[Isolation and properties of poly(A)-mRNA from mouse plasmacytoma MOPC-21].

The non-degradable immunoglobulin polyribosomes were isolated from mouse plasmocytoma MORS-21 according to a previously developed immunochemical procedure. The physico-chemical and biological properties of poly (A)-mRNA isolated from individual polyribosomes were studied. The mRNA preparations obtained can be used as a model for studies of current problems of gene engineering.


[Intracellular and extracellular alkaloids of Penicillium roqueforti].

The alkaloid composition of mycelium and culture liquid filtrate of the fungus Penicillium roqueforti IBPM-F-141 was studied. The new metabolite--3,12-dihydroroquefortine, a derivative of roquefortine, the main component of the alkaloid fraction of this culture, has been isolated for the first time. The structure of 3,12-dihydroroquefortine was determined by chemical and physico-chemical methods. In addition to roquefortine and 3,12-dihydroroquefortine, representatives of a new alkaloid group, the clavine alkaloids, e. g. isofumigaclavine A, isofumigaclavine B and festuclavine, were also isolated and identified. The data on the content of these compounds in mycelium and culture medium are presented.


[Fatty acid composition of glycerolipids from potato leaves].

A method for rapid isolation of glyco- and phospholipids from potato leaves by a two-fold separation in a thin layer of silica gel is described. Using gas-liquid chromatography, the fatty acid compositions of monogalactosyldiglyceride, digalactosyldiglyceride, sulfolipid, phosphatidyl choline, phosphatidyl ethanolamine, phosphatidyl glycerol, phosphatidyl inositol, diphosphatidyl glycerol, phosphatidic acid and non-identified lipid from potato leaves were determined. The monogalactosyl diglyceride was found to contain up to 25% of 7,10,13-hexadecatrienic acid. Trans-3-hexadecenic acid as well as phosphatidyl glycerol is a constituent component of phosphatidic acid, diphosphatidyl glycerol and the non-identified lipid.


Smooth pursuit eye movements and attention in psychiatric patients.

The effects of two putative attention-engaging maneuvers on tracking performance were studied in three groups of subjects: inpatients (n = 19), outpatients (n = 19), and controls (n = 20). One method involved realerting subjects during tracking by repeating instructions to track carefully. The second method, a signal detection task incorporated into the tracking stimulus, required that subjects signal their perception of brief interruptions of the tracking light by pressing a hand-held button. The tracking performance of inpatients was significantly inferior to that of both outpatients and controls, whereas tracking performance of these two latter groups did not differ. Verbal realerting did not significantly improve tracking performance in any group; moreover, during the administration of these instructions there was an increase in tracking errors in inpatients. Inpatients also made more tracking errors than comparison groups during signal detection trials. Other subject factors of possible relevance to tracking performance, e.g., age, gender, and level of arousal, were found not to covary with tracking accuracy in a manner which would explain the observed group differences. It is unlikely that voluntary inattention is the basis for the observed impaired tracking in hospitalized psychiatric patients; the data are more consistent with an interpretation based on heightened distractibility or information overload in these patients.


"Mental set" in controls, postalcoholics, chronic schizophrenics, and "organics".

Subjects consisted of (normal) controls, postalcoholics, chronic schizophrenics, and "organics" (a miscellaneous group of patients with acquired organic brain disorders including posttraumatic encephalopathy, Alzheimer's disease, Behçet's disease, Huntington's chorea and poststroke encephalopathy). "Mental set" was measured by comparisons of simple auditory-manual reaction times (RTs) at preparatory intervals (PIs) of 2, 5, and 10 sec following "warning" light flashes. First, the PIs were varied randomly over 48 trials (irregular procedure); then, each of the three PIs was held constant for 16 successive trials (regular procedure). Overall RTs increased significantly and progressively from controls to postalcoholics to chronic schizophrenics to organics. Mean differences between irregular and regular RTs at each PI were either significantly less for postalcoholics, chronic schizophrenics, as well as chronic schizophrenics and organics show distinct impairment of "mental set," which may be a sign of organic brain dysfunction, if other factors such as severe cultural deprivation can be excluded.


Hemispheric functioning in paranoid and nonparanoid schizophrenia.

Letter-naming and dot enumeration tasks, designed to elicit left and right hemisphere functioning, respectively, were presented tachistoscopically to paranoid and nonparanoid schizophrenics, nonschizophrenic psychiatry controls, and normal subjects. Types of information-processing used by paranoid and nonparanoid schizophrenics were also examined. All groups identified letters with greater accuracy with left hemisphere presentation. Group differences in the letter task disappeared once education was controlled. No hemisphere effect was found for dot enumeration but group differences emerged. As predicted, paranoids and controls processed the dots serially and hence decreased in accuracy over frame size. Nonparanoids processed in an automatic mode, revealing the same degree of accuracy over all dot sizes. The poorer performance of the nonparanoids in dot enumeration is discussed in terms of the task requiring bilateral processing and the nonparanoids' failure to integrate the processing of left and right hemispheres.


The natural history of acute organic mental syndrome after bilateral electroconvulsive therapy.

Thirty-one patients undergoing electroconvulsive therapy (ECT) were followed prospectively for the development of acute organic mental syndrome (AOMS); 15 patients (48.4%) developed AOMS during ECT. For these 15 patients, the average number of ECTs before development of AOMS was 5.5 with average duration of AOMS being 20.1 days. Comparison of these 15 patients to the 16 patients who did not develop AOMS for diagnoses, demographic data, pre-ECT laboratory data, and medications, differed only in exposure to psychoactive medications and prior presence of major medical illness.


Catechol-O-methyltransferase activity and classification of depression.

Red blood cell catechol-O-methyltransferase (COMT) activity was compared across different depressive diagnoses. In a sample of 88 depressed inpatients, using defined criteria, no difference was found in respect of enzyme activity and the following categories: primary, secondary, delusional, nondelusional, endogenous, nonendogenous (neurotic), characterological depressions. COMT did not vary with age or sex. A significant increase in COMT activity was noted in agitated, depressed males, as compared to other groups.


Changes in neuropsychological performance during treatment for alcoholism.

A battery of 24 neuropsychological tests was administered to drug-free alcoholic inpatients (n = 91) within 7 days of their last drink and again 17 days later. Comparisons between this group and a nonalcoholic group of medical inpatients (n = 20) also given the same test battery twice indicated very little improvement due to abstinence (short-term improvement) in the alcoholics after controlling for practice effects. Similarly, when early postwithdrawal performance of the alcoholics was compared to an alcoholic control group (n = 32), which took the test battery only once 21 days after their last drink, little evidence for short-term recovery of cognitive functions was obtained. Insofar as decisions about the initiation of therapeutic treatments which rely on cognitive processes are based on neuropsychological performance, we conclude that such treatments may commence as soon as the clinical symptoms associated with acute withdrawal have subsided.


The adaptive role of maladaptive neurosis.

A hypothesis is proposed which postulates that repeated failure in social competition may lead to a "neurotic" maladaptive vicious cycle. It is proposed that by magnifying genetically transmitted differences in fitness, this mechanism emphasizes the superiority of the better endowed, both in mate choice and in fitness of offspring. Species displaying high plasticity and flexibility, the concomitants of high intellectual ability, may be more susceptible to neurosis, hence may be more likely to be influenced by the vicious cycle mechanism operating at the ontogenetic level. Such species would display an accelerated rate of adaptation and intelligence. Some of the implications of the hypothesis for sexual selection, change in status, and preventive mental health are discussed.


Increased sleep motility and respiration rates in combat neurotic patients.

Noctural rates of body movements and respiratory rates were studied in 11 combat neurosis patients and 9 normal controls. Patients had significantly higher rates of body movements in sleep stage 2, and significantly higher respiratory rates in NONREM sleep and in the second REM period than normals. In patients the rates of body movements were positively correlated with sleep efficiency indices. Since some of these patients were suspected of having non-restorative sleep syndrome, it is suggested that increased sleep motility and autonomic activity might be related to this sleep disorder.


Squamous metaplasia of the endometrium. Endometrial response to intrauterine presence of fibroblast-carrying Ivalon sponge.

Squamous metaplasia of the endometrium was detected in 3 women out of ten in which fibroblast-carrying Ivalon sponge (produced by implanting the sponge subcutaneously for 6 to 8 weeks) was inserted into the uterus following dilatation and curettage. The experiments were carried out in view of previous successful similar procedures in rabbits to produce fibroblastic bridges inside the uterus, and to avoid the patients from undergoing major surgery (hysterectomy) if possible, and at the same time to use the experiment as a model of contraception procedure. Since no improvement was experienced by the patients, which continued to have excessive blood loss, hysterectomies were performed at a later date, and the specimens were thoroughly examined. The possible effect of the Ivalon sponge (acting as IUCD) on the endometrium is discussed.


Anti-tumour effect of an aromatic retinoic acid analog in a mouse syngeneic transplantable sarcoma.

Anti-tumour activity of an aromatic retinoic acid analog has been tested on Sarcoma J in syngeneic system. Tumour complete regression rate and median survival time of progressors mice are significantly improved. These results are at variance with previous observations suggesting the lack of activity of this compound on transplanted murine tumours. Arguments in favour of an immunological stimulation responsible for the observed anti-tumour effect are presented and discussed.


The effect of insulin on the growth of transplanted tumors in mice.

The growth of four murine transplantable tumours, Ehrlich ascites or solid tumour, an aplastic carcinoma, B-16 melanoma, and a thymoma, were suppressed in mice treated daily with insulin (2 IU). Since insulin increased the number of plaque-forming cells and the phagocytic activity of the liver and spleen cells, the retardation of the tumour growth was ascribed to immunological mechanisms.


The effect of propranolol on renal sodium handling in patients with cirrhosis.

Beta-adrenergic blockade by oral propanolol in five cirrhotic patients caused changes in the handling of an acute sodium load. Fractional sodium excretion following an acute saline load increased from 0.69% +/- 0.29 to 1.49% +/- 0.11 (103 microEq/min +/- 7.5 to 129 microEq/min +/- 18) before propranolol administration. After 3 days of oral propanolol 1 mg/kg day, the fractional excretion of sodium by saline loading increased from 0.52% +/- 0.19 to 2.17 +/- 0.19 (109 microEq/min +/- 9 to 178 microEq/min +/- 11). This change was not accompanied by changes in GFR, RPF or in the renin-aldosterone system. The possibility that these changes are caused by a change in the sodium transport at the tubular cell level induced by the beta-adrenergic blockade, is entertained.


Porphobilinogen synthetase activity response to increased levels of reduced glutathione produced by methylene blue, in blood, liver and kidney.

We have studied the effect of methylene blue on GSH and GSSG levels in rat blood, liver and kidney. Methylene blue treatment increases GSH levels and PBG-synthetase activity in erythrocytes while liver and kidney GSH and GSSG levels remain constant. These results indicate that methylene blue effect on PBG-synthetase activity in rat erythrocytes is mediated by an increase in blood GSH levels.


Antipyrine metabolism and liver function in patients treated with high-dose medroxyprogesterone.

The effect of high-dose medroxyprogesterone acetate (MPA, 250 mg intramuscularly for six days) on hepatic drug-metabolism and liver function was investigated in eleven females with endometrial carcinoma. Antipyrine plasma clearance, an index of hepatic drug-metabolizing ability, improved significantly during this treatment, and the serum total bilirubin level was lowered, whereas other liver function tests, including alkaline phosphatase, and albumin values in the serum, remained unchanged. The results demonstrate that therapy with MPA has an inducing effect on hepatic enzyme activity and antipyrine metabolism. The findings may be of importance when prescribing drugs for females receiving large doses of MPA.


Glucagon and epinephrine effect on blood glucose levels in rats carrying Yoshida solid sarcoma and Walker-256 carcinosarcoma.

Changes in blood glucose in response to glucagon and epinephrine administration, in rats bearing Yoshida solid sarcoma and Walker-256 carcinosarcoma have been studied, and in rats carrying Yoshida tumor which had received previously intraperitoneal glucose. The response to glucagon by tumor-bearing rats follows the control pattern but at a lower level of blood glucose. Rats which had received glucose before glucagon administration responded to this hormone as the control animals. These results indicate that glycogen metabolism in the host liver is not diturbed by the presence of the tumor.


Primary liver cancer in Cote d'Or (Burgundy). Results of three year's systematic registration in a well defined French population.

The registry of digestive tract cancers set up for the department of Cote d'Or (455, 727) was used to study primary liver cancer. The crude annual incidence rate was 10.4 per 100 000 for males, 2.3 per 100 000 for females. Among other cancer registries annual age standardized rates: 7.6 per 100 000 in males, 1.4 per 100 000 in females are in the intermediate range, close to the figure reported in Geneva and higher than incidence rates reported elsewhere in Europe. Most cancers were hepatocullular carcinomas (83%). Significant etiological factors were the sex ratio (5, 4), alcoholic cirrhosis associated with primary liver cancer in 61% of the patients. The one year crude survival rate was 8%.


A general-purpose implantable multichannel telemetry system for physiological research.

The majority of physiologically significant parameters can be accurately measured with relatively simple transducers and with a minimum of sophisticated electronics; such parameters include temperature, pressure, and electrical activity and generally require less than a 200 Hz bandwidth. In most experiments, however, measurements at multiple sites are needed to characterize fully a particular response, and the use of totally implantable telemetry systems becomes attractive as the problems of percutaneous leads in conscious animals are compounded in proportion to the number of sensors. These systems have been produced in limited quantities because a large number of components and long assembly times are necessary to provide simple amplifications and signal processing in a small implantable package. A new six-channel system incorporates all signal processing on a single integrated circuit, and only one CMOS divider chain and an integrated telemetry transmitter are required for support. This high level of integration accelerates assembly time and increases reliability by minimizing the interconnections. Such advancements are essential before the full potential of implantable telemetry can be realized. This paper details the performance of this system during initial applications requiring pressure, bioelectrical, or temperature telemetry.


Integrated power controllers and RF data transmitters for totally implantable telemetry.

Data transmitters and power/source controllers are common elements in all totally implantable instrumentation systems. Two custom-designed integrated circuits have been developed for these elements and have significant impact on the realization of compact reliable telemetry packages. The first is an elapsed-time power switch that can remotely turn on implanted battery-powered systems with a short RF burst; to prevent accidental battery drainage, it will automatically turn off after a preprogrammed time (1-5 min). The second is a precision RF transmitter capable of operation up to 125 MHz in either FM or pulse-coded format and requires only two nonintegrated inductors. These IC systems are basic building blocks for a large number of totally implantable telemetry applications.


Applications of totally implantable telemetry systems to chronic medical research.

The motivation for the development of advanced totally implantable telemetry systems is to improve the quality of medical care through a more detailed understanding of basic physiological processes. Three research protocols in electrophysiology, hepatic hemodynamics, and cardiac pharmacology are described which rely on new implantable instrumentation; these devices allow chronic measurements in the conscious animal of such diverse parameters as aortic and ventricular pressures; atrial, ventricular, and bundle of HIS electrograms; aortic and coronary blood flow, and total hepatic blood flow by measuring velocity profiles in the portal vein and the hepatic artery. The compact size and high reliability now achievable with these telemetry systems provides new tools to the researcher for the study of the body in health and disease.


Nylon-fiber-induced neutrophil fragmentation.

We have investigated the effects of mechanical elution of neutrophils from nylon-wool fiber (NWF) using the scanning electron microscope and biochemical analysis of elution fractions. We have determined that mechanical removal of neutrophils from nylon-wool fiber disrupts neutrophils adherent to nylon-wool fiber and augments release of granules, release of peripheral cytoplasmic fragments, and release of lactic dehydrogenase, a soluble cytoplasmic enzyme. Mechanical shearing of the adherent cell, and not adherence per se, causes the fragmentation. The extent of fragmentation is proportional to the NWF surface area available to neutrophils and is maximal at the temperature for optimal adherence and spreading. Agents that decrease cell spreading (n-ethylmaleimide and cold) diminish fragmentation. Cytochalasin B, an agent that destabilizes the neutrophil cortex, increases fragmentation. Fragmentation may be an important contributing cause of the abnormal morphology, function, and in vivo survival of nylon-wool-fiber procured human neutrophils. The prevention of fragmentation would appear to be necessary to insure the procurement of optimally functioning cells. Elution of NWF-adherent neutrophils in the cold might be a practical way to diminish neutrophil damage during clinical filtration leukapheresis.


Central nervous system relapse in malignant lymphomas: risk factors and implications for prophylaxis.

The records of 292 patients with malignant lymphoma other than Hodgkin's disease, registered in our protocols from 1967 to 1977, were reviewed to identify those with central nervous system (CNS) involvement. Thirty-one patients were encountered with this complication, an incidence of 11%. Patients with a diffuse histology had a higher frequency of CNS recurences (27/174 = 16%) in contrast to only 4/118 (3%) for those with nodular types. However, if only patients with diffuse histology in CR are considered, the frequency of CNS relapse is 13.5% (13/98). The risk factors that predict for the development of this complication were studied using multivariate analysis. Diffuse poorly differentiated lymphocytic and diffuse undifferentiated lymphomas were found to be associated with a high risk of CNS relapse. Prior chemotherapy, bone marrow involvement, age less than 35, and extranodal disease were also identified as high-risk factors. Using the information generated by a logistic regression model, patients with malignant lymphoma of diffuse type can be classified into three categories when first seen: low-risk group, intermediate, and high-risk group. CNS prophylaxis is recommended for the intermediate and high-risk group, while only close follow-up is advised for the low-risk group patients who have one adverse characteristic.


Activated protein C inhibits platelet prothrombin-converting activity.

Bovine platelets that have been activated by thrombin facilitate the conversion of prothrombin to thrombin in the presence of calcium ions and factor Xa. Activated protein C, a vitamin-K-dependent plasma protein, inhibits this platelet prothrombin-converting activity. The inhibition is time dependent and is not reversed by increasing concentrations of factor Xa. However, factor Xa is able to protect the platelet prothrombin-converting activity from inactivation by activated protein C. The activated protein C causes a parallel loss of factor Xa receptor sites and platelet prothrombin-converting activity. Activated protein C may contribute to the regulation of clotting through inactivation of the platelet prothrombin-converting activity.


Detection of circulating crosslinked fibrin derivatives by a heat extraction-SDS gradient gel electrophoretic technique.

A technique has been developed to identify and quantitate unique plasmic degradation products of crosslinked fibrin in plasma. In this method, fibrin derivatives are extracted by heat precipitation and dissolved with disulfide bond reduction, after which the crosslinked gamma-gamma chain remnants are identified by SDS-polyacrylamide gradient gel electrophoresis and quantitated by densitometric analysis. A heterogenous group of gamma-gamma chains with molecular weights between 100,000 and 76,000 daltons was identified in lysates of crosslinked fibrin during plasmic degradation in vitro. Three stages of crosslinked fibrin degradation have been arbitrarily defined based primarily on the extent of degradation of these gamma-gamma polypeptide chains. As little as 20 microgram of crosslinked fibrin digests added to 1 ml of normal plasma could be detected by the heat-extraction--gel-electrophoresis technique, identifying the gamma-gamma derivatives with molecular weights of 96,000, 86,000, 82,000, and 76,000 daltons. Plasmic derivatives of gamma-gamma chains were not found in normal plasma, but they were identified in the plasma of patients with disseminated intravascular coagulation and deep-vein thrombosis, both before and in increased quantity during successful thrombolytic therapy.


Induction of unscheduled DNA synthesis in human bone marrow cells by bifunctional alkylating agents.

A technique has been developed for handling human bone marrow cells intended for the examination of DNA repair synthesis. DNA-repair synthesis, induced by melphalan and nitrogen mustard, was measured as the incorporation of 3H-thymidine, registered by autoradiography as unscheduled DNA synthesis (UDS). Comparison of various cell populations disclosed considerable differences in their UDS level, this generally being greatest for the blast populations. During maturation of both myelopoietic and erythropoietic cells, there was a decrease in the UDS level, which was lowest for the end-cell stage. The lymphocytes and monocytes differed considerably in their capacity for UDS. The developed technique would appear to offer an opportunity for determining the capacity for DNA-repair synthesis in malignant bone marrow cells, a factor that has been linked to sensitivity to alkylating agents.


Thrombocytosis-induced suppression of small acetylcholinesterase-positive cells in bone marrow of rats.

Transfusion of platelet concentrates was used to establish a thrombocytosis of approximately three times normal platelet levels in male rats. This thrombocytosis resulted in a rebound thrombocytopenia to 60% of normal counts. Examination of the small acetylcholinesterase (ACh-E) positive cells of the marrow at this time showed a reduction to 50% of normal levels without significant changes in control animals. A second group of experiments indicated that this suppression developed as early as the third day posttransfusion, persisted until day 7, and returned to baseline levels by day 9. Incorporation of 75SeM indicated that the reduction in platelet count was due to decreased platelet production. Little or no changes were observed in the hematocrit or WBC. This evidence supports the hypothesis that these cells are early cells in the megakaryocytic series. They are the earliest cells of the series seen to be affected by thrombocytosis. Feedback control by platelets or platelet extracts of this cell population may represent one level of regulation of megakaryopoiesis.


Effect of prothrombin complex concentrates on factor VIII inhibitor levels.

Factor VIII inhibitor levels were measured on 261 occasions in 76 hemophilia-A inhibitor patients before and after prothrombin complex concentrate infusion at 13 treatment centers. A rise in inhibitor level to at least twice the pretreatment value occurred in 35 treatment episodes (13.5%), in 27 patients (36%). In 16 patients (21%), such an anamnestic immune response occurred with the first treatment. Factors predisposing to anamnestic responses may include patient idiosyncrasy, low pretreatment inhibitor levels, and exposure to concentrate over several days.


Decreased platelet thrombogenecity in association with increased platelet turnover and vascular damage.

Platelet turnover is increased when platelets interact with prosthetic surfaces and damaged vessel wall. To determine whether the resulting increase in young platelets is associated with an increased tendency to thrombosis, we induced a state of increased platelet turnover in rabbits by inserting a sterile cannula into the abdominal aorta and tested for platelet thrombogenecity by measuring the deposition of circulating platelets onto a second injury site in the carotid arteries. Platelet half-life was decreased and platelet turnover was increased after the aortic cannulation, although the circulating platelet count remained unchanged. Platelet thrombogenecity determined 20 hr after cannulation was significantly decreased when compared to sham-operated animals. Ear bleeding studies demonstrated that the platelets circulating in cannulated animals were hemostatically less effective than those in sham-operated animals. This effect was intrinsic to the platelet and was associated with a platelet function defect. These data suggest that platelets exposed to a damaged or foreign surface interact with the surface and then circulate in a less reactive state.


Unicellular or multicellular origin of human granulocyte-macrophage colonies in vitro.

The assumption that human granulocyte-macrophage colonies have a unicellular origin and thus are true clones has been directly tested. Cells from seven females heterozygous for the common glucose-6-phosphate dehydrogenase (G-6-PD) gene (GdB) and the variant GdA were cultured in semisolid medium for granulocyte-macrophage colony growth and the enzyme type of individual colonies was determined. When the colony density was less than 20/dish, more than 95% of colonies had either type A or type B G-6-PD, but not both. At colony densities greater than 30/dish, between 15% and 75% of colonies had both enzyme types and therefore arose from more than one cell. These results are consistent with a unicellular origin for the colonies only when they are cultured at low densities. With increasing colony density, there was a greater frequency of colonies with both type A and type B activity, suggesting that accurate enumeration of committed stem cells can only be performed at low colony concentrations.


The alpha-globin gene adjacent to the gene for HbQ-alpha 74 Asp replaced by His is deleted, but not that adjacent to the gene for HbG-alpha 30 Glu replaced by Gln; three-fourths of the alpha-globin genes are deleted in HbQ-alpha-thalassemia.

Two Chinese patients with HbQ-alpha 2 74 Asp replaced by His beta 2-alpha-thalassemia, one HbQ-alpha 2 74 or 75 Asp replaced by His beta 2 carrier, and one HbG-alpha 2 30 Glu replaced by Gln beta 2 carrier were studied to determine the number of alpha-globin genes in their chromosomes. DNA was isolated from white blood cells and bone marrow cells and studied by liquid hybridization and by hybridization of DNA fragments obtained by restriction enzyme endonuclease digestion (Ecr to nitrocellulose filters. The liquid hybridization analysis showed that in HbQ-alpha 2 74 Asp replaced by His beta 2-alpha-thalassemia, as in HbH disease, only one-fourth of the usual number of alpha-globin genes is present. Hybridization patterns of DNA restriction enzyme fragments showed that in HbQ-alpha 2 74 Asp replaced by His beta 2-alpha-thalassemia one chromosome has both alpha-globin genes deleted and the other chromosome, which carries the alpha-mutant gene, has one alpha-globin gene deleted. Our results show that the HbQ-alpha 74 Asp replaced by His structural gene is located adjacent to a deleted alpha-globin gene, whereas the alpha-globin gene adjacent to HbG-alpha 30 Glu replaced by Gln gene is not deleted.


Molecular basis of hemoglobin-H disease in the Mediterranean population.

We investigated the molecular basis of hemoglobin-H disease by hybridization and restriction endonuclease mapping of the DNA in the Mediterranean populations. Of the 12 patients studied from Cyprus and Sardinia, 8 had the typical deletion defect with a single remaining alpha-globin gene. The nondeletion type of alpha-thalassemia was found in 3, and a "dysfunctional" gene in one. We conclude that the predominant cause of alpha-thalassemia in these populations is gene deletion.


A molecular basis for hemoglobin-H disease in American blacks.

We have applied gene counting and restriction endonuclease mapping techniques to the study of two American black families in which there were one or more cases of HbH disease. We found deletions of three of the four normal alpha-globin genes in individuals with HbH disease. In two of these individuals, the chromosome containing the single alpha gene could have originated by crossing over between mispaired alpha genes, resulting in a deletion of about 4.2 kilobases (kb).


Suppression of the desquamating effect of smoking on the human endothelium by hydroxyethylrutosides.

In a group of volunteers, smoking two cigarettes produced a significant increase in the number of circulating endothelial cells. This effect was suppressed in another group by a preventive oral administration of a hydroxyethylrutoside preparation. The results fully confirmed our earlier experimental findings in rats.


Increased reactivity of isolated rabbit saphenous vein after treatment with estrogen and progesterone.

The effect of estrogen and progesterone on the reactivity of isolated rabbit saphenous veins to adrenergic stimulation by norepinephrine, methoxamine, phenylephrine, and electrical stimulation and the effect of progesterone on the reactivity to barium ions were studied. 8 days after ovariectomy, a saphenous vein was removed and studied in vitro. After 1 and 4 days of hormone therapy, the contralateral vein was removed and its reactivity was compared with that of the first vein and with that of veins from untreated, sham-operated control animals. The reactivity to adrenergic and noradrenergic stimulation was increased after 4 days of treatment with progesterone (5 mg/day); treatment for 4 days with estrogen (100 micrograms/day) increased the reactivity to norepinephrine, electrical stimulation, methoxamine, and phenylephrine. The results with progesterone suggest that the increased adrenergic responsiveness is not related to a mechanism controlling adrenergic transmission in veins.


Abnormal biochemistry of vascular smooth muscle plasma membrane as an important factor in the initiation and maintenance of hypertension in rats.

Tissue wet weight as well as total protein content, 5'-nucleotidase activity, alkaline phosphatase activity and Ca2+ accumulation associated with a plasma membrane fraction isolated from spontaneous hypertensive rats (SHR) and rats with deoxycorticosterone (DOC) induced hypertension were investigated. Enhanced alkaline phosphatase activity and reduced ATP-dependent Ca2+ accumulation preceded the development of hypertension in SHR and these effects were reversed by DOC withdrawal followed by lowering of blood pressure in DOC hypertension. Increased arterial tissue wet weight and 5'-nucleotidase occurred only at the later stage of hypertension in SHR and the increased tissue wet weight was not reversed by DOC withdrawal in DOC hypertension. These observations suggest that enhanced alkaline phosphatase and reduced ATP-dependent Ca2+ uptake may play a significant role in initiating hypertension, while increased arterial wet weight and 5'-nucleotidase activities may participate in the maintenance of hypertension.


Adult microvascular disturbances as a result of juvenile onset diabetes in Db/Db mice.

The arterioles in the cremaster muscle of 8 to 10-week-old Ob/Ob, Db/Db and stroptozotocin diabetic mice are characterized by a decreased number of arterioles, loss of vascular tone and a reduced cross-sectional area of the vessel walls. The present study was designed to determine if these abnormalities persist to adult life or if additional abnormalities develop to cause vascular dysfunction. The diameters, wall thickness to lumen ratios and vessel wall areas of comparable types of innervated arterioles in 24- to 28-week-old normal and Db/Db mice are equivalent, except that the smallest arterioles of Db/Db have thin vessel walls. However, blood flow at rest is only 3.0 +/- 0.9 ml/min/100 g of cremasteric muscle tissue in Db/Db mice as compared to 5.5 +/- 1.3 ml/min/100 g in normal mice. After all vascular control is abolished, the arterioles of Db/Db dilated, but significantly (p less than 0.05) less than in normal animals. The minimum distance between adjacent capillaries (wall to wall) during the passive state was 28 +/- 1.7 micron in Db/Db mice and 21.8 +/- 0.6 micron in normal mice; this indicates a major decrease of vascularity in the adult Db/Db mouse. The results obtained indicate that the reduction in numbers of arterioles and loss of vascular tone in juvenile diabetic mice persists to adult life but arteriolar wall characteristics become normal in adult life.


Red cell filtration by paper filters.

A method for the assessment of red cell filterability with paper filters is described. Two milliliters of a washed red cell suspension with a hematocrit of 50% was filtered through a filter paper cone in a glass funnel and the filtration half-time (FT1/2) was measured. The filter papers were calibrated by previous measurement of the filtration time for the suspending solution, the calibration time (CT). A linear correlation between CT and FT1/2 was found for individual red cell suspensions (p less than 0.001) as well as for a normal population (p less than 0.001). Consequently, the index FT1/2/CT should represent a more reproducible parameter than FT1/2 and experimentally this appears to be the case. In fact, elimination of erratic values in a normal population was realized. Furthermore, discrimination between normal and abnormal values was improved and the coefficient of variation of single measurements passed from 28.4 to 9.4%. The reproducibility and reliability of this extremely simple method are therefore decisively enhanced without complication of the procedure.


Erythropoietin in aplastic anemia.

The level of erythropoietin (Ep) was measured in sera and urine from aplastic anemia patients. Increased levels of Ep were demonstrated in sera from all 25 patients studied. An elevated level of Ep was found in the urine of 17 of 23 patients in whom the urine was tested. No correlation between blood hemoglobin and Ep level was observed. A higher serum Ep level was noted in patients with aplastic anemia than in patients with sideropenic anemia of the same severity. To explain the discrepancy diminished Ep consumption in bone marrow of aplastic anemia patients is discussed.


Erythrocyte rheology in acute cerebral thrombosis. Effects of ABO blood groups.

Within a few hours after a cerebral thrombosis in 220 patients, the flow-properties of the red blood cells (RBC) were analyzed by a filtration test that expresses quantitatively the deformability and aggregability of the RBC by the filtration indexes pT. Abnormal deformability of the RBC washed clean of plasma was found in 27.5% of the patients. Aggregability disorders, caused by the plasma trapped between the unwashed RBC, were found in 78.6% of the patients: computation of correlation coefficients between pT indexes and fibrinogen, which was found abnormally high in 88.2% of cases, demonstrated significantly that in the patients with A and B blood groups these aggregability disorders were due to fibrinogen and that they were caused by other components of plasma in patients with O and AB blood groups. All these disorders can account for blood hyperviscosity.


Demonstration of vitamin B12 deficiency by a simple cytochemical reaction in the peripheral blood smear.

A simple, rapid and inexpensive cytochemical method for the detection of vitamin B 12 deficiency was applied in several types of anemias and matched with the levels of vitamin B12 and folic acid in the serum of the patients. It was found that in patients with low vitamin B12 levels the stained erythrocytes and the erythroid precursors showed a yellowish brown discoloration, which was not detected in folic acid deficiency and all other types of anemias. This test therefore may be used for differentiation between B12 and folate deficiency whenever megaloblastic anemia is diagnosed.


[Carcinoma of the kidney in hairy cell leukemia (author's transl)].

In a 59-year old man hairy cell leukemia was diagnosed by blood smear, bone marrow smear, and bone marrow cytochemistry 1 year before he died from heart failure. No cytotoxic drugs had been given. Interestingly enough, besides hairy cell leukemia, autopsy revealed a carcinoma of the kidney that had not featured any clinical symptoms.


[The effect on gas mixing of a He-O2 mixture in chronic obstructive lung diseases (author's transl)].

In order to estimate the role played by gaseous diffusion in the mixing disorders of chronic obstructive lung disease (COLD), the effect of breathing a gas mixture lighter than air has been studied. Twenty four patients with severe airflow obstruction have been tested in the following way: in a random order they breathed two different mixtures with the same PO2 : air and helium-oxygen (heliox) for 20 min. Ventilation was monitored during the whole of each run; during the 2 last min arterial blood was sampled. While breathing heliox a slight, non-significant, increase in ventilation has been observed with a slight but statistically significant decrease of PaO2 (p less than 0.01), of PaCO2 (p less than 0.05) and increase of pH (p less than 0.01). These changes suggest a slight increase of distribution disorders with alveolar hyperventilation. For these results to be consistent with stratification, improvement of the diffusion due to low density should have been masked by other phenomena; the possible effects of ternary diffusion, increased viscous resistances and change of transfer factor have been looked at. No conclusive evidence has been found of such counter-effects. Therefore it looks unlikely that stratification be the major factor in distribution impairment in COLD.


Indoor spread of respiratory infection by recirculation of air.

Stimulated by an outbreak of measles that was spread throughout a school by the ventilating system, we looked into the possibility of preventing this hazard in air conditioned buildings. The amount of air recirculated by air conditioning systems increases as the temperature difference between indoor and outdoor air increases and often exceeds 70 per cent. Germicidal u.v. radiation in central supply ducts seems almost ideally suited for disinfecting recirculated air, being effective, safe, and cheap. The effectiveness of disinfecting recirculated air in blocking person to person transmission of airborne infection can be predicted to be great at the beginning of a potential outbreak and negligible during an established epidemic. Infection introduced by the air conditioning process, recently implicated in causing Legionnaires' Disease, might also be prevented. Air disinfection would supplement immunization in the control of respiratory infection and might be cost effective.


Redistribution of pulmonary blood flow in interstitial lung diseases: the chest radiograph as a physiologic tool.

Posteroanterior radiographs of the chest showed enlargement of vessels in the upper lung fields in 18 of 29 patients with interstitial lung diseases, despite normal pulmonary wedge pressures and normal or reduced pulmonary blood volumes. The degree of such redistribution ("diversion") did not correlate either with the severity of pulmonary hypertension observed at cardiac catheterization or with radiologic assessment of predominance of disease at the lung bases. Diversion did correlate with several indices of disease severity: reduction in vital capacity, reduction in diffusing capacity, reduction in pulmonary blood volume and radiographic severity of parenchymal abnormalities. Furthermore, diversion correlated with lung height, a variable which was not statistically related to the other indices of disease severity. Distension of upper lung vessels occurs in interstitial lung diseases as the result of a decreased hydrostatic gradient over which the lung is perfused (decreased lung height), partial obliteration of the vascular bed (decreased pulmonary volume), and, more speculatively, decreased extravascular pressure (increased lung recoil).


Ellepsis and akairial disproportion in the hypothyroid rat.

Renal structural and functional changes observed in rats during hypothyroidism have been employed to illustrate the concepts of "ellepsis" and "akairia" that have emerged from the work of Cournand and Richards. Ellepsis--the inadequate homeostatic response--is evident in the failure of corrective adjustments in glomerular filtration rate to prevent the excessive natriuresis and detrimental salt loss typical of this disorder in the rat but not in man. A slowing in overall bodygrowth is associated with an inappropriate (akairial) disproportion in the growth of glomeruli and tubules. Comparison of the changes in body weight, glomerular diameters, and tubular lengths in euthyroid and hypothyroid (radioiodine) littermates showed that glomeruli continued to grow in proportion to total body weight following administration of radioiodine while tubular growth almost ceased. Since disproportional failure of pulmonary growth has also been observed in these studies (0.829 +/- SEM 0.040 g in hypothyroid rats as compared with 1.14 +/- 0.034 g in euthyroid weight-matched controls), it may be profitable to look for abnormalities in respiratory homeostasis in the hypothyroid rat.


Oxygen transport and oxygen consumption in shock.

A review of data from patients in shock, or with very low cardiac output, shows that oxygen consumption is maintained above 90 ml . min-1 . m-2, even at the lowest values of arterial oxygen transport. CAIN [3] has found a limiting value of oxygen delivery in anesthetized, hypoxic dogs of about 10 ml . kg-1 . min-1, below which oxygen consumption falls dramatically. No comparable value has been established for man in shock.


Regional lung expansion and vertical pleural pressure gradients in normal human subjects.

Using 133Xe and a single slow inspiration from near residual volume (RV) to total lung capacity (TLC), we measured regional lung volume continuously in six regions as a fraction of volume at maximal inflation in 57 normal non-smoking subjects (age: 20 to 82 years). We found that regional initial (i.e., near RV) volume/TLC increased significantly with aging in all regions for females whereas the increase in males was significant only in the upper regions. These results suggest that the aging process in the lung is accelerated in females. Some variability in regional volume measurements occurred when inspiration started from FRC rather than near RV. Although the patterns of regional expansion generally confirm those previously reported, it was found that the volume of vertically adjacent regions do frequently become equal and cross-over one another. Using the measurements of static compliance, regional V/TLC at FRC, and a passive model based upon an isotropic distribtion of intrinsic elasticity throughout the lung, the mean vertical pleural pressure gradient between upper and middle regions and middle and lower regions were estimated as 0.246 cmH2O/cm and 0.267 cmH2O/cm respectively. We believe that the regional expansion patterns which we observed can be explained by the interaction between a variable thoraco-diaphragm/abdominal motion and a passive elastic lung.


Dyspnea.

Dyspnea is the medical term for the patient's or subject's complaint of shortness of breath. It encompasses the respiratory discomfort experienced in many different diease states as well as the shortness of breath felt by a normal subject during or after strenuous exercise. Several parameters which have been shown to correlate with the onset or severity of dyspnea are described, including reduced vital capacity, the ratio of minute ventilation to vital capacity, reduced breathing reserve, the work of breathing, and the oxygen cost of breathing. Attempts at quantitation of dyspnea have usually consisted of measuring physiological parameters associated with the sensation, such as the "dyspneic index". The direct measurement of respiratory sensations using modern psycho-physical methods is at an early stage of development. Since the observation that the existence of dyspnea is often unrelated to any disturbance of arterial blood gas composition, it has been generally held that the mechanism of dyspnea is primarily neurophysiological. The neural pathways may conceptually be divided into those which transmit the "dyspnea message" from the respiratory apparatus to integrating centers in the brain, and those concerned with subsequently bringing the sensation to the level of consciousness. It seems likely that there is no single sensing mechanism and neural pathway which will be able to explain dyspnea in the diverse populations of patients and subjects who experience unpleasant respiratory sensations. Three theories concerning mechanisms of dyspnea are briefly described: "length-tension inappropriateness", vagal afferent activity especially from the J-receptors, and the recent concept of diaphragmatic fatigue. Some specific characteristics of the shortness of breath experienced in certain disease states are described, including chronic bronchitis and emphysema, bronchial asthma, pulmonary fibrosis and congestive heart disease.


Hypoxic pulmonary vasoconstriction and the concept of hyperexis.

Professor Cournand has a special interest in hypoxic pulmonary vasoconstriction, and Professor Richards, his colleague, had a special interest in hyperexis, two seemingly unrelated phenomena in physiology. But at the end of a series of studies on cardiac output, when younger members of the Laboratory were assessing the effect of granulomatous lung disease on the calculation of output by the Fick principle, the pulmonary vessels in the diseased lung showed behaviour consistent with hyperexis, and the individual interests of the two men unexpectedly converged.


[Twelve year FEV1 changes and smoking habits among 556 workers in the Paris-area (author's transl)].

The aim of the study was to analyse the effects of smoking, in particular to show its causal role in the development of airflow obstruction, and to look at changes in smoking habits. The study was conducted among 556 men, aged 30 to 54 in 1960, surveyed twice, in 1960 and 1972. The hypothesis of tobacco as a causal factor of airflow obstruction is strengthened, following this study, by three results: 1) FEV1 slope was related to tobacco consumption, even after adjustement for FEV1 level (42 ml/yrs for non-smokers, 51 ml/yrs for heavy smokers); 2) FEV1 loss with age increased with the amount of tobacco consumption: one pack a day smoked for 25 years was equivalent to an aging of 5 years; 3) FEV1 loss decelerated if the subject gave up smoking, thus preventing any further risk. What appeared to be a spontaneous regulation in smoking habits was observed. The men who stopped smoking were those with low respiratory status. In this population, men who were ex-smokers in 1960 and maintained this status until 1972 had a FEV1 slope similar to that of the non-smokers.


[The prognostic value of haemodynamic tests in chronic bronchitis (author's transl)].

The prognostic value of several functional respiratory and haemodynamic variables was studied in a group of 212 patients with chronic bronchitis, who were examined in steady state, without cardiac or respiratory failure, at rest and when possible during moderate exercise (195 patients). Follow-up interval ranged from 5 to 12 years. Results were processed using two methods: estimation of actuarial survival rate and discriminant analysis. Survival rate curves for the patients showed a reduction relative to the general population of the same ages: 74% within five years compared to 91% in the general population, 56% within nine years compared to 82%. Survival rate was significantly lower in patients with PPA above 30 mmHg, or driving pressure (PPA--PW) above 15 mmHg, or pulmonary vascular resistance higher than 210 dyn . s . cm-5, or when PPA increased more than 10 mmHg during exercise. Discriminant analysis underlined the predictive value of three haemodynamic variables: PPA change from rest to exercise, pressure developed by the right heart (PPA--PRVED) and stroke volume: together, they predict the death of 3 over 4 patients with the criteria chosen.


Measurement of human pulmonary arterial volume in vivo.

A method of measuring pulmonary arterial transit time (PATT), from the pulmonary valve to the precapillary vessels, using the gamma-emitting isotope technetium-99m and external counting probes, has been applied in patients coming to cardiac catheterization. The method was successfully applied in 36 of 39 patients. The dose of 99Tc for a single determination was 1 mc. Agreement between right and left lung transit times was good, average difference between the two lungs being less than 7% of mean PATT. Reproducibility between duplicate injections was 9.4 +/- 1.2% (SEM). Pulmonary arterial volume (PAV) was calculated as the product of PATT and flow. In 11 normal patients average PAV was 92 ml . m-2 and constituted 30% of total pulmonary blood volume (PBV). In ten patients with pulmonary hypertension secondary to lung disease average PAV was 129 ml . m-2, constituting 38% of PBV, while, in seven patients with left ventricular disease and a similar degree of pulmonary hypertension, PAV was also 129 ml . m-2, but constituted only 29% of PBV. Thus, in pulmonary hypertension secondary to lung disease the pulmonary arteries are enlarged out of proportion to the remainder of the pulmonary vascular bed. In seven patients with carcinoma of the lung, in whom one main branch of the pulmonary artery was occluded with a balloon catheter, PAV fell significantly less than would be predicted, indicating a distension of the unoccluded portion of the arterial tree. Distensibility in the unoccluded part of the arterial tree was calculated to be 4.5% per cmH2O pressure.


Cardiac performance at rest and during exercise in normal subjects.

Hemodynamic profiles at rest and during bicycle exercise are described in 50 normal male subjects. In nine of these, the hemodynamics at rest and during exercise in the supine position have been compared to those in the sitting position. In the supine position, the observed and derived hemodynamic parameters at rest and during exercise (mean +/- standard deviation) were: heart rate 77 +/- 11 vs 127 +/- 17 beats . min-1, brachial arterial mean pressure, 12.4 +/- 1.2 vs 15.0 +/- 1.6 kPa (93 +/- 9 vs 113 +/- 12 mmHg), pulmonary arterial mean pressure 1.9 +/- 0.5 vs 3.2 +/- 0.8 kPa (14 +/- 4 vs 24 +/- 6 mmHg), left ventricular end-diastolic pressure 1.2 +/- 0.4 vs 1.7 +/- 0.7 kPa (9 +/- 3 vs 13 +/- 5 mmHg), cardiac output 6.3 +/- 1.5 vs 12.0 +/- 3.0 1 . min-1, stroke volume 88 +/- 22 vs 95 +/- 23 cm3, and left ventricular stroke work 0.93 +/- 0.27 vs 1.26 +/- 0.34 J . beats-1. Comparison of hemodynamic data in the supine and sitting position showed that pulmonary capillary wedge pressure, left ventricular end-diastolic pressure, cardiac output, stroke volume, and left ventricular stroke work were lower and heart rate higher in the sitting position, while brachial arterial and pulmonary arterial mean pressures were similar in the two positions. During exercise, the absolute values of pulmonary capillary wedge pressure, left ventricular end-diastolic pressure and stroke volume were lower and heart rate higher in the sitting position, while cardiac output and left ventricular stroke work were similar in the two positions. Comparison of changes from rest to exercise in the supine and sitting postures revealed similar increases in heart rate, pulmonary capillary wedge pressure, left ventricular end-diastolic pressure, cardiac output, and stroke volume in the two positions.


Anthropometric indices independent of age for nutritional assessment in schoolchildren.

The merits of three indices based on weight (W) and height (H) were examined in the age group six to 15 years: W/H, W/H2, W/H3. The analysis was based ona survey of 1673 schoolchildren of both sexes from a rural housing block in Delhi. It showed that the index W/H2 was invariant with age in the range six to 15 years and that the other two indices were biased with respect to age. The index W/H2 was found to be of value for the proper assessment of nutritional status in the schoolchildren of a developing country.


The relationship between breast and bottle feeding and respiratory illness in the first year of life.

The relationship between breast or bottle feeding and the incidence of bronchitis and pneumonia in the first year of life was examined in a birth cohort of nearly 2000 children born in Harrow, England, in 1963--65. Fewer episodes of acute bronchitis and pneumonia were reported in children who were breast-fed than in children who were bottle-fed. Firstborn children were more likely to be breast-fed than subsequent children. Mothers who smoked were less likely to breast-feed their babies. Although birth order and parental smoking have been shown to be associated with bronchitis and pneumonia in the same cohort, the association between feeding pattern and respiratory illness history persisted when these and other important factors were taken into account.


The use of birthweight and gestation to assess perinatal mortality risk.

Using extensive international data it is shown in detail how mortality is related to birthweight and gestation. It is demonstrated that the widely used 'birthweight for length of gestation' standards can be seriously misleading. A new 'high risk' classification is proposed.


Deaths from ischaemic heart disease and infant mortality in England and Wales.

Death rates from ischaemic heart disease (IHD) in English and Welsh counties are correlated, in both men and women, with the infant mortality rates of those counties when the individuals whose deaths are considered were young, thus confirming previous findings in Norway. In England and Wales, however, there is an equally good correlation between deaths from IHD and infant mortality patterns up to and including that for the same time period as the IHD deaths. The British data provide no grounds for concluding from these relationships that living conditions during early life per se bear a causal relationship to deaths from IHD.


A study of persons aged 65 and over in the Leeds Metropolitan District.

A study of the elderly living in the community and in institutional care in the Leeds Metropolitan District is outlined. Four populations of persons aged 65 and over were examined: those living in their own homes; in sheltered housing; in social services aged persons' hostels (Part III accommodation); and in hospitals. Findings on one key concept--coping ability--are discussed. Those living in their own homes were most able to cope. Many living in institutions were well able to cope in the community according to the criteria of mobility and functional ability. The relationship between age, morbidity, and coping ability were examined. Women were more likely to report the presence of a long-term illness than men. Housebound respondents in the community were twice as likely to be suffering from non-traumatic locomotor disorders, eyesight disorders, and cerebrovascular disease than respondents in the community sample taken as a whole.


Screening and diagnosis of hyperthyroidism: an attempt at test reduction.

A sequencial strategy for the diagnosis of hyperthyroidism has been prospectively appraised on 410 patients using a pocket calculator-aided diagnostic system. It was found that for 64% of the patients final diagnosis could be established from nine clinical signs, ankle jerk time and free thyroxin index. For the 36% of doubtful subjects, T3 determination permitted the reduction of uncertainty to 9%. No misdiagnosis was observed. By comparing this strategy with the physician's usual diagnosis process, in which all clinical signs and several thyroid function tests were used, it appeared that the number of tests was reduced by 65% for T3 requests and by 70% for other tests (99mTc uptake and TRH). The cost-saving was estimated to be about 28%. The interest of this calculator-aided decision model resides in the possibility for the general practitioner to refer only doubtful and hyperthyroid subjects to a thyroid unit.


Teachers' smoking.

Children take up smoking for many reasons and it is suggested that the example set by schoolteachers may have some influence. Smoking by male teachers appears to have some effect on boys' smoking, particularly in their first two years at secondary school. Thus, in any comprehensive study of what causes children to take up smoking and in any attempt to prevent this by means of health education, the influence of teachers as well as that of relatives and friends must be considered.


The use of a Kolmogorov--Smirnov type statistic in testing hypotheses about seasonal variation.

This paper presents a non-parametric method for testing departures from a uniform seasonal variation in incidence of disease. The method may be used either with exact dates of incidence when they are available or with monthly totals. It is equally valid for sinusoidal and non-sinusoidal departures from uniformity. A simulation study shows it to be much more powerful than other non-parametric alternatives and nearly as powerful as Edwards's test in detecting sinusoidal departures.


Consciousness, information processing and schizophrenia.

The symptoms of schizophrenia can be interpreted as the result of a defect in the mechanism that controls and limits the contents of consciousness. This defect can be understood as excessive self-awareness. Normally most of the complex information processing which is continuously required by even simple acts of perception, language and thought goes on below the level of awareness; whereas in schizophrenic patients some of this processing, or the results of this processing, not in themselves abnormal, become conscious. This excessive awareness can account for the typical symptoms of schizophrenia and explains many of the specific cognitive abnormalities found in schizophrenic patients.


First rank symptoms of schizophrenia: questions concerning clinical boundaries.

The phenomenological criteria of prominent Anglo-American researchers on certain so-called passivity experiences, sense deceptions and delusional phenomena, reflecting their interpretations of Kurt Schneider's first rank symptoms of schizophrenia, are  examined. In this way the frequent discrepancies and difficulties in deliminiting the clinical boundaries of these phenomena more clearly come to light.


A method for the study of therapeutic factors in group psychotherapy.

A method is described for the study of therapeutic factors in group therapy in which patients and their therapists prepare brief reports at regular intervals about those events in treatment which they regard as important; these reports are then assigned by independent judges to a classification of therapeutic factors which has been specifically devised for this purpose. The feasibility, validity and reliability of the method are discussed and its potential application to group therapy research and training briefly mentioned.


The validity of addict notifications.

Two representative samples of males first notified as addicts during 1969, one by hospitals and the other by penal establishments, were followed up for five years. It was found that 95 per cent of the hospital sample, but only 30 per cent of the penal sample, were addicted to opiates at some time during this follow-up, as judged by Home Office records. Notification may depend as much upon the setting and circumstances in which doctors see their patients as on their clinical judgement of a 'notifiable' case of addiction.


Deviancy, delinquency and drug use.

A system for monitoring drug use was based on the data from annual surveys of two contrasting population groups, a general cross-section of young people and a cross-section of antisocial deviants. Correlation of deviancy and drug use established that drug use, both licit and illicit, was more extensive among those who suffered parental deprivation, whose parents were divorced or separated, who had psychiatric illness and particularly those who had committed antisocial acts. The degree of antisocial deviancy correlated with the extent of drug use.


Self-poisoning--a complication of epilepsy.

From 1972 to 1976 130 epileptics presented 171 times to the Western Infirmary, Glasgow, as medical emergencies with self-poisoning. They constituted 3.5 per cent of 3,733 patients poisoning themselves on 4,121 occasions. Repetition of self-poisoning was commoner in epileptics (18.5 per cent) than in non-epileptics (7.0 per cent). The 130 epileptics have been compared with a non-epileptic group of self-poisoners matched for age, sex, and number of repetitions and have been found to have less alcohol excess but significantly more psychopathy. Possible explanations and prophylactic measures are discussed. In view of the relative incidence of epilepsy and self-poisoning in the community, and of epilepsy among self-poisoners in this and other studies, it is concluded that self-poisoning is a common complication of epilepsy.


EEG abnormalities and transsexualism.

A consecutive series of 46 transsexuals, 35 men and 11 women, showed EEG abnormalities in 48 per cent and borderline abnormalities in another 24 per cent. Women showed the abnormalities in a significantly higher proportion than men. Those with the EEG abnormalities were slightly younger at inception, suggesting that they sought help at an earlier age, and their transsexualism became obvious to their families earlier. Those with personality disorders had EEG abnormalities more frequently, but not significantly so. This group of transsexual patients seemed to have a low sex drive, and those with abnormal EEGs even more so; but again the differences were not significant. The possible significance of these findings for the understanding of transsexualism is discussed.


Morbid jealousy featuring as obsessive-compulsive neurosis: treatment by behavioral psychotherapy.

Morbid jealousy can occasionally be indistinguishable from obsessive-compulsive neurosis and then be partially amenable to broad-spectrum behavioural treatment. This can involve the partner and includes (a) methods to reduce jealousy and (b) other methods where appropriate, such as social skills training, and sex and marital therapy. This pilot study describes such treatment of four jealous out-patients. Rituals improved in three patients but ruminations in only one. Of three patients who were depressed at the start of treatment, two improved in rituals and in mood. The patient who failed was poorly motivated and did not comply with treatment.


Torticollis caused by an infratentorial tumour: three cases.

Three cases with torticollis caused by an infratentorial tumour are presented. A father and his son both had a Lindau tumour, and another patient had an ependymoma. It is stressed that torticollis may be the predominant or only sign of an infratentorial tumour, and that torticollis should always be suspected to have an organic origin.


Electroconvulsive therapy in Sweden.

In spite of a decrease in the number of electroconvulsive treatments (ECT) administered during the decade 1966-1975, ECT is still commonly used in Sweden. About 4 per cent of all patients admitted for psychiatric treatment during 1975 received ECT. Affective disorders and confusional states appear to be the main indications. Treatment is usually unilateral, with general anaesthesia and muscle relaxants, generally using the same type of ECT machine.


Mental imagery and pictorial memory.

Previous research has failed to show consistent effects upon memory performance of individual differences in the use of mental imagery. A test of pictorial memory was devised which varied the ease with which the stimulus patterns could be verbally encoded. A factor analysis related performance in this task to a variety of other individual characteristics. The recall of material which could not be readily verbalized defined a factor within the solution which showed significant loadings of age and performance in the Progressive Matrices, but not of subjective ratings of the vividness of experienced imagery. The recall of material which could be readily verbalized did not contribute to the factorial structure of the results. It was concluded that the two sorts of pictorial material are remembered in quite different ways.


Depth of processing and anxiety in facial recognition.

Subjects selected on the basis of test anxiety scores made a judgement about each face in a series of slides. These orienting tasks involved either abstract traits (e.g. dependability) or physical features (e.g. weight), and decisions were made relative to either an absolute criterion or self-reference. A subsequent recognition test revealed superior performance by low-anxiety subjects and by subjects who evaluated abstract features during study, but there were no depth by anxiety interactions. The reference point for the decision had little effect overall, but the anxiety deficit was more apparent when the absolute reference point was involved.


Communication and language in severely deaf adolescents.

One of the most important psychological effects of early severe or profound deafness is an impairment in natural language-processing ability, with a consequent reduction in communicative skill secondary to the sensory deficit. Prelingual damage blocks the development of certain sequential/syntactical skills necessary for the acquisition of normal linguistic competence. Educators of the deaf in the UK have typically attempted to improve linguistic ability using amplification and intensive training in lip-reading, but evidence from several psychological studies suggests that communication systems based upon manual signing are more productive of both linguistic and basic cognitive skills. This paper reports an experimental study of the communicative characteristics of both oral and total communication systems as a function of language structure. For almost all types of structure investigated, the total system was found to be the more effective method of communication.


The British use of the Barber Suggestibility Scale: norms, psychometric properties and the effects of the sex of the subject and of the experimenter.

The Barber Suggestibility Scale, as a measure of hypnotic susceptibility, was administered to 130 British undergraduate students by 13 student experimenters in a 2 x 2 factorial design withe sex of the subject and the sex of the experimenter as the two variables. The results showed no significant differences among the scores obtained by the 13 experimenters and no significant effect of either the subject's sex or the experimenter's sex though there was some tendency towards an interaction effect. The distribution of scores from the present sample was similar to the American norms reported by Barber (1965) except for slightly lower means on certain test-suggestions. The scale also showed satisfactory internal consistency and item-scale correlations. A principal components analysis revealed evidence for a general factor underlying the scale in addition to three special factors associated with direct motor, motor challenge and cognitive suggestions which confirms the work of Hilgard (1965) on the Stanford scales. The distinction between objective and subjective responses to suggestions is discussed and some improvements are recommended in the scale. It was concluded that the BSS appears to be a simple and reliable measure of hypnotic susceptibility and is suitable for British usage.


Semantic interference from subliminal stimuli in a dichoptic viewing situation.

In Expt 1 subjects named words, shapes or colours presented to one eye while words or shapes were presented to the other eye subliminally. The subliminal stimuli were found to slow naming responses when they had the same name as the stimulus to be named or a closely related name, compared with random letter strings or blank cards. This result was replicated in a second experiment which also included unrelated words as subliminal stimuli. On these trials latencies were midway between those for trials with blank cards or random letter strings as the subliminal stimuli, and trials with the same name or a closely related name as the subliminal stimuli. The results imply that stimuli related in meaning compete for common analysing mechanisms.


Noise and the "rehearsal-masking hypothesis".

This study examines the proposal that continuous loud noise impairs short-term recall by masking the inner speech necessary to rehearse material in memory (Poulton, 1976 a, 1977 b). The "masking hypothesis" contrasts with previous theories which relate recall impairment in noise to the latter's action in over-arousing the individual or inducing changes in attentional deployment. Separate groups performed a visual, serial eight-consonant recall task in either 92 dBA "noise" or 75 dBA "quiet" and in "normal" or "suppressed" rehearsal conditions. The masking hypothesis predicted that noise would impair recall relative to quiet in normal rehearsal conditions. But where the rehearsal of both groups was already suppressed by a concurrent articulatory task, recall would not differ between the groups through noise-masking then being irrelevant. Total correct recall scores appeared to confirm the masking hypothesis but the pattern of serial order recall showed differences between noise and quiet in suppressed rehearsal conditions which seemed better explained by an attentional influence of noise. Further, reduced commission and acoustic confusion errors in noise were not consistent with the predictions of the masking hypothesis. It was concluded that noise-masking could not be refuted but that attentional changes due to the arousing action of noise might also be active determinants of recall.


Myelographic features of the normal sacral sac.

One hundred and sixty normal sacral sacs at myelography have been studied and the results analysed statistically. The features which may have clinical relevance are discussed.


A comparison of two techniques of detecting vesico-ureteric reflux.

Indirect voiding radionuclide cystourethrography has been compared with micturating cystourethrography in 57 children with urinary tract infections. A quasi-quantitative technique utilizing a mini-computer to optimize the images from the gamma camera has been shown to be at least as sensitive as conventional radiological techniques but to give these results without catheterization, at a lower radiation dose and at lower cost.


A small computer at the radiology reception desk.

An intelligent terminal has been used at a radiology reception desk to maintain a master patient index and to assist documentation. It also yields valuable management information.


Real-time ultrasound. A new method for studying gall-bladder kinetics.

Real-time ultrasound has been found to be a satisfactory method for studying changes in gall-bladder size. It is superior to many other methods since it is non-invasive, harmless, and does not rely on the metabolism of a contrast agent. We have also found it easy to identify and compensate for changes in the gall-bladder axis. Rapid serial images are easily obtained and show similar contraction patterns to those resulting from conventional techniques.


The influence of location of the crossing needle on dose distributions from planar implants.

Three typical planar radium implants with one uncrossed end were investigated for optimization of the crossing needle location. Isodose distributions in a plane 0.5 cm from the plane of the implant were calculated and the sizes and shapes of the areas receiving at least 85% of the maximum dose were evaluated. The merits of each implant geometry are discussed along with certain clinical considerations. As a refinement to the Paterson-Parker rules of geometry, it was found that an optimum distribution is achieved when the crossing needle is located near the physical ends of the parallel needles.


Changes in the neuroglial cell populations of the rat spinal cord after local X-irradiation.

A 16 mm length of cervical spinal cord of young adult female rats was irradiated with 4000 rad of 250 kV X rays. Counts of astrocyte and oligodendrocyte nuclei were made in the dorsal columns of both irradiated and control cervical cords during the latent period before the onset of radionecrosis. The numbers of both astrocyte and oligodendrocyte nuclei were reduced one month after exposure to radiation. Both cell populations showed an apparent recovery but this was subsequently followed by a rapid loss of cells prior to the development of white-matter necrosis. The oligodendrocyte population in unirradiated spinal cords increased with age, and mitotic figures were observed among the neuroglia of both irradiated and control cervical spinal cords. A slow, natural turnover of neuroglial cells in the cervical spinal cord is proposed and the relevance of this to the manifestation of delayed white matter necrosis is discussed.


Some radiobiological consequences of mycoplasma contamination of mammalian cells in tissue culture.

Cells of the mouse Ehrlich ascites carcinoma grown in vitro became contaminated with an arginine-splitting mycoplasma. The slopes of the radiation dose-survival curves of the contaminated cells, assayed by colony-forming ability, were extremely variable; eventually it became impossible to grow colonies at all. Experiments on the feeder cell requirement showed that, whereas for clean cells the maximum plating efficiency was obtained within a range of 5 X 10(4) and 4 X 10(5) feeder cells in a 5 cm dish, contaminated cells would only produce colonies in the presence of between 10(4) and 3 X 10(4) feeder cells. Doubling the concentration of arginine in the medium allowed contaminated cells to grow with maximum plating efficiency within an increased range of 10(4) and 4 X 10(5) feeder cells. The mycoplasmas were apparently behaving as feeders, reducing the requirement for added feeder cells, but also depleting the medium of essential arginine. The cells were eventually decontaminated by passing them through a mouse as an ascites tumour.


Skin and gonadal dose reduction during hip radiography of the bull.

Radiology is being used to an increasing extent in the clinical diagnosis of hip lameness in bulls. Consequent gonadal doses may have important implications in later breeding programmes. Skin and gonadal doses were recorded during hip radiography of 18 bulls. An additional 0.13 mm copper filtration reduced skin dose by more than one third, but had no effect on gonadal dose. The average radiation dose to the gonads was approximately halved by completely surrounding the scrotum with lead sheeting 0.95 mm in thickness.


False aneurysm of the superior mesenteric artery--a complication of pancreatitis.

Early recognition of pseudocyst formation in pancreatitis has been a very important contribution of diagnostic ultrasound. Furthermore, haemorrhage or abscess formation, an additional complication, can also be suspected by this diagnostic modality. False aneurysm formation of a larger, neighbouring artery is not easily recognized by ultrasound. It is for this reason that this case report is made.


Breast cancer and prostaglandins: a new approach to treatment.

The effect of the non-steroidal inhibitor of prostaglandin synthesis, flurbiprofen, has been studied on a transplanted mouse mammary tumour of spontaneous origin. Daily administration of 2.5 mg/kg flurbiprofen signficantly reduced the growth of this NC adenocarcinoma transplanted subcutaneously into the right flank of WHT/Ht mice. Histological examination showed that primary tumours excised at 3 weeks from treated mice tended to have a more prominent lymphocytic infiltration. There was a non-significant tendency for mice treated with flurbiprofen alone to survive longer after tumour excision and to develop less local metastases, although scar recurrences seemed unaffected. The effect of adjuvant chemotherapy and local radiotherapy on local metastases and survival time tended to be greater when flurbiprofen was also given. This work supports and extends the basis for prospective clinical trials to evaluate the role of prostaglandins in human cancer and the value of prostaglandin synthesis inhibitors in cancer therapy.


Radionuclide venography for the demonstration of the proximal deep venous system.

The majority of pulmonary emboli originate in the deep veins of the lower limb. Fatal emboli usually arise from thrombi that have extended into the femoral or iliac veins or lower inferior vena cava. It is often impossible to demonstrate this area, the proximal venous segment, using conventional ascending venography when there is deep venous occlusion. The alternative methods available--retrograde, pertrochanteric and transfemoral venography--are invasive. Radionuclide venography (RNV) has been developed as a less invasive alternative. It has been found to be accurate in the proximal deep venous system when compared with conventional ascending venography, and in the presence of proximal occlusion it gives images unobtainable by other means. The radiation dose is extremely low and a perfusion lung scan is obtained without further injection of isotope. RNV appears to be the best method for monitoring the progress of thrombolytic therapy for major venous occlusion.


Nature of the disturbance in the body fluid compartments during and after surgical operations.

Haematocrit and plasma protein concentrations have been measured in patients undergoing surgical operations in order to estimate relative changes in the volumes of the extracellular and plasma compartments. That these provide valid estimates of volume changes has been shown by applying them to patients known to have lost extracellular fluid. Further confirmation that changes in haematocrit, as indices of falls in plasma volume, are valid even after surgery is provided by measurements of red cell mass, using red cells labelled with 99Tcm. When these methods were applied to patients undergoing abdominal and non-abdominal operations, only the abdominal group showed a significant fall in plasma volume. This fall was caused not by a loss of crystalloid from the extracellular space as a whole, but by a loss of plasma; the magnitude of this loss correlated significantly with the duration of operation. These changes were also demonstrated using the radioisotope dilution indicators 125I (RISA) and 131I (RISA).


A lung colony clonogenic cell assay for human malignant melanoma in immune-suppressed mice and its use to determine chemosensitivity, radiosensitivity and the relationship between tumour size and response to therapy.

A lung colony assay for clonogenic cells of human tumours in immune-suppressed mice is presented. The assay was used to determine the chemosensitivity of two malignant melanomas. One tumour reproduced the spectrum of chemosensitivity associated clinically with three cytotoxic agents. The other melanoma reproduced the chemosensitivity demonstrated in the patient from whom the tumour was biopsied. The importance of tumour size as a determinant of response to melphalan was investigated and the clonogenic cell survival in smaller tumours was found to be slightly but significantly lower than in larger tumours. An invesitgation of the importance of size as a determinant of response to radiotherapy demonstrated that 0.5-mm diameter tumour nodules were significantly more sensitive to irradiation than 2-cm diameter nodules. The hypoxic fraction of the larger tumours was 65 per cent, which is higher than that reported for experimental animal tumours or a human pancreatic tumour. This could be a factor in the clinical radioresistance of malignant melanoma.


The interpretation of mammographic ductal enlargement in cancerous breasts.

The xeromammograms of 128 women with breast cancer were coded radiologically according to Wolfe's gradings. The mastectomy specimens were then histologically examined for the presence of ductal abnormality. The ducts were found to be normal in the cases coded as normal radiologically but they were not always abnormal histologically when considered to be abnormal radiologically. 'Ductal prominence' may be due to duct ectasia, intraduct hyperplasia or periductal collagenosis.


The value of measuring intravascular platelet aggregates in the prediction of postoperative pulmonary dysfunction.

A modified Swank screen filter technique was used to investigate, first, whether intravascular platelet aggregates (IPA) could be detected in patients immediately after surgery and then, the relationship between IPA levels and postoperative pulmonary function. The test, as modified, achieved an excellent reproducibility (r = 0.95) and a close correlation with the number of aggregates identified in samples of femoral vein blood by subsequent scanning electron microscopy (r = 0.93). In 20 patients IPA levels were measured 30 min and 3 h after surgery and pulmonary function (arterial PO2, physiological dead space and alveolar/arterial PO2 gradient) was evaluated preoperatively and on days 1 and 7 postoperatively. Patients with elevated IPA levels suffered a greater mean fall in arterial PO2 at 7 days (1.8 kPa) than did patients with normal IPA levels (0.6 kPa) (P less than 0.05). This was explained by a marked increase in the pulmonary arteriovenous shunt as indicated by the alveolar/arterial PO2 gradient (2.3 kPa v. 0.4 kPa, P less than 0.01). Those patients with increased pulmonary shunting and arterial hypoxia 1 week after surgery also had a greater fall in the platelet count on the first postoperative day. The screen filtration technique is a reproducible test which measures IPA accurately and may be used to predict pulmonary function 1 week later. This suggests that treatment to inhibit IPA may reduce postoperative pulmonary dysfunction.


Regulation of enterokinase synthesis in animal and human small intestine by luminal signals: its implication in upper gastrointestinal surgery.

Enterokinase is an enzyme produced by the mucosa of the small intestine. Its sole function is to activate trypsinogen to trypsin. In animals and man the duodenum and proximal jejunum have high levels of activity whereas the remaining small bowel has minimal levels. A reproducible assay was developed for measuring mucosal enterokinase activity applicable to operative and endoscopic biopsies. Anaesthetic and operative techniques were developed for small intestinal resections in guinea-pigs to ensure their long term survival. Transposition of high-enterokinase-secreting segments of guinea-pig small intestine to low-enterokinase regions and vice versa showed no alteration of enterokinase activity in the transposed segments. Similarly, resection of the enterokinase region in five proximal pancreaticoduodenectomy operations in man revealed no induction of enterokinase in the remaining jejunum at endoscopy 6 months later. Isolation of high-enterokinase-secreting segments of small bowel from their luminal continuity by fashioning of Thiry--Vella fistulas led to a decay of enterokinase activity to minimal levels within 12--16 h. Perfusion of these fistulas with trypsin and sodium, or chymotrypsin and sodium, prevented this decay. If the enterokinase was allowed to decay over 24 h its activity could be restored to 80 per cent of its normal level by perfusion for 24 h with trypsin and sodium. Trypsin and sodium acti in combination on an enterocyte membrane receptor to stimulate enterokinase synthesis.


Plasma exchange and Raynaud's phenomenon--its assessment by Doppler ultrasound velocimetry.

In a group of 47 patients with Raynaud's phenomenon, Doppler ultrasound velocimetry was used to establish the severity of the disease by detecting the patency of the digital arteries. In conjunction with small digital occlusion cuffs, digital artery systolic pressure was measured on either side of the finger. A significant variation in systolic pressure was detected in each finger, and on each side of individual fingers. A more sensitive index of the severity of the disease was noted when the digital systolic pressure was compared to the brachial systolic pressure. Plasma exchange, a potent method of lowering whole blood viscosity and plasma fibrinogen, was used to treat 18 of these patients. There was a significant improvement in digital vessel patency at both 21 degrees C and 13 degrees C after plasma exchange. Both the digital artery systolic pressure and the pressure index improved significantly after treatment.


Long term results of autogenous vein bypass grafts in femoropopliteal arterial occlusion.

The results of 329 consecutive autogenous vein grafts carried out between January 1962 and June 1973 have been reviewed. The 5- and 10-year mortality rates were 14.6 per cent and 18.7 per cent respectively. The corresponding patency rates were 70 per cent at 5 years and 34 per cent at 10 years, the lowest patency (27.8 per cent) occurring in below-knee anastomoses with grafts of 5 mm or less in diameter. As other have noted, the state of the popliteal--tibial run-off vessels had a considerable influence on long term patency rates. In severely ischaemic limbs, the limb salvage rate following this operation was 77 per cent. An analysis of symptoms, associated disease and complications is presented and discussed. No valid conclusions could be made regarding the effect of lumbar sympathectomy and postoperative anticoagulants on long term patency. This review has confirmed the findings of earlier studies that a satisfactory 5-year patency rate and a gratifying limb salvage rate can be achieved with an extremely low operative mortality rate of 0.37 per cent. Despite the presence of widespread atherosclerotic arterial disease, the 5-year mortality rate is 14.6 per cent, indicating that an attempt at reconstructive surgery is usually well worth while.


Lesser curve superficial seromyotomy--an operation for chronic duodenal ulcer.

Lesser curve superficial seromyotomy has been investigated in the dog and in man. The anatomical basis for the operation, which produces an easily performed denervation of the parietal cell mass, is discussed. Acid studies in the dog confirmed that the operation was capable of producing secretory inhibition in keeping with vagotomy of the parietal cell area. A consecutive series of 25 patients with chronic duodenal ulcer has been treated by lesser curve myotomy without a drainage procedure. The operation has the advantages of being easily performed and the risk of damage to the nerve of Latarjet or of ischaemic necrosis of the lesser curvature is obviated. In 20 insulin tests performed within the first month postoperatively all patients have been negative within the first 75 min and there were 4 late positive responses. Early clinical results have been encouraging, there has been no dumping or diarrhoea and all patients are well. It is suggested that further investigation of lesser curve myotomy is warranted.


Antibiotic-associated colitis--a review of 66 cases.

We have reviewed 66 cases of antibiotic-associated colitis since March 1975, which have been associated with a 27 per cent mortality. We believe antibiotics may predispose patients to this condition which is caused by a toxin produced by Clostridium difficile. Although the disease is rare, it is more common than previously reported. The presentation, methods of diagnosis and treatment are discussed.


Anorectal Crohn's disease.

Four hundred and twenty-three patients with Crohn's disease have been reviewed, 48 of whom had isolated anorectal involvement--an incidence of 11.4 per cent. These patients were compared with 48 randomly selected and sex-matched cases who presented with isolated ileocolic disease. The age of the anorectal patients (53.6 +/- 18 years) was greater than that of the controls (34.2 +/- 12 years). The duration of follow-up was 6.0 +/- 4 years and 12.6 +/- 8 years respectively. Rectal bleeding, diarrhoea and perianal disease were more common in the anorectal group. Twenty-two patients (46 per cent) with anorectal disease and 40 (83 per cent) in the ileocolic group underwent definitive surgery. There were 4 (18 per cent) postoperative deaths in the anorectal group and none among the controls. The incidence of recurrence was lower among the anorectal patients (21 per cent) compared with the ileocolic group (40 per cent). However, the estimated probability of recurrence, based on the duration of follow-up, the number of deaths during follow-up and the actual incidence of recurrence, is similar in both groups.


Bone scanning: its lack of value in the follow-up of patients with breast cancer.

Three hundred and fifty-four women with primary operable breast cancer had a bone scan performed within 6 weeks of a simple mastectomy. Eight (2.3 per cent) were positive, but 7 of these patients had radiological evidence of bony metastases. Follow-up bone scans 1 year postoperatively on 278 patients showed only 12 (4.3 per cent) positive, and of these, 9 had other radiological evidence of metastatic disease. At 2 years postoperatively there were 13 (9.2 per cent) positive bone scans amongst 141 patients. Only 2 of these 13 had no other evidence of metastases. Although a bone scan is a useful investigation in patients with bone pain, there is no place for routine bone scanning in either the staging or follow-up of women with operable breast cancer.


Adjuvant cytotoxic liver perfusion for colorectal cancer.

Colorectal liver metastases develop by malignant cells entering the portal venous circulation. A randomized prospective clinical trial was commenced in 1975 to assess the value of adjuvant umbilical vein cytotoxic perfusion (with 5-fluorouracil) following colorectal resection. One hundred and fifty-four patients without macroscopic liver secondaries have so far entered the trial. The mean age, sex, site and stage of the disease were similar in the control and perfusion groups and there was no statistically significant difference in postoperative complications or hospital stay (17.1 +/- 7.9 days control, 15.8 +/- 7.4 days perfusion group). So far, 23 deaths have occurred in the control group (20 due to recurrent disease) and 7 in the perfusion group (5 due to recurrent disease). Liver metastases were present in 13 control patients and 2 perfusion patients. These results show an encouraging trend and suggest that adjuvant cytotoxic liver perfusion may reduce the development of colorectal liver metastases and hence improve the subsequent prognosis.


Anticoagulant activity and operative blood loss after intrapulmonary heparin.

The safety and efficacy of heparin given by the intrapulmonary route are further assessed in this study. A single dose of heparin (2000 units/kg) was given by intratracheal instillation in dogs and measurements of plasma heparin concentration, whole blood clotting time and partial thromboplastin time made at intervals for 48 h. These values rose progressively and in parallel for 7 h and remained elevated for 48 h. A series of operations was performed on dogs within 3 h of a single dose of intrapulmonary heparin (1500 units/kg). Operations involving minimal dissection (small bowel resection) and extensive dissection (resection of muscle) were performed in two separate groups. Within each group the animals were randomly given heparin or saline. In the limited dissection group there were no differences in operative blood loss, wound healing, or sequential haemoglobin and haematocrit measurements. In the group subjected to muscle resection there was increased postoperative wound drainage and a slightly greater fall in haemoglobin and haematocrit in those given heparin. It is concluded that heparin is absorbed from the lung causing significant changes in coagulation parameters. Even with the relatively high dose of 1500 units/kg, operations were performed with minimal hazard. Intrapulmonary heparin may have important clinical applications after further investigation.


The distribution, size and density of the apocrine glands in hidradenitis suppuritiva.

The distribution, size and density of the apocrine glands in hidradenitis suppuritiva as compared with those in axillary hyperhidrosis and normal controls have been studied. There are no significant differences in the size or density of the apocrine glands in hidradenitis suppuritiva as compared with normal controls. The apocrine glands in axillary hyperhidrosis are significantly larger than those in axillary hidradenitis and in normal controls. A simple method that can be used to demonstrate the distribution of the apocrine glands preoperatively is described. This has proved useful in delineating the area which it is necessary to excise to obtain complete apocrine gland excision in the diseased area. The apocrine gland-containing skin in the diseased region does not always correspond exactly to the hair-bearing area in that region.


Continent anal ileostomy with mucosal proctectomy: a bloodless technique using a surgical ultrasonic aspirator in dogs.

At present, mucosal proctectomy with ileo-anal anastomosis is a difficult, time-consuming operation involving much blood loss, often associated with impaired postoperative continence. A new operation has been devised in our department in which a surgical ultrasonic aspiratory, the CUSATM System (Cavitron Corporation) was used to fragment directly and strip bloodlessly mucosa from the rectal wall in 20 dogs as part of a simple ileo-anal sleeve anastomosis. All dogs were closely followed for up to 10 months. The only operative mortality occurred in the first dog where the upper rectum sloughed because the superior haemorrhoidal artery was divided. Preoperative weight was regained within the first 2 months. Initially stools were loose and frequent. Within 2 weeks the daily stool count was 5-6 with gradual thickening to semisolid consistency by 6 weeks. Finally 3-4 normal stools were passed daily. Postoperatively, all dogs remained contingent.


Modulation of the immune response and control of tumour spread by a new synthetic compound.

A small molecular weight biofunctional polymer, NED 137, has been investigated for its anti-neoplastic effect. Through its effect on the immune system, particularly the induction of B cell differentiation to antibody producing cells, this synthetic compound can retard tumour growth and prevent the development of distant metastases. Reactivity to tumour developed following administration of the NED 137. No toxicity has been observed. The polymer NED 137 is now being tested in phase I and phase II clinical trials.


The effect of epidural analgesia on postoperative sodium balance.

The effect of a high epidural blockade on postoperative sodium (Na) retention has been studied in 8 patients undergoing cholecystectomy, with a further 8 patients, who received conventional anaesthesia and analgesia, acting as a control group. Preoperatively, all the patients received 90 mmol of Na per day and were in Na balance at the start of operation; this intake was continued for 48 h after the operation by intravenous infusion, and the epidural blockade was maintained with regular supplements of bupivacaine throughout. In addition to urine Na excretion and blood pressure changes, plasma levels of aldosterone, cortisol, renin activity and glucose were measured at appropriate intervals. The Na retention in both the epidural and control groups was the same (139 mmol and 135 mmol respectively at 48 h), but there were significant differences in the measurements of all the other factors. It is concluded that the epidural was providing effective blockade, but that the factors which cause Na retention were not affected by the epidural blockade. These results are at variance with another study of the effect of epidural blockade on postoperative Na retention (Bevan, 1971), and the possible reasons for this are discussed.