Live, attenuated influenza A/England/42/72 (H3N2) virus vaccine: a field trial.

Two doses of a live, attentuated influenza A/England/42/72 (H3N2) vaccine virus (inhibitor-insensitive Alice strain) were administered intranasally to 130 university students, and placebo was given to 134 students. Fourfold or greater rises in titer of hemagglutination-inhibiting antibody occurred in 68% of all vaccine recipients and in 88% of those with initial titers of less than 1:8; the geometric mean titer of hemagglutination-inhibiting antibody increased from 1:15 to 1:77. A 3.2-fold rise in titer of neuraminidase-inhibiting antibody occurred in 24% of the students. Side effects produced by administration of the vaccine include mild rhinitis and sore throat, which were found only during the first four days after administration of the first dose. Inhibitor-insensitive virus was shed only by three of 31 intensively studied vaccine recipients; these three subjects all had initial serum titers of hemagglutination-inhibiting antibody of less than 1:8. No transmission of vaccine virus to spouses was detected. During a 12-month interval after vaccination, the geometric mean titer of hemagglutination-inhibiting antibody in serum and the prevalence of antibody decreased minimally among the 47 vaccine recipients still available for study.


Induction of resistance in Staphylococcus aureus and Klebsiella pneumoniae by exposure to cephalothin and cefoxitin.

Six strains each of Staphylococcus aureus and Klebsiella pneumoniae were exposed to subinhibitory, but serially incremental, concentrations of cephalothin and cefoxitin in a totally defined liquid culture medium. After exposure to cephalothin, the level of resistance to both drugs increased; the gain was greater against cephalothin and among the strains of K. pneumoniae. After exposure to cefoxitin, resistance to both drugs developed; this resistance was greater against cefoxitin and among the strains of K. pneumoniae. Acquired resistance was not lost after serial subculture in drug-free medium. Qualitative tests revealed no cephalosporinase activity in the resistant straphylococci and in four of the strains of K. pneumoniae. Two strains of K. pneumoniae, which had been isolated from a patient before and after failure of treatment with cephalothin, respectively, had no demonstrable cephalosporinase activity as isolated but developed activity after exposure to cephalothin in vitro.


JC Papovavirus in progressive multifocal leukoencephalopathy.

Brain tissue from seven patients with progressive multifocal leukoencephalopathy was tested for the presence of papovaviruses. JC virus, ahuman papovavirus, was identified in all seven cases. Virus was isolated in tissue culture from extracts from each of four patients and was detected by immunofluorescence in sections from the other three. The new osolates were indistinguishable from the prototypical JC strain serologically and in all biological characteristics examined. Thus JC virus has, to date, been associated with 20 cases of progressive multifocal leukoencephalopathy.


Double-blind clinical assessment of ribavirin (virazole) in the prevention of induced infection with type B influenza virus.

The prophylactic effectiveness of oral administration of ribavirin (1-beta-D-ribofuranosyl-1,24-triazole-3-carboxamide, virazole) against artificially induced influenza B infection was evaluated in a double-blind clinical trial. Fifteen seronegative men received ribavirin capsules (600 mg/day in three divided doses), and 15 other men received placebo capsules two days before the inoculation of 6.4 X 10(4) 50% tissue culture infective doses of influenza virus B/Georgia/26/74 and for eight days after challenge. Ten men (69%) in each of the two groups developed mild to severe influenzal illness. Of these, five placebo-treated men developed severe febrile illness, while only one drug-treated man had illness of comparable severity. Illness of moderate severity was observed in three placebo-treated conrols and two drug recipients. There was no difference between the frequencies of isolation of virus or the anitbody responses in the two groups. Ribavirin suppressed signs and symptoms induced by influenza B challenge, but its effectiveness was marginal.


Comparative clinical and laboratory evaluation of the prophylactic capacity of ribavirin, amantadine hydrochloride, and placebo in induced human influenza type A.

The comparative prophylactic effectiveness of oral treatment with ribavirin (1-beta-D-ribofuranosyl-1,2,4,triazole-3-carboxamide; virazole) and amantadine hydrochloride against artificially induced infection with influenza A virus was evaluated in 29 seronegative men who received ribavirin capsules (200 mg) three times daily, placebo capsules three times daily, or amantadine capsules (100 mg) twice daily. Medication was started two days before the inoculation of 2 X 10(4) 50% tissue culture infective doses of A University of Maryland/2/74 (H3N2) influenza virus and was continued for eight days after challege. Nine of the 10 subjects who received ribavirin, eight of the nine subjects who received placebo, and six of the 10 subjects who received amantadine developed influenzal illness. Significantly less virus was isolated from the amantadine-treated group than from the placebo-treated or the ribavirin-treated group. Antibody responses of the ribavirin-treated and placebo-treated groups were quite similar to each other; however, prophylactic treatment with amantadine significantly reduced titers of serum antibody and febrile responses. In a separate clinical trial involving challenge with A/Dunedin/73 (H3N2) influenza virus, ribavirin also failed to show prophylactic effectiveness.


Superinduction of interferon with metabolic inhibitors: possible mechanisms and practical applications.

Ten years have passed since cycloheximide was first shown to enhance endotoxin-induced production of interferon in mice, in the first demonstration of what was later called the superinduction of interferon. Various inhibitors of protein and RNA symthesis, as well as combinations of these inhibitors, have been shown to act as superinducing agents of interferon production stimulated by polyriboinosinic-polyribocytidylic acid. The evidence that superinduction is due to the suppression of a mechanism of post-transcriptional regulation of interferon synthesis is rather convincing. The notion (first proposed about six years ago) that this modification is caused by a protein "repressor" remains the most plausible, albeit still unproved, hypothesis. The availability of systems that translate with fidelity interferon messenger RNA isolated from induced cells should prove most useful in the elucidation of post-transcriptional control mechanisms of interferon synthesis and of interferon superinduction. Meanwhile, superinduction has become a useful tool for the production of large quantities of interferon. In particular, this technique has been successfully applied to the production of interferon from human diploid fibroblasts. The clinical potential of this material remains to be critically examined.


A perspective from controlled investigations of chemotherapy for viral respiratory infections.

Failure to translate discoveries about the etiology of viral respiratory infections into effective vaccines has stimulated research into antiviral chemotherapy. Volunteers whose antibody status before challenge is known and who have been exposed to a known dose of virus at a defined time provide an objective system for controlled observation of antiviral chemotherapy. A perspective on experience with drugs of five different categories of mechanisms of action is presented. Prophylactic and possibly therapeutic control of influenza and rhinovirus infections is possible. Field trials have confirmed that some regimens have beneficial effects and have shown the clinical restrictions of others. Chemotherapy is enhanced by immunoprophylaxis, and vice versa. If the potential of antiviral chemotherapy for clinical use is to be realized, complex virologic problems (some related to drugs and others unrelated) must be overcome. The groundwork is laid for new directions and new successes in the prevention and treatment of viral respiratory diseases with antiviral drugs.


Defective leukotaxis in patients with lepromatous leprosy.

Serums from patients with lepromatous leprosy show a high incidence of a chemotactic inhibitor. This inhibitor acts directly on leukotactic factors (bacterial chemotactic factor, C3 fragment, and C5 fragment) to render the factors irreversibly inactive. Functionally, the inhibitor acts as a chemotactic factor inactivator. While normal serum shows no inhibitory activity under the conditions employed, inhibitory activity causing more than 30 per cent reduction of the bacterial chemotactic factor was found in the serums from 14 of 19 patients with lepromatous leprosy. Although exceptions were noted, a correlation was found between the presence of the inhibitor and depressed skin reactivity to a series of antigens (Lepromin, Trichophytin, Candida, PPD, and mumps antigen) used for elicitation of delayed-type hypersensitivity reactions. The presence in leprosy serums of this inhibitor may be responsible, at least in part, for some of the defects of cellular inflammatory responses in patients with lepromatous leprosy.


A method for the immunoassay of insulin in the presence of insulin therapy-induced antibody.

Antibodies produced by exogenous insulin therapy interfere with the measurement of immunoreactive insulin (IRI) by conventional methods. A modified acid-alcohol extraction method is described which allows for accurate measurement of total IRI in the plasma of insulin-treated patients. Total extractable IRI includes both IRI bound to antibody and free IRI. Free IRI can be separated from antibody-bound IRI by Sephadex G-50 chromatography. The amount of insulin bound to antibody is calculated as the difference between total extractable IRI and the free IRI. The accuracy of these methods is demonstrated by recovery experiments. Suggested applications of these techniques to clinical states are offered.


Platelet-bound ristocetin aggregation factor in normal subjects and patients with von Willebrand's disease.

Antiserum specific for that part of the factor VIII complex designated ristocetin aggregation factor (VIIIRAF) was prepared by immunizing rabbits with VIIIRAF derived from the plasma of a hemophilic patient with circulating antibody to factor VIII procoagulant activity (VIIIcoag). The rabbit antiserum prevented ristocetin-induced platelet aggregation and platelet retention by glass-bead columns. Although the antiserum also inactivated VIIIcoag in normal plasma, it did not inactivate VIIIcoag which had been dissociated from VIIIRAF by chromatography in 1 M NaCl, thus establishing the antigenic specificity of these two factors. When the VIIIRAF antibody was conjugated with fluorescein isothiocyanate and used to examine platelets from normal subjects and patients with von Willebrand's disease, the normal platelets showed a granular fluorescence similar to that observed with antifibrinogen serum whole von Willebrand platelets showed no fluorescent staining. The normal platelets retained the VIIIRAF granules during 18 hours incubation and 5 washings in artificial medium while the von Willebrand platelets failed to acquire granules after 18 hours in normal plasma. When the unstained platelets from patients with von Willebrand's disease were suspended in normal plasma and then aggregated by the addition of ristocetin, the aggregates not only stained brightly for VIIRAF, but fluorescent granules could be seen on individual platelets in the aggregates. These observations suggest that ristocetin causes the binding of VIIIRAF to platelets as well as platelet-to-platelet adhesion.


The mechanism of glycerol-induced acute renal failure.

Ten rabbits with transparent ear chambers were grafted with small pieces of kidney. The resulting vessel anastomosis and restoration of renal blood flow allowed continuous microscopic observations of functioning renal tissue in vivo. When the grafts were well established, acute renal failure was induced in the rabbit by glycerol injection. All cases showed similar changes. Within minutes the brisk blood flow within the renal grafts became progressively more sluggish until complete stasis was established. The initial change was a blanching of intertubular and glomerular capillaries with progressive dilation and stasis of renal veins. Only after almost complete cessation of blood flow in most graft vessels, generally after a further 10 minutes, was any change in arteries or arterioles observed. The afferent arterioles and then larger arteries showed constriction followed by complete stasis. The ear chamber vessels (nonrenal) continued to flow normally. Blood flow was slowly re-established in the grafts and by the next day was normal in the surviving rabbits. These studies provided visual in vivo evidence that the mechanism of glycerol-induced acute renal failure is mediated by a reversible renal ischemia and that the factors responsible act particularly on renal vasculature. However, the mechanism whereby blood flow ceases is obscure and it cannot be attributed to arterial or arteriolar constriction.


The facial tics.

The abnormal movements of the facial muscles are classified and the diagnosis and treatment considered in light of 22 cases of hemifacial spasm. Forms of treatment which give only temporary cessation of spasm and require complex and unpleasant treatment to be oft repeated are seldom tolerated for long by the patient. Permanent cure of spasm can only be obtained when the facial nerve or its branch to the muscle is permanently divided or the muscle itself excised. Neurotomy as practised by German (1942) and Scoville (1955) has not been found satisfactory in the present series. Neuro-anastomosis at different sites in the course of the 7th nerve is discussed and shown to be of value in patients with severe widespread spasm and in those in which the spasm is more localised. This method results in only temporary palsy of the facial muscles, the duration of the palsy depending on the site of the division of the facial nerve.


Facial nerve paralysis caused by carcinoma developed in thorotrastoma in the parotid gland.

A carcinoma developed in a thorotrastoma of the right parotid gland and caused facial paralysis 28 years after a sialography with radioactive thorotrast. The literature is reviewed, and another case is reported in which facial nerve paralysis occurred without evidence of malignancy.


Rhabdomyosarcoma of the middle ear and mastoid.

A case of embryonal rhabdomyosarcoma of the middle ear and mastoid is presented. The patient was treated by irradiation and Actinomycin D, and survived 4-5 months.


Placental lactogen (chorionic mammotrophin) in the field vole, Microtus agrestis, and the bank vole, Clethrionomys glareolus.

Placental lactogen has been detected in the field vole, Microtus agrestis, and the bank vole, Clethrionomys glareolus, using a co-culture technique. In field voles this activity could be detected from about day 8 of pregnancy to shortly before term, and stimulated both mouse and vole mammary gland to secrete in vitro. Partial immunological cross-reaction was detected in a radioimmunoassay system between rat prolactin and either extracts of vole pituitaries or media on which vole pituitaries had been cultured; vole placental lactogen showed no cross-reaction with rat prolactin. One site of origin for this hormone is probably the trophoblastic giant cells.


Site of origin of the pulsatile secretion of luteinizing hormone in long-term ovariectomized rats.

If long-term ovariectomized rats are treated with the long-acting barbiturate, sodium phenobarbitone, the well-known pulsatile secretion of LH is depressed, resulting in a constant, still raised, plasma LH level. This indicates that in all probability ovariectomized rats secrete LH in both a tonic and a pulsatile way, only the latter being sensitive to phenobarbitone treatment. Constant infusions of synthetic LH-RH into phenobarbitone-treated ovariectomized rats induced a steadily increasing plasma LH concentration without pulsations, whereas pulsatile infusions of the releasing hormone, following a constant infusion, resulted in a pulsatile secretion of LH. This indicates that the pulsatile secretion of LH in ovariectomized rats is the result of a pulsatile secretion of the hypothalamic releasing hormone; the pituitary gland itself is not the site of origin of the phenomenon.


[Recommendations of the German Society for Clinical Chemistry. Performance of clinical-chemical tests on pharmaceuticals (author's transl)].

In the Federal Republic of Germany, the recommendations of professional bodies for the testing of pharmaceuticals, which were published rather a long time ago, do not refer to clinical-chemical investigations (Report of the executive committee of the German Pharmacological Society and the Commission for the establishment of guide lines for the testing of pharmaceuticals, Naunyn-Schmiedeberg's Arch. Exp. Pathol. Pharmakol 245 (1963) Supplement p. 20; and Report of the Executive Committee of the German Society for Internal Medicine for the establishment of guide lines for clinical testing of pharmaceuticals, e.g. Klin. Wochenschr. 43,698 (1965)). Since the results from animal experiments are of only limited value for the interpretation of the human response to pharmaceuticals, it is essential that clinical chemical studies should be very carefully planned. The German Society for Clinical Chemistry has therefore summarized the body of collective experience in the testing of pharmaceuticals. The following guide lines should also ensure that the accuracy and interpretive value of the results from different investigators are comparable. The recommendations also contain a program for the clinical chemical investigation of body functions. Additional tests are necessary for the assessment of many pharmaceutical preparations. In certain cases (e.g. topical application), a more restricted type of investigation may be sufficient at a later stage of testing.


Human B-lymphocyte antigens expressed by lymphocytic and myelocytic leukemia cells. I. Detection by rabbit antisera.

A previously uncharacterized human B-lymphocyte antigen has been detected by rabbit antisera raised to papain digests of spleen cell membranes. The unabsorbed sera reacted in both cytotoxicity and immunofluorescent tests with normal B lymphocytes and cultured B-cell lines but not with normal T lymphocytes or cultured T-cell lines. The cytotoxicity titers against B cells were as high as 1:32,000, whereas the same sera undiluted were negative against T cells. By immunofluorescent staining 6-14% of unfractionated normal lymphocytes and 48-85% of B-rich lymphocyte preparations were positive. Normal peripheral blood granulocytes, platelets, erythrocytes, and phytohemagglutinin blasts were negative. The antisera reacted with the same high titers against leukemia cells from approximately 70% of the patients with acute lymphocytic leukemia, acute myelocytic leukemia, chronic myelocytic leukemia, and seven of eight cases of chronic lymphocytic leukemia. From absorption studies it appeared that the same antigen was being expressed by leukemia cells and normal B lymphocytes. Using immunofluorescent staining the anti-B-cell antisera were able to detect positive leukemia cells in the bone marrow of patients with advanced leukemia and to monitor the elimination of these cells after chemotherapy. Soluble B-cell antigen was found in the serum of some leukemia and lymphoma patients do but not in normal serum.


Natural hybridization between parthenogenetic and bisexual lizards: detection of uniparental source of skin grafting.

Skin graft evidence is used to directly identify the unisexual parent of natural hybrids produced between the bisexual species Cnemidophorus inornatus and the unisexual Cnemidophorus neomexicanus. Reciprocal grafts transplanted among there suspected hybrids between Cnemidophorus inornatus and Cnemidophorus neomexicanus are rejected as well as grafts from the hybrids to C. neomexicanus, indicating that the hybrids are each genetically different from each other and that C. neomexicanus has the ability to reject foreign grafts. Allografts among C. neomexicanus and xenografts from C. neomexicanus to the hybrids are not rejected, indicating that C. neomexicanus is genetically homogeneous and that the hybrids possess genomes genetically identical to C. neomexicanus. Electrophoretic analysis of the hybrids and their probable parents supports the evidence obtained from skin grafting that C. neomexicanus is one of the parents, and suggests that C. inornatus, rather than C. tigris, is the bisexual parent. Chromosome spreads obtained from the hybrids reveal a triploid number of 69, a number consistent with their presumed origin from unreduced diploid ova (2N = 46) from C. neomexicanus and haploid serum (N = 23) from C. inornatus. Preliminary evidence is presented of the first hybrids known between Cnemidophorus inornatus and Cnemidophorus  uniparens. Histological examination of the tests suggests that these hybrids are sterile. Included is a list summarizing all known hybrids between bisexual and unisexual species of the genus Cnemidophorus.


Influence of atmospheric oxygen concentration on acetylene reduction and efficiency of nitrogen fixation in intact Klebsiella pneumoniae.

Oxygen-limited (N2-fixing) chemostat cultures of Klebsiella pneumoniae supplied with a N-free medium were established by introducing low atmospheric O2 concentrations into the gas supply of anaerobic glucose-limited N2-fixing chemostat cultures; the molar growth yield for glucose and the efficiency of N2 fixation (mug N fixed/mg glucose consumed) were increased (by up to 82%) from the anaerobic values. Acetylene-reducing activity was inhibited reversibly by O2 in samples from O2-limited and anaerobic glucose-limited chemostat cultures. Oxygen uptake rates in samples from these chemostat cultures were similar, but C2-H2-reducing activity in samples from O2-limited chemostat cultures was more tolerant of low atmospheric O2 concentrations, in part because of a higher population density. In the absence of glucose, O2 was required at a low atmospheric concentration for C2H2 reduction in samples from either O2-limited or anaerobic glucose-limited chemostat cultures. The possibility is discussed that ATP generated from oxidative phosphorylation can be used for N2 fixation in K. pneumoniae.


RP4-mediated conjugation in Acinetobacter calcoaceticus.

The P class R factor RP4 was transferred from Escherichia coli K12 to Acinetobacter calcoaceticus. RP4 conferred similar levels of antibiotic resistance in A. calcoaceticus to those in the E. coli K12 donor. Only slight instability of RP4 in A. calcoaceticus was detected. Transfer of RP4 between strains of A. calcoaceticus was by conjugation and was accompanied by transfer of chromosomal genes. Possible polarity of marker transfer was observed and linkage between a number of chromosomal markers was demonstrated.


Relationship of structure to function in bacterial endotoxins: serologically cross-reactive components and their effect on protection of mice against some gram-negative infections.

Rabbit antisera were prepared against the heptoseless Re mutants, Salmonella minnesota R595 and S. typhimurium SLI102, as well as against purified R595 glycolipid coated on autologous erythrocytes. The antisera cross-reacted with the endotoxic glycolipids extracted from Re mutants of various bacterial strains, including S. minnesota R595, S. typhimurium SLI102, Escherichia coli D3Im4, E. coli D2If2 and E. coli F515, as shown by passive haemagglutination and gel diffusion tests. The anti-Re sera also cross-reacted with the RESI preparations (a purified 'lipid A' fraction) from the endotoxic lipopolysaccharides of various heterologous smooth Gram-negative bacteria including Serratia marcescens. Psuedomonas fluorescens and E. coli 0127. However, the same antisera failed to protect mice against infection by Gram-negative bacteria such as Klebsiella pneumoniae type II, S. typhi 0901, P. aeruginosa 119 and E. coli. The results suggest that although the lipid moieties of the lipopolysaccharides in the cell wall of Gram-negative bacteria share cross-reactive immunodeterminant groups, these groups may not be accessible to antibody against them.


Isolation and composition of an alkali-soluble glucan from the cell walls of Saccharomyces cerevisiae.

An alkali-soluble glucan was obtained from the cell walls of Saccharomyces cerevisiae NCYC1109 and baker's yeast by extraction with cold, dilute sodium hydroxide under nitrogen. The glucan, which represented approximately 20% of purified glucan was homogeneous and was shown to be free from contamination by other cell-wall polysaccharides by ultracentrifuging, gel filtration and electrophoresis. In addition to glucose, the glucan contained traces of mannose and nitrogen, but no hexosamine. Structural analyses revealed the presence of 80-85% (1 leads to 3)-beta-D linkages, 8-12% (1 leads to 6)-beta-D linkages and 3-4% branched residues linked through C-1, C-3 and C-6. The molecular weight of the glucan was estimated to be about 250000. Electron-microscopic examination of the cell walls after alkali extraction showed that an amorphous surface layer had been removed revealing numerous bud scar structures.


The isolation of nuclei from the filamentous fungus Aspergillus nidulans.

A method has been developed for isolating nuclei from the filamentous fungus Aspergillus nidulans. In this procedure, the mycelia from 14 to 16 h spore-derived cultures of A. nidulans NRI, a stable diploid strain, were frozen with liquid nitrogen and homogenized in a Waring blender. After homogenization, the mycelia were warmed to 4 degrees C and the nuclei were purified from the homogenate by differential centrifugation followed by sedimentation through 2.1 M-sucrose. The final nuclear yield was 15 to 20%, based on DNA estimations. The purified nuclear pellet was free of whole cells. The morphology of the isolated nuclei resembled that of the in situ nuclei; they contained a nucleolus, chromatin, and had a surrounding double membrane. The purified nuclei were characterized by a DNA:RNA:protein ratio of 1:2.8:8.7.


Uptake of galactose into Escherichia coli by facilitated diffusion.

Strains of Escherichia coli devoid of systems for the active transport of galactose (galP mgl) still grow on galactose but at rates that are a function of the galactose concentration of the medium: half-maximal growth rates require more than 2 mM-galactose to be present. Evidence is presented that galactose is taken up by such strains by facilitated diffusion on a carrier specified by the umg gene (or by a gene highly co-transducible with it) which is thus a part of, or closely associated with, an enzyme II for glucose of the phosphoenolpyruvate-phosphotransferase system. However, the entry of galactose does not require phosphotransferase activity, and the sugar taken up appears in the cells as free galactose.


Comparative ultrastructural studies of insect granulosis and nuclear polyhedrosis viruses.

Optical diffraction studies indicated that the periodic lattice structure in electron micrographs of the capsids of two granulosis and two nuclear polyhedrosis viruses were indistinguishable. The capsid is composed of stacked rings spaced 4-5 nm apart. Comparison of the intracellular forms of Bombyx mori nuclear polyhedrosis virus with negatively stained virus particles leads to encourage the more general use of the term 'capsid' instead of 'intimate membrane' and the term 'virus membrane' in place of 'developmental membrane'. These terms are consistent with those currently used for most animal and plant viruses.


Cleavage of T4-induced proteins during phage morphogenesis: characterization of peptides.

Polypeptides of low mol. wt. have been extracted from T4 coliphages and from Escherichia coli B cells infected with a wild type and various amber mutants of bacteriophage T4. Six peptides were fractionated by chromatography on phosphocellulose: three of them were cleaved from proteins synthesized late in infection and related to phage head. The remaining three peptides have been shown to arise from early-labelled phage-induced proteins. Two of these six small petide fragments were found in the head of the T4 phage.


Genes 46 and 47 of phage T4: possible compensation for loss of their function.

The gene 46 and 47 functions of phage T4 are required for normal DNA replication, recombination, u.v. repair and host DNA breakdown, and yet am mutants defective in these genes characteristically form tiny plaques on Escherichia coli strains lacking an am suppressor. Our results imply that this limited growth is not due to misreading of am codons or partial function of nearly complete poly-peptides terminated at the am mutation. Thus it appears that genes 46 and 47 are not entirely essential, perhaps because other phage or host products can partially compensate for their loss.


The effect of host-cell starvation on virus-induced lysis by MS2 bacteriophage.

Infection of glucose, sulphur or nitrogen starved cells with MS2 virus results in the production of progeny virus but the absence of cell lysis and the failure of progeny virus release. Addition of glucose of sulphur to the correspondingly starved cells results in the normal release of virus within 40 to 60 min. Return of nitrogen to nitrogen-starved cells, however, does not result in the release of virus, even after 1 1/2 h. In experiments with uninfected, starved cells it was found that glucose or sulphur starved cells begin dividing within 45 min after the limiting compound is returned. In contrast, nitrogen-starved cultures have not begun to divide 1 1/2 after the return of nitrogen. The correlation between the time it takes for starved, infected cultures to resume lysis after the return of the limiting compound and the time similarly starved, but infected, cells normally begin division after addition of the limiting compound supports the hypothesis that lysis by RNA phage is related to cell division and may result at the time of cell division from failure of the cells to divide properly.


Reflection-impulsivity and behavioral problems in emotionally disturbed boys.

In order to investigate the difference in the behavioral problems presented by cognitively impulsive and reflective emotionally disturbed boys, the parents of 17 impulsive and 13 reflective boys in residential treatment were asked to rate their sons' behavior. Results indicated that in contrast to reflective emotionally disturbed boys, impulsives were more likely to talk of others blaming them unfairly, threaten to harm themselves, hit and bully other children, and be excessively rough in play. On the other hand, reflectives were more unwilling to talk with adults outside the family. Results were discussed in terms of supporting both previous research and Kagan and Kogan's (6) "fear of failure" hypothesis.


Venery, the spinal cord, and tabes dorsalis before Romberg: the contribution of Ernst Horn.

Usually Heinrich Romberg is credited with having established tabes dorsalis as a clinicopathological entity in the 1840s. But Romberg's teacher, Ernst Horn (1774 to 1848), had inspired five different students to write their doctoral dissertations on the same subject. These five theses, published between 1817 and 1827, as well as M. Steinthal's most comprehensive later description, were triggered by Horn's observation of the lower spinal cord atrophy which he found in one of his tabetic patients at autopsy. The dissertations are analyzed together with the prior literature reflected in them as it deals with the spinal cord. Discussions of the putative influence of the spinal cord on the vagaries of male sexual function, and vice versa, began with "consumption of the backbone", referred to in the Hippocratic corpus. "Venery"--if not veneral disease as we understand it--was thought throughout the centuries to be the prime cause of tabes. One may presume that the rising concern with public health and with national aims--a kind of "moral rearmament"--caused the subject to be so vigorously pursued by members of the young medical generation in early 19th-century Germany.


Comparison of dantrolene sodium and diazepam in the treatment of spasticity.

The effects of dantrolene sodium and diazepam were compared in a double crossover study of 42 patients with spasticity due to stable multiple sclerosis. Both drugs reduced the findings of spasticity, clonus, and hyperreflexia, and the complaints of muscle stiffness and cramping. Each drug had different side effects which suggest indications and contraindications for its use in spastic patients.


Chymopapain in the treatment of ruptured lumbar discs. Preliminary experience in 48 patients.

The results of chemonucleolysis in 48 patients with lumbar disc disease revealed marked improvement in 58%, slight improvement in 23%, and no improvement in 19%. Serious anaphylactic reactions occurred in two patients. These results and those of other neurosurgical and orthopaedic studies are summarized and compared with the 70% improvement rate obtained with a placebo in a recent double blind controlled cooperative study. Only those few investigators participating in the double blind study are now permitted to use intradiscal chymopapain. It is concluded that the ultimate place of chemonucleolysis, if any, in the treatment of ruptured lumbar discs remains to be determined.


The fine structural localization of S-100 protein in rodent cerebellum.

This report describes the first fine structural locations of S-100 protein in the hamster cerebellum. Innovations in tissue fixation as well as tracer preparation enable localization of S-100 protein to several critical cellular and subcellular sites. Certain neuronal elements, Purkinje cells, contain S-100 protein in both cytoplasm and nucleus. Specific membrane structures including plasma membranes and the nuclear membranes of Purkinje cells are strikingly positive. Localization of S-100 protein to the pericapillary astrocytic endfeet as well as regions of the synapse are of particular biological interest. The clear nuclear localization of the molecule suggests a role in the genetic expression of the developing mammalian brain.


Body-background defects with 99mTc-DTPA after renal transplantation: case reports.

Photon-deficient areas adjacent to transplanted kidneys were seen in the early phases of several dynamic studies obtained with 99mTc-diethylenetri-aminepentaacetic acid (99mTc-DTPA). The causes included hematoma, urinoma, and lymphocele. These fluid collections do not readily exchange as part of the extracellular space and, if sufficiently large, may be visualized as photon-deficient areas in the normally homogeneous background of 99mTc-DTPA studies.


Ridge augmentation: an evaluation and follow-up report.

An evaluation was made of results of follow-up studies, ranging from nine months to about 3 1/2 years, of six patients who had mandibular ridge augmentations at the University of Minnesota Hospitals. Clinical observations, patients' subjective feelings, and measurements of vertical loss of the original graft were the main considerations in the studies. Although there was almost continual resorption of the bone grafts after surgery patients were satisfied with the procedure and the current dental function.


Adhesive bonding of arch bars for maxillomandibular fixation.

From a preliminary evaluation, many of the disadvantages of the conventional arch bars appear to be overcome with this new technique. Of particular importance is that no anesthetic is required during placement of the arch bars except when needed for aligning displaced segments or open reductions. The laboratory work can be delegated to a technician, and operating time rarely exceeds an hour. Further evaluation is being done.


Morphological changes in indefinitely surviving enhanced ectopic rat cardiac allografts.

The histological changes of ectopic cardiac allografts in rats have been studied. These consisted of (a) a diffuse chronic inflammatory cell infiltrate of the myocardial interstitium accompanied by variable degrees of fibrosis (b) variable degrees of intimal hyperplasia of the coronary arteries with segmental disruption of the internal elastic lamina.


Optimum levels of CPAP for tracheal extubation of newborn infants.

Arterial oxygen tension and functional residual capacity were studied in 16 intubated, spontaneously breathing newborn infants recovering from respiratory disease. Studies were made at 2 cm H2O continuous positive airway pressure, at zero end expiratory pressure, and following extubation. The study showed that PaO2 and FRC at 2 cm H2O CPAP were the same as observed following extubation, but that both values were significantly lower at ZEEP.


Defective neutrophil motility in children with measles.

The random migration and chemotactic ability of neutrophils from ten patients with uncomplicated measles was found to be grossly impaired when compared to a group of normal children. Chemotaxis to endotoxin activated serum and to hydrolysed casein was markedly depressed, but serum from measles patients, when activated by endotoxin, generated and chemotactic activity and did not contain leukotactic inhibitors. The defect in neutrophil motility was confirmed in vivo by abnormal Rebuck skin windows. The defect was temporary, and recovery of normal chemotaxis was observed by the eleventh day after the onset of the rash.


A controlled study of intrathecal antibiotic therapy in gram-negative enteric meningitis of infancy. Report of the neonatal meningitis cooperative study group.

Eighteen institutions collaborated in evaluating the comparative efficacy of combined ampicillin and gentamicin therapy with and without intrathecal administration of gentamicin on the clinical and bacteriologic responses of 117 infants with meningitis caused by gram-negative enteric bacteria. There was a random distribution of patients within the two study groups with regard to age on enrollment, birth weight, sex, race, number of infants greater than 30 days of age, the etiologic agent, and their antimicrobial susceptibilities. There were no statistically significant differences (P greater than 0.05) in mortality, morbidity, or days that cerebrospinal fluid cultures remained positive among the infants in the two treatment groups. The case fatality rate for all patients was 32%; that for full-term infants (18%) was significantly lower (P less than 0.01) than that for low-birth-weight infants (45%) or for the patients greater than 30 days of age (48%). Fifty-one of the 80 (64%) survivors were assessed as normal on follow-up examinations performed up to four years after illness.


Enterotoxigenicity and invasive capacity of "enteropathogenic" serotypes of Escherichia coli.

Forty-two strains of Escherichia coli that agglutinated in pools of antisera used to identify "enteropathogenic" serotypes were tested for heat-labile and heat-stable toxin production and for their ability to invade intestinal mucosa. None of the strains tested were enterotoxigenic or enteroinvasive as determined by the adrenal cell (heat-labile toxin), the suckling mouse (heat-stable toxin), or guinea pig eye (invasive capacity) assays. Our observations suggest that serotyping of E. coli is an unreliable method to identify isolates that are capable of causing gastroenteritis, at least as determined by available in vitro techniques.


Fulminant neonatal sepsis and necrotizing enterocolitis associated with a "nonenteropathogenic" strain of Escherichia coli.

During 1973 a nonendemic mucoid strain of Escherichia coli entered the nursery of a hospital in Houston. This organism caused septicemia and was associated with a high incidence of necrotizing enterocolitis. The illness was fulminant and characterized by apnea, abdominal distension, and shock. Diarrhea was not a feature of the symptom complex. The epidemic organism was nontypable. Assays for invasiveness, enterotoxin production, and Kl antigen were negative. Surveillance revealed a colonization rate of 14%, an attack rate in colonized infants of 19.5%, and a mortality rate of 87.5%. These data suggest that in certain instances the specific bowel flora may increase the incidence and severity of NEC.


A nursery outbreak caused by Serratia marcescens--scalp-vein needles as a portal of entry.

Serratia marcescens rarely causes infections in newborn infants. We recently studied an epidemic caused by a multiply-resistant, serotype 014:H12 Serratia marcescens that involved 42 infants. Cutaneous abscesses at previous intravenous infusion sites occurred nine times, usually required surgical drainage, and were the most striking infections during the outbreak. Six infants developed Serratia bacteremia and two died with Serratia meningitis; 34 patients were colonized with Serratia but remained uninfected. An epidemiologic investigation of the 83 infants at risk in the nursery assessed factors predisposing them to colonization or infection with the epidemic organism. Colonization of the throat, umbilicus, gastrointestinal tract, or skin was frequent among infants as was carriage of Serratia on nursey employees' hands. Infected and colonized infants were the most important reservoir for Serratia in the nursery and cross-infection between infants readily occurred. Scalp-vein needles appeared to provide a portal of entry of Serratia in colonized infants, predisposing them to abscess formation and bacteremia.


A simple monophasic medium for axenic culture of hemoflagellates.

An inexpensive, easily prepared monophasic medium which supports continuous culture of Leishmania donovanì (approximately 4 X 10(7) cells/ml/day 5) and L. tarentolae (approximately 3.5 X 10(7) cells/ml/day 5) promastigotes has been developed. This medium, designated HO-MEM, is a modified Eagle's minimal essential medium with Spinner's salts and 10% fetal calf serum. Epimastigotes of Trypanosoma cruzi, Costa Rica strain, also grew well in HO-MEM (approximately 2 X 10(7) cells/ml/day 5) but cells of the Corpus Christi strain grew poorly in the medium. The initial inoculum for all of the above culture systems was 3 X 10(5) cells which means that there was approximately 100-fold increase in cell number within 5 days of culture. Average doubling time for L. donovani in HO-MEM during log growth phase was 10 to 12 hr; this shortened to 9.25 hr at mid-log growth (day 2). The optimal pH range for L. donovani was 7.2 to 7.4 and optimal culture temperatures were 25 to 26 C. A change was seen in the average size distribution of L. donovani promastigotes during the growth cycle with smaller cells predominating each succeding day of culture. HO-MEM is a good medium for transformation of L. donovani amastigotes to promastigotes (60 to 80% in 48 hr).


Viruslike particles in malaria parasites.

The ultrastructural appearance of viruslike particles in several malaria parasites at different times in sporogony is described in detail. Emphasis is placed on particle size, 42 to 52 nm, density and the presence or absence of geometric configuration of particle aggregations in P. berghei ookinetes, and P. gallinaceum early oocysts. This particle appearance is compared with that noted in later oocysts of P. berghei, P. gallinaceum, and P. c. bastianelli and with negatively-stained particles obtained by fractionation of A. stephensi mosquito medguts heavily infected by P. berghei oocysts. Although particles are dispersed in later oocysts, particle size and shape is similar to that noted in the aggregates found in early forms. Aggregations of particles in a geometric configuration in ookinetes and early oocysts is associated with a particle of smaller diameter and the absence of a limiting membrane or envelope. This suggests an incomplete or nascent virus particle form. The observations of such particles in malaria and other blood parasites is compared with the present findings.


The effect of axial crown overcontour on adolescents.

The relationship between axial crown overcontour and the health of the subjacent gingival investing tissues was investigated by placing standardized axial over-contoured facings on the buccal, axiogingival aspect of 42 premolar teeth. The gingival tissues were evaluated on the basis of clinical criteria, evaluation of standardized photographic records and by comparing gingival sulcular fluid production at test and control sites. Of the 42 test sites examined, 27 showed clinical signs of gingival inflammation and alteration of normal soft tissue architecture after a period of 42 to 49 days. There was a significant correlation as measured by die Spearman rank correlation technique between data derived from clinical examination and data obtained from interpretation of standardized photographic material. Evaluation of Test Site to Control Site Gingival sulcular fluid score quotients was suggestive of some degradation of the gingival tissues at the test sites, but no significant correlation was found. It may be concluded that alteration of normal crown form by overcontouring the buccal, axial third of a tooth may be a factor which predisposes the subjacent gingival tissues to inflammatory disease.


Measuring periodontal disease in ancient populations: root and wear indices in study of American Indian skulls.

As an example of the collaboration of periodontologists and physical anthropologists, the skulls of two Indian populations were studied. A root index to assay periodontal disease and a wear index to evaluate occlusal wear, were developed. The first Indian population, living 400 years ago, had more decay, loss of teeth and caries; the second population, living 4,000 years ago, exhibited more periodontal disease. Starting with a sample of eight teeth, two from each quadrant, the statistical analysis showed that a smaller number of teeth would give a reliable assessment of past oral health. Based on our findings, the canines proved to be good indicators for general wear and the incisors for periodontal disease. A six-tooth index of varying teeth studied is proposed for the root index and the wear index in future studies of oral health of ancient populations.


Relationship between acute toxicity in mice and polymorphic forms of polyene antibiotics.

Marked differences in LD50 values were found between various batches of polyene antibiotics (mepartricin and  nystatin) after intraperitoneal administration in suspension to mice. Such differences do not seem attributable to the particle size but to different molecular spatial arrangements of the products, which modify their solubility and biological availability. In the samples obtained by chemical treatments of some batches of the polyene substances, it has been possible to change the toxicity drastically and then to bring it back to its original value.


New synthesis of substituted pyrrolo[1,2-alpha][1,3]diazepine and its pharmacological activity.

A facile route for the synthesis of the substituted pyrrolo[1,2-alpha][1,3]diazepine nucleus from readily available starting material is reported. The compound was tested for antimalarial activity in mice, antineoplastic activity in mice, acute hypotensive activity in rats and dogs, effect on cholesterol-lipoprotein levels in rats, anti-inflammatory activity in rats, antiviral activity in mice, CNS depressant or stimulant activity in mice, diuretic activity in fasted rats, and antidiabetic activity in rats. Hypotensive activity of relatively short duration was observed in rats. The compound lacked positive pharmacological activity in the remaining tests.


Synthesis and antimalarial activity of dibenz[c, e]azepine derivatives.

A series of 6-alkyl-2,10-bis(trifluoromethyl)-5H-dibenz-[c,e]azepines were synthesized via a condensation reaction between 5,5'-bis(trifluoromethyl)-2,2'-diformylbiphenyl and the appropriate amine. These compounds were screened for antimalarial activity and were  found to be inactive.


The respective roles of cytology and colposcopy in obstetric and gynecologic practice.

The use of cytology in evaluating the state of the uterine cervix is well recognized and accepted in the United States. The role of colposcopy has not been completely defined although its acceptance is slowly gaining ground in many clinics. It is the purpose of this article to compare the two methods and to discuss the relationship of these methods to each other. Most attention will be directed to cytology and colposcopy of the cervix. However, the applications of both methods to evaluation of the vulva and vagina will also be considered.


Studies on the origin of the alpha-haemolysin produced by Escherichia coli.

Synthesis of alpha-haemolysin by Escherichia coli was proportional to the amount of meat-broth factor present in the medium and not to bacterial growth. The meat-broth component required for the synthesis of haemolysin was found to have several physical and chemical properties in common with alpha-haemolysin itself. Both molecules are trypsin-sensitive, acidic substances with similar elution volumes when subjected to gel-filtration chromatography with Sepharose 6B. Isotopic labelling experiments in which the bacteria were grown on 14C-labelled meat broth showed that partially purified haemolysin preparations contained molecules of mammalian origin. Similar experiments in which 14C-glucose was used to label bacterial molecules showed that little or no material of bacterial origin was present in the haemolysin preparation. These data suggest that alpha-haemolysin may be produced by bacterial modification of a molecule present in meat broth rather than by synthesis de novo within the bacterial cell.


The importance of prolonged incubation for the synthesis of dimethylnitrosamine by enterobacteria.

Tests with 140 strains representing Escherichia coli, Klebsiella aerogenes, K. ozaenae, Proteus mirabilis, P. vulgaris, P. rettgeri and P. morganii in a defined medium supplemented with 0-09M dimethylamine (DMA) and 0-1M potassium nitrate showed that at least 89% of the 136 strains able to reduce nitrates produced up to 9mM dimethylnitrosamine (DMN) in 70h at 37 degrees C. Four nitratase-negative strains produced DMN from DMA in the presence of sodium nitrate. Prolonged incubation was the most important factor in determining DMN production. Stasis and persistent infection in the urinary tract, by simulating prolonged incubation of a culture, may be of importance in determining whether the potential carcinogen, DMN, could be produced in vivo by bacterial action on DMA and nitrate in urine.


A continuous study of morphological phase in the swarm of Proteus.

Continuous study, at intervals of 1 h, on the advancing edge of the swarm of Proteus vulgaris confirms that this is almost permanently composed of elongated swarmers, and that short, non-swarming forms arise in the interior of the culture where motion has already ceased. Previous errors have probably arisen from inaccurate sampling.


The influence of antibiotic treatment on resistance patterns of coliform bacilli in childhood urinary-tract infection.

The occurrence of coliform bacilli carrying resistance-transfer factors (R factors) in children was studied. The frequency of R+ coliform bacilli as causes of urinary-tract infection acquired outside hospital was found to be similar to that in adults from the same geographical area and in the same years. The frequency of R+ coliform bacilli in the faeces in our children was also similar to that in the adult population, and oral chemotherapy produced similar changes in the faecal flora.


Melanoidin and aldocyanoin microspheres: implications for chemical evolution and early precambrian micropaleontology.

Two new classes of organic microspheres are described. One of them (melanoidin) is synthesized from amino acids and sugars in heated aqueous solutions. The other (aldocyanoin) is formed in aqueous solutions of ammonium cyanide and formaldehyde at room temperature. The general properties of these microspheres, including conditions of synthesis, size and shape, mechanical and pH stability, and solubility, are compared with corresponding properties of other "protocell" model systems. It is concluded that melanoidin and aldocyanoin microsphreres are plausible candidates for precellular units in the primitive hydrosphere. Since the bulk of the organic carbon in early Precambrian sediments is insoluble kerogen-melanoidin, it is suggested that some Precambrian "microfossils" may be abiotic melanoidin microspheres of the type described herein.


Identity of sensory and motor systems that are critical to the immobility reflex ("animal hypnosis").

This review presents an analysis of the sensory and motor mechanisms as they are now understood that cause the immobility reflex (IR). Of the sensory systems that conceivably could trigger and sustain the IR, as commonly induced experimentally by inversion and manual restraint, evidence has been presented to eliminate some senses (vestibular, vision, sound, many visceral sensations, olfaction, taste, temperature), while incriminating tactile and proprioceptive influences. Of the motor systems which could cause the profound immobility during IR, neurosurgical and electrophysiological evidence identifies the locus of the inhibitory neurons in the brain stem and/or spinal cord. The evidence reviewed leads to a unified working hypothesis of IR mechanisms. IR is considered to be caused by a group of neurons in the brain stem which inhibit spinal motoneurons, either directly or indirectly, when those inhibitory neurons are activated by a specific pattern of tactile and proprioceptive input. Modulation of the IR control system appears to come from the limbic system, which under fear-producing conditions, potentiates the IR in part by release of epinephrine. Inhibition of the IR control system appears to come from the neocortex, as well as the brain stem reticulum, when it is activated by nonspecific, arousing somaesthetic sensations that produce generalized activation of the neocortex and skeletal muscle.


Prospective evaluation of hemostatic techniques for liver injuries.

The methods of hemostasis used for liver injuries were evaluated prospectively in 637 patients treated at Detroit General Hospital during a 5-year period. Variables evaluated included severity of injury, presence or absence of bleeding, and methods of hemostasis, The liver injury was either not bleeding or was controlled by temporary pack compression during laparotomy in 325 patients: none of these patients, including the 284 in whom no hemostatic procedure was used, rebled postoperatively. Active bleeding at laparotomy was directly related to the severity of liver injury, and required some hemostatic procedure in 312 patients. The methods of hemostasis were liver sutures (244 patients), nonanatomic resection (30 patients), anatomic resection (21 patients), hepatic artery ligation (nine patients), hepatotomy with intraparenchymal vascular control (five patients), and temporary internal pack with later re-operation (three patients). Rebleeding occurred in eight of the 243 patients who survived (seven after liver sutures and one after nonanatomic resection) and four required re-operation for control of bleeding. Sixty-nine patients with active bleeding died. Death on the table in 38 patients was related primarily to uncontrolled bleeding from liver and major vessel injury. Postoperative rebleeding from the liver occurred in 14 of 31 patients who died after surgery: following initial control by liver sutures (seven patients); anatomic resection (four patients); and hepatic artery ligation (three patients). There was no apparent relationship between any hemostatic procedure and the subsequent appearance of the hepatic ischemia or parahepatic abscess. Based on this experience, the merits and detriments of individual hemostatic procedures are presented.


Foreign body granulomas of the ear.

Foreign body granulomas of the ear are seldom looked for, but probably common occurrences. They may be due to exogenous or endogenous material which became implanted in the course of trauma or treatment in the external or middle ear. They provoke inflammation which may be subclinical, clinical, or masked by concurrent infection. They can aggravate chronic infection, initiate acute local inflammation, or jeopardize surgical success. Histologically, the foreign material is seen lying freely or partially encapsulated within chronic inflammatory tissue, in close proximity to foreign body giant cells. Medical treatment can only succeed when the offending agent is surgically removed.


Disseminated intravascular coagulation in the urologic patient.

Gram-negative septicemia and metastatic prostatic cancer are frequent causes of disseminated intravascular coagulation. The clinical manifestations of this condition as well as the laboratory data vary considerably, depending on the patient's compensatory mechanisms in relation to the magnitude and duration of the thromboplastin or endotoxin release. Treatment centers primarily on correcting the underlying disorder. Secondly, deficient clotting factors and platelets should be replaced in the appropriate patient. Heparinization is often unnecessary. The use of drugs that inhibit the protective fibrinolytic mechanism is contraindicated in disseminated intravascular coagulation.


Obstructive uropathy in the transplanted kidney: evaluation by gray scale sonography.

A case is presented in which linear gray scale echography demonstrated pyelocaliectasis and documented its subsequent improvement while helping to exclude other causes for the patient's clinical condition.


Renal autotransplantation for upper ureteral stenosis.

In 2 cases of irreparable upper ureteral damage autotransplantation of the kidney with pelvioureteral anastomosis proved to be a satisfactory alternative to nephrostomy drainage or nephrectomy.


Unilateral and bilateral bladder neck suspension (modified Pereyra) operation for stress urinary incontinence.

Stress urinary incontinence can be corrected by a short, simple, minor suturing technique, a modification of the Pereyra operation. Success depends upon careful selection of patients, the proper tightness of the suture over a proper-size catheter and the use of intermittent endoscopy during the operation. Successful outcome up to 7 months has been achieved in 7 of the 8 patients but reoperation was necessary for the successful outcome in 1 of the 2 failures.


Bacteremic infections due to clindamycin-resistant streptococci.

We have recently observed four patients with bacteremic infections due to group A streptococci that were highly resistant to clindamycin and only moderately susceptible to erythromycin. Two of the infections developed while the patients were receiving clindamycin. The organisms were not beta-hemolytic under standard conditions nor were they M or T typable. We urge that all streptococci isolated from patients with serious infections be grouped serologically and be tested for antibiotic susceptibilities, especially if therapy with antibiotics other than penicillin is to be considered.


Effect of coronary vasodilators on cardiac dynamics of the normal dog and the dog with experimental coronary sclerosis.

Observations are presented about the effects of four kinds of coronary vasodilators (dipyridamole, oxyfedrine, prenylamine and trimetazidine) on coronary circulation in the heart with coronary sclerosis which has been induced by intravenous injection of allylamine in the dog. Following results are obtained: 1) All of the drugs examined increase coronary blood flow and decrease coronary vascular resistance in the dogs with coronary sclerosis as well as in normal dogs. 2) An amplitude of response of coronary circulation to the coronary vasodilators is significantly  less in the dogs with coronary sclerosis than in the normal dogs. 3) The clinical value of coronary vasodilator has been discussed.


[Studies on the intravenous administration of sulbenicillin (author's transl)].

Basic and clinical investigation on the intravenous administration of sulbenicillin in moderate dose (510g daily) was carried out to evaluate its clinical effect in systemic infections due to gram-negative bacilli. The following results were obtained. (1) In human subjects received 5 g intravenous drip infusion, the peak blood levels were found at the end of infusion. In 6 cases with normal renal function (Ccr greater than or equal to 70ml/min.) the peak blood level was 181 mcg/ml on the average and the half-life 1.1 hours, while in 3 cases with impaired renal function (Ccr less than 70 ml/min.) the peak level 216 mcg/ml and the half-life longer than 2 hours. The height of the peak level seemed to be subjected to the duration of infusion. The renal excretion of sulbenicllin was 55.2% on the average both in cases with normal and impaired renal functions. (2) Sulbenicillin, 510g daily divided in 2 doses, was administered to 15 cases including 6 cases with acute pyelonephritis, 3 with acute cystitis, 3 with biliary tract infection, 2 with respiratory tract infection and 1 with acute prostatitis. All the cases except 3 cases with acute pyelonephritis had underlying diseases. Escherichia coli was isolated from 10 cases, Klebsiella from 2, Pseudomonas aeruginosa from 1, and unidentified gram-negative bacilli from 1. Eleven cases responded to the treatment, but 4 cases failed. In 11 cases with susceptible bacteria, 8 cases responded bacteriologically (2 cases recurred), and 3 cases failed to respond. A case with biliary tract infection due to E. coli did not respond to 5 g daily treatment, but responded to 5 g twice daily. Two cases due to organisms which were not inhibited by 200mcg/ml in vitro did not respond to the treatment. (3) A moderate decrease in red blood cell number and hemoglobin content was observed in one case. A transient increase in transaminase and alkaline phosphatase level was observed in other cases.


A clinical study of the effect of coenzyme Q on congestive heart failure.

Expecting activation of myocardial energy liberation, coenzyme Q was applied as a treatment to 55 patients suffering from congestive heart failure. Daily doses of 50 to 100 mg of coenzyme Q7 were injected intravenously in 21 cases for 3 to 35 days. Daily doses of 60 mg of coenzyme Q7 were administered perorally in 17 cases for 14 to 196 days. Daily doses of 30 mg of coenzyme Q10 were administered perorally in 17 cases for 7 to 182 days. Clinical effects were evaluated within 4 weeks by the criteria using a scoring method of severity of congestive heart failure which was devised by the authors. In summary a certain effect was found in 20 cases and a mild effect was observed in 29 cases. No significant changes were observed in heart rate and blood pressure. Exanthema appeared in 2 patients of the group of coenzyme Q7 intravenous injection. In conclusion the therapeutic effect of coenzyme Q was thought to be mild but stable in supplement to digitalis therapy in cases of congestive heart failure.


An investigation of leukocyte function and phagocytosis of immune complexes in patients with rheumatoid arthritis.

By means of the nitroblue tetra-zolium (NBT)-dye test, patients with chronic rheumatoid arthritis (RA) were studied. It was found that patients with rheumatoid factor (RF) in their sera displayed higher levels of NBT-dye reduction than those without RF did. In RF(+) serum, the authors observed a remarkable activation of NBT-dye reduction in phagocytosis of immune complexes and 1gG-coated latex particles. A fluorescent antibody technique and immuno-electron microscopy showed an increased phagocytosis of gamma-globulin in peripheral polymorphonuclear leukocytes (PMN) from patients with activated levels of NBT-dye reduction. From these results, it is likely that PMNs from patients, particularly from those possessing high values of NBT-dye reduction, displayed the activated levels of phagocytosing autologous globulin.


Release of migration inhibitory factor from mouse T and B cells activated by insoluble phytomitogens.

The production of macrophage migration inhibitory factor (MIF) was studied with mouse B spleen cells and with the low density subpopulation of thymus cells (T cells) stimulated by phytomitogens. MIF was released from mouse B cells when stimulated by Sepharose-PWM but was not released by Sepharose-Con A. MIF was produced by the low density subpopulation of thymus cells stimulated by Sepharose-Con A. MIF from B cells could not be distinguished from that of the low density subpopulation of thymus cells by gel filtration on Sephadex G-100 column. The molecular size of both MIF was calculated to be 45,000-55,000 dalton.


Application of double staining technique and incident light fluorescence microscopy to immunofluorescence studies on renal diseases.

A method, by which the more precise localization of immunofluorescent deposits in the glomerulus is easily demonstrated with the fluorescence microscopy, was described. By means of this method, the deposits even in the Bowman's space could be identified, as well as the deposits in the subepithelial, subendothlial and mesangial regions. From this result, it was suggested that this method should be widely used for the immunofluorescence studies on human renal biopsied sections, in order to elucidate the relationship between the localization of deposits and renal diseases.


The application of immunofluorescence to the study of renal disease. I. Influences of various conditions of specimens and conjugates on the fluorescent patterns of kidney.

Some basic problems in immunofluorescence were reexamined, limiting the object to kidneys. As to thickness of sections, 4 mum was demonstrated to be the most reasonable also to kidney specimens. Treatment of PBS for a short time before staining was recommended not only for cleanup effect but also for the possibility to disclose covered antigenic determinants. It was also established that fluorescent antibody with adequate F/P molar ratio, as well as with strict specificity, should be used, in order to prevent "false positives".


Studies on the properties of a streptococcal preparation OK-432 (NSC-B116209) as an immunopotentiator. I. Activation of serum complement components and peritoneal exudate cells by group A streptococcus.

The inhibition of transplanted tumors in animals, which were previously injected with a streptococcal preparation, OK-432, has been suggestible to be induced by direct or host mediated effects. In this paper, it was examined of immunopotentiating ability of Group A streptococcus (Su-strain), which is a active component of OK-432, with respects to reticuloendotherial system and serum complement components. Human fresh serum incubated with the heated streptococcus (HSu-coccus) was analyzed by means of immunoelectrophoresis. Activated component of C3 proactivator was observed in gamma region as immunoprecipitin line developed by rabbit anti human C3 proactivator serum, and conversion of C3 component (beta1C) to beta1A was observed in alpha region by rabbit anti human beta1C/beta1A serum. The activation of serum complement components might be occurred via alternate pathway, because EDTA inhibited the activation but EGTA did not. Meanwhile, the peritoneal exudate cells from mice injected intraperitoneally with HSu-coccus were examined with respects to cell population and their antitumor effect. On the 7th day after injection of HSu-coccus, about 90% of the peritoneal cells was lymphocytes, and 70% of these lymphocytes was susceptible to rabbit anti mouse thymus cell serum or to AKR anti thetaC3H serum. When L1210 leukemia cells preincubated with these peritoneal cells were inoculated intraperitoneally into BALB/c mice, the leukemic cells could not allowed the growth, resulting in prolongation of life-span of the experimental animals. These results suggested that nonspecific effector activity of T-derived lymphocyte induced by HSu-coccus could be one of the factors participating in antitumor activity of OK-432. Additionally, the results obtained with OK-432 were most the same as those with HSu-coccus in these respects. Further, the relation between the stimulation of leucocytes and activation of complement components was discussed.


Cauda equina pseudoclaudication syndrome.

Intermittent claudication is known as a specific symptom in patients with chronic occlusive arterial lesions. Clinically it is important that neurogenic intermittent pseudo-claudication should be differentiated from true intermittent claudication. Nevertheless confusion still exists in differential diagnosis between these two entities. This paper deals with general review of intermittent pseudo-claudication and a particular emphasis is placed on the different concepts of the pathophysiology and the differential diagnosis from the standpoint of vascular surgery. Recently one case of the neurogenic intermittent pseudo-claudication was encountered and presented in this paper.


Computer-aided-instruction in the emergency department.

The Massachusetts General Hospital Laboratory of Computer Science created a library of computer-aided-instruction (CAI) programs in 1972. An experimental network of Cai programs, made possible by National Library of Medicine (NLM) support, was set up in July 1972, operating over commercial communication lines. Programs developed by Massachusetts General, Ohio State University and the University of Illinois Medical College were made available to users with terminals in about 36 cities through a local telephone number. During the first two years of the program over 80 institutions participated. A trial of the Massachusetts General programs, in conjunction with the Continuing Education Committee of the American College of Emergency Physicians, was conducted in five representative community hospitals. The hospitals put up the cost of the terminals and the telephone charges. Results of the study showed that 12 of the 40 (30%) emergency physicians in the target population took 10 or more programs. They gave the programs a favorable overall rating--1.6 on a scale of 1 (strongly positive) to 5 (strongly negative).


Auditing the quality of care in emergency departments.

A methodology for evaluating the quality of emergency department care in the form of a retrospective process audit for emergent and urgent cases was developed and tested in the Philadelphia General Hospital Emergency Department. A physician panel develped criteria against which the management of six "chief complaints," as indicated on the medical record, was measured. Then nonphysician auditors examined records retrospectively for a three-week period, covering every day and shift for a total sample of 389 cases. The physician panel made an implicit review of those records that varied from the criteria. The results of the review in four diagnostic areas showed that for chest pain 51% (36) did not meet the provisional standards; for abdominal pain 35% (35) did not; for wounds 51% (51) did not, and for sore throats 43% (22) did not. These results were presented to the ED staff and charts were re-audited after one month. The results of this second audit are being tabulated though preliminary findings indicate an improvement in the percentage of cases meeting the criteria.


Intravenous fructose for acute alcoholism: a double blind study.

To test the clinical efficacy of fructose intravenously for acute alcoholism, 20 acutely intoxicated patients were treated in a randomized, double blind fashion with 1000 cc of 10% fructose and 10% glucose over two hours. In the first hour of infusion, fructose was significantly superior to glucose (p less than 0.05) in improving the mental and neuromuscular status of the most impaired patients. Although no side effects were observed and no patient developed metabolic acidosis, the study suggests an awareness of a potential for acidosis during the use of intravenous fractose therapy.


Postburn respiratory injury.

A common and frequently overlooked concommitant of burn injury is postburn pulmonary damage. The lesion may be secondary to inhalation or mechanical obstructive or toxic problems; or it may be associated with indirect damage from hypovolemia, shock, central nervous system disturbances or drugs. Therapy comprises establishing a clear airway; administration of sufficient humidity and oxygen to maintain adquate arterial pO2; sequential pO2 monitoring; surface decompression of the thorax; systemic antibiotics and sequentially increasing--and later decreasing--airway support. The diagnosis of postburn pulmonary injury is clinical. Aggressive, sequential management of the patient, supported vigorously by laboratory evaluation, is essential.


[Clinical and pharmacokinetic researches of doxycyclin vibravenös in childhood (author's transl)].

Doxycyclin is one of the first efficacious depot antibiotics. It is used in two applications as Vibramycin (R) (peroral and Vibravenös (R) (parenteral). Doxycyclin has a favourable effect not only on different gram-positive and gram-negative bacteria but also on a lot of other germs as mycoplasms, rickettsias, protozoons and large viruses. The tissue invasions is a good one, because there is only a low fraction of free Doxycyclin and further a high lipid activity. Pharmacokinetic investigations of different age-groups show that good serum-levels can be reached because of the sensitivity of numerous germs. The levels are higher, as our experiences demonstrate, if the dose of 4 mg/kilo/weight is injected in two single doses. Our investigations are reported on 49 patients with diseases of the respiratory tract and on 25 patients with diseases of the urogenital tract. Doxycyclin was very useful especially in different forms of pneumonias. The results in infects of the urogenital tract are not so good ones. The compatibility of Doxycyclin can be characterised as very good for children.


[Electrocardiogramme in anaphylactic shock in humans (author's transl)].

Twenty clinical cases described in the literature were gathered, in which electrocardiographic tracings had been recorded. Electrocardiographic changes were found in all cases, such as sinus tachycardia (12 times), impaired electrical conduction (5 times), ventricular overexcitability (7 times), high P-wave (6 times), changes of the ST (10 times), and of the T-wave (18 times). The reason for these changes might be of a complex nature. Based on experimental investiagations mentioned in the discussion, it may be assumed that beside a direct effect on the myocardial cells, the following mechanisms could have influenced the electrical heart potentials: 1. a constriction of the coronary vessels, 2. a pulmonary vascular constriction, 3. an aggregation of thrombocytes, 4. a peripheral vascular dilatation, 5. a bronchiolar constriction.


[Tubular response to antidiuretic plasma activity in the transplanted kidney (author's transl)].

Reabsorption of osmotically free water (TmcH2O) was studied in 10 patients after renal transplantation. A rising or constant free water reabsorption was observed under hydropenia and increasing tubular solute load. These findings suggest that in the transplanted kidney the functioning nephrons respond in a normal way to plasma ADH-activity. The excretion of plasma-hypotonic urine reflects decreased antidiuretic activity as in overhydration rather than tubular unresponsiveness to ADH. The excretion of plasma-hypertonic urine indicates tubular reabsorption of osmotically free water due to ADH, and this in general rules out overhydration. Daily estimation of urinary and plasma osmolality will be useful in judging the actual state of hydration after renal transplantation.


[The course of postoperative deep vein thrombi as judged by repeated phlebographies].

Phlebography was carried out in a prospective randomised, controlled study during which dextran and small doses of s.c. heparin have been compared in general surgical and urological patients, in 31 persons with proven deep vein thrombois diagnosed with the 125I-fibrinogen test. In 16 out of the 31 patients a second phlebogram coule be performed two weeks later. In this study all thrombi occurred intraoperatively. In 24 of the 31 patients, the appearance of thrombi was multilocular. Independent of the prevention instituted and irrespective of the therapy, the following phenomena could be seen 14 days after the first phlebogram: 9 thrombi retracted, 6 disappeared completely and 1 occluded the vein completely. 2 thrombi disappeared without any therapy whatsoever, the 4 others disappeared in patients receiving heparin and/or coumarin for treatment.


Experimental Bence Jones cast nephropathy.

C3H mice received intraperitoneal injections of a single dose of 50 to 200 mg. of purified lambda Bence Jones protein. Control animals received injections of comparable amounts of ovalbumin. The mice which received 200 mg. of lambda Bence Jones protein developed extensive cast formation in the distal renal tubules. By electron microscopy, the casts were found to contain elongated crystalloid structures. In some areas, these crystalloids appeared to penetrate into or be engulfed by tubular epithelial cells. By immunofluorescence, only lambda Bence Jones protein was detectable in the casts during the first 5 days. Thereafter, Tamm-Horsfall protein was also found in increasing amounts. The casts induced an inflammatory response characterized by the sequential appearance of polymorphonuclear leukocytes and mononuclear cells. The secondary tubular cell changes included atrophy, degeneration, and regeneration. Giant cells were present around many casts, but it could not be determined whether these derived from tubular epithelial or mononuclear inflammatory cells. Elevated blood urea nitrogen was found terminally in most animals. Smaller doses of the same protein as well as preliminary studies with two other lambda Bence Jones proteins failed to produce comparable changes. This experimental model of Bence Jones nephropathy closely resembles the morphologic features of so-called "myeloma kidney" in man.


Prevention of postthymectomy autoimmune thyroiditis in mice.

Several immunologic procedures are described, by which the postthymectomy autoimmune thyroiditis in (C3H/HeMs X 129/J)F1 female mice was clearly prevented. These include the grafting of a neonatal thymus or a cell injection from adult thymus, spleen, and lymph nodes, but not from bone marrow. Their preventive effects, however, depended on the timing of treatments. In general, the earlier the treatment was given, the better the effect was. Thymus cells from 7-day-old mice were effective, whereas spleen cells from the same donors and neonatal thymus cells were ineffective. Neonatal thymectomy or 500-rad irradiation decreased the number of effective cells in the spleen. All of these data suggest that the cells responsible for the prevention of postthymectomy thyroiditis are T-cells, and that ontogenetically these cells first acquire their preventive ability in the thymus after birth and then migrate to the peripheral lymphoid tissues. The minimal effective dose of adult spleen cells was 15 X 10(4). Although 10(7) spleen cells from the mice thymectomized 3 days after birth failed to prevent the disease, the same dose of cells from those thymectomized at 7 days clearly prevented it. This suggests that qualitative rather than quantitative differences exist in peripheral T-cells of mice thymectomized 3 days after birth and those of normal mice or mice thymectomized at 7 days when the animals get to adulthood.


Immunochemical study and cellular localization of human pepsinogens during ontogenesis and in gastric cancers.

Gastric pepsinogens were studied by immunoenzymologic and immunohistochemical methods in non-cancerous adult gastric mucosa, in fetal stomach, and in gastric carcinomas. In noncancerous adult mucosa, immunoenzymologic methods showed that pepsinogen II (previously called Pg I-II) was found mostly in fundic or mediogastric extracts, whereas Pg IV was predominant in antropyloric extracts. Pg II was localized by immunofluorescence techniques in the chief cells of deep glands found near the muscularis. Pg II was localized by immunofluorescence techniques  in the chief cells of deep glands found near the muscularis. Pg III was present in the superficial zone of deep glands and Pg IV in the surface epithelium and in the superficial glands of the mucosa. In fetal stomach, only Pg IV (which we called the "fetal pepsinogen") was identified by standard immunoelectrophoresis. It was localized by immunofluorescence in the superficial epithelium. However, bidimensional immunoelectrophoresis and immunofluorescence did reveal low levels of Pg II and Pg III by the 8th or 9th week of ontogenesis. Pg II and Pg III were localized in the rudimentary glands near the superficial epithelium. Important differences were noted when gastric carcinomas were compared with normal mucosa. Pg II or Pg III were often absent in the tumor extracts, but Pg IV was regularly and, at times, exclusively identified regardless of the location of the tumor. By immunofluorescence Pg IV was often the only pepsinogen that was characterized in dedifferentiated cancerous cells; this was also true of the calciform cells of some metaplastic gastric mucosa. Pg III was observed rarely, and Pg II never, in cancerous cells. The biochemical modifications of the cancerous tissue closely resemble those of fetal tissue.


Conjugated polyene fatty acids as fluorescent membrane probes: model system studies.

The use of conjugated polyene fatty acids as probes of membrane structure is examined, alpha- and beta-parinaric acid (cis, trans, trans, cis- and all trans-9, 11, 13, 15-octadecatetraenoic acid) and synthetic lecithins containing an alpha-parinaric acid chai in position 2 have been prepared, and their absorption and fluorescence properties have been determined. Their absorption spectra are at sufficiently long wavelength to be unobscured by cellular chromophores such as nucleotides and aromatic amin acids. Parinaric acid absorption does, however, overlap tryptophan emission which allows fluorescence energy transfer. Potential uses of these fluorescent probes are presented with studies on mode systems with known physical properties. Dipalmitoyl phosphatidylcholine exhibits a sharp phase transition 1 degree wide at 42 degrees C, as monitored by the fluorescence intensit of parinaric acid. The magnitude of the transition is independent of probe concentration, but the width of the transition and hysteresis are dependent upon such factors as the probe concentration and whether or not sonication is used in sample preparation. Using both fluorescence and absorption properties of the probe, we show that the addition of cholesterol to the dispersion broadens and decreases the magnitude of the transition. These results are interpreted in terms of a change in the polarizability of the acyl chains of a lipid bilayer undergoes a thermal transition. Lipid-protein interactions are studied by the binding of alpha-parinaric acid to bovine serum albumin. Fluorescence enhancement, absorption spectral shifts, and quenching of tryptophan fluorescnece are observed when alpha-parinaric acid binds to bovine serum albumin. Calculations based on these measurements are consistent with two binding sites of KB approximately 10(8) (M-1) and three to four binding sites of KB approximately 10(6)-10(7) (M-1), similar to known values for the binding of other long-chain fatty acids. Biosynthetic incorporation of beta-parinaric acid into the E. coli fatty acid auxotroph 30E betaox has been accomplished and phase transitions in cells and isolated phospholipids are shown.


The role of cell membrane in the antiviral effect of interferon.

The mechanism of interferon action in human fibroblasts has been studied by use of both antisera to human fibroblast interferon and the antisera to the surface of human fibroblast cell. The anti-interferon serum completely neutralized the antiviral effect of human fibroblast interferon. Interferon antiserum prevented the intracellular antiviral state from developing when added to the medium of the cells in which interferon synthesis had already been induced by poly (I-C). This suggests that development of the antiviral state involves interferon interaction with the external part of the producing cell. Treatment with the serum directed against the surface of human fibroblast cells failed to inhibit the antiviral activity of human interferon in these cells. In addition, the effect of gangliosides on the antiviral activity of human interferon was studied and it was found that human interferon binds to gangliosides and that this interaction leads to inactivation of the antiviral effect of interferon. Pretreatment of human fibroblasts with gangliosides had no effect on the sensitivity of these cells to exogenous interferon.


The tricho system: hypertrichosis, radiation, and cancer.

Five women in their 6th to 8th decades were treated for facial hypertrichosis in Erie, Pennsylvania, 30 to 40 years ago. The epilations were performed with an X-ray device called "Tricho System," which was manufactured, sold, and proclaimed safe by its physician-inventor. The beauty shop operator who administered these treatments may or may not have received "instruction" by the company in the operation of the equipment. At varying intervals, each of the 5 women developed radiodermatitis and basal cell and/or squamous cell carcinoma at the sites of epilation. All presented to the plastic surgical service at the Hamot Medical Center in Erie, Pennsylvania. Two underwent massive radical resective surgery, 2 required extensive excision and resurfacing, and 1 refused resective surgery although she had had a previous surgical attempt 17 years earlier. Case histories are presented in detail. This series is representative of the epidemic nature of Tricho-System-induced disease.


Hemodynamic and functional changes in xenogenic, perfused, isolated lungs.

Hyperacute pulmonary rejection was reproduced by perfusion of the isolated lung with heparinized heterologous blood. The cat lung was perfused with dog venous blood at a pressure of 30 mm. Hg. Pulmonary hemodynamic and functional studies showed that blood flow decreased to 14 per cent of the control and pulmonary vascular resistance increased sevenfold. Dynamic pulmonary compliance decreased only slightly to 83 per cent at 15 minutes, but normal pH, PO2, and PCO2 were maintained in the pulmonary venous blood even 15 minutes after the start of perfusion, because perfusion was decreased to a greater extent than ventilation.


Therapeutic use of helium-oxygen mixture in continuous positive airway pressure for early weaning from mechanical ventilation after cardiovascular surgery in infants.

Therapeutic use of helium-oxygen mixture in continuous positive airway pressure (He-CPAP) was employed for early weaning from mechanical ventilation of 11 infants who underwent cardiac surgery from August, 1974, to April, 1975. With the use of He-CPAP, a 20 to 30 mm. Hg elevation of PaO2 was usually observed and respiratory distress was reduced, as compared to results obtained with nitrogen-oxygen CPAP. In all cases, He-CPAP resulted in the possibility of relatively early removal of the endotracheal tube. Therefore, He-CPAP is recommendable for intermediate respiratory support between mechanical ventilation and nitrogen-oxygen CPAP.


Successful surgical correction of an embolized prosthetic valve poppet: case report.

Embolization of a prosthetic valve poppet, a rare complication following valve replacement, has been, until recently, generally fatal. Immediate recognition followed by replacement of the poppet or valve and extraction of the embolized poppet is the only feasible approach. Recently, a patient was seen was seen shortly after the onset of acute pulmonary edema with wide-open mitral regurgitation. A diagnosis of extrusion of the poppet from a previously placed prosthetic valve was confirmed and a successful mitral valve replacement accomplished. The nonradiopaque poppet, subsequently localized by an ultrasound B-sac, was removed from the lower abdominal aorta at a later operation. We believe this to be the second reported case of survival following successful reoperation for embolization of a prosthetic poppet.


Long-term follow-up of aortic valve replacement with the fresh aortic homograft.

The long-term results of aortic valve replacement with the fresh aortic homograft, performed in 114 patients at Stanford University Medical Center from 1967 to 1971, were evaluated. There were 10 operative deaths (8.8 per cent), only 3 (5 per cent) in the period from 1968 to 1971. There were 6 late deaths in the first year (5.8 per cent) and 8 in later years (1.5 per cent per year); 12 late deaths were due to cardiac causes, 6 of them to valve dysfunction. The homograft was replaced later with a prosthetic valve or heterograft in 22 patients (3.2 per cent per year): for regurgitation in 20 and for calcific stenosis in only one. Infective endocarditis occurred in 5 cases, accounting for one operative death, 2 late deaths, and 2 reoperations with survival. Systemic thromboembolism occurred in 6 patients, 3 with mitral valve disease, one with atrial fibrillation, and one with infective endocarditis; none was a proved instance of embolism from bland thrombus on the aortic homograft valve. Of 53 patients followed for 5 years or more with the homograft intact, 47 have minimal or no disability, despite aortic diastolic murmurs in many. We conclude that long-term results are good in the majority of patients, with aortic regurgitation requiring reoperation being the leading complication. These results may serve as a basis for comparison of more recently introduced methods of aortic valve replacement.


Intraventricular repair of single ventricle associated with transposition of the great arteries.

Intraventricular repair was performed successfully in a 6-year-old body having a ventricle associated with d-loop and d-transposition in situs solitus of the atria and viscera. A spiral Teflon patch was utilized to partition the ventricle. Complete heart block did not result, and the patient is doing well 8 months after the operation. Details of the pre- and postoperative studies, as well as details of the surgical technique, are presented. A review is presented of the operative procedures that have been designed for the correction of a single ventricle associated with transposition of the great arteries and have been reported previously in the literature. The advantages for use of the techniaue employed in the present case are discussed.


Reconstruction of right ventricular-pulmonary artery continuity with a valved external conduit: unusual technical considerations.

The Hancock conduit containing a porcine xenograft valve has been used as part of the repair in 14 patients having complex congenital heart disease. The single death in this series resulted from the consequences of pulmonary vascular disease in a patient with truncus arteriosus. Several unusual technical considerations such as previous pulmonary artery banding, angulated Waterston anastomoses, and dextroversion required modifications in the standard approach to the correction of several of the anomalies encountered. This conduit has provided a satisfactory method to establish right ventricular-pulmonary artery continuity.


Effective preservation and transportation of lung transplants.

To evaluate a system for preserving and transporting lungs before transplantation, we removed the left lungs of 37 dogs, flushed them with a hypertonic solution having an electrolyte composition resembling intracellular fluid, and immersed them at 4 degrees C. for 7 to 24 hours. Some lungs were maintained at exactly 4 degrees C. during transport by means of a mixture of solid and liquid l-hexadecene. The lungs were allografted into immunosuppressed dogs whose right pulmonary artery was immediately ligated. Twelve recipients (32 per cent) survived 5 days or more solely on the function of the preserved lung. Four survived 10, 19, 40, and 40 days with lungs that had been preserved for 7 to 21 hours. Survival of recipients of preserved lungs (5 +/- 2 days) was equivalent to that of 75 comparably immunosuppressed recipients of nonpreserved allografts (6 +/- 1 days). One group of 10 dogs receiving lungs flushed against outflow resistance survived 12 +/- 5 days. In recipients of preserved allografts, arterial oxygen tensions remained in the normal range up to 5 weeks after transplantation, and radiographic infiltrates in the transplant were no greater than those present in recipients of nonpreserved transplants. Thus lungs transported and preserved up to 21 hours can provide total pulmonary function after transplantation and can function at least as well as nonpreserved transplants. The effectiveness and simplicity of this method are such that it might be considered for use in man.


The reform of ambulatory care: a financial paradox.

The purpose of this paper is to examine the financial factors which have effectively constrained the movement toward major reform in the out-of-hospital medical care area within this country. Analysis of the current economic picture in the health field leads inescapably to the conclusion that the major wave of new out-of-hospital programs predicted in the early 1970s is not likely to occur in the immediate future. The financial constraints are so substantial that the expansion of new forms of delivering ambulatory care services (HMOs, restructured OPDs, neighborhood health centers, etc.) into low- and moderate-income communities will proceed more slowly than was originally anticipated. The facts outlined in this paper clearly indicate that many new ambulatory care projects designed to serve low- and moderate-income people will face serious financial difficulties and will place a heavy burden on the resources of sponsoring institutions. In the future, widespread reform in the out-of-hospital area will await major improvements in the way this country finances its ambulatory care services.


[Chemotactic activity in the fluid of bullous pemphigoid blisters].

By a modified Boyden technique, chemotactic activity was present in bullous pemphigoid blister fluids but was also present in the corresponding sera. Heat inactivation (56 degrees C for 30 minutes) only partially reduced the blister fluid chemotactic activity, but almost completely inhibited the activity present in pemphigoid sera. Control blister fluids exhibited some chemotactic activity, but in contrast to pemphigoid blister fluids, this activity was almost entirely abolished by heat inactivation. The chemotactic activity remaining in heat inactivated pemphigoid blister fluid was inhibited by N-CBZ-alpha-glutamyl-L-tyrosine and by antiserum to C5 but not with antiserum to C3. Our studies suggest that complement-dependent chemotactic activity is present in bullous pemphigoid blister fluids, findings which further implicate complement activation in the pathogenesis of this disease.


Aging in mammalian cell population: a review.

Research on in vitro aging and development is reviewed within a framework provided by three aspects of population growth--birth, canalization and death. Although there are periodic changes in the birth rate coupled to periodic changes in the in vitro environment, there do not appear to be any age-related changes in the birth rate of dividing cells. There appear to be distinct subpopulations of dividing and nondividing cells, each with its own characteristic morphological and functional properties; thus, Weiss-Kavanaugh theory may be applicable to the growth, maturation and senescence of mammalian cell populations. Substantial cell losses occur during subcultivation and transfer; correction for these losses requires substantial reinterpretation of existing experimental findings. The various measures of age are poorly correlated with one another; there is wide variation from population to population. A uniform measure of age has been found in the cell generation, the number of ancestors of a given cell. Studies of intrinsic variation in development can provide additional insight into the developmental process. The framework of birth, canalization and death permits reduction in the number of competing hypotheses of aging in mammalian cell populations. Additional experimental evidence is needed to discriminate among the remaining hypotheses.


Natural history of bell's palsy: the salivary flow test and other prognostic indicators.

Fifty-one patients with Bell's palsy were evaluated within two days of onset and followed for six months without surgical intervention or effective medical treatment in order to observe the natural history of the disease. Sixty-three percent had a complete return while 37 percent had incomplete return. Age, the presence of pain, and taste alterations had no prognostic value. The progression of the palsy, response to maximal stimulation and salivary flow testing were approximately 80 percent accurate in predicting outcome. The salivary flow test was the most useful prognostic indicator since salivary flow became reduced within two days of onset in the patients likely to develop denervation while the other tests did not become altered until 3 to 14 days after onset. In patients with Bell's palsy, the salivation test seems to be the only method capable of predicting denervation before it begins; therefore, it should be ideal for selecting patients for appropriate treatment.


Prognostic significance of lymph node histology in patients with squamous cell carcinoma of the larynx, pharynx, or oral cavity.

In a double-blind retrospective analysis, sections of lymph nodes regional to head and neck squamous cell carcinomas were microscopically examined to assess morphologically the immunologic pattern of response. Patients whose nodes showed evidence of immunologic stimulation had five-year survival rates significantly higher than those whose nodes showed no evidence of immunologic stimulation. None of the patients whose nodes showed the lymphocyte depletion pattern survived five years. The stage or histologic grade of the tumors did not influence these correlations. Metastases occurred much more frequently in patients whose nodes showed immunologic activity than in those whose did not. The data support the concept that immunologic capacities are important host defense mechanisms against malignancy. Histologic assessment of immunologic activity in regional nodes seems to be an important parameter for predicting survival.