A new histochemical technique of use in the interpretation and diagnosis of adenocarcinoma and villous lesions in the large intestine. The periodic acid-thionin Schiff/potassium hydroxide/periodic acid-Schiff (PAT/KOH/PAS) procedure has been used to investigate the histochemical staining characteristics of the mucins found in adenocarcinoma and villous lesions of the large intestine. The 46 blocks examined represented 58 lesions from 37 patients, all of whom had had resections for carcinoma of the colon. tin sharp contrast to normal colon, none of the adenocarcinomas stained red with the PAT/KOH/PAS. With two exceptions the poorly and moderately differentiated adenocarcinomas stained blue, whereas of the well differentiated lesions half were blue and half purple. The malignant villous lesions demonstrated the same trends, although a larger percentage were purple. None of the benign lesions stained blue. It is suggested that malignancy in the colon is accompanied by an increase in blue staining in the PAT/KOH/PAS technique and that such staining may be of value in the interpretation of highly atypical adenoma where it might identify the onset of malignancy. This change in staining indicates a distinct alteration in the chemistry of the mucins which we interpret as a reduction in the degree of side chain O-acylation of their constituent sialic acids.


Histochemical comparison of the epithelial mucins in the ileum in Crohn's disease and in normal controls. A comparison of routine and special histochemical methods that were applied to the epithelial mucins of small intestine from patients with Crohn's disease and from normal controls showed that the normal small intestine (ileum) goblet cells secrete a predominantly non-sulphated sialomucin and that, in contradistinction to the colon, the neuraminidase insensitivity of the sialic acids of the small intestine was not due to either O-acylation at C4 or an ester substituent at C1. Presumably this implies that the protection against enzyme attack afforded to the mucosa by the mucin coat in the small intestine utilises a different mechanism from that in the colon and that, although in many respects the small intestinal mucins in Crohn's disease, and in normal controls are similar, there is an increase in side-chain O-acylated sialic acids in such mucins in Crohn's disease. This difference has not been described before, probably because it can be seen only after staining such sections by the PAT/KOH/PAS and the PBT/KOH/PAS techniques.


Haemostatic disorders and respiratory distress in the newborn. Coagulation and fibrinolysis studies were performed on 64 newborns; 16 premature infants with hyaline membrane disease (HMD), 17 newborns with other forms of respiratory distress syndrome (RDS) (8 of them were premature), 31 healthy newborns (11 of them were premature). All the babies were studied once in the first 48 hours of life. There was no significant difference between sick and healthy babies for 5 parameters; platelet count, factor VIII, fibrinogen, fibrin(ogen) degradation products, euglobulin lysis time. Factor II, VII and X were low in all infants, and premature infants had significantly lower levels compared to full term newborns. Factor V, plasminogen, alpha 2 macroglobulin (alpha 2M) and antithrombin III (AT III) levels were significantly lower in sick infants. Except for AT III, these deficiencies were not related to prematurity. No significant difference was found between HMD and other RDS. Of the 33 sick infants, 5 developed laboratory findings consistent with disseminated intravascular coagulation (DIC). The results indicate that the coagulation and fibrinolytic abnormalities reported are not specific to HMD.


Automated fluorescent analysis for cytotoxicity assays. Classical measurements of cytotoxicity using dye exclusion and microscopic evaluation are both time-consuming and inaccurate. Using a cell sorter (TPS) a single dye system has been developed which stains live and complement killed cells with different fluorescence intensity. After exposure of target cells to antibody and complement, ethidium bromide is added to the target cells at a high enough concentration to stain complement killed cells very intensely. The cells are then diluted and lysed to produce single nuclei, permitting live cells to be stained but less intensely than the dead cells. Fluorescence intensity is measured on single nuclei at a rate of 10,000 per minute. For these studies anti-T antisera was titrated for complement dependent cytotoxic activity using normal mouse spleen cells, spleen cells from an anti-thymocyte serum treated mouse, and nylon wool purified mouse splenic T-cells. This procedure makes possible, reliable and reproducible measurement of cytotoxic activity on 5,000 cells per determination.


Methods for the identification of human B lymphocytes. Complement-receptor lymphocytes and monocytes were identified by a rosette method using trypsin treated sheep erythrocytes (Et), sensitized with affinity column purified IgM (19S) antibodies against sheep erythrocytes (E) and mouse complement deficient in C5. Fc receptor mononuclear cells were identified by a rosette method using Et and IgG (7S) antibodies against E. Identification of the cell-type rosetting was facilitated by myeloperoxidase staining of dry mounted rosetted preparations. Comparison of lymphocytes with receptors for activated mouse complement and lymphocytes with stable surface immunoglobulin detected by immunofluorescent assay, strongly suggests that these cells constitute the same population in the peripheral blood of healthy humans.


Deficiency of factor XII-dependent plasminogen proactivator in prekallikrein-deficient plasma. Normal human plasma contains a factor XII (Hageman factor)-dependent plasminogen proactivator in its gamma globulin fraction. On the basis of both fibrin plate and clot lysis assays, this plasminogen proactivator activity was shown to be absent from the gamma globulin fraction of prekallikrein (Fletcher factor)-deficient plasma of two unrelated patients. This observation suggests that factor XII-dependent plasminogen proactivator is identical to plasma prekallikrein.


On the differentiation of prospective ectoderm to a ciliated cell pattern in embryos of Ambystoma mexicanum. The differentiation of the ectoderm in Ambystoma mexicanum (Harrison stage 26--27) was examined under in vivo and in vitro conditions by scanning electron microscopy under different experimental conditions. About one out of three flank epidermal cells was found to be ciliated in the undistrubed or control embryos. The shape of ciliated cells in the explants from the animal region was only slightly affected. In no case was it possible to find two adjacent ciliated cells, implying that these cells prevent the appearance of cilia in the cells in direct contact. Transformation to ciliated cells is suppressed by hypertonicity but favoured in a hypotonic medium. The differentiation of epidermis is also dependent upon the synthesis of RNA and some kind of sulphated glucosaminoglycan, corroborated by the inhibitory effect of actinomycin and selenate. The differences between the test series and the controls are discussed with regard to factors controlling embryonic epidermal differentiation.


The Golgi rapid method in clinical neuropathology: the morphologic consequences of suboptimal fixation. Cytologic changes in neurons of the neocortex of mice consequent to suboptimal fixation have been investigated systematically in Golgi-rapid preparations. With few exceptions, there is no alteration in cellular morphology if the brain is refrigerated after death, and fixed by immersion within 3 hours. With latencies of fixation of 6 hours or more, autolytic changes supervene which modify the general histologic appearance and the morphology of individual cells. In general, the degree of tissue and cellular change is proportional to the latency between death and tissue fixation. Similar alterations in cellular morphology and general tissue appearance are found in Golgi-rapid impregnations of human brains obtained at autopsy. However, the degree of tissue autolysis in the human specimens bears a less predictable relationship to the latency of fixation after death. The duration of preterminal metabolic encephalopathy appears to be equally decisive as a determinant of tissue preservation.


Glossal double fissures in pre- and post-natal human specimens. Glossal double fissures were found in a similar proportion of both pre- and post-natal tongue specimens. The condition was found in both sexes and in subjects of Negro, Caucasian and mixed ethnic origins. In cross-section, the area bounded by the fissures varied from raised to flat or depressed. Histologic analysis suggested that the double fissure appearance was a reflection of the topography of the subjacent muscle bundles and that true fissuring, when present, was probably a secondary phenomenon akin to acquired plication.


Urinary excretion of alpha-fetoprotein in rats on a cirrhogenic carbon tetrachloride regimen. Alpha-fetoprotein was detected in the serum and urine of 2- to 9-mth-old rats subjected to protracted CCl4 poisoning. During the first 3 mth of the experiment, urinary excretion of AFP was found in 30-40 per cent. of the animals, increasing to 70 per cent. thereafter. The liver lesions progressed from acute parenchymal necrosis to cirrhosis, but hepatocellular carcinomas did not develop. Uptake of tritiated thymidine by the hepatocytes increased significantly but was constant throughout the experimental period. The findings are compared to the observations made during 3mDAB-induced hepatocarcinogenesis in the rat.


Cytolethal effects of glucocorticoids in human lymphoblastoid cell lines. Glucocorticoid hormones penetrate rapidly into intact lymphoblastoid cells and are retained with the same high affinity and specificity as with cytoplasmic extracts. Optimal conditions for lethal glucocorticoid responses in vitro were determined for a series of human lymphoblastoid cell lines by using different glucocorticoid preparations, and steroid solvents and by varying the cell density. Kinetic studies revealed that lethal glucocorticoid effects are dose-dependent and that continuous exposure of cells to steroid is necessary for progression of lethal effects to occur. Even under optimal conditions, human lymphoblastoid cells only exhibit a marked cytolethal response to glucocorticoids at concentrations which greatly exceed both physiological and therapeutically attainable steroid levels. They are also greatly in excess of steroid levels required to saturate the cytoplasmic receptors of intact or disrupted lymphoblastoid cells. It is suggested that either lethal steroid mechanisms in vitro differ fundamentally from those in vivo or the pharmacological activity of glucocorticoids in vivo does not involve a direct cytolethal action.


Sexual precocity in a male due to thoracic polyembryoma. A 7-year-old boy with sexual precocity of recent onset was found to have elevated levels of chorionic gonadotropin, alpha fetoprotein, and testosterone. Removal of a retropleural, posterior mediastinal mass with an intraspinous epidural extension was followed by prompt declines in the plasma concentrations of the tumor markers and cessation  of adolescent development. The neoplasm proved to be a polyembryoma, unusual in the multiplicity of its embryoid bodies and extra gonadal location. Following local irradiation and two years of systemic chemotherapy, the patient, now 13 years of age, has done well except for evidence of testicular tubular insufficiency.


Gingival fluid and serum in periodontal diseases. I. Quantitative study of immunoglobulins, complement components, and other plasma proteins. 1. Gingival fluid from severely inflamed periodontal tissue represents a 15 to 30% dilution of serum with respect to the proteins studied, with the exception of C3 and in some subjects, C4. 2. A marked decrease in C3 levels is found in most, if not all, gingival fluids, and a marked decrease of C4 levels is found in some gingival fluids. This suggests that complement might be activated during periodontal inflammation. 3. The concentrations of proteins in the gingival fluid are not related to their molecular weight.


Histamine enhances anaphylactic histamine release from bovine lung and leukocytes via histamine H2-receptor. Chopped lung and isolated leukocytes of calves sensitized to horse plasma release histamine when incubated with the antigen. Low concentrations (10(-9) and 10(-8) M) of exogenous histamine enhanced both spontaneous and antigen-induced histamine release. The enhancement of antigen-induced histamine release was inhibited by metiamide but not by mepyramine, whereas the enhancement of spontaneous histamine release was not significantly affected by either histamine antagonist. At higher concentrations of exogenous histamine (10(-6) to 10(-4) M), uptake and metabolism significantly interfered with the method. These results indicate the existence in bovine lung and leukocyte of a positive feedback mechanism which regulates histamine release via an H2-receptor. This is in direct contrast to the reported situation in the human leukocyte, and suggests that histamine fulfils an important role in the intrinsic control of allergic reactions in cattle.


[Concentrated irradiation of bone metastasis (author's transl)]. One hundred patients with bone metastasis of various histological types have been submitted to a concentrated irradiation: 2 sessions of 850 rads or 650 rads over 3 days. Pain disappeared in 65% of the cases in a 3 to 7 days delay, for a mean duration of two months. The mean survival of this groups of patients is 4.3 months. The concentrated irradiation is well tolerated. Authors emphasize the value of this kind of treatment for patients with plurifocal metastasis and short survival.


Quantum chemical studies of N-substituent variation in the oxymorphone series of opiate narcotics. Quantum chemical calculations were performed on six N-derivatives of oxymorphone including N-methyl- (oxymorphone), N-allyl- (naloxone), N-dimethylallyl- (nalmexone), N-methylcyclopropyl- (naltrexone), N-methylcyclobutyl-(nalbuphone), and N-phenethylnoroxymorphone using the PCILO method. The object of the study was to identify conformational features of the N-substituents which might be responsible for the intrinsic observed pharmacological properties of opiate agonism and antagonism. Both axial and equatorial N-substituent conformers were considered, as well as possible interactions of the C14-OH group with such substituents. Variations of agonist/antagonist potency ratios within this series could not be explained by differing relative energies of equatorial and axial conformations or by varying rates of interconversion between the two. Direct effects of the C14-OH group on conformations of N-substituents also could not account for their relative agonist/antagonist potencies. Consistent with a previous hypothesis, the observed potencies and binding data could be explained most consistently by the availability of several low-energy equatorial conformations of N-substituents and their interactions with the C14-OH group through a common anionic receptor site.


Application of chromosome banding techniques to the study of primary chromosome structural changes. Some comments are provided for the benefit of new workers on the use of chromosome banding techniques for the recognition, classification, scoring, and break point location of primary chromosomal structural changes.


[Diagnostic value of thermography and Tc 99m bleomycin scintigraphy for nodules of the thyroid (author's transl)]. The combined interest of thermography and 99mTc Bleomycin scintigraphy in the differential diagnosis of a cold thyroid nodule was evaluated in 86 patients. In all cases a histological examination was performed. Of the 30 malignant nodules (clinically suspect and solitary nodules) 21 (70%) showed concentrations of 99mTc Bleomycin while only 7 of the 12 solitary malignant nodules did so. Among the 54 benign nodules the false positive rate was 54%. Thermography was positive in 26 (87%) of the 30 malignant nodules and in only 8 (67%) of the 12 solitary malignant nodules. For the 54 benign nodules the false positive rate was 72%. The combined results of the study do not provide any improvement in diagnostic accuracy. Thus it can be said that applications of 99mTc Bleomycin and thermography in the diagnosis of solitary hypofixiant nodules are of limited value.


Polymer cryoprotectants in the preservation of biological ultrastructure. I. Low temperature states of aqueous solutions of hydrophilic polymers. The solid states formed by vitrified and frozen aqueous solutions of some hydrophilic polymers, able to act as biological cryoprotectants, have been studied by differential scanning calorimetry and freeze fracture electron microscopy. Glass transitions, devitrification, recrystallization and melting behaviour of aqueous solutions of polyvinylpyrrolidone, hydroxyethyl starch and dextran have been established. The vitrified polymer solutions exhibit a characteristic microspheral morphology which is not induced by the quench cooling process but is an inherent feature of the solutions themselves.


Polymeric cryoprotectants in the preservation of biological ultrastructure. II. Physiological effects. A study has been made of the physiological effects of three non-penetrating polymeric cryoprotective agents on sixteen different plant and animal cells and tissues. The cryoprotectants, when used at concentrations at which they are effective in preventing ice-crystal formation, generally have a lower toxicity to cells and tissue than similar concentrations of glycerol. The relatively low toxicity of these substances suggests that they would be more suitable as cryoprotectants for morphological and analytical studies than the commonly used low molecular weight compounds.


Polymeric cryoprotectants in the preservation of biological ultrastructure. III. Morphological aspects. Two high molecular weight polymers, polyvinylpyrrolidone (PVP) and hydroxyethyl starch (HES), have been used as cryoprotectants for preparing specimens to be freeze fractured. Solutions of 25% (w/w) suppress the formation of intracellular ice in single cells and tissue blocks from both plants and animals to the extent that fine structural details of the cell can be elucidates. The mode of action of these cryoprotectants, together with the structures they reveal and the peculiar advantages attached to their use, is discussed.


Ultrastructure of the acinar cells in the submandibular gland of the nine-banded armadillo. There are two discrete lobes comprising the armadillo submandibular gland. These two lobes can be defined grossly, histochemically and morphologically with the light and electron microscope. The minor lobe stains more intensely with PAS and AB. When viewed in the electron microscope, the secretory granules of the acinar cells within this lobe appear mucous-like. The granules of the demilune cells are slightly different in appearance. The secretory granules of the acinar cells in the major lobe contain many dense foci embedded in a fibrillar matrix, a substructure not described previously. The demilune cells of this lobe contain secretory granules with a mucous-like structure which is consistent throughout the entire lobe. As in the minor lobe, these demilune cells stain very intensely with PAS and AB.


Strategies and techniques for the reduction of sexual anxiety. In this paper 14 anxiety-reduction techniques are discussed: use of bibliotherapy, use of audiovisual materials, in vivo desensitization via written, programmed exercises; self-exploration/masturbation training; orgasmic reconditioning; simulated orgasm experiences; implosion techniques; sex word desensitization; sexual assertion training; therapist modeling/self-disclosure; systematic desensitization; and cue-controlled relaxation. The sex therapist can integrate these techniques into the sex therapy contract with individuals or couples and use them either singly or in a sequential multiple technique format to reduce sexual anxiety.


Embryotoxicity of irradiated and nonirradiated catalytic convertertreated automotive exhaust. This study was undertaken to examine the relative embryotoxicity in chick embryos of photochemically reacted and unreacted diluted automotive exhaust emissions from a system equipped with a catalytic converter. Clean air controls and H2SO4 aerosol controls equivalent in concentration to those found in the catalytic exhaust atmosphere were also studied. From day 1 through day 14 of development, continuous exposure to nonirradiated exhause resulted in decreased survival, lowered embryonic weight, a small increase in heart/body weight ratio, and altered hematocrit and serum enzyme activities (LDH and GOT). Irradiated exhaust had little effect on survival or on embryonic weight but resulted in a higher liver/body weight ratio as well as altered hematocrit and serum enzyme activities. Interactions or cumulative effects of different compositions of exhaust atmospheres may play a role in differing biological responses between unreacted and irradiated exhaust. Sulfuric acid aerosol had a minimal effect on survival and resulted in only a slight decrease in embryonic weight and serum LDH activity, with no other apparent effects. In previous studies where the catalytic converter was not used, more pronounced effects on survival, increased heart/body weigh ratio, elevated serum GPT activity, and liver discoloration were observed. Thus, the introduction of an oxidizing catalytic converter appeared to alleviate some but not all of the embryotoxic effects of automotive exhaust.


Properties of influenza C virus grown in cell culture. Influenza C virus was propagated successfully in primary chicken embryo lung (CEL) and fibroblast cells and in Madin-Darby canine kidney (MDCK) cells. In other cell lines, either no virus or only noninfectious hemagglutinin (HA) was produced. In productively infected cells (CEL), HA and infectious virus appeared by 24 h and reached a maximum by 36 to 48 h, cell-associated virus remaining at a constant low level. Infected Vero cells produced noninfective HA by 24 h which also remained predominantly cell associated until 60 to 72 h, when the cells disintegrated. Viral antigen was demonstrable on membranes of both CEL- and Vero-infected cells at 24 h; Vero cells yielded membrane vesicles containing HA, but none of the spherical or filamentous viral particles synthesized in CEL cells. Influenza C virus produced in cell culture or in eggs differed in several important respects from A and B viruses and from Newcastle diseases virus. All influenza C preparations, regardless of infectivity or source, lacked detectable neuraminidase activity, yet retained the ability specifically to inactivate receptors only for influenza C. Influenza C HA was not inhibited by soluble glycoproteins highly active against HA of A virus. A rat serum glycoprotein uniquely inhibited influenza C by binding to the surface components of virious.


A course in emergency care for first-year medical students. A 52-hour course in emergency medicine for first-year medical students was developed from the Department of Transportation's (DOT) training program for emergency medical technicians (EMT). The objective of the course was to train students to provide life support and emergency care in the field at the level of competence of the EMT. Ninety-four percent of the first class met these standards on written examination. Problems in the course included over-simplified presentations by paraprofessional faculty and an overemphasis on inhospital management by physician faculty. The program is well received by students and allows for introduction of clinical material into the first-year curriculum. The DOT training program for the EMT provides a useful model that, with slight adaptation, is appropriate for the first-year medical student.


Cell antigens recognized by rabbit antibodies specific for oligomannosyl determinants. Rabbit antibodies to cell wall mannans of various microbial strains and their mutants were found to be cross-reactive to cell carbohydrates of mammalian sperm and 4-6-days-old blastocysts. Immunochemical studies indicate that oligomers of alpha1 yields to 2, alpha1 yields to 3, alpha1 yields to 6, and probably also alpha yields to 4 linked mannose residues of sperm carbohydrates are available for antibody binding. At least 80 percent of binding activity of a yeast mannan antibody to sperm can be effectively inhibited by specific haptens or digestion with exo-alpha-D-mannosidase, an enzyme activity highest in testicular tissue. In order to determine the role of this enzyme in the metabolism of the cross-reactive mannan antigens of sperm, the relative amount of a specific alpha-linked oligomannosyl determinant of bovine sperm from homozygous normals was compared to that of hetero-zygous carriers of alpha-mannosidase deficiency. Extensive cross-reactivity between the microbial and mammalian oligomannosyl determinants suggest that these are conserved structures in cell carbohydrates, although the organization of these units in the microbial cell wall lipopolysaccharide has very little similarity to the carbohydrate moieties of mammalian glycoproteins.


Impact of the "Rand report" on alcoholics, treatment personnel and Boston residents. Interviews with patients and staff at six alcoholism treatment centers, respondents in a random telephone sample, and a sample of homeless men considereded to need alcoholism treatment revealed little change in treatment program goals, no increase in patients seeking treatment, and few changes in drinking attributable to the "Rand report."


Endodermal sinus tumor of the ovary and alpha fetoprotein: a case report. Yolk sac tumors of the ovary are associated with elevations in serum levels of alpha fetoprotein (AFP). Thus, an antigenic marker is provided for evaluating therapeutic results in selected patients. A patient with a pure endodermal sinus tumor of the ovary is presented who underwent serial determinations of AFP. The effectiveness and limitations of serial AFP levels as demonstrated by this case are discussed in addition to the surgical and chemotherapeutic management of patients with yolk sac tumor of the ovary.


Reduced active thyroid hormone levels in acute illness. In acute and subacute disease the active thyroid hormones, triiodothyronine (T3) and tetraiodothyroacetic acid (tetrac), are decreased while serum-thyroxine (T4) levels tend to be slightly reduced. Conversely, the inactive metabolite, reverse triiodothyronine (reverse T3), is increased indicating a diversion of T4 metabolism from an activating to an inactivating pathway. With convalescence the serum levels of T3, tetrac, and T4 recover while reverse T3 decreases to normal. These changes occur without significant alterations in serum levels of thyroid-stimulating hormone, indicating maintenance of euthyroidism throughout disease.


A controlled study of therapeutic portacaval shunt in alcoholic cirrhosis. A controlled study of therapeutic end-to-side portacaval shunt was carried out from 1968 to 1971 in 89 patients with alcoholic cirrhosis. Recurrent gastrointestinal bleeding was less common and chronic hepatic encephalopathy was more common in patients with shunts than in patients without shunts. The survival-rate was lower, but not significantly, in patients with shunts. No overall benefit of the operation could be demonstrated in cirrhotic patients with the selection criteria and the type of surgical shunt used in this study.


Impaired red cell deformability in peripheral vascular disease. By means of a recently developed technique, red-cell deformability was measured in 44 patients with peripheral vascular disease and in 44 age and sex matched normal control subjects. 28 patients had intermittent claudication and 16 rest pain or gangrene. The ability of the red cells to deform was significantly reduced in patients and significantly less in patients with rest pain or gangrene than in those who only had intermittent claudication. A reduction in red-cell deformability by retarding blood-flow through the microcirculation may be an important factor in states of peripheral vascular insufficiency.


Breath-hydrogen test for small-intestinal bacterial colonisation. Breath-hydrogen production after oral glucose administration was examined in patients suspected of having small-intestinal colonisation and compared with the 14C-glycine-cholate breath test (14C-G.C.) and with bacteriological examination of the small intestine. Of 17 patients, 12 had bacteriological evidence of small-intestinal colonisation. Each breath test showed 8 of the 12 patients to be colonised, but only 5 patients gave positive results with both tests. Nevertheless, using both tests only 1 patients out of 12 with small-intestinal colonisation would have been missed. There were no false-positive results in the 5 bacteriologically normal patients when the breath-hydrogen test was used. It is concluded that simultaneous use of these two relatively simple breath tests may improve the indirect diagnosis of small-intestinal colonisation.


Aplastic anaemia: Evidence for an immunological mechanism. The soft agar culture assay (C.F.U.-C) has been used in vitro as a measure of haemopoietic capacity of bone-marrow. In a patient with aplastic anaemia pretreatment of the patient's bone-marrow with horse anti-human-thymocyte globulin and complement (A.T.G. + C) prior to culture led to a dramatic increase in ability to form colonies in the soft agar assay; and co-culturing marrow from a normal donor and from the patient resulted in a distinct reduction in the number of expected C.F.U.-C. These findings point ot an immunological or autoimmune mechanism in this patient by selective destruction of the suppressing cells in the patient's marrow with A.T.G. and by suppression of normal myelopoiesis following addition of the patient's marrow to normal marrow.


Mitochondrial calcium overload: A general mechanism for cell-necrosis in muscle diseases. It is suggested that the mechanism of muscle-cell necrosis in various muscle diseases is explained by an increased net influx of calcium into cells which triggers a "vicious cycle" of mitochondrial calcium overloading and energy depletion. If correct, this hypothesis may offer the basis of a more rational treatment of some muscle diseases even before their primary aetiology is known.


Gastric and duodenal ulcer and their associated diseases. Assessments of likely associations between ulcer and other diseases are hindered by the frequent lack of controls, by controls which are inadequate, and by inadequate descriptions of techniques used. The inherent biases in some of the techniques have also probably been insufficiently appreciated. Ulcer is common in the community and much of the evidence adduced to suggest ulcer/other-disease associations may well be describing oridinary ulcer frequency which has been underestimated. With such problems in mind, few of the proposed associations bear examination. Ulcer is probably unusually frequent in patients undergoing treatment for chronic renal failure. It is possibly more frequent in association with hyperparathyroidism and in cirrhotics, in cardiovascular disease (except hypertension), and in chronic respiratory disease. Evidence for other associations is not compelling.


The floating-bed.

The floating-bed. The classical concept of hospital care has gross limitations. Specialist consultation is episodic; hospitalisation has rigid admission and discharge policies. Floating-bed admission for 2 nights every 2 weeks provides an additional service which reduces the number of beds necessary for the elderly and should be able to contain the rapid increase in demand occasioned by the rising number of elderly patients, particularly those over the age of 75 years.


Haemophilus influenzae and haemophilus parainfluenzae in chronic obstructive pulmonary disease. The importance of nonencapsulated strains of Haemophilus influenzae and H. parainfluenzae in the pathogenesis of chronic obstructive pulmonary disease (C.O.P.D.) has been investigated in 150 patients observed at two-month intervals from 1968 to 1975. H. influenzae was distinguished from H. parainfluenzae by demonstrating requirements for both X and V factors. H. influenzae was isolated more often from sputum cultures from patients with severe C.O.P.D. (13.8%) than from patients with mild disease (4.4%, P less than 0.01). In contrast, H. parainfluenzae was isolated with equal frequency from sputums of patients with mild (40%) or severe (43%) disease. H. influenzae was present in the sputum more often during exacerbations of acute respiratory illness (15.4%) than during sympton-free periods (9.6%, P less than 0.01), while isolation rates of H. parainfluenzae did not increase during periods of illness (35% versus 39%). Antigens specific for the H. influenzae species and for the H. parainfluenzae species were used in a complement-fixation test to detect antibody rises in sera collected from the patient population. Fourfold or greater rises in titre of antibodies to H. influenzae were detected on 76 occasions in 53 patients, and 46 of these rises were associated with acute respiratory illnesses. In contrast, no antibody rises were detected with the H. parainfluenzae antigen. These observations indicate that nonencapsulated strains of H. influenzae may have pathogenic potential in patients with C.O.P.D., whilst H. parainfluenzae should be considered as normal flora.


Changes of vasopressin in hypertension: Cause or effect? Plasma concentrations of arginine-vasopressin (antidiuretic hormone) have been measured in 40 patients with benign essential hypertension and 12 patients with malignant-phase hypertension. Values tended to be low in the benign phase and high in the malignant phase. 5 normal subjects were infused with synthetic arginine-vasopressin, producing plasma concentrations up to five times the highest value recorded in malignant-phase hypertension, without any effect on blood-pressure. There is no evidence that vasopressin has a direct role in the pathogenesis of benign essential hypertension or its transition to the malignant phase. On the contrary, abnormal vasopressin concentrations may be caused by hypertension.


Secretory IgA against enterotoxins in breast-milk. A pool of colostrum from Guatemalan mothers (Guatemalan colostrum)) obtained 2-4 days post partum inhibited the induced fluid accumulation in rabbit ileal loops when incubated with Vibrio cholerae or Escherichia coli enterotoxin. There was a linear relationship between the quantity of colostrum used and the protection achieved. Pools of Guatemalan breast-milk obtained 15-30 days post partum and North American breast-milk had the same effect when tested with E. coli and V. cholerae enterotoxins, respectively. The antitoxic activity of a given pool correlated with its IgA content but not with the concentration of IgG or IgM. Guatemalan colostrum globulins were precipitated by ammonium sulphate. The globulins were filtered through a 'Biogel A5' column and fractions obtained. When tested in rabbit ileal loops the antienterotoxin activity in these fractions closely paralleled their IgA but not their detectable IgG or IgM content. We hypothesise that IgA antibody to enterotoxin, present in breast-milk of normal mothers, is probably a manifestation of natural immunity. The passive transfer of these antibodies to the infant may explain why breast-milk prevents E. coli diarrhoea in the neonate.


A new approach to the management of familial hypercholesterolaemia: Removal of plasma-cholesterol based on the principle of affinity chromatography. Reduction of plasma-cholesterol by the removal of low-density lipoproteins (L.D.L.) in an extracorporeal system is described as a possible approach in the treatment of familial hypercholesterolaemia. L.D.L. were removed from the blood by their interaction with heparin linked to agarose beads in the presence of calcium ions. Plasma-L.D.L. was markedly decreased in two patients with heterozygous familial hypercholesterolaemia. The technique is specific for the removal of L.D.L., as the concentration of high-density lipoproteins was not affected. The treatment was well tolerated by all three subjects (i.e., two hypercholesterolaemic patients and a normal volunteer), and there were no undesirable effects. Several haematological parameters, clinical-chemistry tests, including serum enzymes, and immunoelectrophoresis of plasma proteins were all unaffected by the treatment.


Improvement of medication compliance in uncontrolled hypertension. 38 hypertensive Canadian steelworkers who were neither compliant with medications nor at goal diastolic blood-pressure six months after starting treatment were allocated either to a control group or to an experimental group who were taught how to measure their own blood-pressures, asked to chart their home blood-pressures and pill taking, and taught how to tailor pill taking to their daily habits and rituals; these men were also seen fortnightly by a highschool graduate with no formal health professional training who reinforced the experimental manoeuvres and rewarded improvements in compliance and blood-pressure. Six months later, average compliance had fallen by 1.5% in the control group but rose 21.3% in the experimental group. Blood-pressures fell in 17 of 20 experimental patients (to goal in 6) and in 10 of 18 control patients (to goal in 2).


Fetal haemoglobin and malaria.

Fetal haemoglobin and malaria. The distribution and growth of Plasmodium falciparum was compared in red blood-cells containing either adult or fetal haemoglobins. In in-vitro cultures, cord blood-cells were invaded more readily, but there was a paucity of parasites in cells containing haemoglobin F in the blood of infected infants aged 3-6 months. These findings suggest that P. falciparum may preferentially invade young, metabolically active erythrocytes. There was a significant retardation of parasite growth in vitro in cells containing haemoglobin F. This latter finding suggests a further mechanism for the resistance to malaria in the first months of life and for high gene frequencies (in areas in which malaria was endemic) of the thalassaemias and related haemoglobinopathies in which the rate of decline of fetal-haemoglobin production is retarded.


Insulin rather than glucose homoeostasis in the pathophysiology of diabetes. Hepatic glucose efflux is very sensitive to changes in plasma-insulin and it is postulated that this provides an important feedback control of insulin secretion. In diabetes this hepatic "insulin sensor" increases the basal plasma-glucose until the impaired beta cells are sufficiently stimulated to secrete normal basal insulin concentrations. Glucose regulation thus becomes of secondary importance to the maintenance of basal insulin secretion, which is teleologically needed for the "anabolic" requirements of cell growth. This hypothesis provides an explanation for the "normal" basal plasma-insulin concentrations found in diabetes in spite of impaired beta-cell function. This maintenance of basal insulin secretion accounts for the discrepancy between the marked hyperglycaemia and minimal ketosis of maturity onset diabetic patients.


Part-time senior registrar posts: Wessex reviewed. A Government memorandum guided regional boards on how to set up schemes for re-employment of women doctors to ensure that they could train part-time in the hospital service with the aim of gaining consultant posts. Of the 14 senior registrars who have held part-time contracts in Wessex during the past 5 years, 2 are now full-time consultants and 8 have completed their higher qualifications. A high standard of qualification and training can be achieved on a part-time basis but subsequent employment prospects need to be more flexible: regional health authorities should create more part-time consultant posts.


The sporadic case of haemophilia A.

The sporadic case of haemophilia A. Plasma samples from 41 mothers of haemophilic sons in "simplex families" (families with only one affected member) have been tested for factor VIII and factor-VIII-related antigen. The results suggest that 39 of these women are likely to be carriers of haemophilia.


Serum-alpha1-fetoprotein in patients with testicular tumours. Serum-alpha1-fetoprotein (A.F.P.) was assayed in 88 men with testicular teratomas and 34 with seminomas. 61% of teratoma patients with clinically evident disease had serum-A.F.P. greater than 25 ng/ml, whilst it is highly unlikely that any patient with a pure seminoma had a titre above this level. A.F.P. concentrations correlated with response to radiotherapy and chemotherapy and predicted relapse in some patients. Serum-A.F.P. should be measured in all patients with testicular tumours.


Prognostic significance of in-vitro complement fixation in liver biopsy specimens from patients with acute viral hepatitis type B. The prognostic significance of in-vitro complement fixation (V.C.F.) by hepatitis-B core antigen/antibody immunocomplexes in hepatitis-B surface antigen (HBsAg) positive liver biopsy specimens was prospectively evaluated in 47 patients presenting with acute viral hepatitis type B. 34 of 37 V.C.F.-negative patients made an uneventful recovery and became HBsAg negative; in all patients with a V.C.F.-positive test chronic hepatitis and persistent antigenaemia developed. The V.C.F. test is a simple and reliable prognostic indicator of persistent infection and of progression of apparently acute hepatitis to a chronic liver disorder.


Persistent hypophosphataemia and osteomalacia in dialysis patients not on oral phosphate-binders: Response to dihydrotachysterol therapy. Four patients who had been on regular haemodialysis for periods of 3 1/2 to 7 years became hypophosphataemic with plasma-phosphate concentrations of 2.5 mg/dl or less before dialysis. None of them had been taking oral phosphate-binders for 2 years or more. Histologically all the patients had an excess of osteoid on bone biopsy. Intestinal absorption of phosphate and calcium was impaired, despite normal or high serum-25-hydroxycholecaliferol concentrations. Treatment with oral dihydrotachysterol resulted in corrections of the phosphate malabsorption and increases in plasma-phosphate concentration. The initial low plasma-phosphate values in these patients before dialysis probably reflected a state of phosphate depletion caused by the combination of malabsorption, loss during dialysis, and a low dietary intake.


A pseudohemipharetic form of Parkinson's disease. Parkinson's disease can present as a progressive hemiparesis without tremor. The presence of mild cogwheel rigidity in a hemiparetic patient may suggest the diagnosis, as may the normal findings on brain scan and electroencephalogram in a patient with gradually evolving hemiparesis. The response to appropriate medication has been prompt and excellent. It is important that Parkinson's disease be considered in the differential diagnosis of a progressively evolving hemiparesis.


Drug-based prevention of pressure-sores. A double-blind clinical trial was carried out in 85 patients undergoing surgery to the upper shaft of the femur and to the hip-joint. In the control series, 27% developed pressure-sores before discharge from hospital. In the group in which 80 I.U. of corticotrophin (A.C.T.H.) in gelatin solvent was administered, only 12% developed pressure-sores. 19% of the patients with fractures to the upper shaft of the femur developed sores because accurate timing was not always possible. Prevention was complete in the case of total-hip replacement which is an elective procedure where A.C.T.H. can be administered at the right time to prevent disruptive damage to the microcirculation. It is suggested that the administration of A.C.T.H. should form part of the management of all high-risk surgical situations.


Relation between Carp (multiple-sclerosis associated) agent and multiple sclerosis. It is suggested that the Carp (multiple-sclerosis associated and scrapie associated) agents may be the V-R.N.A. form of slow (D.N.A.) viruses which are the aetiological agents of the two diseases.


Detection of Serratia outbreaks in hospital. Infections due to Serratia marcescens were studied in 23 different hospitals. A retrospective study was done in 4 hospitals; all isolates were compared by serological typing, antibiograms, bacteriocin production, and bacteriocin  sensitivity. 2 of the hospitals were having cross-infection problems due to antibiotic-resistant strains, but the other 2 had little or no cross-infection. Outbreaks were studied in 19 other hospitals. 9 of these outbreaks were classified as "common source" since contaminated "sterile solutions" were incriminated as the cause in each. One hospital had a "pseudo-outbreak," in which Serratia from E.D.T.A. blood-collecting tubes contaminated blood-cultures as they were collected. All 10 of these strains from common-source outbreaks were generally sensitive to antibiotics. Outbreaks in 9 other hospitals resulted from cross-infection and were caused by strains which were very resistant to antibiotics. Guidelines for detecting outbreaks are given and control measures are suggested.


Cimetidine in the treatment of active duodenal and prepyloric ulcers. 44 patients with endoscopically confirmed duodenal (36) or prepyloric (8) ulcers have received in a double-blind trial either the histamine H2-receptor antagonist cimetidine (30 patients) or placebo (14 patients) for six weeks. At three weeks 67% of patients treated with cimetidine and 17% of those receiving placebo had endoscopically healed ulcers (chi2 = 8.49; P less than 0.005). At six weeks all except 3 patients receiving cimetidine (90%) had healed ulcers compared with 36% receiving placebo (chi2 = 11.11; P less than 0.001). Those receiving cimetidine had less daytime and nocturnal pain than patients on placebo. The differences were statistically significant for daytime pain during four of six weeks. The cimetidine-treated patients consumed significantly less antacids than placebo-treated patients and these patients' overall assessments of their wellbeing were significantly better. All patients on cimetidine had a significant reduction (P less than 0.0005) of their basal and pentagastrin-stimulated acid secretion, but no reduction in acid secretion was measured in the group who received placebo.


Finger Clubbing: A quantitative survey by analysis of the shadowgraph. Finger-clubbing has been measured from the magnified silhouette of the right index finger (shadowgram) in 125 subjects, comprising children and young adults. The profile and hyponychial angles were both found to be good discriminators of clubbing and to be independent of age and sex. The normal profile angle was 168.3 degrees +/- 3.6 and the mean normal hyponychial angle was 180.1 degrees +/- 4.2. Patients with cystic fibrosis and cyanotic congenital heart-disease were found to have grossly elevated values of these angles. Some asthmatics were found to have a moderate degree of clubbing with significantly elevated values of these angles. The shadowgram proved a convenient objective method for recording the degree and progress of fingerclubbing in clinical practice.


Peripheral and autonomic nerve function in diabetic ketoacidosis. Peripheral and autonomic nerve function was assessed at intervals over a 3-month period in seven diabetics after ketoacidosis. There was marked improvement in motor conduction velocity and terminal latency of both ulnar and common peroneal nerves in all patients. Five had one or more abnormal autonomic function tests but there were no consistent changes during the same period. It is postulated that peripheral nerves may be more susceptible to acute metabolic damage than autonomic fibres.


Evidence for immune-complex formation in patients with amyotrophic lateral sclerosis. Immune complexes have been found in several chronic diseases of unknown aetiology and identification of the constituents of the complexes might lead to recognition of aetiological agents. Sera and renal tissues from patients with amyotrophic lateral sclerosis (A.L.S.) were studied for evidence of immune complexes. C1q precipitation testing demonstrated that sera from 10 of 25 patients with classic A.L.S. bound significantly more radiolabelled C1q than sera from 15 controls. In renal glomeruli studied for deposition of host 1gG, C3, fibrinogen, and albumin by means of direct immunofluorescence, 9 of 33 patients with A.L.S. (27 biopsy and 6 necropsy specimens) had moderate amounts of both IgG and C3 of granular basement membrane and mesangia. This pattern of immunofluorescence is characteristic of immune complex deposits. Of these 9, 8 had rapidly progressive neurological courses, whereas among the remaining 18 patients with no evidence of immune-complex disease, 9 of 12 available for clinical follow-up had stable or slowly progressive courses.


Unabsorbable carbohydrates and diabetes: Decreased post-prandial hyperglycaemia. Two test meals were taken in random order on separate days by 8 non-insulin-requiring diabetic volunteers after 14-hour overnight fasts. Addition of 16 g guar and 10 g pectin to the control meal containing 106 g carbohydrate decreased markedly and significantly the rise in blood-glucose between 30 and 90 minutes and also resulted in significantly lower insulin levels between 30 and 120 minutes. When these meals were fed to 3 insulin-dependent diabetic subjects, a similar flattening of the post-prandial glucose rise ensued. This addition of certain forms of dietary fibre to the diet of diabetics significantly decreases post-prandial hyperglycaemia and would be expected to improve the control of blood-glucose concentration.


Cimetidine in duodenal ulcer. Controlled trial. As part of a double-blind controlled clinical trial of cimetidine (1.6 g daily) in patients with endoscopically proven duodenal ulcer, repeat endoscopy has been carried out in 24 patients after two and/or six weeks' treatment. At six weeks, 9 out of 11 patients on cimetidine and 3 out of 12 patients on placebo had healed (P less than 0.025). A separate open pilot trial in 23 patients has shown no difference in ulcer healing at six weeks between patients taking 0.8 and 1.6 g daily. A total of 32 different patients received cimetidine in the two trials, and ulcer healing was observed in 21 (66%) at six weeks. No patients showed evidence of bone-marrow toxicity. A small but significant rise in mean S.G.O.T., S.G.P.T., and serum-creatinine occurred in 13 patients on cimetidine 1.6 g daily, but not in 13 patients on 0.8 g daily.


Controlled storage of biological energy: The role of plasma lipoproteins. A scheme is advanced whereby plasma-lipoproteins form an integrated controlled pathway for storage of energy as triglyceride. The importance of insulin within this system is indicated and the consequence of possible errors considered. Changes secondary to organ disease are found to fit within the proposed pathway. Although many refinements remain to be added, this hypothesis seems to form a plausible framework within which lipoprotein abnormality and the underlying condition may be better understood and thereby treated.


Host resistance to lipopolysaccharides in the pathogenesis of multiple sclerosis and membranoproliferative glomerulonephritis. Host resistance against bacterial lipopolysaccharides (L.P.S.) and especially against its toxic part lipid A has earlier been demonstrated in biological assays. In this paper an aryl-esterase is shown to be associated with alfa-1-lipoprotein (ArE) and is probably responsible for the detoxification of L.P.S. in man. Furthermore C3 is shown to be activitated by L.P.S. From these facts it is suggested that ArE performs the initial degradation of L.P.S. followed by complement activation and trapping of the L.P.S.--complement complex in the reticuloendothelial system. It is postulated that a deficient host response against L.P.S. can be the triggering mechanism in multiple sclerosis due to the lack of ArE in myelin, and that an infectious-agent/L.P.S. syndrome can activate latent infections in connection with a severe hyperreactivity to L.P.S. Preliminary investigations in patients with membranoproliferative glomerulonephritis have shown low levels of ArE in serum. This change, together with the low C3 values in these patients, may result in deficient L.P.S. detoxification and it is suggested that L.P.S. are at least partly responsible for the production of C3 nephritic factor.


Comparison of levodopa with carbidopa or benserazide in parkinsonism. The therapeutic efficacy and side-effects of two preparations of levodopa with extracerebral decarboxylase inhibitors have been compared in 19 patients with idiopathic parkinsonism in a blind randomised crossover trial. The mean daily dose of levodopa was 658 +/- 64 mg/day (mean +/- S.E.M.) when given together with carbidopa 66 mg/day and 605 +/- 59 mg/day when levodopa was combined with benserazide 151 mg/day. There was no significant difference between the treatment regimens either in beneficial effects on parkinsonian symptoms and signs or in the adverse effects of levodopa assessed by a clinical observer unaware of the treatment given. Of the 19 patients studied, 9 preferred the carbidopa preparation, 8 preferred the benserazide preparation, and 2 had no preference. It is concluded that there is no significant difference in therapeutic effects or adverse reactions between the two commercially available decarboxylase inhibitor-containing preparations. Central-nervous-system actions and side-effects depend on the daily dose of levodopa, regardless of the different ratios of decarboxylase inhibitors to levodopa.


Salivary phenytoin concentrations in epilepsy and in chronic renal failure. Plasma total, plasma unbound (free, therapeutically active), and salivary phenytoin concentrations have been measured in seventeen epileptics and in seven patients with chronic renal failure on long-term phenytoin therapy. Patients with chronic renal failure had low plasma total, but disproportionately high plasma free, drug concentrations indicating impaired protein binding. Even so, their plasma free drug concentrations never fell within the predicted therapeutic range on conventional phenytoin dosage. Salivary drug concentrations correlated closely with plasma free drug concentrations. These observations suggest that phenytoin therapy could be more appropriately monitored by measurement of salivary, rather than plasma, drug concentrations. Avoidance of blood-sampling would be an added advantage, particularly in children and in uraemia. The present results suggest that the optimal therapeutic range of salivary phenytoin would be 4-10 mumol/1.


Therapeutic and pharmacokinetic effects of increasing phenytoin in chronic epileptics on multiple drug therapy. Twenty chronic epileptics receiving phenytoin and either phenobarbitone or primidone have been studied. All patients had frequent seizures and had serum concentrations of phenytoin below 410 mumol/1. Phenytoin dosage was increased to study the effect on the frequency of seizures and the serum concentrations of phenytoin and phenobarbitone. There was no effect on minor seizures but in ten out of sixteen patients major seizures were abolished or reduced. Serum concentrations of phenobarbitone rose as the phenytoin dose was increased. This may cause deviations from the expected relationship between dose and serum concentrations of phenytoin; this would explain deficiencies which were found in a nomogram for predicting the therapeutic dose of phenytoin.


Stimulation of lymphocytes from patients with coeliac disease by a subfraction of gluten. Peripheral-blood lymphocytes from patients with coeliac disease showed a marked increase in D.N.A. synthesis after incubation in vitro with a subfraction of gluten. Lymphocytes from control patients showed no increased D.N.A. synthesis under the same conditions. The possible use of this specific lymphocyte-stimulation assay as a screening test for coeliac disease is discussed.


Comparison of vitamin D and 25-hydroxy-vitamin-D in the therapy of primary biliary cirrhosis. Skeletal demineralisation and low serum concentrations of 25-hydroxy-vitamin-D were observed in patients with primary biliary cirrhosis. Neither oral nor parenteral vitamin-D increased 25-hydroxy-vitamin-D in serum or prevented further skeletal demineralisation. In contrast, oral 25-hydroxy-vitamin-D increased serum-25-hydroxy-vitamin D concentrations in all patients, and bone mineral content either improved or stabilised in all but one, 25-hydroxy-vitamin-D may be the preferred form of vitamin-D therapy in primary biliary cirrhosis.


Effect of pectin on serum lipids and lipoproteins, whole-gut transit-time, and stool weight. Pectin (12g daily with meals) was taken by twelve healthy men aged 22-45 (mean 25 yr) for 3 weeks. This produced a statistically significant mean decrease in total serum-cholesterol of 0.48 +/- 0.18 mmol/1 (+/- S.E.M.)--i.e., 7.9 +/- 2.6%. The decrease was largely due to a reduction in serum-low-density-lipoprotein-cholesterol of 0.45 +/- 0.19 mmol/1 accompanied by a fall in serum-apolipoprotein-B of 0.11 +/- 0.04 g/1. During pectin administration wet stool weight increased from 150 +/- 10 to 186 +/- 15 g/24 h. There was no clear change in total serum-triglycerides, serum very low density lipoproteins, or in whole-gut transit-time.


Clinical and biochemical abnormalities in coppersmiths exposed to cadmium. 5(18.5%) of a group 27 coppersmiths exposed to cadmium fume had stone disease. When compared with a control group of assembly workers in the same factory they had evidence of renal impairment as shown by blood biochemistry and proteinuria. A greater tendency to liver damage was found in the coppersmiths. There was evidence that restrictive airways disease was more common in the coppersmiths than in the control group. Blood-cadmium concentrations were significantly higher in the coppersmiths and in the assembly workers than in a reference population.


The infrasound blood-pressure recorder. A clinical evaluation. Comparisons with direct recordings show that the Physiometrics automatic blood-pressure recorder does not accurately reflect intra-arterial pressure and tends to over-read both systolic and diastolic pressures.


An automated test for the detection of significant bacteriuria. A fully automated technique for the rapid detection of significant bacteriuria is described. The method, which depends on the detection of bacterial adenosine triphosphate (A.T.P.) by bioluminescence, was found to have better sensitivity than a conventional cultural technique which uses a standardised loop. Results were available in 30 minutes. In the 957 urine samples tested, specificity was 84.5% relative to a pour-plate technique; results were not affected by the presence of non-bacterial elements.


Dialysis procedures in acute liver coma. 9 haemodialyses against fluids designed to reduce plasma abnormality were used in four patients with acute liver failure in an attempt to maintain consciousness and buy time for liver regeneration. Dialysis had little effect in two patients. In the third patient spontaneous movements and response to commands were seen during the second dialysis. Arousal occurred during both dialyses in the fourth patient who eventually recovered.


Bacterial overgrowth syndrome without "blind loop": A cause for malnutrition in the elderly. Probable bacterial contamination of the small bowel without an anatomical sump occurred in 5 elderly patients (age 68--94). They presented with severe general deterioration in health rather than with obvious features of malabsorption. This syndrome has not been clearly described before. Bacterial deconjugation of bile salts was indentified by the 14C-glycocholic-acid breath test. Investigations for other causes of malabsorption, including small-bowel biopsy and pancreatic scan, revealed no abnormality. After prolonged ill-health despite an adequate diet in hospital, all 5 subjects made a striking recovery after treatment with antibiotics. This condition may be quite common, particularly in malnourished elderly people.


Prostacyclin-like activity and bleeding in renal failure. Specimens of venous tissue from three normal subjects and three patients with renal failure and very prolonged bleeding-times showed prostacyclin-like activity (inhibition of platelet aggregation) during incubation at room temperature. The specimens from all three uraemic patients showed more prostacyclin-like activity than those from the controls. After repeated washings, when this activity could hardly be detected in the controls, pronounced inhibitory activity was still evident in samples containing venous tissue from the three uraemic patients. These findings may be relevant to the pathogenesis of bleeding in renal failure.


Bone-marrow transplantation in acute leukaemia. Survival in 33 patients with resistant leukaemia treated by marrow transplantation was compared with that of 37 matched patients treated by conventional and experimental chemotherapy. All patients in the transplant group were rendered free of detectable leukaemia for periods of from 36 days to more than 2 1/2 years, while only 6 patients in the chemotherapy group achieved a haematological remission. Overall survival in both groups was poor; however, 5 patients (15%) in the transplant group remain alive and in haematological remission 1--2 1/2 years after transplantation, while no patient in the chemotherapy group survived longer than 13 months. Bone-marrow transplantation appears to offer a small but distinct possibility of long-term survival in patients with acute leukaemia resistant to conventional therapy.


Feto-maternal bidirectional mixed lymphocyte reaction and survival of fetal allograft. Maternal and fetal lymphocytes were tolerant of each other in the bidirectional mixed lymphocyte reaction. This seems to be the principal reason why the mother does not reject the fetal allograft. Tolerance between maternal and fetal cells must be largely due to a genetic mechanism, because the bidirectional mixed lymphocyte reaction between parents and older children was much reduced compared with that between randomly selected pairs of controls. This weak reaction disappeared when immunosuppressive agents were given to one member of the parent/child pair, whereas the mixed lymphocyte reaction between unrelated individuals was not abolished by similar immunosuppression. It is suggested that this genetic mechanism is distinct from the HLA system. Tolerance between maternal and fetal cells was not demonstrated in the unidirectional mixed lymphocyte reaction, suggesting that this tolerance requires the viability of the two cell populations.


Effect of activated charcoal on absorption of nortriptyline. The ability of 'Medicoal', a new effervescent, activated charcoal preparation, to adsorb nortriptyline, has been investigated both in vitro and in vivo. A single dose of the effervescent charcoal 30 min after a dose of 75 mg nortriptyline produced a 60% mean reduction in both peak plasma levels and nortriptyline availability in healthy volunteers. Multiple doses of the effervescent charcoal produced 70% mean reduction in peak nortriptyline levels and availabiltiy. Activated charcoal is recommended for the treatment of tricyclic antidepressant poisoning. In in-vitro tests, a 10 g packet of the effervescent preparation containing 5 g activated charcoal) had an adsorptive capacity of approximately 3000 mg nortriptyline, a dose not usually exceeded in most cases of trycyclic antidepressant overdose.


Immunological mechanism for spontaneous abortion in systemic lupus erythematosus. The incidence of lymphocytotoxic antibodies in patients with systemic lupus erythematosus (S.L.E.) was significantly lower during pregnancies ending in normal live births than in pregnancies ending in spontaneous abortions (P less than 0.005). It was possible to absorb the lymphocytotoxic antibodies from S.L.E. sera with purified trophoblast antigens. The presence of a trophoblast-reactive lymphocytotoxic antibody which fails to disappear during pregnancies which end in abortion suggests an immunological mechanism for spontaneous abortion in S.L.E.


Metabolic immunodepression which increases the risk of cancer. When some metabolic changes occur--namely, when blood levels of free fatty acids (F.F.A.), insulin, cholesterol, or triglycerides rise--cellular immunity becomes depressed. These metabolic changes also promote the division of somatic, non-lymphoid cells, which in turn increases the possibility of malignant transformation. The diametrically opposite effects of these metabolic changes on non-lymphoid cells, on the one hand, and on T-dependent lymphocytes and macrophages on the other, increase an individual's susceptibility to cancer. This normally occurs with pregnancy, rapid growth, stress, and ageing. Many chemical carcinogens raise the hypothalamic threshold to feedback control mechanisms, decrease glucose tolerance, and increase blood-insulin--i.e., all the main changes of "cancer-proneness". Changes in biogenic amine level in the hypothalamus during ageing and stress and after an exposure to some carcinogens are responsible for the elevation of hypothalamic threshold to feedback control.


A comparative trial of polyglycolic acid and silk as suture materials for accidental wounds. A prospective clinical trial compared polyglycolic acid (P.G.A.) suture material with silk in the closure of wounds in 1000 patients attending the accident service of a district hospital. Statistical analysis showed the incidence of inflammatory reaction and suppuration to be significantly lower in wounds sutured with P.G.A. The analysis took into account the site of the wound, and the age and sex of the patients. P.G.A. sutures rather than silk are therefore recommended in the treatment of wounds in an accident service.


Occupational vitiligo induced by p-tert-butylphenol, a systemic disease? Vitiligo, morphologically indistinguishable from true vitiligo, was detected in 54 of 198 men exposed to p-tert-butylphenol (P.T.B.P.) during its manufacture. There is evidence that P.T.B.P. caused vitiligo by a systemic mechanism and that the severity of the disease was related to the intensity of exposure. No association with autoimmune disease was found. Screening for other possible associated disorders revealed mildly abnormal liver-function tests in 6 workers: liver biopsy confirmed liver damage. Of the 144 men exposed to P.T.B.P. who did not have vitiligo, only 2 had any abnormal liver-function tests. It seems possible that the liver damage is related to P.T.B.P.


Effect of coronary bypass surgery on longevity in high and low risk patients. Report from the V.A. Cooperative Coronary Surgery Study. There is considerable uncertainty about the effects of bypass surgery on the longevity of patients with coronary-artery disease and angina. The Cleveland Clinic has reported improved survival after surgical treatment; the Duke University study indicated improvement in a high-risk subgroup only. The Veterans Administration (V.A.) randomised study initially reported improved survival only for patients with significant left main artery (L.M.) disease. Further analysis of the V.A. study shows that survival in the high-risk subgroup was 87% for the surgically treated patients and 74% for those treated medically--a highly significant difference after four years of follow-up. However, exclusion of the L.M. group reduced the difference to a non-significant one of 84% versus 79%. For patients not in the high-risk subgroup, survival at four years (with L.M. excluded) was 93% for those treated surgically and 96% for those treated medically. For all patients the rates were 85% and 86%, respectively. These findings indicate that in the evaluation of the effects of bypass surgery on longevity the characteristics of the coronary-artery disease are critical.


Absorption, hydroxylation, and excretion of vitamin D3 in primary biliary cirrhosis. Oral vitamin D3 was poorly absorbed by 4 out of 6 patients with primary biliary cirrhosis; absorption was negatively correlated with faecal fat excretion. 25-hydroxylation of vitamin D3 given by mouth or intravenously was not impaired in the patients compared with controls of similar vitamin-D nutritional status. Urinary radioactivity derived from the intravenous dose of vitamin D3 was significantly greater in patients than in controls and was positively correlated with the serum-bilirubin concentration. Excretion in the urine may lead to loss of administered and endogenous vitamin D and thus contribute to vitamin-D deficiency in patients with primary biliary cirrhosis.


Factor-VIII consumption in pre-eclampsia. In 50 women with high-risk pregnancies, increased factor-VII consumption, as estimated by the difference between the levels of factor-VIII-related antigen and factor-VIII clotting activity, correlated with the severity of pre-eclampsia, particularly when measured by increases in plasma-urate. Longitudinal studies of the evolution of pre-eclampsia demonstrated that increased factor-VIII consumption usually but not always developed before hyperuricaemia. The earliest time that abnormal factor-VIII consumption was demonstrated was at 18 weeks' gestation in a woman who had had two previous stillbirths. Subcutaneous heparin and oral dipyridamole failed to reverse the coagulation abnormality, and the fetus died in utero at 28 weeks' gestation. The renal and coagulation changes characteristic of pre-eclampsia were also seen in a patient without hypertension. This suggests that the concept of pre-eclampsia may need to be widened to include a non-hypertensive syndrome characterised by these changes in clotting and renal function.


Inhibition of phagocytosis in vitro by obligate anaerobes. A variety of species of obligate anaerobes have been shown to interfere with the phagocytosis and killing of Proteus mirabilis and other aerobic bacteria in vitro. Although all the obligate anaerobes examined showed this activity, the effect was greatest with strains of Bacteroides melaninogenicus and B. fragilis. In contrast, none of the 36 aerobes tested acted in this way. These observations suggest that the presence of obligate anaerobes may be fundamental to the pathogenesis of some types of infections.


Respiratory disease associated with practolol therapy. Six patients who had surgical treatment for sclerosing peritonitis caused by practolol now have a respiratory disorder characterised by dyspnoea, extensive fibrotic pleural thickening, and lesions in the lung parenchyma. Respiratory disease appears to be a further feature of the practolol syndrome.


Reversal of streptozotocin-induced diabetes in rats by intraperitoneal implantation of encapsulated neonatal rabbit pancreatic tissue. Implants of rabbit neonatal pancreas, encased in 'Nucleopore' chambers (0.4 micrometer) reversed streptozotocin-induced diabetes in the rat. Blood-glucose, plasma-insulin, and oral glucose-tolerance test returned to normal. An isolated, perfused, streptozotocin-treated pancreas removed from a diabetic animal did not secrete insulin and removal of implants after 6 weeks from six animals caused all animals to die in hyperglycaemia within 8 days. This shows that the implant did not lead to the re-establishment of endogenous pancreatic function. Implanted diced neonatal pancreas in three chambers removed after 6 weeks secreted glucagon, insulin, and pancreatic polypeptide in vitro. No rejection reactions were seen. Rabbit neonatal pancreatic implants may thus be feasible therapy in insulin-requiring diabetic patients. Implants of other non-syngeneic endocrine cells--i.e., pituitary, thyroid, and ovary--may be useful in other hypoendocrine syndromes.


Infertility in male pesticide workers.

Infertility in male pesticide workers. A number of cases of infertility were discovered among men working in a California pesticide factory. The suspected cause was exposure to the chemical 1,2-dibromo-3-chloropropane (D.B.C.P.). The major effects, seen in 14 of 25 non-vasectomised men, were azoospermia or oligospermia and raised serum-levels of follicle-stimulating hormone and luteinising hormone. No other major abnormalities were detected, and testosterone levels were normal. Although a quantitative estimation of exposure could not be obtained, the observed effects appeared to be related to duration of exposure to D.B.C.P.


Is primary biliary cirrhosis an immune complex disease? Large immune complexes are present in the circulation of patients with primary biliary cirrhosis and result in the activation of complement by the classical pathway. Such large complexes are capable of producing tissue damage. The granulomatous lesions surrounding the small bile-ducts within the liver of patients with primary biliary cirrhosis and the vasculitis, rheumatoid arthritis, and associated lesions are all compatible with immune complex injury. It is postulated that such large complexes could be formed in the vicinity of the bile-ducts by an antigen absorbed from the bile or biliary epithelium. Complexes reaching the systemic circulation might be responsible for the associated extra-hepatic diseases.


Comparison of cost of preparing reagents in laboratory with cost of using commercial kits. A comparison of the cost of laboratory-made reagents with that of commercial kits was made for three serum-enzyme estimations and three serum-hormone estimations. The cost of reagents in kit form could only be justified on economic grounds for serum aspartate transaminase, alanine transaminase, and lactic dehydrogenase if the laboratory performed less than about 35 tests per day. It is unlikely that the use of kits for serum tri-iodothyronine, thyroxine, and thyrotrophic hormone can be justified on economic grounds for any workload. It is estimated that between 2 million pounds and 3 million pounds is spent unnecessarily by the National Health Service each year to purchase commercially prepared reagents for the six tests studied.


[Metabolism and organ functions in experimental hypothermic, bloodless whole-body perfusion with hydroxyethyl starch (HES)]. After surface-induced hypothermia in 12 cats total body washout was performed followed by 60 min bloodless perfusion. In the rewarming period at 28 degrees C, packed red cells were added and at 35 degrees C, ECC was finished. Functional parameters of metabolism, liver, and kidney were measured and followed by histologic examination. Bloodless perfusion does not alter the morphology of the organs examined. Abnormal values of organ function and metabolic data seem to be reversible.


[Immunologic properties, aggregate content and half-life of various human i.v. gamma globulin preparations]. Anticomplementary activity, aggregate content, and elimination of i.v. human gamma globulin (HGG). During storage of HGG globulin aggregate formation increases leading to anticomplementary activity. Seventeen patients suffering from postoperative sepsis showed significantly faster elimination rates of HGG than 6 healthy controls, while there was no difference in albumin elimination.


[Therapeutic Esophagogastroduodenoscopy (author's transl)]. Therapeutic esophagogastroduodenoscopy covers: 1. therapeutic polypectomy (in cases of obstruction, hemorrhage, early cancer I in inoperable patients); 2. palliative treatment of inoperable tumors (when obstruction or bleeding occurs); 3. endoscopic blood staunching (can be performed by drugs, mechanically, or by laser coagulation; 4. removal of foreign bodies).


Effects of topical nasal decongestants on the cilia of a chicken embryo tracheal organ culture system. There is little physiologic data concerning the possible toxicity of nasal decongestants on respiratory cilia. Consequently, a chicken embryo tracheal organ culture system was employed to study the effect on ciliary activity of various preparations and concentrations of the following medications: tetrahydrozoline hydrochloride (Tyzine), xylometazoline hydrochloride (Otrivin), Dristan, Sinex, NTZ oxymetazoline hydrochloride (Afrin), naphazoline hydrochloride (Privine), and phenylephrine (Neosynephrine). Only two dilutions of injectable phenylephrine 0.25% and 0.10% produced essentially no ciliotoxicity when compared to the cilia in control cultures. All the other topical nasal medications in the concentrations tested possessed some toxicity for cilia. The use of these medications should be tempered with the warning of possible cilia damage.


Immune response in dog. 3. Antibody formation in dogs and rabbits to human serum proteins and keyhole limpet haemocyanin. Antibody formation in dogs and rabbits to human serum proteins and keyhole limpet haemocyanin (KLH) following primary, secondary and multiple stimulation was analysed. Primary injection of human serum stimulates the formation of precipitin antibodies to beta2 lipoprotein in dogs, beta2 lipoprotein and beta globulin in rabbits. After a secondary dose the rabbits formed precipitins to a whole range of human serum proteins, while the dogs to beta2 lipoprotein, albumin, beta globulin. When the primary dose of antigen was divided over a period of 8 weeks, the dog produced precipitins to beta2 lipoprotein while the rabbit to a wide range of serum proteins. Secondary stimulation of these animals did not increase the number of precipitins formed. Quantitative analysis of the antibody produced show that the best response was with beta2 lipoprotein followed by albumin and beta globulin. As the immunogenicity of the antigen was greater the differences between the two species were narrow. These differences were less pronounced following the primary injection than after the secondary and multiple stimulations. The primary response to KLH (which represents mainly IgM) is better in the dog than in the rabbit, while the secondary response (IgG) was better in the rabbit. The poorer IgG response in the dog compared to the rabbit, observed in all the experiments, is discussed.


[Contribution to the problem of color reproduction in photomicrography with color films (author's transl)]. In order to define clearly the possibilities and conformities in reproducing stained microscopic specimens we need an exact system of formal co-ordination and conception. Therefore, an assay was made to find practical criterions allowing the choice of the most suited color films for the photomicrography of stained preparations. This was done by splitting up the transfer of information by adequate reproducible colors of the slides with the color space. Examples are given for Eosin bluish, for the mixture of Light green and Xylidin Ponceau and for the colors of Fujichrome R 100.


Audiotape and booklet self-instructional materials in physiology: an evaluation of their effectiveness and acceptability in the pre-clinical curriculum. Audiotape and booklet self-instructional materials in physiology have been evaluated for their effectiveness and acceptability in the pre-clinical course. Learning effectiveness was determined by comparison of pre-test and post-test scores on multiple choice tests, and acceptability was determined by scores on a specially constructed and validated Likert type questionnaire. It is concluded that in three out of the four physiology topics studied, audiotape and booklet was a significantly more effective method of study than the conventional method of text books and lecture notes. Self-instructional material in the form of audiotape and booklet is acceptable to students both in absolute terms and when compared with other methods of learning. Use of the self-instructional material enabled students to achieve the required learning objectives.


The anatomical basis of clinical practice: an anatomy learning programme. In an attempt to optimize medical students' enthusiasm to learn, rather than to be taught, 'The anatomical basis of clinical medicine: An anatomy learning programme' has been introduced into an evolving medical school curriculum. Initially, educational concepts were identified, the aims and goals clarified, then the learning  process and its evaluation techniques were introduced. The programme encompasses the use of a specifically designed course guide, a weekly 35 mm topographic slide presentation, prosection by senior students and then peer-directed group tutorials under the guidance of teachers. Surgical and radiological teaching colleagues cooperate in reinforcing student understanding of the relevance of anatomical concepts and data to clinical medicine. Students are encouraged to dissect personally, use the departmental museum as a learning centre, and at any time take advantage of freely available audio-visual aids. Tutorial situations are used by the students for self-evaluation, while promotional evaluation (an honours-pass-fail system) is based on the tutors' assessments, two 'on demand' multiple choice, two laboratory identification and a final oral examination.


[Histamine release from human leukocytes in children with bronchial asthma, allergic rhinitis and urticaria (author's transl)]. In 20 children with allergic diseases the histamine release of peripheral leukocytes by allergens has been investigated. Considerably higher histamine concentrations in comparison with the control have been found. The histamine release was in agreement with the results of skin tests.


Treatment of chlordecone (Kepone) toxicity with cholestyramine. Results of a controlled clinical trial. Industrial workers exposed to the organochlorine pesticide, chlordecone (Kepone), had signs of toxicity in several organs. The extent of toxicity was proportional to the levels of this chemical in the tissues. In 22 patients, chlordecone was eliminated slowly from blood (half time of 165 +/- 27 days--mean +/- S.E.M.) and fat (half time of 125 days, with a range of 97 to 177), chiefly in the stool. Output of chlordecone in bile was 10 to 20 times greater than in stool, suggesting that chlordecone is reabsorbed in the "ntestine. Cholestyramine, an anion-exchange resin that binds chlordecone, increased its fecal excretion by seven times. In a five-month trial, cholestyramine significantly accelerated elimination of chlordecone from blood, with a half life of 80 +/- 4 days (S.E.M.) (P less than 0.005) and fat (half life of 64 days, with a range of 52 to 85) (P less than 0.05). Cholestyramine offers a practical means for detoxification of persons exposed to chlordecone and possibly to other lipophilic toxins.


Immunological specificity and memory in a scleractinian coral. Tissue transplantation immunity with a specific memory component is demonstrated in populations of Montipora. This highly discriminating immunoreactivity derives from extensive allogeneic polymorphism of histocompatibility (H) markers. An H system of immunorecognition is postulated to have originated in multicellular invertebrates probably beginning with coelenterates.


Electrochemical properties of polycyclic compounds studied by the polarographic method in anhydrous systems. IV. Polarographic study of carcinogenic and noncarcinogenic hydrocarbons in ethylenglycolmonomethylether. An experiment was carried out to determine whether there is any correlation between the values of polarographic reduction potentials of polycyclic hydrocarbons and their carcinogenic activity. A comparison of half-wave potentials of polarographic wave I and II of pyrene benzologs revealed that the carcinogenic ones become reduced in ethylenglycolmonomethylether on a mercury dropping electrode at more positive potentials than the inactive benzo- and dibenzopyrenes. The discussion bears both on the reduction mechanism of the compounds and on the relationship between the half-wave potentials and the absorption electron spectra measured in the same solvent.


[Contribution to the pathogenesis of intrasellar and intraventricular cysts (author's transl)]. The histological structure of Rathke's cyst having an epithelial mono- or multiple layer wall with glands and mucous secreting cells is indicative of their origin from the stomodaeum. These cysts are morphologically and genetically simialr to the so-called cysts of the foramen of Monro (colloid cysts of the third ventricle). According to Stochdorph, the origin of the latter cysts is from ectopic cerebral inclusions of the upper respiratory tract.


Cellular immune responses in Huntington disease. Specificity of brain antigenicity detected with Huntington disease lymphocytes. This study confirms the production of migration inhibition factor by Huntington disease lymphocytes in response to antigen found in Huntington disease but not normal brain tissue. Huntington disease lymphocytes also respond to the presence of multiple sclerosis brain tissue with migration inhibition factor production.


Levels of plasma proteins in human and rat fetal CSF and the development of the blood-CSF barrier. High levels of albumin, alpha-fetoprotein (AFP), IgG, prealbumin and transferrin have been detected in cerebro-spinal fluid (CSF) of human fetuses between 14 and 25 weeks old. The concentration of each plasma protein in CSF was found to vary during the gestational period in relation to its serum levels and rate of synthesis and as a consequence of a reduced permeability of the blood-CSF barrier after 22 weeks. In fact, the higher CSF levels of AFP were detected in fetuses about 16 weeks old, while the highest values of albumin were observed in CSF from fetuses between 20 and 24 weeks old. Experimental work has shown that also in rats the permeability of the blood-CSF barrier is incomplete during fetal and perinatal life. When 125I-labelled albumin and IgG or 14C-oestrogen and testosterone were injected intraperitoneally in newborn rats, the labelled proteins and hormones were detected in fetal blood and CSF four hours after the injection. These results are discussed in view of the suggestion that maternal abnormal states with regard to hormones and antibrain antibodies may affect the development of the nervous system and unfolding of behaviour.


[Hashimoto's thyroiditis. Clinical contribution]. --After a brief account of anatomical and clinical findings of Hashimoto's thyroiditis, 8 cases, personally observed, are presented. The various aspects of this disease and in particular the most recent diagnostic methods are examined and therapeutical possibilities, from the medical and surgical standpoint, are discussed.


[Calusterone (7-beta, 17-alpha-dimethyltestosterone) in the palliative treatment of advanced breast cancer]. Results in palliative treatment of advanced breast cancer with a new androgen, calusterone, are discussed. Sixty post-menopausal patients with metastatic breast carcinoma were treated with 200 mg per day at least three months. The overall response was 28% (17/60); better results seemed to be achieved in advanced post-menopausal patients with osseous and cutaneous lesions. These results agree with those reported by the Cooperative Breast Cancer Group. No undesirable side-effects were observed and calusterone was well tolerated.


Carcinoembryonic antigen, alpha 1-fetoprotein, ferritin, and alpha 2-pregnancy associated glycoprotein in the serum of lung cancer patients and its demonstration in lung tumor tissues. Levels of carcinoembryonic antigen (CEA), alpha-fetoprotein (AFP), ferritin and alpha 2-pregency associated glycoprotein (alpha-2-PAG) were determined in patients with confirmed lung cancer at the time of diagnosis and in serial determinations during and after radio- or chemotherapy. Whereas AFP levels were not elevated in patients with lung cancer, increased levels of CEA, ferritin and alpha-2-PAG were found in more than 50% of the patients. The results suggest that determination of CEA, ferritin and alpha-2-PAG in the serum of patients with lung cancer may be useful to detect metastases or recurrences and to monitor the results of treatment. Furthermore, in this study CEA and ferritin could be demonstrated in extracts of lung tumor tissues by specific antisera.


[Palliative treatment of primary and metastatic tumors of the pancreas]. In primary carcinomas of the pancreas the palliative intervention shows worse results than the radical operation according to our experiences. Deviation is only justified with local irresectable tumours as a symptomatic procedure. In cases of metastatic tumours in the pancreas palliative resection may be the only way in order to eliminate complications (jaundice, pains, hemorrhage, tumour induced pancreatitis) caused by these growths. By means of six cases it is demonstrated that palliative surgery can be remarkably successful in cases of metastasis in the pancreas.


Contamination of human melanoma cell lines by mouse L cells. Five of 8 cell lines from human melanomas originally established elsewhere were found to consist exclusively of mouse cells when examined in our laboratory some months after their receipt. Cytogenetic studies, including G- and C-banding, showed that the mouse cells in all cultures had originated from a single cell line, identified as the L-line. Contamination probably occurred, one year before its discovery, in a laboratory where L cells and human melanoma cells were briefly kept in the same incubator.


[Cerebrospinal fluid gamma globulins in neurological disorders affecting black Africans (author's transl)]. Four hundred C.S.F. electrophoreses were carried out in black West Africans (Ivory Coast) suffering from inflammatory disorders of the nervous system. In the normal state, the C.S.F. of the black African contains more gamma globulins than that of the white (15.8% as opposed to 10%). The study provides indirect evidence of the classical notion of the extreme rarity of DS (Disseminated sclerosis) in the tropics. Hypergammaglobulinorachia was demonstrated in 22% of cases, the two principal disorders responsible being trypanosomiasis (57.3%) and sub-acute sclerosing panencephalitis (16.8%). The oligoclonal distribution described in trypanosomiasis was not found. On the contrary, a homogeneous appearance of the gamma zone was constantly demonstrated (49/50). It is possible that these differences are related to the various phases in the course of the disease, and that oligoclonal disturbation is a marker of the auto-immune phase.


The values of alpha 2-macroglobulin in the serum of persons at work with x-rays. A group of 86 persons (65 women, 21 men) working at the risk of ionizing radiation (IR) was examined for the levels of alpha 2-macroglobulin (alpha2-M), and compared to a group of age matched healthy population. Whereas the difference in men did not reach a level of significance, significant difference was assessed in women: in a subgroup older than 40 y exposed to the IR a rise of alpha 2-M levels was noted in correlation with the age. Multiple correlation coefficients showed a synergistic influence of both age and exposure to IR. The results are discussed from the point of view of the hypothesis that in exposed women a shifting realizes of usual old age changes to younger age group. A possibility is suggested to use the examination of alpha 2-M levels for preventive control of workers at the risk of IR.


Methods for differentiation of collagen, muscular and elastic fibers in stereomicroscopic specimens. The A. describes a technique for demonstrating collagen, muscular and elastic fibers in dry mesoscopic specimens, treated by the Semper method and submitted to dissection under the stereomicroscope. The technique holds essentially to the reconnaissance of these types of fibers in fragments or pellicles of said specimens, stained by the methods of Azan and Weigert-Moore, modified, without needing to take succour in histologic methodology applicable to other preparations, which, according to the A., would cause a break of continuity in the observation, and also in the interpretation of findings, and this is not always easy to be re-instated with ease and precision. The method proposed has the principal aim to correctly distinguish between muscular and collagen bundles practically "in loco" and which are already outside the resolution power provided by the Semper method. In this technique the muscular bundles are stained red, the collagen bundles in sea-blue, and the elastic ones in deep blue, up to their most delicate nets, allowing for a very clear and transparent tridimensional analysis of the functional systems formed by these fibers.


Heredopathia atactica polyneurotiformis: therapeutic and pathogenetic aspects. None of the single manifestations is in itself specific or pathognomonic for this disease except for the disturbance of the metabolism of phytanic acid. Therefore, clinical syndromes that involve similar manifestations without accumulations of phytanic acid should not be included under the term heredopathia atactica polyneuritiformis, or Refsum's disease. Whatever the biochemical mechanism that links phytanic acid accumulation with the clinical manifestations of heredopathia atactica polyneuritiformis, it appears that the observations made on patients following successful dietary treatment leave little doubt that most if not all of the manifestations in this disease are caused in some way by the accumulation of phytanic acid.


Fluorescence staining of gastric mucosa. A study with special reference to parietal cells. Compared with conventional light microscopy, fluorescence visualization of parietal cells was found to be of great advantage after staining with the acid dye Eosin or Azophloxine in combination with Hematoxylin or Periodic Acid Schiff (PAS). All these staining combinations gave a satisfactory result in the body area, whereas PAS-Eosin was superior in pyloric glands. Direct or indirect immunohistochemical method with human parietal cell antibody could also be used for distinct demonstration of parietal cells in paraffin-embedded rat and human gastric mucosa. Results of immunohistochemistry confirmed the reliability of parietal cell enumerations based on fluorescence staining with the acid dyes. Paired visualization of parietal cells and gastrin cells (G cells) in the same tissue section was achieved immunohistochemically. This methodological approach is a prerequisite for a detailed study of the morphological relationship of these two cell types in the transitional zone between the gastric body and the pyloric antrum.


[Research on the immunological and biochemical structure of tumors of the prostate gland]. The study of IgA, IgG and IgM immunoglobulins obtained from tissues of prostate adenoma and adenocarcinoma, as well as of homogenates by electrophoresis in polyacrylamide gels, revealed the presence, the amount and the different conformation of protein fractions in the adenoma and in the adenocarcinoma. Inflammatory processes do not play a significant role. Comparative measures of nucleic acids and of SH groups suggest the existence of molecular mechanisms interpreted in the light of ageing processes.


Human leukaemia associated antigen (LAA): occurrence and characteristics. Serum leukaemia-associated antigen (LAA) is identified as an oncofetal antigen (or antigens) since it is present in fetal liver and in amniotic fluid. Although it is mainly found in patients with proliferative haematological disorders, particularly acute leukaemias and chronic myelogenous leukaemia, LAA is occasionally present in sera from healthy people. In protein fractionation experiments, LAA behaves as a distinct population of molecules and has the characteristics of an alpha2-beta-globulin, not carrying any lipids. The origin of LAA in haematological disorders is unknown. Its presence does not correlate with high white blood cell count, although antibody to LAA has been raised in animals injected with blast cells from leukaemia patients. LAA is distinct from alpha-fetoprotein, and we have observed a reaction of immunological non-identity between LAA and ferritin. This is of considerable interest since ferritin has been reported to be immunologically closely related to alpha2H-globulin which may occur in the same categories of patients as LAA. It is preliminary concluded that LAA as defined by our antisera may be different from alpha2H-globulin and ferritin.


Specificity of transfer factor. In vitro lymphoblast transformation of peripheral lymphocytes to Leishmania major antigen in the presence of transfer factor. The in vivo and in vitro demonstration of specificity of transfer factor (TF) has so far been hampered by lack of a suitable antigen. The host partiality of Leishmania suggested that in the case of leishmania antigen it should be possible to obtain lymphocytes of both donors and recipients of TF which were either sensitized or truly virgin. Lymphoblast transformation of normal donor lymphocytes to leishmania major antigen (LMA) was therefore measured in the presence of TF prepared from donors with a history of cutaneous leishmania infection (LSTFd) and normal donors (NSTFd). A clear augmentation of the lymphoblast transformation equal to that usually seen when lymphocytes from sensitized individuals are exposed to LMA was observed with LSTFd. An insignificant increase in lymphoblast transformation, however, occurred when NSTFd was used together with LMA and when LSTFd or NSTFd was used alone. The results, although limited by the number of TF preparations, tested, clearly substantiate the in vitro specificity of TF.


The diagnostic value of intravenous pyelography in infravesical obstruction in males. Intravenous pyelographies from 104 consecutive patients admitted for infravesical obstruction were studied with special reference to pathology of the upper urinary tract and the bladder, the size of the prostate and the bladder emptying. The incidental findings in the upper urinary tract did not influence the treatment of the infravesical obstruction. Furthermore the radiographic assessment of prostatic size, bladder trabeculation, bladder emptying, bladder stones and prostatic cancer was very uncertain. Thus intravenous pyelography in our opinion should not be performed as a routine procedure in patients with benign prostatic hypertrophy, but only on clinical suspicion of upper urinary tract pathology.