4], circulating IgE in the MS patients was not specifically adsorbed on bovine myelin basic protein (BMBP) immunoadsorbent and does not give a positive immunofluorescence using guinea pig brain sections.


Sensitivity of strains of enteropathogenic Escherichia coli to tobramycin and other antibiotics.

The sensitivity patterns of strains of enteropathogenic Escherichia coli associated with diarrhoeal disease of infants to tobramycin and other antibiotics were estimated. The activity of tobramycin and of gentamicin alone and in combinations against recent isolates of enteropathogenic Escherichia coli was investigated. It was found that all the strains included in the present study were sensitive to tobramycin and gentamicin and most of them were sensitive to colistin and furazolidone. No significant differences in minimal inhibitory concentrations (MICs) and rates of killing were found between tobramycin and gentamicin, and they acted in an additive manner against most of the strains tested.


Mitomycin-C alone and in combination with infused 5-fluorouracil to the treatment of disseminated gastrointestinal carcinomas.

One hundred and thirty-two previously untreated patients with metastatic adenocarcinoma of the gastrointestinal (GI) tract were randomized to receive either a 120-hr infusion of 5-fluorouracil (5FU) with mitomycin-C or mitomycin-C alone. Superiority of the combination treatment was demonstrated with remissions in 30 out of 82 (37%) patients versus 9 out of 50 (18%) with the single drug treatment (P = 0.02). The median survial with 5FU--mitomycin-C was 29 weeks, as opposed to 20 weeks with mitomycin-C alone (P = 0.03). The combination produced significantly more severe myelotoxicity than the single drug, and jaundiced patients experienced more myelosuppression than non-jaundiced patients with both treatments.


Exchange of individual ribosomal proteins between ribosomes as studied by heavy isotope-transfer experiments.

Whether the individual ribosomal proteins undergo exchange between robosomes in vivo during cell growth was examined using heavy isotope transfer methodology. E. coli was grown first in a heavy isotope medium in the presence of [3H] leucine and then transferred to normal medium and allowed to grow for one generation in the presence of [14C] leucine. The "heavy" and "light" ribosomes that were present in such cells were separated by sedimentation and the ribosomal proteins resolved by two-dimensional gel electrophoresis. The individual proteins were burnt in O2 and their contents of [3H] and [14C] labels determined. From the analysis of the data we find that the great majority of the ribosomal proteins of E. coli does not undergo exchange during cell growth. Proteins which were found to exchange to varying levels in different transfer experiments were S1, S2, L7/L12, L9, L10 and L33. All of them except L9 exchanged to the same levels in control experiments in which separately grown heavy and light cells were mixed and processed. These proteins therefore undergo exchange during cell breakage and ribosome isolation. Protein L9 consistently showed appreciably greater exchange in transfer experiments as compared to the controls suggesting that it may exchange in vivo.


Origin of replication, oriC, of the Escherichia coli chromosome: mapping of genes relative to R.EcoRI cleavage sites in the oriC region.

A precise genetic-physical map of the tna-ilv region at 82 min on the genetic map of E. coli is obtained through deletion mapping and analysis by restriction endonuclease EcoRI of plasmids, derived from an F' carrying the genes between aroE and ilv. A locus, designated het, which in its diploid state results in slow growth and heterogeneity of cell size due to distorted cell division, maps between bglB and asn, 30-45 kb counterclockwise of ilv. The pattern of R.EcoRI cleavage sites in the het region is identical with the pattern obtained by Marsh and Worcel (1977) who analyzed DNA labeled preferentially in the region of the DNA replication origin (oriC). We suggest that oriC is identical with the het site and that it can be allocated to a position 32 kb counterclockwise of the ilv operon.


Inhibition of thymidine phosphorylase in vivo provides a rapid method for switching DNA labeling.

Uridine blocks the in vivo conversion of thymine to thymidine in Escherichia coli, thus, one can change DNA labels by labelling first with a thymine label (e.g. 14C) and then, at the time of the change, adding 50 microgram uridine per ml and thymidine (e.g. 3H). The cells immediately start using the thymidine, ignore the thymine for several generations, and are not affected by the uridine.


Caffeine enhancement of radiation killing in different strains of Saccharomyces cerevisiae.

Haploid and diploid wild type strains, and three classes of radiation-sensitive mutants of Saccharomyces cerevisiae were tested for enhancement of UV-inactivation by caffeine in growth medium. In addition, the sensitizing effect of caffeine was studied in a haploid and a diploid wild type strain after gamma-irradiation. The drug sensitized the UV-irradiated cells of all strains except those reported to be only slightly UV-sensitive but highly sensitive to ionizing radiation. After gamma-irradiation, no caffeine-enhancement of killing was observed in stationary phase cells of either the haploid or the diploid strain. However, log-phase cells of both strains were partially sensitized. The results of both sets of experiments suggested that caffeine interferes with a recombinational repair occurring in cells in S or G2 phase.


[Correlation between a novel phenotype towards streptomycin and the binding of an additional protein to the ribosome in mutants of Escherichia coli B].

Mutants of Escherichia coli have been isolated containing streptomycin suppressors that exhibit novel phenotypes with respect to strA alleles. In one class of these mutants, the suppressor effect parallels a strong binding to the ribosome of an additional protein in at least stoichiometric amounts. Transduction experiments confirmed that the level of suppression and the degree of binding of this protein were correlated.


Changes in regulation of ribosome synthesis during different stages of the life cycle of Saccharomyces cerevisiae.

Diploid strains of Saccharomyces cerevisiae, each homozygous for one of the temperature sensitive mutations rna2, rna3, rna4, rna6 or rna8, are temperature sensitive for ribosome synthesis during vegetative growth, but are not inhibited for ribosomal synthesis at the restrictive temperature under sporulation conditions. The continued ribosome biosynthesis at the restrictive temperature (34 degrees C) during sporulation includes de novo synthesis of both ribosomal RNA and ribosomal proteins. This lack of inhibition of ribosome biosynthesis is found even when cells committed to complete sporulation are returned to vegetative growth medium. The ribosomes synthesized at 34 degrees C are apparently functional, as they are found in polyribosomes. Although the rna mutants do not regulate ribosome synthesis during sporulation, all of these diploid strains fail to complete sporulation at 34 degrees C. The cells are arrested after the second meiotic nuclear division but before ascus formation. The failure to complete sporulation at the restrictive temperature and the inhibition of ribosome biosynthesis during growth are caused by the same mutation, because revertants selected for temperature independent growth were also able to sporulate at 34 degrees C.


Re-initiation of tryptophan operon expression in a promoter deletion strain of Salmonella typhimurium.

A genetic and enzymological study was made of five spontaneous prototrophic revertants of a tryptophan auxotroph of Salmonella typhimurium which carries a deletion extending from the closely linked supX locus into the trp operator-promoter region. The revertants were found to have regained initiation of expression of all five trp genes. Recombinational tests showed that in each case the genetic change responsible for re-initiation is cotransducible with the trp-cysB region of the chromosome. Two different mechanisms leading to re-initiation of trp gene expression were established: (a) an extension of the limits of the original deletion resulting in the fusion of the trp structural genes with a nearby gene or gene set located outside the operator end of trp, and (b) translocation of a duplicate set of the trp structural genes to other chromosomal sites, located operator-distal to the normal trp operon, in such a manner that they are functionally fused to foreign genetic units. One revertant which arose by mechanism (a) was shown to have an extended deletion with one new terminus in trp and the other in the nearby cysB locus. All the revertants exhibit constitutive expression of the trp enzymes, with activities varying among strains from five to forty five times greater than the fully repressed wild type level. The protein product of trpA, the first structural gene of the operon, appears to have been partially damaged by the re-initiation event in at least two strains, while in the other strains, the enzyme appears in preliminary tests to be indistinguishable from that of wild type.


A gene involved in the metabolic control of ppGpp synthesis.

A genetic locus has been identified which controls the basal synthesis of ppGpp in growing E. coli. Cells carrying a recessive allele of the relX gene have a very low concentration of ppGpp during balanced growth, and fail to accumulate ppGpp in response to carbon/energy source downshift. Moreover, the recessive relX allele renders the cells unable to grow at 42 degrees C and, when coupled with relA, makes the cells sensitive to the presence of leucine in minimal medium. RelX is cotransduced with fuc and relA and located at approximately 59.4 min on the E. coli genetic map.


Fructose-1,6-bisphosphate, a regulator of metabolism.

Fructose-1,6-bisphosphate affects the rate of a large variety of enzyme reactions. In some instances its role as a physiologic effector is well documented. In many cases the effects of fructose bishosphate on particular enzymes have been demonstrated in vitro but the link to physiologic conditions has not yet been established. It is the purpose of this paper to summarize the scattered findings in fructose bisphosphate as an effector of enzyme reactions and to draw some conclusions about the role of the compound in metabolic regulation.


[Antibody-coaded bacteria in urine sediment of children with urinary tract infections (author's transl)].

In 40 girls and 9 women with recurrent, non-obstructive urinary tract infections, and in 5 patients with nephrolithiasis the site of infection was determined by 108 bladder washout tests. The corresponding sediments were examined for antibody-coaded bacteria using an immunofluorescence test (IFT). The IFT was positive in 18 (72%) of 25 supravesical bacteriurias. Out of 75 vesical bacteriurias 39 infantile and 7 adult (together 61%) specimens contained antibody-coaded bacteria. We think the IFT is of no diagnostic value in localizing recurrent urinary tract infections in girls. For adults such an evaluation is not yet possible due to our small number of cases.


[Clinical experience with the use of continuous positive airway pressure delivered by the nasal route (N-CPAP) (author's transl)].

The nasal CPAP modification of spontaneous positive pressure breathing is technically simple, non-invasive for the patient, and does not interfere with routine infant care, yet provides most of the advantages of other CPAP modifications. Endotracheal intubation is eliminated since airway pressure is delivered by two short canules attached by means of adhesive tape to the patient's nose. The CPAP system was used in the care of 35 newborns and premature infants admitted to the University Children's Clinic Graz, with the diagnosis of respiratory distress (31 cases) or apnea-syndrome (4 cases) between Sept. 1973 and July 1975. The indications for the use of this system was based on the arterial oxygen tension values while breathing 100% O2 for 15 min. 22 of the 28 patients surviving were treated with N-CPAP alone, whereas 13 patients were CPAP-failures and required further ventilation (IPPV,PEEP). In the latter group apnea and 2 cases of pneumothorax necessitated intubation and ventilation, rather than the respiratory distress for which they had been initially treated. All 7 patients who died during this study were from this group of N-CPAP-failures (20% of the total, 54% of all N-CPAP-failures). Keeping ambient oxygen concentrations constant, an increase in arterial oxygen tension was measured in almost all patients surviving on N-CPAP and was initially even seen in those who later died, so that the ambient oxygen concentration could eventually be decreased.


[Clinical studies on the choleretic agent Febuprol (author's transl)].

In previous pharmacological experiments with the choleretic agent Febuprol, healthy subjects showed a significant increase in bile flow and its constituents in the acute experiment. As a consequence of these results we have carried out a double-blind cross-over therapeutic trial with Febuprol in 50 patients with a cholecystopathic symptom complex. After a 14 days' treatment (3 capsules daily) a significant improvement of the typical symptoms (feeling of fullness, pressure in the upper abdomen, meteorism, constipation, flatulence and nausea after food) was recorded in these patients. Moreover a significant lowering of the serum cholesterol level was noteworthy.


[Liver substitution and liver grafting (author's transl)].

The possibilities of an artificial liver substitution are very limited; at most various partial functions of the liver can be substituted for a short time. Technically, the various modifications of hemoperfusion are given first importance, especially hemoperfusion through a carbon filter. But the best possible intensive therapy with substitution of the substances reduced by insufficiency of the liver, e.g. coagulation factors, is the most important measure in the treatment of hepatic coma at the present time. Shortterm biological substitution with extracorporeal perfusion of a primate liver is possibly the most suitable form of liver substitution. Longterm substitution can only be possible and thought of by liver grafting. In recent years some workers have obtained marked improvement, especially reduction of mortality, with clinical orthotopic liver grafts.


[The operative treatment of prolapse of the rectum (author's transl)].

Different kinds of mucosal prolapse at the rectum are differentiated. True and prolapse with protrusion of considerable portions of the rectum principally occur in later life. For younger patients several rather complicated operative procedures for the elimination of anal prolapse come into consideration, but usually they cannot be reasonably accepted by older patients. For this reason a simple method is recommended which carries little risk and yet promises satisfactory result--such as the insertion of a Thiersch ring. Whereas with this technique, if correctly carried out, improvement of the condition is almost certain to be expected, the longterm result over several years is limited, as a followup examination showed. Insertion of a Thiersch ring can, howeever, be repeated without difficulty. This procedure will retain its indication because of its simplicity.


Caffeine.

Most of the population of the world is exposed to caffeine to a greater or lesser extent since it occurs in a number of plants used in the preparation of widely consumed drinks, and has in addition a limited therapeutic use. Chromosomal abnormalities are induced by caffeine in both plant cells and in mammalian cells in culture and it also has some anti-mitotic activity. DNA-repair processes sensitive to caffeine have been demonstrated in a number of cell systems and it has been shown to affect a wide range of other cellular processes. Caffeine has potent mutagenic effects in Escherichia coli and other micro-organisms both when acting alone and in combination with other mutagens. However its mutagenic activity in Drosophila has been disputed and the available evidence suggests that it is neither mutagenic in mammals nor synergistic with other mutagens although at very high doses it appears to have some teratogenic activity in mammals.


Relationships between mutation and transformation frequencies in mammalian cells treated "in vitro" with chemical carcinogens.

An analytical quantitative comparison of data from the literature about frequencies of mutations and transformations induced by mutagenic-carcinogenic compounds in mammalian cells was carried out without any selection of unfitting data. The analysis was performed for equitoxic doses and background level. Data on transformation frequency came from 105 experiments performed with 34 carcinogenic compounds: those on mutation frequency came from 66 experiments performed with 26 mutagenic compounds; 7 compounds were assayed for both these activities. The difference in frequency between structural mutations and transformations was about 10(2)-10(3) and it appears statistically extremely significant. These results seem to indicate an absolute difference between structural mutations and transformations. In the framework of other observations it is suggested that structural alterations in a single gene are perhaps only a component of the steps present in the oncogenetic process. We may regard as "epigenetic" type phenomena the other steps involved in this process.


The mechanism of the mutagenic action of hydroxylamine XII. Phenotypic suppression of amber mutants of phage T7 by hydroxylamine and O-methylhydroxylamine.

The reproduction of phage T7 in the presence of hydroxylamine (HA) (mutagenesis in vivo) results in the phenotypic suppression of some amber mutants. The presence of O-methylhydroxylamine (OMHA) results in a similar effect, indicating a similar mechanism for the action of the two compounds. Since the rate of reaction of mutagen with nucleoside residues under these conditions in negligibly low, one of the most plausible explanations of this effect is the enzymic formation of modified precursors and their incorporation into bacterial tRNAs or phage-induced RNA.


The mechanism of the mutagenic action of hydroxylamine XIII. Reversion of phage MS2 amber mutants in the presence of hydroxylamines.

The replication of the phage MS2 in the presence of either hydroxylamine (HA) or O-methylhydroxylamine (OMHA) (mutagenesis in vivo) results in an increase in the reversion frequency of two amber mutations in the maturation protein. When acting on the extracellular phage (mutagenesis in vitro) the mutagens do not affect the reversion frequency. The most probable mode of mutagenic action of the hydroxylamines on the vegetative MS2 phage involves the enzymic formation of modified precursors and their incorporation into RNA.


High mutagenicity of N-(alpha-acyloxy)alkyl-N-alkylnitrosamines in S. typhimurium: model compounds for metabolically activated N,N-dialkylnitrosamines.

A series of N,N-dialkylnitrosamines (alkyl means methyl, ethyl, n-propyl, n-butyl or tert-butyl group) mono-substituted at the alpha-carbon with an acetoxy group, were tested for their mutagenic action in Salmonella typhimurium TA1530 in the presence or absence of a rat-liver supernatant from 9000 X g. The presumed released of methyl, ethyl, n-butyl and n-propyl carbonium ions from the corresponding alpha-acetoxy derivatives, either by enzymic cleavage or by non-enzymic hydrolysis of the ester group, caused high mutagenicity in the bacteria. As has been demonstrated for certain alpha-acetoxy compounds, the mutagenicity of these compounds was inversely related to their half-lives in aqueous media. N-(Acetoxy)methyl-N-tert-butylnitrosamine and a beta-acetoxy derivative of N,N-diethylnitrosamine were not mutagenic either in the presence or in the absence of hydrolysing rat-liver enzymes. These results support the hypothesis that alpha-carbon hydroxylation is one mechanism involved in the metabolic activation of N,N-dialkylnitrosamines.


Selection with cycloheximide of metabolic and UV-sensitive mutants of Schizophyllum commune and Saccharomyces cerevisiae.

The difference in lethality to cycloheximide between actively dividing and non-dividing cells was exploited to enhance detection of auxotrophic and UV-sensitive mutants in the fungi Schizophyllum commune and Saccharomyces cerevisiae.