Congenital goitre and hypothyroidism with impaired iodide organification and high thyroid peroxidase concentration.

A sibship of thirteen subjects whose parents were first cousins was studied for a defect in thyroid hormone synthesis. Five sibs were goitrous and had congenital hypothyroidism. All but one showed a positive perchlorate discharge test (PDT). Three other subjects were goitrous and euthyroid (one with a positive PDT), and the remaining five sibs were euthyroid with a presumably normal thyroid. However, an abnormally exaggerated TSH response to TRH was observed not only in the hypothyroid patients but also in six of the other subjects, indicating a decreased thyroid feedback at the pituitary level in the presence of a normal serum concentration of thyroid hormones. In two hypothyroid patients a normal serum T3, low serum T4 and a low reverse T3 were observed. Microscopic studies of thyroid tissue from three of the sibs disclosed marked cellular hyperplasia with no lymphocytic infiltration anywhere in the tissue. Peroxidase activity was determined on tissue from three sibs by three different assay procedures. It was within the normal range in one patient and was significantly elevated in the other two. There was no evidence for a qualitatively defective peroxidase. The defect in thyroid function in this family does not appear to involve a peroxidase deficiency. Thyroglobulin isolated from the thyroid glands of two of the goitrous, hypothyroid subjects was poorly iodinated but was judged to be normal by immunoreactive and ultracentrifugation procedures. Although the nature of the thyroid metabolic defect in this family was not elucidated, the evidence suggests a genetic defect, probably involving a recessive gene.


Adrenoleukodystrophy: report of a familial case.

Adrenoleukodystrophy is an unusual disorder in which progressive diffuse demyelination of the cerebrum is associated with adrenal insufficiency, and which is transmitted as a sex-linked recessive trait. This report describes a 36-year-old-male, who first presented 12 years previously with hypogonadothrophic hypogonadism. It is only more recently that he has developed primary adrenal insufficiency, as well as a neurological disorder characterized by cerebellar, pyramidal tract and cerebral cortical abnormalities. One brother died at age 7 with Schilder's disease, while another brother suffered adrenal insufficiency, progressive mental and neurological deterioration and death at age 38 with post-mortem evidence of adrenoleukodystrophy. Histological studies have revealed cytoplasmic striated inclusions, which proved to be lipid in nature, but the precise defect in lipid metabolism has yet to be clarified.


Effects of the H2 receptor antagonist cimetidine on pituitary hormones in man.

The effects of the histamine (H2) receptor antagonist cimetidine on serum levels of prolactin (PRL), growth hormone (GH), thyroid stimulating hormone (TSH), luteinizing hormone (LH), follicle stimulating hormone (FSH) and cortisol were studied in five normal males. Cimetidine, when given by infusion at the dose of 100 mg/h for 5 h, did not alter adenohypophyseal secretion either basally or after pituitary stimulation with LHRH and TRH. However, 400 mg cimetidine given intravenously as a bolus injection significantly stimulated PRL release in all subjects, without affecting any other measured hormone. A dose-reponse relationship existed, and 200 mg cimetidine seems to be the minimum PRL-releasing dose when given as an intravenous bolus injection. These results suggest that cimetidine releases PRL and that this effect is dose-related, but only when large intravenous injections are given.


Radiation-induced hyperprolactinaemia in a treated acromegalic.

A 31-year-old acromegalic was normoprolactinaemic after partial removal of her pituitary tumour. The post-operative external pituitary irradiation lowered the mean growth hormone (GH) level from 75 mU/1 to less than 1 mU/1 within 2 years. However, at the same time hyperprolactinaemia developed. These changes in the GH and prolactin levels were confirmed 3 and 4 years after irradiation. The cause of the hyperprolactinaemia was radiation-induced hypothalamic damage. Therefore it is suggested that similar damage may occur in patients receiving external pituitary irradiation for 'prolactinomas' and that this mechanism may contribute to the persistent hyperprolactinaemia observed in such patients.


Unaltered basal prolactin secretion during short-term oestriol treatment in post-menopausal women.

Six post-menopausal women were submitted, at 1 month interval, to oral oestriol treatment for 14-day periods at daily doses of 2 and 6 mg. Blood samples were collected for LH, FSH and PRL measurements (by RIA) every other day during treatments as well as during a 14-day control period. Through the effect on LH levels was questionable, oestriol resulted in a clear and significant, although moderate, gradual decrease of mean FSH levels. At the doses used, which are effective in thetreatment of menopausal symptoms, but are devoid of any proliferative effect upon the endometrium, oestriol failed to induce any stimulatory effect on basal PRL secretion in these post-menopausal women.


Plasma unconjugated oestriol and unconjugated oestradiol-17 beta in late pregnancy: individual fluctuation of concentrations from day to day and every 10 minutes.

Plasma unconjugated oestriol (E3) and unconjugated oestradiol-17 beta (E2) were determined by radioimmunoassay. In ten normal women in their last month of pregnancy the individual fluctuation of E3 concentrations (mean of the coefficients of variation, CV) from day to day (over 5 days) was 15.6% (range 6.4--26.2%). The individual fluctuation of E2 determined in eight of these women was 16.9 (10.4--25.5) %. In six of the same women who had blood samples collected every 10 min (for 3 h) the individual fluctuation of E3 concentrations was 13.8 (7.0--25.1) %, and of E2 was 16.1 (11.3--26.0) %. The degree of fluctuation of E3 in individuals was in proportion to the mean concentration, unlike E2, suggesting that in clinical practice individual changes in E3 values would be as easy to interpret at low levels as at high levels. The finding that concentrations of plasma unconjugated E3 fluctuate in individuals no more than for E2 or than reported for total E3, and less than reported for 24-h urinary oestrogens, lends practical support to the theoretical preference for the assay of plasma unconjugated E3 to assess fetoplacental function.


Plasma dopamine-beta-hydroxylase activity and blood pressure variability in hypertensive man.

It has been proposed that measurements of plasma dopamine-beta-hydroxylase (DBH) may allow for assessmetn of adrenergic tone and may elucidate a possible neurogenic contribution to essential hypertension. We performed a series of measurements of DBH in fifty-seven normotensive and fifty hypertensive black and white men in order (1) to compare DBH to selected blood pressure patterns and (2) to evalutate the influence of salt intake, posture and race on plasma DBH. Plasma DBH, measured on unrestricted salt intake with subjects supine, was 42 +/- 4 Units/L in white normotensives, greater (P less than 0.05) than black normotensives (26 +/- 6 Units/L). White hypertensives had greater plasma concentrations of DBH than black (35 +/- 3 VS. 24 +/- 5, P less than 0.05). Normotensives did not differ from hypertensives. Dietary salt restriction and upright ambulation increased plasma DBH activity in hypertensives. Although DBH did not correlate directly with blood pressure, high DBH values were associated with lability of blood pressure in hypertensives but not in normotensives. There are two possible explanations for our results: (1) multiple factors influence plasma DBH activity and plasma levels reflect more than adrenergic function, or (2) essential hypertension is a multifactorial disease and excess sympathetic neuronal activity alone is not sufficient to produce sustained hypertension.


Hyperprolactinaemia and hypogonadism in men: response to exogenous gonadotrophins.

Three male patients with pituitary tumours and marked hyperprolactinaemia were investigated. Their prolactin (PRL) levels ranged from 210 to 2500 ng/ml. The subjects had clinical and laboratory characteristics of hypogonadotrophic hypogonadism. All were treated with human chorionic gonadotrophin (HCG) and in one subject human menopausal gonadotrophin (HMG) was given in addition. In all three patients, despite the persistence of hyperprolactinaemia, serum testosterone had risen to normal levels within 4--17 days after starting HCG. Despite the normal testosterone level, impotence persisted in two patients and the third had persistently decreased libido. The hypogonadism in these patients may be related to an absolute reduction in gonadotroph number secondary to destruction by tumour mass. Alternatively, hyperprolactinaemia may inhibit the synthesis or release of the gonadotrophins or LHRH. Despite hyperprolactinaemia, pharmacological doses of HCG induced testosterone secretion in all these three subjects.


Measurement of 1,25-dihydroxycholecalciferol in man by radioimmunoassay.

1 alpha, 25-Dihydroxycholecalciferol (1,25-(OH)2D3) has been measured in human serum by radioimmunoassay. The assay uses a high titre antiserum raised in sheep against 1,25-(OH)2D3-25-hemisuccinate, conjugated to bovine serum albumin. The sensitivity of the assay is 10 pg/tube. Other hydroxylated forms of vitamin D3 cross react with the antiserum and are therefore removed from serum extracts by chromatography on Sephadex LH 20 followed by high pressure liquid chromatography. The mean (+/- SEM) serum 1,25-(OH)2D3 concentration for a group of healthy adult subjects was 41 +/- 2.5 pg/ml. None was detected in anephric patients and the concentration was low or undetectable in patients with chronic renal failure.


A radiological study of the adenoid in normal children.

In this study the radiology of the adenoid is compared in two groups of children: those selected for adenoidectomy and those with a history of head injury who had had a lateral radiograph of the skull. The size of the adenoid was found to be the same in both groups though the nasopharyngeal airway was found to be significantly smaller in the children selected for adenoidectomy. On the basis of measurements in the normal children a lower limit of normal is suggested for the width of the nasopharyngeal airway, this is 2 mm in the case of children below the age of 70 months and 3 mm in the case of children over 70 months old. Only 17% of the children selected for adenoidectomy have abnormally narrow nasopharyngeal airways.


Mineral content of skeletal bones in otosclerosis.

In 63 patients with otosclerosis confirmed by operation, the bone mineral content was determined by photon absorptiometry. The bone mineral content and bone mineral concentration were found to be normal, which lends support to the assumption that otosclerosis is a localized disease and not a manifestation of a generalized disorder of the skeletal system.


The histopathology of the incus after stapedectomy.

Twenty-two temporal bones subjected to stapedectomy were examined by light microscopy for histological changes in the long process of the incus. In 19 cases a stainless steel wire technique had been used and in three a polyethylene tube operation had been performed. Twenty healthy unoperated ears were examined as controls. In all operated ears fibrosis and reduced vascularity of the mucosa was noted. In the polyethylene tube group, 1 ear showed the growth of new bone into the lumen of the tube and 1 showed minor resorption of the long process of the incus. In the stainless steel wire group bone resorption of the long process of the incus. In the stainless steel wire group bone resporption was seen in 5 cases and 1 incus also showed an area of necrosis adjacent to the tip; 2 of the 5 incudes showed some loss of the lenticular process. The main factor relating to bony resorption in this group was the presence of other histological changes resulting from postoperative inflammation. These findings represent a critical histological examination; the hearing results obtained appear to be good, although full audiometry is lacking.


Audio-visual discrimination of speech.

Tests utilizing audio-visual presentations of speech may have more significance than has hitherto been recognized. Such tests appear to offer more reliable, more realistic and more reproducible measures of communication impairments than either auditory speech discrimination tests, or visual speech discrimination tests.


Prenatal diagnosis of xeroderma pigmentosum (group C) using assays of unscheduled DNA synthesis and postreplication repair.

The analysis of DNA repair processes is described in two pregnancies at risk for xeroderma pigmentosum. In both cases, excision repair (measured by unscheduled DNA synthesis) and postreplication repair were analyzed. An affected and an unaffected fetus were identified within 3 weeks after amniocentesis. The cells from the affected fetus were found to be deficient in excision DNA repair, whereas the PRR patterns were intermediate between those of normal and PRR deficient cells. This indicates the possibility of prenatal diagnosis of PRR deficient XP patients (XP variants).


Complex de novo rearrangement of chromosome 9 with clinical features of monosomy 9p syndrome.

A girl with a complex rearrangement of chromosome 9 is reported. She shows the characteristic clinical features of monosomy 9p syndrome. The rearrangement was apparently preceded by four breaks which resulted in a presumptive tiny deletion of the distal end of the short arm, inversion of the rest of this arm and a proven deletion of the secondary constriction region of the long arm. By means of C-banding, it was possible to demonstrate the paternal origin of the rearranged chromosome 9. Finally, it is shown that the region determining the phenotypic expression of monosomy 9p syndrome is seemingly located at band 9p24.


Features of trisomy 18 and 18p- syndromes in an infant with 45,XY,i(18q).

An isochromosome for the long arm of chromosome number 18 - 46,XY,i(18q) - was found in an infant who had features of both trisomy 18 and 18p- syndromes. Findings compatible with trisomy 18 included postmature delivery, prominent occiput, severe congenital heart disease, overlapping fingers, and rocker-bottom feet. Those of 18p- syndrome, which frequently resembles Turner syndrome, were downward obliquity to the palpebral fissures, short, webbed neck, low posterior hairline, and widely-spaced nipples. The infant died of heart failure at 3.5 months of age. Parental karyotypes were normal.


Two abnormal clones in the bone marrow cells of a patient with paroxysmal nocturnal hemoglobinuria.

Paroxysmal nocturnal hemoglobinuria (PNH) is considered to be a clonal disorder, although most investigations have failed to show chromosomal abnormalities. The present patient suffered from PNH and exhibited in bone marrow cells two abnormal clones with 47 chromosomes in addition to cells with 46 chromosomes. One clone showed trisomy 9, a finding previously reported in leukemias and myeloproliferative disorders. Thus, PNH seems to be a clonal myeloproliferative disease.


Five familial cases with a trisomy 16p syndrome due to translocation.

A clinical description is given of a syndrome present in three postnatally and two prenatally detected cases with partial trisomy 16p, caused by a familial translocation t(16;21) (p11;q22). The most consistent features of this syndrome are: low birth weight, small head circumference, low-set ears, palato(gnatho)schisis, micrognathia, thumb-agenesis or hypoplasia, hypertonia, overlapping fingers, single umbilical artery, and psychomotor retardation. The clinical picture was identical to that described by Roberts & Duckett (1978) for a single case.


Immunological investigation in adenine phosphoribosyl transferase (APRT) deficiency.

In a family with partial or total adenine phosphoribosyl transferase (APRT) deficiency, T and B cell function was evaluated by counting rosette-forming cells, by investigating lymphocyte transformation to phytohaemagglutinin (PHA), concanavalin A (Con A) and pokeweed mitogen (PWM), by assaying serum immunoglobulins and determining lymphocyte membrane immunoglobulins by immunofluorescence. Delayed cutaneous hypersensitivity was also assayed. The absence of gross immunological deficiency in the homozygotes, as well as in the heterozygotes, suggests that the APRT-mediated pathway of purine metabolism is relatively unimportant for lymphocyte function.


Circulating immune complexes in various thyroid diseases.

In a study of 171 patients with various thyroid diseases, circulating immune complexes (CIC), measured by a C1q solid phase radioassay, were detected in 26% of the patients as compared to 8% of the control subjects. CIC were found in 33--55% of the patients with a well defined thyroid autoimmune disorder (Hashimoto's goitre, asymptomatic thyroiditis, spontaneous myxoedema and Graves' disease) and also in the same proportion of patients with diffuse goitre. CIC were correlated to the presence of serum antibodies to microsomal thyroid antigen but not to their titre. No relationship was observed between CIC and the age or sex of the patients and the presence of exophthalmos, or between CIC and the different thyroid function tests or serum anti-thyroglobulin antibodies. CIC were found in untreated patients as well as in those treated with prednisone, methimazole or thyroxine.


Characteristics of complexes for arming and inhibiting effector cells for antibody-dependent cell-mediated cytotoxicity.

The size of IgG aggregate effective in the inhibition or arming of human effector cells for antibody-dependent cell-mediated cytotoxicity (ADCC) was investigated using heat- and alkalipolymerized rabbit IgG or purified antibody fractionated by gel filtration. In contrast to the inhibition of ADCC against chicken erythrocytes, which was marked when effector cell were pre-incubated with high molecular weight aggregates (19S or greater), small polymers were most effective in arming for cytotoxicity against antigen-coated chicken red cells. Our data also demonstrate that while the cytotoxic potential of armed cells is short-lived and rapidly lost during culture at 37 degrees C but not 4 degrees C, the reduced capacity of these cells to kill antibody-coated targets is not altered by similar incubation at 37 degrees C. The differences in the size of aggregate active in arming and inhibition, and the stability of the two phenomena are compatible with the hypothesis that large aggregates may cause more cross-linking and redistribution of effector cell Fc receptors than small polymers of IgG.


Inhibition of neutrophil migration by sera from patients with rheumatoid arthritis.

Sera from patients with rheumatoid arthritis inhibited the migration of human neutrophils in 63% (twenty-two out of thirty-five) of the cases tested. The inhibition was not due to a toxic effect of the serum as it was reversed by a chemotactic stimulus. There was a strong correlation between the degree of inhibition of neutrophil migration and the amount of immune complexes present in the sera as determined by the C1q binding activity. It is suggested that the inhibition of neutrophil migration is due to the presence of circulating immune complexes, and that the capacity of immune complexes to inhibit neutrophil migration in vitro may also contribute to the accumulation of neutrophils at sites of immune complex formation in vivo.


A longitudinal study of immunological parameters in multiple sclerosis: cell-mediated immunity and complement profiles.

In a 1 year longitudinal study of twenty-two patients with multiple sclerosis (MS) and twenty-one normal control subjects, peripheral blood leucocytes were stimulated with lipoplysaccharide (LPS), a B cell mitogen, and phytohaemagglutinin (PHA) a T cell mitogen. EA- and EAC-rosette formation was also performed to assay null and B cells respectively, and the serum concentration of the C3 component of complement was determined. For ten multiple sclerosis (MS) patients with stationary phases of the disease, percentages of lymphocytes significantly lower than normal were found with normal leucocyte counts in the peripheral blood. Lymphocyte stimulation by PHA was significantly lower than normal in stable MS, while neither LPS stimulation nor EA- and EAC-rosette formation differed significantly from the controls. The C3 serum concentration was found to be significantly higher than normal. For nine out of twelve MS patients with a fluctuating clinical course, the C3 concentration was elevated during remission, but dropped to normal levels during relapse. None of the other parameters studied could be correlated with the clinical course.


The spleen is required for the suppression of experimental allergic encephalomyelitis by prostaglandin precursors.

In this paper we report a study of the effects of splenectomy on the immunosuppressive action of essential fatty acids (EFA) which is thought to be mediated through prostaglandins (PG) produced in the spleen. Experimental allergic encephalomyelitis (EAE) was induced in normal, splenectomized and sham splenectomized Lewis rats. EFA were administered orally, the animals in the control groups being treated with liquid paraffin. Treatment with EFA significantly suppressed clinical disease in those animals in which EAE was induced by the inoculation of central nervous system material of guinea-pigs or by passive transfer by Con A-stimulated spleen cells. Splenectomy abrogated the suppressive effect of EFA. This observation, together with previous results showing the abrogation of EFA immunosuppression by an inhibitor of the biosynthesis of PG from EFA, led us to postulate a close relationship between EFA, PG and a splenic factor suppressing immunopathological mechanisms in EAE.


Effects of repeated Corynebacterium parvum and BCG therapy on immune parameters: a weekly study of melanoma patients II. Changes in serum immunoglobulins and lymphoid cell subpopulations.

Two groups, each of eight patients, with metastatic melanoma were immunized with either C. parvum or BCG at 3-weekly intervals. The serum IgG, IgA, IgM levels, E-rosettes, EA-rosetts, sIg-bearing cells, 'null cells' and lymphocyte blastogenesis at four PHA concentrations were assayed, before immunization and weekly thereafter for 8 weeks. The pre-immunization E-rosette values were significantly reduced, with a significant increase in 'null cell' values and EA-rosette percentages, when compared with healthy controls. Following C. parvum immunization, significant increases occurred in E-rosette percentages with decreases in EA-rosette and 'null cell' counts. A significant reduction in 'null cell' values also occurred with BCG. Other parameters including PHA blastogenesis did not exhibit statistically significant changes. Different methods of expressing the results (particularly of blastogenesis data) were compared, as were the similarities between the present investigation and a study of the effects of a single immunization. The relationship between the subpopulation changes and lymphocyte cytotoxicity described in an earlier article (Thatcher, Swindell & Crowther, 1979a) is discussed.


Transfer factor therapy in hyperimmunoglobulinaemia E syndrome.

The therapeutic effect of transfer factor (TF) from healthy donors was investigated in two children with extensive intractable atopic dermatitis, recurrent pyogenic skin infections, hyperimmunoglobulinaemia E, defective neutrophil chemotaxis and depressed cell-mediated immunity. Striking clinical improvement was noted in both patients with disappearance of skin infections, pruritus and eczema. No new lesions have occurred 13 months after the completion of therapy in the first patient but a few new atopic lesions have reappeared after 8 months in the second. Both patients are off steroids and antibiotics. Transfer factor administration did not influence the T cell rosette number or the lymphocyte blastic transformation response, but it did cause conversion of the skin-test reactivity in both patients and correction of polymorphonuclear chemotaxis in one of them. Non clinical side-effects were noted but marked and persistent rise of serum IgE was observed in both patients. Our data suggest that patients with hyper-IgE syndrome may be benefited by TF therapy and they lend further support to the notion that T lymphocyte deficiency may be the basis of the eczema in this syndrome.


Re-examination of the EA rosette assay (Ripley) for Fc receptor leucocytes.

Numerous investigations has utilized rosette formation with Ripley antibody-coated human erythrocytes (EA) to identify or deplete Fc receptor-bearing K lymphocytes in whole mononuclear cell preparations. This study examines the interaction between Ripley EA and purified preparations of human lymphocytes, monocytes and neutrophils and demonstrates that this technique is not specific for K lymphocytes. Indeed, 100% of blood monocytes rosette these EA target cells. Moreover, data from both rosetting studies and antibody-dependent cytotoxicity (ADCC) reactions suggest that the avidity of Ripley EA is actually greater for monocytes than for lymphocytes. In contrast to previous reports, 100% human neutrophils were found to possess Fc receptors, as determined by their ability to rosette Ripley EA. Thus, the extent of rosetting and ADCC by all three Fc receptor-bearing leucocytes depends significantly on the degree of antibody sensitization with neutrophils requiring the greatest, and monocytes the least, amount of target-bound antibody for Fc receptor-mediated interaction.


Corticosteroid enhancement of immunoglobulin synthesis by pokeweed mitogen-stimulated human lymphocytes.

The effects of the addition in vitro of corticosteroid on pokeweed mitogen (PWM) induced Ig synthesis by human peripheral blood lymphocytes were studied. IgG in supernatants produced under standardized culture conditions was measured by double antibody radioimmunoassay. The addition of 10(-6)M prednisolone caused a remarkable enhancement of PWM-stimulated IgG synthesis beginning at day 4 of culture and increasing at a faster rate than that in cultures with PWM alone. 10(-6)M prednisolone resulted in a geometric mean enhancement of 5.6-fold of PWM-stimulated IgG synthesis in all twenty-five normal controls studied. This enhancement occurred up to 3 days after the addition of PWM. 10(-6)M and 10(-5)M prednisolone resulted in significantly greater enhancement of PWM-stimulated IgG synthesis than 10(-7)M prednisolone. Hydrocortisone, prednisolone, methylprednisolone, betamethasone and dexamethasone at 10(-6)M were all equally effective in the enhancement of PWM-induced IgG synthesis.


Peripheral lymphocytes changes in the anamnestic response to tetanus toxoid challenge.

Few data are available on the blood lymphocyte response to revaccination in man. The anamnestic response to tetanus toxoid challenge was evaluated by a variety of techniques during the first week after revaccination. Out of twenty subjects used, eight were evaluated before and 5 days after the injections (days 1--8). Analytical cell electrophoresis showed important variation in the B and two T lymphocyte populations. The B cell percentages, assessed by EAC-rosettes and electrophoretic mobility, were found to decrease by days 2 and 3, and return to former levels by day 8, when a rise in specific antibodies was detected. A similar response was found in the T1 population generally considered to be composed of low affinity E-rosette-forming cells. Conversely, a significant increase (50--100%) in circulating T2 lymphocytes (active rosette-forming cells) was found by days 2 and 3, followed by a rapid decrease of these 'differenciated' cells. The increase in the T2 lymphocytes appeared earlier in skin test positive subjects. These changes were correlated with E-rosettes, mitogen stimulation, peripheral leucocyte migration inhibition and transformation in the presence of the antigen. EA-IgG rosettes and ADCC varied similarly. These results may indicate a significant non-specific cell mobilization following revaccination.


Proteolysis of human IgG by human polymorphonuclear leucocyte elastase produces an Fc fragment with in vitro biological activity.

The Fc fragment derived by proteolysis of human IgG by human polymorphonuclear leucocyte (PMN) elastase was tested for in vitro biological activity. This fragment could attach to the specific IgG receptor of Staphylococcus aureus Cowan I cells (protein A) and could be eluted from the cells with dissociating buffer. Taking advantage of this attachment, it was shown that the Fc fragment is capable of attaching to the antigen-combining site of an IgM rheumatoid factor and can bind to the Fc receptor of human PMN. A similar fragment produced in vivo at sites of inflammation could play a role in regulating the inflammatory response.


The reversal of surgically induced reticuloendothelial depression.

The function of the reticuloendothelial (RE) system may be depressed by surgical operation. As this system is an important defence mechanism against tumour growth and metastasis, it would be an advantage if this depression could be prevented by the administration of a suitable agent. The agents studied in this case were levamisole, Corynebacterium parvum (C. parvum) and glucan. As a measure of RE function a carbon clearance test was performed in rats, 1 hr after partial colectomy, animals having received pre-operative treatment with one of these substances. The results show that operation produced a significant fall in clearance (P less than 0.001). Both C. parvum and glucan were very effective in preventing any fall of clearance following operation (P less than 0.01). Both of these produced marked RE stimulation and values in animals given these agents remained above control values even after surgery. Levamisole had some effect in preventing the RE depression (P less than 0.02), but was not as effective as either C. parvum or glucan.


Circulating immune complexes in normal pregnant women and in some conditions complicating pregnancy.

The polyethylene-glycol (PEG) precipitation assay was used to examine the sera of sixty-nine pregnant women, thirty with normal pregnancies, ten with toxaemia of pregnancy, eleven with pregnancy complicated by diabetes and eighteen with case histories of recurrent abortions in order to find evidence of eventual circulating immune complexes (CIC). CIC were not seen in normal pregnancies, but were found in two of the toxaemic group, in two of those with recurrent abortions and in two of those with diabetes. After delivery, these six positive cases were all negative. The presence of CIC may have a determining role in the pathogenesis of some of the cases of the above conditions.


The effect of defibrination on macrophage participation in rabbit nephrotoxic nephritis: studies using glomerular culture and electronmicroscopy.

Recent studies in experimental crescentic glomerulonephritis, using the technique of glomerular culture, have shown that the macrophage is a major cell type present within the glomeruli and developing crescents. It has been suggested that their accumulation is a consequence of glomerular fibrin deposition. The effect of defibrination with ancrod on the cellular events occurring in experimental crescentic glomerulonephritis in the rabbit was therefore assessed in this disease using the techniques of culture of isolated glomeruli, electronmicroscopy or renal tissue, and light microscopy. Defibrinated animals developed only minimal renal impairment, virtually no fibrin deposition in Bowman's Space and only a mild degree of crescent formation, in contrast to the severe renal failure, fibrin deposition and crescent formation that occurred in the untreated animals. The culture of isolated glomeruli and electronmicroscopy of intact renal tissue demonstrated large numbers of macrophages within and emerging from glomeruli of both defibrinated and untreated animals. However, only in untreated animals were macrophages seen to migrate into Bowman's Space, phagocytose fibrin, transform into epithelioid cells and accumulate to form crescents. These studies suggest that fibrin deposition in Bowman's Space is the major stimulus to the macrophage migration from capillary loops and accumulation in Bowman's Space. However, fibrin deposition does not appear to be the stimulus to macrophage accumulation within capillary loops as this event was not affected by defibrination.


Heterogeneity of anti-mitochondrial antibodies: characterization and separation of the antigen associated with the pseudolupus erythematosus syndrome.

It could be shown that anti-mitochondria antibodies (AMA) found in drug-induced pseudolupus erythematosus syndrome (PLE) had a different specificity from those found previously in primary biliary cirrhosis (PBC). The PLE antigen could be easily separated from the PBC antigen either by isopycnic sucrose density gradient centrifugation of cytoplasmic extracts (supernatant 40) or purified sonicated rat liver or kidney mitochondria. The PLE antigen was firmly membrane-bound and, in contrast to the PBC antigen, not solubilized by treatment with various salts or enzymes. The ATP-ase complex, the probable target antigen of PBC-specific antibodies, did not react with sera from patients with the PLE syndrome. There is evidence that the PLE-associated antibodies (M3) occur exclusively in patients who have been sensitized to derivatives of pyrazolone or their metabolites, indicating that PLE antibodies may be specific markers for this type of drug allergy.


Regulation of secondary antibody responses in rodents. I. Potentiation of IgG production by cyclophosphamide.

This paper describes the effects of a single dose of cyclophosphamide on specific IgG production in rats during an established secondary immune response. (PVG X Agus)F1 rats were immunized twice (days 0 and 28) with chicken erythrocytes (CRBC), received cyclophosphamide (100 mg/m2 of body surface area) on day 33 and were killed 8 days later. The production of anti-CRBC IgG antibodies was assessed by testing the supernatants of spleen cell cultures in a cytotoxicity assay with 51Cr-labelled CRBC as target cells and normal rat spleen cells as effector cells. In observations of fifty-nine pairs of treated and untreated rats from eight separate experiments, the administration of cyclophosphamide resulted in: (1) a decrease in the number of spleen cell to a median of 10(8.63) from a median of 10(8.7) (P less than 0.0025); (2) an increase in the anti-CRBC IgG antibody titre of the supernatants of cultured spleen cells to a median of 10(0.67) from a median of 10(0.27 (P less than 0.0025); and (3) the calculated anti-CRBC. IgG antibody production per spleen to be increased in the drug-treated rats to a median of 10(2.26) from a median of 10(2.0) (P less than 0.005). In a cyclophosphamide dose-response study, it was shown that some enhancement of antibody production was induced by doses between 12.5 and 50 mg/m2 and consistently elevated levels of antibody production were associated with doses between 100 and 400 mg/m2.


Long-term deficiency of essential fatty acids in rats and its effect on brain recovery.

1. Nineteen-day old rats were fed an essential fatty acid deficient diet for 37 weeks, thereby making them essential fatty acid deficient for at least 24 weeks. The weights of their brains were 33% less than those of rats on control diets. 2. When the deficient rats were rehabilitated for ten weeks on a diet containing 5% by weight corn oil as a source of essential fatty acids, the weights of their brains were still 30% less than those of the controls. 3. Analysis of the brain lipids showed that, there was a large reduction in the proportions of cerebrosides and sphingomyelin in essential fatty acid deficiency. 4. Essential fatty acid deficiency was also characterised by the appearance of a high proportion of eicosatrienoic acid (20:3) and the reduction of arachidonic acid (20:4) and the other essential fatty acids. 5. Rehabilitation for a period of 10 weeks did not reverse these changes in brain composition. 6. It is considered that the feeding of essential fatty acid deficient diet to rats for a prolonged period of time causes retardation of brain maturity and makes the brain resistant to later dietary manipulations.


The influence of intraperitoneally injected 6-hydroxydopamine on electroshock seizure in chicks and rats.

1. 6-Hydroxydopamine, injected intraperitoneally in rats and chicks, did not induce spontaneous seizures but produced significant alterations in the threshold to electroshock seizure in chicks; the particular effects were dose-dependent and time-dependent. 2. Administration of 6-hydroxydopamine to 3 day old chicks and rats in the first and third days after birth resulted in an increase in the proportion exhibiting tonic seizure with electroshock when tested after 10-12 weeks. 3. When 6-hydroxydopamine was injected intraperitoneally into adult rats and cocks, there was no significant alteration in seizure threshold. 4. The results suggest that 6-hydroxydopamine penetrates the central nervous system of young chicks and rats and that adrenergic mechanisms are probably involved in modulating seizure mechanisms in both the chick and rat.


Effects of atenolol and propranolol when added to long-term antihypertensive diuretic therapy.

The antihypertensive effects of atenolol and propranolol were compared in a double-blind crossover study of 19 patients with essential hypertension (World Health Organization, I and II) who were receiving long-term diuretic treatment (chlorthalidone, 50 mg daily) during the study. After a 3-wk placebo period, a beta-adrenergic antagonist was administered once daily (atenolol, 50 mg daily, or propranolol, 80 mg daily) for a week. If the MAP was more than 108 mm Hg at the end of the week, dosage of the beta-blocker was doubled the following week; when necessary, doubling was repeated to a maximum dose of 640 mg propranolol and 400 mg atenolol daily. Fifty milligrams atenolol had a greater effect than 80 mg propranolol and was as effective as 160 mg propranolol. The dose-response curve flattened off after 160 mg propranolol and 50 mg atenolol daily. The two highest doses of atenolol lowered MAP more than the highest doses of propranolo. Heart rate slowing was the same for both drugs and did not correlate with the fall in blood pressure. PRA was suppressed by all doses of propranolol, whereas atenolol suppressed PRA only at the 2 highest doses, (200 and 400 mg daily). With the lower propranolol doses, the percent MAP change correlated weakly with the percent PRA change (80 mg--r = 0.41, p less than 0.1; 160 mg--r = 0.64, p less than 0.05). Side effects were minimal, and were noted only with 640 mg propranolol; with this exception, the percentage of patients with no complaints rose when placebo was replaced by beta-blockers.


Hydrochlorothiazide-induced sympathetic hyperactivity in hypertensive patients.

Hydrochlorothiazide-induced diuresis and natriuresis is considered to be responsible for the antihypertensive effect of this drug. After short-term treatment there is decreased cardiac output and increased peripheral resistance which we have found to be attended by increased plasma norepinephrine (NE) levels. After longer treatment cardiac output returns to normal and peripheral resistance declines. At this time, plasma NE levels remain elevated, indicating that peripheral resistance reduction is not a consequence of a reduction of the elevated level of sympathetic activity. These results provide a rationale for the combined use of diuretics and drugs which diminish noradrenergic activity in the treatment of hypertension.


Effects in normal subjects of long-term administration of azosemide.

Azosemide is a new loop diuretic which has been shown to affect solute transport proximal to the diluting segment. We assessed the effects of chronic administration of azosemide in normal subjects on low and normal salt diets. In both, there was compensatory renin release and aldosterone secretion, but the subjects on the low sodium diet developed striking hyperuricemia and metabolic alkalosis and were symptomatic, whereas those on the normal diet compensated to the extent that there were only minor changes.


Haloperidol-induced syndrome of inappropriate secretion of antidiuretic hormone.

Several psychotropic drugs have been associated with the syndrome of inappropriate secretion of antidiuretic hormone (SIADH). We report here a patient who on two occasions developed clinically significant hyponatremia while receiving the antipsychotic drug, haloperidol. The criteria for the syndrome of inappropriate secretion of ADH were fulfilled and other causes of SIADH were excluded. We documented inability in this patient to excrete a water load while on haloperidol and normal ability in its absence. This case therefore illustrates SIADH due to haloperidol.


Pharmacokinetics of N1-acetyl- and N4-acetylsulphamethoxazole in man.

The pharmacokinetics of N1-acetylsulphamethoxazole and N4-acetylsulphamethoxazole in man are described. N1-Acetylsulphamethoxazole is deacetylated to sulphamethoxazole and acetylated to N4-acetylsulphamethoxazole. N4-Acetylsulphamethoxazole is excreted almost unchanged in the urine. The renal excretion rate is independent of the urine flow and urinary pH. N4-Acetylsulphonamides are less lipid soluble and more acidic than their corresponding parent sulphonamides.


Phenytoin cumulation kinetics.

Four male subjects were given phenytoin orally in single or twice-daily doses. Subjects were on 2 or 3 different dosing rates from 260 to 600 mg phenytoin sodium daily. Predose blood samples were obtained almost daily. The resulting serum levels, measured by gas-liquid chromatography, ranged from 1 to 18 micrograms/ml. Serum phenytoin concentration-time data were fit to a 1-compartment open model with zero-order input and Michaelis-Menten elimination. The resulting computer-generated parameter estimates (Vmax, 5.28 to 8.41 mg/kg/day; Km, 0.83 to 4.18 mg/1; Vd, 0.74 to 0.97 1/kg) are in agreement with the ranges of values in the literature. The time course of phenytoin cumulation is compatible with the presence of a major elimination pathway exhibiting Michaelis-Menten kinetic behavior.


Effects of nefopam on visual tracking.

The effects of 2 doses of nefopam, d-amphetamine, pentazocine, and placebo were studied in healthy male sleep-deprived volunteers to determine whether the drugs improved or impaired coordination and whether they induced subjective effects. A critical tracking task was used to study hand-eye coordination. D-amphetamine, 10 mg orally, significantly improved tracking performance and made subjects feel better able to perform tasks but more anxious. It also made them feel more alert, steady, sociable, and strong. Pentazocine, 45 mg intramuscularly, caused deterioration in tracking performance and was followed by reports of depression, gloominess, dreaminess, nausea, and injection site pain. There was no significant change in tracking performance or subjective effects after both doses of nefopam and placebo.


d-Propoxyphene kinetics after single oral and intravenous doses in man.

d-Propoxyphene kinetics was studied in 8 healthy male subjects after single oral doses of d-propoxyphene at 65, 130, and 190 mg and after slow intravenous infusion of 65 mg. Total urinary excretion (7 days) indicated complete oral absorption but systemic availability was reduced corresponding to fist-pass elimination of 30% to 70%. There was linearity between oral dose and the corresponding area under the plasma concentration/time curve of d-propoxyphene and the metabolite norpropoxyphene. The kinetic measurements showed 2- to 3-fold interindividual variations: oral clearance, 1.3 to 3.6 1/min; systemic clearance, 0.6 to 1.2 1/min; apparent volume of distribution, 700 to 1,800 1; d-propoxyphene half-life (t1/2), 8 to 24 hr; and norpropoxyphene t1/2, 18 to 29 hr. There were pronounced intraindividual dose-dependent variations in oral clearance in some subjects. The intravenous concentration curves indicated a 3-compartment distribution model.


Drug metabolism in liver disease: activity of hepatic microsomal metabolizing enzymes.

The concentration of cytochrome P-450 and activities of the microsomal enzymes aryl hydrocarbon hydroxylase and ethylmorphine demethylase were measured in hepatic tissue obtained at biopsy from 69 patients. Antipyrine half-life (AP t1/2) was measured simultaneously as an in vivo marker of drug metabolism. Values for each index of the drug-metabolizing system varied greatly, but the mean values in groups of patients with mild hepatitis or inactive cirrhosis did not differ significantly from those of controls. Hepatic cytochrome P-450 content and aryl hydrocarbon hydroxylase activity were lower in patients with severe hepatitis or active cirrhosis than in controls, but ethylmorphine demethylase activity was unchanged in the patients. Drug ingestion was associated with enhancement of drug-metabolizing enzymes in all patients but those with severe liver disease; ethylmorphine demethylase activity was enhanced proportionately more than aryl hydrocarbon hydroxylase activity or cytochrome P-450 concentration. The observation that aryl hydrocarbon hydroxylase and ethylmorphine demethylase activities are influenced to a different extent by liver disease and also by drug ingestion indicates functional heterogeneity of the hepatic microsomal drug-metabolizing system in man. Correlations between t1/2 and hepatic drug oxidases were weak, even when allowance was made for variation in liver size. Thus, the rate of drug metabolism in vivo assessed by measuring AP t1/2 does not appear to be closely related to the activity of some hepatic drug-metabolizing enzymes.


Tobramycin pharmacokinetics in morbidly obese patients.

Tobramycin kinetics were examined in 9 morbidly obese women following a single intravenous (120 mg) bolus. After the injection, serum elimination conformed to a 2-compartment open model with alpha and beta t1/2s of 0.285 and 2.1 hr. The volume of distribution (Varea) was determined to be 0.44 1/kg ideal body weight (IBW) and 0.20 1/kg total body weight (TBW). To normalize Varea to 0.26 1/kg, 58% of the patients' adipose weight (TBW -- IBW) must also be taken into account.


Influence of methylxanthine-containing foods on theophylline metabolism and kinetics.

The metabolism and kinetics of 14C-labeled theophylline have been studied after intravenous doses of 100 mg to healthy subjects, keeping to their usual diets after 7 days of abstention from methylxanthine-containing foods and beverages and again after such abstention while taking caffeine and theophylline in tablet form. The metabolism of oral 14C-theophylline has also been investigated. Metabolites were separated and quantitated by ion-exchange column chromatography, ion-exchange paper chromatography, and liquid scintillation counting. Three major metabolites were found in urine in addition to theophylline, namely 3-methylxanthine, 1,3-dimethyluric acid, and 1-methyluric acid, and 2 minor metabolites were detected but not identified. The elimination kinetics were studied after intravenous administration; theophylline, 1,3-dimethyluric acid, and 1-methyluric acid were eliminated by first-order processes, while elimination of 3-methylxanthine was described by Michaelis-Menten kinetics. Abstention from methylxanthine-containing foods and beverages led to a significant decrease in the urinary elimination half-life of 14C from 9.8 to 7.0 hr (p less than 0.02) due to increases in the elimination constants for theophylline, 3-methylxanthine, and 1,3-dimethyluric acid. When the methylxanthine content of the methylxanthine-containing foods and beverages was replaced by caffeine and theophylline in table form, kinetics and metabolism of theophylline were the same as in subjects on usual diets.


Restoration of selective facial nerve function by the nerve-muscle pedicle technique.

The nerve-muscle pedicle technique for selective reinnervation of paralyzed facial muscles, when combined with a modified muscle-fascia sling and neurotization from the temporal muscle, has been applied in 26 patients to date. The success rate has been 88 per cent for restoration of tonus and 77 per cent for restoration of voluntary motion as well. This procedure offers several significant advantages over other accepted means of reinnervation in patients in whom the seventh nerve itself is not available as a source for restoration of function. It also may have value as a method for rapid restoration of tonus while other means of reinnervation take effect.


Facial nerve grafting: a thirty year retrospective review.

It is axiomatic that nerve grafting be considered as an integral part of every ablative or traumatic injury involving the extratemporal main trunk and branches of the facial nerve. Our experience with 170 autogenous grafts has established the efficacy of the technique and has proved the high regenerative and adaptive capacities of the facial nerve system.


Cross-face nerve transplant.

The two stage principle is one of the most important features of the procedure. It allows starting the operation at a very early stage (one to six months). The donor area in the periphery is very well supplied, therefore as many facial fascicles as necessary can be sacrificed on the healthy side. We have never noticed any functional disturbances. The nerves leading to the buccinator muscle and those which innervate the lateral pull of the mouth are especially suitable. This weakening of the strong pull of the mouth is of great value for symmetry but unfortunately relapse to the original state is common. The selection of the nerve fascicles on the healthy side must be executed in a deep layer below the muscles because all large branches are located here. The end of the sural grafts should positioned far back on the paralyzed side to enable easy anastomoses at the second stage. A face lift incision on the paralyzed side and tightening of the skin are of additional value and provide some support to the elongated muscles. The combination of cross-face nerve transplant with other substitutional methods in which muscles are used for reinnervation is very promising. In our experience physiotherapy is a very important measure. It should be started after the onset of the palsy and continued until restoration of the face is complete. It is usually applied three times a week with exponential current and at a strength of 20 to 60 milliamperes. Each group of muscles receives a 2 to 3 minutes dosage. It is helpful if the patient can use a stimulation apparatus at home daily for short treatments.


I. Hypoglossal facial anastomosis: its significance for modern facial surgery. II. Combined approach in extratemporal facial nerve reconstruction.

The difficulties encountered in extratemporial facial nerve reconstruction after extensive trauma or following resection of parotid tumors often lead to unsatisfactory functional and cosmetic results. So far it has been common practice to use as a "regenerative nerve," the original facial nerve. Using this procedure, however, frequently only a portion of the peripheral branches can be reanastomosed. Above all, the "autoparalytic syndrome" develops in this situation owing to undirected outgrowth of axons, and an aberration of the blinking-reflex motoneurons occurs. Experience has shown that the isolated use of a cross-face transplant is not suitable for satisfactory functional regeneration. Depending on the individual anatomic situation, a number of possibilities are therefore recommended for a combined approach using several "regenerative nerves." In this connection, the particular physiologic properties of these nerves have to be taken into account which can help to improve considerably the functional and cosmetic results.


Program evaluation in a rural community mental health center.

Can a rural community mental health center with limited resources meet the federal guidelines for program evaluation? This case example shows that a rural center can comply with the guidelines through evaluation activities tailored to its special needs and small size.


Resistance to mental health consultation directed at change in public institutions.

Mental health consultants need to be aware that institutions in a community are frequently resistant to change. Official agreement that change is necessary may still evoke resistance by those individuals most threatened in the agency. The consultant's awareness of how such resistance is manifest and used permits some educative counterefforts which may be effective. There is a brief review of the literature, and case examples are given of effective and noneffective consultation.


Community mental health centers and the "seed money" concept: effects of terminating federal funds.

What happens to community mental health centers when federal funding ends? Analysis of the funding patterns of a cohort of "graduate" community mental health centers indicates that these centers remained fiscally viable subsequent to termination of basic federal grants. However, further analysis revealed two distinct funding patterns within the cohort. One group relied primarily on increased third-party reimbursements to offset the end of basic federal grants. The other sought more state funds and additional federal grants available through the Community Mental Health Center Amendments of 1975. As more centers "graduate," federal "floor funding" may be necessary to insure the survival of some of them.


Perceptional differences in the supervision of paraprofessional mental health workers.

Paraprofessional mental health workers and their supervisors completed critical incident questionnaires describing their most and least helpful supervision experiences. A categorical scheme summarizing these critical supervision experiences was developed. A comparative analysis indicated that both the paraprofessionals and supervisors recognized the importance of a supportive supervisory relationship. Paraprofessionals placed more emphasis on their supervisor as a role model, whereas supervisors placed more importance on the paraprofessionals' personal dynamics. The implications of the perceptional differences between paraprofessionals and their supervisors are discussed.


Stimulating equity of services to nonwhites in community mental health centers.

This paper describes a special date-based approach by the National Institute of Mental Health (NIMH) and the Health, Education and Welfare (HEW) regional offices to improve mental health service utilization nationwide for nonwhites and equalize these services with those available to whites.


Social support and social adjustment: implications for mental health professionals.

The general importance of an individual's support network has been recognized in the field of community mental health; yet a more detailed understanding of how a client's available social ties may contribute to his or her adjustment is presently lacking. This study used network analysis to examine differences in the social networks of mental health clients to identify factors associated with positive social adjustment. Subjects were selected from three different types of mental health programs as well as from the general population of Marion County, Oregon. Results generally revealed that subjects from the community sample more often would look to immediate family members for support. Better functioning chronic clients emphasized professional contacts, whereas more poorly adjusted chronic clients would look to friends for support. The results have implications both for understanding the nature of the support available to a client and mobilizing the support resources of the existing network of relationships to aid adjustment to community living.


Social indicators and mental health planning: an empirical case study.

This paper reports data from a series of studies designed to provide an empirical basis for making judgments regarding the utility and validity of social indicators as a method for assessing the need for mental health services. The following findings are included: (a) The methodological sophistication of the social indicators approach used did not greatly affect the utility of the technique as a means of identifying low- and high-need subareas in a large standard metropolitan statistical area. (b) Correlations between social indicator rankings of tracts/enumeration districts and mental health needs as determined by psychiatric scale scores varied in two different counties. (c) The degree of tract/district socioecological homogeneity appears to account for the diverse correlations. (d) Tract and enumeration district social indicator rankings uniquely account for less than 50% of the explained variance of individual mental health scores when analyzed in a regression equation which includes socioeconomic status as a variable.


A computer program for the analysis of crossover designs.

We describe a program, CROSS, which we have written to obtain potency estimates and other parameters for bioassay data from assays of crossover design. The program permits testing of all assays for statistical validity and calculates the complete analysis of variance for assays of balanced design. The form of data input and the complete documentation of assay results make this program particularly useful for anyone carrying out crossover assays on a routine basis. The analysis of variance presented is also useful for more general biological or medical situations.


A data analysis microcomputer package (DAMP) for biomedical signals.

The advent of cheap, powerful microcomputer systems makes the analysis of data via sophisticated techniques available to the personnel who are non-specialists in computing systems. The DAMP package described here is intended for use on personal computers and has therefore been written in BASIC for portability. The analysis techniques are powerful, comprising algorithms to perform sample-data generation, plotting displays, digital data filtering, auto-correlation functions, fast Fourier transforms and autoregressive modelling. The last technique contains a number of options including the display of z-plane plots, frequency response of the model, residual plotting and auto-correlation of the residuals. Illustrative results are shown from psychological mood data and rat locomotor activity. The package is designed both to instruct a user in the techniques of spectral analysis, and also to provide a range of methods for investigating time and frequency behaviour of biomedical data.


DIADEM--a system for the interactive data acquisition and processing in an analytical laboratory.

A conversational program for the acquisition of experimental data in a multi-user, multi-instrument computer system is described. It assists the researcher when recording on-time data. Due to the simple structure of the dialogue, no special knowledge of computer handling is required by the experimenter. Whereas the experimental methods are versatile, a uniform concept of the dialogue and the file structure is realized.


A computer model for hydrodynamic shearing of DNA (Gibb's phenomenon): Part II.

This paper presents an extension of the distribution proposed during hydrodynamic shearing of DNA. In the Fourier least square approximation of uniform random distribution or a square wave, Gibb's phenomena occur at the boundaries. The same behavior occurs at the boundaries of the DNA strands undergoing hydrodynamic shearing of DNA. This hypothesis is corroborated by results from a computer simulation of hydrodynamic shearing of DNA. The evidence helps confirm the kinetic experiments of Britten and Kohne [4]. Furthermore the results predict that sequence very near the end (0.2 LAMBDA) should be the most intact.


A computer program for the analysis of dental arch form using the cubic spline function.

This paper presents the details and logic of a FORTRAN computer program which fits a cubic interpolatory spline to a set of data points digitized from an exact size photographic reproduction of a dental model. It also measures the length of the arc and computes a set of normals to the curve to be used in evaluating the error in the fit of the spline. The program is used in studies of dental arch form and is useful in evaluating changes in the form of the arches due to orthodontic treatment. The measurement of the arc length provides an adequate assessment of space available in the dental arch, which is of importance to the orthodontist.


Computer processing of intracardiac electrograms for conduction studies.

Computer techniques developed to process intracardiac signals recorded in dogs are presented. The signals under measurement are the auricular and ventricular monophasic action potentials and the His bundle electrogram. Computerized measurement of significant timing parameters on simultaneous recordings of these signals can assess quite precisely changes in the normal conduction scheme of the heart provoked by different experimental protocols. Increased accuracy is mainly due to the objective way of defining wave onsets and the processing power of the system used. Signal recording, signal acquisition, automatic waveform measurements, interactive process and production of end result graphs by computer are all described.


Data security in information systems by language analysis.

The paper describes how a language analyser (parser) is used as interface between a user and the functions of an information system. A specific user is at log-on forced into a sublanguage analyser, which only recognizes statements relevant to this specific user. Every attempt to use non-allowed functions is rejected, and the user is guided into his sublanguage. The language analyser is defined completely separately from the semantics of the information system, and it can be automatically generated outgoing from a definition of language functions.


A user's experience with a standard non-linear regression program (BMDP3R).

A study was made to test and compare the behavior of a standard non-linear regression program (BMDP3R) in fitting data from six classical least-squares problems. The use of three program control parameters is discussed and four measures of regression failure are utilized to give a quantitative reference of success. Recommendations are given to aid the user of packaged programs in the parameter estimation of non-linear regression models.


A computer program for survival comparisons to a standard population.

PROPHAZ is a computer program created for the analysis of survival data using the general proportional hazards model. It was designed specifically for the situation in which the underlying hazard function may be estimated from the mortality experience of a large reference population, but may be used for other problems as well. Input for the program includes the variables of interest as well as the information necessary for estimating the hazard function (demographic and mortality data). Regression coefficients for the variables of interest are obtained iteratively using the Newton-Raphson method. Utilizing large sample asymptotic theory, x2 statistics are derived which may be used to test hypotheses of the form C beta = 0. Input format is completely flexible for the variables of interest as well as the mortality data.


Computed tomography in the diagnosis of brain stem gliomas.

Twenty patients with brain stem gliomas were diagnosed by CT. The diagnosis was established on the basis of characteristic appearance, density pattern and mass effect. Differentiation from brain stem metastasis or angioma is frequently possible based on CT findings.


Giant aneurysm of anterior communicating artery simulating 3rd ventricular tumor.

This is a case report of an anterior communicating artery aneurysm simulating a 3rd ventricular tumor with obstructive hydrocephalus demonstrated on CT scan. Angiography showed the "tumor" to be an aneurysm. We believe that giant aneurysms of the anterior communicating artery should be included in the differential diagnosis of suspected 3rd ventricular tumors along with suprasellar masses as seen on CT scans.


CT for the follow-up of cranial trauma.

The author's experience in diagnosing lesions of cerebral trauma with the CT scanner are outlined. The study is divided into acute and chronic lesions. Special attention is drawn to the morphology of subdural and intracerebral haematomas, which is dependent upon their duration.


Computed tomographic presentation of granulomatous reaction from intraventricular shunt.

A case is presented in which the patient was diagnosed as having a large mass lesion arising in the region of the quadrigeminal plate. The patient had been shunted in the past for hydrocephalus. The computed tomographic picture was that of a primary brain neoplasm. At surgery extensive granulation tissue was found. The similarity between the CT presentation of this inflammatory mass and a neoplasm is emphasized.


Evaluation of retroperitoneum with computerized tomography and ultrasonography in patients with testicular tumors.

Results of CT and US examinations in 24 patients with testicular tumors yielded similar sensitivity and specificity in the diagnosis of enlarged retroperitoneal lymph nodes found at laparatomy. Therefore, the choice of either imaging modality may be influenced by other factors such as presence of abundant bowel gas, post-operative wounds, surgical clips in the abdomen, cachexia or obesity.


Clinical application of computed tomography to thyroid disease.

CT examinations were carried out in 62 patients with various thyroid disorders, 42 patients with thyroid nodules, 12 with diffuse abnormality and 8 of others. Evaluation was made whether CT could provide more information compared with other techniques. Cystic thyroid nodules could be differentiated from solid nodules with a reasonably high degree of accuracy. Uncalcified thyroid carcinoma was noticed as an ill-defined nodule with irregular wall, grossly the same in density with the muscle in plain CT, and not opacified by contrast material. CT has the ability to define the nature of the thyroid nodules better than other nontraumatic diagnostic modalities.


Computed tomography of a double inferior vena cava: the "double cava" sign.

Right-sided retroperitoneal adenopathy or right adrenal masses demonstrated by CT in cross sectional display may mimic the CT appearance of the inferior- vena cava. This finding has been recently described as the "double cava" sign. The authors report this sign in a patient who actually has a double IVC. "CT angiography" with the technique described herein, will determine that the retroperitoneal structures demonstrated by CT are indeed vessels rather than enlarged nodes or adrenal masses.


Automated scene analysis of CT scans.

Since the advent of computed tomography, there has been an increasing realization that CT scans contain quantitative as well as qualitative information useful in the diagnostic process. Often however, the use of this information is impeded by the tedious manual outlining of the areas of interest in the scan. To alleviate this problem, we have developed a scene segmentation algorithm which will automatically delineate areas of interest in a CT scan. This procedure uses known information about the expected objects in the scan in conjuction with an algorithm to label those objects. The resultant scene segmentation divides the scan into four anatomical areas: skull, normal brain, high density lesions and CSF. After an area of interest is interactively selected by the clinician, volume, density or other quantitative measures may be computed. Limitations of the algorithm and its clinical applications are discussed.


Measurements of the partial volume phenomenon.

The partial volume phenomenon can produce subtle changes in the reconstructed value of the linear attenuation coefficient which may in turn make the detection of an object more difficult. A model for studying the effects of the partial volume phenomenon is presented along with measurements made on the General Electric CT/T whole body scanner. The results of these measurements indicate that small differences in the linear attenuation coefficient may go unnoticed when the video display format is used exclusively to evaluate the CT image. It is suggested that this display format incorporate profiles of the CT numbers to assist the viewer in the evaluation of the CT scans.


Preliminary report of a new method of whole body CT-scanning.

The authors suggest a new approach to CT-body examination derived from their experience in spinal investigations. They introduce a method of gantry tilt in association with inclination of the patient, and call the new mode "longitudino-axial sectioning". This method makes possible the simultaneous display of several vertebral levels, which is not possible with conventional CT-scanning. They suggest that by extrapolation, the method may be applied to thoracic and abdominal investigations, as well as to the study of joints. In addition, this technique could be the method of choice whenever urinary and biliary tracts have to be investigated for diagnostic and/or interventional purposes.


Restoration of fertility after non-obstructive vasectomy in the rabbit.

This study was undertaken for the purpose of comparing reversibility following long-term sperm obstruction with that following long-term sperm diversion. The rabbit served as the animal model. Sperm obstruction was produced by transection and ligation of the vasa deferentia near the vasal ampulla; sperm diversion by transection of vasa and anastomosis of afferent limb with urinary bladder. After one year. vasal continuity was reestablished by end-to-end vasovasostomy. Restoration of fertility was more successful after sperm diversion than after sperm obstruction. It is concluded that vasocystostomy in the rabbit is a safe and effective method of male fertility control with greater probability for successful reversal than conventional vasectomy.


Salpingitis associated with the presence of nonmedicated IUDs.

Fallopian tube tissue obtained at Pomeroy sterilization of 75 normally cycling women, 75 women 2 to 3 days postpartum, and 75 asymptomatic women who had used a nonmedicated IUD for at least a year was examined histologically. There was an increased frequency of tissue edema and congestion in the postpartum group only. The frequency and extent of acute inflammatory changes in the three groups was not significantly different.


A collaborative study of the progesterone intrauterine device (Progestasert). The World Health Organization Task Force on Methods for the Regulation of Implantation.

A randomised double blind study of a plain T-shaped IUD and an active T-shaped IUD releasing 65 micrograms/day of progesterone, has been completed in four centres. A study of 1320 progesterone-releasing IUD's in parous women for 9660 women months of use significant to 18 months, gave a pregnancy rate of 1.0 +/- 0.4, expulsion of 4.7 +/- 0.6 and removals for pain and bleeding of 6.0 +/- 0.7. A detailed analysis of the menstrual bleeding patterns in these patients gave details of the number and length of bleeding and spotting episodes, count of bleeding days, and count of spotting episodes and days for four one-hundred-day reference periods. While the plain IUD contributed a significant number of intermenstrual spotting and bleeding days, the progesterone-releasing IUD contributed more spotting days.


Interruption of pregnancy with vaginal suppositories containing 16,16-dimethyl-trans-delta 2-prostaglandin E1 methyl ester.

A new synthesized Prostaglandin E1 analogue, 16,16-dimethyl-trans-delta 2-Prostaglandin E1 methyl ester, has been shown to be effective in termination of 1st and second trimester pregnancy following vaginal administration. Suppositories, each containing 1 mg Prostaglandin E1 derivative, were administered five times to each of fifty pregnant women of five to twenty gestational weeks at three-hourly intervals. The procedure was clinically effective in 86% of the patients resulting in 56% complete and 30% incomplete abortions. The cervix of all patients was dilated up to 7 mm in diameter at the second insertion of the suppository. Vaginal bleeding and lower abdominal pain not requiring sedation were observed in all patients. Diarrhea (42%), vomiting (6%), and fever (4%) were the most common side effects. The Karyopyknotic Index of the vaginal smear increased significantly (p less than 0.01) twelve hours after the initial insertion. The superficial cells of the cervix gradually degenerated during the termination procedure.


The hormonal and immunological status of vasectomised men.

The concentration of FSH, LH, testosterone and sperm agglutinating and cytotoxic antibodies have been determined in 87 men at varying time intervals after vasectomy. The results indicated that vasectomy is not associated with statistically significant changes in any of these parameters. Furthermore, no correlation existed between the development of sperm antibodies and the peripheral endocrine status of an individual.


Use-effectiveness and client satisfaction in six centers teaching the Billings Ovulation Method.

Use-effectiveness of the Billings Ovulation Method (OM) is reported for 1139 clients from six centers who were followed for at least 24 months. Method failure rates were 1% when calculated by either Pearl formula or life table analysis. Combined method and user failure rates were 20% when calculated with the Pearl formula, and 16% at 12 months and 23% at 24 months by life table analysis. Pregnancy rates were higher for couples using OM alone, than for couples using OM in combination with additional fertility awareness methods or together with barrier methods. The difference was significant when estimated by the Pearl formula but not when analyzed by the life table. The emotional implications underlying the apparent contradiction between a desire to avoid pregnancy and the deliberate coital use of fertile days are reflected in the differences between method and user failure rates, the high client satisfaction levels reported with "user failure," and 56% continuation rate at 24 months. The will require in-depth exploration.


Copper allergy and copper IUD.

Epicutaneous tests with copper, nickel and cobalt were performed in 37 patients using copper IUD who had shown side-effects to the IUD. None of them was allergic to copper; four were allergic to nickel and one to cobalt. Metal allergy was not considered to be the cause of the side-effects in any of the patients.


Subdermal norethindrone pellets -- a method for contraception?

The mode of action of compressed pellets containing 85 per cent norethindrone (NET) and 15 per cent cholesterol was studied. Four pellets were inserted subcutaneously, in each of five healthy volunteers and left in place for 200--229 days. The NET content of the pellets varied between 23.9 mg and 25.6 mg; and the cholesterol content between 4.2 mg and 4.5 mg. Plasma levels of NET, estradiol and progesterone were determined by radioimmunoassays. Plasma levels of NET varied mostly between 1--2 ng/ml the first month after insertion. After two months plasma levels of NET ranged between 0.5 ng/ml and 1 ng/ml in all volunteers and there was a gradual decrease of the plasma NET levels throughout treatment. Pronounced day-to-day variations in plasma NET levels were recorded. The release rates of NET was calculated to be between 187 micrograms/day and 243 micrograms/day among the five volunteers. Ovulations occurred in four out of five subjects during treatment. This study indicates that the release of gestagen from four NET pellets was only initially high enough to completely inhibit ovulation and that to accomplish full contraceptive efficacy, a higher dose, i.e. more pellets, would have to be inserted.


Use of contraceptives prior to and after conception and exposure to other fetal hazards.

In a large prospective study, set up to determine whether reproductive outcomes are affected by prior contraceptive use, 34,344 women were recruited at their first antenatal visit and followed until pregnancy termination. This paper summarizes the study methods and describes the demographic differences between subjects who used various contraceptives shortly before conception, and those who experienced contraceptive failures. Thirty percent of the women had used oral contraceptives (OCs) during the 5 months prior to conception and 2.4% had continued using them after their LMP. IUDs had been used by 5.8% of women before conception and 1.1% after. If these rates are also true for the whole population of the U.S., they indicate that approximately 70,000 babies are born each year following pill-failures and 30,000 following failures of IUD's. Exposure to other fetal hazards was common, with 48% of pregnant women drinking alcohol, 28% smoking, and 15% receiving diagnostic X-rays. OC use was more common among smokers and drinkers, and OC failures were significantly associated with the use of anti-epileptics, aspirin, and with exposure to radiation.


Pregnancies associated with sperm concentrations below 10 million/ml in clinical studies of a potential male contraceptive method, monthly depot medroxyprogesterone acetate and testosterone esters.

A potential male contraceptive approach was evaluated in clinical trials involving monthly injections of depot medroxyprogesterone acetate and either subdermal implants of testosterone propionate or monthly injections of testosterone enanthate. Pregnancies occurred in partners of 9 men with recent sperm counts of 10 million/ml or below. In 5 of the 9 instances, the sperm counts were less than 1 million/ml. It appears that male contraceptive methods involving spermatogenic suppression may require attainment and maintenance of azoospermia. The pregnancy rate cannot be calculated, because the extent of other contraceptive use is uncertain. There were no spontaneous abortions. 6 pregnancies were carried to term, and all progeny were normal, based on physical examination at birth or 3 months after birth.


Inhibition of implantation by intraluminal administration of concanavalin A in mice.

Important characteristics of endometrial implantation sites are the changes of polarity and molecular composition of the cellular surface. For this reason the masking of surface carbohydrates could lead to an inhibition of the recognition by the blastocyst of the endometrial implantation site. Considering the impact of lectins on carbohydrates, we decided to utilize the intraluminal administration (5 microliter) of different concentrations of concanavalin A (15-60 microgram) in pregnant female mice in the preimplantation phase. An inhibition of 100% of implantation wqs obtained with concentrations of 30 and 60 microgram of the lectin administered on days 3 and 4 of the pregnancy (P less than 0.001). Less important effects were observed on administering 15 or 20 microgram of the lectin (73 and 87% of inhibition) and on utilizing the different doses on days 1 and 2 of the pregnancy. Thus, we conclude that the egg must recognize certain molecules of the endometrial surface (alpha-D-mannopyranose and alpha-D-glucopyranose) in order to implant and that the making of these sites potentially constitutes a new contraceptive approach.


Carbohydrate metabolism prospectively studied in women using a low-estrogen oral contraceptive for six months.

Twenty-four women were prospectively evaluated for their carbohydrate metabolic status before and after six months of using an oral contraceptive containing 0.035 mg ethinyl estradiol and 0.4 mg of norethindrone. At each testing, a 100-gm oral glucose load was administered and blood glucose and plasma insulin values were measured over a three-hour period. Nineteen women with "normal" control tests demonstrated a significant decrease in their fasting glucose values and two of these women (10.5%) had a slight deterioration of their glucose curves. There were no other significant glucose or insulin changes. They had no change in weight and there was a significant reduction in their blood pressure during the treatment time. Five women had "borderline abnormal" control glucose tests, and four of these (80%) improved during the six months of treatment, and two of them (40%) became "normal." Thus, there is no evidence of an adverse effect of this low-estrogen oral contraceptive on carbohydrate metabolism during six months of therapy.


First year clinical experience with six levonorgestrel rods as subdermal contraception.

Previous clinical experience with six levonorgestrel subdermal capsules showed a very good contraceptive effectiveness and continuation rate, but with a high proportion of bleeding disturbances, particularly of increased bleeding. It was hypothesized that bleeding could be reduced by higher plasma levels of the steroid, using subdermal rods instead of capsules, as rods have been shown to have a release rate 3 or 4 times that of the capsules. Fifty volunteers were enrolled in a study of the clinical performance of 6 subdermal levonorgestrel rods. Results were compared with a previous experience with 100 volunteers who wore 6 levonorgestrel capsules for a year in the same clinic. Requirement for volunteers to enter the study were the same for capsules and rods. The proportion of women wearing 6 subdermal rods who had increased bleeding was about one half as for the women using 6 levonorgestrel capsules. On the other hand, women using rods had about twice the incidence of amenhorrea, and about four times more hypomenorrhea (4 days or less of bleeding in a 90-day period). There were no pregnancies among the rod users and the discontinuation rate for medical reasons was not higher than for capsule users in the same clinic.


Comparison of segmented polyether urethane with polyethylene IUDs in rabbits.

A segmented polyether urethane IUD was compared with a polyethylene IUD in rabbits. The contraceptive efficacy of urethane IUDs was excellent. Moreover, the purulent slippery deposit present with the polyethylene IUDs and observed by Davis et al. (1) was absent. Our studies indicate that the polyether urethane IUDs have a high degree of antifertility activity in rabbits and these IUDs have reduced inflammatory response, based on leucocytic infiltration and tissue debris in the uterine lumen. It is suggested that polyether urethane IUDs not requiring copper or other medication can be designed for high contraceptive efficacy, intrauterine compatibility and with the necessary rigidity for proper uterine retention in humans.


The protective influence of progestogen only contraception against vaginal moniliasis.

The incidence of Candida albicans (C.A.) infection of the vagina was evaluated in vaginal discharges obtained from 85 subjects using a large battery of culture media and confirmatory tests. Twenty women using DMPA 150 mg i.m. contraceptive injections for more than one year (long-term users) were compared with forty 2nd trimester pregnant cases with respect to vaginal candidiasis. The basis of comparison was the presence of amenorrhea and high hormonal levels in both groups. However, pregnant subjects showed a 60% prevalence while none of the DMPA cases had a positive culture or smear. Another group of 25 cases was similarly studied once before DMPA injection and again three months following drug administration (short-term use). The pre-therapy samples demonstrated a 32% incidence which was reduced to 8% after three months of use. It therefore appears that progestogen only contraceptives have the advantage of some protective influence against monilial vaginitis. Moreover, the use of these drugs may carry the beneficial potential of use in resistant cases of monilial vaginitis, either as a single approach or better as a supplementary procedure to known antifungal agents.


Reversion of supraventricular tachyarrhythmias by means of atrial stimulation.

Thirteen patients with different forms of supraventricular tachyarrhythmia were treated by means of right atrial pacing. Reversion of arrhythmia was obtained in nine out of ten patients with atrial tachycardia or flutter. The remaining three patients, with atrial fibrillation, did not respond to the procedure. The effective pacing rate in converting arrhythmia ranged from 110 to 2400/min, however in five cases it was lower than the atrial rate. The duration of pacing at an effective rate ranged from 20 seconds to 5 minutes in 5 cases, while in the remaining patients it lasted 10 minutes. In two patients the original arrhythmia was converted to atrial fibrillation during stimulation, but in one it disappeared with pacing at 110/min, and in the other, reversion to sinus rhythm occurred spontaneously 4 hours later. No complications were observed. It is concluded that atrial pacing may be useful aid to treat paroxysmal atrial tachycardia or flutter, and can be considered as an alternative procedure whenever there is no response to customary medical treatment or when transthoracic direct current cardioversion is potentially dangerous.


Polythelia associated with disturbances of cardiac conduction.

The authors examined three groups of persons (hospitalized patients, outpatients, and school girls) and conclude that in the cases of polythelia the cardiac conduction disturbances occur considerably more frequently than in persons without polythelia. When polythelia and conduction disturbances occur frequently in a family, the coexistence of both disorders is most probably of hereditary origin.


Structural rebuilding of pulmonary vessels at various haemodynamic shifts in the lesser circulation.

The rebuilding of pulmonary vessels at hypo- and hypertension in the lesser circulation was studied in 41 puppy dogs, in which hypotension had been induced by stenosing the pulmonary artery. Eighteen animals were successively sacrificed 6--9 months after the surgery. Histological examinations revealed atrophic and sclerotic lesions of the pulmonary arteries. In the remaining 23 animals, various anastomoses were formed between the systemic and pulmonary circulation systems, which led to the formation of hypertrophic and hyperplastic alterations in the pulmonary vessels and to pulmonary hypertension.


The development of the vascular system in man.

On the basis of material comprising 10 developmental stages of man in 35 embryonic series, the authors tried to determine the critical developmental period of the blood vessel wall. This period falls between the 5th and 16th weeks of intrauterine life, that is in the period of the formation of the basic wall structure characteristic of the particular vessel type (i. e. the elastic and muscular arteries, large veins, limb veins, and lymphatics). In limbs the differences between the superficial and deep veins as regards the vessel wall development, were disclosed.


Method of mosaic electrocardiotopography and its practical use in diagnostics of ischaemic heart disease.

The results of mosaic electrocardiotopographic (MECTG) and coronarographic examinations in 217 men with ichaemic heart diseases (IHD) are compared. On the body surface the zones were identified that corresponded with projections of myocardial electric potentials from individual segments perfused from the main coronary arteries. A distinct correlation was found between the MECTG indicators and the condition of the coronary circulation. The informative value of MECTG in the detection of IHD and determination of the extent of myocardial lesion in individual perfused segments, and the contribution of the method combined with coronarography to the diagnostics of noncoronarogenic myocardial lesions are pointed out.


The hypercoagulability states.

Although interest in coagulation has usually centered about the various hemorraghic disorders, it is hyperactivity of the hemostatic system with its thrombotic complications which has a far greater clinical impact. The hypercoagulability states are a vague group of disorders not well defined by the laboratory. They fall into two distinct groups: (1) conditions promoting venous thrombosis by activating the coagulation mechanism and (2) conditions promoting arterial thrombosis by platelet plug formation. Dealing with both of these groups separately the various disorders associated with a hypercoagulable state are discussed as well as their pathophysiologic basis; Special emphasis is placed on the laboratory evaluation of these disorders.


Extrapulmonary factors influencing the ratio of arterial oxygen tension to inspired oxygen concentration in burn patients.

The ratio of arterial oxygen tension to inspired oxygen concentration (PaO2/FIO2) as an index of respiratory function was evaluated in 22 patients with body surface area burns of 15--80%. These results indicate that this ratio is limited in its applicability because extrapulmonary factors, such as cardiac output, oxygen consumption, and arterial oxygen content, can affect this index by alterations in the amount of venous desaturation. Useful estimates of intrapulmonary right to left shunt (Qs/Qt) from PaO2/FIO2 were obtained only when arteriovenous oxygen content differences (avDO2) were between 3--5 ml/dl. There were avDO2 values above and below 3--5 ml/dl in at least 35% of the observations. Under these circumstances, PaO2/FIO2 did not correctly reflect changes in Qs/Qt. Blood gases from central venous catheters did not mirror changes in true mixed venous blood and, thus, can lead to erroneous estimations of Qs/Qt. Rational therapy of reduced arterial oxygen saturation requires measurement of both extra- and intrapulmonary factors contributing to arterial desaturation. Measurement of PaO2/FIO2 alone will not estimate these factors.


Hypoxemia during hemodialysis.

Five mechanically ventilated patients were studied during hemodialysis. The aim was to determine if hypoxemia would develop, and to identify the causes. Respiratory variables (dynamic compliance, peak airway pressure, CO2production); oxygen uptake, and transport variables (alveolar and arterial PO2, pulmonary venous admixture, oxygen consumption); respiratory quotient; pulmonary vascular resistances and white blood cells (WBC) were measured. PaO2 decreased during dialysis, as did PaO2. However, the fall in alveolar oxygen tension failed to explain the hypoxemia. Lung volume did not change significantly, because dynamic compliance, peak airway pressure, and pulmonary vascular resistance were not modified. CO2 losses through the dialysis coil were of little clinical significance. WBC count fell significantly. The authors conclude that ventilation/perfusion and diffusion abnormalities related to leuko-agglutination are responsible for hypoxemia during dialysis.


The so-called ectopic pinealomas. A cooperative study of 15 cases.

We present the results of a cooperative study of 15 cases of suprasellar dysgerminomas (ectopic pinealomas) and a review of cases of the literature with histological confirmation. In all the cases, histological similarities to the germinomas which appear extracerebrally, particularly testicular seminomas, were observed. We were unable to find in the sellar region tumors of true pineal histology and tend therefore to confirm the germinal origin of these neoplasms. From a clinical point of view, we define a syndrome that these tumors produce, consisting of diabetes insipidus as the first sign, visual impairment and endocrine disturbances, with few or no radiological signs in plain studies.


Congenital vascular malformation of spinal cord simulating diastematomyelia.

Diastematomyelia is usually caused by a midline bony, cartilaginous or fibrous spur. A case is presented with splitting of the spinal cord by a large arteriovenous malformation at the thoracolumbar junction. A hairy skin patch, kyphoscoliosis, vertebral anomalies and an arachnoidal cyst were found adjacent to the vascular and neural malformations.


Intracranial tumefactions in children. Surgical mortality.

This paper summarizes a 26.5-year experience in one centre with intracranial tumefactions in children. In 337 craniotomies done on 285 patients, the death rate within 30 days of operation was 6.7% for cases and 5.6% for procedures. Since 1965, the case and operative mortalities have been 2.0 and 1,7%, respectively. There have been no operative deaths in the last 109 patients, 124 craniotomies, done during the past 6.5 years. Operative mortality for primary procedures was 6.0%, 1.5% since 1965. For patients operated upon more than once (52 times on 38 patients), the case mortality has been 5.3%, procedural mortality 3.8%; since 1965 these figures have been 3.8 and 2.8%, respectively. The operative deaths are analysed, and some conclusions drawn. At the present time, surgical mortality from intracranial tumefactions in children should be less than 5%.


A long-term postoperative follow-up in craniopharyngioma.

The long-term postoperative follow-up of children treated for craniopharyngioma is influenced by the patient's age at time of diagnosis, tumor location, texture, interface and adherence to brain, and achievements of the first operation. These factors will be examined as they apply to 51 children treated at the Hospital for Sick Children, Toronto. A brief comment on the role of irradiation treatment is also provided.


Cerebellar abscess in early infancy.

The authors report an unusual case of cerebellar abscess in a 6-week-old infant without an antecedent of sepsis or congenital heart disease. The abscess was treated successfully by percutaneous punction-aspiration and further excision. Shunting procedure was not necessary.


Social interactions of young abused children: approach, avoidance, and aggression.

10 abused toddlers (ages 1-3 years) and 10 matched controls from families experiencing stress were observed during social interactions with caregivers and with peers in their daycare settings. The abused infants more frequently physically assaulted their peers. They "harassed" their caregivers verbally and nonverbally, and they were the only infants who assaulted or threatened to assault them. The abused infants were much less likely than the controls to approach their caregivers in response to friendly overtures; when they did so they were more likely to approach to the side, to the rear, or by turning about and backstepping. In response to friendly overtures the abused infants more frequently avoided peers and caregivers or combined movements of approach with movements of avoidance. A similar behavior pattern has been identified by Main in maternally rejected infants in normal samples.


Child rearing and children's prosocial initiations toward victims of distress.

Maternal rearing behavior was examined in relation to children's reparation for transgressions and altruism as bystanders to distress in others. The children were 1 1/2-2 1/2 years old. Mothers were trained in techniques of observing. They recorded their child's reactions and their own behaviors in everyday encounters with expressions of distress in others (sorrow, discomfort, pain). Distress was also simulated by mothers and investigators. Mothers' empathic caregiving was rated during home visits. Mothers' affectively delivered explanations regarding the distresses their children had caused to others were associated with children's reparations for transgressions. Such explanations were also associated with children's altruism when they were bystanders to another's distress. Empathic caregiving by mothers was positively associated with children's reparation and altruism. Findings are discussed in relation to theories of altruism, conscience, and child rearing.


Effects of infant sociability and the caretaking environment on infant cognitive performance.

40 middle-class mothers and their 12-month-old infants participated in an examination of the extent to which infant sociability and infant home experiences were correlated with cognitive capacity. Results indicated that the measures of the home environment (including Caldwell's Home Observation for Measurement of the Environment [HOME] inventory) were not correlated with the measures of cognitive competence (Bayley Mental Development Index [MDI], Ordinal Scales of Psychological Development) except among firstborns. Measures of the home environment were, however, correlated with measures of infant sociability (assessed inside and outside the test situation): sociable infants had sociable mothers. The infants' reactions to strange adults clearly influenced their performance in testing situations. Strong relationships were found between both measures of sociability and both measures of cognitive competence. The sociable friendly infants received higher scores on both cognitive tests than the less sociable babies did.


Sex differences in children's expression and control of fantasy and overt aggression.

The present study explored sex differences in children's expression and control of fantasy and overt aggression. Fifth-grade boys and girls were presented a TAT-like projective test to measure fantasy aggression and controls over aggression. Overt peer-oriented aggression was measured by peer and teacher ratings. Results indicated that boys were rated more physically and verbally aggressive than girls but not more indirectly aggressive. Boys also produced more physical aggression in fantasy than girls, although the opposite trend was found for indirect aggression; no sex difference was found for verbal fantasy aggression. Finally, girls had a higher ratio of aggression control per total fantasy aggression than boys. The results support the position that while boys, in contrast to girls, are socialized in a way that encourage direct expression of aggression, girls are just as likely to be aggressive as boys when the aggression is indirect. The results are discussed further from the perspective of social learning theory and Maccoby and Jacklin's biological position.