Acquired von Willebrand's syndrome and Ehlers-Danlos syndrome presenting with gastro-intestinal bleeding. The clinical and laboratory findings in a patient with severe gastro-intestinal bleeding and the Ehlers-Danlos syndrome are described. Coagulation studies and a lack of history of previous haemorrhage were consistent with a diagnosis of acquired von Willebrand's syndrome. His response to treatment with blood transfusion, Factor VIII, cimetidine, tranexamic acid and cyclophosphamide is described. Family studies revealed other members with Ehlers-Danlos syndrome but normal coagulation.


Cysticercosis of the fourth ventricle.

Cysticercosis of the fourth ventricle. We have reported a case of a racemose cyst of the fourth ventricle. The clinical and histopathological particularities are described. Among the clinical details, special emphasis is given on the intermittent attacks of obstructive hydrocephalus. Among the microscopical data, the demonstration of both scolex containing crystalline formations and parasite body in a racemose cyst is stressed as the most important finding for the diagnosis of this tapeworm species.


Prognostic significance of cardiopulmonary bypass time and postoperative serum enzyme levels in coronary surgery. The serum activity concentrations of creatine kinase MB isoenzyme (CK-MB) after coronary bypass operations are correlated with the duration of extracorporeal circulation (ECC) and aortic cross-clamping (AC), and the kinetics of serum enzyme appearance in this situation differ from the findings in acute myocardial infarction, as shown in previous papers. In the present investigation, the functional significance of different levels of postoperative serum CK-MB activity was studied in 21 patients by clinical re-examination, including exercise test, after 18 months. The possible long-term effect of extended periods of ECC and AC was further evaluated in another series of 21 patients, with coronary angiography and heart catheterization performed before and one year after coronary surgery. It is concluded that if successful revascularization is achieved by operation, the duration of ECC and AC, and the magnitude of postoperative CK-MB release, appear to have no significance for future myocardial function.


Percutaneous transhepatic portal venography in the diagnosis and management of gastroesophageal varices. Percutaneous transhepatic portal venography is a relatively safe method of obtaining both physiologic and morphologic information in patients with portal hypertension. Precise "road mapping" is performed, as well as measurement of free portal pressure. Additionally, transcatheter obliteration of gastroesophageal varices may produce effective cessation of hemorrhage in patients bleeding from this site, as was done on an emergency basis after failure of intra-arterial vasopressin infusion.


Resection of posterior ventricular aneurysm, replacement of mitral valve, and coronary bypass. A 58-year-old man had sudden and progressive heart failure after a severe myocardial infarction. Aggressive medical treatment consisting of diuretics, vasopressors, and digitalis failed to improve his condition significantly. Cardiac catheterization disclosed a critical stenosis in the left anterior descending branch of the left coronary artery, a large posterior left ventricul aneurysm, and severe mitral insufficiency. Intermittent third degree heart block developed after admission. Surgical correction resulted in a dramatic recovery, and three years after operation he is fully recovered and asymptomatic.


Multiple coronary bypass grafting: current mortality and morbidity. Although coronary artery bypass surgery has become increasingly popular in recent years, recent critical reports have cast doubt on its efficacy in certain groups of patients. Our report reviews a recent experience with multiple coronary bypass grafting for triple vessel disease. From March 1976 to October 1978, 276 patients received from three to nine coronary bypass grafts. Combined procedures including valve replacement and ventricular aneurysmectomy are included. There were two operative deaths (30 days) for a 0.7% operative mortality. Eleven patients (4%) sustained a perioperative infarction. Other nonfatal operative complications are reviewed. The overall safety and low morbidity allow us to recommend coronary bypass surgery to certain controversial subsets of patients, ie, those with high-grade double and triple vessel disease with stable angina.


Alpha 1-antitrypsin deficiency and status asthmaticus in a black teen-ager. The rare occurrence of alpha 1-antitrypsin deficiency in black Americans has led to the suggestion that routine screening of such subjects in needless. Our report of a black teen-ager with deficiency of this protease inhibitor in association with status asthmaticus suggests that at least relatively young black patients with otherwise unexplained chronic pulmonary disease should be tested for this defect.


[Computer processing of genetic patient data]. A code form for genetic patient data has been devised for computer purposes. This form provides for the clinical and laboratory diagnosis of genetic diseases. A Hewlett-Packard 2100 computer is used for storage and retrieval of the data. Three programmes are currently in use for the retrieval of data, namely programme RETREV, for retrieval of individual patient records; programme STAT9A, for the classification of chromosome results of patients referred with similar clinical diagnoses; and programme STA12A, for classification of chromosome abnormalities and for correlation with the indication for referral and other data. The possibilities for expansion of the programmes are discussed.


Popliteal false aneurysm complicating osteochondroma. A case report. A false aneurysm of the popliteal artery, caused by an exostosis in a patient with multiple exostoses, is described.


Intestinal vascular malformations.

Intestinal vascular malformations. Eleven patients with intestinal vascular malformations (VMs), all diagnosed by angiography, are presented. Two of the VMs were incidental findings in patients treated for other problems; the other nine patients all presented with gastrointestinal hemorrhage, and all had resection of the portion of intestine containing the VM. None has rebled. The specimens from these nine patients revealed a variety of histological findings. One VM was the vasculature of small bowel leiomyoma. Three other specimens contained obvious VMs without associated findings, and one specimen contained no identifiable pathology. In the remaining four specimens, a variety of inflammatory conditions were found on histological study, including one case of Crohn's disease and another of ischemic colitis. In only one of these specimens did we identify the VM. None of these last four cases conforms to the degenerative lesions described by Boley and his colleagues. Therefore, we propose a fourth type of VM that is associated with or perhaps secondary to another disease of the intestine. We precisely localized one VM in the duodenum during operation with the Doppler ultrasonic flow detector, thus enabling us to limit the extent of the resection. We also propose the use of this technique for pinpointing the area where sections should be made for histological study.


Cholesterol turnover in hereditary crystalline corneal dystrophy of Schnyder. A patient with hereditary crystalline corneal dystrophy of Schnyder required penetrating keratoplasty because of poor visual acuity. Blood cholesterol was labeled with 14C-cholesterol and 11 days later a penetrating keratoplasty was done. At the time of surgery, corneal levels of cholesterol were much higher than serum levels, showing that cornea is an active site for the uptake and storage of cholesterol in this disorder.


Rosette formation by buffalo (Bos bubalis) T and B lymphocytes. Buffalo (Bos bubalis) lymphocytes were purified and tested for their E and EAC rosette forming capacity as a marker for the detection of T and B cells, respectively. Sheep erythrocytes were found to form 17.7 per cent of E rosette with buffalo lymphocytes. This population of lymphocytes is believed to be T cell. Erythrocytes of guinea-pig, rabbit, hamster, rat, chicken, dog and donkey formed a lower percentage of rosettes. Five to 18.5 per cent of SRBC-EAC rosettes were detected with buffalo lymphocytes which are believed to be B cells.


[Synovial membrane permeability for plasma proteins and protein syntheses in rheumatic diseases]. 1. The permeability of the synovial membrane for proteins is larger in rheumatoid arthritis than in osteoarthrosis, in rheumatoid arthritis with high CRP activity larger than in rheumatoid arthritis with low CRP activity. 2. The diffusion by the synovial membrane in most plasma proteins takes place depending on their molecular weight. Of the 14 proteins tested only haptoglobin and fibrinogen did not follow this regularity. 3. While the non-immune proteins proved in the synovial fluid only come from the blood plasma, the immune globulins IgG, IgA, and IgM as well as lysozyme are partly also locally synthetized and enriched in rheumatoid arthritis. In rheumatoid arthritis lysozyme is present in the synovia not only in free, but in most cases also in cell-bound form.


[DNCB therapy of alopecia areata].

[DNCB therapy of alopecia areata]. Long-term treatment of alopecia areata with dinitrochlorobenzene is effective. During the last two and a half years, 227 patients who suffered, in the majority of cases, from total or subtotal hair loss, were treated by this method. Unilateral application of DNCB induced unilateral regrowth of hair in 88% of these patients. Under continuous treatment of both sides of the head, this initial response was followed by complete regrowth of hair in 78%. The same result could be obtained by application of squaric acid dibutylester, another potent contact allergen. This indicates that the essential mechanism is contact allergy. Possibly, the regrowth of hair is due to the induction of local nonspecific immunosuppression.


Rosette formation with mouse erythrocytes by lymphocytes from normal donors and patients with various diseases. Rosette formation of human lymphoid cells with mouse erythrocytes has recently been proposed as a marker for a subpopulation of B lymphocytes. In this work we studied the percentage of mouse rosette forming cells (MRFC) in normal and pathological conditions and compared them to the percentage of sheep rosette forming cells (SRFC) a marker for T lymphocytes. Peripheral blood lymphocytes (PBL) from normal donors contained 6.2 +/- 1.1% (mean +/- 1 S.D.) MRFC. High percentages of MRFC were found in CLL patients, and a slight increase was observed in patients with systemic lupus erythematosus. MRFC were absent in Bruton's type agammaglobulinaemia, but were normally present in patients with T cell defects. Cryopreservation of lymphocytes in 10% DMSO did not significantly affect the mean percentages of SRFC and MRFC, though a slight increase of the former and a small reduction of the latter was observed. Double binding experiments on peripheral blood lymphocytes showed a predominant association of MRFC with cells staining for surface IgM and/or IgD. In all samples tested, we also observed a small population of MRFC negative for sIgM or sIgD and a few sIgM or sIgD positive cells that did not rosette with mouse erythrocytes.


[Value of 201-thallium serial myocardial imaging in coronary heart disease (author's transl)]. There has been clinical evidence that a perfusion defect on a stress image fills in over time. The diagnostic value of initial and 120 min post exercise redistribution thallium-201 myocardial images (RMI) was determined in 120 pts. with suspected coronary heart disease (CAD), all of whom had coronary arteriography. Significant (greater than or equal to 75%) lesions were present in 88 pts. 30 pts. without CAD showed a normal tracer uptake immediately after exercise. Scintigrams taken 120 min after exercise revealed a decrease of 201-Tl concentration in every area of the myocardium. 80 pts. with CAD showed an area of decreased tracer uptake in the initial scans. 120 min RMI in 51 pts. revealed a segnificant increase (p greater than 0.01) of countrate time ratio in previous underperfused area. In 37 pts. persistent defects were present, in every case the defect correlated with the site of a myocardial infarction as determined by the finding of an akinetic area in the left ventricular angiogram. Thus RMI following a single dose of 201 Tl can differentiate between scar- and exercise-induced transient ischemia.


[Role of T- and B-cells in immunologic memory and the prolonged production of antibodies in the body]. The role of T and B cells in the immunological memory and prolonged antibody production in mice was studied; for this purpose CBA mice were immunized with SRBC in doses of 1 X 10(6) or 1 X 10(9) cells, decapitated 21--25 days later, and their spleen cells were treated with T or B antiserum and transferred in a dose 7 x 10(7) cells to syngeneic recipients treated with cyclophosphamide for suppressing their immunity. The treatment of the donor spleen cells with T or B antiserum resulted in a considerable decrease in the hemagglutinin level, as well as in the number of IgM- and IgG-forming cells. The transfer of T and B cells, mixed in equal amounts, to syngeneic recipients restored the immunological memory of the animals; in those cases when the mixture had the prevalence of T cells the restoration of the immunological memory was even more pronounced. The donor spleen cells treated with T or B antiserum, when tested for their ability to produce IgM- and IgG-forming cells in vitro (prior to their transfer to the recipient), showed a decrease in the production of IgM-forming cells (68%) and IgG-forming cells (74%) only under the action of B antiserum, whereas T antiserum had no influence on the production of IgM- and IgG-forming cells in vitro.


Changes in activity of the organon vasculosum laminae terminalis in the annual cycle in Rana temporaria. In 70 sexually mature male and femal Rana temporaria frogs captured in natural habitat, mean nuclear volumes for the cells of the pars ependymalis and pars parenchymalis of the organon vasculosum laminae terminalis (OVLT) were determined in seven characteristic stages in life. The mean nuclear volume for the cells of the pars ependymalis and pars parenchymalis of the OVLT showed distinct annual fluctuation. Maximum nuclear volume of the cells in both investigated parts of the OVLT were observed during the breeding period (Ist decade of April), and minimum volume of the nuclei of the pars ependymalis at the beginning of hibernation (IIIrd decade of October), and in the pars parenchymalis near the end of active life (Ist decade of September).


Electric field-induced polarization of photosynthetic membranes and reaction centers of Rhodopseudomonas sphaeroides, strain 1760-1. Electric fields of 10(5) V/cm cause the polarization of chromatophore and reaction center films prepared from photosynthesizing purple bacteria. Photosynthetic pigments, and in particular carotenoids, the absorption spectra of which are changed in response to electric fields (electrochromism), may serve as intrinsic indicators of the development of a polarized state. Polarization occurs due to changes in the orientation and the spatial position of different charged groups and particles. The field-induced polarized state can be fixed by exposure to low temperature (-120 degrees C). On being heated, the system relaxes to the initial state and this can be seen as a thermodepolarization current in an electric circuit. The effects of hydration, chemical modification or heat treatment on thermodepolarization current indicate the involvement of macromolecular components in the formation of a polarized state. In light-adapted samples the polarization effect is markedly greater, indicating that conformational changes occur during the primary photoact. It is assumed that the polarization of the reaction centers during electron transfer might be involved in the stabilization of separated charges and in the storage of energy.


[Fatty aldehydes of the plasmalogenic form of phosphatidylethanolamine in the vertebrate brain]. Studies have been made on the composition of fatty aldehydes of plasmalogen form of ethanolamine phospholipid in the brain of 28 fish species (13 cartilaginous and 15 teleost species, exhibiting different level of organization of the nervous system, marine and freshwater, dwelling in different habitats), as well as in the brain of other vertebrates. It was found that in all primitive species of cartilaginous fish high degree of unsaturation of fatty aldehydes is observed; in higher species the degree of unsaturation is much lower. The highest degree of unsaturation of fatty aldehydes was demonstrated for abyssal species of cartilaginous and teleost fishes. In warm-water species which dwell in the upper layers, unlike all other fishes investigated, almost all fatty aldehydes are saturated. The ratio of unsaturated and saturated fatty aldehydes in fish brain depends on the entity of phylogenetic and ecological factors. Studies on other vertebrates show that in warm-blooded animals saturated fatty aldehydes predominate, whereas in cold-blooded-unsaturated ones are more abundant.


Localization of Ca in muscles hindered in contraction by D2O. Electron microscopic autoradiographic investigations have been made to study the localization of Ca in the muscle the contraction of which was broken by soak in 99.8 per cent heavy water. The distribution of autoradiographic grains, originating from Ca-45 ingested by previous incubation, above longitudinal sections of these muscles were compared to the distribution of grains above muscles not treated in heavy water. Considerable difference in grain density was found above the A- and I-bands of the two different kinds of muscle and above their sarcoplasmic reticulum. The investigations concerning the sarcoplasmic reticulum were completed by the study of distribution of autoradiographic grains above the transversal sections of these muscles.


Bound potassium in muscle.

Bound potassium in muscle. Joining to the debate on "bound" or "freely diffusible" muscle potassium, which is still going on nowadays, direct current was perfused through couples of semimembranous and sartorius muscles of frog for 0.5 to 1 hour. It was done in normal, fresh condition on one muscle, and on the other after having it over-stimulated with ac of 110 V supposing that a part of K is immobilly bound in fresh muscles, but in the overtired muscles a part of K is released and becomes mobile. As mobile K+ migrates to the negative electrode, we could really find a difference between the behavior of the K+ content of fresh and over-stimulated muscles, in so far as there was much more K in the overstimulated muscle near the negative electrode than near the positive one, as compared with the K content of the corresponding parts of normal muscle.


Measles-adherent lymphocyte phenomenon of Levy in multiple sclerosis: normal reactivity of blood lymphocytes. The measles-adherent phenomenon described by Levy in multiple sclerosis was investigated by studying the rosetting effect of blood lymphocytes from multiple sclerosis patients and healthy controls on chronically measles infected heteroploid Hela cells (Lu 106). No significant difference in rosetting was observed, irrespective if a lymphocyte/virus infected Lu cell ratio of 10/1 or 50/1 was used. Therefore, the test is not discriminative for multiple sclerosis.


[Changes in blood lymphocytes and their subpopulation in patients with myeloblastic leukemia treated with cytostatic agents]. Quantitative determinations of lymphocytas were done in the active period of the disease, immediately after treatment by the COAP schedule and during remission. In 6 patients the determinations were done several times during 20 weeks of maintenance treatment. It was found that independently of the stage of the disease the absolute lymphocyte count and the counts of B and T populations were low, while that of lymphocyte O population was raised. It was observed that the reduced count concerned all 4 subclasses of lymphocytes B, that is those with surface receptors for IgA, IgM, IgG and IgE immunoglobulins. In remission the values of lymphocytes and their T and B subpopulations increased, failing, however, to reach the normal values. This rise was more pronounced in the case of lymphocytes T. Lymphocyte depression in these patients is explained by the authors as due mainly to intensive cytostatic treatment.


Screening of red-green defects of colour vision with pseudoisochromatic tests. Fifty red-green defectives and 100 normal subjects were examined with the second edition of the Boström-Kugelberg (BK II, 1972) series and the Ishihara complete edition (1976) of pseudoisochromatic plates. The results are related to those obtained with the first edition of the Boström-Kugelberg test (BK I, 1944) and the Boström test (II B, 1950) and to the classification of defects obtained with the Nagel anomaloscope. The 50 red-green defectives were originally selected by using a combination of the BK I and II B tests. The normal subjects also, passed this preliminary test, as well as an examination with the Nagel anomaloscope. In the final examinations performed under standardized conditions, three red-green defectives passed both the BK II and the BK I test, while eight defectives passed the Ishihara test. Combination of BK II or BK I test with the Ishihara test does not improve the result. Only one defective (a borderline case of protanomaly) passed the separate II B test. Normal subjects were not classified as colour defectives with any of the four pseudoisochromatic tests used. All normal subjects passed both the BK II and the Ishihara test. Classified as suspected red-green defectives (one misreading made in standardized conditions) were five normal subjects with the II B test and one normal subject with the BK I test. In the second edition of Boström-Kugelberg series, the plates numbered 3, 5, 11, 16 and 18 are clearly less effective than respective plates of the first edition. Only the plates numbered 1 and 10 have markedly improved in the second edition. Red-green defectives made on average 0.54 misreadings per plate in the BK II test as compared with respective 0.62 in BK I, 0.69 in the Ishihara and 0.56 in the II B test.


Vestibulospinal reflex activity in patients with adolescent idiopathic scoliosis. Postural effects during caloric labyrinthine stimulation recorded by stabilometry. Postural sway has been quantified with stabilometry during caloric labyrinthine stimulation in an erect posture in 49 patients, aged 10--16 years, with adolescent idiopathic scoliosis. Thirty-two healthy children of the same age constituted a control group. The scoliotic patients tended to have an increased postural sway during labyrinthine stimulation on the convex side compared to the effects on the concave side. Significant differences were observed when left and right scoliotic patients were compared with the controls. The results can be explained by an asymmetric sensitivity in the labyrinth or by a dysfunction in the postural control mechanisms at the brain stem level.


Vestibular unitary responses to visual stimulation in the rabbit. Vestibular nucleus (VN) neurons, identified by sinusoidal rotation about the vertical axis, were tested for their response to moving visual field, and to electric stimulation on the optic chiasm (OX) and super colliculus (SC). Incremental responses during the rotation were inhibited by visual stimulus in cerebellectomized animals. Single-pulse stimulation applied to the OX was ineffective in producing a positive response in these neurons as well or in any other unit. Thus, such a visual pathway to VN must be located inside the brainstem and contains multi-synapses. Effects of repetitive stimulations (60 Hz) to OX and SC were more predominant in the cerebellectomized animal than in the intact animal. Cerebellar inhibitory control on visual-vestibular kinkage was suggested.


Lymphocyte subpopulations and development of immune functions in the newborn baby. The distribution and dynamics of T, B and O cell populations were investigated in healthy term and preterm babies of 22-38 weeks gestational age, in relation to gestational age and birth weight, using the single slide method. Children 1-14 years old served as controls.


The influence of trichloroethylene and related drugs on the vestibular system. A previously described experimental model for studying the effect of industrial solvents on the vestibular system of rabbits has been applied to trichloroethylene. Estimation of trichloroethylene and its metabolites in blood and cerebrospinal fluid was performed by gas chromatography. Vestibular function was studied by recording nystagmus, induced by positional changes or accelerated rotation. At blood levels of trichloroethylene above 30 p.p.m. "positional nystagmus" develops. Two metabolites of trichloroethylene, chloral hydrate and trichloroethanol, which are known as central nervous system (CNS) depressants, did not induce this abnormal nystagmus. However, alpha-chloralose, a derivative of chloral hydrate, induced positional nystagmus and also a markedly exaggerated nystagmus developed during rotatory acceleration. It is suggested that solvents like trichloroethylene elicit vestibular disturbances by stimulation of central subcortical vestibulo-oculomotor connections. The stimulation may be caused by a blockage of inhibitory systems.


An experimental model of tryptic haemorrhagic enteropathy of the dog. To study the enteropathy characteristics of the shock state of the dog a simple experimental model has been developed. The cranial mesenteric artery was perfused with 2 micrograms/kg/min norepinephrine for an hour via a diagnostic cardiac catheter inserted under fluoroscopic control. This caused a "pharmacological occlusion" of the artery by local alpha receptor stimulation, and tryptic haemorrhagic enteritis was produced without hypovolaemia or assay operative procedure.


Effect of inhibitors of aerobic and anaerobic metabolism on the membrane potential oscillation induced by veratrine. 1. Veratrine-induced membrane potential oscillation is still apparent after the muscle has been treated with 1 mM KCN, or 1 mM NaN3, or 0.2 mM DNP, to inhibit oxidative metabolism. 2. The frequency of the membrane potential oscillation decreases reversibly in response to 1 mM phlorrhizin either in Na- or Li-Ringer solution. 3. Veratrine causes no membrane potential oscillation but only depolarization in muscles pretreated with 0.5 mM iodoacetic acid, eventually a few abortive waves can be observed. Iodoacetic acid also abolishes oscillation which has already developed. 4. On the basis of the present data it is suggested that rhythmic changes of metabolism may be related to the oscillation of membrane potential.


Chronic electrical stimulation of the thalamic unspecific activating system in a patient with coma due to midbrain and upper brain stem infarction. Chronic intermittent bipolar electrical stimulation of the left nucleus reticulatus polaris thalami was performed in a patient in a state of subcoma due to ischaemic infarction of wide medial parts of the midbrain, mainly the tegmentum, and the right-sided mediobasal parts of the forebrain. Stimulation immediately resulted in autonomic reactions and behavioural arousal reactions during the periods of stimulation. Longterm effect consisted of a rise in the level of clinical responsiveness for a period of seven weeks. A preexistent severe pneumonia disappeared completely after one week of stimulation and returned after seven weeks. The results are discussed on the basis of the pathoanatomical findings and of the physiological functions of the damaged as well as of the stimulated areas.


Studies on cell motility in inflammation. II. The in vivo effect of anti-inflammatory and anti-rheumatic drugs on chemotaxis in vitro. Two systems were used to test the effect of anti-inflammatory and anti-rheumatic drugs on chemotactic activity of cell-free exudates and also on the chemotactic responsiveness of exudate leucocytes. (1) Inflammatory cell-free exudates from treated rats were tested for their chemotactic activity on exudate leucocytes from untreated rats. (2) Polymorph and mononuclear cells from treated rats were tested for their responsiveness to the chemotactic activity of cell-free exudates from untreated rats. Levamisole, coumarin and D-penicillamine were ineffective in (1) and (2). Colchicine reduced chemotaxis of polymorphs in both systems (1) and (2), whereas no effect was observed on mononuclears. Naproxen was more effective in reducing the chemotaxis of polymorphs compared with mononuclears in systems (1) and (2). In contrast, indomethacin and dexamethasone reduced the chemotaxis of both polymorph and mononuclear cells in systems (1) and (21. Of the drugs tested dexamethasone exhibited the highest potency. These results emphasize the necessity for studying both cellular and humoral factors in the evaluation of the action of anti-inflammatory drugs on chemotaxis.


Psychosocial status of patients randomly assigned to medical or surgical therapy for chronic stable angina. Aspects of social and psychologic functioning are compared for 51 patients randomly assigned to surgical or medical management of chronic stable angina. No differences were found between the two groups in work status, social activity, adequacy of family functioning, perceived health, life satisfaction, memory span, extent of anxiety, hypochondriasis and hysteria. However, surgically treated patients were significantly less depressed and more likely to report improvement in health and family functioning after the initiation of treatment. It is concluded that the psychologic and social outcomes appear slightly more favorable in patients treated surgically than in those treated medically.


Idiopathic juvenile osteoporosis.

Idiopathic juvenile osteoporosis. We describe four children with idiopathic juvenile osteoporosis. All patients were initially seen between the ages of 10 and 13 years and spontaneously recovered following puberty. We review 27 similar cases reported in the literature. Theories on the cause of idiopathic osteoporosis in children are critically discussed. It may be that milder forms remain undiagnosed because of the self-limited course and the pain being confused with a variety of rheumatic disorders. It would be worth observing these cases to determine if they are otherwise prone to development of osteoporosis during pregnancy or in later life.


Angioimmunoblastic lymphadenopathy with dysproteinemia. A pathogenetic link between lymphoid proliferation and malignant lymphoma. Two patients with angioimmunoblastic lymphadenopathy with dysproteinemia (AILD) were studied. Both patients had marked increases in all three major immunoglobulin classes, and both lacked suppressor cell activity in vitro. These findings are consistent with the theory that AILD is a defectively regulated immune response to an unidentified antigen(s) and could provide clues to the pathogenesis of other lymphoproliferative disorders as well.


Prevalence of treatment regimens for children considered to be hyperactive. In a representative sample of San Francisco Bay Area school children, 1.2% were identified as hyperactive by parents, teachers, and physicians. Estimates of the prevalence of various treatment regimens indicate that 58% of those so identified received medication in one year, but a much larger number (86%) will be given medication at some time. Initiation of treatment appears to coincide with stressful times in school, and multiple treatment approaches are generally employed.


Autonomic cardiovascular control during submergence and emergence in bullfrogs. Unanesthetized bullfrogs were involuntarily submerged for 25 min in air-saturated water at 21 degrees C. Significant bradycardia was observed while systemic blood pressure was maintained or slightly elevated. Upon emergence, heart rates immediately returned to presubmergence levels or higher. Similar responses were observed in frogs allowed to make voluntary dives in an experimental tank. Heart rates of vagal-blocked (atropine) frogs did not change during submergence or emergence. beta-Adrenergic blockade (propranolol) had little effect on the magnitude of heart rate decrease during submergence or its increase upon emergence. After alpha-adrenergic blockade (phentolamine), frogs developed diving bradycardia while undergoing a fall in systemic blood pressure. It is concluded that, in bullfrogs, 1) bradycardia during submergence is entirely due to increased vagal activity, 2) the immediate cardiac rate increase upon emergence apparently results from a decrease in vagal tone; and 3) there appears to be no substantial reciprocal sympathetic influence on heart rate during alterations in vagal tone.


Amebic liver abscess with hemobilia.

Amebic liver abscess with hemobilia. A patient with hemobilia complicating an amebic liver abscess is described. The diagnosis was based on selective arteriography. The hemobilia did not stop with antiamebic treatment or ligation of the right hepatic artery. Successful results followed right hemihepatectomy.


Circulation of cerebrospinal fluid in the bullfrog, Rana catesbiana. In order to demonstrate features of the cerebrospinal fluid (CSF) path in the amphibian, 2--6 microliters of either Evans Blue-albumin (EBA) or ferrocyanide were injected into the ventricular system of anesthetized bullfrogs. The animals were sacrificed 1 to 135 minutes after injection by either quick freezing (EBA injections) or fixative perfusion (ferrocyanide injections). The contents of the cranial and vertebral cavities were then examined grossly and histologically for distribution of the tracers. In all animals, the tracers were seen throughout the ventricular cavity and in the subarachnoid space surrounding the caudal hindbrain. The site of communication between these two fluid spaces was the posterior tela of the hindbrain. Within this tela, "pores" were found between groups of pavement-like ependymal cells. In many animals, tracer was also observed in the vertebral subarachnoid and epidural spaces, adjacent to spinal nerve roots. In three EBA-injected animals, this tracer was also seen in the subcardinal lymph spaces. These findings suggest that the subarachnoid space in the bullfrog communicates functionally with the ventricular system by way of specialized "pores" in the posterior tela of the hindbrain. There is also indication of movement of fluid within the subarachnoid space which is predominately caudal in direction, with a primary absorptive path for CSF that consists of a perineural route to the lymphatic system.


Lymphocyte markers, serum thymic factor and IgE in IgA deficiency. Eleven patients having a selective IgA deficiency had very low T-cell percentages assessed by using E-rosettes, active E-rosetts and an anti-human anti-T-lymphocyte antigen serum. B-cells were normal or slightly decreased. IgE concentrations were often low. Patients with serum IgA under 50 IU/ml often had elevated serum IgE values and low T-cell percentages. Serum thymic factor dosages were correlated with the E-rosette assay.


Levamisole in systemic lupus erythematosus. Two patients with systemic lupus erythematosus complicated with lupus nephritis were treated with levamisole, an immunomodulator. Clinical features, including urinary protein excretion and creatine clearance, were restored in one patient, also immunoparameters such as ANA, Ig-bearing cell number and PHA-skin test. The other patient did not respond to levamisole but did respond to cyclophosphamide.


Lymphocyte-associated immune responses to canine distemper and measles viruses in distemper-infected gnotobiotic dogs. Cellular immune responses of peripheral blood lymphocytes to canine distemper virus and measles virus were determined in vaccinated or infected gnotobiotic dogs, using the technique of syncytia inhibition. Cross-reactivity between viruses was detected in both groups of dogs. Peak responses in vaccinated dogs occurred 11 days after vaccination and declined to base-line levels by 3 weeks, whereas responses in infected dogs were present 30 days after inoculation. Fractionation experiments with peripheral blood lymphocytes indicated that synctia inhibition is probably mediated by T lymphocytes.


Hereditary multiple exostoses: clinicopathologic features of a comparative study in horses and man. Investigation of hereditary multiple exostoses in horses under controlled research conditions for 10 years and epidemiologic studies that have spanned up to five generations of human families contain notable similarities. The present study demonstrated that a single dominant autosomal gene is responsible for hereditary multiple exostoses in horses and man. Affected individuals transmit this trait to approximately 50% of their progeny, whereas nonaffected individuals do not transmit the condition to their offspring. The tumors in affected horses are most often present at birth. They tend to be bilaterally symmetrical and vary in size, shape, and texture. Those on the legs generally do not appear to enlarge as the animal matures, but others, notably those on the ribs and scapulae, enlarge until skeletal maturity, Histologically, the tumors appear as typical ostosteochondromas in both horse and man. Sarcomatous transformations have not yet been detected after 10 years in horses, although such changes are occasionally reported in the similar disease condition in man. The remarkable similarities of hereditary multiple exostoses in the horse to that in man provide an opportunity for comparative biomedical study.


Abnormal interaction of alpha 1-antitrypsin and leukocyte elastolytic activity in patients with chronic obstructive pulmonary disease. The interaction of serum alpha 1-antitrypsin with leukocyte elastolytic activity was examined in 71 patients with chronic obstructive pulmonary disease and 46 normal subjects. Residual elastolytic activity was present despite adequate amounts of alpha1-antitrypsin in 33 of the 71 patients compared to 6 of the 46 normal control subjects (P less than 0.001). This elastolytic activity was completely abolished by a specific  human leukocyte elastase inhibitor. A crossover study designed to detect the source of this abnormal activity revealed that the plasma fraction containing alpha 1-antitrypsin was responsible for inadequate inhibition in 30 of the 39 cases. The residual elastolytic activity from a given patient did not correlate with the serum alpha 1-antitrypsin concentration, alpha 1-antitrypsin phenotype, or history of smoking. Our data suggest that the abnormal interaction of alhpa 1-antitrypsin with leukocyte elastolytic activity is an important additional variable in the gensis of chronic obstructive pulmonary disease.


[Ampicillin-resistant "Haemophilus": their detection and occurrence in Brussels area (author's transl)]. Three hundred and five strains of Haemophilus (129 H. influenzae, 55 H. parainfluenzae, 97 H. parahaemolyticus, 5 H. haemolyticus, 10 H. paraphrophilus and 9 H. paraphrohaemolyticus) isolated from pathological material over the year 1976, were systematically tested for beta-lactamase production. Only 2 strains of H. parainfluenzae produced this enzyme. Both were able to transfer ampicillin resistance to Escherichia coli K12. All strains but the two beta-lactamase producers were susceptible to penicillin G, ampicillin and cephalotin. However, the correct interpretation of the susceptibility tests needed the microscopic observation of prints of the inhibition zones surrounding the disks: all sensitive strains presented a hazy growth around the disks which corresponded to the presence of spheroplasts; this phenomenon was not observed with the 2 beta-lactamase producing strains of H. parainfluenzae which grew up to the disks but presented a typical bacillary form.


[The enlarged trans-labyrinthine approach of House. The use of this method in the surgical treatment of cerebello-pontine angle tumours (author's transl)]. The authors report a series of 43 cases of cerebello-pontine angle tumours operated by an oto-neuro-surgical team. The approaches used were, once the supra-petrous approach, twice the posterior fossa, 12 times a combined trans-labyrinthine and posterior fossa approach, and 28 times the enlarged trans-labyrinthine route. This last approach, which is now being used exclusively for the last two years, is described in detail. Forty-three tumours operated on broke down into 40 neurinomas, 2 meningiomas and 1 malignant melanoma. The size of the tumours varied from 1 cm to 11 cm in diameter. Overall statistics show 9.3% of deaths and 65% of functioning facial nerves. The statistics for the nelarged trans-labyrinthine route (the last 28 cases) are: 10.7% of deaths and 75% of functioning facial nerves. In the enlarged trans-labyrinthine route, there is no complication and no mortality in the small and medium-sized tumours, i.e. up to 4 cm in diameter.


[The venous drainage of the vestibular labyrinth in man (author's transl)]. The venous drainage of the vestibular division of the inner ear presents two different and separated routes. One, draining the central part of the sensorial areas (maculae and cristae), ends up into the vein of the cochlear aqueduct. The other drains the perypheral part of the sensorial areas as well as the simple endolymphatic walls and ends into the vein of the vestibular aqueduct. The latter vein shows close relationships to the endolymphatic sac.


HLA frequencies, diabetes mellitus and autoimmunity in Turner's patients and their relatives. In a preliminary study of twenty-three patients with gonadal dysgenesis (Turner's syndrome) and their families, correlation was sought between their serum defined HLA allele frequencies and their known tendencies toward abnormal immune responses and diabetes mellitus, since individuals with the latter disorders have been shown to have an increased frequency of certain HLA types. We were unable to demonstrate an association between these major serum-defined histocompatibility antigens, immune homeostasis disturbances and sex chromosome aneuploidy in this group. It is felt, however, that testing involving the patterns of HLA-D and "HLA-D related" antigen frequencies should be obtained to further evaluate the possibility of such an association.


A cascade of chromosomal aberrations in three generations: a fragile 16q, an extra fragment and a rearranged 20. The propositus' grandmother has a fragile 16q and belongs to a large family where several abortions and congenital anomalies were recorded. The portion distal to the fragile site was inherited as an extra fragment by the proposius' father who has it in 11% of his lymphocyte metaphases. This phenotypically harmless fragment has a high affinity for satellited chromosomes and was probably a main factor in the causation of the rearrangement that produced the partial trisomy 20p found in the propositus.


[Oocyte meiosis in a trisomy 18 fetus. Behavior of the supernumerary chromosome and identification of the 18 bivalent]. Associations of the three n degrees 18 chromosomes were studied in a trisomy 18 fetus (the chromosomal constitution of which had been identified by amniocentesis). The three classes of associations observed were those observed in other trisomic organisms:trivalent, trivalent presenting an important asynaptic region, and bivalent accompanied by a univalent. In addition, the sequence was established of chromomeres, the number of which varied from 18 to 23 depending on the degree of chromosome contraction. In elongated pachytene oocyte bivalents each G-band of mitotic metaphase chromosomes could be subdivided into several sub-bands.


Report of a trisomy 8p infant with carrier father. This report describes an infant with fatal congenital heart disease, cleft palate, brain malformations, and trisomy 8p resultant from the paternal balanced reciprocal translocation, rcp(8;15) (p11;p11). Review of six previously reported trisomy 8p patients (resultant from parental balanced translocation in each instance) revealed severe mental retardation in five, short stature in all, and a variety of brain, skeletal, and cardiac defects. The features of the seven trisomy 8p patients reviewed here are not sufficiently similar to suggest a distinct dysmorphic syndrome. In addition the features differ from those in the trisomy 8 mosaicism syndrome, in which the mental retardation and malformations are generally less severe.


Chromosome 6q- and associated malformations. A dysmorphic retarded fourteen-mont-old female with partial deletion of the long arm of chromosome 6 is presented. The breakpoint in 6q was in region 2, probably at band 5. Eight other infants with a deletion involving the long arm of chromosome 6, including five with a ring chromosome 6, have been reported. The affected individuals have in common microcephaly, micrognathia, hypotonia and psychomotor retardation, but do not appear to have a distinctive phenotype.


Oligohydramnios syndrome and XYY karyotype. A case of oligohydramnios syndrome was found to have an XYY karyotype and an inherited 9qh inversion. It is suggested that normal and extra Y chromosomes are a predisposing factor in the aetiology of severe congenital renal anomalies.


Trisomy 12p due to an adjacent 1 segregation of a maternal reciprocal translocation t(12;18) (p11;q23). A 5, 9-12-year-old with trisomy 12 pdue to a maternal reciprocal translocation adjacent 1 segregation is presented. Comparison of his phenotype with that of other patients reported in the literature confirm the existence of a trisomy syndrome.


[Intercalary deletions of 9q].

[Intercalary deletions of 9q]. Two interstitial deletions of different segments of 9q are reported. The first deletion (9/11q22) was seen in an 8-year-old boy with severe psychomotor retardation and descrete facial dysmorphism. The second deletion (9q32q34) was seen in a 5-month-old boy with a very peculiar cranio-facial dysmorphism including brachycephaly, frontal bossing, a deep nasal bridge, a short nose, and absence of triradii b, c and d.


[A satellited Y chromosome].

[A satellited Y chromosome]. A previous report in 1967 on the observation of a satellited Y chromosome found in a French Canadian family line is confirmed by the use of the ammoniacal silver procedure which stains selectively the nucleolus organizer regions (NORs) in acrocentric human chromosomes. There is evidence that this peculiar chromosome results from the translocation to the distal end of the Y chromosome long arms of a satellited segment from a D or G autosome.


[Satellited Y chromosome (Yqs) and nucleolar organizer occurring de novo]. A satellited Y chromosome (Yqs) occurred de novo in a boy born to first cousins. The child had severe mental retardation, facial dysmorphism, congenital heart disease, and amaurosis, and died at 6 months and of age. The chromosome rearrangement was confirmed by R-, G-, C-, Q-, and Ag-NOR banding. Its significance and the difficulty of genetic counseling are discussed.


[Trisomy 13qter by tandem duplication 46, XX, dir dup 13 (q21 qter), 9qh+]. A tandem translocation of chromosome 13-46,XXdup13(q21 leads to qter)--occurred de novo in a patient with the following features: normal birthweight; early feeding difficulties; mild psychomotor retardation; low set hairline on the forehead; thick eyebrows; long, upturned eyelashes; pointed nose; micrognathia; large, flat, posteriorly rotated ears; multiple hemangiomata; normal hematological status. The hypothesis of an unequal crossing-over is discussed, as well as the possibility of constructing a phenotypic map of chromosome 13.


Development of nystagmus in response to vestibular stimulation in infants. Nystagmus in response to perotatory stimulation by torsion swing or ice-cold caloric (ICC) irrigation of the ear canals was studied in 276 infants from birth to 12 months of age. The percentage of positive responses to perotatory stimulation correlated with gestational age and weight at birth during the first 3 months of life and became comparable among groups by 6 months of age. The quality of perotatory nystagmus did not differ among groups. A direct correlation between the caloric-induced intensity and duration of nystagmus with gestational age and weight at birth was noted during the first 3 months of life. Premature infants showed the weakest responses, and term-delivered, large for gestational age children the strongest responses. ICC-induced nystagmus reached comparable levels for all groups by 6 months except for premature infants, in whom comparable responses were attainedby 9 months of age. Vestibular responses mature over time, with patterns that correlate with gestational age and weight at birth.


Colour-blindness in Colombia.

Colour-blindness in Colombia. The frequency of defective colour vision was studied in two neighbouring villages in the Andes Mountains of Colombia using AO H-R-R Pseudoisochromatic plates. The frequency of the red-green colour-blindness in males is almost the same in both villages (2.36-2.53%), being similar to frequencies reported for other mestizo' populations in Latin America. In one of the communities, families in which colour-blindness occurred were wealthier (P is less than 0.05) than non-colour-blind families, but there were no significant differences by colour vision class in numbers of surviving children nor mother's marriage age. These findings are consistent with the idea that in societies at the agricultural level, colour-blindness is selectively neutral. The association of colour-blindness with higher socio-economic status is expected given the history of European conquest in the New World, and suggests that the major cause of varying rates of the defect in Latin American populations is socio-economic heterogeneity and by inference different degrees of European-Amerindian admixture.


Emergence of resistance to cefamandole: possible role of cefoxitin-inducible beta-lactamases. Selection of resistance to cefamandole has been observed, and the drug has failed to protect animals lethally infected with certain Enterobacteriaceae that appeared to be highly susceptible in vitro. Using spectrophotometric assays, some of these organisms were found to produce beta-lactamases highly active against cefamandole. Cefoxitin, a poor enzyme substrate, was found to be superior to both cephalothin and cefamandole in induction of these enzymes. A simple disk induction test was developed and used to examine 147 Enterobacteriaceae for production of these beta-lactamases. The enzymes were found in 69% of cephalothin-resistant, cefamandole-susceptible strains and in only 3% of strains susceptible to both cephalothin and cefamandole. They were most prevalent among isolates of Enterobacter, indole-positive Proteus, and Serratia. Since selection of resistance and therapeutic failures have occurred most often among these genera, the relationship between presence of inducible enzymes and outcome of therapy should be examined further in humans.


Effect of mitogen-induced stimulation on DNase activity in lymphocytes. The effect of mitogen-induced stimulation in spleen cells and thymocytes of BALB/c mice on acid DNase-activity levels was determined. Increase in thymidine uptake induced by either LPS or ConA in spleen cells and by ConA in thymocytes was invariably accompanied by parallel increase in acid DNase activity. Treatment with mitomycin C (spleen cells) or with an excess dose of ConA (thymocytes) led to sharp reduction in acid DNase activity concomitant with marked drop in thymidine uptake. The results obtained suggest that rise in acid DNase activity takes place during the process of lymphocyte activation by mitogens.


Chloramphenicol bioassay.

Chloramphenicol bioassay. An accurate plate diffusion bioassay for chloramphenicol is described, in which the fast-replicating Beneckea natriegens and 1.5% salt agar are used. Zones of inhibition were well defined after 3 h, and the limit of sensitivity of the method was around 2 mug/ml. The concurrent presence of gentamicin did not influence the assay. The assay is simple to carry out and duplicate assays can be performed with as little as 100 mug of capillary blood.


Effects of Fildes enrichment on antibiotic susceptibility testing of Haemophilus influenzae in the Autobac. The results of this investigation showed that the Autobac could be used to determine the susceptibility of Haemophilus influenzae to ampicillin, chloramphenicol, and tetracycline when eugonic broth was supplemented with 1.5% Fildes enrichment. An excellent correlation was obtained between the susceptibilities as determined by the agar dilution minimal inhibitory concentration method and the Autobac. For ampicillin all H. influenzae isolates with minimal inhibitory concentrations of </=1 mug/ml had light scattering indexes of >/=0.60. Those isolates with minimal inhibitory concentrations of >/=4 mug/ml had light scattering indexes of </=0.49. For chloramphenicol and tetracycline all isolates had minimal inhibitory concentrations of </=1 mug/ml and light scattering indexes of >/=0.71.


Iron deficiency in children with coeliac disease on treatment with gluten-free diet. Role of intestinal blood loss. 24 children in whom coeliac disease had been diagnosed between one and 10 years earlier were re-examined for intestinal loss of iron and activity of the disease. Mild iron deficiency by laboratory criteria and by response to iron medication was common. The children with biopsy evidence of flat mucosa or intraepithelial lymphocytosis had a greater iron loss in their stools than those patients with normal, or almost normal, histology. The data suggest that loss of iron was mainly due to intestinal blood loss rather than to shedding of mucosal cells. We conclude that treatment with iron is indicated in many children with coeliac disease as the increased losses of iron persist for long periods although absorption of iron seems to improve or be negligibly affected.


Supressor activity of peripheral blood mononuclear cells in patients with chronic discoid lupus erythematosus. Significantly increased suppressor activity of peripheral blood mononuclear cells was demonstrated in patients suffering from chronic discoid lupus erythematosus.


The role of the surgeon in percutaneous transluminal dilation of coronary stenosis. Percutaneous transluminal dilation (PTD) of coronary artery stenosis is performed by means of a balloon-tipped catheter introduced from a peripheral artery. It was attempted in 45 patients; stenosis was passed in 33 and was successfully dilated in 28 patients (62%). The method failed in 17 patients: in 6 of them an abrupt closure of a stenosed artery or a beginning infarction necessitated an emergency revascularization. There were no deaths or serious complications, but an infarction developed in 1 patient despite immediate bypass grafting. PTD was successful in 5 out of 7 patients who had recurrent angina after previous coronary bypass grafting: in 2 of them stenosis of a distal coronary artery and in 3 a stenosed bypass graft were dilated. PTD is a new method of treatment of coronary artery disease and is an addition rather than an alternative to coronary bypass grafting. The best results can be expected in patients with single-vessel disease, with a short history of angina (less than 1 year), and with narrow, noncalcified proximal stenosis. Some late complications of bypass grafting are also amenable to this method of treatment.


Prophylactic coronary artery grafting in patients with few or no symptoms. Fifty-five patients who underwent prophylactic coronary artery grafting were followed for 4 to 8 years. Sixteen patients had no angina, and 39 were in New York Heart Association Functional Class I. Twenty-one patients had single-vessel disease, 13 had double-vessel disease, and 27, triple-vessel disease. A total of 101 grafts were inserted. There were no operative deaths. Two patients suffered a perioperative myocardial infarction (MI), and 3 were reoperated on for persistent bleeding. Early after operation, 9 of the 45 grafts were occluded. At 1 year, 2 patients had occlusion of all grafts, and 1 had similar findings at 5 years. There were 4 late deaths, 3 related to coronary artery disease. Seven patients sustained a late MI. Thirty-one of the 51 survivors (60.8%) seen late (mean, 69.3 months) after operation were free from angina; 14 were in Class I and 6, Class II. It is apparent from this retrospective study that patients such as these stand to benefit little from prophylactic revascularization. Longevity may be increased, however, in patients who are asymptomatic after MI.


Factors influencing patency of saphenous vein grafts. To determine factors affecting saphenous vein graft patency, 218 grafts in 66 unselected patients were studied angiographically 1 year after operation. Fourteen variables were extracted from the angiograms, electrocardiograms, and intraoperative flow measurements to assess their predictive value. Preoperative coronary vessel diameter and degree of proximal stenosis measured angiographically correlated significantly with graft patency. Graft patency for vessels greater than 1.5 mm in diameter with greater than 70% stenosis was 93% (98 out of 105). Vessel size at operation and the presence of reactive hyperemia greater than 20 ml per minute also correlated significantly with graft patency. Reactive hyperemia increased significantly as the severity of the vessel stenosis proximal to the graft increased, thus suggesting a mechanism for the improved patency rate of grafts to more stenotic vessels. The patency rate of the end-to-side component of a continuity graft (left anterior descending coronary artery and diagonal or marginal artery in 1 graft) was 100% and of the side-to-side component, 77%. This study shows that the patency rate for saphenous vein grafts compares favorably with the reported patency for internal mammary grafts when critical factors such as vessel size (greater than 1.5 mm) and degree of stenosis (greater than 70%) are considered in bypass selection.


Possible hazard of timed-release aspirin in a patient with pancreatic insufficiency. An episode of severe small intestinal hemorrhage occurred in a cystic fibrosis patient having pancreatic insufficiency and receiving timed-release aspirin therapy for disabling hypertrophic pulmonary osteoarthropathy. The increased acidity of small intestinal contents due to decreased bicarbonate secretion observed in patients with pancreatic insufficiency may alter the luminal environment and result in mucosal erosions and/or ulcerations in association with the presence of aspirin. Thus, physicians should be aware of the possibility that timed-release aspirin causes small intestinal hemorrhage in such patients.


Post-capillary venules in the human lymph nodes draining malignant tumours. A total of 275 regional lymph nodes from an equal number of patients with either breast, bronchial, colorectal, gastric or kidney carcinoma were histologically evaluated with special attention focused on the structure of the post-capillary venules (PVC). Three grades of PVC were differentiated on the basis of their endothelial cell morphology and the post-capillary venule score (PCV-S) was calculated for each of the nodes studied. The highest PCV-S was obtained for the control nodes followed in decreasing order by the breast carcinoma series, the renal carcinomas, the gastric carcinomas, the colorectal carcinomas and the bronchial carcinomas. The statistical significances between the PCV-S values obtained were calculated and the possible relationship between these structural changes in PCV endothelium and the T-lymphocyte recirculation was discussed.


T and B lymphocytes in peripheral blood in anesthesiologic personnel. T and B lymphocytes were determined quantitatively in anesthesiologic personnel by the rosette technique. Percentages of T lymphocytes were diminished, while the lymphatic system of the peripheral blood showed signs of stimulation. The drop in percentages of T lymphocytes was greater in physicians compared with anesthesiologic nurses.


Pharmacologic properties of some derivatives of N-(2-carboxyphenyl)-4-phenoxyacetamide. Three new inhibitors of prostaglandin (PG) synthetase: N-(2-carboxy-4-chlorophenyl)-phenoxyacetamide (ZR 29), N-(2-carobxy-4-chlorophenyl/-bromophenoxyacetamide (ZR-32), N-(2-carboxy-4-chlorophenyl)-4' - nitrophenoxyacetamide (ZR-35), in doses of 30-100-200 mg/kg p.o. inhibited edema in an acute inflammatory model, ZR-32 inhibited formation of granuloma. In the chronic inflammatory model, ZR-32 exerted strongest activity in the second and third weeks. ZR-32 demonstrated strong analgesic activity in the test of stimulation with electric current and in the "hot plate" test, besides antipyretic activity. Both compounds weekly irritated the gastric mucosa. In the tests applied, these compounds had no effect on the CNS. Their acute to toxicity was substantially lower than that of acetylsalicyclic aid and indomethacin.


Dominant optic atrophy. The clinical profile. We examined 24 individuals in four family pedigrees with dominantly inherited optic atrophy (DOA); 12 patients met the criteria for diagnosis of DOA and two were suspect. Our data indicate that (1) insidious onset usually occurred in childhood, but subjective visual symptoms may evolve in adulthood; (2) visual function was minimally (20/25) to moderately (20/400) abnormal, could be strikingly asymmetric in an individual (eg, 20/30 in the right eye and 20/200 in the left eye), and showed considerable intrafamilial and interfamilial variation; (3) visual field defects consisted of central and centrocecal scotomas, but no peripheral isopter abnormalities were found; (4) color-vision screening with Hardy-Rand-Rittler plates revealed dyschromotopsias, but only Farnsworth-Munsell 100-hue examination disclosed the typical tritan defects; (5) pattern-reversal visual-evoked responses were characterized by diminished amplitudes and prolonged latencies, consistent with neural conduction defects; (6) disc pallor was limited to the temporal segment in all cases, and 16 of 24 eyes showed focal temporal excavation, which is probably pathognomonic of DOA.


The vestibular aqueduct and endolymphatic sac and duct in endolymphatic hydrops. The histologic features of the endolymphatic sac and duct in 23 serially sectioned temporal bones with idiopathic or secondary endolymphatic hydrops were blindly compared with 22 randomly selected, normal temporal bones. In idiopathic hydrops, the pars rugosa of the endolymphatic sac extended out of the vestibular aqueduct into the dura in 29% of bones, compared with none of normal bones (P less than .01). In the other 71%, the pars rugosa in the vestibular aqueduct was surrounded by dura more commonly than normal. Functional studies are required to assess the relationship of these findings to hydrops. In secondary hydrops (eg, due to labyrinthitis), the endolymphatic duct was obliterated in the isthmus of the vestibular aqueduct by bone or fibrosis in seven of nine bones. Because of similar ossification and fibrosis elsewhere in the vestibular labyrinth, a direct relationship with hydrops cannot be assumed.


Murine cutaneous leishmaniasis: disease patterns in intact and nude mice of various genotypes and examination of some differences between normal and infected macrophages. The course of the disease, cutaneous leishmaniasis, caused by the intracellular protozoan parasite Leishmania tropica, differs markedly amongst various common inbred mouse strains. After intradermal injection of 1 x 10(6) promastigotes to young female specific pathogen-free (SPF) derived mice, persistent infection characterized by an expanding ulcerous lesion is seen in BALB/c and DBA/2 mice. In the strains CBA/H, C3H/He and A/J, lesions resolve within 8 weeks, and in C57B1/6 mice no real lesion typical of cutaneous leishmaniasis develops at the injection site. NZB mice are highly resistant. Macrophages harvested from the thioglycollate-stimulated peritoneal cavity of NZB and C57B1/6 mice appear to differ from macrophages of the other mouse strains in not supporting multiplication of L. tropica organisms in vitro. Nevertheless, hypothymic nude (nu/nu) mice of C57B1/6 genotype, as well as CBA/H-nu/nu and BALB/c-nu/nu mice, develop large lesions with metastases to other cutaneous and visceral locations. In the intact mice in which infection resolves spontaneously, resistance to reinfection is complete. Using mouse antipromastigote sera and an indirect fluorescent antibody test in carefully controlled experiments, L. tropica antigens were detected on in vitro infected macrophages of both highly susceptible BALB/c and relatively resistant CBA/H genotypes. After incubation with a crude soluble antigen preparation from cultured promastigotes, infected BALB/c macrophages differed from infected CBA/H macrophages (and uninfected macrophages of both genotypes) in being unable to sensitize syngeneic recipients for a delayed-type hypersensitivity response to that antigen. When infected and uninfected macrophages were used as "blocking cells" in an in vitro alloreactive cytotoxic T cell system involving cells from congenic mice, evidence was obtained for reduced H-2d expression on infected macrophages of the susceptible mouse strains, BALB/c. The data in this model system of cutaneous leishmaniasis raise the possibility that genetic susceptibility is associated with both a permissive macrophage and defective T cell recognition of parasite antigens on infected macrophages. Defective recognition may be the result of reduced functional expression of H-2d antigens on infected BALB/c macrophages required for efficient recognition by syngeneic T cells of one or more subpopulations.


Identification of histidine residues that act as zinc ligands in beta-lactamase II by differential tritium exchange. 1. Four histidine-containing peptides have been isolated from a tryptic digest of the Zn2+-requiring beta-lactamase II from Bacillus cereus. One of these peptides probably contains two histidine residues. 2. The presence of one equivalent of Zn2+ substantially decreases the rate of exchange of the C-2 proton in at least two and probably three of the histidine residues of these peptides for solvent 3H. 3. It is concluded that peptides containing at least two of the three histidine residues acting as Zn2+ ligands at the tighter Zn2+-binding site of beta-lactamase II have been identified.


Serum complement abnormalities in the antinuclear antibody-positive relatives of children with systemic lupus erythematosus. Serum C3, C4 and total hemolytic complement (CH50) levels were measured for 21 children with systemic lupus erythematosus (SLE) and 81 first degree relatives. The mean serum C4 and CH50 levels of the 12 relatives with antinuclear antibodies (ANA( were depressed to levels equal to those of the index cases. A similar depression was not found for C3, nor was there a depression of C3, C4, or CH50 in the relatives without ANA. If preexistent depression of C4 levels can be documented in the ANA-positive relatives of index cases, it may provide an explanation for the inherited predisposition to SLE in some families.


Antigenic bacterial polysaccharide in rheumatoid synovial effusions. Phenol-water extracted rheumatoid synovial fluids and synovial fluid leukocytes contain an antigen immunologically identical to the Proprionibacterium group bacteria. The antigen was identified by counter-immunoelectrophoresis in 70% of rheumatoid synovial fluid leukocyte pellets and in 60% of rheumatoid synovial fluids. It was also present in 6% of nonrheumatoid fluids and in 22% of nonrheumatoid inflammatory fluid leukocytes. Antigen was not detectable in synovial samples before extraction. Synovial and bacterial antigens were further purified by proteolytic digestion and Sepharose 4B column chromatography. Biochemical and enzymatic studies of bacterial and synovial antigens were similar and consistent with a high molecular weight polysaccharide. Serum antibody to bacterial and synovial antigens was significantly less frequent in rheumatoid sera than in normal controls. The significance of demonstrating a bacterial polysaccharide primarily in rheumatoid synovial effusions is discussed.


T lymphocyte subpopulations in synovial fluid of patients with rheumatic disease. The proportion of T lymphocytes with receptors for the Fc portion of IgG (TG cells) of IgM (TM cells) was determined in synovial fluid and blood of 16 patients with various rheumatic diseases including rheumatoid arthritis, psoriatic arthritis, and ankylosing spondylitis. The percentage of TG cells was low in all synovial fluid samples, whereas in the patients' blood the percentage was higher than or equal to the level found in the blood of healthy subjects. Eight patients also had a lower level of TM cells in synovial fluid as compared to the percentage found in the blood of healthy donors. In the patients' blood the percentage of TM cells was usually within the normal range. Thus the proportion of T cells lacking either receptor (Tnull cells) was higher in synovial fluid than in blood. This pattern of low TG cell and high Tnull cell percentages was found in the synovial fluid of patients with various rheumatic diseases and thus seems to be a general feature of chronic inflammatory joint exudates.


[Admissable and limited extrapolation of pharmacological and toxicological results on man demonstrated on selected examples (author's transl)]. The results of comparative studies with respect to pharmacological, toxicological, pharmacokinetic and clinico-pharmacological effects of the non-steroid anti-inflammatory drugs 4-[4-(2'-fluorobiphenylyl)]-4-hydroxycrotonic acid and 3-(2'-fluoro-4-biphenylyl)-butyric acid as well as the intrinsic activities of their metabolites in vitro are discussed. The variation in gastrointestinal side effects caused by the two compounds in different species can conveniently be explained in terms of different pharmacokinetic pathways. This leads to a species dependent formation of pharmaco-dynamically active metabolites.


Inhibitory effect of cimetidine, an antagonist of histamine H2-receptor, on gastric acid secretion in isolated frog stomach and in anesthetized young chicken. Gastric antisecretory effect of a new histamine H2-receptor antagonist, N"-cyano-N-methyl-N'-[2-T5-methyl-imidazol-4-yl)-methylthioethyl]guanidine (cimetidine), was studied in isolated bullfrog gastric mucosa and in anesthetized young chicken preparation with acute gastric fistulae. Cimetidine inhibited dose-dependently the secretory responses of frog gastric mucosa to histamine, and parallel shift of the concentration-response curve of histamine by cimetidine indicated the competitive character of the antagonism. However, cimetidine inhibited the stimulatory action of methacholine and gastrin as well as histamine on gastric secretion. Cimetidine pretreatment protected the histamine sensitivity of gastric mucosa from the irreversible blocking action of dibenamine. It was also found in the chicken preparation that cimetidine strongly depressed the maximal acid secretory response to histamine as well as to tetragastrin or methacholine. These results may afford the evidence indicating the specific action of cimetidine and the involvement of histamine-related mechanism in the action of the other two secretagogues.


[Lipase and alpha amylase of chick embryo pancreas and of chickens of various ages]. In chicken embryo pancreas on the 19th day the activity of alpha-amylase and especially of lipase is very low; it increases soon after until it reaches its highest level in 36 hours old chick. Then it falls considerably on the 2nd and 10th day of normal diet; finally it starts again: in fact in three months old chickens the activity of alpha-amylase is equal to thirty-six hours old chick's, while lipase's is lower than this last one.


Effect of aluminum hydroxide on diflunisal absorption. 1 The effect of aluminum hydroxide on the oral absorption of diflunisal was studied in healthy subjects. 2 Relative bioavailability of the oral diflunisal dose (500 mg) was estimated by comparison of the areas under plasma concentration versus time curves, and comparison of the amount of drug (unchanged + glucuronides) excreted in the urine. 3 From the AUC-method, a relative bioavailability of 0.60 was calculated. A similar value (F = 0.63) was obtained from the urinary excretion data. 4 The results indicate that co-administration of aluminum hydroxide reduces the bioavailability of oral diflusinal by about 40%.


Surface phenotyping, histology and the nature of non-Hodgkin lymphoma in 157 patients. In a study of 157 patients with lymphoid malignancy, the phenotype of the tumour cells was correlated with the histological classification of the tumour using the Rappaport and the Kiel classifications. The markers used included E, Fc gamma, Fc micron (IgM) and C3d rosetting, estimation of SIg and CyIg, and tests for the expression of HTLA, Ia and ALL. Repeat biopsy specimens were studied in 23 of these patients. The phenotypic features of lymphoblastic malignancy indicated B-cell, T-cell and ALL-positive null-cell tumours in this group. Immunoblastic lymphomas were predominantly of non-capping B-cell type, but T-cell immunoblastic lymphoma occurred in 2 patients. Immunoblastic lymphomas of receptor-silent cells occur, and are ALL- and HTLA-negative. In the category of diffuse, poorly differentiated lymphocytic lymphomas, most cases are of centroblastic and centrocytic tumour of diffuse type, but pure centrocytic tumours and centroblastic tumours occur. The dominant phenotype in this group is of B cells expressing C3d receptors. Nodular poorly differentiated lymphocytic lymphomas (Rappaport) are classified as centroblastic and centrocytic follicular (Kiel) and most express SIg+ C3d+ phenotype. The frequency of this phenotype appeared the same in both diffuse and nodular poorly differentiated lymphocytic neoplasms. The Rappaport group of diffuse well-differentiated lymphocytic lymphoma includes 2 Kiel categories, malignant lymphoma lymphocytic, and malignant lymphoma lymphoplasmacytoid. Cells of the former tumour were considered to be immature B cells resembling those seen in CLL, and characteristically expressing SIg weakly, with a high frequency of single kappa light chain. Cells of the latter tumour are by contrast mature, and are related to the centroblastic and centrocytic follicular tumour by their histogenesis and phenotypic features. Repeat biopsy examinations indicate that T-cell predominance occurs in the prodromal phase of B-cell-predominant tumours of SIg+ C3d+ phenotype. It is concluded that non-Hodgkin lymphoma can be divided into 2 categories: (1) tumours of immature immunologically incompetent cells of lymphoblastic histology and with phenotypic features akin to T, B and Null-cell ALL, and (2) tumours of differentiated lymphocytes expressing the phenotypic features of B lymphocytes, with maturation arrested at one of several stages of an antigen-dependent immune response.


Low natural-killer-cell activity in familial melanoma patients and their relatives. Patients with melanoma who had one or more close relatives with melanoma were studied for their natural-killer-cell (NK) activity against cultured melanoma cells and Chang cells. A high proportion of the patients and their relatives were found to have low NK activity against these target cells. In most of the patients this could not be attributed to general depression of their immune function, since B- and T-cell numbers and the mitogenic response to PHA were within normal limits. The levels of NK activity of the patients and their relatives were found to be significantly correlated, suggesting that the NK activity in these families may have been genetically (or environmentally) determined. Several genetic markers were examined in the patients and their relatives for association with the disease state and NK activity. No association with HLA antigens or ABO blood groups was detected, but there was a low incidence of the Rhesus negative phenotype in the patients (the Rh phenotype had previously been associated with high NK activity). The present results indicate that NK activity has a familial association in families with a high incidence of melanoma, and raise the question whether low NK activity may be one of the predisposing factors in the development of familial melanoma.


Response of intestinal globule leucocytes in the mouse during a Trichinella spiralis infection and its independence of intestinal mast cells. We have previously reported that intestinal mast cells represent a separate population of mast cells which is thymus- (T-) dependent. In this paper we examine whether the appearance of these cells is dependent on thymus-dependent antibodies or thymus serum factor(s). The response of intestinal mast cells and globule leucocytes to a Trichinella spiralis infection was therefore studied in congenitally athymic (nude) mice after treatment with specific anti-T. spiralis hyperimmune serum or normal mouse serum from thymus-bearing litter-mates. However, transfer of both types of serum did not lead to an intestinal mast cell response. It was concluded that the presence of an intact thymus or T-dependent cellular reactions and/or their products are essential for appearance of intestinal mast cells. In contrast infected athymic mice reacted with a minor reponse of globule leucocytes irrespective of the serum transfer. Occasionally metachromatic intra-epithelially located cells with toluidine-blue-positive granules, believed to be globule leucocytes, showed mitotic figures. Metachromatic cells were observed occasionally within the lumen of the gut. These data were interpreted as supporting the idea that the globule leucocyte is a cell sui generis and independent of the intestinal mast cell.


The separation of Willebrand factor from factor VIII-related antigen. The three activities associated with factor VIII--coagulant (VIII:C), antigenic (VIIIR:Ag), and platelet agglutinating or Willebrand factor (VIIIR:WF)--have been separated by sequential antibody affinity chromatography, utilizing a rabbit antibody to factor VIII and a spontaneous human antibody to VIII:C. Normal plasma differentially lost its factor VIII-related antigen following passage over the rabbit antibody column. Subsequent passage of the VIIIR:Ag-depleted plasma over the human antibody column resulted in the loss of VIII:C activity, with retention of the Willebrand factor activity, antigen being partially recovered from the heterologous antibody column. These experiments demonstrate that it is possible to separate two of the factor VIII activities, VIIIR:Ag and VIIIR:WF, which are usually regarded as properties of a single molecule.


Factor VIII procoagulant activity, factor VIII related antigen and von Willebrand factor in newborn cord blood. The mean level of factor VIII procoagulant acitivity (VIII:C) and factor VIII related antigen (VIIIR:AG) was normal in 100 newborn cord plasmas, whereas that of von Willebrand factor (VIIIR:WF) activity was slightly lower than normal. On crossed immunoelectrophoresis, 20 of 50 newborn infants had an increased anodal mobility of VIIIR:AG. When the cord plasma showing an abnormal electrophoretic pattern was mixed with normal plasma, two precipitation peaks with a broad base were found. Similar mixing experiments with the abnormal cord plasma and plasma from a patient with atypical von Willebrand's disease did not normalize the electrophoretic mobility of VIIIR:AG. Gel filtration of the cord plasma with an abnormal electrophoretic pattern of VIII:AG, showed that the three activities were all detected at the position corresponding to a molecular weight of about 800 000. The results suggest the presence of qualitative abnormalities of the factor VIII molecule in half of full-term newborn cord plasma.


Chasing Crohn's.

Chasing Crohn's. The importance of Crohn's disease in oral pathology is briefly discussed. A series of experiments using immunofluorescent tracing techniques is described which culminates in the identification of a Crohn's-specific circulating antibody which reacts with autologous oral mucosa in vitro. It is suggested that this forms the basis of a diagnostic test.


The relationship of K+ efflux at the inner surface of the isolated frog skin epithelium to the short circuit current. Isolated frog skins (without chorion) were incubated with 42K+ Ringers' solution, bathing the internal surface for 2 h. All the K+ contained in the frog skin was equilibrated in specific activity with external 42K+. The kinetics of the washout of 42K+ from the internal surface of the skin exhibits one fast and one slow exponential component. Amiloride reduces the release of 42K+ corresponding to both components without affecting the K+ content of the skin. Ouabain increases the loss of 42K+ of the slow component by 200%. Since the total K+ in the skin decreases to 25% of its original value both compartments are affected. The results suggest that two distinct functional compartments exist defined by two 42K+ release ratios and that because of the large K+ contents of these compartments both are intracellular. The relation with the transepithelial Na+ transport and the morphological identification of these compartments is discussed.


Membranes of Rhodopseudomonas sphaeroides. VI. Isolation of a fraction enriched in newly synthesized bacteriochlorophyll alpha-protein complexes. Radioactivity eventually destined for the chromatophore membrane of Rhodopseudomonas sphaeroides was shown in pulse-chase studies to appear first in a distinct pigmented fraction. The material formed an upper pigmented band which sedimented more slowly than chromatophores when cell-free extracts were subjected directly to rate-zone sedimentation on sucrose density gradients. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis indicated that the purified fraction contained polypeptide bands of the same mobility as light-harvesting bacteriochlorophyll alpha and reaction center-associated protein components of chromatophores; these were superimposed upon cytoplasmic membrane polypeptides. The pulse-chase relation was confined mainly to the polypeptide components of these pigment-protein complexes. It is suggested that the isolated fraction may be derived from sites at which new membrane invagination is initiated.


Selective destruction of 5-hydroxytryptamine receptors by neuraminidase. The responses of isolated frog skin to 5-hydroxytryptamine (increased active sodium transport and decreased passive chloride permeability) are diminished by incubation with the enzymes neuraminidase and N-acetylneuraminic acid aldolase but only in the absence of Ca2+ and presence of EDTA. The responses induced by oxytocin, adrenalin and aldosterone are unaffected by enzyme treatment.


Interferon-sensitive expression of membrane-bound IgM on a human lymphoid B cell line persistently infected with herpes simplex virus. While both primary and chronic herpes simplex virus (HSV) in vitro infections of a Burkitt's lymphoma-derived cell line (Raji) were similarly characterized by the induction of IgG-Fe receptors in about 50% of cells, the persistent HSV infection of Raji cells was also accompanied by an induction of surface-bound IgM in approximately 80% of cells. This IgM induction was suppressed by treating the infected cells with interferon, but not with phosphonoacetic acid, an inhibitor of herpes virus DNA polymerase activity. The fact that only the cell population which had lost this IgM expression was superinfectable would suggest that this Ig may play a protective role (e.g. antibody activity?) against HSV.


A novel lymphocyte differentiating factor in serum of patients with mycosis fungoides and Sezary syndrome. Sera from 13 patients with mycosis fungoides and 2 with Sezary syndrome were tested for activity that induces lymphocyte differentiation. Induction of Thy-1.2 antigen and surface immunoglobulin were used, respectively, to measure T- and B-cell differentiation. The indicator cells were null lymphocytes from the spleens of congenitally athymic nude mice. Normal serum induced some T-cell but no B-cell differentiation. The T-cell-inducing activity was ascribed to thymic hormone and declined with advancing age. A totally different pattern emerged with patient serum. T-cell-inducing activity was significantly more active than in normal serum (p less than 0.001). This activity did not decline with advancing age and was not inhibited by a concentration of ubiquitin, which blocks nonspecific beta-adrenergic induction. B-cell-inducing activity was also present. This novel serum factor (or factors) is a potent inducer of T- and B-lymphocyte differentiation and is associated with neoplastic lymphoproliferation of the T-cell series.


Specificity of lactoferrin as an inhibitor of granulocyte-macrophage colony-stimulating activity production from fetal mouse liver cells. Fetal mouse liver cultures capable of producing both erythropoietin (Ep) and granulocyte-macrophage colony stimulating activity (GM-CSA) were used to study the specificity of lactoferrin as an inhibitor of the production of GM-CSA. Both a granulocyte-derived colony-inhibiting activity (CIA) and lactoferrin inhibited GM-CSA production while having no effect on Ep production. These results demonstrate the specificity of lactoferrin for GM-CSA production.


[T-zone lymphoma--clinical symptoms, therapy, and prognosis (author's transl)]. The clinical symptoms, response to therapy, and prognosis of T-zone lymphoma were analyzed in 32 cases. This recently defined lymphoma entity developed relatively quickly with generalized lymphadenopathy and general malaise. Hepatomegaly and/or splenomegaly and skin efflorescence were frequent presenting symptoms. A few patients showed hyperimmune reactions and occasionally severe autoimmune hemolytic anemia. The erythrocyte sedimentation rate was usually markedly elevated. There was sometimes a polyclonal increase in serum immunoglobulin, sometimes a reduction. Blood and bone marrow smears from a few patients showed occasional atypical lymphocytes. A remarkable finding was the frequent involvement of lung or pleura (40.5% of the patients). The prognosis is unfavorable. Most of the patients were in stages III or IV at the time of diagnosis. Massive infiltration of organs, resistance to routine therapy, and decreasing resistance to infection resulted in death soon after diagnosis. The probability of survival was 0.48 in the first year after diagnosis. The prognosis for patients in stages I and II was clearly better than that for patients in stages III and IV.


Acid alpha-naphthyl acetate esterase in hairy cell leukemia cells and other cells of the hematopoietic system. The activity of alpha-naphthyl acetate esterase at an acid pH (ANAE) was investigated in 10 cases of hairy cell leukemia. All 10 cases, including two cases with only a few tartrate-resistant acid phosphatase-reactive cells, revealed a moderate or strong ANAE reaction. There was a characteristic pattern of activity consisting of small, medium-size, or large distinct granules often distributed in a semicircle in the cytoplasm, but sparing the nucleus of hairy cells. This reaction pattern was not found in T cells, T cell-derived leukemias, normal B cells, a number of B-cell lymphomas, myeloid cells, myeloid leukemias (including monocyte-derived leukemias), reticulum cell sarcoma, or malignant reticulosis. The cells from some B-cell lymphomas and plasmacytoma showed a relatively homogeneous pattern of fine or moderately coarse ANAE-positive granules that was similar to that of hairy cells only in some cases of plasmacytoma. Thus, fine to coarse granular ANAE reactivity is characteristic of hairy cells and is of potential diagnostic value for hairy cell leukemia.


Effect of T-lymphocytes on normal haemopoiesis: studies in congenitally athymic nude mice. The germ-free nude mouse represents a most useful animal for investigating the effects of a congenital deficiency of T-lymphocytes on various physiological processes, including haemopoiesis. Nude mice (nu/nu) of the CBA strain, nonmutant inbred CBA mice, and inbred C3H mice were reared in germ-free isolators and used to compare (1) the haematological parameters of nu/nu mice and CBA mice at different ages and (2) the labelling pattern of circulating leucocytes at various times after a single intraperitoneal injection of 3H-thymidine into 3-month-old nu/nu and C3H mice. The data suggest that the deficiency of T-lymphocytes in nu/nu mice may lead to a disturbance of haemopoiesis in 2 to 6-month animals which is characterised by a mild macrocytosis and a very marked reduction in the proportion of labelled leucocytes which can be seen in the blood after an injection of 3H-thymidine. Despite these perturbations, unstressed nu/nu mice were able to maintain adequate numbers of blood cells (other than lymphocytes) in their circulation. Nine-month-old nu/nu mice did not show a macrocytosis and the disappearance of the marcrocytosis at this age was associated with an increase both in the blood lymphocyte count and in the mass of lymphoid tissue in the spleen and mesenteric lymph nodes.


Interactions of septal evoked responses to stimulation of the fornix and medial forebrain bundle. Gross and single unit septal evoked response to stimulation of the fornix and medial forebrain bundle (MFB) were studied in anesthetized, acutely prepared rats. Stimulation of the fornix and MFB produced short-latency antidromic and synaptic activation of localized groups of septal target cells. In addition, stimulation of either pathway produced inhibition of spontaneous single cell activity. The interactions of these responses were studied by delivering paired stimuli to the fornix and/or MFB. A prior stimulus to the fornix potentiated the responses of cell groups synaptically activated by subsequent fornical stimulation, but briefly depressed the sunaptic activation of septal cells by subsequent MFB stimulation. A prior stimulus to the MFB slightly potentiated the synaptic activation of septal cells by a subsequent MFB stimulus, but depressed the responses of cell groups synaptically activated by a subsequent stimulus to the fornix. These results were discussed in terms of their implications for septal organization and function.


A model for the study of the oral administration of peptide hormones. The intragastric administration of lysine vasopressin (LVP) to rats is used as a model to study the biological activity of orally administered peptide hormones. Using a modification of the antidiuretic assay of Sawyer, LVP given by stomach tube caused a significant antidiuresis that was dose dependent in doses of 300 to 2000 mU. The simultaneous administration of the protease inhibitor, Trasylol, increased the antidiuretic effect of LVP. The synthetic peptide (1-deamino, 4 valine)-8-D-arginine-vasopressin also caused a dose-dependent prolonged and significant antidiuresis. No pressor effect was observed after intragastric administration of LVP in doses up to 40 U/rat. We are now using this model to test other procedures for enhancing the activity of lysine vasopressin administered in the gastrointestinal tract such as encapsulation into liposomes. The information gained with vasopressin will then be applied to insulin with the ultimate goal of making oral administration practical.


Computerized tomography in rhabdomyosarcoma of the head and neck. Rhabdomyosarcoma of the head and neck may be treated with surgery, radiotherapy and chemotherapy or a combination thereof. Precise delineation of the full extent of the tumor in the head and neck is essential. Routine radiographs with hypocycloidal tomography and CT are complementary in defining the full extent of the lesion. Tomography is superior to CT scanning in demonstrating fine bone detail. Demonstration of the soft tissue tumor and its extensions is better seen on CT. The ability to discriminate differences more accurately in densities allows computerized tomography to appreciate better the integrity of the bone margins such as the thin walls of the sinuses.


Clinical staging and immunological findings in chronic lymphocytic leukemia. Several immunological markers were tested in 52 untreated cases of chronic lymphocyte leukemia (CLL) to see whether their frequency differed according to the clinical stage in Rai's system. The leukemic cells in all cases had B-cell features as shown by monoclonal immunoglobulins on the cell surface (SmIg) and/or a high percentage of mouse RBC (M)-rosettes. Of the two B-cell markers, the M-rosette test was the more consistently positive. The frequency of these markers did not correlate with clinical staging. The percentage of T-lymphocytes, low in all cases, was found to correlate inversely with the lymphocyte counts, which were higher in advanced stages. The absolute number of T-lymphocytes was above normal in most cases, but did not relat to staging. At least one of the serum Ig, most commonly IgA, was decreased in 87% of cases. Low Ig were slightly less common in Stages 0-I than in advanced stages (II-IV). The above features were also examined in two groups of CLL patients: with stable (9) or progressive (16) disease. The only difference observed between the two groups was that surface IgM only was present in 1 of the 9 stable cases as compared to 9 of the 16 progressive ones. Our findings do not support the suggestions that surface IgM is a feature of a benign form of CLL or that the absolute number of T-lymphocytes correlates with prognosis.


Cell surface markers on lymphoid cells from Warthin's tumors. T- and B-cell markers were studied on suspensions of lymphoid cells obtained from two Warthin's tumors. Each tumor was composed predominantly of T- lymphocytes and a smaller percentage of B-lymphocytes with a polyclonal distribution of their surface immunoglobulin. These results do not differ from those obtained in normal or reactive lymph nodes. Together with the finding of normal lymph node structures in these tumors, our findings support the concept that the lymphoid component of Warthin's tumor represents pre-existing lymph node tissue.


Distribution of mast cells in the axillary lymph nodes of breast cancer patients. In a study of the pattern of distribution of mast cells in the axillary lymph nodes of 43 consecutive breast cancer patients it was observed that: 1) the pattern of distribution of mast cells in the survivors and nonsurvivors is similar, 2) there is almost complete absence of mast cells in the germinal centers with predominance of them in the T cell areas, and 3) a significant number of mast cells are seen in the afferent lymphatic route and the highest percentages of mast cells found in the medullary sinuses. The significance of these findings as they pertain to the relation of mast cells to the T cell system and to the migratory nature of mast cells is discussed.


Intracerebral tumor and diffuse central nervous system infiltration complicating acute myelogenous leukemia. An intracerebral space occupying lesion was found in a 20-year-old woman with acute myelogenous leukemia (AML) when she was in complete hematological remission. Computerized tomography of the brain demonstrated the tumor in the roof of the third ventricle and its subsequent resolution after cranial irradiation and intraventricular cytosine-arabinoside. This form of central nervous system complication in AML has not been previously reported.


Serum levels of methotrexate by the ligand-binding assay after "high-dose" therapy for osteosarcoma. The method of Arons et al. (Cancer Res. 35:2033-2038, 1975) for assaying methotrexate (MTX) was used to monitor serum levels of the drug attained in 18 patients with osteosarcomas. The patients received either 100 mg or 200 mg of MTX/kg via a 6-hour infusion. With one fatal exception, unacceptable toxicity to MTX was prevented by leucovorin. Serum levels of the drug were assayed routinely at 6, 12, and 18 hours after termination of the infusion. Although significantly higher serum levels of MTX were observed at 6 hours after the infusion of 200 mg MTX/kg than after 100 mg/kg, the variation in rate of clearance of individual patients masked any subsequent dosage-related differences. The mean half-time for clearance of MTX was similar irrespective of the dosage of MTX and was 2.91 +/- 1.51 hr for 53 treatments. The single incidence of toxicity, requiring hospitalization, was accompanied with markedly higher serum levels of MTX at 18 hours, but not at either 6 or 12 hours after termination of the drug infusion, and by a slightly slower rate of clearance, 6.2 hours. Certain minor adaptations were incorporated in the original assay to simplify the analysis of data.


Binding of epidermal growth factor to primary and permanent cultures of mouse epidermal cells: inhibition by tumor-promoting phorbol esters. High affinity binding of epidermal growth factor (EGF) was detected with mouse epidermal cells in primary culture and with 2 epidermal cell lines maintained in permanent culture. EGF binding was inhibited by low concentrations of the tumor promoters 12-O-tetradecanoyl phorbol-13-acetate (TPA) and phorbol didecanoate (PDD), but not by the non-promoting phorbol esters 4-O-methyl TPA and 4 alpha-PDD.


Effect of high-dose methotrexate with citrovorum factor on human granulopoiesis. The present studies were performed to delineate the effect of high-dose methotrexate with citrovorum factor rescue on the measurable compartments of human granulopoiesis, including peripheral blood cells and bone marrow stem cells committed to granulopoiesis-monocytopoiesis. Parameters of granulopoiesis were determined during the first course of high-dose methotrexate with citrovorum factor rescue in five patients, and during four consecutive courses in one patient. The remarkably mild toxicity of high-dose methotrexate with citrovorum factor rescue reported in clinical studies was substantiated on the level of the committed stem cell compartment. The data suggest a higher sensitivity of in vitro colony-forming units in agar culture as compared to the more mature granulopoietic cells and document the exquisite sensitivity and regenerating capacity of erythroid precursors after this type of chemotherapy.