Sickle cell anemia and severe infections due to encapsulated bacteria. Overwhelming infections caused by encapsulated bacteria are an important cause of morbidity and death in children with sickle cell anemia. The most important contributing factors to this increased susceptibility to infections are an opsonophagocytic defect due to an abnormality of the alternate pathway of complement activation, a state of functional hyposplenia, and a lack of specific circulating antibodies as a developmental phenomenon. If the inordinately high, early mortality rate associated with sickle cell anemia is to be prevented, early diagnosis of affected infants is crucial. Prophylactic therapy with penicillin has been advocated in recognition of the fact that a majority of the causative organisms are sensitive to penicillin. However, no controlled studies have proved the effectiveness of such therapy. Immunization with broadly polyvalent vaccines against Streptococcus pneumoniae, Haemophilus influenzae type b, and Neisseria meningitidis may ultimately represent the most effective way to reduce the incidence of catastrophic infections.


Neonatal meningitis due of Escherichia coli K1. Human neonates are uniquely susceptible to serious infections due to Escherichia coli. Investigation of the serotypes of E. coli isolated from neonates with meningitis revealed that greater than 80% of the isolates possessed the capsular polysaccharide antigen designated K1. Cultures of stool from healthy infants, children, and adults have shown that K1 organisms are commonly found in individuals of all ages. Studies of  mother-infant pairs have demonstrated transmission of K1 strains from mother to infant shortly after birth. In the rare infant who develops meningitis due to E. coli K1, serotype analysis frequently reveals that the same organism was isolated from the infant's cerebrospinal fluid and from the stools of both mother and infant. Preliminary investigations of humoral immunity demonstrated an age-related acquisition of antibodies to the capsular polysaccharide of E. coli K1 in healthy infants and children. An animal model was developed in which feeding of E. coli K1 to infant rats resulted in colonization, bacteremia, and meningitis in the animals.


Intestinal colonization and adhesion by enteroxigenic Escherichia coli: ultrastructural observations on adherence to ileal epithelium of the pig. Colonization of pig ileum by enterotoxigenic Escherichia coli that were enteropathogenic for pigs but that lacked K88 antigen (K88-) resulted in morphological characteristics similar to those reported for K88+ strains. Strains of enterotoxigenic E. coli from three different K88-serotypes adhered to the villous epithelium. In sections examined by transmission electron microscopy, adherent bacteria were separated from each other and from epithelial microvilli by peribacterial electron-lucent regions. The enterotoxigenic E. coli had appendages that extended into these regions. The appendages were morphologically characteristic for each strain. It is possible that these appendages were pili, polysaccharide K antigens, or structures resulting from some interaction between pili and polysaccharide. Certain  pili or pilus-like structures may be virulence attributes that facilitate adhesion of enterotoxigenic E. coli to the intestinal epithelium.


Antibody response to group A streptococci in an epidemic of streptococcal pharyngitis. An epidemic of acute pharyngitis involving 280 cases occurred in a kibbutz in Israel during the fall and winter of 1972-1973. Group M and/or T type 12 streptococci was associated with the outbreak. No cases of rheumatic fever and no acute nephritis appeared in spite of the vigorous immune response to both cellular and extracellular antigens of group A streptococci documented in 50% to 80% of patients, suggesting that strain variation may be a feature of rheumatogenicity as well as nephritogenicity of group A streptococcal pharyngitis.


Release of immunoreactive and radioactively prelabelled endogenous (pro)-insulin from isolated islets of rat pancreas in the presence of exogenous insulin. To study the influence of insulin on its own secretion, collagenase-isolated islets of rat pancreas were prelabelled with [3H]leucine for 2 h. After washing the islets, (pro-)insulin release was stimulated by glucose in the presence or absence of exogenous insulin (up to 2-5 mu./ml). Hormone release was unchanged by the presence of exogenous insulin as judged by determination of both immunoreactive insulin and radioactivity incorporated into the proinsulin and insulin fractions of the medium. No direct feedback mechanism for insulin secretion was apparent from this study.


Gonadotrophin release by a highly active analogue of luteinizing hormone releasing hormone in rats immunized against luteinizing hormone releasing hormone. Immunization against luteinizing hormone releasing hormone (LH-RH) in adult male rats produced a progressive decline in LH and FSH in the circulation to low or non-detectable levels. D-Serine-tertiary-butyl6,des-glycine-NH210 LH-RH ethylamide is an analogue of LH-RH having highly active LH-RH properties in the normal rat. Because it is also immunologically different from LH-RH it can stimulate gonadotrophin release from the anterior pituitary gland of rats immunized against LH-RH without interference from the antibody. The analogue stimulated LH and FSH release in rats 15 weeks after immunization against LH-RH when antibody titre was highest, and after long-term (35 weeks) immunization against LH-RH. D-Serine-tertiary-butyl6,des-glycine-NH210 LH-RH ethylamide and related analogues are therefore potentially useful for reversing the effects of immunization against LH-RH.


Phytohemagglutinin-induced differentiation and blastogenesis of precursor T cells from mouse bone marrow. The cells in mouse bone marrow (BM) capable of responding to phytohemagglutinin (PHA) were shown to be precursor T cells in experiments employing athymic mice, immunofluorescence, and specific lysis of T or B cells with cytotoxic antisera + complement. In contrast, the responses of lymph node (LN) and spleen (Spl) cells to this mitogen were shown by the same techniques to rely upon resident populations of mature T lymphocytes in these peripheral lymphoid organs. Cytolysis of T cells with anti-theta (anti-Thy 1), anti-thymocyte, or anti-brain antisera abolished the PHA responses of LN and Spl, but had no appreciable effect on the BM PHA response. Lysis of B cells with anti-mouse gamma globulin or anti-mouse IgM antisera had no significant effect on either Spl or BM blastogenesis in response to this lectin. Immunofluorescent studies with fluoresceinated anti-brain sera demonstrated acquisition of T-cell surface antigens by BM null lymphocytes during the blastogenic response of this tissue to PHA. The results of these immunofluorescence experiments were reproducible even when marrow obtained from nude mice and pretreated with anti-brain serum plus complement was employed. The implications of these findings with regard to prophylaxis against graft versus host disease in BM transplant recipients are discussed.


The adoptive transfer of pregnancy-induced unresponsiveness to male skin grafts with thymus-dependent cells. A majority of C57BL/10Sn females pregnant six or more times by syngeneic males do not reject male skin grafts. The pregnancy induced tolerance of male skin grafts was transferred adoptively to virgin recipients by thymus-dependent cells from multiparous tolerant donors.


Genetic control of lymphocyte activation: lack of response to low doses of concanavalin A in lipopolysaccharide-nonresponder mice. C3H/HeJ mice do not respond to the polyclonal B-cell activator lipopolysaccharide (LPS) from Escherichia coli; this was first described by Sultzer who observed that mice of this strain did not respond to an intraperitoneal (i.p.) injection of LPS as measured by the accumulation of leukocytes in the peritoneal cavity. Neither were C3H/HeJ mice as susceptible to LPS toxcitiy (1). It was later reported that LPS-induced mitogenesis (2,3), adjuvanticity (4), and the appearance of Ia antigens on B lymphocytes as induced by LPS, (5) was also absent in C3H/HeJ mice. However, lymphocytes from these mice respond normally to the polyclonal B-cell activators purified protein derivative of tuberculin (2,6) and dextran sulfate and have also been reported to respond normally to concanavalin A (Con A) (2). Furthermore, the immune responses to sheep erythrocytes (7) and soluble thymus-dependent antigens (4) are normal in C3H/HeJ mice. Unresponsiveness to LPS in C3H/HeJ mice has been found to Be due to a defect in a single gene or a set of linked genes (3,8) which has been mapped between the major urinary protein locus and the locus coding for polysyndactyly on chromosome 4. (1) We have reported that injection of LPS into mice of an LPS-responsive strain causes a shift in the Con A dose-response curve of cultured spleen cells, suppressing the low does response (9). Therefore, we tested the Con A proliferative response in cultures of normal or LPS-activated spleen cells from LPS-responder (C3H/Tif) and LPS-nonresponder (C3H/HeJ) mice. We report here that C3H/HeJ spleen cells respond poorly to low concentrations of Con A (0.05-0.1 mug/ml). Injection of LPS 2 days before culture inhibits the response to low doses of Con A in cultures of C3H/Tif spleen cells but has no inhibitory effect on the dose response profile of C3H/HeJ spleen cells. Furthermore, the low dose Con A response of spleen cells is dependent upon the presence of an Ia-positive cell. (2) The role of Ia-positive cells in the Con A response of C3H/Tif and C3H/HeJ spleen cells is described.


Localization of amyloid-related serum protein SAA-like material to intermediate (10 nm) filaments of cultured human embryonal fibroblasts. Further studies are presented on the intracellular localization of the amyloid-related serum protein SAA previously shown to be produced by embryonal fibroblasts. In cultured embryonal fibroblasts, the fine fibrillar cytoplasmic immunofluorescence obtained by anti-SAA was distinguished from that of microfilaments and microtubules. By using electron microscopy and cells treated with drugs known to specifically alter intracellular fibrils, SAA was localized to 10-nm intermediate size filaments. These filaments form characteristic perinuclear bundles upon treatment with drugs such as demecolcine or vinblastine which disrupt micotubules. The results indicate that SAA is a constituent of the intracellular cytoskeleton.


Drug screening by enzyme immunoassay (EMIT) and thin-layer chromatography (Drug Skreen). Urine samples (n = 300) were examined for drugs by thin-layer chromatography ("Drug Skreen", Brinkmann Corp.) and by the "Enzyme Multiplied Immunoassay Technique" ("Emit", Syav Corp.). The results of both methods were compared for the detection of opiates, barbiturates and amphetamines. In more than 90% of the determinations identical results were obtained with both methods. About 10% of the results of the Emit barbiturate assay differed from those of thin-layer chromatography and therefore had to be further investigated by gas liquid chromatography. It could be demonstrated that the barbiturate determination by the Emit system correlated better with the results of gas liquid chromatography. From the results of this study it is suggested that thin-layer chromatography is used as a screening test, and to confirm positive results with other methods such as Emit. If the abuse of barbiturates or opiates is suspected the corresponding Emit test should also be performed, even in cases of a negative thin-layer chromatography screening. Confirmation with a third method such as gas liquid chromatography is necessary, if thin-layer chromatography and Emit lead to divergent results.


Determination of phenobarbital and phenytoin in serum by a mechanized enzyme immunoassay (EMIT) in comparison with a gas-liquid chromatographic method. The antiepileptic drugs phenobarbital and phenytoin were determined in serum by enzyme immunoassay (Emit, Syva Corp.) and gas-liquid chromatography. The Emit assays were mechanized by the use of an Eppendorf analyzer 5010. The precision of the Emit system was sufficient (coefficient of variation within series 6-13% and from day to day 8-15% with various calibrators and control sera). Moreover the Emit method is rapid, specific and easy to perform. The procedure requires only 10 microliter of serum per determination. A disadvantage however is the high cost of the reagents. A comparison of the results obtained by Emit and gas-liquid chromatography in a series of about 50 patients showed a good correlation between both methods (correlation coefficient r = 0.968 for phenobarbital and 0.978 for phenytoin).


Failure of immunoperoxidase staining to detect acrosin in the equatorial segment of spermatozoa (1). An immunoperoxidase staining procedure that readily demonstrated acrosin in the rostral portion of the acrosome failed to detect acrosin in the equatorial segment of spermatozoa representing the mammalian orders artiodactyla (bull and boar), lagomorpha (rabbit) and primate (human).


The mechanism of action of nitro-heterocyclic antimicrobial drugs. Primary target of 1-methyl-2-nitro-5-vinylimidazole is DNA. The antimicrobial drug 1-methyl-2-nitro-5-vinylimidazole (MEV) preferentially blocked DNA synthesis, was mutagenic and induced coliphage lambda in Escherichia coli. The antibacterial effects of MEV are the consequences of repairable damage to DNA, as shown by hypersensitivity of recA and uvr strains to MEV and related drugs, stimulation by MEV of DNA turnover which was dependent on the product of the uvrA gene, and the presence of cross-links in DNA from MEV-treated bacteria.


The mechanism of action of nitro-heterocyclic antimicrobial drugs. Metabolic activation by micro-organisms. Although the target of the antimicrobial drug 1-methyl-2-nitro-5-vinylimidazole (MEV) has been shown to be DNA (Goldstein et al., 1977) the drug was ineffective in cell-free systems because it was not activated. Both the rate of metabolic activation of MEV and its antibacterial activity were increased when bacteria were grown in limiting oxygen. Mutants of Escherichia coli which were conditionally resistant to nitroimidazoles and nitrofurans were defective in drug activation. The activities of these drugs against E. coli correlated with their rates of metabolism. The antimicrobial spectrum of the drugs appeared to be related to their reducibility by different species.


Regulation of glucosamine utilization in Staphylococcus aureus and Escherichia coli. Glucosamine- or N-acetylglucosamine-requiring mutants of Staphylococcus aureus 209P and Escherichia coli K12, which lack glucosamine-6-phosphate synthetase [2-amino-2-deoxy-D-glucose-6-phosphate ketol-isomerase (amino-transferring); EC 5.3.1.19], were isolated. Growth of these mutants on glucosamine was inhibited by glucose, but growth on N-acetylglucosamine was not. Addition of glucose to mutant cultures growing exponentially on glucosamine inhibited growth and caused death of bacteria, though chloramphenicol prevented death. Uptake of glucosamine by S. aureus and E. coli mutants was severely inhibited by glucose whereas uptake of N-acetylglucosamine was only slightly inhibited. Uptake of glucose was not inhibited by either glucosamine or N-acetylglucosamine. In glucosamine auxotrophs, glucose causes glucosamine deficiency which interrupts cell wall synthesis and results in some loss of viability in the presence of continued protein synthesis.


Genetic determinants of the synthesis of the polysaccharide capsular antigen K27(A) of Escherichia coli. Most of the his+ hybrids from crosses between the Escherichia coli donor Hfr45(O8:K27) and different E. coli O9 recipients expressed the donor O8 antigen specificity and produced the capsular antigen K27. Therefore these hybrids must have inherited the his-linked donor rfb region determining the synthesis of O8- specific polysaccharides as well as his-linked genes involved in K27 antigen synthesis. In the living state these hybrids were inagglutinable in O8 antiserum like the donor cells. However, when E. coli K12 and O8:K42- were used as recipients most of the his+ hybrids were agglutinable in O8 and K27 antisera. The amounts of K27 antigen present in these hybrids, designated as K27i (intermediate) forms, were sufficient to evoke the production of K27 antibodies in rabbits, but insufficient to inhibit O-agglutination of the respective cells. The additional transfer of the trp region of E. coli O8:K27 into such K27i forms frequently resulted in O-inagglutinable K27+ hybrids. This is attributed to the introduction of trp-linked genes which apparently play a role in the synthesis of K27 capsular antigen. Tus it is concluded that at least two gene loci, one close to his and the other close to trp, are required for the synthesis of the complete capsular antigen K27.


Clostridium sporogenes isolates and their relationship to C. botulinum based on deoxyribonucleic acid reassociation. Sixty-two isolates of Clostridium sporogenes from canned foods were examined for cultural properties, heat resistance and DNA-DNA homology to Clostridium botulinum type A190. Sporulation was observed in most of 21 umbonate and rhizoidal colony-forming strains (colony-type I strains), but not in most of the 41 strains with convex and circular or crenate colonies with a mat to semi-glossy surface (colony-type II strains). More than half of the latter strains showed much higher heat resistance than the rhizoidal colony-forming strains. The DNA isolated from colony-type II strains was 81% or more homologous to C. botulinum A190 DNA, forming duplexes which had thermostabilities similar to homologous duplexes of strain A190 DNA. Colony-type I strains differed from C. botulinum by 30 to 40% DNA homology and the DNA duplexes formed between these strains and strain A190 showed deltaT m(e) values of 7-0 degrees C when compared with the T m(e) of homologous DNA duplexes of strain A190.


Morphological distinction between different H serotypes of Escherichia coli. The structure of the flagellar filaments of 50 Escherichia coli strains, each with a different H antigen, was examined. Although the flagella within each strain were structurally identical, there was variability in flagellar surface pattern between strains with differrent H antigens. Investigation of additional strains confirmed that flagella structure was the same in all strains having the same H antigen. In three pairs of strains with cross-reacting H antigens, the antigenic relatedness was associated with identical flagella structure.


Comparison of the flagellins from different flagellar morphotypes of Escherichia coli. The molecular weights of the flagellins of 13 strains of Escherichia coli, each with a different H antigen, were estimated using polyacrylamide gel electrophoresis. In each case only one major polypeptide was demonstrated, although some strains possessed apparently sheathed flagella. Considerable differences in the molecular weight of flagellin accompanied the previously described structural differences between flagella from strains with different H antigens. The relationship between flagellar diameter and the molecular weight of the corresponding flagellins was similar for both unsheathed and apparently sheathed flagella. Crosss-polymerization occurred between seed consisting of fragment of unsheathed flagella and flagellin solution from apparently sheathed flagella and vice versa. Co-polymerization of flagellin from unsheathed flagella and flagellin from apparently sheathed flagella was also demonstrated. These polymerization experiments indicate that the assembly pattern of flagellin molecules is probably the same in all E. coli flagella. The above and other evidence suggests that there is no true sheath, but that the differences in flagellar surface structure between different E. coli flagella are the result of differences in the superficial parts of the flagellin molecules.


Pyrimidine dimer excision and DNA degradation during liquid holding recovery in ultraviolet-irradiated Escherichia coli K12 uvr+ rec. The survival of ultraviolet-irradiated Escherichia coli K12 uvr+re was increased by post-irradiation incubation in phosphate buffer. During this incubation both dimer excision and DNA breakdown were inhibited. It is suggested that the bacteria coped with the remaining dimers in a manner which did not involve excision.


DNA degradation in wild-type and repair-deficient strains of salmonella typhimurium exposed to ultraviolet light of photodynamic treatment. Five mutants of Salmonella typhimurium strain LT2 trp DI (ColEI)+, initiallly detected because they released little or no colicin when tested on solid medium, proved to be sensitive to ultraviotet light (u.v.). Further testing indicated that one of the mutants was deficient in genetic recombination and was probably a recA-type mutant, while three of the others were deficient in DNA polymerase activity and appeared to be typical polA mutants. The fifth mutant was less sensitive than the others to methyl methanesulphonate, showed reduced proficiency in genetic recombination, and was of approximately normal u.v. mutability. This mutant may be a counterpart of the class known as uvrD in Escherichia coli. All five mutants degraded significantly more of their DNA following exposure to u.v. than did the wild-type strain. The recA-type mutant and the possible uvrD mutant also degraded significantly more of their DNA spontaneously than did the wild-type. Treatment with visible light and acridine orange (photodynamic treatment) cause no significant degradation of DNA in the wild-type strain, a highly significant increase in the extent of DNA degradation in a polA mutant, and a decrease in the extent of degradation in the recA-type mutant.


The effect of a drug-resistance factor on recombination and repair of DNA in Escherichia coli K12. The presence in recipient strains of Escherichia coli K12 of the plasmid R46 greatly reduced the yield of recombinants from crosses with several Hfr strains and virtually abolished the formation of recombinants by PI transduction without, however, significantly affecting the transfer of the F prime from a strain carrying Fgal. The R46 plasmid had paradoxical effects on mutability: it appeared to enhance the yield of mutants following irradiation with ultraviolet ligh but it reduced the number of mutants detectable in unirradiated cultures. The effects of this plasmid on ultraviolet survival of the wild type and several mutants defective for recombination and repair have been measured and the results, in the main, confirm similar observation by Tweats et al. (1976). Not only is the survival of the strain habouring R46 greater than that of the parent strain in all the cases studied, but the survival of ultraviolet irradiated bacteriophage lambda is also greater.


Comparison of the effects of bromocriptine and levodopa in Parkinson's disease. The effects of bromocriptine and levodopa were compared in a blind trial in 18 patients with Parkinson's disease. Optimal doses of the two drugs were given in identical capsules: there was no significant difference between the therapeutic effects. There were wide individual differences in response to the two drugs. Side effects were more common with bromocriptine because of side effects.


Changes of lipoamide dehydrogenase and mitochondrial structure in selenium-deficient chicks. A selenium deficiency in chicks produces degeneration and fibrosis of the pancreas. An investigation was undertaken to determine whether or not the activity of lipoic acid is impaired in the pancreas of selenium-deficient chicks. Enzymatic analyses of selenium-deficient chick tissues showed a reduction in lipoamide dehydrogenase both in pancreas and liver at a very early stage of growth. Using both direct measurements and sucrose-gradient cellular fractionation, it was found that the lipoamide dehydrogenase activity of the supernatant increased, and that of the mitochondria decreased in selenium-deficient as compared to normal chick livers. These results indicate an increased fragility of the mitochondrial membranes in selenium-deficient chicks.


Dentine/pulp reactions to full crown preparation procedures. Scanning electron microscopy was used to study the formation of a dentine smear in ten premolars ground with a water-cooled diamond in an air turbine. In another ten teeth the pulp reaction in full crown preparation with the same armamentarium was investigated by histological techniques. The findings revealed the formation of a dentine smear which was easily removed by light polishing with wet pumice, leaving plugs of debris in the tubule apertures. The clinical significance of these findings needs further investigation. No bacteria were demonstrated on the prepared surfaces either in the scanning electron micrographs or histologically when stained with Brown & Brenn stain. Severe, acute pulp reactions were observed subjacent to the dentinal tubules cut in full crown preparation. This technique should therefore be limited to superficial use only.


Determination of optimal continuous positive airway pressure for the treatment of IRDS by measurement of esophageal pressure. We describe a simple and reliable method to determine optimal airway pressure in infants with idiopathic respiratory distress syndrome who require continuous positive airway pressure treatment. Esophageal pressure was monitored in ten infants with IRDS during initial application of CPAP. As the level of CPAP was increased in 2 cm H2O increments, changes in Pes were compared with changes in PaO2. Below optimal airway pressure, Pes as well as PaO2 increased insignificantly. When optimal airway pressure (8.1 +/- 0.8 cm H2O) was applied, there was a marked increase in Pes (3.6 +/- 0.8 cm H2O. p less than 0.001) and PaO2 (39.0 +/- 10.0 mm Hg, p less than 0.01). Further increase in CPAP did not result in any subsequent appreciable increase in Pes while PaO2 decreased slightly and PaCO2 increased. Less than optimal CPAP increases F102 requirements and may increase the associated risk of bronchopulmonary dysplasia, while excessive levels of CPAP may increase the risk of pneumothorax. We suggest that esophageal pressure be monitored routinely to determine the optimal level of CPAP for each infant during the initial application of therapy.


Imidazo[4,5-f]quinolines III: Antibacterial 7-methyl-9-(substituted arylamino)imidazo[4,5-f]quinolines. A series of 7-methyl-9-(substituted arylamino)imidazo[4,5-f]quinolines was prepared and screened against four varieties of bacteria. The compounds possessed antibacterial activity against both Gram-positive and Gram-negative organisms.


Comparison of the effect of somatostatin on gastrointestinal function in the conscious and anaesthetized cat and on the isolated cat pancreas. 1. Somatostatin, 10 microgram kg-1 hr-1, inhibited gastric acid and pepsin secretion stimulated by pentagastrin, 8 microgram kg-1 hr-1, in conscious and anaesthetized cats with chronically implanted gastric fistulae. In the acutely surgically prepared anaesthetized cat, Somatostatin inhibited pepsin secretion but produced little inhibition of gastric acid secretion or mucosal blood flow. 2. Secretin stimulated pancreatic juice volume was not significantly reduced in acutely prepared anaesthetized cats, but there was a limited reduction of cholecystokinin-pancreozymin stimulated pancreatic amylase secretion and gall bladder contraction. 3. Somatostatin had neither stimulatory nor inhibitory effects on electrolyte and amylase secretion in the isolated saline-perfused cat pancreas. 4. The results suggest that some of the effects of Somatostatin may depend on the interaction on the target cell of other factors, nervous or humoral which may vary in different experimental preparations.


[Role of aerobic metabolism in prolonged intensive exercise]. The purpose of this review is to analyze the different factors which intervene with respect to the ability to perform intense exercises of long duration. This ability implies : (a) a high level of maximal oxygen uptake (Vo 2 max) and (b) a great endurance, i.e. the capacity of maintaining for a long time a high percentage of this Vo2 max. First of all, the values Vo2 max usually recorded on normal subjects are given, as well as those of subjects specially trained for endurance events ; then the factors which condition a high level of Vo2 max are described. These factors consist on great capacity in all of the links of the oxygen transport system. These capacities appear to be essentially dependant on the genetic endowment, but their maximal size can only by attained through intensive training. Endurance can be defined as the maximal period of time during which a given percentage of the Vo2 max can be sustained. The values recorded on normal subjects and on those specially trained for endurance events are given, and then the factors conditioning a high level of endurance are studied. Endurance appears to depend on the feeding of muscular fibers with energentic substrates. Training permits the muscles to store large quantities of glycogen. It also seems to enable the organism to increase the percentage of energetic substrates made up by lipids. This latter ability in associated with an alteration of the endocrine reactions induced by exercise. Finally, endurance is accompanied by an ability of the body to store and to eliminate the heat produced during exercise.


Arranging artificial teeth according to anatomic landmarks. A system for arranging artificial teeth that satisfies three goals is desirable. These goals are accuracy, speed, and a facility for communication. Such a system, based upon certain anatomic landmarks that can be identified on an edentulous dental cast, has been described in detail. The dentist with the patient present records the anterior determinant of occlusion by placing the four central incisors according to phonetics and esthetics. All remaining teeth are placed at the laboratory according to anatomic landmarks. Then the dentist returns the trial dentures to the patient for verification, personalization, and perfection. It is the responsibility of the dentist to prescribe requirements of tooth placement in detail if he uses the services of a dental laboratory technician.


A method of refacing cemented veneered crowns. A simple and efficient method has been described for refacing restorations without removing them from the mouth. The impression technique, fabrication of the facing, and its attachment to the crown were described.


A clinical evaluation of semiprecious alloys for dowels and cores. The semiprecious metals investigated and hard dental gold alloys may be manipulated in a similar manner. The semiprecious metals produced accurate and well-fitted dowels needing minimal adjustment. Being harder than type III gold alloy, they would be ideal for casting dowels and cores. Before considering these semiprecious alloys as final restorations, however, they must be further examined for resistance to tarnish and corrosion and their marginal adaptability and burnishability.


Nutrition analysis of prosthodontic patients. A program of nutrition training has been included in the undergraduate curriculum of the University of Washington School of Dentistry. Data obtained indicated that involved patients were receptive and that many showed improvement in dietary habits. Nutritional analysis and counseling can be introduced into a private-practice environment with very little increase in the dentist's work time. Procedures have been suggested that are efficient and effective. It is recommended that nutritional analysis and counseling be used routinely on all prosthodontic patients. This training should be included in the dental school curriculum so that students can become competent and comfortable in its use. To meet this objective, in-service training programs for faculty members are required. Careful attention to systemic factors such as nutrition will allow dentists to provide an enhanced level of care for patients. Concern for the general health of patients must continue to be a necessary part of prosthodontic care.


Construction of a crown to fit a removable partial denture clasp. This technique allows an accurate cast to be made of a prepared abutment tooth with the removable partial denture in place in the mouth. The partial denture is carefully removed from the cast, the crown waxed up, and the removable partial denture re-placed as many times as necessary during wax-up to obtain a crown that accurately fits the clasp.


Construction of a post and core to fit a completed restoration. A simple technique to fabricate a post and core to fit a completed restoration is described. This technique saves the time and effort of remaking the restoration when endodontic treatment and reinforcement of the tooth are required after construction of the restoration.


Coronary risk factor reduction through biofeedback-aided relaxation and meditation. The effects of behaviour modification through education and biofeedback-aided relaxation and meditation on the levels of blood pressure, pulse rate, smoking habits as well as serum cholesterol, triglycerides, and free fatty acids were studied in 18 normotensive, 18 smoking, and 22 hypertensive patients with 18 normotensive controls.The results showed significant reduction in blood pressure, in all the treated groups; highly significant reduction in the number of cigarettes smoked by smokers; and reduction in some of the lipids in all the treated groups, but particularly in the hypertensive group. The therapy appears to be feasible and suitable for wider application. This approach is economical, acceptable to patients, and should be explored further.


Prophylactic antibiotics for women undergoing vaginal hysterectomy. A triple-blind prospective study of women undergoing vaginal hysterectomy was conducted to compare cefazolin, cephaloridine and no antibiotic, Both cefazolin and cephaloridine were given preoperatively, whereas only cephaloridine was given postoperatively. One gram of cefazolin given intramuscularly on call to the operation room was found to be a safe and effective antibiotic for prophylaxis against febrile morbidity. The proper utilization of prophylactic antibiotics seems to be in the immediate preoperative period. The use of antibiotics after the first day of surgery is unnecessary.


Polyhydramnios and acute renal failure.

Polyhydramnios and acute renal failure. Two patients with acute renal failure in pregnancies complicated by polyhydramnios and multiple gestations are discussed. An acute increase in the size of the gravid uterus, overdistended with excess amniotic fluid, and a twin gestation were believed to have been related causally to the observed renal failure.


2-Deaminoactinomycin D, synthesis and interaction with deoxyribonucleic acid. 2-Deaminoactinomycin D has been synthesized and characterized. It binds to DNA by intercalation according to NMR, CD, thermal denaturation, and unwinding studies on the drug-DNA complex. Loss of the 2-amino group does not seriously affect binding parameters relative to actinomycin D; affinity for calf thymus DNA may even be increased, according to deltaTm measurements. The unwinding of circular DNA caused by this compound is at least as large as that effected by actinomycin D and ethidium bromide. Nevertheless, 2-deaminoactinomycin D is less effective than actinomycin D in inhibiting nucleic acid syntheses in L1210 cell culture and in in vivo antitumor activity against P388 leukemia.


Biologically oriented organic sulfur chemistry. 15. Organic disulfides and related substances. 41. Inhibition of the fungal pathogen Histoplasma capsulatum by some organic disulfides. In an extension of promising inhibitory results in vitro against Histoplasma capsulatum, correlated earlier using substituent constants developed by regression analysis with 77 disulfides, one symmetrical and 14 unsymmetrical disulfides were prepared (3--17). About half were active in vitro against H. capsulatum (and one against Candida albicans). Groups that seemed most to lead to promising inhibition among the unsymmetrical disulfides were o-HO2CC6H4, (CH2)4SO2Na, Me2NC(S), p-ClC6H4, and perhaps p-CH3C6H4; the first two also might be used to increase solubility. Earlier inhibitory promise of the morpholino group did not materialize. None of the group 3--17 was significantly active in vivo. The unsymmetrical disulfides were prepared by reaction of thiols with sulfenyl chlorides or with acyclic or cyclic thiosulfonates. Two six-membered heterocyclic disulfides (5 and 6) were prepared by a novel cyclization, in which carbon disulfide reacted with an (N-alkylamino)ethyl Bunte salt, followed by ring closure; an explanation is suggested for formation of a thiazoline when the N-alkyl group is absent. One of the disulfides disproportionated with astonishing ease (31; 0.3--1 h at 25 degrees C).


Biochemical typing of urinary Escherichia coli strains by means of the API 20 E enterobacteriaceae system. With the API 20 E Enterobacteriaceae system of biochemical testing, a biotype, coded numerically, was determined for each of 574 strains of Escherichia coli isolated from patients with urinary tract infection. The serotypes of the strains were also determined. Fifty-five different biotypes were identified, two accounting together for 42% of the strains examined and seven others each accounting for between 8.4 and 1.9%. There was little correlation between biotype and serotype. Fifty pairs of strains were isolated from patients before treatment. In 43 the biotype and serotype of both strains of each pair were the same. In six pairs the biotype, but not the serotypes, differed, the difference being limited to the results of the tests for lysine decarboxylase. The biotypes of the strains of the remaining pair differed widely although their serotypes were the same. It is suggested that this method of biotyping offers a simple but accurate way of discriminating between recrudescent urinary tract infection caused by E. coli and that due to reinfection.


Characteristics of antibiotic-resistant Escherichia coli in the rectum of healthy school-children. During a 3-year period, 771 rectal swabs were taken from abacteriuric school-children. Out of 709 E. coli strains, each isolated from one faecal specimen, 102 were found to be resistant to one or more antibacterial agents, and 607 to be fully sensitive. Another 204 resistant strains were found by selection for antibiotic resistance. The antibiotic-sensitive and the resistant strains were found to be two somewhat different populations, distinguished by a different distribution of O antigen types. Also, the K1 antigen was more common among the sensitive than among the resistant strains. Resistant strains that were not O typable were very seldom haemolytic.


The isolation and nature of campylobacters (microaerophilic vibrios) from laboratory and wild rodents. Faeces voided by eight species of laboratory or feral rodents were cultured for campylobacters by means of selective methods. Campylobacters were isolated from bank voles and from rats, but not from rabbits, laboratory mice, hamsters, guinea-pigs, field mice or field voles. In routine biochemical tests isolates from bank voles resembled a type of Campylobacter fetus that causes infectious infertility in cattle; isolates from rats resembled Campylobacter coli associated with swine dysentery. Electrophoretograms of acid plus phenol soluble proteins revealed striking differences between isolates from rodents, C. fetus and C coli. It is concluded that campylobacters are more widespread in rodents than hitherto realised, and that routine methods for differentiating campylobacters do not allow an adequate correlation with pathogenicity or habitat.


Depression of lactose hydrolysis by yeasts. To investigate the role that the known disaccharidase depression may play in the aetiology of infant gastroenteritis caused by Candida albicans, C. albicans and the rarely pathogenic, Saccharomyces cerevisiae were studied by three different methods. Both types of yeast significantly depressed the lactose-hydrolysis activity of beta-galactosidase, and both depressed lactose hydrolysis in the ligated small intestine of infant rabbits, either in intact animals allowed to survive for 10 h, or in a physiological bath for 20 h. The depression of lactose activity was not temperature dependent; living and inactivated yeast preparations produced comparable degrees of depression of enzyme activity. It is concluded that the depression of lactose hydrolysis is not a virulence factor of C. albicans, but contributes to the often observed disaccharide intolerance associated with candida gastroenteritis in infants.


Delayed foreign-body tumorigenesis in mice infected with lactate dehydrogenase-elevating virus: Brief communication. Female and male CBA/H mice were infected with lactate dehydrogenase virus (LDV). Two weeks later, these mice and noninfected controls received double sc implants of unplasticized vinyl chloride-vinyl acetate copolymer films (0.2 X 15 X 22 mm). Foreign-body (FB) tumorigenesis was delayed in LDV-infected females and males by 2 months. This result could not be explained by an effect of LDV on cellular immunity, inasmuch as cellular immunity does not influence the course of FB tumorigenesis.


Effects of mutations in the immunity system of bacteriophage P1. A mutant of bacteriophage P1 that made an altered c1 repressor is described. The mutant c1 product had two configurations: in lysogens, at high temperatures, it permitted constitutive expression of the normally repressed DNA replication function ban and was insensitive to the action of ant, a product expressed by the virulent mutant P1virs and by the heteroimmune phage P7 (formerly phiamp+) and normally able to overcome c1 repression; in mutant lysogens at low temperatures, the mutant repressor was apparently normal (able to repress ban and sensitive to ant action). Genetic studies of this mutant led to the isolation of a derivative that formed unstable lysogens. These studies suggested that the ban product was normally under c1 control; they further showed that ant overcame c1 repression by inactivating c1 rather than by creating a bypass of repressor activity.


Maintenance of bacteriophage P1 plasmid. Three mutants of bacteriophage P1 affected in their ability to maintain the lysogenic state stably are described here. These mutants were normal in lytic growth, but lysogenic derivatives segregated nonlysogens at abnormally high rates (1 to 30% per division). Cells harboring these mutant prophages were elongated or filamentous. The mutations responsible for this prophage instability fell into two classes on the bases of their genetic location, their effect on the ability to lysogenize recA bacteria, and their suppressibility by ant mutations eliminating antirepressor activity. The two mutants that were able to form recA lysogens showed the same prophage instability and partial inhibition of cell division in recA as in rec+ lysogens. The fact that plasmid-linked mutations can cause prophage instability suggests that P1 codes for at least some of the functions determining its own autonomy and segregation.


In vitro packaging of UV radiation-damaged DNA from bacteriophage T7. When DNA from bacteriophage T7 is irradiated with UV light, the efficiency with which this DNA can be packaged in vitro to form viable phage particles is reduced. A comparison between irradiated DNA packaged in vitro and irradiated intact phage particles shows almost identical survival as a function of UV dose when Escherichia coli wild type or polA or uvrA mutants are used as the host. Although uvrA mutants perform less host cell reactivation, the polA strains are identical with wild type in their ability to support the growth of irradiated T7 phage or irradiated T7 DNA packaged in vitro into complete phage. An examination of in vitro repair performed by extracts of T7-infected E.coli suggests that T7 DNA polymerase may substitute for E. coli DNA polymerase I in the resynthesis step of excision repair. Also tested was the ability of a similar in vitro repair system that used extracts from uninfected cells to restore biological activity of irradiated DNA. When T7 DNA damaged by UV irradiation was treated with an endonuclease from Micrococcus luteus that is specific for pyrimidine dimers and then was incubated with an extract of uninfected E. coli capable of removing pyrimidine dimers and restoring the DNA of its original (whole genome size) molecular weight, this DNA showed a higher packaging efficiency than untreated DNA, thus demonstrating that the in vitro repair system partially restored the biological activity of UV-damaged DNA.


Roles of the early genes of bacteriophage T7 in shutoff of host macromolecular synthesis. Through the use of phage mutants in which various combinations of the early genes are active, and in which late gene expression is blocked, we have examined the roles of each of the five early gene products of bacteriophage T7 in regulating the synthesis of host RNA and proteins. At least two independent transcriptional controls operate during bacteriophage T7 development. The product of gene 0.7, acting alone, leads to a rapid (by 5 min) shutoff of host transcription. In the absence of gene 0.7 function, and in the absence of the phage-specified RNA polymerase, a delayed shutoff of host-dependent transcription begins at approximately 15 min after infection. This secondary control element requires either a functional gene 0.3 or gene 1.1. In the absence of any early gene products, host shutoff is not observed until much later in infection (>30 min). The delayed manner in which the products of genes 0.3 and 1.1 exert their effect suggests that their mode of action is indirect. Under conditions in which the late genes are transcribed (inefficiently) by the host RNA polymerase, gene 1.1 is observed to stimulate the synthesis of lysozyme (the product of a late phage gene). In contrast, when the late genes are transcribed by the phage-specified RNA polymerase (the product of gene 1), the kinetics of synthesis of the phage RNA polymerase itself, and of lysozyme, are not affected by the deletion of genes 0.3, 0.7, 1.1, and 1.3. We conclude that under these conditions, the products of these genes are required neither for regulation of expression of the late genes nor for the shutoff of early phage gene expression.


Genetic and physiological control of host cell lysis by bacteriophage lambda. The timing of host cell lysis at the end of the lytic cycle of phage lambda is under complex control. The lambda S protein stimulates lysis. Another physiological system, the lysis regulator, inhibitis lysis from occurring prematurely. The effects of a series of phage and bacterial mutations on these controls are described. They show that the lambda rex gene plays a role in regulating lysis under suboptimal growth conditions. In certain mutant cells, and especially under anaerobic culture conditions, the rex gene aids in the scheduling of host cell lysis. The data also suggest that the lysis regulator may control the transition of the lambda S protein from an inactive to an active state.


Bacteriophage T4 virion dihydrofolate reductase: approaches to quantitation and assessment of function. This paper is concerned with the physiological role(s) of T4 phage-coded dihydrofolate reductase, which functions both in DNA precursor metabolism and as a virion protein. (i) We have detected enzyme activity in noninfectious particles produced under restrictive conditions by gene 11 mutants. This supports the conclusion of Kozloff et al. (J. Virol. 16:1401-1408, 1975) that the protein lies in the baseplate, covered by the gene 11 protein. (ii) We have obtained further evidence for virion dihydrofolate reductase as the target for neutralizing activity of T4 dihydrofolate reductase antiserum and as a determinant of the heat lability of the virion. This derives from our observation that the reductases specified by T4B and T4D differ in several properties. (iii) We have investigated several anomalous properties of T4 mutants bearing deletions that reportedly extend into or through the frd gene, which codes for dihydrofolate reductase. Evidence is presented that the deletions in fact do not extend through frd. These strains direct the synthesis of material that cross-reacts with antiserum to homogeneous dihydrofolate reductase. Moreover, they are all quite sensitive to the phage-neutralizing effects of this antiserum. In addition, they are restricted by several of the hospital strains, wild-type strains of Escherichia coli supplied by the California Institute of Technology group. (iv) We have attempted to detect dihydrofolate reductase among early-synthesized proteins present in T4 tails. Two such proteins are seen, one of which is evidently the gene 25 product and one that is a bacterial protein. Quantitation of our electrophoretic technique has allowed determination of the number of molecules of some T4 tail components present per virion. (v) Finally, we have compared the T4 dihydrofolate reductase with the corresponding enzyme specified by two plasmids conferring resistance to trimethoprim (Skold and Widh, J. Biol. Chem. 249:4324-4325, 1974). Although the enzymes are similar in some properties, they differ in several important respects, including immunological activity.


Localization of single-chain interruptions in bacteriophage T5 DNA I. Electron microscopic studies. Bacteriophage T5 DNA was examined in an electron microscope after limited digestion with exonuclease III from Escherichia coli. The effect of the exonuclease treatment was to convert each naturally occurring single-chain interruption in T5 DNA into a short segment of single-stranded DNA. The locations of these segments were determined for T5st(+) DNA, T5st(0) DNA, and fragments of T5st(0) DNA generated by EcoRI restriction endonuclease. The results indicate that single-chain interruptions occurr in a variable, but nonrandom, manner in T5 DNA. T5st(+) DNA has four principal interruptions located at sites approximately 7.9, 18.5, 32.6, and 64.8% from one end of the molecule. Interruptions occur at these sites in 80 to  90% of the population. A large number of additional  sites, located primarily at the ends of the DNA, contain interruptions at lower frequencies. The average number of interruptions per genome, as determined by this method, is 8. A similar distribution of breaks occurs in T5st(0) DNA, except that the 32.6% site is missing. At least one of the principal interruptions is reproducibly located within an interval of 0.2% of the entire DNA.


DNA modification of bacteriophage Mu-1 requires both host and bacteriophage functions. It was previously shown that resistance of phage Mu-1 to several restriction enzymes is due to a modification function (called mom) encoded by the phage. More recent studies emphasized that modification of Mu requires not only an active mom function, but also an active dam function supplied by the Escherichia coli host.


Renal artery stenosis in hypertensive renal transplant recipients. Reconstruction of a stenotic renal artery was done on 5 hypertensive renal transplant recipients, all of whom had deterioration of renal function when the stenosis was detected. After reconstruction renal function improved in 4 of the patients. The blood pressure was easier to control in all 5 patients, with 3 becoming normotensive. A high preoperative plasma renin activity returned to normal postoperatively in 4 patients. No recurrences were observed after a followup of more than a year.


Secondary involvement of the bladder in malignant lymphoma. A study of 599 patients who had died of malignant lymphoma between 1952 and 1972 revealed involvement of the bladder in 13 per cent. Bladder involvement was always a secondary event, occurred in association with disseminated disease and was more common in non-Hodgkin's lymphoma than in Hodgkin's disease. Direct infiltration from adjacent pelvic foci as well as discrete apparent metastatic foci was noted. Involvement was usually microscopic although the presence of gross disease was invariably clinically manifest. Cystoscopy and cystography were valuable in the diagnosis of gross lesions. In contrast to primary vesical lymphoma the treatment of secondary vesical lymphoma was symptomatic and an operation was indicated rarely. Local radiotherapy was effective in treating the symptoms of secondary vesical lymphoma.


Lack of specificity of lymphocyte-mediated cytotoxicity against the bladder cancer cell line, T24. We evaluated in vitro lymphocyte-mediated cytotoxicity against the T24 transitional carcinoma cell line and a control melanoma cell line (H894) in a double-blind study involving 25 bladder cancer patients, 19 patients with non-transitional carcinoma and 9 patients with benign conditions using a tritiated proline-labeled tumor cell assay. We found selective reactivity against T24 cells in 16 per cent of bladder cancer patients, 11 per cent of patients with non-transitional cell tumors and 22 per cent of patients with benign conditions. We found no significant differences with respect to the patterns of cytotoxic reactivity among the various patient groups. The use of different methods of lymphocyte purification and different lymphocyte to target cell ratios did not enhance the degree of specificity observed. Prior exposure to alloantigens did not account for the lack of specificity.


Dermal patch urethroplasty: experimental and clinical experience. Our experience with a dermal patch graft urethroplasty is presented in 10 Pitman-Moore minipigs. Histologic review at various post-urethroplasty intervals showed epithelialization of the graft. In addition, several cases in which this technique was used are presented with early followup. The advantages of dermal patch urethroplasty as well as the application of dermal grafts in other areas of the urinary tract are discussed.


The adverse effects of sperm during vasovasostomy. The 119 non-splinted vasovasostomies that were performed on 95 rats demonstrated that sperm granulomas were present in 99 per cent of the 49 anastomoses that failed. Anastomoses performed on vasa that contained no sperm resulted in 95 per cent patency without granulomas. This procedure was accomplished in immature animals followed to adulthood or by testosterone suppression of spermatogenesis in adult rats. Alternatively, normal adults with sperm in the vasa were irrigated with normal saline at the time of vasovasostomy and this resulted in decreased numbers of granuloma and dramatically improved success rates. Sperm granuloma formation appears to be an important cause of failure of vasovasostomy in the rat.


A medical history of the Spanish Habsburgs. As traced in portraits. From the 13th century untill well into the 20th, the Habsburgs were one of the great powers in Europe--for most of this time, the leading dynasty. To preserve the purity of the line, marriages between uncles and nieces, aunts and nephews, and cousins were commonplace. As a consequence, genetic complexities developed, and the famous prognathic "Habsburg jaw," among other noticeable traits, was passed down to succeeding generations. Never has a dynasty been so well documented in paintings, and their portraits provide an unusually complete series of medical illustrations that show the facial characteristics that marked the family in general. The observations are confirmed and extended by information from modern medical sources as well as from the medical records that date to the Habsburgs' own times.


Gram-negative sepsis with acute renal failure. Occurrence from acute glomerulonephritis. Acute intrinsic renal failure occurred in an adult patient with Escherichia coli septicemia. The clinical course did not include any of the circumstances usually present when acute renal failure complicates Gram-negative sepsis. A renal biopsy showed acute proliferative glomerulonephritis. There was no evidence to support other known causes of acute parenchymal renal failure, such as poststreptococcal glomerulonephritis, subacute bacterial endocarditis, or vasculitis. The patient recovered completely with antibiotic therapy, and renal function returned to normal within two weeks. An immunologic mechanism involving E coli was considered responsible for the acute renal failure.


Beclomethasone in steroid-dependent asthma. Effective therapy and recovery of hypothalamo-pituitary-adrenal function. Beclomethasone dipropionate was administered by aerosol to 30 patients whose chronic bronchial asthma required oral corticosteroid therapy. During the initial 12 weeks of the trial, beclomethasone therapy could be discontinued in 12 of 16 patients in contrast to only one of 14 patients receiving the inert aerosol placebo. Patients receiving the placebo were then given beclomethasone, and prednisone therapy was discontinued in five more. During six months of observation, adrenal function improved and steroid toxic reactions decreased in patients in whom oral corticosteroid therapy had been discontinued. Beclomethasone aerosol was generally well-tolerated. Asymptomatic thrush developed in four patients and rhinitis developed in ten patients as prednisone therapy was discontinued.


Sleep aids and sedatives.

Sleep aids and sedatives. Proprietary sleep aids and sedatives can cause delirium, coma and occasionally death in children and adults. The constituents in sleep aids that significantly effect central nervous system activity are bromides, methapyrilene, pyrilamine and scopolamine (hyoscine). Constituent proportions and mixtures vary greatly at different times since manufacturers make frequent adjustments. The effects of toxicity resulting from the misuse of ethylenediamines include nausea, vomiting, blurred vision, incoordination, tremors, dry mouth, constipation and an acute poisoning syndrome. Management of adverse reactions produced by either methapyrilene or pyrilamine consists of dosage reduction or discontinuation. The acute poisoning syndrome requires implementation of general symptomatic and supportive principles.


Accidental hypothermia.

Accidental hypothermia. Accidental hypothermia is an acute medical emergency with a high mortality rate. Physiologic derangements include hypoxemia, hypotension, acidosis, and arrhythmias. Management consists of careful monitoring rewarming, vigorous supportive care, and treatment of underlying and complicating disorders. Active core rewarming is recommended for hypothermia with associated cardiovascular insufficiency or instability and rapid core rewarming for hypothermia with cardiovascular collapse. Otherwise, passive or active external rewarming may be used. Good supportive care with correction of physiologic disturbances and vigorous treatment of underlying and complicating disorders are important in improving the survival rate.


The defense of the lung: studies of the role of cell-mediated immunity. The defense of the lung against infections, toxins and allergens is accomplished by an excretory transport mechanism and by the interaction of cellular and humoral defense systems. Pulmonary alveolar macrophages represent a common effector pathway for both nonspecific cellular phagocytic defenses and for specifically triggered cell-mediated immunity, via T lymphocytes. Nonspecific activation of macrophages is induced by toxic substances. Studies of the immunocytologic system indicate partial compartmentalization and "local" immunity for both cellular and humoral systems. Further studies on pulmonary cell-mediated immunity have characterized an amplification mechanism by which antigen-induced stimulation of T lymphocytes leads to recruitment of nonsensitive lymphocytes through the production of a low-molecular weight "transfer factor." Other lymphocyte-produced mediators (lymphokines) act to attract, aggregate and accumulate macrophages in areas of inflammation. In addition, macrophages are "activated" and show enhanced microbicidal capabilities as well as enhanced resistance to the cytotoxic effects of certain ingested microorganisms. It is postulated that cellular (nonspecific) and cell-mediated (specific) immune defenses play important roles in protection against several categories of microorganisms in a hierarchy of virulence.


Felty's syndrome: an analytical review.

Felty's syndrome: an analytical review. The clinical and laboratory features of 72 patients with Felty's syndrome described within the last ten years have been compared with Felty's five original patients. Felty's syndrome appears to be a variant of rheumatoid arthritis with extra-articular manifestations in which leukopenia (usually due to neutropenia) and splenomegaly occur, although not always at the same time. Both are manifestations of the underlying disease process and are not necessarily otherwise related. The mechanism of the leukopenia is complex and abnormalities in leukocyte function appear to be as important as the leukopenia in predisposing patients with Felty's syndrome to infection. Functional abnormalities of the leukocytes in this syndrome are due in part to immune complex formation. Hypocomplementemia associated with this process may be another cause for the increased susceptibility to infection. It is proposed, therefore, that therapy in Felty's syndrome be directed at the underlying disease process, and gold salts and penicillamine should be considered for this purpose. Splenectomy should be reserved for specific situations, such as hemolytic anemia, severe thrombocytopenia, leg ulcers, and infections associated with profound leukopenia that are not responsive to medical therapy.


The diagnostic process after 25 years.

The diagnostic process after 25 years. In the diagnostic process the first goal of the clinician is to obtain as clear a view as possible of the patient and the associated problems. The second is to conceptualize the patient's problems as disease categories, thereby making the diagnosis. Today we can perceive our patients and their problems in ways that physicians of the past never dreamed of. Major advances are being made with three noninvasive imaging techniques: nuclear medicine, computerized axial tomography and ultrasonics. Motion and change are the essence of the physiological approach to medical diagnosis, and medical images should be viewed as symbolic representations of the patterns and changes in the spatial and temporal distribution of the physical and chemical substances that make up our bodies.


[Prognosis of the outcome of myocardial infarct by means of the "KORA-3" program]. The authors prognosed the outcome of a macrofocal myocardial infarction by the data obtained during the first 3 days of the patients' stay in the hospital. The prognosing was done by using a specially prepared questionnaire adapted to the "KORA-3" identification programme. From among 35 patients freshly admitted to the hospital favourable outcome was forecast for 30 of them (of these 2 died) and unfavourable for 5 (of these 1 survived). On the whole the prognosis proved correct for 32 of 35 patients (91%). The applied method was more effective than prognosing after Schnur and made by physicians.


[Clinical value of the study of myocardial blood flow by the method of Xe133 clearance in ischemic heart disease]. The clearance of intracoronarily introduced 133Xe was employed in investigating the myocardial blood flow in 105 patients, 10 of whom--controls and 95 suffering from various manifestations of ischemic heart disease. Use was made of the biexponential calculation of the clearance curve by taking account of the fast (circulation in normal tissues) and slow exponent (circulation along the cicatricially-altered sections of the myocardium) contributions to the common "effective" myocardial blood flow. In patients with ischemic heart disease a reduction of the myocardial blood flow depending upon the severity of the clinical picture and the degree of the coronary arteries lesion was revealed. A direct correlational dependence between the initial state of the myocardial circulation at rest and the level of the physical efforts tolerance was educed. A conclusion is drawn that the determination of the myocardial circulation by the method of the 133Xe clearance following intracoronarily administration of the substance should be done by taking account of the slow and fast exponents of the clearance curve, these exponents reflecting the circulation in sections of the myocardium differing in their functional activity.


[Surgical treatment of occlusive lesions of the brahciocephalic trunk]. Surgery was performed on 41 patients for an occlusive process in the brachycephalic trunk. As concerns the clinical form of the occlusive process these patients were divided into 4 groups, viz. with symptomless occlusion--4, with transitory form--18, with chronic cerebro-vascular insufficiency--5 and with complete ischemic stroke--14. The diagnosis was established on the ground of routine clinical and instrumental examination findings. The authors consider an angiographic investigation of the patients to be indispensible. In the presence of an angiographically confirmed occlusion of the brachycephalic trunk the authors hold indicated reconstructive surgery in patients of all the mentioned clinical groups. As a basic type of the reconstructive operation is regarded resection of the trunk with prosthetics. The circulation could be restored in all of the patients operated upon. Late follow-up of the surgically treated patients (up to 10 years) proves that in the treatment of arterial insufficiency of the brain the reconstructive operation on the occluded brachycephalic trunk is a highly effective method.


[Fistulating operations with Walser's punch Modifications without scleral flap and with fixed or loose scleral flap (author's transl)]. Long term results of fistulating operations with Walser's punch are reported. A comparison between two methods without and with fixed scleral flap shows that the first method was more often associated with hypotonia, while the latter is more often followed by unsatisfactory pressure regulation necessitating additional drug therapy. That is why a third method of operation was developed. Here the scleral flap is shortened by scissors and not resutured to the sclera. The first clinical results indicate that the method makes use of the advantages of a scleral flap with less risk of an insufficient pressure regulation.


[Observations on cataract incision dehiscence (author's transl)]. 24 patients with rupturing corneal incisions were observed within 6 years from 1971 until 1976. 19 patients had already had cataract extractions performed by us. This complication occurred in 0.5% of cases. All ruptures were investigated regarding the period of time after the cataract extraction, and possible precipitating factors. 10X0 atraumatic nylon sutures were shown to be unsuitable for adaptation of corneal edges.


[Experiences of ear skin-cartilage transplants in tumors of the lid margin (author's transl)]. In cases of lid margin tumors operative procedures are preferred. If the defect after tumor excision is not more than 1/3 of the lid margin, plastic reconstruction is not done; in larger defects a free transplant is preferred to any kind of rotating plastic operation. An exception to this is the case in which the tumor is located on the whole lid margin or its surrounding area. The skin cartilage material taken from the ear or plastic reconstruction has proved satisfactory and in most of the operated 63 eyes satisfactory cosmetic and functional results have been obtained.


[Digital compression as an immediate measure in intraoperative expulsive hemorrhage. Clinical consideraitons and experimental investigations (author's transl)]. Following a short discussion of the predisposing and precipitating factors of an expulsive hemorrhage prophylactic measures are suggested. The authors review critically the recommendation of a posterior sclerotomy as a form of treatment, as proposed in the literature. They prefer an immediate wound closure by means of the index finger as suggested by Kasner. In a simple model using eye bank eyes as well as rabbits eyes they were able to show that at intraocular tensions of 100 mm Hg digital wound closure could be successively replaced by single sutures resulting in a watertight suture without loss of eye contents. For reasons of safety, digital wound closure is recommended as an immediate measure even in merely suspicious cases.


[The responsibility of medicine doctor (author's transl)]. Through the history of Medicine the author considers the mission of medical profession, its highs and downs. He specially analizes the responsibility of the doctors toward their patients. The author considers that anybody who is not able or self-sacrificed and has no true vocation, should no select the Medicine as his profession.


[The changing meaning of the term nephrosis since Noeggerath (author's transl)]. The term nephrosis has changed its meaning considerably since it was coined by Friedrich v. Müller. At the time of Noeggerath, whose 100 anniversary just has passed, nephrosis was defined by morphological terms describing various histological alterations of the renal tubuli which were considered to be degenerative. Today nephrosis is a clinical diagnosis, and usually called nephrotic syndrome. It is characterized by heavy proteinuria and hypoalbuminemia, and can be produced by various etiological causes. In pediatrics the most frequent type is lipoid nephrosis which is characterized by minimal glomerular lesions, negative immunofluorescence and steroid responsiveness. Patients with frequent relapses of lipoid nephrosis are difficult to handle by the physician, therefore the "International Study of Kidney Diseases in Children" and the "Arbeitsgemeinschaft für Pädiatrische Nephrologie" are conducting cooperative therapeutic trials, which results are mentioned briefly.


[Extramedullary tumor formation by acute myeloid leukoses in children (author's transl)]. In rare cases, leukoses can produce tumors before general symptoms and changes in the blood picture appear. Two boys were reported in whom tumors of the eye socket were removed, the tumors were histologically classified as myelosarcoma. During the course of several months, the clinical picture of an acute leukemia developed. The difficulties involved in the exact histologic recognition of myelosarcoma, its localization, the differential diagnosis of tumors of the eye socket in children as well as the therapy and prognosis for children with myelosarcoma were discussed.


[Effect of proscillaridin-4'-methylether on pressure rise velocity in the left ventricle of patients with coronary heart disease (author's transl)]. In a randomized, controlled, double-blind study 2 groups of 7 patients each with coronary heart disease received either 1 mg methylproscillaridin (MP) a cardiac glycoside of the squill intravenously, or placebo to test the inotropic effect of MP. Pressures and dp/dt max were measured in the left ventricle before and after coronary angiography after an average of 62 min (60 to 70 min). There was a significant (p less than 0.05) increase of dp/dt max in the MP-group (Wilcoxon-Mann-Whitney test). Left ventricular enddiastolic pressure was decreased from 16.1 to 13.6 mm Hg in the MP-group, and increased in theplacebo group from 12 to 13.7 mm Hg (mean values). Thus, a positive inotropic effect of the glycoside may be assumed.


The infectivity of drug resistant cases. The present study shows that leprosy bacilli resistant to dapsone, multiply in mouse foot-pad as equally as the dapsone sensitive bacilli would multiply suggesting that the dapsone resistant case will be as infective as the dapsone sensitive case.


Blood DDS levels and acetylation rates of sulphadimidine in leprosy patients. The plasma DDS clearance rates and the acetylation rates of Sulphadimidine were studied in a group of 30 leprosy patients comprising of 17 non-responders and 13 responders to DDS treatment. No differences in the acetylator type or in the plasma DDS clearance were seen between the responders and non-responders. Acetylation rate did not bear any relation to the plasma clearance of DDS in the non-responders. The findings indicate that the resistance to DDS therapy in these patients is not related to any abnormal metabolic disposition of DDS.


The problem of cultivation of Mycobacterium leprae: a review with criteria for evaluating recent experimental work. Some criteria are presented to help evaluate papers appearing in the literature claiming successful cultivation of M. leprae either in the absence or in the presence of tissue-cultured cells. Recently, electrom microscopic studies have definitely shown M. leprae to belong to the genus Mycobacterium and its division to occur through transverse section. A survey  is given of the mycobacterial strains isolated in the last 10 years from leprosy lesions. These strains belong to taxonomically different species and cannot be considered to be M. leprae. No substantial claim was made concerning the in vitro growth of M. leprae and the application of the tissue culture technique has been equally disappointing. The view is expressed that progress towards the in vitro cultivation of M. leprae can be made only as a result of increased knowledge about the intracellular environment and the metabolic activities of this organism, to be obtained by the application of modern biochemical and histochemical techniques.


A story completion approach as a measure of language development in children. A task employing a story completion approach was administered to 120 children who exhibited normal language development. Fifteen boys and 15 girls at four-, five-, six-, and seven-year age levels were tested. The test elicits 14 grammatical structures using 28 stories. Significant differences in structures did not occur between the sexes at any age level but males required more prompting. Significant differences in the total number of correct responses were established between the four and five year olds and between the five and six year olds but not between the six and seven year olds. Performance by age varied according to the grammatical structure. Simple structures were produced most accurately by the younger subjects while the more advanced ones were used by the older subjects. Discussion of results emphasized normal cognitive and language development as well as the clinical significance for the assessment of language behavior.


"Temperance tales". Antiliquor fiction and American attitudes toward alcoholics in the late 19th and early 20th centuries. Much of the American temperance fiction and graphics (the "Temperance Tales") of the mid-1800s to the early 1900s demonstrated a relatively sophisticated understanding of the progressive nature of alcoholism. In explaining the alcoholic process to the public, this fiction contributed to the general belief that the typical alcoholic was a Skid Row-like derelict.


Adjuvant role of radiation in soft tissue sarcoma in adults. Forty-seven patients with soft tissue sarcomas were analyzed retrospectively. Treatment was non-randomized between surgery alone, preoperative radiation of 5,000 rads/5 weeks, postoperative radiation of 6,000 rads/6 weeks following total gross tumor removal, and postoperative radiation (variable dosees) for residual gross or unresectable tumor. Preoperative radiation was not statistically better for local control or survival compared to postoperative radiation after local excision of gross tumor. Wide excision, higher postoperative radiation dosage, and/or enlarged radiation portals perhaps would improve results. Additional adjuvant therapies, such as chemotherapy or immunotherapy, needs to be investigated.


Five-year follow-up results of a collaborative study of therapies for carcinoma of the bladder. Results after 5 years of follow-up in a cooperative trial of therapies for operable bladder cancer confirmed preliminary indications of a beneficial effect of preoperative irradiation. Improved survival was experienced by the one-third of the irradiated patients who experienced complete eradication of the tumor as indicated from the resected specimen 30-60 days after a 30-day course of 4,500 rads. These patients had a 55% chance of surviving 5 years as opposed to a 32% chance for those where irradiation did not eradicate the tumor, or similarly for those not irradiated. A postoperative course of chemotherapy with 5-fluorouracial appeared to act detrimentally when given to patients irradiated preoperatively, but may have had a slight benefit when given after surgery alone.


The diffuse neuroendocrine system and the apud concept: related "endocrine" peptides in brain, intestine, pituitary, placenta, and anuran cutaneous glands. A number of peptides, closely related in terms of their amino acid sequences, have been found to occur in the gastroenteropancreatic system on the one hand and in the brain on the other. A common range of peptides links the pituitary gland and the placenta and 4 groups of peptides, found in anuran cutaneous glands, are related to the brain and intestinal peptides of mammals. The cells responsible for the production of these peptides, in whatever situation they occur, belong to the APUD ("Amine Precursor Uptake and Decarboxylation") series and they share a number of cytochemical and ultrastructural characteristics which reflect their functional similarities. It was originally suggested that the production of common peptides could be explained on the basis of the origin of the cells from a common ancestor. It is now postulated rather that, being derived at different periods of time from the embryonic epiblast--or perhaps, more accurately, ectoblast--they share a common neuroendocrine programme which is manifested by their possession of the acronymous amine-handling characteristics of the series and whose final expression is determined by microenvironmental circumstances. The APUD concept thus links together a whole spectrum of peptides some of which are hormones, or local hormones, others neurotransmitters and yet others probably exotoxins. Its implications are widespread, and far reaching, affecting most disciplines in the field of medical biology.


Scanning electron microscopy of surface changes on dispersed pancreatic beta-cells following stimulation of insulin release. The surface structure of isolated, viable beta-cells was studied by scanning electron microscopy. Suspensions of islet cells wuse. Cells incubated with and without D-glucose were fixed while in suspension, filtered onto Nucleopore filters and prepared for scanning electron microscopy by the critical point drying procedure. After incubation in glucose-free medium the cells were spherical with surface blebs and occasional small pits. Cells stimulated with 20 mM D-glucose and 0.1 mM 3-isobutyl-1-methyl-xanthine exhibited a two-fold increase in the number of blebs and in insulin release. The increased number of blebs was still seen in a Ca++ deficient medium, and may, therefore, not necessarily reflect an insulin extrusion phenomenon. It is concluded that D-glucose induces alternations of the surface morphology in isolated beta-cells in suspension.


Medicaid utilization of services in a prepaid group practice health plan. To provide medical service at lower costs without diminishing either quality or coverage, the District of Columbia enrolled approximately 1,000 Medicaid beneficiaries, voluntarily, in a prepaid group practice (PGP). The project was evaluated over a three-year period (1971-1974) with regard to: 1) rate of utilzation of medical care before and after enrollment; 2) costs of care per capita as compared with those of the 160,000 beneficiaries in the Medicaid fee-for-service universe; and 3) patient satisfaction with the PGP. Results indicate that for the 834 individuals aged 1 through 64 enrolled in the PGP; ambulatory physican encounter rates decreased 15 per cent, drug utilization was down 18 per cent, hospital admissions decreased 30 per cent, and hospital days declined 32 per cent after enrollment. For the same benefit package, annual prepaid per capita costs for the Medicaid PGP enrollees for 1972, 1973, 1974 were only +282, +232, and +286 respectively, representing a 37 per cent saving when compared to the fee-for-service per capita costs of the Medicaid Universe which stood of +373, +435 and +465 over the same period. The instrument used to probe patient satisfaction showed the Study Group was satisfied with the PGP, and received better dental care. The voluntary dropout rate from the PGP was only 2.5 per cent; and out-of-plan utilization was low, indicating good acceptance of the PGP service.


The affinity and spectrum of cross reactivity of antibody production in senescent mice: the IgM response. Experiments were performed to determine whether the IgM component of the primary humoral immune response of senescent mice differs from that of young-adult mice in its affinity, specificity or heterogeneity. For this purpose, mice were immunized with the T-dependent antigen, TNP-KLH, or the T-independent antigen, TNP-LPS. Affinity and specificity of the anti-TNP response were studied at the cellular level by the plaque inhibition technique using the cross-reacting haptens TNP-epsilon-aminocaproic acid )TNP-EACA),DNP-EACA and ONP-EACA. It was found that when the immunogen was TNP-KLH, the peak IgM response was delayed in senescent animals by several days as compared to the response in young adults. However, the number of PFC on the day of peak response was comparable. No age related delay in the peak of response was detected when the antigen was TNP-LPS although the magnitude of response was reduced in old age. The average affinity of the plaque forming cell responses to both immunogens is comparable in young and old mice.


Specific immunotherapy with neuraminidase-modified leukemic cells: experimental and clinical trials. The data presented establish the therapeutic effectiveness of immunotherapy with neuraminidase-treated allogeneic myeloblasts in combination with sustaining chemotherapy in patients with acute myelocytic leukemia. The in vivo and in vitro immunologic tests indicate normal immunocompetence in patients receiving immunotherapy versus control patients treated with chemotherapy alone. These findings correlate well with the improved duration of remission as the direct result of the immunotherapy.


Platelet transfusion therapy.

Platelet transfusion therapy. Platelet transfusions are of unquestionably proven benefit for the correction of thrombocytopenia or functional platelet disorders, and they have allowed for more intensive antineoplastic therapy. With the advent of blood component therapy most modern blood banks now have the capabilities for supplying at least limited quantities of platelets. Refinements in procurement methods will inevitably lead to a greater supply of platelets and the establishment of larger transfusion programs. These programs will need to incorporate facilities for platelet storage, recruitment of suitable donors, selection of special donors for refractory patients, and methods for quality control. As antineoplastic therapy becomes more aggressive, such transfusion programs will become an integral part of the operation of cancer treatment centers.


[Focal epidermal necrolisis. A variation of lupus erythematosus of a new disease?]. Four cases with clinical characteristics closely related to Lupus Erythematosus Disseminatum are reported by the authors. The evolution, progress and the biochemical, immunological and photobiological data were different from those usually found in L.E.D. The histopathological picture was also dissimilar, the most characteristic finding being a sharply limited epidermal necrolysis with focal distribution. In view of the peculiarities of the clinico-pathological syndrome presented by these patients, the authors raise the questions does it represent a special modality of L.E.D. or a new lupus-like disease?


Use of implantation in facial deformities. Augmentation of facial defects remains an area of challenge and controversy. Advocates of alloplastic implants cite the convenience of prepackaged materials, which they feel outweighs the possibility of rejection. Those favoring autografts prefer their long-term predictability, but must contend with resorption and the disadvantages of obtaining the implantation material. The use of supramid mesh may combine the advantages of allopasts with the long-term predictability of autografts after fibrous ingrowth has occurred. Our experience over the past 4 years in 164 cases indicates that supramide mesh may represent a significant advance in augmentation of facial deformities.


Sterol mutants of Saccharomyces cerevisiae: chromatographic analyses. The sterols accumulated by ergosterol deficient mutants of the genes erg6, erg2, erg3, and erg5 (formerly po11, po12, po13, and po15) have been analyzed by gas liquid chromatography. Together with pure sterols obtained from the mutants, they were characterized on SE-30, OV-17, and OV-225. The effects of molecular structure on the retention characteristics of a range of C28 ergostane sterols have been studied. The double mutants obtained by crossing the single mutants were also analyzed and their sterols identified where possible. The effects of the erg mutations on the control of sterol biosynthesis in yeast are discussed.


Accumulation of ergosta-8,14-dien-3beta-ol by Saccharomyces cerevisiae cultured with an azasterol antimycotic agent. 15-Aza-25-methylene-D-homocholesta-8,14-dien-3beta-ol, an antimycotic agent, at a concentration of 75 ng/ml inhibited ergosterol biosynthetis in Saccharomyces cerevisiae strain 3701B resulting in the accumulation of an unusual sterol. Experimental data presented indicate that this sterol is ergosta-8,14-dien-3beta-ol. The accumulation of the compound is supportive of current models of biosynthetic pathways for sterols in yeast and is consistent with inhibition by the azasterol of the delta14 sterol reductase.


Alkaloids of Thalictrum. XXI. Isolation and characterization of alkaloids from the roots of Thalictrum podocarpum. Thirteen alkaloids, hernandezine, thalidezine, N-desmethylthalidezine, isothalidezine, thalistyline, thalistyline methodiiodide, N-desemethylthalistyline, berberine, columbamine, jatrorrhizine, palmatine, thalifendine, magnoflorine and the artifact, 8-trichloromethyldihydroberberine were isolated from the roots of Thalictrum podocarpum Humb. In addition, oxyberberine and thaliglucinone were obtained in very minor amounts and identified by tlc. Of these compounds, N-desmethylthalidezine and isothalidezine are new bisbenzylisoquinoline alkaloids. Sucrose was isolated from the alcoholic extract.  Hernandezine, thalistyline, thalidezine, thalistyline methodiiodide and N-desmethylthalistyline were found to possess antimicrobial activity against Mycobacterium smegmatis at concentrations of 100 microgram/ml or less.


[Study of the sequential stages of Proteus vulgaris L-transformation by scanning electron microscopy]. Consecutive stages of L-transformation caused by penicillin in Proteus vulgaris were studied, from spheroplasts and unstable, easily reversing L-forms to stable L-forms which did not reverse. To maintain natural topography of the culture on the growth medium, millipore filters were placed on the surface of the medium and then were fixed with the culture. All the main elements of L-cultures were found at the stage of spheroplast formation, before the first passage onto the medium for cultivating L-forms, i.e. spherical cells having a diameter from 3.5 to 1 mcm, elementary bodies 1.0-0.6 mcm large, filamentous structures with a diameter to 4 mcm, large bodies having dimensions of 20 mcm and more, and "cell-free" masses. The composition of the structural elements and their reproduction are supposed to be almost the same in the bacterial culture and L-forms at the stage of spheroplast formation.


Catecholamines cause the hypercalciuria and hypercalcaemia in phaeochromocytoma and in hyperthyroidism. Catecholamines induce bone resorption and hypercalcaemia by the beta-adrenergic effect in bone and hypercalciuria by the alpha adrenergic effect in kidney. The interplay between the alpha-adrenergic hypercalciuria and beta-adrenergic hypercalcaemia explains why in some, but not all, phaeochromocytomas hypercalcaemia occurs. The hypothesis predicts hypercalciuria in both phaeochromocytoma and neuroblastoma. In hyperthyroidism, negative calcium balance and hypercalcaemia cannot be attributed to the direct effect of thyroid hormones on the bone but can be explained by augmentation of the catecholamine effects on bone and kidney by thyroid hormones. The hypothesis offers a solution for an apparent paradox in hyperthyroidism of increased urinary cAMP while nephrogenous cAMP is decreased. It also explains why propranolol corrects hypercalcaemia without influencing renal calcium loss.


The problem of human protein requirements: some kinetic and metabolic considerations. Estimated human protein requirements have been substantially lowered by FAO/WHO expert committees over the past two decades. The estimates and methods of calculation are considered in the light of the kinetics of response to protein intake, body protein turnover, amino acid flows in the body, and the concept of nitrogen (N) steady state. Whereas traditional methods of estimation have assumed an essentially linear (first order) response of N retention to absorbed N, animal studies show that response to graded protein intakes obeys saturation kinetics. Corrections for protein quality have also assumed a linear relation between response and supply of limiting amino acid, while animal experiments indicate that this response likewise follows saturation kinetics. Evidence is lacking that the present minimum protein standards for humans can support acceptable internal nitrogen steady states at any age above infancy or foster normal growth in the child. New research approaches to determination of protein requirements are suggested , including study of the kinetics of human response to graded protein intakes and graded variations of quality; development of indicators of nitrogen steady state and correlation with clinical status; and determination of optimum protein-energy ratios by age and sex.


Serratia: opportunistic pathogen of increasing clinical importance. Serratia marcescens can become a formidable nosocomial (hospital acquired) pathogen, and is reported increasingly in the world literature. However, it is only a recently recognized problem in Australia. Serratia can carry an antibiotic-resistance plasmid, and, after entry of the organism into very sick patients, it may be hard or impossible to eliminate. Initial experience of Serratia in 34 consecutive cases isolated in a three-months period is presented. Rapid increase in the number of Serratia infections occurred after the appearance of a resistant strain. Urinary infection was the commonest presentation (91% of cases). The presence of an indwelling urinary catheter in a debilitated patient was the major predisposing factor. Significant bacteraemia followed in four cases with one death. Contamination of burns (surfaces) and surgical wounds was found in four cases. Serratia strains were found to be highly resistant to most antimicrobial agents in routine sensitivity testing, 20% being fully resistant to all tested agents, and nalidixic acid being the most effective inhibitor in the remainder. With bacteriocin typing of Serratia, two types were found to be dominant. These two bacteriocin types were not identified among strains isolated from other sources such as soil, water and local hospitals. Pharyngeal carriage was found in only one case, but faecal excretion of Serratia was found in 11 cases and may be a significant portal of dissemination. Cross-infection from a hospital reservoir of resistant organisms is postulated. A model of cross-infection is also proposed, and methods of control are discussed. In view of the established danger of Serratia in the hospital setting, its isolation can no longer be ignored.


Atavistic regression as a factor in the remission of cancer. It is suggested that the atavistic regression of the mind in intensive meditation is accompanied by a similar physiological regression, and that this may involve the immune system and so influence the patient's defences against cancer.


Methadyl acetate versus methadone: the experience of one hospital. Sixty subjects participated in a double-blind study comparing methadyl acetate (80 mg) with two dosages of methadone (50 mg and 100 mg) in the maintenance of opiate addicts. The safety of all three regimens was supported and methadyl acetate was as effective as methadone in the retention of subjects.


[On the effect of d,l-kavain: experience with neuronika (author's transl)]. To test kawa-pyron L,D-Kavain, one of the constituents of the kawa-rhizom, a double blind study was carried out. 84 paticipants suffering from vegetative symptoms were selected according to Eysenck's personality inventory (MMQ). The first group of 32 were between 20 and 40, the second between 30 and 55 years of age. Each group was diviided into a kavain group and a placebo group. Treatment consisted of 2 capsules per day (with 200 mg kavain in each capsule) respectively 2 placebo for the memebers of the control group. The program testing the effects of treatment was controlled by measurements of memory functions, vigilance, fluency of mental functions, reacton time, and of circulation functions controlled by ergometer (100 watt). We registered a continuous increase in the psychophysical parameters mentioned above during the 3 weeks of treatment. There was no difference between younger and older persons.


Evaluation of two test-kits--API and Oxi Ferm tube--for identification of oxidative-fermentative Gram-negative rods. Two test-kits--API and Oxi Ferm tube--have been compared for accuracy in individual tests and for identification on the genus or species level with conventional biochemical tests on 154 oxidative-fermentative gram-negative rods. The two test systems were found to be reliable and permit identification of the clinically most significant oxidative-fermentative strains.


Special O:K:H serotypes among enterotoxigenic E. coli strains from diarrhea in adults and children. Occurrence of the CF (colonization factor) antigen and of hemagglutinating abilities. O:H serotypes previously found to be prevalent among a number of toxigenic strains from several geographic areas were examined for polysaccharide K antigen type. Members of each O:H serotype had the same type of K antigen and were found to be characterized by a certain fermentation pattern. Some O:H serotypes had no K antigen. The serofermentative types defined were: 06:K15:H16, 08:K40:H9, 015:H11, 025:K7:H42, 025:K98:H-, 078:H11, 078:H12, and 0149:H10. Some strains of the last-mentioned serotype, which were suspected of having caused a food-borne infection, had K88. This serotype belongs to the group of strains causing diarrhea in swine. The surface antigen (CF) described as a colonization factor [5] was demonstrated in 078:H-, 078:H11, and 078:H12 strains; but not in any strain of the other serotypes nor in any of 248 strains belonging to 078 but not isolated from cases of human diarrhea. Presence of the CF antigen was correlated with presence of a mannose-resistant ability to cause agglutination of human red cells. Behavior of the other serotypes as regards hemagglutinating abilities was examined and 025:K7:H42 strains were found to be very similar to the 078 strains in this respect.


Review: ion-selective electrodes in clinical chemistry. The theoretic framework of electrode systems and numerical data for use in serum analysis is given. Original literature and recent applications to serum analysis are compiled for different types of sensors. The interactions of various effects and their relevance in the context of the precision that newer instrumentation offers are discussed. Specifically, the following topics are treated: response to interfering ions (Nicolsky Eq.), concentration to activity conversion (Debye-Hückel formalism), and liquid-junction potentials (Henderson Eq.); Debye-Hückel parameters, selectivity factors, and physiologic activity ranges; solid-state, liquid-membrane, and special electrodes; flow-through systems, precision, and stability.


Radiation scattering and the determination of regional cerebral blood flow by radioisotope clearance. The sources of error involved in the measurement of regional cerebral blood flow (rCBF) with radioactive tracers in man have been studied. This report shows that one of the main sources is the weakness of the energy emitted by the tracers used. Clearance curves obtained with scalp detectors are subject to interference: the radiation measured originates not only in the region studied but also, by scattering, from the rest of the brain. Because of the weak energy levels involved, the scattered radiation contributes significantly to the total measured radiation, and for the same reason it is impossible to distinguish clearly the scattered radiation from that arriving directly. These systematic errors in rCBF measurements were studied quantitatively by in vitro tests and computer simulation, and limits were established for resulting alterations of all varialbes determined (grey and white matter flow, mean flow, compartment weight). It was concluded that the biologic origin of a modification of rCBF can be affirmed only in the case of changes of at least 10%.


Formation of recombinant DNA of bacteriophage lambda by recA function of Escherichia coli without duplication, transcription, translation, and maturation. Genetic recombination of phage lambda DNA mediated by Rec function of Escherichia coli was studied in the absence of duplication, transcription, translation, and maturation. Cells were jointly infected with double amber mutants, lambda D-F-I and lambda S-R-, and incubated in the presence of chloramphenicol and rifampin. The am+ recombinant DNA molecules formed within the cell were detected by in vitro packaging as viable recombinant phages. This system was used to measure the recombination activity of rec- bacteria. In recA or recA recB bacteria, the number of recombinant DNA molecules was about 1% of the rec+ level. In contrast, almost normal numbers of recombinant DNA molecules were formed in recB or recC cells. Therefore, (1) the recombination mediated by recA function does not need de novo protein synthesis; all gene products required for the recombination are present in the cell. (2) It can occur without duplication, transcription, and maturation of recombining DNA molecules. (3) The ATP dependent DNase (exonuclease V) controlled by recB and recC genes is not required for formation of recombinant DNA molecules.