Disproportion in T-cell subpopulations in immunodeficient mutant hr/hr mice. Mice of the HRS strain, which carry the mutant gene hr, were examined for abnormalities in representation of the three T-cell sets Ly1, Ly23, and Ly123 in the spleen. The salient feature of hr/hr mice, which are immunologically deficient, in comparison with +/hr segregants, was a gross disproportion in numbers of cells belonging to the Ly1 and Ly123 sets, at the age of 3--3.5 mo. At this age, Ly123 cells of hr/hr spleen outnumbered Ly1 cells by 2:1, whereas in +/hr spleens Ly123 cells were outnumbered by approximately 1:2. Cells from pooled lymph nodes of hr/hr mice did not show a correspondingly gross disporprotion of Ly1 and Ly123 cells. Total counts of splenic T cells, and of B cells, were not significantly different in hr/hr and +/hr mice.


Phosphorylcholine-specific helper T cells in mice with an X-linked defect of antibody production to the same hapten. F1 male mice with the CBA/N X-linked defect that are unable to produce plaque-forming cell responses to phosphorylcholine (PC) provide normal PC-specific helper T-cell activity when compared to F1 female littermates. Inhibition of helper activity with anti-idiotypic antiserum indicates that PC-specific T cells from both NBF1 female and male mice possess predominantly BALB/c myeloma protein HOPC-8 idiotypic determinants. Therefore, the CBA/N defect cannot be explained as a deletion of genes coding for V-region anti-PC specificities. The demonstration of helper activity in NBF1 male mice, which occurs in the absence of anti-PC antibody synthesis, also demonstrates the endogenous origin of the T-cell receptor.


Monoclonal cytolytic T-cell lines.

Monoclonal cytolytic T-cell lines. Monospecific cloned cytolytic T-lymphocyte lines have been created utilizing T-cell growth factor. The clones were found to retain their cytolytic specificity after prolonged culture and monospecific function was demonstrated by subcloning procedures. Thus, detailed studies of the phenotypic and functional characteristics of monospecific, homogeneous, cytolytic T lymphocytes will now be possible.


T-helper function of parent leads to F1 chimeras. Presence of a separate T-cell subgroup able to stimulate allogeneic B cells but not syngeneic B cells. Parent leads to F1 chimeras were prepared by reconstituting sublethally irradiated H-2 heterozygous mice with marrow cells from one parental strain. Purified parental strain T cells prepared from unprimed chimeras were exposed to sheep erythrocytes in heavily irradiated mice of each of the two parental strains and recovered from thoracic duct lymph of the recipients at either day 1 or day 5 posttransfer. The lymphoborne cells were then tested for their capacity to collaborate in vivo with B cells of the two parental strains. From this approach it was concluded that parent leads to F1 chimera T cells contain two discrete subgroups of T-helper cells, one specific for self H-2 determinants and the other restricted to H-2 determinants of the opposite parental strain. The restrictions mapped to the K-end of the H-2 complex.


Transplantation of cultured thymic fragments. II. Results in nude mice. Nine nude mice were transplanted with cultured thymic fragments derived from syngeneic (three recipients) or allogeneic (six recipients) sources. All transplanted mice survived for periods of up to 8-10 mo thereafter, at which time they were sacrificed. Weight gain had been progressive and the animals were in excellent health. Four nontransplanted littermates housed in the same cages died at the age of 4 mo. In the nontransplanted mice, the usual deficits of T and B cells were observed. In transplanted mice, normalization of IgG1 and IgA levels as well as IgG antibodies to sheep erythrocytes and precipitating antibodies to rabbit serum occurred. Lymphocyte counts and Thy-1 bearing cells increased to approximately 50% of normal values. Proliferative responses to phytohemagglutinin and concanavalin A, mixed leukocyte reactivity, and cell-mediated lympholysis were variably restored from approximately 10-100% of normal. Attained responses were the same in recipients of syngeneic or allogeneic tissues and these, in turn, were equal or superior to responses measured in animals transplanted with whole noncultured thymuses. Skin grafts from third party donors were vigorously rejected, whereas those derived from second party (allogeneic thymus donor strain) may have been accepted or slowly rejected. Cultured thymic fragments, consisting primarily of epithelial elements, can effectively repair the thymic deficiency of nude mice. Experiments to date do not indicate that syngeneic tissues enjoy an advantage over allogeneic grafts in this restoration procedure.


Density of surface immunoglobulin and capping on rat B lymphocytes. I. Changes with aging. The rate of capping and shedding of cross-linked surface immunoglobulins (SIg) was slower in old Lewis rats (greater than 24 mo) than in young Lewis rats (3-4 mo). Analysis of spleen cell populations with the fluorescence-activated cell sorter indicated that with aging there was a loss of cells with a high density of SIg. Cells with the highest density of SIg capped and shed cross-linked SIg faster than cells with a low density of SIg. The alteration in density of SIg may account for the difference in capping kinetics. Colchicine treatment increased the rate of capping of lymphocytes from young animals, but had no effect on the capping kinetics of lymphocytes from old animals.


Selective affinity fractionation of murine cytotoxic T lymphocytes (CTL). Unique lectin specific binding of the CTL associated surface glycoprotein, T 145. We have analyzed the lectin binding characteristics of cytotoxic T lymphocyte (CTL)-derived surface labeled glycoproteins by affinity chromatography of the labeled glycoproteins on a panel of immobilized lectin adsorbents. Evidence is presented for the specific interaction of the CTL-associated glycoprotein T 145 with a lectin derived from Vicia villosa seeds. Conditions are described for the preparation and use of lectin affinity adsorbents for the rapid isolation of T 145 bearing cytotoxic T lymphocytes. Direct proof is given to show that T 145-positive cells arising from a variety of T-cell activations constitute the only subpopulation of cells with ability to perform cell-mediated T-cell cytotoxicity. Specific depletion of the CTLs by adherence to V. villosa adsorbents is shown by their depletion in the nonbound cell fraction and correspondingly enriched recovery in the sugar eluted cell fraction. Specific affinity fractionation of CTLs has occurred in every strain combination tested and irrespective of the actual antigen specificity of the effector cell population.


Anti-self HLA may be clonally expressed. A monolayer absorption technique was used to test the hypothesis that killer cells directed to self HLA-associated minor histocompatibility antigens (H-Y) were divisible into subsets. The results showed that sensitized killer cells, which recognized two combined antigens HLA-A2; H-Y and HLA-B7; H-Y could indeed be divided into two populations. One was directed to HLA-A2; H-Y and the other to HLA-B7; H-Y. These results can be interpreted in the context of the altered self hypothesis. However, when interpreted in the context of the dual recognition hypothesis, they strongly suggest that independant clones of killer T cells exist which are committed to the recognition of self HLA.


Metabolic correlates of fatigue and of recovery from fatigue in single frog muscle fibers. Fatigue and recovery from fatigue were related to metabolism in single fibers of the frog semitendinosus muscle. The fibers were held at a sarcomere length of 2.3 microm in oxygenated Ringer solution at 15 degrees C and were stimulated for up to 150 s by a schedule of 10-s, 20-Hz tetanic trains that were interrupted by 1-s rest periods, after which they were rapidly frozen for biochemical analysis. Two kinds of fatigue were produced in relation to stimulus duration. A rapidly reversed fatigue occurred with stimulation for under 40 s and was evidenced by a decline in tetanic tension that could be overcome by 1 s of rest. A prolonged fatigue was caused by stimulation for 100-150 s. It was evidenced during stimulation by a fall in tetanic tension that could not be overcome by 1 s of rest, and after stimulation by a reduction, lasting for up to 82 min, in the peak tension of a 200-ms test tetanus. Fiber phosphocreatine (PCr) fell logarithmically in relation to stimulus duration, from a mean of 121 +/- 8 nmol/mg protein (SEM, n = 12) to 10% of this value after 150 s of stimulation. PCr returned to normal levels after 90-120 min of rest. Stimulation for 150 s did not significantly affect fiber glycogen and reduced fiber ATP by at most 15%. It is suggested that the prolonged fatigue caused by 100-150 s of tetanic stimulation was caused by long-lasting failure of excitation-contraction coupling, as it was not accompanied by depletion of energy stores in the form of ATP. One possibility is that H+ accumulated in fatigued fibers so as to interfere with the action of Ca2+ in the coupling process.


Contraction transients of skinned muscle fibers: effects of calcium and ionic strength. Calcium and ionic strength are both known to modify the force developed by skinned frog muscle fibers. To determine how these parameters affect the cross-bridge contraction mechanism, the isotonic velocity transients following step changes in load were studied in solutions in which calcium concentration and ionic strength were varied. Analysis of the motion showed that calcium has no effect on either the null time or the amplitude of the transients. In contrast, the transient amplitude was increased in high ionic strength and was suppressed in low ionic strength. These results are consistent with the idea that calcium affects force in skeletal muscle by modulating the number of force generators in a simple switchlike "on-off" manner and that the steady force at a given calcium level is proportional to cross-bridge number. On the other hand, the effect of ionic strength on force is associated with changes in the kinetic properties of the cross-bridge mechanism.


Lymphocyte subpopulations in thymus and blood from patients with myasthenia gravis. Cell suspensions were prepared from hyperplastic thymic tissue and lymphoepithelioma from patients with myasthenia gravis and from presumed normal thymic tissue obtained at cardiac surgery. The mononuclear cells were examined for surface markers. The mean percentages of both T lymphocytes and Fc receptor-carrying lymphocytes were similar in the three groups, whereas there was an increase in C receptor-carrying lymphocytes in the samples from myasthenic patients. Sections from the thymus gland were examined for T and B markers. In the hyperplastic thymus and in lymphoepithelioma, the T lymphocytes were distributed diffusely throughout the cortex and the medulla; in the normal thymus they were predominant in the cortex. The mean percentage of T and B lymphocytes in peripheral blood from patients with myasthenia gravis was normal. Thymectomy involved a transitory decrease in T lymphocytes with a corresponding increase in B lymphocytes.


Evaluating ambulatory care: three approaches. The article describes three approaches to establishing an ambulatory audit program for nursing. These approaches are variations of a single methodology--that of the Joint Commission on Accreditation of Hospitals--used by the University of Minnesota Hospitals and Clinics. The authors discuss three audit topics from ambulatory care; postkidney transplant; desensitization; and well child.


Incorporating research in a service setting. There are similarities between the research process and problem-solving-evaluation mechanisms already in use in nursing service. The author describes the utility of each process and the rationale for implementing research in the nursing service setting. The nursing auit is recommended as the intstitutional mechanism for implementing and sustaining research activities.


The relationship of alpha1-antitrypsin to inflammatory periodontal disease. Alpha1-antitrypsin (alpha1-AT) is a serum protease inhibitor with a well established role in bodily defense against destructive inflammatory diseases. alpha1-AT exhibits inheritable genetic polymorphism (Pi types). Certain Pi types have been shown to predispose to emphysema and, in this study, also appear to be related to increased chronic periodontitis susceptibility.


Non linear volume flow dependence on osmotic pressure difference in frog skin. The volume flow dependence upon the osmotic pressure difference of both impermeant (sucrose) and permeable (NaCl) species has been investigated in leg skin bags of Rana esculenta. It is concluded: 1. The hydration-dehydration error in the flow measurement with leg skin bags is negligible. 2. The flow-force relationship is non-linear. 3. Unstirred layers and solute permeation have little, if any, influence on non linearity. 4. Structural modifications of the skin induced with hypertonic solutions have been observed and may contribute to non linearity, as well as the multiple-barrier effect.


Peripheral Peters' anomaly: a histopathologic case report. The clinical and pathologic findings of a case of congenital bilateral, peripheral corneal leukoma associated with iris coloboma and anterior subluxation of the lens are reported. The changes in the region of keratolenticular apposition include partial absence of Bowman's membrane, stromal vascularization and thinning with large-diameter collagen fibrils, and absence of Descemet's membrane and endothelium. The authors postulate that dysembryogenesis of the tertiary vitreous, with iris coloboma, resulted in apposition of the lens to cornea during the second and third month of gestation and that this apposition resulted in the observed peripheral corneal abnormalities.


Staphyloma: a complication of surgery for hyphema. Anterior staphylomas developed in two young patients as a postoperative complication of hyphema extractions through corneoscleral sections. The patients, aged five and nine years, underwent evacuation of the hyphemas after rebleeding caused medically unmanageable intraocular pressure elevations. Postoperatively, both patients received corticosteroids and had elevation of intraocular pressure. To repair the staphyloma, a scleral overlay patch graft was performed in one patient, but the intraocular pressure remained elevated and the staphyloma gradually recurred. Enucleation of the eye was eventually required. Resection of the staphylomatous area with lensectomy and complete vitrectomy was performed in the second patient. After four years of follow-up this patient continues to do well.


Analysis of primary care prescribing--a "constructive" coding system for drugs. The introduction of a computerized medical information system as part of a project assessing quality in primary care required the coding of drugs prescribed. The development of a simple four-digit system is described, coding drug, therapeutic class, and route of administration. The system allows easy measurement of the use of combined preparations.The drugs used for insomnia and acute bronchitis have been analysed. The results show marked variation with the age of the patient.The potential for medical audit is discussed as it is now possible to link prescribing figures in routine primary care with relevant clinical information.


Free serum ribonucleoprotein in mixed connective tissue disease and other connective tissue diseases. Free ribonucleoprotein (RNP) was found by means of a hemagglutination inhibition assay in 21 sera from 11 of 25 patients with mixed connective tissue disease (MCTD) who had 299 sera studied. Free RNP tended to appear when anti-RNP antibody titers fell or when prednisone was initiated or increased. Five of 72 SLE patients (211 sera) had free RNP in at least one serum. Three of them had anti-RNP antibodies in other sera. Free serum RNP was found in one of 20 patients with scleroderma and in two of seven patients with connective tissue disease "overlap" syndromes without anti-RNP.


Antibody to extractable nuclear antigen in the rheumatic diseases. Two hundred and eighty-four patients with various rheumatic diseases were studied for the prevalence of antibodies to extractable nuclear antigen (anti-ENA) using an improved haemagglutination technique. Anti-ENA rarely occurred in patients with rheumatoid arthritis, scleroderma, polymyositis, dermatomyositis and Sjögren's syndrome. Seventeen per cent (13/72) of patients fulfilling at least four preliminary ARA criteria for systemic lupus erythematosus (SLE) demonstrated anti-ENA. The predominant antibody was directed at ribo-nuclease-resistant ENA (anti-Sm). Antibodies to ribo-nuclease-sensitive ENA (anti-RNP) occurred in the minority of patients with SLE (2/72) and the mixed connective tissue disease syndrome (MCTD). A trend toward an increased incidence of renal disease in SLE patients with anti-Sm was present. Sequential analysis of anti-Sm in patients with SLE showed a fall in titre paralleling the normalization of anti-DNA antibody titres and serum complement values. No case of unrecognized MCTD was uncovered in our rheumatic disease population.


Patterns of clinical disease associated with antibodies to nuclear ribonucleoprotein. Forty-three patients were studied whose sera were monospecific for nuclear ribonucleoprotein by double immunodiffusion. Thirty-four patients had features typical of systemic lupus erythematosus of which 30 fulfilled the American Rheumatism Association criteria. Clinical features such as rashes, serositis and hematological abnormalities occurred with a frequency expected in SLE. Raynaud's phenomenon occurred in 60%, but other features of mixed connective tissue disease were uncommon. Clinical evidence of renal disease occurred in only four patients. In our experience a good prognosis is related more to the presence of anti-nRNP alone in the serum than to any specific set of clinical findings.


Circulating immune complexes in systemic lupus erythematosus. Association with other immunologic abnormalities but not with changes in renal function. In a study of the usefulness of two widely performed tests for immune complexes (IC) in the assessment of disease activity of lupus nephritis the Raji cell assay detected IC in sera of 14 of 32 patients and the monoclonal rheumatoid factor (MRF) test in only five. There was a close correlation of levels of IC with number of organ systems showing disease activity and with serum complement levels and a somewhat less significant correlation with serum levels of anti-DNA. Although in a few patients levels of IC closely paralleled improvement in renal function with treatment, there was no overall correlation of changes of levels of IC with changes in creatinine clearance. Measurement of circulating IC in lupus nephritis cannot at present be justified as a worthwhile clinical measurement in the management of such patients.


Familial aspects of mixed connective tissue disease (MCTD). I. Occurrence of systemic lupus erythematosus in another member in two families and aggregation of MCTD in another family. Three families are reported in which one member had MCTD and another member had either MCTD or systemic lupus erythematosus (SLE). In one family both mother and daughter probably had MCTD. The daughter, however, had prominent SLE features and kidney involvement. In another family, the mother had MCTD and the daughter had SLE; while in a third family one sister had MCTD and the other had SLE with prominent arthritis but negative anti-ribonucleoprotein (RNP) antibodies.


Oral contraceptive therapy and systemic lupus erythematosus. The relationship between oral contraceptive therapy and systemic lupus erythematosus is not well defined. It has been reported that oral contraceptives may induce lupus: they may also exacerbate pre-existing disease. This report concerns a young woman in whom systemic lupus erythematosus developed three weeks after the commencement of oral contraceptive therapy, but who was shown to have had a chronic biological false positive serological test for syphilis for eight months prior to this. The significance of false positive serological tests for syphilis and the effect of female sex hormones on disease activity in systemic lupus erythematosus is discussed.


Functional stimulation of the spinal cord in multiple sclerosis. The authors describe the effect of electrical stimulation of the spinal cord in multiple sclerosis. After considering the nature of multiple sclerosis, the authors describe the background, character, mode and method of delivering electrical fields to the spinal cord. The results of this form of treatment and the implications of these observations in terms of physiologic mechanisms are discussed.


Afferent and efferent components of the facial nerve in the bullfrog (Rana catesbeiana). The afferent and efferent components of the facial nerve were traced within the brain stem of Rana catesbeiana, using three different neuroanatomical techniques. Primary afferent fibers could be traced to the spinal tract of trigeminal nerve and to fasciculus solitarius as far caudally as the first or second spinal segment, using silver degeneration methods. Cobalt filling of of the entire nerve showed the same distribution of afferent fibers, as well as the filling of the cells within the mesencephalic nucleus of trigeminal, indicating the origin of a proprioceptive component of the facial nerve. Cobalt iontophoresis and horseradish perioxidase experiments showed that the motor nucleus of the facial nerve was located just ventral to the fourth ventricle, and caudal to the motor nucleus of trigeminal. The distribution of afferent fibers to fasciculus solitarius and the spinal tract of trigeminal is similar in some respects to the distribution of afferent fibers from the trigeminal and vagal nerves in the bullfrog. The afferent fibers from the three cranial nerves are found as far caudally in the brain stem as the second spinal segment.


Mononuclear cell analysis of peripheral blood from burn patients. Mononuclear and polymorphonuclear cells isolated by Ficoll-hypaque density-gradient sedimentation from peripheral blood of 25 burn patients at 3-to 4-day intervals during hospitalization were subjected to morphologic analysis. The aim was to identify all cells isolated and to examine the cell population characterized as B-lymphocytes. Patterns of response comprised of lymphocytes, monocytes, neutrophils, and precursor cells in varying stages of maturity were delineated. Shortly after thermal trauma, isolated cell pools from all patients contained high proportions of immature cells. In surviving patients during convalescence, the cell pools had increasing proportions of mature cells and corresponding declines in immature cell types. Patients who died did not produce large populations of mature cells at any time during their hospitalization. Cells identified morphologically as lymphocytes were accounted for by E-rosette assay (T-lymphocytes). Cells previously identified as B-lymphocytes appeared morphologically to be monocytes, were positive for Fc and complement receptor activity, and were phagocytically active.


Acoustic neuroma: when should one operate? Reviewing the investigation of 90 tumors of the cerebellopontine angle during the last 13 years reveals a gradual change in the philosophy of management. Newer investigate techniques and an increased awareness of these tumors have led to earlier diagnosis and treatment than formerly. Facial nerve function preservation is the aim in every case, and where possible residual hearing should be preserved. Treatment should be undertaken by the otolaryngologist, preferably in collaboration with the neurosurgeon. Four cases are presented.


Gastric aspiration in localization of gastrointestinal hemorrhage. We compared the findings from gastric aspiration for blood with the site of gastrointestinal (GI) hemorrhage ultimately identified by endoscopy or angiography in 1,190 patients whose cases were analyzed retrospectively and prospectively during a six-year period. Gastric aspirates were positive for blood in 837 patients. An upper GI site proximal to Treitz' ligament was identified in 93%, and none had a lower GI site. A negative aspirate was found in 353 patients; a lower GI site was identified in 60%, and 1% (three patients) had an upper GI site. In these three patients, hemorrhage occurred in clinical settings suggesting ulcer disease, and bleeding duodenal ulcers were found in all three. All of the other 180 patients with a bleeding duodenal ulcer had a positive gastric aspirate.


Control of intractable abdominal bleeding by external counterpressure. Pressure of 20 to 25 mm Hg circumferentially applied to the abdomen and legs for periods up to 48 hours is a safe, effective, and practical adjunct to standard medical and surgical techniques for controlling intra-abdominal hemorrhage. Pressure is distributed uniformly through the abdominal cavity and aids hemostasis by decreasing transmural pressure and blood flow in arteries and veins. Compression of the venous capacitance reservoir causes shunting of blood to vital organs above the diaphragm. The mechanism of action, optimal pressures, physiological effects, indications, contraindications, and possible harmful effects of circumferential pneumatic compression are discussed.


Stabilizing effects of adenosine on the membrane currents and tension components of the bullfrog atrium. The effects of exogenously applied adenosine on the membrane potentials, currents and tension components of the bullfrog double sucrose-gap method. Adenosine above 10(-3)M produced a prolongation of action potential accompanied by a slight augmentation of contraction which was followed by a sustained depression. The recovery was slow. Under voltage clamp conditions, adenosine merely produced a negative inotropic effect depressing Ica-dependent and -independent tensions. In the membrane currents, Inaf, Is(Ica), Ix and background current (Ib) were all depressed. In the presence of adrenaline, the increased Is, Ix and contraction were inhibited by adenosine in a lower dose (10(-5) -10 (-3) M), and the inhibition of Is and Ica-dependent tension were more prominent in the presence of than in the absence of adrenaline. Under the effect of ATP, which has a catecholamine-like action, similar selective inhibitions were observed. It was concluded that adenosine has a sustained stabilizing action on the myocardium to survive, especially in the presence of adrenaline, by depressing the augmented Ica and contraction.


Inhibitory action of hypertonic urea solution on the potassium contracture of the heart ventricular muscle. Effects of hypertonic urea solution on potassium contracture were investigated in a bullfrot ventricular strip. In a medium of three times hypertonic urea, the contracture induced by 100 mM potassium solution was markedly inhibited whereas the twitch contraction was augmented in the hypertonic urea solution. The extent, as well as the time course, of the membrane depolarization produced by high potassium solution was essentially identical in both isotonic and hypertonic conditions. Endogeneous catecholamine does not seem to participate in this inhibition since the treatment with propranolol did not modify the results. Thus, the possibility of the well-known catecholamine-induced inhibition of potassium contracture can be excluded. The myocardial contractility was never suppressed, or even augmented, at this stage of urea perfusion although a prolonged hypertonic urea perfusion gradually suppressed the contractility. It was suggested that hypertonic urea exerts its negative inotropic action on the potassium contracture independently of its positive inotropism on the twitch contraction by accelerating the uptake of the activator calcium ion to some undefined intracellular sites.


Cytotoxicity of adriamycin and daunorubicin for normal and leukemia progenitor cells of man. A colony assay available for a subpopulation of acute myeloblastic leukemia blasts with proliferative potential was used to measure adriamycin (adria) and daunorubicin (dauno) dose-response curves following brief exposure to either drug and washing. The dose-response curves were simple negative exponentials that might be characterized by D10 (dose required to reduce survival to 10%) values. The D10 values ranged from 0.47 to 20.8 microgram/ml for adria (8 patients) and from 0.06 to 0.34 microgram/ml for dauno (3 patients). Controls consisted of committed granulopoietic and T-lymphocyte progenitors. Four measurements of granulopoietic progenitors yielded D10 values from 2.5 to 11.5 mug/ml for adria and from 0.44 to 1.2 microgram/ml for dauno. T-lymphocyte precursors from 4 normal individuals were resistant. However, following incubation of normal leukocytes with phytohemagglutinin, DNA synthesis commenced in T-lymphocyte precursors for 3 additional normal controls, which was associated with an increased data sensitivity with D10 values ranging from 4.4 to 6.2 microgram/ml.


Surface charge characteristics of cells from malignant cell lines and normal cell lines of the human hematopoietic system. Cells from malignant and normal lines of human hematopoietic origin were studied for their surface charge characteristics with the use of the following criteria: 1) the electron microscopic appearance of cell membranes after labeling with cationized ferritin (CF) either before or after glutaraldehyde fixation, 2) electrophoretic mobility, 3) total sialic acid content, and 4) agglutinability with poly-L-lysine (PLL). CF induced a time-dependent redistribution of surface receptors in unfixed malignant cells but not in unfixed normal cells. After 10 seconds of labeling with CF, both normal and malignant unfixed cells showed a uniform and even labeling pattern. After 5 minutes of labeling, malignant cells exhibited a highly pronounced pattern of clusters and patches, as distinct from a random and even pattern exhibited by normal cells. Both normal and malignant cells after fixation exhibited an equivalent random and even labeling pattern with CF, independent of the duration of labeling. The malignant cells studied possessed less sialic acid, had a lower electric mobility, and were agglutinated more readily with PLL than were the normal cells.


Radioimmunoassay for human thymus-leukemia-associated antigen. A competitive radioimmunoprecipitation method was developed for the quantitation of human thymus-leukemia-associated antigen (HThy-L) isolated from human thymus tissue. Antisera to the antigen were raised by immunization of rabbits with purified fractions of HThy-L. The antigen was labeled with 125l by means of a modification of the lactoperoxidase technique and subjected to Sephadex G-100 gel filtration. Analysis of fractions eluted from this column by sodium dodecyl sulfate-polyacrylamide gel electrophoresis revealed two labeled components with apparent molecular weights of 45,000 and 25,000 daltons, respectively. Immunoprecipitation with anti-HThy-L antiserum demonstrated directly that the 45,000-dalton component carried HThy-L antigenicity. This fraction served as the source of labeled antigen in a competitive radioimmunoassay that permitted the detection of approximately 1 ng HThy-L. With the use of this assay, we confirmed quantitatively that the highest amounts of HThy-L were found in extracts of thymocytes, normal thymus tissues, and lymphoblasts for T-cell lines.


Haemophilus influenzae as a cause of Brodie's abscess in an infant. Brodie's abscess is a form of subacute osteomyelitis which is defined by a particular constellation of clinical, radiological and pathological features. Its occurrence in infants is extremely rare. This case documents just such an occurrence. To our knowledge, the pathogen Haemophilus influenzae has not been previously recognized as a cause of Brodie's abscess in particular or subacute osteomyelitis in general. The clinical presentation and diagnostic pitfalls which may be encountered in this age group are discussed.


Cell surface changes in capping studied by correlated fluorescence and scanning electron microscopy. A simple method has been devised for correlating fluorescence microscopy and scanning electron microscopy, whereby the identical cell observed by the former can be observed by the latter. With this methodology, we have studied the sequence of cell surface changes which occur when mouse B lymphocytes, bearing immunoglobulin (Ig) on their surfaces, interact with fluoresceinated anti-Ig antibodies. Initially, the pattern of staining is diffuse; then, rapidly, patching occurs, followed by the sweeping of the patches into a cap. Accompanying these events are: the disappearance of microvilli, the formation of ruffles and lamellipodia at the pole of the cell opposite the capped pole, the presence of a constriction ring beneath the cap, ameboid shapes, and the translocation of the cell in a direction opposite the cap. Whereas the cell body is smooth, the capped pole frequently shows the presence of numerous microvilli. However, not all capping cells show the changes, and cells capped in the presence of cytochalasin B usually show none of them, except that their surfaces are smooth. Furthermore, T-cells undergoing translocation show the same cell surface changes as do B-cells. Whereas the contractile apparatus of the cell is considered to underlie all these phenomena, it is concluded that the cell surface changes do not result from patching and capping per se, but rather are an expression of the cell translocation also induced by the anti-Ig antibody.


Predicting the need for prolonged ventilatory support in adult cardiac patients. Forty-nine cardiac surgical patients had ventilatory function tests and measurements of maximum inspiratory (MIP) and maximum expiratory (MEP) pressures preoperatively. The differences between the values of various function tests were compared for patients requiring less than 24 hours of ventilator support and those requiring more than 24 hours. There was a significant difference in the mean values for the two groups in vital capacity (VC) first-second forced expired volume (FEV) midexpiratory flow between 50 and 75 (MMEF 50--75) and 75--85 percent of expired volume (MMEF 75--85), and MEP. The standard deviations of each of the variables were so large that the clinical usefulness was limited. However, when discriminant analysis was used for more than one variable, the combination of MMEF 75--85 and MEP predicted success or failure to wean in 24 hours correctly in 90 percent of instances. On the basis of these simple tests, patients predicted to succeed should be weaned from ventilator support on recovery from anesthesia. Those predicted to fail should be placed on intermittent mandatory ventilation (IMV) and should be weaned following a planned, logical process.


Unusual complication of the Hancock porcine heterograft: strut compression in the aortic root. A 65-year-old man underwent aortic valve replacement and triple coronary artery bypass grafting which were followed by gradual late postoperative thrombosis of his 25 mm. Hancock porcine aortic heterograft. At reoperation, the valve struts were noted to be angled centrally into the aortic lumen and dense thrombus completely filled all three sinuses. After valve removal and extensive debridement of the aortic anulus, including relaxing incisions, a diameter of only 23 mm. was obtained. A 23 mm. Björk-Shiley aortic prosthesis was inserted and the patient's recovery was uneventful. This previously unreported complication resulted from the insertion of a too-large Hancock porcine heterograft into a relatively small aortic root, resulting in circumferential strut compression, impedance of central flow, and subsequent valve thrombosis.


Supraventricular tachyarrhythmias after myocardial revascularization: a randomized trial of prophylactic digitalization. The success of prophylactic digitalization in reducing the incidence of supraventricular tachyarrhythmias (SVT) was studied in 140 randomly grouped, consecutive patients undergoing myocardial revascularization operations. The test group received either 1 or 1.5 mg. of digoxin the day before operation and were maintained postoperatively on 0.25 mg. of digoxin daily. There was a significant increase (p less than 0.05) in the incidence of SVT in the treated patients (17 of 61 or 27.8 percent) vs. the untreated patients (nine of 79 or 11.4 percent). There was no significant difference in SVT with the two digitalization dosage levels (31.6 percent with 1 mg. vs. 21.7 percent with 1.5 mg.). Prophylactic digitalization demonstrates no benefit in the prevention of SVT following myocardial revascularization and may, in fact, predispose the patient to these arrhythmias.


Cold blood cardioplegia.

Cold blood cardioplegia. The technique of myocardial protection by means of a cardioplegic solution consisting of cold blood (10 degrees C) with potassium (30 mEq. per liter) is described. A disposable cooling coil is used and a separate pump head for coronary perfusion is avoided. The aortic perfusion cannula can be used for venting of the left ventricle and subsequently for venting of air. This method was used in 125 consecutive patients undergoing coronary revascularization and in 73 consecutive pediatric cardiac surgical procedures with excellent results.


Cost containment via expense rationalization in open-heart surgery. Hospital costs and the fees of the surgeon, assistant, anesthesiologist, and cardiologist were reviewed in a community hospital doing 425 cardiac operations in the year 1977. Each item of the bill was analyzed and discussed with each department of the hospital. Changes made in the routine saved approximately $1000 per patient--16% for patients having mitral valves replacement (MVR), 15% for those having aortic valve replacement (AVR), 21% for those having saphenous vein bypass grafts (SVBG), and 23% for pediatric cases. The areas most likely to yield economic reductions without alteration of the quality of care are operating room, patient room, respiratory therapy, and pharmacy. Making the nurses, scrub technicians, surgical assistants, residents, and staff surgeons aware of the cost of each item and periodically discussing the alternatives could yield surprisingly large savings.


A preliminary note on the composition of lymphocytes in human peripheral lymph. Pilot experiments on the composition of lymphocytes in human peripheral lymph, mainly from healthy human volunteers, are presented. The experiments undertaken so far show a reduced proportion of B cells and an increased proportion of "Ia" positive lymphocytes in peripheral lymph as compared to peripheral blood. If confirmed, these data would suggest that lymphocyte circulation through extravascular subcutaneous tissues is a highly selective process.


[Lymphocyte sub-populations and immunoglobulin concentrations in palatine and fancial tonsils (author's transl)]. The number of B- and T-lymphocytes as well as the cytological composition and concentrations of IgG, IgM, and IgA are compared in children's palatine and fancial tonsils. The B-lymphocytes prevail in both organs. IgG is the main immunoglobulin and IgM and IgA follow in their concentrations. No significant differences between palatine and fancial tonsils were detectable at all investigated parameters. Evidence as to the biological equivalence of the organs is disclosed.


Haemophilus influenzae infections in adults: report of nine cases and a review of the literature. Haemophilus influenzae is an aerobic pleomorphic gram-negative coccobacillus that requires both X and V factors for growth. It grows poorly, if at all, on ordinary blood agar unless streaked with Staph. aureus. It grows well on chocolate agar. Because this medium is often not used in culturing specimens from adults and because the organism may be overgrown by other bacteria, the frequency of H. influenzae infections has undoubtedly been seriously underestimated. This is aggravated by the failure of many physicians to obtain blood cultures in suspected bacterial infections and the failure of many laboratories to subculture them routinely onto chocolate agar. H. influenzae, along with Streptococcus pneumoniae, is a major factor in acute sinusitis. It is probably the most frequent etiologic agent of acute epiglottitis. It is probably a common, but commonly unrecognized, cause of bacterial pneumonia, where it has a distinctive appearance on Gram stain. It is unusual in adult meningitis, but should particularly be considered in alcoholics; in those with recent or remote head trauma, especially with cerebrospinal fluid rhinorrhea; in patients with splenectomies and those with primary or secondary hypogammaglobulinemia. It may rarely cause a wide variety of other infections in adults, including purulent pericarditis, endocarditis, septic arthritis, obstetrical and gynecologic infections, urinary and biliary tract infections, and cellulitis. Antimicrobial susceptibility testing is somewhat capricious in part from the marked effect of inoculum size in some circumstances. In vitro and in vivo results support the use of ampicillin, unless the organism produces beta-lactamase. Alternatives in minor infections include tetracycline, erythromycin, and sulfamethoxazole-trimethoprim. For serious infections chloramphenicol is the best choice if the organism is ampicillin-resistant or the patient is penicillin-allergic.


Separation of RRBC-RFC and non-rosette forming cells (non-RFC) of guinea pig T-cell populations and their functional difference. 1. Response of RRBC-RFC and non-RFC to either Con-A or LPS. Guinea pig lymph node cells suspension (LNC-O) was filtered through a glass wool column and the effluent (LNC-G) was further filtered through a nylon column. In this effluent (LNC-NE) about 30 per cent of the lymphocytes was identified as non-rosette forming cells (non-RFC). The non-RFC fraction was separated from LNC-NE fraction by Ficol-Conray specific gravity centrifugation or effluent cells reacted previously to rabbit red blood cells (RRBC). The upper layer after centrifugation, designated non-RFC fraction, was separated. In this fraction 96% of the cells were lymphocytes and about 95% of them were non-RFC, which lacked receptors for rabbit red blood cells (RRBC) or EAC and detectable surface immunoglobulin by conventional techniques. Though the response of the lymphocytes in the non-RFC fraction to mitogenic (Con-A, LPS) or antigenic stimulation was lower in comparison with that in RFC-rich fraction, the response of non-RFC to ConA exceeded the response to LPS. These facts suggest that at least a portion of the non-RFC may be cells from the T-cell line.


Helper and suppressor t-lymphocyte leukemia in ataxia telangiectasia. We investigated the nature of the lymphoid leukemia that developed in one of two siblings with ataxia telangiectasia. The leukemic cells were shown to be T lymphocytes. Furthermore, the neoplastic cells carried a characteristic 14q+ chromosome tandem translocation. This chromosome abnormality had been identified 11 years earlier among the patient's "normal" lymphocytes. The patient's neoplastic T lymphocytes in vitro provided helper and suppressor T-lymphocyte activity equivalent to that of normal T lymphocytes. Some neoplastic T lymphocytes bore a receptor for the Fc portion of IgM (45 per cent Tmu) whereas other carried receptors for the Fc portion of IgG (10 per cent Tgamma). All the Tmu and Tgamma lymphocytes possessed the chromosome 14 abnormality. These data suggest that neoplastic transformation occurred in an uncommitted T lymphocyte that was capable of further differentiation into the distinct pathways for help and suppression, in a lymphoid analogy of chronic myelogenous leukemia.


Evidence of cell-mediated antitumor immunity in rats bearing syngeneic tumors by the leukocyte adherence inhibition test. A modified form of the leukocyte adherence inhibition (LAI) test has been used to follow cell-mediated immunity (CMI) in rats of the Lewis inbred strain (LW), F1 hybrids inbred strains LW x AVN with transplanted syngeneic tumors B77, MC-1, and the random-bred Sprague Dawley strain with spontaneous REF tumor. Peripheral blood leukocytes of animals incubated witha specific tumor extract showed an adherence capacity by 30--40% lower than the same cell population cultured without this specific extract, or with a foreign nonspecific extract. The results are commented in connection with a possible application of this modified form of LAI test in studies of the immunological state of patients with a malignant disorder.


Partial volume summation: a simple approach to ventricular volume determination from CT. The accurate determination of ventricular volume from computed tomography (CT) is not a trivial problem. The direct approach of measuring the area within a visually determined boundary or contour level and multiplying by the nominal slice thickness may be subject to large errors because such boundaries are not, in general, well defined. When the ventricles are filled with a high-contrast material such as metrizamide, we may use the technique of 'partial volume summation,' a simple but accurate, clinically applicable method which may be performed on a standard DeltaScan-50 or similar system.


Determination of ventricular volume following metrizamide CT ventriculography. Volume averaging, relatively slight differences in the mean attenuation coefficients of CSF and white/grey matter, and the irregular contours of the human ventricular system have so far seriously limited the accuracy of CT estimation of ventricular volume. Taking advantage of the high attenuation of metrizamide-containing CSF, we have developed three methods for computing ventricular volume after metrizamide CT ventriculography; these methods depend upon computer analysis of X-ray absorption data obtained from contiguous CT brain slices. All three methods were validated by CT scanning a formalin-fixed cadaver brain containing an apoxy-resin cast of the ventricular system. Calculated ventricular volumes were compared with the actual measured volume of the ventricular cast.


Volume of brain ventricles in man determined by computer tomography. In order to measure the absolute ventricular volumes in ml we developed a method using the numerical prints of CT (EMI, CT 1000) on which--by comparing with corresponding Polaroid photos--the margin between brain tissue and ventricles was drawn. For further evaluation, a curve digitizer and a digital computer were used. In 51 patients without any abnormal findings in CT, we studied the volume of single ventricles. The mean value of the whole ventricular system was 30.9 +/- 5.7 ml. Reproducibility by this method is within a range of 5%.


Chronic headache in the shunt-dependent adolescent with nearly normal ventricular volume: diagnosis and treatment. The shunt-dependent adolescent will occasionally manifest shunt malfunction by intermittent or chronic headache without any obvious signs of increased intracranial pressure (ICP). A small percentage of these patients will have nearly normal ventricular volume, making the diagnosis and treatment difficult. The authors present a comprehensive approach to this problem that uses computerized axial tomography (CT), ICP monitoring, positive contrast or isotope shunt scan, shunt revision, subtemporal craniectomy, or medical management as the individual situation dictates. The CT scan identifies patients with nearly normal ventricular volume. ICP monitoring then determines whether there is shunt malfunction. The shunt scan aids in localization of the malfunction. For distal obstruction, a simple revision is performed. When proximal shunt malfunction occurs, either subtemporal craniectomy or revision is carried out. It has been documented that occasionally ICP is episodically increased in the absence of shunt malfunction. This is secondary to abnormal brain compliance, and subtemporal craniectomy alone or in conjunction with corticosteroids is curative. This comprehensive approach is designed to provide a method for recognizing and treating intermittently increased ICP in the shunt-dependent child.


The calculation of CSF spaces in CT.

The calculation of CSF spaces in CT. Objective digital determination of CSF spaces is discussed, with ventricular and subarachnoid spaces handled separately. This method avoids the difficulty of visual definition of ventricular borders in planimetric measurements. The principle is to count automatically all pixels corresponding to CSF in a given region with a Hounsfield unit and to multiply this number by the pixel size. This will give the total surface area of CSF spaces in square millimeters. The calculation of pixel values for CSF spaces and brain tissue is experimentally formulated taking the intersection of the Gaussian curves for ventricular content and brain tissue. In practice, the determination of CSF spaces is done by first calculating a histogram of the total brain in a given slice defining all CSF spaces. Next a histogram of a region including ventricles with adjoining tissue is calculated and the ventricular size is calculated. By subtraction of the ventricle value from the total CSF space value, the subarachnoid space size is obtained. The advantages of this method will be discussed.


Technical considerations for facilitation of selective percutaneous radiofrequency neurolysis of the trigeminal nerve. Fine points of the technique of selective percutaneous radiofrequency trigeminal neurolysis relative to patient preparation accurate and rapid foramen ovale puncture, electrode positioning, and neurolytic lesions are discussed. These measures. which have evolved from our experience in treating trigeminal neuralgia by this method over the last 4 years, have made the procedure safer and less painful but also significantly more expedient.


Metrizamide washout as a measure of CSF bulk flow. Metrizamide was injected into the ventricular system of three adults and five children with indwelling ventricular catheters and subcutaneous CSF reservoirs. A first-order rate constant, k, for metrizamide washout from one lateral ventricle was determined with reference to ventricular metrizamide concentration on serial (up to six) postinjection CT scans. Lateral ventricular volume, Vv, was estimated after metrizamide injection by a planimetric method and by partial volume analysis, an interactive computerized technique. The rate of lateral ventricular CSF formation, If, was calculated as k X Vv and ranged from 0.0622 to 0.103 ml/min. Precise measurements of lateral ventricular CSF bulk flow depend upon adequate mixing of the injected contrast material with ventricular CSF and accurate measurements of lateral ventricular volume.


Computer analysis of periventricular lucency on the CT scan. Of 53 patients with periventricular lucency, 70% revealed obstructive hydrocephalus, mainly due to infratentorial tumors, and the remainder were cases of communicating hydrocephalus, usually secondary to subarachnoid hemorrhage. Of the patients with PVL, 95% had hypertensive hydrocephalus and 60% showed slightly dilated ventricles. Computer analysis was helpful in displaying PVL objectively and clarifying its nature. In experimentally induced obstructive hydrocephalus, PVL was observed at the acute hypertensive stage. We concluded that the pathogenesis of PVL might be the passive diffusion or acute extravasation of CSF into white matter through the disrupted ventricular wall, rather than transependymal absorption of CSF.


Diagnostic value of CT cisternography with intrathecal metrizamide enhancement, comparison with isotope cisternography. Metrizamide CT cisternography (CTC) was performed for the evaluation of CSF dynamics and the diagnosis of skull-base tumors. Results of CTC in 52 cases examined for the study of CSF dynamics correlated well with those of isotope cisternography. However, the degree and duration of ventricular stasis of metrizamide and its transition into a periventricular low-density area in hydrocephalus were recognized more accurately in CTC. Twenty out of 23 cases with suspected skull-base tumor were diagnosed as positive and confirmed by operation. CTC was especially useful in parasellar, CP angle, and other posterior fossa tumors.


Postmeningitic hydrocephalus in infancy. Ventriculography with special reference to ventricular septa. Postmeningitic hydrocephalus in infancy accounts for at least 30% (maybe even 40%) of all new paediatric hydrocephalics seen in the Cape Province. The causes of the marked racial preponderance are considered. Meningitis is more prone to cause a CSF pathway block at any site in infancy than later in life. On ventriculography ventricular septa in 23%, foramen of Monro obstruction in 13%, multiple CSF pathway block occasionally and intraventricular detritus causing filling defects and irregularities of the ventricular walls are the salient features. Birth trauma with intraventricular bleeding may on occasion cause similar changes.


Prenatal neuroradiology: comparative radiological investigations of the embryonal and fetal brain. In 400 embryos and fetuses of domestic animals and men, prenatal development of the cerebral vessels and ventricles was examined by postmortem arteriography, phlebography, microradiography, and ventriculography. In the ventricular system, qualitative and quantitative changes could be demonstrated and developmental diagrams of the growing ventricular spaces and angles were elaborated. The differentiation of the aortic arches into the major cranial arteries and the complex transformations of the cerebral venous system were documented by angiography within a period of gestation of 4 weeks up to term. Intrauterine angiography was also carried out in living fetuses of cats as preliminary studies of the development of cerebrovascular malformations.


Metrizamide ventriculography and computed tomography in infants and children. Forty-three infants and children underwent conventional or CT ventriculography after instillation of metrizamide into the ventricular system. The procedure had few complications. Anatomic detail of intraventricular obstruction was good. With CT additional physiologic information can be obtained.


T and B lymphocytes in pregnant women.

T and B lymphocytes in pregnant women. The peripheral blood of 27 women in their third trimester of pregnancy and of 16 control subjects was studied for total WBC counts and total numbers and percentages of T and B lymphocytes, including quantitation of the major immunoglobulin subtypes of the B lymphocytes. Although significant differences were found for percentages of total lymphocytes, T Lymphocytes, and B lymphocytes, the absolute numbers varied only slightly between the 2 study groups. A higher percentage and a higher absolute number of IgG-bearing B lymphocytes were found among pregnant women than among controls. It is concluded that significant quantitative alterations in circulating T and B lymphocytes do not occur in the third trimester of pregnancy; therefore, the concept of impaired cellular immunity, which has often been suggested to occur in this setting, is not supported. A review of the literature on T and B lymphocytes in human pregnancy is presented.


Diagnosis of rheumatic disease. 1. Radiographs. Radiographs are a clinician's most valuable tool in differential diagnosis of rheumatic disease and in assessment of its severity. The patterns of joint involvement and the specific bony changes characteristic of osteoarthritis, rheumatoid arthritis, ankylosing spondylitis, Reiter's syndrome and psoriatic arthritis, gout, and systemic lupus erythematosus are discussed here.


[Haemodynamics and shock prevention in acute haemorrhage from the upper intestinal tract (author's transl)]. Acute haemorrhages in the upper intestinal tract derive mainly from smaller low-pressure vessels. Bleeding is generally protracted and is often clinically occult. The clinical signs are a more reliable indicator of the severity of the haemorrhage than are measurements of the central venous pressure, shock index and cardiac output. The considerable tolerance of man to blood loss is probably attributable to the erect standing position. It has the advantage that it provides a large measure of counter-regulatory possibilities; but has the disadvantage that there is only a very narrow margin of safety as regards the development of irreversible shock. Close and consistent co-ordination of diagnosis and therapy is essential in all cases of gastro-intestinal haemorrhage.


Coronary artery surgery: indications and recent experience. The comprehensive experience of coronary artery surgery in a Cardiothoracic Unit over a 31-month period is reviewed. Hospital mortality for elective bypass grafting was 3.9% overall and 2.5% in those with good pre-operative left ventricular function. Major influences on hospital mortality were pre-operative left ventricular function, extent of coronary artery disease and extent of the surgical procedure undertaken in terms of number of aortocoronary grafts inserted, coronary endarterectomy and particularly concomitant valve surgery or aneurysm resection. Follow-up experience shows 74% of grafted patients to be symptom-free and 85% symptomatically improved one year after surgery with 70% symptom-free and 80% improved at two years. Early post-operative deaths appear related to early graft closure and recurrence of symptoms postoperatively to late graft closure or progression of coronary disease in the native circulation. The study provides a guide to the relative risks of coronary artery surgery for symptomatic coronary artery disease and expected symptomatic results in the early follow-up period.


The effect of electric stimulation of caudate nucleus and nucleus accumbens septi on serotonergic neurons in the rat brain. Nucleus caudatus--putamen (CP) or nucleus accumbens septi (A) were stimulated electrically for 30 min in free moving rats. Immediately or 30 min after the stimulation we studied the level of 5-HTP and DOPA accumulated in the mesencephalon+pons+medulla oblongata, after inhibition of activity of aromatic amino acids decarboxylase by NSD 1015, and intensity of histofluorescence of serotonin in the midbrain raphe nuclei. The electrical stimulation of either structure did not significantly change the content of 5-HTP and DOPA, but stimulation of nucleus accumbens depressed the level of serotonin in the neurocytes of dorsal and ventral raphe nuclei.


Cessation of bone loss in chronic renal failure by 1-alpha-hydroxyvitamin D3: a controlled trial. The study was undertaken in patients with chronic renal failure (CRF patients) in order to evaluate 1) the degree and course of skeletal demineralisation and 2) the effect on the bone mineral content (BMC) of long-term treatment with 1alpha-hydroxyvitamin D3 (1alpha(OH)D3). BMC was measured on the radius by 241 Am-photonabsorptiometry and the results were corrected for age, sex and bone width. In a cross-sectional study BMC was measured in 191 normal subjects and in 88 renal patients. In a controlled longitudinal trial 22 CRF patients were treated for 25.6 months with 1alpha(OH)D3, while 22 CRF patients did not receive vitamin D supplements. In CRF patients an accelerated bone loss (approximately 3%/year) and a significantly reduced BMC (mean 87.2% of normal) was found. In the 1alpha(OH)D3 treated patients BMC increased on an average 0.9%/year. This was significantly different from the continued bone loss recorded in the non-treated control patients. The data indicate that 1) CRF patients develop reduced bone mass because of accelerated bone loss; 2) cessation of this bone loss may be achieved by long-term treatment with 1alpha(OH)D3.


Purinogenic immunodeficiency diseases: selective toxicity of deoxyribonucleosides for T cells. Deoxyadenosine at low concentrations and in the presence of an inhibitor of adenosine deaminase (adenosine aminohydrolase, EC 3.5.4.4) is markedly toxic to lymphoblast cell lines of T cell origin but does not impair growth of B cell lines. Deoxyguanosine is also more toxic for T lymphoblasts. In the presence of deoxyadenosine or deoxyguanosine, elevation of the corresponding deoxyribonucleoside triphosphate (dATP or dGTP) occurs in T cell, but not in B cell, lines. The addition of deoxycytidine or dipyridamole results in lower dATP and dGTP levels and prevents deoxyribonucleoside toxicity. These findings provide a molecular basis for the immunodeficiency observed in individuals with several inborn errors of purine metabolism.


Epidermal growth factor: morphological demonstration of binding, internalization, and lysosomal association in human fibroblasts. Using a quantitative electron microscopic autoradiographic technique, we have localized the initial binding step of 125I-labeled epidermal growth factor (125I-EGF) to the plasma membrane of the human fibroblast. After initial binding, labeled EGF is internalized progressively by the cell in a time- and temperature-dependent fashion; when cell-associated radioactivity comes to steady state, approximately 1/3 of the autoradiographic grains are related to the plasma membrane and approximately 2/3 have been internalized. Under these conditions the internalized grains are almost exclusively related to lysosomal structures. When 125I-EGF associates with the cells for 2 hr at 4 degrees or 2 min at 37 degrees, 34% of grains localize to coated regions of the membrane. These coated regions make up less than 2% of the membrane surface. These data directly confirm kinetic studies and suggest that saturable binding of EGF is followed by adsorptive pinocytosis and cellular degradation of the ligand and possibly its cell surface receptor.


Spontaneous and antibody-dependent cell-mediated cytotoxicity by human T cell subpopulations. Human peripheral blood non-T cells, T cells and their subpopulations (Tmu, Tgamma, Tphi, Tgamma-depleted cells, and Tmu-depleted cells) were assayed for their capacity to mediated spontaneous lymphocyte-mediated cytotoxicity (SLMC) or natural killer activity against K562 tumor cell line and antibody-dependent cellular cytotoxicity (ADCC) against chicken erythrocytes coated with antibody. Non-T cells, unseparated T cells, Tgamma cells, and Tmu-depleted (Tgamma-enriched) cells were found to have both SLMC (NK activity) and ADCC. Tmu, Tphi, and Tgamma-depleted cells had minimal or no SLMC and ADCC activity. This study demonstrates that SLMC and ADCC activity in T cells is mediated by Tgamma cell subpopulations. These two cytotoxic reactions were either mediated by two distinct subsets of Tgamma cells or by a single effector cell using two different mechanisms.


Direct evidence for loss of human suppressor cells during active autoimmune disease. These studies indicate that a regulatory subset of lymphocytes is missing in patients with juvenile rheumatoid arthritis but these patients have antibodies in their serum that react with normal T cells. This regulatory subset of T cells is, however, present in patients whose serum shows little or no reactivity with normal T cells. In addition, patients who are deficient in this regulatory subset of lymphocytes significantly higher numbers of cells secreting Ig as measured by a hemolytic plaque assay. The significance of these observations is twofold: first, they represent a positive relationship among the loss of regulation overproduction of immunoglobulin, and the presence of anti-T cell antibodies and second and perhaps of equal importance, is the indication that serum from patients with autoimmune diseases may give us a readily available reagent with which to dissect further functionally distinct subsets of normal T cells in man.


Involvement of the serotonergic system in depression of the caudate spindle. The involvement of the serotonergic system on the caudate spindle recorded from the posterior sigmoid gyrus was examined in cats. L-5-Hydroxytryptophan injected intravenously inhibited the caudate spindle significantly. On the other hand, the caudate spindle was inhibited by high frequency stimulation of the dorsal raphe nucleus where many serotonergic fibers originate: this inhibitory effect was antagonized by cyproheptadine but not by atropine. These results suggest an involvement of serotonergic mechanisms in depression of the caudate spindle.


Electrode placements for transcutaneous electrical nerve stimulation. Even though transcutaneous electrical nerve stimulation is gaining increasing acceptance as a noninvasive method of pain modulation, many professionals have not been adequately instructed in the many techniques involved in electrode placement. Alternative methods are presented that can be used when more commonly used methods fail to obtain satisfactory results. Anatomical and physiological considerations for determining appropriate electrode placement sites are stressed.


Postoperative pain and transcutaneous electrical nerve stimulation. A model to critique literature and develop documentation schema. Since transcutaneous electrical nerve stimulation has become an established noninvasive modality in pain management, one successful clinical application has been in treating acute postoperative pain. Current clinical literature in this area is critiqued. In addition, considerations for documenting a comprehensive, systematic method of implementing and evaluating transcutaneous electrical nerve stimulation for any painful condition are suggested.


Clinical report on the use of specific TENS units. This report provides information demonstrating that TENS can be effective in reducing pain after only a few applications and after short treatment periods. We have found our protocol on selection of TENS units and our treatment regimen to be effective for most of our patients.


Cooperative cross-linking between two sets of membrane receptors: a model for B and T lymphocyte collaboration in immune response. A molecular mechanism for B and T lymphocyte collaboration is proposed. Two sets of polivalent receptors, each one on a cell type, would interact with different epitopes of the antigen, resulting in a cross-linking of the receptors as the initial step in B lymphocyte activation. The mechanism can explain many known featrues of humoral immune response and accords with experimental findings on the blast transformation of B lymphocytes.


How does reduced external K+ concentration affect the rate of Na+ efflux? Evidence against the K-Na coupled pump but in support of the association-induction hypothesis. Recent frog-muscle studies produced the following findings: 1. Contrary to the theory of K+--Na+ coupled pump, reduction of external K+ concentration to near zero did not significantly reduce the rate of efflus of the fraction of cell Na+ conventionally regarded as rate-limited by membrane permeability. 2. Reduction of external K+ concentration profoundly reduced the rate of the efflux of this fraction only if the muscles were exposed to the low K+ while being loaded with radioactive Na+. 3. The data indicate that the fraction of Na+ efflux which in normal cells at room temperature has a half-time exchange (t1/2) of 20-40 min is not rate-limited by membrane permeability but by desorption from cellular adsorption sites. Surface-limited Na+ exchange between free Na+ in the cell and the external environment is represented by a faster fraction with a t1/2 of 2 to 4 min. 4. The data further indicate that the slow-down of the rate of efflux of the (slow) fraction arises from a cooperative shift of those beta- and gamma-carboxyl groups from adsorbing K+ to adsorbing Na+ when external K+ concentration is reduced below a critical level. The enhanced adsorption energy of the newly adsorbed Na+ raises the activation energy, hence a slower rate of exchange is seen as a slow-down in the "efflux curves." It is therefore only when free labeled Na+ is present in the cell water and thus available to the newly emerging Na+ adsorption sites that the effect of low external K+ can be visualized in a labeled-Na+ efflux study. Application of low K+ Ringer's solution after free labeled Na+ in and out of the cells has been washed away only causes enhanced adsorption of non-labeled Na+, which is not detected in isotope efflux study.


The effects of changes of the tonicity of the bathing fluid upon the tension generated by atrial trabeculae isolated from the heart of the frog, Rana pipiens. Raising the tonicity of the fluid bathing frog atrial trabeculae has three effects: an initial sustained relaxation, which depends on muscle length and probably originates from structures other than the contractile apparatus; an increase in contractility, which takes the form of a transient contracture if the muscle has previously undergone a high-potassium or a low-sodium contracture, and a further rise in contractility on return to isotonic fluid (off response). The hypertonic contractures, in high-potassium or sodium-free fluids, are antagonized by local anaesthetics and in Na-free media they are unaffected by removal of extracellular coat, whereas the 'off responses' are insensitive to both experimental manoeuvres. Hypotonic fluids applied in Na-free solutions evoke a phasic and a tonic contracture, neither of which are sensitive to local anaesthetics. The tonic response is reduced by lowering the [Ca]o, and occurs at tonicities where the permeability of the cell membrane is likely to have increased. The phasic part of the hypotonic contracture resembles the 'off response' which follows exposure to hypertonic solution. The effects of hypertonic fluids and of caffeine on frog heart are alike, and are also similar to the responses induced by the same experimental manoeuvres in skeletal muscle. The results can be interpreted by assuming that the intracellular relaxing system in frog heart is sensitive to changes in tonicity, and could be functionally divided.


An O2-Hb "paradox' in frog blood? (n-values exceeding 4.0). O2-Hb dissociation curves have been determined for the anurans, Rana temporaria and Rana catesbeiana, and compared with human blood for the specific purpose of defining the n-value (hill's cooperativity coefficient) at high O2 saturations. The P50 values at normal conditions (see fig. 1) for each species were 24.6 mm Hg for human blood, 37.0 mm Hg for Rana temporaria blood and 53.5 mm Hg for Rana catesbeiana. For human blood the n-value was 2.7 at saturations from 36% to 98% levelling off at the highest saturations. For Rana temporaria Hill plots between saturations from 20% to 98% showed 3 segments. The average n-value increased from 1.6 to 2.4 at about 50% saturation, increasing again at about 80% saturation to 7.3. The pattern in Rana catesbeiana blood was similar with the n-value changing from 1.6 to 3.1 at about 50% saturation, averaging 3.5 between 53% and 89% saturation. Additionally the Bohr effect in Rana temporaria blood more than doubled when compared at 50% and 90% saturation. The data show that for R. temporaria blood the free energy of interaction associated with the binding of 02 to Hb is displaced to the upper segment of the dissociation curve.


Restimulation of PPD-stimulated lymphocytes: decreased responsiveness of prestimulated cells to a second challenge with PPD and PHA. Lymphocytes stimulated with purified protein derivative (PPD) were inhibited in their response to a second stimulation with PPD or phytohaemagglutinin (PHA). The degree of inhibition was related to the PPD concentration during prestimulation, the dose-response curve for inhibition resembling very much that of stimulation. The decreased reactivity was neither due to a toxic effect of PPD nor to altered proliferation kinetics of the prestimulated cells. Lymphocytes preincubated for 6 h or 16 days with PPD were equally refractory, and the non-reactivity persisted even if the cells were incubated without stimulant for 1 week or more. The prestimulated cells were able to suppress the PHA stimulation of fresh lymphocytes. These results indicate that the decreased reactivity of the prestimulated lymphocytes is due to the action of suppressor lymphocytes, generated during the primary stimulation.


Morphological study of autologous rosettes (A-RFC). The morphology of autologous rosette forming cells (A-RFC) has been studied by light and electron microscopy. Autorosette forming cells were obtained from the spleen of adult thymectomized (ATx) or nude mice, and from neonatal thymus grafts during the regeneration phase. Among the autorosettes seen by light microscopy, 76% of them were formed by lymphoid cells which included a high proportion of large lymphocytes (48%). Electron microscopy study performed after isolation of A-RFC by micromanipulation demonstrated that 74% were formed by large lymphoid cells with an immature nucleus. The finding of such large-sized lymphoid cells with immature nuclei is in agreement with our previous results indicating that A-RFC might belong to an immature T cell class.


Functional relationship of macrophages and basophils to the thymus gland. Human thymus epithelium, depleted of thymocytes and macrophages by means of organ culture, was used in chemotaxis experiments with peripheral blood cells. Such cultured thymus epithelium can attract specifically macrophages and basophils. T-lymphocytes were attracted only by short-term (8 day) cultured thymus tissue which still retains some of the original macrophage population. Thymic macrophages formed rosette structures with thymocytes. In other experiments 'activated' rabbit macrophages had the capability to destroy thymocytes, whether autochthonous or allogeneic. The possible role of macrophages and basophils in thymus function is discussed.


Interposition grafting with expanded polytetrafluoroethylene for portal hypertension. If an interposition graft for the decompression of esophageal varices is necessary, Gore-Tex may be the graft material of choice. It is intert, nonthrombogenic and, possibly, thrombo-resistant. These characteristics of Gore-Tex explain the ease with which a graft thrombectomy was performed in one patient when necessary. Final appraisal of a synthetic venous prosthesis requires many months, if not years, of in vivo evaluation. Nevertheless, when an interposition graft is necessary for the decompression of esophageal varices, it appears that a clinical trial of Gore-Tex is reasonable in view of its characteristics.


A screening program for anti-DR typing reagents. A total of 694 sera have been tested in a screening program aimed at identifying monospecific reagents for HLA--DR typing. All sera were first tested on a panel of enriched B and T cells without absorption on platelets. Only sera reacting more frequently on B than on T lymphocytes were absorbed on platelets and retested on the panel. This procedure saved a considerable amount of platelets and proved to be reasonably efficient. One-hundred-and-fifty sera were found to contain an anti-B cell antibody. Significantly less frequent B cell reactivity was found when HLA--A, --B, --C antibodies could not be detected. Twenty-five sera were demonstrated to be specific for well-defined DR antigens.


Advances in nonimplantable electrical stimualtors for correction of urinary incontinence. The nonimplantable electrical stimulators are widely used as rehabilitation aids for correction of urinary incontinence. The advances in the field of the design of nonimplantable electrical stimulators such as automatic vaginal electrical stimulator VAGICON-X and anal pressure controlled electrical stimulator are described. The evaluation of VAGICON-X in patients suffering from stress and urge incontinence as well as preliminary results of acute application of anal pressure electrical stimulation in patients with stress incontinence as presented.


Present state and prospects in the design of multichannel FES stimulators for gait correction in paretic patients. Use of multichannel electrical stimulators (MES) for the rehabilitation of patients with plegic or paretic extremity muscles in one of the most promising trends in rehabilitation. Two clinically oriented therapeutic stimulators are described. The aim and the realization of walking rate dependent functioning, gradually modulated stimulation sequences, mini-computer and hardware closed-loop control of stimulation amplitude are described. The difficulties arising from the poor interface between the technical and biological part of the system prevent the described stimulators from being used as orthotic devices. Experiments with three types of electrodes are given, and the problem of an excessive mounting time for most clinical environments is also stressed.


[Diagnostic criteria of periodontal diseases]. The designation of a periodontal disease and its classification do not permit to draw conclusions as to its targeted therapy. Since the parameters needed for the diagnosis of periodontal diseases are very numerous, they should be reduced by a problem-oriented diagnosis which corresponds to the aims and objectives (treatment plan, course of the disease, assessment of the therapeutical success). The parameters to be determined should be of sufficient validity. Only such parameters should be included in a problem-oriented diagnostic chart. The parameters for indices should be selected according to this principle. The selection of the indices requires co-ordination, at which the respective objective of the examination must be considered.


[Gingival bleeding].

[Gingival bleeding]. Gingival bleeding is not of decisive importance in diagnosticating periodontal diseases, since various endogenous causative factors and exogenous conditions may enhance its occurrence. In the absence of periodontal disease, gingival bleeding might be a symptom of a systemic disease. Because gingival bleeding is in most cases the first sign of an affection of the tooth-supporting structures that the patient observes, it should be, for all the difficulties its substantivation, be considered in history taking and for self-control.


[Reproducibility and evaluation of gingival indices]. The inflammatory condition of the gingivae may be judged by the anamnestic indication to "gingival bleeding" and by assessing the inflammatory changes by means of the P.M.A. index and the Sulcus Bleeding Index. The patients' indications to gingival bleeding are subjective by nature, but they have proved to be highly reliable when they are obtained by three independent examinators. The testing of the P.M.A. index showed that this method is sufficiently reliable. The Sulcus Bleeding Index was not tested.


Ileal conduit hemorrhage secondary to portal hypertension. The clinical features and management of 3 patients who presented with the triad of massive hemorrhage from the ileal conduit, portal hypertension due to liver disease, and portosystemic varices related to the conduits are described. One patient, a class C cirrhotic, was treated conservatively and died of blood loss and hepatic coma. Two patients were managed with splenorenal shunts initially, followed by creation of colon conduits, and are currently doing well. Surgical approximation of areas draining in the portal and systemic circulation with subsequent development or adhesion-related varices probably explains the predilection for involvement of the ileal conduit and may explain the presence of varices in mild to moderate portal hypertension before other signs of hepatic decompensation are evident. Superior mesenteric angiography with special attention directed at the venous phase is necessary to document this entity.


Exsanguinating hemorrhage from urinary ileal conduit in patient with portal hypertension. A patient with an ileal conduit diversion after cystectomy for carcinoma of the bladder is seen with cirrhosis and portal hypertension. Massive bleeding from the peristomal varices developed. Our experiences with conservative treatment is outlined.


[Thrombohemorrhagic complications of acute pancreatitis]. On the grounds of a great clinical material (4,800 cases) and autopsy findings (857 autopsies) it is emphasized that there is a pathogenetic relationship between thrombotic complications and hemorrhages common in acute pancreatitis and the main disease; the thrombohemorrhagic complications playing a tremendous part in the development of its most severe forms and fatal outcome. The authors divide these complications inherent in all the phases of pancreatitis into 2 groups: early and late ones, which differ from one another by peculiarities of pathogenesis, clinical picture and treatment. The diversity of the complications is stressed, and recommendations on their diagnosis, prevention and treatment are set forth.


T and B cell populations in platelet donors. T and B lymphocyte populations were monitored in the peripheral blood of two long-term plateletpheresis donors. The studies showed minimal fluctuation of both populations compared to the normal controls. The evidence so far accumulated seems to indicate that long-term manual plateletpheresis has no appreciable effect on the level of the T and B cell population of the peripheral blood. Further studies are needed to evaluate larger donor pools.


Splenic vein obstruction with bleeding gastric varices: a diagnostic approach. It is important to separate splenic vein obstruction from other causes of variceal bleeding. The authors provide a diagnostic sequence for avoiding errors of management, citing a case to illustrate.


[Lymphotoxin production by human lymphocytes. I. Study of the supernatants of phytohemagglutinin stimulated human lymphocyte cultures]. Lymphotoxin was found to be present in supernatants from 22 human lymphocytes cultures stimulated with phytohemagglutinin in a dose of 5 and 10 microgram/ml. The lymphocytes were obtained from the peripheral blood of 6 apparently healthy persons. Lymphotoxin activity was determined by simple and objective method, i.e. by staining the target cells (mouse L-cells) monolayer with crystal violet, with the following determination of optic densities of the L-cells lysates at 570 nm in the spectrophotometer. As revealed, 1 : 5 dilutions of the supernatants from the lymphocyte cultures incubated for 48 hours inhibited the L-cells growth by from 40 to 60%. With further incubation of the cultures (up to 72 and 96 hours) the cytotoxicity of their supernatants for the target cells showed no increase, whereas the blasttransformation index reaches the maximal value by 72nd incubation hour. Supernatants from unstimulated lymphocyte cultures failed to produce any cytotoxic effect on L-cells.


[Structural organization of the antigen-binding receptors of immunocompetent cells]. It was demonstrated in this work that rabbit antimouse serum against the aggregated immunoglobulins (RAAS) and mouse serum against the aggregated mouse immunoglobulins (MAAS) inhibited the rosette-forming B-cells (RFC) on the 5th day after the immunization of mice CBA with SRBC in a dose of 5 X 10(-8) cells in vitro in 1:20--1:80, and 1:10--1:40 dilutions in 83--55 and 72--39%, respectively. In difference from RAAS, MAAS in a dilution of 1:20 induced a statistically significant suppression of the antigen-binding receptors of RFC of-B type in the intact animals, and on the 8th--9th day after their immunization with SRBC. In vivo MAAS induced inactivation of the antigen-binding receptors of B-lymphocytes only. Results of the work carried out served as a confirmation of the fact that immunoglobulins in the form of an antigen-antibody complex (functioning in the capacity of the antigen-binding receptors) were sorbed on B-lymphocytes of the spleen.


Proliferation of peripheral lymphoid cells from euthyroid and hyperthyroid individuals cultured with human thyroglobulin. Peripheral lymphoid cells from euthyroid and hyperthyroid subjects were tested for proliferative responses to human thyroglobulin in vitro using [3H] thymidine incorporation as assay. Non-fractionated lymphoid cells from both groups displayed weak stimulation. Using a rosette technique for separating sub-populations of lymphoid cells it was concluded that T-cells constituted the responding cells. The results indicate that both hyperthyroid and euthyroid subjects possess clones of T-cells which are reactive against human thyroglobulin.


Cell surface markers in chronic lymphotic leukaemia. Surface markers were applied for the study of the peripheral lymphocyte population in chronic lymphotic leukaemia. The proportion of B-lymphocytes recognized by EAC-rosetting and by surface-bound Ig was found higher in chronic lymphotic leukaemia than in normal controls. On the other hand, the E-rosette test revealed a very low proportion of T-cells. No relationships were demonstrable between the surface markers and the clinical features.


Abnormalities in humoral and cellular immune activity in pancreatitis. I. Study of the humoral immune system. The abnormalities of the humoral immune phenomena in pancreatitis may be summarized on the grounds of published evidence and of the present results as follows: 1. Circulating anti-pancreas antibodies are present in acute pancreatitis as also after its cure, and in chronic pancreatitis. 2. The appearance of soluble immune complexes in pathological amounts was demonstrated in the sera of the patients by radiobioassay in acute pancreatitis of identified aetiology 3 to 4 weeks after onset. On the evidence of follow-up studies over 1 to 8 months the immune complexes were found to persist at increased levels after complete cure of acute pancreatitis. Soluble immune complexes were demonstrable in pathological amounts in the cases of chronic pancreatitis as well. 3. In acute pancreatitis the total serum complement titres decline fast and after a few weeks persistent hypocomplementaemia develops in a number of cases. 4. The possible role of circulating soluble immune complexes and of the complement system in pancreatitis is discussed, and it is suggested on the grounds of the present data that acute pancreatitis is associated with a specific and nonspecific immune sensitization, still demonstrable in a number of cases after a few months.


Agammaglobulinaemia associated with the occurrence of a monoclonal immunoglobulin. A patient is described with a monoclonal immunoglobulin of the IgG class in the serum and no detectable IgM and IgA. Extensive immunological investigations showed the absence of B-lymphocytes in bone marrow and peripheral blood. Moreover, plasma cells were not present in the bone marrow. The monoclonal IgG was synthesized in the gastrointestinal tract. The cellular immune-status of the patient was synthesized in the gastrointestinal tract. The cellular immune-status of the patient was normal. Clinically the patient suffered from gastrointestinal and severe respiratory tract infections. It was concluded that the findings are consistent with the diagnosis congenital agammaglobulinaemia with concurrence of monoclonal IgG. It was postulated that the cell clone in the gastrointestinal tract resulted from an escape of a pre-B cell clone from the recongized arrest of pre-B cells in congenital agammaglobulinaemia.


Potassium permeability of the mesothelium of the frog mesentery. The mesothelium of the mesentery is a single cell layer described to offer no or every little hindrance to diffusion of small water soluble solutes. We have measured the potassium permeability of the mesothelium of the frog mesentery both in vivo and in vitro. The permeability measured in vivo--using K+--sensitive microelectrodes is 2.4 X 10(-5) cm s-1. In vitro measurements using conventional tracer flux technique on isolated mesentery yields a K+-permeability of 5.7 X 10(-5) cm s-1. These values are 15--30 times smaller than values previously reported from in vitro experiments on rat and rabbit mesentery. Also, the permeability is 12--15 times lower than the K+-permeability of the capillary wall determined on single capillaries in the frog mesentery. In the frog mesentery the mesothelium thus represents an important diffusion barrier compared to the capillary wall. This may be critical in experiments where filtration and reflexion coefficients of the capillaries are determined from measurements of fluid exchange across the capillary wall in response to application of hypertonic solutions on the surface of the mesentery.


The anti-inflammatory profile of dapsone in animal models of inflammation. Dapsone has been shown to possess anti-inflammatory activity in a variety of animal models. It possesses oral anti-oedema activity especially pronounced in novel models of acute inflammation, viz. anti-IgG and reversed passive Arthus oedemas. However, it is not very active in the guinea pig u.v. erythema model. It is effective in chronic models such as adjuvant arthritis and the cotton pellet granuloma although multiple administration may also produce cyanosis. Antipyretic and analgesic effects for dapsone have been demonstrated and are similar to those produced by phenylbutazone. It inhibits zymosan-induced beta-glucuronidase release from cultured macrophages and also the activity of this enzyme. Dapsone does not appear to be ulcerogenic in the rat.


Assessment of coronary venous bypass graft function using krypton-81m. Fifteen patients with intractable angina pectoris underwent coronary angiography and coronary arterial bypass graft surgery. After the operation, a continuous infusion of krypton-81m was delivered into each graft. A gamma camera and multichannel analyzer were used to record the regional myocardial distribution of perfusion provided by each graft. The disappearance of myocardial activity at the end of each infusion was used to calculate the flow per unit volume in the myocardial distribution provided by each vessel. Myocardial perfusion provided by the grafts to all the major coronary arteries were recorded individually as high spatial resolution images. Myocardial flow rates in the distribution of each graft were measured using the washout of krypton-81m. The rates were 0.5 to 2.0 ml/g per min in the 13 patients with no evidence of previous myocardial infarction. Krypton-81m was infused into grafts to the left anterior descending coronary artery in two patients with a history and electrocardiographic evidence of previous anterior myocardial infarction. The grafts provided poor perfusion to the anterior and apical portions of the ventricles. An experimental model of myocardial perfusion was used to demonstrate that the washout of krypton-81m can be used to measure flow per unit volume within or above the physiologic range.


Acupuncture anesthesia for open heart surgery: a report of 800 cases. This article reports the utilization of acupuncture in combination with chemical anesthesia and neuromuscular relaxant for patients with cardiac surgery, including valvular disease and by-pass. In 800 patients studied using this type of combination of anesthetic techniques, it was found that this procedure can be successful for cardiac surgery and that it allows light planes of anesthesia with less interference to circulatory regulation. There is a certain advantage of using acupuncture anesthesia when compared with chemical anesthesia, as the pharmacological agents are not used and hence post no metabolic load for the patients. From the 800 patients studied, it seems justifiable to recommend this anesthetic procedure for cardiac surgery.


Re-evaluation of plasmas from patients previously diagnosed as having von Willebrand's disease with the factor VIII-related antigen and ristocetin cofactor assay. Diagnosis of deficiencies of coagulation factor VIII can be difficult to establish in some cases. The use of the factor VIII-related antigen and the use of the ristocetin cofactor assays have increased the reliability of diagnosis of factor VIII deficiency in patients with hemophilia A or von Willebrand's disease, and in carriers of hemophilia A. The authors re-evaluated samples, from frozen storage, of blood from patients previously diagnosed as having von Willebrand's disease. This diagnosis was based on clinical history, family history, bleeding time, factor VIII procoagulant activity, and response to ristocetin in platelet-aggregation studies. Eleven cases were studied by the review of previously obtained data and the addition of the factor VIII-related antigen and ristocetin-cofactor assays. In two of eleven cases, the diagnosis was changed to possible hemophilia A carrier state.


Pelvic lipomatosis: diagnosis by computerized tomography scan. Pelvic lipomatosis is a rare, relatively self-limiting disease characterized by the overgrowth of unencapsulated lipomatous tissue within the pelvis. The diagnosis is suggested, but not substantiated, by the striking roentgenographic changes noted on barium enema and intravenous pyelogram. Previously, pelvic laparotomy with tissue diagnosis was essential for documenting the disease. We report three cases in which computerized tomography was utilized as a safe, noninvasive and accurate method of diagnosis. The role played by partial venous obstruction is discussed in addition to rectal bleeding as a mode of presentation.


Salicylate-induced enzymuria: comparison with other anti-inflammatory agents. N-acetyl-beta glucosaminidase (NAG) enzymuria was used as a marker of renal injury in patients with rheumatic disease. An elevated NAG level was particularly common in patients receiving gold or aspirin therapy. The multiplicity of drugs received and the unknown role of underlying disease in these patients led to a study in healthy volunteers. Customary therapeutic doses of aspirin, choline salicylate, ibuprofen, indomethacin and acetaminophen did not produce enzymuria. Large single doses of salicylates equivalent to 6 tablets of aspirin consistently did produce enzymuria. The size of the individual dose in relation to body weight was more important than the total daily dose. NAG enzymuria appears to be a sensitive tool for identifying potentially nephrotoxic drugs.


Effects of ouabain on potassium transport in the perfused bullfrog kidney. We studied the effect of ouabain on transepithelial and cellular potassium transport in the isolated perfused bullfrog kidney. We used recently developed techniques for estimating the unidirectional reabsorptive and secretory K fluxes (Jr and Js) and measuring the kinetics of cellular K transport. Two hours of perfusion with 1 X 10(-6) M ouabain did not affect GFR, reduced fractional Na reabsorption 57%, increased K excretion 41%, and inhibited Jr 34%. Js rose 68% at 60 min and then returned to the control level. Ninety minutes of perfusion with 5 X 10(-6) M ouabain reduced GFR 28% and fractional Na reabsorption 76%. K excretion rapidly increased 71% within 30 min and then fell to 60% of the control level, while Jr fell 64%. Js rose 42% in 30 min and then fell to 23% of the control level. Both doses reduced K uptake into cellular pools from the circulation and increased the rate coefficients for efflux into tubular fluid. The data indicate that ouabain inhibited reabsorption and transiently accelerated the rate of loss of K from the cells into the tubular fluid. This initially masked the ultimate inhibition of K secretion from the circulation into the tubular fluid.


Effect of angiotensin II receptor blockade by [Sar1-Ala8]angiotensin II in hemorrhagic shock. An angiotensin II receptor antagonist, [Sar1-Ala8]angiotensin II (saralasin), was infused at 60 (microgram/kg)/h into cats to examine its effect in hemorrhagic shock. Aprotinin (1,000 (KIU/kg)/h) was also administered to cats to determine how kinin inhibition effects angiotensin receptor blockade in shock. Saralasin was infused into shocked and sham-shocked cats. Aprotinin was administered to additional cats receiving either saralasin or its vehicle. Hemorrhaged cats treated with saralasin revealed a postoligemic preservation of mean arterial bloood pressure and superior mesenteric artery blood flow (SMAF). Final pressures were 48 +/- 12 mmHg and 81 +/- 9 mmHg with vehicle and saralasin treatment, respectively, and final SMAF were 2.5 +/- 0.5 (ml/kg)/min in cats receiving vehicle and 5.5 +/- 0.6 (ml/kg)/min in those receiving saralasin. Total plasma proteolysis was diminished by both saralasin and aprotinin, exhibiting elevations of free amino-nitrogen groups of 2.5-fold and 2-fold over initial as compared to a 3.5-fold elevation in vehicle-treated shocked cats. Myocardial depressant factor (MDF) activities were also suppressed by saralasin compared to shocked cats receiving vehicle (24 +/- 4 units vs. 59 +/- 3 units). These results indicate that blockade of angiotensin II actions in hemorrhagic shock is beneficial.


Some observations in the fine structure of age changes of the mouse retinal pigment epithelium. Age changes of the fine structure in the CF-1 mouse retinal pigment epithelium were studied from 1--24 months old. The change most characteristic of the senescence of the retinal pigment epithelium was found to be the appearance of wavy undulating 12nm wide filaments having a periodicity of about 80nm after the 12th month. In addition, the retinal pigment epithelial cells of the aging eye were found to have a marked accumulation of lysosomal dense bodies measuring about 0.3 to 1.2 micrometer in diameter especially in the apical portion of the cytoplasm. Extended and enlarged basal cytoplasmic infoldings of the retinal pigment epithelial cells were another prominent age change in the old mouse. In these basal infoldings densely fixed amorphous materials by tannic acid and very fine filaments are recognized. Age-related changes of the retinal pigment epithelial cell of the CF-1 mouse may take place as the degeneration of cytoplasmic materials, the appearance of bundles consisting of parallel undulating filaments, and the extending process of basal infolding from the choroid side.


Experimental rubeosis of the iris in rabbits. Rabbits were subjected to vascular injuries in an attempt to cause ocular ischemia and rubeosis. Occlusion of the ipsilateral common carotid artery showed fluorescein angiographic evidence of iris ischemia, but no rubeosis. Occlusion of two or more vortex veins caused iris ischemia, vasodilation, and angiographically visible neovascular capillaries on the iris. Histology confirmed the presence of thin-walled, superficial neovascular channels. The stimultaneous occlusion of the carotid artery and of two or more ipsilateral vortex veins also produced angiographic and histologic evidence of iris ischemia and neovascularization. These results confirm that venous flow impairment is a more efficient stimulus to neovascularization than ischemia due to arterial insufficiency. Nevertheless, in none of the animals could a neovascular response comparable to human rubeosis be elicited, and it is concluded that vascular lesions to the anterior segment are not an adequate model to study rubeosis.