[Surgical therapy of intestinal complications in abdominal typhus]. At our clinic 185 patients with severe typhoid fever were treated. In 51 cases severe complications required a surgical therapy: 24 times bleeding of small or large intestine, 14 times perforation of the bowel and 13 times acute typhoid cholecystitis. Lethality of typhoid peritonitis with perforation is nowadays--inspite of specific therapy with antibiotics--still between 40% and 50%; lethality at our clinic was 37.5%. Dangerous complications are bleeding and re-perforation, which require an aggressive surgical procedure.


Macrophage dependence of galactose oxidase induced transformation of human lymphocytes. The role of macrophages in the transformation of human lymphocytes by the mitogen galactose oxidase was studied. Monocyte depleted, purified T or B cells did not undergo blastogenesis after treatment with galactose oxidase. When galactose oxidase-treated purified T cells were cultured with macrophages, a slight proliferative response was obtained. B cells treated similarly showed no response. When macrophages were treated with galactose oxidase, and then T & B, T, or B cells were added, proliferative responses were observed in all 3 categories. Finally, supernatants of media in which galactose oxidase-treated macrophages were cultured also demonstrated the property of stimulating lymphocyte transformation. These results are consistent with current concepts of mitogen "presentation" and the elaboration of soluble factors by macrophages in mediating the activation of lymphocytes in response to stimulating agents.


B-lymphocyte activation with an extract of Nocardia brasiliensis. An extract from the pathogenic actinomycete Nocardia brasiliensis was mitogenic for murine lymphocytes. This deoxyribonucleic acid-synthetic response of whole spleen cells peaked after 48 h in culture at concentrations of Nocardia extract ranging from 10 to 200 micrograms/ml. The extract appeared to be a mitogen for B lymphocytes since cultures of spleen cells from congenitally athymic nude (nu/nu) mice and of antithymocyte serum plus complement-treated spleen cells from conventional (+/+) mice responded as well as untreated spleen cells from normal +/+ mice. Furthermore, thymocytes did not respond mitogenically to the extract. Mitogenic responses were stimulated in spleen cells from H-2(a), H-2(b), H-2(d), and H-2(k) mice, including lipopolysaccharide-nonresponder C3H/HeJ mice. This Nocardia extract also stimulated polyclonal B-cell activation to the hapten trinitrophenyl, serum protein human gamma globulin,  and several mammalian erythrocytes in cultures of cells from both euthymic and nude mice. Additionally, the requirement for helper T cells in the primary in vitro immune response to sheep erythrocytes could be circumvented by the addition of this Nocardia extract. These results indicate that an extract from the pathogen N. brasiliensis can nonspecifically activate murine B lymphocytes and raise the possibility that polyclonal activation of B lymphocytes may contribute to the pathogenesis of nocardiosis.


Mitogenic effects of bacterial cell walls, their fragments, and related synthetic compounds on thymocytes and splenocytes of guinea pigs. Stimulation of [(3)H]thymidine incorporation of thymocytes and splenocytes from guinea pigs by various bacterial cell walls and their peptidoglycans, by enzymatic digests, and by synthetic muramyl dipeptides was studied as an indication of mitogenic activity. Cell wall and peptidoglycan preparations, isolated from 19 strains belonging to 18 different species, definitely increased [(3)H]thymidine incorporation of thymocytes as well as splenocytes, regardless of mycolic acid contents as a non-peptidoglycan component. Both the cell walls from Nocardia corynebacteriodes (containing mycolic acids) and those from Streptomyces gardneri (lacking mycolic acids) showed far stronger mitogenic activities on splenocytes than other cell walls (stimulation index, 25 to 30). Furthermore, water-soluble enzymatic digests, notably the endopeptidase digests, which generally were greater in degree of polymerization of peptidoglycan subunits than the glycosidase digests obtained from representative cell walls, were found to have as distinct a stimulating activity on splenocytes as the original cell walls. In contrast, solubilization of the cell walls by enzymes, irrespective of endopeptidases or glycosidases, was accompanied by disappearance of the mitogenic activity on thymocytes. On the other hand, studies with synthetic 6-O-acyl-MurNAc-l-Ala-d-isoGln preparations (6-O-acyl-MDPs) revealed that 6-O-stearoyl-MDP and 6-O-(2-tetradecylhexadecanoyl)-MDP, unlike MDP, had distinct mitogenic activity on thymocytes, whereas their activity on splenocytes was rather weaker than MDP itself. The findings presented here suggest that MDP is the minimal structure for the mitogenic activities of bacterial cell walls on guinea pig splenocytes, but that MDP, though distinctively active by itself, requires a polymerized form to exert effectively its inherent stimulating activities on splenocytes. On the other hand, on thymocytes, MDP, unless it takes a particular form or has appropriate additive groups, cannot exert its mitogenic activities.


Surface markers of porcine lymphocytes and distribution in various lymphoid organs. Three rosette test systems were developed for the classification of subpopulations of porcine lymphocytes and correlated with the presence or the absence of membrane immunoglobulins, as well as agg-P-IgG receptors, by means of various RFC depletion experiments. Among the ED-RFC negative cells, PBL with surface immunoglobulins (SIg), at 4 degrees C, can be subdivided into two about equal populations: (1) One half of these cells have surface stable SIg (B cells) and mu determinants; they possess C3b receptors leading to the formation of rosettes with complement-coated zymosan particles (ZC). (2) The other half have surface labile Ig when the cells are washed at 37 degrees C (L-cells); they possess Fc receptors as detected by EA-RFC, i. e. pig-IgG-coated ox RBC. Receptors for Fc-agg, as detected by agg-P-IgG, were primarily shown on B cells. ZC and EA-RFC are in the highest tissue concentration, in bone marrow and spleen, respectively, and more numerous in adults than in newborns. Moreover, the number of EA-RFC was twofold higher than that of ZC-RFC in spleen, mesenteric lymph node and cisterna chyli. This latter organ was the only one without null cell.


Augmentation of cell-mediated cytotoxicity to a rat lymphoma. II. Characterization of the non-T cytotoxic cells stimulated in vivo by tumour cells as natural killer cells. A variety of tumours injected into rats were found to rapidly stimulate cytotoxicity which was similar to naturally-occurring cytotoxicity of normal rats. Cytotoxic cells from the spleen and peritoneal cavity closely resembled NK cells in their lytic specificity and cell-surface characteristics. Thus, although cytotoxicity could be stimulated "non-specifically" with tumours which were resistant to lysis in vitro by NK cells, the cytotoxic cells exhibited patterns of specificity against a panel of target cells in direct lysis or competitive inhibition assays which were similar to those of NK cells from normal rats. These cells also closely resembled NK cells in being largely non-adherent, non-T cells, and in exhibiting a similar heterogeneity in the expression of Fc receptors. Thus, cytotoxicity which was augmented shortly after tumour inoculation appeared to be attributable to NK cells. However, whilst the majority of NK cells from normal or tumour-inoculated rats shared these properties, significant heterogeneity was observed. Minor populations of cytotoxic cells were adherent, were lysed by a heterologous anti-T-cell antiserum and complement and did not express an Fc receptor, although it was not determined whether the same subpopulation possessed all three characteristics.


"NK-like" cytotoxicity of human lymphocytes cultured in media containing fetal bovine serum. Human peripheral blood lymphocytes (PBL) were found to be highly cytotoxic to a human malignant melanoma target cell line after the PBL were cultured in medium supplemented with 20% fetal bovine serum (FBS). The effector cells had surface markers similar to those of non-cultured NK effectors against melanoma targets. Both NK (without culture) and the culture-induced cytotoxic effectors had Fc gamma receptors, lacked Fc mu receptors and were either heterogeneous for E receptors or had low-affinity E receptors. Cells required to generate the FBS response were sensitive to anti-T serum plus complement, passed through a nylon-fiber column, formed E rosettes, but lacked detectable receptors for the Fc portions of either IgG or IgM. These results suggest that events causing activation of T cells such as culture of PBL in FBS-containing medium, result in the augmentation of NK activity.


The variation of a Midwest Catholic University's drug use pattern from other Catholic University findings: why? For over a decade, survey studies concerning drug use and college students have portrayed a significantly lower pattern of drug use by students attending Catholic controlled universities than other university types. In the spring of 1972 the author conducted a study of the undergraduates of a large Midwest Catholic University to assess various aspects of its drug scene. The involvement with drugs, especially marijuana, on this campus departed substantially from the usual Catholic control-low drug use nexus. The discussion presents a description of this departure and suggest that certain demographic and social characteristics of this Midwest Catholic University, when interacting, suffice to offset the religious control and religiosity influences that usually effect the low drug use--religious control nexus.


The tumor promoter 12-O-tetradecanoyl-phorbol-13-acetate enhances the proliferative response of Balb/c-3T3 cells to hormonal growth factors. Stimulation of Balb/c-3T3 cell growth by TPA requires factors found in serum. We examined the interaction between TPA and serum growth factors in the stimulation of cell growth. The number of cells synthesizing DNA (incorporating 3H-thymidine) within 24 to 30 hours after the addition of TPA and the growth factors to density-inhibited Balb/c-3T3 cultures in serum-free medium was determined by autoradiography. With no additions or with TPA (30--300 ng/ml) alone, only 3--7% of cells synthesized DNA. However, TPA synergistically promoted DNA synthesis in combination with each of the defined serum growth fractions, platelet derived growth factor and platelet poor plasma. TPA also synergistically promoted DNA synthesis in combination with purified growth factors including fibroblast growth factor, insulin (10(-6)--10(-5)M), and epidermal growth factor. In all conditions, TPA enhancement of DNA synthesis also resulted in an increase in cell number. Because TPA synergistically enhanced the activity of each growth factor tested, it did not act identically to any of the growth factors.


[Treatment of newly formed oesophageal varices and peptic oesophagitis after upper polar gastrectomy for portal cavernoma (author's transl)]. The management of peptic oesophagitis after upper polar oesophagogastric resection is difficult, when this upper polar gastrectomy is carried out for prehepatic portal hypertension, the constant presence of newly formed oesophageal varices which often bleed, complicates the problem of the therapeutic indications. We adopted in one case an etiological solution by performing an end-to-side spleno-renal anastomosis after splenectomy which was symptomatic by interposition between the oesophagus and the stomach of part of the descending colon. Modern methods of mechanical suture facilitated this surgical operation.


[Low esophageal stenosis and pyloric obstruction: 2 complications of a Prioton clip]. The authors report a case of digestive hemorrhage due to rupture of oesophageal varices, for which treatment by means of a Prioton oesophageal clip was effective but followed by two rare complications: pyloric stenosis by migration of the balloon of the gastrostomy catheter and retention of the clip which required its removal by oesophagotomy. Analysis of the mechanism of these complications rarely encountered in the literature suggests a method of prevention.


A benzodiazepine-anticholinergic drug synergism in the prevention of stress-induced gastric mucosal erosion in mice. Chlordiazepoxide and clidinium each, as a function of dose, prevent stress-induced gastric mucosal erosion in mice. Clidinium was 2.5 times more potent than chlordiazepoxide. When used in a combination of 2 parts chlordiazepoxide and 1 part clidinium, the protective effect was nearly five times greater than that produced by clidinium alone. Furthermore, the combination dosing proved nearly three times more potent than the potency that was predicted from simple additivity of the individual drug effects. This potentiation appears related to the number of ways in which the combination treatment can decrease autonomic input to the gastric mucosa. Thus, the peripheral cholinergic blockade by clidinium may be potentiated by a central chlordiazepoxide suppression of both sympathetic and parasympathetic activities. Therefore, the combined use of these drugs in the therapy of stress-induced gastric disorder appears to have a rational pharmacologic basis.


Location of the gene for theta antigen in the mouse. III. The position of Thy-1 relative to Lap-1 and Mpi-1. The position of the Thy-1 (theta cell surface antigen) locus on chromosome 9 of the mouse was determined relative to the biochemical markers Lap-1 (leucine arylaminopeptidase) and Mpi-1 (mannosephosphate isomerase). Four-point backcrosses using both male and female heterozygotes showed that the order of these loci is Lap-1--Thy-1--Mpi-1. By observing the segregation of alleles at the Mod-1 (cytoplasmic malic enzyme) locus, which is known to lie distal to these three markers, it was possible to show that Lap-1 is at the centromeric end of this gene group. The overall map for this portion of chromosome 9 as determined by these crosses is: Lap-1--5--Thy-1--7--Mpi-1--14--Mod-1.


Young F mice spontaneously generate cytotoxic T cells against parental targets. Spleen cells from young (AKR/J female x BALB/c) or (BALB/c female x AKR/J)F1 mice can spontaneously generate effector cytotoxic T lymphocytes (CTL), in a 5-day primary in vitro culture, which lyse target cells from AKR/J and BALB/c but not allogeneic mice. These spontaneous CTL responses first appear when spleen cells are taken from F1 mice at 3 to 4 weeks of age, are maximum at about 5 weeks, and have declined by week 7. The fact that these spontaneous CTL responses are never detectable in the spleen cell cultures from any ages of parental AKR/J and BALB/c mice makes them unique properties of the F1 mice.


The cellular mechanism of leukocyte adherence inhibition. Human blood leukocytes from three subjects who had been contact sensitized to dinitrochlorobenzene were used in direct and indirect leukocyte-adherence-inhibition (LAI) reactions in an attempt to elucidate the cellular mechanism of reactivity. The leukocytes were separated and purified by standard procedures. In direct LAI, only T cells or populations containing T cells gave positive reactions (significantly reduced adherence) with the antigen. Supernatants from suitable leukocyte-antigen mixtures contained a soluble leukocyte-adherence-inhibition-factor (LAIF) that reduced the adherence of normal leukocytes. Only T cells or populations containing T cells were active in LAIF production; B cells, granulocytes, and monocytes were inactive. The cellular requirement for the action of preformed LAIF was not restricted: all major types of blood leukocytes were susceptible to its effect.


Cell-mediated immunity in interstitial nephritis. II. T lymphocyte effector mechanisms in nephritic guinea pigs: analysis of the renotropic migration and cytotoxic response. The present studies investigate the effector role of lymphocytes in guinea pigs with an interstitial nephritis. Several observations were made relative to a number of functions expressed by these cells. The results of adoptive cell migration studies suggest that a subpopulation of T cells in nephritic animals traffic renotropically to either normal or damaged kidneys on transfer. Similar lymphocytes were also tested in vitro for direct effector function by utilizing target kidney cell monolayers in a cell-mediated cytotoxicity assay. The kinetics of the observed cytotoxic response were studied over the life span of nephritic animals. Optimal target-cell lysis occurred 12 to 17 days after sensitization, simultaneous with the onset of active histopathologic changes. The cytotoxicity was stoichiometrically titratable and relatively specific for fetal kidney tissue. In addition, cells from the spleen or lymph nodes of diseased animals effectively suppressed this cytotoxic response. These findings demonstrate that a diverse population of T lymphocytes are both capable of damaging the renal interstitium as well as modulating effector-cell functions on a regional basis with the immune system.


A monoclonal antibody to viral glycoprotein blocks virus-immune effector T cells operating at H-2Dd but not at H-2Kd1. A particular monoclonal antibody that binds to the influenza virus HA molecule inhibits HA-specific thymus-derived lymphocytes mediating cytotoxicity in the context of H-2Dd but not of H-2Kd. Another monoclonal antibody blocks both sets of HA-specific effector T cells. This observation, together with related findings from other laboratories, is considered to support the idea that T cell recognition is directed against some association of viral and H-2 glycoproteins, as proposed in the original formulation of the "altered self" concept.


Characterization and measurement of anti-IgG antibodies in human sera by radioimmunoassay (RIA). A sensitive direct binding radioimmunoassay (RIA) was developed which detected low avidity anti-IgG antibodies in sera negative in the latex fixation test (LFT). IgG class antibodies could be detected and were commonly found along with IgM class antibodies. Additionally, the RIA was more reproducible than the LFT, was easily adapted to measure relative avidities of anti-IgG antibodies, and had other technical advantages over the LFT.


Alterations of host defenses paralleling cholesterol-induced atherogenesis. II. Immunologic studies of rabbits. Cholesterol-fed rabbits are more susceptible to experimental infections than similar animals given a normal diet. Multiple tests were employed to estimate functions of reticuloendothelial (RE) phagocytosis, lymphocyte activity, polymorphonuclear (PMN) and macrophage chemotaxis, phagocytosis, and bactericidal activity, as well as enzymatic activity of the macrophages. RE phagocytosis was unchanged in the cholesterol-fed animals. However, most functions of the isolated PMNs and macrophages were significantly reduced. Three of five dehydrogenases and phosphatase were lower in activity from cells obtained from cholesterol-fed rabbits than from controls. Conversely, both B and T lymphocyte activities were significantly higher among the cholesterol-fed animals. These metabolic and functional alterations of cells from cholesterol-fed rabbits may explain the increased susceptibility to infection among these animals. The enzymatic changes found in leukocytes may correlate with those changes in arteries observed during atherogenesis, thereby providing a new prognostic test for risk of atherosclerosis.


Microsphere studies of bullfrog central vascular shunts during diving and breathing in air. Bidirectional central vascular shunts were measured during diving and breathing in air in unanesthetized bullfrogs by using pulmonary trapping of 38 mu mean diameter radionuclide-labelled microspheres. Six animals studied during diving exhibited a strong overall right-to-left shunting pattern comprised of both a predominant (68% mean) right-to-left shunt and a weak (23%) left-to-right countershunt. Five animals with access to air showed a variety of distribution patterns, including predominant shunts in the left-to-right (1 animal) and right-to-left (1 animal) directions, nearly complete mixing (2 animals) and separation of systemic and pulmonary venous returns (1 animal).


Role of subdermal current shunts in the failure of frogs to regenerate. Large, uniform, skin-driven currents (20-40 muamp/cm2) leave the ends of limb stumps of post-metamorphic frogs (Rana pipiens) from about the first through the tenth day after amputation. However, right after amputation, while currents of comparable density may leave the periphery of the cut surface, current densities are greatly depressed in the center of this surface. We suggest that this depression is brought about by shunting through the subdermal lymph space (characteristic of anurans but not urodeles); continues in covert form after formation of a wound epithelium; and helps explain the ability of small, imposed currents to initiate frog limb regeneration.


Potassium modulation of taurine transport across the frog retinal pigment epithelium. Net taurine transport across the frog retinal pigment epithelium-choroid was measured as a function of extracellular potassium concentration, [K+]o. The net rate of retina-to-choroid transport increased monotonically as [K+]o increased from 0.2 mM to 2 mM on the apical (neural retinal) side of the tissue. No further increase was observed when [k+]o was elevated to 5 mM. The [K+]o changes that modulate taurine transport approximate the light-induced [K+]o changes that occur in the extracellular space separating the photoreceptors and the apical membrane of the pigment epithelium. The taurine-potassium interaction was studied by using rubidium as a substitute for potassium and measuring active rubidium transport as a function of extracellular taurine concentration. An increase in apical taurine concentration, from 0.2 mM to 2 mM, produced a threefold increase in active rubidium transport, retina to choroid. Net taurine transport can also be altered by relatively large, 55 mM, changes in [Na+]o. Apical ouabain, 10(-4) M, inhibited active taurine, rubidium, and potassium transport; in the case of taurine, this inhibition is most likely due to a decrease in the sodium electrochemical gradient. In sum, these results suggest that the apical membrane contains a taurine, sodium co-transport mechanism whose rate is modulated, indirectly, through the sodium pump. This pump has previously been shown to be electrogenic and located on the apical membrane, and its rate is modulated, indirectly, by the taurine co-transport mechanism.


Antibodies to single stranded DNA: a diagnostic aid in chronic hepatitis B virus infections. Serial determinations of titers of binding antibodies to single stranded DNA were performed over a period of three years in 43 type B hepatitis patients with persisting HBsAg who had either developed chronic hepatitis or were asymptomatic carriers. Patients with histopathological diagnosis of chronic active or chronic persistent hepatitis, with or without clinical symptoms, showed high titers of anti-DNA throughout the course of the disease, whereas in most of these patients the serum alanine transaminase and bilirubin levels fluctuated widely and were often normal; in such cases the elevation of anti-DNA was frequently the only positive sign present. On the other hand anti-DNA titers were within the normal range in chronic asymptomatic HBsAg carriers who showed no histopathological or biochemical changes. Anti-DNA determinations are proposed as a reliable diagnostic aid to supplement current procedures for assessment of the disease status during the course of chronic hepatitis B virus infections.


Unsuspected bacteremia due to Haemophilus influenzae: outcome in children not initially admitted to hospital. Children  not initially admitted to the hospital accounted for 42 of 94 episodes of bacteremia due to Haemophilus influenzae. Antibiotics were prescribed for 22 of the 42 children who were initially sent home; at second visit, 17 were improved, including all 13 with pneumonia. No antibiotics were prescribed for 20 children; at second visit, 15 had persistent fever or new focal infection and five had resolution of symptoms. New diagnoses of focal infection were made at second visit in three of the 22 treated and in 11 of the 20 untreated children, including three who had a new diagnosis of meningitis (one treated with antibiotics initially; two not treated). Cultures of blood positive for H. influenzae were obtained at second visit in ten children who were not treated initially; no child who was treated initially had a second positive culture. These findings indicate that although young children with bacteremia due to H. influenzae may be mildly ill at first visit, many are at risk for development of serious focal infection, including meningitis.


A quantitative description of membrane currents in rabbit myelinated nerve. 1. Voltage-clamp studies were carried out on single rabbit myelinated nerve fibres at 14 degrees C with the method of Dodge & Frankenhaeuser (1958). 2. A method was developed to allow the ionic currents through the modal membrane to be calibrated exactly under voltage-clamp conditions by measuring the resistance of the internode through which the current was injected. 3. The ionic currents in a rabbit node of Ranvier can be resolved into two components, a sodium current and a leak current. Potassium current is almost entirely absent. 4. The sodium currents in rabbit nodes were fitted by the Hodgkin-Huxley model using m2h kinetics. The kinetics of sodium currents in a rabbit node differ from that in a frog node under similar experimental conditions in two respects: (a) inactivation is faster, tau h for rabbit being 2-3 times smaller around -50 mV; (b) the P(Na) (E) curve for mammal is shifted 10-15 mV in the hyperpolarizing direction. 5. From the kinetics of sodium current, the non-propagating rabbit action potential was reconstructed at 14 degrees C. The transient inward sodium current is responsible for the fast initial depolarization phase of the action potential, while the repolarizing phase is accounted for by leak alone. The computed shape of the action potential was in good agreement with the experimentally obtained action potential. 6. At 14 degrees C, frog and rabbit nodes with similar diameters have similar measured gNa values.


Sarcomere length-tension relations of frog skinned muscle fibres during calcium activation at short lengths. 1. Single twitch fibres were isolated from anterior tibial muscles of the frog, Rana pipiens. The relationship between sarcomere length and steady tetanic tension at 5 degrees C was obtained from these living fibres in the range of sarcomere lengths between about 2.2 and 1.3 microns . These fibres were then either mechanically or chemically skinned. 2. Segments were cut from the skinned fibres and mounted in an experimental chamber using a technique designed to minimize segment compliance at the points of attachment. A piece approximately 1 mm in length remained exposed to the bathing solution. 3. The segments were photographed through a light microscope at magnifications of about 460 or 110 X during activation and relaxation, so that the sarcomere lengths could be determined from a part or the whole of the segment. Activations were done with solutions of pCa either 5.49 or 6.09 and at a temperature of 5 degrees C. Fibre segments which developed striation pattern irregularities during contraction were rejected. 4. The sarcomere length-tension relation obtained from these segments in the sarcomere length range 1.3-2.2 microns was similar to that obtained from the same fibres while still living. The results were similar at the two values of pCa used. 5. These results do not support the view that sarcomere length dependent variation in the amount of calcium which is released during tetanic stimulation is a major determinant of the form of the length-tension relation in living muscle fibres at sarcomere lengths less than about 2.0 microns.


Optical probes of membrane potential in heart muscle. 1. The fluorescent dye Merocyanine-540 and the two weakly fluoresecnet dyes Merocyanine-rhodanine and Merocyanine-oxazolone are shown to respond as optical probes of membrane potential in heart muscle. 2. In frog hearts stained with Merocyanine-540, the absorption at 540 nm decreases by 0.1-1.0% and increase at 570 nm excitation wave-length, the fluorescence increases by 1-2%. The time course of all three optical measurements follows the kinetics of the action potential. 3. Merocyanine-rhodanine exhibits potential-dependent optical responses through a 0.5% decrease in absorption at 750 nm, and Merocyanine-oxazolone has a 1.0% decrease in absorption at 720 nm. Their optical responses have a signal-to-noise ratio of 100/1 and 500/1, respectively. 4. The action spectrum of Merocyanine-rhodanine is triphasic in frog heart with an increase in transmittance from 780 to 700, a decrease from 700 to 600, and increase from 600 to 450 nm. Merocyanine-oxazolone shows only increases in transmittance during membrane depolarization. 5. The optical responses of these probes are linear with respect to changes in membrane potential. 6. Pharmacological agents or ionic interventions do not alter the membrane potential sensitivity of Merocyanine-540. 7. Rapid spectrophotometric measurements at various phases of the action potential indicate that the potential dependent optical signals of Merocyanine-540 are produced by changes in amplitude of fluorescence and absorption bands. The lack of wave-length displacement as a function of membrane potential, i.e. electrochromism, is not the mechanism governing the voltage sensitivity of Merocyanine-540. 8. The data suggest that these Merocyanine dyes bind to the plasma membrane and serve as linear optical probes of membrane potential in heart muscle.


Synapse formation in intact innervated cutaneous-pectoris muscles of the frog following denervation of the opposite muscle. 1. Denervation of one cutaneous-pectoris muscle of the frog induces the formation of new synapses in the intact innervated muscle on the opposite side. After crushing the motor nerve to the left muscle the incidence of polyneuronal innervation in the right intact muscle increased from an average normal value of 16% to an average value of 27% (Rotshenker & McMahan, 1976).2. The formation of the new synapses in the intact muscle is independent of the presence of denervated muscle fibres or degenerating axons peripheral to the site of axotomy. After removing the left cutaneous-pectoris muscle, the proportion of polyneuronally innervated muscle fibres in the right intact muscle increased to an average value of 34%.3. The number of new synapses formed in one muscle is dependent upon the type of the lesion to the motor nerve to the opposite muscle; 40% of the muscle fibres on the right side were found to be polyneuronally innervated after transecting the motor nerve on the opposite side, as compared to 27% after crushing it.4. The delay with which new synapses are formed on the unoperated side is dependent upon the distance from the spinal cord of the axotomy. New synapses were detected 4-8 weeks after cutting the opposite nerve close to the muscle. Placing the site of axotomy close to the spinal cord shortened the delay and new synapses were detected as early as 9 days after the operation.5. The stimulus for the formation of new synapses by an intact nerve is ineffective if the injured nerve on the contralateral side originates from distant segments of the spinal cord. The pattern of innervation in cutaneous-pectoris muscles was not altered following denervation of distant muscles in the hind limb.6. These results suggest that the signal for sprouting and synapse formation may arise in the damaged nerve cells, central to the site of axotomy, and then be communicated transneuronally within the spinal cord to the intact motoneurones on the opposite side.


[Arthrography of the wrist: procedures and normal results (author's transl)]. The results of 31 opaque arthrographies of the wrist carried out under two different circumstances are reported. --In a first group the investigation was made immediately after or within a longer period following injury to the wrist or forearm. The results supply information to the surgeon on the condition of the triangular ligament in dislocation and partial dislocations of the inferior radioulnar joint, caused by an architectural fault in the radius after trauma (fracture of the head, diaphysis, or lower extremity). Simple reduction of the radius, without intervention on the inferior radio-ulnar joint, provides an excellent functional result when the triangular ligament is simply stretched. When it is torn (sprains, dislocation locally or at a distance) results are not very convincing in spite of the many possible procedures available. Arthrography easily reveals the presence of a reflex dystrophy complicating the injury. Both the radiological and clinical signs give characteristic pictures of the condition. --This examination is still only used infrequently for the diagnosis of chronic inflammatory rheumatic diseases. The arthrographic images appear very early, however, and are characteristic of an inflammatory synovial lesion. Examinations were carried out mainly for evaluation before therapy, surgical in the case of a synovectomy, medical for a chemical or isotopic synovial treatment. Arthrography in a acutely inflammed joint is followed by an injection of corticoid, sometimes associated with a local antibiotic. This rapidly relieves the patient and prevents worsening of the acute inflammatory process. Arthrography of the wrist is a simple, painless, rapidly performed examination. There has never been a failure, any incident, or accident. It appears to be the only direct exploratory procedure for this joint. A precise anatomical evaluation can be made from the image which gives a true picture of the different anatomical structures.


Syntheses of N-substituted 2(3,4)-pyridylcarboxylic acid hydrazides with analgesic and antiinflammatory activity. A group of N-substituted 2(3,4)-pyridylcarboxylic acid hydrazides were synthesized to investigate the effects that changes in functionality on the terminal hydrazide nitrogen have on analgesic and antiinflammatory activities. The most active analgesic-antiinflammatory compound was 1-(2-pyridylcarbonyl)-2-(2-pyridyl)hydrazine (10a), which was much more potent than dextropropoxyphene and caused a 100% inhibition of carrageenan-induced paw edema up to 5 h. Pyridylcarbonylhydrazides 5a, 8, and 10c exhibited analgesic activity similar to dextropropoxyphene. Although 10b was an inactive analgesic agent, it exhibited antiinflammatory activity similar to 10a.


Night blindness, characteristic facies, and skeletal abnormalities in two brothers. Two brothers are described with a similar physical appearance characterised by minor periorbital anomalies, malar flatness, a maxillary overbite, retrognathia, sloping shoulders, joint hyperextensibility, and minor radiological anomalies. In addition, they had a slowly progressing night blindness, myopia, and extinguished electroretinograms. The mother had mild expression of some of the physical anomalies and a decreased electroretinogram response to red light. We have been unable to find any report of similarly affected children. The possible modes of inheritance are discussed.


Twice-daily dosing of enteric-coated aspirin in patients with rheumatic diseases. To determine the feasibility of twice daily dosing of enteric-coated aspirin (EntrophenR), a preliminary trial on 10 patients with rheumatic diseases was conducted. Three plasma salicylate levels on 2 separate occasions, 1 day apart, were determined. In 9 of the 10 patients studied at steady-state, therapeutic levels were attained (15-30 mg/dl). There were no gastrointestinal side-effects. One case developed tinnitus which resolved with a small reduction in dosage. On the basis of this short-term study, twice-daily EC-ASA appears to be effective in maintaining adequate plasma salicylate levels, and it seems to compare favourably to ASA given in multiple daily doses. On a long-term basis, it may improve patient compliance.


Myasthenia gravis and lymphoma. A clinical and immunological association. Myasthenia gravis and lymphoma rarely coexist, but the occurrence of myasthenia shortly after the treatment of a patient with poorly differentiated nodular lymphoma suggested that an immunological disorder may have contributed to the development of both diseases; the fundamental defects in this association may be impaired immunological surveillance and impaired regulation of immune responses to autoantigens. The finding of T-cell immunodeificiency, including profound T-cell lymphopenia, impaired delayed hypersensitivity responses, and failure to a thymus-dependent antibody response to Salmonella adelaide flagellin, is consistent with this hypothesis.


The nature of the initial positive inotropic effect of K depletion in bullfrog atrial muscle. In frog atrium, K depletion exerts initial, and late positive inotropic effects. The initial effect on the membrane potential, current and tension components was studied using a double gap method under voltage clamped and unclamped conditions. In both cases, the presence of the initial effect was demonstrated. The effect was clearer in preparations in which a positive inotropic effect to toxic doses of ouabain (10(-6) M) had already been attained. This suggests that the initial phase is independent from Na-pump inhibition. Voltage clamp study revealed that the slow inward calcium current (ICa) was enhanced transiently after K depletion concomitant with an augmentation of ICa-dependent phasic tension. ICa-independent tonic tension was not altered at this initial phase. For the enhancement of ICa, two mechanisms appeared to be involved, one an enhancement of gCa and the other a faster and/or longer opening of the slow channel. These results indicated that an enhancement of ICa together with the well-known prolongation of action potential were the cause of the initial positive inotropic effect of K depletion.


The time-dependent and dose-dependent effects of the sulfhydryl blocker N-ethylmaleimide on the tonic tension in bullfrog atrium. The kinetics of the inhibitory action by N-ethylmaleimide (NEM) on ICa-independent tonic tension in bullfrog atrial muscle was studied under voltage-clamped conditions, using the double sucrose gap method. The higher the concentration of NEM became, the larger was the rate of decrease of the tonic tension. In addition, the tension decreased with time of exposure to NEM. When the rate of the decrease of the tonic tension was plotted as a function of NEM concentration, the curve showed saturation kinetics of the Michaelis-Menten type with respect to NEM concentration, following the characteristics of a carrier-mediated process. Moreover, in the presence of excess Ca or half quantity of Na in Ringer solution, the curve showed sigmoidal kinetics. This probably indicates that the condition of either an excess of Ca or a reduction of Na in Ringer solution is apparently a cooperative effector of the inhibitory action of NEM, suggesting that the carrier protein responsible for the generation of tonic tension may be an allosteric protein. Finally, the relationship between ICa-independent tonic tension and the Na-Ca exchange mechanism which is supposed to be a powerful candidate for generating tension was discussed.


[Variations in electrolytes in the smooth muscle tissue of the alimentary canal (author's transl)]. Electrolytes in the smooth muscle tissue of the alimentary canal were measured and their behavior under various conditions were studied on the basis of values measured. The results are summarized as follows: 1. Organic changes due to edema and the like are more prominent in the region near the wound in cases of damaged intestine. Utmost care should therefore be exercised when surgical treatment including resection of the intestine is given. 2. Variations in electrolytes are slight in cases of mesenteric hematoma, and surgical treatment is not necessary. 3. Variations in electrolytes are rather prominent in cases of intestinal fistula, and full consideration should be given to the balance of electrolytes, particularly supplement of K. 4. In casees of intestinal anastomosis, the rate of variation is the highest near the site of anastomosis and on the third day after surgery. Therapeutically, therefore, attention should be given to prevention of complications such as incomplete suture. 5. In cases of intestinal obstruction, variations are more marked and rapid. It brings about a high degree of disequilibrium of intra-tissue electrolytes in the upper intestinal tract; hence the early and adequate treatments are needed.


[Nature of immunological changes in ischemic heart disease]. Humoral and cellular immunological paramaters were studied in 3 groups of patients with ischemic heart disease. A distinct correlation was revealed between these parameters and clinical symptoms of the disease. It was shown that an immunological reconstruction took place already in the ischemic stage of coronarosclerosis. This reconstruction is expressed by the growth of hemagglutinating and precipitating antibody titers, as well as by the emergence of sensitized lymphocytes and excretion of the lymphocyte migration inhibiting factor. The use of various homogenates (a normal or atherosclerotic aorta, an infarctial myocardium) or the nonspecific mitogen PHA showed the presence of a specific antigenoactive complex in the blood of patients with ischemic heart disease. The complex was capable of penetrating and affecting the vascular wall as well as of producing antitissular (antivascular) antibodies which, together with the other factors, can help lipoprotein penetration through the arterial wall to form atheromatous plaques.


[Association of anomalous macula veins with deuteranopia (author's transl)]. A case is presented with large anomalous retinal veins arising above the macula and running across it downwards, towards and into the inferior temporal vein. There was a decreased visual acuity which could not be accounted for. The literature dealing with this rare anomaly is discussed. This is the first case in which the vascular anomaly was associated with deuteranopia.


Loss and recovery of trabecular bone in the distal radius following fracture--immobilization of the upper limb in children. Computed tomography of the human radius is performed using a special purpose scanning device which incorporates a radionuclide (125I) as radiation source. Parameters decribing the trabecular bone and the compact bone are determined at a distal and a diaphyseal measuring site respectively. Using this measurement technique changes in bone mineralization in the radius were studied in a group of 23 children following immobilization of an upper limb for fracture healing. An immobilization period of between three to six weeks resulted in a reduction of the relevant parameter value of up to 44% (mean 16%) in the distal part of the radius, whereas no significant change could be seen in the diaphyseal part of the same bone. Rapid remineralization of trabecular bone is indicated by the increase of the corresponding parameter value at a rate of up to several percent per week. However, in some of the patients studied complete normalization was not attained during the first six months following cast removal.


Treatment of hemorrhagic shock in dogs with verapamil: effects on survival and on cardiovascular lesions. Dogs were subjected to a standardized hemorrhagic shock procedure. Some were treated with verapamil and others were untreated. It was found that the dogs treated with verapamil were protected from the damaging effects of hemorrhagic shock on the heart. This was true even in treated dogs that had a rapid heart rate maintained by means of an intracardiac pacing electrode. In addition, the treated dogs did not show the intestinal hemorrhage that is usually seen in dogs subjected to hemorrhagic shock. Finally, it was found that verapamil treatment increased the survival rate of shocked dogs in comparison with control dogs which were not treated.


Importance of preoperative myocardial glycogen levels in human cardiac preservation. Preliminary report. One hundred seventeen patients undergoing elective coronary bypass were divided into four groups according to prebypass myocardial glycogen levels and the use of potassium chloride cardioplegia. Myocardial glycogen levels were enhanced with a preoperative fat loading diet and overnight glucose loading. The control group (n = 27) which had mean cardiac glycogen levels of 750 mg/100 gm heart weight and no cardioplegia, had a transmural myocardial infarct rate of 14.4%; 35% had severe atrial arrhythmias 65% had severe ventricular arrhythmias, and 31% had severe vasopressor dependence. The group (n = 30) with low cardiac glycogen (736 mg/100 gm) and with potassium chloride cardioplegia had an infarct rate of 6.4%; 6.7% had severe atrial arrhythmias, 18% had severe ventricular arrhythmias, and 16.7% had severe vasopressor dependence. However, the group (n = 26) which had high cardiac glycogen levels (1,208 mg/100 gm) and no cardioplegia had no myocardial infarctions; 3.8% had severe atrial arrhythmias, 27% had severe ventricular arrhythmias, and only 7.8% had severe vasopressor need. The group (n = 34) which had high glycogen levels (1,516 mg/100 gm) and potassium chloride cardioplegia did best of all with no myocardial infarctions or no severe atrial arrhythmias; 14% had severe ventricular arrhythmias and 2.81% severe vasopressor need. The lessening of vasopressor dependence and severe atrial and ventricular arrhythmias were significant by chi square contingency tables at p less than 0.05 and p less than 0.001, respectively. One cardiac-related death each occurred in the two groups with low glycogen and none in those with high glycogen levels. This suggests that better preoperative cardiac nutrition as represented by enhanced cardiac glycogen helps that heart tolerate anoxic stress whether cardioplegia is utilized or not and is additive to potassium chloride cardioplegia.


Reduction of coronary flow in the native circulation after bypass. Observations in a hydraulic model of the cardiovascular system. The effects of aorta-coronary bypass upon flow in the native coronary artery were investigated in a hydraulic model of the cardiovascular system. An aorta-coronary bypass with a diameter identical to the coronary artery was used, since a graft diameter-to-coronary diameter ratio of one has been described as optimal. Stenoses of increasing severity were created in the simulated coronary artery. Aorta-coronary bypass eliminated the pressure gradients across the stenotic coronary segments. This caused a 50% reduction of flow in the normal or mildly stenotic native coronary artery. A higher percentage reduction of flow occurred in the bypassed artery when it was severely stenotic. Such a reduction of flow in patients may accelerate the atherosclerotic-thrombotic process and contribute to the high prevalence of occlusion of natural vessels following bypass. This disadvantageous hydraulic circumstance should be considered, particularly when bypass of mildly stenotic vessels is contemplated.


[Iatrogenic gastrointestinal hemorrhages. A review of 108 cases (author's transl)]. Macroscopic gastrointestinal hemorrhages caused by the consumption of oral drugs are relatively scarce among patients receiving antirheumatic treatment. On the other hand, in a high percentage of all cases of digestive bleeding, antirheumatic drugs were administered shortly beforehand. A review of 216 cases with hematemesis and/or melena are presented. In 50 percent of the patients there was evidence of previous administration of potentially ulcerogenic drugs capable of causing hemorrhages in the digestive tract. Salicylates predominated among the compounds that were considered to be responsible for hemorrhages (salicylates, corticosteroids, reserpine, and other antirheumatic products). The mechanisms involved in producing iatrogenic hemorrhages were examined and the drugs were classified as precipitating and directly ulcerogenic compounds. Precipitating drugs were those which were able to reactivate a preexisting lesion (reserpine, glucocorticoids, phenylbutazone, etc.). The ulcerogenic drugs included those products that could provoke a lesion of previously unimpaired digestive mucosa (salicylates).


[Cell-mediated and humoral immunity in ulcerative colitis. Acute phase reactants (author's transl)]. Many findings suggest that the alterations in immune response observed in intestinal inflammatory diseases may play a part in their pathogenesis. This observation led us to study 22 patients with chronic ulcerative colitis, of whom seven were in the acute stage and the other 15 were asymptomatic. The T and B lymphocyte populations were determined as well as the serum levels of immunoglobulins and acid alpha-1-glycoprotein as acute phase reactants. The results were compared with those obtained from a control group of 10 normal individuals. No statistically significant differences were observed in the percentages and absolute values of T and B lymphocytes as compared with the controls. nor in relation to the activity of the lesions. Neither were there any observable variations in the serum concentrations of immunoglobulins. On the other hand, analysis of the acid alpha-1-glycoprotein showed highly significant values as related to the degree of activity of the inflammatory lesion (p less than 0.005). Our results confirmed the value of determining serum acid alpha-1-glycoprotein levels as an index of inflammatory activity. The immunitary parameters under study did not vary in the different stages of the disease.


Thymus-independent anti-DNP antibody responses to DNP-casein and DNP-gelatin. Although studies on the molecular nature of thymus-independent antigens suggested that the polymeric structure with repeated antigenic determinants and slow metabolism are responsible for thymus-independence, we found that anti-DNP antibody responses to DNP-casein and DNP-gelatin were thymus-independent as well as macrophage-independent. These antibody responses were not affected by in vivo treatment with carrageenan or anti-thymocyte serum. In addition, responses of athymic nude mice to both antigens did not show any significant differences when compared with heterologous nu/+ mice. The findings were confirmed by in vitro experiments; non-adherent spleen cells or T cell-depleted spleen cells responded well to both antigens to the same extent as normal spleen cells. Since both casein and gelatin are polyclonal B cell activators and are not presumed to be high polymer or slow-metabolizing substances, we suggest that thymus-independence in many kinds of antibody response should be reconsidered.


B cell activating properties of parotid protein. A new biological activity of bovine parotid protein acting on immuno-competent lymphocytes to lead to polyclonal antibody responses was demonstrated. A significant amount of antibody to SRBC or antihapten antibody to TNP-SRBC, BPO-SRBC, or SA-SRBC was produced in mice by adding the appropriate doses of bovine parotid protein, suggesting that this protein may be a nonspecific B cell activator which acts on the B cells in a similar way as casein or gelatin.


D-penicillamine: mitogenic effect on mouse, rat and human spleen lymphocytes. The effect of D-penicillamine (D-Pen) on the proliferation of cultures of normal mouse, rat, and human spleen lymphocytes and peripheral blood lymphocytes was examined. D-Pen in concentrations of 2 x 10(-3) M to 8 x 10(-3) M in serum-free and in serum-containing medium resulted in a highly significant incorporation of 3H-TdR by normal mouse and rat spleen cells. Enhanced incorporation of 3H-TdR by normal human spleen cells only occurred in serum-containing medium. D-Pen in concentrations of 10(-4) M to 10(-3) M in serum-free and serum-containing medium resulted in significant inhibition of 3H-TdR incorporation by normal and mitogen-stimulated mouse and rat spleen cells. Doses of D-Pen greater than 2 x 10(-2) M strongly inhibited 3H-TdR incorporation by both normal and mitogen-stimulated mouse, rat, and human spleen cells and peripheral blood cells. The latter cells were not stimulated or inhibited at lower concentrations of D-Pen. Results from cell depletion and enriching procedures (specific antibody +C' cell killing, employment of athymic, nude spleen cells, adherent and phagocytic cell removal, E rosette cell separation procedures) suggested that target cells in the mouse spleen for D-Pen activation are non-adherent B cells whereas the D-Pen responsive cells in the human spleen probably are T cells.


Action spectrum for lethality of near-UV light on Haemophilus influenzae and lack of mutation. Mutation and inactivation of H. influenzae have been measured following irradiation at various near-UV wavelengths. Inactivation takes place most readily at 334 nm (but is unaffected by absence of excision or postreplication repair), and decreases markedly at longer wavelengths. No induced mutations to resistance to novobiocin or streptomycin or to ability to utilize protoporphyrin instead of hemin were detected at any of the wavelengths used. There were also no detectable induced mutations in an excision-defective strain after 334-nm irradiation. These results are in contrast to the in vitro mutation of purified transforming DNA we previously observed.


Cell-surface labelling reveals no evidence for membrane assembly and disassembly during fibroblast locomotion. As a cultured fibroblast moves, particles or pieces of debris attached to its surface move backwards with respect to both the cell and the substrate1,2, as also do concanavalin A (Con A) receptors in the membrane of the leading lamella3. One suggested explanation is that membrane components from the cytoplasm are assembled and introduced into the surface membrane of the moving cell close to its leading edge and flow backwards to a 'sink'; there the membrane is disassembled, and its components enter the cytoplasm and flow forward within the cell, to be re-introduced later into the surface membrane1,4. However, because cell-surface receptors can be redistributed as a result of cross-linking by external ligands5,6 it has been proposed that the backward flow of Con A receptors and particles may result from such a cross-linking rather than from a flow of intact cell membrane7,8. To investigate these alternatives, I have studied moving fibroblasts by means of a cell membrane label that does not induce the redistribution of its receptors. My results do not seem compatible with the membrane flow model.


Studies of T lymphocyte function and inhibitory factors in minimal change nephrotic syndrome. Plasma obtained from patients with MCNS in active stage suppressed the 3H-TdR incorporation of autologous or homologous lymphocytes stimulated with PHA-P and E rosette formation, while plasma from patients in remission did not. The depressed mitogenic response of lymphocytes from patients in the active stage significantly improved when the patient's plasma was substituted for the plasma from inactive MCNS or healthy persons and fetal calf serum. In the preliminary experiment, it was seen that the inhibitory factors were heat stable at 56 degrees C, unadsorbable to charcoal powder and retained in both the permeable and impermeable fractions of collodion bag.


Structural and functional changes in the renal circulation after complicated pregnancy. Angiographic and histological studies of the intrarenal circulation have been undertaken in 20 patients following complicated pregnancies: 12 patients had had hypertension of pregnancy (group 1); 7 acute renal failure due to either ante- or post-partum haemorrhage and 1 patient post-partum renal failure (group 2). 3 months after delivery all patients had angiographic evidence of structural and functional abnormalities involving intrarenal blood vessels and cortical blood flow. The severity of the structural changes was related to the degree of microangiopathic haemolytic anaemia noted in the acute obstetric complication but not to the height of the blood pressure at this stage. Histological abnormalities of the cortical blood vessels were minimal. At the time of the renal angiogram and biopsy, 3 of the 12 group 1 patients were hypertensive and 3 had impaired renal function, compared with 5 and 1, respectively, in the 8 group 2 patients. Although during the follow-up period (mean 5 years) no further deterioration in renal function in either group has been observed, hypertension developed in 50% of the group 1 patients compared with only 1 of the patients in group 2. The relationship between the late onset of hypertension and the intrarenal vascular and haemodynamic abnormalities is discussed.


Neuroradiological findings in a child with primary leptomeningeal melanoma. A case of primary leptomeningeal melanoma in a child is presented. The patient was studied with multiple neuroradiological methods, however computed tomography (CT) provided the most important information. The CT findings with leptomeningeal tumor, although not completely specific, do suggest the diagnosis, thus providing important information to explain the acute onset of symptoms in a previously healthy child. This case also differs from previously reported cases in terms of the type of hydrocephalus associated with the tumor.


[Study of the efficacy of neuramide in the treatment of pain in cancer patients]. The effectiveness of neuramide as an analgesic was assessed in 71 patients with neuritic pain in an oncological radiotherapy ward. 1-2 vials i.m. twice a day for results in 54%, poor results in 13%, and nil results in 21%. The degree of analgesia was that the drug is useful as an analgesic, anti-inflammatory, cell membrane stabilising, and neurotrophic preparation in certain well-defined pain syndromes, especially those of a secondary nature. Attention is also drawn to its excellent tolerance and the complete absence of side-effects.


[Karyosphere of the oocytes of the common frog, Rana temporaria]. Karyospheres of ca. 200 mcm in diameter were isolated from the common frog oocytes of definitive size. An electron microscope study has revealed in the karyosphere fibrillar nucleoli and micronucleoli, modified synaptinemal complexes sometimes connected with chromatin and fibrillar material containing a great number of, mostly atypical, pore complexes resembling those of nuclear membrane and forming "pseudomembranes". An electrophoresis of the isolated karyosphere has revealed 12 distinct protein bands, of 3 which correspond to the protein triplet characteristic of the nuclear matrix and the rest 9 represent high molecular weight components with the molecular weight from 130 to 200,000 D.


[Value of therapeutic soft contact lenses in the treatment of recurrent corneal erosions]. Among 100 patients treated with soft contact lenses there were 26 showing recurrent corneal erosions. In these particular cases the application of soft contact lenses proved successful if conservative treatment had proved a failure. The treatment is simple under regular slitlamp microscopic control, can be applied to outpatients and does not lead to any complications.


Problem-oriented record. A critical review. After 10 years of experience using the problem-oriented record (POR), Weed proposed that both patient care and clinical education could be improved by changing traditional medical records to a problem-oriented format. The problem-oriented system of record keeping has since been attempted or adopted by many physicians in the United States and abroad. This article will review four aspects of the POR. First, it will define the format of the POR in an ambulatory and ward setting. Second, it will discuss POR implementation. Third, it will attempt to assess the extent to which POR is in use currently. Fourth, it will review the studies that have attempted to evaluate the effectiveness of the POR.


Granulopoiesis in Shwachman's syndrome (pancreatic insufficiency and bone marrow dysfunction). Granulopoiesis was studied in 10 children with Shwachman's syndrome (chronic neutropenia and exocrine pancreatic insufficiency). Marrow proliferative activity assessed by determination of mitotic indices and tritiated thymidine uptake into granulocytic cells was normal. Assay of bone marrow granulocyte colony-forming cells (CFU-C) in a methylcellulose tissue culture system demonstrated normal CFU-C numbers in four patients and reduced numbers in five. The granulocyte colonies formed were indistinguishable from normal colonies morphologically. Production of colony-stimulating activity (CSA) from patients' peripheral blood leukocytes appeared normal when tested on control marrow. No serum inhibitors against CFU-C or CSA could be demonstrated using both control and autologous marrow, and co-culture of patients' peripheral blood lymphocytes with control marrow did not inhibit CFU-C growth. We conclude that in Shwachman's syndrome committed granulocytic stem cells are present, and the numbers detected in vitro vary widely as does the clinical neutropenia. The proliferative activity of recognizable granulocytic cells is normal and neither a deficiency of humoral stimulators nor the presence of serum or cellular inhibitors of granulopoiesis can be demonstrated.


The Langer-Giedion syndrome: report of a 22-year old woman. A 22-year-old woman with the Langer-Giedion syndrome and delayed puberty is presented. Pertinent features include a bulbous nose, sparse hair, protruding ears, multiple cartilaginous exostoses, cone-shaped phalangeal epiphyses, short stature, microcephaly, and mental retardation. She is the oldest patient thus far described with this condition, and is compared to the ten previously published cases. The clinical course of patients with the Langer-Giedion syndrome and the possibility of malignant change in the exostoses have not been established.


Nystagmus duration changes of learning disabled children during sensory integrative therapy. Sensory integrative therapy was administered to 43 learning disabled children categorized according to their pretherapeutic duration of postrotary nystagmus. The duration then was recorded after relatively short or long treatments. Children displaying initial subnormal nystagmic functioning responded to therapy with increases in duration while others displayed decreases, and these effects were more apparent after long therapy. These data support the claims that learning disabled children can be meaningfully categorized according to their nystagmic responses and that attention to their interoceptive sensory functioning may be of clinical significance.


[Gastrointestinal haemorrhage due to aorto-intestinal fistula. 3 cases (author's transl)]. Three types of aorto-intestinal fistula may be associated with gastrointestinal bleeding: primary fistulae from an aneurysm, secondary fistulae related to an aorto-prosthetic anastomosis and paraprosthetic fistulae by intraduodenal protrusion of a graft. The prevalence of secondary and paraprosthetic fistulae increases with more widespread vascular surgery. Only if the diagnosis is always borne in mind in a patient with an aneurysm or an aortic prosthesis makes it possible to recognise an aorto-intestinal fistula in time. Upper GI series and endoscopy are more useful in reaching a diagnosis than arteriography but signs must be sought in the third and fourth parts of the duodenum. The lesion may even be missed on surgical exploration, being concealed before separation of the aorta and duodenum. Infection and the underlying general medical condition are factors in the gravity of the operative prognosis. One of our three patients treated surgically was saved by the insertion of an extra-anatomic bypass. The prognosis in paraprosthetic fistulae, the possible precursor stage of a secondary aorto-digestive fistula, is more favourable.


[Non specific immunity of children with selective IgA deficiency. Aggravating role of abnormal phenotype of alpha-1-antitrypsin (author's transl)]. Among 998 children with recurrent respiratory diseases 26 children with selective IgA deficiency were found. Three groups were considered according to IgA level in serum: group I with IgA under 0.05 g per litre; group II with IgA between 0.05 and 0.3 g per litre; group III with IgA above 0.3 and under 1 g per litre. Non specific immunity was studied in these patients including immunoglobulin levels, alpha-1-antitrypsin (A.A.T.) phenotypes, phagocytosis of staphylococcus aureus by PMN, lysozyme level, complement system. Cellular immunity was evaluated by IDR tests and rosette forming cells (RE). Only non specific immune systems were disturbed in some patients and appeared as aggravating factors in IgA deficient patients. We found: Abnormal phenotypes of ATT in 11 cases; deficiencies of engulfment in 6 cases, of bactericidal activities of PMN in 7 cases out of 16 studied; decrease of lysozyme level in 4 cases out of 17 studied; increase of IgE level in 9 cases with atopic symptoms in 7 patients. In our experience the chief aggravating factor in IgA deficient patients is abnormal phenotype of AAT.


Decrease in epidermal growth factor receptor levels and production of material enhancing epidermal growth factor binding accompany the temperature-dependent changes from normal to transformed phenotype. Normal rat kidney (NRK) cells infected with a temperature-sensitive mutant of Kirsten sarcoma virus (Ts cells) exhibited normal monolayer morphology identical to that observed for uninfected cells (NRK cells) at the nonpermissive temperature, 39 degrees C, but grew as multilayered foci resembling NRK cells transformed by the wild-type virus (KNRK cells) at 32 degrees C, the permissive temperature. NRK cell division was stimulated by epidermal growth factor (EGF), and these cells showed high levels of EGF receptors, as determined by 125I-labeled EGF binding. KNRK cells were unresponsive to EGF and no EGF receptors were detectable. Ts cells also were unresponsive to EGF at both temperatures, but exhibited just detectable EGF binding at 32 degrees C and 10-15% of NRK cell binding at 39 degrees C. Use of EGF added to the culture medium by these cells paralleled the receptor levels. Crossfeeding experiments among NRK, KNRK, and Ts cultures indicated that Ts cells at the permissive temperature and KNRK cells at both temperatures produced a heat-stable substance(s) which stimulated DNA synthesis in NRK cells independent of the presence of serum or of EGF. Conditioned medium from the transformed cultures also significantly enhanced EGF binding to NRK cells. These studies demonstrated a correlation between the transformed phenotype and the receptor levels of a potent cell mitogen, EGF, which was readily reversible in the Ts cultures. In addition, cultures expressing the transformed phenotype produced material that did not compete for the EGF receptor but did enhance EGF binding, in contrast to other reports involving sarcoma virus-transformed cells.


Distribution of 5'-nucleotidase in human lymphoid tissues. Low activity of 5'-nucleotidase (5'-ribonucleotide phosphohydrolase, EC 3.1.3.5) in T lymphoblasts may explain the marked sensitivity of this cell to deoxynucleotide accumulation when compared to B lymphoblasts. The relevance of such observations with cultured cells to the normal immune system requires the demonstration of similar differences in the 5'-nucleotidase activity of normal human lymphocyte subpopulations. Sheep erythrocyte (E) rosette-forming cells from normal thymus, tonsil, and peripheral mononuclear cells have 5'-nucleotidase activities of 1.7, 11.3, and 21.2 nmol/hr per 10(6) cells. Non-E-rosette forming cells from the peripheral blood or tonsil have 5'-nucleotidase activity comparable to the higher levels found in the peripheral E-RFC. Increased levels of 5'-nucleotidase activity may be a marker for post-thymic T lymphocytes. T lymphoblasts have 5'-nucleotidase activity similar to values demonstrated for E-RFC in thymus, whereas cultured B lymphoblasts have 5'-nucleotidase activity 15 times greater than that of T lymphoblasts. On the basis of these observations, the 5'-nucleotidase deficiency in congenital agammaglobulinemia has been reevaluated. In these patients the data indicate that peripheral E-rosette forming cells have the enzyme deficiency, demonstrating an abnormality of T lymphocytes in this disorder of immunoglobulin production.


[Effect of testosterone propionate on the lymphoid system and antibody-producing capacity in golden hamsters]. The effect of testosterone-propionate on the lymphoid tissue and humoral immunological response to SRBC was studied in 224 golden hamsters of both sex. The hormone was injected intramuscularly in a dose of 1 and 5 mg every other day (a total of 10 injections). Testosterone caused thymus atrophy, hypoplasia of the spleen, reduction of the absolute B lymphocyte count in the bone marrow, forming cell count and a fall of the serum hemolysin titre in the immunized animals. The detected changes were found to be more pronounced in female animals.


Synthesis and pharmacological properties of some N-aroylhomotryptamines. Eight amide compounds were obtained by condensation of appriopriate acid chlorides with homotryptamine and its 5-methoxyderivative. The effects of these compounds on the central nervous system were tested. m-Nitrobenzoylhomotryptamine showed the strongest sedative, anticonvulsive and analgesic properties.


Biological effects of allogeneic effect factor on T lymphocytes: in vitro induction of cytotoxic T lymphocytes manifesting preferential lytic activity against H-2-identical tumor cells. The studies reported herein were designed to determine the effects of allogeneic effect factor (AEF), a soluble mediator generated in the course of allogeneic cell interactions, on the differentiation of cytotoxic T lymphocytes in vitro. Normal, unprimed spleen cells from various strains of mice cultured with AEF for 5 days, in the absence of any stimulator cells, developed into cytotoxic lymphocytes capable of lysing target cells in a short-term 51Cr release assay. T lymphocyte-depleted spleen cells did not become cytotoxic when cultured with AEF, and the cytotoxic cells themselves were found to be T lymphocytes. AEF-induced cytotoxic T lymphocytes preferentially lysed H-2-identical target cells. Thus, AEF, as opposed to similar "helper" factors derived from mixed lymphocyte cultures, appears to be unique in its ability to trigger normal, unprimed T lymphocytes to differentiate into cytotoxic T lymphocytes in the absence of specific antigenic stimulation.


Antitubulin agents enhance the stimulation of DNA synthesis by polypeptide growth factors in 3T3 mouse fibroblasts. Colchicine and other antitubulin agents markedly enhanced the stimulation of DNA synthesis by combinations of various growth factors such as epidermal growth factor, insulin, fibroblast-derived growth factor, and vasopressin in serum-free cultures of several quiescent 3T3 mouse fibroblast cell lines. Enhancing effects were observed based on continuous incorporation of [3H]thymidine into DNA as well as by autoradiographic labeling of cell nuclei. The concentration of colchicine and podophyllotoxin required to produce half-maximal enhancement of DNA synthesis stimulated by epidermal growth factor and insulin was 25-50 nM. Lumicolchicine did not produce enhancing effects. The disassembly of microtubules resulting from the action of colchicine, Colcemid, and vinblastine did not inhibit the stimulation of DNA synthesis in quiescent Swiss 3T3 fibroblasts by fetal bovine serum. We conclude that the cytoplasmic microtubule network in 3T3 mouse fibroblasts does not exert a positive regulatory function in the initiation of DNA synthesis but rather can produce a constraint on the initial action of the peptide growth factors in serum-free media.


Receptors for IgA on a subpopulation of human B lymphocytes. Human B lymphocytes from peripheral blood and tonsils and leukemic B cells from patients with chronic lymphocytic leukemia (CLL) were examined for the presence of receptors for IgA. Receptors for IgA were present on 5-20% of B cells from peripheral blood of normal persons, 6-21% of B cells from tonsils removed because of chronic enlargement, and 4-10% of B cells from patients with CLL. Prior incubation of B lymphocytes in medium containing fetal calf serum was normally essential for expression of receptors for IgA. IgM and IgG receptors were also examined on B cells from tonsils and CLL. Receptors for IgM were present on a large proportion of B cells from tonsils and B cells from patients with CLL. Their detection also required incubation of B cells in medium containing fetal calf serum for 2-3 days. In one patient with CLL, IgM receptors were present on only a small proportion of B cells. No significant change in IgG receptors on B cells from tonsils or CLL was observed when freshly isolated B cells and cultured receptors on B cells progressively decreased as a consequence of shedding of free Fc receptors into the supernates.


Allogeneic cytolysis of reconstituted membrane vesicles. The successful use of lipid bilayer model membranes as targets for cytotoxic lymphocytes is described. Lipid vesicles were made from a mixture of dipalmitoyl lecithin, dimyristoyl lecithin, and cholesterol. Membrane proteins of LSTRA or EL4 tumor cells (as source of H-2 antigens), human eye muscle membrane proteins (as supporting proteins), and 51Cr marker were inserted into the lipid vesicles. Incubation of the reconstituted vesicles with lymphocytes sensitized in mixed lymphocyte cultures against allogeneic cells resulted in the specific release of intravesicular 51Cr. Vesicle damage was mediated by thymus-derived lymphocytes. H-2 antigens could be incorporated into vesicles without eye muscle proteins. However, immune damage of the vesicles could not be demonstrated when vesicles inserted with H-2 antigens in the absence of eye muscle proteins were used as targets.


Separation of functional subsets of human T cells by a monoclonal antibody. A monoclonal antibody was produced to human peripheral blood T cells. This hybridoma antibody, termed OKT4, was reactive by indirect immunofluorescence with only 55-60% of the peripheral blood T cell population (OKT4+) and unreactive with normal B cells, null cells, and macrophages. The OKT4- T cell population contained the previously described TH2+ subset that has been shown to contain cytotoxic/suppressor cells. With cell-sorter separation of OKT4+ and OKT4- cells, it was shown that these T cell subsets were functionally discrete. Both gave proliferative responses with concanavalin A, alloantigens, and phytohemagglutinin although OKT4+ cells were much more responsive to the latter. OKT4+ cells alone responded to soluble antigens whereas OKT4- cells alone were cytotoxic after alloantigenic sensitization of unfractionated T cells. However, both OKT4+ and OKT4- cells were required during sensitization for optimal development of cytotoxicity. These data suggest that the OKT4+ subset represents a helper population and that the OKT4- subset contains the cytotoxic effector population. OKT4 could be a valuable reagent for determining alterations of these functional subsets in human diseases.


Horizontal postrotatory nystagmus response in female subjects with adolescent idiopathic scoliosis. Quantitative and qualitative assessment of vestibular function was made in 18 female subjects with adolescent idiopathic scoliosis and a control group of 25 female subjects without scoliosis. The Southern California Postrotary Nystagmus Test, which examines postrotatory nystagmus response, was used to assess the vestibular function of subjects in both groups. The results indicated that subjects with adolescent idiopathic scoliosis had a significantly decreased duration of postrotatory nystagmus as well as irregularities in nystagmus form. The recommendation was made that a neurological examination, including assessment of vestibular function, be incorporated into screening methods for scoliosis.


The ultrastructure of frog mesenteric capillaries of known filtration coefficient. The capillaries of the frog mesentery were investigated by transmission electronmicroscopy. The mean diameter of these vessels was 20 micrometers and a single layer of five to six endothelial cells (on average) contributed to each circumference. Their ultrastructure was very similar to that of mammalian capillaries of the continuous type [Bennett, Luft and Hampton, 1959]. The endotherlial cells, which contained many vesicles, were joined by specialized junctions and surrounded by a continuous basement membrane. Eleven capillaries were examined after the filtration coefficient of their walls had been investigated by the microperfusion micro-occlusion technique of Michel, Mason, Curry and Tooke [1974]. No abnormal appearances were observed even after the vessels had been perfused with protein free solutions which have been shown to increase filtration coefficient five fold. No morphological differences between capillaries were seen to accompany large differences in the filtration coefficients.


Vessel occlusion with transcatheter electrocoagulation: initial clinical experience. Transcatheter electrocoagulation (TCEC) was used for vessel occlusion in combination with embolization by Gelfoam and/or Ivalon in six patients in whom other interventional or surgical techniques were considered dangerous or unfeasible. The technique was effective in decreasing or obliterating the blood supply to variously located lesions in all cases. The only complications were small skin burns in one patient and a small ulceration of the upper lip in another.


Blue rubber bleb nevus syndrome.

Blue rubber bleb nevus syndrome. Two cases of pediatric blue rubber bleb nevus syndrome are reported. The main features of the disease are rubbery blue cutaneous nevi and hemangiomatous, frequently hemorrhagic malformations of the bowel wall. Polypoid filling defects were seen throughout the bowel on barium studies. This entity should be considered in the differential diagnosis of polyposis, and the skin should be carefully examined for nevi when multiple bowel polyps are demonstrated, especially in patients with gastrointestinal bleeding.


Ultrasonographic demonstration of portal vein thrombosis. For screening patients suspected of having portal vein thrombosis, the ultrasound examination is simple to perform, noninvasive, and can be accomplished rapidly. Three patients were studied in whom ultrasound examination revealed portal vein thrombosis that was subsequently confirmed by angiography or surgery. Ultrasonic findings in a series of 100 randomly selected patients are summarized.


Feasibility of absolute activity measurements using the Cleon emission tomography system. Large volume and small discrete sources of Tc-99m were used to study the spatial resolution, sensitivity, linearity and reproducibility of the radionuclide brain images. The spatial resolution is constant both within and perpendicular to the section. For uniform distributions of activity the response is uniform over the field of view, and the mean pixel count rate is a linear function of the radioactive concentration and is independent of the diameter of the source. However, for discrete sources, the sensitivity was found to vary with the position of the source, and the potential of the system for quantitative assessment of the uptake of radioactivity in organs and tumors was limited initially. Later studies, with modified software, show that this undesirable effect has been reduced.


[Intraperitoneal and intragastric administration of Norartrinal in severe digestive hemorrhages]. A total of 23 successful treatments are described, in severe haemorrhages of the upper intestinal tract, which were either primitive (ulcer, gastritis), or secondary (due to stress), in seriously ill patients, by administration of 4 g of Norartrinal intragastrically or intraperitoneally. The absence of adverse reactions, that have been looked for at anatomo-pathological investigations and during surgery, as well as the good results recorded in patients in whom the classical treatment did not result in satisfactory results, recommend this method especially in limit cases.


Interaction of some anti-inflammatory analgesic drugs and hydrocortisone on the EEG effects of pentazocine, chlorpromazine and pentobarbital. Pentazocine administered in doses of 2.5 and 5.0 mg/kg i.v. produced EEG synchronization with dose-dependent relationships. When this drug was associated with anti-inflammatory compounds such as mefenamic acid or indomethacin, the EEG effect was decreased. The same occurred also when pentazocine, 5 mg/Kg, was combined with hydrocortisone. There were no changes on the EEG effects of pentobarbital and chlorpromazine when these drugs were associated with hydrocortisone and sodium salicylate. The significance of these effects is discussed in terms of a possible interaction between the central mechanisms of pentazocine's action and some anti-inflammatory agents and hydrocortisone. Since this interaction does not happen with other drugs which produce EEG synchronization, such as pentobarbital and chlorpromazine, a different mechanism might be involved.


A health centre survey of rheumatism.

A health centre survey of rheumatism. In order to assess the size and nature of the workload in general practice resulting from rheumatic diseases and to assess the value of the National Insurance 'Sick Note' as an index of this, a prospective survey was carried out. The survey was based upon a health centre which provides the primary medical care for the majority of the inhabitants of a small town. During four periods of two weeks at a different season of the year, all patients considered by the family doctor to be suffering from a rheumatic condition were seen by a visiting rheumatologist. Firm diagnostic criteria were applied and functional capacity was assessed and related to both the diagnosis and symptoms. The rheumatic diseases and conditions accounted for about 5% of total attendances and a slightly greater proportion of total surgery time. This is less than suggested by some previous studies of different design. The sick notes provided such a poor index of the size and nature of the problem that information based merely upon retrospective analysis of these is probably of little practical value.


[Partial deficiency of cell-mediated immunity in some cases of bronchiectasis (author's transl)]. Two case-reports are presented to support the hypothesis that bronchiectasis may occasionally be associated with a partial deficiency of T lymphocyte functions. This deficiency would represent another etiology of the heterogenous sino-pulmonary syndrome of which several causes have been identified or postulated: immunoglobulin deficiency, alpha-1-antitrypsin deficiency, mucociliary abnormality, phagocytosis or bactericidia abnormalities, etc.


A note on indomethacin suppositories in rheumatic conditions. The effect of indomethacin suppositories was observed in 102 patients. Some patients had rectal irritation (9%), and a few had difficulty in inserting the suppository. Most patients tolerated the medication well with relief of joint symptoms (the major reason for prescription) and usually with alleviation of dyspepsia (the second commonest reason for giving the drug in this way).


[Contribution to x-ray diagnostics of tumors of the cerebellopontine angle (author's transl)]. A scrutiny of the palette of possibilities in the radiological examination for the discovery and identification of neurinomas of the auditory nerve, shows that, apart from plain roentgenography, which continues to occupy the first rank after clinical examination, computer tomography represents the most important contribution towards identifying tumors of the cerebellopontine angle. For the identification of neurinomas (of the Brunner type) of the medial type this method of examination is the method of choice. We are not so confident with regard to the small lateral neurinomas which are situated within the auditory meatus. We consider that the discovery of these extremely small lateral neurinomas of the auditory nerve remains extremely difficult and is mainly left to positive cisternography. Probably, the discovery of these neurinomas remains one of the happy chances of early radiological diagnosis. Nevertheless, the knowledge acquired during the past few years must be considered an essential step forward in radiodiagnostics, and hence represents a great aid in the curative treatment of the patient.


[Zoster ophthalmicus : a problem in general practice (author's transl)]. The authors describe several cases of zoster, including some patients who developed skin or bone necrosis, and discuss the principal therapeutics proposed at the present time.


Three different acid phosphatase patterns in leukaemic lymphoid T-cells. The acid phosphatase pattern was studied in leukaemic cells from 8 patients with T-cell leukaemia (5 ALL and 3 CLL). In 2 cases the enzyme activity was focal granular with paranuclear localization as earlier demonstrated by other authors, while--in contrast to these findings--the enzyme activity in 4 cases demonstrated universal granular distribution. Almost all the cells from each patient showed the same picture. In the last 2 cases a mixed focal and universal granular pattern was observed, where half the cells possessed the focal form and the other half the universal form of granular activity. The two first-mentioned patterns were observed in cases of T-ALL as well as of T-CLL, while the mixed pattern was seen only in cases of T-ALL.


Isoenzymatic study of leucocytic acid phosphatase in haematologic diagnosis. Isoenzymatic study of leucocytic acid phosphatase under normal conditions identifies 3 isoenzymatic bands, which exhibit a noticeable cell specificity. Band 2 is granulocytic, band 3 lymphocytic and band 4 monocytic in origin. Pathologic deviations in the isoenzymatic pattern are both qualitative and quantitative. For some diseases such as chronic lymphocytic leukaemia there is a well-defined, differential pattern according to immunological B- or T-cell origin. The more significant qualitative aspects are related to the appearance of abnormal bands, especially band 3b, indicating blastic cellularity, and 5, corresponding to hairy cells. The isoenzymatic analysis of acid phosphatase activity is a simple haematologic complementary test, particularly useful in the differential diagnosis of lymphoproliferative disorders with peripheral blood manifestations.


Covariances of mitogenic responses in leukaemic blood lymphocytes: a functional marker system for the human B lymphocyte differentiation. Various polyclonal activating substances have been shown to stimulate human chronic lymphatic leukaemic (CLL) cells to undergo blast transformation, to divide and to secrete monoclonal immunglobulin. CLL cells from different patients show distinct response patterns to these ligands. We have statistically analysed these response patterns and found that responses to certain ligands demonstrate covariance; that is, a high response to one ligand is statistically associated with a high response to another ligand. A factor analysis of these data on the basis of responses of CLL cells from twenty-one patients and from the use of five different ligands in three different concentrations has shown that as few as two factors can account for as much as 63% of the total variance of these responses. On the assumption that these two factors were T-cell dependency of CLL responses and stage of maturity of the responding CLL cell, we have formulated a theory that explains the basis for this functional marker system for CLL cells. It is possible application to the characterization of individual CLL clones has been discussed.


Cryopreservation of human lymphoid cells from various tissues. Normal and pathological lymphoid cells, collected from different sources, were cryopreserved using a programmed freezing procedure. With this cryopreservation technique, the percentage of T and B cell surface markers and the proliferative response to mitogens were not influenced by 21 and 35 days of storage in liquid nitrogen. The recovery percentage of the lymphoid cells was satisfactory when fetal calf serum was added, as a protein source, to the medium during freezing and thawing phases, while a very low percentage of cells was recovered if the fetal calf serum was omitted.


Auto-antibodies in Sjögren's syndrome. With special reference to liver-cell membrane antibody (LMA). Sera from 70 patients with Sjogren's syndrome (SS), of whom 40 had primary and 30 secondary SS, were tested for various auto-antibodies of the IgG, IgA and IgM classes. 20% had liver-cell-membrane antibody (LMA), 90% had anti-nuclear antibodies (ANA), 40% salivary-gland antibodies (SGA), 13% anti-mitochondrial antibodies (AMA), 33% smooth-muscle cell antibodies (SMA), 9% skeletal-muscle antibodies (SKA) and only 1% had parietal-cell antibodies (PCA). In addition, 53% had IgM rheumatoid factor and 6 patients with anti-DNA antibodies all had SLE. 64% had increased serum IgG, 24% IgA and 14% IgM. A significantly higher incidence of ANA was found within all three Ig classes in patients with secondary SS. AMA and IgM-rheumatoid factor were also found to be elevated in this group. On the other hand, SGA occurred most frequently in patients with primary SS. LMA was mainly of the IgG class and IgG AMA and SMA were more often present in these patients than in those with a negative LMA reaction. The results of the investigation suggest inter alia that inflammatory liver disease, although not indicated by either the case history, physical examination or biochemical values, is probably present in patients with SS.


Clinical experience of electronic peroneal stimulators in 50 hemiparetic patients. Fifty hemiparetic subjects were selected from a population of 250 patients according to criteria forsuitable candidates for peroneal stimulation. The patients received from 10 to 120 hours of treatment during 2--5 weeks. The therapeutic results obtained were classified into four groups, ranging from none to excellent improvement of voluntary movement and reduction of spasticity. The clinical results were correlated to different variables where time from lesion, spasticity, and extent of treatment appeared to be the most important ones. The percentage of excellent results decreased with increasing time from lesion and spasticity, and increased with increasing treatment. Orthotic validity (i.e. the beneficial effect of the orthosis) was observed in 76% of the selected cases and in most of them it was very significant. Preliminary tests performed on 9 subjects showed that in cases with orthotic validity the peroneal brace slightly reduces the oxygen consumption of patients and improves their motivation. This work gives a more quantitative perspective of the validity of functional peroneal stimulation and a better indication of criteria for patient selection. The overall validity of an electronic peroneal brace appears to apply to 15% of the total ambulatory hemiparetic population and its therapeutic value is relevant in two-thirds of such cases if sufficient treatment is provided. Application of functional electrical stimulation to non-ambulatory subjects in the acute phase may however lead to a higher percentage of cases of therapeutic validity.


[Alpha-amylase determination in acute pancreatitis: selection of a reference standard]. It has been investigated which of the amylase determinations agrees most closely with the clinical diagnosis in a group of patients with acute pancreatitis and in a group with other diseases producing amylase elevation. By measuring the amylase in a urine specimen related to its creatinine concentration fewer values within the range of reference in patients with pancreatitis and also fewer falsely elevated values in the second group were observed when compared to amylase in plasma, urinary amylase activity per volume or the amylase/creatinine clearance ratio.


Coronary artery bypass surgery at the University of the Orange Free State Medical School. Fifty patients underwent aortocoronary bypass grafting, and 48 of these survived and are alive at present. Seventy-four per cent of these patients were relieved of angina, 16% were improved, and 10% remained the same, and 72% of these patients have resumed their normal daily work. The morbidity of the operation was negligible. The problems that emerged in this small series were involvement of the perforator artery, sudden occlusion of a major vessel during coronary angiography, preservation of the myocardium during surgery for multiplevessel disease, and lastly the question of when a ventricle is too damaged to be operated on. These problems are discussed and suggestions are made as to how to handle them. On the whole, we see this procedure as a useful adjunct in the treatment of occlusive coronary artery disease.


Selectivity of the distal splenorenal shunt. The distal splenorenal shunt is less likely to provoke encephalopathy than conventional shunting procedures, and it may offer a survival advantage for certain cirrhotic individuals, presumably because of its selective nature. This study suggests that the distal splenorenal shunt, even with exceptional efforts to achieve portomesenteric-gastrosplenic (PM-GS) disconnection, is not nearly as selective as it originally was assumed to be. In 11 patients intraoperative pressure determinations showed a significant decrease in portal pressure after end-to-side distal splenorenal anastomosis and no restoration of portal pressure after PM-GS disconnection. Measurements of flow through the shunt were comparable to those reported for portacaval shunts, and shunt flow was not decreased significantly by PM-GS disconnection. Postoperative angiography showed some PM-GS collateral in 17 of 18 patients, and later angiographic studies showed a tendency for progressive collateral development and consequent loss of hepatopetal portal perfusion. The advantages of the distal splenorenal shunt must accrue from gradual, as opposed to abrupt, portal deprivation, rather than from lasting selectivity.


Non-HLA lymphocyte cytotoxins in various diseases. Cold non-HLA lymphocyte cytotoxins were found to be principally reactive against B lymphocytes. These antibodies were studied in 1335 patients with a wide range of diseases such as systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), scleroderma, Hashimoto's disease, asthma, diabetes, lymphoma, psoriasis, leukemia, multiple sclerosis, and also in healthy donors. Antibodies reactive to B lymphocytes in the cold or warm test conditions were not directed against HLA specificities. Since B lymphocytes differ from T lymphocytes principally in that they have surface immunoglobulin, it is postulated that at least one target antigen of cold lymphocyte cytotoxins is not a virus, infectious agent, or a genetically determined structural antigen, but, rather, simply immunoglobulin.


Use of curves for prediction of maternal blood levels of placenta-specific substances for diagnosis of placental function. Maternal blood levels of cystine aminopeptidase (CAP), human placental lactogen (HPL) and beta 1 glycoprotein (SP-1) were predicted and evaluated using the expressions and their charts developed by us to help diagnosis of placental function in women of the third trimester of pregnancy. This study was conducted on the assumption that these placenta-originating substances as markers would behave similarly to the previously reported heat-stable alkaline phosphatase (HSAP). The results realized the following features: (1) CAP, HPL and SP-1, like HSAP, had their normal ranges of values too wide to be based on for diagnosing placental function in general, but it was confirmed that on the individual basis these marker substances could develop adequate "prediction curves" for their values to come well answering to the test in the same way as with HSAP. (2) The expressions for predicted values revealed that these marker substances in their shift in the maternal blood had different critical points start of deviation from exponential rising. Particularly in abnormal pregnancy, their shifting patterns were often dissimilar to one another, with implications that impaired placental function could possibly be confirmed qualitatively by reference to the predicted curve for the values of either of the marker substances.


Does somatostatin in each organ act specifically on that particular organ? Rats with hypercalcemia induced by injection of vitamin D2 had a decreased thyroid somatostatin content, whereas the somatostatin content in their pancreas was almost within the normal range. This suggests that somatostatin in different organs acts specifically on each particular organ as a local hormone or hormone-like substance.


Vitreous surgery techniques in penetrating ocular trauma. Closed vitrectomy techniques provide new capabilities to treat severe penetrating ocular injuries involving posterior segment structures. With these methods, damaged iris tissue, lens, and vitreous can be removed and intraocular opacities can be cleared to identify and treat retinal damage. Removal of damaged vitreous also prevents later cyclitic membrane formation and traction on the retina. The vitrectomy technique can be combined with additional methods to treat other conditions including reactive nonmagnetic intraocular foreign bodies. We present the rationale and technique of vitrectomy, together with the results of treatment in 51 consecutive cases of penetrating ocular trauma. Guidelines are offered for management of severe penetrating injuries.


Anaemia in infancy.

Anaemia in infancy. Anaemia in infancy is a very common clinical problem in the tropics and will continue to be common while infectious disease and poor nutrition prevail. In the diagnosis of anaemia in a child the clinician must expect a number of factors to be involved. On the basis of clinical features it is possible to arrive at a working diagnosis that provides a basis for treatment. Genetically determined abnormalities of haemoglobin, haemoglobin synthesis and red cell enzymes are common in the tropics. Though laboratory tests are required to confirm their presence these conditions can be suspected clinically and often managed without laboratory facilities.