Homograft and prosthetic aortic valve replacement: a comparative study. Homograft aortic valve replacement was done in 103 patients and prosthetic aortic valve replacement in 106 between January 1962 and December 1973. Patients who received homograft and prosthetic valves were compared with respect to age, sex, preoperative functional impairment, infection, dyspnea, angina, hemodynamics, chest X-ray, electrocardiogram, associated operations, early and late mortality, and valve failure. Combined total mortality was 28% (12% operative, 8% first postoperative year, 8% late). Ten percent of valve required replacement. One year after operation, 70% of survivors were asymptomatic, 27% were improved, and 3% were unchanged or between homograft and prosthetic valve replacement. Valve-related failure and infections were more common after homograft aortic valve replacement. Emboli, hemorrhage, and hemolysis were commoner after prosthetic valve replacement. Fungal infections occurred in five homograft patients but in no patient with a prosthetic aortic valve. Severe properative symptoms or recent endocarditis was associated with greater mortality and valve failure in both the homograft and the prosthetic series. Increased mortality and failure was also seen in patients with either preoperative aortic regurgitation with high left ventricular end-diastolic pressure and low cardiac index, or aortic stenosis with cardiomegaly or roentgenographic evidence of congestive heart failure. Therefore, in two series of patients at equal risk, mortality and valve failure were similar for homograft and prosthetic aortic valve replacement.


Myocardial revascularization and mitral repair or replacement for mitral insufficiency due to coronary artery disease. During the past 5 years, 45 patients were operated on for mitral insufficiency due to coronary artery disease. Preoperatively, 33 had angina; 24 were in NYHA Class IV; and 21 were in Class III. The ejection fraction ranged from 0.1 to 0.7 (mean 0.40). The degree of mitral regurgitation ranged from Grade II/VI to Grade V/VI. Mitral repair was performed in 38 (84%) and replacement in seven (16%). At surgery, a ruptured papillary muscle or torn chordae tendineae with a dilated annulus were found in 21 patients and a dilated annulus only in 24. Seventy-six vein grafts and eight internal mammary anastomoses were performed. There were three hospital deaths (7%). Postoperative follow-up of 36 long-term survivors revealed symptomatic improvement in all but one patient. Twenty patients were in NYHA Class I, 15 in Class II, and one in Class III. In eight patients restudied, 17 of 18 vein grafts were patent (94%). Mitral regurgitation decreased from a mean of 2.7 to a mean of 0.6 (P less than 0.001). Average improvement in ejection fraction was 0.14, significant at P less than 0.01. Actuarial studies revealed an 80% survival rate at 5 years.


Operative management of tricuspid regurgitation. From January 1968 to June 1975 tricuspid regurgitation was encountered in 238 patients of a total of 1074 patients undergoing operations on the mitral valve. During this time tricuspid annuloplasty (TA) was performed in 137 patients and the tricuspid valve was replaced (TVR) in 101 patients. Comparison of hospital mortality of 15% (20 of 137) for TA as against 40% (40 or 101) for TVR suggests the superiority of repair over replacement. A new technique for repair makes this operation even more attractive. It satisfies the dual objectives of producing competency but not obstruction by creating a measured orifice. As experience with TA was gained, the incidence of valve replacement dropped from 69% (22 of 32) in the first 2 years of the study to 16% (11 of 70) for the last 2 years.


Hemodynamic evaluation of Fontan operation in tricuspid atresia. Six patients underwent hemodynamic studies at 2 to 34 months (mean 15 months) following a modified Fontan operation. Only one patient had a valve at the inferior vena cava (IVC)-right atrium (RA) junction. Average age at surgery was 12 years (range 5-26 years). Three patients were catheterized twice. Postoperative studies showed four patients to be in sinus rhythm and two in junctional rhythm. Two patients had a RA-left pulmonary artery (LPA) gradient across the conduit of 1.5-10 mm Hg. The RA pressure was elevated an average of 17 mm Hg (10-34). All patients showed good atrial transport function regardless of their rhythm. The average arterial saturation was 92% (87%-97%), which was an improvement of 13% over preoperative values. Residual hypoxemia was due to pulmonary vein desaturation and to atrial right-to-left shunting early after surgery and to atrial right-to-left shunt alone, later. Death followed re-operation for removal of the porcine valves in the patient with two valves inserted. Macroscopically, both valves were found to have fibrous tissue ingrowth that had fixed them in a semi-open position.


Retarded incorporation of [14C]mannose into thyroglobulin of human thyrotoxic thyroid glands. In vitro studies using thyroid slices from human non-toxic goitres and from thyrotoxic glands show retarded incorporation of [14C]mannose into the 19S protein of thyrotoxic glands. This was not found using [14C]galactose with thyrotoxic glands or using either labelled sugar with slices from non-toxic goitres. Experiments with thyroid tissue from rats on a variety of treatment regimes such as iodine supplements, carbimazole alone or with iodine supplements did not show this differential delay of [14C]mannose incorporation. This suggests that there may be some abnormality of carbohydrate incorporation into thyroglobulin in thyrotoxicosis.


Acromegaly caused by pulmonary carcinoid tumours. Two patients are described whose acromegaly was cured by removal of a bronchial carcinoid tumour. One had an enlarged pituitary fossa and evidence is presented that in this patient the tumour was not secreting growth hormone. The evidence available suggests that the tumour was producing a growth hormone releasing substance. It is suggested that some cases of the pluriglandular syndrome may be secondary to small bronchial carcinoid tumours that produce substances as yet unidentified, that stimulate the growth and hyperactivity of other endocrine tissue.


Prolactin and somatomedin studies in the syndrome of growth hormone-independent growth. Three children with hypothalamic mass lesions and continued linear growth in the absence of circulating growth hormone are presented. Serum growth hormone levels were either undetectable or very low both basally and following insulin-induced hypoglycaemia, whereas serum somatomedin levels were normal. Two subjects had elevated serum levels of prolactin, and in one of these prolactin suppression with bromoergocryptine failed to influence either somatomedin levels or urinary excretion of nitrogen, hydroxyproline and calcium. Although only one case was studied in detail these data suggest that maintenance of serum somatomedin and of normal growth in these children was not dependent upon prolactin secretion.


Effect of two serotonin antagonists on prolactin and thyrotrophin secretion in man. The effects of serotoninergic blockade on prolactin and thyrotrophin secretion in man was evaluated by determining the basal and TRH-stimulated serum prolactin and TSH concentrations in normal volunteers before and after a 3 days course of cyproheptadine or methergoline administration. Cyproheptadine, a serotonin antagonist with antihistaminic, anticholinergic and antidopaminergic properties as well, did not affect prolactin secretion, while it reduced the serum TSH response to TRH; methergoline, a specific blocker of central serotonin receptors, decreased basal and TRH-induced serum prolactin levels, without affecting TSH secretion. These results support the existence of serotoninergic stimulatory influences on human prolactin release, while suggesting that human TSH secretion is not modulated by serotoninergic inputs.


Prenatal diagnosis of fucosidosis.

Prenatal diagnosis of fucosidosis. A pregnancy from a family at risk for fucosidosis was monitored. Determinations of fucosidase and mannosidase were performed on the serum and white blood cells of several members of the family, om amniotic fluid and amniotic fluid cells of the fetus at several passages, and on fibroblast cell lines from index cases. The fetus was diagnosed as being free from the disease. This conclusion was confirmed after birth by fucosidase determination in plasma and white cells from cord blood, and in the placenta. Fluctuations in fucosidase activity were observed in extracts from cultured amniotic cells at various passages. The possible causes of this variability are discussed.


True hermaphroditism with XX/XY sex chromosome mosaicism: report of a case. A case of true hermaphroditism with 46, XX/46, XY karyotype is reported. The propositus, reared as a male, showed ambiguous external genitalia with perineoscrotal hypospadias, and internal genitalia represented by bilateral ovotestes, normal uterus and tubes. Periodic menstrual bleedings appeared at puberty. The endocrinologic data demonstrated the secretory activity of both the ovarian and the testicular tissue. The analysis of red cell, lymphocyte and serum markers, done on the propositus and on his parents, failed to show any evidence of double fertilization. On this basis, the origin of the XX/XY condition (mosaicism versus chimerism) and its developmental consequences are discussed.


Hypertrichosis lanuginosa in a mother and son. Hypertrichosis lanuginosa (without gingival hyperplasia) is described in a mother and son; the latter also had photophobia, infantile genitalia, growth retardation, hypotension, low IQ and dental abnormalities (hyperdontia, permanence of deciduous and delayed eruption of permanent teeth). Both have normal dermatoglyphics. Some clinical findings are discussed. The presence of this syndrome in a mother and son supports an autosomal mode of inheritance (with variable expressivity). Hypertrichosis lanuginosa is a pure monomultidysplasia and may be classified with the tricho-odontic sub-group of the ectodermal dysplasias.


Interstitial deletion of the long arm of chromosome no. 7 (7q-) in an infant with multiple anomalies. An infant is reported with partial deletion of the long arm of chromosome no. 7. She presented with hypertonia, seizures, feeding difficulty, and multiple congenital anomalies. The abnormalities include low-set dysplastic ears, hypoplastic orbital bones, upslanting and small palpebral fissures, prominent cheeks with a relatively large mouth, micrognathia, abnormal creases of the hands and a congenital heart defect. With age her hypotonia and feeding difficulty have improved. Her mother has no detectable chromosome abnormality.


The frequency of PKU and hyperphenylalaninemia in Sweden - a study in institutions for the mentally retarded as well as in neonates. In a country-wide screening examination in Sweden, PKU was observed in 75 (4.5 per 1,000) and hyperphenylalaninemia in 14 (0.8 per 1,000) of a total of 16,805 patients in institutions for the mentally retarded. In the national neonatal screening program in 1965-1975, which covered nearly 1 million individuals, PKU was observed in 36 and hyperphenylalaninemia in 19 individuals. The incidences of PKU and hyperphenylalaninemia in newborns are calculated to be 1/26,000 and 1/50,000, respectively. In addition, PKU and hyperphenylalaninemia were diagnosed in 14 and 1 non-institutionalized individuals, respectively, born before September 1965. The total numbers of individuals detected as having PKU and hyperphenylalaninemia in Sweden in the present investigation are 125 and 34, respectively.


Partial monosomy or trisomy resulting from crossing over within a rearranged chromosome 1. Two sibs, both monosomic for the same portion of 1q (q25q32), had similar severe mental and physical retardation. An older sib was found to be trisomic for the same portion of 1q and less severely affected. These partially monosomic and partially trisomic No. 1 chromosomes resulted from meiotic crossover in the mother, who is a balanced heterozygote of the type 46,XX, ins (1) (p32q25q32).


Aberrant axillary breast tissue: A report of a family with six affected women in two generations. A family with bilateral accessory axillary breasts without nipples or areolae in six adult females of two generations is reported. The anomaly is most likely caused by an autosomal dominant gene of variable expressivity which prevents normal regression of the embryonal mammary ridge. Accessory breasts with and without nipples and areolae have been seen in another family in the literature. In the absence of areolae or nipples the trait will usually be undetectable in prepubertal females and in males of all ages.


Structural aberrations of the long arm of chromosome no. 22. Report fo a family with translocation t(11;22) (q25;q11). A chromosomal translocation t(11;22) (q25q11) is described in a family. Four members, in two generations, had the same translocation but showed phenotypic variation. Case reports of chromosome aberrations involving the long arm of chromosome 22 associated with and without chronic myeloid leukemia (CML) are reviewed. It appears that the distal segment of the long arm or chromosome 22 is either translocated or deleted, resulting in congenital anomalies, presumably due to chromosome imbalance. In other instances, a specific breakpoint on 22q results in the origin of Philadelphia chromosome (Ph1) associated with CML.


The subclasses of human IgG antibodies against tetanus toxoid. The subclass of IgG antibodies against tetanus present in the serum of thirty-five human individuals, who received an injection with tetanus toxoid, was determined. Six successive serum samples were obtained from twenty-five normal individuals (laboratory personnel) 0, 3, 7, 14, 28 days and 2-3 months after the injection with tetanus toxoid had been given. Another ten serum samples were obtained from ten persons with a positive IgE-RAST, taken 2 weeks after the injection. Antibodies were determined with a quantitative immunofluorescence method known as the defined antigen substrate spheres (DASS) system. The normal individuals in whose serum a clearly positive IgG binding was found (nineteen) showed activity in all four subclasses. The binding activity in all individuals reached a maximum between 2 and 4 weeks after the injection. The antibody activity in the serum of four individuals whose serum gave weak IgG binding was confined to IgG1. Two individuals did not show any IgG binding activity at all. In the ten persons with a positive IgE-RAST and three of the normal individuals, who also had a positive IgE-RAST, the distribution of the antibodies over the subclasses was the same as in the others.


Macrophage migration inhibition studies of lymphocytes taken from guinea-pigs suffering from experimental polymyositis. An experimental form of polymyositis, induced in guinea-pigs by means of injections of rabbit muscle homogenate in Freund's complete adjuvant (FCA), had been investigated with a view to the analysis of the role of cellular immune response in this disease. We have used the direct macrophage migration inhibition test on peritoneal exudate cells taken from myositic animals, so as to identify those components of muscle against which lymphocytes of myositic animals are sensitized. These lymphocytes were found to be sensitized principally against the myofibrillar fraction of muscle. Moreover, when tested against purified myofibrillar proteins, they were found to be strongly sensitized against myosin and tropomyosin, but not against troponin. A similar migration inhibition technique is now being developed for use as a diagnostic and investigatory tool in the study of human polymyositis.


A quantitative test to detect lymphocytes sensitized against the surface of muscle cells. A test is described which assesses quantitatively the capacity of lymphocytes taken from myositic animals to adhere to skeletal muscle cells in vitro. Lymphocytes were taken from guinea-pigs in which a polymyositis had been induced by injection of rabbit skeletal muscle and complete Freund's adjuvant. These lymphocytes attached themselves preferentially to multinucleate myotubes as opposed to the mononuclear cells in tissue cultures made from chick skeletal muscle. The degree of preference was calculated as a Preferential Attachment (PA) index. This index was high in those animals which developed myositis. In contrast lymphocytes from various groups of control guinea-pigs all gave a PA index of around 1. This test is now being adapted for use in the diagnosis and study of polymyositis in human patients.


Further characterization of a low-molecular weight allergen fragment isolated from the green pea. A low molecular weight allergen fragment present in the pea dialysate fraction was purified by ion-exchange chromatography and gel filtration. The highly purified allergen fragment inhibits both antigen-indiced passive cutaneous anaphlaxix reactions in guinea-pigs sensitized with rabbit anti-pea extract sera and Prausnitz-Küstner reactions in non-allergic volunteers sensitized with the sera of patients sensitive to green peas. Preliminary analysis of the purified allergen fragment indicates that it is a glycoprotein with a molecular weight of 1800 +/- 250.


Uptake and catabolism of antigen by alvelar macrophages of dogs with respiratory hypersensitivity. Processing of antigen by alveolar macrophages. The ability of alveolar macrophages of dogs to bind and metabolize two antigens was studied. The antigens were ragweed antigen E (AgE) and keyhole limpet haemocyanin (KLH). These antigens were chosen because of the availability of dogs with respiratory hypersensitivity to them and because they are of very different molecular weights. It was shown that: (1) antigen processing was identical using macrophages from hypersensitive as compared with normal dogs; (2) in comparison with AgE, much more of the higher molecular weight antigen, KLH, was bound to macrophages and much less degraded during subsequent incubation, leaving a greater proportion of the antigen bound to the cell membrane; (3) respiratory cells which had taken up AgE at 0 degrees C instead of 37 degrees C and were then incubated at 37 degrees C were much more active in catabolizing bound antigen with consequently less membrane bound antigen remaining; (4) increases in catabolism of bound AgE were also found in cells from relatively recently lavaged animals; (5) there was no evidence that cytophilic antibody contributed to the uptake of AgE.


Pinnal anaphylaxis in the mouse. Mediating antibodies and rhythmic variations in the response. The anaphylactic reaction in the pinna of a mouse actively sensitized to horse serum is mediated by IgG1 and IgE antibodies. Anaphylactic sensitivity is subject to diurnal variation, peak sensitivity occurring at 16.00 hours and minimum sensitivity at 10.00 hours. Anaphylactic sensitivity also varied with the season of the year, being lower during June and July than in the rest of the year, when the reaction was fairly constant.


Variability of sequential studies of lymphocyte blastogenesis in normal adults. Sixteen healthy adults had serial studies of delayed-type skin test reactivity and in vitro lymphocyte blastogenesis to several antigens over a period of 7 months. In many subjects blastogenesis varied broadly from month to month without apparent cause. Responses to all antigens usually increased or decreased together on sequential testing. Blastogenesis to coccidioidin appeared to result largely from cross-reaction with histoplasmin. Humoral factors were not demonstrably responsible for these changes. Blastogenesis rose consistently and non-specifically in subjects following revaccination to vaccinia virus. These studies reflect the lymphocyte blastogenesis reaction as a dynamic equilibrium, subject to spontaneous variation, and responding non-specifically to stimuli such as vaccination. Whatever the causes for these changes, it is clear that serial determinations of blastogenesis response to various antigens do not carry the apparent consistency of the skin test response to that antigen, and single tests must be cautiously interpreted.


Serum inhibitory factors (SIF) in patients with acute and chronic hepatitis and their clinical significance. Serum inhibitory factors (SIF) were demonstrated in a follow-up study in eighteen patients with HBSAg-positive viral hepatitis, in nine patients with chronic persistent hepatitis (CPH) and in six patients with progressive viral hepatitis (CAH). In addition these factors were studied in fifteen patients with HBSAg-positive and HBSAg-negative CAH. SIF appeared during the incubation period up to 4 weeks before onset and disappeared in most instances within 4 weeks after onset of jaundice. Sera from patients with CPH showed no marked inhibitory activity when studied over a period of up to 3 years as compared to patients with a progressive course of hepatitis. The presense of SIF may depend upon persistence of virus, and may help to predict the development of chronic hepatitis.


Studies of HLA antigen frequencies, IgE levels, and specific allergic sensitivities in patients having ragweed hayfever, with and without asthma. In order to study genetic and immunological features which might be important in the pathogenesis of asthma, forty-one ragweed allergic seasonal asthmatics were first matched with forty-one ragweed allergic nonasthmatics on the basis of similar total IgE levels. No significant differences were observed in their sensitivity to ragweed antigen E (measured by histamine release), or in their skin response to ragweed antigens E, Ra3 and Ra5. An increased frequency of HLA-B5 was observed in nonasthmatics as compared to asthmatics (P = 0-03). Although frequencies of HLA-A1 and B8 were also elevated in nonasthmatics and HLA-B40 in asthmatics, these differences were not significant. The forty-one asthmatic patients were than paired with forty-one nonasthmatics patients were then paired with forty-one nonasthmatics on the basis of leucocyte sensitivity to ragweed antigen E. Similar HLA differences were found which were non-significant. No significant difference in total IgE levels were found between the two groups. Whereas no differences in IgE synthesis or antigen sensitivity was found in the two populations, the frequency of HLA antigens needs further study in larger groups.


IgM and IgG antibody levels to ampicillin in patients with infectious mononucleosis. By means of a sensitive radio-immunoassay an antibody-like activity against ampicillin was detected in both IgM and IgG immunoglobulin classes of patients with infectious mononucleosis, being fifteen times the level (for IgM) and six and a half times the level (for IgG) of control subjects. Such ampicillin antibody occurred without obvious relation to prior therapy with ampicillin. This antibody which may originate in a similar manner to Paul-Bunnell antibody was nevertheless immunologically unrelated. The possibility is discussed that the ampicillin rash in infectious mononucleosis results from a disseminated reaction of the small blood vessels to circulating ampicillin-antibody complexes.


Cell-mediated immunity to homologous spermatozoa following vasectomy in the human male. Cell-mediated immunity (CMI) to homologous spermatozoal antigens was studied in sixty-two males following vasectomy of a duration of 1-10 years. A group of twenty-two normal, fertile non-vasectomized males was also included in the study. The inhibition in the leucocyte migration test (LMT), in the presence of spermatozoal antigen, was taken as an index of CMI. Twenty of the sixty-two vasectomized males (32.2 percent) showed a positive LMT reaction. When the results were analysed with reference to the duration of vasectomy, it was noted that four cases each (22.2 percent), showed a positive LMT reaction in the groups 0-2 years, and 3.5 years. On the other hand twelve cases gave a positive reaction in the group 6-10 years (46.1 percent). It appears that the incidence of CMI to spermatozoa increases with the duration in vasectomy.


Cell-mediated autoimmunity in coeliac disease. Lymphocyte transformation in response to a crude freeze-dried prepartion of whole jejunal mucosa was studied in fifteen patients with coeliac disease and compared with the findings in fifteen age-matched controls. The transformation ratio was markedly increased in three patients. These observations suggest the possible existence of cell-mediated autoimmunity to jejunal mucosa in some patients with coeliac disease and might be relevant to the development of some of the complications of the disease.


Inhibition of complement-dependent lymphocyte rosette formation by sera of patients with chronic glomerulonephritis. It has been demonstrated that activated C3 products might bind to lymphocyte C3 receptors and inhibit subsequent complement-dependent lymphocyte rosette formation. Sera from patients with various types of chronic glomerulonephritis (GN) have been tested in a complement-dependent rosette inhibition assay using normal donors' lymphocytes as reacting cells. Control subjects consisted of healthy donors and patients with miscellaneous renal and general diseases. Most sera of membranoproliferative GN and of systemic lupus erythematosus, and two-thirds sera of focal glomerolosclerosis patients, significantly inhibited rosette formation. Only 15-40 percent sera of patients with other types of GN were inhibitory. Serum inhibiting activity usually correlated with low serum C3 level (P less than 0.0005), although inhibition could be observed with normal serum C3. However, no correlation was found between a patient's own complement-dependent lymphocyte rosette count and his serum inhibitory activity. These results extend previous findings and suggest that the complement-dependent rosette inhibition assay can be used routinely to detect serum activated complement components either free or bound to immune complexes.


Antigenicity of janin, a new protein from smooth muscle. The exact nature of smooth muscle autoantibodies is still unclear. The antigen(s) which they are directed against remain unknown. Janin, a so far unknown smooth muscle protein, was obtained from smooth muscle tissue extracts and purified by means of three different procedures. Its mol. w. was estimated at 60,000 daltons. It stimulated a specific anti-janin antibody in rabbits as shown by tube test, double diffusion in agar and indirect immunofluorescence. The new protein absorbed eighteen out of 104 human smooth muscle positive sera that were not absorbed with smooth muscle actin, myosin, heavy meromyosin, light meromyosin, tropomyosin and brain tubulin. This would vindicate a view that smooth muscle autoantibodies differ from patient to patient with regard to the autoantigen(s) involved.


Specificity of immediate skin reaction with streptokinase-streptodornase (SK-SD) in humans. Streptokinase-streptodornase (SK-SD) induced immediate and delayed skin test reactions in a high proportion of patients with disorders in which beta-streptococcal infection may be involved. The P-K test and absorption experiments with antigen or anti-IgE suggested that the immediate reaction was mediated by specific IgE antibody against SK-SD. Furthermore, the ratio of specific IgE antibody against SK-SD to total IgE was roughly calculated to be 20 percent. Finally, the RAST technique was applied to detect specific IgE antibody against SK-SD which showed high radiocounts bound to SK-SD-coupled particles in the sera of nephrotic patients who had a strong immediate reaction against SK-SD and a severe disease state.


Age-related changes in localization of injected radiolabelled lymphocytes in the lymph nodes of antigen-stimulated mice. The localization of i.v. injected syngeneic lymph node cells, radiolabelled with 51Cr or 75Se-L-selenomethionine, was studied in male CBA/H mice aged between 3 and 30 months. The following results were obtained. (1) Localization of cells from young adult donors was greater in the s.c. lymph nodes of old than of young recipients, the main increase being between 15 and 17 months of age. Increases in lymph node weight and DNA-synthesis were also seen at this time; but the rise in cell localization was significant even when calculated per unit of tissue weight. Splenic localization either declined slightly with age or, like the liver, showed no significant change. (2) Local antigenic stimulation by a single injection of sheep erythrocytes into one front footpad, 24 hr before lymph node cell injection, resulted in increased localization in the regional lymph nodes of 3-17 month old, but rarely of 24-30 month old mice. (3) No consistent differences in localization were observed between lymph node cells from 4-month and 25-month old donors. Both age-related and antigen-related increases in cell localization were at least partly attributable to an enhanced rate of entry of lymphocytes from the blood to the lymph nodes. Although the changes underlying the decline in antigen-related localization of cells in old recipients have still to be clarified, it is probable that the defective immune responses of old mice result partly from this decline.


The effect of levamisole on cellular immunity in multiple sclerosis. The lymphocyte stimulation test has been standardized in a normal human population using four virus cell-associated antigens (VCAA): human embryonic lung cells infected with the LEC and Norrby strains of measles virus, mumps virus, and vaccinia virus. Following 1 week of treatment with the immunopotentiating drug levamisole, a group of multiple sclerosis (MS) patients was found to have increased lymphocyte stimulation responses toward VCAA and increased delayed hypersensitivity responses towards a battery of skin test antigens. No change in the percentage of short- or long-incubation E rosettes occurred. Measles haemagglutinin inhibition (HI) antibody titres measured before and after the entire course of levamisole therapy (12 weeks) did not change. The neurological status of five out of seven MS patients deteriorated while they were taking levamisole.


The characteristics of binding of Corynebacterium parvum to glass-adherent mouse peritoneal exudate cells. Corynebacterium parvum, strain 10390, whole organisms were shown to bind to the surface of glass-adherent mouse peritoneal exudate cells in vitro. An HCl extract and a lipid extract of the organism were both capable of inhibiting this binding. The attachment of organisms was not affected by trypsin treatment of the cells, indicating that the plasma membrane receptor is not cell-bound antibody in nature. The binding was inhibited by various sugars, most of which are major components of the cell wall of C. parvum. Removal of divalent cations prevented binding. At room temperature some binding occurred in the presence of magnesium ions alone, whereas both calcium and magnesium ions were required at 4 degrees C. The possibility is discussed that the attachment of C. parvum to the plasma membrane of macrophages may lead directly to their activation.


Comparative study of cyclophosphamide, 6-mercaptopurine, azathiopurine and methotrexate. Relative effects on the humoral and the cellular immune response in the mouse. The effects of cyclophosphamide, methotrexate, azathioprine and 6-mercaptopurine on the concomitant development of the humoral and the cellular immune responses of mice to a single antigen, the El4 tumour cell, were investigated. The measurements of cellular and humoral immunity were carried out in the same animal using lymphocyte and antibody mediated lysis of the El4 cell, a measurement system independent of underlying anti-inflammatory effects. A regimen of daily cyclophosphamide had a more pronounced suppressive effect on the humoral response than on the cellular response, in agreement with other investigators. A single low dose of cyclophosphamide stimulated the cellular response and suppressed the humoral response. Single or multiple high doses of cyclophosphamide maximally suppressed both the cellular and humoral response. Azathioprine and 6-mercaptopurine, in contrast to the results of other investigations, caused equivalent inhibition of both the humoral and cellular responses and thus lacked selectivity. Methotrexate also provided equivalent inhibition of both the humoral and cellular responses at all dose levels investigated.


Evidence for suppressor cell activity associated with depression of contact sensitivity in Pseudomonas aeruginosa infected mice. Pseudomonas aeruginosa infection depresses contact sensitivity to 2-phenyl-4-ethoximethylene-oxazolone (oxazolone), and enhances the antibody response to sheep erythrocytes (SRBC) in the mouse. Anti-oxazolone antibody titres were found not to be significantly different in infected and uninfected animals; thus, the major circulating classes of antibodies do not seem to be responsibile for the observed depression of skin reactivity. Low dose (20 mg/Kg) cyclophosphamide (CY) pretreatment induced a further potentiation of antibody response to SRBC, and prevented depression of contact sensitivity in infected mice. On the other hand, when infected animals were pretreated with high doses (200 mg/Kg) of CY, antibody production was completely suppressed, whereas contact sensitivity was unaffected. Since CY treatment is known to selectively inhibit B lymphocytes, and since it can abrogate the infection-induced depression of reactivity to oxazolone, it is suggested that suppressor cells, which may have B-cell characteristics, are stimulated during P. aeruginosa infection in the mouse.


Changes in immunoglobulin class and subclass of anti-DNA antibodies with increasing age in N/ZBW F1 hybrid mice. The immunoglobulin class and subclass distribution of antibodies to double-stranded (ds) DNA has been determined in NZB/W F1 hybrid mice by a double antibody radioimmunoassay. The results show that there are marked age- and sex-related variations in the class and subclass distribution of these antibodies. In young mice of both sexes, the predominant anti-ds DNA antibody was of the IgM class, but as the animals aged, there was an increase in the level of the IgG2a and IgG2b antibodies. An apparent switch from predominantly IgM to IgG antibody occurred in females before males and at about the age of onset of overt immune complex disease in these animals. The possible significance of these results in the pathogenesis of the murine lupus syndrome is discussed.


The use of hydroxy-DL-proline-2-(14)C in the investigation of hydroxyproline metabolism in normal subjects and in patients with renal insufficiency. The metabolism of hydroxyproline was investigated in six healthy subjects and four patients with chronic renal insufficiency (creatinine clearances respectively 40, 10, 7, 2 1/2 ml/min). For this purpose hydroxy-DL-proline-2-(14)C was administered intravenously and the excretion patterns of radio-activity in plasma, urine and expired air (14CO2) were determined. A separation procedure (using thin layer chromatography followed by oxidation with D-amino acid oxidase) made it possible to determine the concentration of hydroxy-L-proline-2-(14)C in the presence of the D-isomer and the degradation products of both. Although the use of a racemic mixture as tracer made conclusions more difficult, it could be shown that in uremic patients the concentration of hydroxy-DL-proline -2-(14)C remained high in the blood for a longer period, the metabolites appeared in the urine later, and the peak respiratory 14CO2 excretion was reached later and was lower than in the healthy subjects. On this basis it was concluded that the metabolism of hydroxyproline is diminished in patients with renal insufficiency.


Effects of D-penicillamine administration to rats, induction of renal changes: preliminary communication. Oral administration of synthetic D-penicillamine to rats induces alterations of the renal mesangium, apparently without involvement of immune mechanisms. Alterations of mitochondria, especially enlargement, were seen in the proximal tubular epithelium. These results are discussed in the light of recent findings in "penicillamine" nephritis and diseased human kidneys in general.


On the pathogenesis of Bartter's syndrome: report of studies in a patient with this disorder. A 25 year old male with features typical of Bartter's syndrome is described. Studies were performed to evaluate the pathogenesis of this disorder. In response to oral water loading the subject excreted free water normally. Normal renal sodium conservation was documented. Autonomy of the reninangiotensin-aldosterone system was excluded by demonstrating appropriate directional changes in plasma renin activity and aldosterone excretion in response to alterations in sodium and potassium intake. During aminoglutethimide inhibition of aldosterone synthesis the subject was able to maintain potassium balance at a normal serum potassium concentration on a potassium intake of 130 mEq/day which suggests that aldosterone is the major cause of the potassium wasting. Decreased vascular responses to intra-arterial infusions of angiotensin II and norepinephrine were documented in the absence of extracellular volume depletion. These findings argue against tachyphylaxis as the explanation for the vascular insensitivity and implicate a defect at some step in the sequence between agonist-receptor interaction and the contractile response. It is proposed that the vascular defect plays a primary role in the pathogenesis of the hyperreninemia by interrupting pressure-mediated inhibition of renin secretion and/or impairing direct feedback inhibition of renin secretion by angiotensin II. A unique finding in our case was the lack of a postural influence on plasma renin activity and plasma aldosterone. An accentuated plasma aldosterone circadian rhythm was observed independent of plasma renin activity and plasma potassium concentration. Dexamethasone suppression of ACTH reduced but did not abolish the circadian rhythm. Thus some factor in addition to plasma renin activity, potassium and ACTH appears to influence aldosterone secretion in this patient.


Effect of urine metabolites from healthy and uremic subjects on gluconeogenesis in slices of rat kidney cortex and liver. A high molecular weight fraction was obtained by extended dialysis of urine of healthy and uremic subjects. After addition to the incubation medium, this fraction inhibited gluconeogenesis by rat kidney cortex slices. From the six subfractions extracted by gel chromatography (Sephadex G 100) fraction IV caused a decrease of glucose formation. The activity of PEP-carboxykinase but not of pyruvate carboxylase was reduced, indicating a decreased formation of phosphoenol pyruvate. The total high molecular weight fraction stimulated glucose release by liver slices from fed but not from starved rats. In the absence of amino acids, urea formation was not stimulated. The activity of pyruvate carboxylase was reduced in both groups, PEP-carboxykinase activity was, however, only reduced in the starved group. The addition of uremic serum caused increased glucose release. Inhibition of PEP-carboxykinase activity by quinolinic acid (15 mM) resulted in inhibition of glucose formation by 35% in the uremic group and 54% in the control group in livers of 24 hr starved rats. Thus in uremia there may be incorporation of serine carbon skeletons into glucose via hydroxypyruvate, not via pyruvate. Chromatography on calibrated columns indicated that about 40% of the urinary fractions had molecular weights in the upper range of the "middle molecules" category. The positive correlation between toxicity and the total amount of high molecular weight substances excreted do not confirm the hypothesis of augmented retention of "toxins" in uremic patients. It must be appreciated that these results refer only to the undialyzable fraction of urine which contains only 0.5% by weight of the total urine solids.


Blood access in hemodialysis.

Blood access in hemodialysis. Four hundred seventy blood access procedures performed on 170 dialysis patients during the period 1962-1975 have been analyzed according to survival of access with respect to age, sex and cause of failure. Subcutaneous forms of blood access have a significantly longer life and are more free of complications than external shunts. Although the mode of access can now be tailored to the individual patient, the arterio-venous fistula remains the least expensive and simplest surgical procedure. It should therefore remain as the first choice of access for most patients.


Pulmonary calcification in chronic renal failure: use of diphosphonate scintiscan as a diagnostic tool. A patient with end-stage renal failure on maintenance hemodialysis for fifty-five months presented with signs and symptoms of cardiorespiratory failure and chest X-ray evidence of cardiomegaly and persistent bilateral nodular lung densities. A lung scan employing a bone seeking radionuclide, 99 Tc Diphosphonate, revealed active uptake in all areas corresponding to the X-ray densities. It was concluded that these densities represented active calcification. Thus, a diagnosis of pulmonary calcification was established without the need to resort to lung biopsy. It is suggested that bone-seeking radionuclides may be employed effectively to help establish an early diagnosis of pulmonary calcification especially in high risk dialysis patients.


Candida peritonitis complicating peritoneal dialysis: successful treatment with low dose amphotericin B therapy. Two patients undergoing peritoneal dialysis with permanent indwelling peritoneal catheters who developed Candida albicans peritonitis are presented. Both patients were successfully treated with low dose intravenous amphotericin B. Sequential candida precipitin assays were performed and the diagnostic application is discussed.


Midtrimester amniocentesis and culture of aminiotic fluid cells. On the basis of the large, well-controlled, prospective study from the NICHD, it can be stated that midtrimester ammniocentesis is safe if properly performed. The details of performance, with emphasis on possible pitfalls, are presented in an effort to encourage more practicing obstetricians to begin performing the procedure in cooperation with their area genetics laboratories (11). Emphasis is also placed on performing this procedure in a manner most likely to produce success. This success is measured not only in obtaining the fluid, but more importantly in gaining useful information from the analysis of the fluid. Although the aspects of diagnosing and preventing genetic disease have been emphasized, perhaps the greatest value of midtrimester amniocentesis is the reassurance afforded the more than 95% of couples when the fluid analysis is normal (19). The consumer demand for amniocentesis is rapidly increasing. Although the medicolegal implications of the techniques are not fully understood at present, it is clear that failure on the part of a clinician to offer indicated diagnostic amniocentesis may make the clinician vulnerable to litigation if the pregnancy outcome is abnormal. The demand for amniocentesis and laboratory analysis of the fluid will soon overtax existing facilities. Until such time as new and expanded facilities are available, discretion must be used in offering the procedures. Governmental action may soon be forthcoming to provide facilities designed to make midtrimester diagnostic amniocentesis available to all for whom it is indicated.


Stress fracture of the pubic ramus stimulating a loose total hip replacement. Severe pain in the groin following total hip replacement may occur suddenly without any trauma. Roentgenograms can be misleading when a radiolucent line is noted about the acetabular component which suggests loosening but in fact may be a stress fracture of the pubis.


Fat embolism syndrome following total hip arthroplasty. This is a case report of total hip arthroplasty in a healthy 38-year-old woman with the unusual complication of fat embolism with no evidence of hypotension or other intraoperative incidence. Prompt recognition of fat embolism and appropriate supportive therapy resulted in the successful resuscitation of the patient and an excellent functional hip joint.


Prevention of thromboembolic phenomena.

Prevention of thromboembolic phenomena. The leading cause of death from total hip replacement is pulmonary embolism. Prophylactic anticoagulation has been effective in decreasing thromboembolic phenomena but has been associated with a high rate of complications. A low dose warfarin prophylaxis combined with anti-embolic hose, elevation of the legs and early ambulation was employed in 415 total hip replacements. Clinical thrombosis occurred in 2.4 per cent and there was 1.45 per cent pulmonary emboli but none resulted in death. Two deaths from non-embolic causes occurred for a mortality rate of 0.49 per cent. Systemic complications of the warfarin were few with 5 mild gastroentestinal hemorrhages but no deaths related to the medication. Wound hemorrhage occurred in 4.6 per cent of patients and it is recommended that severe, deep superficial hematomas be treated with early surgical evacuation. The management program appeared to be safe and effective in preventing postoperative mortality from pulmonary emboli but close monitoring is essential.


Oxygen intake and walking speed before and after total hip replacement. The objective of the study was to evaluate the walking ability and the energy cost of walking in patients before and after total hip replacement. The oxygen intake and the maximum walking speed were measured immediately before and 6 months after operation in 25 patients. Although the oxygen intake did not change significantly in most patients it was decreased in those patients who before surgery had had the worst walking capacity. The average maximum walking speed almost doubled in the 25 patients.


Femoral loosening in total hip replacement. Ten cases of loosening of the femoral component following a Charnley total hip replacement were noted in a series of 160 patients. In 3 patients, the femoral component bent without fracturing. All of the patients were overweight. Loosening occurred despite the fact that the femoral component was in a valgus position in 9 of the 10 cases. Collapse of the cancellous bone in the region of the calcar may be a manifestation of the stress of excessive body weight upon the femoral component.


Conversion of hip joint pseudarthrosis to total hip replacement. Forth hips in 35 patients were converted from pseudarthrosis to low friction total hip arthroplasty (LFA). Pain, function and range of motion were improved in most cases. Gait was improved and number of walking aids required were reduced in most cases. Abduction against gravity and straight leg raising were also improved. Limb length was restored in all but 9 cases. Two cases dislocated postoperatively. One was reduced and did well; the other had a trochanter avulsion with recurrent subluxation. Improvement of function is a prime indication for converting a pseudarthrosis to LFA whereas pain is not so significant a factor. This is a formidable procedure requiring a complete range of prostheses and instruments and complete familiarity with the technique of total hip replacement but the end results are gratifying.


Dislocation and instability complicating low friction arthroplasty of the hip joint. Among the complications in a series of 1,400 consecutive Charnley low friction arthroplasty procedures, there were 8 dislocations, and 3 highly unstable hips. Three dislocations followed severe trauma, in 2 of the 3 there was only fibrous union of the greater trochanter. In all but 2 of the hips, more than one previous operation had been performed. More than one technical fault was evident in most dislocations. Six of the 8 dislocations required reoperation. Meticulous attention to the Charnley procedure, including soft tissue elements of the hip joint is necessary to avoid instability and dislocation following total hip arthroplasty.


Can wear in total hip arthroplasties be assessed from radiographs? The validity of wear measurements from total-hip radiographs was assessed using a wear simulator which consisted of a total hip prosthesis mounted on a Plexiglas orientation jig. Wear was mesured by a micrometer device and uni- and duoradiographic methods of wear measurement were used with a variety of acetabular cup orientations. In the initial calibration studies the duoradiographic technique proved to be more accurate. The source of the inaccuracies of the uniradiographic method was determined analytically by means of a geometrical model. Forty-inch or 72'' source-to-object film-distances provided similar accuracy and the errors in wear measurement varied from  --0.1 +/- 0.4 mm (2 S.D.) to 0 +/- 0.9 mm for wear magnitudes of 1 and 5 mm respectively, regardless of cup position. In subsequent calibration studies the previous radiographs were compiled to represent seven hypothetical patients at various stages of follow-up whose prostheses exhibited between 1 and 5 mm wear. Clinicians assessed the degree of wear, using both the uni- and duoradiographic techniques, under supervision but unaware of the true position and orientation of the wear track. The resulting errors were of the same order as the wear magnitudes being measured. The location of the measurements on the radiographs was then restricted to approximately the true wear axis but again the errors were so large that it was still impossible to make any valid wear assessments. The calibration runs were therefore terminated at this point and it was concluded that wear measurements could not be made from clinical radiographs.


Vascularity of the femoral head. Tc diphosphonate scintigraphy validated with tetracycline labeling. 99MTc diphosphonate scintigraphy and tetracycline labeling were performed on 22 hips in 20 patients in whom the femoral heads were subsequently removed. Twelve of the hips had acute neck fractures, and 10 hips had roentgenographic evidence of avascular necrosis. This technique is of greater value for recent fractures, for once revascularization begins to occur, increased radioactivity is usually found by scintiscan. There was good correlation between roentgenogram, scintiscan and tetracycline fluorescence. 99mTe diphosphonate scintigraphy, which can be performed outside the operating theater with little discomfort to the patient, proved to be a reliable, noninvasive method of assessing the blood flow to the femoral head. 99mTc diphosphonate scintigraphy is not a quantitative technique; it detects the presence or absence of femoral head blood flow, not the adequacy of that blood supply.


Compression fixation of peritrochanteric fractures and early weight bearing. Forty-two patients with peritrochanteric fractures of the femur were treated by open reduction and internal fixation with a 95 degree A-Ocompression plate. In 30 of 42 patients (71%) resumption of weight-bearing was achieved by 4 weeks from the time of surgery. Compressive fixation devices have biomechanical advantages over other types of standard nail-plates.


Congenital dislocation of the hip associated with congenital muscular torticollis. Four recently identified cases of congenital dislocation of the hip associated with congenital muscular torticollis out of 49 consecutive cases of frank dislocation of the hip suggest that: the coexistence of congenital muscular torticollis and congenital dislocation of the hip occurs more commonly than is generally appreciated; the presence of either abnormality should initiate a careful appraisal for the presence of the other; although both conditions are seen more commonly in children delivered by breech extraction, a direct causal relationship has not yet been established although the abnormal uterine position is definitely related to each condition.


Lymphangioma of the thigh following acute trauma. Only 2 cases of lymphangioma of traumatic origin have been previously reported, and in both it was a matter of repeated microtraumas. This is a report of a circumscribed lymphangioma in a 22-year-old man after a severe direct trauma of the thigh. Five months after the trauma a painless, slowly growing mass appeared in this area. Histologically, the removed mass appeared to be a combination of cavernous and cystic lymphangioma. The development of this lesion, which must be considered a hamartoma, may possibly be attributable to a traumatic hematoma and to subsequent reactive fibrosis which may have blocked the lymph drainage possibly from a sequestrated portion of the primitive lymphatic anlage.


Complications following total knee replacement. Forty-two months follow-up examinations on 30 total knee arthroplasties revealed the following significant complications: phlebothrombosis, 13 knees (46%); pulmonary embolism 3 patients (11%); asymptomatic loosening, 8 knees (11.4%); symptomatic loosening, 3 knees (4.8%); superficial infections, 4 knees (5.4%); deep infections, 4 knees (5.4%); peroneal palsy, 3 patients (4.3%). Early detection of thrombophlebitis by 125I fibrinogen scan and possible aspirin prophylaxis were evaluated. In view of the limited number of encouraging results, e.g. excellent 58.6 per cent; good 28.5 per cent; fair 5.4 per cent and poor 7.1 per cent, caution is advocated until extensive time elapses for more clinical experience with total knee arthroplasty.


An unusual case of cystic chondroblastoma of the patella. An unusual case of chondroblastoma of the patella is presented in which the dominant feature was a hemorrhagic cyst. The chondroblastoma was located in a small gritty mass at one pole of the cyst, which could have easily been overlooked.


Scintimetric evaluation of complications after femoral neck fractures. The primary surgical approach to the femoral neck fracture should be one with the lowest mortality and morbidity. Internal fixation appears to be the safe and logical approach for most of the reducible intracapsular fractures. Careful follow-up of these patients then is important. 85Sr scintimetry is a simple and accurate method in the early detection and evaluation of secondary complications in these patients. The 85Sr scintimetric pattern in the normal healing process was defined in relation to time interval after the fracture. At any time after 4 months following fracture, those hips destined for osteonecrosis, with or without non-union, showed significantly more radionuclide uptake over the femoral head than those hips which healed normally. In non-union there was a trend toward increased counts over the fracture site during 6 to 18 months after fracture, but no such tendency was noted in other periods.


Microscopic comparison of the synovial changes in posttraumatic synovitis and osteoarthritis. The similarity of the histopathologic changes in posttraumatic synovitis and osteoarthritis suggests that similar etiologic agents, possibly macro- and microtraumata, were pathogenetic factors in common.


Intrapelvic migration of a threaded Steinmann pin in Parkinson's disease. Intrapelvic migration of a threaded Steinmann pin complicated internal fixation of a displaced femoral neck fracture in an elderly man with untreated Parkinson's disease. Parkinsonian tremors may have contributed to this unusual complication. This case, in the light of a review of the literature, suggests that transfixation pins and wires should not be used in patients with Parkinson's disease. Endoprosthetic replacement combined with chemotherapy is better tolerated by femoral neck fractures in patients with Parkinsonism.


Coccidioidomycosis of bone and joints.

Coccidioidomycosis of bone and joints. Sixteen cases of coccidioidomycosis involving bone and joints were treated with Amphotericin B. In all systemic or disseminated cases Amphotericin B should be prescribed. Local Amphotericin B is useful in joints if the disease is limited, and in patients who do not tolerate Amphotericin B by systemic route. If the patient cannot be treated with systemic Amphotericin B, surgical treatment should be directed to remove all possible infected tissue. Patients with a negative skin test and albuminuria in disseminated coccidioidomycosis should be treated with Amphotericin B and passive immune transfer.


Radiological demarcation of cemented sockets in total hip replacement. The frequency of radiological demarcation of the cement-bone junction in the acetabulum after total hip replacement has been examined in 141 Charnley low-friction arthroplasties followed for an average of 10.1 years. Sixty-nine per cent showed demarcation of various degrees and 9.2 per cent of the series showed evidence of progressive migration of the socket. The vast majority of cases with demarcation were symptomless. In most cases where demarcation was accompanied by migration the operation notes suggested a technical explanation and in three cases low-grade sepsis was responsible. The fact that nearly 30 per cent of cases showed no demarcation even after 10 years supports the idea that there is no fundamental defect in the principle of employing cement in the acetabulum. Better surgical technique may increase the number of cases showing no demarcation.


Comparison of disk excision and combined disk excision and spinal fusion for lumbar disk ruptures. In a series of private patients 77 per cent over-all satisfactory results were obtained from surgical disk excision performed without spinal fusion. Patients in whom spinal fusion combined with discectomy has been recommended by other authors are not much more satisfied than patients with discectomy alone without fusion (81% versus 74% satisfactory). Patients in whom the third party influence prevails were significantly more dissatisfied (only 59% satisfactory). Findings of a definite disk rupture at the time of surgery result in a higher incidence of satisfactory rating than those with degenerative changes or with normal findings.


Rupture of the long tendon of the biceps brachi muscle. An unusual case related to use of the pneumatic tourniquet. Tourniquet paralysis, arterial spasm, aneurysm formation, and the post-ischemic hand syndrome are all complications of penumatic tourniquet use in surgery of the extremities. This is a case report of another complication of tourniquet use, rupture of the long tendon of the biceps brachii muscle. Some underlying pathologic or degenerative condition usually exists before rupture can occur. Both rheumatoid arthritis and local corticosteroid injections into the long tendon of the biceps probably accounted for weakening the tensile strength of the tendon and subsequent rupture in the case described.


Semiconstrained total elbow arthroplasty. Diminution of elbow function may be both embarrassing and severely disabling, especially in patients with multiple arthritic joints. Over the past century, multiple techniques of soft tissue reconstruction of the elbow have been advocated. In general, they do not compare well with total elbow arthroplasty. Arthrolysis has often resulted in little improvement of elbow motion and interposition arthroplasty to instability. Synovectomy may however offer satisfactory relief of disability for the rheumatoid elbow provided that initially there is little evidence of joint destruction. The major problem with rigidly linked total elbow arthroplasty has been a high incidence of prosthetic loosening. Biomechanical analysis has shown that high moments tend to disrupt the osseousmethacrylate junction in the humoral medulary canal. Development of a semi-constrained total elbow prosthesis transfers the developed stress to the collateral soft tissues and reduces prosthetic loosening to approximately 3 per cent. This is about one-tenth of the incidence of loosening of the hinge type arthroplasty. This reduction in prosthetic loosening has been coupled with excellent gains in flexion and estension. However, improvement in forearm rotation has not been predictable, especially in elbows exhibiting preoperative fusion or fibrous ankylosis. Though the semi-counstrained total elbow has only been generally available for 3 years, a review of these results justifies its continued use for elbow reconstruction.


Pathogenesis of renal calculi in distal renal tubular acidosis. Possible role of parathyroid hormone. Elevated circulating levels of immunoreactive parathyroid hormone (PTH), hypercalciuria and renal calculi were found in 3 patients with distal renal tubular acidosis (RTA). Treatment with alkali resulted in a fall of PTH toward normal and a reduction in urinary calcium, but the frequency of urolithiasis was unchanged. In one patient in whom prolonged follow-up was possible, a subtotal parathyroidectomy was performed. This was followed by virtual cessation of stone formation despite persistence of the acidification defect. This study suggests that RTA may be associated with secondary hyperparathyroidism and that the consequent elevation in PTH may play a contributory role in the pathogenesis of renal calculi.


An anomalous flexor digitorum sublimis muscle. A case report. A report of an anomalous flexor digitorum superficialis muscle in a 14-year-old presenting as a painful, enlarging palmar mass was explored and found to lie on the ulnar side of the flexor, separate from the lumbrical. The anomalous flexor digitorum superficialis muscle was found attached to a normal flexor digitorum superficialis tendon supplied by a branch of the median nerve, and resected. The muscle represents a rare lesion to consider in diagnosis of hand masses. A phylogenetic anatomic explanation for the anomaly is feasible.


Stabilization of silastic implant arthroplasty at the trapezometacarpal joint. Instability of the carpometacarpal joint of the thumb may accompany silastic implant arthroplasty. A collapse deformity of the thumb with resultant loss of pinch power impairs hand function. A procedure is described, which allows apical stabilization of the base of the thumb. Compressive forces may then act on the thumb to produce divergence in abduction without collapse instability and yet allow enough motion for convergence in oposition and restoration of asymptomatic three-point pinch.


Injuries of the talus and its joints.

Injuries of the talus and its joints. To understand the mechanism of injury and classify fractures of the talus requires knowledge of the anatomy of the hindfoot, its function and the nature of the traumatic forces. The talus has an irregular shape with articular surfaces for tibia, fibula, calcaneus and navicular. It functions as a complex universal joint between the leg and foot created by the ankle, sub-talar and midtarsal joints. Injury may disturb function and create serious disability. As in the femoral head, osteonecrosis is a serious problem after injury to the talus. The reason for this lies in a peculiar distribution of the arterial circulation which exposes it to some injuries, but not to others. To understand the mechanism of injury is to be better prepared to properly treat these injuries and to more accurately predict their consequences. Injury occurs as motion caused by an extrinsic force is applied to the part, and when the motion is forceful enough to overcome resistance. For the talus and its joints the mechanisms of injury are: extension, flexion, inversion, eversion, and compression. Rotation, medial and lateral, may be important in the production of fractures of the talar trochlea. Combinations of these mechanisms cause complex injuries.


Idiopathic subluxation of the radial head. Idiopathic subluxation of the radial head is a different entity from congenital dislocation. The former is always painful, with marked loss of rotation. The radius articulates with the capitellum and the radial head is concave, possibly representing a lesser stage of dislocation. There also may be a correlation with true posterior dislocation. Since it successfully alleviates pain in this condition, radial head resection is often advisable. However, the operation should be delayed until growth is complete and the danger of disruption of the distal radioulnar joint is avoidable.


Relationship between ultrastructure and "pin test" in osteons. In the 3 types commonly recognizable under the polarizing microscope  (longitudinally, alternately and transversally structured osteons), the lamellar appearance of osteons in electron micrographs (EM) is due to the presence of layers of paralleloriented collagen bundles, with the orientation of the bundles changing abruptly through about 90 degrees in successive layers. On the EM scale, lamellae appear as completely independent entities. All 3 osteon types can be considered as consisting of a series of complete or incomplete lamellae. The quantities of collagen bundles in each of the 2 types of lamella--those with longitudinally or concentrically oriented bundles--is a distinctive feature determining the specific appearance of each type of osteon. This view has interesting implications as regards the nature of the factors which instruct and regulate osteoblasts in determining the cross-parallel arrangement of lamellar bone, and the specific characteristics of the various types of osteon. The mechanical properties of osteons are closely related to their structure. The highest values for ultimate dilating strength were obtained with transversally and alternately structured osteons, and the lowest values with longitudinally structured ones.


Bone morphogenesis and surface charge.

Bone morphogenesis and surface charge. The electrophoretic mobility of variously treated bone specimens, with and without bone morphogenetic activity, has been measured in physiological solutions. The Bone Morphogenetic Principle appears to be associated with a minimum negative surface charge on the implant that corresponds to that of normal undemineralized cortical bone in saline. Demineralization of cortical bone in 0.6 N HCI at 2 degrees consistently increases the bone negative surface charge, and biologically produces an implant with morphogenetic activity. It is suggested that through the mediation of the positively charges ionic layer surrounding the negative implant that the negatively charged mesenchymal cell is able to reside in very close contact with the surfaces of the implant. The binding force can be expected to be directly proportional to the degree of negativity of the implant. However, implants with a positive zeta potentaial will be surrounded by ions with a net negative charge so discouraging the stable positioning of mesenchymal cells in close contact with the implant. The negative surface charge corresponding to that of untreated cortical bone is apparently borderline in permitting such a close contact for a sufficiently long period of time for differentiation to follow.


The cell density of human femoral head cartilage. The human femoral head cartilage in 63 subjects with ages ranging from 16 to 100 years demonstrates that in the course of aging the cell density of the whole cartilage thickness decreases about 40 per cent. The reduction of the cellularity with age is more accentuated in the superficial than in the deeper zone and is even limited to the superficial zone during the latter part of aging. Proportionately the cell loss is similar in the superior and inferior poles of femoral head suggesting a uniform distribution of age related changes. In absolute value, the decrease of the superficial cell density is much higher in the inferior than in the superior pole; the decrease may be related to the propensity of this region to fibrillation.


Comparison of functional performance after McKee-Farrar, Charnley, and Muller total hip replacement. A six-month follow-up of one hundred sixty-five cases. Measurements of functional performance were compared before and at 6 months after 58 McKee-Farrar, 50 Charnley, and 57 Muller total hip replacements in 143 patients. The measurment included: range of motion of the hip, hip abductor and adductor-muscle torque, weight-bearing activity during standing, forces applied to canes or crutches, and multiple components of walking performance. Each group of patients improved significantly after surgery in all of the components measured. Early postoperative differences among the 3 groups were found with respect to pain ratings, impressions of hip status, hip motions, muscle torque, the number of patients using assistive devices, and certain components of walking performance. There is nothing to suggest that the performance of any 1 group is distinctly better or worse than that of any other group 6 months after surgery. On the basis of average values, each group improved in every component of function and it is gratifying that, except for a few patients who developed postoperative infection, each patient could be considered to have successful reconstruction.


Comparison of preoperative, intraoperative and early postoperative total hip replacement with and without trochanteric osteotomy. A series of 100 consecutive patients with total hip replacements in whom trochanteric osteotomy was performed was compared with 100 patients in whom the greater trochanter was left in place. The groups were comparable with respect to age and incidence of osteoarthritis and connective tissue disorders. Although no statistically significant difference was noted among trochanterectomy groups or disease subgroups in terms of preoperative impairment as indicated by preoperative Harris score, 16 patients presented exposure problems necessitating trochanteric osteotomy despite preoperative plans to leave the trochanter in place. Salvage operations after unsuccessful previous operations were performed in 18 patients in the osteotomy group and 11 in the nonosteotomy group. Mean operating time was 3 hours for patients in the osteotomy group and 2 hours for those in the nonosteotomy group. Considerably more intraoperative and postoperative blood replacement was required in the patients having osteotomy. Patients sat, stood, walked, and left the hospital sooner in the nonosteotomy group than in the osteotomy group. Trochanteric bursitis requiring treatment 3 or more months after operation occurred in 17 patients having osteotomy and in 3 patients not having osteotomy. Hematomas developed in 15 patients in the osteotomy group and in 4 in the nonosteotomy group. Ectopic bone formation was observed in 12 of the osteotomy group, 8 with limitation of function, and 5 of the nonosteotomy group; non had symptoms. Six osteotomized patients had troublesome abductor weakness secondary to wire breakage and proximal migration of the trochanter. The rates of infection and thrombophlebitis were low in both groups. When exposure was not difficult, leaving the trochanter intact had many advantages.


Articular interposition of trochanteric wires in a failed total hip replacement. This is a case report of a previously unrecorded complication of trochanteric osteomy in a total hip arthroplasty. The trochanteric wire fixation failed and wire fragments migrated from the osteotomy site into the joint space. Revision total arthroplasty was elected. An additional potential complication of trochanteric osteotomy is noted.


In vitro measurement of bone-acrylic interface pressure during femoral component insertion. Bone-acrylic interface pressure measurements were recorded at the medial interior rasped surfaces of fresh cadaver femurs during digital packing of acrylic bone cement and during insertion and seating of a Trapezoidal-28 femoral total hip component. Plugging of the femoral canal below the tip of the prosthesis stem was an effective means for increasing pressure in the distal femoral canal when the stem was inserted in the early stages of acrylic polymerization (i.e. immediately after dough time). At surgery, this can be accomplished by inserting a small bolus of acrylic down the canal to a depth below the tip of the seated stem and allowing it to polymerize in place. This forms an effective seal which prevents distal extrusion of the acrylic when the cavity is then packed prior to prosthesis insertion. Elimination of cement in the distal canal also avoids any future difficulty of acrylic removal should revision become necessary due to loosening or infection. No significant pressure differences were observed between one and two millimeter thicknesses of acrylic between the metal and bone. Interface pressures developed during finger packing were of the same order of magnitude as those achieved during seating of the femoral component. Use of a rubber diaphragm stretched tightly over the margins of the rasped femoral cavity helped to contain the acrylic and prevent extrusion during finger packing but was ineffective in increasing interface pressure. When this method is used, the acrylic can be poured or injected into the canal and packed before dough stage and thus facilitate increased cancellous penetration when the acrylic is in a state of low viscosity.


Cardiovascular malformations associated with congenital anomalies of the urinary system. Observations in a series of 453 infants and children with urinary system malformations. Thirty-four (8%) of 453 infants and children with urinary system malformations had cardiovascular malformations. Cardiac defects were seen frequently in Potter syndrome, unilateral renal agenesis, and horseshoe kidney. The most frequently encountered types of heart defects were ventricular septal defect (33%), endocardial cushion defect (15%), tetralogy of Fallot (12%), and patent ductus arteriosus (12%).


The effect of high pressure insertion and antibiotic inclusions upon the mechanical properties of polymethylmethacrylate. The properties of self-curing polymethylmethacrylate as affected by the admixing of an antibiotic to the powder-liquid mixture and as affected by insertion technique demonstrated that the antibiotic agent may leach from the surface of the acrylic, but not necessarily from the interior. The compressive and tensile strength, determined on two different commercial formulations, suggests that the antibiotic additive is not detrimental to the mechanical properties. A high pressure insertion technique produces a significant improvement in the mechanical properties of the self-curing acrylic material.


Improved methods for quantitative radiographic evaluation with particular reference to total-hip arthroplasty. The range of magnification factors in 40'' and 72'' radiographs were calibrated using three simple mathods. The relationship between X-ray source to cassette distance, object to cassette distance and magnification factors was determined experimentally for both 40'' and 72'' radiographs. The resulting nomogram showed that: (1) there was no significant magnification difference between centered (AP-hip) and offset (AP-pelvis) radiographs; (2) magnification factors of 40'' films were twice those of 72'' films for the same object to cassette distances; and (3) due to the smaller magnification range of 72'' films (1 to 13%) compared to 40'' films (1 to 26%) there was less chance of error in determining magnification factors for the larger film distances. The skin radiation dosage for the patient was similar in both procedures. Magnification factors were also calculated from 414 A-P radiogrphs of total-hip prosthesis, using the femoral ball as a calibration standard. This provided magnifications of 20 per cent +/- 6(2SD) for 40'' films and by extrapolation on the nomogram gave corresponding values of 10 per cent +/- 3 for the 72'' films. The associated hip to cassette distances (L), also obtained from the nomogram, varied from 125 to 205 mm, average 165 mm. In subsequent clinical trials using 72'' films, it was possible to represent the patients as either small (L less than 145 mm) medium (145 less than or equal to L less than or equal to 185 mm) or large (L greater than 185 mm) with corresponding magnification factors of 8, 10 and 12 per cent, respectively. The error with this simplification was still within +/-21/2 per cent. For 40'' films the corresponding magnification factors for small, medium or large patient categories were 16, 20 and 24 per cent respectively with likely errors within +/-5 per cent. Magnification factors were also calculated from the radiographic image of a 100 mm long rod which had been attached to the patien's thigh. The overall accuracy with this method was comparable to the techniques described above and had the advantage that every radiograph featured its own scale, a particularly important feature for preoperative films which have no implant for calibration purposes. As a result of such simple calibration procedures, it was possible to identify the overall magnification variations and specify particular magnification factors within +/-21/2 per cent (72'' films) or +/-5 per cent (40'' films).


Dislocation and subluxation of the total hip replacement. In 502 total hip replacements, it was noted that 7 (1%) dislocated postoperatively in the first 6 weeks. This was usually related to improper positioning of the implant or to improper positioning of the implant or to unusual positioning of the patient postoperatively. There was no difference noted between the type of implant and the incidence of dislocations. Twenty-eight subluxations (5.5%) occurred. There was no statistical correlation with the percentage of nonunions and the type of prosthesis; however, 22 of the 28 subluxations were in Charnley prostheses. Ninety-three per cent of the subluxations were secondary to hyperflexing activities.


The temperature problem at the bone-acrylic cement interface of the total hip replacement. Loosening of total joint replacements may be caused in part by thermal necrosis of bone in contact with the high temperature of the polymerizing PMMA acrylic cement. This study reports a method to reduce the temperature of the bone-cement interface below the temperature at which bone results in definite necrosis. By precooling the acetubular component to --84 degrees before insertion into the cement, the temperature during polymerization at a simulated bone-cement interface can be reduced from 70 degrees to 49 degrees with an increase of only approximately 51/2 minutes in the cement setting time.


Penetration and flow of acrylic bone cement. Fixation of prosthetic joint components into bone is influenced by the degree of mechanical interdigitation of the acrylic into cancellous interstices. The rheology of polymerizing polymethylmethacrylate was studied by pressurizing acrylic bone cement with a piston apparatus to produce flow into cylindrical cavities one to 3 mm in diameter. The acrylic penetration per unit of applied pressure increased with increasing cavity diameter. This suggests that greater penetration should occur in cancellous bone containing larger interstitial cavities. More than one-half (64 %) of the filling observed in our experiments took place within the first second of pressure application. Short duration, high level pressure pulses are the most effective means to achieve maximum penetration. Clinically, this is accomplished by vigorous finger packing. The cement should be pressurized as early as possible within the rasped cavity (immediately after dough stage if possible). The depth of penetration for 4-minute pressurization averaged three times that for 6 1/2-minute pressurization for the range of hole sizes and pressure levels tested.


Acute hemiplegia in children complicating upper respiratory infections. Report of three cases with angiographic findings. Three children presented with acute onset of hemiplegia following an upper respiratory infection. Angiography revealed irregulaities, beading, and slow flow of a peripheral branch of a middle cerebral artery. In addition, one child had narrowing of the cervical segment of the internal carotid artery. An inflammatory arteritis of the cervical internal carotid artery is presumably the site of the formation of cerebral emboli.


Preliminary field-testing of The Physician's Developmental Quick Screen for Speech Disorders ("PDQ"). A 5-minute procedure for testing children six months to six years. This report describes the development of The Physician's Developmental Quick Screen for Speech Disorders (the PDQ), a screening test designed for use by nonspeech pathologists with children aged six months to six years. Disorders of language, articulation, voice, rhythm of speech, and the speaking mechanism are considered by the PDQ. Validation studies resulted in 90 per cent agreement (p less than .001) between nonspeech pathologists utilizing the PDQ and speech pathologists employing a battery of more established tests.


Cervical adenitis in infancy. Report of four cases due to staphylococci. Four cases of cervical adenitis occurring in infants under four months of age are presented. Coagulase positive staphylococci were recovered in pure culture from the involved lymph node in each instance. Staphylococcal aureus as a cause of lymphadenitis should be suspected in patients who present with acute lymph node swelling and no obvious focus of infection. Antibiotic management of this clinical problem should include therapy specific for the staphylococcus.


Enhanced phenacetin metabolism in human subjects fed charcoal-broiled beef. There were marked individual differences in the plasma levels of phenacetin after oral administration of a 900-mg dose to 9 normal volunteers eating customary home diet. Feeding a diet that contained charcoal-broiled beef for 4 days prior to the administration of phenacetin markedly decreased the plasma levels of this drug without appreciably influencing the plasma concentrations of phenacetin's metabolite, N-acetyl-p-aminophenol (APAP), or the plasma half-life of phenacetin. The average peak concentration of phenacetin in plasma, after a 900-mg oral dose, fell from 1,628 ng/ml, when the subjects were fed a control diet for 7 days, to 352 ng/ml after they were fed the same diet which contained charcoal-broiled beef for 4 days. The average peak concentration of phenacetin rose to 1,885 ng/ml after the subjects were subsequently fed the control diet for 7 days. The ratios of the average concentrations of APAP in plasma to those of phenacetin markedly increased after the charcoal-broiled beef diet. The results suggest that a diet containing charcoal-broiled beef enhances the metabolism of phenacetin in the gastrointestinal tract and/or during its first pass through the liver. This effect greatly decreases the bioavailability of phenacetin.


Influence of dietary protein and carbohydrate on antipyrine and theophylline metabolism in man. This study was undertaken to examine the influence of changes in dietary carbohydrate and protein content on the oxidation of antipyrine and theophylline in man. When the diets of 6 normal volunteers were changed from their usual home diets to low carbohydrate-high protein diets, the plasma half-life of antipyrine decreased from 16.2 hr to 9.5 hr, and the half-life of theophylline decreased from 8.1 hr to 5.2 hr. When the subjects' diets were changed from low carbohydrate-high protein diets to a high carbohydrate-low protein diets, the mean antipyrine half-life increased from 9.5 hr to 15.6 hr and the mean theophylline half-life increased from 5.2 hr to 7.6 hr. These changes in half-lives were accompanied by changes in metabolic clearance rates but not in the apparent volumes of distribution of the drugs tested. Qualitatively similar results were obtained when the subjects were placed on standard diets followed by the standard diets supplemented with carbohydrate or protein. Supplementing the standard diets with carbohydrate caused an increase in drug half-lives, whereas a protein supplement caused a decrease in the drug half-lives. These data demonstrate marked influences of nutritional factors on oxidative biotransformation of drugs in man.


Aminopyrine disposition: studies on breath, saliva, and urine of normal subjects and patients with liver disease. To investigate aminopyrine disposition, breath, saliva, and urine were collected from 25 control patients, 15 patients with hepatocellular disease, and 26 patients with hepatic neoplasm after oral administration of 2 muCi [14C]aminopyrine. The percentage 14C excreted in breath 14CO2 in 2 hr (aminopyrine breath test, ABT) correlated with the breath 14CO2 elimination rate (r = 0.92, p less than 0.01), with the aminopyrine metabolic clearance rate (MCR) (r = 0.85, p less than 0.01), and with the plasma half-life of 4-aminoantipyrine (r = -0.54, p less than 0.05). The ABT permits study of aminopyrine disposition with simplicity, accuracy, and safety.


Interaction between antipyrine and aminopyrine. Aminopyrine administered to normal human volunteers in an oral dose of either 9 mg/kg or 4.5 mg/kg prolonged the plasma half-life and reduced the metabolic clearance rate of antipyrine (18 mg/kg, orally) without changing its apparent volume of distribution. By contrast, this same oral dose of antipyrine given simultaneously with 9 mg/kg aminopyrine failed to alter aminopyrine disposition. Thus, antipyrine and aminopyrine should not be administered simultaneously to measure different steps in hepatic drug oxidation, although in man aminopyrine can be given for this purpose 24 hr after antipyrine. Antipyrine elimination was prolonged to the same extent when aminopyrine was given 5 hr before antipyrine as when the drugs were given simultaneoulsy. Since in man aminopyrine has a biologic halic-life of approximately 2.7 hr, the marked inhibitory effects observed 5 hr after aminopyrine administration may be due to its major metabolite, 4-aminoantipyrine. To define mechanism by which aminopyrine affects antipyrine disposition in vivo, hepatic microsomes were prepared from rats, mice, and dogs, and rates of antipyrine hydroxylation were measured in vitro both in the absence and in the presence of aminopyrine. In these species in vitro inhibition of antipyrine hydroxylation by 4-aminoantipyrine was of a mixed type; antipyrine inhibited competitively aminopyrine N-demethylation in vitro in rats, mice, and dogs. There were some sex and species differences in the Km' V max' and Ki for aminopyrine and antipyrine.


Effect of oral contraceptives on platelet monoamine oxidase, monoamine excretion, and adrenocortical function. Studies with animals indicate that there are cyclical changes in the monoamine oxidase (MAO) activity of brain and uterus, and that these changes may be due to changes in estrogen and progesterone levels. To determine if oral contraceptives (OC) alter the tissue MAO activity of healthy women, we measured platelet MAO activity in 7 control women and in 7 women who were receiving combination estrogen-progesterone OC. The platelet MAO of the control women and the women receiving OC did not differ with the use of tryptamine and serotonin as MAO substrates. The two groups did not differ with respect to the following: serum serotonin, plasma tryptophan, plasma tyrosine, and the urinary excretion of tryptamine, tyramine, serotonin, 5-hydroxyindoleacetic acid, creatinine, 17-hydroxycorticosteroids, 17-ketosteroids, and urinary free cortisol. The subjects receiving OC had higher plasma cortisol concentrations than the controls. Two women in the seventh month of uncomplicated pregnancy, who underwent these studies, had higher plasma cortisol and urinary 17-ketosteroid excretion than control subjects. In the remaining tests the results of pregnant subjects did not differ from those of control subjects. We conclude that tissue MAO activity is not altered by OC or pregnancy.


Correlation between electrocardiographic changes, serum digoxin, and total body digoxin content. Serial electrocardiograms and serum digoxin levels were obtained in four healthy volunteers receiving daily doses of digoxin, 0.25 mg for the first two weeks and 0.5 mg for two more weeks. We found a linear relationship between serum digoxin levels and the "PTQ index" (a function of the PR-interval, corrected QT-time, and T-wave depression). In 3 of the 4 subjects the correlation was statistically significant. The degree of linear correlation was improved when PTQ was correlated with the computer-calculated total body burden of digoxin.


Changes in serum thyroxine, triiodothyronine, and thyrotropin induced by lithium in normal subjects and in rats. Serum thyroxine (T4), triiodothyronine (T3), and thyrotropin (TSH) were measured in 4 normal subjects before, during, and 2 wk after administration of lithium carbonate (1,200 mg/day) for 6 wk. All subjects developed thyroid enlargement associated with increase in TSH. Serum T3 and T4 did not change significantly. In 3 hypothyroid maintained on thyroxine replacement, lithium administration did not alter circulating levels of T4 or T3, suggesting no effect of lithium on the extrathyroidal metabolism of the thyroid hormones. In rats fed a low iodine diet containing 122 mg/kg/day lithium carbonate, goiter, increased 131I uptake, and a decrease in intrathyroidal T3 and T4 with an increase in MIT, DIT, and MIT/DIT were observed at 3 wk. Serum T3 fell significantly only during the third week, while T4 did not change. Thyroid enlargement, secondary to a rise in TSH, appears to play a role in the adaptation of the thyroid gland to lithium carbonate. The exact mechanism for the elevation of TSH has not been elucidated.


Artificial kidneys and clearance calculations. Clearance of solutes by artificial kidneys can be calculated using plasma flow and solute concentration, whole blood flow and plasma solute concentration, and midpoint of dialysis blood or plasma solute concentration and total amount of solute removed. Using these methods, the clearance of procainamide (PA) and N-acetylprocainamide (NAPA)  was determined in 4 patients. In all but one case clearances using total amount recovered were greater than clearances using whole blood flow and plasma concentration. Without exception, clearance determined using amount recovered was substantially greater than clearance using plasma flow and plasma levels, suggesting that both PA and NAPA are removed not only from plasma but also from red blood cells. In vitro clearance of PA, NAPA, quinidine, and phenobarbital by 11 clinically available artificial kidneys and an XAD-4 hemoperfusion column was determined and differences were found.


The mechanism for small-bowel adaptation in lactating rats. 1. To study the relative contributions of luminal nutrition, bile and pancreatic secretions and hormonal factors in intestinal adaptation, lactation hyperphagia was chosen as a model for increased luminal nutrition, either alone (intestinal transection control group) or in combination with (i) exclusion of bile and pancreatic secretions from the jejunum (by transposition of the jejunum above the Ampulla of Vater) or (ii) exclusion of bile, pancreatic secretions and exogenous luminal nutrition from the jejunum (proximal Thiry-Vella by-pass group). 2. The results confirm that in lactation there is mucosal hyperplasia with increases in villus height and crypt depth, and in small-bowel wet and defatted dry-tissue weights per unit length of intestine. 3. There are corresponding changes in absorptive function with increased glucose and water absorption per unit length of intestine. 4. These structural and functional adaptive changes are proportionately greater in ileum than in jejunum. 5. The exclusion of exogenous luminal nutrition, bile and pancreatic secretions from the jejunum did not diminish the degree of intestinal mucosal hyperplasia and functional adaptation seen in lactation. 6. Diversion to the ileum of greater than normal amounts of bile, pancreatic secretions and luminal nutrition did not further increase the degree of mucosal hyperplasia and enhanced absorption seen in the lactating intestinal transection control group. 7. Unlike other models of intestinal adaptation, the changes in small-bowel mucosal structure and function seen in lactation are probably due to hormonal factors.


Neural factors contributing to renin release during reduction in renal perfusion pressure and blood flow in cats. 1. The participation of neural mechanisms in mediating the renin release induced by reduction of renal perfusion pressure was explored in anaesthetized cats by comparing renin release from the two kidneys, one acutely denervated and the other intact. 2. Suprarenal aortic stenosis of 10 min duration reduced renal perfusion pressure to 50 mmHg and halved blood flow to both kidneys, but cause a greater release of renin from the innervated kidney than from the contralateral denervated one (increments of 72 +/- 17 and 29 +/-20 pmol/min respectively). 3. A study of the time-course of the response during aortic stenosis of 30 min duration showed early release of renin from the innervated kidney at a time (5 min) when little release occurred from the denervated one. In later samplings (15 and 30 min) the response of the innervated kidney levelled out at somewhat lower values, and that of the denervated organ progressively increased, but remained smaller than on the side with intact nerves. 4. There was no parallelism between renin release and renal vasomotor changes induced by aortic stenosis, as vasomotor changes were equal in the two kidneys and remained constant from beginning to end of stenosis. It is concluded that a significant part of the renin release induced by aortic stenosis is dependent on neural mechanisms: the neural differs from the non-neural component in being of more rapid onset and probably of shorter duration.


Skin collagen in idiopathic adolescent scoliosis and Marfan's syndrome. 1. Skin collagen from fifteen patients with idiopathic adolescent scoliosis, three with congenital scoliosis, and fourteen patients with various degrees of Marfan's syndrome has been examined. 2. The stability of a polymeric collagen fraction, extracted from the skin of these patients, to depolymerization, has been compared with that from thirty-one matched control subjects. 3. The mean polymeric collagen stability was significantly reduced (P less than 0-01) in the group of fifteen patients with idiopathic adolescent scoliosis. The individual reductions in stability were greater in the younger patients and no reduction was found in two patients aged 19 years who had a mature skeleton. 4. The mean stability of polymeric skin collagen from the group of patients with Marfan's syndrome was not significantly abnormal, although there were individual low values. 5. Polymeric collagen of low stability was present in individual patients from each clinical group. Instability of collagen (from whatever cause) at a time of rapid growth may contribute to the high incidence of scoliosis in adolescent girls. In boys, adolescent scoliosis is less common and the maximum growth rate occurs at a time when collagen stability is less reduced.


Plasma cadmium and zinc in human hypertension. 1. Plasma cadmium and zinc were determined by atomic absorption spectrophotometry in inferior venal caval or peripheral venous blood in thrity hypertensive patients and fifteen normal subjects. 2. The mean plasma cadium in hypertensive patients was significantly higher than in normal control subjects. 3. The plasma cadmium/zinc ratio was significantly greater in hypertensive patients. 4. There was a significant positive correlation between the plasma cadmium/zinc ratio and the mean arterial blood pressure.


Changes in cardiac and hepatic glucocorticoid receptors after adrenalectomy. 1. The total number of specific dexamethasone-binding sites in rat heart and liver cytosol was measured at intervals after adrenalectomy. 2. Between 12 and 48 h after adrenalectomy there was a significant increase in the number of binding sites in both heart and liver cytosol. Affinity was unchanged. 3. Of the [3H]corticosterone bound to liver cytosol proteins after an intravenous injection 98% disappeared within 2 h in vivo. Dissociation of endogenous corticosterone-receptor complexes in liver cytol will thus be substantially complete some hours before the number of receptors increases. 4. It was concluded that there is a true increase in the number of glucocorticoid receptors occurring principally between 12 and 48 h after suppression of endogenous steroids.


Carbon monoxide in alveolar air as an index of exposure to cigarette smoke. 1. A rapid method for the analysis of CO in expired air has been developed, which is suitable for use in studies of smoking. 2. The Bohr equation has been used to calculate the mean alveolar CO partial pressure (PA,CO). 3. The values of PA,CO obtained are highly correlated with direct measurements of venous carboxyhaemoglobin (r = 0-96). 4. The method will distinguish between populations of smokers and non-smokers, and can allow the changes of CO in a smoker throughout a 12 h period to be followed. It provides a measure of the dose of cigarette smoke (vapour phase) that results from smoking a single cigarette.


Effect of acupuncture on bronchial asthma. 1. Needle acupuncture was performed at three sites in twenty patients in a clinical attack of bronchial asthma. 2. In all patients the symptoms of bronchoconstriction improved during the attacks when the correct site was stimulated, and in five patients wheezing was abolished. 3. Stimulation at the correct site produced a significant increase in the mean FEV1-0 (58%) and FVC (29%) but not in maximal mid-expiratory flow rate (MMFR; 76%), when compared with the findings before acupuncture, along with a significant fall in the Pa,CO2 and an insignificant fall in Pa,O2. A mild tachycardia was also observed. 4. After acupuncture a greater improvement in FEV1-0, FVC and MMFR was produced by inhalation of isoprenaline. 5. No significant changes in FEV1-0, FVC, MMFR, pulse rate or arterial blood gas tensions occurred after acupuncture at control sites. 6. In four of the patients during clinical remission acupuncture was performed before and after histamine aerosol challenge, but there was no effect on either the severity or the duration of the histamine-induced bronchoconstriction. 7. It is concluded that acupunture probably reduced the reflex component of the bronchoconstriction, but failed to influence direct smooth muscle constriction caused by histamine.