Target-cell membrane alterations induced by lymphotoxin. Ultrastructural observations.

Upon in vitro stimulation by antigens or mitogens, lymphocytes release a series of lymphokines. One such lymphocyte mediator is lymphotoxin, which appears to be responsible for in vitro lymphocyte-mediated cytolysis. Employing immuno-electron microscopy with ferritin- or peroxidase-labeled antibody, we observed patchy localization of the mediator on the plasma membranes of target L cells exposed to lymphotoxin, often in areas overlying a microfilament web. When studying lymphotoxin-affected cells by electron microscopy of freeze-fracture replicas, we observed aggrlasma membrane, with intervening areas which were frequently particle free. Sometimes the affected cells revealed plasma-membrane lesions suggesting intramembranous "blisters."


Lymphocyte-epithelium interaction during rejection of nonisogeneic rat tracheal grafts.

Rat tracheal tissues were maintained in organ culture for 1 to 2 weeks and then implanted heterotopically into syngeneic and outbred hosts. The grafts and surrounding tissues were removed at regular intervals and examined by light and electron microscopy. Allogeneic grafts were consistently rejected, and a constant pattern of immunologic response was observed during rejection. Infiltration by mononuclear cells occurred initially in the subepithelial region. Subsequently, small lymphocytes migrated through the basal lamina and insinuated themselves between the differentiated epithelial cells. Larger cells resembling activated lymphocytes were also present in the intraepithelial infiltrate. Both type of lymphocytes had cellular processes in contact with epithelial cells, but there was no associated death of epithelial cells. Later, the infiltrate in some areas of the epithelium inclded dividing cells and other large cells exhibiting ultrastructural features suggesting blast transformation. Epithelial cell death was evident during this phase. The sequence of events may reflect a process of recognition and specific cytotoxic action by lymphocytes.


A computer-assisted, goal-oriented psychiatric progress note system.

The authors describe a computer system that develops a structured progress note for inclusion in the medical record. The progress note system reflects a goal-oriented patient treatment process and also provides for retrospective analysis of progress note information to accommodate research and review objectives. The system, which has met with a high degree of clinician acceptance, has resulted in improved case documentation, more timely and comprehensive notes, a higher level of objectivity, and a considerable reduction in the time required to organize and record progress note data.


Present status of coronary artery surgery.

Postinfarction ventricular septal defects are best repaired surgically several weeks after occurrence; however, deterioration of the patient's condition may require emergyncy operation. Ventricular aneurysms are resected when associated with low cardiac output, emboli occur or when present in a patient who is otherwise a candidate for aortocoronary grafting. Mitral valve replacement may be required when coronary disease produces severe malfunction of a papillary muscle or rupture of a chorade tendineae. Acute infarctectomy alone is not recommended at this time. The balloon assist device may result in some patients who are candidates for infarctectomy with aortocoronary bypass graft. Preinfarction angina which is not controlled by medical therapy should be treated by immediate aortocornary bypass. Tachyarrhythmias are not an absolute contraindication to surgery. Stable angina that is unacceptable to the patient under optimal medical therapy and is associated with operable anatomical lesions is the prime indication for coronary artery surgery. Relief of pain and increased exercise tolerance are usual after surgery. Sometimes life may be prolonged.


Arteriovenous malformation in chronic gastrointestinal bleeding.

Arteriovenous malformations of the gastrointestinal tract are uncommon and treatment is problematic because routine barium contrast studies and endoscopy fail to demonstrate the lesion. Diagnosis is by selective mesenteric arteriography, demonstrating a characteristic vascular tuft and very early venous phase. Two cases of arteriovenous malformation are presented and 47 other reported cases are reviewed. Forty-five per cent were found in the cecum; 37, or 80%, involved the distal ileum, cecum ascending colon, or hepatic flexure. Seventy-five per cent of all patients fall into the 50--80 year age range. The literature reveals a recurring pattern of chronic gastrointestinal blood loss, anemia, and delay (even negative abdominal explorations) before the diagnosis is finally made. A more aggressive approach to chronic gastrointestinal bleeding is suggested through the use of selective mesenteric arteriography.


Sequential anastomoses in coronary artery grafting: technical aspects and early and late angiographic results.

The present study concerns itself with the early and late results obtained with aortocoronary vein grafts containing more than 1 coronary anastomosis per graft. The surgical technique is described in detail and some of the hazards are outlined. It is apparent that the use of side-to-side anastomoses (SSAs) leads to a marked increase in blood flow in the proximal portion of the graft (average flow,131 ml/min) and also increases the patency rate of the proximal anastomosis. Thus, 3 of 51 SSAs were obstructed on the early angiogram, and only 1 of the 28 SSAs restudied at one year had become occluded. Although the cumulative--early and late--patency rate (55/66, or 83.3%) of the distal end-to-side anastomoses (ESAs) was not significantly better than that usually seen with conventional vein grafts, it is believed that improvement in the technique and greater awareness of some of its pitfalls will further decrease awareness of some of its pitfalls will further decrease the occlusion rate of distal ESAs. Most occlusions of the ESA appeared related to angulation, which tended to occur in the segment of graft between the proximal and the distal anastomoses. Appropriate modifications in the technique are described that should help to eliminate this difficulty. The use of SSAs allows for grafting of small coronary arteries which, with the conventional single anastomosis technique, are not usually bypassed in view of the high expected failure rate. Thus, of the 9 SSAs performed to 1 mm arteries and studied on two occasions, 8 remained open early after operation and 7 were still patent a year later.


Can the frequency of myocardial infarction be reduced during coronary artery operations.

A prospective experiment was carried out in 56 patients undergoing coronary artery revascularization to determine whether those having a glucose-insulin-potassium (GIK) perfusion during the procedure would have fewer myocardial infarctions (MI) compared with patients given a control perfusion of Normosol-R. Six patients (11%) developed an MI, defined as a 24-hour creatine phosphokinase MB isoenzyme value of 100 IU per liter or greater. Four (13%) had control perfusions and 2(8%) had GIK perfusion. One MI in a double-graft recipient who had GIK perfusion occurred because of a technical surgical error; therefore, the corrected MI rate was 13% in control patients compared with 4% for the GIK group. These data, as well as the more frequent spontaneous defibrillation in patients who had GIK perfusion, suggest that GIK was of benefit.


Combined procedure of coronary artery bypass grafting and valve repair.

The safety of combined operative procedures for valvular and coronary artery disease was reviewed in 27 patients. Twelve patients had aortic valve disease and 15 had mitral valve disease. Forty-seven coronary artery reconstructions were performed, and average of 1.7 per patient. Twenty-two patients underwent valve replacement and 5 had valvuloplasty. Congestive heart failure was the major symptom in 20 patients, and angina was the major symptom in 7. Eight of the patients with congestive heart failure had no angina, but significant coronary stenoses were demonstrated at routine coronary angiography. Coronary reconstruction was performed before valve repair. Two patients died postoperatively (a hospital mortality of 7.4%), and there were 4 late deaths from 2 to 28 months postoperatively. There were no postoperative myocardial infarctions. Contrary to previous reports, coronary artery reconstruction and valve repair need not be associated with an increased risk. Protection of the myocardium by coronary perfusion through reconstructed coronary arteries enables valve repair to be done without greater risk than valve repair alone. All patients considered for valve repair should have coronary angiography.


Hypothermic coronary perfusion for intraoperative cardioplegia.

Hypothermic asanguineous perfusion has been used to arrest 170 hearts at the beginning of 1/2 to 2 hours of intraoperative coronary ischemia. This method of producing cardioplegia has facilitated valve replacement and coronary artery bypass operations. Inadequate myocardial protection has not been experienced since we began using this method of arresting the heart for cardiac operations.


A newly designed arterial monitoring/perfusion cannula for cardiac operations.

A newly designed arterial monitoring and perfusion cannula for cardiopulmonary bypass eliminates the need for cannulation of a peripheral artery for pressure monitoring. The double-lumen cannula is designed as follows: the large central lumen (12 to 26f) acts as the arterial inflow conduit from the pump oxygenator, while a second, smaller lumen (18 gauge)constructed in the wall of the first cannula acts as the pressure-monitoring port and the source for blood sampling and drug infusion. This monitoring/perfusion cannula has been used succesfully in more than 250 clinical patients in a variety of settings--total cardiopulmonary bypass, left heart bypass, and when multiple arterial inflow lines were necessary (as in aortic arch replacement). Use of this cannula is advantageous in the infant and pediatric patient or in the emergency setting, when insertion of a peripheral arterial line can be difficult. Used in conjunction with a Doppler system, the cannula provides accurate, dependable blood pressure monitoring.


Results of reoperation for recurrent angina pectoris.

Although a coronary bypass operation improves the quality of life and possibly prolongs it, a small percentage of patients do not have satisfactory results and require reoperation. From July, 1970, to March 1975, 358 patients underwent coronary bypass for chronic disabling or preinfarction angina. Angina requiring operation recurred in 24 men and 2 women. Hyperlipoproteinemia was present in 19 of the 26 (73%), and 3 patients had early-onset diabetes mellitus. Only 2 of 14 patients with progression of arteriosclerosis were helped by a second operation. Of 7 patients with occluded grafts, local disease, and no progression, 5 were helped by reoperation. Patients with occluded coronary bypass grafts without progression of arteriosclerosis benefit substantially from a second revascularization procedure. Aguarded prognosis must be held, however, for those with progression of arteriosclerosis with hyperlipoproteinemia or juvenile-onset diabetes who undergo reoperation. Patients with initially diffuse disease and graft occlusion also seem to benefit less from a second operation.


Abnormal sella turcica. A tumor board review of the clinical significance.

Sixty of 146 patients with intracranial neoplasms or arterial aneurysms had roentgenographic abnormalities of the sella turcica. These abnormalities were most commonly due to chromophobe adenoma, craniopharygioma, and acromegaly, but ten of them were caused by lesions arising distant to the sella. There were also three cases of empty sella syndrome. Headache, visual disturbance, and sexual dysfunction were the most frequent presenting complaints, with visual field abnormality being most common. Pituitary dysfunction was manifested most frequently by alterations in growth hormone level and gonadotrophin secretion and less frequently by hypothyroidism and adrenocortical insufficiency. When the abnormal sella was associated with evidence of symptomatic intracranial disease, endocrine dysfunction, or visual field compromise as evidence of an anatomically aggressive intracranial neoplasm, specialized neuroroentgenographic localizing procedures were usually positive, and treatment for most of the causative lesions was highly effective.


Coronary artery bypass surgery in a patient receiving hemodialysis.

A 48-year-old man receiving maintenance hemodialysis underwent coronary artery bypass surgery with good results for intractable angina. No complications were observed that could be attributed to the hemodialysis treatment. There appear to be no cogent reasons to arbitrarily exclude this population of patients from consideration for coronary artery bypass surgery.


Primary osteogenic sarcoma: pathologic aspects in 20 patients after treatment with chemotherapy en bloc resection, and prosthetic bone replacement.

Twenty patients with osteogenic sarcoma of the distal portion of the femur and the proximal portion of the tibia received chemotherapy (vincristine sulfate, methotrexate with leucovorin calcium rescue, [citrovorum factor; folinade calcium], and doxorubicin hydrochloride [Adriamycin]), followed by radical en bloc resection and prosthetic bone replacement. Histologic examination of surgical specimens obtained after chemotherapy showed variable degrees of tumor destruction and, in some cases, massive tumor necrosis, attesting to the profound effects of vigorous chemotherapy. This new therapeutic regimen, when feasible, may prove to be the treatment of choice in osteogenic sarcoma.


Transcutaneous electrical stimulation: a double-blind trial of its efficacy for pain.

A double-blind trial was done using a stimulator and a placebo device on patients who had chronic pain to determine the effectiveness of transcutaneous electrical stimulation in controlling pain. Ninety-three patients were studied, and 83 of these completed the Minnesota Multiphasic Personality Inventory (MMPI). Thirty-three patients had low-back pain and 24 had neuropathies. The stimulator was more effective than the placebo during treatment when used over the center of pain (P less than .005) or over an unrelated nerve trunk (P less than .01) and after treatment over the center of pain (P less than .05). The stimulator was significantly more effective than the placebo in neuropathies when stimulating over the related nerve trunk (P less than .005), where the stimulator response was nearly three times better than that of the placebo. The duration of subsequent relief was not significantly different after treatment with the stimulator or with the placebo device. Follow-up showed significant declines in the use and effect of the stimulator with the greatest decline noted by the depressed group.


The effect of tryptrophan on nucleocytoplasmic translocation of RNA in rat liver.

The effect of the administration of tryptophan on the transport of nuclear poly (A)-containing mRNA to the cytoplasm in rat liver was investigated. Administration of tryptophan to fasted rats pretreated with cordycepin and actinomycin D led to decreased levels of nuclear poly (A)-mRNA and a concomitant increase in the levels of polyribosomal poly (A)-mRNA in the cytoplasm as determined by measuring in vivo incorporation of labeled precursors into hepatic RNA. Using isolated hepatic nuclei of rats prelabeled in vivo with [14C]orotic acid, there was greater release of labeled poly(A)-mRNA into the incubation medium from nuclei of tryptophan-treated rats than from nuclei of control animals. The increased release of RNA from hepatic nuclei of tryptophan-treated animals was not related to the cell sap present in the media since cell saps from livers of control and experimental rats gave similar results. These results support earlier findings which suggest that in the rat tryptophan increases the rate of translocation of hepatic poly(A)-mRNA from nucleus to cytoplasm.


Demonstration of granulocytic proteases in plasma of patients with acute leukemia and septicemia with coagulation defects.

To show whether direct proteolysis of coagulation factors may play a role in patients with so-called consumption coagulopathy, granulocytic neutral proteases in the plasma of patients with acute myelocytic leukemia and septicemia were assayed by one- and two-dimensional Laurell electrophoresis. Complexes between serum alpha1-antitrypsin and elastase-like granulocytic protease could be demonstrated in those patients with acute myelocytic leukemia and septicemia who also had moderate or severe coagulation defects. Despite the presence of a high antiprotease potential, addition of the elastase-like enzyme to normal plasma resulted in coagulation defects in vitro comparable to those seen in the patients. These results and the ability of the elastase-like protease to destroy isolated clotting factors suggested that in certain types of coagulation factor deficiencies direct proteolysis rather than consumption of clotting factors due to disseminated intravascular coagulation may be operational.


Enhancement of colony-stimulating activity production by lithium.

Since lithium causes granulocytosis in some patients, its effect upon granulocyte production was investigated using mouse marrow in the agar culture system. When lithium was added to semisolid cultures of mouse marrow, there was no stimulation of colony formation in the absence of colony-stimulating activity (CSA). In addition, lithium did not potentiate the action of already formed CSA. However, lithium did stimulate the production of CSA by lung tissue. Lithium enhancement of CSA production was blocked by puromycin, indicating that lithium action required active new protein synthesis. It was concluded that lithium promoted enhanced granulocyte production in vitro by stimulating the synthesis of CSA.


The radiological diagnosis of meningiomas, the impact of EMI scanning.

A review of the impact of computerized axial tomography on the radiological diagnosis of meningiomas is presented. Seventy-one intracranial and eight orbital cases have been examined by this new method using the 160 X 160 matrix. The diagnostic accuracy of the method is compared with established neuroradiological methods of examination (plain X rays, angiography, pneumography and isotope scanning). The new non-invasive method is undoubtedly the most accurate diagnostic tool yet available. It provided a specific diagnosis of meningioma in 77% of the intracranial cases without contrast enhancement and diagnosed the presence of tumour in a further 19% giving an overall tumour diagnosis of 96%. There were three false negatives (4%). After intravenous injection of contrast medium specific diagnosis of meningioma was made in a further six cases raising the specific diagnostic rate to 86%. Specific identification of intra-orbital meningiomas is more difficult though the presence of retro-orbital tumour was correctly diagnosed in all eight cases examined (100%). In none of our cases was a false positive diagnosis of tumour made. However, there are areas where a specific diagnosis of meningioma can only be made as part of a wider differential diagnosis. Apart from the orbit these include the suprasellar area, the cerebello-pontine angle, and the intraventricular regions. Occasionally also supratentorial gliomas or secondaries can simulate meningiomas.


Dynamic relations between natural vestibular inputs and activity of forelimb extensor muscles in the decerebrate cat. I. Motor output during sinusoidal linear accelerations.

Decerebrate cats were subjected to sinusoidal linear accelerations along the animal's horizontal and vertical axes, while recording the EMG activity of both triceps brachii muscles. This activity was found to be sinusoidally modulated in response to the accelerations and thus phase and gain relations between motor output and input acceleration could be obtained. They were found to be the same for accelerations along each of the three axes. In particular the gain dropped by 14-20 dB over a frequency range from 0.2 to 1.0 Hz and the phase of the motor output showed a lag of 40-60 degrees at 1.0 Hz. Thus, it was concluded that (1) the dynamic behavior of utricular and saccular receptors is the same, (2) the changes in motor activity observed during accelerations along the vertical axis are mostly due to the activation of saccular afferents, and (3) the motor output cannot simply result from vestibular afferent activities being relayed directly to the spinal motoneurons via the vestibulo-spinal tracts.


Dynamic relations between natural vestibular inputs and activity of forelimb extensor muscles in the decerebrate cat. II.  motor output during rotations in the horizontal plane.

Decerebrate cats with the spinal cord sectioned at low thoracic levels were submitted to rotations in the horizontal plane. The position of the animal with respect to the axis of rotation was such that horizontal canal afferents were activated either alone or in combination with macular afferents. The EMG activity from the triceps brachii muscles of both forelimbs was recorded. The main findings were as follows. (1) The motor output to each forelimb extensor is increased by an increase in the activity of the horizontal canal afferents from the contralateral labyrinth. The phase of the motor output with respect to that of the vestibular afferents shows a lag which increases with frequency, reaching about 85 degrees at 1.0 Hz. (2) The macular and horizontal canal inputs are independently processed in the central nervous system and the motor output in response to both inputs applied simultaneously is a linear summation of the outputs expected for each of the inputs.


Dynamic relations between natural vestibular inputs and activity of forelimb extensor muscles in the decerebrate cat. III. Motor output during rotations in the vertical plane.

Decerebrate cats with the spinal cord sectioned at low thoracic levels were subjected to sinusoidal rotations in the vertical plane, while recording the EMG activity of both triceps brachii muscles. The applied stimulus activated utricular and saccular receptors as well as the vertical semicircular canals. Using results presented in preceding papers 2,3, namely the dynamic response characteristics of the motor output to macular inputs and the fact that the responses to otolith and canal stimulation summate linearly 3, it is deduced that the dynamic characteristics of the motor output in response to stimulation of the vertical canals are the same as those to horizontal canal stimulation. The implication of these findings vis-à-vis the problem of central processing of vestibular inputs and the problem of postural stability is discussed.


Weekly high-dose methotrexate-citrovorum factor in osteogenic sarcoma: pre-surgical treatment of primary tumor and of overt pulmonary metastases.

Vincristine-high-dose methotrexate-citrovorum factor (VCR-MTX-CF) was administered preoperatively at weekly intervals to eight patients, four with primary tumors and four with pulmonary metastases. These patients had not received prior VCR-MTX-CF treatment. A similar treatment program was administered to five patients with pulmonary metastases who had received prior VCR-MTX-CF. Among the eight patients who had not received prior VCR-MTX-CF, complete responses were obtained in three with primary tumors (this was followed by surgical excision) and two with pulmonary metastases. Partial responses occurred in two additional patients. Partial responses were also obtained in two patients who had received VCR-MTX-CF. Chemotherapy and surgery in one patient with an extremity lesion resulted in preservation of the limb and useful function. The major toxicity was anorexia and weight loss. Other side effects included stomatitis, myelosuppression, hepatitis and transient renal impairment. The weekly program was highly effective when compared to responses obtained with the tri-weekly schedule utilized in previous studies.


Adjuvant multiple drug chemotherapy for osteosarcoma of the extremity.

Results of treatment for osteosarcoma of the extremity have been poor with metastases usually causing death within 2 years following diagnosis. Because of the great risk of development of metastases, 20 patients have received adjuvant chemotherapy with Adriamycin, cyclophosphamide and high-dose methotrexate-leucovorin rescue for up to 12 months following amputation for osteosarcoma. Sixteen of these patients are surviving; 11 are free of evident tumor from 6 to 34 months following amputation. Five patients were found to have pulmonary metastases while receiving chemotherapy and three patients developed metastases following completion of chemotherapy. One patient died following her third treatment with high-dose methotrexate-leucorovin rescue. Other toxicity included nausea, vomiting, mucosal ulcerations, infections, hematologic abnormalities, changes in kidney and liver functions tests, and minor coagulation abnormalities. The natural history of osteosarcoma may have been modified by the use of these agents for periods exceeding the median time to predicted detection of pulmonary metastases. Microscopic metastases of some patients were eradicated by this adjuvant chemotherapy. For patients who developed metastases, these metastases were delayed in their time of detection and in their number at the time of detection.


Sudden death.

The alert physician can identify and probably alter the risk of sudden death for certain patients (see Table 5). It appears preferable to study the patient who has already been identified as having coronary artery disease because of clinical symptoms such as R/O MI, which has been shown to have a high risk for subsequent sudden death. In addition, the physician must be sensitive to the middle-aged man with multiple coronary artery disease risk factors who suddenly decides to have a routine check or develops nonspecific complaints. Once identified, patients can be educated to minimize delay time  in seeking medical help with crescendo or prolonged angina. Ambulatory ECG monitoring for detection and characterization of ventricular arrhythmias, and exercise stress testing to detect severe ST depression, can facilitate an estimation of the patient's prognosis. A therapeutic plan, including attack on the patient's coronary artery disease risk factors, patient education, and specific medical or surgical therapies may alter the risk of sudden death. Once an infarction has occurred, rapid transport to a coronary care unit or monitoring facility, and administration of intramuscular lidocaine by medical or paramedical personnel when feasible, appear to lessen out-of-hospital mortality.


Fosfomycin treatment of Haemophilus influenzae infection in mice.

Haemophilus influenzae is an important pathogen in respiratory infections in children and often is implicated in otitis media. It is sensitive in vitro to a number of antibiotics, some of which are used clinically for the treatment of such infections. We have checked the in vitro sensitivity of a type b strain of H. influenzae. When tested in Levinthal's broth prepared with laked rabbit blood, the culture was most sensitive to tetracycline, ampicillin and penicillin and was somewhat less sensitive to cephalothin, fosfomycin, cephaloridine, and chloramphenicol. However, when this same strain was used to infect mice, fosfomycin was more active than ampicillin, tetracycline, chloramphenicol, penicillin or the cephalosporins.


[A prospective study of post-operative bleeding from stress lesions. I. Epidemiology (author's transl)].

Among 5776 patients operated on under general anaesthesia there was an increased risk of postoperative gastro-intestinal bleeding from stress lesions among those aged over 70 years, after major surgery, or with complications such as hypovolaemia, septicaemia or respiratory failure (n = 551). In this group of patients the incidence of fatal haemorrhage was 0.5%. Stress lesions were a certain cause of bleeding from the gastro-intestinal tract in 5.1% and a probable one in 5.1%. Time of year, sex, past history of peptic ulcer, or anticoagulation did not increase the risk of bleeding.


[Splenorenal anastomoses in portal hypertension (author's transl)].

The classical splenorenal shunt of Linton modified by Clatworthy is definitely superior to portocaval anastomosis. Between 1968 and 1976 in 225 patients with bleeding oesophageal varices a splenorenal anastomosis was performed in 47 cases, a portocaval in 30 cases and a mesentericocaval in 2 cases. There were 55 palliative operations as compared with 91 conservative therapeutic approaches. Over the last five years central termino-lateral splenorenal anastomoses have been performed almost exclusively.


Nephrotic syndrome of childhood and disorder of T cell function.

In thirty-two patients with nephrotic syndrome (NS) phytohemagglutinin (PHA)-induced lymphocyte proliferation was studied at various stages of the disease. We demonstrated that lymphocyte transformation during acute exacerbation is markedly decreased, especially if cells are cultured in patient serum. During treatment with steroids PHA-stimulation improves. During full remission all patients showed their maximal lymphocyte stimulation. On the basis of these results and reports from the literature we postulate that patients with the NS have a T cell clone which inhibits the transformation capacity of the remaining lymphocytes through production of a heat stable serum factor. The same or a second factor produced by these lymphocytes could at the same time exert a toxic effect on the glomerular basement membrane.


Effects of 1-alkyl-1,2,3,4-tetrahydrocarbazole-1-ethanamines and related compounds, potential antidepressants, on biogenic amine uptake mechanisms.

A new series of compounds structurally related to the potential antidepressant tandamine, i.e., the 1-alkyl-1,2,3,4-tetrahydrocarbazole-1-ethanamines, inhibit the noradrenaline uptake mechanism and are relatively ineffective in inhibiting the serotonin uptake mechanism in vivo. The potency of the most effective compound (9-ethyl-N,N,1-trimethyl-1,2,3,4-tetrahydrocarbazole) is similar to that of desimipramine and is of potential use in the treatment of endogenously depressed patients.


Binding of bacterial endotoxin to murine spleen lymphocytes.

The early events in lipopolysaccharide (LPS)-induced B-cell activation were investigated by studying the binding of 14C-labeled LPS to murine lymphocytes in vitro. In these studies we utilized intrinsically labeled 14C-labeled LPS from Salmonella minnesota or the 14C-labeled glycolipid derived from the Re mutant of S. minnesota (R595). Bone marrow-derived (B) lymphocytes bound more LPS than did thymus-derived (T) lymphocytes. Binding of LPS to murine spleen lymphocytes from strain C3H/HeN was compared with the binding to spleen lymphocytes from strain C3H/HeJ, a strain resistant to certain biological activities of LPS including mitogenesis. Spleen cells from both strains bound LPS equally well, suggesting that unresponsiveness of C3H/HeJ mice to LPS is due to factors other than a defect in binding of LPS. LPS binding to cells appeared to be due to a nonspecific interaction between the lipid moiety of LPS and the lipid components of the cell membrane. Thus, the highly lipophilic, polysaccharide-deficient glycolipid from R595 bound at least 20 times better than did LPS. Furthermore, partial removal of cell surface proteins with trypsin or sialic acids with neuraminidase enhanced glycolipid binding, suggesting that binding is not through a protein- or sialic acid-containing receptor. The binding of glycolipid to lymphocytes was only partially specific since unlabeled glycolipid R595, lipid A, and LPS did not completely inhibit the uptake of 14C-labeled glycolipid R595. In addition, binding could be inhibited by a nonmitogenic phospholipid (phosphatidyl ethanolamine), which also is consistent with a nonspecific lipid-lipid interaction. Experiments were performed to determine the relationship of LPS binding to lymphocyte activation in the lymphocytes. The process of activation of lymphocytes by LPS was a slow one, since LPS was required to be present in culture for at least 24 h in order to obtain significant lymphocyte activation, suggesting that the amounts of LPS bound earlier are either quantitatively or qualitatively insufficient to irreversibly activate the cell.


Reactivity of peripheral blood leukocytes against human foetal cells. II. Cytotoxic potential of preparations enriched or depleted of different leukocyte populations.

Leukocytes separated initially by Ficoll-Triosil sedimentation from the peripheral blood of 62 healthy donors and 64 patients with a variety of cancers were tested for cytotoxicity against cells from a single human foetal lung, by means of a microplate technique based on visual enumeration of surviving target cells. Under these conditions cytotoxicity was primarily observed to be a function of the granulocyte content of the preparations, which was extremely variable (range 0-60%). When the influence of these cells was greatly diminished through depletion by adherence, residual cytotoxicity was still detectable in the majority of samples tested. Complete abrogation of this cytotoxicity by pretreatment with carrageenan implicated cells of the monocyte-macrophage series, which persisted as a small minority (about 2%) in the already depleted effector cell populations. However some cytotoxicity could also be demonstrated in populations, purified by passage through columns containing nylon fibre or Degalan-coated (human Ig-anti Ig) beads, which consisted almost exclusively (about 98%) of lymphocytes, mainly of thymus (T)-dependent type (greater than or equal to 80%). Under these conditions and those in which T-cells were concentrated by formation of spontaneous E rosettes, cytotoxicity appeared to decline with T cell enrichment, suggesting that the cytolytic effects were attributable to cells of the non T-compartment which were present to a variable extent in the different T-cell-enriched populations. Although the absolute identity of these cells was not established, the experiments illustrate potential sources of non-specific cytotoxicity among different effector cell populations against target cells expressing antigens to which the majority of leukocyte donors--in health or disease--were presumably non-sensitized. As such these data have several implications for the interpretation of in vitro cytotoxicity tests against human neoplasms.


Thymus-derived lymphocytes in the Vogt-Koyanagi-Harada syndrome.

Previous investigations have suggested that immunologic factors may play a role in the Vogt-Koyanagi-Harada syndrome, a disease involving the eye, central nervous system, and dermis. Among patients with this disease we have observed a decrease in their peripheral blood lymphocytes, as measured by two types of rosette assays. These results strengthen the concept that an altered immunologic status may be important in the pathophysiology of this disease.


Organ interactions in the regulation of hematopoiesis: in vitro interactions of bone, thymus, and spleen with bone marrow stem cells in normal, Sl/Sld and W/Wv mice.

Hematopoietic cell differentiation is influenced by organ-dependent microenvironmental factors as well as humoral regulators. A technique is described for examining certain aspects of the hemopoietic inductive microenvironment in vitro. Suspension and agar cultures of mouse bone marrow were used to study the effects of organ stromal factors on cellular proliferation and differentiation. Bone, spleen, and thymus fragments from irradiated mice were placed in direct contact with or separated by a Nuclepore membrane from syngeneic marrow cells growing in suspension cultures. Normal adult mouse bone and spleen influenced granulocytic differentiation as well as cell proliferation. In this system, bone marrow and organ fragments from W/Wv and SlSld mice behaved like those of their non-anemic littermates. The most prominent difference between W/Wv and Sl/Sla mice and their normal counterparts was observed in the inductionof CFU-C from splenic precursors un-er the influence of CSA. In both types of anemic mice, in vitro generation of CFU-C from spleen was abnormal in young animals but was corrected by four months of age.


Emergence of insulin receptors upon alloimmune T cells in the rat.

Insulin, as well as other ligands which increase intracellular guanosine 3',5'-cyclic monophosphate (cGMP), augments thymic-derived (T)- lymphocyte effector activity as revealed by alloimmune lymphocyte-mediated cytotoxicity. The observation that insulin binds only to monocytes among circulating nonimmune human mononuclear cells fosterd reexamination of the mechanism by which insulin augments T-lymphocyte function. This report concerns a test of the  hypothesis that the T cell is directly affected by insulin and that an insulin receptor emerges upon T lymphocytes consequent to immune activation. Spleens were removed from rats skin grafted across a major histocompatibility barrier. Lymphocytes were harvested from Ficoll-Hypaque density gradients and subsequently enriched for T cells by passage over one or two nylon wool columns. This population was composed of more than 98% T cells as assessed by surface marker techniques (Ig staining, erythrocyte antibody, and erythrocyte antibody complement rosetting, anti-T staining). There was no loss of augmentation of lymphocyte-mediated cytotoxicity induced by insulin, carbamycholine, and 8-bromo-cGMP in the purified cells when compared to unfractionated cells 7 days after transplantation. 125I-insulin bound saturably to the allostimulated T-enriched lymphocytes with maximum binding at 12.8 +/- 0.2 pg and a dissociation constant at equilibrium of 1.3 nM. In contrast, insulin receptors were not present on nonimmune T-enriched cells or on T cells from animals that received syngeneic grafts. The affinity of the lymphocyte insulin receptor was similar to that of more conventional insulin-sensitive tissues e.g., liver, adipocyte. After 89% of T cells from spleens on day 7 were lysed with anti-thy 1.1 antibody and complement, the ability to measure specific insulin binding was lost. These data confirm a physiologic role for insulin in T-lymphocyte effector function and describe the emergence of insulin receptors concomitant with cell sensitivity to ligand. Such receptors may play a role in hormonal modulation of the immune response.


Effects of sheep digoxin-specific antibodies and their Fab fragments on digoxin pharmacokinetics in dogs.

Intact sheep antidigoxin antibodies and their Fab fragments have both been found to exert profound effects on digoxin pharmacokinetics in [3H] digoxin-treated dogs. Both classes of molecule remove digoxin from the extravascular space and sequester it in the circulation in protein-bound form, a form in which the digoxin is presumably inactive. These two classes of molecule differ, however, in that the intact antibody molecules interfere with digoxin excretion, thereby promoting the retention of the glycoside; this retained digoxin is eventually released in free, active form when the administered antibody is metabolically degraded. In contrast, urinary excretion of digoxin continues in Fab-treated dogs, with significant quantities of digoxin being excreted promptly in the urine in complex with Fab fragments. These differences in urinary excretion, together with the probable decreased immunogenicity of sheep antidigoxin Fab fragments, suggest that such fragments possess potential advantages over intact antibody molecules for use in the therapy of life-threatening digoxin intoxication in man.


Direct myocardial revascularization in young patients: analysis of 100 consecutive cases without operative mortality.

The authors studied a series of 100 patients submitted to direct myocardial revascularization before 40 years of age. One hundred and seventy-three saphenous vein by-passes and 4 mammary artery left descending coronary artery anastomoses were performed. There was no operative mortality and the late mortality was 2%. The period of postoperative clinical evaluation of the patients varied from 12 to 60 months (mean 32.0 months).


Alpha-1 antitrypsin in childhood asthma.

Alpha-1 antitrypsin (AAT) phenotypes and serum levels were studied in two childhood perennial asthmatic populations. The first was an ambulatory, mostly mild nonsteroid-dependent group living in Rochester, N.Y. The second was a more severe mostly steroid-dependent group residing at an asthma residential treatment center in Denver, Colo. The prevalences of alpha-1 antitrypsin protease inhibitor (Pi) tyes were the same for bothe groups and similar to prevalences in a random population. Alpha-1 antitrypsin serum levels were significantly elevated for the mild nonsteroid-dependent group when compared to the more severe steroid-dependent group. The steroid-dependent group had serum levels similar to a group of nonasthmatic control children. These findings indicate that there is not a strong association of alpha-1 antitrypsin Pi variants such as Pi MZ or Pi MS with more severe asthma. Elevated serum levels in the milk perennial asthmatic group may be the result of chronic inflammatory processes. Normal levels in the sterioid-dependent group may be the result of corticosteroid control of inflammation associated with asthma.


A hyperimmunoglobulin E syndrome with normal chemotaxis in vitro and defective leukotaxis in vivo.

A 26-yr-old male with a lifelong history of atopic dermatitis and recurrent severe staphylococcal abscesses was found to have hyperimmunoglobulinemia E. Evaluation of both the humoral and cellular aspects of chemotaxis in vitro showed both neutrophils and monocytes to be normal. However, quantitative neutrophil migration in vivo was significantly suppressed using the patient's own serum as the attractant. This defective migration in vivo was partially corrected by serum from normal donors as the attractant and also partially corrected following plasma infusion in this patient. Evaluation of quantitative leukocyte migration in vivo may be most useful in patients suspected of defects of leukocyte mobility.


Differential diagnosis of rheumatic disease in the elderly.

To illustrate the diagnostic problems of rheumatic disease in patients over 60 years of age, 4 cases are presented: 1) osteoarthritis, 2) late-onset rheumatoid arthritis, 3) polymyalgia rheumatica, and 4) pseudogout with crystalline synovitis. In each case the correct diagnosis should have been suspected from the history and physical examination alone, with the laboratory and x-ray findings providing supportive evidence.


The immunology of arthritis: interpretation of serologic studies. (Summary of presentation).

Results of serologic tests in rheumatic disease require good judgment in interpretation, based upon familiarity with the present knowledge of immunologic mechanisms, including the action of antibodies, auto-antibodies, T-cells and B-cells.


Immunochemical studies of infectious mononucleosis. VI. a radioimmunoassay for the detection of infectious mononucleosis heterophile antibody and antigen.

The coated-tube method of solid-phase radioimmunoassay has been adapted to the detection of heterophile antibodies and antigens of infectious mononucleosis. Disposable plastic hemagglutination trays were coated with purified glycoprotein from horse erythrocytes and the subsequent uptake of antibody from test sera was detected by radio-iodinated horse erythrocyte glycoprotein. In a preliminary survey of sera from patients with infectious mononucleosis and sera from controls, the assay proved highly sensitive and specific. The test system was also useful in a competitive binding assay for immunochemical studies of glycoproteins from other heterophile antigen-positive species.


The role of encapsulation and host age in the clearance of Haemophilus influenzae bacteremia.

Nonimmune rats given intravenous inoculations of 10(8) encapsulated Haemophilus influenzae type b cleared the bacteria at an exponential rate for 10 min; thereafter, the bacteremia plateaued at approximately 10(6) organisms/ml of blood. With 10(8) unencapsulated organisms, the initial clearance rate was significantly faster (P less than 0.001) and was complete by 30 min. The rate of clearance of a mutant strain of H. influenzae type b containing 0.1% as much capsular polysaccharide as the wild type was significantly faster (P less than 0.01), and H. influenzae type b from which a portion of the capsule had been removed physically had an intermediate clearance pattern. The addition of 1-1,000 mug of capsular polysaccharide to an inoculum of 10(8) organisms did not alter the clearance of the capsular polysaccharide-deficient mutant. The quantity of bacteria cleared during the 30 min after inoculation increased with the age of the animal. The initial bacterial clearance rate, corrected for animal and organ weight, also increased with age. These data are consistent with the proposal that physically integrated capsular polymer increases the virulence of H. influenzae type b by rendering it resistant to clearance from the bloodstream and that there may be an age-related increase in phagocytic activity that is reflected in increased clearance.


Cellular immune response to Yersinia pestis modulated by product(s) from thymus-derived lymphocytes.

Resistance to infection with Yersinia pestis was found to depend on whether the macrophage can inactivate and withstand the cytotoxic effects of phagocytized Y. pestis. Serum from mice immunized with antigens of Y. pestis enhanced the resistance of monolayers of normal cultures to the cytotoxic effects of Y. pestis and increased the capacity of peritoneal exudate cells from immune mice to inactivate these bacteria. The enhancing component of the serum was not removed by absorption with heat-killed Y. pestis. Similar enhancement was provided by supernatant fluids of spleen cultures from immunized mice but not by those from unimmunized mice. Pretreatment of spleen cells with rabbit hyperimmune antiserum to mouse brain theta-antigen plus complement caused a reduction in the enhancing capacity of the spleen cell culture fluids. Removal of the glass-adherent cell population from suspensions of primed spleen cells prior to in vitro antigenic stimulation resulted in a loss of activity from the subsequently harvested culture fluids. Thus, the enhancing component of the serum appears to be a product of thymus-derived lymphocytes (T-cells). Furthermore, splenic macrophages seem to be required for the interaction of primed T-cells with heat-killed Y. pestis.


Food and intracranial stimulation responding suppressed with regular-interval shock.

Attenuation of conditioned suppression during intracranial stimulation was compared with that during food reinforcement. Response rates controlled by food and by brain stimulation were equalized on a multiple schedule by adjusting the stimulating current. When foot shock was delivered during timeout periods separating response components, responding for food was significantly more suppressed than responding for brain stimulation. When components were shortened from 10 to 2 minutes, responding maintained by either food or  brain stimulation showed a similar temporal pattern of suppression preceding each shock, but responding in the component involving food remained significantly more suppressed. Explanations for the attenuated suppression during brain stimulation based on neural disruption, stimulus blocking, and analgesic properties were questioned. The increased responding during brain stimulation seemed to reflect greater response strength relative to food reinforced responding.


Studies on delayed hypersensitivity in mice. III. Evidence for suppressive regulatory T1-cell population in delayed hypersensitivity.

T-T-cell interactions involved in delayed hypersensitivity (DH) response have been studied by employing delayed foot pad assay to methylated human serum albumin in C57BL/6J mice. The DH response, one of the T-cell manifestations of cell-mediated immune response is suppressively regulated by T cells and such observation was based on studies of age-associated kinetics of foot pad reaction and effects of cell transfer and adult thymectomy on developing DH response. These suppressively regulatory T cells in DH have a life span of less than 4 wk and a constant derivation from the thymus is required. Such cells are numerous in the young mouse thymus and few in the spleen and thymus of old mice. On the one hand, the presence of a long-lived effector T-cell population was suggested in DH. These cells are numerous in the spleen and are low responders to phytohemagglutinin in vitro. It is assumed that these suppressive T cells interact with antigen-reactive cells at their proliferating stage by recognition of the iodiotypic difference through surface receptors. As in the case of graft-vs.-host and humoral response in vivo, three different subsets of immune competent cells participate in the DH response. These cells consist of one specifically antigen-reactive T cell, one suppressive regulatory T cell, and one bone marrow-derived cell, a macrophage that responds to a chemical mediator from sensitized effector T cells and that develops a DH skin lesion nonspecifically.


Defective colony formation by B lymphocytes from CBA/N and C3H/HeJ mice.

B cells from CBA/N mice did not form colonies in semisolid agar cultures under circumstances where normal B-cell clonal proliferation is linear with respect to the number of functional cells cultured. This was no due to the unresponsiveness of CBA/N cells to mitogens, and under appropriate liquid culture conditions many CBA/N lymphocytes differentiated to plasma cells containing large amounts of IgM in response to LPS. On the other hand, the same cells proliferated and matured poorly in liquid cultures prepared at low-cell density. The frequency of granulocyte-macrophage progenitors and multipotential hemopoietic stem cells in bone marrow, ability of peritoneal macrophages to elaborate soluble enhancing factors, and levels of serum inhibitors were normal in CBA/N mice. Together with the results of cell-mixing experiments, these findings confirm the selective and intrinsic nature of the CBA/N deficiency. It is suggested that the B-cell cloning technique may be of value in selectively enumerating and assessing functional capability of thymus-independent B cells. C3H/HeJ mice which have previously only been known to be hyporesponsive to certain forms of lipopolysaccharide had a subnormal incidence of colony-forming B cells.


Concanavalin A-mediated activation of antigen-primed lymphocytes into secondary cytotoxic lymphocytes.

A secondary specific cytotoxic response is obtained when lymphocytes primed in vivo to a tumor allograft are exposed to Con A in culture. The secondary cytotoxic cells generated are specific to target cells bearing antigens of the primary sensitizing cells and are qualitatively indistinguishable from the response obtained upon secondary antigenic stimulation. The cell-mediated cytotoxicity is independent of concanavalin A (Con A) and is not affected by the Con A-specific inhibitor, alpha-methyl-D-mannose pyranoside. Furthermore, cultures containing a mixture of submitogenic concentrations of Con A and stimulating antigens showed synergy and augmentation of cytotoxic activity. It is suggested that activation of prekiller cells by Con A into CTL may be mediated via the same or similar receptors normally triggered by the stimulating antigens. Functional similarities between ConA and the lymphocyte-defined antigens of the major histocompatibility complex region are discussed.


Hematopoietic thymocyte precursors: II. Properties of the precursors.

The properties of hematopoietic cells which serve as the precursors of cortical thymocytes in irradiated reconstituted mice have been described. These cells have been termed "prothymocytes." They are 10- to 15-mum diameter cells of low buoyant density. They are nonadherent to glass wool and more resistant to the lytic effects of steroids and gamma-irradiation than their progeny. They lack detectable amounts of the surface markers associated with either B or T cells but do bear at least two antigens recognized by antisera to mouse brain.


Two distinct pools of recirculating T lymphocytes: migratory characteristics of nodal and intestinal T lymphocytes.

A pronounced asymmetry in the recirculation from blood to lymph of resting small recirculating T lymphocytes is described. When 51Cr-labeled small T-recirculating lymphocytes (TRL) from intestinal lymph were infused intravenously their relative recovery in intestinal lymph was about twice that in nodal lymph. In contrast, the relative recovery in nodal lymph of 51Cr-labeled nodal TRL was twice that in intestinal lymph. Intestinal TRL migrated in large numbers through the small intestine. Nodal TRL did not. It is proposed that the pool of recirculating small T lymphocytes consists of two major subdivisions, an intestinal pool and a nodal pool. The nodal circulation comprises small TRL which traverse PCV in all lymph nodes (LN) but not the small intestine. The intestinal circulation comprises small TRL which do not traverse PCV in LN, but which do recirculate through the small intestine from which they pass via afferent lymphatics to the mesenteric LN and subsequently via the thoracic duct into the blood. It is suggested that the intestinal circulation is present in the fetus and that its initial development is independent of extrinsic antigen.


Cyclophosphamide-sensitive T lymphocytes suppress the in vivo generation of antigen-specific cytotoxic T lymphocytes.

Murine T lymphocytes sensitized in vitro against either allogeneic lymphocytes or syngeneic hapten-conjugated lymphocytes do differentiate into highly effective cytotoxic T lymphocytes (CTL) (1-3). In vivo immunization of T lymphocytes to the same antigens, however, results in the generation of only marginal cytotoxic activity (1,4,5). Recently we found that the weakness of in vivo generated cytotoxicity is not due to a failure of antigen-induced T-cell sensitization but rather due to suppression of the in vivo differentiation of sensitized CTL precursors into effective CTL(6). In keeping with this finding it was postulated that suppressor cells may regulate the in vivo differentiation of CTL. We now report, that cyclophosphamide-sensitive T cells suppress the in vivo differentiation of antigen-specific CTL. Thus, pretreatment of mice with a single dose of cyclophosphamide (100 mg/kg) converts their state of low responsiveness to a state of high responsiveness.


Phorbol myristate acetate: a mitogen selective for a T-lymphocyte subpopulation.

Phorbol myristate acetate (pma) is a potent mitogen for human peripheral blood lymphocytes (PBL) comparable to phytohemagglutinin (PHA) in potency. Inactivation of PHA-responsive lymphocytes by 5'-bromodeoxyuridine and light treatment left the PMA response intact and nice versa. Experiments separating lymphocytes by rosetting with sheep erythrocytes (SRBC) demonstrated that the PMA-responsive lymphocytes segregate with those that have a high affinity for SRBC to a greater than PHA- or concanavalin A (Con A)-responsive cells. These results indicate that a PMA-responsive population in human peripheral blood resides within the T-lymphocyte population and appears to have a high affinity for SRBC and to be distinct from that responding to PHA and Con A. PMA may be useful clinically to assay the size and function of the high affinity or "active" rosette population.


The family-oriented medical record.

The usual form of the Problem-Oriented Medical Record is primarily focused on the individual, and thus has serious deficiencies for the family-oriented physician. This paper presents a practical, office-tested medical charting system that incorporates features of the Problem-Oriented Medical Record and allows the recording of aspects of the family situation that are of particular importance to the family physician. The essential features of the chart are described and the special features, advantages, and disadvantages are discussed. This record has been developed to avoid the gaps that appear when attempts are made to use individually-oriented record systems in a family-oriented practice.


Regulation by magnesium of intracellular calcium movement in skinned muscle fibers.

The effect of Mg on Ca movement between the sarcoplasmic reticulum (SR) and myofilament space (MFS) was studied in skinned muscle fibers by using isometric force as an indicator of MFS Ca. In Ca-loaded fibers at 20 degrees C, the large force spike induced by Ca in 1 mM Mg (5 mM ATP) was strongly inhibited in 3 mM Mg, and force development was extremely slow. After a brief Ca stimulus in 1 mM Mg, relaxation in Ca-free solution was significantly faster in 3 mM Mg. These changes were due to altered Ca movements, since the effect of 3 mM Mg on steady force in CaEGTA solutions was small. Changes in Mg alone induced force transients apparently due to altered Ca movement. In relaxed fibers, decreasing the Mg to 0.25 mM caused phasic force development. In contracting fibers in Ca solutions, increasing the Mg caused a large transient relaxation. The effects of increased Mg were antagonized by 0.5 mM Cd, an inhibitor of the SR Ca transport system. The results indicate that active Ca uptake by the SR in situ is stimulated by Mg, and that it can affect local MFS [Ca++] in the presence of a substantial Ca source. These results provide evidence that an increased rate of Ca uptake in 3 mM Mg could account for inhibition of the large force spike associated with Ca-induced Ca release in skinned fibers.


Physical form as a determinant of effect of buffered acetylsalicylate formulations on gi microbleeding.

During a 48-day period, 12 male dogs received four buffered sodium acetylsalicylate formulations, quantitatively virtually identical (a homogenenous disintegrating swallow tablet, a swallow tablet in which the sodium acetylsalicylate was contained in a dissolving core, an encapsulated powder, and an aqueous suspension), at 650-mg aspirin equivalent doses twice daily during four 7-day treatment periods (each preceded by a 5-day period of no treatment) in a complete changeover fashion. Mean daily fecal blood losses of 0.75, 1.37, 1.43, and 2.89 ml were observed in the 12 dogs during treatment with the aqueous suspension, the homogeneous tablet, the encapsulated powder, and the core tablet, respectively. These findings indicate that the physical form of buffered acetylsalicylate formulations is a critical factor in the effect of such formulations on GI microbleeding.


GLC determination of indoprofen in plasma.

Implementation of human bioavailability studies with the analgesic indoprofen required a rapid, sensitive, and convenient assay in blood plasma. A procedure based on ether extraction of acidified plasma, derivatization with diazomethane, and GLC analysis using a 3% OV-1 column was sufficiently sensitive for measurement of plasma indoprofen concentrations in the 0.4-16 mug/ml range. An average recovery of 99.0 +/- 7.6% (SD) was achieved when the pentanoic acid homolog was employed as an internal standard.


Effect of narcotics on the uptake of serotonin precursors by the rat brain.

The extraction of 14C-tryptophan and 14C-hydroxytryptophan (5-HTP) from the blood to the brain was measured using an indicator dilution technique. Acute treatment with morphine caused a dose-related decrease in the extraction of tryptophan by the brain and a increase in that of 5-HTP. Naloxone alone had no effect on the extraction of either tryptophan or 5-HTP but completely blocked the effect of 20 mg/kg of morphine on the extraction of both tryptophan and 5-HTP. In contrast to acute treatment with morphine, the extractions of tryptophan and 5-HTP were not significantly altered 48 hours after chronic treatment with morphine. The extraction of 5-HTP remained unchanged and that of tryptophan increased significantly 72 hours after chronic morphine treatment. In equivalent doses, levorphanol decreased the extraction of tryptophan more than its inactive isomer, dextrorphan, whereas levorphanol increased and dextrorphan had no effect on the extraction of 5-HTP. These results suggest that an increase in the rate of central serotonin synthesis after acute treatment with morphine may be due to an increased uptake of 5-HTP from the blood to the brain while that after chronic treatment with morphine may be due to an increased uptake of tryptophan.


Synthesis and inhibition analysis of 2(4)-imino-4(2)-amino-2,4-dideoxyriboflavin, a dual antagonist of riboflavin and folinic acid.

The synthesis of the 2,4-diamino analogue of riboflavin is described. Inhibition analysis in a microbial assay system indicated that this compound has a weak antifolate activity that could be overcome with a minimal amount of folinic acid, but at higher concentrations both folinic acid and riboflavin were required for the reversal of its inhibitory effect.


Effect of Corynebacterium parvum on tumor growth in normal and athymic (nude) mice.

The effect of systemic or local injection of Corynebacterium parvum at the tumor site on the growth of various murine tumors was studied in intact and congenitally athymic BALB/c mice. Systemic injection of C. parvum usually had a marked antitumor effect in both types of mouse. Two lymphomas, which regressed spontaneously in untreated intact mice but not in athymic mice, grew progressively in intact mice given systemic C. parvum, though their growth was inhibited in similarly treated athymic mice. Local injection into the site of the tumor markedly inhibited tumor growth in intact mice but was without effect in athymic mice. C. parvum was believed to exert its antitumor effects by two different mechanisms, only one of which was T-cell dependent. The mechanism not dependent on T-cells was particularly activated by systemic C. parvum injection.


Some observations on the reversibility of methotrexate toxicity in normal proliferating tissues.

Thymidine, in the absence of hypoxanthine, failed to protect normal mice from the acute toxicity of methotrexate, though tumor-bearing animals could be protected with thymidine alone, probably as a result of the availability of DNA degradation products released from drug-sensitive tumor cells. Although metrotrexate induced an early purine deficiency in gut cells, this effect was not detected in bone marrow. Later, purine deficiency became apparent in the gut and bone marrow of methotrexate-treated animals.


Gastrointestinal bleeding following head injury: a clinical study of 433 cases.

The incidence of gastrointestinal bleeding was studied in 433 patients with head injury. This complication has a strong correlation to the severity of the injury. Other factors such as shock, arterial pO2 and glucocorticoid administration were not related to incidence of gastrointestinal bleeding. Forty per cent of patients developed bleeding within 48 hours and approximately and additional 40% within one week. Only nine patients required more than 1,000 ml of blood, and eight of these died and one requiring emergency abdominal surgery lived.


Gastrointestinal blood loss. Effect of aspirin, fenoprofen, and acetaminophen in rheumatoid arthritis as determined by sequential gastroscopy and radioactive fecal markers.

The feasibility of determining the exact site and amount of drug-induced gastric bleeding was tested. Fourteen patients with rheumatoid arthritis received equivalent therapeutic doses of the antinflammatory drugs aspirin, 4 gm/day, and fenoprofen calcium, 2.4 gm/day, in randomized order for seven days. Acetaminophen was given for 14 days just prior to each of these periods. By fiberoptic gastroscopy, antral ulceration and acute mucosal lesions were found in seven patients following aspirin ingestion, in one taking fenoprofen, and in none taking acetaminophen. Fecal blood loss in four-day stool collections, quantitated by autologous chromium 51-labeled erythrocytes shed into the stool averaged 5.0 ml/day while taking aspirin, 2.2 ml/day while taking fenoprofen calcium, and 0.8 ml/day while taking acetaminophen. The mean blood loss was greater for those in whom gastric lesions developed while taking aspirin than for those in whom lesions did not develop. The short-term risk of erosive gastritis was greater for aspirin than fenoprofen.


[The value of RNase-ANA determinations for the diagnosis of Sharp syndrome (mixed connective tissue disease) (author's transl)].

The presence of antinuclear antibodies with speckled pattern is essential for the diagnosis of the Sharp Syndrome (moxed connective tissue disease=MCTD). It is however not a specific finding seen only in this condition. Antinuclear antibodies (ANA) with speckled pattern can be observed in sera of patients with various rheumatic diseases (rheumatoid arthritis, systemic lupus erythematosus, Sjögren Syndrome) and even in healthy persons. Yet, utilizing the differentiation system of the antinuclear antibodies, it seems to be possible to establish the diagnosis of mixed connective tissue disease. The antinuclear antibodies in mixed connective tissue disease show high titres (1:2560--1:20,480), contain IgG and bind complement. The antigen is a ribonucleoprotein (RNP) which is sensitive to ribonuclease treatment. The latter observation allows a differentiation between the ANA in mixed connective tissue disease and the ANA in other conditions, especially in systemic lupus erythematosus and Sjögren Syndrome.


[Polyacrylic acid beads as a marker for B-lymphocytes (author's transl)].

B-lymphocytes can be characterized by the adherence of polyacrylic acid beads. The method was analyzed for specifity and reproducibility.


The impact of coronary artery bypass on late myocardial infarction.

Two hundred consecutive patients undergoing coronary artery bypass for stable and unstable angina pectoris were followed clinically 3 to 53 months (mean 27) and with serial electrocardiograms (ECG's) 3 to 43 months (mean 18.5) postoperatively. Complete (twelve lead) resting ECG data including preoperative, early postoperative (in hospital), and late (post hospital) studies were available in 98 per cent (196/199) of hospital survivors. A total of 2,304 ECG's were examined by two cardiologists for a total follow-up of 3,629 patient months. Myocardial infarction was defined as the appearance of a new, significant (Minnesota Code) Q wave. Fifty-four per cent (108/200) had triple vessel disease and 24 per cent (47/200) preinfarction angina pectoris by strict criteria. There was one hospital death for an operative mortality of 0.5 per cent (1/200). There was one late fatal and three late nonfatal myocardial infarctions. Seventeen patients developed new Q waves in the early postoperative period, a perioperative infarction rate of 8.5 per cent (17/200). The 43 month cumulative myocardial infarction rate, including all early and late postoperative new Q waves and three late deaths from cardiac disease, was 14 per cent. Twenty-two per cent (20/91) showed disappearance of Q waves present at the time of hospital discharge. These data suggest that the late myocardial infarction rate is low in surgically managed patients.


The effectiveness of topical cardiac hypothermia.

The effectiveness of cooling the subendocardial myocardium by five different methods was evaluated in a group of 100 patients. The most effective and consistent method to cool the heart was by total body hypothermia with the heat exchanger in the cardiopulmonary bypass system. Myocardial temperature became equal to vena caval blood temperature after only a one minute lag. The least effective methods of myocardial cooling were those in which a bath of chilled fluid enveloped the outside surface of the heart, with and without aortic cross-clamping. The drop in ventricular septal temperature was so small that topical hypothermia, by itself, may be worthless. Two methods in wich chilled fluid was perfused through the coronary system produced a significant lowering of myocardial temperature. One of these methods employs coronary perfusion with a cold cardioplegic solution in addition to total body hypothermia. It is our current choice for myocardial protection during cross-clamping of the ascending aorta.


Effects of coronary artery bypass surgery on hemodynamic parameters and derived indices of myocardial function.

Pre- and postoperative hemodynamic indices were compared in 116 patients subjected to aorto-coronary bypass after an average interval of 128 days. The patients were separated into three different groups according to graft status: Group 1 (n = 77), all grafts patent; Group 2 (n = 27), one occluded graft out of two or three implanted; Group 3 (n = 12), all grafts occluded. There were no significant major changes of values so obtained in the three groups. Those subjects with initially depressed cardiac indices or elevated left ventricular end-diastolic pressures manifested a significant trend toward improvement when at least one bypass graft was patent. A reduction of cardiac index was noted in patients with occluded left anterior descending coronary grafts only in association with closure of other grafts. Deterioration of cardiac index or left ventricular end-diastolic pressure into the abnormal range was unusual in the study group, even when all grafts were occluded. It is concluded that data relating to the influence of aorto-coronary bypass on standard indices of left ventricular function can be properly interpreted only when certain subsets of patients are studied.


Coronary artery bypass surgery in patients seventy years of age and older.

Fifty patients 70 years of age and older underwent coronary artery bypass surgery for disabling angina pectoris or congestive heart failure or both (two quadruple, 11 triple, 25 double grafts, 12 single). Twenty additional procedures were done (11 mitral valve replacements for papillary muscle dysfunction, six ventricular aneurysmectomies, four aortic valve replacements, and one repair of ventricular septal defect). Surgical mortality rate was 8 per cent (four patients). Total mortality rate was 14 per cent, after a mean follow-up of 17 months. Of 30 patients undergoing coronary artery bypass surgery alone, two died during surgery and none of follow-up. Age alone should not be a contraindication for coronary artery bypass surgery. Surgical risk is acceptable in older patients, and improvement can be expected in the majority of patients.


Perioperative mortality rate in patients with unstable angina selected by exclusion of myocardial infarction.

Coronary bypass surgery may be associated with an increased perioperative mortality rate in patients with unstable compared to stable angina. The mortality rate is excessively high when surgery is performed during evolving myocardial infarction. Elevated plasma MB CPK isoenzyme activity is a remarkably sensitive and specific marker of myocardial damage. Accordingly, we studied 111 patients with unstable angina to determine whether exclusion of patients with initially elevated MB CPK improves the perioperative mortality rate. Plasma MB CPK activity was assayed prior to catheterization and every 2 hours therafter. Of the 111 patients, 16, with initially elevated MB CPK activity, were excluded and managed medically. Catheterization was performed in 59 patients, and severe vessel obstruction was documented in 55. Coronary bypass surgery performed in 47 patients was associated with a mortality rate of 4 per cent. Thus, after exclusion of patients with evolving infarction by MB CPK isoenzyme analysis, catheterization and coronary bypass surgery in patients with unstable angina resulted in a mortality rate comparable to that in patients with stable angina.


Effects of coronary bypass surgery on the electrical activity of revascularized myocardium. Immediate and early postoperativeobservations.

The effect of myocardial revascularization on bipolar epicardial electrograms was recorded with fixed wire electrodes from revascularized left ventricular sites and from control sites on the right ventricle. Studies were performed during and after surgery in 19 patients undergoing aorta-coronary bypass grafting for occlusive coronary artery disease and in 6 additional patients having aortic valve replacement for isolated aortic valve disease. In the latter 6 patients, neither left nor right ventricular electrogram voltage changed immediately following aortic valve replacement; however, left ventricular electrogram voltage gradually decreased for 5 days postoperatively. In the 19 patients with coronary artery disease, electrogram voltage in the revascularized area increased immediately following coronary bypass grafting (+40 to +300 per cent) in 13 patients (68 per cent) and immediately decreased (-20 to -70 per cent) in 6 patients (32 per cent). In 5 of the patients showing immediate increases, temporary occlusion of the bypass grafts for 3 minutes during surgery resulted in a decrease of electrogram voltage in the distribution of the occluded bypass, followed by return to preocclusion levels after release. Postoperative monitoring of electrogram voltage for 5 days in all patients with coronary artery disease revealed that the electrogram voltage in the revascularized area decreased to or below control levels in 16 patients (84 per cent) and remained increased in 3 patients (16 per cent). These observed changes did not correlate with preoperative hemodynamics, number of grafts, graft flow rate, aortic cross-clamp time, cardiopulmonary bypass time, and the early postoperative course. These preliminary observations suggest that coronary bypass grafting does affect the electrophysiological state of the revascularized myocardium. However, the mechanism by which it occurs and its clinical implications remain to be determined.


Injury to ascending aorta by partial-occlusion clamp during aorta-coronary bypass.

Disease of the proximal ascending aortic wall from prolonged, poorly controlled hypertension predisposed to intimal injury after clamp compression. This creates a spectrum of problems: (1) intimal tear with late formation of a localized aneurysm, (2) delayed acute dissecting aneurysm, and (3) intraoperative acute dissecting aneurysm. Principles of management are discussed.


Coagulation factors influencing thrombosis of aorta-coronary bypass grafts.

Thirty patients in whom all aorta-coronary artery vein grafts became occluded within one year of operation, as demonstrated by cardiac catheterization, were evaluated for hypercoagulability. A total of 59 grafts were constructed in these patients. At operation, blood flows of 35 to 90 c.c. per minute were measured through the grafts. In 23 of the 30 patients, the blood was to be hypercoagulable, as evidenced by a low level of antithrombin III activity, high thrombin generation index, high factor VII values, or high platelet adhesivity. Another group of 11 patients (total number of grafts, 23) had all grafts patent at cardiac catheterization. These patients had flows through the grafts ranging from 20 to 125 c.c. per minute. None of the patients with patent grafts had hypercoagulable blood. The status of runoff was comparable between the patients with open grafts and those with occluded grafts.


Gastrointestinal hemorrhage. An unusual complication of total anomalous pulmonary venous drainage.

A newborn boy had exsanguinating gastrointestinal hemorrhage in in the first week of life secondary to an unusual form of infradiaphragmatic pulmonary venous drainage. Autopsy and postmortem angiograms demonstrated huge esophageal varices as the course of the uncontrolled bleeding. The occurrence of massive gastrointestinal hemorrhage should be considered to be a rare but possibly lethal complication in patients with total anomalous pulmonary venous drainage (TAPVD) type III and IV.


[Pathology, clinical appearance and therapy of Ménétrier's disease (author's transl)].

Clinical pathology of Ménétrier's disease is reviewed and 3 own cases are presented. All symptoms are unspecific exception made for the enteral protein loss. Roentgenologic and endoscopic appearance contribute to the diagnostic but only histologic examination is decisive. Gastrointestinal bleeding, acute pyloric stenosis, profuse albumin loss are all clear indications for an operation, but also the possibility of malignancy should be kept in mind. Resection should include all abnormal parts of the stomach. Recurrency of the Ménétrier's disease is only known after incomplete resection.


Epidermal growth factor and the multiplication of cultured human epidermal keratinocytes.

The culture lifetime of epidermal cells of newborn humans is increased from 50 to 150 generations by adding to the medium epidermal growth factor, a polypeptide mitogen. EGF seems to delay senescence of the cells by maintaining them in a state further removed from terminal differentiation. This effect is revealed by a greater ability of the cells to survive subculture and initiate new colonies, but not necessarily by an increased growth rate.


Von Willebrand's disease and pregnancy.

The course of a pregnant patient with von Willebrand's disease, who underwent a successful cesarean section without supportive Factor VIII therapy is described. She had no postoperative bleeding despite a persistently prolonged bleeding time. The significance of the bleeding time, Factor VIII activity, and Factor VIII-related antigen in relation to bleeding tendency and therapeutic management is discussed.


External diseases of the eye.

The child presenting a red, tearing eye can pose a dilemma for the pediatrician. A good history and a careful systematic examination using good light and magnification should lead the physician to the proper diagnosis. The child with no complaints other than discharge probably has a conjunctivitis, while the child with photophobia and a scratchy sensation should make one search for either a foreign body or a corneal problem. Fluorescein dye is invaluable in outlining a corneal scratch, abrasion, dendritic ulcer, or bacterial ulcer; and the use of smears and cultures can help pinpoint the exact cause of the patient's difficulties and help in choosing the proper medication. The care of the patient with a red eye may be difficult; but when properly done, it can be a source of great satisfaction to both the patient and the physician.


Evaluation of neonatal intracranial hemorrhage by computerized tomography.

Computerized tomographic (CT) brain scan was performed on 28 infants with unexplained cardiorespiratory and neurologic deterioration and bloody lumbar cerebrospinal spinal fluid. Fourteen of 20 with intraventricular hemorrhage (IVH) died; the six infants with lesser degrees of IVH survived. Significant subarachnoid hemorrhage (SAH) was demonstrable in three infants and three had negative scans despite bloody CSF. We have found that CT scans provide useful information about the size and extent of neonatal IVH and distinguished it from SAH. It also confirms the diagnosis of post-hemorrhagic hydrocephalus in these infants. Continued use of the CT scan will help us to understand the natural history and the effects of neonatal intracranial hemorrhage among the survivors of intensive care.


Methotrexate and azathioprine treatment of childhood dermatomyositis.

Modern treatment of childhood dermatomyositis with corticosteroids has resulted in greatly improved prognosis and style of life. The immunosuppressive drugs methotrexate and azathioprine have been utilized as ancillary agents in life-threatening disease and in children whose disease could not be adequately controlled with prednisone alone. Two patients are completely well without medication two and seven years after onset; two have received no medications for more than two years and have only subtle signs of any residual illness although they had been profoundly ill for two to three years after the onset of dermatomyositis. A fifth patient, completing the third year of disease, remains ill and continues to require medications but has improved sufficiently to return to regular class in school.


Duck virus hepatitis.

The present report gives a survey of the occurrence in Denmark of DVH, its symptoms,the course of the disease, transmission of infection and the posibilities of prevention and control. As it appears from Figs. 2 and 3, DVH can cause considerable losses for the individual producers, for whom it is difficult to safeguard themselves against new infections because of the resistance and stability of the DVH virus in infected premises. Three possibilities of controlling DVH are pointed out: isolation of the flocks, serum therapy and vaccination.


Juvenile rheumatoid arthritis.

Juvenile rheumatoid arthritis is a diverse group of diseases that includes systemic-onset, polyarticular, and pauciarticular types. Appreciation of the different types and their hallmarks is particularly important to accurate diagnosis, which is determined by exclusion of other known disease entities in children with chronic arthritis (more than three months' duration). Therapy should be directed at the arthritis per se (synovitis), at the extra-articular manifestations, and at the whole child. Salicylates provide the most satisfactory control of the arthritis per se and of the systemic manifestations in most cases. Iridocyclitis should be managed in consultation with an ophthalmologist. Patients should not be regarded as invalids or restricted needlessly. The prognosis for children with juvenile rheumatoid arthritis is good. In most patients, the disease remits without causing permanent joint damage.


Managing chronic leukemias.

Chronic lymphocytic leukemia and chronic granulocytic leukemia vary considerably in their clinical features, laboratory findings, and therapy, but both generally have an ominous prognosis. Chemotherapy remains the mainstay of treatment in both disorders, with adjunctive measures to control complications such as anemia and splenomegaly. Immunotherapy for granulocytic leukemia is still under study but appears promising.


Density of sodium channels in mammalian myelinated nerve fibers and nature of the axonal membrane under the myelin sheath.

The density of sodium channels in mammalian myelinated fibers has been estimated from measurements of the binding of [3H]saxitoxin to rabbit sciatic nerve. Binding both to intact and to homogenized nerve consists of a linear, nonspecific, component and a saturable component that represents binding to the sodium channel. The maximum saturable binding capacity in intact nerve is 19.9 +/- 1.9 fmol-mg wet-1; the equilibrium dissociation constant, Kt, is 3.4 +/- 2.0 nM. Homogenization makes little difference, the maximum binding capacity being 19.9 +/- 1.5 fmol-mg wet-1 with Kt = 1.3 +/- 0.7 nM. These values correspond to a density of about 700,000 sodium channels per node--i.e., about 12,000 per mum2 of nodal membrane. From the difference between the values of maximum saturable binding capacity in intact and homogenized preparation, given the statistical uncertainty of their estimate, it seems that the internodal membrane can have no more than about 25 channels per mum2. The significance of these findings for saltatory conduction and in demyelinating disease is discussed.


In vitro evidence of cell-mediated immunity after exposure of mice to both live and inactivated rabies virus.

Mice exposed to live or beta-propiolactone-inactivated rabies virus generated a strong, specific cell-mediated cytotoxic response which was generally maximal 6 days after inoculation. Release of 51Cr was apparently a function of immune thymus-derived lymphocytes (T cells) because it was abrogated by prior incubation of spleen cells with anti-thymus antiserum and complement but was undiminished by passage of spleen cells through nylon-wool columns. Cytotoxicity was always maximal for interactions in which thymus-derived cells and targets shared H-2 genes but, unlike the situation found in other assays of this type, considerable lysis of allogeneic, virus-infected target cells may also occur. Perhaps the most significant finding from these experiments is that an inactivated virus has been shown to stimulate a potent cytotoxic thymus-derived cell response. Manipulation of this experimental model may allow analysis of the antigens required for stimulation of cell-mediated immunity. A more practical consequence may be the development of more rational protocols for postexposure vaccination against rabies. Prior treatment of mice with antirabies antibody severely depressed the generation of cell-mediated immunity.


Variations in permeability along individually perfused capillaries of the frog mesentery.

When single capillaries in the exposed transilluminated frog mesentery were perfused with solutions containing patent blue V (molecular radius 0-7 nm), unbound T1824 (molecular radius 1-3 nm) and T1824-albumin (molecular radius 3-6 nm), the coloured molecules initially appeared to enter the extracapillary tissues more easily at some places than at others along the length of the vessels. Three patterns of extravascular distribution were observed: (1) High frequency unevenness: patent blue V and unbound T1824 first appeared outside the capillary as spots, bars or bands set at intervals 30-80 mum apart along the length of the vessel. (2) Low frequency unevenness: at later times, the extravascular dye was seen to be unevenly distributed on a much larger scale, with lengths of vessel of up to 400 mum surrounded by little extravascular dye separating similar lengths around which much dye had accummulated. This pattern of distribution was seen for all three solutes. (3) Arteriovenous gradient: perfusions with all three solutes resulted in more extracapillary colouration accumulating around the venous ends of the capillaries. Reasons are given for believing that the distribution of extracapillary solute reflected the distribution of permeability along the length of the capillary. The variations in permeability were attributed to an uneven distribution of small pores along the capillary rather than to presences of large pores.


Computed tomography in head trauma.

Retrospective analysis of 200 cases of documented head trauma demonstrated an accuracy approaching 100% in the diagnosis of intra- and extracerebral collections of blood. Caution must be exercised in the evaluation of trauma 1 to 5 weeks old, since subdural hematomas have the same density as normal brain tissue, and angiography may be necessary. The clinical diagnosis of brainstem contusion is associated with a remarkably high level (54%) of surgically correctable lesions. The use of computed tomography in the evaluation of other traumatic intracranial lesions is discussed.


[Results of coloscopy of polypectomy in the years 1974-1975 at the Basel county hospital].

The diagnostic value of coloscopy was assessed by analysis of the endoscopic findings in 310 patients investigated between January 1974 and December 1975. Altogether, 342 coloscopies were performed with a complication rate of 1.5% (3 perforations, 2 hemorrhages). Polyposis of the colon, inconclusive radiologic findings and search for a bleeding source were the main indications for the endscopic examination of the colon. Special attention was focused on polyposis, its distribution and estension, radiological appearance and histology. 65% of the polyps with a known tendency to become malignant were found beyond the reach of the rigid rectosigmoidoscope. However, 98% were localized below the splenic flexure.


[Intestinal infarct due to spontaneous mesenterial and intramural anticoagulant hemorrhage].

A 69-year-old man who had been anticoagulated for 18 months reported with acute pain in the epigastric region. Laparotomy revealed more than 1 liter of unclotted blood in the peritoneal cavity and, in the mesentery of the medium small bowel, a number of fist-size hematomas and a 30 cm long, hemorrhagic, fibrin-coated small bowel segment gangrenously infarcted in the middle section. It is shown why a spontaneous "anticoagulant" hemorrhage must be regarded as the cuase of the gangrenous intestinal infarction.


Immune reactions in pulmonary fibrosis.

Two groups of fibrosing lung disorders have been studied, namely connective tissue disorders and fibrogenic inorganic dust diseases. Antinuclear factors (ANA) are frequently raised in both, but to varying extents and having markedly different characteristics when analysed in detail. The evidence for immune complex deposition in the lung in human disease is summarized and the relationship between ANA and the radiographic extent of fibrogenic inorganic dust disease is described. The evidence of lymphocyte responsiveness is incomplete, but holds interesting potential. Preliminary studies of histocompatibility antigens are summarized and warrant further investigation.


[Immunological aspects of pulmonary granulomatosis with special reference to sarcoidosis].

A wide variety of exogenous or endogenous aggressors exhibit the capacity to induce pulmonary granulomatous lesions. This lesion is characterized by exacerbation of phagocytic function and tentative development of a specific immune response. In many clinical situations there is a well developed circulating antibody response with deficient cell-mediated immunity of variable degree. Finally, it is argued that the granulomatous lesion may be due to abnormal cooperation between T and B lymphocytes.


Ribavirin: efficacy in the treatment of murine autoimmune disease.

Ribavirin, a drug with known antiviral activity, was given to mice with established lupus nephritis. Ribavirin was effective in prolonging survival, reducing the titer of antibodies to DNA, and reversing proteinuria. Other antiviral agents were not effective in the dosages used.


Functional characteristics of monocytes. 1. Essential role in the transformational response of human blood lymphocytes to phytomitogens.

Phagocytic glass-adherent mononuclear cells in peripheral human blood (morphologically monocytes) have been shown to play an essential role in lymphocyte transformational response to phytomitogens. Lymphocytes from peripheral blood have been exhaustively depleted of monocytes by successive treatments, first with opsonized iron particles with eventual magnetic elimination of phagocytic cells, followed by filtration of the same population through packed glass-sand columns. This subpopulation, enriched in T lymphocytes and containing around 4% B lymphocytes, does not transform in response to concanavalin A, phytohemagglutinin, or pokeweek mitogen unless viable monocytes are added to the culture. Supernatant fluids from monocyte-enriched human blood leukocyte cultures can substitute for monocytes in restoring response. Interaction of the phytomitogen with lymphocyte, while essential, is not sufficient to trigger transformation, requiring a second signal provided by the monocyte probably via release of soluble mediators.


Proliferative haemorrhagic enteropathy in pigs.

An outbreak of proliferative haemorrhagic enteropathy (PHE) occurred in two epidodes and affected 372 adult pigs in the breeding units of a minimal disease piggery; 186 pigs died. In the initial episode breeding sows and boars of all ages were affected, suggesting infection of a fully susceptible population. Animals involved in the first episode of the disease did not show clinical symptoms at a later date and further clinical cases occurred only in animals introduced into the breeding population. Antibiotic feed medication was an effective method of prophylaxis. Bacteria resembling Campylobacter sputorum subspecies mucosalis were isolated from the intestinal mucosa of affected animals.


[Low-risk transfemoral selective coronary arteriography employing Sones catheters and total body heparinization (author's transl)].

Indications, results, and complications in 400 transfemoral selective coronary arteriograms are reported. After the first 100 examinations a sharp decline in serious complications and an increase in complete studies with opacifications of both coronary arteries and left ventricle was achieved. This was thought to be due not only to mounting experience but also to total body heparinization and transfemoral use of Sones catheters with torque control. According to our results transfemoral selective coronary arteriography is considered to be an indispensable examination which may be performed by experienced investigators without hesitation when indicated.


[The treatment of intractable pain by transdermal electrostimulation (author's transl)].

Various kinds of electric currents were examined with regard to their efficacy in the relief of pain when applied transdermally. The most suitable form of current was applied to 39 cases (who had been especially selected in a negative sense) suffering from intractable pain. About half were patients with malignant disease encroaching or causing pressure on nerves or plexuses. The other half consisted of patients suffering from intractable neuralgia totally resistant to all forms of therapy. A diagram of the pulsating direct current is shown. Results were as follows: no effect in nine cases; 5 cases obtained moderate relief of pain for up to 12 hours; the remaining 25 patients reported complete relief of pain already after the first application of current lasting from 12 hours to 3 weeks and--after a series of sessions (3 to 17 treatments)--of up to 12 months. Two of these patients were supplied with a unit for home treatment after their relatives had been trained in the use of the instrument. In these two cases, however, a large number of treatment sessions became necessary. These results warrant continued study of cases of this kind and call for a study of the basic mechanisms possibly underlying these effects. If the present results are confirmed, it is planned to introduce battery-powered miniaturized sets, which patients may use themselves after fixation of electrodes.


Characterization of a splenic factor inhibiting DNA-synthesis in lymphocytes in vitro.

A factor inhibiting DNA synthesis in lymphocytes from lymph nodes and thymus of guinea pigs and rats has been isolated from the calf spleen. A crude extract was obtained by homogenization of the spleen in saline, centrifugation at 1,200 and 46,000 g, heat precipitation at 60 degrees C, acetone precipitation, followed by lyophilization at the acetone precipitate. The active material was partly purified and characterized by gel chromatography, ion exchange chromatography, ultrafiltration and preparative electrofocusing. The active factor was found to be acidic and heat stable (60 degrees C, 10 min) with a molecular weight between 75,000 and 17,000 daltons. At preparative electrofocusing inhibiting material focused at pH 4.0. The splenic factor inhibited the DNA synthesis in lymphocytes from guinea pigs and rats, but not the DNA synthesis in HeLa cells. During the purification, material which enhanced the uptake of 3H-thymidine in DNA of lymphocytes was separated from the inhibitor. The stimulating factor had a molecular weight below 10,000 daltons as judged by ultrafiltration and gel chromatography. At preparative electrofocusing stimulating material focused around pH 8.5.


Diagnostic and prognostic significance of electrocardiographic and CPK isoenzyme changes following coronary bypass surgery: correlation with findings at one year.

The incidence of ECG (14 per cent) indication of acute myocardial infarction complicating coronary artery bypass surgery is documented, corroborating the findings of prior series. An additional 32 per cent of patients had appearance of myocardial specific CPK-MB in serum during the immediate postoperative period. All patients surviving to 1 year following surgery (93 of 103) were asked to return for repeat cardiac catheterization to determine the presence and extent of interim ventricular contraction abnormalities. Sixty-five (70 per cent) of the group returned for evaluation. Preoperative and 1 year postoperative left ventriculograms were compared to determine if new contraction abnormalities would confirm the specificity of perioperative QRS and isoenzyme changes, and if the absence of new abnormalities would confirm their sensitivity. The majority of patients (65 per cent) had new areas of asynergy. However, 73 per cent of these were confined to the apex and thus could have been produced by the vent employed during cardiopulmonary bypass. QRS changes were 100 per cent specific and CPK-MB appearance was 78 per cent specific but they were only 20 and 54 per cent sensitive, respectively. Indeed, 46 per cent of those with new asynergy which was non apical had neither QRS change nor CPK-MB appearance. Thus QRS changes were always--and CPK-MB appearance was usually--associated with new asynergy but, in addition, many patients with no perioperative indication of infarction developed new areas of left ventricular contraction abnormality within the first postoperative year.