Sensitive and convenient quantitation of antibody binding to cellular antigens using glutaraldehyde preserved cells. As a preliminary step in the identification and isolation of antibodies to human cancers, we have developed a sensitive and convenient assay for antibody binding to cellular antigens. The basis for the method is antibody binding to glutaraldehyde-fixed cells (AbGfC) and quantitation with radioiodinated staphylococcal protein A (SpA). Glutaraldehyde fixation of intact cells, which does not appear to effect the ability to form antigen-antibody complexes, provides a convenient and standard supply of target cells which may be stored at 4 degrees C and used in the assay over a period of several months. The amount of antibody specifically bound to the cells is quantitated by the addition of 125I-labeled SpA. The sensitivity of the method was compared with two complement-dependent cytotoxicity methods (trypan blue exclusion and 51Cr release assays) and tested with two antisera to human lung cancer and one antiserum to a membrane antigen of a murine lymphoma. These comparisons indicated much greater sensitivity when compared with the trypan blue exclusion assay and equivalent sensitivity with greater dose response characteristics when compared with the 51Cr release assay.


Alveolar macrophages. I. A simple technique for the preparation of high numbers of viable alveolar macrophages from small laboratory animals. A simple technique is described for the collection of substantial numbers of alveolar macrophages by repeated in situ endobronchial lavage. Macrophage recoveries are maximized by the inclusion of the local anaesthetic lignocaine in the lavage fluids. The technique is suitable for mice, rats and guinea pigs, and yields up to 2.4, 6.7 and 25.3 X 10(6) viable macrophages per animal from these 3 species respectively. A one-step adherence procedure yields alveolar macrophages in excess of 95% purity.


Immunoregulation in infection caused by Mycobacterium tuberculosis: the presence of suppressor monocytes and the alteration of subpopulations of T lymphocytes. This study was designed to characterize qualitative and quantitative alterations, occurring before and during chemotherapy, in the mononuclear cells of patients with infections caused by Mycobacterium tuberculosis. A hemolytic plaque-forming (PFC) assay indicated that the production of antibody to sheep red blood cells by pokeweed mitogen (PWM)-stimulated lymphocytes was suppressed in treated and untreated patients as compared with that in normal adult donors (P less than 0.001). The removal of adherent cells from the suspensions of mononuclear cells significantly enhanced the responses to the PFC assay for both the untreated (P less than 0.01) and treated (P less than 0.05) patients. Mononuclear cells from patients with tuberculosis, however, did not suppress the PFC responses of allogeneic normal mononuclear cells (P greater than 0.02). Thymus-derived (T) lymphocytes were proportionally reduced in untreated subjects (P less than 0.001) but returned to normal levels after four to six weeks of therapy (P greater than 0.2). Both groups of patients had a consistent reduction in the absolute number of circulating T cells. However, untreated patients had a relative increase in the percentage of TG cells (the subpopulation of T cells with receptors for the Fc portion of IgG) (P less than 0.001) and a concomitant decrease in TM cells (the subpopulation with Fc receptors for IgM) (P less than 0.05). These alterations in the subsets of T cells were reversed after four to six weeks of therapy.


Lipopolysaccharide pseudomonas vaccine: efficacy against pulmonary infection with Pseudomonas aeruginosa. Pneumonia due to Pseudomonas aeruginosa occurs with increased frequency and high mortality in certain populations of patients. The potential of vaccination with a heptavalent lipopolysaccharide pseudomonas vaccine for specific protection of respiratory tissues from infection with Pseudomonas was evaluated with a guinea pig model of experimental pseudomonas pneumonia. Animals routinely responded to vaccination with a fourfold rise in titer of serum hemagglutinating antibody to Pseudomonas. Of 25 control animals, all but nine died after lung challenge with Pseudomonas, whereas vaccinated animals had a greater survival rate (22 of 25 animals survived; P less than 0.01). Rates of clearance of viable Pseudomonas from lung tissue were significantly greater in vaccinated animals than in controls during the first 6 hr after infection. Both gross and microscopic findings of lung tissue damage from pseudomonas pneumonia were less in vaccinated than in control animals. Thus, lipopolysaccharide pseudomonas vaccine appears to produce a local protective response in respiratory tissue against Pseudomonas.


Antibodies to Neisseria gonorrhoeae: a study of the urethral exudates of 232 men. The results of a study of the antibodies that react with Neisseria gonorrhoeae in the urethral exudates of 232 men who attended a clinic of the Department of Sexually Transmitted Diseases at Glasgow, Scotland, are presented. Of 132 men with gonorrhea, antibodies to the gonococcus were identified by use of an indirect immunofluorescent antibody test in 129 (98%): IgA antibody was found in all 129 (98%), IgG antibody in 119 (90%), and IgM antibody in 64 (49%). IgA antibody to the gonococcus was found in the secretions of only one (1%) of another 100 patients who did not have gonococcal urethritis (50 had nongonococcal urethritis and 50 had no evidence of urethritis). IgG antibody was found in 13 (26%) of the 50 men with nongonococcal urethritis and in none of the 50 men who had no evidence of urethritis. When treatment of gonorrhea was successful, the titers of IgA and IgM antibody declined rapidly and were generally undetectable within 14 days; the titers of IgG declined more slowly and could still be detected 28 days after treatment.


Pseudomonas aeruginosa bacteremia: susceptibility of 100 blood culture isolates to seven antimicrobial agents and its clinical significance. The susceptibility of 100 blood culture isolates of Pseudomonas aeruginosa observed during 4 1/2 years was tested for tobramycin, netilimicin, gentamicin, amikacin, pirbenicillin, ticarcillin and carbenicillin, singly and in combination. For aminoglycosides, the agar MICs were twofold to threefold greater than tube dilution MICs but for the penicillins they were similar. For aminoglycosides and ticarcillin, the MBCs were twofold greater than the tube dilution MICs. The MBCs were not achieved at concentrations as high as 512 micrograms/ml for 40% of the isolates for pirbenicillin and for 10% for carbenicillin. Tobramycin and pirbenicillin had the lowest MICs for the aminoglycosides and penicillins, respectively. Synergism was tested and observed between tobramycin + ticarcillin and amikacin + ticarcillin. No overall increase in resistance to gentamicin or carbenicillin was seen from 1974 to 1977. However, patients given repeated courses of gentamicin had more resistant strains. Following the administration of 1.5 mg/kg/dose of gentamicin, peak serum concentrations failed to achieve the MIC for the microorganism in 22% of the patients. The MIC was achieved in all patients receiving the same dose of tobramycin. The overall fatality rate was 67% with one third of the patients dying within 36 hr. There was no relationship of patient fatality rate and MIC for the microorganism. Although in the rapidly fatal group of all patients receiving inappropriate therapy died, the fatality rates of appropriately or inappropriately treated patients in the ultimately fatal and nonfatal groups were similar. Underlying host disease was the major determining factor in patient survival.


Molecular heterogeneity of Hageman trait (factor XII deficiency): evidence that two of 49 subjects are cross-reacting material positive (CRM+). We have studied plasmas of 49 individuals with homozygous Hageman trait from 42 kindreds, all of which contained less than 1% of the Hageman factor (factor XII) clotting activity of pooled normal plasmas. Forty-seven plasmas contained less than 1% of Hageman factor antigen. In two other, unrelated individuals with Hageman trait, nonfunctional material immunologically indistinguishable from normal Hageman factor was detected in plasma by radioimmunoassay at concentrations of 39% and 80%, respectively. These plasmas did not contain circulating anticoagulants against Hageman factor and, as in ordinary Hageman trait, displayed impaired surface-mediated plasma reactions such as fibrinolysis and kinin generation. Upon immunodiffusion against anti-Hageman factor serum, these plasmas formed a single precipitin line of complete identity with normal plasma or purified Hageman factor. Upon immunoelectrophoresis, the precipitin line had the same mobility as normal Hageman factor. Nonfunctional Hageman factor and normal Hageman factor behaved identically on a Sephadex G-150 column (apparent MW = 100,000) and on sucrose density-gradient centrifugation (4.5S). Nonfunctional Hageman factor was adsorbed to kaolin as readily as normal Hageman factor, suggesting that the binding site to negatively charged surfaces is different from functional sites. Antiserum raised against Hageman factor-like material in a CRM+ Hageman trait plasma specifically inactivated Hageman factor activity in normal plasma. The plasmas of three heterozygotes in these families contained approximately twice as much Hageman factor antigen as Hageman factor activity, whereas those of 16 heterozygotes in ordinary (CRM-) Hageman trait families contained approximately equal amounts of activity and antigen. The present study indicates that rarely homozygous Hageman trait may be CRM+ and that this defect is genetically determined.


Lysosomal hydrolases in neuronal, astroglial, and olidodendroglial enriched fractions of rabbit and beef brain. Arylsulfatases A, B, and C, beta-galactosidase, and acid phosphatase were assayed in neuronal, astroglial, and oligodendroglial fractions isolated from adult rabbit and beef brains. The specific activities of all acid hydrolases were lower in beef cells compared to rabbit cells. The lysosomal enzymes of the rabbit neuronal fraction showed 10--25 time higher activities than the oligodendroglial fraction and 5-fold higher activities than the astroglial fraction. In beef brain, the specific activities of these enzymes were similar in oligodendroglia and astrocytes but 4--10 times lower than in neurons. The low activity of arylsulfatase A and beta-galactosidase in oligodendroglial cells may suggest that the low turnover of cerebroside and sulfatide in myelin may be regulated in part by the enzymes that catalyze their degradation.


Purification of phospholipase C from Bacillus cereus by hydrophobic chromatography on palmitoyl cellulose. Phospholipase C (phosphatidylcholine choline-phosphohydrolase, EC 3.1.4.E) from Bacillus cereus (IAM-1208) was adsorbed to palmitoyl cellulose from a crude enzyme solution at pH 5--9. The adsorption was not influenced by ionic strength up to 2 M NaCl. The adsorbed enzyme was eluted almost completely by washing the cellulose with a suitable detergent, such as Triton X-100, Adekatol SO-120, Cation DT-205, or sodium deoxycholate. The enzyme was then purified by column chromatography on a palmitoylated textile (palmitoylated gauze) with an overall recovery of 91% and a 467-fold increase in specific activity over that of enzyme in the crude culture supernatant. Subsequent fractionation with acetone and chromatography on a Sephadex G-75 column separated two nearly homogeneous phospholipase C's. The enzyme adsorbed on palmitoyl cellulose was active, although its activity was about one-fourth that of free phospholipase C. Therefore, the enzyme appeared to be adsorbed to the cellulose through a hydrophobic site that was distinct from the catalytic site on the enzyme molecule.


Synthesis of DNA and lecithin in tissue culture and oestrogen receptor activity in rat mammary tumours dependent on and independent of the ovary. Dimethylbenz(alpha)anthracene (DMBA)-induced and transplanted rat mammary tumours (2 lines) were examined for oestrogen receptor activity, and for sensitivity to hormones in vivo (by ovariectomy) and in vitro (by tissue culture). In vivo, the growth of all tumours induced by the administration of DMBA in random-bred Sprague-Dawley rats was found to be dependent on the ovary, whilst in all transplanted tumours (12 TG-3 and six TG-5 lines), maintained in an inbred strain of Sprague-dawley rats, growth was found to be independent of the ovary. In vitro, the capacity for DNA synthesis in DMBA-induced tumours was better maintained after 24 h when insulin (10 microgram/ml) and corticosterone (5 microgram/ml) or insulin, corticosterone and prolactin (each 5 microgram/ml) were present in the medium (five out of 12 and eight out of 11 tumours respectively); no effect of hormones in the media was detected after 48 h. In the transplanted tumours, no effect of hormones on DNA synthesis was detected after either 24 or 48 h of culture. Synthesis of lecithin was not detectably influenced by the presence of hormones in either DMBA-induced or transplanted tumours. Oestrogen receptor concentrations were, on average, significantly higher in the DMBA-induced tumours than in either line of transplanted tumour. For 22 DMBA-induced tumours and 15 transplanted tumours, the effect of hormones in vitro ('response') was directly correlated with receptor concentration at time 0 (Spearman's rho = +0.59) and inversely correlated with the rate of DNA synthesis ('basal') at time 0 (Spearman's rho = -0.62). No single parameter or pair of parameters permitted accurate distinction between the tumour types.


The temporal stability of the Drosophila oocyte. Individual female Drosophila melanogaster were maintained without yeast for up to 18 days. Some of the females did not lay any eggs during this holding period. The females produce mature oocytes (stage 14) by day 3 and from day 5 onward the females each held about 60 mature oocytes. The nulliparous females were mated and its was shown that the first egg produced by females held up to 18 days before mating could be viable and develop into a normal, fertile adult. On day 2 each female contained about 500 oocytes in post-oogonial stages of oogenesis. The first 500 fertilized eggs were collected from females that had been held nulliparous for 7-10 days before mating. No period of significantly reduced viability was found. It is concluded that the developmental program of Drosophila eggs can be interrupted between oogenesis and fertilization for at least 15 days without loss of the ability to produce normal, fertile adult progeny.


Alloantigen-specific idiotype-bearing receptors on mouse T lymphocytes. I. Specificity characterization and genetic association with the heavy-chain IgG allotype. The present study describes the qualitative reactions of a xenogeneic anti-idiotype (Id) antiserum produced in a mouse-gamma-globulin-tolerant rabbit (5,936) against B6 anti-CBA IgG antibodies. The results showed that such an anti-Id antiserum reacts specifically against anti-H-2k antibodies and against H-2k alloantigen-activated T cells from the following pairs of congenic mice: B10 (H-2b) and B10.D2 (H-2d); and A.BY (H-2b) and A.SW (H-2s), but not against C3H.SW (H-2b) and C3H.OH (H-2o); and BALB/b (H-2b) and BALB/c (H-2d). CB 20 (BALB/c mice with the Ig-1b allotype) anti-CBA T blasts also express idiotypic determinants that react with rabbit 5,936 antiserum. Thus, positive reactions are obtained between rabbit 5,936 anti-Id antiserum and anti-H-2k IgG preparations and T blasts from mice carrying the Ig-1b or Ig-1e allotype, but not from mice carrying the Ig-1a allotype. These reactions are qualitatively independent of the H-2 genotype of the Id-producing mice. Such a finding strongly suggests that the Id-bearing receptor molecules on mouse T cells are coded for by genes that are associated with the Ig heavy-chain-linkage group and not to the mouse histocompatibility complex. Furthermore, the anti-Id antibodies studied react preferentially against anti-H-2k antibodies or T cells with specificity toward the IAk-region-associated serological specificities. Thus, genes associated with the Ig heavy-chain-linkage group seem to be structural genes for at least T-cell receptors with specificity for IA-region-coded membrane antigens.


[Radioenzymatic micromethod for the determination of UDP-glucuronic acid (author's transl)]. A new senitive and specific micromethod for determination of UDP-glucuronic acid is described Extracts from 2.5 mg of liver are incubated with twice washed guinea pig microsomes (as a source of UDP-glucuronyl transferase) and [14C]p-nitrophenol. The content of UDP-glucuronic acid is calculated from the [14C]p-nitrophenyl glucuronide/[14C]p-nitrophenol radioactivity ratio and the known amount of introduced [14C]p-nitrophenol. These values are corrected for losses of UDP-glucuronic acid by a calibration experiment, containing in addition to the aforementioned constituents, a known amount of UDP-glucuronic acid. The mean concentration of UDP-glucuronic acid in mice liver was found to be 171 mumol/kg wet weight.


The quality of medical care: a concept in search of a definition. Patient care has two components: technical and interpersonal. The quality of technical management depends on the balance of its expected benefits and risks. The quality of the interpersonal process consists in conformity to legitimate patient expectations and to social and professional norms. Since this conformity is expected to result in social and personal benefit, a unified definition of quality can be derived by including the benefits and risks of both aspects of care. When the patient's health and welfare are judged by professional criteria, and the cost of care is not considered, one has an "absolutist" definition of quality. By contrast, an "individualized" definition accepts the informed patient's valuation of the consequences of care, and includes the cost to the patient as an unwanted consequence. The "social" definition includes monetary cost even when not borne directly by the patient, may place a different valuation on patients and their interests, and pays attention to the social distribution of the cost and net benefits of care. Thus, the physician who wishes to do the best for each patient may be in conflict with what society dictates to be the best of all. The health care professions must resolve this moral dilemma.


Genetics analysis of spore germination mutants of Bacillus subtilis 168: the correlation of phenotype with map location. The isolation and characterization of 29 new germination (Ger) mutants of Bacillus subtilis 168 is described. These were classified, along with previously described mutants, into seven groups according to map location. The mutations in 26 GerA mutants mapped between cysB and thr; detailed mapping of two of these has located them very close to citG. These mutants were deficient in germination in alanine, but responded to the germinative combination of asparagine, glucose, fructose and KCl. One GerB mutant mapped on the origin-proximal side of hisA; it was normal in germination in alanine, but deficient in termination in a mixture of asparagine, glucose, fructose and KCl. Two GerC mutants were linked to lys, but were separable from a temperature-sensitive growth deficiency mapping between lys and trp. The GerC mutants had a similar germination phenotype to the GerA mutants. Three GerD mutants did not germinate in either of the above germinants or in Penassay Broth. They were located on the side of ery distal to cysA. The GerE mutant, which did not germinate in any of the three germinants, was located very close to citF and possessed an altered spore coat. The two GerF mutants were defective in germination in all three germinants and mapped on the origin proximal-side of hisA, but much closer to his than did the GerB mutant. A phosphoglycerate kinase-negative mutant altered in germination mapped between cysB and hisA (GerG). These mutants have established a minimum of seven locations important to germination, and will be useful in the development and appraisal of theories of spore germination.


Molecular characterization of a small Haemophilus influenzae plasmid specifying beta-lactamase and its relationship to R factors from Neisseria gonorrhoeae. The ampicillin-resistant Haemophilus influenzae strain Ve445 which caused purulent meningitis and septicaemia in a newborn child in Germany contained a 4.4 megadalton (Mdal) plasmid (pVe445) and produced a TEM type beta-lactamase. The transformation to ampicillin resistance of a sensitive Escherichia coli strain with isolated pVe445 DNA proved that the structural gene for the beta-lactamase resided on this plasmid genome. Molecular DNA-DNA hybridization studies and electron microscope DNA heteroduplex analysis indicated that pVe445 probably contained 38 to 41% of the ampicillin translocation DNA segment (TnA) found on R factors of enteric origin. The TnA fragment present in pVe445 most likely does not contain both of the inverted repeat sequences of TnA. DNA-DNA polynucleotide sequence studies indicated that the 4.4 Mdal plasmid pVe445 was unrelated to the 30 to 38 Mdal H. influenzae R plasmids but was closely related to the 4.1 Mdal ampicillin resistance specifying H. influenzae plasmid RSF0885 isolated in the U.S.A. The H. influenzae plasmid pVe445 shared 91% of its base sequences with the beta-lactamase specifying Neisseria gonorrhoeae plasmid pMR0360 (4.4 Mdal) and had 85% of its base sequences in common with the beta-lactamase specifying N. gonorrhoeae plasmid pMR0200 (3.2 Mdal). All of the four 3.2 to 4.4 Mdal beta-lactamase specifying R plasmids of H. influenzae and N. gonorrhoeae investigated probably have a common evolutionary origin.


Mechanisms for vitamin A transfer from blood to milk in rhesus monkeys. In order to study vitamin transport during lactation tritium labeled vitamin A, attached to serum lipoproteins or retinol-binding protein (RBP), was injected intravenously into eight Rhesus monkeys. The turnover rate of vitamin A in plasma and its appearance in milk was quantitatively and qualitatively investigated. The turnover of plasma RBP-retinol, which was somewhat faster in lactating than in non-lactating animals, exceeded that of lipoprotein-vitamin A by a factor of three. Tritium--vitamin A appeared in milk mainly as retinylesters. The fractional rate of transfer was about 60% higher for vitamin bound to RBP than for other forms of plasma vitamin A. Consequently, about 90% of the vitamin A appearing in milk will normally be derived from the retinol-RBP complex. The importance of the lipoprotein-mediated transfer of vitamin A will probably increase during a high intake of the vitamin.


The effect of protein-energy malnutrition on the development of bones in newborn rats. Collagen synthesis, 45Ca uptake, and the half-life of 45Ca in mandibles and long bones of rat pups suckled on dams fed 25 or 6% protein diets were determined. Collagen synthesis in both mandibles and long bones was impaired in the malnourished group at an early age. Protein-energy malnutrition appears to affect different developmental processes in these two bones. The principal interference with collagen synthesis in the mandible occurs when bone proline is converted into hydroxyproline. In contrast, proline uptake from the blood for deposit in bone matrix is the step of collagen synthesis mainly affected in long bone. In addition, the critical growth period of mandible was different from that of long bone. The calcium complex fraction (calcium bound to protein plus that in inorganic salts) was the main compartment affected in the malnourished group. However, the efficiency of calcification per milligram of matrix in the calcium complex fraction of the mandible and long bone was approximately the same in the control and malnourished groups, thus suggesting that accumulation of calcium occurs in parallel with the formation of bone matrix regardless of the nutritional conditions. The half-life of 45Ca in the various calcium fractions of both types of bone was 72 hours in both the control and malnourished groups except the calcium complex portion of the long bone of the control group, which was about 100 hours.


Physical and biochemical changes of the mandible and long bone in protein-energy malnourished newborn rats. The activities of alkaline and acid phosphatases, the linear dimensions and volumes of mandibles and long bones, and the level of calcitonin in serum of rat pups suckled on dams fed 25 or 6% protein diets were determined. In both mandibles and long bones, alkaline phosphatase activity corresponded to the calcification pattern, and acid phosphatase activity paralleled organic matrix formation. The calcitonin level in blood serum of the malnourished pups differed from that of controls only on day 5. The linear dimensions and volume were consistently more affected in long bones than in mandibles. These results may be explained in terms of the critical growth periods of these bones. In the mandible, the critical growth period appears to occur prenatally, whereas in the long bone it occurs postnatally, when the nutritional stress of this experiment was applied. Long bones were thus generally more affected than mandibles.


Is Fourier analysis performed by the visual system or by the visual investigator. A numerical Fourier transform was made of the pincushion grid illusion and the spectral components orthogonal to the illusory lines were isolated. Their inverse transform creates a picture of the illusion. The spatial-frequency response of cortical, simple receptive field neurons similarly filters the grid. A complete set of these neurons thus approximates a two-dimensional Fourier analyzer. One cannot conclude, however, that the brain actually uses frequency-domain information to interpret visual images.


Kinetics of biotransformation of clonazepam to its 7-amino metabolite in the monkey. The pharmacokinetic behavior of the 7-amino metabolite of clonazepam administered exogenously and formed endogenously from the parent drug was studied in a group of rhesus monkeys using constant rate intravenous infusions. Plasma levels of the 7-amino metabolite and/or clonazepam were determined with a GC-CI-MS method. The biological half-life of the 7-amino metabolite (2.2 +/- 1.0 hr) was shorter than that of clonazepam (4.9 +/- 0.2 hr). Total body clearance of the metabolite (0.83 +/- 0.16 liters/hr/kg) was larger than that of the parent drug (0.55 +/- 0.09 liters/hr/kg). The kinetics of in vivo biotransformation were described by a two-compartment model in which formation and disposition of the metabolite follow first-order processes. The fraction of a dose of clonazepam appearing in the systemic circulation as 7-amino metabolite was 0.70 +/- 0.30. This value may underestimate the actual fraction formed, if the metabolite is susceptible to first-pass metabolism following in situ formation.


Possibility for error in FDA diffusion assays. Computational procedures specified for the FDA single-dose diffusion assay for antibiotics may cause substantial error in estimated sample potency. An unrecognized mistake in reference solution concentration is the source of error. It is caused by correcting responses from standard and sample plates differently. The error can be avoided by correcting both standard and sample responses to the observed reference response.


Familial band-shaped keratopathy.

Familial band-shaped keratopathy. A brother and sister out of a consanguinous family of four siblings are presented as prototypes of primary band-shaped keratopathy. The disease manifested sever progressive changes of secondary nature over two years of follow-up. Histology and treatment are described.


Acetazolamide binding to two carbonic anhydrase isoenzymes in human erythrocytes. Acetazolamide binding to high activity and low activity carbonic anhydrase isoenzymes in red blood cells was studied. Inhibitory constants of 0.041 and 2.72 microM and maximum binding capacities of 17.2 and 155 microM, respectively, were found.


Urate excretion: drug interactions.

Urate excretion: drug interactions. A derivative of probenecid, 2-nitroprobenecid, was studied in chimpanzees and Cebus monkeys. The uricosuria induced by the drug could be diminished by the infusion of p-aminohippurate (chimpanzee) or hippurate (monkey). Both hippurates inhibited the secretion of the drug and it is likely that the diminished response was the result of decreased access of 2-nitroprobenecid to its site of action. In contrast, pyrazinoate diminished the response to 2-nitroprobenecid without disturbing its renal disposition (both species). This action of pyrazinoate is attributed to its ability to inhibit the secretory flux of urate. The effect of pyrazinoate is diminished at high levels of 2-nitroprobenecid, i.e., it appears as if pyrazinoate causes a shift to the right of the concentration-response curve of 2-nitroprobenecid. A mathematical model is developed which seems to explain this apparent shift in the concentration-response curve. This model requires that the transepithelial fluxes for urate be very large. In the chimpanzee the action of salicylate resembles that of pyrazinoate but it is less prominent.


Behavioral effects of self-administered cocaine: responding maintained alternately by cocaine and electric shock in squirrel monkeys. Squirrel monkeys responded under a fixed-interval schedule of intravenous cocaine injection that alternated with a fixed-interval schedule of either presentation of electric shock or termination of a stimulus associated with electric shock. As the dose of cocaine was increased from 10 to 1000 microgram/kg/injection, responding maintained by cocaine injection or alternately by electric shock first increased and then decreased. The lowest doses of cocaine that reliably maintained self-administration often increased responding maintained by electric shock; the highest doses of cocaine that continued to maintain self-administration often decreased responding maintained by electric shock. When saline was substituted for cocaine, responding that had previously been maintained by cocaine injection occurred irregularly and at very low rates, whereas rates and patterns of responding maintained by electric shock were characteristic of fixed-interval schedules. When the fixed-interval schedule of cocaine injection was replaced by intravenous injections that occurred without regard to antecedent responding, the effects of cocaine on responding maintained by electric shock were found to be independent of the way in which cocaine was administered.


Pulpal response to an epimine plastic.

Pulpal response to an epimine plastic. Pulpal reactions to three dental materials, Scutan, a self-curing resin, and zinc oxide-eugenol cement, were comparable. The pulpal reactions to Scutan appeared to be milder than those to a self-curing resin or to zinc oxide-eugenol cement.


Dietary protein and human pregnancy performance. Low birth weight is an important predictor of neonatal mortality and morbidity. Women of low socioeconomic classes give birth to disproportionate numbers of low-birth-weight infants and eat poorer diets than those of higher classes. Although maternal weight gain in pregnancy is positively associated with birth weight, and although animal studies demonstrate the important effects of protein restricti-n on reproductive performance, the significance or lack thereof of diet in general and of protein intake in particular in pregnant women in generally well-nourished populations has not been established. The conflicting data on human pregnancy performance and diet are critically reviewed.


Multivariate analysis and quantitative structure-activity relationships. Inhibition of dihydrofolate reductase and thymidylate synthetase by quinazolines. Quantitative structure-activity relationships (QSAR) have been established for the inhibition of dihydrofolate reductase and thymidylate synthetase by 2,4-diaminoquinazoline-glutamic acid analogues. For dihydrofolate reductase from both human acute lymphocytic leukemia cells and murine L1210R cells, QSAR's obtained with 50 quinazolines were similar. On the other hand, for the inhibition of thymidylate synthetase from murine L1210S cells and from Lactobacillus casei, QSAR's formulated on the basis of data measured with 33 compounds were different, indicating that the two enzymes are dissimilar. The use of multivariate statistics including cluster analysis, factor analysis, and discriminant analysis is shown to facilitate the formulation of a satisfactory correlation equation. The procedure is demonstrated by the development of QSAR for the inhibition of thymidylate synthetase.


Synthesis of 5-selenium-substituted uracil derivatives. Inhibition of thymidylate synthetase by 5-hydroseleno-2'-deoxyuridylate. 5-Selenium-substituted derivatives (diselenides) or uracil, 2'-deoxyuridine, and 2'-deoxyuridylic acid were synthesized via the addition of methyl hypobromite to the 5,6 double bond, followed by reaction of the adducts with sodium diselenide. The physical and chemical properties of these compounds (including their facile reduction by dithiothreitol and rapid reoxidation) were similar to those of the corresponding 5-sulfur analogues. 5-Hydroseleno-2'-deoxyuridylic acid was as potent as 5-mercapto-2'-deoxyuridylate in inhibiting thymidylate synthetase from L. casei (ki approximately 6 X 10(-8) M) but the nucleoside III was considerably less active than 5-mercapto-2'-deoxyuridine in the inhibition of growth of the leukemia L1210 cell in culture.


Synthesis of some 4-substituted 8-amino-6-methoxyquinolines as potential antimalarials. The 4-vinyl, 4-ethyl, and three 4-[beta-(arylthio)ethyl] derivatives of primaquine and other 8-aminoquinoline antimalarial agents were prepared for antimalarial evaluation. 8-[(4'-Amino-1'-methylbutyl)amino]-4-ethyl-6-methoxyquinoline (4-ethylprimaquine), which showed activity approximately equal to that of primaquine against Plasmodia cynomolgi in Rhesus monkey, was the most active of the compounds tested. 4-Ethylprimaquine was also less toxic than primaquine, as measured in the Rane mouse screen.


Slow onset anti-rheumatic drugs in rheumatoid arthritis: could the presence of antinuclear antibody influence the therapeutic results? The therapeutic value of sodium aurothiomalate, D-penicillamine and levamisole was evaluated in three comparable groups of 20 rheumatoid arthritis (RA) patients. There was no intergroup difference after a 3-month follow-up and all were significantly improved (p less than 0.001). To verify if, in these patients, the presence of antinuclear antibodies (ANA) had influenced the therapeutic results, each group was retrospectively subdivided according to the ANA status. To start with, all the sub-groups were statistically comparable on the basis of measures of disease activity. The D-penicillamine group could not be analyzed. In the gold treated group, the ANA negative patients were more improved than the ANA positive (p = 0.03), and very significantly more than the levamisole-treated ANA-negative patients (p = 0.005). The ANA negative patients taking levamisole had less pain relief (p = 0.01) and showed a tendency for less overall improvement (p = 0.15) than the ANA positive patients. This preliminary study supports the idea that systematic ANA testing in RA may be of practical and theoretical value.


Synthesis and pharmacological evaluation of cis-3,4,4a,9a-tetrahydro-1H-pyrano[3,4-b]benzofuran-1-ones. Tricyclic analogues related to the antilipidemic drug clofibrate. The chemistry and pharmacology of two delta-lactones, cis-6-chloro-9a-methyl-3,4,4a,9a-tetrahydro-1H-pyrano[3,4-b]benzofuran-1-one (2) and the 9a-demethyl analogue 3, are reported. Lactones were prepared from dihydrobenzofuran precursors possessing geometrical configurations confirmed both by synthesis and 1H NMR spectroscopy. All cis-dihydrobenzofurans exhibited Jvic = 9.0-10.8 Hz, whereas their trans isomers exhibited Jvic = 5.0--6.0 Hz in agreement with predictions based on the Karplus equation. The pharmacological profiles for 2 and 3 were compared to that of clofibrate (1) in normal male Sprague-Dawley rats. Using equimolar doses (0.4 mmol/kg, po, twice daily for 7 days), 1 exhibited both anticholesterolemic and antitriglyceridemic activity, lactone 2 exhibited only antitriglyceridemic activity, and 3 was inactive as an antilipidemic agent. No correlation was observed for inhibition of hepatic HMG-CoA reductase activity and serum cholesterol lowering.


Synthesis and biological activity of 8-oxadihydropteridines. A series of 6-substituted and 6,7-disubstituted pyrimido[4,5-b][1,4]oxazines (8-oxadihydropteridines) was synthesized through the condensation of an alpha-halo ketone and 2,5-diamino-4,6-pyrimidinediol. The resulting 8-oxadihydropteridines were assayed as potential antifolates in a dihydrofolate reductase enzyme system. The 2-amino-4-hydroxyoxa-dihydropteridines were found to possess greater biological activity than the corresponding 2,4-diamino compounds. The pteroic acid homeostere 2-amino-4-hydroxy-6-phenethyl-8-oxadihydropteridine was the most potent of the compounds tested.


Detection of gonococcal antigens in urine by radioimmunoassay. A method of detecting gonococcal antigens by solid-phase radioimmunoassay with radioactively labelled antibody is described. A specificity test has been developed that enables this method to be used to detect gonococcal antigens in urine sediments. When sediments from samples of urine from male patients with gonorrhoea were tested, 31 (74%) of 42 gave positive results, clearly distinguishing them from sediments from urine samples from men with non-specific urethritis, none of which was positive. Ten of 14 urine sediments from urine samples from women with gonorrhoea gave positive results, as did 3 of 18 sediments from urine samples from women patients without gonorrhoea. These experiments demonstrate that gonococcal antigens can be detected in urine by radioimmunoassay; the method could be useful in diagnosis if, after refinement, its sensitivity and specificity were to be increased.


Inhibitors in urine of radioimmunoassay for the detection of gonococcal antigens. Several substances in urine were found to inhibit the radioimmunoassay of added gonococcal antigens. The supernatants of two-thirds of urine samples from male patients with either gonorrhoea or non-specific urethritis (NSU) were inhibitory. The inhibition caused by many, but not all, samples was reduced or completely abolished by the addition of soybean trypsin inhibitor (STI); STI-sensitive inhibition is thought to be due to proteolytic enzymes, probably from pus cells. Their inhibitory effect was shown to be due to their action on gonoccocal antigens and not on antibodies in the assay system. Some supernatants contained other inhibitors unaffected by STI; some of these were dialysable and others were not. Sediments from the urine of patients with NSU or gonorrhoea were often strongly inhibitory, but treatment with STI annulled all but very slight inhibition. STI-treated sediments could, therefore, be used in an assay designed to detect gonococcal antigens.


Infection of artificial air pouches in the connective tissue of mice with Neisseria gonorrhoeae. Artificial air pouches in the connective tissue of mice were evaluated as a means of studying Neisseria gonorrhoeae infections. Animals inoculated with type-1 N. gonorrhoeae cells developed an infection characterised by infiltration of polymorphonuclear leucocytes. Viable cocci could be recovered from the air pouches for up to 10 days after infection and intracellular cocci were evident in electronmicrographs within connective-tissue fibroblasts for at least 35 days, indicating that a persistent infection had been established. The mouse air pouch should be of value in the study of gonococcal and other infections.


Urinary chorionic gonadotropin levels in pregnant golden lion tamarins. Preliminary observations. We have established the interval over which urinary chorionic gonadotropin can be detected by a radioimmunoassay during pregnancy in the golden lion tamarin. Preliminary findings indicate the potential value of this radioimmunoassay system for (1) diagnosis of pregnancy at about four weeks after fertilization; (2) estimation of the expected time of delivery; and (3) identification of individual monkeys having an apparent high risk of spontaneous abortion.


Lung lecithin synthesis in primates as related to respiratory distress syndrome. Lecithin is synthesized de novo in the lung by two biochemical pathways, choline incorporation and phosphatidylethanolamine methylation. These studies in the Macaca mulatta fetus and neonate have demonstrated the relative contributions of the two pathways and the timing in monkey gestation of increased pulmonary lecithin production.


Cellular and shunt conductances of toad bladder epithelium. Toad urinary bladders were mounted in Ussing-type chambers and volt-age-clamped. At nonzero voltages only, small fluctuations in current, delta I, and therefore in tissue conductance, delta Gt, were detected. These fluctuations were caused by the smooth muscle of the underlying tissue which could be monitored continuously and simultaneously with the current, I. Inhibition of the smooth muscle contraction with verapamil (2 X 10(-5) M) abolished the fluctuations in I and Gt. Amiloride (10(-4) M) had no significant effect on the magnitude of delta Gt, oxytocin increased Gt without affecting delta Gt, and mucosal hypertonicity produced by mannitol increased delta Gt. These results are consistent with the hypothesis that two parallel pathways exist for passive current flow across the toad urinary bladder: one, the cellular pathway, was not affected by smooth muscle activity; the other, the paracellular pathway, was the route whose conductance was altered by the action of the smooth muscle. Thus the relationship between the cellular and shunt conductances of the epithelium of the toad urinary bladder, under a variety of conditions, can be investigated by utilizing the effects of the movement of the smooth muscle.


Fine structural comparison of the antennal nerve in the homeotic mutant Antennapedia with the wild-type antennal and second leg nerves of Drosophila melanogaster. In D. melanogaster the cross-sectioned nerve of the leg-like antenna in the homeotic mutant Antennapedia was ultrastructurally compared with the nerves of the morphologically related second leg and the wild-type antenna. The nerves of the normal antenna and the second leg differ from one another in both the numbers and arrangement of axons. According to these criteria the nerve of the homeotic appendage was structurally identified as a leg nerve. Most of the antennal nerves studied showed a consistent grouping of axons in the profile. This suggests that the assemblage of the axons does not occur randomly, but in an ordered fashion.


Transurethral treatment of urethral diverticula in women. Six women with urethral diverticulitis and a history of having had previous operations for diverticula were subjected to transurethral diverticulotomy with a knife electrode. Each patient had multiple diverticula, some compartmented, located in the mid or most proximal segments of the urethra. All patients have been relieved of the symptoms and infection during the postoperative period, varying from 1 1/2 to 7 years.


The vesicoureteral hiatus and paraureteral diverticula. Two ureteral sheaths and the vesical musculature combine to form a watertight ureterovesical junction but the precise anatomy and function of each component are still somewhat contentious. The morphology was studied in postmortem specimens of children with and without paraureteral diverticula and urethral obstruction, and function by deductive reasoning from radiographic and surgical observations in living children. Waldeyer's fascia (the superficial sheath) of the ureter was found to seal the potential space between the tunnel wall and the ureter, and deficiencies were associated with hiatal hernias. The deep sheath provided anchorage of the ureter to the trigone and through the attachments of the superficial sheath to the bladder wall. Both sheaths and the tunnel muscles could be identified clearly and dissected precisely at operations involving the ureterovesical junction to facilitate the surgical procedures.


The hydrodynamics of pyelorenal reflux.

The hydrodynamics of pyelorenal reflux. Our study was done to determine the hydrodynamics of pyelorenal reflux. It is considered important in the pathophysiology of chronic pyelonephritis. An animal model of pyelorenal reflux was studied. The model seems to approximate closely the findings in man, both in the pressure required and the types of pyelorenal reflux observed.


A longitudinal study of patients with superficial bladder carcinoma successfully treated with weekly intravesical thio-tepa. Herein is reported further results of a prospective clinical investigation to determine the effect of weekly intravesical bladder instillation of thio-tepa in the treatment of superficial bladder cancer. Patients with superficial bladder carcinoma were treated according to 2 protocols. The first protocol consisted of patients with persistent tumor who were treated with weekly thio-tepa for 8 weeks. Of the 33 patients 18 responded to this therapy, and they and 24 other patients who had been rendered free of tumor by transurethral resection alone were assigned to the second protocol in which patients either were treated with monthly instillations of thio-tepa or they were observed every 3 months in a prescribed fashion. Monthly thio-tepa instillations had no significant effect in lowering the recurrence rate in either group. However, in the patients who had responded to weekly thio-tepa benefit was noted in terms of 1) fewer recurrences, with 8 of 18 (44 per cent) previously pre-treated patients having a recurrence versus 19 of 24 patients (79 per cent) previously untreated, 2) delay in tumor recurrence with an interval free of tumor of 15.1 months in pre-treated patients versus 4.3 months in the untreated group and 3) diminished frequency of new tumors (0.33 recurrences yearly) in comparison to the untreated group (1.78 recurrences yearly). The remaining patients are free of tumors at 15.7 months average followup.


Steroid hormone receptors in the prostate. Specific receptors for dihydrotestosterone and estradiol-17-beta have been identified in cytosols of the human and baboon prostate. Binding of radioactive estradiol-17-beta to the 0.4 M potassium chloride extractable component of human prostate nuclei also was demonstrated. Cyproterone acetate and diethylstilbestrol, agents of known high affinity for dihydrotestosterone and estradiol-17-beta receptors, respectively, did not bind significantly to sex hormone binding globulin and, therefore, were useful as competitors in distinguishing binding of dihydrotestosterone and estradiol-17-beta to sex hormone binding globulin and to their specific receptors. Displacement of [3H]-estradiol-17-beta binding by diethylstilbestrol in cytosols of 11 needle biopsy specimens (mean equals 16.8 mg.) from prostatic cancer patients was analyzed. These preliminary data indicated a trend towards greater competition by diethylstilbestrol for high affinity binding sites in differentiated tumor specimens from men who were not receiving estrogen therapy. Objective and subjective responses to hormone therapy were recorded in these patients, whereas the disease in those men with low displacement assay values progressed.


Sarcocystis in free-ranging herbivores on the National Bison Range. Heart, esophagus, diaphragm and skeletal muscle obtained from various herbivores on the National Bison Range were examined grossly for Sarcocystis. Sarcocystis was found in 81, 50, 50, and 13% of the mule deer, (Odocoileus hemionus), white-tailed deer (O. virginianus), elk (Cervus elaphus), and bison (Bison bison), respectively.


Acute hemodynamic effects of intravenous fat emulsion in dogs. An intravenous infusion of Intralipid-10% was observed to exert a negative inotropic effect on left ventricular performance in a canine isovolumetric left heart preparation. There was no effect on diastolic compliance, however. Intravenous fat emulsion also produced significant decreases in systemic vascular resistance. The mechanism of these actions has not been elucidated, but it is postulated that free fatty acid (FFA) components or their metabolites directly affect the contractile properties of both myocardium and smooth muscle. These results suggest that until suitable clinical studies can be obtained, caution should be exercised in administering intravenous fat emulsions, particularly at maximum rates of infusion or in conjunction with sodium heparin in patients with known cardiac dysfunction.


Exerience with the Broviac catheter for prolonged parenteral alimentation. Home hyperalimentation is now recognized as a technique which allows patients with severe short bowel syndrome or inflammatory bowel disease to return to a near normal life style. The success of this program is dependent on the longterm use of a catheter through which intravenous fluids are infused. In the past 20 months, we have inserted 32 catheters into 22 patients for purposes of home parenteral nutrition. In a 1 to 20-month follow-up, the average duration of catheter insertion was 6 months, the longest has been 19 months in 2 patients. One patient with superior vena cava thrombosis has had a catheter inserted via a femoral vein which has been functioning well for 5 months. Thirteen catheters have been removed: 3 for obstruction, 2 for sepsis, 1 due to breakage of the catheter, 4 for slippage (3 were pulled out by the patient, and 1 was removed because of inability to psychologically accept the presence of the catheter). The removal of 6 of these 13 catheters was necessitated by breaks in the proper techniques of catheter care, which include daily dressing changes and heparinization of the catheter at least once daily. Techniques of catheter insertion and catheter care will be presented


Permanent total parenteral nutrition: psychological and social responses of the early stages. Permanent Total Parenteral Nutrition (TPN) is a life-saving but complicated procedure which has profound effects upon the lives of patients and their families, but there is a dearth of information on the the psychosocial consequences of this unique form of therapy. The authors worked with 19 consecutive TPN patients in hospital and after discharge and observed their reactions. It was found that the earliest stages were the most difficult, with anxiety, depression, fear, and negative body image predictable and universal experiences. Major adjustment problems centered around the loss of the basic function, eating. This artificial form of feeding forced multiple alterations in the patients' life styles. Their ability to cope with this intrusive procedure was related to the level of restitution of physical health, ego strength, and the family and hospital support systems. If, in addition to being a life-sustaining procedure, TPN is to restore the psychological stability of patients, all team members must be aware of the psychosocial factors involved.


Subjective distresses of nasogastric tube feeding. Health care professionals assume that tube feeding is an unpleasant, distressing experience for patients, which is only partially substantiated by experience. Thirty patients were interviewed via a tube feeding and hospital experience checklist (a 47-item interview schedule). Common experiences were operationally defined as those felt by at least 50%; subjectively distressful experiences were those identified by patients as causing distress. The most common and most distressful experiences of nasogastric tube feeding were: sensory irritations and sensory deprivation. The psychosensory irritation experiences were: thirst, sore nose or throat, dry mouth, runny nose, a tube in the nose, taking food through a tube, breathing through the mouth, breathing with a tube in the nose, taking food in a treatment type container, and taking food with a different texture and smell than usual. The psychosensory deprivation experiences were: an unsatisfied appetite for certain foods, deprivation of tasting, chewing, swallowing food, and drinking liquids, limited mobility, and deprivation of regular food. Except for burping, gastrointestinal symptoms were not common though they were usually distressful. This information has been used to develop teaching programs which are being tested for effectiveness in reducing distress associated with nasogastric tube feeding.


Evolution of the technique of home parenteral nutrition. Experience with use of the artificial kidney in the home led to the concept of self-infusion of parenteral nutrients at home. Originally called an artificial gut, the term has been changed to home parenteral nutrition. The original method proposed for circulatory access, a side-arm on an A-V shunt, failed and forced the development of a right atrial catheter which proved to be both safe and longlasting. A safe and rapid self-mix system of nutrient preparation was developed which made the patient independent of the hospital pharmacy. A wearable infusion device proved workable but was abandoned because it was unnecessary and greatly interfered with patient rehabilitation. A portable infusion system has been developed which facilitates patient mobility during infusions as well as patient travel.


Computer optimization of enteral hyperalimentation. A computer program has been developed to allow the generation of written orders for the logical progression of enteral hyperalimentation by the technique of continuous nasogastric infusion. Data required for entry include name, age, sex, height, usual and current weights, degree of stress, and if indicated, restrictions of nitrogen, fluids, sodium and potassium. A specific formulation may be requested, or the computer will pick a single nutrient solution or combination of two solutions that will best meet the requested constraints. Output includes entered data with English and Metric interconversion, surface area, and estimates of basal energy expenditure, protein wastage, protein and caloric requirements. If requested, daily orders are written to include a reasonable progression of infusion rates and concentrations of the solutions(s). Daily values are printed for the total amounts to be infused of fluid, calories, protein, sodium, potassium, and mOsm. The programs have been demonstrated to run in either on-line or batch mode. The system is easily accessible by physician, dietician, nurse, or other interested professionals.


Total parenteral nutrition solution preparation utilizing amino acid sources with and without pre-added electrolytes: a time and cost comparison. A comparison study of the time and cost of preparation of total parenteral nutrition solutions using a crystalline amino acid source with pre-added electrolytes and an amino acid source without electrolytes is presented. Four pharmacists and 4 technicians each prepared 4 solutions, utilizing each of the two amino acid sources. Both time of preparation and time of checking were measured. Utilizing list prices as acquisition costs for ingredients and the average salary for pharmacists and technicians at Medical University Hospital to determine the labor ocst, the average cost of preparing each solution was determined. The results of this study demonstrated that a potential savings of 10.3% and 9.9% was possible for pharmacist-prepared and technician-prepared solutions, respectively, when amino acid solutions containing pre-added electrolytes are utilized. The authors concluded that the use of crystalline amino acid solutions with pre-added electrolytes could offer substantial savings of labor and money for the hospital pharmacy. These solutions could also represent a significant cost savings to home-prepared parenteral nutrition formulas.


Effect of nutritional status and 5-fluorouracil on protein synthesis in parenterally alimented LEW/Mai rats. LEW/Mal rats bearing transplantable adenocarcinomas were maintained parenterally for 4 days on 1) a regimen adequate in amino acids and glucose and 2) severely hypocaloric glucose. Rats from both groups were given 17.5 mg 5-fluorouracil (FUra)/kg/day as a continuous infusion for 3 days. Cumulative nitrogen balance, fractional tissue protein synthesis rates, and liver and muscle distribution of FUra and its metabolites were determined. Results were compared to those found with a series of control rats that were not treated with FUra. No changes attributable to FUra were found in the starved rats (1.25 g glucose/day). In the fed rats (15 g glucose plus 2.5 g amino acids/day), FUra decreased the liver and diaphragm fractional protein synthesis rates and the nitrogen retention.


Inhibition of phorbol ester-induced tumor promotion in mice by vitamin A analog and anti-inflammatory steroid. The effects of a vitamin A analog, TMMP ethyl retinoate [or ethyl-9-(4-methoxy-2,3,6-trimethylphenyl)-3,7-dimethyl-trans-2,4,6,8-nonatetraenoate] (abbreviated Ro 10-9359), and an anti-inflammatory steroid, fluocinolone acetonide (or 6 alpha, 9 alpha-difluoro-11 beta, 16 alpha, 17,21-tetrahydroxypregna-1,4-diene-3,20-dione cyclic 16,17-acetal) (abbreviated FA), given alone or together were studied in a two-stage carcinogensis system. The phorbol ester 12-O-tetradecanoylphorbol-13-acetate (TPA) was used as the tumor promoter in a 7,12-dimethylbenz[a]anthracene (DMBA)-initiated mouse skin system. Two stocks of female mice, CD-1 and Sencar, which differ in their degrees of sensitivity to skin carcinogenesis, were used. A dose-dependent inhibition of carcinogenic expression, as determined by a decreased number of papillomas per animal, was observed in each mouse stock with the use of both FA and Ro 10-9359 when given alone. When FA and Ro 10-9359 were given together, an enhanced effect on the lowering of tumor incidence was noted. FA effectively inhibited tumor formation in the sensitive mouse stock even when the steroid was given 1 day prior to TPA treatment under conditions of unusually high doses of initiator (DMBA) and/or promoter (TPA). These results suggest that both anti-inflammatory steroids and retinoids inhibit tumor promotion and can be effectively used as a combination regimen for increased chemopreventive response.


[Macular changes due to corticosteroids (author's transl)]. After fives years administration of high doses of corticosteroids, an nine-year-old girl developed a Cushing's syndrome with osteoporosis. Striate and circular pigmental fissures appeared in the macula of both eyes with opening of the circle to papilla.


[Diabetic ketoacidosis and hyperosmolar diabetic coma in childhood. Low-dose continuous intravenous infusion of insulin (author's transl)]. Continuous intravenous infusion of low doses of insulin has been successfully used since 1972 in the treatment of "diabetic coma". The achieved levels of plasma insulin satisfy the transport of glucose and the inhibition of lipolysis. We are to report upon 8 children (mean age: 8.5 years), 6 with diabetic ketoacidosis and 2 with hyperosmolar diabetic coma. Blood sugar levels of 300 mg/dl or less were reached after averagely 8 hours of therapy and an average consumption of 0.8 U insulin/kg. Sodium and potassium levels, osmolality and acid base parameters for the first 24 hours are described. Low-dose continuous intravenous insulin infusion was effective, simple and safe in all cases. The presently recommended dosage of 0.1 insulin/kg x hour is to be used flexibly (range: 0.05--0.2 U/kg x hour). The administration of bicarbonate should be cautiously used for patients with severe acidosis. Infusion of hypotonic solutions as part of the treatment of the hyperosmolar diabetic coma can be dangerous. A new therapeutic regime based on our results is proposed.


The effectiveness of non-physicians as providers of family planning services. Population growth and advances in contraceptive technology are discussed in relation to changes in birth control attitudes and practices and the expansion of public family planning programs. The literature describing training, utilization, and effectiveness of non-physicians in providing family planning services is reviewed. Studies comparing physician and non-physician provision of oral contraceptives and IUD insertions are discussed. On the basis of extensive supporting data, the author concludes that many functions which formerly were in the physician's province are as safely and perhaps more appropriately performed by persons with less medical sophistication. Recommendations are made regarding the present and future role of nurses as primary care providers in family planning.


Comparative normal levels of serum triiodothyronine and thyroxine in nonhuman primates. Normative values were obtained for triiodothyronine and thyroxine from four species of Old World primate (chimpanzees, rhesus monkeys, African green monkeys and talopoin monkeys) and a single species of New World primate (squirrel monkeys) represented by two subspecies, Colombian and Bolivian. The Bolivian squirrel monkeys exhibited the lowest values for both triiodothyronine and thyroxine. Male talapoins had the highest levels of thyroxine. Significant differences were found in levels of triiodothyronine and thyroxine between males and females of the same species and between the two subspecies of squirrel monkeys. Triiodothyronine:thryroxine ratios were consistently lower in the males of all species examined.


Baseline blood chemistry determinations in the squirrel monkey (SAimiri sciureus). Sera from 129 squirrel monkeys, Saimiri sciureus, were analyzed for 15 chemical constituents. The values obtained were then analyzed for statistical significance causing the following sets of variables: (1) colony-bred versus noncolony-bred, (2) karyotype (3) vendor, (4) sex and (5) dietary iodine supplementation versus nonsupplementation. Calcium, inorganic phosphorous, albumin, uric acid, blood urea nitrogen, glucose, alkaline phosphatase and potassium were high in colony-bred animals. Cholesterol, total protein and chloride were lower in colony-bred animals than in noncolony-bred animals. No differences were seen in total bilirubin, lactic dehydrogenase, serum glutamic oxaloacetic transaminase and sodium. When the noncolony-bred animals were separated by karyotype, total protein was higher and chloride was lower between animals from Peru versus from Guyana. Colombian animals had total protein values lower than Peruvian and lactic dehydrogenase values higher than Peruvian. Colony-bred Peruvian monkeys had serum glutamic oxaloacetic transaminase values higher than colony-bred Colombian monkeys. No differences were observed between monkeys from different vendors. Chemical constituents higher between noncolony-bred males and females were calcium and alkaline phosphatase. There were no differences observed for colony-bred males and females. Dietary iodine supplementation appeared to increase both total bilirubin and calcium.


A comparison of bacterial flora isolated by transtracheal aspiration and pharyngeal swabs in Macaca fascicularis. The pulmonary flora of 30 monkeys (Macaca fascicularis) was sampled by the transtracheal aspiration technique and the pharyngeal swab method, and the results were compared. The transtracheal aspiration technique yielded lower numbers of bacteria in both aerobic and anaerobic cultures. The bacteria isolated by transtracheal aspiration were predominately pure culture, thereby lowering the possibility of contamination from commensal flora. Bordetella bronchiseptica was isolated from 23.3% of the monkeys by transtracheal aspiration, but this organism was not isolated when samples were collected with pharyngeal swabs.


Immobilization of a chronic intravenous catheter in the saphenous vein of African green and rhesus monkeys. Long-term immobilization of intravenous catheters in the saphenous vein of nonhuman primates was accomplished through the application of a lightweight fiberglass tape casting system developed for human orthopedic use. The advantages of this technique are that it (a) permits successful retention of superficial vein catheters, (b) eliminates the need for deep vessel surgical procedures when only blood collection or perfusion protocols are being implemented and (c) permits repeated use of a single preparation without maintaining the animal under rigid restraint.


Nasogastric intubation technique for bile sampling in the baboon (Papio ursinus). A duodenal tube was introduced into the duodenum of the fasted baboon via the nasal passage. After the application of vacuum for several minutes, the baboon received an intravenous injection of pancreozymin and cholecystokinin which caused contraction of the gall bladder. Aspiration of the bile sample was carried out via the duodenal tube.


Clinical description of tetanus in squirrel monkeys (Saimiri sciureus). Nineteen cases of clinical tetanus developed in Bolivian squirrel monkeys (Saimiri sciureus) which were housed in outdoor corrals with soil-based floors. The disease was initially characterized by stiffness in gait followed by extensor rigidity, trismus and opisthotonus. Eleven of the 19 monkeys (58%) had evidence of external wounds. The case fatality rate was 100%. Tetanus accounted for 12% of adult female and 19% of adult male mortalities in the colony. Immunization with tetanus toxoid was effective in reducing the incidence of tetanus.


Glomerular basement membrane thickness following islet transplantation in the diabetic rat. Glomerular basement membrane (GBM) thickness was measured in diabetic rats prior to and following islet transplantation. Over the course of the experiment (from 7 to 13 months of diabetes) GBM thickness in diabetic animals exceeded that of littermate controls. After 7 months of diabetes a group of animals received successful intraportal transplants of neonatal pancreatic tissue. GBM thickness at 2 and 6 months following islet transplantation matched the thickness in nontransplanted diabetic rats and exceeded that in control animals. Failure to reverse GBM thickening in diabetic rats following islet transplantation may be due to very slow rates of GBM tunover in the rat. Previous work has demonstrated normalization of urinary albumin excretion after islet transplantation, suggesting that GBM thickening, per se, is not a significant factor causing albuminuria in rats with longstanding diabetes.


Achalasia of the esophagus associated with Hodgkin disease. Esophageal achalasia has not been reported in the literature as a complication of Hodgkin disease. Involvement of the esophagus is rare but when present, consists mostly of bleeding, ulceration or diverticuli. A case is reported in a fifty-one year old female with achalasia of the distal third of the esophagus associated with Hodgkin disease, Stage II B.


Quantitative analysis of mating behavior in aging male Drosophila melanogaster. Dynamic changes in quantitative aspects of mating behavior of the male fruit fly as its life unfolds, from eclosion through maturity (peak performance) and "physiological death" (loss of fertility followed by complete loss of ability to mate), towards actual death, have been identified in this work by observations and measurements on 28 male fruit flies of the Oregon R strain studied individually. At weekly sessions from the first day of their imaginal life until their natural death, each fly was given the opportunity to mate with up to three virgin females during a one-hour period. Length of the latency period of each accomplished mating and duration of copulation were recorded. After mating the females were allowed to lay eggs for 24 hours and the number of offspring was counted 26 days later. The period between 1 and 4 weeks of age is characterized by peak and fairly constant performance: multiple matings, short latencies, long durations of copulation, and high degree of fertility (number of offspring); then a decline sets in, in some measures slower than in others, as the flies age. Large intra- and inter-individual variabilities were, however, found which obscure possible correlations between individual measures of mating ability and length of life. At the individual level, a preliminary analysis showed a good correlation (r = 0.80 and 0.79) between life span and week of last mating (onset of impotence) or week of last fertile mating (onset of sterility). At the population level it was found that a number of measures, i.e. number of remaining maters at each age, number of remaining fertile maters and total number of matings, had an age-course similar to survivorship but anticipated it by 4--6 weeks. Other measures, such as number of multiple matings and number of offspring declined with age faster than survivorship.


[Two cases of meningitis due to Listeria monocytogenes (author's transl)]. Two cases of meningitis due to Listeria monocytogenes in a 73-year-old man and a 77-year-old woman are described. Both patients were admitted to an Emergency Department in acute state, probably caused by cerebral stroke. Neither presented clinical symptoms of meningitis. No other concomitant conditions which might weaken the patient's general state were known to be present. The first patient died after 16 hours, the second after 5. The analysis of the cerebrospinal fluid gave the following information: Case 1: 1,500 cells, 80 percent of which were polynuclear neutrophils; Pandy's reaction was positive; albumin 1.5 g/l and glucose 0.65 g/l. Case 2: 197 cells/mm3, 90 percent of which were polynuclear neutrophils; Pandy's reaction was positive; albumin and glucose were 0.60 and 0.10 g/l respectively. Samples of the cerebrospinal fluid were cultured in various media and pure cultures of Listeria monocytogenes, subtype 4b, were isolated. The source of the infection could not be determined in either of the two cases.


Serum alpha-lipoprotein responses to variations in dietary cholesterol, protein and carbohydrate in different non-human primate species. Serum alpha-lipoprotein responses to variations in dietary cholesterol, protein, and carbohydrate were studied in different nonhuman primate species. Chimpanzee, rhesus, green, patas, squirrel and spider monkeys all showed significant interspecies differences in serum total cholesterol responses to 1.84 mg/kcal exogenous cholesterol. Dietary cholesterol significantly increased the alpha-lipoprotein cholesterol in all species except rhesus and chimpanzee. Among these species, there was no relationship between the basal serum lipoprotein profile and subsequent lipoprotein responses to dietary cholesterol. Although the level of dietary protein at 6%, 12%, and 37% of calories had no appreciable main effect on serum total cholesterol in spider monkeys, very low protein diet (6% of calories) produced a significant elevation in alpha-lipoprotein cholesterol. Serum alpha-lipoprotein responses to exogenous cholesterol (1.84 mg/kcal) was highest for the very low protein diet and lowest for low protein diet (12% of calories). Diets with high sucrose (76.5% of calories) and low saturated fat (12.5% of calories) containing no added cholesterol were tested in squirrel and spider monkeys and produced a consistent serum total cholesterol response; the alpha-lipoprotein response was significantly higher in squirrel monkeys than in spider monkeys. The above findings have implications in experimentally induced and comparative atherogenesis.


Hypolipidemic effects in monkeys of ML-236B, a competitive inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A reductase. The fungal metabolite ML-236B, a competitive inhibitor of 3-hydroxy-3-methylglutaryl CoA reductase, has been shown to be significantly effective in lowering serum cholesterol levels in cynomolgus monkeys at doses of 20-50 mg/kg per day. Levels of serum phospholipids and triglycerides were, however, not significantly changed by the administration of the drug. Of the serum lipoprotein fractions, a beta-lipoprotein corresponding to low density lipoprotein was preferentially reduced by the drug treatment. Fecal excretion of neutral sterols was unaffected but that of bile acids and slightly elevated by the administration of ML-236B.


[A study of the serological response of Sudanese children to three associated immunizations (measles, tetanus, meningococcal A meningitis) (author's transl)]. The authors first emphasize the efficiency and economic value of associated immunizations in developping countries. They report the first data collected in a campaign of immunization with a single injection of an extemporaneous mixture of antimeasles, antitetanus and antimeningococcal meningitis vaccines. This campaign took place in the Republic of Suddan from may 1976 to july 1977 and concerned 87 children. The specifications of each vaccine as well as the procedures of vaccination and serological control are given. The study of serological rates shows: -- a good response for measles with, in Africa, an optimal âge of 6 months and a new injection 6 months later; -- a low and late antibodies rise in tetanus with a good immunological memory giving way to an acute rise under a 2nd injection one year later; -- an immediate increase of the basic low rate of meningococcic antibodies existing in most Suddanese children before the injection. The authors consider the advantage of using also anti C meningococcal vaccine and to add an inactivated poliomyelitic vaccine. They give notice of the good stability in tropical environment of the vaccinal mixture they used.


Lethal effect of protamine and histone on competent Bacillus subtilis cells. Inhibition of genetic transformation by protamine in sublethal concentration. Under experimental conditions of genetic transformation, protamine and total histone were bactericidal for Bacillus subtilis cells. The abilities to cause lethality were very similar for both, either protamine or histone, with no antagonistic effects amongst these natural polycations. With both basic proteins acting simultaneously the enhancement was higher than a summation of the separate lethal effects. Sublethal concentration of protamine added at the beginning of transformation time, produced a strong inhibition of transforming efficiency. The same concentration added later than 10 min from the start of transformation had no inhibitory effect. These facts together with the absence of inhibition by simple pretreatment of DNA alone as well as the cell protection by protamine against lytic activity of lysozyme, suggest a protamine-cell surface interaction which impedes DNA uptake events.


Physico- and immunochemical properties of staphylococcal protein A extracellularly produced by a set of mutants from Staphylococcus aureus Cowan I. Mutant strains of Staphylococcus aureus have been isloated using a simple cosedimentation technique. While the parental strain contains predominantly a cell-bound protein A, the mutant strains exclusively produce extracellular protein A. The mutant forms of protein A all have lower molecular weights than that of protein A from the parental strain. They showed the same antigenicity as the parental protein A and gave similar reactivity with immunoglobulin to the parental one except for one mutant. A conspicuous spur was observed between the parental protein A and that produced by the mutant against normal dog serum in the micro-Ouchterlony immunodiffusion test.


Serotype-dependent inhibition of glucan synthesis and cell adherence of Streptococcus mutans by antibody against glucosyltransferase of serotype e S. mutans. A crude glucosyltransferase (GTase) preparation was obtained from the culture supernatant of Streptococcus mutans strain MT703 (serotype e) by 50% ammonium sulphate precipitation. Antiserum specific against the GTase was prepared by immunizing rabbits intramuscularly with the GTase in Freund incomplete adjuvant, followed by GTase without adjuvant intravenously. Gamma globulin fractions of the antiserum and normal serum were partially purified by 1/3 saturated ammonium sulphate precipitation. The antibody strongly inhibited the GTase activity (greater than 90%) of type c, e and f S. mutans, whereas the GTase of type a, d and g was not affected by the antibody. The GTase from type b S. mutans was slightly inhibited. The adherence of viable cells of type c, e, and f S. mutans to a glass surface due to synthesis of glucan by the cell-associated GTase was also significantly inhibited by the antibody to the enzyme. These results suggest that type c, e, and f and types a, d, and g S. mutans can be separated into two major groups in terms of the immunological relationship of GTase.


The evolution of an immune system.

The evolution of an immune system. A model for the molecular evolution of an imune system is presented. It suggests how a system of cell surface-fixed antigen receptors, called FR, to be thought of as "primitive" but still functional antibodies, could evolve into the "modern" labile T cell and antibody system, the receptors for which may be called CER (clonal expansion receptors). Perhaps the most significant insight to be gained from the theory concerns the conclusion that the immune system of an embryo may be primed by the interaction between two types of cells with complementary surface specificities. In the first type of cell the interacting molecule is an FR molecule coded by a gene of the Major Histocompatibility Complex (MHC) which has undergone a somatic mutation; in the second type it is a CER molecule also coded by a gene which has undergone a recent somatic mutation. It is believed that this insight eliminates some of the problems experienced in understanding generation of diversity, and renders unnecessary some of the more complex hypotheses about immune networks. The mechanism of action of immune response genes is easily explained by the theory.


A case of pulsating proptosis.

A case of pulsating proptosis. The long-term follow-up of a case of unilateral pulsating proptosis is reported. The clinical signs in this patient were due to a defect in the bony wall of the orbit which is an unusual manifestation of neurofibromatosis.


Creutzfeld-Jakob disease and corneal grafts. The possible danger of surgical transmission of Creutzfeld-Jakob disease from one human being to another has been reported in three instances. Although laboratory attempts at transmission of this disease by corneal grafting have so far failed in animals, it is emphasized that great care should be exercised in the selection of donor material for corneal grafts and renal transplants.


[Determination of serum digitoxin by means of a solid-phase enzyme-linked immunosorbent assay (author's transl)]. A solid-phase ELISA-technique for clinical applications is described. It requires little apparatus other than a photometer and allows the rapid determination of serum digitoxin levels. It differs from the original technique only in the sample volume being smaller and a digitoxin calibration curve being required. Concurrent assays by a reference method (86Rb-erythrocyte assay) gave results in excellent agreement with the values obtained by the modified ELISA-technique on samples from patients under long-term therapy with digitoxin (r = 0.95).


Neutron energy spectra of d(49)-Be and p(41)-Be neutron radiotherapy sources. Zero-degree neutron energy spectra for the p(41)-Be and d(49)-Be reactions were measured by time-of-flight for neutrons with energies above 1.9 and 1.4 MeV, respectively. Spectral changes resulting from the addition of copper, aluminum, and polyethylene filters to unfiltered beams were determined. Integral yields, average energies, filter material attenuation coefficients, and kerma fractions were computed for these spectra. Calculated spectra for neutron beams filtered by various thicknesses of polyethylene compared favorably with experimental results


Variation in output factor caused by secondary blocking for 7-16 MeV electron beams. The effect of secondary blocking on the output for 7-16 MeV electron beams is investigated for the two most widely used methods of field shaping, i.e.,(a) shield on surface, and (b) shield at end of cone with subsequent air gap. For those two methods differences in output on the order of 10% are observed. These effects are explained in terms of the blocking geometry and its influence on scattered radiation.


Computer algorithm for electron beam treatment planning. A computer algorithm has been developed for electron beam treatment planning. The method uses a limited amount of stored experimental dose distribution data, performs interpolation, and stores generated beam information on an optimized fan line-depth line grid. Experimental verification of the computer program showed agreement within +/-5% for beam generation and air gap correction.


Photon contamination in 8-20-MeV electron beams from a linear accelerator. The amount of x-ray contamination near the surface of a phantom irradiated with electron beams was measured directly. Measurements were done to ascertain if photon contamination in the beam contributes a higher dose to the more superficial layers of an irradiated medium than indicated by conventional methods. A 1.4-kG magnetic field was used to deflect the electron beams generated by a Philips SL/75-20 linear accelerator. The electron energies studied were 8, 10, 12, 14, 17, and 20 Mev. After sweeping the electron beam, a significant amount of photon contamination was measured in all cases. The characteristic qualities of the photon contamination were measured directly in a water tank. They were found to agree with those of bremsstrahlung spectra generated in a thin target with a virtual source at the location of the scattering foil.


On the constancy in composition of polystyrene and polymethylmethacrylate plastics. Variations in the atomic composition, and mass and electron densities of polystyrene and polymethylmethacrylate (PMM) plastics were assessed from experimentally determined mass attenuation coefficients for 125I and 137Cs gamma rays. The means and standard deviations in the mass densities of 16 samples of PMM and 10 samples of polystyrene were found to be 1.174 +/- 1.4% and 1.042 +/- 0.6% g/cm3, respectively. Based upon transmission measurements on various solutions of ethyl alcohol in water, the standard deviations in the effective atomic numbers of PMM and polystyrene were determined to be 0.77% and 1.3%, respectively. Based upon experimentally determined mass attenuation coefficients for 137Cs, the standard deviations in electron density for PMM and polystyrene were 0.5% and 1.2% respectively. Similar measurements on tap water and two grades of distilled water failed to detect any differences in atomic composition.


HnRNP core proteins: synthesis, turnover and intracellular distribution. Our present data indicate that the Mr 34-40,000 polypeptides which are involved in the binding of a large fraction of hnRNA sequences, including mRNA, are for the most part metabolically stable species in mouse ascites tumor cells. An exception to this generalization is the smallest of 30S RNP core polypeptides, the Mr 34,000 protein, which has a relatively high turnover rate. The relationship of the various synthesis and degradation rates to the physiological state of mammalian cells remains to be determined, as does the pathway of assembly and disassembly of RNP substructures during re-utilization of the proteins and during their turnover. Immunofluorescent studies, which have confirmed the expected nucleoplasmic or euchromatic localization of the RNP core proteins, have also indicated that these species are stable during mitosis, at which time they are dispersed through the cell away from the condensed chromosomes. The proteins appear to relocate in the nucleus as soon as the nuclear envelope is reformed.


[Selection and some properties of recombinant clones of lambda bacteriophage containing structural genes of Drosophila melanogaster]. The lambdagt clones containing fragments of D. melanogaster genome were prepared and characterized by hybridization of their DNA with complementary RNA synthesized on the lambdagt DNA, C fragment of lambdagt DNA and total D. melanogaster DNA, and also with mRNA and a stable cytoplasmic poly(A)-RNA both isolated from D. melanogaster cells grown in culture. The technique for a simple selection of hybrid clones is described. The hybridization with mRNA allows one to select the clones containing structural genes of D. melanogaster. It was found that in all cases when the clone contains the structural gene it also contains the reiterated base sequences of the D. melanogaster genome. Several clones containing D. melanogaster DNA fragments with a size of (2--4) X 10(6) daltons which hybridized with a relatively large portion of mRNA were selcted for further analysis.


[Conformational regulation of functional activity of photosynthetic membranes of purple bacteria]. In reaction centres of photosynthetic membranes of R, rubrum the efficiency of redox interactions of the photoreduced primary electron acceptor with secondary acceptors and photooxidized bacteriochlorophyll has a marked and reversible dependence on temperature over the range from -20 degrees to -80 degrees. Similar temperature dependences were observed for correlation times of the rotational diffusion of a spin probe bound to the hydrophobic region of the membrane and of a spin label bound to SH-groups of the protein constituent of the membrane, as well as for characteristics of resonance absorption of the Mössbauer probe (57Fe), embedded in the membrane by biosynthesis. Using the same indicators of intramolecular mobility, a correlation has been observed between photoactivity and structure of the membrane in experiments involving hydratation changes of samples. The data suggest the existence of a close interrelationship between the conformational mobility of the constituents of the photosynthetic membrane and their specific reaction capacity.


[Isolation and properties of B. subtilis DNA-binding proteins inhibiting ATP-dependent deoxyribonuclease]. The fraction inhibiting ATP-dependent DNAase and some other enzyme activities was found in B. subtilis cell extracts. Two methods of its isolation were elaborated. It is established that the inhibiting activity fraction represents a set of some positively charged thermostable proteins of low molecular weight (M 9000--25 000). The inhibiting effect of the proteins in question may be attributed to their ability to form a complex with DNA. The complex is formed in low ionic strength conditions. The elevation of NaCl concentration to 0,3 M removes some proteins from the complex and causes the complete loss of inhibiting activity. At 0,5 M NaCl DNA-protein complex is completely dissociated. The discovered proteins seems to be localized in DNA-membrane cell fraction. It is supposed that these proteins (or some of them) are the structural ones of the bacterial nucleoid.


[How Johannes Brahms died].

[How Johannes Brahms died]. In 1896, when he was 63 years old, Johannes Brahms, who had always been demonstrably in good health, developed an icterus of increasing intensity together with a considerable enlargement of the liver and loss of weight. Since infectious hepatitis could scarcely come into the question, from the medical point of view a neoplasm in the region of the liver as well as cirrhosis of the liver were considered. While hepatic carcinoma is a relatively rare disease in Europe even today and Brahms, on the other hand, had consumed copious quantities of concentrated alcoholic drinks during his lifetime, cirrhosis of the liver is the most probable diagnosis, especially as at the end hemorrhages from esophageal varices and the lower intestinal segments occurred.


[Pain after nerve injuries (author's transl)]. After cut injuries to nerves, about 70% of the persons injured are stricken with painful hypersensitivity, and at least 50% with non-causalgic pain. Clinical reports on peace-time injuries have had scarce regard to both forms. In about 80% of the injured, the painful hypersensitivity sets in within 6 months of the surgical reconstruction and ceases in half of the the patients up to the end of the second year; in the other half the disturbances seem to persist much longer. Non-causalgic pain commence earlier than the painful hypersensitivity, often already shortly after the trauma. Complete remission of this pain is rare. In the event of greater intensity, both painful hypersensitivity and non-causalgic pain entail the risk of abuse of analgesics. As to differential diagnosis, non-causalgic pain must be discriminated from genuine causalgia in which continuous pain is superimposed by paroxysms of pain.


[Children's eating habits at breakfast and snacks between meals (author's transl)]. Detailed inquiries into the eating habits of 86 children attending schools and kindergartens was carried out and a nut-nougat cream spread was evaluated in a 14-day investigation. The selection of food for the snacks requires some correction according to these results e. g. for salt biscuits, sweets, soft drinks. 22% of the parents still compel their children to eat everything up, more than 1/3 leave the purchase of snacks to the children. The nut-nougat cream enjoys enormous popularity as a spread for bread so that even large food undertakings cannot face this development with equanimity. From the nutritional physiology aspect this product is only to be considered positively if spreading of any fat under it can be avoided -- a question of explanation and education, because only then will a superfluity of calories be prevented.


[Cerebral attacks in childhood and adolescence. Types, diagnostic and therapeutic possibilities (author's transl)]. General practitioners, pediatricians, welfare and school medical officers are frequently first confronted with cerebral attacks in childhood and adolescence. The diagnostic and therapeutic possibilities have been considerably widened in recent decades, they are more differentiated and more extensive. The prognosis of many attacks is therefore often favorable today. Close cooperation between the practitioner and specially equipped departments (neuropediatric and child psychiatric outpatients and clinics) is, however, indispensable for a successful therapeutic procedure and should be further intensified in the future. The phenomenology and incidence, frequency and age-dependence of childhood attacks are discussed and also the present state of diagnostic and therapeutic perspectives in general and hospital practice.


[A computer-controlled monitoring and therapy system for shock compensation in severe burns (author's transl)]. A computer-controlled control loop for the automatic diagnosis of shock and infusion therapy is reported. External information (off-line) and vital parameters measured with serial devices (on-line) are used by the computer for the automatic control of infusion pumps. By this method the critical shock phase could be prevented in five seriously burned patients. The construction of the system also permits its use in other shock conditions.


[Therapeutic experience with osyrol 100/Lasix in the treatment of congestive heart failure (author's transl)]. Under general practice conditions 18 patients with congestive heart failure which did not respond satisfactorily to digitalization and saluretic therapy were treated with Osyrol 100/Lasix for a period of 3 months while retaining the digitalis medication. The application gave good to satisfactory results in over 90% of the cases. This very good result in patients with previously unsatisfactory response underlines the high therapeutic efficacy of this preparation. The findings of this study confirm that Osytol 100/Lasix is a reliably effective, well tolerated preparation with a low risk and is particularly suitable for the ambulant treatment of patients with congestive heart failure.


[Treatment of alcoholic toxic fatty liver. A placebo-controlled trial with hepavis (author's transl)]. A placebo-controlled double-blind study of 30 patients with advanced chronic fatty liver was intended to show how far treatment with a liver preparation, in this case Hepavis, is superior to alcohol abstinence alone. Examination of the laboratory parameters, especially of gamma GT shows that treatment with Hepavis with simultaneous withdrawal of alcohol produces a rapid normalization or improvement of the laboratory findings and consequently an accelerated improvement in the course of the disease. This leads to the conclusion that the pathological activity of the liver cell is reduced more quickly by the constituents of Hepavis than without suitable therapy, and that a more favorable prognosis for the fatty liver as a potential precurser of cirrhosis is to be attained. Not only is elimination of the lipogenic factor, alcohol, essential in the treatment of fatty liver, but also treatment with hepatotropic substances.


[Postnatal infections with problem organisms (author's transl)]. Two problems are discussed: hospital infection of neonates and potentially fatal neonatal infections caused by group B streptococci and E. coli K1. The incidence of hospital acquired infections in a neonatal intensive care ward was 12.4%. Premature infants with an average weight of 1673 g were particularly prone to infection. On the average, infected patients stayed in hospital 34.8 days, uninfected patients 6.8 days. The most common infections were sepsis, skin infections, infections of the upper and lower airways and meningitis. Group B streptococci are among the most frequent pathogens of potentially fatal postnatal infections. The "early" form (usually sepsis) and "late" form (usually meningitis) are presented in detail.


[Perforation of the uterus by intrauterine pessaries (author's transl)]. This study presents 4 cases of perforation of the uterus caused by intrauterine devices. The marked complications and frequent difficulty in relocating the I.U.D. are also described. Three devices had to be removed by laparotomy because adhesions made non-invasive removal impossible. In these three cases, the intestine was perforated spontaneously. The last pessary is still within the uterine wall at the present time. To lower the complication rate, intrauterine devices should only be inserted by physicians experienced in gynecological techniques.


[Therapy of cerebrovascular insufficiency. A psychometric double-blind trial with a slow-release form of xantinol nicotinate (author's transl)]. Of 80 geriatric patients with cerebral insufficiency, 40 received 1000 mg of a slow-release form of xantinol nicotinate (XN) and 40 a placebo twice daily for 12 weeks. According to the co-variant analytical evaluation of the placebo/verum differences with the initial values as covariable after 12 weeks' application, XN influenced most of the investigated geriatric complaints favorably and improved the general intellectual capacity. Central activation and concentration are already improved after 6 weeks' treatment with XN.


[Special diagnostic and therapeutic methods for changes affecting urodynamics in diseases of the urogenital tract (author's transl)]. Special diagnostic and therapeutic methods for changes affecting the urodynamics of the urogenital tract are reported from the urological point of view. First of all the causal connection between disorders of drainage and urinary infection are referred to. Then the special methods of investigation to clarify these urodynamically active urethral changes are mentioned. The radiological visualization of the urethra during miction and the retrograde introduction of contrast media are particularly stressed. In connection with this the endoscopic verification of these pathological changes is emphasized. A number of very demonstrative pathological changes in the region of the entire subvesicular urinary tract are demonstrated both by X-ray and uroscopic pictures. Finally the therapeutic possibilities are reviewed in relation to the findings.


[The value of echography in the care of patients with chronic renal insufficiency (author's transl)]. Echography permits information on the shape of the kidneys and ureteral system without reference to their function, and on the perirenal tissue. This is illustrated by a typical example. Echography also provides rapid orientation in the recognition of collections of fluid in the preformed body cavities, which can rapidly bring the affected patient into a life-threatening condition, particularly in the shape of a pericardial effusion. For this reason the inclusion of echography in the investigation program in the care of patients with chronic renal insufficiency is recommended.


[The effect of weather on blood sugar fluctuations in insulin-dependent patients. Medical meteorological observations (author's transl)]. In agreement with the results of urinary sugar examinations obtained by other authors it was established that there are probable connections between biochemical parameters and climatic events and that the reaction of the blood sugar to meterological changes may be an index for the changing responses of the body to weather as a stress factor. Further investigations, especially on the temporal distribution of hypoglycemias should contribute to a clearer explanation of the undoubtedly important correlation which could be shown to be helpful in the optimal stabilization of diabetics.


Mutagenic effects of sodium azide in Drosophila melanogaster. The mutagenic effects of sodium azide (NaN3) were studied at low pH in male Drosophila melanogaster using the sex-linked recessive-lethal test. No significant increase in the mutation frequency was observed after abdominal injection of azide solutions buffered at either pH 3.8 OR 4.6. However, a weak mutagenic effect was noticed in the flies fed for 3 days on 0.1 mM azide (pH 4.6) solution.


Effects of N-nitrosopiperidine substitutions on mutagenicity in Drosophila melanogaster. N-Nitrosopiperidine (NP) and various derivatives were fed to Drosophila melanogaster males over a wide concentration range in order to assess their mutagenic potency in the induction of X-linked recessive lethals and chromosome loss. NP was effective in inducing lethals, as were its halogen and methyl-substituted derivatives, with the exception of 2,6-dimethyl NP. (Methyl substitutions at the alpha carbon atoms reduce or eliminate mutagenic activity.) Substitution of halogen groups on the piperidine ring enhanced the mutagenic activity, with the 3-chloro compound being the most mutagenic. In contrast, substitutions with a hydroxyl, carboxyl, or keto group resulted in a loss of mutagenicity. None of the compounds tested increased the frequency of chromosome loss or breakage in mature sperm.