Separation of folate binding protein from human serum by DEAE-cellulose column chromatography. On diethylaminoethyl-cellulose column chromatography, the folate binding protein in the serum of 21 patients eluted in the early effluents as a single sharply defined peak. The chromatographic behavior of the folate binder remained unchanged whether or not the serum was, before chromatography, complexed with tritium-labeled pteroylglutamic acid ([3H]PGA), dialyzed, or charcoal-adsorbed. Heating to 100 degrees C for 10 min dissociated the [3H]PGA-binder complex while destroying the folate binding property. The presence or appearance of this folate binder in increased amounts in the serum of patients with various diseases may be related to conditions of increased tissue turnover.


Methotrexate in blood, urine, and cerebrospinal fluid of children receiving high doses by infusion. Methotrexate was determined in plasma (31 patients), urine (eight patients), and cerebrospinal fluid (two patients) after high doses (35 to 150 mg/kg) by infusion, with citrovorum factor rescue. Concentrations in plasma were proportional to dose at 6, 24, 72 h after beginning treatment, but this trend was very minimal for samples obtained at 48 h. Clinical toxicity probably will not be serious if the methotrexate concentration in the serum is less than 4.5 X 10(-6) mol/liter at 48 h after the start of a 6-h infusion. In both of the two patients so examined, therapeutic concentrations appeared in cerebrospinal fluid after intravenous infusion of the drug. A kinetic enzymic method, radioassay, and radioimmunoassay all yielded similar results for drug concentrations.


Ultramicro gas-chromatographic analysis for anticonvulsants, with use of a nitrogen-selective detector. We describe a procedure for determining phenobarbital, primidone, and diphenylhydantoin simultaneously in 50-mul volumes of serum by use of gas chromatography and a detector with heightened sensitivity and selectivity for nitrogenous compounds. The drugs, together with an internal standard, 5-allyl-5-phenyl barbituric acid, are extracted from serum by the procedure of MacGee [Anal. Chem. 42, 421 (1970)]. The drugs are converted to their methyl derivatives by a modification of the procedure of Greeley [Clin. Chem. 20, 192 (1974)] and then analyzed on a column containing 3% OV-1, with a temperature program, and detected by a nitrogen-selective detector. The method is reproducible to about 7%. Sensitivities of 0.5 mg/liter for 50-mul serum samples are attained routinely. Mephobarbital interferes with the analysis because methylation yields the same product as methylated phenobarbital. Total analysis time for a single sample is 15 min.


Simple determination of 3alpha-hydroxy fraction and 3beta-hydroxy fraction of urinary 17-ketosteroids. We describe a method for determination of the 3alpha-hydroxysteroid fraction and 3beta-hydroxysteroid fraction of 17-ketosteroids in urine. The method includes enzymatic hydrolysis with beta-glucuronidase and extraction with ethyl acetate and color development of 3beta-hydroxysteroids by 3beta-hydroxysteroid oxidase and of total 17-ketosteroids by the Zimmermann reaction. The value for 3alpha-hydroxysteroids is calculated by subtracting the value for 3beta-hydroxysteroids from the value for total 17-ketosteroids. Recovery was assessed and results compared with those by an accepted method. Results were satisfactory for measuring these fractions of 17-ketosteroids.


Determination of carbamazepine in blood or plasma by high-pressure liquid chromatography. We described a sensitive and precise high-pressure liquid-chromatographic method in which 5-(p-methylphenyl)-5-phenylhydantoin is used as the internal standard in determining carbamazepine in whole blood or plasma. Carbamazepine is well separated from normal blood constituents in less than 8 min, and other commonly used anticonvulsants do not interfere with the analysis. The sensitivity of this method is adequate to quantitate 0.25 mg of carbamazepine per liter in 2 ml of sample, and the lower limit of detection is 100 ng. Twenty specimens were analyzed by a gas-chromatographic method and by the present method; the resulting correlation coefficient was greater than .980.


Equilibrium binding studies of insulin antibodies in diabetic subjects. Equilibrium binding of insulin to human insulin antibodies from diabetic subjects has been studied by two methods. Results obtained by using a nondissociating gel filtration assay differed from those obtained by a conventional competitive binding method. Both methods yield data consistent with two classes of insulin binding site, having association constants of approximately 10(9) and 10(7) liter/mol. The principal differences are the higher association constant and lower number of binding sites for the high-affinity binding component, observed with the gel filtration method. In the conventional competitive binding assay, damaged radioligand, dissociation of the binding complex, or limitations of ligand availability may be responsible for the erroneous results. Data from nine diabetic patients indicate that insulin resistance and stability of diabetes cannot be explained by the binding properties of insulin antibodies alone.


Rate of decay and distribution volume of MB isoenzyme of creatine kinase, intravenously injected into the baboon. We determined the decay constant and distribution space of the MB isoenzyme of creatine kinase after intravenous injection of 440 to 720 U, in a group of seven adult baboons. The rate of decay of the isoenzyme was monoexponential, with a mean decay constant of 0.00175 min-1 (SD, 0.00019). The mean distribution volume obtained by extrapolation of the monoexponential curve to zero time was 5.22% (SD, 1.06) of body weight. We have determined these parameters with the purpose of using this isoenzyme in the baboon as an experimental model for measuring myocardial infarct size.


Direct use of ion-exchange papers in hemagglutination-inhibition tests for drug abuse. I modified a procedure for screening urine specimens for evidence of drug abuse, to permit direct use of commercially available ion-exchange papers in hemagglutination-inhibition assay for drug detection. Small circles punched out of the papers, which previously had been impregnated with drug-containing urine, were used in the detection step, leaving the remainder of the specimens on paper available for confirmatory analyses. The procedure is useful in screening for the presence of opiates, methadone, and (or) barbiturates.


Reduction of sample size on the Technicon SMA 6/60 continuous-flow analyzer. The manifold of the Sequential Multiple Analyzer SMA 6/60 (4 + 2) has been modified to decrease serum sample size to 90 mul, by using a common diluent for all six channels and recycling the discard of each dialyzer into the next one. The modification can be made in less than 4 h without the need for any additional parts; the modified manifold requires one-third fewer pump lines and fewer reagents, thus reducing operating costs and simplifying instrument maintenance, while retaining the same precision, speed, low carryover, and linearity of the production model.


Ultramicromethod for determination of plasma uric acid. We describe an ultramicromethod for determination of uric acid by a manual procedure. Hydrogen peroxide, formed when uric acid is oxidized in the presence of uricase, oxidatively couples two molecules of p-hydroxyphenylacetic acid in the presence of peroxidase to produce a highly fluorescent compound. The specificity of the uricase reaction is retained, and the fluorometry results in a higher sensitivity (but a lower precision) than that obtained by applying spectrophotometric methods. As little as 50 ng of uric acid can be determined, and only 10 mul of plasma is required. Values obtained for human plasma are higher than those obtained by the spectrophotometric method.


Evaluation of benefits of screening tests done immediately on admission to hospital. Evidence was sought of improved inpatient progress and reduced hospital costs when a battery of investigations were done at the time a patient was admitted to hospital. The outcome in 500 admission-tested patients was compared with that in two other groups of 500 control patients. No significant differences were found among the three groups in a variety of indices of inpatient progress. Because of an estimated 64% increase in the cost of investigating inpatients with admission testing, the total cost of hospital care was increased by about 5%. Under the conditions of this study, admission testing added to the cost of hospitalization, without associated evidence of benefit to the patient.


Alkaline phosphatase. II. Conditions affecting determination of total activity in serum. Results of previous experiments on isolated purified isoenzymes of alkaline phosphatase from humans have been confirmed on sera containing relatively large activities of the different isoenzymes. The most remarkable finding is that activation by N-ethylaminoethanol is much more pronounced, in the case of the intestinal and placental isoenzymes, than is activation by diethanolamine. For several reasons, it is suggested that N-ethylaminoethanol is the buffer of choice, 0.1 mol/liter concentration for routine measurements and 1 mol/liter in those cases where the determination of the intestinal or placental isoenzymes is important. Mg2+ could be omitted because its addition increases the activity only marginally. Normal values for adults with use of 0.1 mol/liter N-ethylaminoethanol are 59 +/- 36 (2 SD) U/liter (n = 126).


Analysis of variation in automated determination of sodium, potassium and calcium ions in human serum. The concentration of sodium ion (Na+), potassium ion (K+) and calcium ion (Ca2+) in patient sera were assayed simultaneously on two separate flame photometers and then evaluated by analysis of variance (ANOVA). Two different experimental designs were devised in order to separate the error components assignable to pipetting, dilution, and instrumental measurement. Within-series variability was compared with the between-series variability. Similar statistical treatment of results from quality control samples gave estimates of variances between days, between dilutions, between instruments, and between channels, as well as the interaction terms and instrumental measurement errors. The total (overall) coefficients of variation (CV) were 1.15, 1.60, and 1.38% for Na+, K+, and Ca2+, respectively. The adequacy of the quality-control system to predict expected variation in patient specimens was verified by comparing errors from patient-sample duplicates and from control samples.


A new rapid assay of oestrogens in pregnancy urine using the substrate native fluorescence. A simple and rapid method is described for the quantitative determinations of free and conjugated oestrogens in pregnancy urine. The oestrogens are precipitated with ammonium sulphate and freed from non-oestrogenic compounds by solvent extraction. The conjugated oestrogens are hydrolysed by a beta-glucuronidase from Escherichia coli, and the total free oestrogens are extracted into ether and their fluorescence intensity at 310 nm in this solvent is determined. The method is rapid and precise for oestrogen levels at concentrations greater than 2 mug/ml (7 mumol/1). It is proposed that this method, which measures oestradiol and oestriol levels, be applied routinely to monitor feto-placental function in pregnancy. It offers advantages over other currently used assays in that less manipulative and technical skill is required to give a high level of precision and accuracy. An accurate estimate can be produced within 30-60 min of receipt of a 24-h uring specimen. Two variations of the method are also described. In one the ammonium sulphate precipitation step is omitted so as to give an even quicker assay procedure which determines conjugated oestrogens in the urine, and in the other oestriol only is determined.


A novel specific assay of 25-hydroxy vitamin D. The synthesis of 25-hydroxy-[26-2H3]vitamin D3 is described. A fixed amount of this compound (usually 250 ng) is added to a fixed amount of serum (usually 2.5 ml) and the mixture is extracted with a chloroform/methanol mixture. The extract is chromatographed on a Sephadex LH-20 column together with a trace amount of 25-hydroxy-[263H3]vitamin D3. The chromatographic fraction corresponding to 25-hydroxy vitamin D3 is converted into trimethylsilyl ether and the amount of unlabeled 25hydroxy vitamin D3 is determined from the ratio between the mass fragmentographic recording at m/e 131 (base peak of unlabeled 25-hydroxy vitamin D3) and m/e 134 (base peak 25-hydroxy-[26-2H3]vitamin D3). The relative standard deviation of the method was about 5%.


Determination of plasma cholesterol: comparison of gas-liquid chromatographic, colorimetric and enzymatic analyses. The efficacy of methods for plasma cholesterol analyses based on gas-liquid chromatographic (GLC) or enzymatic cholesterol determinations was tested on commercially available standard serum, plasma obtained in a study of an age stratum of the population and on plasma from a number of patients from an out-patient department. These results were compared with colorimetric cholesterol determinations on chloroform/methanol extracts from plasma using the ferric chloride/sulphuric acid reagent. The GLC-based procedure gave values 12% lower than the colorimetric determinations. This discrepancy seemed to be explained, to a marked extent, by the fact that cholesterol metabolites interfere with the colorimetric determinations. The GLC-based method was apparently accurate since it has the advantage of specificity and is easy to standardize with the internal standard technique. Enzymatic total cholesterol analyses gave slightly (2%) lower values than the GLC-based analyses, apparently because of an incomplete hydrolysis of cholesterol esters. Enzymatic analyses of free cholesterol gave similar results to those of the GLC-based method.


Abnormal serum lactate dehydrogenase isoenzyme in a case of laryngeal carcinoma and thyrotoxicosis. An abnormal lactate dehydrogenase (LDH) isoenzyme was found in the serum of a patient with laryngeal carcinoma and hyperthyroidism. On electrophoresis it migrated as an additional band between LDH-1 and LDH-2. Follow-up studies suggested that this higher molecular weight, rather thermostable LDH isoenzyme, might have originated from the cancer tissue, though a possible relationship with the thyrotoxic state cannot be excluded.


Seasonal variation of urinary excretion of total metanephrines. Results of 1414 measurements of urinary excretion of free and conjugated (total) metanephrine and normetanephrine (total metanephrines, tMN) and of 1630 measurements of vanilmandelic acid (VMA) excretion were analysed according to the month of sample collection. These collections had been carried out as a part of a study of hypertension at out institute over the 5-year period between 1970 and 1975. The means and scatters of tMN were significantly varied depending on the season of the year; the mean during 3 months of summer was 380 mug/day and the mean for 3 winter months 800 mug/day. The scatter of tMN in winter months was wider. A minor seasonal variation was observed for VMA: the means of summer and winter months were 3.8 mg/day and 4.5 mg/day, respectively. The results suggest a seasonal difference of catecholamine catabolism.


Molecular alterations in congenital erythrocyte pyruvate kinase deficiencies. The molecular heterogeneity of congenital pyruvate kinase deficiencies becomes apparent from the results of immunological studies. In one case, a quantitative defect is plausible; in the second case, the most likely hypothesis is a molecular alteration of the binding site for the activator, with preservation of the antigenic specificity; in the third case an abnormal protein, extremely unstable and devoid of antigenic reactivity, carries catalytic activity. In no case can any cross-reacting material be detected.


Molecular sieving by glomerular basement membrane isolated from normal and nephrotic rabbits. Analog chromatography with glomerular basement membrane isolated from normal and nephrotic rabbits was performed to see if there was a molecular sieving effect by the basement membrane. In a normal glomerular basement membrane column, 125I-labeled human serum globulin and 131I-labeled human serum albumin were eluted at the same position, probably at the void volume of the column. However, 125I-labeled insulin and tritiated water appeared with a delay and gave separated peaks. In nephrotic glomerular basement membrane, 125I-labeled human globulin, 131I-labeled serum albumin, 125I-labeled insulin and tritiated water gave four distinctly separated peaks in that order. By analogy with Sephadex, the sieving effect of glomerular basement membrane was demonstrated.


Glyceride content of amniotic fluid cells as an index of fetal maturity. A simple biochemical method has been used to determine the content of neutral lipid of washed cell pellets prepared from 114 samples of amniotic fluid. This was done to improve the large standard deviation of the conventional orange fat cell measurements. By relating the content of neutral lipids to the total protein content of the pellet, the error of cell counting is minimized. The resultant glyceride/protein ratio increases 20 times within the last 8 weeks of pregnancy. The results are not altered by associated diabetes, hydramnios or Rh isoimmunization.


Simple solid-phase radioimmunoassays for total tri-iodothyronine and thyroxine in serum, and their clinical evaluation. 1. Simple solid-phase radioimmunoassay methods for total tri-iodothyronine and thyroxine in serum or plasma are described. By using antibodies that are covalently coupled to microcrystalline cellulose, virtually identical assay procedures can be used for the determination of both hormones. An alkaline sodium glycinate buffer provides better assay conditions than the buffers often recommended for thyroid hormone radioimmunoassay. 2. Assay results are unaffected by moderate sample haemolysis. Plasma samples stored at room temperature for more than nine days often show an apparent increase in concentration of both thyroid hormones. 3. Serum tri-iodothyronine and thyroxine concentrations in healthy euthyroid subjects, and in euthyroid pregnant women are reported. In a series of 100 consecutive patients referred to a thyroid clinic the tri-iodothyronine assay discriminated better than the thyroxine assay between hyperthyroid and euthyroid patients. The thyroxine assay was much better than the tri-iodothyronine assay in discriminating between hypothyroid and euthyroid patients.


Direct measurement of serum non-caeruloplasmin copper in liver disease. The serum non-caeruloplasmin copper concentrations were measured in normal subjects and patients with various types of liver disease by a sensitive direct method involving complexing the copper and measurement by atomic absorption spectrophotometry. In normal subjects the mean concentration (+/- S.D.) was 10.1 +/- 1.6 mug/100 ml, males having a slightly higher value (10.7 +/- 1.3 mug/100 ml) than females (9.2 +/- 1.8 mug/100 ml). In patients with various non-hepatic diseases concentrations were raised (15.8 +/- 8.9 mug/100 ml), as also in hepatitis (14.7 +/- 4.3 mug/100 ml), cholestasis (16.1 +/- 6.4 mug/100 ml) and cirrhosis (16.3 +/- 8.7 mug/100 ml). Heterozygotes for Wilson's disease and patients treated for Wilson's disease had concentrations (12.9 +/- 5.9 and 9.8 +/- 3.7 mug/100 ml, respectively) which did not differ significantly from normal whereas untreated patients had very significantly raised concentrations (22.9 +/- 4.5 mug/100 ml). Direct measurement of serum non-caeruloplasmin copper is more accurate than indirect measurement and may help in assessing the effect of treatment but it is concluded that measurement of this fraction of serum copper will not enable Wilson's disease to be differentiated from other forms of liver disease.


The relationship between serum creatine kinase and thyroid hormones: in vivo and in vitro studies. Creatine kinase activity was measured in sera submitted for thyroid investigations. Although, as groups, hypothyroid and hyperthyroid subjects had higher and lower creatine kinase results than normal, the assay was not satisfactory as a screening test for predicting thyroid status in the individual. Attempts to inhibit the serum enzyme in vitro using high concentrations of thyroxine and tri-iodothyronine were unsuccessful. The inverse relation between serum creatine kinase and thyroid status is unlikely, therefore, to be due to a direct inhibitory effect of the hormones on the enzyme.


Evaluation of the specificity of a luteinizing hormone beta and alpha subunit assay. A non-specific antihuman FSH antiserum which is able to bind 125I-labelled FSH, LH, LHbeta and LHalpha subunits, has been shown to contain at least three different antibody populations directed against different parts of the LH and FSH molecule. This antiserum has been used to develop a rather specific radio-immunoassay for determination of the common alpha subunit. Further, by gel filtration it is shown that the LH IRC2/69 preparation contains about 30% of intact LH and about 10% of alpha and LHbeta subunit, respectively. In contrast, the LH 68/40 preparation contains about 96% of intact LH and only small amounts of alpha and LHbeta subunit. Also, a considerable difference in the content of the alpha sub-unit was found between two different FSH preparations. The contamination of the preparations of the intact hormones is shown to have a marked influence on the cross-reactivity of the substances in an LHbeta and alpha subunit radioimmuno-assay.


Isoelectrofocusing: a method of multiple applications for hemoglobin studies. A microanalytical screening of hemoglobins by isoelectric focusing on acryl-amide gel columns is described. Addition of this technique to our regular analytical procedures revealed many mutants, praticularly some neutral ones which were not resolved by other conventional procedures. Extension of this technique to a quantitative scale permitted rapid isolation of some unstable mutants in an almost pure form ready for functional studies. The natural color of the separated components is often indicative of their nature and in cases like the sulfhemoglobin, Hbs M, they are of diagnostic value. The heme-losing, abnormal, unstable mutants, on the addition of external cyanhemin, take them up and change their isoelectric pH. This is an attractive visible procedure for their diagnosis. From all these results, it appears that isoelectric focusing as a single method brings more information than the other conventional procedures and hence can be considered as a semi-routine investigation for hemoglobin studies before deciding on a much longer procedure.


Automated assay of ceruloplasmin by kinetic analysis of o-dianisidine oxidation. Automated procedures for the kinetic assay of serum ceruloplasmin activity using a bichromatic and a centrifugal analyzer are described. The method is based on the oxidase activity of ceruloplasmin at pH 5.0 with o-dianisidine as substrate. Enzyme activity is reported in I.U./l, based on the molar absorption coefficient of o-dianisidine consumed. The substrate is stable and is not subject to non-enzymatic oxidation. Comparison with a manual reference end-point assay using the same substrate indicates good correlation of the bichromatic and centrifugal methods. The analytical precision is comparable to the manual assay for both methods.


Simultaneous estimation of urinary steroids by semi-automated gas chromatography. Investigation of neo-natal infants and children with abnormal steroid synthesis. Development of a method for multicomponent analysis of urinary steroids on open-tubular columns is described. The urinary steroid conjugates were hydrolysed enzymatically, extracted on Amberlite XAD-2 columns, purified on columns of Sephadex LH-20, then analysed as methyloxime trimethylsilyl ethers on a gas chromatograph on which up to 24 samples may be automatically injected. All major urinary steroids from 17-oxosteroids to cortisol metabolites were analysed and these were quantified relative to internal standards, 5alpha-androstane-3alpha, 17alpha-diol and cholesteryl butyrate added to the samples prior to derivatisation. The precision of the full technique and reproducibility of repetitive automatic solid injection was found to be acceptable for the purpose of profile analysis. Examples of urinary steroid profiles in normal infants and infants with disorders of adrenal steroid production and excretion are given.


An evaluation of three commercially prepared anion-exchange resin columns for separation of tetraiodothryonine in serum. Three different commercially prepared anion-exchange resin columns for thyroxine (T4) separation from serum for the "T4 by column" assay were evaluated using the protocol of the supplier. The claims by the suppliers for the distribution and recovery of T4 in the first and second thyroxine-containing eluates were experimentally evaluated by the addition of a tracer quantity of purified [125I]T4. The average experimentally determined elution ratios of recoverable T4 (sum of T4 in first and second eluates) with these commercial columns were: Bio-Rad, 92.2:7.8 (90:10 claimed); Oxford, 87.8:12.2 (94:6 claimed); and Curtis Nuclear, 88.7:11.3 (80:20 claimed). The percent recoveries of T4 in the first thyroxine-containing eluate were: Oxford, 82.3 + 9.70 (x +/- 1 S.D.); Bio-Rad, 91.75 +/- 2.09; and Curtis Nuclear, 74.20 +/- 6.14. Mean serum T4 values obtained by the column method with all commercial columns tested were lower than competitive protein binding radio-assay (CPBR) values if the former values were not corrected for recovery. When individual recovery correction factors were applied to column results, improved correlation and better correspondence of "T4 by column" mean values with the CPBR values were noted. It is concluded that the largest part of the total variability of the "T4 by column" assay is contributed by the chromatographic step when the colorimetric step is performed with an automated technique.


Semi-automated competitive protein binding analysis of serum thyroxine on reusable Sephadex columns and its advantages over radioimmunoassay. Competitive protein-binding analysis of serum thyroxine on small, reusable, Sephadex columns has been further studied and improved. The improved, semi-automated procedure results in reduced working time and costs. It has also been established that triiodothyronine crossreacts only 1/6 to 1/9 as well as thyroxine, and can be ignored because it represents only about 1/80 of the total serum iodothyronine content. The economic and methodological advantages of the improved method over radioammunoassay and other displacement assays are discussed.


A quantitation of lactate dehydrogenase non-linearity. It was the objective of this study to quantitative the non-linearity seen in the lactate dehydrogenase reaction and relate these findings to the wide variation between reported values from various sources. Data are based upon two sample groupings: 1200 routine samples and 200 selected elevated specimens rangingg from 200 to 2000 I.U. (LD-L). This sample population demonstrated a rate of activity decrease rangin from 2% to 13% per minute, dependent upon activity level.


Metabolism of alpha-aminoadipic and alpha-ketoadipic acids: studies using rat and beef liver, and human leukocytes. The reported studies have shown that alpha-DL-amino [1-14C]adipic acid is metabolized to radioactive alpha-ketoadipic acid and then to 14CO2 in rat and beef liver homogenates. It was also demonstrated that alpha-keto [1-14C]adipic acid is decarboxylated to 14CO2. The effects of several co-factors and other variables, i.e. alpha-ketoglutarate, pyridoxal phosphate, NAD, thiamine pyrophosphate (TPP), FAD, LA, and pH have also been delimited. These reactions and the effects of the co-factors were also established in freshly drawn leukocytes. Using the methods outlined, a technique for studying the metabolism of alpha-amino-adipate and alpha-ketoadipate in the leukocytes from 10 ml of blood was developed.


The effects of therapy for mild hypertension on circulating level of dopamine beta-hydroxylase. Circulating dopamine beta-hydroxylase levels and norepinephrine excretion were measured in 76 mild hypertensive patients. Levels of dopamine beta-hydroxylase, norepinephrine excretion and blood pressure were obtained both before and after the initiation of therapy. Data from 20 patients exhibiting a diastolic blood pressure decrease of 10 mmHg or more were compared with data from 10 normotensive individuals. Changes in dopamine beta-hydroxylase levels were similar for the two groups and were not related to blood pressure changes. Intra-individual variation was small in both groups. There were no detectable functional relationships between diastolic pressure and urinary norepinephrine, norepinephrine and dopamine beta-hydroxylase or dopamine beta-hydroxylase and diastolic pressure. It dose not seem likely that dopamine beta-hydroxylase levels can replace urinary catecholamines as a commonly used index of sympathetic activity.


Membrane permeability in normal human lymphocytes and lymphocytes from patients with chronic lymphatic leukaemia. The rate of release of intracellular enzymes from the lymphocytes of patients with chronic lymphatic leukaemia has been shown to be slower than that from normal lymphocytes, despite their lower enzyme contents. Addition of ATP, ADP and AMP to the medium reduces enzyme efflux in a manner similar to that in normal lymphocytes. Iodoacetate, however, causes a marked increase in enzyme leakage from both normal and leukaemic cells. It appears therefore that the membrane permeability of leukaemic lymphocytes is at least partly dependent upon the intracellular energy content. Since the ATP contents of the leukaemic cells were lower than those of normal lymphocytes, however, it is concluded that some additional factor is concerned in reducing permeability to enzymes in chronic lymphatic leukaemia. The possibility that the immunoglobulin associated with the cell membrane of leukaemic cells may play a part in reducing its permeability has been explored, but washed and unwashed cells were found to lose enzymes at similar rates. The lower permeability of the membranes of such cells may partly explain their longer lifespan in chronic lymphatic leukaemia.


A simple and rapid procedure for the preparation of human LDH-1 and LDH-5 using an ion-exchange mini-column. A simple and rapid preparation of LDH-1 and LDH-5 from heart and liver homogenates is described. The preparation is carried out on a 3 ml mini-column of DEAE-Sephadex A-50. The fractions of heart homogenate containing LDH-1 were eluted with an NaCl gradient after salt elution of other isoenzymes. This semi-purified fraction was re-applied to a second column and the whole cycle was repeated. This procedure takes less than 90 min to complete and a 70% yield of LDH-1 can be obtained. The fractions of liver homogenate containing LDH-5 were eluted by simple washing of the gel column with Tris-HCl buffer. The semi-purified fraction was re-applied to a second column and the wash procedure was repeated. This preparation took less than 30 min to complete and a 70% yield was obtained. No apparatus other than a small mini-column is required for this purification.


A new device for ultrafiltration. The ultrafiltrability of calcium and inorganic phosphate in human serum. The various problems concerning the ultrafiltration of blood serum are outlined, and a novel ultrafiltration device, which overcomes all these problems is presented. Its main advantages are the following: (1) The deposition of protein on the filter is prevented by producing a flow across the filter surface. (2) The pCO2 remains constant, since the fluid is not in contact with a gas space. (3) The minimum serum volume is only 0.4 ml (4) Six samples can be processed simultaneously. (5) All commercially available filter types can be used. The machine, tested by measuring the ultrafiltrability of calcium, inorganic phosphate, sodium and chloride in human serum, proved to be a reliable laboratory tool. The precision of the determinations were comparable to respective serum analyses. The ultrafiltrabilities obtained, without correction for water content of serum, were 55.6 +/- 2.9% for calcium, 88.3 +/- 5.0% for inorganic phosphate, 95 +/- 1.7% for sodium, and 103 +/- 0.7% for chloride (means +/- S.D.).


Specific 5alpha-dihydrotestosterone binding in labial skin fibroblasts cultured from patients.with male pseudohermaphroditism. The cytoplasm of skin fibroblasts serially subcultured from the labium majus of normal human females binds 5alpha-dihydrotestosterone (5alpha-DHT) with high affinity and low capacity. Such binding was absent from the strains of two male pseudohermaphrodites with unambiguous female external genitalia: one of these was from a patient with the clinical features and a family history typical of complete testicular feminization; the other merited the same diagnosis on anatomic and endocrine grounds, but had an XYY karyotype in multiple tissues, including the testes. Normal cytoplasmic binding was found in strains from two prepubertal male pseudohermaphrodites with bilateral inguinal testes: one had unambiguous female external genitalia, the other had clitoromegaly; the former had normal specific nuclear binding of 5alpha-DHT, and thereby the target cell capacity for pubertal masculinization. Measurement of specific 5alpha-DHT binding by cultured labial skin fibroblasts should be an early step in the investigation of male pseudohermaphroditism with female external genitalia.


Partial deletions and trisomies of chromosome 13; mapping of bands associated with particular malformations. New techniques of human karyotyping have allowed us to define accurately the banding pattern of six new cases with partial duplication of deficiency of chromosome 13. It now seems possible to draw a rough map of chromosome 13, correlating observed malformations and phenotypic features with specific chromosome regions. Partial monosomy shows clinical features which are the antithesis of the corresponding trisomic phenotype (Lejeune 1966).


The distribution of the third complement component and other polymorphic traits in rheumatoid arthritis. The distribution of C'3 phenotypes in 61 seropositive rheumatoid arthritis patients and 464 normal blood donors in Tokyo was examined by high-voltage agarose gel electrophoresis. The allele of the common European variant, C3(F), is absent in Japanese, but another F allels, C3(Frare), is present with a frequency of 0.025 and 0.013 in RA patients and blood donors, respectively; the difference is not statistically significant. The distribution of phenotypes for several other enzyme systems was also determined in an attempt to detect association with RA Again, no statistically significant differences were found.


Mental retardation, malformation syndrome andpartial 7p monosomy [45, XX, tdic (7;15) (p21;p11)]. A mentally retarded and malformed girl is described. Her karyotype was 45,XX,tdic (7;15) (p21;p11), i.e. she was monosomic for bands 7p22 and a part of 7p21. Only one of the two centromeres of the dicentric chromosome appeared to be functioning. The C-band positive material was retained by both centromeres (or adjacent to them). However, the Cd-band positive structure was absent in the presumably nonfunctioning centromere region.


Familial partial trisomy 6q syndromes resulting from inherited ins (5;6) (q33;q15q27). Two cases are reported of familial partial trisomy 6q syndrome due to segregation of ins(5;6) (q33;q15q27) in three generations. The common clinical features include growth and mental retardation, feeding difficulty during infancy, microcephaly with downward slanting palpebral fissures, flattened nasal bridge with anteverted and flared nares, long philtrum, high arched palate, partially opened and protruding mouth with receding chin, deep transverse creases of the ears, three creases on the 4th fingers, clinodactyly of the 5th fingers with a single crease, and other dermatoglyphic findings. These characteristic features of two patients appear to make partial trisomy 6q a clinically recognizable syndrome.


Specific removal of DNA antibodies in vivo with an extracorporeal immuno-adsorbent. The selective removal of circulating antibody specific for DNA was affected with an immuno-absorbent consisting of DNA-cellulose incorporated into agar gel. Antisera to DNA obtained from patient with systemic lupus erythematosus was circulated in vitro through experimental and control columns by a dual channel haemodialysis pump and serial aliquots were withdrawn and assayed for antibody. A 65% reduction in DNA binding of serum was achieved at a flow rate of 210 ml/min over a 4-hr period with no release of 125I-labelled DNA from the column into the serum. For in vivo studies, 2-6-3-8 kg rabbits were actively immunized with methylated bovine serum albumin conjugated to single-stranded DNA (MBSA-ssDNA). Whole blood was pumped from the femoral artery through an immuno-adsorbent composed of ssDNA-cellulose in an agar matrix. Results showed significant reductions in ssDNA binding activity over various periods after connection of the rabbit's circulation to the immuno-adsorbent with only minimal changes in BSA binding during the same period. Little release of incorporated 125I-labelled DNA from the column as assayed in the blood and tissues of the experimental animals occurred during the procedure. The immuno-adsorbent columns showed no residual cellular debris or thrombotic material. These results suggest that this immuno-adsorbent system may be used to specifically withdraw circulating DNA antibodies in vivo. Such a system may have clinical potential for specific therapy of systemic lupus erythematosus.


Cell-mediated immunity to gluten fraction III in adult coeliac disease. Peripheral blood lymphocytes were obtained from twenty-seven healthy control subjects, twenty-one coeliac patients on a gluten-free diet and fourteen patients on a normal diet. When the cells were cultured in vitro in the presence of 2 and 4 mg of gluten fraction III, there were significant increases in the mean ratios of response for lymphocytes from gluten-free coeliacs compared to healthy controls after 4, 5 and 6 days of culture, but for those on a normal diet significant increases were found only when using 4 mg of gluten on the 4th and 5th days of culture. When three further patients were changed from a normal to a gluten-free diet, the ratios of response for their lymphocytes increased. The results suggest that certain coeliacs may exhibit a weak delayed hypersensitivity reaction to gluten. Its more ready demonstration in patients on a gluten-free diet could be explained on the release of sensitized lymphocytes from the intestinal mucosa into the peripheral circulation after gluten withdrawal.


Human sperm antigens and antisperm antibodies. III. Studies on acrosomal antigens. Acrosome of human sperm possesses two distinct antigens that are immunogenic, and will elicit autoantibodies that are detectable by immunofluorescence (IF). The first antigen, Acl, diffuse in distribution, is probably glycoprotein in nature since it is removed by trypsin and periodate. It is readily removed from cells after incubation in acid buffer or phosphate-buffered saline (PBS), stable at 60 degrees C and not affected by trypsin inhibitor. The second antigen, Ac2, discrete in distribution, is resistant to trypsin treatment. It remains stable after incubation in acid buffer or PBS, is unstable at 60 degrees C and becomes more diffuse in distribution when incubated in acid buffer or trypsin inhibitor. The use of spermatozoa pretreated with acid buffer permits detection of anti-Ac2 antibody that coexists with anti-Ac1 antibody in the same serum sample. Both Ac1 and Ac2 antigens are demonstrable in spermatozoa from the ejaculate, epididymis and the testis; in spermatids and spermatocytes. Ac1 antigen appears to show extensive cross-reaction with micro-organisms and with antigen(s) of human adrenal gland; and anti-Ac1 antibody is found frequently in the serum of men before vasectomy. In contrast, Ac2 antigen does not show cross-reaction with micro-organisms or tissue antigens tested; and its antibody is found mainly in the male and primarily after vasectomy. Thus, anti-Ac2 antibody may be more indicative of an immune response to sperm, and should be sought in diseases related to sperm immunity.


Cell-mediated immune response of patients with meningiomas defined in vitro by a [3H]proline microcytotoxicity test. Cell-mediated cytotoxicity (CTX) of meningioma patients was assessed postoperatively by a [3H]proline microcytotoxicity test. Autologous and allogeneic tumour cells were used for prelabelling with isotope and peripheral blood lymphocytes added in a ratio of 200:1. After 60 hg the plates were washed and residual CMP counted. Control target cells consisted of normal skin fibroblasts. CTX was calculated in percentage reduction compared to cultures incubated with control lymphocytes. Specific CTX on meningioma cells (i.e. not destroying control cells) greater than 20% was considered 'positive' if significant at P less than 0-05. Fifteen of twenty-three meningiomas showed specific CTX (65%). Among eight CNS tumours of different type and thirteen non-malignant diseases and normals only three (14%) were specifically cytotoxic for meningioma cells. A cross-reaction could be demonstrated between autologous and allogeneic meningioma target cells. However, no activity of lymphocytes from patients with meningiomas on glioblastoma cells and foetal brain tissue could be found at the ratio used for evaluation. Evidence is presented indicating that a cellular immune response as measured in the microcytotoxic test may be dependent on a residual or recurrent tumour in the body.


Variations of blood lymphocytes during work studied by cell surface markers, DNA synthesis and cytotoxicity. Highly purified peripheral blood lymphocytes from healthy individuals were obtained from samples collected before and after a standardized bicycle ergometer test. The physical activity resulted in a marked increase of circulating lymphocytes. The proportion of T lymphocytes estimated as cells forming rosettes with sheep red blood cells after incubation in the cold decreased, whereas a corresponding increase of cells with receptors for C3, IgG-Fc or surface immunoglobulin was noted. Moreover, after work an increase of cells simultaneously reacting with cell surface markers usually designed as T- or B-cell markers occurred. The reactivity of lymphocytes collected after work in response to Con A, PHA, PWM and PPD was impaired, whereas the slight response to LPS was unchanged. The K-cell cytotoxicity of lymphocytes collected after work increased. The data indicate that physical activity leads to the mobilization of lymphocytes from as yet undetermined sites and with changed composition and reactivity.


Time course studies on rat IgE production in N. Brasiliensis infection. We present here a study of the relationship in time between the elevation of total serum IgE, the parasite-specific IgE response, and the potentiated IgE response to unrelated antigen which occurs in rats following infection with the worm parasite N. brasiliensis. During a first infection the potentiated IgE response (to egg albumin) and elevation of total IgE occur synchronously rising to a peak on days 12-14 after infection, with the fastest rate of increase occurring between days 8 and 10. N. brasiliensis-specific IgE rises to a peak some 2-3 weeks later when both total IgE and the potentiated response have largely declined. A strain difference is shown in that Wistar rats produce far lower levels of total and parasite-specific IgE than Hooded Listers. Events following reinfection differ in that total IgE rises more rapidly, very high levels being reached 6 days after reinfected together with a secondary specific IgE response to N. brasiliensis. The total IgE level, however, rises by a far greater factor than parasite-specific IgE and declines rapidly while the parasite-specific response declines slowly over many weeks. The egg albumin response is not repotentiated. It is proposed that the total IgE response and the potentiated IgE response which forms a small component of it results from the release of a non-specific IgE-stimulating factor produced by N. brasiliensis-specific T cells. In this scheme the same or similar cells are involved in the production of N. brasiliensis-specific IgE through a separate specific helper function.


Surface immunoglobulins of lymphocytes in plasmacytoma. V. The effect of RNA-rich extract from mouse plasmacytoma MOPC 104E on the immune response. BALB/c mice with the plasmacytoma MOPC 104E producing monoclonal IgM-lambda with antibody activity to alpha-1,3 dextran were found to have B lymphocytes with surface immunoglobulins with the immunochemical characteristics of 104E IgM capable of binding alpha-1,3 dextran. RNA extracted from this plasmacytoma induced the synthesis of such surface immunoglobulins on normal B lymphocytes in vitro and in vivo. Injection of 200 mug of MOPC 104E RNA into normal mice 72 hr prior to the administration of the antigen kept the immune response to dextran-S intact, but suppressed that to other antigens, such as DNP-Ficoll and LPS, T cell-independent antigens, and SRBC and BSA which are T cell-dependent. The effect of the RNA was abolished by RNase but not by pronase and DNase. RNA extracted from LPC-1 tumour (gamma2a-k without known antibody activity) significantly suppressed the immune response to dextran-S and to other antigens in normal mice. Thus, opposite effects of MOPC 104E RNA on the response to specific and non-specific antigens strengthen the hypothesis that the immune deficiency in plasmacytoma bearing mice is due to the conversion of normal surface immunoglobulin of a population of B lymphocytes to the idiotype of the respective myeloma globulin.


Autoimmune implications of vasectomy in man. The frequent development of sperm antibodies following vasectomy does not appear to be related to the formation of other autoantibodies. We have examined serum taken from 346 men before and 6 months after vasectomy for seven different autoantibodies. The occurrence of positive results is comparable to any normal population.


Injurious effect on rat liver mitochondria by lymphocytes from patients with primary biliary cirrhosis. Lymphocytes from primary biliary cirrhosis (PBC) patients were shown to have an injurious effect on rat liver mitochondria, as was demonstrated by the inhibition of mitochondrial respiratory control by these cells. The incubation of the PBC patients' lymphocytes with isolated rat liver mitochondria produced a significant inhibition of mitochondrial respiration in the presence of ADP. However, no significant effect on respiration was seen with control lymphocytes of normal persons or with lymphocytes from patients with alcoholic cirrhosis and miscellaneous liver diseases. The results suggest that this injurious effect of PBC lymphocytes on mitochondria might be a consequence of sensitization in vivo of the PBC patients' lymphocytes by the mitochondrial antigens.


Determination of endogenous middle molecules in normal and uremic body fluids. Methods have been developed which allow the separation and quantitation of middle molecules in biological fluids. The methods involve a newly developed high speed gel filtration technique (HSGF) combined with gradient ion exchange chromatography (GEC). The solutes were detected at 254 an 206 nm. The molecular weight range of the fractions isolated by HSGF was assessed with standards of known molecular weight. By the HSGF method normal and uremic plasma and urine were separted into 10 to 11 peaks based upon differences in molecular size. One of these peaks, no.7, which was present in uremic plasma but not detected in non-uremic plasma contained middle molecules (mol wt 1000-2000). Amino-acid analysis before and after acid hydrolysis showed this peak to contain a mixture of peptides. Using the GEC method peak 7 was further separated into 7-8 new peaks (7a,b,c, etc.). Plasma from six normal subjects and six non-uremic patients with various diseases yielded only two peaks, 7f and g, whereas urine from normal subjects, and plasma and urine from uremic patients contained all or most of these peaks. Amino-acid analysis of peak 7c, which was frequently found prominent in severly uremic patients indicates that it consists of a small peptide chain containing 8-10 amino acids.


Absence of glomerular renal tubular epithelial antigen in membranous glomerulonephritis. Renal biopsies from 24 patients with membranous glomerulonephritis were examined by indirect immunofluorescence for the presence of autologous renal tubular epithelial antigen (RTE). Staining of the luminal layer of proximal tubular epithelium was found in all cases, as with normal human kidney, but granular staining along glomerular capillary walls was not observed. The role of RTE in the genesis of human membranous glomerulonephritis has not been confirmed.


Clinical evaluation of an automated cleaning device for dialyzers. This paper describes the clinical evaluation of dialyzer efficiency after cleaning and sterilization using an automated dialyzer cleaner. In vivo clearance measurements of small molecules and an in vitro measurement of BSP showed no diminution after 5 uses, and ultrafiltration rate did not decrease with an increase in dialyzer use. Scanning and transmission electron microscopy of the membrane showed an increase in accumulation of cellular debris and fibrin with increasing use. Our experience using the automated dialyzer clearner for more than one year leads us to conclude that it is an effective way to clean dialyzers and that no patient ill-health occurs as a result of re-using dialyzers cleaned by this technique.


Sodium polystyrene sulfonate resin candy for control of potassium in chronic dialysis patients. A stable candy with 5.0 g sodium polystyrene sulfonate resin per piece was developed. In vitro testing indicated decrease in potassium concentration of 1.0 mEq per gram of resin. Six chronic dialysis patients with predialysis serum potassium of 5.2 mEq per liter or greater participated in a two week blind trial. No change in diet or dialysis routine was made during the study. Analysis of serum potassium by paired "t" test showed mean potassium decrease of 0.7 mEq per liter during treatment (P less than 0.001). Patient compliance and acceptance was excellent during the trial. Use in the treatment of chronic hyperkalemia may be worthwhile in the care of long-term dialysis patients.


Development of renal scarring in an adult with recurrent urinary tract infection. An adult patient is described with recurrent urinary tract infections who developed renal scarring while under observation. Intravenous urography (I.V.U.) and renal arteriography were performed during an initial attack of pyelonephritis and I.V.U.s were repeated at intervals during follow-up, when the patient was having recurrent infections. Over 2 years the right kidney size diminished from 10.5 to 7.0 cm, the cortex became irregular and calyceal clubbing occurred. During a further 2 years, when on regular treatment, attacks became less frequent but left-sided symptoms predominated. Repeat I.V.U. at the end of this period showed that the left kidney size had reduced from 12 to 10 cm, again with the development of cortical irregularity and calyceal clubbing. Biochemical evidence of renal impairment developed. At no time were obstruction, reflux or associated pathology demonstrated and there was no history of analgesic abuse. Recurrent infection is suggested as the etiology of the scarring.


An automated cleaning device for dialyzers: machine design and technology. The expansion of dialysis services and the introduction of disposable dialyzers have led to an increase in cost of hemodialysis. Many centers have attempted to reduce the cost of dialysis by using dialyzers on multiple occasions after cleaning and sterilization. Manual techniques for cleaning dialyzers are tedious, using valuable technician time and possibly leading to an increase in exposure to Hepatitis B surface antigen. These disadvantages can be avoided by the use of the automated device in this paper. We have also evaluated the dependability of the machine and the reduction in dialysis costs realized from its use.


Techniques of EEG frequency analysis for evaluation of uremic encephalopathy. In an effort to provide nephrologists with practical, objective, and quantitative methods for evaluating uremic encephalopathy and the severity of uremia, we investigated five techniques for EEG frequency analysis, the selection of EEG samples for analysis, and the normal values for dominant frequency and the percent of EEG power from one through six Hz. The five techniques consisted of 1. handcounting, 2. use of a tape recorder and sonic analysis system to determine EEG power versus frequency, 3. use of the tape recorder and sonic analysis system to determine EEG voltage versus frequency, 4. on-line measurement of % EEG voltage from one through six Hz, and 5. use of base line crossovers to count the number of waves occurring at each frequency. All techniques were found to be satisfactory. The most significant difference between techniques depended on whether wave amplitude influenced the analysis (techniques 2, 3, and 4) or did not (techniques 1 and 5); in the former case slow wave activity was more evident than in the latter case. Our experience indicated that the determination of relative EEG power from each frequency (EEG power versus frequency or power spectral density) was the most practical and revealing mode of analysis, but any of these techniques would be valid and useful if employed with awareness of the difference in the normal range obtained by different techniques.


Psychological aspects of chronic pelvic pain. The patient with chronic pelvic pain represents a real challenge to the physician. The challenge is not primarily to relieve the pain, but to form a relationship with the patient and to try to learn about and help her with psychosocial distress. In this process the physician must use himself or herself as a human instrument to try to relieve suffering in the global aspect of the word.


Psychophysiologic infertility: an overview. It has been recognized for centuries that commotion in the mind very often is reflected in the functions of the body. A few years ago 50% of cases of infertility were classified as emotionally determined. Today only about 5% are so classified because the identification of defects in chemistry or physiology rules out the diagnosis. Many infertile women with physical defects have significant emotional disorders, and many infertile women with no demonstrable physical defect have no significant emotional disorders. The diagnosis of psychophysiologic infertility can be made only after identification of intrapsychic conflicts arising from cultural, environmental, or experiential factors that have modified function, chemistry, or structure. The gradual elucidation of the functions of the limbic system and more understanding of the roles of the neurotransmitter amines have led to the present understanding of the psychophysiology of infertility. It has been shown that the neurotransmitter amines influence the production of reproductive hormones and hormone-releasing factors. Many types of stress change the concentration, production, and modification of these transmitter compounds. Investigators have tried without success to identify specific emotional problems that eventually produce infertility. Infertile women do have more emotional disorders, however, and some seem to be cause-effect related. Infertility protects some women against significant psychic conflicts and becomes a defensive process. Removal of this defensive process without quieting the internal commotion can have deleterious effects. When one or both members of a marriage desire children, the identification of one as infertile puts a significant stress on the relationship. Interpersonal and intrapsychic turmoil results, which may require professional help to quiet. The treatment of psychophysiologic infertility should include identifying specific areas of conflict and then attempting to modify responses, attitudes, and affects that cause or intensify the conflicts. Through a learning experience, anxious and insecure patients can be helped to tolerate the anticipation of pregnancy and parenthood. Even those who do not achieve pregnancy can be helped to maintain their feelings of self-worth and self-esteem.


Is scoliosis reversible? In Vivo observations of reversible morphological changes in the production of scoliosis in mice. Without altering the osseous or muscular structure of Balb/c mice, the author was able to produce and reverse scoliotic deformation during the period of growth and development. Two series of investigations were performed, each involving extensive histological, morphological, and roentgenographic documentation: (1) control mice were maintained and sacrificed for examination at designated intervals and (2) experimental mice, whose right hind- and forequarters were surgically bound to allow only unilateral motion, were sacrificed and examined at corresponding intervals. The unilateral restriction of experimental animals were released at scheduled 5-day intervals during the 45-day period. These mice were then examined for restoration of normal histological and roentgenographic appearance. Changes in vertebral morphology were apparent after 35 days of restriction. Release at this time allowed restoration of normal vetebral appearance with the exception of a slight, measurable reduction in size. The results indicate that (1) limited activity retarded growth and (2) unilateral restriction caused geometrical variations (structural and morphological). Both of these alterations proved reversible once normal function  (reciprocal motion) was restored to the murine spine.


Fracture of a vertebral body end plate and disk protrusion causing subarachnoid block in an adolescent. An apparently unique case of retroprotrusion of a portion of the vertebral end plate plus L4 disk in a 16-year-old boy demonstrated a complete myelographic block. The block was produced by a large fragment of bone which had broken off the inferior end plate of the body of L4 and was protruding into the spinal canal. Removal of the bony block and protruding disk resulted in complete resolution of symptoms.


The treatment of developmental coxa vara by abduction subtrochanteric and intertrochanteric femoral osteotomy with special reference to the role of adductor tenotomy. Regardless of the method of fixation, results were good in 84.5 per cent of abduction trochanter osteotomies for developmental coxa vara in 32 hips. Operative treatment is recommended after 18 years of age. Inadequate correction occurred only in children in whom an adductor tenotomy had been omitted. Unsatisfactory correction was caused more frequently by faulty surgical technique than by bony remodelling. The latter was not seen after the age of 6 years.


Traumatic coxa vera. A case report of spontaneous correction in a child. Residual coxa vara is a common complication of femoral neck fracture in a child. Factors favoring the development of this complication are delayed reduction and avascular necrosis. The present case report is a 10-year follow-up of spontaneous correction of traumatic coxa vara in a child. This is of interest because residual coxa vara following a hip fracture in an adult is a deformity in which there is little if any corrective remodeling.


Traumatic anterior dislocation of hip joint with vascular damage. Closed reduction of an anterior dislocation of the hip joint in a 15-year-old boy failed because of interposition of capsule, iliopsoas and rectus femoris muscles. The immediate complications were compression of the common femoral artery, tear of the femoral vein, and fat embolism 24 hours after the injury. The sequelae were periarticular ossification and avascular necrosis of the femoral head. The definitive treatment was a Charnley total hip arthroplasty.


A case of cerivco-thoracic anomaly simulating traumatic fracture-dislocation. A patient who sustained severe head trauma had a simulated C7, T1 fracture dislocation. Anteroposterior tomography of the cervico-thoracic junction disclosed anomalous vertebral-costal articulations. The rotation of the spine and the abnormal posterior articulations were secondary to anterior costal bridging. Tomography of the costo-vertebral facets in patients with unusual rib configurations may help delineate cases of thoracic spine rotation.


Surgery of the clavicle in Sprengle's deformity. Surgery for Sprengel's deformity can produce less lowering of the scapula than desired and occasionally can result in an injury to the brachial plexus or brachial artery. The method used to produce better correction and to avoid complications was a softening of a clavicle by the morcellization technique of Robinson et al. We feel that the procedure is a simple one which helps to improve the degree of correction and to avoid neurovascular complications. The procedure should be combined with the Woodward correction for Sprengel's deformity.


The influence of age on the results of open sternomastoid tenotomy in muscular torticollis. The ideal age for surgery for muscular torticollis, the complications and results of open sternomastoid tenotomy were investigated in 60 patients operated on at different age-groups. Under the age of 1, tethering of the scar to the deeper structures was common and was mainly responsible for the lower percentage of good results (42.1 per cent). In the age-group 1 to 4 years, satisfactory correction of facial asymmetry, head and tilt and limitation of neck movements, was achieved with overall 66.7 per cent good results. However, in patients above the age of 5, not only was the correction of the secondary deformities uncertain but the late complications like loss of sternomastoid column, disfiguring scar and presence of lateral bands were more common. Only 33.3 per cent had good results in the 5 to 8 year age-group and none in the above 9 years age-group. The best time for surgery in muscular torticollis is in the patient between 1 and 4 years of age.


The upper limb-cardiovascular syndrome, (Holt-Oram syndrome). Two families recently studied demonstrate the variability of expression of upper limb-cardiovascular syndrome. Four other patients with upper limb and cardiac anomalies and no significant family history may represent spontaneous mutations or examples impenetrance in antecedent generations, rather than phenocopies of the syndrome. Children under the care of the orthopedist for congenital anomalies of the upper limb should have a complete cardiac assessment.


A valgus angulation fracture of the proximal humeral epiphysis. The case presented illustrates a previously unreported form of valgus angulation of a proximal humeral epiphyseal fracture. For reduction this fracture requires traction and adduction, not abduction, of the arm.


Osteoid osteoma of the trapezium. First case report of roentgenographically demonstrated progression in the trapezium. Osteoid osteoma in the trapezium seems not to have been reported previously. This occurred in a 16-year-old boy who had complete and instant relief of pain following excision. There was progression of the lesion from roentgenographically normal appearing bone to bone with typical changes of osteoid osteoma.


Congenital flexion and ulnar deviation of the metacarpophalangeal joints of the hand. A case report. A 2-year-old boy with congenital ulnar deviation and flexion deformity of the metacarpophalangeal joints (incidentally associated with ipsilateral metatarsus varus) was treated by surgical centralization of the extensor tendons. The operation improved function. Early splintage in infancy may avoid the need for surgical treatment in many cases.


Open reduction of fractures of the neck of the proximal phalanx in children. Fractures through phalangeal necks of proximal phalanges in children, which are angled so as to produce a dislocation or subluxation at the next distal joint, require open reduction. The technique includes a zigzag incision, a splitting of the extensor tendon, and the use of crossed Kirschner wires of .035 mm. Infections have not occurred from allowing the wires to protrude through the skin. The end results are better than those reported from conservative management of this fracture. The earlier the surgery the better the end results.


Osgood-Schlatter's disease and tibial tuberosity development. The growth plate of the tibial tuberosity does not develop until several months after birth and is structurally different than most growth plates that are loaded primarily in compression. Histologically, it is particularly different from the juxtaposed proximal tibial growth plate. The physis of the tibial tuberosity is composed primarily of fibrocartilage and fibrous tissue, with bone being added to the anterior portion of the tibial metaphysis by membranous bone formation. Initially very little of the growth plate is comprised of columnated cells, but by the time of maturation of the tuberosity, with the exception being the most distal region, the columnar portion has extended distally and is found under most of the tuberosity. These structural features would be an adaptation to the strong tensile forces exerted in this region. That human "traction" apophyses may be histologically different from "compression" epiphyses seems not to have been demonstrated previously. Osgood-Schlatter's disease would appear to be an inability of the developing secondary ossification center to withstand tensile forces, resulting in avulsion of segments of the ossification center, and eventual formation of extra bone(s) between the fragments.


The accessory soleus muscle.

The accessory soleus muscle. This is a report on the EMG diagnosis and surgical treatment of a tumor-like mass in the ankle of a 13-year-old boy with an accessory soleus muscle.


Ewing's sarcoma of the great toe. A case report. A case of Ewing's Sarcoma originating the great toe is reported. Because of the rarity of its appearance outside the pelvis and long tubular bones, Ewing's Sarcoma is often misdiagnosed when it occurs in the distal portion of the extremities. Ewing's Sarcoma may be difficult to distinguish from infection. Biopsy is recommended for any indolent or refractory lesions presumed to be infectious. Bone scanning with Technetium Polyphosphate is a useful tool for diagnosis and evaluation of this tumor. Vigorous integrated chemotherapy and radiotherapy had little effect in this patient with metastatic disease.


The development of a total wrist arthroplasty. For many individuals the preservation of wrist motion is essential for augmentation of fine motor control of the hand and fingers. When significant functional disability exists at the wrist, currently available surgical treatment includes soft tissue arthroplasty, carpectomy, or arthrodesis. A total wrist joint arthroplasty offers the patient the potential of a pain-free, stable, and mobile wrist. Based upon the principles of total joint replacement as applied to the hip and knee, the prosthesis is secured to the carpus and radius with methylmethacrylate cement, following removal of the navicular, lunate, and head of the capitate. The design of the prosthesis provides for the two planes of motion normally seen at the wrist; 90 degrees of flexion and extension and 50 degrees of radial ulnar deviation are permitted by the design. Candidates for total wrist arthroplasty are patients who exhibit far-advanced disease at the wrist and who might be considered as candidates for arthrodesis, but in whom the permanent loss of motion would represent a significant handicap. To date 17 arthroplasties have been performed in 14 patients. The longest follow-up is 14 months. All but 2 patients have gained a useful range of motion. All patients have noted dramatic relief of pain and deformity, permitting them to perform tasks which were preoperatively impossible.


Küntscher intramedullary reaming and nail fixation for nonunion of the forearm. Twenty cases of nonunion of forearm fractures were treated by the Küntscher method of intramedullary reaming and nailing. Fifteen fractures healed per primam; 2 required renailing; 2 did not heal but the patients benefited from the stabilizing effect of the nail; 1 was lost to follow-up. Even infected cases could be treated successfully by this method, but extensive experience with all the details of the surgical technique may constitute the difference between catastrophic failure and success. Excision of sinus tracts and sequestrectomy were done as a preliminary procedure.


Küntscher intramedullary reaming and nail fixation for nonunion of the humerus. Thirteen cases of nonunion of the humerus were treated by intramedullary reaming and nail fixation. Rigid stabilization which was usual after operating upon other long bones was not always secured in these cases, and supplementary plaster immobilization was necessary. Seven fractures healed and 3 fractures required re-nailing before healing. Three fractures did not heal in spite of reoperation, but in 2 of these cases the nail provided stability and controlled pain and motion at fracture site. Nonunion of the humerus is a difficult problem, irrespective of the method of treatment.


Dyschondrosteosis and Madelung's deformity. Report of three kindreds and review of the literature. Dyschondrosteosis is a syndrome of Madelung's deformity, mesomelia and mild short stature that is transmitted by autosomal dominant inheritance. Most examples of Madelung's deformity are due to Dyschondrosteosis. Three affected kindreds are described, two having radiographically proven male to male transmission. A possible association with mental retardation has been postulated on the basis of its presence in four of eleven affected individuals in three kindreds. Dyschondrosteosis exhibits little functional impairment or cosmetic deformity suggesting that therapy is usually unnecessary.


Fat embolism syndrome: A comparison of hematologic coagulation and lipid changes in two animal models. In considering intravenous injection of lipid as a model of fat embolism, contamination is frequent and purity must be demonstrated. Musculoskeletal trauma causes mild arterial hypoxia whereas intravenous pure triolein 0.1 mg/kg does not. Trauma produced a leukocytosis and elevated sedimentation rate not found in the lipid injected dogs. Evidence for consumptive coagulopathy was found in the trauma group but only a mild thrombocytopenia resulted from intravenous triolein. The traumatized dogs demonstrated an increase in the triglyceride level, an increase in the cholesterol phopholipid ratio and an increase in the cholesterol containing beta and prebeta lipoprotein fractions, all of which could lead to formation of pulmonary fat emboli containing cholesterol.


The femoral stem/cement interface in total hip replacement. A study of the cement prosthesis interface has been carried out on the femoral component of 5 total hip relacements which had been in place between 7 weeks and 5 years. In every case a thin layer of connective tissue at varying stages of organization was present between the prosthesis and the cement. This suggests that the prosthesis is not rigidly fixed to the cement and is capable of micromovement. The gap presumably comes about by a combination of factors which include thermal expansion of the femoral stem, shrinkage of the cement and organization of the film of blood or tissue fluid present on the stem at the time of implantation. This information must be used when construction mathematical models of joint replacements, but its clinical significance is not yet fully clear.


Camptomelic dwarfism. Report of a case and review of the salient features. A typical case of camptomelic dwarfism exhibits the characteristic clinical features of: rhizomelic dwarfism, anterior bowing of the tibia with cutaneous dimpling, talipes equinovarus, peculiar facies with micrognathia and characteristically death in the first 6 weeks of life.


Dysplasia epiphysealis hemimelica. A case report. Experience with a 9-year-old girl with Dysplasia Epiphysealis Hemimelica in the right lower extremity demonstrates that avoidance of confusion leading to medical--legal problems and promotion of effective management would have been possible by early recognition of the condition.


The effects of phosphate and vitamin D therapy on osteopenic, hypophosphatemic osteomalacia of childhood. Two severely osteopenic adolescent males with clinical manifestations of adult onset hypophosphatemic osteomalacia were resistant respectively to physiological and pharmacological doses of vitamin D. Clinical improvement ensued following initiation of pharmacological doses of vitamin D and phosphate. Non-decalcified bone biopsies obtained before and during therapy exhibited correction of an isolated mineralization in the second. The response to treatment was reflected in striking changes in tetracycline-labelled calcification fronts in both patients.


The Guillain-Barre syndrome in children. Orthopedic management and patterns of recovery. Eleven cases of Guillain-Barre Syndrome in children between 1955 and 1973 demonstrate clinical course and residual permanent motor deficits. The rate of recovery from muscle paralysis and the long-term permanent muscle loss, and the resultant paralytic deficits may require treatment: tendon transfers, opponensplasties, spinal fusions, and Lambrinudi operations. The late permanent motor paralysis and residual joint deformities secondary to GBS in children has a higher incidence and severity than in adults, and an intensive rehabilitation program in imperative. Frequent, extended follow-up, and muscle testing records are absolutely essential in children.


Operative and non-operative treatment of rachitic lower extremity deformities. A long term study with forty-six year average follow-up. The long term sequelae of rachitic deformities includes degenerative arthritis. Surgery at an early age will be beneficial in preventing degenerative arthritis in children with severe deformities. Of the many metabolic processes involved with Vitamin D, there must be some that vary quantitatively so that a small alteration may produce rickets in one child, go completely unnoticed in another, and persist in still another as a subclinical disease. Furthermore, it is entirely probable that some children then diagnosed as having classical D-deficiency rickets, in fact, would now be found to have D-resistant states.


Multifocal subacute pyogenic osteomyelitis in a child. A case report. The clinical features of multifocal subacute pyogenic osteomyelitis are: insidious onset; the absence of toxic reaction; radiographic appearance of a bone neoplasm. In a 14-year-old boy, immobilization and appropriate antibiotics produced symptomatic improvement and radiographic evidence of healing reactive bone above both bone lesions.


Skeletal growth and development of the achondroplastic dwarf. Certain patterns in growth and development can be seen in the typical achondroplastic dwarf. Height is approximatley 5 standard deviations below average size for age through the age of 14. Sitting height is within normal limits at all ages. On the average the femur is 8 standard deviations and the tibia 7 standard deviations below normal size. Compared to normal, both femur and tibia exhibit approximately a 50 per cent inhibition in growth. A slight decrease in the deviance from the norm is observed for all parameters during growth until the time of the adolescent growth spurt when an increased deviance is seen. Related to normal children of the same sex and age, females are more severely affected than male achondroplastic dwarfs. The skeletal development of the hand is irregular, often having extra metacarpal epiphyses and a wide variance in skeletal maturation assessment between the carpals and the rest of the hand. The skeletal age is generally below chronological age until the adolescent growth spurt when a rapid maturation pattern occurs. Standard skeletal age assessment techniques cannot be applied to the achondroplastic individual.


Iliac apophyses. Prognostic value in idiopathic schliosis. Fusion of the iliac apophyses with the crests of the ilium is of greater prognostic value than completion of excursion of the iliac apophyses. Completion of fusion of the vertebral ring apophyses coincides with fusion of the iliac apophyses to the crests. For accurate evaluation of the progression of the scoliotic curve, patients should be followed a few years after fusion of the iliac apophyses although progression after this stage is rare.


Scoliosis treated by cast correction and spine fusion. The foregoing long term follow-up examinations of 8 cases demonstrate that the increase of the scoliotic deformity can be prevented by spinal fusion. Correction can be maintained by fusion. One of the best methods of correction is a combination of traction and lateral bend. Spinal pain can be eliminated by fusion. Corrective holding casts can prevent increasing deformity during during the period of vertebral growth and may maintain some correction of the deformity.


A biplane radiographic method of determining vertebral rotation in postmortem specimens. Vertebral axial rotation can be measured by accurate identification of three bony landmarks: the tips of the superior articular facets; the inferior bases of the pedicles; the tips of the inferior articular facets. Geometric solution for the movement of these three points in space does not require an initial unrotated view, and can be proved with accuracy of up to 4 degrees in the thoracic spine and 3 degrees in the lumbar spine under experimental conditions. The method is applicable to the problem of measurement of structural scoliotic deformities on routine clinical roentgenograms.


Adolescent scoliosis patients. Personality patterns and effects of corrective surgery. Personality patterns of 84 adolescent scoliosis patients were assessed and an evaluation made of certain psychological effects of corrective surgery. Results indicate the following: Scoliosis has fewer psychologically debilitating effects on younger adolescents (those under 16) than it does on older adolescents; scoliotic boys show comparatively better general personality integration than girls; scoliotic girls are less disturbed in psychosexual development than are boys. Postoperatively, boys can be expected to show less overt incapacitation than girls; psychologically, boys will require a longer period of recuperation than will girls; boys can be expected to present fewer immediate management problems than girls; the internalization of a sense of "difference" from the normal in adolescent scoliotics increases in direct relation to age. Consequently, the eariler surgical correction can be undertaken the better. Important differences exist between the psychological "set" of male and female adolescent patients. For boys, self-acceptance is at the core. Postoperative surgical care should thus focus on reinforcing characteristics of personal adequacy, namely, the ability to compete, and fulfill reasonable goals. For girls, acceptance by others is paramount. Postoperative care is best directed toward strengthening feelings of attractiveness (of any personal characteristic), worth, and, above all, future interpersonal possibilities.


Surgical treatment for spondylolisthesis in the adult. There are 3 common types of spondylolisthesis: dysplastic; isthmic; degenerative. This classification, presented anew in an article published in this volume, evolved from a discussion by the members of the International Society for the Study of the Lumbar spine. The surgical treatment is designed to correct a combination of symptomatic and mechanical abnormalities characteristic of each type.


Late results of removal of the loose posterior element (Gill's operation) in the treatment of lytic lumbar spondylolisthesis. This study presents the late results of the Gill operation for the treatment of lytic lumbar spondylolisthesis in 75 patients. The observation time ranged for 5 to 20 years, averaging 12 years. Primary results were excellent, good or fair in 83 per cent at the end of 1 year. However, the figures dropped to 75 per cent when the cases were evaluated 5 or more years after operation. The worsening of the results during the observation time seems to depend on the degeneration of the intervertebral disk. Progression of olisthesis was observed in 27 per cent of the patients, usually in connection with progression of disk degeneration. This progression did not affect the clinical result of treatment. Nine patients had a lumbar disk herniation, 8 from a segment above the level of defect and 1 at that level. On 9 patients a fusion was later performed as a secondary operation. In these the late result was still unsatisfactory in all but 2. The operation is contraindicated in adolescents except in exceptional cases with signs of compression of the cauda equina. It is not recommended for patients below the age of 30 years. The main indication for the Gill operation is painful spondylolisthesis with nerve root symptoms in patients over 40 years of age.


Guidelines for the management of lumbosacral spondylolisthesis associated with scoliosis. Lumbosacral spondylolisthesis, when it is associated with scoliosis, presents special problems which require special consideration in management. Lumbosacral spondylosisthesis associated with a major thoracic curve, presents two separate problems. Treatment of the lumbosacral spondylolisthesis depends upon the severity of the lesion and symptoms. The thoracic curve is treated as required, depending upon the severity of the scoliosis and the stage of spinal maturation. Lumbosacral spondylolisthesis associated with a thoracolumbar or lumbar curve requires treatment of the curves above, along with the spondylolisthesis. Do not fuse the lumbosacral joint in an uncorrected position.


Spinal instrumentation in the treatment of severe progressive spondylolisthesis. By using A-frame instrumentation and direct distraction force, an exceptional correction can be obtained in patients with severe spondylolisthesis. Adolescent progressive spondylolisthesis should be considered as an entity separate from the lumbosacral anomalies such as spondylolysis and grades 0 and 1 spondylolisthesis without progression. An aplastic relationship appears to exist between the sacrum and the posterior superior wing of the ilium in the adolescent with progressive spondylolisthesis. Complications have been minimal but long-term observations of patients are necessary to evaluate the contribution of instrumentation in the treatment for severe progressive spondylolisthesis.


Spondylolisthesis following surgical fusion for scoliosis: a case report. This is a case report of a 25-year-old woman who developed spondylolisthesis following surgical spine fusion for treatment of congenital scoliosis. Increased biomechanical stresses and the possibility of an undetected pars interarticularis defect existing prior to fusion are considered as etiological factors in this progressive lesion.


Long term follow-up of patients with idiopathic scoliosis treated surgically: a preliminary subjective study. An 8 to 14-year follow-up study of 51 surgically-treated patients with idiopathic scoliosis was performed to determine the impact upon their total life styles, and the differences in comparable but non-surgically-treated patients. Forty-nine per cent were already married and raising families and 70 per cent had been educated beyond high school. Ninety-four per cent were actively employed although 20 per cent had met with some type of job discrimination. None of the unemployed was rejected because of back symptoms. Eighty-six per cent of the patients experienced either no back symptoms or just an annoying but nonrestrictive type of low back pain. Most of the patients experiencing significant back pain were found to have tight hamstrings. Only 4 per cent of the patients required hospitalization for back symptoms and another 4 per cent relied on the use of a lumbar corset to relieve their back strain. Seventy-eight per cent of the patients were quite active in sports and other strenuous activities. Fifty-one per cent of the patients were motivated for cosmetic reasons to undergo the corrective surgery. Postoperatively, 33 per cent were still self-conscious of their scar and 43 per cent were bothered with a residual deformity. Only 10 per cent, however, expressed an overall dissatisfaction with the total result.


Compression fixation of subtrochanteric fractures. Compression fixation with a blade plate was used in the treatment of 11 fresh and 9 nonunited subtrochanteric fractures. Fifteen fractures united as fixed. Three settled into varus with eventual union in 2 and a fibrous nonunion with metal failure in one. One fracture became infected and the patient died of metastatic fibrosarcoma and one was lost to accurate long-term follow-up. The average Harris Hip Rating for 18 patients was 84, an average of 24 postoperatively. In each instance, technical errors accounted for suboptimal results. Compression fixation is designed for the subtrochanteric region for either fresh or nonunited fractures.


Heterotopic bone formation after total hip arthroplasty. Heterotopic bone formation is a common complication of total hip arthroplasty. A certain degree of heterotopic bone formation occurs in about one-half of the patients in degrees ranging from very mild to moderate involvement. The patients do not necessarily have any clinical disability; only 2 per cent of the patients developed severe heterotopic bone radiographically, and unsatisfactory functional results. There is no sex predilection for heterotopic bone formation except that the condition appears more severe in females. All ages are equally affected. The underlying disease process in the hip does not influence the occurrence of heterotopic bone. The incidence was significantly greater in patients who developed postoperative hematomas, prolonged wound drainage, or superficial infection. When surgical exposure is difficult and retraction of soft tissue aand soft tissue damage takes place, the incidence is much greater. Patients who have undergone previous surgical procedures about the hip present a greater risk in regards to development of disabling heterotopic bone formation. The etiology of heterotopic bone formation is not known. The following steps should be taken to avoid or greatly minimize the development of heterotopic bone: meticulous exposure with most careful retraction, copious irrigation with antibiotic solution, debridement of devitalized tissue prior to closure, instillation of drainage tubes, intraoperative and postoperative antibiotics, and carefully controlled postoperative anticoagulation.


Classification of spondylolisis and spondylolisthesis. A working classification of spondylolysis and spondylolisthesis which encompasses the salient features of the disorder, has been presented. It is based on both etiological and anatomical factors.


Combined trochanteric and ipsilateral shaft fractures of the femur treated with the Zickel device: a case report. An unusual double fracture of the femur in the trochanteric and shaft areas of a 39-year-old clerical worker has been successfully treated by open reduction and internal fixation with the Zickel device. Only one other instance of the application of this method to a double fracture seems to have been reported previously. Recovery was uneventful, prompt, and the patient showed good evidence of healing at the 10-month followup examination. The described case represents the seventh report of this unusual lesion in the literature.


Pycnodysostosis presenting with bilateral subtrachanteric fractures: case report. A 50-year-old woman had bilateral subtrochanteric fractures over a period of 9 months; both fractures were found to be in osteosclerotic femora. The patient was multiparous with 5 normal children. Since subtrochanteric fractures represent only 5 per cent of all femoral neck fractures the occurrence of bilateral subtrochanteric fractures in a relatively young woman suggested an unsuspected underlying disease. Clinical and laboratory investigations showed no evidence of systemic, metabolic, infective or malignant disease. The patient's short stature, peculiar facies in association with osteosclerosis in medullated long bones and typical radiographic findings: hypoplastic claviculae, absent ungual tufts of distal phalanges, hypoplastic paranasal sinuses, and obtuse mandibular angles suggested the proposed diagnosis of pycnodysostosis, a rare autosomal recessive osteosclerotic condition, that has been described in less than 50 cases, including only one Jew. Despite 2 technically difficult surgical hip operations, a 3-year follow-up showed good remedullarization of both fractured femora and no limitation in the patient's daily activities.


The use of banked autologous blood in total hip replacement surgery. Fifty patients anticipating total hip replacement, with an average age of 63, donated 125 units of blood in an organized autologous transfusion program. All but 3 patients demonstrated the ability to respond to oral iron and maintain adequate hemoglobin levels for subsequent phlebotomies. No complications were encountered and the program was well received by the participating patients. The advantages of autologous transfusion are numerous, including the avoidance of the risk of serum hepatitis, blood reactions, blood incompatibilities. Autologous transfusion constitutes a source of blood availability in the elective procedure of total hip replacement. This procedure is safe, practical and well tolerated.


Indicators of recovery from fractures of the hip. Patients with similar injuries who were at a similar level of function before the injury differ in the extent of recovery. In an attempt to identify important factors that affect recovery, we collected extensive physical, psychological and sociological data on a group of 108 elderly people with fractures of the hip in order to study the influence of the many variables on their recovery. We found that of all the items studied, those that best indicated the degree of recovery were: (1) the physical therapist's rating of functional ability; (2) how often the patient got outside the home prior to injury; (3) the patient's mental clarity.


Ligament length patterns, strength, and rotational axes of the knee joint. Using intact fresh specimens, the cruciate ligament lengths for positions of flexion and internal-external rotation were computed using a non-invasive technique; using photographic methods, the centers of transverse rotation on the tibia and the direction of the flexion axis were also obtained. The anterior cruciate was found to be particularly effective in restraining internal tibial rotation; the ability of the posterior cruciate to restrain external rotation, however, depended strongly on the transverse axis location. Ligament length changes during flexion were found to be small in the absence of rotary torque and anteroposterior forces. The average internal rotation occurring during flexion was 37 degrees, half of which took place during the first 15 degrees of flexion. Ultimate rupture strengths of approximately 60 kh for the cruciates were measured, with stiffnesses of 16 kg/mm.


Solitary intraosseous neurilemmoma of the tibia: review of intraosseous neurilemmoma and neurofibroma. This is a case report of a 59-year-old woman with a neurilemmoma involving the tibia, a site not previously reported for this tumor. Neurilemmoma, a benign neoplasm which rarely involves bone, arises from the Schwann cells in the nerve sheath. It is a distinct pathological entity separate from solitary neurofibroma, and arises from the connective tissue coats of nerves, but which also involves bone. The incidence of the 2 types of nerve sheath tumors is obscured by the tendency of some authors to use the terms interchangeably. Forty-eight cases of true intraosseous neurilemmoma have been reported in the literature. Of 18 cases of solitary intraosseous neurofibroma primary in bone, all were in the jaw and 6 were malignant. The diagnosis of intraosseous neurilemmoma may be missed because of its rarity and roentgenologic appearance of cystic bone disease which is not distinctive except that it resembles other commonly encountered bone lesions. A positive diagnosis is based only on the microscopic pathology. Complete local resection generally produces an excellent result without recurrence.


Total elbow replacement.

Total elbow replacement. This is a report of a total elbow low friction arthroplasty consisting of a vitallium humeral component and a high density polyethylene ulnar component equipped with a special snap-lock fit joint. The immediate results in 16 patients are most encouraging.


Flexion and extension contracture of the elbow: surgical management. In those cases in which a contracted capsule at the elbow limits flexion or extension, surgical treatment is warranted. A wide exposure is necessary to identify vital structures and perform an adequate anterior capsulectomy. A direct approach through the triceps is recommended for posterior capsulectomy. In 6 cases, the results were good when the contracture of the capsule was not associated with skin contracture or bony deformity.


Corrective surgery for the deforming hand arthropathy of systemic lupus erythematosus. A 33-year-old woman with deforming but non-erosive hand arthropathy typical of SLE had recurring digital subluxations and swan neck deformities after soft tissue procedures. Stronger grip and pinch as well as improved appearance were achieved with thumb MCP fusion and finger MCP silastic implants.


Acute hematogenous osteomyelitis complicating closed fractures. Five cases of acute hematogenous osteomyelitis occurring at the site of closed fractures are reported. This is a serious and potentially lethal complication resulting in directly in the death of 3 of the 5 patients. This is an unusual occurrence seen infrequently, and subsequent delay in diagnosis is frequent. An awareness of this complication (which usually occurs in the face of decreased resistance to infection) coupled with careful inspection of the fracture site, evaluation of the patient as a whole, and a high index of suspicion will allow earlier diagnosis and possibly more successful early treatment. Because of the pathophysiology of this lesion and the usual delay in diagnosis, initial treatment should include wide surgical drainage of the abscess with proper debridement and bony resection. This may involve procedures which at first glance may appear to be mutilating. In these patients with decreased resistance to infection, the initial appropriate choice of antibiotics is essential.


Etiology of spondylolisthesis.

Etiology of spondylolisthesis. The etiology of spondylolisthesis is multiple according to the type of the vertebral slipping. In fact all the following basic pathological processes may be involved: congenital malformation of the upper sacrum in the dysplastic spondylolisthesis; growth dysplasia of the vertebral arch in the "isthmic spondylolisthesis" where an hereditary background and mechanical stresses play a determining role; degenerative conditions of the intervertebral joints in "degenerative spondylolisthesis" of Newman or the "pseudospondylolisthesis" of Junghanns; infections and benign or malignant tumors destroying the articular bolt maintaining the vertebral line; traumatic lesions such as multiple fractures of the bony hook or much more rarely an isolated bilateral fracture of the pars interarticularis.


Evaluation of microbial contamination of surgical gloves during actual use. The contamination rate of gloves is about the same for all scrubbed personnel, be they single or double gloves (33%). More holes are noted in the gloves of personnel who use their hands more strenuously. A double pair of gloves does not reduce the amount of contamination but does reduce the number of holes. The contamination could not be associated with the hole in the glove in our study. The amount of contamination beneath the glove does not influence its exterior contamination. Contamination generally comes from somewhere else in the operative field environment.


Metabolic balances of strontium in man.

Metabolic balances of strontium in man. Stable strontium balances were determined in man under strictly controlled dietary conditions in control studies and during both oral and intravenous administration of stable strontium. The diet contained about 1 mg strontium per day and most of this (88%) was excreted in stool while 17.5 per cent was excreted in urine, so that the balance was very slightly negative. During the oral intake of 1536 mg strontium per day, given as the lactate, the urinary and the fecal strontium excretions increased markedly and the balance became strongly positive. During the 6-day periods of intravenous infusions of stable strontium as the gluconate, 30-40 per cent of the infused amount was excreted in the urine and 5-10 per cent in stool. A high percentage of the strontium retained during both oral and intravenous administration was excreted in 30 days after the discontinuation of the strontium administration and there was no evidence of long term retention. The administration of stable strontium, given either orally or intravenously, was associated with an increase of the urinary calcium excretion.


The relation between densitometric and quantitative histological analysis of bone specimens from the iliac crest. Roentgendensitometric measurements were correlated with quantitative histological analysis of cortical and cancellous bone from a standard anatomical site on the iliac crest. The point-count method was used to quantitate spongy bone in 8 mu thick sections. Measurements of the thickness of the cortices were made with a micrometric eyepiece. The reproducibility of the method for the roentgendensitometric analysis was found to be about 1 per cent of the mean for all variables. The correlation between roentgendensitometric and histological analysis was found to be low (r=0.44) and could be ascribed mainly to variation in the thickness of the cortices which again was only slightly correlated with the percentage of spongy bone (r=0.39). Both the determination of the amount of bone mineral and of bone by quantitative histometric analysis are required for diagnosis of skeletal system disorders.