Direct radioimmunoassay of plasma aldosterone in normal subjects. A direct radioimmunoassay of plasma aldosterone concentration using an antibody of high specificity is described and compared to a previous chromatographic radioimmunoassay. A significant correlation was found between the plasma aldosterone concentration determined by this direct radioimmunoassay and by a radioimmunoassay including paper chromatography in 38 plasma samples obtained from patients with hypertension of various etiology. This direct radioimmunoassay of plasma aldosterone concentration is simpler and less time-consuming. A significant and similar correlation between plasma aldosterone concentration and plasma renin activity (active renin) and renin concentration (total renin) was found in normal subjects on a regular and a low sodium intake. Plasma aldosterone concentration in normal subjects was significantly and negatively related to age and to the 24-h urinary sodium excretion.


[Fast and accurate method for theophylline analysis in preterm babies using gas chromatography and nitrogen selective detector (NFID) (author's transl)]. The combined utilization of (a) a weak polar OV-1 phase, (b) an on-column methylation using a methylating agent commercially available, (c) a nitrogen selective detector (NFID) and (d) a small volume of sample, allows the development of a fast (less than 20 min) and accurate method for theophylline analysis in preterm babies. With 50 microliter of capillary whole blood sample, its limit of sensitivity was 0.5 microgram/ml of theophylline. This method is most desirable for theophylline monitoring in treating apnea of premature infants.


Simultaneous quantitation of catecholamines and metabolites in urine. A semi-automated fluorimetric method for the quantitation of urinary catecholamines (dopamine, noradrenaline and adrenaline) combined with manual methods for the quantitation of their metabolites (homovanillic acid, normetanephrine, metanephrine and vanillylmandelic acid) is described. It provides a sensitive and reproducible analytical technique for routine use. Values obtained in healthy adults are given.


Infrequency of urinary excretion of beta-aminoisobutyric acid by healthy humans. Urinary beta-aminoisobutyric acid (BAIB) levels were measured by modified ion-exchange chromatography. Daily BAIB levels are reported for a group of apparently healthy individuals, a subject with infective hepatitis and two human genetic variants who were high "excretors" of BAIB. The frequency of high "excretors" of BAIB was found using low-voltage paper electrophoresis. The frequency among 403 male European subjects was 5 (1.2%) and lower than previous estimates in the United Kingdom. The percentage recovery of fed BAIB suggests that Oriental "excretors" may have a different type of genetic lesion from non-Oriental "excretors". The clinical usefulness of urinary BAIB assays and qualitative screening is reviewed.


Platelet phospholipid in stroke.

Platelet phospholipid in stroke. A study of platelet phospholipids in patients with stroke has been undertaken comparatively with patients without predisposition to thrombosis. An increase in the phospholipid/protein ratio in platelets was observed in patients with acute cerebrovascular accident. A significant increase of palmitoleic acid is observed in platelet phospholipids of these patients; it is accompanied by a decrease of linoleic acid. These modifications are reflected in plasma where linoleic acid is greatly diminished but where an important increase of palmitic acid is noted besides palmitoleic acid. A possible relation between higher clotting activity of platelets and those modifications in their phospholipids is discussed.


Use of patient data in the control of urea, creatinine and electrolyte estimations. Analysis of urea, creatinine and electrolyte results from patients in two distric general hospitals is considered as a means of comparing and evaluating laboratory performance in these tests. The raw patient data, consisting of partially overlapping normal and abnormal subpopulations, is analysed by a procedure for resolving overlapping Gaussian distributions. This method permits determination of reference values from hospital populations and in a modified form can also be used to provide a regular indication of the precision of the biochemical estimations. The information derived from such a mathematical treatment of patient results is compared to that obtained from participation in a national quality control scheme.


The effect of age, sex and other factors on blood chemistry in health. Quantitative data is presented concerning the influence that age, sex, the menopause, oral contraception, blood group and time of blood collection have on 19 commonly-determined blood chemistry values. The data were derived from 1000 healthy blood donors in whom blood sampling conditions were standardised to conform with those applying to hospital out-patients. Statistical techniques were used to allow for the effects of analytical variation and to enable the effects of the various factors and their interactions to be expressed in a practically useful manner. Age and sex effects are shown to be the rule and to interact in many instances. Creatinine, urea, glucose, cholesterol, potassium and globulin show a tendency to increase in concentration with age, while total protein, albumin, calcium, inorganic phosphate and iron levels tend to fall progressively. Evidence is given to suggest that many of the changes occurring in women at about 50 years should be attributed to hormonal changes. In all instances when the menopause has a significant influence there is a rise in the concentration of the constituent concerned. It is proposed that other laboratories should assemble age and sex stratified reference ranges from (a) figures given for the mean values for defined age and sex groups, adjusted if necessary to allow for different analytical bias, (b) figures given for nonsystematic biological variation, and (c) their own measurements of analytical precision. Details of the necessary procedure are given, allowance being made for logarithmic transformation of the results where necessary.


The sulpiride test in panhypopituitarism. The results obtained with a new test of prolactin (PRL) release in six panhypopituitary patients as compared to fourteen normal subjects (eight females and six males) are presented. The test consists of the i.m. administration of 100 mg of sulpiride and the measurement of plasma PRL by a double antibody radioimmunoassay techniques at--15, 0, 15, 30, 45, 60, 75, 90, 105 and 120 min. Mean baseline PRL values were not significantly different in the three groups. After sulpiride a 800-4200% increment of prolactin over control values was noted in the females and 1200-3500% increment in the males. The peak values were obtained at 15 or 30 min (6030+/-670 mu/l +/-SEM in the females and 5550+/-870 mu/l in the males). The mean values were not significantly different in the two sexes until the sixtieth minute but were significantly higher (P less than 0.05) in the female thereafter. In the hypopituitary patients a complete failure of response was noted. These results show that the sulpiride test possesses a considerable potential as a screening procedure in the diagnosis of pituitary insufficiency.


Assessment of prolactin release in pituitary dwarfism with the sulpiride test. We report here the results obtained with a new test of prolactin (PRL) release in six normal pre-pubertal boys, eleven children with short stature of non-pituitary origin and in thirteen pituitary dwarfs. The test consists of the administration of 100 mg of sulpiride i.m. and the measurement of PRL in serum samples up to 120 min after injection. Baseline PRL concentrations were not clearly different in the three groups. After sulpiride a marked increase (3--10 times over control values) in PRL was noted in all normal and short children without pituitary disease. A complete failure of response was observed in ten of the thirteen pituitary dwarfs. It is concluded that sulpiride has considerable potential in the differential diagnosis of children with stunted growth.


Behaviour of plasma renin activity and aldosterone during the first 72 h of life. Plasma renin activity (PRA) and plasma aldosterone concentrations (PAC) were determined in fifty normal newborns during the first 72 h of life. PRA was elevated in all cases and tends to increase from the first (6.79 +/- 0.69SE ng/ml/h) to the third day of life (8.24 +/- 0.96SE ng/ml/h). PAC was also elevated and rose from 24.06 +/- 3.23SE ng/dl on the first day to 39.20 +/- 4.25SE ng/dl on the third day. No significant correlation was observed between PRA and PAC. Serum sodium was within the normal range, whereas serum potassium was slightly elevated during the first 48 h of life. The physiological significance of the high levels of PRA and PAC in newborns is not clear at present. Many factors may be involved in the increased activation of the renin-angiotensin-aldosterone system: low blood pressure, hypersensitivity of the macula densa to catecholamines, relative insensitivity of the immature kidney to aldosterone, hyperkalaemia and other control mechanisms for aldosterone secretion all of which probably operate simultaneously during the first days of life.


Effects of iodides on the hypothalamic-pituitary-thyroid axis in neurological endemic cretinism: evidence for compensated thyroidal failure in adult life. Thyroid function studies, performed after iodide administration to five patients with neurological endemic cretinism, were indicative of hypothyroidism. All five subjects had either a low serum thyroxine (T4) or a high basal thyrotrophin (TSH) level and a clearly exaggerated TSH response to thyrotrophin releasing hormone (TRH). These findings are in sharp contrast with those we have previously described in goitrous patients without cretinism from the same geographical area. One interpretation of our observations is that there is an underlying mild defect in thyroid hormone synthesis in endemic cretinism predisposing to iodine induced hypothyroidism.


Plasma steroid and gonadotrophin profiles in ovulatory but infertile women. A group of twelve patients with a history of infertility lasting at least 2 years despite evidence of regular ovulatory cycles, were selected from an Infertility Clinic after thorough investigation had revealed no other obvious cause for their infertility. Daily plasma gonadotrophin and steroid concentrations were measured in twenty cycles from these women and the results compared with the hormonal profiles obtained from a group of eleven control 'normal' women. No significant differences were found in the concentrations of LH, FSH or oestradiol although plasma progesterone concentrations were significantly lower in the infertile women, particularly during the first half of the luteal phase. In the absence of any other demonstrable defect, it was assumed that the decreased progesterone secretion was directly or indirectly implicated in the pathogenesis of their infertility, and a number of therapeutic regimes (progesterone supplementation of the luteal phase or additional stimulation by either anti-oestrogens or exogenous gonadotrophins) were assessed for their efficacy in correcting this defect. Although plasma progesterone concentrations after most of these regimes were significantly increased, none of the patients in this series conceived.


Double heterozygosis for hemoglobin C-beta thalassemia: description of a Spanish family. Hemoglobin C-beta thalassemia in a Spanish family. A spanish family is described with two abnormal genes: 1) hemoglobin C in heterozygosis with normal hemoglobin, introduced by the subject's mother, and 2) heterozygotic betathalassemia for which the father is a carrier. In the subject and his sister, both abnormal genes coincide with the presence of hemoglobin C and hemoglobin F, simulating homozygosis for hemoglobin C. The clinical condition shows medium intensity chronic hemolysis. In the subject's brother, mother and grandmother, simple heterozygosis of hemoglobins A-C is seen, with no apparent clinical manifestations. The father shows subjaundice with some acute hemolytic episodes. Hypotheses are discussed which might explain the presence of these hemoglobins in Spain.


Phenotypic and genetic analysis of the silver-Russell syndrome. A family is reported in which two half-siblings present clinical findings suggestive of the Silver-Russell syndrome (SRS). The available published literature on SRS is reviewed and the variable expression of the syndrome demonstrated. A review of published pedigrees of the syndrome suggests that in a small percentage of cases, SRS has a genetic etiology.


Serum IgM in retinitis pigmentosa: a genetic study. Because of a published report that serum immunoglobulin M (IgM) was elevated in some cases of retinitis pigmentosa (RP), a genetic study was undertaken to determine if a particular pattern of inheritance was associated with elevated IgM. Seventy-five RP patients in 37 families were ascertained and classified by pattern of inheritance into six groups. Serum IgM was quantitated by the radial immunodiffusion technique. Fifty-one controls were also studied. Methods of adjusting the IgM values for sex, age, and race were derived, but only a sex adjustment was used, since no effect of age on IgM was found in this sample, and there were few data on race. There was no signifcant difference in mean IgM levels between RP patients and controls. The variance of the RP group was slightly greater than that of the controls. One-way analysis of variance of the six genetic categories of RP and controls was performed on the raw data and on the data after log transformation. The F-ratio was not significant, indicating that there was no difference in serum IgM levels among the seven groups. Possible reasons for the discrepancy in results between this study and the previous report are presented.


Familial reinclusion of permanent molars. Reinclusion of permanent molars was found in 55 individuals from 9 families. Inheritance is clearly autosomal dominant with complete penetrance. The provisional assignment of its gene locus to the same linkage group as the gene locus of blood group P (Bosker & Nijenhuis 1975) could not be confirmed.


The micro-sperm immobilization test: the use of only motile spermatozoa and studies of complement. A technique is described which shows how to obtain a suspension of only progressively motile spermatozoa, from semen, by active penetration into an overlying buffer layer. About 60% of the number of motile spermatozoa in the original semen sample can be obtained as an output in the removed buffer layer. With this method many more semen samples, in particular those with less than 70% motile spermatozoa, can be used than otherwise would have been possible. Moreover, with such a suspension of only motile spermatozoa the sensitivity of the micro-immobilization test is substantially improved, due to the absence of non-specific clumping, the minimization of specific tail-to-tail agglutination and an optimal end-point reading because of the absence of background immotility. As the complement source, a 1:8 dilution of rabbit or guinea-pig serum in human AB serum was found to be most suitable. The 1 microliter sperm suspension is initially mixed with 2 microliter of serum and incubated for 30 min, and then a further 2 microliter volume of complement is added, which is incubated for 2 hr with the serum-sperm mixture, and the test is read under an inverted microscope.


IgG rheumatoid factor in subacute bacterial endocarditis: relationship to IgM rheumatoid factor and circulating immune complexes. With recently developed radioimmunoassays, we have been able to study the levels and properties of IgG rheumatoid factor (IgG RF) and IgM rheumatoid factor (IgM RF) in patients with subacute bacterial endocarditis (SBE), as well as the relationship of these autoantibodies to circulating immune complexes. We found significantly elevated amounts of IgG RF and IgM RF in SBE sera. The IgG RF chromatographed on Sepharose 6B as an intermediate complex, indistinguishable from the pattern seen in rheumatoid arthritis. RF levels peaked later in the course of SBE than did levels of circulating immune complexes. With antibiotic treatment RF levels declined, although not as fast nor as completely as circulating immune complexes. These results suggest that both IgG RF and IgM RF in SBE may be part of a polyvalent antibody response to elevated levels of circulating immune complexes which do not themselves contain RF.


The in vitro effect of thymic humoral factor and levamisole on peripheral blood lymphocytes in systemic lupus erythematosus patients. The in vitro effect of thymic humoral factor (THF) and levamisole on E rosette-forming cells in the peripheral blood of seventeen patients with systemic lupus erythematosus (SLE) was studied. Patients with active disease showed a low number of E rosette-forming cells. A significant rise in the number of E rosettes was obtained after incubation with both THF and levamisole. No such effect was observed on lymphocytes from patients with inactive disease and normal controls. In seven patients, three with active disease and four with well-controlled disease, short-term cultures were performed. The effect of THF on E rosettes was found to be the same before and after the short-term cultures. Possible mechanisms, by which THF (on the one hand) and levamisole (on the other) may increase the number of E rosettes in vitro, are discussed.


Immune sperm agglutination: are only motile spermatozoa involved? Human sperm-agglutinating sera was examined using the tray agglutination technique (TAT) with whole diluted semen, and also with a suspension of only progressively motile spermatozoa-obtained from the same semen sample by the penetration of motile spermatozoa in an overlying medium layer. The titres of tail-to-tail (T) agglutinating sera were considerably lower with the latter sperm suspension, but head-to-head (H) agglutinating sera gave similar titres with the two types of sperm suspensions. Attempts to increase titres of T-agglutinating sera with only progressively motile spermatozoa were made by reducing the progression rate of the spermatozoa, and by increasing the concentration of the sperm cells. However, significant titre differences remained. Moreover, the agglutinates obtained were very small, and difficult to observe with the routinely employed magnification of x40. The lower titres still remained where seminal plasma was used as the penetration medium, indicating that a loss of coating antigen(s) was not the cause of lower titres. It seems likely that spermatozoa are attached to each other only weakly in T agglutination, much more weakly than in H agglutination. It is considered that immotile sperm cells that are present in whole diluted semen reinforce the T agglutination process, producing the higher titres.


Cryoimmunoglobulinaemia in patients with primary renal disease and systemic lupus erythematosus. I. IgG- and DNA-binding assessed by co-precipitation. Sera were tested for cryoglobulin precipitates from 206 consecutive patients with renal disease, ninety-eight normals and sixteen patients with systemic lupus erythematosus (SLE) without evident renal disease. Cryoprecipitates were detected in 17% of test subjects overall and 2% of normals; the incidence was highest in patients with SLE, regardless of detectable renal disease. Cryoprecipitates usually were comprised of IgG and IgM or IgG, IgM, and IgA in thirty-six out of forty-two instances, although a single immunoglobulin class was detected in five patients. Co-precipitation experiments showed IgG-binding by virtually all sera forming cryoprecipitates; isolated cryoprecipitates bound radiolabelled homologous IgG, and Fc fragment and sometimes IgG subclass proteins preferentially. Freshly forming cryoprecipitates sometimes co-precipitated DNA, whereas all isolated cryoprecipitates co-precipitated DNA from dilute solutions. The data are compatible with the current hypothesis that cryoimmunoprecipitates are immune complexes that are insoluble in vitro in the cold, that they usually comprise mixed immunoglobulins with anti-IgG activity, and may contain a mixture of antigens and antibodies.


Changes of serum anti-thyroid antibodies during and after pregnancy in autoimmune thyroid diseases. Changes of serum anti-thyroglobulin haemagglutination antibodies (TGHA) and anti-thyroid microsomal haemagglutination antibodies (MCHA) were observed during pregnancy and after delivery in Graves' disease and autoimmune thyroiditis. Both TGHA and MCHA decreased as pregnancy progressed, and sometimes they became negative in late pregnancy. Transient increases of TGHA and MCHA were observed after delivery and the antibody titres reached peaks about 3-4 months post-partum in more than halft the patients. In some patients, antibodies developed after delivery. Similar transient increases of antibodies were observed after spontaneous and therapeutic abortion. These changes seem to be induced by physiological and immunological changes occurring during pregnancy and after delivery.


Rubella serology by solid-phase radioimmunoassay: its potential for screening programmes. Sera from 269 adult females who had experienced naturally acquired or vaccine-induced infection by rubella virus, including immune persons challenged intranasally with rubella vaccine (RA27/3) as well as sera from 100 patients attending antenatal clinics, were tested for rubella antibodies by the conventional haemagglutination inhibition tests (HAI), as well as a newly developed solid-phase radioimmunoassay (RIA) for rubella immunoglobulin G (IgG) antibodies. Following both naturally acquired and vaccine-induced infection, titres by RIA were approximately ten-fold higher than by HAI. The RIA test was particularly useful in assessing the true immune status of those with apparently low levels of HAI antibody and has the added advantage that pre-treatment of sera to remove inhibitors of haemagglutination and red cell agglutinins is unnecessary. The RIA test has potential for the large-scale screening programmes which need to be carried out if the Department of Health and Social Security recommendation, that women attending antenatal and family planning clinics be screened for rubella antibodies, is to be effectively met.


Cryoglobulinaemia and circulating immune complexes in tropical splenomegaly syndrome. Large amounts of cryoglobulins and soluble immune complexes were detected in the sera of thirteen patients with tropical spenomegaly syndrome (TSS). Complexes were detected by three different methods: radiobioassay, a modified rheumatoid factor-binding activity method and a modified Clq-binding assay. Protein precipitable by 4% polyethylene glycol (PEG) was also measured. The cryoglobulins contained IgM, IgG and in some cases, C3. It is likely that in TSS, marked immune complex formation is associated with hypergammaglobulinaemia and that continuous engulfment of these complexes by cells of the reticuloendothelial system (RES) is the cause of the hepatosplenomegaly.


Production of leucocyte migration inhibitory factor (LIF) in infectious mononucleosis. Spontaneous release and lack of response to concanavalin A. The spontaneous release of LIF from blood lymphocytes was studied in patients with infectious mononucleosis. Mononuclear cells were separated from the blood and cultured for 22 hr, and LIF activity in the supernatant was determined. Supernatants depleted of LIF activity by means of anti-LIF antibodies or by treatment at 80 degrees C for 30 min were employed as controls; these two methods gave essentially similar results. In nine out of eighteen patients, spontaneous LIF production was demonstrated during the acute stage of the illness; this was not seen in any of the normal persons studied. 6 weeks later, spontaneous LIF production had ceased in most patients. Concanavalin A stimulated all normal lymphocytes to LIF production, but in sixteen out of seventeen patients with infectious mononucleosis this response was absent or diminished. At the follow-up study 6 weeks later, the lymphocyte response to concanavalin A was still suppressed.


Circulating immune complexes in ulcerative colitis.--II. Correlation with serum protein concentrations and complement conversion products. Several serum proteins were quantified in twenty-two patients with active ulcerative colitis, and the findings were related to disease activity and occurrence of circulating immune complexes (IC). Conversion of C3 was significantly more frequent in the IC-positive group (eight patients) as compared to the IC-negative group (fourteen patients). Factor B was demonstrable in fifteen out of the twenty-two patients and seven out of the eight IC-positive patients had detectable levels of factor B. There was no difference between the IC-positive and the IC-negative group as regards serum concentrations of the complement factors C3, C4 and factor B, or serum orosomucoid, albumin, IgM and IgG. In contrast, the serum IgA levels tended to be reduced in the IC-positive group. C3 and factor B were significantly elevated in four patients with severe disease activity. In addition, C3, factor B and C4 concentrations showed a positive correlation to the serum orosomucoid levels. The serum concentrations of orosomucoid and albumin were inversely correlated to each other.


An in vivo investigation of the negative chronotropic effect of cholic acid in the rat. 1. Experimental obstructive jaundice in the Wistar rat causes a significant decrease in heart rate. 2. Intravenous administration of cholic acid in vivo elicits a dose-dependent negative chronotropic effect. 3. Atropine or vagotomy significantly reduces, but does not abolish, the negative chronotropic effect of cholic acid. 4. Ganglion blockade and decerebration diminishes the negative chronotropic effect of cholic acid, but to a lesser extent than atropine or vagotomy. 5. Sympathetic depletion by reserpine slightly potentiates the response to cholic acid. 6. The effect of cholic acid injected cranially into the common carotid artery is less than when administered into the jugular vein. 7. The haemolysis caused by cholic acid does not appear to be involved in the negative chronotropic effect. 8. It is concluded that cholic acid causes both a direct as well as a vagally mediated negative chronotropic effect in the Wistar rat.


Comparative studies on the pharmacological actions of antiarrhythmic drugs in isolated rate papillary muscle. 1. The effects of ajmaline, cocaine, phenytoin, lignocaine, procainamide, propranolol, quinidine and trimetazidine on the contractility and the refractory period of isolated rat papillary muscles were compared. 2. At the higher concentrations used, all drugs suppressed the contractile tension of the rat papillary muscles. 3. The effects of these drugs on the refractory period were compared at concentrations at which the contractile tension was suppressed by 30% of the control. At this point, lignocaine, procainamide, ajmaline and quinidine prolonged the refractory period more than two-fold while the effects of propranolol and phenytoin were slight, cocaine and trimetazidine had little or no effect.


Comparative study of chronotropic and inotropic effects of dopamine and seven derivatives on the isolated, blood-perfused dog atrium. 1. The effects of seven dopamine amino acid conjugated derivatives were compared with those of dopamine on sinus rate and contractile force using the isolated, blood-perfused dog atrium preparation. 2. Each of these dopamine derivatives induced dose-related positive chronotropic and inotropic effects. 3. The positive chronotropic and inotropic effects were obtained with the same rank order of potency for each effect with six of the dopamine derivatives. Their rank order and relative potency (dopamine = 1000) were: N-Ileu-dopamine (3) greater than N-Glu-Pro-dopamine (1) = N-Ala-Glu-dopamine (1) greater than N-Gly-Gly-dopamine (0.3) = N-gamma-Glu-dopamine (0.3) greater than N-Gly-Gly-Leu-dopamine (0.1) greater than N-Gly-Gly-Pro-dopamine (0.01). 4. In doses producing equal positive inotropic effects, the positive chronotropic effect of N-Gly-Gly-Leu-dopamine was much less than with the other derivatives tested. Its potency compared to dopamine (= 1000) was 0.3 for the inotropic and 0.1 for the chronotropic effect. 5. The duration of action of doses of the derivatives producing approximately equal positive inotropic responses was in the order N-Ileu-dopamine = N-gamma-Glu-dopamine = N-Gly-Pro-dopamine = N-Ala-Glu-dopamine greater than N-Gly-Gly-dopamine = N-Gly-Gly-Leu-dopamine = N-Gly-Gly-Pro-dopamine greater than dopamine.


Effects of monosodium glutamate-induced obesity in mice on carbohydrate metabolism in insulin secretion. 1. The syndrome of obesity induced by neonatal injection of monosodium glutamate (MSG) has been further studied in mice. In confirmation of previous studies stunting and decreased pituitary and gonadal weights were observed. 2. After weaning food intake was consistently less in MSG-treated than control mice. Body lipid stores were significantly elevated in MSG-treated mice by 2 weeks of age and increased progressively up to 4 months. 3. Plasma glucose was comparable between MSG-treated and control mice in the fed state whereas after an overnight fast MSG-treated mice exhibited relative hypoglycaemia. 4. Obese MSG-treated mice did not exhibit resistance to exogenous insulin and disposed of an intravenous glucose load more rapidly than control mice. 5. Hyperinsulinaemia was present inconsistently in both fed and fasted mice and in response to administered glucose. 6. Neonatal administration of MSG provides a useful additional model for studying the role of the hypothalamus in obesity.


Effects of thiopentone sodium, methoxyflurane and halothane on haematological parameters in sheep during prolonged anaesthesia. 1. Satisfactory surgical anaesthesia in sheep was achieved by i.v. injection of thiopentone sodium per se (20 mg/kg); and also with thiopentone/methoxyflurane and thiopentone/halothane anaesthetics (2--3% and 1.5--2%, respectively). 2. Cardiac arrhythmias were not observed during thiopentone sodium, thiopentone/methoxyflurane and thiopentone/halothane anaesthesia. However, during thiopentone anaesthesia, one sheep displayed a high degree of sinus tachycardia followed with ventricular tachycardia. 3. Pneumograms recorded during thiopentone sodium and thiopentone/methoxyflurane anaesthesia showed no irregularity, but in thiopentone/halothane anaesthesia, 30% of the sheep developed Cheyne-Stokes periodic respiration. 4. Packed cell volume (PCV) and haemoglobin (Hb) were significantly decreased in thiopentone/methoxyflurane and thiopentone anaesthetized sheep, but not in animals anaesthetized by thiopentone/halothane. 5. White blood cell count (WBC) was significantly decreased only in thiopentone/methoxyflurane anaesthetized sheep, but was not remarkable in thiopentone and thiopentone/halothane anaesthetized animals. 6. A significant lymphocytopenia occurred in thiopentone/methoxyflurane and in thiopentone/halothane anaesthetized sheep, but not in the thiopentone anaesthetized animals. This was accompanied with an increase in neutrophils. 7. Clotting time fell, but the extent and time course was different in thiopentone, thiopentone/methoxyflurane and thiopentone/halothane anaesthesia. 8. From these data, it is suggested that thiopentone sodium, thiopentone/methoxyflurane and thiopentone/halothane have different effects on different blood parameters during prolonged anaesthesia, and may be clinically significant.


Prevention of acute gastric ulceration in the rat by cimetidine, a histamine H2-receptor antagonist. 1. Intraperitoneal injections of cimetidine into rats markedly reduced gastric acid production. When given at a dose of 50 mg/kg body weight, rate of acid production fell from a mean of 2.73 mumol/min (s.d. = 0.32) to a lowest level of 0.81 (s.d. = 0.28): the difference was highly significant (P less than 0.005). When given in a dose of 100 mg/kg, the rate of acid production further fell to 0.18 mumol/min (s.d. = 0.12;P less than 0.001). 2. Treatment with cimetidine in doses of 100 mg/kg 8-hourly during a 24 h period of restraint prevented the development of acute gastric ulceration in the rat. Pretreatment with cimetidine also protected against the ulcerogenic effects of intragastrically administered bile or lysolecithin. 3. The marked sustained reduction of acid production most probably accounts for the protective effects of cimetidine against ulcer production in the rat stomach.


The natural history of focal segmental glomerulosclerosis with and without mesangial hypercellularity in children. The clinical courses and biopsy findings of twenty-four children with focal segmental glomerulosclerosis (FSG) were reviewed retrospectively to determine whether the presence of significant mesangial accentuation and proliferation (MAP) has prognostic implications. At the latest assessment, 10 of 13 patients with significant mesangial involveme,t (MAP [+]) had glomerular filtration rates less than or equal to 90 ml/min/1.73 m2, with four in renal failure. In contrast, all of eleven children with no significant mesangial involvement (MAP [-]) maintain glomerular filtration rates greater than 90 ml/min/1.73 m2, (P less than 0.001). Of no prognostic importance were: age at onset of disease, type of onset, or presence or absence of hematuria. The preponderance of males in the MAP (+) group was a statistically significant difference (P less than 0.001). The two groups did not differ in regard to either the type of clinical course or the length of the period of observation, and there was no obvious effect of therapy in either group of patients. Immunofluorescence data were of no value in differentiating between the two groups. Our results imply that FSG with significant mesangial accentuation and proliferation is a unique glomerular disease of childhood, with a clinical course characterized by rapid progression to renal insufficiency. FSG without mesangial involvement, on the other hand, appears to have an excellent prognosis over long periods of time. At present, these two diseases can be differentiated only by renal biopsy.


Interactions between prazosin, clonidine and direct vasodilators in the anaesthetized rat. 1. Prazosin, clonidine, hydrallazine and diazoxide were administered intravenously, alone or in various combinations, to anaesthetized rats. 2. Prazosin and clonidine were equipotent. Their combined hypotensive effects in no instance exceeded the maximum effect attainable with either agent alone. The hypotensive effects of hydrallazine or diazoxide were, in contrast, additive to those of either prazosin or clonidine. 3. Pressor responses to clonidine were antagonized by prazosin. Prazosin may prove useful in hypertensive crises provoked by clonidine.


Clinical, pathological and genetic aspects of a form of cystic disease of the renal medulla: familial juvenile nephronophthisis (FJN). A combined clinical, pathological and genetic study of 13 cases of FJN is reported. The clinical features are conistent with those described in the literature, except that short stature is not a feature in this group. Hyperplasia of the juxtaglomerular apparatus has been seen in 5 of 9 cases where histology was done. The genetic studies support the view that FJN is an autosomal recessive hereditary disease. Because their patterns of inheritance differ, FJN and medullary cystic disease (MCD) are separate entities. We suggest simplification of the nomenclature to: medullary cystic disease of childhood type, formerly FJN and medullary cystic disease of adult type, formerly MCD.


The effect of an angiotensin antagonist (saralasin) on arterial pressure and plasma aldosterone in hemodialysis-resistant hypertensive patients. The effect of an angiotensin II antagonist (saralasin) on arterial pressure, plasma renin activity (PRA) and plasma aldosterone concentration (PAC) was assessed in seven dialysis-resistant hypertensive patients. During saralasin infusion performed before hemodialysis, mean arterial pressure fell by 8 to 18.3% in six out of the seven subjects; arterial pressure was normalized in three of them. After hemodialysis (6 subjects), a normal arterial pressure was achieved in five patients. One patient was resistant to saralasin before and after dialysis. A negative correlation (r = 0.62) was obtained between pre-infusion PRA and the change in mean arterial pressure induced by saralasin. Post-infusion PRA increased in saralasin responsive patients, the change in PRA being correlated (r = 0.82) with the pre-infusion PRA. Plasma aldosterone concentration was variably affected by saralasin; a negative correlation between pre-infusion PAC and the absolute change in PAC during saralasin was obtained (r = 0.72). The role of angiotensin II in the maintenance of a high arterial pressure in chronic dialysis patients was demonstrated. In saralasin-resistant patients, more vigorous ultrafiltration is proposed.


Glomerulonephritis associated with Hemophilus aphrophilus endocarditis. A 65 year old man developed endocarditis and septicemia due to Hemophilus aphrophilus, a Gram-negative coccobacillus. Renal rather than cardiac failure was the principal feature of his illness and renal biopsy was compatible with glomerulonephritis secondary to septicemia. Rapid recovery of renal function and improvement of the glomerular lesion followed antibiotic treatment of the septicemia. This case illustrates the renal damage that can occur in association with septicemia due to rarer infectious agents. As with more common organisms, specific antimicrobial therapy leads to rapid improvement of the nephropathy.


Cholic acid and the heart: in vitro studies of the effect on heart rate and myocardial contractility in the rat. 1. Cholic acid has a dose-dependent negative chronotropic effect on isolated atria of Wistar rats. 2. The positive inotropic effect of cholic acid is the result of a negative chronotropic effect and can be eliminated by electrical pacing. 3. Cholic acid does not appear to exert its negative chronotropic effect through cholinoceptors and alterations in bath concentrations of calcium and potassium does not influence this effect significantly. 4. Cholic acid is a functional antagonist of isoprenaline. 5. It is suggested that cholic acid exerts its negative chronotropic effect by forming a monolayer on the surface of the cell membrane, thereby mechanically interfering with membrane function.


The effects of amphotericin B therapy on the intrarenal vasculature and renal tubules in man. A study of biopsies by light, electron and immunofluorescence microscopy. Renal morphology was studied by light and electron microscopy in 10 patients after 25 mg/kg body weight of amphotericin B as part of a controlled study designed to evaluate the possible protective effects of mannitol against the nephrotoxicity of amphotericin B. Five patients received amphotericin B 1 mg/kg body weight every other day and five received amphotericin B and mannitol 1 g/kg body weight in the infusion. Small arterial and arteriolar changes were present in all biopsies and were characterized by focal vacuolization of medial smooth muscle cells. Electron microscopy suggested formation of these vacuoles by fusion of dilated endoplasmic reticulum. A few small vacuoles were also seen in renal biopsies of age matched patients who did not receive amphotericin B. Vacuoles in biopsies of the amphotericin treated patients were considerably larger (P less than 0.001) and much more numerous (P less than 0.001) than in controls. It is hypothesized that the vacuoles in the amphotericin B treated group represent the morphologic effect of intrarenal vasoconstriction caused by amphotericin B therapy. Nephrocalcinosis was observed in all biopsies and appeared to originate by precipitation of calcium salts in tubular casts.


Modification of brain biogenic amines by met5-enkephalin amide in the rat. 1. Gross changes in behaviour and whole brain levels of noradrenaline, dopamine, serotonin and 5-hydroxyindoleacetic acid were examined in rats for 3 min following intracerebral injections of met5-enkephalin amide or morphine. 2. Both the enkephalin and morphine depressed respiration and induced a cataleptic-like state, but only the enkephalin produced wet-shake responses. 3. All doses of met5-enkephalin amide (150,200 and 600 microgram) and morphine (134 and 200 microgram) increased the brain levels of 5-hydroxyindoleacetic acid, whereas only the large doses modified the levels of noradrenaline and serotonin. 4. The similarity of the effects of these two compounds indicates that morphine may act through an enkephalin-like mechanism.


Simultaneous hemofiltration/hemodialysis: an effective alternative to hemofiltration and conventional hemodialysis in the treatment of uremic patients. Hemofiltration and hemodialysis were performed simultaneously with the Polyacrylnitrile membrane in a single pass dialyzate flow system. Due to the combination of convective mass transfer and diffusion, the clearances of both small and large molecules were significantly higher than during hemofiltration or hemodialysis alone. The removal of excess water was better tolerated than during hemodialysis. Six patients have been treated by this technique for 6 months 3 X 3 hr/week without side effects, and the new procedure appears to be the method of choice to shorten dialysis time.


Concentration of guanidines in normal human plasma. 1. The concentration of methylguanidine and guanidinosuccinic acid has been measured in normal human plasma and discrepancies between various published methods for measuring methylguanidine have been resolved. Previous methods have been modified to allow these guanidines, together with guanidinoacetic acid and creatine, to be measured on the same serum sample. 2. Mean values in six normal subjects were as follows: methylguanidine 1.62 mumol/1 (s.d. = 1.3); guanidinosuccinic acid 0.66 mumol/1 (s.d. = 0.22); guanidinoacetic acid 7.06 mumol/1 (s.d. = 1.29); creatine 80.9 mumol/1 (s.d. = 37.9).


Intrarenal mechanism for renal vasoconstriction resulting from stimulation of the ureter in the dog. 1. The mechanism responsible for ipsilateral renal vasoconstriction resulting from mechanical stimulation of the ureter was examined using the pharmacological antagonists saralasin, SQ20881, indomethacin, atropine and phentolamine. 2. A segment of PE tubing was implanted in the left ureter, patency being well maintained. Three to four days later renal blood flow was measured bilaterally and antagonists administered intravenously. 3. The mechanism responsible for vasoconstriction could not be attributed to either increased intrarenal noradrenaline or angiotensin, nor to a decreased activity of prostaglandins, kinins or acetylcholine. 4. Histological and bacteriological examination also proved negative. 5. Thus, additional evidence of an unidentified intrarenal mechanism causing vasoconstriction is presented.


Shunt nephritis.

Shunt nephritis. A case of nephritis occurring in a 40-year old patient with a ventriculojugular shung infected with staphylococcus albus is described. Circulating antistaphylococcal antibodies could be demonstrated. Renal manifestations disappeared after treatment with systemic antibiotics and surgical removal of the shunt.


Scintigraphy in the diagnosis of osteonecrosis. Scintigraphy, using 99mTc diphosphonate, has the potential for diagnosing osteonecrosis before irreversible changes are visible in routine roentgenograms. If obtained within weeks of an avascular insult, a cold area will appear on scintiscan. However, months later, the revascularization and reparative processes of the dead bone produce a hot area on scintiscan.


Alcoholism associated ischemic necrosis of the femoral head. Early diagnosis and treatment. Thirty-eight hips in 26 patients with alcoholism associated ischemic necrosis of the femoral head (INFH) have been evaluated by measurement of intraosseous pressure, (IOP) pressure response to a 5 ml saline load injected intraosseously and intraosseous venography. All stages of INFH were characterized by elevated IOP and/or an increased pressure response to the saline load compared to normal controls. Intraosseous venography in INFH was characterized by poor or absent visualization of the main efferent veins draining the proximal femur, diaphyseal reflux and delayed evacuation of dye from the bone. It has been possible to identify both a preradiologic and even preclinical stage of INFH. Core decompression, the removal of an 11 mm plug of bone from the head and neck of the femur, has been carried out on all hips in the study. All patients had pain prior to surgery. Eight patients in Stage I (preradiologic stage) are symptom free and without radiologic progression at follow-up, average 24 months. Only one of 5 patients in Stage II (no collapse of the femoral head) has shown X-ray progression while all remain asymptomatic. In Stage III (collapse, without acetabular involvement), core decompression offers relief of symptoms but does not appear to prevent further head collapse.


Radiographic findings in commercial divers. The primary method of detecting and recording the changes of dysbaric osteonecrosis is bone and joint radiographic survey. This is not the routine medical and orthopedic roentgen technique, but is a special purpose examination with special technical requirements. The findings indicate selective sites of damage and each should have meticulous study. Fine detail and heavily penetrated radiographs produce needed bony, especially trabecular, and detail and allow the film reviewers to exlude simulating lesions. The incidence of osteonecrosis in American commercial divers has been found to be quite low and considerably less than in other types of compressed gas workers and shell divers. The major radiographic observation is an area of sclerosis, but other changes occur. Juxta-articular lesions can lead to joint damage and are, therefore,  potentially disabling. The immediate significance of a lesion in the shaft of a long bone is in its value as a basis for disqualification of an individual for further work in dysbaric environments.


Orthopedic aspects of sickle cell anemia and allied hemoglobinopathies. The study of 23 cases of hemoglobinopathies in Nigeria using electrophoresis, showed that 16 cases were HB-SS, 5 cases HB-SC, and 2 cases HB-S Th. There were infarcts of long bones, which were usually multiple in the diaphyses in 17 cases, septic arthritis of big joints in 4 patients and aseptic necrosis of the hip in one, and in the hip and knee in one. Infection was proved by culture in only the 4 joints and 7 of the affected long bones, 8 of the causative organisms were Salmonella and 3 were Staphylococci. Only 2 of the infected cases needed sequestrectomy and the other 9 responded to simpler methods like aspiration and incision of abscess U.L.A. without resulting in a sinus formation. The aseptic necrosis in the hip may simulate Perthe's disease and dysbaric osteonecrosis, the massive periosteal reaction may simulate Caffey's disease and hypervitaminosis A, and give rise to difficulties in diagnosis when hemoglobinopathies are not suspected.


Transtrochanteric anterior rotational osteotomy of the femoral head in the treatment of osteonecrosis affecting the hip: a new osteotomy operation. "Transtrochanteric anterior rotational osteotomy of the femoral head" is a new approach to the treatment of idiopathic avascular necrosis of the femoral head. The results of 41 hips with a follow-up suggest that the procedure prevents the progression of the collapse of the femoral head and preserves joint surfaces. Cases with extensive lesions and with bilateral involvement require long-term follow-up investigations in a large series of cases. This method does not preclude prosthetic replacement at a later date. The method is also applicable to the treatment of slipped capital femoral epiphysis, partial defects of the femoral head in weight-bearing area due to trauma and tumor and osteoarthritis of the hip with localized changes in weight-bearing area.


Management of osteonecrosis in sickle-cell anemia and its genetic variants. Osteonecrosis secondary to sickling disorders differs from most other forms of osteonecrosis, because vaso-occlusive episodes generally involve many other organs. For this reason optimum management and care of these patients requires a team approach. The spectrum of clinical symptoms and bone involvement varies widely from one patient to another, even among patients with the same abnormal hemoglobin patterns. Although the efficacy of conservative therapeutic measures has not been definitely established, these may be all that can be offered because of the patient's other problems. Before contemplating surgery, the surgical and anesthetic risks should be evaluated and measures taken to prevent complications. The varus osteotomy, Chiari pelvic osteotomy, prosthetic or total hip replacement, and the Neer shoulder prosthesis may benefit a limited number of carefully selected patients.


The forgotten popliteus muscle. Its usefulness in correction of anteromedial rotatory instability of the knee. A preliminary report. The popliteus muscle is an important factor in stability of the knee. Advancement of the popliteus muscle and tendon complex was useful for surgical correction of anterior and anteromedial instability in 8 cases.


Chondrocalcinosis following osteochondritis dissecans in the femur condyles. Chondrocalcinosis, defined as radiopaque deposits in the joint cartilages and in semilunar cartilages of the knee joint, develops frequently in patients in whom osteochondritis dissecans is diagnosed after the epiphyseal line of the distal end of the femur is closed. Chondrocalcinosis occurred in 2/3 of the cases surgically treated for osteochondritis. The incidence was greater than in knees treated by arthrotomy for ruptured semilunar cartilages. However, the latter show chondrocalcinosis much more frequently in patients without history of injury or arthrotomy. Osteochondritis patients with chondrocalcinosis more often may have joint effusion than patients with other conditions. The chondrocalcinosis is not confined to that part of the joint which was the site of the osteochondritis lesion. The presence of chondrocalcinosis can be correlated with a poor prognosis of the knee including severe gonarthrosis.


Body type and rotational laxity of the knee. Forty young adult males were somatotyped according to the Health-Carter Modified Method and were separated into 2 groups. One group was a meso-endomorphic body type (5-6-1) and the other was ectomorphic body type (3-2-4). Measurement of rotational laxity of the knee in 90 degrees flexion showed a statistically significant increase (p less than .001) in external rotation and total rotation in ectomorphs compared to meso-endomorphs. Rotational laxity of the knee is associated with body type. Lateral radiographs were used to measure patellae alta in each group. No statistical difference was found, and patellae alta does not appear to be associated with body type.


A theoretical analysis of cast wedging with practical applications. Cast wedging using vector and geometrical analysis demonstrated that the open wedge produces distraction of the fracture, the closing wedge shortening, and that the opening--closing wedge can perfectly correct skeletal deformity. The level of wedging should lie at the axis intersection, i.e., at the intersection of the long axes of the 2 major fracture fragments. An open wedge at the axis intersection is recommended for tibial shaft fractures immobilized with long leg casts; an opening--closing wedge at the axis intersection, for fractures immobilized with "pins and plaster".


Computed tomography of orthopedic tumors of the pelvis and lower extremities. An analysis of 6 representative cases of tumors of the pelvis and lower extremities demonstrates the clinical usefulness of computerized tomography (CT) in preoperative evaluation. CT provides information regarding precise size of the mass, its location and relationship to muscle bundles and fascial planes, definition of the margins of the mass, relation to neural, vascular and bony structures not previously available by plain film and angiography. This information is of particular value to the orthopedic surgeon in evaluating the feasibility of en bloc resections of tumors and in planning reconstructive procedures.


Persistence or recurrence of pain: a sign of surgical failure is osteoid-osteoma. Excision of an osteoid-osteoma brings prompt and permanent relief from symptoms. Recurrence of pain indicates persistence or failure to totally remove the nidus (9 of 73 patients), and only rarely a true recurrence. Long symptom-free intervals may follow partial excision of the lesion.


Intracortical and subperiosteal lesion of unknown etiology. A painful intracortical and subperiosteal lesion of the fibula with a 14 year follow-up is reported to regress to a painfree state. Infection is favored in the differential diagnosis. Biopsy with histological and radiographical correlation are essential for exclusion of: osteoid osteoma, osteoblastoma, periostitis, glomus tumor, eosinophilic granuloma, enostosis, hemangioma of bone, giant cell tumor, simple cyst, aneurysmal bone cyst, non-ossifying fibroma, polyostotic fibrous dysplasia, hyperparathyroidism, Paget's disease, localized area of avascular necrosis, stress fracture and even metastatic disease.


Traumatic hip dislocation with ipsilateral femoral shaft fractures. A traumatic dislocation of the hip joint associated with an ipsilateral femoral shaft fracture is a rare injury resulting from severe trauma. Initially the dislocated hip joint is often unrecognized and consequently reduction is delayed. Early diagnosis and reduction of the hip joint improves the functional prognosis. The maximum functional recovery is possible only with greater awareness of this combined injury. Examination of the hip joints by clinical roentgenography in the critically injured patient, especially those with head injuries, or physical signs masked by extremity swelling, should be a routine procedure.


An electron microscopic study of the origin of osteoblasts in implants of demineralized bone matrix. Correlated light microscope and ultrastructural observations of allogeneic intramuscular implants of rat demineralized bone matrix demonstrate the interrelationships between various osteogenetic and non-osteogenetic cell types and suggest that the bone morphogenetic response is evoked from cells of a common origin. Endothelial cells may play a prominent, essential, as well as primary role in the bone morphogenetic response.


Biomechanics and comparison of two operative methods of treatment of complete acromioclavicular separation. Sixty-three complete acromioclavicular separations were treated by 2 operative methods. Acromioclavicular wiring gave 73% acceptable results while wire or Dacron coracoclavicular loop gave 94% acceptable results. Complications, especially broken, bent, or backed-out wires were common with acromioclavicular wiring. Of 44 patients treated by acromioclavicular wiring, 5 required late distal clavicle resection and 4 of these had retained menisci. Loop fixation is mechanically superior since the loop is in the direction of the tensile forces. In acromioclavicular wiring, however, the fixation Kirschner wires are subjected to high bending moments. Loop fixation avoids violation of the acromioclavicular joint but does not restrict rotation of the clavicle. The operation is simple to perform and postoperative immobilization is minimal. Woven Dacron may be superior to surgical wire for loop fixation in that unlike wire it does not require removal by a second operation. Woven Dacron may also stimulate coracoclavicular ligament reconstitution.


Microradioscopic quantitation of periosteal resorption in secondary hyperparathyroidism of chronic renal failure. The feasibility of expressing periosteal resorption (PR) in hand bones quantitatively as a measure of skeletal involvement of hyperparathyroidism, was tested by measuring the length of surface irregularities in medial and lateral surfaces of the middle phlanges of digits II--IV in one hand. Measurements were made to 0.1 mm by microradioscopy of fine detail radiographs using a X 6 measuring magnifier. Randomly numbered unidentified radiographs from 60 normal subjects and 61 chronic renal failure patients were measured by Reader 1 twice at 4 weeks interval and by Reader 2 once. There was no significant systematic difference between the readers, or for Reader 1 over the 4 weeks interval. The intraobserver precision was estimated to be +/- 3.8 mm. Relative to the normal ranges (0--9 mm, mean 2.54) such precision is sufficient for diagnostic purposes and for comparison of groups. Diagnostically, this method was found to be more sensitive than the currently used gradient of PR (0 to 3+): definite abnormalities were detected in 30 of 61 patients by quantitative microradioscopy, and in 22 by the grading method. A further advantage is that the numerical expression is better suited for statistical analysis of data than the results by grading.


Epidemiology of traumatic and nontraumatic osteonecrosis. In reviewing the epidemiology of traumatic and nontraumatic osteonecrosis the only common denominator appears to be that of circulatory compromise. Causative mechanisms seem to be quite distinct. A number of factors may predispose to postfracture hip necrosis, i.e. the type of fracture, the quality of reduction and union of the fracture. For postdislocation necrosis, causative factors include the type of dislocation as well as the timing and nature of the reduction. For nontraumatic osteonecrosis, an array of consistently associated systemic disorders appears to be largely linked by frequent lipid elevations. Alcoholism and corticosteroid use account for the bulk of cases and there is consistent predisposition to males and bilateral involvement. Multifocal lesions attest to the systemic basis for this form of necrosis.


Effect of vitamin D in fluoride-treated rats. Fluoridated drinking water (30 mg and 100 mg F per liter) was used to induce rachitic changes in rats fed a vitamin D free diet containing calcium and phosphorus in a ratio of 1 : 1. Supplements of vitamin D3 (70 IU of cholecalciferol per week) completely prevented the rachitogenic effects of fluoride. This protective effect occurred despite evidence that vitamin D enhanced the intestinal absorption of fluoride.


Epiphyseal transplant in amputations. Effects on overgrowth in a rabbit model. Bony overgrowth of the stump is a recognized complication of amputated limbs in children. Transplantation of an epiphysis inhibits bony overgrowth in rabbits. The mechanism of inhibition as well as its applicability to other species warrants further investigation.


The role of fat embolism in the etiology of corticosteroid-induced avascular necrosis: clinical and experimental results. Case reports since 1957 implicate corticosteroids in excess of physiologic requirements as a cause of nontraumatic osteonecrosis. Both laboratory and clinical studies demonstrate marked alterations in lipid metabolism with hyperlipemia, fatty liver and systemic fat embolism. Intra-arterial infusion of fat produces embolic vascular obstruction, focal marrow necrosis and osteocytic death in the femoral head of the rabbit. Induced hypercortisonism in rabbits produces severe hyperlipemia, fatty liver, systemic fat emboli, terminal vascular obstruction in bone and associated areas of osteocytic death representing avascular necrosis. Osteoporosis develops without fracture. Histologic evidence of vasculitis, thrombosis, or microfracture is lacking. The specific biochemical pathway of corticosteroid lipid alterations is unknown.


Cortisone induced bone changes and its response to lipid clearing agents. Thirty-two rabbits were used experimentally to study the effect of cortisone in bone, lungs, kidneys, and liver. Cortisone does induce abnormal increases in the serum cholesterol, fatty metamorphosis of the liver and the fatty emboli of the subchondral vessels of the femoral heads. Clofibrate therapy appeared to modify the cortisone induced changes as evidenced by a lower serum cholesterol level, prevention or lessening of the increase in the marrow fat cell size. This might significantly improve microcirculation of the femoral head.


Suppression of renal excretion of digoxin in hypokalemic patients. Inulin and digoxin clearances were simultaneously measured in 19 normokalemic and 4 hypokalemic patients. In normokalemia the renal digoxin clearance exceeded the inulin clearance, indicating both glomerular filtration and active tubular secretion of digoxin. The tubular secretion increased with increasing plasma digoxin concentration. In hypokalemia, however, the tubular secretion of digoxin was significantly reduced but increased after the plasma potassium level was raised to normal.


Experience with steroid-induced avascular necrosis of the shoulder and etiologic considerations regarding osteonecrosis of the hip. Nineteen of 97 patients with steroid-induced osteonecrosis had a lesion involving the head of the humerus, on one or both sides. The lesion usually began as a subchondral osteolytic area which often progresses to collapse. Articular cartilage separated from subchondral bone, either becoming detached as a free cap or at a later stage reattaching. Present evidence suggests that osteonecrosis of the femoral or humeral head should  properly be classified as either traumatic (macrovascular injury) or embolic (microvascular injury) in nature. In 14 patients conservative treatment resulted in satisfactory function with only intermittent symptoms, and including pendulum exercises and avoidance of abduction, particularly against resistance. Five patients required replacement of 6 humeral head replacement arthroplasties with Neer's prosthesis.


Dysbaric osteonecrosis. Etiological and pathogenetic concepts. Dysbaric osteonecrosis appears to be independent of decompression sickness. The 2 conditions, however, may share etiologic and pathogenetic factors. The incidence of osteonecrosis is influenced by the number of hyperbaric exposures, extent of pressure, decompression profile and possibly by the rate of compression and degree of obesity. Though etiology and pathogenesis are unclear, osteonecrosis is probably due to ischemia, with gas bubbles causing direct or indirect circulatory impairment. In vitro experiments, as well as human and animal studies, suggest multiple pathogenetic mechanisms: intraosseous vessel compression by extravascular bubbles; vessel obstruction by bubbles, fibrin thrombi, platelet aggregates, clumped erythrocytes or coalesced lipids; and narrowing of arterial lumina by bubble-induced myointimal thickening. Obstructing materials, whether autochthonous or embolic, may result from blood-bubble interface reactions. Rheologic changes and blood flow redistribution could play contributing roles. It seems likely that multiple pathogenetic factors act in concert or sequentially. Proposed nonischemic changes, such as hyperoxic injury gas-induced osmosis, or autoimmunity, lack sufficient supporting evidence. The peculiar vulnerability of bone may be related to gas supersaturation of the fatty marrow; sensitivity to extravascular gas pressure because of tissue rigidity; poor vascularization; and the presence of uranium 238 which promotes nucleation and subsequent gas bubble formation.


Urinary excretion of beta-aminopropionitrile and cyanoacetic acid. Human serum did not convert beta-aminopropionitrile (BAPN) to the deaminated, nonlathyrogenic metabolite, cyanoacetic acid (CAA). Instead, its enzymic activity for oxidizing benzylamine was inhibited by BAPN (I50 = 2 X 10(-3) M). BAPN was found in the urine within one hour of oral administration. Oral 250 mg BAPN at 6-hr intervals each day for 21 days resulted in urinary BAPN recoveries approximating 16% of the total dose. BAPN was not detected in urine in specimens collected later than 7 hr after cessation of BAPN dosage. Urinary CAA appeared more slowly than BAPN and increased gradually to approximately three times that of urinary BAPN. After BAPN was discontinued, there was prolonged urinary excretion of BAPN-derived CAA. These along with earlier findings in experimental animals suggest that unexcreted BAPN is sequestered in tissues where it is metabolized to CAA before slowly released.


Absorption of oral intramuscular chlordiazepoxide by alcoholics. The effect of chronic alcoholism on oral and intramuscular plasma levels of chlordiazepoxide (CDX) was assessed. A 50-mg oral dose of CDX resulted in significantly higher plasma levels in the 2 hr following CDX than a 50-mg intramuscular dose administered to acute withdrawing alcoholic subjects. The same CDX dose was administered 7 days later and the same differences were observed between the mean oral and intramuscular plasma levels during the first 2 hr after administration of CDX. Peak concentration occurred significantly sooner after the oral than intramuscular dose of CDX in both the initial dose and the dose given a week later. It was also observed that the areas under the curve for CDX were significantly greater initially than 1 wk later. It is suggested this effect may be at least partially the result of the longer CDX half-lives initially than a week later. The active metabolite, N-desmethylchlordiazepoxide, peaked significantly earlier with the oral dose than with the intramuscular dose after the patient was alcohol free for a week.


Metabolism of cocaine in man.

Metabolism of cocaine in man. Following ingestion of [N-14CH3]cocaine (10 mg, 2.3 muCi) by 2 healthy subjects, breath, saliva, serum, and urine samples were collected serially. Labeled CO2 production was monitored as a measure of N-demethylation of cocaine. The cumulative excretion of 14CO2 in 5 hr was 2.4% and 6.2% of the administered dose with half-lives of 2.3 and 1.4 hr, respectively. The greater N-demethylation was found in a subject with lower plasma cholinesterase activity. Radioactivity excreted in 0 to 28 hr urine reached 65% to 75% of the dose. Ecgonine methyl ester, a product of cocaine hydrolysis by plasma cholinesterase, was identified as a major metabolite in the urine of both subjects and accounted for 32% to 49% of the urinary metabolites.


Doxepin kinetics.

Doxepin kinetics. The kinetics of doxepin (DOX) hydrochloride were studied in 7 volunteers after the oral administration of 75 mg. Peak plasma concentrations of DOX ranged from 8.8 to 45.8 ng/ml and were reached within 4 hr. The disappearance of DOX was biphasic and followed first-order kinetics. The mean DOX half life (t1/2) was 16.8 hr and in individuals ranged from 8.2 to 24.5 hr. The mean apparent volume of distribution was 20.2 L/kg and ranged from 9.1 to 33.3 L/kg. The estimated first-pass metabolism of DOX ranged from 55% to 87% of the oral dose assuming complete absorption. Significant quantities of the metabolite desmethyldoxepin (DMD) were produced. Peak levels of DMD ranged from 4.8 to 14.5 ng/ml and were reached between 2 and 10 hr after administration. The mean t1/2 of DMD was 51.3 hr and in individuals ranged from 33.2 to 80.7 hr. There was no correlation between the DOX and DMD t1/2s. The amount of DMD produced correlated with the plasma concentration of DOX and appears to explain the correlation between the steady-state concentrations of DOX and DMD in patients given DOX.


Protriptyline kinetics.

Protriptyline kinetics. The kinetics of protriptyline were examined in 8 subjects after a single oral dose of 30 mg protriptyline hydrochloride. Peak protriptyline levels ranged from 10.4 to 22.3 ng/ml and were reached 6 to 12 hr after the oral dose. The mean protriptyline half-life (t1/2) was 74.3 hr and ranged from 53.6 to 91.7 hr in individual subjects, confirming the long t1/2 of protriptyline reported by Moody and associates. The estimated first-pass metabolism of protriptyline was relatively small, ranging from 10% to 25% of the oral dose, assuming complete absorption. The mean volume of distribution was 22.5 L/kg and ranged from 15.0 to 31.2 L/kg. No relationship was found between the kinetics of protriptyline and those of doxepin studied previously in 7 of the 8 subjects.


Kinetics of netilmicin and gentamicin.

Kinetics of netilmicin and gentamicin. The kinetic parameters of netilmicin were studied in normal human subjects. In the intravenous study a steady-state was obtained in 4 subjects by the constant infusion of 2 mg/kg of netilmicin during the first hour followed by 0.5 mg/kg/hr for each of three successive hours. Creatinine clearance was greater than the simultaneous serum and renal clearance of netilmicin. In the intramuscular study 6 subjects received a single injection of 1 mg/kg of netilmicin followed by the same dose of gentamicin 1 wk later. A mean peak serum levels of 3.9 microgram/ml was found for both antibiotics, but the mean serum half-life of netilmicin was shorter than that of gentamicin. Doubling the intramuscular dose of netilmicin approximately doubled the peak serum level. In both studies 75% to 90% of the netilmicin was recovered in the urine within the first 24 hr. Netilmicin appears to be primarily excreted by glomerular filtration. The apparent volume of distribution was similar to that reported for other related aminoglycosides. Netilmicin and gentamicin have similar kinetic parameters. There were wide individual differences among normal subjects with both drugs.


Allopurinol kinetics.

Allopurinol kinetics. A spectrophotometric assay for measuring allopurinol and oxipurinol has been developed which can detect as little as 5 X 10(-8) M of each in serum and urine. With this assay, serum disappearance characteristics of intravenous and orally administered allopurinol have been investigated in man. Serum concentrations of both allopurinol and oxipurinol reach levels above 1 X 10(-5) M within minutes of intravenous administration and within 1 or 2 hr of oral administration of 300 mg allopurinol. Patients receiving 300 mg allopurinol daily show a mean serum concentration of 3 X 10(-5) M oxipurinol (range, 0.9 to 9 X 10(-5) M). Serum half-lives of allopurinol and oxipurinol were 39 +/- 11 min and 13.6 +/- 2.8 hr, respectively. Estimates of renal clearance were 13.6 and 18.9 ml/min for allopurinol and 23.2 and 30.6 ml/min for oxipurinol in 2 patients studied. The metabolic conversion of allopurinol to oxipurinol in man does not appear to be altered by long-term therapy with allopurinol, which suggests that this conversion takes place by way of an enzymatic reaction not strongly inhibited by either substrate or product. These results suggest the possibility of a nonxanthine oxidase enzymatic pathway for this conversion.


Timolol kinetics in chronic renal insufficiency. A single-dose kinetic study of oral timolol, 20 mg, was undertaken in 3 groups of volunteers with varying degrees of renal function--(1) 10 normal subjects (N); (2) 9 patients with moderate chronic renal insufficiency (MCRI; C cr, 20 to 50 ml/min); (3) 4 patients with end-stage renal disease (ESRD)--to assess the need for dosage modification as renal function diminishes. There were borderline statistical differences in absorption between groups. The mean peak concentration (C max) was 84.3 +/- 44.8 ng/ml at 0.8 +/- 0.4 hr for N and 87.1 +/- 22.8 ng/ml at 1.7 +/- 1.2 hr (p, NS) for MCRI. N and MCRI mean half-lives (5.2 +/- 2.6 hr and 4.0 +/- 1.2 hr) were not statistically different. Salivary levels correlated with plasma levels in 3 N and 1 MCRI patient. Group differences in blood pressure and pulse response to timolol seems to reflect differences present at baseline with percent change from baseline identical for the two groups except at 12 to 24 hr. Administration of timolol on an interdialysis day revealed similar kinetic and physiologic response in the normal and the MCRI group. During dialysis, timolol, 20 mg, induced significant hypotension and bradycardia.


Complications of rhytidectomy.

Complications of rhytidectomy. A review of the more common and/or more serious complications which may follow rhytidectomy has been presented. The surgeon who performs face lift surgery must be aware of these complications, their incidence, their management, and, in many instances, how they can be prevented, as prevention is the best treatment for postrhytidectomy problems.


Blepharoplasty.

Blepharoplasty. In summary, the author has presented a brief historical review of the various operations under the general heading of blepharoplasty for the removal of redundant and "baggy" eyelid skin. The various conditions encountered which contribute to the aging eyelid and periocular area have been described as they relate to examination of the prospective candidate for this surgery. The need for individualizing the surgical procedure to correct the defects present has been stressed. The author's preoperative care, the surgical technique employed, and the postoperative treatment needs are discussed. Selected cases are presented as examples of the variety of conditions encountered and the methods of management.


Eyebrow, face, and neck lifts for males. Alternate locations to skin excisions adjacent to the eyebrows for correction of eyebrow ptosis have been presented. Excisions in the upper forehead or in the scalp permit flexibility in width and length of skin or scalp to be excised and may be extended laterally to produce a temporal lift which not only improves the lateral canthal area of sagging skin but also may improve the lower eyelid surgical correction results (Figs. 1 and 3). By use of adequate lipectomy and full-width platysma muscle flaps to support the new neck contour, better and longer lasting results have been accomplished. The currently used techniques for eyebrow, face, and neck lifts for males produce better and longer lasting results than could have been accomplished with previously used techniques. The continued search for improvement in techniques by many surgeons in different areas of the world has enabled these longer lasting and better results to be accomplished.


Complications in blepharoplasty.

Complications in blepharoplasty. I believe that if one follows the precautions outlined, including a time-tested surgical technique and thorough clinical history and physical examination, the operation of blepharoplasty should prove to be one of the most gratifying aesthetic operations.


The coronal incision in rhytidectomy--the brow lift. Rhytidectomy is not a routine procedure applicalbe to all patients. Variations of technique must be chosen for each individual case. Integral correction of the face is important and brow-lifting must often be done. Our criteria for selecting the coronal incision for the brow-lift are discussed and the surgical techniques are described in detail. Results are analyzed and a simple method for evaluation is presented.


Postoperative make-up techniques.

Postoperative make-up techniques. Guiding the postoperative patient to a happy self-acceptance is the common endeavor of the make-up artist and the cosmetic surgeon. It is my hope that this article will somehow help the patient bridge the gap which so many are unable to cross unassisted.


Chemical peel.

Chemical peel. Chemical face peeling as described in this article produces gross and microscopic changes in the skin which are permanent. The most important aspect in assuring the success of this procedure is the proper selection of patients. The primary use of this procedure is for the purpose of eliminating wrinkles, whether as the primary or ancillary procedure, such as regional peeling. Chemical peeling of the face is a valuable adjunct in the treatment of the aging face and can produce some rather dramatic results with the careful selection of patients and meticulous attention to detail in carrying out the peel, as well as the exact adherence to the post peel instructions by the patient.


Radiological evaluation of the cardiac apex in Jamaican children. The position of the clinical apex beat projected on chest radiographs was compared to different points on the cardiac outline which have been regarded as the radiological apex. Good correlation was found between the clinical apex and the most lateral point of the left cardiac border, but not with the cardiophrenic angle or the lower end of the long diameter of the heart. The mid-clavicular line cannot be used to define the upper limit of the normal sized heart on radiographs as in clinical practice, because in many of the subjects the heart extended outside the mid-clavicular line.


The hypertransradiant hemithorax: the importance of lateral decentring, and the explanation for its appearance due to rotation. Experimental evidence is presented indicating that 80% of the increase in unilateral film blackening on the chest radiograph resulting from rotation of the patient is due to asymmetrical absorption of the X-ray beam. Scatter contributes 20% to this increase in blackening. The effect on the radiograph of lateral decentring is also described. In the rotated patient, the hypertransradiant hemithorax always occurs on the side to which the patient is rotated, and is independent of the projection. If this rule is broken, then decentring or a thoracic abnormality is present.


Radiographic aspects of occult pulmonary haemorrhage. Patients with leukaemia, on anticoagulant therapy, or with disseminated intravascular coagulation may develop occult pulmonary haemorrhage; it will mimic pulmonary oedema, pulmonary hemosiderosis or opportunistic infections. It can be diagnosed by bronchopulmonary lavage. The radiographic changes are described and the differential diagnosis discussed in a series of 12 such patients.


The radiological appearances of plasma cell granuloma of the lung. The clinical, radiological and pathological features of plasma cell granuloma in 4 patients are presented. The natural history of the condition is benign. 30% of cases occur in children. The radiological appearances are not specific and consist of an intrapulmonary mass which is not accompanied by pleural effusion. Tomography is helpful in demonstrating calcification and cavitation, but these features are unusual. Successful treatment requires surgical removal.


Traumatic lung cysts following minor blunt chest trauma. Relatively minor chest trauma may cause lung cysts. The authors illustrate two patients in whom lung cysts were seen on chest radiographs taken within hours of injury. The condition may thus mimic rupture of the diaphragm with herniation of the bowel.


Inspiration chest radiography by lateral recumbency. In lateral recumbency the uppermost lung is in a state of relative inspiratory apnoae. This physiological phenomenon may be exploited to obtain inspiratory chest films in children and uncooperative adults and as an improvement on the sitting film of patients unable to stand. It also tests to some extent the pulmonary compliance and the mobility of the diaphragm.


CT scanning in middle fossa arachnoid malformations. The typical appearances of middle foss arachnoid malformations as seen by computed tomography, are presented in six cases out of 3700 unselected CT scans performed in the last two years. These lesions have well-defined borders, the anterior border often conforming to the configuration of the greater sphenoid wing, and the posterior border merging into the Sylvian fissure medially. They exhibit the same attenuation coefficients as cerebrospinal fluid (CSF), in the range of 0 to +8 EMI units. Their size is variable. They produce less mass effect than might be expected, even when their size is considerable. Their appearance does not change after infusion of contrast material. Although arachnoid malformations occur in many intracranial sites, the site of predilection appears to be the middle cranial fossa. The clinical presentation and subsequent management of the six cases is briefly described. The pathogenesis and common clincial presentation associated with these lesions is discussed.


Ultrasonic examination of the gallbladder: a review. Ultrasonography is a helpful, non-invasive, and relatively inexpensive adjuvant to oral cholecystography for evaluating the gallbladder and its diseases. This method can be highly accurate in detecting gallstones and is specially useful when there is non-visualisation in radiographic contrast studies. Various ultrasound patterns of gallstones are described. All these patterns should demonstrate a sonic shadow in association with an intraluminal defect. Sonography is particularly useful in demonstrating cholelithiasis and organ dilatation in suspected acute cholecystitis. In addition to gallbladder disease, this technique simultaneously offers pertinent anatomical information about the porta hepatis. This information would otherwise require additional diagnostic investigation. Because, in many instances, sonography is non-specific, or blind to certain gallbladder non-calculous filling defects, and because of present lack of uniform standard quality control methods for performing this procedure, it should be considered only as a complementary, imaging procedure to oral cholecystography.


The retrorectal space.

The retrorectal space. Ninety-nine adults with an enlarged retrorectal space on barium enema examination have been evaluated. Measurements were based on previously described methods using the lateral view of the barium filled rectum. In 38.4% of the cases there was no lesion (normal variations). The rest were classified as inflammatory conditions, tumours, and miscellaneous lesions. It is concluded that an increased width of the presacral space per se does not necessarily connote a lesion. Pathological widening of the space is usually associated with changes of the contour of the rectum, abnormalities of the sacrum, or other alterations of the presacral soft tissues.


The radiological assessment of gastric acid output in chronic renal failure. The presence of hypertrophied gastric and duodenal mucosa as seen in the barium meal examination has been widely accepted as indicating an increase in gastric acid content. The present study of 31 uraemic patients undergoing maintenance haemodialysis suggests that in the uraemic patient this is not the case. Nineteen showed hypertrophy of the gastric mucosa radiologically but only eight had an abnormal pattern of gastric secretion. Of the 12 patients with a normal gastric and duodenal mucosal pattern, four showed an increase in the acid output of the stomach. It is concluded that the radiologist should beware of equating hypertrophy of the gastric and duodenal mucosa with a high gastric acid output in the chronically uraemic patient.


Gastrointestinal tract tuberculosis: a study of 102 cases including 55 hemicolectomies. Tuberculosis continues to be a major health problem in India. Our experience of 102 cases of gastrointestinal tract tuberculosis is presented. Eighty-one of these patients experienced obstructive symptoms, 62 had radiographic evidence of intestinal obstruction, and four had bowel perforation. Lymphadenopathy was present in 16 patients and pulmonary tuberculosis in 28. The commonest sites of bowel involvement were ileo-caecal, ileum and ascending colon. Duodenal lesions were seen in three cases and in another three there was isolated appendicular involvement. Right hemicolectomy was necessary in 55 of the 74 patients who had surgical exploration. Histopathological reports were available in 88 subjects. The various radiographic manifestations of tuberculosis of the bowel are discussed. Radiologically and sometimes even on histopathology, differentiation of ileo-caecal tuberculosis from Crohn's ileo-colitis may prove impossible.


The double contrast barium enema: improvements to lateral decubitus views including the use of a wedge filter. The prognostic importance of early detection of colonic carcinoma is emphasised and the contribution of an accurate barium enema technique is stressed. Horizontal beam lateral decubitus films are routine in double contrast barium enemas, and it is still common practice in many departments to support the cassette for these views either in the bucky tray or with sandbags. The lateral decubitus views of 100 patients using these methods of cassette support were reviewed. A large number of the films (67%) were technically so unsatisfactory due to unilateral under- or over-penetration that they did not provide acceptable visualisation of the colon. The cause of these technical faults, and the methods by which they may be overcome, are described. In addition, a wedge filter was designed to reduce the absorption by dependent soft tissues in obese patients.


The reasons for failure of endoscopic retrograde cholangio-pancreatography in patients with jaundice. The results of 100 attempts at endoscopic retrograde cholangio-pancreatography (ERCP) performed in patients with jaundice have been reviewed. The examination provided a diagnosis in 75% of cases. The reason for failure to cannulate the correct duct was obstruction at the lower end of the common bile duct in 15 patients and distortion of the duodenum in seven. There was no cause for the failure in only two patients. Even with a perfect technique it will not always be possible to obtain an endoscopic cholangiogram. However, as the commonest cause of failure is obstruction, transhepatic cholangiography should usually succeed when ERCP fails.


Duplication of the colon.

Duplication of the colon. Colonic duplication is a rare congenital abnormality that can present diagnostic difficulties to the radiologist. Three new cases are reported to illustrate the different types of this anomaly. A classification is presented in which the condition is divided into two types: in type I lesions the duplication is limited to the colon and in type II lesions there are associated duplications of the genito-urinary tract. The wide spectrum of possible pathological, clinical and radiological features are reviewed.


The radiology of ileosigmoid knot.

The radiology of ileosigmoid knot. The findings on the radiographs of 14 cases of ileosigmoid knot are presented and analysed. The clinical features and pathology of the condition are briefly described. The key radiological features consist of a dilated loop of pelvic colon, evidence of small intestinal obstruction and retention of faeces in an undistended proximal colon. The dilated loop usually lies in the right side of the abdomen and the limbs taper inferiorly into the right lower quadrant. Medial deviation of the distal descending colon is an inconsistant but highly specific finding. The radiographs readily permit distinction from primary volvulus of the small intestine and from non-obstructive surgical emergencies such as perforated viscus and ruptured ectopic pregnancy. The combination of radiographic findings may however be simulated by volvulus of the right colon, closed loop small intestinal obstruction and by volvulus of the pelvic colon complicated by peritonitis. The differential diagnosis is discussed and the value of sigmoidoscopy, rather than barium enema, emphasised.


Symptomatic gastrointestinal metastases secondary to bronchogenic carcinoma. Gastrointestinal metastases secondary to bronchogenic carcinoma are relatively uncommon and most are found incidentally at autopsy examination in patients with advanced or widely disseminated lung cancer. Occasionally gastrointestinal metastases occurr relatively early in the course of the disease and give rise to a variety of clinical symptoms and radiological abnormalities. Recognition of these abnormalities is important in order that appropriate palliative therapy may be undertaken. The clinical. radiological and pathological findings in 12 patients with symptomatic gastrointestinal metastases secondary to bronchogenic carcinoma were reviewed. Clinical symptoms varied according to the site of metastatic involvement and included dysphagia, epigastric pain, nausea, vomiting, gastrointestinal bleeding, anaemia and signs of intestinal obstruction or perforation. The sites of metastatic involvement were: oesphagogastric junction (2 cases); stomach (2 cases); duodenum (1 case): jejunum (3 cases); ileum (2 cases), colon (2 cases). The radiological findings are discussed and illustrated.


Residual Patopaque in renal cysts: an addition to the differential diagnosis of intra-abdominal heavy-metal densities. Single or multiple heave-metal densities seen on abdominal radiographs give rise to several diagnostic possibilities. These include pills or foreign bodies in the gastrointestinal tract, barium in colonic diverticula, and bullets or shrapnel. This communication describes two patients in whom heave-metal densities observed on abdominal radiographs were caused by residual Pantopaque from prior renal cyst puncture.


Parathyroid hormone-like biological activity in urine. 1. The parathyroid hormone-like biological activity of concentrated urine was measured by the increase of plasma calcium concentration after intravenous injection of the sample into chickens. 2. Urine was tested in hypoparathyroid patients, normal volunteer subjects, primary hyperparathyroid patients before and after surgery and patients with secondary hyperparathyroidism. 3. In primary and secondary hyperparathyroidism the biological activity was significantly higher than in urine from normal subjects, which was in turn significantly higher than the activity in the urine of hypoparathyroid patients. This bioactivity diminished after surgical removal of a hyperparathyroid adenoma. 4. Decreased activity after trypsinization indicated the peptidic nature of the hypercalcaemic substance.


The occurrence of folate-derived pteridines in rat liver. 1. It has previously been shown that folate polyglutamates in the rat are catabolized almost exclusively via cleavage of the C-9--N-10 bond, resulting in the formation of pteridines and p-aminobenzoylglutamate. The latter catabolite is rapidly excreted, appearing in the urine as acetamidobenzoylglutamate and is undetectable in rat liver. 2. The pteridines catabolites on the other hand are retained to a much greater extent by the liver, forming an ever-increasing proportion of the retained radioactive tracer. 3. A possible role for these pteridines as cofactors in brain metabolism is discussed.


The mechanism of renomedullary antihypertensive action: haemodynamic studies in hydronephrotic rats with one-kidney renal-clip hypertension. 1. The protective action of the renal medulla was studied in one-kidney renal-clip hypertension in rats with unilateral hereditary hydronephrosis and almost complete atrophy of the medulla of the affected kidney. 2. Rats were unilaterally nephrectomized. The first group had a normal kidney remaining, and the animals from the second and third groups were left with a hydronephrotic kidney and received renomedullary and renocortical autotransplants respectively. Two weeks later all rats were made hypertensive by placing a silver clip (0.2 mm) on the renal artery. 3. From the fourth day after clipping until the end of the experiment blood pressure was found to be significantly (P less than 0.01) lower in rats with medullary transplants than in the other groups. No differences in renal excretory function, plasma volume and plasma renin activity were found between the groups either before or during development of hypertension (5 and 21 days after clipping). Early in the course of hypertension (5 days) cardiac output was significantly (P less than 0.05) lower in the rats with medullary transplants than in the other groups, although an increase in plasma volume was noted in all three groups. At that time no difference in total peripheral resistance was found between the groups. 4. The results are consistent with the hypothesis that the renomedullary antihypertensive substance(s) mitigates hypertension by preventing a hypertensive haemodynamic response to sodium/volume overload.


Excretion of conjugated bilirubin in the isolated perfused rat kidney. 1. Renal mechanisms of conjugated bilirubin excretion have been studied in isolated rat kidneys perfused with a protein-free dextran medium, containing conjugated bilirubin isolated from human bile. 2. In nine perfused kidneys with a low glomerular filtration rate (GFR) (less than 0.5 ml/min) and depressed tubular function, there was a significant linear correlation between conjugated bilirubin clearance and GFR (r = 0.97). 3. In contrast, nine kidneys with a normal GFR (greater than 0.8 ml/min) and good tubular function exhibited substantial tubular reabsorption of filtered conjugated bilirubin (mean 74%). Reabsorption was proportional to the filtered conjugated bilirubin load and a tubular transport maximum was not observed even at high concentrations (144 mumol/1). 4. The fractional reabsorption of bilirubin was unchanged by the addition of sodium aminohippurate to the medium. Perfusion with an albumin medium (10 g/1) resulted in a tenfold reduction in conjugated bilirubin clearance. 5. These observations indicate that non-protein-bound conjugated bilirubin is freely filtered by the glomeruli and then largely reabsorbed in the tubules. Evidence of tubular secretion was not obtained. 6. Chromatographic separation of bilirubin conjugates showed that the proportion of di- to mono-conjugates in the urine was greater than in the perfusate. Whether this incicated further conjugation by the kidney of the monoconjugates or differential clearance of the conjugates was not established.


Thyroid function and blood pressure in two new strains of spontaneously hypertensive and normotensive rats. 1. The influence of thryoid function on the development of hypertension was studied in strains of spontaneously hypertensive (SH) and normotensive rats. 2. Surgical thyroidectomy decreased systolic blood pressure more markedly in SH rats than in normotensive rats. The effects of oral administration of 5 and 100 micrograms of thyroxine 24 h-1 100 g-1 were studied in the thyroidectomized animals. In the two strains the blood pressure returned to control levels only after administration of the larger dose. 3. The evolution of body weight, total plasma tri-iodothyronine (T3) and tetraiodothyronine (T4) concentrations were followed as a function of age in SH rats and normotensive rats from 5 to 21 weeks. At each age, SH rats showed significantly larger body weight and decreased T4 concentrations. Plasma T3 in SH rats was lower than in normotensive rats until 15 weeks of age, after which the difference was not significant. At 11 weeks, plasms free T3 and T4 concentrations were slightly lower in SH rats than in normotensive rats. 4. The more marked hypotensive effects of surgical thyroidectomy in SH rats cannot be related to increased thyroid function.


The causation of splenomegaly in schistosomiasis in mice. 1. Mice were infected with fertile bisexual Schistosoma mansoni and compared with similar animals infected with unisexual worms or sterile bisexual worms. 2. A significant increase in splenic weight occurred in all infected animals. 3. Administration of well-tolerated doses of 6-mercaptopurine abolished the increase in relative splenic weight in animals infected with ordinary S. mansoni. 4. In splenectomized uninfected mice leucocytosis but no other haematological changes developed. 5. In splenectomized mice lower values for packed cell volume were observed 8 weeks after, but not 12 weeks after, infection with S. mansoni. 6. Slight prolongation of the life-span of erythrocytes occurred in splenectomized infected mice. 7. It is concluded that anaemia in schistosomiasis depends to a significant extent on immunity developed to adult schistosomal worms and can develop in the absense of schistosomal ova. 8. The anaemia resulting from such an immune response may be suppressed by administration of 6-mercaptopurine. 9. Such anaemia occurs even in splenectomized mice; thus hypersplenism is not necessary for its development although splenectomy slightly prolongs the erythrocyte life-span.


Changes in absorptive and peptide hydrolase activities in rat small intestine after administration of 5-fluorouracil. 1. Glucose absorption, water absorption and dipeptide hydrolase activities have been determined in isolated rat small intestine at 1, 3, 5 and 21 days after a single intraperitoneal injection of 5-fluorouracil. 2. Absorption rates and enzyme activities were elevated 1 day after treatment, but were reduced to 40% of control values at 3 and 5 days. Changes were seen regardless of whether absorption was expressed per unit length or per unit dry weight of intestine. 3. There were highly significant positive correlations between glucose or water absorption rates and peptidase activities, especially in proximal jejunum. The most significant correlation was observed between water absorption rate and jejunal L-Leu-Gly hydrolase activity. 4. Malabsorption may account for some of the gastrointestinal side effects associated with treatment with 5-fluorouracil. Enzyme measurements may be useful as an index of intestinal function.


Effect of carbamazepine on plasma and urine arginine-vasopressin. 1. Five normal subjects were studied before and during treatment with carbamazepine. 2. Plasma sodium, plasma and urine arginine-vasopressin and urine osmolality were measured during a day of water deprivation, before and during drug treatment. 3. During treatment with carbamazepine plasma sodium increased wheras plasma and urine arginine-vasopressin and urine osmolality decreased. Plasma and urine arginine-vasopressin were signifi"antly correlated with urine osmolality. However, carbamazepine did not affect the osmolality of urine produced by the kidney, in response to endogenous arginine-vasopressin. 4. Plasma and urine arginine-vasopressin were significantly correlated with plasma sodium on both control and drug-treatment days, but the relationships of plasma and urine arginine-vasopressin to plasma sodium were different during carbamazepine treatment, as compared with the control period. 5. It is suggested that the threshold of the hypothalamic osmoreceptors for release of arginine-vasopressin is modified by carbamazepine, and that this may be either a direct action or secondary to another action of the drug.