alpha-Amanitin resistant RNA polymerase II from Aedes albopictus cell mutants resistant to alpha-amanitin. Spontaneous and EMS-induced alpha-amanitin-resistant Aedes albopictus cells have been isolated and characterized. Two mutant sublines, one of intermediate resistance (alpha A2) and the other highly resistant (Ama18) contained RNA polymerase II activity, the resistance of which in vitro to alpha-amanitin correlated well with the resistance of these cells in vivo. The resistance of these cells to alpha-amanitin can likely be attributed to the presence of an altered RNA polymerase II.


Reversible retention of synchronized HeLa cells in G2 of the mammalian cell cycle. The rate of progression of cycling HeLa cells from G2 into mitosis is greatly reduced by the amino acid analogue, p-fluorophenylalanine, but a small percentage of cells continually escapes into mitosis. Most of a presynchronized population can be held for several h in G2, thereby facilitating analyses of cells at this late stage of the cell cycle. They are reversed from the block by the addition of phenylalanine and resume progression within about 1 h with predictable kinetics but without a significantly enhanced synchrony. The mechanism of action of the analogue is consistent with the hypothesis that synthesis of false proteins interferes with the correct assembly of division-relevant structures.


A comparison of nuclear and nucleolar matrix proteins from rat liver. The comparison of the gel electrophoresis patterns of nuclear and nucleolar matrix proteins reveals marked differences between these structures. The nucleolar matrix contains 5 prominent protein bands ( mol.wt.: 8.2; 7.0; 5.6; 4.0 and 3.0 x 10 4 ) which are not found in nuclei. It is suggested that the nucleolar matrix has a distinct structure participating in selective interactions.


Relationship between DNA alkylation and specific-locus mutation induction by N-methyl- and N-ethyl-N-nitrosourea in cultured Chinese hamster ovary cells (CHO/HGPRT system). Chinese hamster ovary (CHO) cells in culture were utilized to determine the cytotoxicity, specific-locus mutation induction, and DNA alkylation which result from treatment of the cells with a range of concentrations of N-methyl-N-nitrosourea (MNU) or N-ethyl-N-nitrosourea (ENU). With [3H]MNU over the concentration range 0.43--13.7 mM, methylation of DNA was found to increase linearly, with a mean value of 56.7 pmol residue per mumol nucleoside per mM. With [1-3H]ENU over the concentration range 1.7--26.8 mM, ethylation was linear, with a mean value of 3.8 pmol residue per mumol nucleotide per mM. Mutation induction at the hypoxanthine-guanine phosphoribosyl transferase (HGPRT) locus was quantified by determination of the frequency of resistance to 6-thioguanine under stringently-defined selection conditions. The mutation frequency increased linearly with MNU or ENU concentration (0.01--2.0 mM); mean values were 2800 and 840 mutants per 10(6) clonable cells per mM, respectively. At equal levels of DNA alkylation, ENU was found to be approx. 4.5 times as mutagenic as MNU.


Senescent changes in rodent hepatic epoxide metabolism. Age-related alterations in epoxide metabolism were examined in subcellular fractions of liver from 3-, 12- and over 24-month-old male rats and mice. Using styrene oxide as the substrate, glutathione-S-transferase activity remained unchanged while the activity of epoxide hydrase increased with age in both species. The microsomally-mediated binding of benzo[a]pyrene to DNA was also increased in the old animals. Thus, senescent rodents retain or increase their ability to metabolize epoxides. The effect on epoxide metabolism of pretreatment of the senescent rodents with polychlorinated biphenyls was also examined. Glutathione-S-transferase activity was induced only in old animals. However, epoxide hydrase activity, while inducible in all age groups of rats, increased only in young mice. Therefore, there is an age-related difference in response of epoxide metabolizing enzymes to polychlorinated biphenyl treatments between rats and mice.


Aryl hydrocarbon hydroxylase induction in mouse liver cells--relationship to position in the cell cycle. The inducibility of aryl hydrocarbon hydroxylase (AHH) by benzo[a]-pyrene (BaP) has been studied in synchronously grown cultures of mouse liver cells. These cells (NMuLi cl 8) have low basal levels of AHH which can be induced greater than 100-fold by BaP. Cells were synchronized in G1(G0) by serum starvation and in S by release from serum starvation in combination with excess thymidine. When released from G1(G0) by replating at lower cell density in fresh medium with 20% serum, cells began entering S with a lag of 12 h. Addition of BaP (1 microgram/ml) 8 h before serum stimulation, at the time of stimulation or 7.5 h after stimulation all gave similar induction kinetics: the AHH activity peaked as the cells began entering S regardless of when the BaP was added. Cells blocked in various parts of S by excess thymidine were inducible for AHH activity as efficiently as cells moving through S and into G2. These results indicate that the inducibility of AHH is greater when cells are actively proliferating and may be a contributing factor to why growing cells are more sensitive to mutagenesis and transformation than quiescent cells.


DNA damage and DNA repair in cultured human cells exposed to chromate. DNA damage and DNA repair have been observed in cultured human skin fibroblasts exposed to potassium chromate but not to a chromic glycine complex. DNA repair synthesis (unscheduled incorporation of [3H]thymidine (TdR)) was measured in cells during or following exposure to chromate and was significant for chromate concentrations above 10(-6) M. Maximal DNA repair was observed at about 10(-4) M chromate. DNA repair capacity was found to be saturated at this concentration. Chromate was stable for at least 8 h in culture medium and produced approximately a linear increase in repair with duration of exposure. DNA damage as determined by alkaline sucrose gradient sedimentation was detected after treatment for 1.5 h with 5 . 10(-4) M chromate. Exposure to 10(-7) M chromate solution for 7 days inhibited colony formation while acute (1 h) treatment was toxic at 5 . 10(-6) M. The chromic glycine complex was toxic above 10(-3) M for a 1-week exposure but was not observably toxic after a 1-h treatment. These results indicate that chromate and not chromic compounds may be the carcinogenic form for man. The nature of the ultimate carcinogen is discussed. These findings illustrate the utility of the DNA repair technique to study the effects on human cells of inorganic carcinogens and mutagens.


Sister chromatid exchanges induced in cultured mammalian cells by chromate. Chromate compounds induced sister chromatoid exchanges (SCEs) and chromosome aberrations in cultured mammalian cells. Similar increases in SCE frequency were observed in human fibroblasts exposed to the compounds K2Cr2O7 and K2CrO4. Marked increases in SCE frequency in cells exposed to chromate for a 48-h period were detected at concentrations between 10(-7) and 10(-6) M. Chromosome aberrations (primarily chromatid breaks) were also produced in human cells exposed to K2CrO4 at concentrations between 8 . 10(-7) and 3 . 10(-6) M. K2CrO4, but not the trivalent compound CrCl3, induced SCEs in Chinese hamster ovary (CHO) cells at low concentrations.


Quantitative and qualitative aspects of the binding of N-hydroxy-2-acetylaminofluorene to hepatic chromatin fractions. The binding of a chemical carcinogen to components of hepatic chromatin in male rats was examined. After a single injection of N-[3H]hydroxy-2-acetylaminofluorene ([3H]OH-AAF) covalent binding to chromatin RNA, protein, and DNA occurs. The amount of carcinogen bound to RNA was approximately 5 times greater than to DNA, and 10 times that of the protein. However, loss of carcinogen from RNA with time was rapid, whereas a persistent binding to DNA equal to 15% of the initial values was observed. To localize the initial and persistent DNA-bound carcinogen, the genome was fractionated using two different chromatin fractionation procedures. The procedures used yielded 3 chromatin fractions based on physical characteristics, degree of association with nascent RNA and in vitro template capacity. Based on those parameters, these chromatin fractions have been tentatively classified as template expressed euchromatin, a repressed heterochromatin, and a highly condensed pelleted heterochromatin. With both the glycerol gradient chromatin fractionation procedure and the selective MgCl2 chromatin precipitation procedure, the initial (2 h) binding of carcinogen was greatest on the euchromatin DNA. Loss of carcinogen from the DNA, however, was also significantly faster from the euchromatin when compared to the heterochromatin and the pelleted heterochromatin. By 10 days after a single injection of the carcinogen, the largest amount of bound fluorene residues was located on the pelleted heterochromatin DNA, an apparently repressed portion of the genome, while less than 5% of the initial values were found on either the eu- or heterochromatin. When the rats were fed a 2-acetylaminofluorene-containing diet, loss of carcinogen from the pelleted heterochromatin DNA was enhanced, while loss from the euchromatin DNA was reduced. The covalent nature of the carcinogen modification of DNA was confirmed by thin-layer chromatography (TLC). These studies also demonstrated 2 separate carcinogen-purine base adducts which were identified as N-(guanin-8-yl)-N-AF and 3-(guanin-N2-yl)-N-AAF based on either co-chromatography with an authentic standard or on published Rf-values, respectively. The pelleted heterochromatin DNA had a significantly greater proportion of the 3-guanine-N2 adduct when compared to DNA from either the eu- or heterochromatin.


Effects of styrene oxide on chromosome aberrations, sister chromatid exchange and hepatic drug biotransformation in chinese hamsters in vivo. In vivo inhalation exposure to styrene oxide (25, 50, 75 and 100 ppm) for 2, 4 or 20 days (25 ppm only) had no effects on chromosomal aberration rates or sister chromatid exchange (SCE) frequencies (BrdU/labelling performed in vitro) in the bone marrow cells of Chinese hamsters. The only positive response in aberration frequency was obtained when styrene oxide was injected in lethal concentration (500 mg/kg body weight, i.p.) into the animal. One animal out of six showed slightly elevated SCE values after this high dose. The response of the hepatic drug metabolizing enzymes to styrene oxide exposure was found to be rather weak, which may be due to rather high activity of epoxide hydratase in Chinese hamsters as compared to e.g. mouse.


The effects of bromosulphophthalein, indocyanine green and bilirubin on the biliary excretion of methylmercury. The effects of three ligands for ligandin on the biliary excretion of methylmercury were investigated in male rats injected intravenously with 1.0 mg/kg Hg as Me203 HgCl. Bromosulphophthalein and indocyanine green inhibited the biliary excretion of methylmercury, while bilirubin had no such effect. None of the compounds tested which inhibited the biliary excretion of methylmercury decreased bile flow or changed the hepatic concentration of mercury of non-protein thiols. The possibility of the involvement of ligandin in the biliary excretion of methylmercury is discussed.


Correlation of biochemical and morphological changes induced by chemical injury to the lung. Comparison has been made of injury to the rat pulmonary alveolar parenchyma evoked by intravenous injection of N-nitrosomethylurethane, intratracheal instillation of 3-methylcholanthrene or repeated inhalation for up to 15 days of carbon tetrachloride, trichloroethylene or gasoline vapour. Biochemical analyses, including assessment of rates of RNA and DNA synthesis and secretion of pulmonary surfactant, were correlated with morphological changes determined by electron microscopy. Single doses of N-nitrosomethylurethane or 3-methylcholanthrene inhibited incorporation of [14C] orotate into lung RNA 1--3 days after treatment. Daily exposure for 30 min to carbon tetrachloride or trichloroethylene vapour caused less marked reduction in orotate incorporation. Ultrastructural examination revealed that 3-methylcholanthrene toxicity was characterised by cytoplasmic change including disruption of surfactant lamellaie of Type 2 pneumocytes and variable degenerative changes Type 1 pneumocytes. Eight to ten days after treatment, the morphological evidence of hypertrophy/hyperplasia and transformation of Type 2 pneumocytes correlated well with biochemical evidence of stimulated incorporation of [3H]thymidine. Inhalation of carbon tetrachloride or trichloroethylene vapour produced milder responses including occasional degenerative changes in Type 1 pneumocytes, reduced numbers of surfactant lamellae in Type 2 pneumocytes and no change in [3H]thymidine incorporation. In contrast to the gradation of injury produced by the various chemicals, all procedures caused a marked and reproducible reduction in secretion of pulmonary surfactant as determined by endobronchial lavage. Following solvent inhalation, reduced recovery of surfactant was detected within 5 days of repeated exposure and thereafter no further change in this depressed level resulted from continued exposure for a further 10 days. The data are discussed in terms of a generalised pattern of response by pulmonary alveolar tissue to chemical injury and the apparent sensitivity of surfactant secretion as an indicator of damage to the lung.


Chromatin proteins as a possible target for antitumour agents: alterations of chromatin proteins in dibromodulcitol treated Yoshida tumors. The effect of dibromodulcitol (DBD) on Yoshida sarcoma chromatin components has been investigated. Measurements on the radioactivity of nuclear components after in vivo treatment with [3H]DBD for 1 h indicated preferential drug binding to the high molecular weight component of the nuclear residual acidic protein (non-histones) and also to Histone 1 (H1) (very lysine rich, F1). Two-hour DBD treatment resulted in partial degradation and reduced [3H]leucine incorporation into the same fractions of chromatin. However, 6 h after DBD treatment, the synthesis of the degraded chromatin proteins began and by 24 h was completed. During the same treatment period the composition of chromatin showed a remarkable alteration; 2 h after DBD treatment the amount of the nuclear residual acidic proteins relative to DNA decreased by approx. 50%, but returned to control value 24 h after drug treatment. This in conjunction with the data on [3H]leucine incorporation suggests that certain chromatin proteins are degraded and subsequently newly synthesised after DND treatment resulting in an exchange of chromatin components. The formation of a nucleohistone complex between H1 and DNA was inhibited by pretreatment of H1 and DBD, dianhydrodulcitol (DAD) and bischloroethylnitrosourea (BCNU).


Mathematical model for adriamycin (doxorubicin) pharmacokinetics. Adriamycin (doxorubicin), an active antineoplastic drug, is rapidly distributed across cell membranes and is concentrated within cells. Binding to protein and to tissue readily occurs. The drug is metabolized to both fluorescent and nonfluorescent compounds, the liver being the main organ of biotransformation and elimination. A multicompartment, open model that accounts for these processes has been derived. The model assumes an initial volume of distribution of 60% of body weight and includes two peripheral adriamycin compartments and a subsystem for adriamycinol, a major metabolite. Plasma and urine concentrations of adriamycin and adriamycinol were determined for four patients treated with adriamycin (60 mg/m2), and these concentrations were used to calculate rate constants for the model. Concentrations were measured by fluorescence assay after thin-layer chromatographic separation of parent compound and metabolites. Differential equations were solved by the SAAM computer program. Evaluation of adriamcinol pharmacokinetics suggests that the previously reported high concentrations of adriamycinol immediately after IV infusion of adriamycin are an artifact of the fluorescence method and that observed plasma concentrations of adriamycinol are the sum of adriamycinol concentrations and approximately 10% of the adriamycin concentrations. Corrected peak plasma concentrations of adriamycinol occur 2--12 h after infusion of adriamycin.


Gas-chromatographic estimation of urinary oxalate and its comparison with a colorimetric method. We describe a simple, specific gas-chromatographic method for urinary oxalate. Its specificity was evaluated by precipitating the oxalate as its calcium salt from urine, followed by methylation of the oxalate with boron trifluoride/methanol and subsequent gas-chromatographic separation and quantitation of the dimethyl oxalate. [U-14C]Oxalate and n-decanoic acid are used as internal standards. Analytical recoveries ranged from 93.8 to 97.7% for oxalate-supplemented urine. Twenty replicate analyses of urines containing typical concentrations of oxalate gave CVs of 10.0, 9.1, and 8.3% for low, medium, and high concentrations, respectively. Day-to-day precision (CV) for single analyses repeated on 20 days was 8.6% for the low urinary oxalate concentration. The lower limit of detection of urinary oxalate is 25 mumol/L. Results by our method correlated well (r = 0.95) with those by a colorimetric method (Clin. Chim. Acta 36: 127, 1972) but averaged 68.4% of those obtained colorimetrically (n = 75 samples, p less than 0.001). The expected range for our method is calculated to be 80 to 500 mumol of oxalate per 24-h urine (mean +/- 1 SD: 280 +/- 100).


A statistical method for determining normal ranges from laboratory data including values below the minimum detectable value. Determination of normal ranges from laboratory data containing undectable values is a frequently encountered problem in the radioimmunoassay of peptide hormones. In the past, such determinations usually have been based on the mid-point method or the one-end Winsorized method. A graphic method involving the use of probability paper has also been reported. We propose that the maximum-likelihood estimation is a more appropriate statistical method for the determination of normal range from this type of data (Type I censored data). With this method, the mean and standard deviation, and hence the tolerance limits, can be estimated. We used the maximum-likelihood estimation method to determine the normal range of serum thyrotropin values obtained from 93 healthy subjects, based on a log normal distribution. Although the serum thyrotropin content was undetectable in 14% of the subjects, a normal range could be calculated. Using tolerance limits for 95% coverage of the population with 90% confidence, we calculated the normal range of thyrotropin to be 0.51-5.75 milliunits/L, with a mean value of 1.71 milliunits/L, and predicted that 91.4% of undetectable serum thyrotropin values will fall within the normal range.


Kinetic determination of serum sorbitol dehydrogenase activity with a centrifugal analyzer. We describe a mechanized method for centrifugal analyzer determination of sorbitol dehydrogenase in serum, based on conversion of D-fructose to sorbitol with simultaneous oxidation of NADH, in triethanolamine buffer at pH 7.4 and 30 degrees C. The standard curve for this assay is linear to 200 U of activity per liter of serum. The mean within-run precision (CV) of the assay is 0.8%. Results correlate well with those by a spectrophotometric method. In sera from 20 apparently healthy adult humans, sorbitol dehydrogenase activity averaged 1.7 (SD +/- 0.8; range, 1-3) U/L. The mean activity (U/L) for a group of 30 rats was 4.4 (SD, +/- 0.2; range, 3-6); for 20 dogs, 5.8 (SD, +/- 0.7; range 3-9); and for 30 mice, 26.8 (SD +/- 2.1; range, 22-34). To determine the utility of measuring this enzyme in the serum of rats for assessment of hepatotoxicity in drug-safety studies, we compared sorbitol dehydrogenase activity with that of alkaline phosphatase, aspartate aminotransferase, and alanine aminotranferase in the sera of rats treated with thioacetamide or in which the common bile duct has been ligated.


Radioimmunoassay of progesterone in saliva: application to the assessment of ovarian function. We report a specific radioimmunoassay that has the required sensitivity (7 pg per assay tube) for determining progesterone concentrations in 400 microL of mixed saliva collected from normal women. The assay is precise: intra and inter-assay variation (CV) never exceeded 11.0 and 8.0%, respectively. The assay was used to determine progesterone in saliva samples collected daily for not less than 28 days by normal women and by patients having abnormal ovarian function. Four normal women provided matched saliva and plasma samples for accurate dating of the menstrual cycle by plasma progesterone, estradiol, lutropin, and follitropin. Nine further subjects collected saliva samples only, and from these data a provisional "normal range" was established. Progesterone concentrations in saliva during the follicular phase of the cycle were low (less than 100 pmol/L) but rose beginning on day 12 to reach peak values of 230-550 pmol/L on day 21. Thereafter, progesterone concentrations in saliva declined to values generally less than 170 pmol/L at the commencement of menses. Saliva samples from three patients attending an infertility clinic were also studied to assess ovarian function.


The performance of delta check methods.

The performance of delta check methods. The percentage of mislabeled specimens detected (true-positive rate) and the percentage of correctly labeled specimens misidentified (false-positive rate) were computed for three previously proposed delta check methods and two linear discriminant functions. The true-positive rate was computed from a set of pairs of specimens, each having one member replaced by a member from another pair chosen at random. The relationship between true-positive and false-positive rates was similar among the delta check methods tested, indicating equal performance for all of them over the range of false-positive rate of interest. At a practical false-positive operating rate of about 5%, delta check methods detect only about 50% of mislabeled specimens; even if the actual mislabeling rate is moderate (e.g., 1%), only abot 10% of specimens flagged a by a delta check will actually have been mislabeled.


Is antiglycolysis required for routine glucose analysis? We obtained -68 pairs of simultaneously drawn serum and fluoride-oxalate plasma samples from patients and analyzed them by a continuous-flow (AutoAnalyzer II) glucose oxidase method. Glucose concentrations ranged from 370 to 3530 mg/L. Glucose concentrations for samples obtained in the fluoride-oxalate preservative averaged 42 +/- 35 mg/L (mean +/- SD) higher than serum. The magnitude of this difference was independent of glucose concentration. Linear-regression analysis of 270 pairs for which the time from collection to separation was recorded indicated that the difference between serum and plasma increased by 0.32 mg/L per minute of delay over a time span of 15 to 295 min. These differences are smaller than those described in standard textbooks. We conclude that, with the specimen-handling process used in our hospital, serum glucose determinations are clinically acceptable.


Assay of urinary 4-hdyroxy-3-methoxymandelic (vanillylmandelic) acid by liquid chromatography with electrochemical detection. We describe a method for the assay of urinary 4-hydroxy-3-methoxymandelic acid (vanillylmandelic acid) based on separation on a microparticulate reversed-phase column and direct electrochemical detection. The method can be used after extraction from urine or by direct urine injection after 100-fold dilution.


Assay of 4-hydroxy-3-methoxyphenylacetic (homovanillic) acid by liquid chromatography with electrochemical detection. We describe a method for the assay of urinary 4-hydroxy-3-methoxyphenylacetic acid (homovanillic acid), based on its separation on a microparticulate reversed-phase column and direct electrochemical detection. Patients with neuroblastoma, pheochromocytoma, and Parkinson's disease have increased amounts of this compound in their urine.


Blood thyroxine concentration is lower in low-birth-weight infants. From out data bank, we analyzed results for thyroxine concentration in blood samples spotted on filter paper from different age groups (one to nine days postpartum) of our low-birth-weight and normal population. It was significantly lower in the low-birth-weight infants in almost all the age groups, and in both groups it significantly declined after postnatal day 5. The influence of weight is more important in the low-birth-weight population, but does not completely explain the smaller values. The results indicate that blood samples used in screening for congenital hypothyroidism in the neonate should be taken on postnatal days 3 to 5, and if a recall specimen is collected on days 5 to 9, one should expect the thyroxine concentration in the second specimen to be lower than in the first.


Identification and quantitation of phenylethylene glycol in human and rat urine, and its elevation in phenylketonuria. Phenylethylene glycol has been identified in rat and human urine using gas chromatography/chemical ionization/mass spectrometry. A method was developed for the quantitative analysis in urine of this phenylalanine metabolite and of p-hydroxyphenylethanol, a metabolite of tyrosine, by converting them to the pentafluoropropionyl derivatives and measuring them by selected ion monitoring. In human urine, about 90% of the phenylethylene glycol was present in a conjugated form (releasable by glusulase), but the reverse was true for rat urine, with about 90% being present in the unconjugated form. The excretion of free phenylethylene glycol (expressed as ng/mg creatinine) was 2.7-fold higher in a group of untreated phenylketonuric patients than in the control group, but the phenylketonuric patients excreted abnormally low amounts of 3-methoxy-4-hydroxyphenylethylene glycol. Intraperitoneal injections of L-phenylalanine in rats resulted in a small increase in the excretion of phenylethylene glycol. On the other hand, the injection of phenylethanolamine resulted in an 82-fold increase in the excretion of phenylethylene glycol, but phenylethylamine had no effect. These results indicate that the conversion of phenylethylamine to phenylethanolamine is the rate limiting step in this metabolic pathway.


Studies on a child suspected of having a dficiency in 3-hydroxy-3-methylglutaryl-Co A lyase. The urine of a child who presented with hyperammonemia was found to contain elevated levels of 3-hydroxy-3-methylglutaric acid, 3-methylglutaconic acid and 3-methylglutaric acid. An increased excretion of these organic acids has been reported previously in a child with 3-hydroxy-3-methylglutaryl-CoA lyase deficiency. Enzyme studies using cultured fibroblasts from this patient, however, indicated that the 3-hydroxy-3-methylglutaryl-CoA lyase activity was not markedly reduced.


The contribution of drinking water lead to maternal blood lead concentrations. The association between domestic water lead concentrations and blood lead concentrations has been examined in 232 mothers at delivery. The blood lead was found to vary significantly with the cube root of the water lead. This association was stronger for first flush water lead rather than for running water lead. This study emphasises the danger to mothers and to their children of environmental lead over-exposure in areas of soft acid plumbosolvent water.


Preparation of vitamin B-12-free serum for the use in vitamin B-12 radioassays. In radioassays for serum vitamin B-12, the separation of free and bound vitamin is usually made with charcoal absorption. The specificity of this separation depends on the amount of charcoal and the protein content and constitution of the medium. The large difference in protein concentration between the samples for the dilution curve and the serum samples introduces an uncontrolled variable in the test. In order to equalize the experimental circumstances, the standard dilutions were made in serum freed from vitamin B-12 after boiling the serum for 20 min in a 4-fold dilution with glutamic acid buffer at pH 3.3 and subsequent passage over a CH-Sepharose 4-B column complexed with hog intrinsic factor (IF). The vitamin B-12-binding capacity of such an affinity column prepared from 1 g CH-Sepharose and 20 mg IF, suffices for the absorption of vitamin B-12 in 3000 ml serum from which 300 series of vitamin B-12 standard solutions can be made. Our first results with this method confirm that the charcoal absorption radioassay has become more accurate by the use of vitamin B-12-free serum in the standard dilutions.


Acylglycines. the gas chromatograph/mass spectrometric identification and interpretation of their spectra. The gas chromatographic retention time (methylene units) and mass spectra of a series of acylglycine compounds as their trimethylsilyl (TMS) derivatives are presented. A general scheme for the interpretation of these compounds is developed from the mass spectra of known compounds and is shown to be in agreement with data derived from other sources (e.g. stable isotope and high resolution mass spectra). These data should provide information for the identification of these compounds in physiological fluid of both normal and diseased patients. In addition, the general interpretation scheme should provide the investigator with an approach to the interpretation of the spectra of unknown acylglycines.


Separation and quantification of urinary di- and polyamines by gas chromatography with electron capture detection. A sensitive and specific gas chromatographic assay procedure employing electron capture detection has been developed for the assay of free and total di- and polyamines in human urine. Urine samples, hydrolysed with hydrochloric acid where necessary for the measurement of total amine output, were evaporated to dryness and, after the residues had been taken up in water, purified successively on Porapak Q and Dowex 50 X2 columns. Following evaporation of eluate, pentafluoropropionyl derivatives were made and analysed gas chromatographically using temperature programming. Di- and polyamines can be measured accurately at the picomole level and normal urinary output values calculated using this method agree well with those noted by other workers.


Erythrocyte membrane autophosphorylation in Duchenne muscular dystrophy: effect of two methods of erythrocyte ghost preparation on results. We have compared the effects of two slightly different methods of erythrocyte ghost preparation on membrane autophosphorylation in Duchenne muscular dystrophy. Addition of 1 mmol/l EDTA to two of the washing steps altered the differences between patients and controls. These data support the known sensitive interrelationship of Ca2+ and erythrocyte membrane autophosphorylation, underline the importance of strict adherence to methodology when comparing data, and have suggested a new direction of investigation.


Study of a case with severe red-cell pyrimidine 5'-nucleotidase deficiency. A deficiency of erythrocyte pyrimidine 5'-nucleotidase was found in a 23-year-old male suffering from severe congenital hemolytic disease. Results from exhaustive metabolic exploration are given and compared with reticulocyte-rich blood from subjects with auto-immune hemolytic disease. Evidence is given that the 20% apparent P5N residual activity corresponds to a non-specific acid phosphatase.


Electrophoretic and kinetic studies of a mutant red cell pyrimidine 5'-nucleotidase. Human red cell pyrimidine 5'-nucleotidase (P5N) was studied by partial purification and condensation in a patient with an extremely low red cell P5N activity and chronic hemolytic anemia. The residual P5N in the red cell of the patient was characterized by an increased Michaelis constant for cytidine 5'-monophosphate, a marked shift of the pH optimum to the acidic side, normal electrophoretic mobility and normal heat stability. These data indicate that, in this patient, severe enzyme deficiency is caused by a structural gene mutation. This variant is clearly distinguished from a previously reported case and it is designated P5N Kagoshima.


Increased erythrocyte lipid peroxidation in hereditary xerocytosis. Xerocytosis is a chronic hemolytic anemia with abnormal membrane function manifested by an increase in passive potassium permeability. Xerocytes demonstrate a greater susceptibility to hydrogen peroxide manifested by the production of malondialdehyde (MDA). Xerocyte membrane phospholipid and fatty acid analysis is normal except for a slight increase in phosphatidyl choline, a commensurate decrease in sphingomyelin, as well as a decrease in linoleic acid. Metabolism and glutathione stability are normal as well as plasma vitamin E levels in patients with xerocytosis. The increased susceptibility to oxidant stress is exaggerated in the "older aged" xerocyte population and correlated well with decreased intracellular potassium concentration.


A comparative study on estradiol receptor assays in human breast cancer tissue. Standard dextran-coated charcoal assays for measuring the estrogen receptor content in human breast cancer tissue are compared. A single-point assay, using the estrogen antagonist nafoxidine as competitive inhibitor, showed good qualitative agreement with a three-point Scatchard plot assay, using radio-inert estrogen to assess the non-specific binding. Based on statistically evaluated dividing points, 116 (66.3%) of the 175 analysed primary tumor specimens were positive in the single-point assay compared to 121 (69.1%) in the Scatchard plot assay. Use of the additional dissociation constants in the evaluation of the Scatchard plot assay data gives a complete qualitative agreement between the two assays. We conclude that, in spite of the lack of specific controls inherent in the Scatchard plot assay, the single-point assay using diethylstilbestrol instead of nafoxidine is equally useful, especially if biopsy specimens are too small to provide the larger number of aliquots necessary for multiple steroid receptor analyses. Factors affecting the quantitative differences between the two assays are discussed.


Interference of the measurement of lactate dehydrogenase (LDH) activity in human serum and plasma by LDH from blood cells. This study was performed to find a reliable method to measure lactate dehydrogenase (LDH) activity in blood samples. Human plasma contains thrombocytes whose number depends on the speed of centrifugation applied to the freshly-drawn blood sample. They do not disturb the measurement of LDH in plasma, provided the plasma sample has not been subjected to procedures that may destroy the integrity of the thrombocytes, e.g. standing overnight at 4 degrees C, freezing, or treatment with ultrasonic waves. Centrifugation of plasma at a minimum of 1174 x g eliminates the presence of thrombocytes. The serum of healthy human subjects invariably contains higher LDH activity than the plasma: the difference is 30 +/- 18 U/l (mean +/- S.D.). LDH-isoenzyme analysis shows that a large part of the LDH activity difference is caused by lysis of erythrocytes in the clot. Liberation of 30 U LDH per litre is not associated with visible hemolysis.


Determination of antimony in biological materials by electrothermal atomic absorption spectroscopy. An electrothermal atomic absorption method for the determination of antimony in biological fluids, derived from Triostam or Pentostam, is described. Comparison of the results obtained by this method has been made with hydride generation atomic absorption and by measuring the gamma emission of 125Sb-Pentostam. Using electrothermal atomic absorption, the concentrations and distributions of the pentavalent and trivalent antimony drugs, either in free or liposome-entrapped forms, have been determined in vitro after incubation with human blood. The effect of entrapping Pentostam within liposomes has also been studied in vivo in mice, and its concentration and distribution compared with results obtained using the free drug.


An abnormal macro lactate dehydrogenase isoenzyme not due to immunologlobulin binding. We report here on the lactate dehydrogenase (LD) of a patient who presented with an additional LD isoenzyme band between LD 3 and LD4 found during routine examination. The abnormal LD was found to be of increased molecular size, which was not due to complexing with immunoglobulins. The abnormal LD was purified by affinity chromatography, labelled and electrophoresed on a SDS-polyacrylamide gel. Autoradiography suggested abnormal aggregation as the cause of increased molecular size.


Rapid assessment of endogenous creatinine in physiological samples analyzed by reversed-phase liquid chromatography with spectrophotometric detection. An improved and direct analysis of endogenous creatinine levels using the reversed-phase mode of high performance liquid chromatography (RPLC) is described. The analysis is rapid, the sensitivity of the spectrophotometric detection is in the nanomole range, and the sample preparation requires only filtration to remove the particulate matter. Identification of chromatographic peaks was achieved by means of absorbance ratios, stopped-flow UV spectra and prechromatographic incubation of samples with creatinine amidohydrolase. Reported in this paper are representative chromatograms of samples of amniotic fluid, urine, and cerebrospinal fluid (CSF). The ranges of creatinine concentrations in 10 samples of amniotic fluid, urine and CSF were 0.774--1.850, 99--454.5 and 0.648--1.05 mg/100 ml, respectively. This highly specific and simple assay offers several improvements over previously used methods.


The effect of clomiphene on uncastrated and castrated male transsexuals. Clomiphene was administered at a daily dose of 100 mg for 5 consecutive days to two groups of male subjects. There were three uncastrated male transsexuals (Group A) and nine castrated male transsexuals (Group B). In the uncastrated subjects Clomiphene enhanced the secretion of follicle-stimulating hormone (FSH), luteinizing hormone (LH) and testosterone (T) starting from day 3 of treatment. The magnitude of the increment ranged from 150%--250% over the mean basal plasma level for LH, 113%--262% for FSH and 12%--68% for T. In contrast, Clomiphene suppressed both FSH and LH in the castrated subjects. Equal suppression of both the gonadotrophins were observed. The levels of FSH and LH in plasma on day 3 were suppressed to 66.4% and 66.2% of their respective mean basal levels. Two days after the termination of treatment, suppressions were maintained. These results suggest that Clomiphene acts as an anti-oestrogen in uncastrated male transsexuals and in castrated male transsexuals who have subphysiological levels of oestradiol it acts as a weak oestrogen.


Dissociated thyroxine, triiodothyronine and reverse triiodothyronine levels in patients with familial goitre due to iodide organification defects. The thyroid function of patients with three different types of organification defect was studied. All patients were characterized by a high thyroidal 131I uptake and a positive perchlorate discharge. Patients with Pendred's syndrome who had goitre and congenital nerve deafness were mostly euthyroid with normal circulating thyroid hormone levels. Only two of them had compensated euthyroidism with elevated total T3, high basal TSH and delayed return to basal value with TRH. The patients who were euthyroid with large goitres and normal hearing had elevated total T3 and an exaggerated TSH response to TRH. The thyroid function of these two groups of patients contrasted with that of goitrous cretins, who were clinically hypothyroid with low circulating total T4, increased T3 and decreased rT3 levels. The data suggest that in patients with intrathyroidal iodine deficiency secondary to organification defect, there is preferential T3 production in an effort to maintain euthyroid state, and this is further substantiated in the case of gross thyroid insufficiency either by enhanced peripheral conversion of T4 to T3, or reduced metabolic clearance of T3 and increased clearance of rT3, resulting in elevated T3 and decreased rT3 levels.


Treatment of Cushing's disease in juveniles with interstitial pituitary irradiation. Nine juvenile patients (five boys and four girls aged 10--18 with Cushing's disease were treated with pituitary implantation of 198Au and/or 90Y. No patient had any surgical complication from the procedure. At the latest assessment, 3 months to 17 years after operation, Cushing's disease was in remission in all the patients; the response time following operation was a few days to 3 months. Radiology of the pituitary fossa at time of pituitary implantation was normal in all patients and remains so. The final height in six patients is 149--172 cm (59--67.5 inches) and three patients who continue to grow have increased by 13, 6 and 3 cm since implantation. Only one patient required full pituitary hormone replacement therapy, and he had been previously treated by external irradiation, and one other patient failed to complete puberty. In all the other seven sexual maturation is normal and one has fathered two children. We conclude that pituitary implantation with interstitial irradiation is a satisfactory form of treatment for Cushing's disease in juveniles.


Effect of age on testicular function in patients with Klinefelter's syndrome. Testicular function in the patient with Klinefelter's syndrome parallels the alterations seen with age in the normal subject. Significant decreases are seen in the Klinefelter group in the plasma level of testosterone and in the plasma testosterone/oestradiol ratio. Testicular function in the patient with Klinefelter's syndrome appears very much like that seen in a chronologically older subject.


Effects of long-term treatment with metergoline in patients with idiopathic oligospermia. The effect of metergoline, an ergoline derivative with antiserotonin as well as dopaminergic properties, was studied in forty-five male patients with idiopathic oligospermia. Metergoline treatment (6 mg daily for 5 months) had no demonstrable effect on spermatogenesis; moreover, it did not influence the serum levels of LH, FSH, testosterone and oestradiol although it significantly reduced prolactin levels. It is concluded that, in all likelihood, serotonin plays little or no part in the pathogenesis of idiopathic oligospermia and that pharmacological reduction of normal prolactin levels has no therapeutic effect on this disease.


A study of the aetiology of gastritis following gastric surgery. II. Studies of cell-mediated immunity. Crude gastric antigen is shown to cause leucocyte migration inhibition in five out of ten patients with pernicious anaemia. We did not find any migration inhibition using leucocytes from twenty patients with severe post-operative gastritis, including fifteen with atrophic gastritis.


A modified assay for antibody against the nicotinic acetylcholine receptor in myasthenia gravis. Myasthenia gravis is an autoimmune disease which may be detected by the presence of serum antibodies against the nicotinic acetylcholine receptor at the neuromuscular junction. Immunoprecipitation assays have been developed to measure these immunoglobulins and calculate titres. These assays require the labelling of the receptor with 125I-alpha-bungarotoxin which binds irreversibly. However, the standard immunoprecipitation assay may significantly underestimate the titres of some myasthenic patients. We have discovered patients with antibodies specific for the alpha-bungarotoxin binding site of purified rat muscle receptor. If labelled toxin is already present on the receptor, these antibodies are unable to bind to the protein. This phenomenon may lead to underestimates of the actual antibody titre. To circumvent this problem, we have designed a modified immunoprecipitation assay to evaluate titres.


Immunological behaviour following rubella infection. Several immunological tests were performed on eighty-five patients with rubella. There was a decrease in total leucocytes, neutrophils and T cells, an increase in IgG and the complement components of C4, C9 and CH50, and a marked insensitivity to dinitrochlorobenzen (DNCB) and purified protein derivative (PPD) in many patients. Furthermore, atypical lymphocytes with lobulated nuclei, autoantibodies and reduced blastogenesis were found in some patients. These abnormal findings disappeared within 1 month. These marked immune abnormalities, although transient, may indicate an inhibition of DNA synthesis in lymphocytes which may have some bearing on the high incidence of embryopathy in pregnant women.


Receptors for IgM on human lymphocytes. III. Specificity of receptors. Receptors for the Fc portion of IgM (RFcmu) can be detected on a large percentage of human peripheral lymphocytes. To approach an understanding of the function of these receptors we have examined the relative efficiencies of different preparations of human IgM and their F(c)5 mu fragments in binding to RFcmu. This was measured by blocking rosette formation between lymphocytes and IgM-sensitized ox erythrocytes (EAmu). IgM from pooled normal human serum completed blocked formation of IgM rosettes (EAmu-RFC) at much lower concentrations than IgM preparations from individual Waldenström's macroglobulinaemic patients (WM). The differences in effectiveness of these IgM preparations in inhibiting EAmu-RFC suggested the existence of receptors for subclasses of IgM on different subpopulations of human lymphocytes. F(c)5 mu fragments of IgM were more effective in blocking EAmu-RFC than the parent molecule, which was in turn more efficient than the 8S subunit. These results indicate that F(c)5 mu may have more Fc regions exposed per molecule for binding to the matrix of RFcmu than pentameric IgM and that Fc multivalency may be important for the stable binding of IgM to RFcmu.


Age-related changes in human thymus.

Age-related changes in human thymus. Thymic biopsies obtained during open heart surgery were examined for age-related involution of the parenchyma and changes in cell surface characteristics. In parallel with the parenchymal atrophy, E-rosette-forming cells continuously decreased with age and were progressively replaced by an increasing proportion of 'null' lymphoid cells. These changes appeared to be independent of each other. The significance of these findings in the context of the host's immune mechanism is discussed.


Effect of different components of the thymic stroma on the onset of AKR leukaemia. Spontaneous leukaemia in AKR mice is characterized by an accumulation of thymocyte precursors prior to the onset of the disease. An insoluble thymic fraction (ITF), previously shown to provoke such an accumulation when injected to normal mice, caused a significant acceleration of death by leukaemia when given to pre-leukaemic AKR mice. Conversely, the injection of a soluble thymic factor (STF), believed to further differentiate thymocyte precursors, was shown to markedly delay the onset of leukaemia. These results are interpreted as reflecting the specific immune functions of T cells at different stages of maturation.


Random monocyte migration: an in vitro correlation with the delayed hypersensitivity skin reaction. The in vitro random migration and chemotactic activity of peripheral blood monocytes and neutrophils was compared with the delayed hypersensitivity skin test to streptokinase-streptodornase in fourteen normal subjects. A significant positive correlation (P less than 0.001) was observed between the random migration of monocytes and the size of the skin test reaction. No significant correlation was found with random neutrophil migration or monocyte and neutrophil chemotactic responses. These results indicate that the in vitro random mobility of monocytes is related to the in vivo expression of a delayed-type hypersensitivity skin reaction.


Fibrin deposition in disposable dialyzers before and after re-use. We have estimated the degree of fibrin deposition as well as changes in dialyzer efficiency of Gambro Optima 13.5 mu dialyzers, re-used up to six times in six regular dialysis patients. After each dialysis the dialyzer was rinsed and left filled with formaldehyde. The patients were given I-125-fibrinogen before the study. The radioactivity from the dialyzer was continuously measured during each dialysis and rinsing procedure. Urea and creatinine clearances were determined 30 min after start of each dialysis. After the last re-use the dialyzer membranes were removed and divided into sections and the radioactivity of each section was measured. Twice as much fibrin deposition was found near the blood inlet of the dialyzer as near the outlet. A higher fibrin deposition was found after each re-use than after the initial dialysis. The clearances of urea and creatinine were scarcely influenced by the re-use. The half-life of fibrinogen in the patients was in the same range as in normal subjects.


Reduction of dialyzer fibrin deposition with sulphinpyrazone. To determine whether sulphinpyrazone reduces thrombus formation within artificial kidneys, dialyzer 125I-fibrinogen and platelet and fibrinogen levels during dialysis were compared during a non-treatment control period and while patients were receiving sulphinpyrazone. Mean fibrin deposition within the dialyzers, measured as gram X 10(-3) of clottable fibrinogen, was significantly less during sulphinpyrazone treatment (2.5) than during the control period (5.3). Arterial blood platelet counts and plasma fibrinogen levels during dialysis were higher on treatment despite similar predialysis values during control and treatment periods. The results indicate that sulphinpyrazone reduces fibrin formation within artificial kidneys and, since the reduction in deposition of fibrin alone is insufficient to explain the higher plasma fibrinogen levels during treatment with sulphinpyrazone, suggests that this therapy reduces fibrinogen consumption within the patient during hemodialysis.


Plasmapheresis in glomerulonephritis.

Plasmapheresis in glomerulonephritis. Plasmapheresis together with immunosuppressive drug therapy has been used in the treatment of 17 patients with glomerulonephritis [Goodpasture's syndrome (4), systemic lupus erythematosus (4), mesangiocapillary glomerulonephritis (2), glomerulonephritis associated with cirrhosis (2), nonspecific mesangial proliferative glomerulonephritis (3), Henoch-Schoenlein purpura glomerulonephritis (1) and glomerulonephritis associated with infective endocarditis (1)]. Use of the Haemonetics Model 30 blood cell separator, exchanging two liters of plasma with 5% albumin in Hartmann's solution has provided a safe, effective but relatively expensive procedure, capable of producing a marked reduction of fibrinogen, complement components, anti-glomerular basement membrane antibody and immune complex concentrations. Removal of one or more of these factors is felt to be at least partly responsible for the improvement in renal function and clinical well-being demonstrated in patients with Goodpasture's syndrome, systemic lupus erythematosus and other forms of glomerulonephritis associated with the presence of circulating immune complexes.


Comparison of the effects of lactate and acetate on clinical peritoneal clearances. Peritoneal clearances of urea, creatinine, inulin and dialyzate protein concentration were compared in ten patients using dialysis solutions containing either lactate or acetate. No significant differences were found between solutions containing lactate or acetate.


Echocardiographic assessment of left ventricular function in patients with chronic uremia. Cardiac function was determined non-invasively in 7 patients (average age 24 years) with chronic uremia. Each was on maintenance hemodialysis. Echocardiograms and carotid pulse tracings were recorded 30 minutes prior to dialysis, and again 30 minutes, 24 and 48 hours following hemodialysis. End-diastolic and end-systolic diameters averaged 5.4 +/- 0.2 and 3.4 +/- 0.1 cm, respectively before and 5.0 +/- 0.2 and 3.2 +/- 0.1 cm immediately after hemodialysis (P less than 0.05 for both). Calculated stroke volume fell from 92.1 +/- 8.8 to 76.7 +/- 10.5 ml (P less than 0.025). Heart rate increased minimally, and average cardiac output was not significantly increased. Following dialysis, body weight and systolic and diastolic blood pressures fell significantly. Thus preload as well as afterload declined. Because of the fall in both stroke volume and end-diastolic volume, a shift along the ventricular function curve downwards and to the left occurred implying diminished cardiac pumping function. Nonetheless the indices of myocardial contractility were normal and showed no change from pre-dialysis value. During the 48 hour interval following hemodialysis all measured and calculated values returned to pre-dialysis levels. Thus organic heart disease as evaluated by non-invasive techniques does not appear to be a necessary sequel to kidney failure, at least in young patients in a hemodialysis program. Gross abnormalities of myocardial function may be absent for at least seven years after the onset of chronic uremia.


Transport of uremic toxins through conventional hemodialysis membranes. Human mononuclear phagocytes cultured in vitro were tested after preincubation with uremic plasma dialyzed in vitro and the effects of pre and post hemodialysis plasma were compared with the effect of dialyzates equilibrated with uremic plasma in vivo. Factors in uremic blood plasma inhibiting phagocytosis of Candida albicans could not be removed by means of conventional hemodialysis with cuprophan (CPN) or polyacrylonitrile (PAN) membranes. Hemofiltrates of uremic blood plasma produced by PAN membranes caused a significant inhibition of phagocytes in our test system while CPN hemofiltrates did not.


Salivary phosphate and calcium concentrations in uremia. Phosphate concentration was found to be significantly elevated in the saliva of uremic patients (dialyzed and non-dialyzed) when compared to normal subjects and to dialysis patients after parathyroidectomy. Salivary calcium concentrations were similar in all groups examined. As increased salivary phosphate was found also in primary hyperparathyroidism, we attribute our findings to the secondary hyperparathyroidism of the uremic state.


Hair zinc compared with plasma zinc in uremic patients before and during regular hemodialysis. Plasma and hair zinc concentrations were measured by atomic absorption spectrophotometry in 34 control subjects, 20 nondialyzed uremic patients and 18 patients treated with regular hemodialysis. Plasma zinc levels were low in both nondialyzed and hemodialyzed patients. Hair zinc levels were low in the nondialyzed uremics, but at least partialy restored to normal in patients on hemodialysis. In both patient groups, hair zinc was positively correlated with plasma zinc. In the nondialyzed patients haie zinc depletion in end-stage renal disease progresses with increasing degree of renal insufficiency and tends to be reversed by regular hemodialysis.


Increase of IgM-bearing peripheral blood lymphocytes in patients with idiopathic membranoproliferative glomerulonephritis (MPGN) and their family members. The number of Immunoglobulin-bearing and E-rosette forming peripheral blood lymphocytes, serum levels of immunoglobulins and complement and urinary sediments were examined in patients with idiopathic membranoproliferative glomerulonephritis (MPGN) and their immediate family to determine if familial factors might be related to the development of this disease. Twenty-five patients with MPGN (22 Type I and 3 Type II), 24 family members and 36 age-matched healthy persons were examined. All patients showed an increase in the number of IgM-bearing peripheral blood lymphocytes. All families showed some members with increased numbers of IgM-bearing lymphocytes. There were no significant correlations between the numbers of IgM-bearing peripheral blood lymphocytes and the levels of serum immunoglobulins and complement.


Urinary protein excretion in healthy children. The urinary total protein excretion was determined in 270, 18-24 hr urine samples from 130 healthy children of different age groups using the tannic acid-Fe3+-method of Yatzidis [1977]. The daily protein excretion of premature infants in the first month of life varies between 14-60 mg, with a mean of 29 mg, and that of fullterm newborn infants between 15-68 mg, with a mean of 32 mg. Protein excretion increases with age and amounts to 29-238 mg (mean 83 mg) in 10-16 year old children. Thus, the urinary protein concentration during the neonatal period is high when compared to adult values. This explains the "trace" and "positive" reactions frequently obtained in this period of life with Albustix. In 92 urine samples proteins were fractionated by sodium dodecyl sulphate gel discelectrophoresis. Hemoglobinuria was found during the first weeks of life and tubular type proteinuria was found in newborns and infants. The present data suggest that the proteinuria is due to ineffective proximal tubular reabsorption of low molecular weight microproteins as a result of glomerulo-tubular imblance in early life.


Sustained intra-atrial reentrant tachycardia. Electrophysiologic study of 20 cases. Twenty cases of sustained tachycardia due to intra-atrial reentry were investigated in patients aged 17 to 80 years (mean 47). The average frequency of the tachycardia was 128.6/min (extremes 95 and 180). Three modes of onset of the tachycardia were observed: atrial extra-stimulus (19 times), progressively accelerated atrial pacing (9 times) and atrial escape beat (10 times). The tachycardia was stopped in all cases by a premature stimulation. When spontaneous, the termination was either sudden (10 times) or preceded by a progressive slowing (9 times) or an alternating phenomenon of long-short cycle (13 times). Precise atrial mapping allowed to localize the first atrial depolarization less frequently in the sinus node area (1 case) than in the mean right atrium (21 cases), the low right atrium (2 cases), the interatrial septum (2 cases), and the left atrium (4 cases). The macroscopic size of the reentry circuit was demonstrated in only 3 cases. A junctional reentry was accurately ruled out in all cases thanks to the existence of a second or third-degree AV or VA black, or by studying the sequence of retrograde atrial activation. A true junctional reciprocating tachycardia was associated with the intra-atrial reentry in 2 cases.


The acute cardiac electrophysiological effects of intravenous sotalol hydrochloride. The cardiac electrophysiological effects of sotalol were studied in ten patients (pts) aged 20--65 years undergoing intracardiac stimulation studies for palpitations (7 pts) or dizzy spells (3 pts). The following measurements were made: 1. basic sinus cycle length (SCL): 2. SINUS NODE RECOVERY TIME (SNRT) following overdrive pacing; 3. intra-atrial (PA), atrio-His (AH) and His-ventricular (HV) conduction intervals during regular atrial pacing; 4. effective refractory periods of the atria (AERP), AV node (AVERP) and ventricular myocardium (VERP). AV nodal functional refractoriness (AVFRP) was also determined. All measurements were repeated 10--15 min after i.v. administration of 0.4 mg/kg of sotalol. Results were analysed by the Wilcoxon Signed Rank test. Significant increases in SCL (p less than 0.01), AH (p less than 0.01). SNRT (p less than 0.01), AVERP (p less than 0.02) and AVFRP (p less than 0.01) were observed. These effects are consistent with the beta-blocking action of sotalol. The acute increase in AERP (p less than 0.01) is, however, not a common property of other beta-blockers and may be related to the 'class III' cellular effect of sotalol. These results are discussed in relationship to the electrophysiological effects of other beta-blocking drugs.


Human electropharmacology of the calcium antagonist dimeditiapramine (Ro 11-1781) in coronary patients. The electrophysiological effect of dimeditiapramine (Ro 11-1781), a Ca2+ antagonist, was evaluated in 20 patients with coronary heart disease. Electrophysiological measurements, including sinus cycle length, sinoatrial conduction time, intra-atrial conduction time, atrial, atrioventricular, nodal and ventricular refractory periods and intraventricular conduction time were recorded before and after the intravenous administration of Ro 11-1781. At a dose which is effective against cardiac arrhythmias, Ro 11-1781 produced no statistical significant changes in the sinoatrial and intraventricular conduction time. Similarly, neither the sinoatrial nor the ventricular refractory period was affected. Ro 11-1781, however, increased the atrioventricular conduction time and decreased the systolic blood pressure to a statistically significant extent. The tolerance was very good.


The echocardiographic association of mitral valve prolapse and mitral anulus calcification. Mitral anulus calcification (MAC) and mitral valve prolapse (MVP) are frequently diagnosed conditions. We studied two patients with mild or moderate mitral regurgitation who demonstrated both MAC and MVP on angiography and echocardiography. M-mode echocardiography is probably the definitive test for confirming the presence of MVP. Echocardiography is moderately sensitive in the diagnosis of cardiac calcification, such as MAC, but M-mode echocardiography may not detect the MAC in the majority of patients with both MVP and MAC demonstrated by angiography.


Coronary artery spasm: its role in the pathogenesis of myocardial ischemia. The role of coronary artery spasm in the production of myocardial ischemia has recently become the focus of increased attention. This phenomenon is now well established as a causative mechanism underlying the resting chest pain attacks in Prinzmetal's variant angina. There is also evidence that coronary spasm may play a more significant role in the broad spectrum of ischemic heart disease than can be documented by current techniques. The autonomous nervous system constitutes a major element in the pathophysiology of spasm. Coronary arteriography, in spite of important limitations, remains the only technique for final documentation of this phenomenon, but radionuclide scintigraphy appears to be promising. Nitroglycerin is effective for the relief of the acute attack, while long acting nitrates and the calcium antagonists: nifedipine, perhexiline and verapamil are useful in the prevention of recurrences.


Avulsion fracture of the tibial attachment of the posterior cruciate ligament. Indications and results of delayed repair. In a series of delayed repair in 8 instances of avulsion fracture of the tibial attachment of the posterior cruciate ligament, 6 were isolated avulsion fractures of the tibial attachment of the posterior cruciate ligament and 2 were associated with the fractures of the tibial condyle. Staple fixation was used exclusively. The detachment of the posterior horn of the meniscus was observed in 6 of 8 cases. Four cases, in which the surgery had been carried out within 7 weeks after the injuries, had excellent results. The other cases in which the surgery had been carried out more than 11 weeks after the injuries, had less than satisfactory results. Pain on motion or synovial effusion disappeared but residual anteroposterior instability remained. Repair of the avulsion fracture of the posterior cruciate ligament is recommended in cases of delayed or non-union with symptoms.


Predictive range of motion after total knee replacement. Evaluation of 145 consecutive total knee arthroplasties pre- and postoperatively revealed that regardless of the preoperative deformity (varus, valgus, and flexion contracture), normal alignment of the knee with full extension was obtainable. The amount of flexion to be achieved postoperatively may be determined by the amount of flexion the patient had preoperatively, especially if the degree of flexion was less than 75 degrees. The prosthesis design, sex, age and diagnosis of rheumatoid arthritis were found not to correlate with postoperative motion and stability. In the osteoarthric knee, however, statistical analyses at 6 and 12 months generally showed less postoperative than preoperative range of motion.


Characteristic features of injuries in the knee in women. There are anatomic and physiologic differences in the knee joints and supporting structures of males and females. These variations are most noticeable in the reduced muscle mass and increased mobility in women. Injuries to the knee in women differ from men because of these variations. Meniscal lesions are uncommon in women but sprains and strains occur more frequently. Internal derangements of the knee in women are often the result of their increased hypermobility. These include recurrent patellar subluxation and popliteal cysts. Meniscal tears in females are over-diagnosed and may result in unnecessary meniscectomies even in the hands of experienced orthopaedic surgeons. Arthrography and arthroscopy should increase diagnostic accuracy. Injuries in the knee in women may be reduced by better education as to the type of injury sustained, by better protection to the knee in supporting activities and by screening those women who might be more susceptible to injury.


Bone peg fixation in the treatment of osteochondritis dissecans of the knee joint. Seventeen patients between 15 and 26 years of age, were treated for osteochondritis dissecans of the knee by bone peg fixation. The fragment is attached with 2 or 3 matchstick-size bone graft taken from the proximal tibia. The average follow-up period was 3.2 years, union of the fragment occurred in all cases, and results were rated excellent or good in 16 of 17 patients. Preservation of the normal contour of the distal femur and stabilization of the osteochondral fragment was achieved. Stimulation of local blood supply by bone grafting may have promoted healing and a second procedure for removal of pins or screws was unnecessary.


Dorsal defect of the patella with cartilaginous involvement. A case report. This is a report of a symptomatic cartilaginous defect associated with the dorsal patellar defect. Previously regarded as only an osseous curiosity, this defect can be associated with symptoms of pain after long periods of standing and exercise. Treatment by curettage of the area with debridement of the overlying fibrillated cartliage relieved the pain and produced radiographic evidence of healing of the osseous defect.


Bilateral fracture of the surgical neck of the humerus in a patient with osteomalacia. Bilateral fractures of the humeral surgical neck occurred in a 62-year-old woman, subsequently found to have osteomalacia secondary to primary biliary cirrhosis. Treatment was conservative with good result. After an extensive search of the literature, this is believed to be the first reported case of bilateral fractures of the surgical neck of the humeri without associated posterior dislocation. There has also been no previous report of fracture as the presenting symptom of primary biliary cirrhosis.


Massive synovial cyst of the shoulder causing vascular compromise. A case report. A 47-year-old paraplegic patient is described who developed a massive synovial cyst of the upper extremity. The cyst developed in combination with a tear of the rotator cuff and the long head of the biceps tendon and involved the fasica surrounding the long head of the biceps. The increased pressure in the cyst resulted in a compartment syndrome of a portion of the long head of the biceps muscle. A review of the literature revealed no similar case.


Osseous deformity from osteomyelitis variolosa. A case report. Smallpox osteomyelitis (osteomyelitis variolosa) with gross clinical and radiologic deformities of the elbows, hands and feet occurred in a 53-year-old Vietnamese refugee. This disease, once common in Asia and Africa, may cause permanent damage to joints and growth centers in the course of the acute infection in childhood. The roentgenographic features are sufficiently diagnostic to exclude congenital dysplasia of the skeletal system, leprosy, or sequelae of thermal injury, and other joint disorders.


The laterality of fractures and dislocations with respect to handedness. The left/right frequency of fractures and dislocations with respect to handedness was investigated in 2,716 patients with isolated fractures or dislocations of the appendicular skeleton. For both left- and right-handed patients, upper limb fractures proximal to the wrist occurred more frequently on the left: fractures distal to the wrist, however, occurred more frequently on the patient's dominant side. No lateral tendencies were observed for lower limb injuries. A combination of endogenous and exogenous forces probably account for these findings. Awareness of these tendencies may lead to improved trauma management.


Trigger thumb in successive generations of a family. A case report. Although heredity has been previously suggested as a cause of congenital trigger thumb (stenosing tenovaginitis), no cases in succeeding generations have been reported. The occurrence of 2 cases in a father and son adds credence to a hereditary etiology.


Pathologic fractures of the hand in Paget's disease. The radiologic features of Paget's disease of the bones of the hand are similar to involvement in other bones. Widening of the diameter of the bone and loss of cortical medullary distinction with a mottled coarsening of the trabecular pattern are the most characteristic features. In 2 cases reported here, there was a mixture of lysis and sclerosis with a preponderance of lysis. In the lytic phase the bone structure may be weakened and predisposed to pathologic fracture. Prior to the trauma that precipitated the fracture, both cases were asymptomatic. However, the occurrence of fractures in the involve bones led to the consideration of more ominous possibilities in a differential diagnosis. Recognition of the occurrence of Paget's disease in the bones of the hand or without superimposed pathologic fracture may prevent unnecessary surgical intervention.


The operative treatment of congenital scoliosis. A report of 23 patients. Spinal fusion was performed in 23 patients with congenital scoliosis. Various procedures were used including posterior fusion and without instrumentation. No surgical procedure proved to be superior for obtaining correction regardless of the use of supplemental instrumentation. The use of Knodt or Harrington Instrumentation could not be correlated with a lower pseudoarthrosis rate, shorter postoperative immunobilization period, or a decrease in postoperative loss of correction. The morbidity associated with these surgical procedures was high (48%). Thoracic curves were more prone to lengthen or develop kyphoses postoperatively. A high incidence of varied congenital anomalies was found in association with congenital scoliosis. A through work-up including an intravenous pyelogram and myelogram is strongly recommended prior to the operative treatment of congenital scoliosis.


Colchicine use in the damaged disk syndrome (DDS). Report of 50 patients. Fifty patients with acute and chronic damaged disk syndromes responded (68% good or excellent results) to minimal colchicine usage (0.6 to 1.2 mg per day), indicating that more complicated measures may be avoided in many distressed patients who suffer from disk disease. The usefulness of colchicine is slightly better in the acute than in the chronic disk syndrome, but any disk-suffering patient deserves a therapeutic trial of this possibly valuable medicament, before progressing to more complex, invasive procedures.


Bilateral sacroilac dislocations in an adolescent. A case report. This is a case report of a 15-year-old female who sustained bilateral closed sacroiliac dislocations. She was successfully treated with bilateral skeletal traction and manual closed reduction. The sacroiliac joints redislocated partially despite further traction. Reduction by traction and pelvic sling was then recovered and further displacement was prevented. She regained full range of motion of her hips. This is an uncommon injury produced only by severe trauma.


Effect of tourniquet time on postoperative quadriceps function. Postoperative weakness of quadriceps function following knee arthrotomy has often been attributed to pain inhibition or lack of motivation. However, the delayed recovery may be the result of a slowly resolving axonal compression syndrome caused by the pneumatic tourniquet. Forty-eight patients who underwent knee arthrotomy were evaluated including postoperative electromyographic testing and clinical follow-up. Thirty of these patients (62.5%) developed postoperative EMG changes. Abnormalities were noted in various muscle groups but most commonly involved the quadriceps alone or quadriceps and gastrocnemius. An effort was made in 20 patients to substantially decrease the duration of tourniquet compression by limiting tourniquet inflation to intracapsular portions of the procedures. Fewer EMG changes and more rapid clinical recovery were noted in patients with decreased tourniquet times, suggesting that it is beneficial to minimize the duration of tourniquet compression. In all patients who returned for serial testing, the EMG abnormalities eventually resolved.


The use of methylprednisolone and hypertonic glucose in the prophylaxis of fat embolism syndrome. In a prospective randomized trial of prophylactic therapy in fat embolism syndrome (FES) 64 patients with femoral and/or tibial shaft fractures uncomplicated by other significant injuries were treated with hypertonic glucose (A), methylprednisolone (B), and placebo (C). Clinical findings and several laboratory parameters were used to establish the diagnosis. Two of the 23 patients in the placebo group (C), 3 of the 21 patients in the hypertonic dextrose (A) group and none of the 20 patients in the methylprednisolone (B) group developed clinical fat embolism syndrome. All patients with fat embolism syndrome were hypoxemic (pO2 less than 65 mm Hg) and exhibited central nervous system symptoms. Four out of 5 were hypocalcemic and 3 patients had thrombocytopenia. There was a high incidence of subclinical hypoxemia or subclinical fat embolism syndrome (29% in A Group, 15% in B Group and 39% in C Group). A comparison between groups of the mean pO2 for each patient demonstrated a statistically significant difference between the methylprednisolone group and the control group (p less than 0.025) as was the comparison of proportions of pO2 less than 70 mm Hg (methylprednisolone versus control p less than 0.01, glucose versus control p less than 0.03). Methylprednisolone given prophylactically may reduce the incidence of fat embolism syndrome and can reduce the degree of hypoxemia associated with long bone fractures of the lower extremmity.


Incidence and pathogenesis of alcohol-induced osteonecrosis of the femoral head. Anteroposterior pelvic roentgenograms of 790 patients admitted for treatment of alcoholism were examined for evidence of osteonecrosis of the femoral head. Laboratory data on these patients, obtained shortly after admission, demonstrated that average serum cholesterol levels were within normal limits and average serum triglyceride levels were moderately elevated only in those individuals classified as having a severe addition to alcohol. Non-juxta-articular radiographic abnormalities of the femoral head, neck and shaft were common but no changes were observed which were considered to be early indications of structural insufficiency. Two patients had advanced idiopathic bilateral osteonecrosis of the femoral head. One of these patients had undergone one total hip replacement prior to his current admission. This study indicates that there is a very low incidence of osteonecrosis among alcoholics (less than 0.3%). However, alcoholism may lead to osteonecrosis in certain predisposed individuals. A combination of several factors such as systemic fat embolism, elevated circulating levels of inflammatory fatty acids or prostaglandins, and osteoporosis and Charcot-like effects, which are also associated with corticosteroid-induced osteonecrosis, seem to be involved and may contribute, as well, to other instances of femoral head osteonecrosis.


Lipid composition of the tissues of human knee joints. I. Observations in normal joints (articular cartilage, meniscus, ligaments, synovial fluid, synovium, intra-articular fat pad and bone marrow). The composition and lipid profiles of the following tissues of the human knee joint were determined: articular cartilage, meniscus, ligaments, synovial fluid, synovium, intra-articular fat pad and bone marrow. The tissues were obtained from fresh cadavers and from surgical specimens. The lipid profiles of articular cartilage, meniscus and ligaments were similar to reported analyses of other tissues that are also rich in collagen. The lipid profiles for the remaining tissues were more like the profiles found in the fat depots and fatty tissues of the human body. Both the phospholipid and fatty acid patterns of these tissues were similar within statistical deviation. These results suggest that the per cent compositions of fatty acids and the phospholipid family profile ratios have limited range variability in the "normal" tissues of the human knee. On the other hand, the per cent neutral lipid compositions and their individual profiles showed great variations among the different tissue tissues of the knee.


Silver polymethyl methacrylate antibacterial bone cement. An improved antibacterial bone cement was sought based on the addition of low concentrations of inorganic silver compounds to polymethyl methacrylate. Composites with AgCl, Ag-AgCl, Ag2O, Ag2SO4 and Ag3PO4 in concentrations of 0.05% to 1% by weight, were tested in vitro against bacterial cultures. All were effective, but Ag2SO4 was especially so, even after 7 weeks of incubation in normal saline. Compressive strength of the cement was not affected by these additions, except in the case of Ag2O. Biocompabibility tests in rabbit muscle for up to 12 weeks showed no significant difference between the Ag -PMM and plain PMM in tissue reactivity, both being minimal. These features, coupled with the broad spectrum of antibacterial activity and low allergic potential of silver, make Ag-PMM an attractive alternative to conventional organic antibiotic/bone cement composites.


Optimal orientation of transfixation screws across oblique fractures lines. Torisonal, compression, and bending forces were applied to long oblique fractures of rabbit tibiae that were fixed with 2 screws in different positions. Torison, bending and compression tests were applied to the tibiae. Results for torsional load show that screws should be perpendicular to the fracture plane. For compressive load, screws should be fixed perpendicular to the long axis of the bone. When bending moments are applied in the same plane as the plane of the screws, there is no preferred position of the screws across the fracture. When bending moments are applied perpendicular to the plane of the screws, screws should be positioned perpendicular to the fracture plane.


Articular pathology of ankylosing spondylitis. The essential articular pathology of AS may be said to reflect the occurrence, severity, and overall bias of (a) synovitis which tends to produce articular erosion, and (b) an inflammatory enthesopathy which results in capsular ossification in diarthrodial joints and syndesmophyte formation in cartilaginous joints, both of which are primarily responsible for bony ankylosis. Nonspecific secondary mechanisms contribute to the final picture. These include enchondral ossification, which produces synostosis, osteoporosis and altered stress distribution which make the axial skeleton susceptible to trivial trauma, the destructive effects of which are sometimes described as spondylodiskitis.


Radiology of seronegative spondyloarthropathies. Radiographic manifestations of the seronegative spondyloarthropathies superficially resemble the findings of rheumatoid arthritis although they differ in both distribution and pattern of disease. Ankylosing spondylitis has a predilection for the axial skeleton; psoriatic arthritis may involve distal interphalangeal joints; and Reiter's syndrome is most commonly associated with asymmetrical lower extremity alterations. The absence of osteoporosis and the presence of bony proliferation are also noted in these disorders. Sacroiliitis and spondylitis, which can be observed in any of these disease, may have distinctive features. In ankylosing spondylitis, bilateral saroiliac joint alterations and typical syndesmophytes are common; in Reiter's syndrome and psoriasis, asymmetrical saroiliac joint changes and bulky spinal outgrowths may be observed. The physician should be aware of typical roentgen findings in each of the spondyloarthropathies.


Radionuclide joint imaging in the seronegative spondyloarthropathies. Radionuclide joint imaging (RJI) of the peripheral and axial skeleton is a recent advance in the detection of early articular inflammation and has proven useful in establishing the extent and pattern of this involvement. The bone-seeking agents--the radiophosphates--are the radiopharmaceuticals presently favored for RJI in adults. They are more sensitive than the clinical examination in detecting inflammatory joint disease in all peripheral joints with the exception of the shoulders, elbows and knees. Radiophosphate may also be used to evaluate the axial skeletion for inflammatory involvement. The sacroiliac joints may be evaluated by a new technique, quantitative saroiliac scintigraphy (QSS). Studies to date have demonstrated that QSS is most sensitive in early sacroiliitis, a time when conventional radiography is normal or shows equivocal abnormalities. While extremely sensitive as a screening procedure for inflammatory articular disease, RJI is nonspecific diagnostically. Radiophosphate uptake by bone occurs in metabolic bone disease, osteoarthritis, trauma and juxta-articular bony abnormalities such as osteomyelitis and bone infraction. The results obtained by radionuclide joint imaging must be supplemented by the clinical findings and conventional investigations to establish a specific diagnosis.


The clinical spectrum of ankylosing spondylitis. Ankylosing spondylitis is more common in young men than in young women and is insidious in onset. Typically, patients complain of pain and stiffness around the sacroiliac region. At the disease progresses, pain is often felt in the mid-lumbar, thoracic and cervical regions resulting in a significant reduction in the range of motion of the entire spine. About one fourth of the patients display involvement of proximal synovial joints. Acute anterior uveitis may precede AS or can occur when the disease is otherwise in apparent remission. Each patient with established disease should be carefully evaluated for cardiovascular, pulmonary, and neurologic complications. Early detection of AS is important, since proper management may well prevent the severe fixed deformities of the spine and root joints that is liable to occur in these patients.


The clinical spectrum of psoriatic arthritis. Epidemiologic, clinical, radiologic and serologic evidence suggests that psoriatic arthritis is a specific entity and not the coincidental occurrence of 2 common diseases, psoriasis and rheumatoid arthritis. Psoriatic arthritis may be defined as psoriasis associated with inflammatory arthritis (peripheral arthritis or spondylitis or both) and usually a negative serologic test for rheumatoid factor. Clinical characteristics of the disease include: almost equal distribution between males and females; peripheral arthritis involving only a few small joints in asymmetical fashion; involvement of distal interphalangeal joints; sausage digits; arthritis mutilans; ankylosing spondylitis; goutlike onset; and higher frequency of nail involvement than occurs in uncomplicated psoriasis. The rash may present with arthritis, or, equally, may precede or succeed joint involvement. With regard to pain and disability, the prognosis in psoriatic arthritis is better than in rheumatoid arthritis.


The seronegative spondyloarthropathies of childhood. Most chronic arthritis in childhood is seronegative. Within "JRA" several distinct subgroups exist: one of these (pauciarticular disease type II) affects predominantly boys more than 8 years of age. It is clearly associated with sacroiliitis, HLA-B27, family history of spondyloarthropathy, and subsequent ankylosing spondylitis in an as yet underfined percentage of patients. This type of disease is probably classified appropriately with the spondyloarthropathies, although patients often may fulfill diagnostic criteria for "JRA" in the first years of their disease, and accounts for about 15% of "JRA." The other JRA subgroups do not appear to have features of seronegative spondyloarthropathy. Reiter's syndrome and psoriatic arthritis exist in children, but appear to be rare. The arthritis of inflammatory bowel disease in childhood resembles that in adulthood. The recognition of spondyloarthropathy in children, particularly the sizable group of patients with "JRA" pauciarticular disease type II, is of practical importance to permit proper therapy, follow-up and prevention of deformity.


A unifying concept for the spondyloarthropathies. A group of diseases--ankylosing spondylitis, psoriatic arthritis, Reiter's disease, ulcerative colitis, Crohn's disease, juvenile chronic arthritis (Still's disease), Whipple's disease, and Behçet's syndrome, which previously were thought to be variants of rheumatoid arthritis, now appear to be distinct from that disease but linked together in a group termed "seronegative spondyloarthropathies." Detailed studies have been made of the clinical, radiologic, and serologic features of these individual diseases. Extensive family studies have been done epidemiologically and through examining pedigrees. These have demonstrated clinical interrelations and familial aggregation. Ankylosing spondylitis is a feature of all the groups. Studies in which B27 was found more frequently in each of these groups confirm the interrelation and suggest a genetic predisposition with a gene related to B27. There is other evidence for environmental factors such as infection in certain of the diseases. The findings have important implications in the management of the disorders.


Cruciate ligament stents in reconstruction of the unstable knee. A preliminary report. Cruciate ligament stents have been developed to severe as internal splints which provide excellent temporary stability while allowing full range of motion of the knee during postreconstruction rehabilitation. Forty-three patients with disabling chronic knee instability were treated at one center using similar reconstruction techniques with either the anterior or posterior cruciate stent. When both cruciate ligaments were absent, only the posterior was used. All stents are intended only as temporary internal splints and all patients were advised that the structures were expected to break eventually. Followup of 15 patients with anterior cruciate stents revealed only 50% satisfactory overall results. Overall results were satisfactory in 80% of 20 patients with posterior cruciate stents. Longer implant survival is needed, and this must be accomplished by building more flexibility into the stent core and by improving surgical technique with more precise instrumentation.


Radionuclide assessment of peritoneo-venous shunt patency. LeVeen shunt patency can be easily assessed by sequential scintigraphy with a gamma camera after an intraperitoneal injection of Tc-99m-macroaggregated albumin (Tc-99m-MAA). If the shunt is patent, the particles of MAA reach the pulmonary capillary bed and the lungs are visualized. The activity in the lungs is easily discerned without any interference from radioactivity in the peritoneal cavity. The study is semiquantitative since the intensity of lung activity is directly proportional to the shunt patency and flow rate across shunt tubing.


Scintiphotographic evaluation of LeVeen peritoneo-venous shunt patency using intraperitoneal Tc-99m-MAA. A simple method is described for assessing the patency of LeVeen peritoneo-venous shunts. Following the intraperitoneal injection of 5 mCi of Tc-99m-MAA pulmonary radioactivity is monitored using a gamma scintillation camera. Lung visualization indicates shunt patency, while lack of lung uptake implies shunt obstruction.


Radionuclide pulmonary arteriography.

Radionuclide pulmonary arteriography. Radionuclide pulmonary arteriography offers a unique method for visualizing the main pulmonary artery and its major branches. Since the radioactive particles that are injected intravenously become lodged in the pulmonary capillaries and pre-capillary arterioles, there is no interference from the systemic circulation. Normally, the main pulmonary artery is visualized for no longer than 4 or 6 seconds; prolongation of the duration of visualization may be indicative of, for example, pulmonary hypertension and pulmonary embolism. The patency of the left and right pulmonary arteries may be determined and sites of occlusion identified.


Gallium scan: clue to diagnosis of starch peritonitis. A patient with starch peritonitis was given a gallium scan which showed diffuse uptake in the abdomen and intense uptake in a noninfected incision six weeks after surgery. The accumulation of gallium in a noninfected surgical incision later than one week after surgery, accompanied by diffuse abdominal uptake, may indicate the presence of starch peritonitis.


Unusual Tc-99m and I-123 images in metastatic thyroid adenocarcinoma. A patient with metastatic thyroid carcinoma showed discordance of I-123 and Tc-99m imaging results. In addition, despite close histologic similarities, the metastatic lesions differed considerably in their ability to trap Tc-99m.


An evaluation of the 24-hour RAIU test performed with an Anger camera and a pinhole collimator. RAIU measurements obtained with a conventional thyroid uptake probe have been compared with those obtained with an Anger camera and a pinhole collimator. Although the field distribution for the pinhole collimator deviates markedly from the IAEA recommendations, the group data from the comparative measurements in this series were identical, with a confidence level of 99%. However, in several cases the data from differing measurement regimes for individuals varied markedly.


Displacement of the abdominal aorta by a pseudocyst of the pancreas. Cystic lesions are generally thought not to displace the abdominal aorta. A case involving a large cystic mass near the pancreas which was proven to be a pancreatic pseudocyst is presented, with a dynamic nuclear angiogram and a CT scan of the abdomen showing displacement of the aorta.


Chronic middle ear disease and auditory perceptual deficits: is there a link? Data are presented indicating a correlation between chronic recurrent otitis media of early childhood and in increased likelihood of subsequent auditory processing deficits in a group of children referred for evaluation of impaired learning. Helpful appendices are added for a better understanding a central auditory processing skills.


Auditory brain-stem response audiometry in children. Auditory Brain-stem Response (ABR) Audiometry, also called Brain-stem Evoked Response Audiometry, is an effective procedure for assessing the hearing of children who cannot or will not perform satisfactorily on behavioral audiometric tests. Although ABR audiometry has limitations, it does permit an estimate of hearing status in nearly all children regardless of their age or developmental level.


EEG abnormalities in diabetic children: influence of hypoglycemia and vascular complications. The effect of diabetic control upon EEG has seldom been studied. In the present investigation, a significant positive correlation between EEG abnormalities and degree of diabetic control was found, but no definite increase was noted in relation to the duration of diabetes. Eighty per cent of our patients having more than 5 severe hypoglycemic attacks showed evidence of abnormal EEG, suggesting that hypoglycemic coma or convulsions are closely related to EEG abnormalities (minor hypoglycemic episodes had no effect on the EEG). With the sensitive technique of fluorescein angiography, we demonstrated a clear correlation between incipient retinal angiopathy and EEG abnormalities. The factors that most positively relate to pathologic electrocerebral (EEG) activity in diabetic children are frequent and severe hypoglycemic attacks, comas and/or convulsions, and vascular changes in the retina.


Haemoperfusion in the management of digoxin toxicity: is it warranted? Several recent publications have encouraged the use of hemoperfusion to remove digoxin from the body of overdosed patients. The usefulness of haemoperfusion in removing digoxin from the body has therefore been examined using pharmacokinetic simulation techniques and published data. Haemoperfusion for a period of 4 hours with a clearance of 100 ml/min removes less than 7% of the amount of digoxin in the body (including that in the gastrointestinal tract at the beginning of haemoperfusion), regardless of the time after the dose that haemoperfusion is started. Dramatic therapeutic benefit in digoxin intoxication is unlikely to be a consequence of the amount of digoxin removed from the body by haemoperfusion. If therapeutic benefit is derived from a transient decline of digoxin concentration in plasma, it may be expected to be negated as the drug redistributes from tissues.


Observations on vesico-ureteric reflux and intrarenal reflux: a review and survey of material. Objectives of this study were to evaluate some of the factors influencing vesico-ureteric reflux and intrarenal reflux. Reflux occurs in about one-third to a half of Caucasian children with urinary tract infection and although not greatly influenced by examination technique or sex it is affected by age, diuretics and race. Intrarenal reflux occurs in about 10% of cases with total reflux and does not appear to cause scars on its own. Autopsy studies can provide valuable information on papillary morphology and reaction to pressure, but information is of doubtful reliability in the first months of life and in fixed specimens. The literature pertaining to vesico-ureteral reflux, intrarenal reflux and related research projects is briefly reviewed.


The use of information theory in evaluating the contribution of radiological and laboratory investigations to diagnosis and management. Using information theory, the value of radiological and laboratory investigations has been assessed in the diagnosis and management of 67 patients suspected of having inflammatory polyarthritis. There were only three changes in diagnosis made as a result of the investigations. Both the radiological and laboratory tests supplied a small but significant amount of information in improving the physician's confidence in diagnosis. Changes in management occurred more frequently but the final management decision differed from the pre-investigation decision in only 17 of the 67 patients (25%). Radiological examination failed to decrease uncertainty using a simple 'change in uncertainty' measure. Both types of investigation supplied a limited bu significant amount of information towards the final management decision, although the contribution from radiology was only significant when view before the receipt of the results of the laboratory tests. In view of the limited value of the investigations - particularly radiology - in this study, it is important to fully asses present and future diagnostic procedures especially in relation to patient management.


Technical problems in arthrography of the painful hip arthroplasty. Arthrography following hip replacement has been reviewed. The problems encountered have been analysed with particular reference to technique and accuracy. The accepted criteria for loosening have not been consistently reliable and have led to false positive interpretation of loosening of the acetabular component. The reasons for false negative results are also considered.


The radiology of lymphomatoid granulomatosis in the lung. This paper describes the salient clinical and radiological features of two patients with lymphomatoid granulomatosis of the lungs. We have, in addition, reviewed the previously documented 22 cases in which radiographs were published along with their case histories. The commonest radiographic appearance, that of bilateral multiple pulmonary nodules, should not be mistaken for multiple metastases.


Water soluble radiculography in the erect posture: a clinico-radiological study. A technique for water-soluble radiculography is described involving radiography in the standing and stooping positions. Seventy-eight radiculograms have been reviewed and correlated with clinical and operative findings. Thirty patients had an anterior thecal deformity demonstrated on radiographs exposed in the standing position, which was not completely reduced in the stooping position. Twenty-eight of these patients underwent operation and in 25 patients a disc prolapse was confirmed. Only a small number of patients (11) had a disc protrusion at operation. Of these patients, eight had an anterior thecal deformity on radiographs exposed in the standing position which was completely reduced in the stooping position.


A correlation of the surgical and radiculographic findings in lumbar disc herniation. The findings on plain radiographs and at water-soluble radiculography are compared with those at laminectomy in 50 patients with lumbar disc protrusions. Predictions of the level of disc protrusion based on the plain radiographic appearances could be made in 71%. Water-soluble radiculography accurately demonstrated 50 of 52 protrusions (96%). No abnormality was found at surgery at three other disc levels where equivocal radiculographic appearances failed to eliminate the possibility of disc protrusion. When all the levels examined surgically are included the water-soluble radiculogram was accurate at 57 levels out of 62 (92%). The immediate morbidity of radiculography is described and significant side effects were shown by 23% of patients.