Measurement of digital blood pressure after local cooling.

A double-inlet plastic cuff was designed for local cooling and systolic blood pressure measurement on the middle phalanx of the fingers. With a tourniquet on the proximal phalanx of one finger, cooling for 5 min made the digital artery temperature equal the skin temperature. The difference between the systolic pressure in a control finger and in the cooled finger give the reopening pressure in the digital arteries. At 30, 25, 20, 15, and 10 degrees C, respectively the percent decrease of the finger pressure was 0.2 (0.2), 1.5 (2.5), 8.5 (3.7), 11.4 (3.4), and 15.3 (3.1) in normal young women. In patients with primary or secondary Raynaud's phenomenon, the arterial tone showed an abrupt increase that most often led to complete closure of the digital arteries. The pathological response was expressed as an increased threshold temperature or a well-defined closing temperature that showed only small variations during standardized conditions.


Acoustic helium analyzer for closing volume measurement.

An acoustic gas analyzer was developed to measure helium during the closing volume (CV) test. It is based on the principle that altering the composition of a gas mixture will change the velocity at which sound is transmitted through the gas. The change in transit time for an acoustic burst across an in-line (breathe-through) cell is measured as a function of He concentration in the expired air during the CV test. Although CO2 and H2O vapor affect the signal, so it is not specific for He, the system provides good records of CV. A comparison of measurements in 21 normal subjects demonstrated no differences for CV measured in the same breath by the bolus technique using the acoustic gas analyzer and by the resident gas method using a nitrogen analyzer. Differences in closing volumes measured by the He bolus technique and the resident gas method might exist in patients with some kinds of pulmonary disease, and the suggestion is made that CV measurements by the two methods might assist in describing pulmonary alterations in patients with bronchopulmonary disease.


Dimer formation of bromocresol purple anions on the phosphorylated intermediate of sarcoplasmic reticulum.

The mechanism of spectral shift and absorption intensity change of the divalent bromocresol purple (BCP) anion was further investigated and it was characterized as a spectrophotometric membrane probe. At high concentrations (1-40 mM), the absorption intensity of th BCP anion at 590 nm (monomer band) decreased markedly with increase of the dye concentration, while another absorption band appeared at 554 nm. Analysis of the change of absorption intensity showed that the mared decrease resulted from dimer formation of BCP (polymer formation at concentrations higher than 20 mM). Wavelengths of maximum absorption (lambdamax) of the BCP anion were determined in various solvents and comparison of these lambdamax's with lambdamax of the BCP anion bound to SR showed that the hydrophobicity of the area of BCP anion binding to SR corresponded to a refractive index of 1.429. While the BCP anion bound to SR showed a monomer spectrum, a dimer band appeared for the BCP anion bound to SR-Pi (phosphorylated protein) with a marked decrease in the absorption intensity at the monomer band, indicating that two polar groups, binding sites for the BCP anions, closely approached each other in the SR-Pi configuration.


The states of tyrosyl and tryptophyl residues in a protein proteinase inhibitor (Streptomyces subtilisin inhibitor.

The states of tyrosyl and tryptophyl residues of a dimeric protein proteinase inhibitor, Streptomyces subtilisin inhibitor (Sato, S & Murao, S. (1973), Agric. Biol. Chem. 37, 1067) were studies by solvent perturbation difference spectroscopy with methanol, ethylene glycol, polyethylene glycol, and deuterium oxide as perturbants, and by spectrophotometric titration at alkaline pH. It appeared that all three tyrosyl residues per monomer of the inhibitor were exposed on the surface of the molecule, and their apparent pK values were estimated separately to be 9.58, 11.10, and 12.42. The single tryptophyl residue per monomer of the inhibitor appeared to be partially buried in the protein molecule.


Phospholipase C from Clostridium novyi type A. II. Factors influencing the enzyme activity.

The apparent activity of phospholipase C[EC 3.1.4.3] of Clostridium novyi type A toward phosphatidylcholine, sphingomyelin, and phosphatidylethanolamine increased in the presence of sodium deoxycholate (SDC). The effects of divalent cations on phospholipase C activity were examined in detail at various concentrations of these cations. These effects varied with substrate. Hydrolysis of phosphatidylcholine by this enzyme significantly increased in the presence of Mg2+ or Ca2+. Hydrolysis of sphingomyelin was inhibited by Ca2+, but increased in the presence of Mg2+. Phosphatidylethanolamine-hydrolyzing activity increased only slightly in the presence of Mg2+ and Ca2+. Zn2+ rather inhibited hydrolysis of these substrates. The effects of divalent cations and detergent appear to be directly related to the physical state of the phospholipid micelles used as substrates. When phosphatidylcholine, sphingomyelin, or phosphatidylethanolamine was used as a substrate, phospholipase C activity was completely inhibited by 2.5 mM EDTA or o-phenanthroline (concentration in the final incubation mixture: 0.5 mM), and was fully restored by Zn2+ alone. Both Ca2+ and Mg2+ were ineffective for reactivation. The isoelectric point of the enzyme was 7.1 +/- 0.1.


Studies on the surface structure of the intracytoplasmic membrane in the photosynthetic purple bacterium Chromatium vinosum by means of chemical modification.

By means of a chemical modification technique, the surface structure of the intracytoplasmic membrane (chromatophores) of the photosynthetic bacterium Chromatium vinosum was investigated. Trinitrobenzenesulfonate was employed to modify the primary amino groups of phosphatidylethanolamine and proteins. The experimental results indicate that upon the chemical modification of intact cells, the amino groups on the inner surface of the chromatophores are trinitrophenylated, while upon the modification of isolated chromatophores, the amino groups of the outer surface are trinitrophenylated. Phosphatidylethanolamine is essentially equally distributed on the inner and outer surfaces of the chromatophores, while most proteins exist at the outer surface. In particular, a protein fraction, which is soluble in a mixture of chloroform/methanol, is located at the outer surface exposing a part of the amino groups in the aqueous phase.


Studies on glycosphingolipids of fresh-water bivalves. IV. Structure of a branched globoside containing mannose from spermatozoa of the fresh-water bivalve, Hyriopsis schlegelii.

1. A second novel globoside, provisionally named Lipid II in the previous study, was obtained from spermatozoa of the fresh-water bivalve, Hyriopsis schlegelii. The structure of this globoside was established by the results of partial acid hydrolysis, methylation studies, and oxidation with chromium trioxide. 2. The structure was shown to be GlcNAcbeta(1 leads to 2)Manbeta(1 leads to 3)[Xylbeta(1 leads to 2)]Manbeta(1 leads to 4)Glcbeta-(1 leads to 1)-ceramide. It is structurally related to the previously described globoside (Lipid I), except that a branched xylose is linked to the heterooligo saccharide chain of the latter lipid. 3. The predominant fatty acids were palmitic and stearic acids, and octadeca-4-sphingenine was the principal base, amounting to 70% of the total. The fatty acid and long-chain base compositions show nearly the same distribution in both of these globosides.


Studies on the glycosphingolipids of the starfish, Asterina pectinifera. I. The isolation and characterization of ceramide mono- and di-hexosides.

Ceramide mono- and di-hexosides were isolated from the starfish, Asterina pectinifera. These glycolipids had both a novel ceramide which contained almost entirely phytosphingosines (long-chain bases) and a high content of 2-hydroxy fatty acids. The long-chain base composition of the glycolipids shows an unusual pattern with both branched bases (iso-C16, iso-C17, iso-C18, anteiso-C17, and anteiso-C18) and normal ones (C16, C17, and C18). Of these, iso-C16- and anteiso-C18-phytosphingosines had been undetected up to now. The glycolipids were identified as glucosyl and lactosyl ceramides. Lactosyl ceramide had not been previously reported in starfish, although the wide occurrence of this glycolipid has been demonstrated in other organisms.


Effect of estradiol-17beta on the metabolism of bile acids in the rat.

The effect of estradiol-17beta on the metabolism of bile acids has been studied in male rats. 1. A 3-day acute treatment with 100 microgram/100 g body weight of the hormone caused a decrease in serum cholesterole and an increase in hepatic cholesterol. A chronic treatment with the same quantity twice a week for 3 weeks induced hypercholesteremia, which continued for 10 days after the final dosage, but there was no change in hepatic total cholesterol. 2. Fistula bile of both groups of treated rats collected during 30 min was analyzed for bile acid components. Hyodeoxycholic acid and/or chenodeoxycholic acid increased relative to cholic acid in both groups, as compared with the controls. 3. Kinetic study of the metabolism of bile acids in the chronically treated rats revealed a more than twofold enlargement of the pool size but an almost unchanged half-life of chenodeoxycholic acid. As for cholic acid, essentially no change in pool size or half-life was observed. 4. These results indicate that chronic treatment of male rats with estradiol-17beta causes an increase in elimination of hepatic cholesterol via the bile acid pathway.


Na+-dependent activation of NADH oxidase in membrane fractions from halophilic Vibrio alginolyticus and V. costicolus.

Membrane-bound NADH oxidase activities from slightly halophilic marine Vibrio alginolyticus and moderately halophilic V. costicolus required 0.3 and 0.5 M Na+, respectively, for maximum activity; other cations such as Li+,K+,Rb+,Cs+,Mg2+, and Ca2+ were relatively ineffective as replacements for Na+. The concentration of Na+ required to give half-maximum activity with the NADH oxidase from V. alginolyticus was 82 mN. This value was reduced to 6.4 and 13.8 mM in the presence of 400 mM K+ and 10 mM Mg2+, respectively, indicating that K+ and Mg2+ cooperated with Na+ for activation. The same pattern of cation dependence was observed with the NADH oxidase from V. costicolus. The NADH oxidase from nonhalophilic Escherichia coli, however, had no specific requirement for Na+. Thus, Na+-dependent activation of NADH oxidase appeared to be a characteristic feature of these halophilic bacteria. All NADH oxidases examined were influenced by the species of anion present and the order of activating effect followed the lyotropic series:SO4(2-), CH3COO- greater than Cl- greater than NO3- greater than SCN-. Chaotropic anions such as NO3- and SCN- were inhibitory to the NADH oxidases, irrespective of the halophilic nature of the bacterial source.


Biogenesis of the mitochondrial matrix enzyme, glutamate dehydrogenase, in rat liver cells. I. Subcellular localization, biosynthesis, and intracellular translocation of glutamate dehydrogenase.

1. The presence of glutamate dehydrogenase in the microsomal fraction of rat liver was confirmed. The identities of mitochondrial and microsomal glutamate dehydrogenases were proved by immunochemical methods and by SDS polyacrylamide gel electrophoresis of purified enzymes. 2. Synthesis of glutamate dehydrogenase by the membrane-bound ribosomes of rough endoplasmic reticulum was determined. Newly synthesized enzyme molecules were discharged on the cytoplasmic surface of endoplasmic reticulum membranes. 3. A precursor-product relationship was found between microsomal and mitochondrial glutamate dehydrogenases. About six hours were needed for the transport of glutamate dehydrogenase from the site of synthesis to mitochondria. 4. The half-life of glutamate dehydrogenase was about 5.5 days, which was somewhat longer than that of mitochondrial total protein determined in the same experiment. 5. Mitochondrial-type malate dehydrogenase was also present in the microsomal fraction. Subfractionation of smooth microsomes revealed the existence of particular light microsomal vesicles in which both glutamate dehydrogenase and malate dehydrogenase were concentrated. These vesicles may participate in intracellular transport of matrix enzymes from microsomes to mitochondria.


Biogenesis of the mitochondrial matrix enzyme, glutamate dehydrogenase, in rat liver cells. II. Significance of binding of glutamate dehydrogenase to microsomal membrane.

1. Glutamate dehydrogenase and malate dehydrogenase solubilized from liver microsomes were able to rebind to microsomal vesicles while the corresponding dehydrogenases extracted from mitochondria showed no affinity for microsomes. 2. Competition was noticed between microsomal glutamate dehydrogenase and microsomal malate dehydrogenase in the binding to microsomal membranes. Mitochondrial malate dehydrogenase or bovine serum albumin did not inhibit the binding of microsomal glutamate dehydrogenase to microsomes. 3. Binding of microsomal glutamate dehydrogenase to microsomal membranes decreased when microsomes was preincubated with trypsin. 4. Rough microsomal glutamate dehydrogenase was more efficiently bound to rough microsomes than smooth microsomes. Conversely, smooth microsomal glutamate dehydrogenase had higher affinity for smooth microsomes than for rough microsomes. 5. A difference was noticed among the glutamate dehydrogenase isolated from rough and smooth microsomes, and from mitochondria, which suggested the possibility of minor post-translational modification of enzyme molecules in the transport from the site of synthesis to mitochondria.


Distribution of neuraminidase in Arthrobacter and its purification by affinity chromatography.

Neuraminidase [sialidase, EC 3.2.1.18] was found to be widely distributed in bacteria belonging to Arthrobacter. Among these bacteria, Arthrobacter ureafaciens, A. oxydans, and A. aurescens produced relatively potent neuraminidase activities. For the production of this enzyme, not only colominic acid, a homopolymer of N-acetylneuraminic acid, but also N-acetylneuraminic acid, the reaction product of this enzyme, are effective as sources of carbon. An affinity adsorbent specific for neuraminidase was prepared by cross-linking colominic acid with soluble starch by means of epichlorohydrin. Neuraminidase from A. ureafaciens could be purified on this affinity column. The purified neuraminidase was shown to be free from protease, N-acetylneuraminic acid aldolase, phospholipase C, and glycosidases. Aminoff's assay procedure for sialic acid was modified to avoid the centrifugation step. The modified procedure gave a higher molecular extinction coefficient.


Bacteriophage phiNS11: a lipid-containing phage of acidophilic thermophilic bacteria. II. Purification and some properties of the phage.

An improved procedure for the purification of a lipid-containing acidophilic thermophilic bacteriophage, phiNS11, is described. The procedure involves Cs2SO4 discontinuous density gradient, Cs2SO4 equilibrium density gradient and sucrose gradient centrifugations. The phage has an icosahedral shape, 75 nm in diameter, with spike-like structures radiating from the vertices. It contained about 12% by weight of lipid, 13--14% of DNA and 74--75% of protein. The phage was stable between pH 2 and 5, but rapidly inactivated above pH 6. It was highly sensitive to organic solvents and detergents. Some other basic properties such as the buoyant density and UV spectrum of the purified phage are also described.


Bacteriophage phiNS11: a lipid-containing phage of acidophilic thermophilic bacteria. III. Characterization of viral components.

Components of a lipid-containing phage phiNS11 were characterized. The phage had five protein components, the molecular weights of which were 59,000, 44,000, 33,000, 23,000, and 18,000. Viral lipid consisted of six components, which were also found in the host bacterial lipid. The relative amounts of these viral lipid components were very similar to those of the bacterial lipid. The phage contained omega-cyclohexyl fatty acids characteristic of Bacillus acidocaldarius as the main fatty acids. The phage nucleic acid was a linear double-stranded DNA, the molecular weight of which was 9.3--9.4 X 10(6) daltons. The guanine plus cytosine content of the DNA was determined to be about 52% from chemical analysis, buoyant density (1.711 g/cm3 in CsCl) and melting temperature (90.6 degrees C in 0.15 M NaCl plus 0.015 M sodium citrate). The phage contained two kinds of polyamine; spermidine and spermine.


Affinity chromatography of trypsin and related enzymes. IV. Quantitative comparison of affinity adsorbents containing various arginine peptides.

In order to study the mechanism of substrate binding of trypsin by affinity chromatography, we synthesized various L-arginine-terminated oligopeptides having different chain length and amino acid sequences, and immobilized them on agarose gel. The interaction of beta-trypsin with these adsorbents was studied by a quantitative affinity chromatographic procedure which gave the dissociation constant (Kd) of the trypsin-immobilized ligand complex. This procedure proved to be very useful and to give information equivalent to that obtained by kinetic procedures. The contribution of the amino acid residue at P2 of the ligands to the affinity was studied by using tripeptide (Gly-X-Arg) Sepharoses, and alanine was found to be more effective than glycine or valine. This conclusion was supported by a kinetic experiment in which Ki values of the corresponding soluble tripeptides (Ac-Gly-X-Arg) were determined. A significant decrease in Kd was observed when the ligand was elongated from dipeptide to tripeptide. However, Kd decreased only slightly when the ligand was elongated further. This suggests that a tripeptide is sufficiently long as a ligand. On the basis of these results, the mode of substrate binding of trypsin is discussed.


Bovine platelet myosin. II. Fluorescence of the tryptophanyl groups.

The intrinsic fluorescence of bovine platelet myosin was found to change upon addition of the substrate or its analogs in a manner similar to that of rabbit skeletal muscle myosin. The result suggests that the mechanism of ATP cleavage is analogous for myosins from diverse origins.


New fluorogenic substrates for alpha-thrombin, factor Xa, kallikreins, and urokinase.

Twenty peptide-4-methylcoumarin amides (MCA) were newly synthesized and tested as possible substrates for alpha-thrombin, factor Xa, kallikreins, urokinase, and plasmin. These fluorogenic peptides contained arginine-MCA as the carboxyl-terminus. Release of 7-amino-4-methylcoumarin was determined fluorometrically. Of these peptides, the following were found to be specific substrates for individual enzymes: Boc-Val-Pro-Arg-MCA for alpha-thrombin, Boc-Ile-Glu-Gly-Arg-MCA, and Boc-Ser-Gly-Arg-MCA for factor Xa, Z-Phe-Arg-MCA for plasma kallikrein, Pro-Phe-Arg-MCA for pancreatic and urinary kallikreins, and glutaryl-Gly-Arg-MCA for urokinase. Moreover, these peptide-MCA substrates were resistant to plasmin.


Structure of two glycoasparagines isolated from the urine of patients with aspartylglycosylaminuria (AGU).

The structures of two glycoasparagines composed of one mole each of N-acetylneuraminic acid, galactose, N-acetylglucosamine, and asparagine were determined by periodate oxidation, enzymatic degradation, and methylation analysis. The structures were NANAalpha2 leads to 3Galbeta1 leads to 4GlcNAcbeta leads to Asn and NANAalpha2 leads to 6Galbeta1 leads to 4GlcNAcbeta leads to Asn, respectively.


Skin replacement with Bioplast fibrin in Ophthalmology.

The study includes 40 cases of skin replacement performed by an ophthalmologist over a period of 4 years. An absorbable implant material, Bioplast fibrin, was used as a graft following the extirpation of 12 eyelid tumors, the treatment of eight fresh, destructive skin injuries, and the removal of deforming scars around the eyes, in 20 cases. The biocompatible implant provided barrier properties preventing infection or excessive fluid loss. The resorption rate was adjusted to 3-4 weeks. These grafts were gradually replaced by new epithelial tissue growing in from the periphery of the wound edge. The new tissue had the elasticity and cosmetic appearance of surrounding skin. Thus, small periorbital skin tumors can now be removed without the necessity of doing a split thickness skin graft to cover the defect.


Tolerance of mouse macrophages in vitro to barium sulfate used in orthopedic bone cement.

Barium sulfate, used as a radio-opaque marker in some orthopedic bone cements, has been shown to escape into the surrounding tissues. This may present a potential hazard. In particular, phagocytic cells may be exposed to relatively high internal levels of barium once the particles have been phagocytosed. Mouse peritoneal macrophages exposed to barium sulfate for periods up to 144 hr showed a marked cytoplasmic vacuolization from which they recovered only partially. Barium sulfate did not appear to damage the cell membrane as judged by lactice dehydrogenase release. In the relatively low doses and with the periods of exposure described here, barium sulfate does not appear to present a serious toxic hazard in the short term. It is possible, however, that longer exposures and larger doses may result in the death of phagocytic cells which have ingested barium sulfate.


Human platelet and fluorochemical interaction.

Since the fluorochemicals have become of interest for the development of artificial red blood cells, oxygenators, liquid breathing, and as a radiographic contrast medium, their interaction with biological substances is of importance. Fresh human platelets were placed in contact with four different fluorochemicals for a period of 50 min. The platelet function as measured by aggregation was determined before and after fluorochemical contact. Appropriate controls were also evaluated. No significant differences were found between the aggregation of platelets contacted with fluorochemicals and the aggregation of platelets from the same donor unexposed to fluorochemicals.


Clinical influences on bone cement monomer release.

Monomer losses for two self-curing acrylic cements were similar via laboratory serial weighing experiments. Both the P/L ratio and mixing duration substantially influenced subsequent monomer losses, but ambient temperature variation during mixing had little effect. Greater losses were encountered during the mixing and setting intervals than during the molding interval. Patient potential exposure to monomer occurs during the molding and setting intervals; therefore, handling procedures reducing losses in these intervals are important to the surgeon. The least monomer loss during both molding and setting occurred at the manufacturers' recommended P/L ratio, which strongly indicated the need to mix all contents supplied. Mixing loss increased with amount of spatulation. However, once the mass was well mixed (about 300 steady spatulations), no further decreases in the molding and setting interval losses were promoted by overmixing. Because of the lower monomer loss rate during the molding interval, postponed cement insertion may not be warranted in light of losing mechanical locking efficiency. The actual ramifications of a threefold reduction in potential patient exposure (3.5 down to 1.2 wt% of total monomer) via modified handling techniques have not yet been clinically evaluated.


Membrane permeability for inorganic phosphate ion.

The need for a more efficient removal of inorganic phosphate ions from the blood of uremic patients has led to the quest for blood-compatible semipermeable membranes with a high permeability for phosphate ions. Commercial hemodialysis membranes, various hydrogel-type membranes and a number of collodionbased charged membranes were compared. Positively charged collodion membranes were found most promising for future application in hemodialysis or hemoperfusion systems.


Open reduction of unstable thoracolumbar spinal injuries and fixation with Harrington rods.

The results of treatment of sixteen patients with unstable thoracolumbar spinal injuries are recorded. Early open reduction, stabilization with Harrington rods, spine fusion, application of a plaster jacket until consolidation, and early mobilization was the treatment. Distraction rods were used in twelve patients and compression rods, in four. Nine patients with incomplete paraplegia showed marked neurological recovery, while five with complete paraplegia regained only some sensation. Two patients had no neurological involvement. Solid fusion was achieved in fifteen patients after a minimum of three months of plaster-cast immobilization. In one patient stabilization failed. There was a loss of 5 degrees on average (range, 2 to 23 degrees) in the correction of the kyphosis. Lateral angulation after surgery did not occur. The treatment allowed easier postoperative nursing and early mobilization of the patient.


Spinal injury at the level of the third and fourth cervical vertebrae from football.

Acute traumatic lesions of the spine at the third and fourth cervical levels without associated fracture are not common. The eight lesions in this report occurred as a result of injuries sustained during tackle football. They included acute intervertebral disc herniation, anterior subluxation of the third cervical vertebra on the fourth, unilateral dislocation of the joint between the articular processes, and bilateral dislocation of the joints between the articular processes. The mechanism of injury was the use of the top or crown of the helmet as the primary point of contact in a high-impact collision when blocking, tackling, or head-butting. To avoid a seemingly inevitable increase in the incidence of these lesions occurring from tackle football, coaches and officials will have to modify the current techniques of blocking tackling, and head-butting.


Scoliosis in chickens.

Scoliosis developed in 55 per cent of sexually mature birds (68 per cent of male and 46 per cent of female birds) in a highly inbred line of chickens originally produced from white Leghorns. The curve could first be detected at five to six weeks of age and progressed until spontaneous fusion of the thoracic vertebrae occurred. Studies of these chickens indicated that abnormalities of growth and development of the spine are not the primary cause of the scoliosis. Preliminary studies of the paravertebral musculature also indicated that simple muscle imbalance is not responsible for the curve. Initial studies of collagen extracted from the scoliotic line of chickens showed it to be more soluble than similar collagen extracted from white Leghorn controls.


Herbert total knee prosthesis: combined laboratory and clinical assessment.

We tested the Herbert knee prosthesis, which was designed to restore intrinsic stability with limited degrees of freedom for rotation to severely damaged or deformed knees, in a knee simulator. These tests indicated a tendency for the prosthesis to fracture through the medial femoral housing after cycling for the equivalent of one to three years of normal use. In a clinical series of thirty-five knees treated with the prosthesis, there were five failures similar to those produced by laboratory testing. On the basis of this combined study, the Herbert prosthesis appears to have design characteristics that seriously limit its usefulness for long-term knee replacement. Testing in a knee simulator in this case appeared to be a valid predictor of clinical failure.


Femoral stem failure in total hip replacement.

Reported here are four fractured femoral components from a consecutive series of 200 total hip reconstructions. All four had been placed in patients who weighed ninety-one kilograms or more and who were more than 1.8 meters tall. In each patient, roentgenograms made prior to the time of failure of the prosthesis revealed roentgenographic lucency, which was interpreted as cement failure. Metallurgical examination revealed fatigue failure and some abnormality in each prosthetic stem. Review of all 200 total hip replacements suggested that there was failure to position the prosthesis in strong valgus in there four hips and in thirty others. In the four failures, the contributing influences of large size of patients, inadequate valgus positioning of the prosthesis, inadequate support by cement, and metallurgical inadequacies of the prosthesis used are discussed.


Deep infection following total hip arthroplasty.

Deep sepsis is a serious postoperative complication of total hip arthroplasty, causing additional suffering, loss of function, need for additional treatment, and possibly early death. In a series of sixteen patients, the only effective treatment was complete extirpation of all implants combined with appropriate long-term administration of antibiotics. In fifteen patients the original operative objectives were not achieved.


Multicentric giant-cell tumor of bone.

The presence of more than one distinct giant-cell tumor in the same patient is rare; seven cases have been reported in the literature. The present series involves eleven patients with thirty-five individual tumors. Multifocal giant-cell tumors may pose a diagnostic problem. It is difficult to distinguish a multicentric giant-cell tumor from a primary giant-cell tumor with metastatic spread. This problem is magnified when the second lesion is not noted at the onset or is metaphyseal in location. Moreover, these lesions present a therapeutic challenge to the surgeon. Multiple lesions tend to exhibit the same aggressive clinical behavior as a solitary giant-cell tumor. A high recurrence rate after curettage indicates that aggressive surgical management is necessary.


Arterial thromboembolism in patients receiving systemic heparin therapy: a complication associated with heparin-induced thrombocytopenia.

Arterial thromboembolism is a recognized complication of systemic heparin therapy. Characteristic of the entity is arterial occlusion by platelet-fibrin thrombi with distal ischemia occurring four to twenty days after the initiation of heparin therapy, preceded by profound thrombocytopenia with platelet counts in the range of 30,000 to 40,000 per cubic millimeter. The clinically apparent occlusion may be preceded by gastrointestinal and musculoskeletal symptoms that appear to be ischemic in origin, and might serve to warn the clinician of these complications. Previous reports of these phenomena as well as recent studies of the effect of heparin are reviewed. The common factor relating thromboembolism and thrombocytopenia is heparin-induced platelet aggregation. Appropriate treatment consists of discontinuation of heparin, and anticoagulation with sodium warfarin if necessary. Vascular procedures are performed as indicated.


Turnover of collagen in the adult rat after denervation.

Unilateral denervation of the hind limb in a group of adult rats prelabeled with radioactive proline induced a significant turnover of collagen in tendons, ligaments, menisci, and bones. After two or three months of disuse, there were significant losses (15 to 29 per cent) of old collagen from the four structures studied. Dilution of the radioactivity of the old collagen with new collagen involved partial to complete replacement of 3 to 20 per cent. The incomplete replacement of destroyed collagen with new collagen resulted in a net decrease of collagen mass ranging from 5 to 14 per cent. A significant turnover of collagen in two-year-old rats that showed little loss in collagen mass means that the new collagen produced would have fewer cross-links and would probably be weaker than the old, mature collagen.


Survival of articular cartilage after controlled impact.

Survival characteristics of forty-three specimens of living human bone and articular cartilage from the knees of eight renal-transplant donors were studied, using a drop-tower device. Autoradiography and light and scanning electron microscopy revealed no evidence of chondrocyte death or structural damage until stress levels of twenty-five newtons per square millimeter were reached, corresponding to strains on the order of 20 to 30 per cent and involving energy absorption of one millijoule per cubic millimeter. The data for strain rates of 500 and 1000 s-1 suggest that impact loads sufficient to fracture a femoral shaft of an automobile occupant are nearly sufficient to cause chondrocyte death and fissuring in the articular cartilage of either the knee or the hip if the load-bearing areas measure less than 500 square millimeters.


The ultrastructure of the growth plate in slipped capital femoral epiphysis.

Core biopsy specimens of the proximal femoral growth plate from three patients with slipped capital femoral epiphysis were studied by light and electron microscopy. In the resting zone, the cartilage matrix was composed of large, densely packed collagen fibrils. The cartilage matrix in the zones of chondrocyte hypertrophy where the slippage occurred contained only scattered fine collagen fibrils in a homogeneous ground substance. The change in composition of cartilage matrix in the distal region of the epiphyseal plate may predispose that region to slippage.


Double innominate osteotomy.

We performed double innominate osteotomy in twenty-five patients with acetabular insufficiency resulting from congenital dislocation of the hip and other lesions. Following iliac (Salter) osteotomy, the second osteotomy was carried out medial to the obturator foramen in the interval between the symphysis pubis and the pubic tubercle. In children more than six years old, adolescents, and adults, addition of the pubic osteotomy increased the amount of acetabular rotation and coverage of the femoral head that could be achieved. An additional benefit was that the femoral head could be shifted medially, decreasing the length of the femoral lever arm. The improvement in center-edge angle in the twenty-five patients averaged 27 degrees, and the acetabular index decreased an average of 19.5 degrees. The center of the head shifted medially an average of 1.5 centimeters. Hip stability was achieved in twenty-three of the patients.


The painful migrated ununited greater trochanter in total hip replacement.

The migrated painful ununited trochanter following total hip replacement can provoke a significant degree of functional disability. Although this condition is infrequently observed after total hip replacement, its occurrence causes definite problems for its operative management. A technique employing the trochanteric bolt for reattachment of the migrated painful trochanteric fragment is described. The results of this approach in five patients to date are relief from pain and decreased disability in all five. The factors promoting migration of the osteotomized fragment include the quality of the trochanteric bone, the stresses placed on the osteotomy site by the patient during the postoperative period, and the precise method of reattachment of the trochanter at the time of total hip replacement.


Joint débridement--a complement to high tibial osteotomy in the treatment of degenerative arthritis of the knee.

The management of unicompartmental osteoarthritis of the knee by high tibial osteotomy is enhanced by an associated joint débridement. A review of 120 patients who underwent the combined procedure, with follow-up to thirteen years, indicated that good or satisfactory results may be achieved in 82 per cent and that such results may be maintained over a prolonged period of review. This paper summarizes a long-term review of a series of one of us (D. L. M.), who since 1961 has practiced the combined procedure of tibial osteotomy and open joint débridement. The patient group was reviewed by him one year following surgery and then independently by the second author (R. P. W) in 1974, when 105 of the original 120 patients were available for detailed follow-up. Controversy surrounds the role of débridement when associated with osteotomy. This paper discusses both the rationale for and the results of combining these procedures. The over-all results confirm that these procedures are indeed complementary.


Cervical facet fusion for control of instability following laminectomy.

Cervical laminectomy may compromise the stability of the spine. Posterolateral facet fusion can be used to stabilize the spine after laminectomy and prevent progressive deformity. The procedure includes passing wires through drill holes in the articular processes and binding two longitudinal struts of bone to the posterior columns of the articular processes. Sixty-three p atients with cervical laminectomy and facet fusion were reviewed, and fifty-two of them were followed for one to seventeen years. The reasons for fusion were to control overt spinal instability and deformity or to eliminate motion which may contribute to spondylosis. Solid fusion occurred in fifty of fifty-two patients at a mean of 6.5 months and provided continuing stability without progressive deformity. Although facet fusion is a complex procedure, it provides secure stabilization, does not interfere with decompression, and permits early mobilization of the patient.


Treatment of sick sinus syndrome with permanent cardiac pacemaker. (Sick sinus syndrome and artificial pacemaker).

Twenty nine patients with sick sinus syndrome were treated from November, 1972 through July, 1976. Six cases had sinus bradycardia, 14 cases had sinoatrial block/sinus arrest and 9 cases had bradycardia-tachycardia syndrome. Twenty five patients received the implantation pacemaker with good result. There was found that an adequate pacing of the heart was effective for the control of the attack of tachyarrhythmia in the case with bradycardia-tachycardia syndrome.


Pseudotumor of the heart: subepicardial hematoma of the right atrium.

A 28-year-old man with a huge subepicardial hematoma of the right atrium, which is so rare that a review of the literature has failed to disclose similar case, is reported. Suspecting of rhabdomyoma, we excised free wall of the right atrium and a part of lateral wall of the superior vena cava. The excised part was reconstructed with expanded polytetrafluoroethylene (Gore tex). This synthetic material has a few merit and application of this one to the reconstruction in the venous system seems more promising. He was discharged with a regular sinus rhythm, normal heart size three months after the operation. The histologic examination of the excised material revealed amorphous blood clots and chronic granulation tissue containing hemosiderin-cells. The cause of the hematoma was not clarified even by microscopic examination.


Cor triatriatum associated with large atrial septal defect and partial anomalous pulmonary venous return. Case report.

A rare variant of cor triatriatum is presented with a large true atrial septal defect and partial anomalous pulmonary venous return into the right atrium. The correct diagnosis was made at the operation and abnormal left atrial septum was excised completely and a new interatrial septum was created with pericardial patch in such a position that the abnormally drained right upper pulmonary vein was left in the left atrium. It was thought to use the abnormal left atrial septum to close the atrial septal defect by excising only the right lateral border of this abnormal septum and resuturing it to the right atrial wall to close the true atrial septal defect. This thought could not be realized because of the small size of this abnormal septum and large size of the atrial septal defect. This technique can be realized in small or medium sized atrial septal defects associated with cor triatriatum.


Isolated mitral valve injury from non-penetrating cardiac trauma. Report of a case with successful repair.

Isolated mitral valve injury from non-penetrating cardiac trauma was low in incidence. A successfully operated case of a patient with acute mitral insufficiency from non-penetrating cardiac injury due to a traffic accident was reported and discussed. This isolated mitral valve lesion, of which the posterior leaflet was torn away from the annulus with intact chordae tendineae and papillary muscle, was very rare in the literature. And, particularly, the preoperative non-invasive findings such as echocardiogram and ACG were mostly useful and important in our case. This case was the fourth successful repaired case on blunt isolated mitral valve injury in the literature.


Ascending aorta to femoral arteries bypass without opening the abdominal cavity. Choice treatment in cases of complete occlusion of the infrarenal aorta.

In two cases which needed a revascularization of the inferior limbs, it was possible to utilize the subrenal aorta (the first case was affected by an infrarenal aortic occlusion; the second by an infection of a previously inserted aortofemoral graft), the AA. elected to perform a bypass with a dacron graft between the ascending aorta and femoral arteries according to the technique already proposed by Kaplitt. Having accomplished the proximal anastomoses to the ascending aorta through a midsternal incision, the graft was placed into a properitoneal tunnel down to both inguinal regions. This tunnel was obtained in the anterior abdominal wall by a blind blunt dissection entering the properitoneal space at the inferior end of the sternal incision. In this way the opening of the abdomen is avoided. On account of its poor risk, this procedure is advisable not only in cases of infrarenal aortic occlusion but almost in all aged and poor risk patients who require a revascularization of the inferior limbs.


Effects of multiplication stimulating activity (MSA) on AIB transport into myoblast and myotube cultures.

The effects of a somatomedian analog, Temin's multiplication stimulating activity (MSA), on amino acid transport into muscle cells have been characterized in a series of experiments on myoblasts and myotubes in culture. Addition of MSA to serum-starved L6 myoblasts increased the rate of aminoisobutyrate (AIB) uptake 50-150% within five hours. This early effect on transport was followed by increases in cell number, protein content and 3H-thymidine incorporation. Kinetic analyses indicated that MSA increased the maximal velocity of AIB uptake but had no effect on the KM for AIB. When myoblasts were allowed to fuse (and dividing cells eliminated by addition of 10(-4) M cytosine arabinoside) the AIB transport system(s) remained similarly responsive to MSA. In myoblasts and in myotubes, both the basal and MSA-stimulated rate of AIB uptake were sodium-dependent processes; little stimrulation occurred if sodium was absent from the labeling medium. Further suggesting the involvement of cations in response to hormone, MSA stimulated uptake of the potassium analog, 86Rb+, and increase net intracellular potassium in both myoblasts and myotubes. MSA was active at concentrations equivalent to in vivo levels of somatomedins; neither insulin nor growth hormone had any effect at or near physiological concentrations.


Popliteal artery entrapment. (Report of a case).

A case of popliteal artery entrapment syndrome caused by an anomalous gastrocnemius muscle is described. The diagnosis, made before operation, was facilitated mainly by the presence of a "hot knee" in the affected leg. The etiology of this clinical sign is described and its diagnostic value, especially in obscure cases is accentuated. In this respect the usefulness of thermometric study and of thermography is presented. The literature of the condition is reviewed.


Prognostic factors in peripheral vascular injuries.

A series of 73 patients suffering from peripheral vascular injuries is presented. The injury had been severe in most patients and associated injuries were present in a high percentage of cases. 46% of patients had long bone fractures, 52% had a major peripheral vein injured and 41% had peripheral nerve injuries. End to end anastomosis of the artery had been used in 51% of the cases and vein graft interposition in 46%. 71 patients survived the injury and 56 patients had a viable limb on discharge, or a success rate of 76.7%. Factors which weighed heavily on the prognosis are analyzed. The deleterious effect of the tourniquet is emphasized. Bleeding and shock were more severe in patients with an associated major peripheral vein injury. The latter had a definite influence on limb survival and was responsible for frequent thromboembolic complications. The associated fracture too weighed heavily on the prognosis, as well as infection, and loss of tissue. The associated injuries had a major influence on the final functional result. Function was poor in 10% of patients because of severe neurological deficits or extensive destruction and loss of tissue.


Free fibosomes and growth stimulation in human peripheral lymphocytes: activation of free ribisomes as an essential event in growth induction.

During the initial ten hours of growth in lymphocytes stimulated by phytohemagglutinin, the cells are converted from a state in which over 70% of all ribosomes are inactive free ribosomes, to one in which over 80% of ribosomes are in polysomes or in native ribosomal subunits. In this initial period, there was a neglible increase in total ribosomal RNA due to increased RNA synthesis, and abolition of ribosomal RNA synthesis with low concentrations of actinomycin D did not interfere with polysome formation. Therefore, the conversion is accomplished by the activation of existing free ribosomes rather than by accumulation of newly synthesized particles. The large free ribosome pool of resting lymphocytes is thus an essential source of components for accelerated protein synthesis early in lymphocyte activation, before increased synthesis can provide a sufficient number of new ribosomes. Free ribosomes accumulate once more after 24 to 48 hours of growth, when RNA and DNA synthetic activity are maximal. This reaccumulation of inactive ribosomes at the peak of growth activity may represent preparation for a return to the resting state where cells are again susceptible to stimulation. Activation of free ribosomes to form polysomes appears to involve modification of at least two steps: (a) dissociation of free ribosomes with stabilization as native subunits, and (b) adjustment of a rate-limiting step at initiation.


Transvenous instrumental dilatation for obstruction of the hepatic portion of the inferior vena cava.

In this report, we shall describe a new nonoperative method of treatment for membranous obstruction of the hepatic protion of the inferior vena cava. A specially designed instrument similar to a Tubbs' dilator was inserted through the peripheral vein and advanced to the portion of obstruction along the previously placed Fogarty catheter under fluoroscopic control. The fracture of obstruction was successfully performed in two patients.


Osmotic properties of human lymphocyte.

The osmotic properties of human lymphocytes isolated from 15 ml of venous blood were examined. Measurements of the permeability of the membrane to water under an osmotic gradient were also made. The Boyle-Van't Hoff relation held very well for the human lymphocyte when the cells were shrunken in hyperosmotic media to concentrations twice isosmotic. The volume of osmotically inactive material or "b" value averaged 32% of the mean corpuscular volume. These values were independent of temperature. Ponder's R ranged between 0.8 and 0.9. The average value for Lp, the hydralic coefficient was 0.46 mu/min atm +/- 0.02 (S.E.M.) at 25 degrees C. No significant effect of age, sex, or race was noted. The effect of temperature between 10 degrees C and 37 degrees C was measured and heats of activation between 11.1 and 17.4 kcal/mole were calculated with a mean of 14.1 kcal/mole +/- 1.6 (S.E.M.). Concanavalin A at 10 microgram/1.5 X 10(6) lymphocytes produced blastogenesis of 25% or more of the lymphocytes without clumping, agglutination, or toxicity. The mean corpuscular volume increased by 21% after 72 hours due to an increase in the "b" value which increased by 80%. The volume of free water remained constant. Histograms of the distribution of cell volumes showed that volume changes were uniform throughout the population with no evidence of agglutination of clumping. The significance of these results is discussed in the context of membrane fluidity and the state of intracellular water.


Gel filtration analysis of vanadium in Ascidia nigra blood cell lysate.

Fractions from a Sephadex gel filtration of homogenized Ascidia nigra blood cell lysate were analyzed for vanadium by atomic absorption spectroscopy. The results were unaffected by temperature from 4-21 degrees C, and by ionic strength in the range 0.09-1.0 M (NaCl). Appreciable loss of vanadium in the supernatant was experienced above pH 2.2. Experiments at pH 2.1 under anaerobic conditions show that the green chromogen and the vanadium-containing bands elute separately. Under these experimental conditions, the vanadium-containing species is of relatively low (congruent to 1,000) molecular weight.


Cytotoxicity of commonly used solvents at elevated temperatures.

At 43 degrees C (but not at 41 degrees C), organic solvents used to dissolve water-insoluble chemotherapeutic agents become themselves lethal to cells. This finding is not unique to Chinese hamster cells (HA-1); mouse mammary sarcoma cells (EMT-6) behave similarly. The solvent concentrations involved are in the range of those needed to make drug solutions. Hence experiments measuring drug-cell interactions at elevated temperatures must include controls which independently measure solvent effects.


Haemodynamics at rest and under effort in chronic arteriovenous fistulae (AVFs).

Latero-lateral femoro-femoral arteriovenous fistulae (AVFs) were surgically created in mongrel dogs. After 7-9 months during which the dogs were trained on a treadmill, devices suitable for recording arterial pressure and aortic and coronary flow were chronically implanted. Haemodynamic parameters of the dogs were controlled either at rest or after effort, keeping AVFs open or manually closed. The results, when statistically processed, showed that haemodynamic changes induced by occlusion of AVFs at rest and under effort are similar from a qualitative point of view, but considerably more marked after muscular exercise. Under effort the shunt index calculated rose to a higher extent than cardiac output. The decrease in heart rate after AVFs occlusion was significantly correlated with flow in the fistulae. However, the Nicoladoni-Branham phenomenon ought to be used for indirect evaluation of the shunt flow.


Use of homologous vein grafts for chronic hemodialysis.

The Authors propose using of homologous saphenous vein grafts, coming from a normal saphenectomy by stripping in patients affected by primary varicose veins. The graft is preserved in a particular solution at 4 degrees C in a normal refrigerator and transplanted in uremic patients, which have no more vessels suitable for creating a conventional arteriovenous fistula.


The effect of histamine on the growth of cultured fibroblasts isolated from normal and keloid tissue.

Cultured fibroblasts derived from human keloid tissue are presented as a possible model system for studying the genetic regulation of cell growth. Histamine is shown to have a marked effect on the growth of cultured fibroblasts. A small increase in growth rate is seen during the log phase of the culture cycle and a 50% increase in cell number is observed during the plateau phase. Differences in the extent of growth stimulation are observed between strains isolated from different individuals. While most strains showed approximately 50% stimulation, a few were not stimulated and some strains gave a 100% or greater increase in cell number due to histamine. This phenotypic difference in extent of growth stimulation in response to histamine cannot be attributed to the gene or genes for keloid formation. However, elevated levels of histamine in vivo may be a contributing factor to the abnormal cell growth observed in this disorder. The extent of growth stimulation due to histamine decreases with repeated subculturing.


Mass isolation ofpolytene nuclei from Chironomus salivary glands.

In this paper we describe a method for the rapid mass isolation of polytene nuclei from Chironomus salivary glands. The procedure for the isolation of glands involves 5 principal steps; (a) freezing Chironomus larvae in liquid propane; (b) breaking open frozen animals in a pre-cooled mortar; (c) thawing the fragments in sucrose medium, free of divalent cations; (d) pressing the suspension of broken animals through a system of regularly spaced capillary constrictions of free organs; and (e) enrichment of glands by differential sedimentation and removal of contaminating material under a dissecting microscope. The nuclear isolation procedure is a large scale modification of a method previously described by Robert, using digitonin as a non-ionic detergent to solubilize cytoplasma and secretion without affecting the nuclear membrane. Nuclei obtained by this method show structural integrity and an unchanged chromosomal banding pattern. Their incorporation of UTP is within the same range as reported by other authors for nuclei by hand dissection.


Influence of the time in culture on cellular and neuronal properties of neuroblastoma x glioma hybrid cells. With an appendix, mathematical description of the kinetics of the loss in cell volume.

The stability of a clonal mouse neuroblastoma x rat glioma hybrid cell line was examined. Cell volume and cellular content of DNA and protein were measured as functions of the passage number. They decreased with the number of serial subcultivations. Cellular volume was linearly related to cellular DNA and protein. Thus, measurements of cell volume can be used to monitor the loss of DNA from hybrid cells. After about 60 passages a stable population of hybrid cells arose, as judged by the constancy of cellular volume and by the decreased coefficient of variation of the cell volume distribution. A mathematical model for the kinetics of the simultaneous loss of cellular volume, DNA and protein is introduced. Several neuronal properties were investigated. The specific activity of the neurotransmitter enzyme choline acetyltransferase decreased by more than 50% during 56 passages. After 70 subcultivations, the hybrid cells were still capable of extending processes, action potentials could still be elicited electrically or by iontophoretic application of acetylcholine, and the cells still responded to prostaglandin E1 as they do at low passage number.


Effects of colchicine and vinblastine on the phytohaemagglutinin-induced transformation of lymphocytes.

The effects of 2 microtubular-disruptive drugs, colchicine and vinblastine, on the phytohaemagglutinin (PHA)-induced blast transformation and mitogenic stimulation of human lymphocytes were studied. Both drugs markedly inhibited cell growth and DNA synthesis and lowered the mitotic index. No microtubules were seen with the electron microscope in cells treated with PHA plus colchicine or vinblastine. Moreover, the PHA-induced development of all organelles was partially inhibited by these drugs, especially that of the Golgi complex. As compared to cells treated with PHA alone, the dictyosomes were fewer, not so clearly localized in one area of the cytoplasm, and contained a decreased number of cisternae and an increased number of vacuoles. These results indicate that cytoplasmic microtubules play an important role in the PHA-induced blast transformation and mitogenic stimulation of lymphocytes. It is suggested that the microtubules function in the structural organization of the cell and particularly the Golgi complex. In the drug-induced absence of microtubules this and other organelle systems do not respond as usual to PHA stimulation, which could largely explain the decreased cell growth. This in turn suggests that lowered mitotic activity is a result of inhibition of cell growth, as a critical amount of G1-associated cell growth is believed to be required for the initiation of DNA synthesis and thus mitosis.


Changes in the surface properties of rabbit polymorphonuclear leucocytes, induced by bacteria and bacterial endotoxin.

Rabbit peritoneal polymorphonuclear leucocytes were induced to aggregate by a variety of bacterial species. In the absence of serum, Gram-negative bacteria were more effective at inducing aggregation than Gram-positive. The most effective micro-organism tested, Acinetobacter sp. 199A, was readily phagocytosed and also induced extracellular secretion of the granule enzymes peroxidase and lysozyme. Isolated endotoxin from this bacterial species was highly effective in inducing aggregation and granule enzyme release. Endotoxin-induced aggregation was associated with a large increase in the amount of lactoperoxidase-catalysed iodination of surface protein. Only one iodinatable protein was detected, of molecular weight 150 000. It is postulated that phagocytosis of Gram-negative bacteria, followed by granule enzyme release, accelerates the rate of membrane recycling and that this brings new adhesive protein to the surface more rapidly.


A light- and electron-microscope study of nuclear structure throughout the cell cycle in the euglenoid Astasia longa (Jahn).

The structure of nuclei of Astasia longa in synchronized cultures was examined at the light- and electron-microscope levels. Three types of nuclei, differing mainly in chromatin conformation, were observed during interphase and were tentatively classed in the G1, S and G2-periods. The fibrillar nucleolar regions exhibited a most complex organization and appeared to consist of convoluted, coarse filaments or nucleolonemata approximately 0.15 micrometer in diameter. Chromosome condensation was evidenced first by the longer, thicker profiles of chromatin observed in late prophase. Furthermore, the nucleolus, that persists throughout mitosis, began to elongate at late prophase. Furthermore, the nucleolus, that persists thorughout mitosis, began to elongate at this stage, simultaneously with the appearance of short, unoriented profiles of intranuclear microtubules. Chromosome condensation was complete by mid-metaphase and the nucleolus was elongated into a cylindrical shape with irregular extremities. Microtubule profiles were longer than in prophase; they were now oriented parallel to the nucleolus and frequently lay closely appressed to its sides. In anaphase, the chromosomes segregated into 2 groups, one towards each extremity of the dumb-bell-shaped nucleolus. The telophase chromosomes assumed a random orientation with respect to the still intact nucleolus. Throughout the division stages the persiting nucleolus maintained its ultrastructural organization and consisted partly of conspicuous nucleolonemal profiles which tended to be oriented along the major axis of this organelle. Nucleolar separation into 2 fragments occurred late in telophase and was followed by a reformation of daughter nuclei and initiation of cell fission during cytokinesis.


Structural cross-bridges between microtubules and mitochondria in central axons of an insect (Periplaneta americana).

The distribution of microtubules and mitochondria in central axons of an insect (Periplaneta americana) is assessed by comparison between counts on micrographs and computed axon random 'models'. These studies show that the observed multiple association of microtubules with individual mitochondria is statistically highly significant. Electron micrographs of thin sections show that linkage is effected by physical cross-bridge, possibly comprising components from the microtubule and mitochondrion. Linear particle arrays are described on the outer mitochondrial membrane in freeze-fracture replicas, and tentatively related to the bridges seen in thin sections. The results are discussed in terms of proposed roles of microtubules in neurons and other cells.


Ultrastructure of the adrenal cortex in frozen thin sections.

Pieces of both unfixed and fixed rat adrenal cortex were frozen and cut with a cryoultramicrotome. In unstained frozen sections of unfixed adrenals patches of heterochromatin were seen in the nucleus, while numerous round uniformly dense structures, the mitochondria, could be identified in the cytoplasm. Lipid droplets appear as small ligh round areas. Staining the sections with potassium permanganate, phosphotungstic acid, or uranyl acetate, or immersing them in glutaraldehyde, increased the contrast of cell organelles. In frozen sections of fixed material, membranes became visible in negative contrast. Mitochondria display vesicular cristae, whereas the Golgi complex, lysosomes and peroxisomes are easily recognizable. The possibility of cutting frozen sections of unfixed material with reasonable morphological preservation allows the fine-structural localization of steroids in adrenal cells after applying autoradiographic emulsion to the sections.


Behaviour of kinetochore fibres in Haemanthus katherinae during anaphase movements of chromosomes.

A laser light source along with a new method of preparing endosperm cells of Haemanthus katherinae for differential interference contrast (DIC) microscopy has led to increased visibility of kinetochore fibres. Little information is available concerning the behaviour of these fibres during anaphase in living cells. In metaphase, kinetochore fibres are seen as distinct bundles of microtubules, here referred to as 'filaments', extending from the kinetochore to the 'diffuse' pole. They possess an apparent globular substructure which corresponds to the moving 'particles or states' described previously from ciné films. In early anaphase, the filaments of each kinetochore fibre lose their parallel orientation characteristic of metaphase and splay out so that the more peripheral filaments intermingle with those of other kinetochore fibres. This process begins at the poles and proceeds as a wave toward the kinetochores as chromosomal movement progresses. This behaviour has been examined in relation to a number of proposed models for the mechanism of chromosome movement and has been found to place some constraints on some models but to be consistent with any model that hypothesizes that chromosomes move as a consequence of cumulative cohesive lateral interactions of microtubules.


Localization of histone gene transcripts in newt lampbrush chromosomes by in situ hybridization.

Denatured 3H-labelled DNAs containing histone gene sequences originating from the echinoderms Psammechinus miliaris, Echimus esculentus and Strongylocentrotus purpuratus have been in situ hybridized to RNA transcripts on newt lampbrush chromosomes. Autoradiographs of the hybridized lampbrush preparations show labelling restricted to four or fewer lateral loop pairs all lying within the heteromorphic regions of chromosome I, also one or two loop pairs on chromosome VI, one loop pair on chromosome X and one loop pair on chromosome XI. For oocytes from a single newt, coincident label distribution is found with DNA's of diverse echinoderm origin; however different newts show some specific individual diversity in label distribution, including heterozygosity in the case of loops on bivalents VI and X. The more conspicuously labelled loops, particularly those on chromosome I, show a pattern of labelling which is explicable if the newt histone DNA sequences are confined to short intercepts of lateral loop axis. Transcription is initiated prior to the histone DNA sequences, proceeds through the histone DNA sequences, and beyond, and the histone RNA sequences are cut from the transcripts before the termination of transcription.


Development of a chemical use classification system to facilitate reporting under the Toxic Substances Control Act.

A classification system was developed to enable manufacturers and processors of industrial chemicals to report categories of proposed categories of use of such chemicals to the Environmental Protection Agency in accordance with the Toxic Substances Control Act. To accommodate the two aspects of chemical use (i.e., function and application), a faceted classification scheme was designed. The function facet contains categories denoting the action for which a chemical is specially fitted or used, for example, adhesives or fuels. The application facet contains categories denoting the process or product in which a chemical is used, such as synthetic rubber manufacture. Linking these two facets in a single notation code provides a comprehensive indication of a chemical's use or uses. A variety of existing relevant classification schemes and reference tools were used as input sources for the chemical use classification. The practicability of the classification system was tested using a small sample of manufacturing and processing companies.


CHEMFILE: an in-house information system for the chemical indexing of Abstracts on Health Effects of Environmental Pollutants (HEEP).

The inclusion of a Chemical Abstracts Service (CAS) Registry Number index in HEEP has led to the need for a special database designed to link substance names with their appropriate CAS chemical compound Registry Numbers. Begun in 1968 as a tape record with batch mode updates and few record modification capabilities, the information system, which we call CHEMFILE, has evolved to its current form of disk storage with on-line access for file maintenance.


Database development in a regulatory agency.

A general discussion of the history and problems associated with the collection of information and the development of a database in a regulatory agency is presented. The proceedings of the U.S. Consumer Product Safety Commission for obtaining chemical formulation information for specified consumer products is discussed. Guidelines for database administrators faced with data collection activities in a regulatory agency are provided.


[Replacement of the extra-hepatic common bile duct in the dog by an elastomere silicone prosthesis. Its possible application in biliary surgery].

From an experimental study of the prosthetic replacement of the common bile duct in the dog by an silicone elestomere prothesis, according to the technic of double intubation with a 2 1/2 year follow up in the oldest cases, and complete reconstitution of a well-structured new bile duct, the author propose using a similar prosthesis in biliary surgery: --firstly, the carcinoma of the bile ducts, using an internal prosthesis hepatico-gastric, hepatico-jejunal or duodenal, which is eliminated internally; --secondly, in stenosis or operative wounds of the bile ducts, using either removable tutor prosthesis, or segmental prostheses lost internally.


[Results of a series of 100 highly selective vagotomies for duodenal ulcer (follow up of 6 months to 5 years) (author's transl)].

The authors analyse a series of 100 highly selective vagotomies for duodenal ulcer; 92 operated patients were followed up for 6 months to 5 years. The mortality was nil, the digestive sequelae were rare or mild. The recurrence rate was 4.4 p. cent and the proportion of good or very good results according to Visick's classification was 87 p. cent. The authors emphasise the necessity for broad dissection of the cardia for complete vagotomy.


[Comparative anatomical result of conservative treatment and surgery in severe recent sprains of the ankle (author's transl)].

Severe recent sprains involving the lateral ligament of the ankle have been the object of numerous publications in recent years. Most authors have recommended the extension of the indications for open surgery. This lesion which was previously treated by immobilisation or even immediate physiotherapy is now operated on by numerous surgeons. In view of the very subjective character of the patient's opinion, and of the opinion of surgeons, it seemed logical to compare the radiological result in two series of similar severity operated on or treated by simple plaster immobilisation. One may note that the results observed are very similar, even when the accident gives rise to considerable separation of the tibio-talus joint line. Perhaps the figures published here will contribute to make surgery less often indicated.


[Original surgical technic for the treatment of flail chest (author's transl)].

Solid internal fixation of fractures of the ribs and thorax producing a flail chest is described using a new technic which permits early mobilisation of the patient, immediate spontaneous respiration, abolition of pain, early respiratory physiotherapy, and reduces the danger of respiratory complications due to artificial ventilation, and permenent sequelae due to a secondary deformity of the thoracic cage. Our experience of the method has permitted us to determine its indications and limits.


[Enzymatic changes in the lymph in the thoracic duct and right lymphatic duct during extracorporeal circulation in the dog (author's transl)].

The authors analysed the various enzymes in the lymph of the thoracic duct and the right lymphatic duct in a series of 15 dogs submitted to extracorporeal circulation, the experimentors noted a series of diffuse cellular lesions which involved transiently the main organs. This lesion seems only to occur at first; independent of the duration of the by-pass, probably due to hypoxia following the rapid and massive introduction of priming. Our conclusion from this research is that lymph analysis is more revealing for knowledge of enzyme behaviour than blood analysis. A differential study of lymph in the right lymphatic duct and in the thoracic duct is surprisingly much less important.


[Stenosing odditis: diagnosis and treatment. Report of 109 cases (author's transl)].

Stenosing odditis represents only 4.5 p. cent of all benign lesions of the extrahepatic bile ducts. Their diagnosis is made by peroperative radiomanometry, but clinically they are suggested by a past history and serious clinical signs. The pancreatic involvement is rarely macroscopic (10 p. cent of cases of which 5 p. cent are severe) and acute pancreatitis due to stricture of the sphincter without gall stones is exceptional. Associated biliary lesions are frequent; in 50 p. cent of cases, of lithiasis of the common bile duct or pancreatitis, in 66 p. cent of cases of residual odditis. The treatment is surgical. Sphincterotomy should be reserved for young subjects with a slightly dilated common bile duct, or when necessary to extract a gall stone from the lower end of the bile duct. Biliary by pass operations are all the more indicated when the patient is elderly or the common bile duct more dilated. Local complications are the most frequent and the most serious after sphincterotomy; the local complications of biliary by pass operations are usually very simple. The late results of biliary by-pass operations are better than those of sphincterotomy, which confirms that the pancreatic complications of odditis are rare or well tolerated. The presence of chronic pancreatitis in association is not an aggravating factor.


[Surgery of aneurysm of the thoracic aorta. Operative results in 47 cases (author's transl)].

The authors report personal experience of surgical treatment of 47 aneurysms of the thoracic aorta, showing that the symptoms, the etiology, the treatment and the prognosis are variable depending on the site of the aneurysm. One may note regression of syphilis as a cause and an increase in the number of degenerative and traumatic aneurysms. In aneurysms of the ascending aorta, total replacement of the ascending aorta with reimplantation of the coronary arteries, according to a simplified technic, seems to give the best immediate and long term results.


[Hepatic adenoma and oral contraceptives (author's transl)].

The authors report a new case of hepatic adenoma apparently related to oral contraception continued for more than 9 years with a pill containing mestranol. The clinical presentation suggested an attack of hepatic colic with swollen gall bladder. The preoperative diagnosis of a tumour of segment VI of the liver was made by radiological examination of neighbouring organs. Hepatic arteriography, hepatic radioisotope scan using technetium phytate and echotomography. Surgical removal of segment VI confirmed by histological study showed that it was an adenoma with multiple foci, associated with hepatic involvement. One of the tumours was the site of central included hemorrhage, responsible for the clinical syndrome. In connection with this case the authors review the possible relationship between hepatic adenoma and oral contraception.


[Peroperative cholangiography in liver trauma (author's transl)].

Peroperative cholangiography is the simplest means of assessing pedicular lesions situated in the depth of a traumatic breach in the liver. Its interest is illustrated by a series of 13 cholangiographies which greatly facilitated the therapeutic indications, conservative operation or partial liver removal depending on the lesions encountered. Its use should be more widespread and should reduce the frequency of reoperations following initially inadequate surgical exploration.


[Treatment of post-traumatic dislocation of the patella. Critical study of 29 cases (author's transl)].

The treatment of post-traumatic dislocation of the patella depends on careful examination. One should propose surgery in most cases, for not only one may leave a foreign body within the joint, but above all correction of the extensor apparatus is necessary in more than 50 p. cent of cases, to avoid a recurrence. The quality of the results depends on the preoperative analysis of the knee. Our study of 29 cases confirmed this.


[Eosinophil ileitis (author's transl)].

Eosinophilic ileitis is observed mainly in three coastal areas: Holland, Japan and Brittany. It presents in the form of a parietal inflammation, stenosing the intestinal lumen or a sessile tumour of limited volume. The symptoms are generally those of appendicitis but a past history of allergy and the discovery of eosinophilia greater than 10 p. cent may lead to the diagnosis of eosinophilic granuloma which only histology can confirm. Surgical treatment consists of segmental resection of the small intestine. The pathogenesis of the granuloma, which was for long attributed to the presence in the wall of the intestine of ascaris larvae, is at present debated. Are there non-parasitic eosinophilic granulomas? The case reported here is perhaps an example.


Determination of theophylline and its metabolites by liquid chromatography.

A high pressure liquid chromatographic assay has been developed for the separation and quantitation of theophylline and its metabolites (1-methyl uric acid, 3-methyl xanthine, and 1,3-dimethyl uric acid), theobromine, and dyphylline in biological fluids, viz. human serum, urine, and saliva. The serum has been rendered protein-free by passage through a filter with a nominal molecular weight limit of 10,000. The filtrate is injected onto a reverse-phase column and the separation achieved by utilizing a polar mobile phase and dyphylline (dihydroxypropyl theophylline) as the internal standard. The results for two normal subjects are included to illustrate the applicability of the technique.


Studies on the pathogenesis of the incomplete forms of androgen resistance in man.

The affinity and turnover of the specific dihydrotestosterone binding protein have been assessed in fibroblasts cultured from genital skin from a variety of control subjects and from 4 patients with incomplete hereditary male pseudohermaphroditism due to androgen resistance (incomplete testicular feminization and Reifenstein syndrome). Whereas the amount of dihydrotestosterone binding in the 4 mutant cell strains is low, both the affinity of the protein for dihydrotestosterone as assessed by the concentration at which half-maximal binding occurs (averaging 0.2 nM) and the turnover of the binding protein (average half-life of 11--13 h) are within the normal range. Since no qualitative abnormality could be detected, these data suggest that the mutations in these two disorders affect the synthesis of the dihydrotestosterone binding protein.


Differential effects of L-dopa and apomorphine on glucagon secretion in man: evidence against central dopaminergic stimulation of glucagon.

In 6 normal subjects, L-dopa (500 mg PO) and apomorphine (0.6 mg sc) increased circulating growth hormone and suppressed prolactin levels in a parallel and quantitatively similar fashion, but only L-dopa induced a rise in plasma glucagon, glucose, and insulin levels. The failure of apomorphine to affect glucagon secretion, despite a substantial effect on growth hormone and prolactin, was also observed in insulin-dependent diabetics known to exhibit A-cell hyperresponsiveness to various stimuli. In view of the highly dissimilar molecular and pharmacologic characteristics of L-dopa and apomorphine, these data do not exclude a local dopaminergic effect of L-dopa at the pancreatic level, but strongly militate against a central dopaminergic pathway for glucagon stimulation.


Anti-insulin IgE in diabetics.

Anti-insulin IgE and IgG were estimated in sera of diabetic patients. Using a paper radioimmunosorbent technique, detectable titers of anti-insulin IgE were found in all insulin-treated diabetics who were non-allergic to insulin. Patients with generalized insulin allergy, and immune-type insulin-resistance had higher titers of anti-insulin IgE. Anti-insulin IgG was present in all insulin-treated patients. The titers were significantly higher in insulin-resistant diabetics. Four of the 12 cases with insulin allergy had undetectable anti-insulin IgG titers. The ratios of 125I-insulin bound by IgE and IgG were significantly higher in 11 (91%) patients with systemic insulin-allergy. It is suggested that a relative excess of anti-insulin IgE may be associated with the insulin allergic state.


The placental transfer of propylthiouracil, methimazole and carbimazole.

The placental transfer of 35S-labelled methimazole (MMI), carbimazole and propylthiouracil (PTU) has been examined in the rat in late pregnancy and in patients undergoing therapeutic abortion. Although rapid equilibrium of fetal and maternal serum radioactivity (FS:MS ratio 1:1) occurred after iv administration of 35S-carbimazole or 35S-MMI in rats, a persistent fetal to maternal ratio of less than one was observed after 35S-PTU administration. Results from human studies after a single oral dose indicate that, as in the rat, the placenta appeared to be more permeable to 35S-MMI than to 35S-PTU as shown by the marked difference in fetal serum:maternal serum ratios and amounts accumulated in the fetus. Localization of radioactivity in the human fetal thyroid was also observed after administration of 35S-labelled MMI, carbimazole or PTU.


Cushing's syndrome associated with galactorrhea, amenorrhea, and hypothyroidism: a primary hypothalamic disorder.

A 19-year-old woman presented with a unique constellation of endocrinopathies, including Cushing's disease, post-partum galactorrhea, hypothalamic hypothyroidism and hypothalamic amenorrhea. There was no evidence of granulomatous or neoplastic disease in pituitary or hypothalamus. The potential role of excess glucocorticoids and disturbances in normal hypothalamic regulation of anterior pituitary function in the pathophysiology of this syndrome is discussed.


Serum albumin and antibodies in the diagnosis of thyroid cancer.

Anti-thyroglobulin antibodies, anti-thyroid microsomal antibodies, serum thyroglobulin, and carcinoembryonic antigen were assayed in sera of patients with a history of thyroid irradiation and in patients with thyroid cancer. In irradiated patients, the frequency of positive results for each test was increased above the frequency found in a control population, with a significant increase at P less than .05 for TGHA and TG levels. However, the tests (with the exception of serum thyroglobulin) did not clearly segregate irradiated patients with benign or malignant lesions from those with no clinically detectable abnormalities. Elevations of serum thyroglobulin above 300 ng/ml were found only in patients with thyroid cancer, but in these patients the diagnosis was usually clinically obvious.


The effect of flutamide on testosterone metabolism and the plasma levels of androgens and gonadotropins.

Flutamide, a nonsteroidal antiandrogen, was given to 11 men with prostate cancer, in doses of 750 to 1500 mg daily for 0.5--7 months. Four patients had a clinical remission and seven showed no response. All the patients showed a profound change in the peripheral metabolism of testosterone: markedly increased conversion to androsterone (A) and correspondingly decreased conversion to etiocholanolone (E); the A/E ratio rose to levels never before observed consistently in any group of healthy or diseased humans. This change was probably due to alteration by flutamide of the relative activities of steroid 5alpha and 5beta reductase in favor of the former. 24-Hour mean plasma testosterone was increased in five of the six patients studied for this parameter, for the group as a whole, testosterone rose from 279 ng/dl to 484 ng/dl (P less than .05). 24-Hour mean values for plasma dihydrotestosterone, dehydroisoandrosterone, LH and FSH showed no significant change, for the group as a whole, in the same six patients. Since flutamide did not change the metabolic clearance rate or volume of distribution of testosterone tracers, the increased plasma levels of the hormone were probably due to increased production.


Cyproheptadine inhibition of stimulated plasma renin activity.

Plasma renin activity (PRA) was stimulated by oral frusemide (60 mg) in 4 normal male subjects. Cyproheptadine (Periactin), a serotonin antagonist, was then administered (2 mg orally four times daily) for 7 days and the PRA response to frusemide re-evaluated in the 4 subjects. A highly significant mean inhibition (P less than 0.01) of frusemide stimulated PRA was demonstrated after cyproheptadine administration. Our results show that serotonin, presumably acting via central pathways, may play a role in renin regulation and that this pathway can be inhibited by cyproheptadine.


Efficacy of intravaginal and intranasal administration of micronized estradiol-17beta.

Absorption of micronized 17beta-estradiol (E2), after intravaginal administration of 1 mg dose, suspended in saline, is extremely rapid and sustained. A mean peak increment of circulating E2 concentrations of more than 110 times the basal level is achieved at 2 h and remains elevated more than 6 times the basal level even at 24 h. Increments in estrone (E1) are smaller and slower than those of E2 with a mean peak concentration of less than 10% of E2 and remain 3 times the basal level at 24 h. With 0.5 mg dose, the incremental changes in E2 and E1 as well as the degree of gonadotropin suppression are essentially the same. In contrast, intranasal administration of E2 of 1 mg dose induces a rapid but short-lasting increase in both serum E2 and E1 levels. The mean increments of E1 exhibited a higher and sustained elevation with a rise in mean E1/E2 ratio well above unity beginning 1 hr after intranasal application. These findings indicate intravaginal but not intranasal routes of E2 absorption are quantitatively much greater and circumvent the local conversion of E2 to E1 observed after oral administration of E2, and thus represent a practical and highly effective means of delivering E2 into the circulation.


Inhibition of exaggerated gastrointestinal glucagon responses in chronic pancreatitis by somatostatin.

Oral glucose administration caused an exaggerated release of cross-reacting gastrointestinal glucagon-like immunoreactivity (GLI) and a slight early rise in immunoreactive glucagon (IRG) concentration in patients with chronic pancreatitis, who have impaired insulin release. Intravenous administration of 200 microgram of somatostatin, followed by infusion of 200 microgram over 2 1/2 h, abolished the GLI and insulin responses, but did not change glucose tolerance. This contrasts with the relatively minor effects of somatostatin on GLI responses in control subjects where the clear deterioration in glucose tolerance may relate to inhibition of insulin release.


Immunoreactive luteinizing hormone, follicle stimulating hormone and their subunits in tissue culture media from normal and adenomatous, human pituitary fragments.

Fragments from 4 human pituitaries removed at surgery from one gonadectomized man and three women (one with Nelson's syndrome, one with Forbes Albright syndrome and one with chromophobe adenoma) were grown in tissue culture. The tissue culture medium was changed at weekly intervals, pooled and applied to a Sephadex G-100 column for gel filtration. In each eluate luteinizing hormone (LH), follicle stimulating hormone (FSH), alpha subunit and the beta subunits of LH and FSH were measured by specific radioimmunoassays. For comparison the pituitary standard LER 907 was similarly studied. LH and FSH were measurable in all studies. LH eluted over a broad area whereas FSH eluted as a much sharper peak. In all culture media and in LER 907 large quantities of alpha subunit were detected. The beta subunits of LH and FSH were not present in the LER 907 standard. LHbeta subunit was present in the culture medium of the pituitary fragments from the castrated man and from the women with Nelson's syndrome and Forbes Albright syndrome but not in that of the woman with chromophobe adenoma. FSHbeta subunit was detectable only in the latter case.


Renin-renin substrate kinetic constants in the plasma of normal and estrogen-treated humans.

The renin-renin substrate Michaelis constant (Km) and maximal velocity (Vmax) were determined in the plasmas of normal subjects. The mean Km was 0.7 microgram/ml. Under these conditions, the in vitro reaction of renin with physiologic concentrations of renin substrate will proceed at only 70% of its maximal velocity. Following estrogen administration, Km doubled to a value of 1.3 microgram/ml. Vmas increased by 81%. Analysis of the changes induced in the in vitro reaction velocity demonstrated that estrogen-induced acceleration of the renin reaction is dependent upon both an increase in renin substrate concentration as well as an increase in Vmas. The latter appears to be quantitatively more important. These findings suggest the emergence of modifying factors in the renin-renin substrate interaction following estrogen administration.


Effect of starvation on the production and metabolism of thyroxine and triiodothyronine in euthyroid obese patients.

The metabolic clearance and production rates of thyroxine (T4) and triiodothyronine (T3) were measured in 9 obese euthyroid patients prior to and during prolonged starvation. The metabolic clearance rates (MCR) and serum concentrations of T4, and, therefore, the metabolic degradation or production rates of T4 were unchanged during starvation. Serum T3 concentrations decreased strikingly during starvation, from 145 +/- 7 ng/dl (mean +/- SE) to 66 +/- 9 ng/dl (P < 0.001), while the mean MCR of T3 was unchanged, with the result that T3 degradation or production rates were markedly decreased (36.4 +/- 4.5 μg/d vs. 11.2 +/- 0.7 μg/d; P < 0.001). These findings suggest that the decrease in serum T3 concentration observed during starvation results from a decrease in the peripheral conversion of T4 to T3.


Failure of L-tryptophan to stimulate prolactin secretion in man.

The effect of oral L-tryptophan (90 mg/kg BW) on prolactin secretion in eight normal women studied either in the early or late follicular phase of the menstrual cycle was compared to the effect of a placebo alone. Plasma prolactin levels were measured before and at frequent intervals over a period of 240 min after the administration of the amino acid or placebo. Plasma free L-tryptophan concentrations were determined prior to and 60 min after ingestion of the amino acid in two of the women. Despite a 25-fold increase in plasma free L-tryptophan levels following the administration of this amino acid, the prolactin response to L-tryptophan was not significantly different from a placebo.


Metoclopramide increases plasma aldosterone concentration in man.

Plasma Aldosterone (PA) response to metoclopramide (10 mg i.v.) was studied in 11 normal, 2 hypophysectomized subjects and in one patient with bilateral adrenal hyperplasia. All the subjects were kept on a normal sodium and potassium intake. Four normal subjects were pretreated with 1 mg of dexamethasone in order to inhibit endogenous ACTH. In all subjects metoclopramide elicited a prompt rise of PA comparable to that obtained with angiotensions or ACTH. No significant change of blood pressure, serum electrolytes, plasma renin activity, Plasma Cortisol (PC) was detected. The lack of PC response to metoclopramide and the PA increase in dexamethasone pretreated subjects rule out an ACTH mediated effect. The increase of PA in hypophysectomized subjects, in whom metoclopramide did not stimulate any prolactin release, rules out a prolactin mediated effect. Metoclopramide increases plasma aldosterone concentration probably via a direct action on the adrenal glomerular zone or throught another unknown mechanism.


Detection of circulating antigen during acute infections with Toxoplasma gondii by enzyme-linked immunosorbent assay.

The serodiagnosis of toxoplasmosis is usually based on demonstration of antibodies by means of different serological methods. However, for confirmation of active toxoplasmosis, examination of paired sera is still needed. In this study a description is given of a sensitive enzyme method (enzyme-linked immunosorbent assay) with which it is possible to detect circulating antigens during the acute stage of mouse and human toxoplasmosis. Preliminary investigations of human sera suggested that circulating antigens are only found during a short period (active phase) of the toxoplasma infection and that they can be found in cases of fresh infections as well as during reinfections. The possible clinical relevance is discussed.


Nosocomial urinary tract infections caused by two O-serotypes of Providencia stuartii in one hospital.

Providencia stuartii nosocomial urinary tract infections occurring in the same hospital over an 18-month period of retrospective study were shown, by serotyping and biotyping, to have been caused by two endemic strains. Two episodes, involving 38 patients in one ward and 11 patients in another, were caused by a mannitol-positive strain of serotype O55. Transmission of the strain through the movements of one patient appeared to have been the basis for the introduction of the agent from one ward to the other. In another episode, involving two patients in a third ward, the infections were caused by a mannitol-negative strain of serotype O49. The study demonstrated the usefulness of serotyping and biotyping in epidemiological studies of infections caused by P. stuartii.


Comparisons of Venezuelan encephalitis virus strains by hemagglutination-inhibition tests with chicken antibodies.

Twenty strains of Venezuelan encephalitis (VE) virus inoculated intravenously in large doses into roosters produced hemagglutination-inhibition (HI) antibodies detectable in plasmas within 7 to 10 days. No signs of illness occurred, and there was no evidence of viral growth in tissues since blood concentrations of infectious virus steadily decreased after inoculation. HI antibodies in early plasmas were specific for VE virus and did not cross-react significantly with two other North American alphaviruses, eastern and western encephalitis viruses. VE virus strains could be distinquished by virus-dilution, short-incubation HI, but not by plasma-dilution neutralization tests, by using early rooster antibodies. The distinctions by HI test were similar with some strains to, but different with other strains from, those described by Young and Johnson with the spiny rat antisera used to establish their subtype classifications of VE virus (14, 28). Nevertheless, results of HI tests with rooster antibodies correlated with equine virulence, as did results with spiny rat antibodies, and distinguished the new strains of virus that appeared in Middle America during the VE outbreak of 1969 from preexisting strains.


Presumptive diagnosis of anaerobic bacteremia by gas-liquid chromatography of blood cultures.

By quantitative gas-liquid chromatography of glucose-containing blood cultures at the moment of first signs of growth, a presumptive diagnosis of anaerobic bacteremia could be made in 24 out of 26 cultures yielding obligate anaerobes upon subsequent culture. With Bacteroides sp. (20 strains isolated), elevated levels of isovaleric acid (greater than or equal to 0.1 mumol/ml) and/or succinic acid (greater than or equal to 5 mumol/ml) were detected in the medium used. An exception to this were two strains of Bacteroides thetaiotaomicron that did not produce sufficient quantities of these acids. In the case of butyrate-producing gram-positive cocci (four strains), butyric acid in amounts of greater than or equal to 0.8 mumol/ml was detected. Propionibacteria (five strains) produced propionic acid in amounts of greater than or equal to 3.9 mumol/ml. No false positive results were found in 103 blood cultures with growth of aerobic or facultatively anaerobic bacteria only.


Canine brucellosis: bacteriological and serological investigation of naturally infected dogs in Mexico City.

Bacteriological investigation of canine brucellosis in Mexico City revealed a high rate (11.8%) of Brucella canis infection in a sampling of 59 stray dogs. When conservative criteria were employed in the interpretation of serological test results, there was general agreement between the serological and bacteriological findings; however, some animals with localized male genital tract infections could not be judged as infected solely by serological tests. All Mexican field isolates were identified as B. canis; however, some diversity was observed as regards nitrate reduction, growth in the presence of basic fuchsine, and the degree of mucoidness. The seemingly high prevalence of B. canis infection in Mexico City dogs suggests the need for further inquiry into the possible public health significance.


Occurrence of e antigen in acute hepatitis B.

The occurrence of e antigen in 44 patients with acute hepatitis B was studied in order to determine if e was related to the outcome of the illness. In 13.6% of cases e was detected, and in none of these did the carrier state develop. The HBsAg carrier state developed in 4.6% of the patients and in none of these was e antigen detected. Anti-e was detected in only three cases. Only in the very early acute phase of illness e was detected and the time serum samples were taken for the detection of e was considered to be very significant. The occurrence of e was not found to affect the duration of HBs antigenaemia in those patients who recovered completely.


Streptococcus milleri in the appendix.

The appendix was investigated as a possible habitat of Streptococcus milleri. Both normal and inflamed appendices were examined and the isolation rates compared. S. milleri was present in a quarter of the normal appendices and more than half of those associated with apendicitis--a difference that was statistically highly significant. The isolation rates throughout were indepencent of age. There was a pronounced connection between the presence of S. milleri in the appendix and the purulent manifestations of appendicitis. S. milleri was isolated from other abdominal sites associated with appendicitis. The frequency of isolation was increased by culture in an enrichment broth containing nalidixic acid and sulphadimidine.


Prolonged erythrocyte T-polyagglutination in two children with bowel disorders.

In vivo erythrocyte polyagglutination of microbial origin is usually a transient condition. In two children with bowel disorders, erythrocyte T-polyagglutination persisted for 12 months in one case and for seven months in the other. Both cultures required both transfusions to support surgery. Washed red cell concentrates were transfused instead of whole blood to prevent dangerous destruction of T-transformed erythrocytes by anti-T antibodies normally present in the plasma of blood donors.


Dermatitis herpetiformis: a comparative assessment of skin and bowel abnormality.

We reviewed 18 patients with a clinical diagnosis of dermatitis herpetiformis who were being treated with dapsone and were on an unrestricted diet. Diagnosis was confirmed by finding IgA deposits in the dermal papillae of unaffected skin. Dapsone was discontinued and biopsy of affected skin was carried out when the typical rash reappeared. The biopsy findings were graded according to the severity of the histological changes. Small bowel tissue from each patient was examined and graded by stereo- and routine microscopy. Thirteen specimens (72%) were stereomicroscopically abnormal; all 18 showed villous atrophy, either partial or subtotal; and in 13 (72%) the interepithelial lymphocyte count was increased. No correlation was found between the histological severity of the skin and the small bowel lesions. Seemingly the severity of the skin rash in dermatitis herpetiformis is no guide to the degree of small bowel abnormality.


A comparative study for the enumeration of peripheral blood white cell counts below 2.0 x 10(9)/1 using counting chambers and the Coulter Counter model "S".

Low white cell counts are performed in many laboratories by a visual method as the method of choice. In this study, the visual count has been compared to that obtained by the Coulter Model "S". The results obtained by the two methods show very close correlation, thus allowing the Coulter Model "S" to be used with confidence for all low white cell counts provided certain precautions are taken.


Evaluation of a new test system for rubella haemagglutination inhibiting antibodies.

A recently available kit for the determination of rubella haemagglutination inhibiting antibodies (Rubindex, Ortho diagnostics) was was compared with the method used routinely in this laboratory. Rubindex compared favourably in that no significant difference in titre was found in 95.1% of 287 sera tested. Difficulty occurred with some sera from cases of Mycoplasma pneumoniae infection, rheumatoid arthritis, and a small number of normal sera containing human "O" cell agglutinins. This was overcome by treatment of the sera with 2-mercaptoethanol. Rubindex had the advantage that all reagents were provided in kit form and the trypsinised human "O" cells provided had a longer shelf life than chick erythrocytes.