Immune status in Crohn's disease. I. Leukocyte and lymphocyte subpopulations in peripheral blood. Proportions and absolute numbers of circulating leukocyte populations and lymphocyte subpopulations (T- and B-cells) were determined in 33 patients with Crohn's disease (group CD), and were compared with those of age- and sex-matched healthy subjects. Group CD comprised 15 patients with newly diagnosed, short-standing, and untreated CD (group CD 1) and 18 patients with long-standing, previously drug treated CD (group CD 2). All CD groups showed a significant absoulte leukocytosis, based on a significant absolute and relative increase of the neutrophils, and, as far as group CD and CD 1 were concerned, also of the absolute number of monocytes. In group CD 1, absolute lymphocyte and relative as well as absolute T-cell numbers were close to normal. In contrast, in group CD 2 absolute as well as relative numbers of lymphocytes and absolute numbers of T-cells were highly significantly reduced, whereas the reduction of the relative T-cell concentration barely reached significance. The proportion of B-cells was significantly above normal in all patient groups, the absolute number in group CD only. Also group CD 1 showed considerably, though statistically insignificantly, higher than normal absolute B-cell numbers. In group CD 1 , there was an inverse correlation between absolute T-cell numbers and disease activity, and between absolute lymphocyte numbers and duration of disease. These data indicate that there is no gross numerical reduction of the carriers of the cell-mediated immunity as a primary predisposing factor for CD, but that a reduction of these cells occurs in the circulation after the disease has started.


Peroperative endoscopic diagnosis of small intestinal bleeding. Two patients with recurrent bleeding from vascular anomalies in the small intestine are described. In both patients intestinal angiography had shown either pathological vessels or extravasation of blood into the proximal part of jejunum, but during explorative laparotomy the source of bleeding had not been found. The diagnosis was made by performing peroperative endoscopy. After resection of the involved small bowel segment one patient with cavernous hemangioma has remained asymptomatic. In the other patient, who suffered from a combination of multiple arteriovenous malformations and a congenital platelet defect, limited surgical resection did not influence the need of blood transfusions. This investigational approach should become the method of choice in patients suspected of bleeding from the small intestine.


[Clinical evolution of hemorrhage in the proximal portion of the digestive tract. Comparison of its management with and without endoscopy]. To determine if endoscopic study of the esophago-gastro-duodenal portion of the digestive tract diminishes morbimortality of patients with hemorrhage in this area, a comparative study was made. The results for the first group were obtained from 92 cases of patients with hemorrhage in which endoscopic studies were performed. The results for the second group were obtained from 88 cases of patients with hemorrhage in which no endoscopic study was made. Both groups were comparable in age, sex, magnitude of bleeding and medical management; even though there were more patients in the second group that did not require blood transfusions. No statistically significant differences were found in the number mortality. Diagnostic centainty was higher in the endoscopic group (82.6% versus 36.3% P less than 0.002). The number of the patients released without diagnosis was higher in the group not undergoing endoscopic examination (23.4% versus 8.5% P less than 0.005). The conclusion that endoscopic examination improves the quality of diagnosis in patients with upper digestive tract hemorrhage, but does not diminish morbimortality, is reached. The possible reasons for this are discussed.


Immunological tolerance to the thymus-independent antigen dextran can be abrogated by thymus-dependent dextran conjugates: evidence against clonal deletion as the mechanism of tolerance induction. Tolerance to the alpha1--6 epitope of native dextran B512 was found to be very stable and could not be broken by the injection of dextran conjugated to several substances, such as protein A, keyhole limpet haemocyanin, edistin, concanvalin A or Staphylococcus bacteria, strain Cowan. However, when tolerant mice were injected with dextranase, all the above conjugates induced a strong anti-alpha1--6 immune response. In contrast, native dextran itself never induced a response in tolerant, dextranase-treated mice. It was concluded that tolerance only affects the specific B-cell subpopulation that can respond to the polyclonal B-cell-activating (PBA) property of dextran, whereas other specific B cells having PBA receptors for, e.g., signals delivered by collaborating T cells remain in a resting state. These B cells can respond in a specific immune response against the tolerogen after removal of the antigen, which blocks the Ig receptors and therefore prevents them from passively focusing the antigen. Thus, immunological tolerance is not caused by clonal elimination of the antigen-specific clone, but only affects a small subfraction of cells with Ig receptors against the tolerogen.


Transient increase of IgG Fc receptor-bearing T lymphocytes following positive PPD skin testing. In tuberculin-sensitive individuals, IgG Fc receptor (FcR)-bearing lymphocytes in the peripheral blood increased transiently following PPD-tuberculin skin test. This rise in circulating FcR-bearing cells appeared to peak about 36--48 h after the intradermal inoculation of PPD and seemed to occur largely in the T cell population. Skin test-negative individuals showed no significant changes in their circulating FcR-bearing cells following PPD inoculation. Peripheral blood lymphocytes from PPD-sensitive individuals were fractionated into non-T cell and T cell-enriched populations by E rosette sedimentation technique. FcR-bearing cells in the T cell-enriched population were eliminated by EA rosette sedimentation: i.e. FcR-negative T cells. Then, equal numbers (1 X 10(5) cells each) of non-T cells and unfractionated or FcR-negative T cells were recombined in culture. Prior to PPD inoculation, there was no significant difference between these two cell mixtures in the in vitro cellular response to PPD or mitogens. When these cell populations were obtained 36--48 h after PPD inoculation, however, the combination of non-T cells and FcR-negative T cells responded to PPD much better than the combination of non-T cells and unfractionated T cells, whereas the mitogen-induced cellular proliferation of these two cell mixtures did not differ from each other.


Functional characterization of lanatoside-C-responsive cells. Lanatoside C, a digitalis glycoside previously shown to be a polyclonal B-cell activator (PBA), was found to stimulate immature cells residing in fetal liver, bone marrow and spleen but also to activate cells from peripheral lymph nodes and peripheral blood. The proliferative response obtained in spleen cells was not affected by macrophage removal, whereas anti-Ig or anti-Ia antiserum pretreatment partially inhibited the responses. Removal of T cells by a pretreatment with anti-Thy 1.2 antiserum plus complement caused a marked increase in the proliferative response of the remaining cells, suggesting the existence of a naturally occurring suppressor T cell for glycoside-induced mitogenesis. Synergy experiments with 'classical' PBAs and lanatoside C, given simultaneously or subsequently, suggest an overlap between the lanatoside-C-responding cell population and the dextran sulphate (DxS)- and lipopolysaccharide (LPS)-sensitive cells. Since DxS-induced activation of B cells is dependent on macrophages, it is suggested that lanatoside C may be used as a functional marker for direct activation of immature B cells.


[Cefuroxim, a new beta-lactamase stable cephalosporin]. In vitro activity of cefuroxime, a new cephalosporin stable to bacterial beta-lactamases, was compared with that of cefalothin and other cephalosporins by serial dilution test in more than 600 bacterial strains. Cefuroxime was more active than cefalothin on most strains of Gram negative bacilli (except Salmonella species) and also on most strains of cefalothin-resistant bacteria. In comparison to cefalothin, cefoxitin and cefamandol, cefuroxime exerted the strongest activity on meningococci, streptococci of group A and B and also on Citrobacter freundii. It was as active as cefamandol and more active than cefalothin and cefoxitin on Haemophilus influenzae (also in ampicillin-resistant strains). Pharmacokinetic studies were performed in 10 healthy adult volunteers after i.v. injection of 0.75 g, 1 g, and 1.5 g cefuroxime and of 1 g cefalothin. Cefuroxime was superior to cefalothin by slower renal excretion, longer half-life, lesser or no metabolization and better tissue penetration. Cefuroxime is well tolerated and should be administered in adequate doses corresponding to the severity of the disease and the susceptibility of the causative agent.


Eye-specific termination bands in tecta of three-eyed frogs. An extra eye primordium was implanted into the forebrain region of embryonic Rana pipiens. During development both normal and supernumerary optic tracts terminated within a single, previously uninnervated tectal lobe. Autoradiographic tracing of either the normal or supernumerary eye's projection revealed distinct, eye-specific bands of radioactivity running rostrocaudally through the dually innervated tectum. Interactions among axons of retinal ganglion cells, possibly mediated through tectal neurons, must be invoked to explain this stereotyped disruption of the normally continuous retinal termination pattern.


Intramural coronary artery as a cause of unstable angina pectoris. A patient with an anomalous intramyocardial course of the LAD coronary artery, causing angina pectoris, is described. The patient had symptomatic relief after an aortocoronary artery bypass operation. Intramural coronary arteries may be clinically significant. In cases where medical management does not provide relief, surgical correction of the anomaly may give symptomatic improvement and improved exercise tolerance.


Hodgkin's disease - a 'B' neoplasm?

Hodgkin's disease - a 'B' neoplasm? Lymph node tissue from 2 patients with Hodgkin's disease was studied by light microscopy using the immunoperoxidase technique with a panel of monospecific antisera. Hodgkin's mononuclear and Reed-Sternberg cells were shown to exhibit features characteristic of B cells. The possibility that Hodgkin's disease is a B-cell neoplasm is discussed.


Platelet-binding of the von Willebrand factor. The aggregation of platelets by the antibiotic, ristocetin, requires a plasma cofactor (VIII:vWF) and one or more specific binding sites on the platelet membrane. The interaction between VII:vWF and the platelet was examined using VIII:vWF labelled with 125I. In the presence of ristocetin (1.5 mg/ml), from 70 to 90% of the 125I-VIII:vWF became platelet-bound. By contrast, only 21% was bound with thrombin (2.5 microgram/ml), and 2.2% with buffer alone. Fractionation of the platelets revealed that peak radioactivity was present in the membrane fraction. Treatment of ristocetin-reacted platelets with either chymotrypsin, 100 microgram/ml, or trypsin, 75 microgram/ml, resulted in the partial release of the membrane-bound radioactivity. It is concluded that VIII:vWF binds to the platelet membrane in the presence of ristocetin.


Heparin neutralizing activity in patients with renal disease on maintenance haemodialysis. Heparin neutralizing activity (HNA) was increased in plasma of patients with end-stage renal disease treated by maintenance haemodialysis. It was not raised in non-dialyzed patients with chronic renal failure, nor in patients with normal renal function who had been exposed to the extracorporeal circulation of the heart-lung bypass 48--72 hr before testing. It is postulated that the trauma of extracorporeal circulation causes platelets to release HNA which is not cleared by the dialysis membranes of the artificial kidney but is by the human kidney. This may have therapeutic implications for heparin dosage schedules during haemodialysis.


Mitogenic activity of an extract of Trypanosoma gambiense. An extract obtained by repeated freeze/thawing of a freshly isolated strain of Trypanosoma gambiense caused stimulation of lymphocytes obtained from healthy adult donors and from cord blood. The active factor had some stimulatory effect on purified B and T lymphocytes and in two of five subjects increased IgM production by lymphocytes cultured in vitro. A trypanosome-derived mitogenic factor may play some part in the pathogenesis of the hypergammaglobulinaemia characteristic of African trypanosomiasis.


Antagonism between donor and host B cells in allotype congenic chicken chimeras. B cell chimerism was analyzed in juvenile chickens given injections of major histocompatibility complex-compatible lymphoid cells. The allelic products of donor and host-derived B cells were monitored with antisera directed against M1 (IgM) and G1 (IgG) isotype-specific allotypes. Injection of peripheral blood lymphocytes and spleen cells suppressed host allotype levels whereas purified T lymphocytes were ineffective. Pretreatment of recipients with cyclophosphamide was more effective than irradiation in promoting both engraftment and host B cell suppression. Host allotype suppression endured for several months after cell transfer and was attributable to B cell deletion, as ascertained by the lack of cells which expressed surface M1. In partially suppressed chickens, host G1 was inhibited to a greater degree than M1 allotype. Host recovery was followed by donor B cell rejection when low numbers of donor cells and/or inadequate host conditioning was used. Selective M1 chimerism occurred when limiting numbers of spleen cells were transferred into cyclophosphamide-treated hosts, whereas selective G1 chimerism resulted after the transfer of large numbers of peripheral blood lymphocytes or spleen cells into unconditioned recipients. We consider that these findings can be attributed to a B cell surveillance mechanism which may be similar to that postulated previously to explain resistance to haemopoietic and tumour cells.


[Influence of T-lymphocytes in bladder cancer on appearance and infiltration of recurrences (author's transl)]. Intrinsic body defences against cancer depend on cells of the lymphatic and reticulo-endothelial systems, the T-lymphocytes playing a central role in the immunological rejection of tumor. The mononuclear cell infiltrate in tumor tissue is largely composed of immunocytes of the T-lymphocyte series. A heavy concentration of lymphocytes in stroma of bladder tissue affected with cancer appears to indicate a good prognosis. After removal of the primary tumor, recurrences are noted only after a relatively long interval, infiltration of the tumor into bladder muscle being hindered by immunocyte activity. It is clear, from comparison with dinitrochlorbenzol skin testing, that the extent of lymphocyte infiltration in tumor tissue is a measure of the cellular immune status of a patient with cancer.


Acute electrical stimulation for urinary incontinence. Acute or maximal electric stimulation of the pelvic floor muscles has been used in incontinent patients who are suitable candidates for electrical stimulation, but unwilling or unable to use the anal plug electrodes. Seventeen of 20 patients had relief or improvement of their incontinence. However 5 of these 17 patients had a relapse of symptoms on follow-up, requiring a repeat treatment with acute or maximal electrical stimulation.


[Cryoelectrocoagulation in acute gastroduodenal hemorrhages]. Separate and combined cryoelectrocoagulation in acute gastroduodenal bleeding is a fairly effective method of local hemostasis. The applied cryoagent--liquid freon induces local freezing of the stomach mucous membrane practically immediately. Initially gasiform freon cleans mechanically the bleeding site of blood, which facilitates considerably the following electrocoagulation or freezing with liquid freon.


[Immunoglobulin receptors of antigen-stimulated B-lymphocytes]. Albino mice were immunized with a suspension of sheep erythrocytes. On the fifth day following treatment the animals were killed and B lymphocytes were isolated from their spleen tissue. Both the complement-fixation test and the immunofluorescence method were employed to specify the number of immunoglobulin receptors on the membrane surface, and disk electrophoresis was used to separate the protein fractions of the solubilizates from their membranes. Normal lymphocytes, obtained from unimmunized animals, were used as controls. It was established that: 1. The immunoglobulin receptors gradually decreased in number is the stimulated lymphocytes. On the fifth day of immunization their amount was 6.6 times lower than that in the normal lymphocytes. 2. The receptors in the normal lymphocytes proved diffusely scattered on the cell surface, while those in the stimulated lymphocytes were concentrated into clusters at one of the cell poles. The biologic nature of the observed changes is briefly discussed. It is concluded that the mature antibody-producing cell is not dependent on the antigen.


[Foundations and indications for selective coronary perfusion scintigraphy]. By means of coronarography in the most favourable case only the morphology and function of the vessels up to a diameter of 0.1 mm may be established. By the selective coronary perfusion scintigraphy this gap is closed, for it allows a judgment also of the terminal vascular system of the myocardium. The basis of this method is an occlusion of the arterioles and capillaries by radioactively labelled microspheres, in which case, however, only every 10,000th to 20,000th vessel is embolized for a short time. Thus the proper selective perfusion scintigraphy is for the patient a procedure which is not stressing, which, however, demands a sounding of the coronary vessels. On the basis of our own previous results this investigation method is indicated in the diagnostics of the ischaemic heart disease also in its atypical form, in the indication to the vascularisation operation with aortocoronary bypass and its postoperative control as well as in the cardiomyopathies. Also in load examinations and in pharmacological tests by their use as double nuclide method an enlarged information can be got. The importance of the perfusion scintigraphy is among others shown in patients with normal coronarogramme, but with perfusion disturbances which can be proved by means of this method. The most comprehensive invasive diagnostics in the diseases mentioned is at present achieved by the combination of coronarography, ventriculography and selective perfusion scintigraphy.


[Clinical studies on the connection between preceding abruptio placentae and abortus and subsequent complications during the afterbirth phase (author's transl)]. 2176 vaginal deliveries at Jena University Hospital were selected at random to check whether in these patients it is possible to establish the connection postulated by some authors between preceding premature termination of pregnancy and the mass incidence of afterbirth haemorrhages, as well as of necessary surgery in the afterbirth phase. There was no significant increase of afterbirth complications following abruptio placentae and abortus, whereas there are partly statistically significant differences in the incidence of surgery reauired in children of normal weight of underweight.


[Comparative study of the biological activity and toxic effect of 1alpha-hydroxycholecalciferol and ergocalciferol in rats]. Single administration of 0.25 microgram of sunthetic Ialpha-hydroxycholecalciferol (IalphaOHD3) into nephrectomized rats, maintained at D-avitaminous diet, improved the active transport of calcium ions against the concentration gradient in small intestine of these animals, whereas ergocalciferol was biologically inactive under the same conditions. Administration of IalphaOHD3 during 5 days at a dose 0.025 microgram normalized calcium content in blood serum of rats with D-avitaminosis, Increased doses of IalphaOHD3, administered into intact animals, caused transient hyperphosphatemia, hypercalcemia, calcinosis of internal tissues (kidney heart, aorta) as well as death of some animals. IalphaOHD3 exceeded 400-fold the hypercalcemic and calcinose effects of ergocalciferol. LD50 for IalphaOHD3 was equal to 100 microgram/kg, if it was administered during 5 days per os. Tissue calcinosis was developed after administration of a daily dose 10 microgram/kg, moderate hypercalcemia was caused by a daily dose 1 microgram/kg or 0.25 microgram per an animal; this amount is only 10-fold higher as compared with the physiologic requirement. Ergocalciferol caused hypercalcemia and metastatic calcification only at a dose 4000 microgram/kg. Clinical use of IalphaOHD3 at doses, exceeding the physiologic requirements, has to be prohibited due to high activity of the preparation and to toxicity of its increased doses.


The properties of the extraocular muscles of the frog. I. Mechanical properties of the isolated superior oblique and superior rectus muscles. The mechanical properties of two extraocular muscles (superior oblique and superior rectus muscles) of the frog were studied and compared with those of a frog's skeletal muscle (iliofibularis muscle) which contains the same types of muscle fibres as the oculorotatory muscles. The extraocular muscles are very fast twitching muscles. They exhibit a smaller contraction time, a smaller half-relaxation time, a higher fusion frequency, and a lower twitch-tetanus ratio than the skeletal muscles. The maximum isometric tetanic tension produced per unit cross-sectional area is lower in the extraocular muscles than in skeletal muscles. However, the extraocular muscles show a higher fatigue resistance than the skeletal muscles. With respect to the dynamic properties there are some differences between the various oculorotatory muscles of the frog. The superior rectus muscle exhibits a faster time-course of the contraction, a higher fusion frequency, and a higher fatigability than the superior oblique muscle. An increase of the extracellular K+-concentration evokes sustained contractures not only in the extraocular muscles but also in the iliofibularis muscle; between these muscles there are no striking differences in the mechanical threshold of the whole muscle preparation. The mechanical threshold depends on the Ca++-concentration of the bathing solution and it is found in a range between 12.5 and 17.5 mM K+ in a normal Ringer solution containing 1.8 mM Ca++. The static-mechanical properties of the extraocular muscles of the frog and the dependence of the active developed tension on the muscle extension are very similar to those which are known to exist in the extraocular muscles of other vertebrates. In tetanic activated frog's oculorotatory muscles a linear relationship exists between length and tension. A variation of the stimulation frequency does not change the slope of this curve but causes parallel shifts of the curve. The peculiar properties of the extraocular muscles of the frog are discussed with respect to the muscle fibre types in these muscles and to the diameter of the muscle fibres.


The properties of the extraocular muscles of the frog. II. Pharmacological properties of the isolated superior oblique and superior rectus muscles. The pharmacological properties of the superior oblique and the superior rectus muscles of the frog's eye were investigated in comparison with those of a skeletal muscle (iliofibularis muscle) of the same animal. Acetylcholine causes sustained contractures of the extraocular muscles; this effect is increased by physostigmine and decreased or abolished by d-tubocurarine. Also the applications of succinylcholine, choline or caffeine are able to evoke contractures. There are no striking differences in pharmacological properties between extraocular and skeletal muscles of the frog. The time-course of the contractures and the sensitivity of the muscle preparations to the drugs which evoke contractures are identical in extraocular and iliofibularis muscles. In comparison with skeletal muscles there is no higher sensitivity of the extraocular muscles against curare-like drugs. The existence of adrenergic receptors could not be found neither in extraocular nor in skeletal muscles of the frog. It is concluded that in frogs no pharmacological differences exist between the muscle fibre types which compose the extraocular and the skeletal muscles.


The properties of the extraocular muscles of the frog. III. Morphological, mechanical and pharmacological properties of the isolated retractor bulbi muscle. Some morphological, physiological, and pharmacological properties of the retractor bulbi muscle of the frog were tested. The enzyme-histochemical investigation shows that the retractor bulbi muscle contains twitch muscle fibres only. Two types of twitch muscle fibres, which are especially different in their diameter and in the content of mitochondria, build the muscle in an irregular arrangement; tonic muscle fibres were not observed. On the average, the isolated retractor bulbi muscle has at room temperature a contraction time of 26 ms, a half-relaxation time of 28 ms, a fusion frequency of 75 stimuli/s, and a twitch-tetanus ratio of 0.28. The fatigability of this muscle is higher than in oculorotatory eye muscles but lower than in skeletal muscles of the frog. An increase of the extracellular K+-concentration elicits in retractor bulbi muscles a quickly transient contracture; the mechanical threshold of the muscle fibres is found in a range between 20 and 25 mM K+ in Ringer solution. Similar short-lasting contractures, which are probably caused by twitch fibres, rich in mitochondria, are also evoked by application of depolarizing drugs like acetylcholine. The properties of the retractor bulbi muscle are compared with those of the sartorius muscle of the frog, which likewise contains twitch muscle fibres only.


[Effect of electric cardiac stimulation in experimental supraventricular tachycardia]. Experimental supraventricular tachyarrhythmia was produced in dogs by the local application of aconitine on the left auricle. The effect of various types of stimulations (right auricular, right ventricular, double-delayed right auricular and right ventricular-right auricular double-delayed stimulation) was studied for the suppression of supra-ventricular (overdrive) tachyarrhythmia. It was found that the electric stimulation of the heart is an effective method of suppressing tachyarrhythmias, though there is a significant difference in the anti-arrhythmic effects of the electric stimulations of various types. For suppression of the supraventricular tachyarrhythmia caused by aconitine, delayed double-right auricular stimulation seemed to be the most effective with respect to the right ventricle. The bioelectric features of aconitine arrhythmia and the mechanism of the antiarrhythmic effect of the electric stimulation of the heart are discussed.


[A case of diphtheric myocarditis, Anatomoclinical study with histology of the conduction system]. Presentation of a case of diphteric myocarditis. The histological examination of the conduction system can explain the rhythm disturbances in the present case with the EKG characteristics of the sick sinus syndrome and the intraventricular conduction disturbances. The anatomical lesions are variables in their topography and age, explaining the variability of the troubles of the rhythm during the first weeks of the disease. The fibrotic scars and the ageing changes of the conduction system are probably the reason for the late constitution of AV block and sick sinus syndrome, years after the acute episode.


Inotropic effects of calcitonin in man.

Inotropic effects of calcitonin in man. The Authors have studied th haemodynamic response of ten normal subjects to the intravenous administration of 160 MRC.U. of Calcitonin in 60 min, by serial measurement of the systolic time intervals. The analysis of results pointed out a minor inotropic effect starting from the 10th minute from the beginning of the infusion. Little but significant decrements (P less than 0.01) in the duration of the pre-ejection phase of the isovolumetric contraction time, as well as a significant increase (P less than 0.01) in the LVET/PEP ratio, have been noted. A negative chronotropic effect (P less than 0.05) has been noted starting from the 30th minute. The mechanism by which Calcitonin can modify the myocardial inotropism in the normal subject is till now unknown, and it could be related to the interference of this hormore on the endocellular movements of Calcium, and on the cellular levels of cyclic AMP.


"Torsades de pointe": a distinct entity of ventricular arrhythmia? Seven cases of an unusual type of ventricular arrhythmia, already named "Torsades de pointe" by French authors, are presented. It is characterized by a changing pattern of the ventricular complexes, spontaneous onset and cessation, and refractoriness to defibrillation and antiarrhythmic drugs which decrease intraventricular conduction. Prior to its onset, Q-T prolongation is almost universally seen in the ECG. Hypokalemia, myocardial depressants and bradycardia are common causes. Isoproterenol and rapid cardiac pacing are recommended as the treatment of choice. This arrhythmia is a distinct entity, quite different from typical ventricular tachycardia or fibrillation.


[Aneurysm of Valsalva's sinus, apropos of 7 surgical cases[]. The authors describe 7 cases of rupture of the Valsalva sinus. Until rupture the aneurysm is silent. Aortic insufficiency and left to right shunt are major components of this syndrome. Surgical treatment under extra-corporal circulation needs aortotomy and an approach of the ruptured extremity to close the defect and maintaining the integrity of the valvular structures.


Placebo effect in the treatment of angina pectoris. The interference of placebo effect in the treatment of angina pectoris has been studied in a group of patients with stable angina pectoris, selected on the basis of normal electrocardiogram at rest and a pathologic ergometric electrocardiographic test. It was found that the patients could be divided, according to the results of the exercise test, into two groups: placebo responders and place-bo-non-responders. The anti-anginal effect of beta-blocking agents has been clearly demonstrated only in the placebo-non-responders group. No statistically significant effect of beta-blocking agents was observed in the placebo-responders group. This result shows that it is necessary, in double blind trials, at first to separate placebo-responders from placebo-non responders. Otherwise the correct evaluation of a drug can be modified by the placebo-responders group.


Phentolamine infusion in cor pulmonale due to chronic obstructive pulmonary disease. Continuous phentolamine infusion, produced a marked decrease in pulmonary arterial pressure and pulmonary vascular resistance with an increase in cardiac output, in the majority of a group of 13 patients with chronic obstructive pulmonary disease and cor pulmonale. Changes in vital capacity, forced expiratory volume in one second, arterial blood gas values and peripheral blood pressure were not significant except in one patient. The changes in the pulmonary circulation are probably due to the alpha blocking effect of phentolamine, although a direct effect of the drug on vascular smooth muscle can not be excluded.


Extent of the inferior myocardial infarction assessed by the frontal plane of the vectorcardiogram. A correlation was made between the vectorcardiographic changes and the peak value of the L.D.H. in the serum of 21 patients with acute inferior (diafragmatic) M.I. The following vectorcardiographic variables showed changes proportional to the increase in serum L.D.H. The correlation was found to be statistically significant. The direction of the 0.025 sec vector (r = 0.63, P less than 0.005). The duration of the initial superior forces of the QRS loop (r = 0.87, P less than 0.001). The maximal leftward deviation of the initial superior QRS loop forces (r = 0.65, P less than 0.005). The maximal superior deviation of the initial QRS loop forces (r = 0.68, P less than 0.05). The ratio of the maximal superior deviation over the maximal inferior deviation of the QRS loop "QY/RY" (r = 0.76, P less than 0.001). The area under the initial superior forces of the QRS loop and over 0 degrees +/- 180 degrees axis in squared milimeters (r = 0.88, P less than 0.001). It is suggested that V.C.G. is a usefull means in assessing the extent of inferior M.I.


B and T lymphocytes in cerebrospinal fluid and blood in multiple sclerosis, optic neuritis and mumps meningitis. B and T cells were defined in cerebrospinal fluid (CSF) and blood of 18 multiple sclerosis (MS), five optic neuritis, and 17 mumps meningitis patients by counting immunoglobulin-bearing lymphocytes for B cells, and the capacity of rosette formation with sheep erythrocytes of T-cell determination. Patients with MS and mumps meningitis had significantly higher T-cell values in CSF compared to blood, while the B cell value was significantly lower in CSF in mumps meningitis only. MS patients also displayed significantly lower B-cell values in blood compared to mumps meningitis patients and blood donors. No significant differences were observed between MS patients in exacerbation and in remission.


Functional analysis of lymphoid cells from mouse bone marrow in vitro. The present results show that mouse bone marrow (BM) cells responded in vitro against phytohaemagglutinin (PHA), concanavalin A (Con A) and lipopolysaccharide (LPS). In addition, BM cell suspensions contained relatively many cells with ADCC (antibody-dependent cell-mediated cytotoxicity) activity. BM cells were fractionated according to various cell surface characteristics. The results of these experiments were compared with previously published reports, showing that pre-T and pre-B cells could be separated on Ig anti-Ig columns (Ig = immunoglobulin). The combined results showed that pre-T cells may fractionate together with cells with the following characteristics: they displayed ADCC activity and had Fc receptors (FcR) and/or membrane Ig. Pre-B cells fractionated with cells with the following characteristics: they responded to LPS but had no ADCC activity. They were not adherent and/or phagocytic and were Ig-, FcR- and C3 receptor (C3R) negative.


The prevalence and possible significance of IgD granulocyte-specific antinuclear antibodies in neutropenic and non-neutropenic cases of rheumatoid arthritis. Sera from 21 rheumatoid arthritis patients with accompanying neutropenia (less than or equal to 2000 neutrophils/microliter) and 45 rheumatoid arthritis patients without neutropenia were studied for the occurrence of IgD granulocyte-specific antinuclear antibodies. Such antibodies were found in 67 per cent of the neutropenic and 18 per cent of the non-neutropenic cases (p less than 0.001). The titres of IgD granulocyte-specific antinuclear antibodies varied independently of the titres of IgD and complement-fixing granulocyte-specific antinuclear antibodies, but showed some covariation with granulocyte-specific antinuclear antibodies of the IgA and IgM classes most probably reflecting a broad polyclonal antibody response to phagocyte nuclear antigens in the serologically highly active neutropenic cases. Gel filtration studies on selected sera containing IgD granulocyte-specific antinuclear antibodies indicated participation of these antibodies in immune complexes. It is thus possible that IgD granulocyte-specific antinuclear antibodies may have some significance for the rheumatoid inflammatory processes.


The effects of aromatic amino acid decarboxylase inhibitors on plasma concentrations of 5-hydroxytryptophan in man. 5-Hydroxytryptophan has been found to be beneficial when administered alone or in combination with extracerebral aromatic amino acid decarboxylase inhibitors for therapeutic purposes in various disorders in which myoclonus is prominent. In five subjects the effect of decarboxylase inhibitors on the accumulation and elimination of 5-hydroxytryptophan in plasma was studied. The plasma concentrations of 5-hydroxytryptophan were increased about ten fold by pretreatment with the decarboxylase inhibitors, carbidopa and benserazide. Half-lives of 2.2--3.0 hrs. were obtained following oral administration of a single dose of 5-hydroxytryptophan with or without pretreatment. In one subject the half-life of 5-hydroxytryptophan in plasma increased to 5.5 hrs. during long-term treatment with carbidopa.


A prospective study of gentamicin ototoxicity. Twenty patients were included in a prospective otoneurological study performed to assess the ototoxicity in gentamicin therapy. Gentamicin was administered intravenously, and the serum level was currently determined. Audiographic and electronystagmographic studies were carried out at the institution and discontinuation of the treatment and again a few weeks later. Ten patients exhibited ototoxic actions, predominantly cochlear, 4 of the cases being fully reversible. Two patients developed severe hearing loss, associated in one with bilateral extinction of vestibular function. Low serum levels of gentamicin did not rule out the possiblity of ototoxicity. These results urge the continuing of prospective studies and indicate that gentamicin should be used only as a link in the primary treatment of severe infection or in cases in which other, less toxic agents have failed.


New aspects of cerebrospinal fluid dynamics in humans investigated by sequential gammacamera cisternography, with data evaluation by the digital multichannel analyzer. Part 3: Physiopathology of the ventricular reflux. Although well described and intensively used for diagnostic purposes, the ventricular reflux as a gammacisternographic phenomen has not yet been satisfactorily explained, and its physiopathology is a subject of controversy. Based on our method of quantitative gammacisternography and gammaventriculography we study the evolution of the tracer concentrations in two main chambers:--the basal cisterns together with the upper cervical canal, considered as a functional unity (the distribution area) and--the ventricular system. We propose the mathematical analysis of a theoretical model which represents the normal and pathological situations of these two chambers, as a method for measuring ventricular volume and ventricular tracer clearance. From the correlation in results with patients and models, we suggest turbulence as the main factor in generating backmixing or total mixing, the appearance of which is called ventricular reflux. We deny the existence of a real inversion of CSF flow. The spinal canal velocity of isotope flow is proposed as additional evidence of turbulence. The normal general dynamics of CSF are delineated, and we propose the following factors that lead to ventricular reflux:--partial obstruction to epicortical CSF flow;--total obstruction to epicortical CSF flow. Their principal characteristics are given, and the importance of using their quantitative parameters in descriptions of patients is stressed. Different aspects in the evolution of hydrocephalus, transependymal resorption, and factors involved in hydrodynamic changes etc. are discussed.


Idiopathic differentiated histiocytosis. Eighty-nine cases variously diagnosed as histiocytosis X, eosinophilic granuloma, Hand-Schuller-Christian disease, Letterer-Siwe disease, or malignant histiocytosis from one institution were reviewed. Follow-up data were obtained for all patients. On the basis of clinicopathologic correlation, the following distinct groups were identified. 1. Disseminated histiocytosis (12 patients) with involvement of more than two organ systems at the time of recognition of the disease, affecting children less than 3 years of age (the patient's general condition is poor and hepatosplenomegaly is common. The patients do poorly, and all the patients in this group of the present study died. 2. Histiocytosis confined to bone, whether monostotic (36 patients) or polyostotic (eight patients). This type is self-healing, does not disseminate, and does not require intensive therapy. Clinically the patients are older and in good general condition during the course of the disease. Histologically histiocytes in these two groups are cytologically benign, and the whole process is inflammatory rather than neoplastic. Presence of giant cells, eosinophils, and necrosis are usually associated with better prognosis. Many neoplastic diseases and infectious processes manifest as histiocytosis. More than a third of the cases of this study diagnosed as histiocytosis proved to be other processes. This confusion contributes to differences of various reports and difficulty of interpretation of findings.


Aortoduodenal fistula: role of endoscopy in diagnosis. A patient with an aortic by-pass graft presented with intermittent gastrointestinal bleeding. A definitive diagnosis of an aortoenteric fistula involving the third part of the duodenum was made at endoscopy. Diagnosis of an aortoenteric fistula is often difficult with angiography and barium contrast studies, frequently being negative. Since the majority of these fistulas involve the distal duodenum, early endoscopy should be considered when an aortoenteric fistula is suspected.


Patency of saphenous vein grafts five or more years after coronary bypass surgery. The state of preservation of 48 coronary saphenous vein grafts was investigated by angiography in 27 patients from 60 to 79 months, average 64.6 months, after their insertion. Thirty-nine of the grafts (81.2 per cent) were patent; of these, 24 (50 per cent) were in excellent, six (12.5 per cent) in good, six (12.5 per cent) in fair and three (6.2 per cent) in poor condition. Nine grafts (18.8 per cent) were occluded. The rate of graft patency in this series compares favorably with that in shorter follow-ups and presages their further prolonged viability. Atherosclerotic obstructive graft disease may emerge as an important cause of late graft deterioration in an occasional patient.


Severe factor VIII and factor IX deficiency in females. A survey of 11 hemophilia centers produced data concerning 28 females with extremely low levels of factor VIII or IX coagulant activity. Ten of the 28 have hemophilia A, six have hemophilia B, and 12 have severe von Willebrand's disease. The 16 females who have severe factor VIII or factor IX deficiency as an isolated defect exemplify several of the possible genetic explanations for the occurrence of hemophilia in females. All 16 bruise excessively, and several have had recurrent hemarthroses. Three of these girls, ages five, 10 and 23 years, have evidence of chronic hemophilic arthropathy. The 12 females with severe von Willebrand's disease are either homozygous for von Willebrand's disease or severely affected heterozygotes. All 12 have mucous membrane bleeding. In addition, five of the 12 have recurrent hemarthroses and three have evidence of chronic joint disease. However, the major problem in the adult females with von Willebrand's disease has been extreme menorrhagia. One of the seven adults underwent irradiation sterilization and another had a hysterectomy because of menorrhagia. The others have been managed with anovulatory drugs or plasma infusions and EACA. Despite menorrhagia, five pregnancies and deliveries have been uneventful in three of these women.


Distinction between the common symptoms of the phosphate-depletion syndrome and glucocorticoid-induced disease. A phosphate depletion syndrome developed in a steroid-dependent asthmatic patient. Initially, the clinical picture was confused with steroid-associated myopathy rather than the phosphate depletion syndrome which has similar symptoms. The classic biochemical findings led to the correct diagnosis. Cessation of phosphate-binding antacids and phosphorus repletion rapidly corrected the biochemical findings and led to the patient's clinical improvement. Platelet phosphate metabolism was evaluated; it was found to correlate with the phosphorus-depleted state and clinical recovery with phosphate repletion. Attention is drawn to the clinical entity of phosphate depletion which may mimic steroid-induced side effects, both of which may occur in patients receiving steroids and antacids.


Measuring the interventions used in the short-term interpersonal psychotherapy of depression. This paper describes a method for measuring the interventions employed by psychotherapists in the short-term interpersonal treatment of depressive disorders. The psychotherapy techniques are described, and the methodology for measuring these techniques is presented. These are illustrated with the findings of the collaborative Boston-New Haven project.


The mortality of bleeding esophageal varices in a private university hospital. The mortality of patients with bleeding esophageal varices was studied in a private hospital where the modalities of treatment are considered optimal. Of the sixty-two patients in the study, twenty (32 per cent) died. Mortality was higher (p is less than 0.02) for those who had ascites or bilirubin more than 5 mg/dl, albumin less than 3 gm/dl, prothrombin time more than 4 seconds of control, or blood transfusions of more than 5 liters. The lower mortality in this study as compared with other studies among indigent population is the result of either private patients having less severe liver disease or having more effective care of both.


A study of the craniofacial skeleton.

A study of the craniofacial skeleton. Multivariate analysis of craniofacial profiles demonstrated the complex interaction between the brain case and facial skeleton during growth and between various occlusal categories. Only by investigating craniofacial growth data still further will it be possible to establish normative standard growth patterns that can withstand critical scientific appraisal.


Serum IgE levels in patients with selective IgA deficiency. In this study serum IgE levels were measured by a double-antibody radioimmunoassay in 31 patients with serum IgA concentration less than 0.01 mg/ml who were followed in the arthritis and allergy clinics. On a group basis there was no significant difference in mean serum IgE levels between the IgA deficient patients and normal subjects of the same age. However, in the absence of atopic disease, IgA deficient patients had significantly lower serum IgE levels. When atopy was associated with IgA deficiency IgE levels were the same as in the normal subjects but significantly lower than those of atopic non-IgA deficient patients. IgE levels in those with recurrent respiratory tract infection were not different. Adults with anti-IgA antibodies had significantly lower IgE values. IgE levels in patients with RA, JRA or SLE were not significantly different. Selective IgA deficient patients may have a relative deficiency of serum IgE depending on the comparison group.


Histological evaluation of cutaneous wound healing in presence of nitrous oxide in rats. Three-centimetre linear incisions were made in 90 young male Lew/f Mai rats by scalpel through skin to the investing fascia of the left flank. The skin was undermined sharply for a distance of 0.5 cm along both sides of the entire length of the incision. The wound site was closed per primam with Michel clips and left uncovered. Following emergence from anesthesia, rats were randomly allocated to one of three groups of 30 rats each: one group breathed air only and acted as control; the second was exposed to 20% N2O for 24 hours daily until sacrificed (continuous group); the third was exposed to 20% N2O for 8 hours daily until sacrificed (intermittent group). Ten rats from each of the three groups were sacrificed after 3, 7, or 10 days postincision. After sacrifice, sections from the wound stained with hematoxylin and eosin or reticulin were examined microscopically. No histological evidence of an effect on wound healing of skin occurred in rats exposed to 20% N2O.


Inhibitory activity of unstimulated alveolar macrophages on T-lymphocyte blastogenic response. Unlike peritoneal macrophages from normal rats, which stimulate T-lymphocyte blastogenic responses, alveolar macrophages are highly inhibitory. However, alveolar macrophages collected from lungs previously exposed to an inflammatory agent develop the capacity to cooperate with T cells in these responses. Recent reports in this journal indicate that underlying inflammation greatly enhances the susceptibility of the lung to sensitization by inhaled antigen. It is suggested that inflammatory-induced changes in the population of alveolar macrophages, which abolish the inhibitory activity of the latter on proliferation of T cells, are intimately involved in the increased susceptibility of the lung to the development of cellular hypersensitivity that accompanies inflammation.


Isoniazid hepatotoxicity in children.

Isoniazid hepatotoxicity in children. One hundred sixteen children, including 50 less than 10 years of age, received isoniazid therapy for tuberculous infection. Determinations of serum glutamic oxaloacetic transaminase concentrations at time of institution of therapy, 6 to 20 weeks later, and again at the completion of the therapeutic course, showed no evidence of hepatotoxicity. Clinical symptoms were never such that discontinuation of therapy was necessary.


Effect of central nervous system-acting drugs after selective destruction by neurotoxins of 5-hydroxytryptamine fibers in the brain. Some behavioral effects of CNS-acting drugs have been studied in two animal species after functional impairment of central serotonergic activity. In rabbits, pretreatment with p-CPA or with 5,6-DHT counteracted the hyperthermia induced by d-amphetamine or apomorphine; the same pretreatments were ineffective in modifying pyrogen-induced fever. These data indicate a modulatory role of the 5-HT system in the hyperthermic response to dopaminergic agonists, such as d-amphetamine and apomorphine, and rule out 5-HT involvement in the hyperpyrexia induced by pyrogen. A previous intraventricular injection of 5,6-DHT significantly potentiated the increase in body temperature induced by 5-HTP in combination with a MAO inhibitor. Pretreatment with p-CPA, instead, strongly inhibited the hyperthermic response to 5-HTP. In unanesthetized fowl, at the time of the most dramatic degenerative signs of indoleaminergic neurons induced by 5,6-DHT, as documented by histofluorescence pictures, intraventricular infusion of 5-HT induced more intense behavioral, electrocortical, and body temperature modifications than in control animals. These results suggest the existence of receptor supersensitivity after 5-HT nerve ending degeneration but not after brain 5-HT depletion. The hyperthermic effect of a presynaptically acting drug, fenfluramine, was counteracted in rabbits and in fowl pretreated with either p-CPA or 5,6-DHT. Since identical behavioral, electrocortical, and body temperature effects have been observed after 5-HT or 5,6-DHT infusion into the third ventricle of fowl, it may be concluded that 5,6-DHT behaves also as a central 5-HT receptor agonist.


Effects of serotonin neurotoxins on rotational behavior in the rat. Injections of p-CA or 5,7-DHT into the MRN caused decreases in 5-HT and 5-HIAA levels in the cortex and striatum. They also caused a decrease in 5-HT turnover in the cortex and an increase in striatal DA turnover. The unilaterally injected rats showed contralateral rotation after amphetamine or apomorphine administration. There was a significant correlation among the rate of rotation, the decrease in cortical 5-HT turnover, and the increase in striatal DA turnover. Injection of 5,7-DHT into the SN produced the same biochemical and behavioral changes as did MRN lesions, suggesting that the changes induced by MRN lesions might be due to a direct projection from the raphe to the substantia nigra. Injection of 5,7-DHT into the MFB caused ipsilateral rotation after injection of amphetamine or apomorphine and a decrease in DA turnover in the striatum. There was a significant correlation among the rate of rotation, the decrease in 5-HT turnover in the cortex, and the decrease in striatal DA turnover in the MFB-lesioned rats. These effects might be due to a projection from the DRN to cell bodies in the striatum.


[In vitro study of cellular immunity in atopic and in contact eczema (author's transl)]. Peripheral blood lymphocytes from 20 atopic dermatitis patients, 10 contact dermatitis and 50 healthy subjects were studied by the following methods: E rosettes, active E rosettes anti-HTLA serum (T cells), surface immunoglobulins (B cells), Ea rosettes (Fc-gamma-receptor bearing cells) stimulation by PHA, ConA, PWM. In contact dermatitis the results only indicated significantly low percentages of active E rosettes (whereas E rosette, HTLA, surface immunoglobulins, Ea rosettes are normal) and a poor response to PHA and ConA. In atopic dermatitis the presence of a T cell defect was assessed by low percentages of E rosettes. However normal results obtained with an anti-HTLA serum indicated that this T cell defect was not quantitative but could be due to intrinsic lymphocyte abnormalities or serum factors. Moreover the percentage of B cells was significantly increased. The stimulation index was lower after ConA than after PHA stimulation. This could be in favor of a T suppressor cell impairment. The place of this T cell defect in atopic dermatitis and the possible correlations with the Sczentivanyi's theory are discussed.


[Genetic structure of Staphylococcus epidermidis strain No. 17 possessing penicillinase and bacteriocinogenic activity]. The studies on the genetic structure of Staphylococcus epidermidis, strain 17 showed that this strain possessed a factor of bactericinogenicity of the one type, which was an extrachromosomal element not bound with penicillinase activity. The loss of the bacteriocinogenicity factor spontaneously or under the effect of acridine orange at a temperature of 37 degrees C was not observed. Passages of the strain at a temperature of 44 degrees C for 5 days and acridine orange proved to be the most effective eliminating factors. The loss of the bacteriocinogenicity plasmid did not result in changing any biochemical properties of the strain but was accompanied by a loss of the immunity to bacteriocin of the initial strain. The study of the growth regularities of the initial strain and its variant deprived of the bacteriocinogenicity plasmid showed that multiplication of the cells in the presence of the plasmid practically started without the latent period.


CP-45,899, a beta-lactamase inhibitor that extends the antibacterial spectrum of beta-lactams: initial bacteriological characterization. CP-45,899 {3,3-dimethyl-7-oxo-4-thia-1-azabicyclo(3.2.0)heptane-2-carboxylic acid, 4,4-dioxide, [2S-(2alpha,5alpha)]} is an irreversible inhibitor of several bacterial penicillinases and cephalosporinases. In the presence of low concentrations of CP-45,899, ampicillin and other beta-lactams readily inhibit the growth of a variety of resistant bacteria that contain beta-lactamases. CP-45,899 used alone displays only weak antibacterial activity, with the notable exception of its potent effects on susceptible and resistant strains of Neisseria gonorrhoeae. CP-45,899 appears to be somewhat less potent but markedly more stable (in aqueous solution) than the recently described beta-lactamase inhibitor clavulanic acid. The spectrum extensions provided by the two compounds are similar. A 1:1 mixture of CP-45,899 and ampicillin displays marked antimicrobial activity in mice experimentally infected with ampicillin-resistant Staphylococcus aureus, Haemophilus influenzae, Klebsiella pneumoniae, and Proteus vulgaris.


Safety and efficacy of chronic cerebellar stimulation. It is our conclusion that CCS is both efficacious and safe as a therapeutic measure for neurologic disease. As indications become more concise and patients can be chosen who are not as incapacitated as those in our first group, this should become even more apparent. In order to be certain that calibration of the stimulating equipment is accurate each apparatus should be calibrated by the group treating the patient. We are now making this a routine aspect of our follow-up recheck examinations.


Control of spasticity and involuntary movements--cerebellar stimulation. By stimulating the medial aspect of the superior surface of the cerebellum with relatively short, low current stimulating pulses, spasticity and some involuntary movements have been reduced. Voluntary movements, as a result, are able to come through better; however, if the child has little voluntary ability, he is at least more relaxed, thus allowing the parents to care for him more easily. The children and adults with cerebral palsy have not been transformed from their previous status, although CCS has allowed them to become more independent, more ambulatory, and more communicative.


Chronic dorsal column stimulation via percutaneously inserted epidural electrodes. Preliminary results in 31 patients. 31 patients suffering from intractable pain associated with chronic low back syndrome, terminal cancer, and other disorders have been studied after an average 6 months' treatment by electrical stimulation of the spinal cord applied via electrodes inserted through a Tuohy needle into the epidural space. As judged by three different subjective rating methods, epidural stimulation successfully relieved otherwise intractable chronic pain in from 23 to 26 of the 31 patients. Reported improvements in the ability to perform various everyday activities, and elimination of drug usage by many patients, corroborate this finding. The side effects of stimulation, both as reported subjectively and as measured objectively by sensory testing, were not clinically significant. Spontaneous electrode displacements, leading to loss of analgesia and requiring minor surgery for repositioning, were encountered frequently, as were lead wire failures necessitating replacement. The partially implanted, externally powered stimulation system presently in use also suffers from problems of reliability and convenience to the patient.


Safety and clinical efficacy of implanted neuroaugmentive spinal devices for the relief of pain. When applied under the circumstances of minimal patient risk, as documented in this paper, implanted neuroaugmentive spinal devices are a reasonable means of therapy for selected severe pain problems. With presently developed screening techniques, a 50% good-to-excellent result was obtained in 198 patients predominently consisting of 'failed back surgery syndrome' (94%). These figures represent a very significant improvement in success of treatment for this group of patients when compared to other present modes of therapy. With continued optimization of the use of spinal neuroaugmentive devices, it is likely that future clinical success can be significantly improved.


Electrical stimulation of the conus medullaris in the paraplegic. A 5-year review. In 1970 we carried out the first electrode implantation of the conus medullaris of a 17-year-old male paraplegic to control the emptying of his paralyzed bladder. Our patient has used electromicturition for 6 years to successfully empty his bladder and prevent urinary infection. To date, a total of 11 paraplegic patients have been implanted (6 males, 5 females). The cause of the paraplegia was the result of trauma, and the implants were performed from 16 days to 15 years postinjury. All the patients had experienced numerous urinary infections and required constant catheter drainage, and it was the opinion of our urologic associate that current methods of control of the bladder problem were of no avail. The bladder was considered to be atonic in 7 patients and spastic in 4. The results indicate that after a follow-up of 1--6 years, 8 patients have complete control of voiding by electrical stimulation (4 female, 4 male). 2 of the males required partial sphincterotomy to improve emptying, but none of the females experienced sphincter interference. One male quadriparetic patient died 7 months postimplantation of pneumonia and hepatitis. There have been no infections related to the implantable device; however, 1 female broke the connecting wires to the spinal cord electrode during a paraplegic basketball game. In addition to the induced electrical contraction of the bladder, we have observed increased autonomic activity below the level of the spinal cord transection, improved defecation, reduction of spasticity in the paralyzed legs, penile erection in males, and reduction of decalcification of the long bones. This group of patients represents the longest use of an implantable electronic device to control bladder function.


Electrostimulation of the nervous system for patients with demyelinating and degenerative diseases of the nervous system and vascular diseases of the extremities. The results of electrostimulation of the spinal cord for symptoms other than that of pain are recorded in this publication. 50% of patients with multiple sclerosis, primary lateral sclerosis and hereditary spino-cerebellar disorders were observed to have enduring favourable changes in neurological function during the 15 to 27 months they have been followed. The patients who were the least severely disabled had the greatest amount of increased function and were benefitted the most by the stimulation. Those who had the fewest neurological pathways affected make the most rapid progress. For example, the patient with only an ataxic or spastic gait was observed to improve faster than the patient with an ataxic and a spastic gait. The long-term effect of electrostimulation of the spinal cord on patients with these diseases is unknown at the present time. The purpose of the stimulation is to increase neurological function so that the patient can live a better life style. It is not thought that the electrical current is responsible for a 'cure' of the basic disease process. Electrostimulation of the posterior spinal roots and spinal cord, while not new, has not been used extensively for the treatment of patients with arterial disease. The patients who have responded the most dramatically to electrostimulation are those with vasospastic disorders. A larger percentage of patients showed a greater response to implanted stimulation than to transcutaneous stimulation. Electrostimulation of the nervous system is not designed to replace standard therapeutic measures of treatment of patients with vascular disease but to supplement them.


PABA screening test for exocrine pancreatic function in infants and children. P-Amino-benzoic acid (PABA) is split specifically by pancreatic chymotrypsin from the synthetic tripeptide N-benzoyl-L-tyrosyl-PABA. The urinary excretion of absorbed PABA serves as an index for exocrine pancreatic function. The peptide (0.015 g/kg) was administered orally to 20 controls (aged between 5 months and 16 years), 6 patients with exocrine pancreatic insufficiency caused by cystic fibrosis (CF), and 9 newborn infants. In the controls the mean 6-hour PABA recovery was 58.5% (+/- 11.2 SD). Recovery in patients with CF was lower (P less than 0.001) with no overlap. In newborn infants the mean 6-hour PABA recovery was 23.4 (+/- 17.7 SD); overlapping in 3 instances with the results in CF patients. This simple, noninvasive test thus appears promising and merits further investigation in younger infants, especially newborns.


Effect of uptake inhibitors on the depletion of brain norepinephrine and serotonin after alpha-methyl-m-tyrosine administration to rats. The depletion of brain norepinephrine after alpha-methyl-m-tyrosine injection into rats was antagonized by pretreatment with an uptake inhibitor (protriptyline or chlorimipramine) but was not completely prevented. Administration of protriptyline after alpha-methyl-m-tyrosine injection, at a time when norepinephrine had been depleted, partially reversed the depletion. Serotonin depletion after alpha-methyl-m-tyrosine was not altered by pretreatment with fluoxetine, an inhibitor of uptake into serotonin neurons. Apparently part of the norepinephrine (but not serotonin) depletion occurring after alpha-methyl-m-tyrosine injection is due to the action of amine products that enter the norepinephrine neuron via the membrane uptake pump and whose presence within the nerve terminals is maintained by the uptake pump.


Acute renal failure secondary to interstitial lupus nephritis. A patient with systemic lupus erythematosus (SLE), followed up over a six-month period, exhibited numerous immunologic abnormalities and varied renal pathologic features. Initial findings included minimal glomerular lesions, serum antibodies directed solely against nuclear RNA protein, and lupus band test showing pure IgM deposition. These findings suggested a good prognosis. Subsequently, the patient developed acute renal failure secondary to an interstitial lupus nephritis, without progression of the glomerular abnormality. Serum antibodies to the nuclear non-nucleic acid macromolecule and single stranded and native DNA were demonstrated concurrently. New skin deposits of IgG and IgA in addition to IgM also were observed. This patient demonstrates the potential progression of lupus renal disease despite the initial favorable prognostic indicators.


Experience with implanted electrodes at Rancho Los Amigos Hospital. Implanted units, manufactured by Medtronic, Inc., have been implanted in 31 patients for treatment of drop-foot. The principal problem encountered in this series is inflammatory reaction, which was observed in 7 patients and was serious enough in 5 to require removal. Theree have been no failures of the implanted equipment for periods of up to 7.3 years, although there is currently a question in 1 patient. There has also been no documented damage to the nerve due to chronic stimulation. Fine wire electrodes have been implanted intraneurally in a series of animals and in 3 patients. Preliminary results look encouraging, and this approach seems to hold considerable promise for a new generation of electrode design.


Instrumentation problems with implanted neuroaugmentive devices. An analysis of the technical problems encountered in the implantation of 218 neurostimulation systems during the period 1971--1977 is reviewed. Multiple transmitter and antenna failures were seen. The most significant failures involved lead conductors and/or insulation in the internal portion of the system. The failures seen often required surgical revision. The observed incidence of lead wire failure appears to increase in relation to age of the devices. This survey indicates that significant material and design changes in the neuroaugmentive devices surveyed are necessary.


Depression of cell-mediated immunity in diabetes. Parameters of cell-mediated and humoral-mediated immunity were measured in ten infection-free, insulin-dependent, controlled diabetic patients and in ten similar but nondiabetic patients awaiting elective operations. Tests performed included total and differential leukocyte counts, neutrophil reduction of nitroblue tetrazolium, mitogen response of lymphocyte to phytohemagglutinin, ratio of thymus-derived to bone marrow-derived lymphocytes, serum immunoglobulins IgA, IgG, and IgM, macrophage inhibition factor, serum zinc, and reaction to skin test antigens. Diabetics had a significantly (P less than .05) decreased mean response response to phytoheagglutinin stimulation and a lowered ratio of thymus-derived to bone marrow-derived lymphocytes. These findings support the concept of depressed cell-mediated immunity in the controlled, adult diabetic and might explain the propensity of the uncontrolled diabetic to increased frequency and severity of bacterial infection.


Combined left ventricular aneurysm and coronary artery bypass surgery: long-term results of 100 consecutive patients. Forty-four percent of 2,367 patients who had operations for the complications of coronary atherosclerosis between 1971 and 1977 were noted to have major left ventricular wall motion abnormalities. Of this group, 100 patients required left ventricular aneurysm resections or plications (4.2%). There were 85 men and 15 women. Their average age was 52 years (range, 30 to 68 years). Concomitant coronary  artery bypass grafting was required in 95 patients. The operative mortality was 7% and the actuarial survival at six years was 78%. Patients were followed for an average of 31 months (range, 3 to 72 months). Eighty-eight percent of the survivors had excellent or good results with improvement of their functional status to the New York Heart Association classes I and II. Age, congestive heart failure, and poor residual left ventricular function had an adverse effect on the outcome of these patients. Concomitant coronary artery bypass grafting seems to have favorably influenced their outcome and functional recovery. Surgical judgment is of great importance in selecting which patients require left ventricular aneurysm resection.


Pain suppression by peripheral nerve stimulation. Chronic effects of implanted devices. This is a study of the long range effects of pain suppression obtained by electrical stimulation of peripheral nerves. These cases were followed during 12--46 months and evaluated personally and by questionnaires. Selection for surgery was done exclusively on the basis of the results of a preoperative peripheral nerve stimulation test. Of 37 cases observations, 18 were considered significantly relieved; that is, more than 50% of the intensity and/or duration of pain was consistently admitted. The results obtained in the acute preoperative trial could be reproduced indefinitely in some cases for as long as 46 months. Correlation of the results with the disease producing the pain revealed as benefitting for painful syndromes associated with peripheral nerve disorders, amputation, soft tissue injuries (nerves?), and some recurrent lumbar disc surgeries. Sciatic, ulnar and occipital nerve implantations were particularly rewarding. The best and worse results were analyzed. The complications appear to be largely preventable and of no serious consequences. Our analysis suggests that most failures take place within 2 years from implantation. Experience seems to be accumulating showing that a number of patients may receive sustained relief beyond this period.


Changing indications for the surgical treatment of unstable angina. From 1970 to 1977, 127 patients were operated on for unstable angina. On the basis of response to intensive medical therapy, patients were classified into a medically controlled, semielective surgery group (54 patients) and a medically uncontrolled, emergent/urgent surgical group (73 patients). There were five operative deaths. 1/54 in the medically controlled group (1.8%) and 4/73 (5%) in the medically uncontrolled group; 4/5 operative deaths occured with left main coronary stenosis. There were five late deaths during a follow-up period of 12 to 84 months, 37.5 with an actuarial survival of 83.5%. If patients with unstable angina can be medically controlled, operation can be delayed and the operative long-term survival is similar to that of elective coronary bypass. Patients who cannot be controlled medically, particularly those with left main coronary lesions, should be operated on urgently with selective use of preoperative balloon support.


Esophagogastric variceal hemorrhage: its treatment by percutaneous transephatic coronary vein occlusion. The angiographic technique percutaneous transhepatic coronary vein occlusion was used to treat esophagogastric variceal bleeding in 38 patients. There were two categories of patients: those actively bleeding who had not been controlled by continuous vasopressin infusion and/or Blakemore tube tamponade, and those with portal hypertension who were not actively bleeding at the time of transhepatic portal venography but who were at high risk for recurrent variceal hemorrhage. Coronary vein occlusion was achieved in 33 patients by (1) metal clip and cotton devices(one); (2) balloon catheter occlusion (two); (3) heat-treated autogenous clot and powdered absorbable gelatin sponge (Gelfoam) (13); and (4) Gelfoam strips soaked in sodium tetradecyl sulfate (17). Percutaneous coronary vein occlusion was effective in controlling 81% of the patients with actively bleeding varices. In patients who were not actively bleeding, percutaneous transhepatic coronary vein occlusion seemed to afford good protection for recurrent variceal hemorrhage.


Adjuvant methotrexate and leucovorin in head and neck squamous cancer. Two-year follow-up of a pilot project. A series of 17 patients with stage III and IV head and neck cancer received three cycles of methotrexate and leucovorin calcium during an interval of two weeks prior to surgery and/or radiotherapy. The dosage of methotrexate was sequentially escalated to produce mucositis (the usual dose-limiting toxicity). All patients have been followed up for a minimum of two years (range, 24 to 44 months). Two recurrences and two second primary tumors occurred in seven patients with stage III cancer, and one recurrence and one postoperative death (pulmonary embolism) occurred in ten patients with stage IV cancer. Seventy-six percent of patients survived, with 71% disease free. Mucositis occurred in 88% but was transient and prevented oral fluid intake in only one patient. Bone marrow suppression was usually mild and did not delay surgery. Escalation of dosage was thought to be important in achieving these encouraging results. A controlled trial is under way to better define the degree of efficacy of this regimen of adjuvant chemotherapy.


Rheumatic disease: exercise or immobilization? Though it may be true that, in the absence of a dependable cause, there is no single cure for inflammatory diseases of the locomotor system, nevertheless there is no reason for therapeutic nihilism. Much can be done to induce a remission in the disease while at the same time suppressing inflammation, relieving pain, preventing or correcting deformities, easing stiffness and increasing muscular control of the joints. However, no drug regime can be expected to achieve this, and reliance on drugs alone invariably leads to disappointing results, both for the doctor and patient. Hence every patient also should have a properly organized and supervised regime of physical methods of treatment. The relative value of rest or exercise remains controversial, and different considerations play a role in some of the disease processes. Thus in patients with active rheumatoid synovitis there seems no doubt that at first, extra rest to the inflamed joints is essential, but as the disease process is brought under control, the patient can be mobilized and made more active. In patients with ankylosing spondylitis, the emphasis should be placed on activity and exercise.


Laboratory diagnosis of rheumatic diseases. Laboratory investigations have been perhaps the most important factor in the development of our understanding and classification of rheumatic diseases. Provided they are used and interpreted appropriately, they can assist considerably in the diagnosis and management of these diseases. They are an important adjunct to clinical findings, but not a substitute for them.


Early radiologic signs of rheumatic disease. The radiographic manifestations of rheumatic disease are varied. Proper interpretation of the observed roentgen abnormalities requires knowledge of the underlying pathogenesis and characteristic distribution of the disease. With this knowledge the physician may provide accurate and early diagnosis in many patients with arthritis.


Bleeding oesophageal varices.

Bleeding oesophageal varices. At the Royal Prince Alfred Hospital, most patients with bleeding varices have been poor-risk alcoholics. A high proportion were receiving a State pension. The early mortality due to bleeding varices was 53%. This figure comprised a 60% mortality following conservative management and 40% after urgent shunt. All patients having urgent operations which were not portal decompression died. No patient who had an elective shunt died. In a mean follow-up period of 15.4 months, a further 14% of survivors died. No form of conservative management appeared to have much effect on the natural history of the bleeding. A blood replacement of more than five litres indicated that spontaneous cessation of haemorrhage was unlikely. Shunt operations usually controlled haemorrhage, but hepatorenal failure was common after the urgent shunts. The cost of operation was greater than that of conservative management, but in neither case was it considered excessive.


The effect of deoxyuridine, vitamin B12, folate and alcohol on the uptake of thymidine and on the deoxynucleoside triphosphate concentrations in normal and megaloblastic cells. Deoxyuridine suppression of labelled thymidine uptake tests were performed in the bone marrows of 58 patients with megaloblastic anaemia (haemoglobin less than 10.0 g/dl) and invariably gave values (range 10.3-58.8%) above the range in 16 control marrows (range 1.0-9.0%). Folinic acid corrected the test equally well in either folate or vitamin B12 deficiency, even at concentrations as low as 60 ng/ml. Folic acid also corrected the test equally well in either deficiency but was only effective at concentrations down to 5 microgram/ml. Vitamin B12 (100 microgram/ml) only corrected the test in vitamin B12 deficiency and 5-methyltetrahydrofolate only corrected the test in folate deficiency at the concentrations tested between 60 and 1.2 microgram/ml. Among 16 patients with subnormal serum levels of both vitamin B12 and folate, vitamin B12 partially corrected the test in eight, including all five with pernicious anaemia, but had no effect in the other eight. Despite the clear-cut results of the dU suppression test, measurement of the deoxythymidine triphosphate (dTTP) concentration in normal and megaloblastic phytohaemagglutinin stimulated lymphocyte cultures or short-term bone marrow cultures gave no clear-cut differences between normal and megaloblastic cells after addition of deoxyuridine nor did the addition of vitamin B12, folic acid or folinic acid either alone or with deoxyuridine produce consistent changes in the dTTP concentration in lymphocytes or bone marrow cells in megaloblastic anaemia. Alcohol caused a rise in deoxyadenosine triphosphate concentration in normal PHA-stimulated lymphocytes which was concentration dependent but caused no consistent change in any of the other three deoxynucleoside triphosphate (dNTP) concentrations. Diphenylhydantoin (10(-3)M, 10(-4)M) had no consistent effect on any of the four dNTP concentrations.


A comparative study of the buoyant density distribution of normal and malignant lymphocytes. Density distribution patterns of normal and malignant lymphocytes were compared following centrifugation to equilibrium on linear density gradients. For normal lymphocytes differences in the distribution patterns were observed between: (1) B and T cells, (2) central and peripheral cells, and (3) resting and activated cells. The findings suggested that cell density is determined by cell lineage the degree of differentiation and the stage of functional activation. Marked differences in the density distribution profiles were also observed among certain types of morphologically distinguishable lymphoproliferations. To some extent density analyses enabled the discrimination between CLL, follicular lymphomas and lymphoblastic lymphomas as well as between O-ALL and T-ALL. Density profiles of malignant lymphocytes failed to disclose any features specific for malignancies. But they revealed some similarities with distinct subsets of normal lymphocytes, i.e. between: (1) CLL and bone marrow lymphoid cells, (2) follicular lymphomas and follicular centre cells, and (3) lymphoblastic lymphomas and activated lymphocytes. These findings are further evidence supporting the hypothesis that the malignant transformation of phenotypically different lymphoproliferations takes place at different levels of lymphocyte differentiation.


Stimulation of in vitro granulocyte--macrophage colony formation by mouse heart conditioned medium. Medium conditioned by mouse heart tissue was found to contain colony-stimulating factor(s) (CSF) which produced in vitro colonies of granulocytes and/or macrophages with bone marrow cells of CBA mice. The action of this CSF type (CSFMHCM) was compared with that of post-endotoxin mouse serum (CSFES on colony formation by density subpopulations of colony-forming cells (CFU-c), separated by isopycnic centrifugation in a continous albumin density gradient. The number, size and morphology of colonies were examined. Mouse heart conditioned medium produced slightly more colonies and of larger size than endotoxin serum but the density distribution of their CFU-c were similar. Low density CFU-c produced predominately pure granulocytic colonies and high density ones predominately pure macrophage colonies with both types of CSF. There was no apparent relationship between colony size and CFU-c density.


Use of a simple visual assay of Willebrand factor for diagnosis and carrier identification. A visual assay of factor VIII-related Willebrand factor (VIIIR:WF) is described which utilizes formaldehyde-fixed platelets, end points being read in microflocculation tiles. Four dilutions of a sample can be assessed simultaneously, and the correlation with aggregometric assays is high (r = 0.91). Measurement error is 8.0% for a single assay in triplicate and less than 5% if an assay is repeated three times. The method has been used for 2 years by the coagulation genetics group at Chapel Hill for diagnosing subjects with von Willebrand's disease and assigning genotypes to members of families transmitting this disorder. Its utility in classifying known carriers of haemophilia A has also been examined, both in conjunction with assays of VIII:C and in a three-way test with assays of VIII:C and VIIIR:Ag. As predicted by the Lyon hypothesis, the rate of false negative diagnosis was higher than false positive diagnosis, but the overall rate of misclassification on single plasma samples was 7/51 = 13.7%. The error rate was the same whether discrimination was based upon assays of VIII:C vs. VIIIR:Ag, VIII:C vs. VIIIR:WF, or VIII:C vs. VIIIR:Ag vs VIIIR:WF, the same individuals being misclassified by each method. The observed rate of misclassification was well within the rates reported by others and very similar to our previous experience. We have concluded that this method of assaying VIIIR:WF is highly useful for diagnosing vWd, detecting inhibitors to VIIIR:WF, and examining large numbers of column fractions. It is a useful supplement, although it cannot yet substitute for, assays of VIIIR:Ag in detecting carriers of haemophilia A.


Streptococcus suis type II (group R) as a cause of endophthalmitis. A case is reported of a patient with bilateral endophthalmitis, meningitis, sensorineural deafness, labyrinthitis, and septicaemia due to Streptococcus suis type II (group R). The organism is known to produce epidemic meningitis, septicaemia, and purulent arthritis in piglets, but human infection is rare, and no other case reports of ocular infection are known. The organism was sensitive to penicillin at a minimum inhibitory concentration of 0.03 mg/1.


Does intracellular sodium regulate sodium transport across the mucosal surface of frog skin? A method has been devised to functionally remove the serosal membrane of frog skin. Skins treated in this way have no spontaneous potential. However, if sodium  gradients are placed across the tissues diffusion potentials and hence short-circuit currents of either sign, depending on the direction of the gradient, could be recorded. These short-circuit currents were completely imhibited by amiloride only from the mucosal face. However, the concentration of amiloride causing 50% inhibition of the short-circuit curent (Km) in treated skins was 2.3 . 10(-3)M, when a sodium gradient was applied from serosa to mucosa, whereas both in untreated skins without a sodium gradient and in treated skins with a mucosal to serosal sodium gradient, the Km of amiloride was 2 . 10(-7)-4 . 10(-7)M. The mechanism by which amiloride is able to inhibit the short-circuit currents of either sign is discussed.


Exploring fast electron transfer processes by magnetic fields. Photoinduced electron transfer generates radical pairs which recombine with 10(-9)10(-8)s by electron back-transfer to either singlet or triplet products. The product distribution determined by the spin motion of the unpaired electrons in the radical pairs is affected by external magnetic fields. The analysis of the magnetic field effect furnishes new information about electron transfer processes. Light-induced electron transfer in polar solvents and in the bacterial photosynthetic reaction center are discussed as examples.


Modulation of the primary electron transfer rate in photosynthetic reaction centers by reduction of a secondary acceptor. Photosynthetic application of picosecond spectroscopic techniques to bacterial reaction centers has led to a much greater understanding of the chemical nature of the initial steps of photosynthesis. Within 10 ps after excitation, a charge transfer complex is formed between the primary donor, a "special pair" of bacteriochlorophyll molecules, and a transient acceptor involving bacteriopheophytin. This complex subsequently decays in about 120 ps by donating the electron to a metastable acceptor, a tightly bound quinone.Recent experiments with conventional optical and ESR techniques have shown that when reaction centers are illuminated by a series of single turnover flashes in the presence of excess electron donors and acceptors, a stable, anionic ubisemiquinone is formed on odd flashes and destroyed on even flashes, suggesting that the acceptor region contains a second quinone that acts as a two-electron gate between the reaction center and subsequent electron transport events involving the quinone pool.Utilizing standard picosecond techniques, we have examined the decay of the charge transfer complex in reaction centers in the presence of the stable semiquinone, formed by flash illumination with a dye laser 10 s before excitation by a picosecond pulse. In this state the decay rate for the charge transfer complex is considerably slower than when no electron is present in the quinone acceptor region. This indicates fairly strong coupling between constituents of the reaction center-quinone acceptor complex and may provide a probe into the relative positions of the various components.


[Pharmacology of several aromatic amino acid decarboxylase inhibitors]. D,L-beta-(3,4-dihydroxyphenyl)lactic acid (I), D,L-beta-(5-hydroxyindolyl-3)lactic acid (II), and L-alpha-methyl-DOPA (III) inhibited the aromatic amino acid decarboxylase (AAAD) competitively. In difference from the compound III, I and II were not AAAD substrates. Compound II selectively suppressed decarboxylation of L-5-hydroxytryptophane. Compounds I and III potentiated the excitation caused in mice by L-DOPA and failed to influence the excitation due to L-5-hudroxytryptophane (L-5-HTP). Compound II attenuated the excitation caused by L-DOPA and L-5-HTP. Pyridoxine hydrochloride and pyridoxalphosphate attenated the excitation caused by L-DOPA and L-5-HTP. Compounds I and III eliminated this action of vitamins B6.


Postpartum haemorrhage after induced and spontaneous labour. The labour records of 1000 consecutive deliveries were studied to compare the incidence of postpartum haemorrhage after induced labour with that after spontaneous labour. The discovery of an increased incidence of postpartum haemorrhage in the induced group prompted further analysis of the incidence of haemorrhage among 3674 normal deliveries. This analysis confirmed that the incidence of postpartum haemorrhage was increased after induction of labour; among primiparous patients the increased incidence after induced labours was nearly twice that after spontaneous labours, even when only normal deliveries were considered. These findings indicate that postpartum haemorrhage is another complication of induction that needs to be taken into account when induction is being considered.


Do primary afferents from tooth-pulp cross the midline? Compound action potentials were recorded from the pulps of canine teeth in cats during stimulation of the inferior dental nerve, trigeminal ganglion or brain stem on one side. Recordings were also made from the inferior dental nerve while stimulating the canine pulps. No evidence for pulpal fibres crossing the midline was found.


Transient potassium currents in slow muscle fibers. Transient changes in potassium conductance in chronically depolarized slow muscle fibers have been studied using a voltage clamp method. The transient behavior included current decays from initial to steady state for hyperpolarizing and depolarizing voltage clamp steps. A two-pulse voltage clamp sequence (conditioning step followed by test step) showed the initial potassium test current to depend sigmoidally on conditioning potential implicating the involvement of a membrane-bound charged group in regulating potassium current.


Unexpected longevity of a patient with malignant pleural mesothelioma: report of a case. A 53-year-old male with untreated malignant pleural mesothelioma and with seven years survival time since the appearance of clinical symptoms is reported. Histopathological and immunological findings were at variance with those usually seen with mesothelioma. Both lymphocyte surface markers and lymphocyte function values were found to be within normal range; in contrast, in eleven mesothelioma patients who progressed and died, both numerical and functional defects in T and B lymphocytes were seen. There was potential for neighborhood asbestos exposure.


Comparative effects of citrovorum factor and carboxypeptidase G1 on cerebrospinal fluid-methotrexate pharmacokinetics. A comparison between citrovorum factor (CF) and carboxypeptidase G1 (CPDG1) rescue with respect to cerebrospinal fluid (CSF)-methotrexate (MTX) disappearance was studied in a patient with recurrent medulloblastoma who had a ventriculoperitoneal shunt. CPDG1 rescue resulted in a prolonged CSF-MTX half-life of 16.5-23 hours in comparison with CF rescue where the CSF-MTX half-life was 6.5-7.2 hours. There was a positive clinical response measured by loss of bone pain, increased physical activity, and almost complete clearing of CSF blast cells. CPDG1 rescue after high-dose MTX may provide more intense and selective treatment for meningeal neoplasms.


[Histochemistry as a diagnostic technic in the classification of hematopoietic-system tumors]. 106 tumours involving the haematopoietic system were examined using a wider range of histochemical methods, particularly enzymatic ones. The results were compared with other diagnostic techniques. A critical analysis of the results showed that as regards the purely diagnostic aspect the significance of histochemistry was severely limited to practically no more than tumours of the granulocytic series (myeloperoxidase and chloracetylesterase activities). Proof of alpha--mannosidase activity appeared to be greatly promising in the group of histiocytosis X. In the rest of the series, particularly in the lymphatic and thrombocytic series, the diagnostic significance of histochemistry proved to be either limited or non-existent. Considering the present state of methods used, the main advantage of histochemistry is in that it helps add details to the metabolic profile of the tumour under study. Some of the problems of the conception of the so called markers are discussed.


[Upper digestive fiberscopy in paediatrics in hiatal hernia and gastrointestinal haemorrhage]. On the basis of their experience of upper digestive fiberscopy in paediatrics in hiatal hernia and gastrointestinal haemorrhage, the authors wish to point out the value of this technique as a complement to radiological investigations. They indicate the possibility, in a specialised centre of the everyday use of currently available fiberscopic equipment, from the neonatal period onwards, and emphasize the definite contribution of endoscopic findings in the definition of indications for surgery in the pathological states which they have chosen to illustrate here.


Interrelations of the renal kallikrein-kinin system and renal prostaglandins in the conscious rat. Influence of mineralocorticoids. To investigate possible relationships between mineralocorticoids, the renal kallikreinkinin system, and renal prostaglandins, we studied the effects of aldosterone and deoxycorticosterone acetate (DOCA) and of an inhibitor of kallikrein, aprotinin, on the urinary excretion of kallikrein and prostaglandin E-like substance (PGE) by the conscious rat. Aldosterone (0.25 mg/day, sc), injected into six rats for 14 consecutive days, increased PGE and kallikrein excretion from 52.3 +/- 8.7 (mean +/- SE) ng/day and 29.8 +/- 3.0 U/day to 141.5 +/- 30.7 ng/day (P less than 0.02) and 105.6 +/- 28.1 U/day (P less than 0.05), respectively. Similarly, injections of DOCA (5 mg/day) into 14 rats increased the excretion of PGE and kallikrein, measured before and after 10 days of treatment, from 41.6 +/- 3.9 ng/day and 39.4 +/-4.9 U/day to 194.3 +/- 20.7 ng/day (P less than 0.001) and 90.6 +/- 14.7 U/day (P less than 0.001), respectively. Injections of aprotinin for 4 days (50,000 KIU twice daily, sc) in conjunction with DOCA into eight rats pretreated with the steroid for 10 days decreased the urinary excretion of kallikrein and PGE, measured on the 4th day of aprotinin administration, by 61% (P less than 0.01) and 80% (P less than 0.001), respectively. Urinary potassium excretion decreased throughout the course of aprotinin treatment, whereas sodium excretion and urine volume decreased during the first 2 days but subsequently returned toward control values. This study demonstrates that mineralocorticoids enhance the urinary excretion of PGE, and this effect appears to be a consequence of activation of the renal kallikrein-kinin system by the steroids. Thus, changes in the intrarenal activity of the kallikrein-kinin system may modulate renal prostaglandin release.


Improvement of myocardial perfusion and left ventricular function after coronary artery bypass grafting in patients with unstable angina. Changes in myocardial perfusion and left ventricular function were evaluated pre- and post-operatively (3--6 months) in 14 patients with unstable angina who underwent coronary artery bypass surgery. Perfusion was studied with intracoronary and intragraft injections of radiolabeled macroaggregated albumin particles. Of 20 abnormal perfusion areas identified preoperatively, 13 demonstrated improved perfusion post-operatively. Segmental analysis of the left ventriculogram demonstrated improved wall motion in 29 abnormally contracting segments; 18 normalized. Areas which showed improvement of left ventricular perfusion were invariably associated with improvement of left ventricular wall motion. Five patients showed improvement in perfusion and contraction in areas of apparent old myocardial infarction. Thirteen of the 14 patients had significantly less angina whether or not there was evidence of improved perfusion. However, only those patients who demonstrated improved perfusion had a significant improvement in their treadmill exercise tolerance postoperatively. Thus, patients with unstable angina have perfusion defects which may be reversed as a result of saphenous vein graft surgery. Reversal of these perfusion abnormalities results in improved left ventricular performance and better exercise tolerance postoperatively.


Combined aortic valve replacement and myocardial revascularization: results in 220 patients. During a 7.5-year period ending in June 1977, 220 patients underwent combined aortic valve replacement and myocardial revascularization. Early (30-day) mortality was 5.4% (12 patients), and was significantly affected by the development of perioperative myocardial infarction. For 23 patients with electrocardiographic and enzymatic evidence for definite infarction, hospital mortality was 17%; for 66 patients with probable infarction mortality was 5%; and for 116 patients without evidence for infarction mortality was 3%. The difference in mortality between the definite and no infarction groups was significant (p less than 0.01). The incidence of perioperative infarction was influenced by the type of myocardial protection employed during the operative procedure. Definite infarction occurred in 24% of 41 patients who had mild (28-32 degrees C), intermittent hypothermic coronary perfusion, in 9% of 142 patients with hypothermic ischemic arrest (myocardial temperature 20 to 27 degrees C) and in none of 22 patients with hypothermic, potassium-induced cardioplegia (myocardial temperature 8--18 degrees C). The difference in the rate of infarction between the coronary perfusion and the two hypothermic ischemic arrest groups was significant (p less than 0.01). The mean duration of followup for 100% of the hospital survivors was 22.5 months. Cumulative survival was 88% at 1 year and 77% at 3 years. These figures do not differ significantly from those for patients without coronary artery disease having isolated aortic valve replacement in our institution, and are superior to those reported for patients with coronary and aortic valve disease undergoing only aortic valve replacement. We conclude that combined aortic valve replacement and myocardial revascularization should be performed in all patients in whom the lesions coexist. Hypothermic ischemic arrest, preferably in combination with potassium-induced cardioplegia, provides the most myocardial protection during operation.


Sequential changes of alpha1-antitrypsin after surgical trauma. alpha1-Antitrypsin, an acute phase reactant, is known to rise following surgery [1,2]. It has not been previously reported, however, that the rise is preceded by an initial drop. Our study on a large group of surgical patients confirms the rise, but also shows that a significant drop in alpha1-antitrypsin levels occurs prior to the increase, if the serum samples are obtained immediately after completion of surgery. The observed decrease was independent of age, sex, type of surgery performed or the anesthetic administered. It is postulated that the decrease in serum levels is the result of migration of alpha1-antitrypsin to the tissues injured during surgery.