Correlation between the numbers of two types of children when the family size distribution is zero-truncated negative binomial.

Let family size N be a random variable formed from two types of children B and C (B + C = N). The correlation coefficient between B and C has been recently studied by Rao et al. [1973]. We consider this problem when the frequency of fertile childless families (N = 0) is not available or cannot be estimated. Assuming the distribution of N is zero-truncated negative binomial, a formula for the correlation coefficient is derived. Applying this formula to the data of Reed and Reed [1965] gives a correlation coefficient of 0.27. The corresponding empirical coefficient for non-zero size families calculated directly from the data is 0.24.


Inhibition of DNA synthesis by 1-beta-D-arabinofuranosylcytosine.

From sonicated log-phase L-cells (L929) crude enzyme fractions (particulate and soluble) were prepared by differential centrifugation, and assayed for replicative DNA polymerase activity. Treatment of the cells with ara-c in small doses (0,01/mug/ml) for 4 hours (1/2 Ts) resulted in 11 percent inhibition of their DNA synthesis, while the total DNA polymerase activity was inhibited by 14 percent. However, when assayed as soluble or particulate enzyme activities, the particulate fraction (replicative DNA polymerase) was found inhibited by 42 percent while the soluble fraction (reparative DNA polymerase) was stimulated by 14 percent. The DNA synthesis of L-cells treated with ara-c, and pulse-labeled with 3H-TdR for 2, 5 or 10 minutes at 23 degrees is inhibited by 5 percent, 22 percent and 23 percent respectively. When cells labeled at this temperature are lysed on alkaline sucrose gradients and their DNA is sedimented by ultracentrifugation, the incorporation into DNA smaller than 10S (Okazaki pieces), is found to be normal or slightly inhibited. However the incorporation into high molecular weight DNA (more than 35S) is inhibited by about 50 percent. Chase experiments (at 37 degrees) after ara-c treatment and labeling at 23 degrees indicate that the decrease of labeling in high molecular weight DNA at least to some extent is caused by inability of the cells to incorporate medium sized DNA (17-20S) into this fraction, because 17-20S DNA is accumulated with prolongation of the chase. The experiments indicate that the primary action of ara-c on DNA synthesis "in vivo" in mammalian cells may be an inhibition of DNA chain polymerisation.


Contribution of kidney basement membranes and collagen to the urinary excretion of hydroxylysyl glycosides.

Glucosyl-galactosyl-hydroxylysine and galactosyl-hydroxylysine are two substances present only in collagen and in basement membranes. The purpose of this study is to estimate to what extent the kidney contributes to urinary hydroxylysyl glycoside excretion. "In vitro" perfusion of isolated kidneys allows the measurement of hydroxylysyl glycosides independently of the important amount of interstitial collagen present in the whole body. It is shown that the kidney parenchyma contributes no more than 10 percent of the glycosylated hydroxylysine excreted in urine. GBM is not the only renal source of glucosyl-galactosyl-hydroxylysine in urine. Tubular basement membrane and intersitial collagen of kidney may contribute to the excretion by the isolated organ.


[Thermogenesis of mammary epitheliomas. III. Study, by means of fluvography, of the termal conductivity of mammary tissue and of the influence of tumor vascularization].

The effective thermal conductivity of different "in vivo" and excised breast tissues and the specific heat power of a series of 24 breast carcinomas have been measured "in situ" by means of intratissular thermometric and fluvographic needle probes, and using a mathematical model operated with a computer. The thermal conductivity which depends directly on the capillary blood flow is higher within irrigated tissues than in the excised ones and demonstrates significant changes according to the adipose, fibrous or glandular structure of the breast; furthermore, it is much higher within cancerous tissues, more especially in the surroundings of the tumour. The heat power changes largely from one cancer to another and may reach values higher than those measured on the most thermogenic normal tissues. At hand of comparison with thermography, radiography and arteriography, these results are discussed from the three following points of view: a) the vascularisation of cancers and the shell model of tumour growth; b) the distribution of arterial, venous and tumour temperatures and the origin of the cancerous heat; c) the heat transfer from cancer to skin and the formation of the malignant cutaneous thermal pattern pictured by thermography.


Congenital cataracts associated with disorganized meridional rows in a new laboratory animal: the degu (Octodon degus).

A new laboratory animal, Octodon degus, a hystricomorph rodent, was found to display a naturally occurring congenital cataract. Histological examination of the lens epithelium revealed that a marked disorganization of the meridional rows is associated with the opacity. Studies of offspring of cataractous parents indicates that the disorganization precedes cataract appearance. These findings are discussed in reference to a general theory of meridional row involvement in a number of types of cataracts.


Smoking during pregnancy, stillbirth and abruptio placentae.

In a prospective investigation on 9,169 pregnant women which showed a substantial increase in stillbirths among smokers, a large proportion of this increase is due to abruptio placentae. The percentage of smokers in this category rises to 46% while it is only 12% in the group of livebirths. Smoking appears to be an important risk factor in this occurence, the etiology of which is little known. The effect of parity and its possible interaction with smoking are discussed.


Gm and Inv allotypes in premature infants.

Using haemagglutination inhibition tests specific for Gm allotypes and similar tests for IgG4, the placental transfer of the four IgG subclasses from mother to foetus has been confirmed. The Gm phenotype of a cord serum is often identical to that in the corresponding maternal serum. However in 31 cases out of the 90 tested, Gm allotypes were present in the cord serum that were not present in the maternal serum. These allotypes produced by the foetus in utero are dependent on a paternal gene. The logarithm of the IgG level increase proportionately with gestational age (r = 0.59 p less than 0.001).


Study of the mode of cyclophosphamide action on the rabbit arthritis according to Glynn's model.

A knee joint arthritis is induced in rabbits previously immunized by an intradermal injection of emulsified egg albumin (E.A.) a complete adjuvant, then by an intra-articular injection of E.A. alone. Histologically, the synovium shows at first an Arthus phenomenon and later an immune cellular reaction. Several immunological parameters are studied in these rabbits. Cyclophosphamide (CY), injected intravenously, in a high dose, during a short period from the day of the first immunization, inhibits in the same time the arthritis index, E.A. skin test, humoral and synovial anti-E.A. antibodies and lymphocyte response to P.H.A. Cy, injected I.V., in a low dose, for a long period from the day of the intra-articular immunization, decreases only the arthritis index, but does not modify the various immune reactions to E.A. These results suggest that, according to the timing and the dose, CY inhibits synovial inflammation either by a strict anti-inflammatory action, or by an immunosuppressive effect on the initial phase of the immune reaction inducing subsequently a synovial inflammation.


A vascular permeability factor elaborated from lymphocytes. I. Demonstration in patients with nephrotic syndrome.

P.H.A. and Concanavalin A stimulated lymphocytes culture supernatants were comparatively studied in 23 volontary normals and in 46 patients with nephrotic syndrome. Intradermal injections to guinea-pig demonstrated a permeability increasing and pro-inflammatory factor. Vascular permeability (immediate reaction) is determinated by blue Evans technique. Delayed reaction is assesed by the cutaneous inflammatory process (erythema, induration); pathologically it is defined as polymorphonuclear and mononuclear infiltration. Differences are highly significant between nephrotic patients and normal subjects. This biological activity is not observed with control supernatants (medium plus normal human serum and P.H.A. or Conca A). Positive results were also found with M.E.M. eagle culture supernatants of nephrotic stimulated lymphocytes. To date lymphokines have been studied especially in animals. In human, they have been found only after concentration. Variations in lymphokine production may be present in some pathologic states.


Separation of human lymphoid cells by preparative cell electrophoresis. II. Free-flow electrophoretic separation of human blood cells.

By means of free-flow electrophoresis the different types of human blood leukocytes can be characterized by their electrophoretic distributions. In addition a separation of cells according to their electrophoretic mobility and at least an enrichment of certain cell types is achieved. The data given in this paper confirm that reproducible results can be obtained using this separation method and indicate that it can best be used to study populations of lymphocytes.


Deformation and fragmentation of human red blood cells in turbulent shear flow.

By means of glutaraldehyde fixation, human erythrocytes are "frozen" while suspended in turbulent shear flow. As the shearing is increased in steps from 100 to 2,500 dyn/cm2, the deformed cells evolve gradually toward a smooth ellipsoidal shape. At stresses above 2,500 dyn/cm2, approximately, fragmentation of the cells occurs with a concomitant increase in free hemoglobin content of the suspending medium. The photographic evidence suggests that the cells rupture in tension in the bulk flow.


Axon voltage-clamp simulations. I. Methods and tests.

This is the first in a series of four papers in which we present the numerical simulation of the application of the voltage clamp technique to excitable cells. In this paper we describe the application of the Crank-Nicolson (1947) method for the solution of the parabolic partial differential equations that describe a cylindrical cell in which the ionic conductances are functions of voltage and time (Hodgkin and Huxley, 1952). This method is compared with other methods in terms of accuracy and speed of solution for a propagated action potential. In addition, differential equations representing a simple voltage-clamp electronic circuit are presented. Using the voltage clamp circuit equations, we simulate the voltage clamp of a single isopotential membrane patch and show how the parameters of the circuit affect the transient response of the patch to a step change in the control potential. The stimulation methods presented in this series of papers allow the evaluation of voltage clamp control of an excitable cell or a syncytium of excitable cells. To the extent that membrane parameters and geometrical factors can be determined, the methods presented here provide solutions for the voltage profile as a function of time.


Axon voltage-clamp simulations. II. Double sucrose-gap method.

This is the second in a series of four papers on the simulation of the voltage clamp of cylindrical excitable cells. In this paper we evaluate the double sucrose-gap voltage-clamp technique for the squid and lobster giant axons. Using the Crank-Nicolson method of solution of the cable equations and differential equations representing the voltage clamp circuit we studied the effect of length of the sucrose gap "node" on the voltage profile along an excitable cell during a simulated voltage clamp. The voltage gradients along the region of the cell within the node produce "notches" in the current recording as well as changes in the magnitude of the sodium and potassium current for a given voltage step. Our results show that good voltage clamp control requires node lengths less than one-half the axon diameter.


Axon voltage-clamp simulations. A multicellular preparation.

In this paper we extend the simulation of the voltage clamp of a single nerve fiber to a bundle of axons. These simulations included not only the description of the voltage clamp circuit and a single unidimensional cable to represent the preparation in the "node" region of a double sucrose gap used previously but also a series resistance and a shunt pathway. The output of the voltage control amplifier is applied across the membrane plus the series resistance, producing a voltage drop across the series resistance due to the current generated by the membrane in response to a depolarizing voltage step. Since the membrane current has an inward and an outward phase, voltage drops of opposite sign are produced across the series resistance. During the transient current and at all points along an axon, the potential deviation produced by the series resistance is opposite to the deviation produced by the longitudinal gradient. Only at a command potential equal to the sodium equilibrium potential, the membrane potential transiently matches the command potential. For the attempted voltage clamp of an axon, values of series resistance larger than 50 omega-cm2 allowed propagated action potentials in the membrane. In spite of the presence of propagated action potentials at the calbe membrane, the recorded current does not show "notches" and it has a phase of inward current and a phase of outward current. It is concluded that, in a multicellular preparation with series resistance, the recording of a square voltage pulse does not indicate voltage control of the transmembrane potential. The presence of a shunt pathway produces inaccurate values of current density. Neither series or shunt resistance produce "notches" in the current records.


Kinetics of the cooperative association of actin to actin filaments.

The cooperative formation of actin filaments from monomers was followed by light scattering and electron microscopy. The results are well described by a simple model mechanism in which the growth and destruction of filaments occurs by stepwise addition or dissociation of protomers. All steps except the dimerisation step are assumed to have identical rate constants. These were found to be 5 X 10(3) M-1 - sec-1 and 3 X 10(-2) sec-1 for the association and dissociation, respectively (at pH 7.5 and in the presence of 10(-3) M calcium chloride). The equilibrium constant of elongation as obtained from the critical concentration is 1.7 X 10(5) M-1. The corresponding equilibrium constant of dimerisation is about 10 million times smaller (cooperativity parameter sigma = 2 X 10(-7)). This makes the nucleation extremely difficult and cooperativity very high. A best fit of the model to the experimental data is achieved when the destruction of a dimer is much faster than the addition of a third protomer (fast monomer- dimer pre-equilibrium). The size of the nucleus from which propagation becomes faster than dissociation is 3.


Synchronization in two interacting oscillatory systems.

Nonlinear phenomena arising from the interaction of two oscillating systems of chemical reactions are studied experimentally. The system of two connected flow-through continuous stirred tank reactors (cells) with controlled exchange of reaction mixture is used. The Belousov reaction (oxidation of malonic acid by bromate in sulphuric acid with ceric/cerous ions as catalyst) served as model system. The frequency of oscillations was controlled by change of the reaction temperature. Phenomena such as synchronization of oscillations at a common frequency, synchronization at multiples of a common frequency, rhythm splitting and amplitude amplification were observed, depending on the degree of interaction and the differences in the original oscillation frequencies. Mathematical modelling of the above phenomena failed, probably due to insufficient knowledge of a kinetic model.


Basic polypeptides as histone models: circular dichroism of complexes of model polypeptides with DNA.

Circular dichroism (CD) was used to study the complexes of DNA (in 0.15M NaCl) with two polypeptides considered as models of the histone molecules. CD spectra in the region of DNA absorption were studied with respect to the concentration used for annealing and to the molecular weight and composition of the DNA used. The properties of supernatants after centrifugation of aggregated complexes were examined. The effect of selectively bound antibiotics (actinomycin D and netropsin) on CD sprectra of complexes was investigated. The induced CD of proflavine molecules bound to DNA in the various complexes was also studied. It was concluded that changes in the CD spectra of DNA in complexes with the polypeptides are due to the formation of chiral superstructures, even if some conformational changes of DNA molecules themselves may also be decisive in some cases. The superstructure is affected by the composition of DNA, the role of (G + C) rich segments being particularly important.


Nonlinear phenomena in oscillatory systems of homogeneous reactions - experimental observations.

An oscillating system of homogeneous chemical reactions (oxidation of malonic acid by bromate with ceric/cerous ion system as the catalyst) was followed experimentally in several reactor configurations, operated both as close and open systems. Characteristic nonlinear phenomena observed include: damped oscillations of concentrations of reaction components in a well stirred batch reactor, undampted oscillations and sudden changes of oscillatory behaviour (jump to a new steady state) in CSTR and interaction of oscillations in the two connected CSTRs. In a tubular reactor stationary and travelling concentration waves were observed. In the system of CSTR connected with a tubular reactor spreading of waves from CSTR to the tubular reactor, and vice versa was followed. In the flow through tubular reactor the formation of non-monotomic concentration profiles was measured, which were basically stationary with respect to changing flow-rate. The course of oscillations in CSTR was simulated on the basis of a semiempirical reaction kinetics model. An attempt to simulate quantitatively the behaviour of the distributed system with the common type of Fickian diffusion balance equations failed. Difficulties in the proper description of the transport of ions through the concentration gradient and the gradient of the electrical potential found in this system are discussed.


Hairy cell leukemia: functional, immunologic, kinetic, and ultrastructural characterization.

A diagnosis of hairy cell leukemia was made by optic microscopy, phase-contrast microscopy, electron microscopy, scanning microscopy, and histochemistry of the abnormal blood cells. In vivo these cells were found to have a half-time in the blood of approximately 150 hr. In vitro they had the capacity to adhere firmly to plastic, making it possible to obtain a pure population of hairy cells. Neither T-rosette formation nor phytohemagglutinin (PHA) transformation could be demonstrated in these cells. On the other hand, the presence of immunoglobulins on the surface of the hairy cells (HC) by immunofluorescence, and the synthesis and secretion by these cells of IgM type lambda-chains shown by radioimmunodiffusion, were in favor of their B-type lymphocyte origin. Similarities to chronic lymphocytic leukemia were apparent.


DNA-metabolizing enzymes in normal human lymphoid cells. VI. Induction of DNA polymerases alpha, beta, and gamma following stimulation with phytohemagglutinin.

At least three distinct DNA polymerases, named alpha, beta, and gamma, have been isolated from normal mammalian cells. The function of these enzymes in regard to DNA replication and repair remains unclear. Stimulation of blood lymphocytes with the plant mitogen phytohemagglutinin (PHA), is known to increase total DNA polymerase activity. In this study, we measured the change of each of these activities as lymphocytes intered a mitotic cycle. Aliquots of a pool of normal human blood lymphocytes were incubated with PHA for 0, 24, 48, and 72 hr, respectively, and the various DNA polymerase activities quantitated at each point. No significant DNA polymerase activity was detected in unstimulated cells. Low levels of polymerase beta were found at 24 hr. The average DNA content per cell doubled between 24 and 48 hr, and during this interval all three DNA polymerases increased to easily detectable levels. By far the greatest fractional increase in activity of all three polymerases was seen between 48 and 72 hr, after the average doubling of cellular DNA. In summary, these blood lymphocytes lack significant levels of DNA polymerases; stimulation with PHA induces all three of the major DNA polymerase species. In both these respects, these cells differ from other proliferating mammalian cell systems. The possible significance of this difference is discussed.


A new hematologic syndrome with a distinct karyotype: the 5 q--chromosome.

Five patients, four women and one man, age 32-8- yr, all whites, had refractory anemia with the same abnormal bone marrow karyotype, i.e., a partial deletion of the long arm of the No. 5 chromosome. The hematologic syndrome was practically the same in these five cases. Examination of the blood revealed a moderate to severe, generally macrocytic anemia with slight leukopenia but normal or elevated platelet count. The bone marrow showed a depressed erythroid series and some abnormalities of the granulocytic series with an occasional excess of myeloblasts. Most of the megakaryocytes had a nonlobulated nucleus. These features, as well as cytogenetic, electron microscopic, isotopic, platelet function, and immunologic studies, are described in detail. The relationship of this newly established syndrome to other hematologic diseases is discussed. The syndrome constitutes another example of the association between a specific abnormal chromosome and a distinct hematologic disorder.


Ultrastructural changes of endothelium associated with thrombocytopenia.

In a study of the relationship between thrombocytopenia and increased vascular fragility, changes in the endothelium of capillaries and postcapillary venules of the tongue were examined by electron microscopy. Adult male albino rabbits (4 kg) were maintained thrombocytopenic (platelets less than 20,000/cu mm) up to 24 hr by one to three injections of guinea pig antirabbit platelet serum. Within 6 hr the normal projections and folds of the lumenal surface of the endothelial surface were largely effaced. In addition, the endothelium became thinner. In places, pores and membranous diaphragms were observed. Endothelial junctions appeared normal. Identical findings were observed if rabbits were made thrombocytopenic by administration of intraperitoneal busulfan. Intravenously administered Thorotrast was observed in endothelial cells and in the extravascular spaces within 3 min after injection into thrombocytopenic animals, while it was seen only intravascularly in control rabbits. With the spontaneous restoration of circulating platelets, the endothelium reverted to normal.


Elevated platelet count and megathrombocyte number in sickle cell anemia.

Eight adult patients with sickle cell anemia were followed over a 6-mo period. During this time all patients had elevated plateletcounts, 1.7-fold (mean, 438,398 +/- 86,223), and megathrombocyte numbers, 2.3-fold (mean, 79,535 +/- 38,907), during asymptomatic periods. These data are interpreted as suggesting that the elevated platelets and megathrombocytes in asymptomatic sickle cell patients result from lack of splenic sequestration. During three crises in two patients, both megathrombocyte number and platelet count fell significantly. It is speculated that platelets may be associated with the pathology in this disease. Platelet function studies performed during crises, therefore, must take into account the number of megathrombocytes.


Iron metabolism, sickle cell disease, and response to cyanate.

In an attempt to understand the variability of the hematologic response to oral sodium cyanate, iron metabolism was studied in a group of 39 patients with sickel cell disease. Eleven of the 39 patients were found to have no stainable iron in the marrow despite the fact that patients with sickle cell disease are generally considered to have hemosiderosis. The mean per cent saturation and total iron-binding capacity were in the low-normal range in sickle cell patients whether or not stainable iron was present in the bone marrow aspirate. Serum ferritin concentrations, on the other hand, were found to be high in both groups (greater than 500 mu g/liter) when compared to controls (60 mu g/liter). The high serum ferritin levels denoted significant total-body iron deposition which may be unavailable for normal metabolic processes. One patient with no stainable iron in the bone marrow aspirate did respond to iron therapy alone with an increase in hemoglobin concentration. Serum ceruloplasmin levels were also found to be high in sickle cell disease patients. The ability to respond to oral cyanate therapy was correlated with the amount of stainable iron in the bone marrow aspirate. These studies emphasize the necessity of a reevaluation of iron metabolism in the pathophysiology and treatment of sickle cell disease.


Glucose 6-phosphate dehydrogenase deficiency and sickle cell anemia: frequency and features of the association in an African community.

The glucose 6-phosphate dehydrogenase (G6PD) genotype was determined in 100 male patients with homozygous sickle cell anemia (SS) by a combination of quantitative assay, cytochemical testing, and starch-gel electrophoresis. Of the 100 patients tested, 16 were found to be G6PD deficient (GdA-), AND 84 G6PD normal (22GsA and 62 GdB). This distribution of G6PD genotypes did not differ significantly from that observed in the general population. The level of G6PD activity in GdA- SS patients was nearly always higher than in G6PD-deficient subjects who did not have an associated hemolytic state, but it was nearly always lower than in G6PD-normal subjects. The clinical course of sickle cell disease, including the degree of anemia, was not milder in GdA- than in G6PD-normal patients but could not be proved to be significantly more severe. It was concluded that in this community the incidence of G6PD deficiency in sickle cell anemia was not greater than would be expected by chance, and there was no evidence that the coexistence of the GdA- gene in SS patients ameliorated their disease.


Clinical and laboratory observations on serum folate-binding protein.

We studied the effect of serum folate-binding protein (FBP) on folate radioassays and the relationship of the serum level of unsaturated FBP to the serum folate level in various clinical states. Our modification of a heat-extracted radioassay was compared to a whole serum radioassay. Our results confirmed the existence of elevated serum levels of unsaturated FBP in some normal subjects, in some women taking oral contraceptives, and in most patients with uremia. Elevated levels of unsaturated FBP will produce falsely low results in folate radioassay unless the FBP has been destroyed by heat, as was done in the modified radioassay here presented. In normal and uremic subjects, serum folate and unsaturated FBP levels tended to correlate, whereas in patients taking large doses of folic acid the level of unsaturated FBP fell as the level of serum folate rose.


The influence of temperature on red cell deformability.

This study was undertaken to examine the influence of temperature on physical properties of red cell membranes. Red cells adhering to cover slips were subjected to fluid shear stress in a rotating disc apparatus for 1 min or for 10 min at temperatures ranging from 2 degrees to 50 degress C. They were fixed while subject to shear stress by addition of glutaraldehyde and then processed for examination and photography by reflected-light microscopy. Cell dimensions were obtained with a computerized planimeter. At shear stresses under 2 dynes/sq cm, cells changed shape from biconcave discs to tear drops, the dimensions of which were influenced very little by temperature or duration of shear stress. Above 2 dynes/sq cm, filamentous processes or "tethers" developed at attachment points of cells to cover slips. Tether length and the percentage of cells possessing tethers increased markedly with increasing temperature and duration of shear stress. At approximately 48 degrees C, a dramatic change occurred over a narrow temperature range such that cells were markedly elongated and irregularly deformed by a shear stress of 1 dyne/sq cm or less. These observations demonstrate that elongation of human red cells subjected to fluid shear stress in a rotating disc system is markedly influenced by temperature as well as by magnitude and duration of shear stress. They also indicate that significant increases in red cell membrane fluidity occur between 2 degrees and 24 degrees-37 degrees C and again between 48 degrees and 50 degrees C.


Abnormal erythroid maturation in mice induced by isoniazid.

Defective arythropoiesis characterizes the sideroblastic anemias. The present studies were undertaken to assess the effects of isoniazid, an inhibitor of heme synthesis, on erythropoietin-induced erythroid maturation in hypertransfused mice. Isoniazid was administered at intervals during a wave of induced erythropoiesis, and the effects were assessed in both the bone marrow and peripheral blood. The data showed that isoniazid interfered with heme synthesis and erythroid maturation. The most inhibitory effect of isoniazid was noted at the intermediate normoblast stage. A transient increase in the reticulocyte nonheme iron pool was also found.


Limitation of splenic growth as studied by heterotopic splenic implants.

Multiple spleens were implanted in the subcutaneous tissue or the peritoneal cavity of inbred rats which had undergone splenectomy. The total weight of regenerated implants was compared to the weight of implanted tissue. The weight of recovered tissue was not a function of implanted spleen mass; rather, it approximated the unit ratio of the animal's own spleen. Those animals receiving more than ten spleens died by days 3-6 postimplantation, probably as a result of massive necrosis that occurred during the process of regeneration. When implants were made in a temporal sequence of two spleens every 3 days, the first set was uniformly successful, whereas regeneration was aborted in subsequent sets of implants. These observations are consistent with the conclusion that certain factors control the total mass of spleen in any one animal.


Hereditary stomatocytosis: membrane and metabolism studies.

A defect in the protein kinase-mediated phosphorylation of erythrocyte membrane proteins, previously unrecognized in stomatocytosis, was discovered in a boy with hereditary stomatocytosis and severe hemolytic anemia. The high-sodium, low-potassium erythrocytes of this patient were remarkably permeable to both sodium and potassium. The rate of ouabain-inhibitable active cation transport was more than ten times normal and was sustained by an increase of similar magnitude in glycolysis. The deformability in vitro of fresh stomatocytes was reduced and deteriorated further after a brief period of incubation with glucose. Ferrokinetic studies showed that these rigid cells were sequestered by the spleen. When stomatocytes were deprived of glucose in vitro, ATP depletion and ATPase cation pump failure rapidly ensued. Because of their permeability defect, such depleted cells rapidly became swollen and lysed. Prolonged entrapment in acidic, hypoglycemic regions of the spleen would recapitulate these unfavorable events in vivo. In this regard, splenectomy was followed by an improvement in erythrocyte survival, although evidence of continuing hemolysis was obtained.


A new form of hereditary persistence of fetal hemoglobin in blacks and its association with sickle cell trait.

A new form of hereditary persistence of fetal hemoglobin (HPFH) producing 3%-8% Hb F in heterozygotes and an elevation of F-cell counts as measured by both the Kleihauer test and an antibody fluorescent procedure was found during the study of a black family. Individuals with this anomaly also had sickle cell trait. A sickle cell homozygote who had apparently inherited the HPFH determinant had 20.3% Hb F. Both types of gamma-chains were present in equal proportions in the Hb F of these individuals. A population study revealed other AS individuals with increased Hb F synthesis, three of whom were sibs. The presence of this previously unrecognized form of HPFH might explain the mild clinical manifestations and the hemoglobin phenotypes of sickle cell homozygotes with unusual elevations of Hb F.


The relationship between anemia, fecal stercobilinogen, erythrocyte survival, and globin synthesis in heterozygotes for beta-thalassemia.

Erythrocyte survival, fecal stercobilinogen, and the alpha/beta-chain synthesis ratio in recticulocytes and bone marrow (six cases only) were determined and related to the hemoglobin levels in ten heterozygous carriers of beta-thalassemia with different degrees of anemia. Erythrocyte survival values were low, though not related to the degree of anemia, whereas stercobilinogen values and changes in the peripheral blood alpha/beta-chain ratios were so correlated. In the case of bone marrow, on the other hand, the ratio between alpha-chain and beta-chain synthesis was virtually 1, irrespective of the degree of anemia. It is suggested that the severity of anemia in heterozygous carriers is independent of peripheral hemolysis and entirely attributable to destruction of erythroblasts within the marrow.


Thymidylate synthetase activity in bone marrow cells in pernicious anemia.

The tritium release assay for the demonstration of thymidylate synthetase activity has been applied to the measurement of enzyme activity in the bone marrow of four patients with pernicious anemia and nine normal subjects. On the average, an approximately ninefold increase in enzyme activity was observed in patients with pernicious anemia. In the absence of 5, 10-methylene-tetrahydrofolate, enzyme activity was reduced in both normal and in pernicious anemia cells. Addition of 5, 10-methylene-tetrahydrofolate to the assay medium resulted in a far greater activation of thymidylate synthetase activity in megaloblastic bone marrow cells than in the cells of control subjects.


Use of cell separation and short-term culture techniques to study erythroid cell development.

Cell populations highly enriched for the different stages of erythroid cell maturation were obtained by three sequential operations: harvesting of erythroid cells after induction of erythroid hyperplasia in the spleens of mice, elimination of the more mature erythrocytes by immunologic techniques, and separation of the residual nucleated erythroid cells as a function of size by the velocity sedimentation technique. The resulting cell fractions were studied both directly and after overnight incubation in the presence or absence of erythropoietin. In short-term culture, erythropoietin stimulated proliferation of pronormoblasts and basophilic normoblasts but probably not cells at later stages of differentiation. Erythropoietin also appeared to recruit increased numbers of pronormoblasts. In this experimental system, erythroid cell differentiation was able to proceed in the absence of erythropoietin, but without proliferation of these early erythroid cells. These techniques have provided a model system for the study of erythroid cells at different stages of maturation isolated from a uniform source at one point in time. The morphologic observations indicated that erythropoietin stimulates erythroid cell proliferation at several early stages of the maturation pathway.


Congenital neutropenia: neutrophil proliferation with abnormal maturation.

A child with congenital neutropenia was studied using bone marrow culture and ultrastructural and cytochemical techniques. The patient's marrow cells formed a large number of granulocytic colonies of normal size in culture, and her peripheral blood leukocytes produced adequate colony-stimulating factor. No serum inhibitors were identified. The patient's promyelocytes from direct marrow and culture appeared normal in ultrastructure, and primary granules, contained peroxidase and acid phosphatase activity. Myelocytes and rare segmented neutrophils from direct marrow specimens demonstrated atypical notched nuclei, myelin figures in Golgi lamellae and primary (azurophilic) granules, and no identifiable secondary (specific) granules. These data indicate an intrinsic neutrophil defect which allows normal proliferation of precursor cells, but results in abnormal granulogenesis and apparent inability to form secondary granules.


Correction of poor platelet transfusion responses with leukocyte-poor HL-A-matched platelet concentrates.

Matching donor-recipient pairs for HL-A antigens provides a logical starting point for selecting donors for recipients with extensive prior transfusion histories. However, during the course of continued exposure to even HL-A-matched platelet concentrates, further sensitization occurs, as indicated by progressively poorer post-transfusion increments and transfusion reactions. There is evidence that such sensitization may be due to non-HL-A antigens. Finally, it is postulated that the poor post-transfusion platelet increments obtained when standard platelet concentrates are used result from the leukoagglutinin antigen-antibody reaction involving the platelet as an "innocent bystander." The standard platelet concentrate can be purified by a simple method of centrifugation (178 g times 3 min), removing about 96% of the contaminating white blood cells with concomitant loss of about 21% of the platelets. The use of these leukocyte-poor platelet concentrates can restore compatible transfusion increments in highly alloimmunized thrombocytopenic recipients. The luekocyte-poor concentrates can diminish undesirable transfusion reactions following imcompatible platelet transfusions.


A hitherto undescribed plasma factor acting at the contact phase of blood coagulation (Flaujeac factor): case report and coagulation studies.

This paper reports an asymptomatic coagulation defect responsible for an abnormality at the contact phase of blood coagulation in vitro, distinct from Hageman factor and Fletcher factor deficiencies. Coagulation studies in a 50-yr-old French woman without bleeding tendency revealed the following results: whole-blood clotting time in glass tubes and activated partial thromboplastin time with kaolin and ellagic acid were greatly prolonged; one-stage prothrombin was normal; no circulating anticoagulant was detected, and the infusion of normal plasma corrected the coagulation defect with an estimated half-life of 6.5 days; the levels of factor VIII, IX, XI, and XII were normal; mutual correction was obtained with a Fletcher factor-deficient plasma; the level of whole complement was normal. Studies of the contact phase of blood coagulation and contact-induced fibrinolysis showed the same abnormalities as in Hageman factor- and Fletcher-deficient plasmas. These results indicate that the patient's plasma is deficient in a previously undescribed coagulation factor, which participates in the initial stage of the blood coagulation process in vitro. Family studies revealed consanguinity in the propositus' parents. The assay of this newly described factor in the propositus' children revealed a partial defect, compatible with a heterozygous state, in three of the four tested children. This indicates a recessive inheritance of this new blood coagulation defect.


Enhanced prostaglandin synthesis contributes to the venoconstrictor activity of ergotamine.

Spiral strips from dog saphenous veins were contracted by 2.5 X 10(-9) M ergotamine, a concentration giving about 50% of maximal response. Phentolamine (3.6 X 10(-6) M) reduced these effects by 60% and indomethacin (2.8 X 10(-7) M) by 30%. Indomethacin was more effective in reducing ergotamine-induced increase of prostaglandin E-like activity in the bathing fluid than those induced by noradrenaline or potassium chloride. Arachidonic acid was more effective in increasing tension in ergotamine-stimulated than in noradrenaline- or potassium-stimulated veins. These findings suggest that the long-lasting venoconstrictor activity of ergotamine is mediated mainly by alpha-adrenoceptors but that enhanced formation of prostaglandin E-like substance(s) may also contribute.


Reactivity of aorta and portal vein in germfree rats.

The responsiveness of conventional and germfree rat aortas and portal veins to vasoactive agents were compared in vitro. The results indicate: (1) aortas and portal veins from germfree rats exhibit an attenuated reactivity to angiotensin, vasopressin and epinephrine but not to KC1; (2) the dose-response curves for epinephrine and the peptides were shifted to the right concomitant with a decrease in maximum contractile tension, and (3) CaC12 dose-response curves obtained on potassium-depolarized aorta were not different from one another, whereas those obtained on portal veins from germfree animals were shifted to the right with a concomitant decrease in maximum response. In addition, aortas and portal veins from germfree rats were found to exhibit a higher total Ca content (but not Mg or water) when compared to conventional animals.


Comparison of net fluxes of Li and Na in vascular smooth muscle.

The rat tail artery enriched by incubation in a lithium-substituted medium loses Li at three distinct rates upon return to a normal medium at 37 degrees C. The first is very rapid with a single exponential rate constant of the order of 1 min-1, while the second and third are considerably slower with rate constants of the order of 3h-1 and 0.6h-1, respectively. Both slow components are cellular since they combine into a single component when active Na transport is inhibited by the absence of external K, by ouabain, or by low temperature. None of these procedures affects the rapid loss of Li from extracellular locations. It follows that cell Li can be measured simply by washing out extracellular Li at 2 degrees C, a procedure which removes only a small definable amount from cells. The influx of Li into cells during incubation in Li-substituted medium follows 1st order kinetics and exchanges 1:1 with cell K after a delay of about 20 min at 37 degrees C. This delay in influx is associated with active Na transport since it is abolished by the absence of external K, by low temperature, and by ouabain. The activation energy required for the influx of Li and of Na in K-free media is consistent, in the main, the passive diffusion through a restricted area although there is a suggestion in the case of Na that an additional mechanism (e.g. carrier) may be involved.


Triglyceride lipase activity in bovine aorta.

The cell-free supernatant from homogenized bovine aorta hydrolyzed triglycerides, beta-naphthylesters of lauric and stearic acid and Tween 20, 40 and 60. The rate of hydrolysis decreases as the acyl chain length of the substrates increases. The activity against triglycerides of short-chain fatty acids and monoacylesters could be partially separated from that of glycerol-trioleate lipase by ammonium sulfate fractionation. The activity of glycerol-trioleate lipase remained unaffected by heating for 5 min at 60 degrees C or by addition of bile acids, whereas the activity causing hydrolysis of triglycerides with short-chain fatty acids and monoacylesters decreases up to 60% by analogous treatment.


Effects of neomycin on 45Ca binding and distribution in canine arteries.

The effects of neomycin (7.0 mM) on 45Ca movements and distribution were investigated in canine aortae and in canine carotid and terminal mesenteric arteries. Uptake of 45Ca was measured in calcium-free solution; the 45Ca tissue spaces in the carotid and terminal mesenteric arteries were 2--4 times greater than those observed in the aorta. Exposure of the aortae and the terminal mesenteric arteries to 1.5 mM Ca++ during the washout elicited large increases in 45Ca efflux in both preparations (increase in terminal mesenteric greater than aorta). Moreover, in all three arterial preparations, neomycin reduced 45Ca uptake and induced a sustained increase in 45Ca efflux (effects on terminal mesenteric larger than or equal to carotid greater than aorta). The terminal mesenteric and carotid arteries may accumulate and bind 45Ca at superficial membrane sites (readily exchangeable 45Ca) to a greater degree than does the aorta. If Ca++ located at these membrane sites contributes directly to the maintenance of mechanical responsiveness, then agents which alter membrane binding of Ca++ (e.g. neomycin) may exert a stronger action on these highly reactive vessels. Thus, contractile responsiveness in peripheral arteries may depend upon depots of superficially bound Ca++ to a greater degree than in the more centrally located aorta.


The effect of several viper venoms on prothrombin Padua.

The effect of four viper venoms (Oxyuranus scutellatus, Notechis scutatus scutatus, Echis carinatus, Naja nigricollis) on prothrombin Padua has been studied. Using Oxyuranus scutellatus venom and Notechis scutatus scutatus venom, prothrombin activity resulted to be moderately decreased similarly to what observed with other one-stage and two-stage methods. On the contrary, using Echis carinatus venom a normal level was obtained. No clotting was observed using the Naja nigricollis venom, regardless of the concentration used. The normal level of factor II obtained with Echis carinatus venom as compared with the low levels obtained with the other venoms, suggests that it acts on a different site of the prothrombin molecule.


[Quantitative determination of human bone marrow proliferation kinetics during three culture days].

In order to obtaon of human bone marrow cells, fresh bioptic material was homogenized and the cell suspensions were incubated for 72 hs in a fluid medium. After 24, 48 and 72 hs of incubation the total cell number of the culture was determined. At the same time differential counts of stained smears were performed. Both, erythrocytopoiesis and granulocytopoiesis showed regeneration, maturation, and an absolute increase of the number of precursors and of mature cells. The quantitative data obtained in vitro during 24 hs correspond with our data of kinetics obtained by observed mitotic duration and cell differential countings in vivo. However, after a longer cultivation time we found a diminution of divisible precursors, and an increase of mature erythroblasts as well as an excessibe survival of the PMNs.


[Fine structure of megakaryocytes in aleukemic megakaryocytic meyelosis].

Megakaryocytes from a case of aleukemic megakaryocytic myelosis were examined by electron microscope. They were considerably increased in number and their ultrastructure was different from normal megakaryocytes in certain aspects. Myelinfigures became demonstrable in the cytoplasm in increased number. An effective development of the demarcation membran system could not be observed.


Lymphocytosis induced by polymethacrylic acid. Dose-effect and toxicity.

Intravenous polymethacrylic acid (PMAA) significantly increases the number of lymphocytes in the blood of the rat. The relationship between dose-effect and lymphocytosis is linear. The lethal dose in 30 days of PMAA is 120 mg/kg b.w. and the half-lethal dose 80 mg/kg b.w. The treatment with 40 mg/kg b.w. intravenous PMAA gives no toxic histological changes either in the lymph organs, the liver or the kidneys. Thus, PMAA appears to be, at present, a most suitable agent by which to provoke experimentally, migration of the reserve lymphocytes into the blood.


Toxicity of methylmercury: effects on different ages of rats.

LD50 of methylmercury chloride has been shown to be dependent on the ages of the rats. As the age increases, the LD50 decreases, i.e. the younger rats could tolerate higher doses of methylmercury than the older one. The LD50 were 39.6 +/- 2.3, 33.1 +/- 2.1, 30.3 +/- 1.0, 27.1 +/- 1.0, 24.7 +/- 1.5 and 23.9 +/- 1.1 mg Hg/kg for the 200 g, 300 g, 350 g, 400 g, 450 g and 500 g rates respectively. The elimination of mercury from blood showed little correspondence to age during the 30 days duration. The onset of neurological symptoms after receiving 25 mg Hg/kg of methylmercury chloride occurred between 8 to 15 days post dosing in the surviving rats. Rats unaffected during the latency period did not show neurological signs if their blood-mercury levels decreased to below 100 ppm. Young and old rats showed marked differences in the distribution of mercury in the blood. In the erythrocyte membrane, the eight week old rats retained a higher concentration of the toxic metal than did the 19.5 week old rats. Also,  there was significant differences in the ratios of mercury content in the red blood cells to that of plasma; young rats showing 115:1 and for the old ones being 5:1. The permeability of erythrocyte membrane to mercury might play an important role in the age factors on the suceptibility of methylmercury intoxication.


The effect of DDT on spermatogenesis of the juvenile rat.

Juvenile male rats of Wistar/Han strain were fed DDT suspended in olive oil. They received either 500 mg/kg at the 4th and 5th or 300 mg/kg daily at the 4th till 23rd day of life. After certain interval the testes were examined histologically, and at the 60th and 90th day of life fertility was proved. The spermatogenetic cells showed an increase of the physiological degeneration in the course of spermatogenesis and a decrease of their total number. The number of Leydig cells was diminished. In parallel, the litters of normal female rats mated to treated males were smaller than those of controls. The hypothesis is suggested that the damage of the seminiferous epithelium can be explained by a lack of local testosterone.


Persistence of parathion and its oxidation to paraoxon on the soil surface as related to worker reentry into treated crops.

Soil and dust samples from beneath citrus trees contained relatively high concentrations of paraoxon and parathion for at least 45 days after parathion was applied at normal rates. These data indicate that parathion dripping on dry soil from sprayed crops, or sprayed directly on the soil surface, can persist for long periods and be oxidized to the highly toxic paraoxon. The residue concentrations are much higher on the loose dust particles than in the bulk soil. The data indicate that the soil or grove floor should be considered as a possible contributing source of toxicant along with foliage, or dust on foliage, to workers reentering treated fields. In any event, the data confirmed the high rates of oxidation of parathion to paraoxon on particulate matter, whether on foliage (SPEAR et al., 1974) or at the soil surface. The particulate matter appears to contribute to the accumulation of paraoxon, either by enhancing oxidation of parathion to paraoxon or by decreasing dissipation of paraoxon.


Rapid determination and confirmation of low levels of hexachlorobenzene in adipose tissues.

The described procedure can be utilized for rapid, simple quantitation and confirmation of hexachlorobenzene in fatty tissue at levels as low as 5 ppb without the use of sophisticated and expensive equipment. Interferences can be circumvented in many instances without additional separation by selection and preparation of the appropriate derivative.


Uptake and excretion of organophosphorus and carbamate insecticides by fresh water fish, motsugo, Pseudorasbora parva.

Fresh water fish, Motsugo was reared in aquarium water tank containing about 1 ppm of 3 organophosphorus and 3 carbamate insecticides for about 30 days. The persistence of these insecticides in water and uptake and excretion of insecticides by fish were examined. Among organophosphorus insecticides, malathion is the most unstable in water, and degraded more than 99% for 7 days. Fenitrothion is moderately stable, and degraded 97% for 29 days. Diazinon is the most stable, and degraded 72% for 30 days. Among carbamates, carbaryl is the most unstable in water, and degraded more than 95% for 6 days. BPMC is moderately stable, and degraded 80% for 32 days. XMC is the most stable, and degraded 45% for 34 days. As for the uptake of the pesticides by fish, organophosphorus insecticides were generally higher than carbamate insecticides. The concentration of diazinon in fish reached to 211 ppm of the maximum level after 3 days, and that of fenitrothion reached to 162 ppm of the maximum level after 4 days. Afterwards, the concentration of both the insecticides decreased gradually due to the metabolism and excretion of the insecticides in fish. Uptake of malathion was very low and metabolized rapidly, and its concentration became to less than 0.01 ppm after 7 days. Among carbamate insecticides, the concentration of carbaryl in fish after one day reached to 7.5 ppm which was the maximum level of uptake. On the other hand, the concentration of BPMC in fish after 4 days became to 4.8 ppm, which was the maximum level, and decreased gradually. The concentration of XMC in fish was only 1.4 ppm after one day, but the metabolism rate of XMC in fish was fairly slow. Therefore, 0.55 ppm of XMC in fish remained even after 34 days. Moreover, in the test tank of diazinon, fenitrothion and BPMC, the appearance of deformed fish with spinal curvature of back bone came out at the rate of 10 to 30%.


Painful ophthalmoplegia: report of a case with cerebral involvement and psychiatric complications.

The diagnosis of Tolosa-Hunt syndrome should be suspected in the presence of recurrent "painful ophthalmoplegia." The most useful tests are the rapid (within 48 hours) response to steroids and positive findings on orbital venography. It should be emphasized that Tolosa-Hunt's syndrome may not be a "pure syndrome." Perhaps it is only an occasional presentation of another rather poorly understood syndrome, that of "recurrent cranial neuropathies." The present patient had at least three episodes of painful ophthalmoplegia prior to this hospitalization. During the last hospitalization, he presented with painful ophthalmoplegia, showed a rapid response to steroids, had narrowing of the carotid artery on arteriogram and an abnormal orbital venogram. However, during his hospitalization he developed involvement of cranial nerves II, III, V, VI and VII, papilledema, pyramidal tract signs and severe psychiatric disturbances, all of which remitted. This, coupled with the abnormal pneumoencephalogram and electroencephalogram and organicity on psychological testing, suggests cerebral involvement in our case.


Ventricular perfusion for ventriculitis.

A system of ventricular perfusion of appropriate antibiotic solutions in the management of neonatal ventriculitis is described. The technique of perfusion as well as considerations in the appropriate selection of antibiotics and perfusates is detailed. The procedure was successfully utilized in a consecutive series of nine children refractory to conventional modes of therapy.


Four cases of "locked-in" syndrome and review of the literature.

The clinical features, pathology, the autopsy studies, EEG correlation, and the cause of death were discussed. The difference between the locked-in syndrome and classical akinetic mutism was discussed. The importance of reaching a correct diagnosis was stressed to allow a different nursing care program for the conscious "locked-in" patient. Two of our cases were short-term survival, two were long-term survival, one of whom (Case 4) is still living and is the longest survival reported in the literature.


False localization of seizure activity in the EEG.

Traditional theories of EEG localization are discussed, along with their limitations and contemporary attempts to minimize false localization. Sources of error include: erratic epileptiform activity, local destruction of generators, evoked responses, and autonomous secondary foci. Several cases are presented which are thought to represent false localization by virtue of incompetent generators. It is emphasized that "epileptiform activity" and "epileptogenicity" are not synonomous.


The effect of anoxia on the ventricular fibrillation threshold in the rabbit isolated heart.

1. The ventricular fibrillation threshold (VFT) was measured in the isolated heart of the rabbit perfused via the aorta with McEwen's solution at 37 degrees C by applying a single 10 ms pulse of current during the vulnerable period of late systole. The arrhythmia induced was either fibrillation or a rapid tachycardia. 2. Gassing the McEwen's solution with 5% CO2 in N2 (anoxia) instead of with carbogen caused a negative inotropic and chronotropic effect and significantly lowered the VFT. Although anoxia releases noradrenaline from the heart the effect of anoxia on the VFT was not prevented by beta-adrenoceptor blockade with propranolol or pindolol or by previous treatment with reserpine. 3. Perfusion with adenosine (5 muM) which is released from the heart muscle by anoxia, or with dipyridamole (10 muM) which protects the adenosine from binding or destruction by the tissues, or with both combined failed to alter the VFT significantly. Furthermore neither adenosine nor dipyridamole significantly altered the effect of anoxia on the VFT. 4. Anoxia, adenosine and dipyridamole significantly increased the duration of the induced arrhythmia when compared with that of the controls. 5. Anoxia and adenosine significantly shortened the vulnerable time, i.e., the minimal time after the R-wave of the ECG at which the pulse had to be applied to induce the arrhythmia. 6. Perfusion with the McEwen's solution gassed with 5% CO2 in air (hypoxia) significantly lowered the VFT but the effect was not as great as with anoxia. Isoprenaline when infused lowered the VFT but this effect was not potentiated by hypoxia. 7. The results indicate that (a) anoxia lowers the VFT in the perfused isolated heart of the rabbit and that this effect is not due to adenosine or noradrenaline released by the anoxia and (b) hypoxia does not sensitize the heart to the arrhythmic effect of isoprenaline.


Influence of anti-hypertensive drug treatment on vascular reactivity in spontaneously hypertensive rats.

1. The effect of prolonged anti-hypertensive drug treatment on the blood pressure of conscious spontaneously hypertensive rats (SH-rats), and of age-matched normotensive Sprague-Dawley rats was determined during the development of hypertension in SH-rats and in the early stages of established hypertension. A comparison of the vascular reactivity to noradrenaline (NA) and 5-hydroxytryptamine (5-HT) was also made in isolated perfused mesenteric artery preparations from treated and control SH- and Sprague-Dawley rats. 2. Chronic treatment from age 4 to 16 weeks with hydrallazine alone, or a combination of hydrallazine/hydrochlorothiazide/reserpine, ad libitum in the drinking water, prevented the development of hypertension in SH-rats and also reduced the vascular reactivity to NA and 5-HT in isolated vessel preparations from treated compared to control rats. 3. Similar drug treatments started in early established hypertension reduced blood pressure in SH-rats over the 12 week treatment period (from age 8 to 20 weeks) without affecting vascular reactivity to NA and 5-HT in the isolated vessel preparation. 4. Drug treatments had little effect on blood pressure of age-matched Sprague-Dawley rats and no effect on vascular reactivity to NA and 5-HT in the isolated perfused mesenteric artery preparation from treated compared to control rats. 5. These results indicate that the development of increased vascular reactivity and of hypertension in SH-rats occurs simultaneously and, therefore, the vascular changes may be a consequence of the structural changes induced by the raised blood pressure. 6. In established hypertension, no regression of vascular changes was observed despite prolonged reduction of blood pressure. The role of an increased vascular reactivity in the maintenance of hypertension is therefore questionable.


An increased reactivity in hypertensive rats unaffected by prolonged antihypertensive therapy.

1. Isolated perfused mesenteric arteries obtained from chronic experimental hypertensive rats (deoxycorticosterone/NaCl) exhibited an increased reactivity to noradrenaline, 5-hydroxytryptamine and adenosine 5'-triphosphate (ATP) when compared with similar preparations from age-matched normotensive animals. 2. The dose-response curves to all three vasoconstrictor agents obtained from hypertensive animals exhibited a steeper slope, and higher maximum without any significant change in the threshold dose suggesting that adaptive/structural changes in the blood vessels had taken place. 3. Ten week treatments with antihypertensive combinations of hydrallazine, hydrochlorothiazide and reserpine or hydrallazine and mecamylamine lowered the systolic blood pressures of the hypertensive rats to those of normotensive animals and also reversed secondary changes such as periarteritis nodosa of the mesentery and cardiac hypertrophy. 4. The reactivity of these blood vessels to all these vasoconstrictor agents from the hypertensive rats with a normalized blood pressure was similar to those obtained with untreated hypertensive animals. 5. The persistent increased reactivity in the hypertensive rats after long-term anti-hypertensive treatment suggests that the hyperresponsiveness is secondary to the elevated blood pressures and that the adaptive/structural changes of the blood vessels in chronic hypertensive rats cannot be reversed by prolonged antihypertensive therapy.


The effects of lysergic acid diethylamide on the response to field stimulation of the rat vas deferens and the rat and cat anococcygeus muscles.

1. The effect of lysergic acid diethylamid (LSD) on the response to field stimulation in vitro of the rat vas deferens and anococcygeus muscle was examined. 2. LSD in concentrations from 10(-9) to 10(-6) M caused an increase in tone or rhythmic activity in both tissues, effects identical to those produced by guanethidine or tyramine. The motor effects of all three drugs were abolished by phentolamine 2 x 10(-6) M. Methysergide 2 x 10(-7) M given before LSD reduced the motor effect but was ineffective once the LSD contraction had developed. 3. LSD 10(-9) to 10(-6) M reduced and eventually abolished the response to motor adrenergic nerve stimulation in the anococcygeus muscle with no effect on the response to noradrenaline (NA) and no evidence of differential sensitivity according to the number of stimulating pulses. In the vas deferens LSD abolished the initial twitch component with no effect on the secondary slow contraction. LSD had no effect on the response to inhibitory nerve stimulation in the anococcygeus. 4. These results suggest that in the anococcygeus LSD closely resembles guanethidine in its effects as an adrenergic neurone blocking drug with indirect sympathomimetic actions. In the vas deferens these properties would explain the block of the initial twitch component in the motor response to field stimulation and the increase in rhythmic activity but do not explain the resistance of the secondary slow component of the motor response.


Release of prostaglandin-like substances by Shigella endotoxin and its inhibition by non-steroidal anti-inflammatory compounds.

1. The effects of intravenous and intraocular injections of Shigella endotoxin on the inflammatory response, the release of prostaglandin-like substances into the aqueous humour, and the effects of indomethacin on the inflammatory response were studied in the rabbit eye. 2. Both intravenous and intraocular injection of endotoxin released 12.8 ng to 72 ng of prostaglandin-like substances per ml of aqueous humour and increased the permeability of the blood-aqueous barrier as shown by the rise in aqueous humour protein (26-52 mg protein/ml of aqueous humour). 3. Indomethacin, 0.25% administered topically completely inhibited the release of prostaglandin-like substances but was found to have inconsistent inhibitory effects on the clinical signs of inflammation and on the blood-aqueous barrier. Indomethacin was less effective in eyes receiving the higher dose of endotoxin. 4. It is suggested that prostaglandins and possibly other chemical mediators are involved in endotoxin-induced ocular inflammation.


Reduction of antigen-induced contraction of sensitized human bronchus in vitro by indomethacin.

1. Contraction of passively sensitized human bronchus induced by antigen challenge in vitro, was reduced by the prostaglandin F2alpha synthetase inhibitor, indomethacin. 2. Prostaglandin F2alpha was released during challenge and this release was inhibited by indomethacin. 3. There was a significant correlation between prostaglandin F2alpha release and antigen challenge-induced contraction, suggesting that this substance may contribute to the bronchoconstrictor response of sensitized human bronchus to antigen.


Prostaglandin release from cat and dog spleen.

1. The output of prostaglandins from the spleens of cats and dogs was studied. Comparison is made between the results found in the two species. 2. The release of prostaglandins was investigated in isolated saline-perfused spleens and in incubates of spleen slices. Release in response to nerve stimulation, and exposure to adrenaline or noradrenaline was compared with resting release. 3. A resting release of prostaglandins was found in the dog but not in the cat spleen. 4. Whereas stimulated dog spleens released microgram quantities of prostaglandins E2 and F2alpha, prostaglandin output from the cat spleen under similar conditions was undectectable or barely detectable. 5. The identity of the prostaglandins released from the dog spleen (prostaglandins E2 and F2alpha) was confirmed by mass spectrometry. 6. The species difference in prostaglandin output from the spleen is discussed in relation to the hypothesis that endogenous prostaglandins modify the responses of this organ to nervous stimuli.


The role of H1 and H2-receptors in the coronary vascular response to histamine of isolated perfused hearts of guinea-pigs and rabbits.

1. The effects of histamine on the isolated perfused hearts of guinea-pigs and rabbits were examined. Records of contractile force, heart rate and coronary perfusion pressure were obtained. 2. Histamine exerted positive inotropic and chronotropic effects which were antagonized by burimamide and attributed to stimulation of H2-receptors. 3. The coronary vascular response to histamine differed between guinea-pigs and rabbits. In guinea-pig hearts, three phases were apparent: (a) An initial vasodilatation preceding any effects on heart force and rate was antagonized by mepyramine and therefore mediated by histamine H1-receptors in the coronary circulation. (b) A secondary vasoconstriction was attributed to the increased myocardial compression during the positive inotropic and chronotropic responses. (c) The final, more predominant, component was a prolonged vasodilatation probably associated with the increased metabolic activity of the heart. 4. The latter two components were abolished together with the myocardial responses by burimamide. The remaining coronary vascular response was biphasic, consisting of a vasodilatation immediately followed by vasoconstriction. Both were antagonized by mepyramine and therefore mediated by H1-receptors. 5. The coronary vascular response of rabbit hearts was similar but no direct vasodilatation was observed and it was concluded that histamine receptors in the coronary vasculature involve only vasoconstriction.


Attainment and adjustment in two geographical areas. II--The prevalence of specific reading retardation.

Specific reading retardation was found to occur in a minimum of 9-9 per cent of ten-year-old 'indigenous' children in one inner London borough. This rate was nearly three times that (3-9 per cent) in Isle of Wight children. There was a comparably higher rate of general reading backwardness in London (19-0 per cent vs 8-3 per cent). Since the same epidemiological methods were followed in the two areas, and since the reading-retarded children had similar psychological characteristics in both cases, it is concluded that there is a real difference between London and the Isle of Wight in the prevalence of reading retardation and of reading backwardness.


Attainment and adjustment in two geographical areas: III--Some factors accounting for area differences.

It was found that emotional disorders, conduct disorders and specific reading retardation were all twice as common in ten-year-old children attending schools in an inner London borough as in children of the same age on the Isle of Wight. The correlates of these disorders in the two areas were investigated in order to explore possible reasons for these differences in prevalence. It was possible to identify four sets of variables (family discord, parental deviance, social disadvantage and certain school characteristics) which were associated with child disorder and deviance within both the two areas. As in almost all cases these same adverse factors were more commonly found in London, it may be concluded that the high rates of psychiatric disorder and specific reading retardation in London ten-year-olds are due in part to the fact that a relatively high proportion of London families experience marital discord and disruption, that many of the parents show mental disorder and antisocial behaviour, that families often live in poor social circumstances, and that the schools are more often characterized by a high rate of turnover in staff and pupils. The evidence suggests that these problems stemmed from living in an inner London borough, but further research is required to identify what it is about life in a metropolitan area that predisposes to the development of disorder and deviance.


Studies of adoptees from psychiatrically disturbed biological parents: psychiatric conditions in childhood and adolescence.

Psychiatric problems were assessed in two groups of adoptees by interviewing the adopting parents. One group of 59 adoptees, the "experimental', were born of psychiatrically disturbed biological parents; the other group, the "control' of 54 adoptees, had psychiatrically "normal' biological parents. Both groups had been separated from biological parents at birth. The incidence of psychiatric conditions requiring professional care was significantly higher in the experimental than in the controls (37 per cent vs. 14 per cent). In the experimental group more males than females were disturbed (59 per cent vs. 30 per cent). Most of the excess of disordered males were diagnosed hyperactive. There was some evidence of correlation of the type of psychiatric diagnosis of the biological parent with that of the adoptee.


Objectives and training in psychiatry.

The recommendations on postgraduate training made by the World Health Organization, the Nuffield Provincial Hospitals Trust and the Royal Medico-Psychological Association are examined in the light of modern concepts of educational objectives. In this country no well defined, specific, assessable and detailed objectives have yet been formulated for postgraduate training in psychiatry.


The mental health of Jehovah's Witnesses.

The function of religion in human society is complex. The part played by religion in psychiatric disorders is even more obscure. Previous literature and theories are divided into two groups: one school believes that intense religiosity is a symptom-complex indicative of psychiatric disorder, while the opposing view is that religious belief in some way acts as a defence mechanism protecting the individual and his psyche. The present study of 50 Jehovah's Witnesses admitted to the Mental Health Service facilities of Western Australia suggests that members of this section of the community are more likely to be admitted to a psychiatric hospital than the general population. Furthermore, followers of the sect are three times more likely to be diagnosed as suffering from schizophrenia and nearly four times more likely from paranoid schizophrenia than the rest of the population at risk. These findings suggest that being a member of the Jehovah's Witnesses faith may be a risk factor predisposing to a schizophrenic illness. Further studies would be interesting in investigating whether pre-psychotic people are more likely to join the sect than normal people and what part (if any) membership has in bringing about such a breakdown.


Cross-national study of diagnosis of the mental disorders: a comparative psychometric assessment of elderly patients admitted to mental hospitals serving Queens County, New York, and the former borough of Camberwell, London.

In a cross-national comparison of the frequency of occurrence of various diagnoses among elderly psychiatric patients admitted to public mental hospitals in London and New York, a short battery of psychological tests was administered to all patients independently of psychiatric examination. The psychological assessment was focused on the differentiation between dementing and affective disorders. The test performance showed a highly significant difference between the two groups as diagnosed, and when patients were allocated to groups on the basis of tests alone these allocations showed a high rate of agreement with initial psychiatric diagnosis. There was a similar high rate of agreement between test allocation and hospital diagnosis in the U.K., but this was not so in the U.S. No significant differences were found between the test performance of U.K. and U.S. patients, except on the WAIS Vocabulary and the Angles Error measurement of the Bender-Gestalt test. When the effects of age and Vocabulary score were eliminated these differences disappeared. The hypothesis that the diagnosis of affective disorder would be confirmed by a relatively greater improvement in test performance over time in this group of patients was not upheld by the non-parametric analysis of change scores. However, an analysis of covariance utilizing age and initial score did indicate the expected differential improvement.


The prediction and predictability of speech in schizophrenic patients.

Previous research suggests, though by no means consistently, that schizophrenic patients may be less able than normals to predict the speech of other people, and that schizophrenic speech is less predictable than normal speech. The present experiment tests these two suggestions and also a third possibility, that the difference between schizophrenic and normal speech is less marked for schizophrenics asked to make the predictions than for normals. Twelve schizophrenic patients recently admitted to hospital, and twelve comparable, psychiatrically normal, orthopaedic patients, were asked to predict both schizophrenic and normal speech, using Cloze Procedure, under both fourth-word and fifth-word deletion. The first hypothesis was upheld, but the second and third received only very limited support. The findings are discussed in the light of previous work, and suggestions are made for future research.


Immediate effects of improved hospital environment on behaviour patterns of mentally handicapped patients.

In 1972 three old hospitals were closed and patients transferred to a new hospital for the mentally handicapped. Four to six weeks before transfer, disturbed and a sample of non-disturbed patients were rated on a selected scale; they were again rated four to six weeks after transfer. The disturbed patients numbered 39 per cent of the total and both men and women shared a significant improvement, though the men did not improve to the same extent as the women. There was also a significant improvement among the non-disturbed patients, though this did not apply to the epileptic patients.


The removal of retained gallstones from the common bile duct: experience with sodium cholate infusion and the Burhenne catheter.

The use of cholic acid T tube infusion and of the Burhenne catheter has been investigated in the management of gallstones retained in the common bile duct following biliary surgery in 9 patients. Four of 7 patients treated with cholic acid infusion showed disappearance of the stones during treatment. The stones in a fifth subject were removed by a combination of cholic acid infusion (1 stone disappeared) and instrumentation with a Burhenne catheter (a second stone removed). Use of a Burhenne catheter was unsuccessful in 3 of 4 patients. Details of the technique of cholic acid infusion are given, and possible complications of the treatment are discussed. The use of cholic acid infusion for the dissolution of stones in the common bile duct is recommended.


Long term changes in total body water, total exchangable sodium and total body potassium before and after ileostomy.

In 10 patients with inflammatory bowel disease, total body water, total body potassium and total exchangable sodium were measured both before and 6 months after the establishment of a permanent iseostomy. All 10 patients underwent elective surgery for their inflammatory bowel disease but all were malnourished before surgery when their body composition was first measured. Six months later, when the body composition was again determined, all the patients were in good health and had normally functioning ileostomies. As a group they had gained 6-8 kg in body weight and 372 mEq total body potassium over the 6-month period. When the 'normal' total body water was calculated for each patient, a deficit of 12-4 per cent for the group was found before surgery and this was still present (11-1 per cent) 6 months later. The concentration of exchangable sodium in the body water fell from an abnormally high level before surgery to within the normal range 6 months later. These data show that defictis in total body water occurring preoperatively are not repaired in the months following the establishment of a well-functioning ileostomy, and that a reduction of total exchangeable sodium is present in patients with an ileostomy who are otherwise well. It is suggested that these findings should encourage the surgeon managing patients with intractable inflammatory bowel disease to strive for good nutrition and normal body composition before embarking on excisional surgery and the establishment of a permanent ileostomy.


Results of surgery for Crohn's disease in the Glasgow region, 1961-70.

During the period 1961-70, 283 patients in the Glasgow region have been studied with regard to the outcome of 418 surgical procedures performed for Crohn's disease. Resection was followed by an overall recurrence rate of 33 per cent, but in disease confined to the large bowel the rate was 18 per cent. Exploratory operations and bypass procedures were followed by a recurrence rate of 70 per cent. Evidence is provided that recurrence following bypass procedures for small bowel disease and ileocolitis occurs at a later stage than after exploratory operations alone. By the end of the study 77 per cent of patients in this series had required one or more resections.


Signifance of faecoliths in the diagnosis of acute appendicitis.

Three cases are presented which demonstrate the significance of faecoliths in the diagnosis of acute appendicitis in infants. A wide spectrum of symptoms is noteworthy. The usefulness of a plain X-ray of the abdomen in infants with acute abdomen is stressed.


The changing pattern of hospital admissions for divertical disease of the colon.

Hospital admissions for symptomatic diverticular disease of the colon were studied during two periods, 1958-61 and 1968-71, in a relatively closed community in north-east Scotland. There was a significant increase in the numbers admitted, from 206 to 366. In the earlier 4-year period among patients aged 70 years and over there was a preponderance of females, but in the later study period the risk of developing symptomatic disease was almost as great among elderly males. Most of the elderly female patients were widowed city dwellers. The proportion of patients requiring operation for or dying from diverticular disease declined, but perforation remained as a frequent complication carrying a high mortality.


The nature of haemorrhoids.

An anatomical and clinical study aimed at uncovering factors likely to be helpful in understanding the true nature of haemorrhoids is described. The main finding was of specialized 'cushions' of submucosal tissue lining the anal canal; it is argued that piles are merely the result of their displacement.


Localization of parathyroid adenomas by computer-assisted parathyroid scanning.

In an attempt to localize adenomas of the parathyroid glands 36 patients with suspected hyperparathyroidism were studied with a computer-assisted double isotope scanning technique. Six patients were excluded from the statistical analysis because of uninterpretable scans. A definite localization was made with the computer-assisted scan in 16 patients. In 14 of these patients the site of the tumours was correctly predicted. In 14 patients no localization was seen on the scan. Four of these patients were classified as false negatives. In 14 out of the 16 correctly localized tumours two-thirds had weights equal to or less than 1-5 g.


True recurrence of hyperparathyroidism: proposed criteria of recurrence.

Although recurrent hyperparathyroidism should not be rare on theoretical grounds, only a few cases of proved recurrence have been reported in the literature. In the present author's series only 4 patients (1 per cent) had true recurrence. Criteria for recurrence were: 1. Histological identification by biopsy and frozen section of all the parathyroid glands at the first operation. 2. Complete removal of the enlarged gland(s). 3. A normocalcaemic period of at least 1 year. 4. The finding of a tumour at the site of a previously normal-sized gland. The low incidence of recurrent hyperparathyroidism might be explained by the long period of time needed for the recurrence to develop. However, since diagnosis of hyperparathyroidism is now more easily made and patients are treated surgically earlier in the course of the disease, the incidence of true recurrence might be expected to rise. A meticulous exploration during operation and careful follow-up of the patients are therefore required.


Recurrent pleural effusion in chronic relapsing pancreatitis.

A case of recurrent pleural effusion occurring in a patient with chronic relapsing pancreatitis is presented. Although it is one of the less common manifestations of the pleuroplumonary complications of pancreatitis, the presence of such a lesion is of diagnostic importance when the enzyme content of the effusion is elevated above the levels in the serum. In most of the reported cases resolution has occurred with conservative therapy, but failure to do so necessitated subtotal pancreatectomy, following which the patient made an uneventful recovery.


Xanthogranulomatous pyelonephritis: a report of 2 cases.

Two cases of xanthogranulomatous pyelonephritis are reported in Negroes. The clinical findings are similar to those in previously reported cases. In 1 case nephrolithotomy was followed by the development of a perinephric abcess 8 months later. Late diagnosis has limited experience with more conservative management, which should be reserved for demonstrably focal disease.


An incision for en bloc nephrectomy.

A surgical approach is described for en bloc removal of a large renal mass, enabling easy removal of such a mass with early palpation and ligation of the renal pedicle and with the minimum of assistance. The principle underlying the approach is that of detaching the costal margin and the free ribs from the abdominal musculature. In the experience of the author the wound always heals by first intention. No complications have been encountered and the patients have been discharged from hospital within 10 days of operation.


Undetected aorto-iliac insufficiency: a reason for early failure of saphenous vein bypass grafts for obstruction of the superficial femoral artery.

A series of 29 femoropopliteal bypass operations is described. The patients were selected carefully to exclude those with clinical and aortographic evidence of aorto-iliac disease. A pulsatility index was calculated from the velocity waveforms recorded over the common femoral and popliteal arteries. The pulsatility index is the ratio of the amplitude of the waveform to its mean height over one cardiac cycle. There was a highly significant difference in the result of the operation between patients with a pulsatility index of 4 or more in the common femoral artery and patients with a pulsatility index of less than 4. We concluded that calculation of this pulsatility index provides useful additional evidence when selecting patients suitable for a femoropopliteal bypass.


Nodular fasciitis: an unusual cause of extradural spinal cord compression.

A case of nodular fasciitis causing extradural spinal cord compression with a successful outcome following removal is reported. Such a tumor within the spinal cord has never been reported. The pathogenesis of a nodular fasciitis in this situation and its differential diagnosis is discussed.


Peritoneal nesothelioma.

Two patients with primary peritoneal mesothelioma are reported. They had abdominal symptoms, no symptoms referable to the respiratory system and normal chest X-rays. There was no clinical evidence of impaired respiratory function. One of the patients had a history of brief asbestos exposure over 20 years before diagnosis. The procedure for obtaining compensation is outlined and the protean uses of, and hence possible exposure to, asbestos are noted. In screening programmes consideration should be given to both pulmonary and abdominal symptoms. Laparoscopy may have a part to play in earlier diagnosis of peritoneal mesothelioma.


The negative cholecystogram in gallbladder disease.

Seventeen cases of radiologically negative gallbladder disease are presented. In all it was possible to explain the symptoms on the basis of the 'disappearing stone' hypothesis. It is suggested that cholecystectomy should be advised in such patients provided that the symptoms are sufficiently characteristic and sufficiently severe.


Observations on peripheral and central temperatures with particular reference to the occurrence of vasoconstriction.

The importance is emphasized of the inadequacy of the term 'body temperature', but that both core temperature and the peripheral temperature must be considered. The assessment of vasoconstriction is informative, and advantage should be taken of the exact information that can be provided by an electro-thermometer as opposed, for example, to a touch of the hand. The core temperature is taken from the rectum, the nasopharynx or tympanic membrane, and the peripheral temperature from the great toe. If the peripheral temperature falls the loss of body heat is prevented and the core temperature rises. If this is not understood or not recognized misguided attempts may be made to try to reduce the raised central temperature by cooling the skin. This can result in a further rise of central temperature. The recognition of peripheral vasoconstriction enables a proper assessment to be made of its basic cause and of the necessary treatment. The most important cause is hypovolaemia from blood loss and a detailed account is given of how this should be recognized, especially by a study of the gradient between central and peripheral temperatures. Such studies should be a routine in any severe illness, whether medical or surgical, in which circulatory deterioration is likely, especially after major operations or injuries. Study of the temperature of the heel (hindfoot) as well as of the toe (forefoot) can indicate a selective shutdown of peripheral circulation that reveals an especially critical circulatory state.


Aorto-iliac reconstruction with special reference to the extraperitoneal approach.

We have used the extraperitoneal approach for aorto-iliac reconstruction for lower limb ischaemia in over 130 patients. The operative exposure is excellent. Operating time is shortened and the upset to the patient much less than in the transperitoneal approach. We now believe that the method is suitable for use in the majority of aorto-iliac reconstructions. Patency rate 4 years after surgery for claudication is 89 per cent.


Oesophagogastrostomy without a drainage procedure in oesophageal carcinoma.

Ten patients with carcinoma of the lower third of the oexophagus who had oesophagogastrectomy followed by oesophagogastrostomy without a drainage procedure were investigated 6 months postoperatively. Postoperative symptomatic evaluation and modified Visick grading of the results were carried out by an independent observer. Objective assessment included fibre-optic endoscopy of the oesophagus, stomach and duodenum, gastric acid secretory studies and measurement of gastric emptying times following the ingestion of a barium food mixture. Eight of the 10 patients had an excellent or very good result and the remaining 2 were graded as satisfactory. No evidence of macroscopic oesophagitis or gastritis was detected and pyloric obstruction was never observed. Gastric emptying time was not prolonged. The results obtained support the concept that a drainage procedure is unnecessary after oesophagogastrostomy.


Antrectomy with Roux-en-Y anastomosis in the treatment of peptic oesophagitis with stricture.

A series of 8 patients with severe oesophageal strictures secondary to reflux oesophagitis who have been treated by antrectomy with Roux-en-Y anastomosis is described. There was 1 postoperative death. The remaining patients have been completely relieved of heartburn and all have had a dramatic improvement in their dysphagia. This method of treatment is strongly recommended for patients who have had prior surgery to the hiatus which has failed, and for those who are too elderly or frail to withstand a direct attack on their oesophageal stricture.


Gastric mucosal resection in the treatment of peptic ulcers: a 1-10 year clinical follow-up.

The clinical results of gastric mucosal resection are reported after a 1-10-year follow-up in which 76 per cent of patients were followed up for more than 5 years. There were 3 postopertive deaths in 152 patients. Mucosal antrectomy with vagotomy for duodenal ulcer in 96 patients, and for recurrent ulcer in 9 patients, has not been followed by a single recurrence. Gastric mucosal resection alone for the treatment of gastric ulcer in 21 patients resulted in 1 recurrence. Although vagotomy combined with resection is currently out of fashion for the initial treatment of duodenal ulcer in Britain, mucosal gastric resection has technical advantages in combination with vagotomy for the cure of recurrent ulcers following duodenal ulcer surgery.


Primary gastric tuberculosis: a case report.

A case of primary gastric tuberculosis is reported in a 34-year-old Negro male. The difficulty in diagnosis is emphasized. Surgical resection with postoperative anti-tuberculosis chemotherapy was followed by satisfactory recovery.


Congenital hepatic fibrosis: aspects of diagnosis and surgical management.

Five cases of congenital hepatic fibrosis are described. In all the patients the diagnosis was delayed as a result of either failure to perform liver biopsy or misinterpretation of the histological features. Four patients had multiple operations for the control of haematemesis or the relief of portal hypertension. It is stressed that a high index of suspicion, the use of endoscopy and a liver biopsy are essential to avoid delay in diagnosis. The patients have a good prognosis provided that the diagnosis is established at an early stage and portacaval anastomosis performed.


Splenic-gonadal fusion.

Various aspects of splenic-gonadal fusion are discussed and 1 case of the continuous type is reported. A plea is made to include this condition in the differential diagnosis of scrotal masses, particularly those on the left side.


Abdominoscrotal hydrocele.

The number of cases of abdominoscrotal hydrocele reported in the leterature has been brought up to date, which, including the 3 cases reported here, is 83 of which 21 are from India. The pathogenesis of this lesion is discussed. It is concluded that all cases of abdominoscrotal hydrocele are due to progressive involvement and distension of the patent processus vaginalis which is cut off from the general peritoneal cavity. A new classification of abdominoscrotal hydrocele is suggested on the basis of experience gained from the 3 cases reported here.


Triorchidism with normal spermatogenesis: an unusual cause for failure of vasectomy.

The wife of a vasectomized man became pregnant by her husband. He was examined and a supernumerary testis with intact vas and with normal histology and normal spermatogenesis were discovered.


Immediate operative fitting of upper limb prosthesis at the time of amputation.

Three patients are described--2 with an above-elbow amputation and 1 with a through-wrist amputation--in whom a temporary prosthesis was applied on the operating table and in all of whom function was rapidly established. The patients did not become one-handed, with the result that they have all continued to wear their prosthesis throughout their working hours and use their artificial hand for all everday functions. The value of this technique in making the patient accept the prosthesis and therefore to make full use of it suggests that this procedure should be more widely applied in patients who require upper limb amputation.


The bacteraemia associated with burns surgery.

Fifty-four surgical procedures on 39 burnt patients were studied with serial blood cultures. In 25 (46 per cent) of these procedures the cultures were positive. In spite of the absence of prophylactic systemic antibiotics there were no clinical manifestations and not one of the bacteraemias developed into a septicaemia. The role of natural immunity in controlling the bacteraemia is discussed and it is suggested that prophylactic systemic antibiotic therapy covering burns surgery is unnecessary in the presence of normal immunoglobulin levels.


A rabbit model of perforated appendicitis with peritonitis.

No satisfactory animal model simulating acute perforating appendicitis followed by peritonitis in man has hitherto been achieved. A technique has been developed in New Zealand White rabbits to fulfil these desiderata. The bacterial flora associated with the ensuing peritonitis is similar to that found in man both as regards aerobes and anaerobes and their concentrations. The method effectively produces the required model in 70 per cent of rabbits subjected to the experiment. Satisfactory postoperative survival is achieved enabling therapeutic studies.


The effect of noxytiolin in experimental peritonitis.

The evidence for the value of noxytiolin (Noxyflex) in peritonitis is contradictory. In a controlled trial of the effect of noxytiolin in pertonitis in rabbits we have found a significant increase in mortality in the trial group compared with a control group, but no significant difference when a dose equivalent to the recommended human dose is used. The postoperative course is adversely affected in the animals receiving noxytiolin.


Results of modified Robert Jones operation for clawed hallux.

The results of modified Robert Jones operation for clawed hallux carried out on 36 feet were reviewed by clinical and radiological investigations. Twenty-nine feet (80 per cent) achieved good results while 3 feet (8-5 per cent) obtained fair results and in 4 feet (11 per cent) the results were poor. Better results were obtained in the poliomyelitis cases than in the other groups. Correction of deformity appears to be achieved by the transferred extensor hallucis longus elevating the first metatarsal neck and by the flexor hallucis longus flexing the rigid toe obtained by interphalangeal arthrodesis. Tendon regeneration which is associated with recurrent clawing remains a problem. Internal fixation should be used for the interphalangeal arthrodesis.


Carcinoma arising in thyroglossal duct remnant: case reports and review of the literature.

Two cases of thyroglossal duct cyst carcinoma are presented and the world literature is reviewed. There are only 74 cases reported to date. In nearly all the cases the clinical diagnosis was thyroglossal cyst. Although the great majority of the tumours were papillary adenocarcinomas, 13-15 per cent were of other histological types. The treatment has been quite variable, but the most common initial treatment was Sistrunk's (1928) operation. Following the establishment of the diagnosis of malignancy, thyroidectomy was done in several cases, but it failed to show any evidence of malignancy in most of the thyroids removed, which establishes firmly the de novo origin of these tumours from the thyroglossal duct remnant. In only one case had tumour disseminated to distant organs, the lung, liver, etc. The scepticism as to whether some of the carcinomas associated with thyroglossal duct remnants may not in fact represent metastases from a small primary tumour of thyroid gland is examined. It appears that, though a possibility of primary or metastatic tumour in the thyroid does exist, the probability does not appear to be high. From our own experience it is suggested that local excision followed by radiotherapy, irrespective of recurrence, may be worth considering for the treatment of such carcinomas.


Secondary carcinoma of the thyroid gland.

Two patients are described who presented with clinically solitary thyroid nodules which were found to be due to metastatic disease from the kidney and colon respectively. Removal of the solitary metastatis in one patient resulted in disease-free survival for over 5 years.