The selection of students for medical education: select bibliography, 1970-75.

The problems of student selection are constantly in the mind of medical school administrators and medical teachers. When reviewing current policies there is clearly a need to study the recent journal literature, but the term 'student selection' is not a subject heading in Index Medicus; consequently no convenient listing of journal articles on this important topic is readily available. To assist administrators and medical teachers a bibliography has now been prepared. The references are taken from Index Medicus 1970-75 and presented here in a quick-reference alphabetical format. To the list has been added World Health Organization publication EURO 6203 which is considered an important document on the subject. The bibliogrraphy therefore provides a concise reference to the recent literature on student selection for medical education.


Membrane anomalies of neoplastic cells.

Neoplastic cells exhibit numerous membrane anomalies. Those involving the plasma membrane have attracted the greatest attention, although ample evidence indicates that the membranes of mitochondria, endoplasmic reticulum and lysosomes are also profoundly implicated. The information on these topics is briefly reviewed and it is concluded that of the multiple membrane anomalies observed, those responsible for high aerobic lactate production, abnormal plasma membrane transport and release of hydrolytic enzymes may figure prominently in malignant behaviour, i.e. invasiveness and metastasis. It is proposed that the membrane polymorphism of neoplastic cells can be explained in terms of the Changeux membrane lattice hypothesis. In particular it is suggested that the concerted behaviour of tumor cell membranes might deviate from normal due to one or more of the following processes: (a) insertion of a new protein (or lipid); (b) alteration of existing proteins (or lipids); (c) change in the proportion of phospholipid; (d) change in the proportion of glycolipid; (e) change in the proportion of cholesterol; (f) change in the steady-state of membrane ligands. The validity of this proposal is evaluated in terms of recent advances in membrane molecular biology.


A controlled trial of intravenous salbutamol and aminophylline in acute asthma.

In a randomized double-blind trial an intravenous injection of salbutamol (100mug) was compared with an intravenous injection of aminophylline (250mg) in 23 patients with acute exacerbations of asthma. Salbutamol (11 cases) and aminophylline (12) produced a mean proportionate increase in FEV of 26% and 23% respectively. Blood gas pressures showed a trend to improvement with a mean rise in oxygen tension of 2mm Hg(0-2kPa) in the aminophylline group and of 6mm Hg (0-8kPa) in the salbutamol group. Electrocardiogram patterns also showed overall improvement, and mean decreases in pulse rate of 8 beats per minute and 2 beats per minute were noted in the aminophylline and salbutamol groups respectively. Differences in results did not reach conventional levels of significance and no serious side effects were noted. It was concluded that in the doses and routes of administration compared, salbutamol was as effective as aminophylline.


[Treatment of organic brain psychosyndrom in the old age. A double blind study with Hydergin (author's transl)].

The efficacy of Hydergin was compared against placebo in a 15 weeks cross-over trial in 51 patients with cerebral insufficiency. The daily dosage was 3 mg of Hydergin. Criteria of evaluation consisted of clinical rating and electroencephalographic registrations, which were evaluated visually and partly automatically. The clinical symptoms as well as the electroencephalographic criteria (base line activity, theta- and delta activity) were both positively influenced by Hydergin. The base-line activity was stabilised and the alpha activity of the power spectrum increased. The most impressive result was the carryover effect of Hydergin, which could still be demonstrated in the post trial period. In case of "dizziness" the good results were limited to the period of active treatment. The relations between symptomatic and more basic therapy  of cerebral insufficiency will be discussed.


Fusion of two F-prime factors in Escherichia coli studied by electron microscope heteroduplex analysis.

A fused F prime factor was obtained from a mating of a recA donor carrying an F'- factor containing the genes metBJF, ppc and argECBH (KLF5) with a recA recipient carrying an F' factor containing att80, trp and lac (f155). lysogenization of this fused F-prime factor with gammacI857hphi80 phage followed by thermoinduction produced the transducing phages phi80 dmetBJF and phi80 dppcargECBH. This kind of fusion provides a general procedure for the construction of transducing phages carrying genes from different regions of the E. coli genome. To understand the mechanism of this fusion, the parental F prime factors (F155 and KLF5) were analyzed by the electron microscope heteroduplex technique. F155 has a length of 176 +/- 3 kilobases including two substitutions. The F sequence 0 F-2.8 F has been substituted by 53 kb of chromosomal DNA including the lac operon and the F sequences 8.5 F-16.3 F has been substituted by 27 kb of a chromosome sequence including att80 and the trp operon KLF5 contains 221 +/- 4 kilobases of DNA (molecular weight, 148 megadaltons). It contains complete F and the segment of the E. coli chromosome from polA to rif. The F sequence 2.8 F-8.5 F known to be involved in F specific recombination in recA+ and recA backgrounds occurs twice on KLF5, once at each of the junctions of F DNA with chromosomal DNA. The population of closed circular plasmid molecules extracted from KLF5-containing strains is heterogeneous. It is proposed that this heterogeneity is due to intramolecular recombination events occurring in KLF5 between the duplicated 2.8 F-8.5 F sequences. Such recombination can account for the genetic instability of KLF5 observed in both recA+ and recA hosts. The F sequence 2.8 F-8.5 (also called gammadelta) is one of the characterized integration sequences on F. A model for the fusion of the parental F prime factors is proposed in which recombination between gammadelta sequences brings att80 close to the metBJF genes. This is followed by a deletion of an F' lac factor. The resulting fused F' factor still carries two gammadelta sequences and is therefore expected to be unstable. The closed circular molecules isolated from the fused F' containing strains show two different sizes of molecules. Genetic and physical analyses of these molecules are in agreement with the predicted instability of the fused F' factor and the existance of the gammadelta sequence in the phi80 dmet phages isolated from fused F' and previously analyzed by the electron microscope heteroduplex technique.


Genetic studies of the ribosomal proteins in Escherichia coli. IX. Mapping of the ribosomal proteins, S2 and S20, by intergeneric mating experiments between Serratia marcescens and Escherichia coli K12.

Episomes of E. coli K12, which cover thrleu region of the chromosome, were transferred to Serratia marcescens. Ribosomal proteins from these hybrid strains were analyzed with phosphocellulose column chromatography. Two E. coli 30S ribosomal proteins, S2 and S20, could be detected in the ribosome of the hybrid strain in addition to all ribosomal proteins of S. marcescens.


[Prosthetic rehabilitation by removable prostheses supported with wire in Kennedy class 1 cases and its 1st modification no. 1].

Prosthetic rehabilitation in cases of short dentition raises difficult problems, because a support must be found for free-end denture bases on both the edentulous crest and the remaining teeth. A prosthesis employing a wire device for the damping and distribution of forces and thus better able to supply this mixed support is described. Overloading of the abutments is avoided, along with the excessive reabsorption of the alveolar crest caused by classic damped appliances. Clinical experience in a series of cases treated over a period of ten years points to the effectiveness of this type of prosthesis.


Isolation and characterization of Co1E2 plasmid mutants unable to kill colicin-sensitive cells.

After transfer from a mutagenized host, twenty one Co1E2 plasmid mutants were isolated after screening 10,000 clones for abnormal colicin production. Analysis by SDS polyacrylamide slab gel electrophoresis of proteins synthesized after mitomycin C-induction of mutant cultures, indicates that all but two of the mutations are in the structural gene from colicin E2. Of these, nine produce fragments of colicin in both whole cells and minicells and some are suppressed by nonsense suppressors. Studies with a nonsense mutant producing only a small colicin E2 fragment (Co1E2-421) suggest that colicin E2 in not involved in plasmid DNA replication, in the control of its own synthesis, or required for cell death when cells become committed to colicin production. The two plasmid mutants outside the colicin gene segregate plasmid-free cells at 33 degrees, 37 degrees and 43 degrees. One segregates fairly rapidly (about 4% per generation) though the colicin-producing cells make normal amounts of colicin, whilst the other segregates more slowly and the colicin-producing cells make much reduced amounts of colicin.


[Tooth decoration in pre-colombian America].

A form of body decoration that developed in precolombian America is described and examined. The vestibular face and shape of the front teeth were altered in various ways, details of which are clear from archaeological discoveries (crania, teeth, ceramics, and statues). The various technical, social and cultural aspects of this practice are discussed with reference to their place in a civilisation whose works are still admired today.


The molecular events involved in the induction of petite yeast mutants by fluorinated pyrimidines.

The fluorinated pyrimidines 5-fluorouracil (5FU) and 5-fluorocytosine (5FC) induce the cytoplasmic petite mutation in the yeast Saccharomyces cerevisiae with high efficiency. It was found that in order to induce the mutation, 5FC must first be deaminated to 5FU. However, mutagenesis does not depend on the further conversion of 5FU to its deoxyriboside (5FUDR) and subsequent blockade of intracellular thymidine synthesis, since 5FUDR itself was found not to be mutagenic, and 5FU-induced mutagenesis was not antagonised by supplying thymidine monophosphate (dTMP) to a dTMP permeable strain. In any case, observations of the molecular changes accompanying petite induction in log phase cells ruled out the possibility that mutagenesis resulted simply from the dilution out of replication blocked mitDNA molecules, since the appearance of mutants coincided with the synthesis of altered mitDNA molecules. In different strains, the resulting defective molecules were either maintained, giving rise to suppressive rho- petites, or completely degraded, to give pure clones of neutral rho0 mutants. It is suggested that this degradative process was a conseuqence of the incorporation of 5FU into RNA.


[Clinico-experimental study of a new antibactorial agent for local use in stomatology].

Tibezonium iodide is a new drug having antibacterial activity for the therapy and the prevention of mouth infections. Before testing its therapeutic efficacy, its effect on the bacterial flora of the human saliva was verified as follows. Salivary samples, collected before and after the administration (double-blind, cross-over) to volunteers, were counted for bacteria. The drug reduced the bacterial count in the saliva with statistical significance in both the pharmaceutical forms. Subsequently the drug was tested in different dental or oral conditions. To 90 patients suffering from marginal paradentitis or other diseases with this type of complications tablets were administered. The results obtained in this group were satisfactory or almost satisfactory in 73.5% of the cases examined. The patients treated with bubble-gums were 70. All of them were suffering from the same kind of disease of the first group; a few of them had alveolitis following tooth extraction. The results in these subjects were satisfactory or almost satisfactory in 77% of the cases examined. Tibezonium proved to be particularly effective in marginal paradentitis and in piorrhoic paradontosis. Bubble-gums should not be used in subjects with dental mobile prosthesis.


The conditions required for the induction of petite yeast mutants by fluorinated pyrimidines.

Cytoplasmic petite mutagenesis by 5-fluorouracil (5FU) was prevented by temperature sensitive mutations which blcoked either nuclear transcription or cytoplasmic translation. However, 5FU was also ineffective in resting cells and in cells exposed to alpha-mating factor, showing that cell division or nuclear DNA synthesis is required for the mutagenic event to take place. In addition, the mutagenic effect of 5FU was completely prevented by daunomycin, and since this agent preferentially inhibits respiratory growth and was shown to selectively block RNA synthesis in the mitochondria, it was concluded that petite mutagensis resulted from incorporation of 5FU into mitochondrial RNA. Since inhibition of mitochondrial protein synthesis by erythromycin had little immediate effect on the mutagenicity of 5FU, it was deduced that the RNA in question is not directly involved in mitochondrial translation, and may have a regulatory function.


Cloning bacterial genes with plasmid gammadv.

recombinant molecules recovered from transformed E. coli cells consisted of a biologically functional bacterial DNA fragment and, excep


Stability of "spacer" sequences of pre-ribosomal RNA in Escherichia coli.

"SPACER" SEQUENCES OF AN RRNA gene transcript were detected with high efficiency by hybridization with DNA of the specilized transducing phase phi80rrn. Hybridization-competition studies revealed that 20 to 23% of the 30S precursor rRNA, obtained from E. coli mutant strain AB301/105, consist of "spacer" sequences. The "spacer" sequences formed hybrids with E. coli DNA, but not with Vibrio DNA. Experiments with RNA labeling in the presence of rifampicin showed that more than 80% of the spacer sequences arrive in full-length 30S pre rRNA chains before any cleavage of the RNA occurs. The hybridization assays also permitted the detection of "spacer" sequences in pulse-labeled rRNA of wild-type cells, in which the 30S pre-rRNA is already cleaved during its synthesis. Many of these "spacer" sequences degraded to alcohol-soluble materials with a half-life time of 1.2 min. The half-life was not lengthened by the treatment of cells with chloramphenicol, which stabilizes bulk mRNA. However, unstable "spacer" sequences transcribed in cells deficient in RNase III exhibited slower degradation, with a half-life time of about 9 min, whereas the cleavage of 30S pre-rRNA to smaller RNA species occurred with a half-life of about 3 min. These results are consistent with the notion that a rate-limiting action of RNase III in the initial attack leads to degradation of "spacer" sequences in rRNA gene transcript; and that degradation is not at all connected with ribosome translocation.


Mapping missense and nonsense mutation in gene cI of bacteriophage lambda: marker effects.

Amber and missense mutations in gene cI of bacteriophage lambda were mapped by reciprocal four-factor crosses, selecting recombinants between the outside markers (N amber and O amber). Distances between cI missense mutations were additive. Several cI amber mutants recombined with other cI mutations with a higher frequency than expected from the map location. Multiple exchanges in the N-O region occurred at a frequency greater than expected by chance. This "high negative interference" was especially marked in crosses with the cI amber mutations that were strong recombiners. A new ind mutation, ind2, was found near tsU51, to the left of the previously-known ind1 mutation, which is located almost in the center of gene cI. The mutation c50 maps to the right of tsU50 and c71. Mutations c60, and ts71, which differ in phenotype, are apparently at the same site.


A ribosomal RNA gene of Escherichia coli (rrnD) on lamnda daro E specialized transducing phages.

Lambda-transducing phages carrying segments of the Escherichia coli chromosome in the aroE-trkA region have been isolated and shown by hybridization to carry an rRNA gene (rrnD). The most likely gene order is trkA aroE rrnD. The EcoRI and SmaI endonuclease cutting pattern of the rrnD gene is identical with the one of rrnB, differented from rrnC.


Yeast cell-cycle mutant cdc21 is a temperature-sensitive thymidylate auxotroph.

Genetic tests with the yeast cell-cycle mutant cdc21 isolated by Hartwell indicate that the CDC21 gene in yeast is the same as the TMP1 gene, whose mutant alleles confer an auxotrophic requirement for thymidine-5'-monophosphate (dTMP). Yeast strains carrying cdc21 can grow at 37 degrees in the presence of dTMP provided that they are premeable to this compound. The gene is shown to be linked to ade2 on Chr. XV, and a case of intragenic complementation between cdc21 and another tmp1 allele is reported.


The host specificity system in Escherichia coli SK.

E. coli SK has its own enzyme system providing DNA host specificity which differs from the known types of specificity in E. coli K12 and E. coli B. Modification and restriction are observed when the PBVI or PBV3 phages are transferred from E. coli SK to E. coli B or K12 (and back). A methylase has been isolated from E. coli SK cells and partly purified. This methylase catalyzes in vitro transfer of the labelled methyl groups from S-adenosylmethionine (SAM) to DNA of both phage and tissue origin which gives rise to 5'-methylcytosine (5'MC) and 6'-methylaminopurine (6'MAP). The methylase preparations isolated from the cells at the stationary growth have proved to be 1.5-1.7 times as active as the enzyme from the cells at the logarithmic growth stage. The extract of E. coli SK cells infected with the phage SD cannot methylate DNA in vitro. This fact is due to de novo synthesis of the enzyme which disintegrates SAM down to 5'-methyltioadenosine (5'MTA) and homoserine (HS). This enzyme is not found in the cells infected with the SD phage in the presence of chloroamphenicole. The activity of the enzyme which disintegrates SAM is the highest between the 4th and the 5th minutes of infection. Thus it may be assumed that this enzyme, most probably, is an early virus specific protein and prevents in vivo methylation of the phage DNA.


The extracellular metalloprotease of Serratia marcescens. 2. Comparison with trypsin and substrate specificity.

The proteolytic activity of the extracellular protease of Serratia marcescens was compared with that of trypsin on N, N-dimethyl casein. The peptides produced from exhaustive hydrolysis of alpha casein by the protease and by trypsin were of similar size as measured by gel filtration on P-10 Agarose. We conclude that the protease of S. marcescens in an endopeptidase with trypsin-like activity on proteins, producing oligopeptides. End group analysis of the peptides formed by the S. marcescens protease suggests that the protease has a unique substrate specificity, hydrolyzing only a peptide bond whose carboxyl group is donated by proline. The protease was inactive on the synthetic peptides with proline donating the carboxyl group, but hydrolyzed various types of natural proteins. Its narrow and novel substrate specificity makes this enzyme a potential tool for the determination of the primary structure of proteins.


Loosening and unfolding of E. coli 50 S ribosomal subunits: dependence on magnesium content and temperature.

Reversible change of 50 S ribosomal subunits to 40 S particles takes place in cold buffered 0.5 M NH4Cl solutions either containing Mg++ (up to 0.1 M), or free from Mg++ and even supplemented with EDTA (1 mM). The 40 S particles were stable only within a definite temperature range. Heating of the samples caused completely irreversible unfolding of the 40 S particles. This "melting" appeared to be co-operative and took place within a very narrow range of temperature, which for samples containing Mg++ was a linear function of the log of Mg++ concentration. The results suggest that two types of bonds maintained the compact structure of the ribosomal subunits: ionic bonds involving Mg++ and heat-labile weak interactions between ribosomal components.


[Pathophysiology and laboratory diagnosis of collagen diseases (author's transl)].

Beginning with lesions of the capillary wall, rheumatoid arthritis is morphologically expressed by an aseptic inflammation of the synovia with following necrosis of the cartilage and the underlying bone tissue. Only little is known regarding the pathogenesis but most porbably immune mechansims are involved. There is evidence for the participation of type IV and type III-reactions i.e. sensitized lymphocytes as well as immune complexes. Equally the etiology of RA is totally unknown. Once the inflammatory process has reached some activity, in most cases it shows the character of a selfpertetuation as in other autoimmune diseases. Laboratory examinations include BSR, blood count, measurement of Fe, Cu, RF, complement, streptolysins, staphylolysins, ANA, and in doubtful cases synovial  biopsy. Furthermore, effusion fluid of the joint may be examined for RF, ANA, complement, rhagocytes, crystals, protein content etc.--Among the collagen diseases sensu strictori, systemic lupus erythematosus is the most important. The underlying process may be characterized as vasculitis due to immune complexes and local activation of the complement system, the complexes containing native and/or denatured DNA, and antibodies mostly of the IgG class. Laboratory examinations include the demonstration of ANA but should concentrate on the measurement of DNA-antibodies using radioimmunological or at least a sensitive and specific immunofluorescence technique. The value of the various tests is discussed.


Comparative mutagenicity of N-nitrosamines in a semi-solid and in a liquid incubation system in the presence of rat or human tissue fractions.

The rat liver microsome-mediated mutagenicities of a series of N-nitrosodialkylamines and heterocyclic N-nitrosamines were determined in a liquid incubation system using Salmonella typhimurium TA1530. The influence on mutation frequency of the concentration of co-factors for mixed-function oxidase and composition and molarity of the buffer was investigated, using N-nitrosomorpholine as substrate. The mutagenicity of the N-nitroso compounds in the liquid incubation system under optimal reaction conditions at equimolar concentration was compared quantitatively with that obtained in a soft-agar incorporation assay. N-Nitrosodi-n-pentylamine and N-nitrosodi-n-butylamine showed no enzyme-mediated mutagenicity in the liquid incubation system, and metabolically activated N-nitroso-dimethylamine and N-nitroso-diethylamine showed negligible mutagenic activity in the soft-agar assays. In contrast with these results with the N-nitrosodialkylamines, the mutagenic effects of heterocyclic N-nitrosamines were similar in the liquid incubation system and in soft-agar incorporation assays. The heterocyclic N-nitrosamines showed rat-liver microsome-mediated mutagenicity in the following descending order: N-nitrosomorpholine greater than N-nitrosopyrrolidine greater than N-nitrosopiperidine greater than N-nitroso-N'-methylpiperazine. Seven human liver specimens converted all heterocyclic N-nitrosamines into mutagens; this activity was similar to that of rat liver, except that for N-nitroso-N'-methylpiperazine, fractions from three human liver biopsies were three to 30 times more active than those from untreated rats. The specific reversion of S. typhimurium TA1530 to histidine prototrophy provides experimental evidence that all the N-nitrosamines studied were converted by liver microsomal enzymes into monofunctional alkylating agents.


Lethal effects of pyrimidine dimers induced at 365 nm in strains of E. coli differing in repair capability.

Photoreactivation (PR) after 365-nm inactivation was measured in four strains of Escherichia coli differing in repair capability. Photoreactivation was observed in the recA strains K12 AB2480 and K12 AB2463 indicating a significant role of pyrimidine dimers in the lethal action of 365-nm radiation in these strains. Significant PR was not observed in the uvrA strain, K12 AB1886, or in the repair proficient strain, K12 AB1157, after 365-nm inactivation. Biological evidence indicated that stationary phase cells had not lost the capacity for photo-enzymatic repair after fluences of 365-nm radiation of 2 X 10(6) J/m-2 or less. It is proposed that pyrimidine dimers, although induced, are not significant 365-nm lethal lesions in uvrA and wild-type strains because of their efficient dark repair.


Effects of a short heat pulse on phenomena related to DNA repair in ultraviolet-irradiated Escherichia coli.

Mutational synergism between heat and UV light in Escherichia coli was examined for evidence supporting various possible synergistic mechanisms. UV and heat lethality were only additive or slightly synergistic after 30 sec at 50 degrees C. The order of treatment did not affect the mutational synergism. Synergism is not peculiar to induction of mutation from streptomycin sensitivity to resistance. Neither DNA breakage nor alteration of post-replication repair rates was seen after a 5 min 50 degrees C heat pulse. Synergism was observed with temperatures as low as 43 degrees C. A strain deficient in excision repair but not post-replication repair exhibited mutational synergism, suggesting that synergism may involve the differential heat alteration of the error-prone post-replication repair process.


Mutagenicity of K-region epoxides of polycyclic aromatic compounds: structure-activity relationship.

The mutagenicity of several K-region arene oxides was tested in histidine-dependent mutants of Salmonella typhimurium. Benzo(a)pyrene-4,5-oxide and pyrene-4,5-oxide as well as some substituted phenanthrene oxides were mutagenic in strains TA 1538 and TA 98 which detect frame-shift mutagens. Structure-activity relationships are discussed from the standpoint of chemical reactivity. The absence of direct correlation between electrophilic reactivity and mutagenicity may suggest that primilarily physical properties, such as relative position of the epoxide group and molecular shape of arene oxides, are important for the emergence of mutagenicity of arene oxides.


Effect of dimethyl sulfoxide (DMSO) on radiation-induced heteroallelic reversion in diploid yeast.

Dimethyl sulfoxide has cryoprotective and radioprotective properties. It is also an efficient scavenger of radicals produced by raiolysis of water. Gamma-induced reversions of diploid yeast in the presence of this chemical during irradiation have been studied. The dose-modifying factor was in the same range as for survival. When the yeast was irradiated in the frozen state the observed protection by DMSO disappeared. The results are discussed in terms of direct and indirect actions of radiations and the radical-scavenging ability of this chemical.


Genetic effects induced in Saccharomyces cerevisiae by cyclophosphamide in vitro without liver enzyme preparations.

Cyclophosphamide induced forward mutation in Saccharomyces cerevisiae strain S288C and mitotic recombination in strains D3 and D5 but not in strain D4. The yeast cells were treated with the compound in phosphate buffer without recourse to metabolic activation protocols. Elevation of the treatment temperature increased the genetic activity of cyclophosphamide. Respiration-deficient isolates of strains S288C and D3 were more sensitive than the respiratory competent parent strains were for inducing forward mutation and mitotic recombination, respectively. Cyclophosphamide was incubated in phosphate buffer alone for increasing time intervals; strain D3 cells were added to aliquots for each time interval and incubated for an additional 30 min. The frequency of induced recombination increased as the time of compound incubation increased, showing that spontaneous degradation of cyclophosphamide to genetically active breakdown products was responsible for the genetic damage induced in the yeast cells.


A comparative study of different experimental protocols for mutagenesis assays with the 9-azaguanine resistance system in cultured Chinese hamster cells.

Both spontaneous and EMS-induced mutant frequencies were determined in cultured cells from V79 Chinese hamsters using three different experimental protocols. After optimal expression time was attained, mutation frequencies only remained constant when a protocol was used in whcih the cell density was maintained below critical values both before and during mutant selection. The identification of such a plateau allows, besides more reliable and reproducible estimates of mutation frequency, reduction in the size of experiments for quantitative evaluation of mutagenicity. Determination of mutation frequencies over a wide range of expression times becomes in fact unnecessary.


Comparison of two naltrexone treatment programs: naltrexone alone versus naltrexone plus behavior therapy.

During a period of one year naltrexone was given to twenty-nine subjects. Fifteen of these subjects concurrently participated in a comprehensive behavior therapy program. The subjects in this naltrexone/behavior therapy group were maintanine on naltrexone for nearly twice as long as naltrexone group clients who received no therapy. If the chances for readdiction are reduced by increased time on naltrexone, then the data states the naltrexone should be dispensed as part of a broader therapeutic strategy. Follow-up data, which will be collected during the next year will test the validity of this hypothesis.


Interim report on clinic intake and safety data collected from 17 NIDA-funded naltrexone studies.

In 17 studies of naltrexone, a totoal of 1,536 patients had been logged in as potential study subjects as of February 29, 1976. Of these, 883 had been started on study medication, including 107 on placebo as controls. A relatively high rate of attrition was seen in all studies over the first two months of study medication; this attrition rate tended to flatten out at about the fourth month. Of the 883 subjects beginning study medication, 47 (5.3%) were subsequently terminated for medical reasons. The data available on 45 of these subjects indicate equivalent percentages, both with respect to the total number of dropouts in the two study medication groups (naltrexone: 39 of 676, or 5.0%; placebo: 6 of 107, or 5.6%) and to the number of dropouts which the clinic reported as "possibly drug-related" (naltrexone: 6 out of 676, or 0.9%; placebo: 1 of 107, or 0.9%). However, one of the "possibly drug-related" dropouts developed idiopathic thrombocytopenic purpura after the administration of naltrexone for approximately 13 months during four separate treatment admissions. Statistical review of the data and subsequent analyses of the five double-blind, placebo-controlled studies administered by the National Academy of Sciences revealed no significant medication-group differences with respect to the physical/psychiatric or laboratory data. A review of the symptom data and analyses indicates that the frequency of occurrences of certain of the gastrointestinal tract symptoms recorded was somewhat higher in those subjects treated with naltrexone. Specific symptoms involved included "Loss of Appetite", "Abdominal Pain or Cramps", "Nausea or Vomiting", and "Constipation". However, the relative severity of these symptoms for all subjects experiencing any symptomatology was not statistically differentiable with respect to study medication group.


Clinical experiences with naltrexone in 370 detoxified addicts.

Our studies have shown no evidence of toxicity and few side effects from naltrexone. It is a valuable adjunct in treating addicts who wish to be opiate free. Patients who drop out and return to treatment tend to remain longer with each successive readmission. Naltrexone has special potential for persons, such as an opiate-abusing physician for whom methadone maintenance is clearly inappropriate. A double-blind study has suggested that it may have value as a transitional treatment for detoxified methadone maintenance patients. Differences between naltrexone and cyclazocine suggest that a treatment combining these drugs should be explored.


Cell length, cell growth and cell division.

When cells of E. coli reach a certain critical length, which is constant in all growth conditions and eqqal to twice the minimum cell length, they abruptly increase their rate of elongation and divide about 20 min later. Chromosome replication terminates at about this same cell length but is not the signal for the change in rate of cell elongation.


Evaluation of six short term tests for detecting organic chemical carcinogens and recommendations for their use.

Six short term tests for detecting carcinogenicity have been evaluated using 120 compounds, of which half were carcinogens and the rest non-carcinogens. The results obtained indicate that the Ames test and a "cell transformation" assay are both sufficiently sensitive to carcinogenicity, or the lack of it, in the compounds studied to enable them to be employed for detecting potential carcinogens. The consequences of using short term tests under various screening conditions have been explored. In order to have confidence in the results obtained for new or previously untested compounds it is important to use such tests in a carefully controlled manner.


Intralesional BCG application in malignant melanoma.

Immunotherapy of malignant melanoma with BCG may be divided into two basic groups: 1. treatment of minimum residual disease. 2. direct intralesional application of BCG. In 19 patients with a histologically confirmed malignant melanoma, direct intralesional application of BCG was used to treat relapsing patients. In 10 of the 19 patients (group A) the relapse was confined to the primary region without signs of distant dissemination. In the remaining 9 patients (group B) signs of the lesion were present prior to BCG application. Our clinical and cytological evaluation bore on local reactions, systemic side reactions and response of non-injected lesions. In patients without signs of distant dissemination, local regression, characterized by a flattening and disappearance of lenticular metastases with scar formation, was achieved in 8/10 patients, while in the noninjected lesions, regression was noted in only 4/10 patients. In 4 patients of group A complete remission lasting 4-6 months was achieved. In the group of patients with signs of distant dissemination, local regression was observed in 6/9, while noninjected lesion regressed in only 1/9. Systemic response to BCG was characterized by febrile reactions with, in the majority of the patients, nausea till vomiting, muscular pain, pain of joints. In the majority of the patients the reaction passed away within 24 hr. A pretreatment with antipyretic and antihistaminic drugs proved of great help. The effect of BCG on the subsequent fate and survival of the patients is not discussed.


Malignant lymphoma with isolated kidney involvement.

A case of reticulum cell sarcoma with kidney involvement is described. The diagnosis was established by open renal biopsy only when the disease was far advanced. Treatment with combination chemotherapy and radiotherapy brought about very short remission and the patient died in uremia. Autopsy showed isolated kidney involvement with only metastasis in thyroid gland.


[A case of paravertebral lumbar meningomyelocele (author's transl)].

A case reported here is one year-old girl, who was admitted to our neurosurgical service because of gradually increasing swelling in the left lumbar region, and maldevelopment and paresis of the left leg since birth. From the level of L-2 to S-1, there was a 8 X 7 xm subcutaneous swelling of lipomatous consistency with well-defined margins. Of particular characteristics was that the swelling didn't cross the midline and was entirely located in the left paravertebral region (Fig. 1). In the spine no gap could be felt between the spinous processes. There was no evidence of hydrocephalus, but she bad marked right sided scoliotic deformity of the lumbar region, and dislocation of hip joint and club-foot on the left side. Rectum-bladder-vaginal fistula with defect of anus and hypoplasia of kidney on the left side were also detected. Skiagram of the lumbosacral spine revealed marked right-sided scoliosis at the level of L-1 and hypoplasia of left pedicles, accompanied with marked dilation of transverse diameter of spinal canal between the level of L-1 to S-2. Defect of laminae of lumbosacral spine was not definately determined. Conray myelogram showed presence of cyst protruding laterally to the left paravertebral region probably through defect of lamina on the left side at the level of L-5 (Fig 2). At operation, it was confirmed that meningomyelocele protruded out laterally through the defect of half of lamina at the level of L-5. Massive lipoma was noted inside as well as outside the dura mater. Neural elements were replaced inside the spinal canal and the dura repaired. The postoperative period was uneventful. Diagram of defect of lamina at the level of L-5 and its relationships to the meningomyelocele sac is shown in Fig. 3. Meningocele or meningomyelocele which lays in the paravertebral lumbar region is very rare (Table 2), but the possibility of this disease should always be considered when we examine the patients with lipomatous or cystic swelling in the paravertebral lumbar region, especially when the patients present the neurological symptoms or signs.


[Diencephalic cyst--in relation to other midline dysraphism (author's transl)].

The abnormal midline cyst of diencephalic origin was termed "diencephalic cyst" by Brocklehurst in 1973. Since then, several case reports of so-called "diencephalic cyst" have appeared, but its clinical picture, especially its relation to other midline dysraphisms, does not seem to be well understood. Our experience with four cases of so-called "diencephalic cyst" were reported and their relation to holoprosencephaly as well as simple agenesis of corpus callosum was discussed. (1) In all of these cases, there was an abnormal space in the midline which freely communicated with the lateral ventricle. In the first two cases, their clinical pictures as well as the features of contrast studies were typical of alobar holoprosencephaly. In the third case, the absence of the olfactory tract, the incompletely separated cerebrum, and the monoventricle were confirmed at autopsy. In the last case, the ventricle was also incompletely separated. From these observations, such a malformation should better be considered as a variant of holoprosencephaly, and it would not be appropriate to classify this malformation, as Brocklehurst claimed, as "a maldevelopment lying between the group associated with anterior neuropore closure and prosencephalization (anterior encephaloceles and holoprosencephaly) and the group associated with maldevelopment of the hind brain (cerebellar and fourth ventricle encephaloceles and Dandy-Walker cyst of the rhombencephalon)." (2) This malformation is apparently formed before the 40 mm stage of the embryo, since by this time the diencephalic roof has already sunk to the level of the adult form. This maldevelopment should be clearly differenciated from simple agenesis of the corpus callosum which is formed after the 60 mm stage of the embryo. In simple agenesis of the corpus callosum, the deep venous system might take an abnormal course, but is well formed, whereas in holoprosencephaly or so-called "diencephalic cyst", the internal cerebral vein as well as the straight sinus and the inferior sagittal sinus is absent. (3) In all of our cases, there was an abnormal space posterior and inferior to the elevated lateral sinus. Autopsy done in two cases revealed that this abnormal space was a Dandy-Walker cyst in one case, the the dorsal sack of diencephalic origin in the other case. The latter case tells that in the cases of holoprosencephaly the lateral sinus does not necessarily mark the boundary between the cerebrum and the cerebellum. (4) "Diencephalic cyst" often accompanies severe hydrocephalus. However, even with successful surgical treatment of hydrocephalus, the outcome of intelligence in these cases would be grave.


Alpha-adrenergic regulation of growth hormone release after electroconvulsive therapy in man.

When electroshcok therapy was administered to male psychiatric patients without anticonvulsive premedication, serum growth hormone (GH) increased; the increase was not prevented by an infusion of 20% glucose (5 ml per min) 20 min prior to electroshock. Therefore, the GH rise is not caused by muscle exercise during convulsions. Infusing 30 mg of phentolamine 40 min prior to electroshcok inhibited the GH response. Phentolamine's effect shows that the stress-induced GH release that follows electroconvulsive therapy is mediated by alpha-adrenergic neurons.


Effect of photoperiod on gonadotropin releasing hormone-induced LH release in the immature rat.

Female rats raised from birth under a light/dark (LD) or constant light (LL) regimen were given injections at either 24, 29, 33 or 35 days of age of either 5 IU PMSG or 0.1 ml saline. Two days following PMSG or saline injection, the rats were given injections of either 1,000 ng synthetic gonadotropin releasing hormone (GnRH) or 0.1 ml saline. Blood samples were taken before and 20 min after injection for LH determinations. PMSG caused a rise in basal LH levels, which was greater in LL than in LD animals. GnRH administration resulted in an LH surge in both LD and LL rats at all ages tested. The LL animals released greater amounts of LH in response to GnRH than did LD animals. In PMSG-primed animals there were no differences in the GnRH-induced LH surge due to either age or photoperiod. It is concluded that PMSG and LL enhance the pituitary's response to GnRH.


A linkage study of depression spectrum disease: the use of the sib-pair method.

Genetic linkage was studied in depression spectrum disease, a subgroup of unipolar depressive illness defined by presence of familial alcoholism and/or antisocial personality, using a version of the sib pair method of Penrose. Rigorous research diagnostic criteria were used and the diagnoses were made blind, i.e., without knowledge of the genetic marker results. Possibility of linkage was suggested (p less than 0.005) with the alpha-haptoglobin (alpha-Hp) and third complement component (C3) loci. However, the likelihood that these two markers are not on the same chromosome, and the limitations of the sib pair method, permit these findings to be treated as suggestive only and indicate that these two promising markers should be investigated further, using a more definitive method of linkage detection such as the lod score method.


Copper jacketed bullets in the central nervous system.

Bullets fired from hand guns are often partially or fully jacketed with copper - a fact that can usually be recognized on radiographs. The copper content of the metallic foreign body (MFB) appears to be more toxic than unjacketed lead and sometimes leads to migration of the MFB through brain tissue. Therefore, it appears wise to attempt to recognize and remove copper containing MFBs when they lie in contact with the central nervous system. Plain lead missiles and those partially clad with copper often leave traces of lead along their paths, while those that are completely copper clad do not. Partially clad missiles tend to show some separation of lead and copper - revealing two differing metallic densities on the radiographs.


Schools of public health--their doing and undoing.

The heretofore untold story of Abraham Flexner's role in the establishment of the first endowed schools of public health (Johns Hopkins and Harvard) provides an unusual window through which to view the historic struggle of public health doctors to resolve their identity problem. They have become a profession, nominally a part of and yet fundamentally different from that of the physician in patient care. Nonetheless, the primary qualification for leadership in public health still is considered an M.D. degree rather than a Dr.P.H. or some equivalent. The author analyzes the characteristic inability of public health leaders to support their grand visions in times critical for decision, and calls on the modern community health educator, planner, and organizer to face the explicit question that all but a few of his public health forebears have sidestepped: Is public health a brance of medicine? Are education and training for clinical medicine desirable preparation for a career in public health, or does this simply doom one essential profession to remain subordinate to another?


Analgesics and the stomach.

A review of the literature on the gastrointestinal side effects of the analgesic drugs has disclosed a disparity between generally held views and the scientific evidence. This is largely due to the paucity of large long term controlled trials since the cost of these is very high. The problems in mounting a large observational study with population controls are discussed against a backgrwound of exploratory work in Australia and New Zealand and the conclusion is reached that a comprehensive survey is needed. The difficulties in mounting such a survey are discussed.


Lamellar keratoplasty for recurrent pterygium.

Lamellar corneoscleral keratoplasty technique for recurrent pterygium is described. The importance of accurate placement of the graft and its usefulness as a tissue barrier to regrowth of the pterygium is postulated. In fifteen eyes with severe recurrent pterygium followed from six months to four years, there have been no further recurrences after using this technique.


An interlocking slip knot for cataract sutures: preliminary report.

A new method of tying a knot for cataract surgery is demonstrated. Its purpose is to provide a safe, interlocking slip knot, using nylon suture, removable merely by pulling on the free ends. Cases are presented showing the safety and effectiveness of the ISK.


[Reconstruction of tumor defects in the oral cavity and mesopharynx].

A superiorly based cervical skin flap (eventually including the sternocleido-mastoid muscle) has been used in combination with a deltopectoral flap for the one-stage reconstruction of large defects of the oral cavity and mesopharynx. The results obtained in 17 patients show that the presented method is of particular value in cases presenting with unfavorable tissue conditions resulting from heavy irradiation.


[Rhinoscleroma with sinuso-orbitary invasion].

The authors present the case of an 11-year-old child with a slowly progressive tumoral invasion resulting in bilateral nasal obstruction, massive facial deformation, and an exophthalmos of the left eye. There was no impairment of the child's general health. The histological investigation revealed the presence of Mikulicz' cells and von Frisch's bacilli. The resultant diagnosis was rhinoscleroma.


Did Ptolemy understand the moon illusion?

Ptolemy is often wrongly credited with an explanation of the moon illusion based on the size-distance invariance principle. This paper elucidates the two Ptolemaic accounts: one in the Almagest, based on atmospheric refraction, and the other in the Optics, based on the difficulty of looking upwards. It is the latter passage which has been thought to refer to size-distance invariance, but it is more probable that it refers to the idea that the visual rays are diminished by the force of gravity (i.e. that the retinal image is reduced in size). Alhazen was probably the first author to explain the illusion by the size-distance invariance principle, and Roger Bacon the first to explain the enlarged apparent distance of the horizon by the presence of intervening objects. Della Porta was the first to credit Ptolemy with these explanations, and this mistake was repeated by many subsequent authors.


[A method of studying insulin secretion in humans: the glucose stimulation test, followed by tolbutamide].

Various parameters of the insulin secretion in man may be appreciated and calculated by studying the insulin response to an intravenous pulse of glucose followed 120 minutes later by one of tolbutamide. The relative insensitivity of the B cell to glucose, probable marker of a constitutional pancreatic predisposition to diabetes may be assessed in a given individual whatever his age and body weight. The glucose intolerance per se is due to, or accompagnied by various B cell dysfunctions according to its etiology. This is illustrated by the results observed in chronic pancreatitis, liver cirrhosis, aged or obese subjects.


[Dominant generalized cortical hyperostosis with multiple involvement of the cranial nerves].

The authors report an observation of dominant generalized cortical hyperostosis with multiple and unilateral involvement of a certain number of cranial nerves. In other members of the family, who present with the same bone disorder, involvement of the cranial nerves was limited to the facial nerve, either uni or bilaterally, with a partially or totally regressive evolution. This cranial nerve involvement, which is classic in the recessive form (first described) of generalized cortical hyperostosis, has until now, never been reported in the dominant form of this disorder.


Studies on the ability of partially iodinated 16S RNA to participate in 30S ribosome assembly.

Deproteinated 16S RNA was iodinated at pH 5.0 in an aqueous solution containing TlCl3 plus KI for 1-5 hours at 42 degrees C. Under these conditions 33 moles of iodine are incorporated per mole of RNA. As judged by sucrose gradient sedimentation, the iodinated RNA does not exhibit any large alteration in conformation as compared to unmodified 16S. The iodinated RNA was examined for its ability to reconstitute with total 30S proteins. Sedimentation velocity analysis reveals that the reconstituted subunit has a sedimentation constant of approximately 20S. In addition, protein analysis of particles reconstituted with 16S RNA iodinated for 5 hours indicates that proteins S2, S10, S13, S14, S15, S17, S18, S19, and S21 are no longer able to participate in the 30S assembly process and that proteins S6, S16 and S20 are present in reduced amounts. The ramifications of these results concerning protein-RNA and RNA-RNA interactions occurring in ribosome assembly are discussed.


Study on the structure-function relationship of polynucleotide phosphorylase: model of a proteolytic degraded polynucleotide phosphorylase.

It is already known that modification of E. coli polynucleotide phosphorylase by endogenous proteolysis induces drastic changes in both phosphorolysis and polymerisation reactions. The structural parameters of the proteolysed polynucleotide phosphorylase are described. The phosphorolysis of polynucleotide, which is quite progressive for the native enzyme, is shown to be only partially progressive for the degraded enzyme, owing to the loss of polymer attachment sites.


Repeating restriction fragments of human DNA.

Human DNA digested with Hae III showed multiple repeats of a 170 base pair fragment. The most prominent band was the 340 base pair dimer, estimated to be 0.8% of the entire genome. Eco R1 and Hha I yielded fragments with similar electrophoretic mobility to the Hae III dimer. In each case this band was markedly enriched in DNA reassociating at a 0t of less than or equal to 1. Hybridization of the Hae III dimer to gels eluted on to filters demonstrated that the multiple Hae III fragments and Eco R1 fragments contained compatible sequences. These sequences may comprise a distinct subclass of DNA.


7-Methylguanine specific tRNA-methyltransferase from Escherichia coli.

A 7-methylguanine (m7G) specific tRNA methyltransferase from E. coli MRE 600 was purified about 1000 fold by affinity chromatography on Sepharose bound with normal E. coli tRNA. The purified enzyme catalyzes exclusively the formation of m7G in submethylated bulk tRNA of E. coli K12 met- rel-. The purified enzyme transfers the methyl group from S-adenosyl-methionine to initiator tRNA of B. subtilis and 0.8 moles m7G residues are formed per mole tRNA. It is suggested that the enzyme specifically recognizes the extra arm unpaired guanylate residue.


Secondary structure of nucleic acids in the folded chromosome from E. coli.

The circular dichroism of membrane-free folded chromosomes from E. coli was measured and analyzed. The spectrum can be explained as a simple linear combination of the individual spectra of E. coli RNA, and E. Coli DNA in the B form. No contribution from A form or C form DNA was detected. There was evidently some real variation in the ratio of the two nucleic acids from preparation to preparation, but the average value was 24% RNA and 76% DNA. No significant light scattering was observed and the analyses indicated no contribution to the circular dichroism from scattering artifacts. Apparently, combining DNA, RNA, and protein into membrane-free folded chromosomes does not change the secondary structure of the DNA or RNA from that found for the free nucleic acid in the same solvent system.


Structlre of transfer RNA molecules containing the long variable loop.

A structure is proposed for the type II tRNA molecules containing the long variable loop and the tertiary base interactions here are compared with type I tRNAs having the short variable loop. The type II tRNAs are similar to the type I tRNAs in their tertiary base pairing interactions but differ from them generally by not having the tertiary base triples. The long variable loop, which is comprised of a helical stem and a loop at the end of it, emerges from the deep groove side of the dihydrouridine helix, and is tilted roughly 30 degrees to the plane formed by the amino acid-pseudo-uridine and anticodon-dihydrouridine helices found in yeast tRNAPhe. The fact that many of the type I tRNAs also lack the full compliment of base triples suggests that the tertiary base pairs may alone suffice to sustain the tRNA fold required for its biological function. The base triples and the variable loop appear to have little functional significance. The base type at position 9 is correlated with the number of base triples and G-C base pairs in the dihydrouridine stem.


Kinetic studies on the cleavage of adenovirus DNA by restriction endonuclease Eco RI.

The kinetics of cleavage of DNA from Adenovirus Type 1 (Ad1), Type 5 (Ad5) and Type 6 (Ad6) by restriction endonuclease EcoRI was investigated by quantitative evaluation of the fluorescence from ethidium stained DNA fragments separated on agarose gels. The apparent rate constants of cleavage at different cleavage sites have been determined and large differences in the cleavage rates of the individual sites within one type of DNA were found. From the kinetics of cleavage information on the sequence of the DNA fragments can be obtained. The order of the fragment A, B, C, D of Ad6 DNA obtained after complete cleavage by restriction endonuclease Eco RI was found to be A-D-C-B; the order of the corresponding fragments A, B, C of Ad1 and Ad5 DNA was found to be A-C-B.


The nucleotide sequence of asparagine tRNA from Escherichia coli.

The nucleotide seuquence of Escherichia coli asparagine tRNA was determined to be pU-C-C-U-C-U-G-s4U-A-G-U-U-C-A-G-D-C-G-G-D-A-G-A-A-C-G-G-C-G-G-A-C-U-Q-U-U-t6A-A-phi-C-C-G-U-A-U-m G-U-C-A-C-U-G-G-T-phi-C-G-A-G-U-C-C-A-G-U-C-A-G-A-G-G-A-G-C-C-AOH. Its D-stem and D-loop have almost the same sequence as Escherichia coli aspartate tRNA.


The kinetics of bisulphite modification of reactive residues in E. coli tRNA2Phe.

E coli tRNA2Phe was modified at 25 degrees C with 3M sodium bisulphite, pH6.0, for periods of up to 48 hours, Three cytadinine residues, at position 17, 74 and 75 from the 5' end were each deaminated to uridine. The 2-methylthio-N6-isopentenyl adenosine at position 37 formed a 1:1 bi-sulphite addition product which was stable to alkaii. No other residues were permanently modified. The rate of modification of each residue was first order with respect to remaining unmodified nucleotide, the time of half reaction, t1/2, being different for each residue. C17 reaction reacted at twice the rate of cytidine in PolyC, indicating that it occupied a very exposed position in the tRNA.


[User-oriented programs for semi-automated evaluation of radio in vitro tests].

Most of the programmes for the evaluation of radio in vitro tests proceed from the anticipation that the best method should give an approximation of standard values by a curve as perfect as possible. According to our experiences this demand, however, is not decisive for a good standard curve, as in principle all standard values can be incorrect. The application of relatively simple linearising transformations and an additional curve (recovery of a normal serum) guarantees the necessary precision in the programme described. After a short description of the contents of the system, the programme for the assessment of CPBA - methods is shown, by help of which the sample changer - calculator-system determines the absolute concentration of the substance to be measured. This makes the starting point for the more complex RIA programme which methodologically takes into consideration the special problems of these tests.


[Goodpasture's syndrome. A new case].

The authors report a new observation of Goodpasture's syndrome in a 21 years old patient. Diagnosis was made by renal biopsy after discovering, by immunofluorescence techniques, linear deposits of IgG and C3 on the renal basal lamina. Anti-basal lamina antibodies of the plasma were not found. In spite of therapy by steroids, a rapid worsening of renal functions accompanied a nephrotic syndrome. Supplementing hemodialysis helped patients to survive without recurrence of hemoptysis. Heparinotherapy prescribed on the creation of an arteriovenous fistula seemed to have brought a temporary improvement of the renal function.


Effect of immunosuppressors, anticoagulants and antiphlogistic drugs on experimental Masugi glomerulonephritis: I-imuran.

The effect of Imuran on experimental Masugi glomerulonephritis was checked in rabbits. The animals were grouped in biologically most similar pairs: one of the mates was treated with Imuran (4 or 8 mg/kg daily) the other served as control. Clinical and laboratory investigations were supplemented by histological and immunofluorescent studies of renal specimens taken on the 1st, 3rd, 7th, 10th, 21st, and 35th day of observation. The course of glomerulonephritis appeared much milder in Imuran-treated animals with a morphological counterpart in the form of reduced glomerular exudation and cellular proliferation. Only a slight and inconstant decrease of deposition of rabbit gamma-globulin and fibrin was observed in treatment animals in later stages of the experiment. Without denying a slight immunosuppressive effect, the authors admit that, in doses below 8 mg/kg daily, Imuran exerts a rather antiininflammatory effect on experimental glomerulonephritis.


Ultrastructural studies of the mechanism of changes developing in pemphigoid using peroxidase-labeled antibodies.

The application of peroxidase-labeled antiserum to human gamma globulin allowed the immunological reaction in vivo to be localized in the basement membrane, particularly in its part termed the lucid zone. The bulla is formed between the basal cell membrane and the dark lamina of the basement membrane.


Endonuclease II, apurinic acid endonuclease, and exonuclease III.

An endonuclease of Escherichia coli active on a DNA treated with methylmethane sulfonate has been separated from an endonuclease active on depurinated sites. The former enzyme is disignated here as endonuclease II, while the latter enzyme is designated as apurinic acid endonuclease. Endonuclease II is also active on DNA treated with methylnitrosourea, 7-bromomethyl-12-methylbenz[a]anthracene, and gamma-irradiation. A third fraction which contains activities for both depurinated and alkylated sites needs further study. Endonuclease II, molecular weight 33,000, has been purified 12,500-fold and does not have exonuclease III activity. Apurinic acid endonuclease, molecular weight 31,500, has been purified 11,000-fold and does not have exonuclease III activity. Exonuclease III, molecular weight 26,000, has been purified 2300-fold and does not have endonucleolytic activity at depurinated reduced sites or at alkylated sites in DNA. Therefore, these are three separate proteins. Exonuclease III can produce, presumably by its exonucleolytic activity, double-strand breaks in heavily alkylated DNA under conditions where it does not make single-strand endonucleolytic breaks at either depurinated-reduced or alkylated sites.


Activation of long chain fatty acids with acyl carrier protein: demonstration of a new enzyme, acyl-acyl carrier protein synthetase, in Escherichia coli.

A soluble enzyme activity which catalyzes the synthesis of acyl-acyl carrier protein from acyl carrier proteins, a long chain fatty acid, and ATP has been demonstrated in E. coli. The reaction requires high concentrations of both Ca++ and Mg++ for activity, and cleaves ATP to AMP and PPi. The fatty acyl product has been identified as acyl-acyl carrier protein by its solubility, thioester linkage, molecular weight, charge, and biological activity. Several criteria indicate the enzyme is distinct from acyl-CoA synthetase. The fatty acid specificity of the enzyme suggests a role of acyl-acyl carrier protein synthetase in the incorporation of fatty acids into phospholipid.


Change in membrane potential during bacterial chemotaxis.

To find out if there are changes in membrane potential during bacterial chemotaxis, we measured the membrane potential of Escherichia coli indirectly by use of the permeating, lipid-soluble cation triphenylmethylphosphonium. Addition of attractants or repellents to the bacteria brought about a hyperpolarizing peak (as well as additional, later changes in membrane potential). This peak was shown to be a part of the chemotactic mechanism based on the following evidence: (i) All attractants and repellents tested gave this peak while chemotactically inert chemicals did not. (ii) Mutants lacking galactose taxis failed to give the peak with galactose but did with another attractant and with repellents. (iii) Methionine, required for chemotaxis, is also required for production of this peak. (iv) A mutant in a control gene )flaI), unable to synthesize flagella and cytoplasmic membrane proteins related to motility and chemotaxis, failed to give the peak. (v) Paralyzed (mot) mutants gave little or none of the peak. Generally nonchemotactic (che) mutants, on the other hand, did give this peak. Very likely there are ion fluxes that bring about this change in membrane potential. We discuss the possible role of the mot gene product as an ion gate controlled by a methylation-demethylation process in response to attractants and repellents acting through their chemoreceptors.


Induction of sigma factor synthesis in Escherichia coli by the N gene product of bacteriophage lambda.

Thermoinduction of cells of E. coli carrying prophage lambdacI857 within the bfe gene brings about not only "escape synthesis" of core subunits of the DNA-dependent RNA polymerase (RNA nucleotidyltransferase, nucleosidetriphosphate:RNA nucleotidyltransferase, EC 2-7-7-6), but also a striking stimulation of sigma factor synthesis. The latter phenomenon, termed sigma induction, is generally observed after lambda phage infection or prophage induction. A series of experiments with various bacterial and phage strains led us to conclude that the N gene product of lambda is directly involved to the sigma induction. These and other results obtained with mutants defective in transcription termination factor rho suggest the involvement of a rho-sensitive site in the control of sigma gene expression in E. coli.


Novobiocin and coumermycin inhibit DNA supercoiling catalyzed by DNA gyrase.

Novobiocin and coumermycin are known to inhibit the replication of DNA iing of DNA catalyzed by E. coli DNA gyrase, a recently discovered enzyme that introduces negative superhelical turns into covalently circular DNA. The activity of DNA gyrase purified from a coumermycin-resistant mutant strain is resistant to both drugs. The inhibition by novobiocin of colicin E1 plasmid DNA replication in a cell-free system is partially relieved by adding resistant DNA gyrase. Both in the case of coliclls. DNA molecules which are converted to the covalently circular form in thepresence of coumermycin remain relaxed, instead of achieving their normal supercoiled conformation. We conclude that DNA gyrase controls the supercoiling of DNA in E. coli.


HLA membrane antigens: sequencing by intrinsic radioactivity.

Radiochemical sequence data are presented for the amino termini of mixed HLA antigens A1 and B8 isolated from a human lymphoblastoid cell line. Cells were labeled intrinsically in small-scale tissue culture with 14C-labeled amino acids and [14C]pyruvate. The specific activities obtained were sufficiently high and uniform to permit direct radiochemical sequencing of the antigens. HLA antigens were isolated by adsorption to a solid-phase anti-beta2-microglobulin immunoadsorbent followed by electrophoresis. The method should be generally applicable and useful for sequencing all parts of the molecule.


Modified recombination and transmission of mitochondrial genetic markers in rho minus mutants of Saccharomyces cerevisiae.

A large number of primary petite (rho-) clones were isolated after ethidium bromide mutagenesis of various grande (rho+) strains of S. cerevisiae that contained the mitochondrial genetic markers, CR, ER, OIR (or OIIR), and PR. From the frequency of coretention of markers in the petites, we have deduced a probable circular order of the markers in the grande mitochondrial genome. From these primary clones several series of pure and stable petite clones were obtained and analyzed genetically. (a) In general, the omega allele is retained or lost together with the region carrying both CR and ER markers. (b) The petites that have retained only the CR marker fall into two classes: some have kept the omega allele of the grande strain they issued from; others exhibit a new omega expression. (c) The proportion of diploid petites in petite X grande crosses is independent of the presence of the omega allele. (d) In most cases, the coordinated transmission of markers observed so far in all grande X grande nonpolar corsses does not exist anymore in petites.


Genetic analysis of a transposable suppressor gene in Saccharomyces cerevisiae.

We have demonstrated in Saccharomyces cerevisiae the transposition of a gene coding for an efficient ochre (UAA) suppressor from a centromere-linked site on chromosome III to two new sites in the yeast genome. One site is on chromosome VI, very close to, if not allelic with, SUP11, one of eight genes coding for a tyrosine-inserting suppressor. The second site is on chromosome III, unlinked to the centromere and distal to the mating type locus. This site is very close to those mapped for the recessive lethal amber suppressors, SUP-RL1 and SUP61.


[Oskar Vogt and the founding of the Berlin Kaiser Wilhelm Institute for Brain Research under conditions of imperialistic scientific policy].

The building up of the Berlin Institute for Brain Research finished in 1931 is the result of inconsistant developmental needs immanent to neuro-sciences on the one hand and science policy interests of imperialistic groups in the Weimarian Germany on the other hand. The theoretical and organizational analysis of the institutional concept realized by plans of Oskar Vogt gives evidence for its usefulness on principle for recent plannings of new brain research institutions too. But only after destroying the fascist dictatorship realistic developmental perspectives for brain research grew up in either German states depending on their various socio-economic conditions.


[Critical remarks on the concept of "osteopathia antiepileptica"].

A study of the available specialized literature shows that it is not yet possible to provide clear evidence for a direct causal relationship between anticonvulsive medication and skeletal demineralization caused by it. Therefore, it is strongly recommended that such disorders of ossification be not overhastily described by terms declaring the changes in bones to be complications caused by drugs used in antiepileptic therapy. Relationships between the tetanic and epileptic syndrome are discussed by reference to the author's own clinical experience and to the latest results obtained in the field of calcium and vitamin D metabolism, with special consideration being given to a corresponding intermediate group that is characterized by the presence of components of both of the syndromes referred to above.


The role of imagination in the disease process: pre-Cartesian histroy (the role of imagination in the disease process).

Ancient and Renaissance physicians implicated the soul's imaginative faculty in the genesis and remission of disease. The theory stated that images of objects of desire or aversion aroused emotions, which in turn set up humoral imbalances, disturbing digestion and other vital functions, culminating in various forms of pathology. This concept explained the therapeutic efficacy of 'placebos' in forms such as spells, charms and talismans. The theory merits close attention by contemporary physicians and researchers.


Emotional symptomatology in obese patients treated with fenfluramine and dextroamphetamine.

Emotional sympomatology data on 78 obese females treated for 3 weeks with fenfluramine, dextroamphetamine, or placebo were evaluated. These obese females were shown to be considerably less emotionally disturbed than neurotic females, and similar in emotional symptomatology to other females seeing physicians for nonpsychiatric complaints. Even within these marginally sympatomatic patients, fenfluramine and dextroamphetamine were significantly more effective than placebo in reducing anxious, depressive, and anxious-depressive symptomatology. Fenfluramine was particularly effective in alleviating anxiety in patients who were initially higher in anxiety. Most important, fenfluramine produced significantly greater weight loss than dextroamphetamine in patients with higher levels of anxiety and depression, while dextroamphetamine was an especially effective anorexic in low anxious patients. Differences in initial anxiety and depression, even within relatively normal patients, may well affect results obtained with fenfluramine and dextroamphetamine in the short-term treatment of obesity.


Chronic mania in childhood: case report of a possible association with a radiological picture of cerebellar disease.

The case-history of a woman with psychiatric symptoms since childhood is reported, the best label for which was that of "chronic mania". Cerebellar atrophy was suspected on radiological grounds. The literature on chronic mania in childhood and on cerebellar damage and mental changes is reviewed and the view is put forward that cerebellar dysfunction may play a part in the production of some psychiatric symptoms.


Comparative trial of L-tryptophan and amitriptyline in depressive illness.

Depressed patients who were suitable for drug treatment were allocated randomly to treatment for four weeks with either amitriptyline in doses reaching 150 mg daily or with L-tryptophan in a maximal dose of 8 G daily. Both in-patients and out-patients were included. The trial was double-blind and ratings were made at the start of treatment and weekly for the subsequent four weeks: the patients were then followed for a further six months. Both groups of patients improved steadily over the course of four weeks and there were no marked differences between the treatment groups though there was some tendency for the improvement of the tryptophan-treated patients to fade between the third and fourth weeks. Within the tryptophan group anxious patients improved least. It is concluded that L-tryptophan probably has some antidepressive action in patients with depressive illness of moderate severity.


[Craniolacunia (author's transl)].

The radiological and pathological features of craniolacunia are discussed in the light of 13 personal cases, two of which are presented.


[Human behaviour and instrumental disciplines (author's transl)].

The influence of human behaviour on the development of instrumental disciplines is discussed with special reference to medicine and radiology in research, application and teaching.


Activation and cytotoxic activity of macrophages: a short review.

Interaction of sensitized T-lymphocytes with specific antigen, as well as several other nonimmunological stimuli, will induce the appearance of new properties in macrophages collectively referred to as "activation". The importance of macrophage activation in various physiological processes is only just beginning to be understood. A growing body of evidence strongly suggests that activated macrophages may play a dual role: firstly in protecting the host against certain interacellular pathogens, and secondly in modulating cell proliferation and adversely affecting cells with abnormal growth properties. It is expected that the ability of activated macrophages to discriminate between normal and tumor cells will receive increasing attention. If confirmed, this property may be of major importance with regard to immunotherapy of tumors.


Cell-membrane activation of macrophage function.

A number of short-term macrophage functions are stimulated immediately on contact of suitable external materials with the macrophage plasma membrane. These include locomotion and chemotaxis, phagocytosis, and exocytosis of lysosomal hydrolases. They are probably contractile events and may be initiated by a transient increase in permeability to divalent cations either of the plasma membrane or of hypothetical intracellular cations stores. Such permeability changes may follow interaction of hydrophobic substances with the membrane bilayer or follow contact with substances which induce clustering of membrane proteins. It is conjectured that similar substances might induce long-term events such as DNA and protein synthesis, mitosis and activation of cytotoxic function in macrophages, but that to do this, contact of the substance with the macrophage must be prolonged.


Lymphocyte-macrophage interactions in BCG-treated mice.

Fresh living Bacillus Calmette-Guérin (BCG), injected i.v. into (C57Bl/6xDBA/2)Fl mice, activated peritoneal macrophages rendering them highly cytotoxic for tumor cells in vitro. This cytotoxic activity was already maximal 14 days after injection of 1 mg of BCG and remained stable when 3 or 5 mg of BCG were given. At the same time spleen cells of the BCG-treated mice showed strongly depressed responses to the T-cell mitogens, PHA and Con A, irrespective of the dose of BCG injected. The inhibitory effect was shown to be mediated by suppressor cells which had characteristics of macrophages since they could be removed by carbonyl iron and magnet treatment and were adherent to plastic. In contrast to it was observed after injection of 1 mg of BCG, these suppressor cells alone did not account for the depression of T-cell responses induced by higher doses of BCG. Nylon-nonadherent cell populations obtained from spleen cells treated with 3 or 5 mg BCG partially retained the inhibitory activity suggesting that suppressor T cells were also induced after injection of high doses of BCG.


[The effect of antiaggregating agents - acetylsalicylic acid (ASA) and dipyridamol - on the rejection of allotransplanted canine kidneys in presensitized animals (author's transl)].

The effect of antiaggregating agents - acetylsalicyclic acid (ASA) and dipyridamol - on the rejection of allotransplanted canine kidneys in presensitized animals were studied. Blood flow dropped more markedly in the control group than in the group treated with ASA and dipyridamol. 24 hours after transplantation the blood flow in this group was significantly higher than in the control group (p 2,5 %) and in the third group treated with dipyridamol alone. The cellular rejection started earlier and was more pronounced in the control group. Only in this group vascular rejection and microthrombi were demonstrated. Urine output ceased 24 to 60 hours after transplantation. The immunosuppressive, antiphlogistic and platelet antiaggregating effect of the combined ASA and dipyridamol therapy is thought to be responsible for the better results in this group. In this experimental model the combined treatment of ASA and dipyridamol results in a later onset of cellular rejection, in better blood-flow of the kidney and later onset of anuria.


[Evidence of donoroganspecific humoral antibodies in hyperacutely and acutely rejected canine lungallotransplants (author's transl)].

A method to eluat donororganspecific antibodies enabling direct and specific access to the pattern of humoral rejection after lung allotransplantation is demonstrated. The antibodies were evaluated quantitatively and qualitatively by elution of lung-grafts immunoglobulins and by a consequent investigation of the eluates using the passive haemagglutination- and indirect immunflourescence- test against donors' lung-antigen. Humoral antidonorlung-antibodies could be proved in all rejected grafts belonging to sensitized as well as to unsensitized recipients. There can be seen a highly significant correlation when comparing the results of the passive haemagglutination and indirect immunfluorescence test (r = 0,93, p less than or equal 0,01). On the other hand negative results of the investigations of eluates by lungantigens of other dogs show the specifity of humoral graft rejection. The suprising fact that there does not exist an essential difference between the results of sensitized and nonsensitized animals reveals a humoral immunresponse in hyperacute as well as in acute rejection.


Mucous elements in the nose.

A review of studies of the nasal mucous elements by whole-mount methods. Goblet cell development is described till the 30th week of gestation, by which density is still very small. Density must increase towards and after birth. Some problems concerning intraepithelial, anterior nasal as well as Bowman's glands are discussed. The development of the small sero-mucous glands is described and their distribution and density discussed.


[Clinical trial with a nonamphetaminic anoretic].

The anorexigenic activity of a new compound tricyclic in nature and non-related to amphetamine, mazindol, was studied. The experiment was carried out in 20 patients (17 females and 3 males) aged 17-55 years with a minim overweight of 15% above ideal body weight. Simultaseously, another group of 20 patients (16 females and 4 males) aged 16-55 years with a minim overweight of 15% above ideal body weight were given placebo treatment. Both groups received treatment for a period of eight weeks.


[Treatment of malpighian epitheliomas of the floor of the mouth with gingival involvement].

Within the clinical context of carinomas of the upper respiratory/digestive tract (special underlying features, frequency of multiple localisations), pelvi-gingival tumours pose special problems essentially related to the proximity of the mandible. Over the past 15 years, treatment protocols at the Institut Gustave-Roussy have been progressively oriented towards a surgical solution preceded by short period of chemotherapy and followed by  radiotherapy on an "as required" basis. In certain instances (bone resection with defect, especially naterior), such excision surgery results in serious functional and aesthetic impairment and cannot be envisaged in the absence of concomitant reparative surgery. The latter is clearly defined as far as the soft tissues are concerned thanks to the use of facial or thoracic flaps, whilst solutions for restoring bone continuity remain imperfect. The difficulties of covering a bone transplant and the need for postoperative radiotherapy compromise its future. From a tumour standpoint, the results are aggravated essentially by the existence of bone involvement or of histological lymph node invasion. Furthermore, it is closely related to the manifestations of the malignant disease in general. The survival obtained with the current therapeutic protocol is 38% at 3 years and 32% at 5 years.


[Surgical repair after wide excision in cancer of the oral commissure].

The possibility of reconstruction following vast losses of substance makes it possible to propose curative treatment for very advanced cancer, with a satisfactory quality of survival. Such vast losses of substance may be treated in a two-stage procedure using a delto-pectoral flap, the distal extremity of which is folded over upon itself.


[A pediculate commissural flap. Its use in the closing of orostoma in irradiated areas].

The arch-like pediculated commissural flap utilizes the cutaneous layer of the lower lip, the chin and the sub-mental region which are usually not affected by radiation fields in tumours of the longue, the floor and the gum. Its vascularisation which at first sight appears paradoxical, results from anastomoses between the sub-mental facial artery and the mental branches of the lower dental artery, and those of the buccal artery, a branch of the internal maxillary and the labial coronaries. Used successfully on five occasions, and in one or two operative phases, this flap enables rapid closure of an orostoma within an irradiated field using the only suitable tissue in the immediate vicinity.


Dynamics of the h-LH and h-FSH response after the stimulation test with Gn-RH-LH/FSH in man.

A study was carried out on a number of 17 subjects concerning the dynamics of LH and FSH response after stimulation with Gn-RH-LH/FSH. The results show a stimulation 10 minutes after quick i.v. injection of synthetic RH, with a peak at 20-30 minutes and a persistence of the response of up to 180 min. The variation of the response is proportional with the dose, the response to stimulation being higher for LH than for FSH. The response in the normal adult male is of 82-858% for LH and of 157-250% for FSH. In aged subjects there is an increased response capacity showing that the hypophysis still reacts at an advanced age, with variations depending on the individual characteristics. In Sheehan's syndrome the basal values of FSH and LH are low, with a slight response after stimulation with RH, suggesting the possibility of a partial regeneration of the hypophysis if any intact areas were left after the initial necrotic process.


Acute effects of intermittent positive pressure breathing in patients with chronic obstructive lung disease.

The immediate effects of intermittent positive pressure breathing (IPPB) on air were studied in seven patients (age 55-73 years) with advanced chronic obstructive lung disease (COLD) and with chronic respiratory insufficiency. Dynamic lung compliance was reduced by an average of 25% by IPPB, while inspiratory resistance increased by 40%. Distribution of inspired gas, as determined by nitrogen washout, became more even with IPPB. Respiratory frequency was not altered, whereas total ventilation increased by 25% during IPPB and PaCO2 was reduced. Oxygen uptake was reduced by 6%. PaO2 did not change during IPPB but had decreased by an average of 20% 10 minutes after IPPB and then slowly improved; PaCO2 did not change after IPPB. The pressures in the right atrium, pulmonary artery, and in pulmonary wedge position all increased approximately 2 mm Hg (approximately 2 cm H2O) with IPPB, while intrathoracic pressure rose on an average by 5 cm H2O, the transmural pressures thus being lowered during IPPB. The pulmonary vascular resistance was not significantly altered by IPPB, whereas the systemic vascular resistance rose 25%. Cardiac output was reduced approximately 20% and venous admixture almost 50%.


Antimicrobial effect of four different toothpastes.

The study was undertaken to evaluate the antimicrobial effect of a commercial toothpaste, claimed to contain active chlorhexidine gluconate. Two traditional toothpastes and a 0.5% chlorhexidine gel were used as negative and positive control pastes. To exclude the effect of mechanical cleaning, all the agents were applied twice daily to the tooth surfaces by means of individually constructed acrylic cap splints. Ten dental students used each paste in a 4-week cross-over double-blind study comprising four test periods of 4 d duration. The students were allowed normal mechanical oral hygiene during the 3 d between the test periods. At the beginning and the end of each test period the tooth surfaces in the right halves of the jaws were scored for the Plaque Index, after which disclosing solution was used and the teeth of the left halves of the jaws were scored for stained plaque. Of all the toothpastes tested, only the chlorhexidine gel exhibited an antimicrobial effect comparable to that of efficient mechanical oral hygiene measures. The effect of the toothpaste with claimed chlorhexidine content did not differ from that of the two traditional toothpastes.


Effect of acupuncture on the pain perception thresholds of human teeth.

The effect of acumpuncture on the pain perception threshold of maxillary incisors and canines as determined by a Bofors Pulp Tester was studied in 33 dental students 19-30 years of age. Test teeth were cleaned with pumice and 10% alcohol, air-dried, and insulated at the approximal surfaces with strips of rubber dam. Based on a comparison of bipolar and monopolar stimulation the latter method was chosen, with the cathode placed on the incisal third of the facial surface, the indifferent electrode in the subject's hand. In separate groups of subjects thresholds were assessed four times at intervals of 15 min without acupuncture (1), with acupuncture performed manually (2) and electrically (3), and during electrical stimulation with surface electrodes over acupuncture points (4). On separate days acupuncture and surface stimulation was applied unilaterally at the points S2 (cheek), Li4 (hand), or S44 (foot). Compared with control threshold (8.44 muA) acupuncture was accompanied by a small increase, most pronounced after 45 min (1.51 muA, P less than 0.0005). However, the hypalgesia observed was insufficient to justify acupuncture as a means of pain control in conservative dentistry.


Anti-colon antibodies in ulcerative colitis. A clinical study.

145 consecutively admitted patients with ulcerative colitis were clinically classified. A female:male ratio of 1.46:1 was found. Clinical symptoms and signs presumed to indicate hypersensitivity were present in 30% (95% confidence limits 23-39%). Circulating anti-colon antibodies were found in 20% (95% confidence limits 14-28%) with a female preponderance of 2.63:1. None of the following factors were significantly correlated to the presence of anti-colon antibodies: the age or sex of the patients, the degree of colonic involvement, duration of disease, age of onset, family history of disease, or manifestations of hypersensitivity associated with ulcerative colitis.20


Portal venous and systemic endotoxaemia in patients without liver disease and systemic endotoxaemia in patients with cirrhosis.

Systemic endotoxaemia without evidence of gram-negative bacterial infection occurs in liver diseases in man. The endotoxaemia is probably due to impaired hepatic clearance of endotoxin absorbed from the gastrointestinal tract, but portal venous endotoxaemia has never been reported in man. By means of the limulus gelation test, portal venous blood from 21 patients without parenchymal liver disease and arterial blood from 21 patients without parenchymal liver disease and 31 patients with cirrhosis was examined for endotoxin. Portal venous endotoxaemia was found in 9 of 21 samples and systemic endotoxaemia was found in 2 of 21 samples from patients without liver disease. Systemic endotoxaemia in cirrhosis occurred with a frequency of 15/31. No relationship to gram-negative bacteraemia was found. Leucocytosis was only seen in endotoxin-positive patients with cirrhosis. In cirrhosis higher levels of E. coli O antibodies were found in endotoxin-positive than in endotoxin-negative patients, supporting the view that the limulus gelation test specifically detects endotoxin (i.e. E. coli O antigen). The study suggests that endotoxin is a normal constituent of portal venous blood in man. The normal human liver clears endotoxin from the portal venous blood. This effect is diminished in cirrhosis, most probably owing to decreased phagocytic function of the liver. The increased humoral immune response in cirrhosis may be related to spillover of endotoxin from the liver.


[Management of loss of substance in massive facial injuries].

In a communication illustrated by numerous photographs, the author describes the methods normally used in the treatment of open facial trauma. The first basic principle is the treatment of those parts of the facial skeleton fractured by the cutaneo-musculo-mucosal lesion caused by the accident. All of the fixation procedures used in closed fractures are valid. Choice depends upon the type of fracture. Loss of bone substance should be treated by immediate graft only in cases where there is no secondary infection, on condition that the mucosal and cutaneous layers which will be used as a covering are of good quality. The second rule is that lesions of the soft tissues should be treated at the same time, after having ensured repair of any bony injuries. Reconstruction may be a veritable jigsaw puzzle and magnifying instruments are useful under such circumstances. The mucosal, muscular and cutaneous layers are closed in succession. In the case of loss of substance, various forms of plastic surgery may be used in relation to the type of lesion. The following procedures are used, in descending order of frequency: -Sliding of neighboring tissues. -Free grafts--whole or partial thickness of skin. -Unipediculated flaps. -Cylindrical flaps. The third rule is that it should not be attempted to close a large defect at all costs, especially if the quality of the tissues is not excellent. In cases of this sort, it is preferable to approximately draw together the edges of the wound using large interrupted sutures on buttons. Closure of the loss of substance is delayed until later. Plastic surgery carried out by amateurs may result in catastrophe. Errors in operative technique always have irremdiable consequences for the injured patient. Prudence and caution are thus the golden rule.


Membrane bound IgG on erythroblasts in pure red cell aplasia following thymectomy. A case report.

A case of pure red cell aplasia appearing 6 months following thymectomy is reported in a 43-year-old man. Immunofluorescence studies of the patient's bone marrow have demonstrated the presence of membrane-bound IgG on the majority of erythroblasts and some mature erythrocytes. It is suggested that the IgG represents anti-erythroid autoantibodies. The number of Ig-bearing lymphocytes in peripheral blood was decreased as was the level of immunoglobulins indicating a B-lymphocyte deficiency. T-lymphocyte functions were without remarks. The patient was initially treated with corticosteroids and oxymetholone. He responded well to this therapy but relapsed 9 month later. Cyclophosphamide treatment was started and followed by a complete haematologic remission.


Specific antisera against human blood cells applicable in the indirect immunofluorescence technique.

The preparation of antisera against various cells of the human peripheral blood applicable in the indirect immunofluorescence technique (IIFT) is described. Such antisera will be a great interest for the study of cell-specific membrane antigens, for example during haematopoiesis. Purified erythrocytes, lymphocytes, neutrophils, monocytes, and thrombocytes from healthy donors were injected into rabbits. The antisera thus produced were not spontaneously specific. Only by extensive absorption of the crude antisera with purified cells from healthy donors was it possible to obtain antisera that were specific for erythrocytes, lymphocytes, and thrombocytes. By injection of small doses of leukocyte lysate and by absorption of the resulting antiserum with mononclear cells a specific antineutrophil serum was produced. So far it has not been possible to prepare a specific anti-monocyte antiserum. The specific antisera were applicable in the IIFT on paraformaldehyde-fixed cells in suspension and on cells on slides.


Colonization and clinical superinfection with gram-negative bacilli in influenza.

Among 197 influenza A patients admitted to Roslagstull Hospital, abundant growth of gram-negative bacilli was found in 74 cases (38%). When assays for antibodies with the patients own strains as antigen were performed on paired sera with the indirect immunofluorescence technique, titre increases were obtained in 21 out of 55 patients (38%). In this last group signs of secondary infection, as secondary pneumonia, prolonged or recurring fever or late occurrence of leukocytosis and granulocytosis, were significantly more common than in patients without gram-negative findings. An analysis of possible interference by other bacteria did not invalidate the observations. Findings of gram-negative bacilli occurred most often in patients more than 50 years of age. The bacteria were probably hospital acquired in 32 out of 55 patients. Antibody responses took place both in the IgM and the IgG fraction.


HLA-antigen b27 in cases with joint affections in an outbreak of salmonellosis.

An outbreak of infection with Salmonella typhi murium occurred in southern Sweden in the summer of 1974. About 330 persons were infected; 91 were hospitalized. 13 of the 91 patients (9 men and 4 women) had symptoms of aseptical polyarthritis. The 13 patients with arthritis were HLA typed with a standard microlymphocytotoxicity test. 13 salmonellosis patients from the same epidemic but without arthritis and 446 healthy blood donors served as controls. Nine (69%) of the 13 patients with arthritis had HLA-B27 compared to 1 (8%) of the control patients and 44 (10%) of the blood donors. The observed association between HLA antigen B27 and reactive arthropathy following salmonella infection could be due to a function of a disease predisposing gene closely linked to HLA-B27.


Concentration of doxycycline in bowel tissue and postoperative infections.

An investigation on the relation between the effect of doxycycline as prophylactic antibiotic in colonic surgery and levels of doxycycline in serum and bowel tissue with reference to MIC-values of bacterial strains isolated at surgery or after postoperative septic complications is presented. 200 mg doxycycline orally 4-6 hours preoperatively resulted in a serum concentration of 4.0 +/- 0.3 mug/ml at the onset of operation. Tissue samples removed at surgery were assayed for doxycycline. High levels were observed in bowel tissue, ileum 7.5 +/- 1.2 mug/ml and colon 3.9 +/- 0.3 mug/ml. The effects of dosage, time of administration and bowel pathology on tissue levels are discussed. Aerobic and anaerobic bacterial strains were tested for in vitro susceptibility to doxycycline using a standardized disc-diffusion method according to Eriksson and Sherris. 75% of the strains belonged to sensitivity groups 1 and 2 (sensitive-fairly sensitive). That is, MIC-values in 75% of the strains were below the average serum and intestinal tissue concentration during the operation. The implications of these results are that the dosage and time of administration of the drug must be adjusted so that serum and tissue levels are adequate during surgery.


Antibiotic prophylaxis in colorectal surgery. doxycycline compared to a combination of benzylpenicillin and streptomycin. A preliminary report.

The aim of the study was to evaluate the effect of two different regimens of antibiotic prophylaxis in colorectal surgery. The study comprises 57 consecutive cases. The mechanical preoperative preparation was essentially the same in all cases and the operative technique was standardized as far as possible. Antibiotic prophylaxis was started immediately before surgery and continued for three days postoperatively. Thirty-six patients received doxycycline 200 mg i.v. per day and 21 patients were given benzylpenicillin 10 million I.U. 4 times a day and streptomycin 500 mg twice a day. No major infectious complications (e.g. septicaemia, abscessess) were seen in either group. There were three wound infections in the doxycycline group and four in the penicillin-streptomycin group.


Microcalorimetry as a tool for evaluation of antibacterial effects of doxycycline and tetracycline.

The heat effects produced by a strain of Escherichia coli in the presence of doxycycline and tetracycline were determined by calorimetric measurements using batch and flow microcalorimeters of the heat-conduction type. There was a clear difference in the capacity of the two tetracyclines to suppress the metabolism of the test bacterium as indicated by the heat production registered. In the presence of doxycycline or tetracycline in a concentration of 0.4 mug/ml (half the minimum inhibitory concentration, MIC), the time interval between the start of the experiment and a heat production of 2 muW/ml was 4.5 h for tetracycline and 7.3 h for doxycycline. When the antibiotics, in a concentration of 1.6 mug/ml (2 X MIC), were added to the culture during the logarithmic growth phase, tetracycline depressed heat production much less than doxycycline. Almost immediately after the addition of the two tetracyclines studied, heat production decreased sharply. The heat production rose again 1 h after tetracycline had been added, but remained at a low level for at least 16 h after doxycycline.--The results suggest that there are differences in the kinetics of the antibacterial action of doxycycline and tetracycline. Microcalorimetric studies provide new information for determining antibacterial activities of antibiotics, information that cannot be obtained by means of conventional bacteriological techniques. Such studies might be of value for the establishment of optimal dose regimens.