Use of fructose, sorbitol, or xylitol as a sweetener in diabetes mellitus. Non-nutritive sweeteners have been utilized in the diet of diabetic patients as agents to replace glucose and sucrose. Since saccharin might be removed from the market place, the nutritive sweeteners, fructose, xylitol, and sorbitol, are being considered as possible atlernatives. This review considers the effects of these nutritive sweeteners on the main dietary concerns in the diabetic diet, i.e., control of blood glucose levels, obesity, and hyperlipidemia. The potential side effects of these agents are also reviewed.


Appraisal of codeine as an analgesic in older patients. In an investigation of a new oral analgesic agent, codeine was chosen as the reference drug because of its established reputation as an effective agent for the relief of pain. Thirty-five patients with cancer pain were studied. Their average age was 58 years, During a 5-day hospital stay they received, on each of three days, either codeine (120 mg or 60 mg) or placebo. At hourly intervals after ingestion the nurse observer collected data on pain intensity and the degree of pain relief, and the patients independently charted the hourly intensity. Statistical analysis failed to show any significant superiority of either dose of codeine over placebo. Moreover, codeine is known to have a constipating effect. Re-appraisal of the value of codeine as an analgesic agent in elderly patients seems justified.


Prentice in Lahr and Karlsruhe.

Prentice in Lahr and Karlsruhe. Charles F. Prentice's father was born in England and his mother in Germany. Charles' boyhood days were spent chiefly on Staten Island, New York. At age 16 he attended "Gymnasium" in Lahr, Germany. his mother's ancestral hometonw. During the three subsequent years he studied mechanical engineering at the institute now known as the University of Karlsruhe, West Germany. Illustrations include scenes in Karlsruhe and Lahr and transcripts of his academic records.


Infections following clenched-fist injury: a new perspective. Fifteen cases of clenched-fist injury were studied by aerobic, anaerobic, and 10% CO2 cultures. Anaerobic bacteria and Eikenella corrodens were prominent pathogens, being recovered in 60% and 20% of cases, respectively. These organisms are more susceptible to penicillin than to penicillinase-resistant penicillins or cephalosporins. All clenched-fist injuries should be cultured in aerobic, anaerobic, and 10% CO2 atmospheres. We recommend the use of both penicillin and a penicillinase-resistant penicillin as initial empiric therapy.


Correlation of phaga type, biotype and source in strains of Salmonella typhimurium. A series of 2092 cultures of Salmonella typhimurium isolated from human, animal and other sources in 57 countries were differentiated into 204 phage types and 19 primary and 147 full biotypes. Different biotypes belonged to the same phage type and different phage types to the same biotype, so the combination of typing methods differentiated strains more finely than either method alone: 574 different ;phage type/biotypes' were distinguished in 1937 cultures belonging to the 204 recognized phage types.The combination of biotyping with phage-typing was valuable in studying the phylogeny and spread of epidemic strains by distinguishing clones of different biotype within the same phage type and by confirming the relationship between cultures isolated from widely dispersed clones and that between cultures isolated before and after a clone had undergone variation in phage type, biotype, colicin type or antibiotic-sensitivity pattern.A widespread outbreak of infection with S. typhimurium phage type 141 in Scotland comprised independent dissemination of three clones of different biotypes, 1f, 9f and 31bd. During its epidemic spread in cattle in Britain between 1962 and 1969, another strain underwent variations in phage type (type 44 to type 29), biotype (type 26a to types 26d, 26bd, 26dgi, 26dz and 26i) and antibiotic sensitivity. A group of 275 non-fimbriate, non-inositol-fermenting and non-rhamnose fermenting (FIRN) strains, particularly associated with avian infections and thought to be clonal in origin, contained 27 phage types and 22 full biotypes in the primary biotypes 29-32.


Refractoriness to migration inhibitory factor of macrophages of LPS nonresponder mouse strains. The responsiveness to macrophage migration inhibitory factor (MIF) of peritoneal exudate cells (PEC) from the LPS unresponsive C3H/HeJ and C57BL/10ScCR mice was assessed by the indirect agarose microdroplet macrophage migration inhibition assay. No migration inhibition with PEC from C3H/HeJ nor C57BL/10ScCR mice was detected, whereas PEC from both C3H/HeN and C57BL/10Sn mice were significantly inhibited by even a 1/32 dilution of MIF-containing supernatants. Responsiveness to MIF of C3H/HeJ PEC could, however, be induced. In vivo inoculations of Mycobacterium bovis, strain BCG, 7 days before in vitro assay rendered C3H/HeJ PEC responsive to MIF. The lack of responsiveness to MIF by C3H/HeJ PEC appeared related to some form of suppression, since a mixture of PEC from C3H/HeN mice with 10 to 15% PEC from C3H/HeJ mice resulted in undetectable migration inhibition at any MIF dilution. In contrast to the usual lack of responsiveness of their macrophage to MIF, C3H/HeJ mice were able to produce MIK in response to PPD as well as their counterpart C3H/HeN mice after BCG sensitization. These results demonstrate that macrophages from C3H/HeJ and C57BL/10ScCR mice are unable to be inhibited in their in vitro migration of MIF (possibly being directly or indirectly influenced by a suppressor cell), whereas lymphoid cells from at least one of these strains, the C3H/HeJ mice, can produce MIF in response to antigenic stimulation.


Guinea pig macrophage agglutination factor is antigenically distinct from migration inhibition factor and immunoglobulin. Lymph node cells from guinea pigs with specific delayed hypersensitivity release macrophage agglutination (MAggF) and migration inhibition factors (MIF) upon exposure to antigen or concanavalin A in serum-free medium. MAggF in culture supernatants was absorbed neither by immunoabsorbents made with a rabbit anti-guinea pig lymphokine serum that removed MIF, nor by immunoabsorbents made with rabbit anti-guinea pig Ig. These results suggest that MAggF is antigenically distinct from MIF and Ig.


Induction of B cell priming by neonatal injection of mice with thymic-independent (type 2) antigens. Mice injected at birth with the thymus-independent type 2 antigen TNP-AECM-Ficoll have augmented anti-TNP antibody responses when their spleen cells subsequently are challenged in vitro with TNP-coupled thymic independent or thymic dependent antigens. This neonatal priming effect was shown to occur in neonatal nu/nu mice and thus does not appear to require T lymphocytes. The primary explanation for the priming effect seems to be an increase of approximately 10-fold in the numbers of TNP-specific precursors of antibody-forming cells. The neonatal injection of TNP-AECM-Ficoll induces little or no antibody formation directly. It appears, therefore, that some thymic independent antigens can deliver a signal to immature B cells, which causes clonal expansion, but is unable to induce differentiation into antibody-forming cells.


A sensitive haemolytic assay of mouse complement. Under appropriate conditions the haemolytic activity of mouse complement can be measured in a 51Cr release assay. Modifications that increase the sensitivity are the following: (a) mouse 7 S anti-SRBC antibodies as amboceptor; (b) low amount of target cells; (c) ionic strength of 0.13 M NaCl in the test medium; (d) incubation temperature of 30 degrees C; (e) incubation time of 90 min; (f) total reaction volume of 1 ml.


Detection of antisalivary duct antibody from Sjögren's syndrome by an autoradiographic method. A new technique to detect anti-salivary duct antibody (ASDA) has been developed by using autoradiographic, rather than immunofluorescent methods. The antibody activity detected by autoradiography is probably classic ASDA. Both techniques may be consecutively performed on the same tissue section without attenuation of either. Some of the potential advantages of the radiolabelling of ASDA are pointed out, and a few preliminary experiments using the labelled antibody as a marker are presented.


A fluorescent immunoassay for the quantification of C-reactive protein. A sensitive fluorescent binding immunoassay (FBIA) was developed for measuring C-reactive protein (CRP), at a level of 20 ng/ml, in human and mouse sera. The advantages of the FBIA over radioimmunoassays are the long shelf-life of the FITC-labelled antibody, the re-use of the antibody bound microbeads, the short assay time and the use of inexpensive instruments.


Quantitative immunofixation of proteins following zone electrophoresis in agarose gel: application to the determination of the stoichiometry of the alpha1-antitrypsin-elastase interaction. A method for the quantitative determination of proteins by immunofixation-agarose gel electrophoresis is described. The proteins are separated electrophoretically and the resulting circular zone overlaid with specific antibody-impregnated filter paper (10.2 microliter/cm2). Following incubation for 20 h at room temperature the plates were processed, stained and the areas of the precipitin zones determined by planimetry. Intra-plate variation (coefficient of variation) for alpha1-antitrypsin (30 samples) and elastase (30 samples) at concentrations of 0.25, 0.5 and 1.0 mg/ml was 2.2--5.8% and inter-plate variation ranged from 2.9% to 5.2%. Overall, the analyses showed that the method is the statistical equivalent of rocket immunoelectrophoresis. The lowest concentration used was 0.25 mg/ml which corresponds to a sensitivity of 1.25 microgram (5 microliter per sample well). It is conceivable that lower amounts could be successfully determined. Application of the method to the determination of stoichiometry of the alpha1-antitrypsin--elastase interaction permitted the simultaneous quantitative determination of inactivated alpha1-antitrypsin (an acidic protein) and excess elastase (a basic protein) in alpha1-antitrypsin--elastase reaction mixtures (molar ratio elastase/alpha1-antitrypsin = 1.3) and thus by difference, the amount of elastase and and alpha1-antitrypsin in the alpha-antitrypsin--elastase complex. The results showed that the molar combining ratio of inhibitor to enzyme was 1.086 : 1 or 1 : 1. Conventional inhibition experiments (residual elastase activity as a function of increasing amounts of alpha 1-antitrypsin) showed this ratio to be 1.79 : 1 but 1.03 : 1 when the inactivation reaction, as determined by quantitative immunofixation, was taken into account. The quantitative immunofixation method should be applicable to interacting systems which, like elastase and alpha1-antitrypsin, result in complexes with electrophoretic mobilities intermediate to the parent proteins.


Reactive hyperemia in cutaneous tissue in generalized scleroderma. Reactive hyperemia following ischemia in cutaneous tissue of human fingers was studied in 6 normal persons and 9 patients suffering from generalized scleroderma. Ischemia lasting 6 or 12 min was induced by inflating a cuff placed around the proximal phalanx to 300 mm Hg. Blood flow was measured by the local atraumatic 133Xenon wash-out technique. The following parameters were calculated: (1) Maximum blood flow was calculated from the steepest part of the wash-out curve following release of the cuff. (2) Excess cumulative blood flow, i.e., the integrated blood flow from release of cuff until preischemic blood flow values were obtained, minus preischemic blood flow times duration of ischemia. (3) Repayment, i.e., excess cumulative blood flow in percent of preischemic blood flow times duration of ischemia. Maximum blood flow, excess cumulative blood flow and repayment was decreased in the patients compared to normals. This might be due to structural changes of the blood vessel walls and/or functional changes of the vascular smooth muscle cells in scleroderma.


Transfer of erythromycin resistance from clinically isolated lysogenic strains of Streptococcus pyogenes via their endogenous phage. Endogenous bacteriophage from clinically isolated, erythromycin-resistant strains of Streptococcus pyogenes, upon induction by treatment with mitomycin C, were demonstrated to cause transduction of antibiotic resistance yielding transductants resistant to relatively high concentrations of erythromycin. Transduction of resistance to erythromycin via endogenous phage may play a significant role in the emergence of streptococci with multiple resistance in the clinical environment.


Wound infections due to group A streptococcus traced to a vaginal carrier. An epidemic of surgical wound infections caused by group A Streptococcus affecting 18 patients in a community hospital was studied. Onset of symptoms shortly after surgery (median time, 16 hr) in 17 patients suggested acquisition of infection in the operating room, and a case-control investigation linked the presence during surgery of one particular nurse with postoperative streptococcal infection. During the first month of the epidemic, the nurse had streptococcal cellulitis of the finger and may thus have directly contaminated wounds or dressings. However, the last six wound infections occurred after her skin lesions had resolved and after nasopharyngeal and skin cultures were repeatedly negative for group A streptococci. Subsequent investigation showed that the nurse was colonized vaginally with group A streptococci of the same M and T types found in the infected patients and that this organism was disseminated into her immediate environment by airborne or droplet spread. Vaginal as well as rectal carriers of streptococci should be sought whenever outbreaks of streptococcal wound infection in which a cutaneous or nasopharyngeal carrier cannot be readily identified.


Analysis of increasing antibiotic resistance of Klebsiella pneumoniae relative to changes in chemotherapy. Three antibiotic-resistant strains of Klebsiella pneumoniae responsible for outbreaks of systemic infection in a hospital nursery were analyzed. Each organism emerged after prolonged use of a drug to which it was resistant. The first strain (RO16) produced neomycin phosphotransferase and contained three plasmids with molecular weights of 24, 25, and 30 X 10(6) daltons, respectively. Resistance to ampicillin, carbenicillin, neomycin, and kanamycin was transferred by conjugation at a frequency of 10(-6). The second strain of K. pneumoniae (RO106) produced gentamicin adenyltransferase and maintained aminoglycoside resistance only when propagated in antibiotic-containing medium. DNA analyses revealed eight species of plasmid DNA: one species with a molecular weight of 70 X 10(6) daltons apparently accounted for conjugal transfer of resistance to ampicillin, carbenicillin, chloramphenicol, and streptomycin. The third strain (RO180) was resistant primarily to colistin and lacked plasmids. Control of the outbreak due to this strain was achieved by aminoglycoside therapy.


Reovirus-like agent and enterotoxigenic Escherichia coli infections in pediatric diarrhea in the Philippines. Of 82 children hospitalized with diarrhea in the Philippines during January-June 1976, 14 (17%) had infections due to a reovirus-like agent as determined by detection of viral particles in stools by electron microscopy (12 [15%] of 82) and/or by a rise in titer of antibody to the serologically related Nebraska calf diarrhea virus (eight [20%] of 39). Escherichia coli producing heat-labile enterotoxin were found in six (7%) of 82 ill children and two (4%) of 49 healthy control children, while E. coli producing heat-stable enterotoxin were isolated from three children with diarrhea and two without gastroenteritis. Thirty-eight percent of enterotoxigenic E. coli isolated from children with diarrhea, but only 6% of isolates from healthy control, were of serotypes similar to those of enterotoxigenic E. coli isolated in previous studies of these pathogens by other investigators in geographically diverse areas (serotypes O6:H16, O8:H9, and O78:H12) (P less than 0.05). Eight (10%) of the children had infections with multiple enteric pathogens.


The nasal: paranasal block technique. Preparation and uses. A new technique for removing nasal: paranasal blocks at autopsy is described. The technique allows the removal of these cavities without disfigurement of the head after the brain has been removed. The importance of the technique in relation to training on endo-nasal micro-surgery, and histopathological study of nasal and paranasal disorders is emphasized.


A fatal denture in the oesophagus.

A fatal denture in the oesophagus. An unusual case is described of a denture in the oesophagus which caused a fatal haemorrhage from the aorta. The post-mortem examination confirmed that a projection from the denture had impinged upon the aortic wall, after perforating the oesophagus, with subsequent erosion of the aorta.


Inhibin from cultures of rat seminiferous tubules. Medium from cultures of mature rat seminiferous tubules contained a substance which suppressed, in a dose-related manner, the luteinizing hormone releasing hormone (LH-RH)-stimulated secretion of FSH by cultured rat pituitary cells. The secretion of LH was suppressed to a lesser extent and the basal secretion of both LH and FSH was inconsistently affected. Gel filtration on Sephadex G-100 did not fractionate the activity. The active material did not inhibit the secretion of TSH or destroy LH-RH and the activity was not due to testosterone or oestradiol in the medium. Control media from liver cultures were inactive. It is concluded that inhibin is present in media from cultures of rat seminiferous tubules.


Association between 5-hydroxytryptamine release and insulin secretion. The efflux of radioactivity after loading with trace amounts of tritiated 5-hydroxytryptamine ([3H]5-HT) or 5-hydroxytryptophan ([3H]5-HTP) was studied in perifused beta-cell-rich pancreatic islets from ob/ob mice. Analysis of the effluent revealed that more than 90% of the radioactivity was released as [3H]5-HT after loading with [3H]5-HTP. Increasing the concentration of glucose in the perifusion medium from 3 to 20 mmol/l enhanced the efflux when islets from fed mice were used and this effect was potentiated by the phosphodiesterase inhibitor 3-isobutyl-1-methylxanthine (IBMX). Whereas 20 mM-glucose alone did not stimulate the efflux of 5-HT from islets isolated from mice starved for 3 days, a stimulatory effect was observed in the presence of IBMX. Stimulation of the efflux of radioactivity by glucose was inhibited if calcium was omitted from or adrenaline added to the medium. The results are consistent with the concept of exocytotic release of 5-HT occurring in response to stimulation of insulin secretion, although basal non-exocytotic transport must also be occurring across the beta-cell membrane.


Ontogeny of lens crystallins in marine cephalopods. The ontogeny of the lens crystallin antigens throughout development of three marine cephalopod embryos, Loligo vulgaris, Sepia officinalis and Octopus vulgaris has been investigated using the indirect immuno-cytochemical staining against respective homologous anti-total lens protein antiserum. The cellular mechanism of lens development appears to be the same in all species investigated and so does the ontogeny of the lens crystallins. The first positive immuno-fluorescence reaction appears simultaneously and in equal intensities over the lens and lentigenic area confirming the relationship between the two.


Antigenic drift in influenza A viruses. I. Selection and characterization of antigenic variants of A/PR/8/34 (HON1) influenza virus with monoclonal antibodies. Antigenic variants of A/PR/8/34 [HON1] influenza virus were selected after a single passage of the parent virus in embryonated chicken eggs in the presence of monoclonal antibodies to this virus. The monoclonal antibodies were produced by a hybridoma and were specific for an antigenic determinant on the HA molecule of the parent virus. Seven antigenic variants were analyzed with 95 monoclonal anti-HA antibodies prepared in vitro in the splenic fragment culture system. Three subgroups of antigenic variants were distinguished. The antigenic changes were primarily recognized by monoclonal antibodies to the strain- specific determinants of the parental hemagglutinin (HA) molecule. Monoclonal antibodies to HA determinants shared (in an identical or cross-reactive form) by parental virus and more than three heterologous viruses of the HON1 and H1N1 subtypes were unable to recognize the antigenic change on the variants. Similarly, heterogeneous antibody preparations could not differentiate between parental and variant viruses. The results are compatible with the idea that the HA of PR8 has available a large repertoire of antigenic modifications that may result from single amino acid substitutions, and that antigenic changes can occur in the strain- specific determinants on the HA molecule in the absence of concomitant changes in the cross-reactive HA determinants. The findings suggest that antigenic drift, in order to be epidemiologically significant, probably requires a series of amino acid substitutions in, or close to, the antigenic area on the HA molecule.


Macrophage stimulation by bacterial lipopolysaccharides. II. Evidence for differentiation signals delivered by lipid A and by a protein rich fraction of lipopolysaccharides. Stimulation of macrophages to lyse tumor cells is a property common to lipopolysaccharide (LPS) extracted from a variety of smooth and rough bacterial strains by several different preparative procedures. The relationship between macrophage stimulation and the structural characteristics of LPS is defined. In protein-free LPS, lipid A bears the stimulatory signal which results in the differentiation of elicited macrophages into killer cells. The polysaccharide moiety is neither stimulatory itself nor does it block the activity of complete LPS on macrophages. Extraction of LPS by the butanol or Boivin procedures produces preparations in which LPS is complexed through its lipid A moiety to a protein rich component, LAP. Isolated LAP delivers a macrophage differentiation signal which is independent of lipid A. The presence of these two structurally distinct constituents in the cell walls of gram-negative bacteria broadens the biological environments in which they can stimulate macrophages in vivo.


Alteration of some functional and metabolic characteristics of resident mouse peritoneal macrophages by lymphocyte mediators. Resident mouse peritoneal macrophages were incubated in Sephadex G-100 fractions of supernates from concanavalin A-stimulated lymphocytes. A significant effect of the lymphocyte supernatant fractions containing mediators on macrophage 5'-nucleotidase, glucose-1 14C oxidation, cell maintenance, and migration is reported. The 5'-nucleotidase was depressed to an extent similar to that seen in activated macrophages obtained from Listeria-infected mice. On the other hand, glucose-1-14C oxidation was enhanced, but not to the same degree as seen in the counterparts in vivo. Whereas migration inhibitory factor (MIF) and cell adherence-augmenting activity were found in a number of adjacent fractions, the metabolic effects were found predominantly in a single fraction. Resident peritoneal macrophages or those elicited by the injection of a lymphocyte-derived chemotactic factor were more responsive with respect to the biochemical changes than caseinate-elicited macrophages. On the other hand, caseinate-elicited macrophages appeared to be more sensitive with respect to the effects of mediator(s) on cell retention. A possible dissociation between MIF and cell-adherence augmenting activity, on the one hand, and the entities that stimulate glucose-1-14C oxidation is reported, based on fractionation studies, and loss of the latter activity upon storage of lymphocyte supernates.


Antigen-specific helper factor in man.

Antigen-specific helper factor in man. Supernates of tetanus toxoid (TT) antigen-stimulated human T cells were studied for the presence of an antigen-specific T-cell helper factor (ASF). Supernates were circulated over an immunosorbent column consisting of insolubilized TT antigen. The material which bound to the column was eluted with 3 M NaCNS and was shown to contain a factor which in the presence of TT-induced specific IgG anti-TT antibody synthesis in autologous B cells without causing readily detectable proliferation. ASF activity was partially inhibited by antisera directed against the B-cell alloantigens of the ASF donor. Immunosorbent columns containing such antisera removed ASF activity. Immunosorbent columns containing antisera to human immunoglobulin heavy chain determinants did not remove ASF activity; whereas immunosorbent columns containing rabbit idiotypic antiserum directed against anti-TT antibodies completely removed ASF activity. ASF was destroyed by treatment with proteolytic enzymes; its molecular weight was estimated by Sephadex G-100 gel column chromatography to be between 25,000 and 75,000 daltons.


The cellular basis of allograft rejection in vivo. I. The cellular requirements for first-set rejection of heart grafts. The nature of the cells required for first-set graft rejection in vivo was examined by using an adoptive transfer system to restore heart-graft rejection in irradiated rats. Highly purified inocula of peripheral T lymphocytes were shown to quantitatively account for the restorative ability of adoptively transferred cells. These T cells were shown to be long-lived small lymphocytes which are not recently derived from the thymus during adult life. They belong to the pool of T cells which constantly recirculate from blood to lymph as shown by their rapid appearance in the lymph of iradiated syngeneic rats after intravenous injection. Neither B lymphocytes nor antibodies in the circulation or in the graft itself are required for first-set graft rejection.


The cellular basis of allograft rejection in vivo. II. The nature of memory cells mediating second set heart graft rejection. An adoptive transfer system was used to study the cellular basis of memory in animals immunized by grafting with major histocompatibility complex incompatible tissue. Memory was characterised by a large (greater than 100 fold) increase in the potency of lymphocytes to precure graft rejection. This increase in potency endured for at least 1 yr after sensitization. The memory cells were shown to be Ig-- small lymphocytes which were long lived and which did not recirculate from blood to lymph in normal recipients although they did home to lymphoid tissue from which they could be recovered several months later. The thymus was not required either for the generation of memory cells or their maintenance. Cells carrying memory for alloantibody synthesis did recirculate normally but alloantibody synthesis was shown not to be required for rejection.


Treatment of impetigo and ecthyma.

Treatment of impetigo and ecthyma. A comparison of the treatment of superficial skin infections using intramuscular benzathine penicillin G alone or combined with hexachlorophene scrubbing was conducted in 127 children. Of 72 children treated with benzathine penicillin alone, 94.4 percent had a good result. Of the 55 children receiving hexachlorophene scrubbing in addition to penicillin, 85.5 percent had a good result. The healing rate was higher (93 percent) in those children whose skin cultures grew Group A beta hemolytic streptococci. When staphylococcus aureus was the only pathogen isolated, the healing rate was 86 percent. Regardless of the pathogens isolated, the healing rate was not increased with scrubbing. Since scrubbing with hexachlorophene offered no improvement in the healing rate and since it adds to the expense and discomfort of treatment, it should be eliminated as part of the treatment.


Calcium buffering in presynaptic nerve terminals. I. Evidence for involvement of a nonmitochondrial ATP-dependent sequestration mechanism. A latent ATP-dependent Ca storage system is enriched in preparations of pinched-off presynaptic nerve terminals (synaptosomes), and is exposed when the terminals are disrupted by osmotic shock or saponin treatment. The data indicate that a fraction of the Ca uptake (measured with 45Ca) is associated with the intraterminal mitochondria; it is blocked by ruthenium red, by FCCP, and by azide + dinitrophenol + oligomycin. There is, however, a residual ATP-dependent Ca uptake that is insensitive to the aforementioned poisons; this (nonmitochondrial) Ca uptake is blocked by tetracaine, mersalyl and A-23187. Moreover, A-23187 rapidly releases previously accumulated Ca from these (nonmitochondrial) storage sites, whereas the Ca chelator, EGTA, does not. The proteolytic enzyme, trypsin, spares the mitochondria but inactivates the nonmitochondrial Ca uptake mechanism. Chemical measurements of total Ca indicate that the ATP-dependent Ca uptake at the nonmitochondrial sites involves the net transfer of Ca from medium to tissue fragments. This system can sequester Ca when the ambient-ionized Ca2+ concentration (buffered with EGTA) is less than 0.3 micrometer; brain mitochondria take up little Ca when the ionized Ca2+ level is this low. Preliminary subfractionation studies indicate that the nonmitochondrial Ca storage system does not sediment with synaptic vesicles. We propose that this Ca storage system, which has many properties comparable to those of skeletal muscle sarcoplasmic reticulum, may be associated with intraterminal smooth endoplasmic reticulum. This Ca-sequestering organelle may help to buffer intracellular Ca.


Cation transport in Escherichia coli. IX. Regulation of K transport. Kinetics of K exchange in the steady state and of net K uptake after osmotic upshock are reported for the four K transport systems of Escherichia coli: Kdp, TrkA,  TrkD, and TrkF. Energy requirements for K exchange are reported for the Kdp and TrkA systems. For each system, kinetics of these two modes of K transport differ from those for net K uptake by K-depleted cells (Rhoads, D. B. F.B. Walters, and W. Epstein. 1976. J. Gen. Physiol. 67:325-341). The TrkA and TrkD systems are inhibited by high intracellular K, the TrkF system is stimulated by intracellular K, whereas the Kdp system is inhibited by external K when intracellular K is high. All four systems mediate net K uptake in response to osmotic upshock. Exchange by the Kdp and TrkA systems requires ATP but is not dependent on the protonmotive force. Energy requirements for the Kdp system are thus identical whether measured as net K uptake or K exchange, whereas the TrkA system differs in that it is dependent on the protonmotive force only for net K uptake. We suggest that in both the Kpd and TrkA systems formation of a phosphorylated intermediate is necessary for all K transport, although exchange transport may not consume energy. The protonmotive-force dependence of the TrkA system is interpreted as a regulatory influence, limiting this system to exchange except when the protonmotive force is high.


Quantification of cell fusion by twenty-one strains of Newcastle disease virus using flow microfluorometry. The cell-fusing ability of Newcastle disease virus (NDV) was quantified using flow microfluorometry (FMF). The rate of polykaryocyte formation, fusion dependence on multiplicity of infection, and cell fusion differences for 21 NDV strains were measured using this technique. No correlation was found between the virulence of a virus strain and its cell fusion index calculated from the FMF data.


A survey of partial denture design in general dental practice. The objects of this investigation were to discover the methods by which general dental practitioners communicated partial denture designs to dental laboratories and to ascertain the extent to which certain design criteria were being followed. The results of the survey showed that the responsibility for design appeared to be largely delegated to the technician. In most instances cobalt-chromium dentures were produced which would assist in maintaining oral health; however, this was not the case with acrylic dentures.


An etiologic shift in infantile osteomyelitis: the emergence of the group B streptococcus. Twenty-one infants from six to 52 days of age (mean 23.3 days) with osteomyelitis were studied between 1965 and 1977. The etiologic agents were group B streptococcus (8), staphylococcus aureus (6), gramnegative bacilli (4), Streptococcus pneumoniae (1), and unknown (2). Patients with group B streptococcal osteomyelitis were characterized by an uncomplicated neonatal course, single bone involvement with a predilection for involvement of the proximal humerus, and lack of inflammatory signs. In contrast, patients with osteomyelitis due to other organisms frequently had had manipulative procedures predisposing to infection and were more likely to have multiple bone involvement, fever, and leukocytosis at the time of diagnosis. Functional impairment was detected in only one of 17 patients evaluated a mean of 36 months after diagnosis.


Lithium carbonate treatment of select behavior disorders in children suggesting manic-depressive illness. Twelve children with severe chronic behavior disorders who benefited from treated with lithium carbonate over an extended period of time (6 to 33 months) are described. Behavioral features common to all included hostility, aggressiveness, and distractibility. Nine had cyclic mood swings, with periods of withdrawal and periods of manic excitement; six of these had neurovegetative disorders. These nine children may have manic-depressive disease of childhood. Three children had no cyclic symptoms, though their hostile and aggressive behavior was similar to that of the cyclic group; they responded similarly to lithium. Family histories were strongly positive for manic-depressive disease, depression, and alcoholism. A double-blind placebo-controlled crossover study in four patients supported the specific behavioral effect of lithium.


An immunologic investigation of atypical gingivostomatitis. A fluorescent antibody investigation was conducted to determine first the difference, if any, in the presence of tissue-bound antibodies in normal gingiva and atypical gingivostomatitis gingiva, and second to determine if the serum of atypical gingivostomatitis patients had auto-antibodies directed against any specific structures of normal gingiva. The immunofluorescent tests produced two signficant results: 1. Most of the mononuclear inflammatory cells present in AGS gingiva had an antibody halo on the cell membrane surface. This could indicate that AGS is the result of hypersensitivity reaction. 2. The serum of AGS patients did not contain detectable auto-antibodies for normal gingiva which would be one indication that AGS is not an autoimmune disease.


A clinical study of gingival inflammation in renal transplant recipients taking immunosuppressive drugs. The relationship between the gingival inflammation and plaque scores of patients who had received kidney transplants and were taking immunosuppressive drugs to combat rejection pheomena was compared with data from a control group. Equivalent plaque scores were associated with less gingival inflammation in the patients taking the immunosuppressive drugs. While there was no signficant difference between the plaque scores of the two groups the control group displayed signficantly more gingival inflammation. The implications of these results with respect to possible etiological mechanisms operating in periodontal disease are discussed.


Fluorescence--TLC densitometric determination of diazepam and other 1,4-benzodiazepines in serum. A sensitive fluorescence--TLC densitometric procedure was developed for the specific determination of diazepam (I) and its two metabolites, desmethyldiazepam (II) and oxazepam (III), in serum. After extraction from serum with benzene, the compounds were separated by TLC and converted with a sulfuric acid spray to greenish-yellow fluorescence spots with Rf values of 0.72, 0.43, and 0.17, respectively. Quantitation of the TLC plate was accomplished by scanning with a densitometer at 380 nm. The sensitivities of the assay were 18 (I), 6 (II), and 5 (III) ng/ml of serum. This procedure was also was applicable to other 1,4-benzodiazepines in biological fluids.


Endotoxic shock in the rabbit: the effects of prostaglandin and arachidonic acid administration. A rabbit model was used to determine the effects of prostaglandins and arachidonic acid on cellular integrity and survival during endotoxic shock. Prostaglandins A2, E1 and F2alpha were infused intravenously at a rate of 1.0 microgram/kg/min for 105 min beginning 15 min after the administration of an LD60 dose of Escherichia coli endotoxin. While each of the prostaglandins tested significantly attenuated the accumulation of lactic acid dehydrogenase in the plasma of shocked animals, none were able to protect against the increase in the plasma activities of glutamic pyruvic transaminase or cathepsin D during the shock state. Prostaglandins A2, E1 and F2alpha did not significantly enhance the survival of the treated animals as compared to vehicle-treated controls. In contrast, arachidonic acid 15 microgram/kg/min i.v.) significantly prevented the accumulation of lactic acid dehydrogenase and glutamic-pyruvic transaminase activities in the plasma of shocked animals, and also significantly increased the number of survivors in this group 48 hours after the endotoxin administration. In summary, while the treatment of endotoxic rabbits with prostaglandins of the A, E and F series was of no survival value, the treatment of these animals with a substrate of the prostaglandin synthetase complex resulted in a dramatic increase in the survival rate. The mechanism of action of arachidonic acid in this regard is not clear.


Analgesic studies of codeine and oxycodone in patients with cancer. II. Comparisons of intramuscular oxycodone with intramuscular morphine and codeine. The relative analgesic potency of single graded intramuscular doses of oxycodone and morphine was evaluated in a double-blind study in patients with chronic pain due to cancer. When both intensity and duration of analgesia are considered (total analgesic effect), oxycodone was 2/3 to 3/4 as potent as morphine, while in terms of peak analgesia, it was 8/10 to equipotent. In doses producing equivalent peak effect, oxycodone had a shorter duration of action than morphine. Intramuscular oxycodone was also compared to intramuscular codeine in a similar patient group. In terms of total analgesic effect, oxycodone was 10 times as potent as codeine, while in terms of peak analgesia it was 12 times as potent. These relative potency relationships of oxycodone, taken in conjunction with the oral/parenteral potency ratios of codeine and oxycodone established in the previous paper and several previous relative potency assays involving morphine, oxymorphone and codeine, demonstrate a highly consistent pattern of analgesic structure-activity relationships encompassing morphine, oxymorphone, codeine and oxycodone. The results of these studies do not appear to support the hypothesis that, in man, the analgesic activity of codeine is due to its O-demethylation to morphine.


Analgesic studies of codeine and oxycodone in patients with cancer. I. Comparisons of oral with intramuscular codeine and of oral with intramuscular oxycodone. The relative analgesic potency of oral and intramuscular codeine was evaluated in a double-blind crossover comparison of graded single doses in patients with chronic pain due to cancer. When both duration and intensity of analgesia are considered (total effect), oral codeine was 6/10 as potent as the intramuscular form. This is a high oral/parenteral analgesic relative potency ratio compared with morphine, metopon and oxymorphone and correlates well with the results of recent studies which have determined the oral vs. intramuscular bioavailability of codeine in man. Oral and intramuscular oxycodone were also compared in a similar patient group. Like codeine, oxycodone retained at least 1/2 of its analgesic activity when administered orally. We hypothesize that the high oral/parenteral relative potency ratios of codeine and oxycodone relative to morphine and its congeners are not due to more efficient absorption after oral administration, but rather that methylation at position 3 in codeine and oxycodone protects these drugs from rapid first-pass metabolism.


Properties of the calcium-extruding mechanism of liver cells. 1. The movements of Ca2+ between liver slices and the suspending medium have been followed with a Ca2+-specific electrode and with measurements of the efflux of 45Ca. 2. A net entry of Ca2+ into the tissue occurred during anaerobiosis. Reoxygenation of the medium resulted in a net extrusion of Ca2+ which was reversed by the addition of a respiratory inhibitor (Amytal), an uncoupler of oxidative phosphorylation (pentachlorophenol) or the divalent-cation-specific ionophore, A23187. 3. The net extrusion of Ca2+ was dependent on the presence of Mg2+ in the medium, but was not prevented by ouabain or by incubation in a Na+-free medium. Extrusion was not prevented by cytochalasin B or colchicine. 4. The undirectional efflux of 45Ca required Mg2+ to attain its maximal rate, and the magnitude was not affected by the presence of ouabain or the absence of Na+ from the medium. 5. It is concluded that extrusion of Ca2+ from liver cells is a metabolically dependent transport process that occurs independently of the exchange of Na+ between tissue and medium.


The swing-lock partial denture: an alternative approach to conventional removable partial denture service. There are many common problems associated with the use of conventional clasp removable partial dentures. An alternative modality in many instances is the swing-lock removable partial denture. Its advantages, disadvantages, indications, and contraindications are discussed. The procedures of fabrication, placement, and adjustments are described.


A new metal-ceramic crown.

A new metal-ceramic crown. A new method of attaching porcelain to precious metals using tin oxide coatings is described. Platinum foil is bonded to aluminous porcelain and forms an inner protective skin, thereby reducing the formation of microcracks and increasing the strength of the crown. An improvement in translucency of the crown is obtained by using thick layers of porcelain, and the technique still allows the use of a porcelain butt fit at the critical labiocervical margin.


Bond strength of three cements determined by centrifugal testing. 1. Each tooth preparation and crown should be used to test only one cement, since recementation will alter the bond strength associated with the second trial. 2. Recementation of a restoration should include a thorough cleaning of the preparation and the restoration. 3. Although zinc polycarboxylate cement possessed the highest bond strength, there were no statistically significant differences among the cements tested. 4. No correlation was found between bond strength and any individual property of compressive strength, tensile strength, or film thickness. 5. Values of ADA film thickness predicted the order of values of film thickness determined by a simulated clinical method.


Basic wax contouring for complete dentures. The form and contour of the polished surface of the denture base is an important factor in the appearance and function of complete dentures. It is the responsibility of the dentist to insure that the dental laboratory technician reproduces the proper anatomic contour of the denture base. With attention to details in the final wax-up, the finishing procedures will be minimal. The use of high shine is all that is needed to polish. If anatomy is lost in the investing procedure, and it is necessary to recarve it with acrylic resin burs, then it will be necessary to use both coarse and fine pumice and high shine to complete the dentures (Figs. 15 to 17). When one applies these basic principles, a denture surface is produced that will be both refreshing and natural in appearance and aid in the stability of the dentures in function. To our patients who are contemplating prosthodontic replacements, it should remove the fear of having to submit to accepting an unnatural restoration.


Layered silicone rubber technique for flasking removable partial dentures. A method for flasking removable partial dentures using a layered silicone rubber technique has been described. The silicone investment protects the stone teeth from fracture during removal of the removable partial denture from the investment. Then the occlusal changes can be accurately corrected following processing.


Vertical displacement of distal-extension ridges by different impression techniques. A study was conducted to compare tissue displacement resulting from different techniques and impression materials for distal-extension ridges. Impression techniques used were Applegate's functional fluid wax and a single-impression technique with mercaptan rubber. A mucostatic impression technique using irreversible hydrocolloid served as control. The results showed a statistically significant difference in tissue displacement between the casts made from the functional fluid wax technique and the single-impression technique with mercaptan rubber and the casts in the control group.


Direct pattern technique for posts and cores. The technique described results in a well adapted cast post and core with good retention (Figs. 18 and 19). The chances of perforation of the root and trauma to the patient are reduced, and the expense of the procedure is minimal. This system is adaptable to single- or multirooted teeth and continually produces good results with minimal problems.


A technique for restoring abutments for removable partial dentures. A technique was presented to restore a removable partial denture abutment so that the removable denture can continue to be used. The technique uses cold-curing acrylic resin in a rubber base impression form. The technique can be adapted to both direct and indirect procedures.


Technique for attaching the master cast to its split mounting index. A technique that allows the master cast to be easily removed and attached to its split mounting index has been described. The cast is attached to its split mounting index by means of a machine screw and a disposable mounting stud.


Acrylic resin blockout for interim removable partial dentures. A technique using autopolymerizing acrylic resin as a blockout material has been described. This technique greatly simplifies the laboratory construction and insertion phases of the complex interim removable partial denture. It is not suggested that the acrylic blockout replace the wax blockout if a heat-cured denture base is not indicated. Wax should be used if a "sprinkle-on" autopolymerizing acrylic resin is used for the denture base.


Balint reassessed: the doctor, his patient, and the illness: a reappraisal. Psychoanalytical theories seek to explain human behaviour. I believe that they are not scientific, whereas it appears that Balint thought they were. I suggest instead that they are better regarded as myths and part of an artistic discipline. Whereas most of the problems brought by patients to general practitioners can be understood in scientific terms, others can be understood only in artistic terms.These two terms reflect fundamentally different kinds of problems, and different language must be used to discuss them. Neither the two sets of terms nor the two kinds of problem can be confused without giving rise to error. I argue that Michael Balint came to a false conclusion about the nature of the general practitioner's task, about the way the problems posed by his difficult patients may be identified, and about some of the training doctors should receive.Balint's main contribution remains. He showed us that scientific skills alone are not enough if we are to understand our patients fully. He also showed us how a descriptive science of human behaviour in the consulting room was possible.To these insights must be added new understanding. Popper (1963) has provided us with a clear line of demarcation between science and the rest of our knowledge. This idea suggests that general practitioners should reaffirm the importance to them of the intellectual discipline of science. If they wish their understanding and practice to be comprehensive they must also affirm the importance of the arts. What they must not do is to confuse one with the other.


Richard Quiller Couch--an outstanding nineteenth century general practitioner. The boom in metal mining in the mid-nineteenth century produced a fearful mortality among miners. The history of this problem is described by the life and work of Mr R. Quiller Couch, a Cornish mine surgeon and general practitioner. He was a remarkable man and an outstanding general practitioner.


The rise of the general practitioner in the nineteenth century. It was the Apothecaries Act of 1815 which led to the emergence of general practice as we know it today and it was this one Act which produced a flood of changes on the medical scene that are without parallel in our history. Students were soon to undergo new forms of training in new medical schools and hospitals, and many medical associations and journals were founded. The term ;general practitioner' was soon in use. The driving force behind all these changes was the Society of Apothecaries and the new general practitioners, and all too often they were opposed by the two Royal Colleges. It was only at the beginning of the twentieth century that these new practitioners were allowed to call themselves ;doctors'.


Some aspects of the pathogenesis and comparative pathology of toxoplasmosis. Some aspects of the pathogenesis and comparative pathology of toxoplasmosis are described. The general pattern of infection, with or without necrosis, and tissue cyst formation as it occurs in all species is dealt with. The wide pathological manifestations of toxoplasmosis as seen in sheep, cattle, pigs, horses, dogs, cats, chinchillas and man are reviewed.


Comparison of ion current noise predicted from different models of the sodium channel gating mechanism in nerve membrane. The theoretical power density spectrum S(f) of ion current noise is calculated from several models of the sodium channel gating mechanism in nerve membrane. Sodium ion noise experimental data from the frog node of Ranvier [Conti, F., et al. (1976), J. Physiol. (London) 262:699] is used as a test of the theoretical results. The motivation for recent modeling has been evidence for a coupling between sodium activation and inactivation from voltage clamp data. The two processes are independent of one another in the Hodgkin and Huxley (HH) model [Hodgkin A.L., Huxley, A.F. (1952), J. Physiol. (London) 117:500]. The noise data is consistent with HH, as noted by Conti et al. (1976). The theoretical results given here appear to indicate that only one case of coupling models is also consistent with the noise data.


Intracellular chloride activities in rabbit gallbladder: direct evidence for the role of the sodium-gradient in energizing "uphill" chloride transport. Intracellular chloride activities, (Cl)c, in rabbit gallbladder were determined by using conventional (Kcl-filled) microelectrodes and Cl-selective, liquid ion-exchanger, microelectrodes. The results indicated that in the presence of a normal Ringer's solution, (Cl)c averages 35mM; this value is 2.3 times that predicted for an equilibrium distribution across the mucosal and baso-lateral membranes. On the other hand, when the tissue is bathed by Na-free solutions, (Cl)c declines to a value that does not differ significantly from that predicted for an equilibrium distribution. These results, together with those of Frizzell et al. (J. Gen. Physiol. 65:769, 1975) provide, for the first time, compelling evidence that (i) the movement of Cl from the mucosal solution into the cell is directed against an electrochemical potential difference (23mV); and (ii) this movement is energized by coupling to the entry of Na down a steep electrochemical potential difference. Finally, our data suggest that (i) Cl exit from the cell across the basolateral membrane may be coupled to the co-transport of a cation or the countertransport of an anion; and (ii) the mechanism responsible for active Na extrusion from the cell across the baso-lateral membrane is rheogenic (electrogenic), and is not the result of a neutral Na-K exchange.


Structures of membrane proteins.

Structures of membrane proteins. The possible conformations of integral membrane proteins are restricted by the nature of their environment. In order to satisfy the requirement of maximum hydrogen bonding, those portions of the polypeptide chain which are in contact with lipid hydrocarbon must be organized into regions of regular secondary structure. As possible models of the intramembranous regions of integral membrane proteins, three types of regular structures are discussed. Two, the alpha helix and the beta-pleated sheet, are regularly occurring structural features of soluble proteins. The third is a newly proposed class of conformations called beta helices. These helices have unique features which make them particularly well-suited to the lipid bilayer environment. The central segment of the membrane-spanning protein glycophorin can be arranged into a beta helix with a hydrophobic exterior and a polar interior containing charged amino-acid side chains. Such structures could function as transmembrane ion channels. A model of the activation process based on a hypothetical equilibrium between alpha and beta helical forms of a transmembrane protein is presented. The model can accurately reproduce the kinetics and voltage dependence of the channels in nerve.


Dose-incidence variations of reticulum cell sarcoma in mice with irradiated bone marrow. The average final incidence of reticulum cell sarcoma (RCS) in untreated control (C57BL/Cnefemale X C3H/Cnemale)F1 male mice was 57% and was not significantly changed by single acute whole-body doses of X-rays up to 400 rads. Higher doses sharply decreased this incidence to very low levels. In a syngeneic chimera system, however, irradiation (400 rads) of bone marrow prior to transplantation significantly increased the frequency and rate of RCS relative to transplantation of unirradiated marrow. An endogenous repopulating system was tested; marrow was irradiated in situ by a limb-shielding technique. The results indicated a biphasic dose-incidence curve with a peak at 500 rads. The rising part of the curve was in agreement with and extended the conclusion from the exogenous system, whereas the descending portion at higher doses paralleled the trend observed in the whole-body X-irradiated animals. Finally, the irradiation of two hind legs resulted in a higher frequency of RCS than did irradiation of only one leg at the same dose levels.


Malaria infection in transplant recipient. A case of P. malariae infection occurring in a kidney transplant recipient is reported. The diagnosis was delayed because of atypical clinical presentation secondary to altered immune response. Serologic tests for antimalarial antibody are not reliable and diagnosis is established by visualization of the parasites in the peripheral blood smear. We can only guess what role this infection played in rejection of the transplant and whether earlier diagnosis and treatment would have saved it.


Emergency approach to fingertip injuries. An efficient, reliable, and immediate method of treating full-thickness skin avulsions of fingertips in an Emergency Room is presented. A series of patients are discussed.


Management of flexor tendon lacerations in the hand. Flexor tendon injuries in the hand present a real challenge in treatment. Poorly chosen or poorly executed treatment may lead to a functionless finger at best, impairing total hand function. A variety of approaches to treatment of flexor tendon injuries is available to the specially trained surgeon and a particular method is selected based on the merits of the case in question. Primary tendon repair is a viable choice under the proper conditions, while delayed primary repair allows a somewhat broader application of this technique. Flexor tendon grafting remains a very useful operation for the surgeon caring for tendon injuries of the hand.


Clinical skin banking: a simplified system for processing, storage, and retrieval of human allografts. A simplified procedure for the harvest and preservation of human allograft skin for burn treatment is outlined. In establishing a skin bank to serve the San Diego County Regional Burn Treatment Center, our primary goals were to deliver a low-cost product, monitored to be free of significant bacterial contamination. Our own innovations include the use of Falcon 2070 tubes as packaging material, and the use of microwave energy for the safe, rapid thawing of liquid nitrogen stored tissue.


Evaluation of the effect of a single dose of tinidazole (Fasigyn) in giardiasis. The effect of tinidazole in a single dose in the treatment of giardiasis has been evaluated in 165 cases, found in 5 villages in Kazeroon, Southern Iran. A reduction of 94.5 per cent in the positive stool tests in treated cases was obtained, while this reduction was only 10 per cent in 30 control cases. No side-effect has been observed in 87 per cent of treated cases and side reactions in the remaining cases were mild and transient.


Bacteriophage P22-mediated specialized transduction in Salmonella typhimurium: high frequency of aberrant prophage excision. The temperate bacteriophage P22 mediates both generalized and specialized transduction in Salmonella typhimurium. Specialized transduction by phage P22 is different from, and less restricted than, the well characterized specialized transduction by phage lambda, due to differences in the phage DNA packaging mechanisms. Based on the properties of the DNA packaging mechanism of phage P22 a model for the generation of various types of specialized transducing particles is presented that suggests generation of substantial numbers of specialized transducing genomes which are heterogeneous but only some of which have terminally redundant ends. The primary attachment site, ataA, for phage P22 in S. typhimurium is located between the genes proA,B and supQ newD. (The newD gene is a substitute gene for the leuD gene, restoring leucine prototrophy of leuD mutant strains.) The proA,B and supQ newD genes are very closely linked and thus cotransducible by generalized transducing particles. Specialized transducing particles can carry either proA,B or supQ newD but not both simultaneously, and thus cannot give rise to cotransduction of the proA,B and supQ newD genes. This difference is used to calculate the frequency of generalized and specialized transducing particles from the observed cotransduction frequency in phage lysates. By this method, very high frequencies of supQ newD (10(-2)/PFU)- and proA,B (10(-3)/PFU)-specialized transducing particles were detected in lysates produced by induction of lysogenic strains. These transducing particles most of which would have been produced by independent aberrant excision events (which include in situ packaging), were of various types.


Bacteriophage P22-mediated specialized transduction in Salmonella typhimurium: identification of different types of specialized transducing particles. The temperate bacteriophage P22 mediates both generalized and specialized transduction in Salmonella typhimurium. Specialized transduction by phage P22 is different from, and less restricted than, the well characterized specialized transduction by phage lambda, due to differences in the phage DNA packaging mechanism. Phage lysates produced by induction of lysogenic strains contain very high frequencies of supQ newD- and proA,B-specialized transducing particles (10(-2)/PFU and 10(-3)/PFU, respectively), most of which are produced by independent aberrant excision events of various types. In a model, 12 different modes of transduction mechanisms were characterized by: (i) the structure of the specialized transducing genomes after injection into a new host cell, i.e., linear or circular, and (ii) the requirements for the transduction process, i.e., host recombination functions, phage integration functions, or presence of a prophage. By using different recipient strains and phage helper strains, it was possible to show that most specialized transducing particles (ca. 99%) contain linear genomes that cannot circularize upon injection into a new host cell and that require the presence of an integrated prophage as a site for a recombinational event to give rise to a transductant. Only 0.1% of all specialized transducing particles were shown to transduce by integration, suggesting that transducing genomes containing terminally redundant ends represent only a minor fraction of all transducing particles that are produced. However, it should be pointed out that the frequency (approximately 10(-5)/PFU) of these specialized transducing genomes that can circularize upon injection into a new host cell is as high as or even higher than the frequency of specialized transducing particles of phage lambda. The remaining approximately 1% of all specialized transducing particles can transduce by any one of the other mechanisms described.


Early events in the replication of Mu prophage DNA. To determine whether the early replication of Mu prophage DNA proceeds beyond the termini of the prophage into hose DNA, the amounts of both Mu DNA and the prophage-adjacent host DNA sequences were measured using a DNA-DNA annealing assay after induction of the Mu vegetative cycle. Whereas Mu-specific DNA synthesis began 6 to 8 min after induction, no amplification of the adjacent DNA sequences was observed. These data suggest that early Mu-induced DNA synthesis is constrained within the boundaries of the Mu prophage. Since prophage Mu DNA does not undergo a prophage lambda-like excision from its original site after induction (E. Ljungquist and A. I. Bukhari, Proc. Natl. Acad. Sci. U.S.A. 74:3143--3147, 1977), we propose the existence of a control mechanism which excludes prophage-adjacent sequences from the initial mu prophage replication. The frequencies of the Mu prophage-adjacent DNA sequences, relative to other Escherichia coli genes, were not observed to change after the onset of Mu-specific DNA replication. This suggests that these regions remain associated with the host chromosome and continue to be replicated by the chromosomal replication fork. Therefore, we conclude that both the Mu prophage and adjacent host sequences are maintained in the host chromosome, rather than on an extrachromosomal form containing Mu and host DNA.


Isolation of genotypic variants of Autographa californica nuclear polyhedrosis virus. A nuclear polyhedrosis virus (MNPV) isolated from a lepidopteran (Noctuidae) insect, Autographa californica, was cloned by successive plaque purification using virions containing only one nucleocapsid per envelope as inoculum. The ability to clone the virus by this method was demonstrated by the isolation of nondefective, genotypic variants of the virus with similar but not identical restriction endonuclease fragment patterns. Five distinct variants were identified by genotypic analysis with HindIII, EcoRI, SalI, and Bam HI restriction endonucleases. The characteristic genotype of each variant was maintained upon passage in insect larvae. The isolation of these virus variants demonstrates (i) the heterogeneity of the uncloned virus preparation and (ii) the ability to clone MNPVs by plaque purification of media-derived nonoccluded virions. The A. californica MNPV is being considered for commercial use as a pesticide in the United States, and the cloning of the virus, in view of the heterogeneity detected, may be advisable. The cloning and genotype analyses are also significant with regard to understanding the genetic nature of multiply embedded NPVs (those NPVs containing more than one nucleocapsid per envelope in the occluded form of the virus) and indicate that further genetic analysis of these viruses is possible.


Localization of Escherichia coli RNA polymerase binding sites on bacteriophage S13 and phiX174 DNA: alignment with restriction enzyme maps. Escherichia coli RNA polymerase has been shown to bind to a limited number of Hind and Hae III restriction enzyme fragments. On S13 replicative form DNA there are three major binding sites, and the locations correlate with promoter sites at the beginning of genes a and B and a site overlapping gene D and the beginning of gene E. Two less definite binding sites have been localized, one in gene F and one at the gene G-H junction. In phiX174 replicative form DNA, five sites, each with apparently similar binding properties, have been located, four of which correspond exactly to binding sites in S13. One site, at the beginning of the B gene, could not be assigned to exactly the same location found in S13. This was due in part to differences in the restriction cleavage maps in the area of the DNA and possibly to the higher background of nonspecific binding in the phiX174 experiments. The location of two of the phiX174 sites at the beginning of genes A and D-E corresponds very well with transcription data, but the site at the start of the B gene indicates the promoter site is closer to the initiation sequence of the B protein than was previously suggested on the basis of transcription data.


Isolation of a bacterial host selective for bacteriophage T4 containing cytosine in its DNA. An Escherichia coli B strain, B834 galU56, has been isolated which supports growth of bacteriophage T4 with cytosine in its DNA while restricting growth of T4 with hydroxymethylcytosine. This host is partially deficient in uridine diphosphoglucose as determined by the ability of DNA isolated from T4 grown on it to accept glucose in an in vitro assay. In this mutant an intact rgl restriction system recognizes unglucosylated hydroxymethylcytosine residues in phage DNA, while the absence of a functional rB restriction function prevents degradation of unmodified DNA containing cytosine.


Single stage urethroplasty as treatment for stricture disease. The use of a full thickness free skin graft for a single stage urethroplasty in stricture disease has been popularized recently by Devine and Horton. From 1973 to 1977, 40 patients at our hospitals have been treated with single stage urethroplasty using this technique. Excellent results have been noted on followup evaluation.


Simplified correction of female stress incontinence. A simplified operation for female stress incontinence, using a pair of double-prong needles, is described. A 90.4 per cent cure was achieved in 62 patients followed for a mean of 11.2 months. Merits of this procedure include operative simplicity and brevity, short hospitalization and a high rate of cure.


Evaluation of the dermal graft inlay technique for the surgical treatment of Peyronie's disease. The results of treatment with the dermal graft inlay technique for 7 patients with Peyronie's disease and the inability to achieve intercourse are discussed. All 7 patients were unable to attain tumescence postoperatively. We believe that patients who require surgical therapy for Peyronie's disease and who have functional impotence should be treated with silicone penile implants.


Enterobius vermicularis (pinworms), introital bacteriology and recurrent urinary tract infection in children. The relationship between pinworm infectation and introital cultures was investigated in 2 groups of girls. Those children with recurrent urinary tract infections were compared to agematched controls who had never had a urinary tract infection. We found a higher incidence of enteric organisms on the introital area and pinworm ova on the perianal skin in the group of girls with recurrent infection.


Hypocupremia induced by zinc therapy in adults. Hypocupremia occurred in an adult with sickle cell anemia who received zinc as an antisickling agent for two years. The hypocupremia was associated with microcytosis and relative neutropenia. Administration of copper resulted in an increase in RBC size and leukocyte counts. We have since observed hypoceruloplasminemia of varying degrees in several other sickle cell anemia patients who were receiving oral zinc therapy. This complication was easily corrected by copper supplementation.


Differences in etiology of pneumonias in nursing home and community patients. Comparison of 35 elderly patients hospitalized with pneumonia acquired in nursing homes and 35 elderly patients hospitalized with community-acquired pneumonia showed that 16 (47.1%) of the nursing home patients had received previous antibiotic therapy compared with two (5.9%) of the community patients. Klebsiella pneumoniae was isolated in 14 (40%) of the nursing home patients, but in only three (8.6%) of the community patients. Staphylococcus aureus was also more frequent in nursing home patients (nine, 25.7%) compared with community patients (five, 14.3%). Persons hospitalized with nursing home-acquired pneumonia should be treated initially with antimicrobial agents active against K pneumoniae and S aureus unless the clinical picture strongly suggests otherwise.


Septic bursitis.

Septic bursitis. In 12 cases of septic bursitis seen during 11 years, 11 patients were men and one patient was a woman, with a mean age of 51.3 years. The olecranon bursa was involved in nine cases. Staphylococcus aureus was grown from nine of ten culture-positive fluids. Bursal fluid WBC counts ranged from 1,550/cu mm to 165,000/cu mm, associated with low glucose levels in two cases, but not in three. Treatment with antibiotics and needle aspiration or surgical drainage was successful.


Carl Jung.

Carl Jung. Physicians should be prepared to provide prophylactic medications for travelers to malarious areas and to treat patients with malaria. Chloroquine hydrochloride is the suppressive agent of choice for treatment of mild infections due to all species of malaria except for those due to chloroquine-resistant strains of Plasmodium falciparum. For treatment of severe infections with P falciparum and for treatment of all infections due to chloroquine-resistant strains of P falciparum quinine is the suppressive agent of choice. Chloroquine is also the prophylactic agent of choice for most travelers. To prevent infection with P vivax or P ovale, primaquine must also be given. A RBC glucose-6-phosphate dehydrogenase level should be obtained before administration of primaquine. For prophylaxis of chloroquine-resistant strains of P falciparum, no completely satisfactory regime is presently available in the United States.


Therapy and prophylaxis of malaria.

Therapy and prophylaxis of malaria. Physicians should be prepared to provide prophylactic medications for travelers to malarious areas and to treat patients with malaria. Chloroquine hydrochloride is the suppressive agent of choice for treatment of mild infections due to all species of malaria except for those due to chloroquine-resistant strains of Plasmodium falciparum. For treatment of severe infections with P falficparum, quinine is the suppressive agent of choice. Chloroquine is also the prophylactic agent of choice for most travelers. To prevent infection with  P vivax or P ovale, primaquine must also be given. A RBC glucose-6-phosphate dehydrogenase level should be obtained before administration of primaquine. For prophylaxis of chloroquine-resistant strains of P falciparum, no completely satisfactory regimen is presently available in the United States.


Medical treatment of Serratia arthritis with trimethoprim-sulfamethoxazole. A patient with moderately severe rheumatoid arthritis and diabetes mellitus receiving steroids developed septic arthritis due to Serratia marcescens. Treatment with a new cephalosporin analogue, intra-articular and intramuscular gentamicin, and chloramphenicol alone and in combination proved ineffective. Finally, trimethoprim-sulfamethoxazole therapy, given for a protracted period, eradicated the infection without the need for surgical drainage.


[Effect of apressin and its combination with obzidan on central hemodynamic indices in the treatment of hypertension]. Apressine, obsidan and a combination of these two drugs were used for treating 44 patients suffering from hypertension, mainly stage IIB. When apressine was used to treat patients with the hypodynamic type of circulation, arterial pressure decreased due to considerable diminution of the arterial tone. Tachycardia developed simultaneously and the cardiac output increased, which restrained the hypotensive effect of apressine. The addition of the beta-blocking agent obsidan corrected, while its preliminary prescription prevented the development of the noted reflex stimulation of cardiac activity. This made it possible for the main valuable properties of apressine to become manifest, namely those which reduced the tone of the arteries and produced the hypotensive effect. Small doses of apressine and of the beta-blocking agent may be used and prolonged treatment applied with no side-effects.


[Effect of adaptation to physical loads on the contractile function and mass of the left ventricle of the heart]. Echocardiography was used to examine 20 highly trained athletes and 12 untrained persons at rest and during increasing physical load. It was established that in untrained persons the stroke volume in moderate and large physical loads increases mainly due to an increase in the diastolic output with the systolic output unchanged. In highly trained athletes the stroke volume with an equal load increases due both to growth in the diastolic output and to considerable decrease in the systolic output, i.e., due to the more complete ejection of blood from the cavity of the ventricle. As a result in trained patients a sufficient minute output in physical exertion is attained with less external work of the left ventricle and myocardial tension.


[Role of computer technology and mathematical modelling in the treatment of patients after operations on the heart]. On the basis of ten-year experience in theoretical studies and experimental tests mathematical models of hemodynamics were built for the follow-up of parameters of the cardiovascular system which cannot be determined by means of any other modern methods. Three years of clinical studies of the Hewlett-Pachard monitoring computer system and its modification helped to elaborate the mathematical backing, a bank of mathematical models, original automatic programs for measuring the cardiac index, the index of myocardial viability, etc. The automatic system provides for an individual approach in assessing the patient's condition in actual time and for control of the treatment.


[On keratoplasty indicated in progressive infection of the cornea (author's transl)]. A report is given about 9 patients with acute inflammatory process of the cornea. In all cases a penetrating keratoplasty was performed. This procedure is indicated in progressive infections of the cornea, mostly caused by bacteria. Some aspects of this proceeding are discussed.


[Experiences with timolol in treatment of glaucoma (author's transl)]. Timolol is a beta-adrenergic blocking agent that produces a significant decrease in intraocular pressure. Timolol ophthalmic solution 0,25% and 0,5% was compared to pilocarpine 1%, 2% and 4% in a randomized, double-masked study involving 40 patients with primary open angle glaucoma or ocular hypertension. Each patient was followed for 6 months. Timolol lowered the 1OP 30% compared to the pretreatment pressure, Pilocarpine 20%. Timolol was well tolerated in general, but 3 patients showed a superficial keratopathy. 30 other glaucoma patients with previously unsufficient pressure control received Timolol alone or in combination with a topical cholinergic agent or/and a systematic carbonic anhydrase inhibitor. The results are presented in detail.


On the rejection reaction against corneal grafts and first trails with tissue-typed and HLA-adapted donor material (author's transl). Rejection is a very important, in fact the most important cause of corneal graft failure since the improvements in the surgical grafting techniques. The percentage of rejections is especially high with regrafts and grafts in highly vascularised eyes. Therefore we tried to improve the prognosis of these particular groups by using tissue typed donor material matched as well as possible.


[Corneal covering of cornea in ulcerative keratitis: clinical and histological observations (author's transl)]. Clinical and histological findings are demonstrated in 4 cases with ulcerative keratitis treated by covering with full-thickness cornea. In only two cases the initial keratitis healed with scarring and a keratoplasty could be performed. The donor cornea is resorbed very slowly, remnants of Descemet-membrane of the graft are seen even after 20 months. Immunological reactions could not be observed.


[Immunological aspects of acute lymphoblastic leukemia (ALL) in children (author's transl)]. The prognostic significance of the immunological classification of ALL in children is described. While the prognosis of patients with the most frequent O- or common-ALL (frequency 70-85%) is comparatively good, prognosis of patients with T-ALL, which is most probably identical with acid phosphatase positive ALL,and with the rare B-ALL is worse. The therapeutic implications of the immunological classification is discussed.


The early cellular response to M. leprae. An ultrastructural study. The ultrastructural changes that develop in mouse peritoneal macrophages from 10 minutes up to 14 weeks after exposure to Mycobacterium leprae are presented. Phagocytosis occurred by a process of engulfment by cytoplasmic processes and incorporation into a phagosome, into which lysosomal enzymes were subsequently introduced. Electron transparent zones (E.T.Z.) were not observed around phagocytosed bacilli in this study, however discrete droplets of lipid-like material appeared in the cytoplasm of macrophages, between 2 and 4 weeks after ingestion of the micro-organisms. Phagosomes with double limiting membranes were observed in macrophages harvested as early as 40 minutes after exposure to M. leprae, contrary to the observations of Evans and Levy (1972).


Primary sulphone resistance. A preliminary report. A case of lepromatous leprosy proven to be a primary sulphone resistant one, has been reported. Bacilli from the case were found to be resistant as checked by their continued growth in the foot pads of mice receiving diet containing 0.001% D.D.S. A study to identify such cases is being systematically persued.


Introductory rifampicin therapy in lepromatous leprosy: a six month follow-up study. A double-blind comparative trial of 300 mg of Rifampicin given daily as against 50 mg D.D.S. administered likewise for an initial period of 3 months has been undertaken on 24 untreated cases of lepromatous leprosy. All the patients have been followed up for 6 months. The results revealed that patients in the former group became non-infective, as concluded from M.I. and mouse foot-pad results, within 3-4 weeks and their nasal ulcers healed faster. Clinical improvement was slightly better in the former group while no bacteriological differences were noticed in the two groups. E.N.L. was milder and slightly less common in the Rifampicin group.


Mycobacterium leprae in the striated muscle of tuberculoid leprosy patients. Striated muscle specimens from 24 untreated proved cases of tuberculoid leprosy and five healthy normal individuals were studied histopathologically for the evidence of leprous pathology. Atrophy or damage to the muscle fibre was not observed in any patient. Nineteen (79.16%) cases showed evidence of leprosy in striated muscles. Seventeen (70.83%) cases showed scanty histiocytic infiltrate between the muscle fibres. Thirteen (54.16%) cases had acid fast bacilli mostly inside the muscle. There was no correlation between the location of the bacilli and that of the histiocytes; in two cases, acid fast bacilli were seen without the histocyte. The bacilli were solidly staining and were lying singly in the undamaged muscle. There was no evidence of tuberculosis and, in the Control group, none showed any AFB or infiltrate. The presence of lepra bacilli did not depend upon the location of the muscle. Two of the muscle specimens not underneath the cutaneous lesions also had acid fast bacilli. 21.05% of these cases also showed simultaneous involvement of liver and lymph nodes. These are strong evidences of systemic nature of disease in tuberculoid leprosy as well.


Evaluation of bacteraemia in leprosy patients. Thirty five patients of leprosy have been screened for bacteraemia by haemolysis (HL), leucocyte adherence (LA) and buffy coat (BC) methods and the results have been compared. The HL method has yielded not only higher number of acid-fast bacilli (AFB) but also has detected more frequently AFB in blood of leprosy patients as compared to other methods. Further, it has been established that the skin over the cubital fossa does not play any significant role in contaminating blood samples while sampling blood by venepuncture.


Double-blind comparison of cefazolin and cephalothin in open-heart surgery. Ninety-nine patients undergoing cardiac surgery were randomly assigned to treatment with cefazolin and cephalothin to compare the effectiveness of these cephalosporins in the prevention of postoperative infections. The incidence of infections was low with both antibiotics (cefazolin 2.1 percent, cephalothin 4.6 percent). Intraoperative serum cefazolin levels were more evenly distributed, whereas a wide dispersion of cephalothin levels was observed. There was no measurable antibiotic detected in cardiac tissue samples in the majority of the cases. Adverse reactions (skin rashes) occurred only in three patients, all receiving cephalothin. It is concluded that cefazolin is as safe and effective as cephalothin in the prevention of postoperative infection in patients undergoing open-heart surgery.


The adenoma-carcinoma sequence.

The adenoma-carcinoma sequence. Evidence has been presented to show that most carcinomas of the large bowel develop in an adenoma, and that the life history of this sequence, although variable, probably takes on average 10 to 15 years. However, when the absolute numbers of adenomas and carcinomas are compared, it is apparent that the transition is uncommon. On a statistical analysis the malignant potential of adenomas is related to their size, growth pattern, and degree of epithelial atypia. If the adenoma-carcinoma sequence is the norm, then a study of these criteria in adenomas at different sites in the colon and rectum would resolve the disparity in published series between the distribution of adenomas and carcinomas.


Increase in the ratio of 18S RNA to 28S RNA in the cytoplasm of mouse tissues during aging. The possibility of alterations in cytoplasmic RNA in mouse liver, kidney and brain during aging was investigated. The cytoplasmic RNAs in these organs gave similar profiles of optical density at 260 nm with three major peaks at 28S, 18S and 4S on sucrose gradient centrifugation. However, the ratio of the amounts of 18S and 28S RNA increased significantly with age in the brain and liver. The polyacrylamide gel electrophoretic patterns of extracts of the three tissues under both native and denaturing conditions were nearly identical regardless of the age of the animals. Since most of the minor components separated on gels were probably in vivo degradation products of ribosomal RNA, these results suggest that the extent of apparent and hidden breaks in ribosomal RNA does not change during aging.


Properties of human malignant glioma cells in vitro. The properties of human glia and glioma cells in culture are reviewed. Glia-like cells from non-neoplastic brain show all accepted hallmarks of normalcy: limited life span, low terminal cell density, strong density dependent inhibition of proliferation, diploidy and contact inhibition of membrane mobility. Twenty five glioma lines have been studied. They all showed infinite life span, increased terminal cell density, relaxed density dependent inhibition of proliferation, aneuploidy and deficient contact inhibition of membrane mobility. So far all attempts to explain these departures from normal on the basis of a single metabolic defect have failed. Instead, all tested lines have shown an individual mosaic of structural and/or metabolic abnormalities characteristic for each line. This was particulary well demonstrated in studies of the glycosaminoglykans. The possibility is discussed that a malignant phenotype can a rise and exist in an almost infinite number of ways. The essential feature may be the acquisition of infinite growth potential which will set the stage for multiplication of genetic variants with an ever increasing fitness for proliferation and spread.


Training and continuing education for on-line searching. Training of searchers of the National Library of Medicine's (NLM) computer system has evolved from an intensive eight-month programme on batch retrieval through a highly compressed three-week course on interactive searching to the current five-level programme. The five-level curriculum consists, in order, of a computer-assisted instruction program (*MEDLEARN*), the Initial Training course, a three to six month in-service practicum, the Advanced Training course, and continuing education. Each stage in the programme is intended for the more sophisticated user and deals with increasingly complex and refined searching techniques. Various types of media are incorporated into the instruction which seeks to tie together theoretical and rote material through an extensive amount of practical experience at the terminal. This modularized curriculum provides the flexibility required to teach the use of a dynamic system to a diverse student population. At the present time, approximately 400 students per year are availing themselves of NLM on-line training.


MEDLINE users, usage and economics.

MEDLINE users, usage and economics. The on-line services of the National Library of Medicine (NLM) have grown in terms of both numbers of institutions using the service and in terms of total service provided. About 10 billed institutions are added per month with a total of 675 such institutions at the end of 1977. Total searches have now reached 900 000 per year. NLM services account for about 45% of all the bibliographic searching in the US. The effect of prices has been significant.


MEDLINE data communications.

MEDLINE data communications. A primary objective of the Data Communication Component (MEDLINE) of the Biomedical Communications Network (BCN) is to provide low-cost, reliable, nationwide and international access to the NLM on-line services. The network has evolved over several years and continues to change as new technologies and user requirements emerge. Today, TELENET and TYMNET form the backbone of the network complemented by a variety of other communication resources. This paper discusses the evolution of the network, and the domestic and international communication services.


The MEDLINE hardware and software.

The MEDLINE hardware and software. The National Library of Medicine's computer system has developed from a second generation computer to the large IBM multiprocessor system that is now used to maintain the MEDLINE file, provide retrieval services, and produce the computer photocomposed products of the NLM. On-line maintenance facilities have been developed for the final steps in the input and file maintenance processes. The retrieval program, ELHILL, and its supporting programs now provide more bibliographic searches than any other system in the world. The photocomposed products, including Index Medicus, are produced through the use of flexible publication programmes which have allowed NIH to use several different photocomposers.


The on-line user network: organization and working procedures. The National Library of Medicine's on-line user community has grown from a small group of 25 institutions in October 1971 to more than 900 in January 1978. Management of the MEDLINE User Network, co-ordination of on-line data-bases, and provision of user support services are an important function of the MEDLARS Management Section (MMS). MMS is the point of contact for on-line users; a service desk is maintained to provide immediate assistance; and technical materials describing the various data-bases are prepared including the monthly NLM Technical Bulletin and the On-Line Services Reference Manual. Other management and support activities include the preparation of statistical reports; handling of on-line centre applications received from the Regional Medical Libraries; co-ordination of codes and passwords for users; and the distribution of off-line prints, off-searches, and tape copies of the data-bases. A monthly current awareness service is also provided. The working procedures for these support activities are described.


MEDLINE searching and retrieval.

MEDLINE searching and retrieval. The development of MEDLINE searching philosophy and methodology is described. Searcher requirements and capabilities in moving from a batch-mode linear operation to the iterative searching and retrieval provided by the random access mode of MEDLARS II are discussed. A detailed tutorial on searching methodology for individual queries is covered. Elements of search formulation include requestor interview, query analysis, presearching, technics of selecting terminology, formulation logic, adapting indexing protocol in the search, on-line man-machine interface, and retrieval analysis. Similar searching technics are utilized in producing the two basic types of MEDLINE publications, recurring bibliographies (RBs) and literature searches (LSs). RBs are co-operative ventures between the NLM and professional organizations or other government agencies. LSs are NLM sponsored non-recurring bibliographies on a topic of current but also general interest to the medical community. All publications are produced through the retrieval and publication systems of MEDLARS II and graphic arts composing equipment. At the beginning of the 1978 publication year there were 27 RBs in routine production including Index Medicus. Through 1977, over 375 LSs had been produced.


Selection of MEDLINE contents, the development of its thesaurus, and the indexing process. The operation of MEDLINE requires three ongoing activities by persons having subject matter knowledge. These are literature selection, thesaurus maintenance and indexing. MEDLINE is intended to give access to the most generally useful biomedical literature rather than to provide indiscriminate comprehensive coverage. Literature is selected with the guidance of a group of health-science educators, editors and librarians who review periodicals under consideration for inclusion and re-evaluate those that are already regularly indexed. The MeSH thesaurus provides the descriptors that are used for subject indexing. Its hierarchical structure facilitates both general and specific searching. The appearance of new concepts and terminology in the literature requires a dynamic MeSH, but MeSH changes may complicate the process of searching backward in time. Maintaining MeSH requires finding a balance between the need for adaptability and the need for stability. Quality indexing requires accuracy and consistency in the assignment of subject headings. To this end, indexers receive didactic training plus practice under supervision. Precedents for indexers are detailed in an extensive Indexer's Manual and in MeSH annotations. Work of all indexers is reviewed on at least a sampling basis, and special sessions are held each year to familiarize indexers with MeSH changes.


[Alcohol induced changes of protein metabolism (author's transl]. An early manifestation of alcoholic liver injury is the accumulation of protein, as well as fat, in the liver. The increase in soluble proteins is associated with retention of water and swelling of the hepatocyte, resulting in hepatomegaly. Though "in vitro" ethanol inhibits hepatic protein synthesis, no consistent effects have been found after acute alcohol administration "in vivo". Moreover, after chronic alcohol consumption, the synthesis of liver protein is increased rather than decreased. Alcohol consumption, however, delays the secretion of proteins from the liver into the plasma, promoting accumulation in the liver of proteins which are primarily destined for export. The altered secretion is associated with decreased hepatic content of polymerized tubulin and visible disruption of microtubules, an organelle which may maintain the architectural organization required for transport of macromolecules. The alteration of microtubules has been linked to consequences of ethanol oxidation in the liver.


[Alcohol-induced changes of porphyrin metabolism (author's transl)]. Alcohol is a agenrphyrinogenic agent which may cause disturbances in porphyrin metabolism in healthy persons as well as biochemical and clinical manifestations of acute and chronic hepatic porphyrias. After excessive alcohol infestion in man a secondary hepatic coproporphyrinuria develops transiently, which persists in alcoholic liver disease. The alcohol-liver-porphyrinuria syndrome ranges first among the secondary hepatic disturbances of porphyrin metabolism. In acute hepatic porphyrias (acute intermittent porphyria, porphyria varigata and hereditary coproporphyria) alcohol induces delta-aminolevulinic acid synthase because in these porphyrias the control mechanisms of porphyrinogen and heme synthesis in liver are disturbed ("molecular regulatory diseases"). On the contrary, in chronic hepatic porphyrias, which are already associated with liver damage ("membrane diseases"), alcohol potentiates the disturbance of the decarboxylation of uro- and heptacarboxyporphyrinogen, which is followed by a hepatic accumulation of uro- and heptacarboxyporphyrin and their sometimes extreme urinary excretion. Alcohol may transform a symptomatic coproporphyrinuria into chronic hepatic porphyria. One can deduct from experimental and clinical studies that in liver alcohol inhibits the enzymes coproporphyrinogen oxidase, delta-aminolevulinic acid dehydratase and uroporphyrinogen decarboxylase and induces delta-aminolevulinic acid synthase. Abstinence from alcohol is an important measure in the therapy and prophylaxis of all hepatic porphyrias.


[Interaction between alcohol consumption and drug metobolism in the liver (author's transl)]. Alcohol interacts with a number of drugs in a paradoxical way; when alcohol and drugs are coingested, effect of drug on the body appears to be prolonged and enhanced, not only by additive process at the target organ but also by means of impaired absorption and metabolism of drug (= drug tolerance). By contrast, chronic alcoholics, who have proliferated endoplasmic reticulum and adaptively induced drug-metabolizing enzymes in the liver, when sober, require larger doses of drug than usually in order to produce a proper effect (= drug tolerance). The induction of drug-detoxifying enzymes by alcohol, however, could result in the enhancement of the hepatotoxic effect of some chemicals such as carbon tetrachloride. Clinical importance of alcohol-drug interactions is such that physician must be cautious about the ingestion of alcohol by his patients taking other medications and that he should rely heavily on careful patient observation to determine efficacy or toxicity of drug prescribed for alcoholic patients.


[Clinical aspects of alcohol induced liver injury (author's transl)]. Chronic alcohol consumption results in early biochemical and ultrastructural alterations of the hepatocyte which in turn may lead to alcoholic fatty liver as well as alcoholic hepatitis and via the central hyaline sclerosis to fibrosis and cirrhosis of the liver. Already at the stage of the alcoholic fatty liver an isolated increase of serum gamma-glutamyltransferase activity can often be observed; it results from hepatic microsomal enzyme induction and may facilitate early recognition of alcoholic liver injury. To establish the diagnosis, however, a histological examination of the liver is necessary. The therapy of alcohol-induced liver injury is based upon an absolute alcohol abstinence since alcohol itself or one of its metabolites are hepatotoxic.


[Effect of alcohol on the human and animal pancreas (author's transl)]. In Germany alcohol is responsible for 40--60 per cent of cases with chronic or chronic relapsing pancreatitis. The histologic lesions for a long time remain clinically asymptomatic. Their degree depends on the duration and the total amount of alcohol which is ingested. Promoters of alcoholic damage to the pancraes are a high intake of fat and protein and a genetic disposition. Acute application of alcohol leads to an inhibition of pancreatic secretion when the entrance of gastric acid into the duodenum is prevented. Otherwise a weak stimulation occurs with release of secretin. Chronic application of alcohol after a few months abolishes the initially seen inhibition and leads to an increase of enzyme secretion of the gland. The raised concentration of protein in the pancreatic juice is the cause of precipitation of protein plugs, and thus probably leads to the alterations which are typical for chronic pancreatitis.


[Legal and organizational bases of health care in the textile industry of the Congress Kingdom of Poland in the 19th and beginning of 20th cent. (forms of insurance, work safety and sanitary regulations)]. The origins of state interventionism in the field of health care in the textile industry of the Congress Kingdom of Poland go back to the first half of the XIX-th century. It could not, however, be developed earlier than in the last quarter of this century, at which time it resulted from the class struggle of textile workers, mainly in Lódź and Zyraŕdów. Legal and organizational patterns of health care were of foreign origin, but soon they were modified and adapted to the local conditions of the Congress Kingdom of Poland. It has to be underlined that it was the textile industry that stimulated legal and organizational changes in the field of industrial health care, not only in the Congress Kingdom of Poland but also in the whole contemporary Europe.