Causes of enlarged sternal bursas (breast blisters). Bursas were taken weekly as normal turkeys developed from 3 to 22 weeks of age, and no specific bacterial or viral infection was found. Bacterial cultures were also made of condemned bursas taken at processing. Of 144 collected, 91% were sterile; the others had staphylococci, streptococci, or coliform organisms. Experiments with turkeys measured the effect of strain, body conformation, completeness of breast-feather cover, protection of the keel with sheepskins, age when put on range, and type of range on the incidence of enlarged sternal bursas. The strain difference of 25.4% breast blisters against 11.5% was highly significant (99% confidence). In one experiment the effect of feather cover was significant at the 95% level of confidence (61.7% breast blisters with no feather cover, versus 40% with complete feather cover). The effect of protecting the breast with sheepskin was significant at the 95% level of confidence in reducing incidence of breast blisters. There was no significant difference in the incidence of breast blisters in relation to body conformation, age, or type of range.


Influence of rofenaid-40 feed medication on an experimental Salmonella infection in chickens. Rofenaid-40 administered at 0.02% in feed to chickens experimentally infected with Salmonella typhimurium resulted in less colonization and shedding of S. typhimurium than in unmedicated chickens. The antibacterial sensitivity pattern of S. typhimurium isolated from infected birds had not changed after exposure to Rofenaid for 56 days.


Quantitation in morphology: possibilities and limits. Methods of structural measurement (morphometry) play an increasing role in investigative pathology. Basic methods of surface and volume measurement and their use in pathology are discussed. This paper demonstrates on the example of the pulmonary gas exchange apparatus that a morphometric approach, using methods of stereology, can yield results of high significance in assessing the structural alterations underlying a gas exchange deficiency.


Glomerulopathies in human renal allografts. The present study discusses the light, electron and immunofluorescence microscopy as well as some clinicopathologic correlations of rejection change in human renal allograft glomeruli. It is based on examination of 126 tissue specimens from 54 grafts obtained from 50 patients (1966-1973). The most frequent and characteristic lesion was membranous transplant glomerulopathy (MG) with irregular fibrillar thickening of capillary walls but without conspicuous hypercellularity. This thickening was caused by subendothelial depositsdifferent from classical fibrinoid lesions. During further progression, widening and peripheral extension of mesangium with degenerative changes became apparent. Advanced MG was encountered most frequently in the 2nd year after transplantation (TPL) at moderate to medium proteinuria and hypertension. It was accompanied by endarteristic rejection changes, and renal insufficiency set on usually in the course of the 3rd year. Nevertheless, the course, symptoms, and graft survival exhibited considerable variations. - The morphology and manifestations of destructive segmental transplant glomerulopathy  (SG) depended on the time of its development. In the early stage (within about 3 months after TPL), the lesion was characterized by areas of fibrinoid insudation and necro(bio)sis associated with severe vascular changes, most frequently obliterative arterio(lo)pathy (OA). The ultrastructure was characterized by endothelial defects with host's polynuclear reaction and focal intravascular coagulation. The grafts thus affected failed soon, their function usually subsiding within the first trimester  at a moderate, but gradually increasing proteinuria and severe persistent hypertension. The late from of destructive SG presenting as fibrohyaline obliteration of the loops with foam cells always accompanied advanced MG with severe arterial lesions. - Fluorescence microscopy revealed both linear and focal fixation of antisera, which, however had no apparent correlation with the microscopical and clinical presentations.


[Studies on the number of fat cells and connective tissue cells in white adipose tissue in chronic starvation and after refeeding. I. Investigations on aurothioglucose-obese NMRI-albino-mice(author's transl)]. Former investigations (Rakow et al., 1970, 1971 b) on epididymal fat pads of lean NMRI-Albino-mice during starvation and refeeding have shown that the number of fat cells (adipocytes) remained unchanged while the number of cells o connective tissue decreased during starvation and increased during the refeeding period. In the present paper the problem has been investigated whether these variations could be demonstrated also in NMRI-albino-mice obesified by administration of aurothioglucose. The investigations were performed with male NMRI-Albino-mice rendered obese by administration of aurothioglucose (800 mg per kg body weight). These animals were fed 2.5 g Altromin 1115 R daily for six weeks. After this they were fed Altromin 1115 R and additional oat flakes ad libitum for three (exp. groups HW3) and seven (exp. groups HW 7) days respectively. After this time the animals were sacrificed. The epididymal fat pads were removed and weighed. One of both pads of each animal was used for chemical investigations. After PCA-treatment (0.5 n, 90 degrees C. 15 min.) the DNA (Burton, 1956) and RNA (Ceriotti, 1955) was determined in the supernatant. After NaOH-treatment (0.5 n, 37 degrees C, 24 Hrs) the noncollagen protein content (Lowry et al., 1951) of the sediment was estimated. After HCl-treatment (25%, 110 degrees C, 20 hrs.) the collagen content (Stegemenn, 1958; modified by Rauskolb, 1967) was determined. The remaining fat pad was used for calculations of cell numbers in the fat cell and connective tissue cell compartment. For this reason fat cells were isolated according to Rodbell (1964). The fat cell diameters were determined microscopically and the average masses of the fat cells were estimated. From the wet weight of the fat pads and the average fat cell mass the number of fat cells was calculated. The remaining suspension of fat cells and cells of connective tissue was utilized for cell smears. These smears were stained with Schiff's reagent (Feulgen et al., 1924; Graumann, 1952). With an integrating microdensitometer (Deeley, 1955) the average relative DNA-content of single cell nuclei were measured and the ploidy patterns were estimated. From the whole DNA-content of the fat pads and the DNA-content of the fat cell population the number of cells of the connective tissue was calculated...


The role of bone marrow in different phases of the cellular repopulation of irradiated mouse thymus. In one series of experiments, the cellular repopulation of the thymus was investigated in mice exposed first to 200 R on the whole body and, after various intervals, to 700 R with one leg protected or unprotected during the exposure. When no protection was made, the mice were transplanted with syngeneic bone marrow cells in a defined number immediately after irradiation. Repopulation was fastest when the interval between exposures was 5 days, and most delayed when it was 14 days; with a 30 day interval the speed of repopulation was intermediate, and resembled that of a control group exposed to only the second dose. In another experimental series, thymus repopulation was studied after exposure of mice first to 200 R with one leg protected or unprotected and, after an interval of 5, 14 or 30 days, to a second dose of 700 R on the whole body. In all cases, syngeneic bone marrow cells were grafted intravenously after the second irradiation. The thymus repopulation was enhanced by protection of the leg when 14 day interval separated the exposures. In the other cases, no enhancement was noted. The findings were interpreted to indicate that the cellular composition of the thymus and, in particular, the frequency of the proliferating stem cells at the time of the exposure determines thymic repopulation for about two weeks after irradiation. After this period, repopulation is due to new precursors from the bone marrow which seeded the thymus.


Specific cyanylation and cleavage at cysteine-104 human hemoglobin alpha-chain. A novel approach to the problem of the alpha-chain tryptic core in the study of haemoglobin variants by "fingerprinting" methods. 1. A new approach to the analysis, by "fingerprinting", of the tryptic core region of human haemoglobin alpha-chain is described. 2. The alpha-chain is cyanylated at its single cysteine residue (alpha104) and then split, by exposure to mild alkali, at the N-peptide bond of the resulting beta-thiocyanoalanine residue. 3. The two cleavage fragments, alpha1-103 and alpha104-141, are separated by gel filtration, and the fragment alpha104-141, which contains all the residues of the alpha-chain tryptic core, is digested with pepsin. 4. Preparative "fingerprints" of these peptic peptides yield eight major peptides, which provide complete sequence information for the whole region alpha104-141. 5. The utility of the method is demonstrated by repeating the determination of the substitution in haemoglobin Hopkins-2, a known alpha-chain core variant in which histidine-alpha112 (G19) is replaced by an aspartic acid residue.


Nitrogenase of Klebsiella pneumoniae. A stopped-flow study of magnesium-adenosine triphosphate-induce electron transfer between the compeonent proteins. Stopped-flow kinetic data have been obtained for a rapid electron-transfer reaction between the component proteins of nitrogenase from Klebsiella pneumoniae, which was induced by MgATP. Up to three equivalents of the Fe-containing protein were rapidly oxidized by one equivalent of the Fe-Mo-containing protein in a unimolecular reaction, k2 = 2 x 10(2)S-1. Evidence for a tight complex between the component proteins, KD(complex) less than 0.5 muM, which was formed with a rate k1 greater than 1 x 10(7)M-1-S-1, has been obtained. MgATP bound to either the Fe-containing protein or to the two-protein complex with a rate k3 greater than 2.5 x 10(6)M-1-S-1 and with KD(MgATP) = 0.4mM, before the electron-transfer reaction.


The kinetic of degradation of chondroitin of sulphates and hyaluronic acid by chondroitinase form Proteus vulgaris. Km and Vmax. were determined for the degradation by chondroitinase of chondroitin 4-sulphate, 4-sulphate-proteoglycna, chondroitin 6-sulphate, dermatan sulphate and hyaluronic acid. Degradation of chondroitin 4-sulphate was inhibited by hyaluronic acid but not by keratan sulphate. The results are discussed with regard to the use to the use of chondroitinase as a sleective reagent for the degradation of tissue glycosaminoglycans.


Studies on the high-sulphur proteins of reduced mohair. The isolation and amino acid sequence of protein scmkb-m1.2. The complete amino acid sequence of mohair protein, SCMKB-M1.2 (97 residues), was determined. The protein was isolated from reduced and carboxymethylated mohair by chromatography on DEAE-cellulose phosphate. Peptides for sequence determination were obtained by digestion with trypsin, pepsin, chymotrypsin, thermolysin and papain, and were fractionated by DEAE-cellulose chromatography, paper chromatography and electrophoresis. The sequence of the peptides were determined by the Edman degradation method (by use of both the Beckman Sequence and a non-automatic procedure), and by partial acid hydrolysis. The protein is closely homologous to wool protein SCMKB-IIIB2, and also contains acetylated alanine as N-terminal amino acid.


Purification of D-alanine carboxypeptidase from Escherichia coli B on a penicillin-Sepharose column. 1. A soluble D-alanine carboxypeptidase from Escherichia coli strain B was purified on a p-aminobenzylpenicillin-Sepharose column. This one-step chromatography followed by an (NH4)2SO4 precipitation yielded an enzyme purified 1200-fold and some of its properties are reported. 2. The pure D-alanine carboxypeptidase was devoid of D-alanine carboxypeptidase II activity and migrated as a single protein band on analytical disc gel electrophoresis. 3. Triton X-100 in the purification procedure is an absolute requirement for obtaining a stable enzyme. 4. The enzymic activity of D-alanine carboxypeptidase was greatly affected in solution of high salt concentrations and varied somewhat with the nature of the cation tested.


Insulin release and the microtubular system of the islets of Langerhans. Identification and characterization of tubulin-like protein. 1. Incubation of islets of Langerhans in vitro in the presence of colchicine produced a progressive inhibition of the insulin-secretory response to glucose, which was dependent on the time of incubation. 2. The uptake of [3-H]colchicine by islet cells was a rapid process, equilibrium being reached in less than 30 min. Part of the colchicine taken up was bound to protein material, which was recovered largely in a post-microsomal supernatant fraction prepared from the islets. In contrast with this rapid uptake, the binding of colchicine by islet-cell proteins in intact islets or in islet homogenates was a slow process, and equilibrium was not reached for 60-90 min. After an initial 30 min delay, the time-course of the binding of [3-H]colchicine to islet-cell proteins paralleled that for the inhibitory effect of colchicine on insulin release. 3. Some purification of the colchicine-binding material present in islet homogenates could be achieved by precipitation of the protein with 2mM-CaCl2 (2.8-fold). However, ion-exchange chromatography on DEAE-Sephadex produced a further 27-fold purification on elution with 0.6M-NaCl. 4. Colchicine-binding protein prepared from islets by ion-exchange chromatography showed an intrinsic association constant for colchicine of 1.4muM and an apparent molecular weight on gel filtration of 110000. 5. These results suggest that colchicine-binding protein in islet cells closely resembles tubulin extracted from the other tissues. The delayed effectiveness of colchicine in inhibiting insulin secretion is not due to poor penetration of colchicine into the cells but rather to slow binding of the alkaloid to islet-cell tubulin. It seems likely that, as in other tissues, this binding prevents polymerization of the tubulin into microtubules, and thus interferes with the release process.


Synthesis of alternative membrane-bound redox carriers during aerobic growth of Escherichia coli in the presence of potassium cyanide. Aerobic growth of Escherichia coli with an oxidizable substrate as carbon source in the presence of low concentrations of KCN leads to the synthesis and integration into the membrane of menaquinone and cytochromes b558, a1 and d in addition to the redox carriers normally present under aerobic growth conditions, namely ubiquinone and cytochromes b562, b556 and o. The results are discussed with reference to other phenotypic and genotypic modifications to the electron-transport chains of E. coli.


The therapeutic activity of 1-(p-chlorobenzoyl)-5-methoxy-2-methylindole-3-acetic acid monohydrate glucosamide in rheumatoid arthritis (double blind trial). A new nonsteroidal anti-inflammatory agent, 1-(p-chlorobenzyl)-5-methylindole-3-acetic acid monohydrate glucosamide (glucametacine, Teoremac¿), was used in the treatment of a total of 39 patients including 31 cases of rheumatoid arthritis, 3 of ankylosing spondylitis, 1 of psoriatic rheumatism, 1 of chronic chondrocalcinosis and 3 of arthrosis. Teoremac was given for 14 days at a dosage of 420 mg/day. The drug was shown to be more or less active in all the patients except 4. The improvement in the various clinical parameters of rheumatoid arthritis studied was statistically significant. The side effects recorded were headache, which was severe in only 1 case, and "minor" disturbances of the gastro-intestinal tract. A double blind crossover trial was carried out in 15 patients with rheumatoid arthritis to compare the action of Teoremac (420 mg/day for 14 days) with that of indometacin (100 mg/day for 14 days). Under the conditions of the trial, the clinical findings showed Teoremac to be slightly superior to indometacin, but the difference was not significant statistically.


[Insulin precursors--a historical synopsis. First diabetes treatment trials using pancreas extracts]. The highly interesting and successful attempts to treat diabetes with pancreas extracts deserve a historical review. Some of these experiments were performed long before the isolation and use of insulin by the Canadians Banting, Best, Macleod and Collip in 1921--22. Successful isolation of insulin, known as acomatol and pancreatin, was first carried out before the Canadian research-workers published their results. Particular credit goes above all to Paulesco, Reuter and Zuelzer.


Experimental Shwartzman phenomenon in the heart muscle. Intravenous injection of E. coli culture caused a sudden death in rabbits which were injected Streptococcus culture into the myocardium 24 h before the experiment. Pretreatment of animals with Trasylol-R, before injection of E. coli culture, caused an increase of survival time. In isolated Langendorff perfused heart from myocardially Streptococcus culture injected animals, E. coli culture filtrate caused a transitory increase and then a continuous decrease in coronary perfusion pressure together with an increase in heart rate. These findings are shown to be prevented by previous addition of Trasylol to the perfusion medium. According to these results it is speculated that a Shwartzman-like phenomenon can also occur in the heart muscle. The possible role of the activation of tissue kallikrein system in the production of this phenomenon is discussed.


Septic arthritis in sickle-cell thalassemia. Pathophysiology of impaired response to infection. The knee of a boy with sickle-cell thalassemia became infected with Salmonella enteritidis, sensitive to ampicillin. Doses of ampicillin that achieved anti-bacterial titers of 32 in synovial fluid failed to eradicate the organism. The synovial fluid exhibited severe hypoxia, hypercapnia, and lactic acidosis. Methods were developed to estimate the oxygen saturation of blood in regional venous capillaries, the degree of periarticular sickling, changes in the viscosity of local blood, and the articular ratio of blood flow to oxygen utilization. The results suggest that local vascular insufficiency associated with sickling may affect host response to infection and efficacy of antibiotics. The Salmonella C1 readily transformed to an L form on hypertonic medium, thus acquiring resistance to ampicillin and other cell-wall inhibitors.


[Phalloidin antagonists. 2. Protective effect of disilybine in phalloidin poisoning of isolated hepatocytes]. Phalloidin produces marked protrusions on the surface of isolated hepatocytes prepared from rat livers. This typical in-vitro effect of the mushroom toxin is prevented or inhibited by preincubation with disilybin. The antagonistic effect depends on the concentration of disilybin and might be caused by an inhibition of phalloidin binding.


Influence of D-penicillamine on the immune response of mice. Studies on the influence of D-ss, ss-dimethylcystein (D-penicillamine, Metalcaptase-R) on the primary immune response of mice after immunization with sheep red blood cells show, that D-penicillamine up to doses of 20 mg/kg has no effect on the synthesis of hemagglutinating antibodies. Plaque forming cells in the spleen were not significantly reduced after administration of 80 mg/kg. A striking inhibition of the formation of immune rosettes is demonstrated. 80 mg/kg led to a significant reduction of rosette forming B-lymphocytes in the spleen.


Use of a dynamic method in calibration of dye-dilution curves during cardiac surgery. A simplified dynamic method of calibration for dye-dilution curves is described. The method involves appropriate matching of the fluid volume in the mixing chamber, the blood withdrawal rate, and the calibration dose of dye. It was used to compare the observed versus calibrated pump output of a heart-lung machine with individual dye-dilution curves obtained from 15 patients during total cardiopulmonary bypass. The results indicate that the difference (range+14% to-8%) between the two is statistically insignificant. The method is rapid and relatively simple. It is particularly useful for cardiac output determination during unsteady clinical conditions because of the ability to calibrate dye curves at the time they are recorded.


Procainamide and phenytoin. Comparative study of their antiarrhythmic effects at apparent therapeutic plasma levels. The antiarrhythmic effects of procainamide and phenytoin were studied in 81 patients admitted to the coronary care unit at the University Hospital in Linköping because of a suspected or proven diagnosis of acute myocardial infarction, and who developed ventricular arrhyhmias, requiring treatment, during the first 8 hours in hospital. Patients were randomly allocated to a procainamide of phenytoin group. The drugs were given as intravenous and oral loading doses followed by oral maintenance therapy. Plasma levels of the two druge were frequently determined and the electrocardiogram was continuously recorded during the 24-hour trial and analysed minute by minute. A significantly higher frequency of therapeutic failure was found in the phenytoin group (23 of 35 patients)compared to the procainamide group(13 of 39 aptients) during the first 2 hours after initiation of therapy. Four patients in the phenytoin group and 2 in the procainamide group developed symptoms probably caused by the trial drugs, necessitating discontinuation of therapy. The mean plasma levels were usually within the apparent therapeutic range (for phenytoin 40-72 mumol/l (10-18 mug/ml), and for procainamide 17-34 mumol/l (4-8 mug/ml). Seventeen patients (68%) in the phenytoin group and 10 patients (48%) in the procainamide group had plasma concentrations within this range when the therapeutic failure was observed. Nine patients died in hospital but only one of them during the trial. The results of this investigation clearly demonstrate the overall superiority of procainamide over phenytoin as an antiarrhythmic drug in short-term therapy after acute myocardial infarction.


Dose-response effect of single and combined clofibrate (Atromidin) and niceritrol (Perycit) treatment on serum lipids and lipoproteins in type II hyperlipoproteinaemia. The dose-response effects of clofibrate and niceritrol on serum cholesterol and triglycerides (TG) were studied in 29 patients with Type IIa and IIb hyperlipoproteinaemia. In 17 patients, clofibrate and niceritrol were then given as combined treatment, and the effects of this combination on serum lipoproteins were studied. Clofibrate was given in three doses: 1.5,2 and 2.5 g/day. The optimum effect on serum TG and cholesterol in patients with Type IIa was observed with the 1.5 g dose and higher doses did not lower the serum lipids further. In patients with Type IIb the optimal clofibrate dose was 1.5-2 g/day. Niceritrol was then given in three doses: 3,45 and 6 g/day. In patients with Type IIa the serum TG concentration was not significantly affected by any dose used, whereas the reduction of the serum cholesterol concentration was dose dependent. In patients with Type IIb the reduction of both serum TG and cholesterol was dose dependent. Combined treatment with 2 g clofibrate and 3 g niceritrol resulted in a normal lipoprotein pattern i 15 out of 17 patients. The reduction of the serum lipids was approximately the same as during treatment with 6 g niceritrol/day. No additional side-effects were observed during combined treatment.


The influence of treatment of the paralesional skin with dithranol on healing in psoriasis. Application of dithranol confined to the normal skin surrounding thirty-six psoriatic lesions produced improvement in twenty-four lesions, which was significantly more than the improvement noted in four of thirty-six control lesions left untreated. Such healing was temporary and slower than in lesions treated conventionally. It is suggested that the apparently normal skin around a psoriatic lesion under treatment influences the psoriasis.


5-Fluorouracil in the treatment of common warts of the hands. A double-blind study. A double-blind study was carried out to compare the action of 5-fluorouracil and 10% salicylic acid varnish with that of a 10% salicylic acid varnish on common warts. Fifty per cent of the lesions disappeared with the combined preparation and only 4% with the varnish containing salicylic acid alone. The presence of warts on the hands of 45.8% of the female workers of a fowl slaughterhouse is described.


A controlled trial on the use of topical 5-fluorouracil on viral warts. A double-blind controlled trial was performed on the use of topical 5% 5-fluorouracil ointment as a treatment for viral warts. The results showed the 5-fluorouracil to be better than the placebo.


Photoaffinity labeling of the ribosomal A site with S-(p-azidophenacyl)valyl-tRNA. S-(p-Azidophenacyl)valyl-tRNA, an analog of valyl-tRNA which has a photoaffinity label attached to its 4-thiouridine residue, was bound to the ribosomal A site at 10 mM Mg2+. Binding was stimulated 25-fold by the presence of elongation factor EFTu. Photoactivation of the p-azidophenacyl group by irradiation resulted in covalent linking of 6% of the noncovalently bound tRNA to the ribosomes. Covalent linking was dependent on the simultaneous presence of ribosomes, poly(U2,G),EFTu.GTP, required irradiation, and did not occur when S-(phenacyl)valyl-tRNA, a nonphotolyzable analog, replaced S-(p-azidophenacyl)valyl-tRNA. The attached tRNA was distributed approximately equally between both the 30S and 50S subunits. At the 30S subunit, 30% of the tRNA was bound to protein while 70% was linked to 16S RNA. At the 50S subunit, however, negligible binding to the 23S RNA was observed. More than 90% of the tRNA was attached to low molecular weight material according to sodium dodecyl sulfate-sucrose gradient analysis, and more than 87% of this fraction consisted of tRNA-protein complexes as assayed by phenol solubility and electrophoretic mobility before and after protease treatment. These results, in conjunction with our previous report (I. Schwartz and J Ofengand (1974), Proc. Natl. Acad. Sci. U.S.A. 71, 3951) which showed that covalent linking of this same tRNA derivative at the ribosomal P site resulted in attachment solely to the 16S RNA, demonstrate that 16S, but not 23S or 5S rRNA, is an important component of the tRNA binding site in the region of the 4-thiouridine residue and furthermore show that ribosomal A and P sites are topologically distinct.


Purification and properties of nucleic acids from an unusual cytoplasmic organelle in the flagellate protozoan Crithidia oncopelti. A simple, rapid method for preparing bipolar bodies from sonicated (rithidia oncopelti cells, with a yield of 2-5%, is described. Apart from 2-4% contamination with unbroken cells the fraction was considered pure with respect to contamination by other nucleic acid-containing organelles, as judged by light and electron microscopy. A light satellite DNA, f bouyant density 1.695 g/ml in neutral CsCl, and derived from the bipolar body, had a Tm of 81.6 degrees C in0.15 M NaCl/0.015 M sodium citrate (pH 7.0) and a kinetic complexity of 2.7 with 109. The bipolar body fraction also contained ribonucleoprotein particles with and s20,w of 67 S, in contrast to cytoplasmic ribosomes (87 S). Bipolar body ribosomes contained rRNA components which migraged coincidentally with Escherichia coli rRNA (molecular weights 1.07 with 10-6 and 0.56 with 10-6) on polyacrylamide gel electrophoresis. Cytoplasmic ribosomes contained rRNAs of molecular weights 1.30 with 10-6 and 0.83 with 10-6. Bipolar body rRNA accounted for up to 10% of the rRNA extracted from cells. The properties of these bipolar body nucleic acids provide good evidence for the bacterial nature of this subcellular component.


Photoinduced convalent crosslinkage, in situ, of Escherichia coli 50 S ribosomal proteins to rRNA. Irradiation of aqueous solutions of Escherichia coli 50 S ribosomal subunits with 253.7 nm light results in the covalent crosslinkage of the rRNA and protein components. Neither peptide bond cleavage nor protein-protein crosslinkage accompanies the crosslinkage reactionmin addition, substantial photoinduced modifications in the primary structure of the ribosomal proteins, other than crosslinkage to rRNA, are not detected. The crosslinkage of the ribosomal proteins to the rRNA proroceeds in two discrete, dose-dependent steps. The first step, requires an input of up to 3 with 10-20 Quanta of 253.7nm radiation, and results in the crosslinkage of less than half of the ribosomal proteins to the rRNA. The second step requires an input of greater than 3 with 10-20 Quanta of 253.7 nm radiation, and results in the crosslinkage of the remaining ribosomal proteins to the rRNA. The possible relationship of the nature of the corsslinkage reaction to the spatial orientations of the rRNA and protein molecules in the intact 50 S ribosomal subunits is discussed.


The characterization of energized and partially de-energized (respiration-independent) beta-galactoside transport into Escherichia coli. Unidirectional fluxes of [14C]lactose by whole cells of Escherichia coli under highly energized and partially de-energized (in the presence of CN-) conditions are analyzed kinetically. When the cells are energized, the value for V influx is 0.45 +/- 0.01 mM internal concentration increment/s and Kt is 0.26 +/- 0.03 mM. At an external concentration of 0.61 mM the steady-state internal concentration is 0.25 M, reached after about 1h. The maximum steady-state concentration ratio is 2-10(3). The efflux process under these conditions is non-saturable, being linearly dependent upon internal concentration over the range 25-250 mM with a first-order rate constant of 8.8 +/- 0.2-10(-4) S-1. The transport in the presence of CN- is active, with a maximum concentration ratio (internal concentration/external concentration) of 104, and the uptake is mimicked by anoxia (less than 70 ppm O2). The effects of CN- are to lower the V for influx and to change the efflux from a non-saturable to a saturable process with a value for Kt (60 mM) intermediate between that for energized efflux (greater than 250 mM) and influx (0.3-0.6 mM), the latter value not changing appreciably. Partial de-energization thus affects both the influx and efflux processes.


The effects of organic solvents on Escherichia coli DNA polymerase III. The polymerizing ability of Escherichia coli DNA polymerase III is enhanced by a variety of water-miscible organic solvents of which dimethyl sulfoxide at 17% (v/v) is the most effective tested. The extent of stimulation depends on the organic solvent used and its concentration, but shows no obvious correlation with the chemical structure of the solvent or its dielectric constant. Kinetic studies indicate that the mechanism of stimulation is complex.


Degradation of double-stranded RNA by a monomeric derivative of ribonuclease BS-1. Double-stranded RNA, resistant to the action of pancreatic monomeric RNAase A, is actively degraded by seminal dimeric RNAase BS-1. Evidence is presented that a monomeric derivative of seminal RNAase degrades double-stranded RNA as efficiently as the parent dimeric molecule. This finding is discussed in the light of the hypothesis previously advanced that two active sites simultaneously available on an enzyme molecule may be responsible for degradation of double-stranded polyribonucleotides.


Isolation and properties of the transcription complex of Escherichia coli RNA polymerase. A procedure is described which permits complete separation of a transcription complex formed with template DNA, growing RNA chain and functioning RNA polymerase, from RNA polymerase molecules which have bound to DNA but not initiated RNA synthesis. The method is based on the marked stability of the transcription complex to dissociation by high concentrations of CsCl or CS2SO4 which enable banding the complex after equilibrium centrifugation. With use of the newly developed procedure, affinity of Escherichia coli RNA polymerase to T7 phage DNA was found to increase during initiation of RNA synthesis but then decrease concomitant with elongation of RNA chain presumably due to migration of the enzyme to DNA sites of weak affinity. Under the conditions of maximum affinity, the transcription complex contained one core polymerase for each T7 DNA if it was isolated by centrifugation in CsCl; in contrast, 2-6 enzyme molecules remained attached on the complex when the centrifugation was carried out in Cs2SO4. Thus, RNA polymerases bound to different sites of transcription initiation appear to be distinguished based on the affinity of interaction. Attempts are also described to isolate the transcription complex in vivo by Cs2SO4 centrifugation by Brij 58-deoxycholate lysate of lysozyme-treated Escherichia coli cells. The isolated complex contained approx. 50 polymerase molecules per Escherichia coli genome as well as other unidentified proteins.


Perspectives on acute enteric disease epidemiology and control. This paper reviews the major epidemiologic features of the acute enteric diseases and outlines a plan for their prevention and control in developing countries. Annual mortality from enteric diseases ranges from 10 per 1000,000 in highly developed countries to as much as 500 per 100,000 in developing countries. Most agents of enteric disease are spread by one of two routes: direct person-to-person contact or ingestion of contaminated vehicles (food or water). An effective control program should therefore focus on common epidemiologic factors, rather than on agent-specific remedies such as vaccines or antibiotics. The major operational components of such a program should include oral fluid replacement therapy, improvements in environmental sanitation, health education to promote personal hygiene and proper food handling, and epidemiologic surveillance to monitor public health needs and evaluate the impact of health measures.


The use of Opsite, a vapour permeable dressing, on skin graft donor sites. A trial of a moisture vapour permeable dressing (Opsite) on split-skin graft donor sites of 53 patients has been carried out. The main advantages were freedom from pain, early healing and lack of bulky dressings. The disadvantages were post-operative leakage of fluid from under the Opsite and fragility of the newly healed donor site for the first few days. An occlusive dressing for the first 48 hours post-operatively is suggested to help overcome the leakage problem, and care of the healed donor site, with particular emphasis on not removing Opsite that is adherent to it, is stressed.


Burli (mycobacterial) ulcers in Caucasians in Nigeria. Seven Caucasians with Buruli ulcers have been treated. The disease did not behave differently in them from its behaviour in Africans nor has liability to infection any racial basis. Surgical removal with or without skin grafting is the treatment of choice.


The length: breadth ratio of skin flaps on the trunk: two new long narrow flaps. Our experience of skin flaps on the trunk is reviewed. A single-pedicle flap based on the sterno-clavicular region and a bipedicled longitudinal back flap have length: breadth ratios much in excess of random pattern flaps.


[Allergen-induced bronchoconstriction in asthma: antagonistic effect of a synthetic anticholinergic drug (author's transl)]. In ten allergic patients, the effect of inhaltion of increasing quantities of grass pollen on specific airways resistance (SRaw, measured by plethysmography) was estimated after preliminary inhalation of a placebo and of a synthetic anticholinergic drug (SCH 10000). After placebo, the inhalation of grass pollen induced in all cases a bronchoconstriction (mean increase of SRaw : 170 %). After SCH 1000, and for the same quantity of pollen inhaled, seven patients were entirely protected against the bronchoconstrictor effect of the allergen ; for the whole group, the observed bronchoconstriction was significantly lower (p less than 0.01, mean increase of SRaw : 60 %). The possible mechanisms of this protection are discussed. The results suggest that SCH 1000 could be used as a preventive drug in pollinic asthma.


Hypospadias repair using polyglycolic acid sutures. A two-stage hypospadias repair is described and the results of 50 consecutive cases are reported in which polyglycolic acid sutures were used.


Aggressive non-irradiated basal cell carcinoma of forehead treated by free flap transfer. A case of recurrent basal cell carcinoma resistant to repeated excision is reported. The forehead defect was covered with a deltopectoral free flap transfer in which 1 artery and 2 veins were anastomosed.


Gonadotrophin-releasing hormone treatment for induction of follicular maturation and ovulation in amenorrhoeic women with anorexia nervosa. Follicular maturation and ovulation can be induced in amenorrhoeic women with anorexia nervosa by long-term treatment with 500 mug of luteinizing hormone releasing hormone (LH-RH) every eight hours. In some women, however, treatment with LH-RH alone results in ovulatory menstrual cycles with indications of luteal phase insufficiency. Human chorionic gonadotrophin (HCG) was therefore given with LH-RH during three treatment cycles. This resulted in ovulation and normal corpus-luteum function, as shown by the occurrence of a single pregnancy in the only involuntarily sterile patient. During the prolonged LH-RH treatment the LH response to LH-RH increased in parallel with the increased oestrogen secretion while the follicle-stimulating hormone response to LH-RH decreased. These changes in the pituitary responsiveness to LH-RH may result from modulating effects on the pituitary by the sex steroids.


Value of prednisone in combination chemotherapy of stage IV Hodgkin's disease. Report from the British National Lymphoma Investigation. A combination of mustine, vincristine (Oncovin), procarbazine, and prednisione (MOPP) and the same combination without prednisone (MOP) were compared in the treatment of stage IV Hodgkin's disease in a prospective randomized trial. The complete remission rates were 80% with MOPP and 44% with MOP; the difference was highly significant. Prednisone seems to be an important component of the MOPP combination in the management of stage IV Hodgkin's disease.


Failure of low-dose heparin to improve efficacy of peroperative intermittent calf compression in preventing postoperative deep vein thrombosis. The possible benefits of adding a low-dose heparin regimen to the technique of peroperative intermittent calf compression for preventing deep vein thrombosis (D.V.T.) were assessed in a randomized trial in 84 surgical patients. The efficacy of peroperative intermittent calf compression was not enhanced by a low-dose heparin regimen, but neither was it worsened. Age, weight, duration, operation, and malignant disease did not affect the relative effectiveness of the two regimens of prophylaxis. The results confirmed that venous stasis is the principal cause of D.V.T.


Immunopotentiation with levamisole in resectable bronchogenic carcinoma: a double-blind controlled trial; Study Group for Bronchogenic Carcinoma. A long-term multicentre double-blind study was designed to test the immunotropic effects of levamisole in patients undergoing operation for primary bronchial carcinoma. They received levamisole 50 mg three times a day by mouth or placebo for three days every fortnight, starting three days before surgery. Unless there was clinical evidence of recurrence, cytostatic drugs, corticosteroids, and radiotherapy were prohibited. In the 111 patients who have been followed up for one year the incidence of side effects was similar in both groups. Recurrences occurred in 10 out of 51 patients (seven deaths) receiving levamisole and in 20 out of 60 (12 deaths) receiving placebo. Further analysis showed that there were fewer recurrences on levamisole in patients with squamous cell carcinomas and medium and large primary tumours and fewer suspected and proved recurrences and deaths from metastases on levamisole in patients with extended tumours. Distant recurrences tended to be less common with levamisole, whereas the disease-free interval in relapsing patients was almost identical in the two groups. These interim results show that levamisole seems to exert its beneficial effect by preventing immunosuppression due to surgery.


Application of the enzyme-linked immunosorbent assay (ELISA) in the serodiagnosis of syphilis. The enzyme-linked immunosorbent assay (ELISA) technique, using an ultrasonicate of Treponema pallidum as antigen, has been evaluated as a serological test for syphilis. It is concluded that the test is simple, reliable, and relatively quick and that its sensitivity in all stages of syphilis is equal to the FTAABS test. Because its specificity is probably also high, ELISA might be used in future as a first-line screening test for the serodiagnosis of syphilis.


Automation of a flocculation test for syphilis on Groupamatic equipment. A flocculation reaction employing a cardiolipid antigen was used for syphilis screening on Groupamatic equipment in parallel with conventional screening reactions: Kolmer CF, RPCF, Kahn, Kline, and RPR. The positive samples were confirmed by FTA-200, FTA-ABS, TPI, and in some cases by TPHA. There were 5,212 known samples which had already been tested by all methods and of which 1,648 were positive, and 58,636 screened samples including 65 positives. Half of the samples in the first series were taken without anticoagulant; the remainder were collected in potassium EDTA. The percentage of false positives with the Groupamatic was about 1-4 per cent. The percentage of false negatives among positve (greater than or equal+) samples varied from 0-18 to 1-3 per cent.; on the other hand the sensitivity was less good for samples giving doubtful and/or dissociated reactions in conventional screening reactions. The specificity and sensitivity of this technique are acceptable for a blood transfusion centre. The reproducibility is excellent and the automatic reading of results accurate. Additional advantages are rapidity (340 samples processed per hour); simultaneous performance of eleven other immunohaematological reactions; no contamination between samples; automatic reading, interpretation, and print-out of results; and saving of time because samples are not filed sequentially and are automatically identified when the results are obtained. Although the importance of syphilis in blood transfusion seems small, estimates of the risk are difficult and further investigations are planned.


Treatment of trichomoniasis in the female. A comparison of metronidazole and nimorazole. The effectiveness of metronidazole (Flagyl) and nimorazole (Naxogin) has been compared by using these drugs in the recommended dosage in alternate patients in a series of 218 consecutive cases of vaginal trichomoniasis. Follow-up tests in 100 patients treated with metronidazole and 97 treated with nimorazole indicated cure-rates of 95 and 82 per cent. respectively. Male consorts were examined and given treatment on epidemiological grounds in about 70 per cent. of both treatment groups. Both drugs were free from significant side-effects. The causes of treatment failure in trichomoniasis are discussed and the desirability of relating dosage to the patient's body-weight is suggested. This factor may be especially important in deciding the dosage given on epidemiological grounds to the male consorts. It may also be an important advantage in the current trend of treating trichomoniasis in both sexes with larger doses over a much shorter time.


Electron microscopy of experimental axonal degeneration in photochemically modified Golgi preparations: a procedure for precise mapping of nervous connections. A new version is presented of a procedure for bleaching (deimpregnating) silver chromate Golgi preparations through ultraviolet (UV) light irradiation followed by thiosulphate treatment, leaving only scattered particles of metallic silver. This version gives a better ultrastructure of the tissue than obtained before. Moreover, the results of studying a specific connection in such material are reported. The perforant path, connecting the entorhinal area with the hippocampus and fascia dentata, was transected in the rat and after a 2-day survival the brain was subjected to Golgi impregnation followed by the deimpregnation procedure. Blocks of tissue containing impregnated fascia dentata granule cell dendrites were selected for electron microscopy. Postsynaptic thickenings associated with degenerated boutons could be discerned within the deimpregnated dendrites, proving that the entorhino-dentate fibres end on the dendrites of the granule cells (smooth surfaces as well as spines) and that they end at asymmetric junctions (of Gray's type 1). While this conclusion was as expected from previous experimental studies carried out with different methods it is thought that the same strategy for cell-to-cell mapping of nervous connections may be used also in other parts of the central nervous system.


A Golgi and electron microscopical study of nerve cells in layer I of the cat auditory cortex. The nerve cells of the plexiform layer of the cat auditory cortex were studied in Golgi rapid preparations, and by electron microscopy. In the Golgi material 178 cells were found. Thirty were horizontal cells (Cajal's cells) with spiny dendrites and a long axon with horizontal trajectory. Seventy-two small cells had smooth dendrites and a short axon branching profusely around the perikaryon, within the plexiform layer. Twenty-eight were slightly larger cells, morphologically similar to the small ones, but their axons and dendrites were longer, extending to layer II. Twenty-five cells had large bottle-shaped perikarya, spiny dendrites reaching layer II, and a vertically oriented axon branching in layer II, and sometimes reaching layer III. In addition, 23 small modified pyramidal cells, similar to those of layer II, were found within the boundaries of layer I. In the most superficial 50 mum of the cortex horizontal cells were found, but the other categories were very rare. The 3 categories of short axon cells were preferentially localized between 50 and 150 mum from the pial surface. By electron microscopy two classes of cells were found. The first had abundant mitochondria, well defined Nissl bodies and few axosomatic synapses. The second had few mitochondria, undefined Nissl bodies and 6-8 axosomatic synapses per profile. Desmosome-like membrane specializations were found between perikarya of the second class and pyramidal dendrites or their spines. It is suggested that the first class of cells found by electron microscopy may correspond to the horizontal cells while the second class may correspond to the 3 categories of short axon cells.


In vivo localization of brain sulci by arteriography: a stereotactic anatomoradiological study. The authors studied the course of the cortical arteries using the Talairach stereotactic system (orthogonal 4.8 m teleradiography, with rigid fixation of the skull in the stereotactic frame) in both anatomical specimens and normal bilateral carotid angiographies of epileptic patients. Anatomoradiological correlations between arterial patterns and underlying brain surface were identified by detailed 3-dimensional analysis of brain-skull preparations, where gyri and injected arteries were dissected progressively with stereotactic X-ray and photographic pictures taken at each step. The vascular landmarks so identified were studied in stereoscopic arteriographies that give a direct visualization of the spatial relationships of the arterial tree moulding the cortical surface thus allowing the recognition of the localization of the principal gyri and sulci. The latter were drawn on stereotactic diagrams. The basic sulcal pattern as shown by the arteries is strikingly symmetrical in both hemispheres of the same individual, in spite of variability in branching of the arterial tree. The disposition of the vascular landmarks in the retroinsular region reflects the left-right asymmetry of the planum temporale that can be recognized in vivo. This can give a clue to the study of anatomofunctional correlations with regard to speech dominance. A limited first series studied in this respect strongly suggests a close relationship between anatomical and functional asymmetry of the human cerebral hemispheres. Generally speaking, the authors feel that 3- dimensional, anatomical interpretation of angiography permits a direct localization of brain structures including the cortex, that can be used instead of indirect localization landmarks in stereotactic explorations, and further, that the wealth of anatomical information that can be drawn from angiography with their method may be helpful in diagnosis or for planning surgery.


Heat destruction of some bacterial strains attached to broiler skin. 1. Heat destruction of bacteria attached to the skin did not occur at a logarithmic rate provided the temperature was above 51 degrees C. 2. It was concluded that the bacteria are protected by their location in the skin surface rather than by polymers produced during attachment. 3. An analogous process is considered to take place during the scalding of broilers, since bacteria which survived were difficult to remove from the carcasses during further processing.


Further studies on the attachment of bacteria to skin. 1. A proportion of the bacterial flora of the skin is present in the surrounding water film and can be removed by adequate rinsing. 2. The remainder of the flora is attached to the skin in such a manner that numbers can be reduced only 10-fold during spray-cooling or spin-chilling. 3. The reduction process was found to be independent of bacterial type or the extent of previous contamination. 4. The significance of the "water film flora" is discussed with respect to the attachment of bacteria and the cleaning of carcasses.


The effectiveness of in-plant chlorination in poultry processing. 1. Sampling carcasses after plucking or after the post-evisceration spray-wash showed that 10 or 20 ppm available chlorine in the processing-plant water supply caused little reduction in carcass contamination. 2. When 20 ppm chlorine was used in the water supply to parts of the processing-plant other than the mechanical immersion chilling system, counts of faecal and spoilage bacteria from carcasses were reduced approximately 10-fold after passage through the chilling system; bacterial carry-over of chlorine from the final spray-washer. 3. Artificial contamination of carcasses with a readily identifiable strain of Escherichia coli confirmed the occurrence of cross-contamination during plucking and evisceration; in-plant chlorination reduced neither the proportion of carasses contaminated nor the numbers of organisms transferred at these stages. 4. In most cases the chlorine-resistance of poultry spoilage pseudomonads was greater than that of E. coli; hence in-plant chlorination is to be recommended for processing-plant water supplies which carry such spoilage organisms.


Althesin and thiopentone: a clinical comparison. Althesin was compared with thiopentone in a double blind study of 200 patients undergoing gynaecological operations. Althesin in a dose of 0.05 ml/kg was found to be an excellent induction agent, virtually devoid of undesirable side effects; however, when used as the principal anaesthetic (supplemented only by 66 per cent nitrous oxide in oxygen), the incidence of disturbing movements was high. Recovery time from Althesin was one-third of that after thiopentone. The patients recovering from Althesin were remarkably clearheaded with a low incidence of "hangover".


Percutaneous transtracheal ventilation for anaesthesia and resuscitation: a review and report of complications. Percutaneous transtracheal ventilation with intermittent jets of oxygen under high pressure has been used for approximately five years. This paper briefly reviews published reports on the use of this technique for resuscitation and during anaesthesia. Complications occurring in the reports reviewed are tabulated. The complications occurring in a series of 80 patients (52 elective prior to anaesthesia and 28 for acute respiratory distress) at the Pittsburgh Eye and Ear Hospital are documented. This includes three detailed case reports. No deaths and few serious complications have so far been reported, particularly with the elective use of transtracheal ventilation. This technique has established itself as an important adjunct in life support. When used in properly selected cases, its continued use appears justified.


Antazoline therapy of recurrent refractory supraventricular arrhythmias--a preliminary report. Seven patients with chronic or recurrent supraventricular tachyarrhythmias were selected for a trial of antazoline therapy because sinus rhythm or a controlled ventricular response could not be achieved with quinidine, procainamide, digitalis or propranolol. Sinus rhythm was established by either intravenous administration of antazoline or direct-current countershock, and has been maintained in all for 4 to 16 months by oral administration of antazoline. Side effects were minor. Antazoline is a sufficiently promising antiarrhythmic agent to warrant large-scale controlled studies.


Aldosterone and renin in essential hypertension. A review of some recent laboratory findings indicates definite disturbances in aldosterone metabolism and regulation in patients with mild essential hypertension: (a) a significant mean increase in plasma aldosterone concentration in patients with mild and stable essential hypertension, in contrast to the absence of any difference in patients with labile borderline essential hypertension when in a normotensive phase, compared with control subjects; and (b) a significant mean decrease in metabolic clearance rate of aldosterone, associated with a 12% decrease in hepatic blood flow and an increased binding of aldosterone to a transcortin-like plasma globulin. The secretion rate of 18-hydroxy-11-deoxycorticosterone is above the upper range of normal in 60% of patients with mild, uncomplicated essential hypertension. The incidence of low-renin hypertension, when age and race are taken into account, is much lower than previously assumed. Unless measurements are repeated over a long period, one or two low values of plasma renin cannot be considered a permanent marker indicating a special category of patients with essential hypertension. Tonin, a new enzyme discovered by Boucher, which forms angiotensin II directly from a plasma protein, from the tetradecapeptide substrate and from angiotensin I, is present in most tissues, but in highest concentration in the submaxillary gland. This enzyme is under the control of beta-adrenergic receptors.


Effect of chronic renal failure, dialysis and transplantation on motor nerve conduction velocity in children. Ulnar and peroneal motor nerve conduction volocities (MNCVs) were measured in 47 children in a dialysis-transplantation program. Mean peroneal MNCV was significantly decreased from normal in children with mild renal failure (serum creatinine concentration, 1.5 to 2.9 mg/dl), whereas ulnar MNCV was significantly decreased only when the serum creatinine value was at least 9 mg/dl. Both ulnar and peroneal MNCVs remained unchanged during long-term hemodialysis or peritoneal dialysis; however, after individual dialyses ulnar MNCV increased. After renal transplantation ulnar MNCV returned to normal within a year and peroneal MNCV within 3 years. Before dialysis was required and during long-term dialysis most plasma magnesium values were elevated; ionized calcium activity was decreased in about 50% of determinations. After transplantation and the concentration of divalent cations rapidly returned to normal. These children differed from adults studied in that (a) there was no correlation between severity of renal failure and MNCV, (b) long-term dialysis did not improve MNCV and (c) peroneal velocities did not recover for 3 years after transplantation.


Surgical management of bacterial meningitis. A variety of associated lesions may require the neurosurgeon's assistance in the management of bacterial meningitis. As treatment of this infection of the central nervous system proceeds, the surgeon will have to decide about the concurrent or subsequent operative treatment of congenital dysraphic states, paraneural infections, compound fractures or penetrating wounds of thecranium or spine, or infected bypass shunts for cerebrospinal fluid (CSF). In patients with intractable meningitic infections the surgeon may have to insert a ventricular drainage-irrigation system to permit adequate perfusion of the CSF pathways with antibiotic. Hydrocephalus or subdural effusions complicating meningitis may bring the patient to the surgeon long after the infection has been cured. This paper examines these problems and outlines the current principles of management.


Combined androgen and antimetabolite therapy of advanced female breast cancer. A report of the cooperative breast cancer group. A clinical trial of androgen and antimetabolite therapy of advanced female breast cancer was conducted in 110 patients by the Cooperative Breast Cancer Group. An objective regression rate of 20% was achieved in women receiving oral testolactone, 6% in patients given intravenous fluorouracil alone, and 14% when the androgen and antimetabolite were administered together. This randomized trial according to the CBCG protocol did not produce the high regression rate noted previously in a nonrandomized, nonprotocol evaluation of these drugs.


Proliferation-dependent cytotoxicity of anticancer agents: a review. One of the factors of importance in determining the killing of mammalian cells following exposure to a variety of anticancer agents is the proliferative state of the cell population. Generally, proliferating cells are much more sensitive to anticancer agents than are nonproliferating cells. In this review, the cellular aspects of this differential sensitivity are discussed with the hemopoietic stem cell population and tissue culture cells as the focus for the analysis. This phenomenon is not only of concern to the cell biologist but also has implications with regard to scheduling of anticancer agents against human tumors.


Chromosome studies in acute leukemias developing in patients with multiple myeloma. Chromosomal findings are reported in three patients with acute myelomonocytic leukemia and in one with reticulosarcoma leukemia who had been treated for multiple myeloma with melphalan and X-ray. All four patients had striking chromosomal anomalies. An iatrogenic causation of aneuploidy is suggested. This is supported by chromosomal findings in patients with acute leukemia following polycythemia vera and Hodgkin's disease; practically all of the leukemias have been aneuploid. A comparison is made of such "secondary" acute leukemias with "primary" acute leukemias that are aneuploid in only 40% of the cases. Chromosomal changes are not considered to be the initial event in leukemogenesis.


A mutant of escherichia coli defective in removing 3' terminal nucleotides from some transfer RNA precursor molecules. The conversion of precursor RNA into bacteriophage T4 proline and serine transfer RNAs includes two steps for the enzymatic removal of nucleotides from the 3' ends of RNA chains. Neither of these steps occur following infection of a mutant of Escherichia coli that was previously shown to block the suppressor function of T4 serine transfer RNA. Cell-free extracts of this mutant are furthermore deficient in a wild type enzyme activity that removes nucleotides from the 3' ends of one of the RNA chains described above. The relation of this enzyme to other 3' ribonucleases is not known. We subsequently examined the mutant for its ability to support the biosynthesis of other bacteriophage transfer RNAs.  In one instance that is analogous to the proline-serine precursor RNA, maturation of the precursor RNA was blocked during infection of mutant cells. In another instance, precursor RNA maturation was normal, even though this involved the removal of 3'nucleotides. These observations point to the possible existence of at least two 3' ribonucleases for the biosynthesis of transfer RNAs.


Mitochondrial DNA synthesis in cell cycle mutants of Saccharomyces cerevisiae. Mitochondrial DNA replication was examined in mutants for seven different Saccharomyces cerevisiae genes which are essential for nuclear DNA replication. In cdc8 and cdc21, mutants defective in continued replication during the S phase of the cell cycle, mitochondrial DNA replication ceases at the nonpermissive temperature. Replication is temperature sensitive even when these mutants are arrested in the G1 phase of the cell cycle with alpha factor, a condition where mitochondrial DNA replication continues for the equivalent of several generations at the permissive temperature. Therefore the cessation of replication results from a defect in mitochondrial replication per se, rather than from an indirect consequence of cells being blocked in a phase of the cell cycle where mitochondrial DNA is not normally synthesized. Since the temperature-sensitive mutations are recessive, the products of genes cdc8 and cdc21 must be required for both nuclear and mitochondrial DNA replication. In contrast to cdc8 and cdc21, mitochondrial DNA replication continues for a long time at the nonpermissive temperature in five other cell division cycle mutants in which nuclear DNA synthesis ceases within one cell cycle: cdc4, cdc7, and cdc28, which are defective in the initiation of nuclear DNA synthesis, and cdc14 and cdc23, which are defective in nuclear division. The products of these genes, therefore, are apparently not required for the initiation of mitochondrial DNA replication.


Effect of procaine hydrochloride on DNA repair in Escherichia coli. Liquid-holding recovery and rejoining of gamma-radiation-induced DNA single-strand scissions in Escherichia coli could be effectively inhibited by procaine hydrochloride at the concentration of 20 mM. At this concentration, the drug also reversibly altered cellular permeability barrier as evidenced from the uptake of acriflavin by bacterial cells.


Myocardial sodium extraction at varied coronary flows in the dog. Estimation of capillary permeability of residue and outflow detection. Sudden injections of boluses containing both 131I-albumin and 24NaCl were made into the coronary artery inflow of isolated blood-perfused dog hearts. Indicator dilution curves were recorded using gamma emissions from both the intact heart and the coronary sinus outflow, with plasma flows, Fs, ranging from 0.3 to 1.8 ml/g min-1. Three measures of sodium extraction, E, during transcapillary passage were obtained from each site by comparison of the sodium and albumin curves. The most useful estimates of E were "instantaneous extractions" obtained from the later part of the upslope and the peak of the venous dilution curves (coronary sinus) or from the corresponding early phase of washout of the externally monitored curves (intact organ). Extractions were lower at higher flows. Permeability-surface area products, PS, were computed (1) by the formula PS equals -Fsloge(1 - E), (2) by fitting the observed dilution curves with a Krogh capillary-tissue cylinder model, and (3) by the approximating formula PS equals -Fsloge (1 - 1.14E). The two latter approaches provided a correction for back diffusion of tracer from tissue to blood. For sodium, the values of PS averaged 0.88 +/- 0.36 (SD) ml/g min-1, (n equals 52). At high flows, with Fs greater than 1.0 ml/g min-1, the values of PS averaged 1.01 +/- 0.38 ml/g min-1 (N equals 11). Assuming S equals 500 cm2/g and plasma to be 93% water, our findings suggest capillary permeabilities for sodium of about 3.1 times 10(-5) cm/sec.


Influence of surgery on survival in 145 patients with left main coronary artery disease. A total of 145 patients with greater than 50% obstruction of the left main coronary artery (LMC) were studied by coronary arteriography. Of the 140 who survived cardiac catheterization, 121 were considered operable by coronary arteriography, and 19 were inoperable. Of the 121 operable patients, 32 were treated medically, and 89 had aortocoronary bypass surgery. Surgical mortality was 11%. The follow-up was from 1 to 72 months with a mean follow-up of 15 months. A survival table was plotted over a 24-month period. At 90 days survival in surgical patients was 85%, medical patients 72%, and inoperable patients 64%. At one year 82% of surgical patients were alive compared with 61% of medically treated operable patients (P less than 0.05). Thereafter, the survival rate remained stable up to 23 months. Survival in inoperable patients was 38% at one year. Improved surgical survival was associated with the presence of preoperative collateral vessels and a left ventricular stroke index greater than 18 g-m/m2. The study demonstrates that survival is improved significantly by surgery in LMC patients. Since mortality occurs early after coronary arteriography, surgery should be offered early to operable patients.


Logistic and technical considerations in the treatment of the wounded heart. As improvements in the prehospital care of traumatically injured patients have paralleled advancements in cardiovascular surgery, changing concepts in the management of the patient with blunt and penetrating injuries of the heart have occurred. More critically injured patients now arrive at a hospital facility still alive than in former years. Between 1951 and 1974, 350 patients with heart injuries were treated at Harris County Hospital District facilities. Gunshot wounds now predominate, compared with stab wounds in former years. Thirteen patients had rupture of the heart secondary to blunt trauma. Patients arriving with cardiac arrest and cerebral signs of preterminal activity had a 67% survival rate when cardiorraphy was performed in the Trauma Center. In the last four years, 50 patients without cardiac arrest, but frequently with pericardiocentesis as a preoperative adjunct, had an 87% survival rate.


Postoperative hemodynamics following aortic cross-clamping during aortocoronary bypass surgery. Forty-one patients undergoing aortocoronary bypass surgery were divided into two groups: an "unclamped" group (17 patients) in whom the aorta was not cross-clamped during operation and a "clamped" group (24 patients) in whom the ascending aorta was cross-clamped during performance of distal anastomoses. Myocardial protection was provided during aortic clamping by cooling the anoxic heart with cold saline immersion. Immediate postoperative hemodynamic function was assayed in both groups, as was cardiopulmonary bypass time and cardiopulmonary bypass time/graft. Cardiopulmonary bypass time was 107 minutes in the unclamped group and 87 minutes in the clamped group (P less than 0.05). Cardiopulmonary bypass time/graft was 48 minutes in the unclamped group and 40 minutes in the clamped group (P less than 0.01). Results of hemodynamic studies with values for the unclamped group listed first were as follows: cardiac index (L/min/m2) 2.3 and 2.5 (NS), stroke index (ml/beat/m2) 23 and 25 (NS), left ventricular minute work index (kg-m/min/m2) 3.03 and 2.81 (NS), and stroke work index (g-m/min/m2) 31 and 30 (NS). These data indicate that aortic cross-clamping during performance of distal anastomoses expedites the performance of aortocoronary bypass surgery and does not adversely affect postoperative hemodynamics.


The role of sulfinpyrazone in the prevention of arterio-venous shunt thrombosis. The effect of sulfinpyrazone on the incidence of thrombosis of arterio-venous shunts was investigated in a double-blind crossover study in 45 patients on chronic hemodialysis over a period of 12 months. The incidence of thrombosis was reduced from 0.64 thrombi per patient month when on placebo to 0.21 thrombi per patient month when on sulfinpryazone (P less than 0.001). The therapeutic effect was more striking in men than in women and became evident within a week of starting the drug. The side effects were minimal, requiring withdrawal from the study of only one patient. This crossover study strengthens the findings in the previous report that sulfinpyrazone is of value in the prevention of thrombosis.


The status of cardiac transplantation, 1975. Since December 1967, 263 human cardiac transplant operations have been performed throughout the world. Eighty-two of these were performed at Stanford University Medical Center, In 1974, 27 such operations were performed, 15 at Stanford Survival rates for the entire Standford series are 48% at one year and 25% at three years; survival rates at one and three years for patients surviving the first three critical months after transplantation are 77% and 42%, respectively. Recipients under the age of 55 years, with New York Heart Association Class IV cardiac disability, are selected for transplant procedures according to criteria dictated by experience over the past seven years. A routine immunsuppressive regimen for organ transplantation, incorporating prednisone, azathioprine, and antithymocyte globulin is employed early postoperatively, and prednisone and azathioprine are used for indefinite maintenance therapy. Acute cardiac graft rejection in nearly all recipients is diagnosed by clinical signs, electrocardiographic changes, and percutaneous transvenous endomyocardial biopsy. Ninety-five percent of acute rejection episodes are reversible with appropriate immunosuppressive treatment, but infectious complications are common and have accounted for 56% of all postoperative deaths. The Stanford experience in cardiac transplantation has demonstrated the potential therapeutic value of this procedure. Maximum survival now extends beyond five years. Satisfactory graft function has been documented in long-term surviving patients, the majority of whom have enjoyed a high degree of social and physical rehabilitation.


The qualitative nitroblue tetrazolium (NBT) test as a means to differentiate between infection and rejection in renal transplant patients. In order to determine whether immunosupression depresses the response of the NBT test to bacterial infections and to note the effect of allograft rejection on this test, a prospective study was carried out on 30 renal transplant recipients. 12 of 30 renal transplant patients developed bacterial infections and in these patients NBT readings were elevated. 12 of the remianing 18 patients who developed rejection episodes showed normal NBT results. All patients were on high doses of steroids and other immunsuppressive agents. We conclude that the NBT test may be of value in diagnosing bacterial infection in the immunsuppressed allograft recipient, and may also be an useful adjunct in the differentiation between allograft infection and bacterial infection.


Successful renal transplantation in focal glomerular sclerosis: report of two cases. The fate of renal allografts has provided much useful information about the pathogenesis of certain glomerular diseases. Idiopathic nephrotic syndrome with focal glomerular sclerosis (FGS) has been reported to recur in transplants. Two patients are reported with idiopathic nephrotic syndrome who progressed to renal failure. Immunopathologic and ultrastructural studies appeared to exclude immune pathogenic mechanisms in both patients, and light microscopic findings were characteristics of FGS. The nephrotic syndrome in one patient was initially steroid-dependent. Both patients underwent bilateral nephrectomy prior to renal transplantation. Graft function and urine protein excretion were normal in both patients 2 and 4 years respectively after transplantation, and transplant biopsies revealed no evidence of recurrent FGS. These results indicate that renal transplantation in patients with idiopathic nephrotic syndrome and FGS is not invariably followed by recurrent glomerular disease and suggest that the responsible pathogenetic mechanism(s) may not always persist.


Prostaglandin in calcium and bone metabolism. The effect of prostaglandins on bone resorption and formation is reviewed. The prostaglandins probably play a role in pathological changes in bone, e.g., those occurring in immune responses and neoplastic disease. Their physiological role is unknown.


Clinical aspects of thyrocalcitonin.

Clinical aspects of thyrocalcitonin. Thyrocalcitonin (TCT) is useful as a diagnostic and therapeutic agent in selected human diseases. Elevated plasma levels of TCT occur in patients with medullary carcinoma of the thyroid gland. Asymptomatic relatives of these patients harboring microscopic foci of tumor may have abnormal plasma levels of TCT in the basal state or after provocative stimuli. In both instances the plasma levels of TCT can be used in the diagnosis and management of this thyroid neoplasm. Elevated plasma levels of TCT have also been described recently in subjects with certain extrathyroidal neoplasms or renal failure. Moderate elevations are seen during normal pregnancy and in the neonatal period. Although exogenous TCT has actions on several organs, including bone, the kidneys and the gastrointestinal tract, its physiological role in man, if any, is still unknown. The recently reported measurements of TCT in normal subjects should facilitate the clarification of this issue. TCT has been used as a therapeutic agent in Paget's disease of bone, hypercalcemia of diverse etiologies, osteopenia and several other skeletal disorders. The dramatic improvement of patients with Paget's disease has been a unique therapeutic action of TCT. The therapeutic responses in hypercalcemic subjects given TCT are encouraging but more information is needed about the pharmacology of the hormones in these subjects before conclusions can be formed. At present the therapeutic role of TCT in osteopenia is hypothetical and the results of ongoing and future studies are needed to determine its effects.


High density polyethylene prosthetic femoral head replacemnt in the dog. A high density polyethylene (RCH 1000) femoral head prosthesis was inserted in 5 large dogs. Periodic clinical and roentgenographic evaluations, and histopathological examination of the replaced joints as well as biomechanical evaluation of the prosthetic joints were done at intervals from 3 weeks to 15 months. HDP is NOT suitable for movable weight-bearing prosthesis articulating with cartilage or bone. Wear of the cartilage and the polyethylene occurred within a few weeks of function and became extensive proportionally to the length of use. The accumulating wear particles of HDP caused a significant foreign body granulomatous reaction which resulted in erosion of bone adjacent to the acetabulum in one hip.


Hypochondroplasia.

Hypochondroplasia. Hypochondroplasia is a hereditary form of short-limbed dwarfism which somewhat resembles achondroplasia, but which is clinically, roentgenographically, and genetically distinct. The pertinent findings in 6 new cases are: moderate rhizomelic shortness of stature; normal craniofacial appearance and hand configuration; and later recognition of the presence of the abnormality than in achondroplasia (which can be recognized at birth). A review of the 35 previously described cases in the literature reveals a preponderance of affected females and a high incidence of spontaneous mutation, although when once evident the trait is passed as an autosomal dominant. Two of our patients had seizures, and mental deficiency may be an associated finding although it is by no means usually present. Orthopedists should be aware of this entity, which may be somewhat more common than has been thought, because of the different implications for ultimate height, which is greater in hypochondroplasia than in achondroplasia, the lack of cauda equina compression findings, and the need for genetic counseling.


A comparison of patellectomy with prosthetic replacement of the patella. Eight adult mongrel dogs were used to compare patellectomy with prosthetic replacement of the patella. All of the dogs who underwent patellectomies displayed functional disturbances when examined four weeks postoperatively. None of the dogs with patellar prostheses displayed discernible functional disturbances. All but one of the dogs with patellectomies developed pathological alterations in the patellar bed of the femur. None of the dogs with patellar prostheses had pathological alterations in the patellar bed of the femur.


Radiotherapy in osteosarcoma.

Radiotherapy in osteosarcoma. Radiation therapy in the treatment of osteosarcoma has been considered with respect of the subclinical metastatic disease in the lung and the primary lesion. Emphasis is given to the necessity of coordinating the management plan of the primary lesion with an adjuvant program. Evaluation of the efficacy of a conservative treatment of the primary lesion by radiation therapy and chemotherapy is considered a proper subject for clinical study. A proper biopsy technique and several practical aspects of technique of radiation therapy in management of osteosarcomas of bone are important factors in survival time of individual patients.


The problem of chondromalacia patellae.

The problem of chondromalacia patellae. Daily activity subjects the human patella to forces often several times the individual's body weight. Healthy cartilage can adjust to these forces if they are not too excessive, concentrated, or repetitive. Such abnormal stresses most frequently occur with the disturbance of normal patellar mechanical function. Chondromalacia patellae is the result common to a wide variety of unusual traumata. Treatment must be directed primarily not toward the damaged patellar cartilage but toward a correction of the mechanical abnormality causing it. Until proven otherwise, a young female complaining of knee joint pain, particularly if bilateral, should be considered as suffering from a subluxating patella, with or without chondromalacia patellae.


Reconstructive surgery in the myelomeningocele hip. In 17 myelomeningocele patients with subluxating or dislocated hips, 31 posterolateral iliopsoas were treated by transfers, as described by Sharrard, in addition to complimentary procedures to balance muscle power and center the hip joint. Surgical goals are to stablize the hips within the acetabulum and prevent the occurrence of severe fixed flexion and adduction contractures of the hip and secondary lumbar lordosis. Surgery is performed at about 1 year of age with bilateral adductor transfer to the ischium, followed in 2 weeks by the posterolateral transfer of the iliopsoas muscle, first on one hip and 2 weeks later following with the other hip. Adductor transfer to the ischium reduces the adductor and secondary flexor power of the adductor longus and anterior fibers of the adductor brevis. After transfer it provides some extensor power. The range of abduction is increased. The transferred iliopsoas muscle has a better mechanical advantage in its new function as an abductor and extensor, and the hips were better centered radiographically than the cases with iliopsoas transfer alone. Fewer bony procedures were required to center the hips when the iliopsoas transfer was performed in children before the age of 1 1/2 years.


Talectomy in the treatment of the myelomeningocele patient. This paper is an analysis of a series of 11 pediatric myelomeningocele patients in whom 20 talectomies were performed for correction of rigid equinovarus of paralytic vertical talus deformities. In most of the patients talectomy achieved a satisfactory correction of the foot deformity with maintenance of the correction for up to 5 years of follow-up in this study. Failure of the procedure related to two factors: (1) severe external rotational contracture of the hips in patients with high spinal lesions; (2) incomplete removal of the talus because of extensive scarring and fibrosis due to prior infection or surgery. Correction of the external rotational deformity of the hip or a derotational supramalleolar osteotomy of the tibia can prevent the first cause of failure. An intra-operative X-ray of the foot can prevent the latter.


Folic acid dosage for chronic hemodialysis patients. The doses of folic acid, necessary to avoid folic acid deficiency in patients being maintained on hemodialysis, have been estimated to be between 1 and 5 mg daily. To more precisely define an adequate dose of folic acid, 6 anephric patients were studied. The patients were maintained on hemodialysis and received, in a crossover fashion, 1 mg and 5 mg of folic acid for 3 wk. In a second crossover study, 3 anephric patients were first maintained on 0 and then on 1 mg of folic acid after each dialysis for 3 wk periods. Pre- and postdialysis folic acid blood levels were measured and dialyzer clearances of folic acid were determined. The results of this study support the conclusion of the Food and Drug Administration report suggesting that daily doses of 1 mg of folic acid are adequate to sustain therapeutic folate levels. The data further indicate that the administration of 1 mg of folic acid after each dialysis, rather than 1 mg of folic acid daily, can provide adequate folate.


Reconstruction of cranial defects.

Reconstruction of cranial defects. We have found that small defects, particularly those within the hairline, are easily reconstructed with methy methacrylate prepared at the operating table. Larger defects, especially in children and active adults, are benefited by autogenous bone grafts and we prefer split rib. When the fabrication facilities are available the preformed silicone implants offer much to the surgeon. They may be sculptured to correct difficult contour problems such as in the supraorbital or forehead region and are especially useful to fill in defects where the bone is present, but depressed. These three methods have many advantages over the metallic implants. There is little complaint of the implant being cold when the patient is exposed to cold weather and a very important fact is that these methods not only provide a radiolucent reconstruction, but also do not affect EEG examination.


Mandibular reconstruction. Current state of the art. At the present time several techniques of bone grafting for restoration of mandibular defects are being employed. These methods are well established by clinical trials and animal research. Other methods are in the experimental stage. Regardless of the technique utilized it remains paramount that the surgeon plan the initial procedure with great care as each failure results in diminished blood supply to the graft bed and makes subsequent procedures less likely to succeed. The well known principles of bone grafting involve establishing good nutritional status of the patient, proper preparation of the graft bed by insuring adequate soft tissue and adequate blood supply, elimination of infection from the graft bed, provision of adequate fixation and immobilization of the graft, and careful closure of soft tissues to prevent hematoma formation. These principles remain inviolable if the procedure is to succeed.


A statistical approach to the recognition of inferior wall myocardial infarction by the Q/R ratios. To sharpen ECG criteria for diagnosis of inferior wall myocardial infarction (IWMI), the distribution of Q duration and Q/R ratios in leads 3 and aVF in four groups have been analyzed. Two of these groups are teaching samples (200 ECGs of patients with various diagnoses, but in whom no myocardial infarction was found on post-mortem, and 123 ECGs of patients in whom IWMI was found on post-mortem examinations) and two control samples (408 ECGs of healthy men and 60 ECGs of patients with clinically proved IWMI). The chosen combination of conditions Q/R3 greater than 25 percent and Q/RaVF greater than 10 per cent gives minimal number of errors for the teaching samples. The diagnostic rule gave 5-7 percent errors over the control samples. It is shown that use of Q duration greater than 0.04'' gives less satisfactory results in the diagnosis of IWMI.


Mode of action of 5-fluorocytosine and mechanisms of resistance. Mode of action of 5-fluorocytosine (5-FC) and mechanisms of resistance to the drug are discussed on the basis of experiments performed with Candida albicans ATCC 26790 and with 50 selected clinical isolates of C. albicans belonging to serological type A or B and representing various degrees and models of 5-FC resistance (sensitivity). Incorporation of 5-fluorouridylic acid into RNA appeared as a prerequisite to antifungal activity, although at a given incorporation rate, growth inhibition varied considerably from one strain to the other. The amino acid pool was unbalanced, and there was evidence for disturbance of protein synthesis. These dysfunctions of RNA probably account for growth inhibition and cell death, whereas up to the present, there was no proof of formation of 5-fluorodeoxyuridylic acid nor of subsequent inhibition of thymidylate synthetase. Incorporation of fluorinated pyrimidine into RNA was lower in normally sensitive type B strains than in normally sensitive ones of type A, whereas the frequency of 5-FC-resistant mutants was the same. The two serological types did not differ in the activity of cytosine permease nor in that of cytosine deaminase. Among 29 clinical isolates with 6-FC resistance (or impaired sensitivity) no instance of cytosine permease deficiency was found. Two isolates (belonging to the serological type A) were deficient in cytosine deaminase, whereas the majority was probably deficient in uridine monophosphate pyrophosphorylase or had a surplus of de novo synthesis of pyrimidines. Relative 5-FC resistance was more common than complete resistance.


Kinetics and mechanisms of action of 'folate synthesis inhibitors', alone or in combination, on Escherichia coli. III. Pyrimethamine, trimethoprim and sulfamethoxazole. The inhibitory activity of pyrimethamine (PMA) is 1/290 of the activity of trimethoprim (TMP) against E. coli as evaluated from a plot of C.ko/ko-kapp VS. C. Even at high concentrations the effect of PMA in contrast to TMP seems to be cateriostatic. Combinations of TMP and PMA reveal an additive effect. In PMA-treated cultures, the slope of the logarithmic growth curve decreases after an initial inhibited growth, and a second steady state is established. This second steady state has a different reason than the one observed in TMP-treated cultures; whereas the second phase in TMP-inhibited cultures depends on the number of germs, in the case of PMA it depends on the number of generations. Using prewashed cell cultures, it was shown that there is no influence on the two steady states in PMA-inhibited cultures; for TMP, however, it was shown that the presence of the first phase is due to an antagonist excreted into the culture medium. These observations hint at differences in the mode of action of TMP and PMA in addition to differences in the affinity to the target enzyme dihydrofolate reductase. Combination of PMA with sulfamethoxazole (SMZ) at concentrations where both drugs are acting only bacteriostatically leads to effects considerably greater than would be expected from simple additivity. The kill rate observed is the same as observed for TMP/SMZ combinations despite of the considerable lower activity of PMA and SMZ. The results support the assumption that it might be possible to select drug combinations considering the best pharmacokinetical fit and not necessarily the most effective drugs in the series studied.


Mucolytic and antibiotic effect of a new compound in chronic bronchitis. The purpose of the study was the objective evaluation of the mucolytic and antibiotic properties of Fluimucil Antibiotic, a molecular combination of acetylcysteine and thiamphenicol. The preparation was administered to 45 patients in the dose of 3 tablets daily each containing 500 mg of thiamphenical. Statistical analysis of the data obtained showed mucolytic effects on the 4th to 5th day of treatment and marked antibiotic activity. The evaluation is positive particularly if the relatively low dose of antibiotic normally used in chronic bronchitis is considered. The preparation Fluimucil Antibiotic can be recommended for the treatment of chronic bronchitis also in view of its good tolerability.


The effect of co-trimoxazole on antitoxin response to tetanus toxoid. The effect of a 4-day course of co-trimoxazole (Septrin) on antitoxin response to tetanus vaccine was assessed in a double-blind study involving 22 healthy adults. The tetanus antitoxin levels were measured by in vivo and in vitro methods for up to 8 weeks after the first of two injections of tetanus vaccine, given 4 weeks apart. No sigificant difference was observed in the level of tetanus antitoxin produced in subjects who received co-trimoxazole (Septrin) in recommended therapeutic dosage during the first 4 days of the trial from that in subjects who received placebo tablets. The results indicate that a 4-day course of co-trimoxazole (Septrin) does not affect antibody production.


Results obtained with combination therapy of VM-26, natulan and prednisolone in generalized Hodgkin's disease. By evaluating the results obtained in 50 patients the authors stated that VM-26 given in combination with Natulan and Prednisolone is a drug of value in the therapy of generalized Hodgkin's disease. It cause milder side effects than drugs previously used in combination therapy. Complete or partial remissions were obtained in 84% of patients treated. 75% of the therapy-resistant cases proved to be Hodgkin's sarcoma by the postmortem examination. Remission lasted longer in stage III than in stage IV and the previously untreated patients responded better than the treated one. Definite correlation could not be revealed between histologic type and duration of remission.


Antimalarials: screening of (orally administered) silver solfonamides against Plasmodium berghei. Orally administered silver sulfadiazine is effective against Plasmodium berghei. Attempts to synthesize an active analogue with antimalarial activity failed. Although several of the analogues were chemically stable (like silver sulfadiazine) in sodium chloride, none of the analogues were biologically active. This suggests that the antimalarial activity of silver sulfadiazine is stereo-specific.


In vitro and in vivo microbiological evaluation of Cephapirin, a new antibiotic. The microbiological properties of cephapirin, a new semisynthetis cephalosporin, have been studied. This antibiotic, if compared with ampicillin, shows a greater activity against gram positive bacteria, a lack of sensitivity to staphlococcal beta-lactamase, and a lower sensitivity to those produced by gram-negative bacteria. Useful therapeutic of cephapirin levels can be detected in human serum 6 h after administration of 500 and 1,000 mg parenterally.


Doxycycline in the treatment of upper and lower respiratory tract infections. A field trial. As part of the Pan-European multi-centre trial of doxycycline in the treatment of respiratory tract infections during the winter of 1973/1974, a field trial was carried out in Austria. 95 physicians provided 540 case reports for evaluation. Very good or good results were obtained in 93.9% of patients and the rate of improvement as indicated by fall in temperature, reduction in cough, sputum and pain, and easing of inflammatory symptoms was rapid; 77.8% of patients showed complete remission of acute symptoms after 3 days of treatment. Only 5.6% of patients suffered from side-effects which were mostly mild. Comparison with a previous field trial in Austria in 1968/1969 showed that doxycycline has retained its efficacy over the years.


A multi-centre trial of alpha-6-desoxy-5-oxytetracycline (doxycycline). 23 physicians in Italy took part in a multi-centre clinical trial of doxycycline in the treatment of respiratory tract infections. The case records of 290 patients were assessed with respect to both subjective and objective improvement and clinical cure: most patients were considered improved by the third day and cured by the fifth. The recommended dose of doxycycline was 200 mg on the first day and 100 mg daily thereafter; only 11 of the patients had to continue treatment beyond the tenth day. The antibiotic was extremely well tolerated; gastrointestinal side-effects occurred in 10 patients. Overall, 88.6% of the patients achieved a very good or good result.


Treatment of acute respiratory tract infections with doxycycline in general practice. A multi-centre general practitioner trial was carried out in the Netherlands during the winter of 1973/1974. This trial was part of a larger pan-European study. There were 13- cases studied in the Netherlands who were only treated with doxycycline, by 17 physicians. All patients included in the trial had an acute infection of either the upper or lower respiratory tract. tthere were 64 females and 66 males. The results were excellent at 100 patients (76.9%) had a very good result, 21 patients (16.2%) had moderate or fair results, and only 7 patients (5.4%) had poor or negative results. Doxycycline was well tolerated as no side-effects were noted in 122 of the patients (93.8%). In the 8 patients who experienced side-effects they were mild and self-limiting.


Vibramycin in paediatrics. An evaluation of the onset of action and efficacy. The effectiveness of and tolerance to doxycycline (Vibramycin, Pfizer) was investigated in a group of 188 children and the radpidity of both subjective and objective improvement was assessed in a second group of 58 children. Doxycycline was found to be very effective. It was possible to analyse the results of treatment in 245 out of the total of 246 patients. Cure was obtained in 168 patients (68.6%) and marked improvement was seen in 59 (24.1%). The overall success rate was thus 92.7%. 18 patients (7.3%) failed to respond; these either had a history of relapsing infections or were infected with resistant organisms. Doxycycline also proved to be rapid in its effect. Rapid subjective improvement was seen in 48 out of 58 patients (84.2%) and rapid objective improvement in 41 patients (70.7%). Tolerance to doxycycline was very good. Treatment had to be interrupted in only one out of 246 patients; there were initial gastrointestinal symptoms in 4 patients. Doxycycline showed itself to be a very suitable antibiotic for use in day-to-day paediatric practice.


A comparative trial of doxycycline and ampicillin in the treatment of acute sinusitis. A double-blind comparative clinical trial of doxycycline (200 mg on the first day followed by 100 mg daily for a total of 7 days) and ampicillin (250 mg 4 times daily for 7 days) was performed in 44 patients with acute or chonic sinusitis. Significantly superior results were observed with doxycycline; 90% of the patients responded to doxycycline and 35% to ampicillin. The incidence of side-effects was low and these were of a minor nature, in no case with either drug was discontinuance of treatment necessary. These results imply that in treating chronic bronchitis an antibiotic should be given which is effective not only against the responsible organisms but which is able also to penetrate those tissues (such as the sinuses) that act as a reservoir for these organisms. Doxycycline meets these requirements.


Doxycycline in respiratory tract infections. Report of a retrospective study in Spain during the winter 1972-1973. In the winter of 1972-1973 a multicentre trial of the treatment of upper and lower respiratory tract infections was carried out in Spain using doxycycline. 85 physicians participated in the study and treated 1,653 patients. The infections included acute bronchitis, acute exacerbation of chronic bronchitis, pneumonia, bronchopneumonia, tonsillitis, pharyngitis, trachetis, sinusitis, and otitis media. The majority of the patients were adult out-patients although some children and adolescents were included: 1,011 of the patients were male and 642 female. A number of the signs of respiratory infection such as temperature, cough, pain and inflammatory symptoms were examined. A rapid reduction in intensity and severity was noted in all of these parameters. Tolerance to the antibiotic was excellent. Only minor side-effects were reported and these were mild and mainly limited to the gastro-intestinal tract - in no case was treatment discontinued. The total number of side-effects was 37; they occurred in 31 out of the 1,653 patients. The overall evaluation of results showed a very good or good response in 85% of the patients. It appears from this multicentre study that the efficacy of doxycycline has in no way decreased over the 7 years of its extensive use in Spain. It remains a fast acting and effective antibiotic in upper and lower respiratory tract infections irrespective of age, sex or diagnosis.


Doxycycline in the treatment of respiratory tract infections. Results of a pan-European multi-centre trial. In the winter of 1973-4, general practitioners from seven European countries took part in a multi-centre trial of doxycycline in the treatment of infections of the respiratory tract. The carefully designed protocol was observed by all participants. A total of 1,747 patients were admitted to the trial; their ages ranged from 6 years to over 80. The commonest diagnoses (50%) were acute bronchitis and acute exacerbations of chronic bronchitis. On the recommended dosage of 200 mg doxycycline on the first day, followed by 100 mg daily thereafter (though 200 mg could be continued daily in severe cases), 87% of patients achieved good or very good results. Both subjective (pain) and objective (sputum volume and viscosity, temperature, cough) measures showed rapid improvement, usually by the third to fifth days. Side-effects were minimal and mainly gastrointestinal and caused only 4 patients to discontinue treatment. Overall, doxycycline proved its effectiveness and rapidity of action.