Anaphylaxis in the monkey: hemodynamics and blood flow distribution.

Aggregate anaphylaxis was induced in eight ovalbumin-sensitized monkeys (Macaca irus). Hemodynamics, blood flow distribution and myocardial performance were studied. Following challenge, severe circulatory shock developed. Systemic arterial and left atrial pressures decreased and pulmonary arterial and right atrial pressures increased. There was a tenfold increase in pulmonary vascular resistance, and cardiac output was markedly reduced (-75%). A redistribution of the blood flow to vital organs (brain, heart and liver) occurred, at the expense of flow to other regions (muscles, kidneys, pancreas and spleen). There was also a redistribution of the blood flow within the myocardium, resulting in an unchanged right ventricular blood flow, despite a decrease in total myocardial blood flow. Right ventricular stroke work was reduced in spite of high filling pressures, whereas the decrease in left ventricular stroke work coincided with low filling pressures. It is concluded that the initial main cause of the low outflow state was an increased resistance in the pulmonary circulation followed by acute right heart failure.


Release of gastrin from the skeletal muscles and from the antral mucosa in cats induced by sulfonuric drugs.

The present observations indicate that sulfonuric drugs release gastrin both from peripheral nerves in striated muscles and from endocrine-like cells in the gastrointestinal tract. Gastrin appears in perfusates of extirpated cat legs after administration of tolbutamide or glibenclamide (5-50 mg/kg or 5-500 microgram/kg perfused tissue respectively) to the perfusion medium. Furthermore gastrin is released into the portal vein of cats after i.v. administration of glibenclamide (5-50 microgram/kg). The finding that sulfonuric drugs not only release insulin from beta-cells in the pancreas, but also gastrin from gastrin producing cells in the stomach as well as from nerve fibers in the skeletal muscles, indicate that sulfonuric drugs have more wide spread effects than previously assumed. Possible consequences of the drug induced release of peptides from peripheral nerves as well as of the release of gastrin from the gastrointestinal tract are discussed.


Some aspects of tuberculoid leprosy and chemotherapeutic trials.

The author describes the progress made in our knowledge of tuberculoid leprosy since the original case of Jadassohn in 1898. The numerical importance of T patients in different parts of the world is reviewed and their role in the transmission of the disease discussed. An analysis is made of the subgroups into which T leprosy is divided according to the clinical symptoms, bacteriology, histopathology and immunology in the Madrid classification as well as in the Souza-Lima-Souza Campos and Ridley-Jopling studies. The author concludes that a majority of T patients are immunologically stable and belong to two well defined groups, the first called T annular in the Souza-Lima-Souza Campos study and TT in the Ridley-Jopling classification and the second called T reactional by S.L.-S.C. and BT by R.J. Taking into account the high proportion of T cases in most epidemiological situations, their generally accepted good prognosis under treatment and the present availability of several drugs of proved efficacy, the author suggests to carry out in T leprosy under controlled conditions a trial of a number of therapeutic regimens of not more than 12 months duration. Follow-up periods will make possible medium and long-term evaluation of results after 3 and 5 years respectively of the initiation of the chemotherapeutic regimens. The practical implications of effective and well tolerated short-term therapy in T leprosy is stressed. Its widespread use in field programmes will represent among other advantages a considerable economy in personnel and drugs costs. The use of a single protocol is recommended. The one worked out by THELEP for therapeutic trials in lepromatous leprosy could be adopted with a few changes made necessary because of the morphological and bacteriological differences between L and T leprosy. It is suggested that, if the results of the trial are successful, similar regimens could be tried in indeterminate leprosy.


Glibenclamide and glipizide in maturity onset diabetes. A double-blind cross-over study.

The effects of glibenclamide and glipizide on the concentrations of S-glucose, S-insulin and S-lipids and on the 24-hour urinary glucose excretion were studied in 37 patients with maturity onset diabetes. A double-blind, cross over double-dummy technique was used. The fasting S-insulin concentration was higher during glibenclamide therapy, while the increase in insulin concentration one hour postprandially was stronger during  glipizide therapy, supporting the concept that glibenclamide has a more prolonged and glipizide a more fast-acting effect on insulin secretion. The S-glucose concentration was lower in the fasting state as well as one hour postprandially during glibenclamide therapy which, together with a lower 24-hour urinary glucose excretion, indicates that glibenclamide has a stronger blood glucose-lowering effect. Although statistically significant, the differences were marginal from a clinical point of view. The lipid levels remained unchanged.


Clinical significance of abnormal heterogeneity of transferrin in relation to alcohol consumption.

An abnormal microheterogeneous component of serum transferrin, with a higher isoelectric point than the normal main component, was studied by means of isoelectric focusing and direct immunofixation in 98 alcoholic patients, 22 patients with liver diseases and 100 controls. Its relation to acute and prolonged ethanol intake was studied in healthy volunteers. The abnormal transferrin component was found to be a sensitive indicator of prolonged, high alcohol ingestion, and was observed in 81% of patients with an admitted consumption of more than 60 g ethanol/day, and normalized after at least 10 days of abstinence. It occurred in 1% of the controls and in none of the cases with liver diseases without current alcohol abuse. There is evidence of a reduced sialic acid content in the abnormal transferrin. No similar change has been found in a number of other glycoproteins. This test may be a useful and sensitive tool for the detection of chronic alcohol consumption.


Free light chains of immunoglobulins in amyloidosis.

Monomeric (M) and dimeric (D) forms of free light chains in serum have been measured by a sensitive radioimmunoassay in eight patients with amyloidosis without monoclonal proteins. Significantly elevated concentrations of D lambda chains were demonstrated in two of four patients with localized amyloidosis. The two patients had a significantly increased D/M ratio of both kappa and lambda chains. One patient had localized amyloidosis and normal concentration of monomeric and dimeric light chains had an abnormal fragment of light chains. A low kappa/lambda ratio was found in patients with localized amyloidosis. Four patients with secondary amyloidosis and renal insufficiency had increased amounts of free light chains. The concentration of light chains and the D/M ratio in this group corresponded to the impairment of renal function.


Ventilation-perfusion studies in suspected pulmonary embolism.

The results of ventilation-perfusion (V-Q) imaging and pulmonary angiography were retrospectively analyzed in 146 patients with suspected pulmonary embolism (PE) to define the frequency of PE associated with various scintigraphic patterns. When the radionuclide images demonstrated at least two moderate-sized or one large area of V-Q mismatch, the probability of PE was 92%. However, only one of three patients with a single moderate-sized V-Q mismatch had PE, while small V-Q mismatches were not associated with PE in any of 19 patients. Matched V-Q abnormalities in lung regions that were radiographically normal were infrequently due to PE (4.8%). When a perfusion defect was substantially smaller than a corresponding radiographic abnormality, the frequency of PE was low (7.7%). Conversely, when a perfusion defect was substantially larger than the corresponding radiographic abnormality, there was a high probability of PE (87%). Matched perfusion and radiographic abnormalities indicated an intermediate probability of PE (27%). Patients with suspected pulmonary embolism may be classified into groups with low, intermediate, or high probability of pulmonary embolism on the basis of size and number of perfusion defects and a careful comparison of perfusion defects with ventilatory and radiographic findings.


What becomes of pulmonary infarcts?

In 32 patients, 58 angiographically proven pulmonary infarcts were followed for 3 months or longer by serial chest radiography. Complete clearing was seen in 29 (50%) of the infarcts on chest radiography. In the other 29 infarcts that left residual findings, linear scars were identified in 14, pleural diaphragmatic adhesions in nine, and localized pleural thickening in six; in all cases the features were diminutive when compared with the original abnormality. Follow-up perfusion lung images at similar time intervals to the chest films were available for 44 infarcts. Seven of these showed complete resolution and the other 37 showed a residual but much smaller perfusion defect. None of the patients had known preexisting pulmonary disease. The frequency of permanent radiographic scarring seemed to be the same at all ages.


CT of the esophagus: I. Normal appearance.

The thoracic esophagus is easily demonstrable throughout its entire length on thoracic computed tomography (CT). The soft tissue planes separating the esophagus from its adjacent mediastinal structures are normally distinct. Blurring or distortion of these tissue interfaces is a reliable indicator of disease. The normal CT anatomy of the esophagus and mediastinal relationships are described. Air in the esophagus is considered a normal finding.


CT of the esophagus. II. Carcinoma.

Thoracoabdominal computed tomography (CT) scanning was performed prior to treatment on 30 patients with proven carcinoma of the esophagus. Operative, bronchoscopic, and/or autopsy data were reviewed and showed that CT correctly identified the extent of medistinal spread in 27 patients and intraabdominal metastases in 22 patients. The ability of CT to reliably predict the extent of disease should help the surgeon and radiation oncologist plan optimal therapy.


Unusual features of pulmonary sling.

Patients with an anomalously placed left pulmonary artery ("pulmonary sling") typically have signs and symptoms of respiratory obstruction in the neonatal period. Experience with four previously unreported patients confirmed this. Typical radiographic features include unilateral air trapping (usually on the right side), an abnormal position of the esophagus, and a soft tissue mass interposed between the trachea and esophagus. Less common findings include a normal esophageal position, left-side air trapping, and delayed egress of neonatal pulmonary fluid. Both typical and atypical features were seen; the more unusual aspects are emphasized.


Late complications at repair site of operated coarctation of aorta.

Late complications at the repair site of coarctation of the aorta include aneurysms and persistent coarctation. Aneurysms are usually due to failure of the surgical anastomosis and can occur many years after repair. Continued aortic coarctation may be due to either repair failure or failure of the anastomotic site to grow with the patient. Three cases are presented and the literature reviewed.


Primary hemangiopericytoma of lung: radiography and pathology.

Two cases of primary hemangiopericytoma of the lung are reported. The massive tumors had radiographic features of round or oval contour, homogeneous opacity, well circumscribed smooth outline without calcification, and no compression of the surrounding lung tissue. They were rather homogeneous histologically, well encapsulated, and centrally located, but extended peripherally by replacement, instead of compression, of the pulmonary parenchyma. Review of the literature about 34 other cases suggests these are the usual characteristics of primary hemangiopericytomas of the lungs.


CT as a primary diagnostic method in evaluating intraabdominal abscess.

In 19 cases, a correct diagnosis of intraabdominal abscess was made by CT body scanning. There was one false-positive diagnosis and initially one false-negative diagnosis. CT proved to be an efficient imaging method for diagnosis, for planning of therapeutic procedures, and in monitoring response to operative or conservative treatment. It has advantages over ultrasound and gallium scanning especially in severely ill, postoperative, and obese subjects. In addition, needle aspiration under CT control is readily performed and can be undertaken at the same examination. Confirmation of the diagnosis and therapeutic aspiration with or without introduction of a drainage catheter can then be undertaken.


Evaluation of contrast markers for CT aspiration biopsy.

Precision percutaneous needle aspiration biopsy under guidance of computed tomography is facilitated by injection of a small amount of contrast material during the biopsy procedure. CT scan immediately after biopsy clearly documents the biopsy site. There was no adverse effect of the contrast agents on the quality of staining or preservation of cellular architecture. To the contrary, the aspirates obtained after contrast injection were generally better preserved and better stained than the control specimens. This may be due to a decrease in drying, with the more fluid aspirates obtained after contrast injection.


Antral mucosal diaphragms in adults.

A group of 53 patients with the diagnosis of antral mucosal diaphragm is reported. In over 50% of the cases the diaphragm was considered an asymptomatic lesion. In addition, an autopsy study in 29 unselected cases is reported with demonstration of five antral mucosal diaphragms in different forms. On the basis of these findings, it is evident that the antral mucosal diaphragm in the adult is not an acquired lesion secondary to peptic ulcer disease, but may be congenital. In addition, techniques of radiologic evaluation of the diaphragm for significant narrowing of the central aperture using the compressed barium tablet, and for significant gastric outlet obstruction using the "barium burger" examination, are described.


Colitis in the elderly: ischemic colitis mimicking ulcerative and granulomatous colitis.

Eight patients over age 60 years had sudden onset of acute abdominal pain and rectal bleeding in the absence of prior inflammatory bowel disease. Several improved on medical therapy alone; those who required surgery suffered no recurrence up to 6 years. Although the pathologic specimens on these patients were first considered to represent ulcerative colitis or Crohn's disease, their histories and clinical courses are much more consistent with ischemic colitis. Since there are only a limited number of reactions that the bowel can muster against a host of damaging processes, histologic criteria alone are usually not sufficient to separate ischemic disease of the colon from ulcerative colitis and Crohn's disease. This is also true of radiographic features. Thus the diagnosis of ischemic colitis rests on clinical onset and course after treatment.


Percutaneous transhepatic portography. III. Relationships between portosystemic collaterals and portal pressure in cirrhosis.

The relationships among collateral veins, gastroesophageal varices, extrahepatic shunting, and free portal pressure were studied by percutaneous transhepatic portography in 57 patients with cirrhosis of the liver. The size of esophageal varices was related to the size of the coronary and short gastric veins and to the portal pressure. The size of gastric varices was related to cephalad collaterals from the spleen and splenic vein, but not to portal pressure. Portosystemic shunting was associated with collaterals in the lower abdomen, but not with varices or portal pressure.


Transhepatic obliteration of esophageal varices using the stainless steel coil.

Coronary veins in seven of eight patients with bleeding esophageal varices were successfully catheterized and embolized with Gelfoam followed by multiple steel coils. Bleeding immediately ceased in all seven, but recurred within 1 month in six. One had not rebled on 3 month follow-up. Therefore, steel coils do not prevent recurrent bleeding any more effectively than other embolic materials used for this purpose.


Three methods for determining anteversion and retroversion of a total hip prosthesis.

Three new methods to assess the degree of anteversion or retroversion of the femoral component of a total hip prosthesis are described. Compared with previously described methods, the new methods make few physical demands on the recently operated patient. The only requirement is that the affected femur be held in a neutral position parallel to the x-ray table. The methods are relatively easy to perform and are accurate and objective.


Fibrous lesions in the lower extremities in neurofibromatosis.

Multiple fibrous lesions have been noted in the lower extremities of patients with neurofibromatosis (Recklinghausen's disease). These lesions are probably a combination of fibrous cortical defects, nonossifying fibromas, and intraosseous neurofibromas. When several fibrocystic lesions frequent the knee areas in an adolescent, neurofibromatosis should be suspected.


Peritendinitis calcarea of flexor carpi ulnaris.

Calcific tendinitis of the flexor carpi ulnaris presents a characteristic radiographic appearance of amorphous calcification near the pisiform. This calcification frequently is associated with acute symptoms and may be related to certain occupations and hobbies. Knowledge of the pertinent anatomic and radiographic criteria permits accurate diagnosis.


Computed tomographic mammography (CTM).

Breasts of 724 patients were studied by physical examination, mammography, and computed tomographic mammography (CTM) using a scanner designed for evaluation of the breast. Among cases in which CTM was not accompanied by use of contrast material, there were 60 malignant lesions, of which 10% were missed by mammography, 32% by CTM, and 8% by both. Among cases where CTM was supplemented by a 50 ml injection of 75% contrast material, there were 63 malignant lesions, of which 14% were missed by mammography, 16% by CTM, and 3% by both. Among cases where CTM was supplemented by a 300 ml infusion of 30% contrast material, there were 41 malignant lesions, of which 7% were missed by mammography and 5% by CTM, but none by both. Clinically, 22% of the malignant lesions in the infusion series were occult. There were 44 benign lesions in patients studied with the infusion technique. With mammography 68% were suspicious for malignancy, and with CTM, 56%.


Amniography in second trimester diagnosis of myelomeningocele.

Twenty-eight fetuses, at 14-22 gestational weeks, were examined by amniography to identify a thoracic, lumbar, or sacral myelomeningocele. The end point was a fluoroscopic spot film with the fetal back in profile, to show the presence or absence of a bulging midline mass. Fetal irradiation was 0.66 rad +/- 0.36 (SD). There were 26 true negatives and one indeterminate examination. The one true positive was in a patient who had just had negative real-time ultrasonography. It is suggested amniography be used (1) when ultrasonography and amniotic fluid alpha fetoprotein determination disagree about the presence of a neural tube defect, and (2) for further confirmation when both these tests are positive.


CT of septo-optic dysplasia.

Two girls, aged 7 1/2 and 12 years, clinically suspect for septo-optic dysplasia, were investigated by computed tomography (CT). The clinical picture in both cases associated blindness with hypoplasia of both optic discs, and short stature with growth hormone deficiency. Diabetes insipidus was also present in one case. CT demonstrated agenesis of the septum pellucidum and thin optic nerves. In the case with diabetes insipidus the pituitary stalk was enlarged. It is shown that CT accurately delinerates the altered anatomy of septo-optic dysplasia. CT is recommended rather than pneumoencephalography as the definitive neuroradiologic investigation of these patients.


Radiology in Nicaragua: Lessons from a radiologic paramedic training effort.

The authors, during repeated visits and a sabbatical period, participated in the initiation of a program to train radiologic technologists in Nicaragua. The training program, its objectives, and the level of development of Nicaraguan radiology in 1977-1978 are described. The results achieved and problems encountered are discussed. Although the training was effective, all of the goals could not be accomplished because of political unrest. Nevertheless, lessions were learned and conclusions reached concerning future efforts to improve radiologic services in countries such as Nicaragua. These relate to economics, language barriers, governmental control, and the attitudes of native physicians and radiologists.


Long-term results of myocardial revascularization.

During 1970 to 1977, among 1,733 patients who underwent isolated coronary bypass grafting, the operative mortality was 2.5 percent. Actuarial 5 year survival is 88.1 percent. At an average follow-up of 46 months (range 13 to 108), 90 percent of patients remain angina-free or with symptomatic improvement. The 5 year survival rate of patients with single vessel coronary artery disease is 97.9 percent. In patients with multivessel disease, operative survival appears to be favorably influenced by the presence of normal preoperative ventricular function. Late survival is significantly better in patients with multivessel disease with normal preoperative ventricular function or with complete revascularization. Risk of perioperative myocardial infarction has been appreciably reduced by the introduction of cold potassium chloride cardioplegia. Late myocardial infarction has occurred at an average annual risk of 1.46 percent. These data show that long-term survival and a small incidence of late myocardial infarction after myocardial revascularization are more likely in patients who undergo complete revascularization before significant left ventricular myocardial damage has occurred.


Estimating fat body mass from antrhopometric data.

Regression equations have been derived for the calculation of fat body mass in boys from 4 to 12 1/2 years old and girls 4 to 19 years old. Height and weight give a good prediction of fat body mass, but the addition of skinfold thicknesses to the regression equations reduces the number of large errors in the estimates. The regression equations and the limits of accuracy are given.


Decreased chemotactic and random migration of leukocytes during Intralipid infusion.

The soybean oil emulsion Intralipid was given intravenously to 12 healthy subjects for 2 hr. During the infusion an impairment of the chemotactic and random migration of leukocytes was noted. It was correlated to the dose given and to the degree of hypertriglyceridemia induced. Migration was fully restituted 22 hr after the infusion. Also when added in vitro Intralipid caused an impairment of leukocyte motility that followed a dose response pattern.


Free amino acid levels in the blood of patients undergoing parenteral alimentation.

Free amino acid levels were determined in the blood of patients undergoing parenteral alimentation. During amino acid infusions, alanine, valine, glycine, isoleucine, leucine, proline, threonine, serine, methionine, phenylalanine, and lysine levels increased. Bivariate regression analysis was then done to determine the average rise in each amino acid when 1 mmole/hr of that amino acid was infused and when 1 mmole/hr of glucose was infused. This analysis was done on both arterial plasma and arterial wh-le blood increments. The average rise in the amino acid level with 1 mmole of infusion per hour varied from 32 to 133 mumole/liter. Only alanine levels were positively correlated with glucose infusion, while the branched chain levels were all negatively correlated. In no instance could a significant positive arteriovenous difference across the forearm be correlated with the infusion of an amino acid, despite amino acid levels as much as five times normal. Methionine, proline, valine, threonine, and lysine showed the greatest rise in blood concentration per millimole of amino acid infused per hour suggesting that their degradation or use in protein synthesis was limited. While the blood concentration rise in glycine was only about half as much per millimole per hour infused as was found in the previously mentioned group of amino acids, high rates of infusion of this amino acid resulted in large increments inglycine levels. It may be desirable to reduce the amounts of these amino acids in parenteral amino acid formulations.


Plasma zinc and the clinical features of malnutrition.

Human protein-energy malnutrition and zinc deficiency have common clinical features. These were related to the plasma zinc concentrations in 42 severely malnourished children. A low plasma zinc concentration was strongly associated with nutritional edema but not with the degree of edema or the plasma albumin concentration. In the absence of edema, there were significant relationships between plasma zinc concentrations and stunting, skin ulceration, and wasting. Infection was not necessarily associated with a lower zinc concentration. From these data it can be predicted that a malnourished child with edema, skin ulceration, stunting, or severe wasting, will have a low plasma zinc concentration.


Folacin deficiency and requirement in the squirrel monkey (Saimiri sciuresus).

Acute folacin deficiency was studied in eight young squirrel monkeys (Saimiri sciureus). Half of the animals were fed a semipurified deficient diet (no added folic acid) and half were fed a control diet (0.84 mg of added folic acid per kilogram of dry diet). Monkeys fed the deficient diet lost weight and suffered from diarrhea and dehydration leading to the death of one of the animals after 6 weeks. Folacin deficiency also was studied in six older animals fed diets containing varying levels of added folic acid. Monkeys fed diets containing 0.14 or 0.27 mg of added folic acid per kilogram of dry diet slowly developed alopecia, a scaly dermatitis, and a mild macrocytic anemia. When these animals were fed the deficient diet, they lost weight rapidly, the alopecia and dermatitis worsened, excretion of formiminoglutamic acid in the urine increased, and a severe megaloblastic anemia with profound intramedullary hemolysis developed. Deficient monkeys had low plasma and red blood cell folacin values but maintained normal plasma vitamin B12 values. Repletion of the animals fed the deficient diet with injections of folic acid reversed both the hematological and physical deterioration. The folacin requirement for maintenance of body weight in these animals was 28 micrograms of total folacin per kilogram of body weight per day. More  than 75 micrograms of total folacin per kilogram of body weight/day may be needed to assure growth and normal hematological parameters and bone marrow cytology.


Evaluation of the moving intermediate zone concept for determing susceptibility of pseudomonads to gentamicin by the standardized disk agar-diffusion test.

The usefulness of the moving intermediate zone concept for improving the performance of the standardized disk agar-diffusion test in measuring susceptibility of the fluorescent group of pseudomonads to gentamicin was studied. For this purpose, a 3-mm moving intermediate zone lying --3 mm and --6 mm below that measured for the quality control microorganism Pseudomonas aeruginosa, ATCC 27853, and a wider moving intermediate zone lying --2 mm and --7 mm below that for the quality control microorganism were investigated. Data from the authors' previous study of the usefulness of using fixed breakpoints and fixed zones for assessing susceptibility of the fluorescent pseudomonads to gentamicin were used for this analysis. The results indicate that both the 3-mm moving intermediate zone and the wider 5-mm moving intermediate zone produced unacceptably high rates of error for testing the susceptibility of the fluorescent group of pseudomonads to gentamicin by the standardized disk agar-diffusion test.


Assignment of the red cell antigen, Targett (Rh40), to the Rh blood group system.

Statistical and serological evidence from a large kindred and two unrelated adults indicates that Targett (Tar) is an antigen in the Rh blood group system and that its presence is assocciated with a weak expression of the Rh antigen D. In the numerical notation the Tar antigen is designated Rh40.


Effects of biorhythms on blood flow distribution in the pregnant uterus (Macaca mulatta).

Ten rhesus monkeys were studied between 143 and 161 days of gestation. The unanesthetized animals were confined to restraining chairs and maintained in a controlled environment with continuous monitoring of spontaneous uterine dynamics. Forty-five determinations of blood flow distribution were made using radionuclide-labeled microspheres. The microsphere injections confirmed a circadian pattern of uterine blood flow. These biorhythms are related to alterations in distribution of blood flow to placental and nonplacental portions of the uterus. Myometrial blood flow is highest during the period of light. It is correlated positively to aortic blood pressure (r = 0.490, p less than 0.05) and inversely to uterine artery blood flow (r = -0.508, p less than 0.05). Placental blood flow is highest during the period of darkness. The flow rates are significantly correlated to intra-amniotic pressure (r = -0.602, p less than 0.05) but not to aortic blood pressure (r = -0.185, p less than 0.05). The data indicate that blood flow distribution in the primate uterus is modulated by factors in addition to physiologic pressure-flow relationships. Extrapolation to the human has potential significance.


Complement in tears from normal humans.

Tears from ten normal persons were used in hemolytic assays to test for activity of total hemolytic complement (tested in all ten subjects), activities of each of the nine complement components (tested in two subjects), and activity of the alternate pathway (tested in two subjects). A modified radial-immunodiffusion method was used to confirm the presence of C3 and C4 complement proteins in the tear samples from all ten subjects. Factor B protein was detected in tears from two of four normal subjects tested. In dilutions up to 1:4, hemolytic activity was observed in tears from five of the ten subjects. Samples from the remaining five subjects had CH50 activity at dilutions up to 1:2. In control tests, human serum had CH50 activity at 1:32. No lysis occurred in Veronal-buffered saline or in serum and tears heated to 56 degrees C for 30 minutes. Complement proteins C3 through C9 displayed hemolytic activity in tears from each of two subjects tested for complement components. The classic and alternate complement pathways in tears can be included among the defense mechanisms of the ocular surfaces.


Treatment of Pseudomonas endophthalmitis associated with prosthetic intraocular lens implantation.

Eight patients were treated for Pseudomonas endophthalmitis associated with the implantation of contaminated intraocular lenses. All patients showed clinical signs of infection (loss of red reflex, diminished visual acuity, and intraocular lens coagulum) and P. aeruginosa was isolated from vitreous aspirates and unused lenses of the same lot. Antibiotic treatment was initiated with systemic penicillin G, cephalothin, and chloramphenicol as well as subtenon-injected gentamicin. After identification of the organism, treatment was continued with systemic carbenicillin and gentamicin and subtenon-injected gentamicin. The intraocular lens was left in place for the first 48 hours of treatment in all eight patients. Five patients were successfully treated without removal of the intraocular lens and attained visual acuity of 6/6 (20/20) to 6/15 (20/50). Three patients (the two most seriously infected and one in whom antibiotics were discontinued) eventually lost their infected eye. Vitreous concentrations of gentamicin were good in one patient (1.7 micrograms/ml) and undetectable in another. Carbenicillin concentrations in vitreous (96 and 140 micrograms/ml) were high in two patients sampled. Endophthalmitis in the presence of a prosthetic intraocular lens can be successfully treated in some patients without removal of the prosthesis.


Rescreening for gonorrhea: an evaluation of compliance methods and results.

To evaluate the cost-effectiveness of a routine rescreening (RS) culture several weeks after treatment for gonorrhea, as well as the specific efforts to ensure return visits, we followed 438 consecutive patients, 347 men and 91 women. Return visit compliance rates were 70 per cent for a test-of-cure culture, 27 per cent for a six-week RS, and 15 per cent at 12 weeks. The program detected seven cases of gonorrhea at $796 per case. In our clinic, RS is not a cost-effective way go control gonorrhea.


A Marxian interpretation of the growth and development of coronary care technology.

Cost containment efforts will fail if they continue to ignore the structural relationships between health care costs and private profit in capitalist society. The recent history of coronary care shows that apparent irrationalities of health policy make sense from the standpoint of capitalist profit structure. Coronary care units (CCUs) gained wide acceptance, despite high costs. Studies of CCU effectiveness, using random controlled trials and epidemiologic techniques, do not show a consistent advantage of CCUs over non-intensive ward care or simple rest at home. From a Marxian perspective, the proliferation of CCUs and similar innovations is a complex historical process that includes initiatives by industrial corporations, cooperation by clinical investigators at academic medical centers, support by private philanthropies linked to corporate interests, intervention by state agencies, and changes in the health care labor force. Cost-effective methodology obscures the profit motive as a basic source of high costs and ineffective practices. Health-policy alternatives curtailing corporate involvement in medicine would reduce costs by restricting profit.


Infection rates of Ascocystis-infected Aedes triseriatus following ingestion of La Crosse virus by the larvae.

The La Crosse (LAC) virus infection rate of Aedes triseriatus larvae that ingest LAC virus does not appear to be increased by concomitant infection of larvae by the gregarine parasite, Ascocystis barretti. Infection rates ranged only from 0--2.6% in adult Ae. triseriatus reared from groups of A. barretti-infected larvae that had ingested LAC virus (California encephalitis group) at dosages of 2.0--7.7 log10 SMICLD50/ml. Females resulting from orally infected larvae transmitted LAC virus to suckling mice. Larvae that were infected with A. barretti and devoured carcasses of adult mosquitoes containing 4.7 log10 SMICLD50/ml failed to become infected. A. barretti spores developing in transovarially infected mosquitoes did not harbor LAC virus; thus, A. barretti does not appear to be a mechanism for virus dispersal.


The enzyme-linked immunosorbent assay (ELISA) for malaria. I. The use of in vitro-cultured Plasmodium falciparum as antigen.

Using the Panama II strain of Plasmodium falciparum obtained from continuous in vitro culture as antigen, the micro enzyme-linked immunosorbent assay (ELISA) was used to test serum samples from 50 persons from the southeastern United States and serum specimens collected weekly from four non-immune and nine semi-immune patients infected with P. falciparum. None of the 50 sera from the United States had ELISA antibody titers greater than 1:80. The nine semi-immune patients had rapid ELISA antibody responses (titers greater than 1:2560) following patent parasitemia. ELISA titers remained elevated despite disappearance of patent parasitemia, and declined gradually following curative antimalarial therapy. The ELISA responses observed in the four non-immune patients were more variable, though positive titers appeared rapidly with patent parasitemia. Maximum titers were lower than those observed in semi-immune patients. These results demonstrate that P. falciparum obtained from continuous in vitro culture is an excellent antigen for the micro-ELISA test for malaria. However, further assessments of the ELISA are needed to identify the conditions associated with positive responses.


The development of a "high volume tissue schizonticidal drug screen" based upon mortality of mice inoculated with sporozoites of Plasmodium berghei.

A biological test system has been developed to assess the prophylactic activity of compounds against sporozoite-induced Plasmodium berghei malaria in mice. The procedure was designed to serve as the foundation of an effort to develop tissue schizonticidal drugs in a manner parallel to that of a previous system employed in the U.S. Arym Antimalarial Drug Development Program to screen compounds for blood schizonticidal activity. In tests with 35 known antimalarial compounds, the new screen was found to be in agreement 93% and 80%, respectively, when assessed compound activity was compared with results obtained in a definitive mouse causal prophylactic test and a rhesus monkey radical curative system.


Plasmodium fragile and Macaca mulatta monkeys as a model system for the study of malaria vaccines.

Pladmodium fragile and the Macaca mulatta monkey are presented as a model system for the study of malarial vaccines. Four animals were immunized with culture-grown P. fragile merozoites and subsequently challenged with culture-produced parasites. One animal failed to develop a detectable parasitemia following primary challenge. Two other immunized animals had primary infections which were short-term. the parasitemias in these three monkeys following secondary challenge were short-term and the immunity was apparently sterilizing. The fourth immunized monkeys had recrudescences of the primary and secondary infection but differed markedly from the four control animals. Indirect fluorescent antibody titers increased as a result of the immunization and were indicative of the level of immunity. Because of the many similarities to the human-P. falciparum model system, the P. fragile-M. mulatta system appears to be particularly well suited for a number of malaria vaccine studies.


Antibody-dependent killing of bloodstream forms of Trypanosoma cruzi by human peripheral blood leukocytes.

Bloodstream forms of Trypanosoma cruzi were found to be destroyed by human lymphoid cells, neutrophils, or eosinophils in the presence of specific antibodies. Nonspecific immunoglobulins present in normal serum did not mediate the cytotoxic reaction. Cells or antibody had no significant lytic effect on the parasite when tested separately and purified, non-activated human adherent cells were inactive antibody was present or not.


Use of micro-ELISA for quantitating antibody to Trypanosoma cruzi and Trypanosoma rangeli.

Of 229 residents of a Panamanian village where both Trypanosoma cruzi and Trypanosoma rangeli are endemic, 52% had antibody to one or both species by the enzyme-linked immunosorbent assay (ELISA), 26% were positive by complement fixation, 17% were positive by direct agglutination, and 32% were positive on the basis of clinical impression. Although the sensitivity of ELISA makes it the procedure of choice for sero-epidemiologic studies, there does appear to be some serologic cross-reactivity between the two species. Sera from 55 Panamanians and 33 Bolivians were reactive with antigens of T. cruzi and T. rangeli, thus making definitive diagnosis by serologic methods impossible. Although the presence of antibodies to both species suggests serologic cross-reactivity, the possibility of dual infection must be considered also. Fifty-four Panamanians and 20 Bolivians had antibody to only one species.


Presidential address: Eponyms in biliary tract surgery.

A selected group of men whose eponyms are currently used in biliary tract surgery are described. The eponyms chosen comprise two areas: gross anatomy (Glisson, Wirsung, Santorini, Winslow, Heister, and Vater) and operative anatomy (Kocher, Courvoisier, Morison, Hartmann, Calot, Roux, and Oddi). A brief review of biliary tract disease from antiquity until the 17th century places these men in proper historical sequence. A condensed biographical sketch of each man's life and work is provided and a few closing comments are made about eponyms.


Acute acalculous cholecystitis: a complication of hyperalimentation.

In a 5 year period, eight patients in whom acute acalculous cholecystitis developed during intravenous hyperalimentation are reviewed with emphasis on factors contributing to pathogenesis. Gallbladder distention, biliary stasis, and bile inspissation, thought to be important in the pathogenesis of this disease, are enhanced with the use of hyperalimentation, and this potential complication is being seen with increasing frequency in seriously ill or injured patients who are being fed parenterally. In addition to hyperalimentation, sepsis, hypotension, multiple transfusions (more than 10 units), prolonged fasting, and ventilatory support were frequent common denominators. Typical findings of pain, tenderness, and a mass in the right upper abdominal quadrant are infrequent, and the diagnosis rests on a high index of suspicion and ultrasonography. This syndrome may be preventable by the stimulation of gallbladder emptying with intermittent fat ingestion or parenteral infusion of cholecystokinin.


Safe, cost-effective postoperative nutrition. Defined formula diet via needle-catheter jejunostomy.

To assess the safety and cost-effectiveness of needle-catheter jejunostomy for the purpose of feeding defined formula diet, we studied 199 consecutive patients who underwent major elective and emergency abdominal operations between July 1975 and June 1978 and in whom a needle-catheter jejunostomy was inserted. The complication rate was 2.5 per cent (1 per cent major and 1.5 per cent minor) during 7,238 patient-days of catheter exposure during which over 6 million calories were administered. There were no catheter-related deaths, bowel obstructions, bowel perforations, or intraperitoneal administration of feeding formula. The presence of a route of intestinal access and the use of defined formula diet in 111 patients who were unable to eat for over 10 days postoperatively resulted in a gross cost savings of almost $50,000 and a net savings of almost $33,000 by avoiding the necessity for central total parenteral nutrition. We belive the technique of needle-catheter jejunostomy is both safe and cost-effective in the administration of defined formula diet in the postoperative period, and we suggest that other surgeons gain experience with the technique to define its role in their own therapeutic armamentarium.


[Animal experiments on the biomechanical vibration behaviour of the bulbus (author's transl)].

Mechanical vibration may have a detrimental effect on visual performance. This particularly seems to be the case if the natural frequency of the bulbus is excited. Experiments with animals were made with the aim of calculating the biomechanic transmission of vibration between the cranium and bulbus. Postmortem experiments using pig crania have shown that in vivo application of the method of sewing miniature accelerometers onto the cornea may be possible. Our experiments with monkeys gave typical resonance curves for the transmission of vibration of the bulbi with maxima between 25 and 31.5 Hz. Transferability of the results to the human eye is discussed.


[Identification of antithrombin III in human aqueous humor (author's transl)].

Using radial immunodiffusion it is possible to identify and to quantitate antithrombin III in human aqueous humor. The importance of antithrombin III as a cofactor of heparin is stressed.


Cardiac tamponade caused by caval catheter--a radiological demonstration of an unusual complication.

An adult male developed shock some hours after the start of intravenous alimentation. The caval catheter, which had been inserted through the right subclavian vein, was later radiographically demonstrated to be in the pericardial sac. We reviewed the literature on this and other complications of caval catheters. From this information and our own experience we offer some suggestions for prevention and management of some of the complications of caval catheters.


Immunogenetic studies of rhesus monkeys. 6. Absence of the human Xga blood group on rhesus erythrocytes.

It was not possible to demonstrate Xga on the erythrocytes of any of 140 rhesus monkeys of both sexes tested with human antiserum rendered specific for Xga by absorption.


Effects of intravenous injection of leukocytic endogenous mediator on cardiohepatic functions in rhesus macaques.

A crude preparation of leukocytic endogenous mediator administered IV over a 10-minute period into a rhesus macaque at a dosage of 10 ml/kg of body weight resulted in hypotension, tachycardia, vasodilation, hypoalbuminemia, and hypoproteinemia. Decreases in cardiac and hepatic functions and biphasic changes in peripheral polymorphonuclear leukocytes also were seen. All measured changes, except hepatic functions and plasma albumin values, returned to base-line values within 24 hours. Data indicate that presently utilized crude leucocytic endogenous mediator preparations contain a heretofore undescribed, and as yet unidentified, component. Induced early cardiovascular changes may be related in part to certain compounds likely to be in the crude preparation.


Binding of canine IgM and IgG to protein A of Staphylococcus aureus: a simple method for the isolation of canine immunoglobulins from serum and the lymphocyte surface.

The binding of normal canine serum IgG and IgM to staphylococcal protein A is described. Virtually all (greater than 99%) of IgG and up to 90% of IgM could be removed from canine serum, utilizing this phenomenon. The nature of the bound material was confirmed by immunodiffusion in agar, radioimmunoassay, and sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Attempts to elute differentially IgG and IgM from protein A-Sepharose columns, using gradients of pH or the chaotropic agent sodium thiocyanate, were unsuccessful. This phenomenon provides a basis for the isolation of canine IgM from serum. Lymphocyte surface IgM, studied by lactoperoxidase-catalyzed membrane radioiodination and solubilization in nonionic detergent, also showed the property of binding to staphylococcal protein A.


Prolactin and colibacillus-induced fluid transport in ligated intestinal segments.

Two experiments, using the ligated intestinal segment technique, were conducted to determine whether the pituitary hormone prolactin (PRL) could reduce Escherichia coli-induced fluid loss into the small intestine of 2- to 3-week-old pigs. Inoculation of 10(6) to 10(8) enteropathogenic E coli organisms into ligated jejunal segments caused a significant accumulation of luminal fluid within 12 hours. In the first experiment, intraluminal inoculation with 0.5 mg of ovine PRL along with the bacteria did not have any effect on fluid accumulation. Systemic IV treatment of the animals with 1.0 mg of ovine PRL at 3-hour intervals, beginning either immediately after or 9 to 10 hours before intestinal ligation, did not significantly (P less than 0.05) reduce fluid accumulation as compared with control animals. In the second experiment, IM administration of 100 microgram of thyrotropin-releasing hormone (TRH) at 3-hour intervals, beginning 6 hours before intestinal ligation, significantly (P less than 0.05) increased circulating PRL concentrations, as measured by radioimmunoassay. However, TRH treatment did not reduce the accumulation of luminal fluid in E coli-inoculated segments.


Cell-mediated immune responses in cattle vaccinated with Brucella abortus strain 19 vaccine and nonexposed control animals of the same age.

Cell-mediated immune (CMI) responses in cattle vaccinated with Brucella abortus strain 19 vaccine during calfhood were studied by an in vitro lymphocyte stimulation assay. Cattle were grouped in six groups according to the age after vaccination, and CMI responses of these groups, as well as of individual animals, were compared. Lymphocytes were prepared from peripheral blood of these cattle by the Ficoll-diatrizoate technique. Lymphocytes were then cultured with B abortus-soluble antigen. Culture results were assayed for [3H]thymidine incorporation into DNA by liquid scintillation spectrometry. On a group basis, B abortus-soluble antigen induced lymphocyte stimulation responses in lymphocytes from all the groups, except the sixth group which contained animals that had been vaccinated the longest time (18 to 24 months before this experiment). Animals that had been vaccinated for 3 to 6 months had the highest lymphocyte stimulation response. Seroagglutination tests were conducted simultaneously with the lymphocyte stimulation test, but there was no apparent correlation between the concentrations of humoral antibodies and the CMI responses as measured by in vitro specific lymphocyte stimulation. The lymphocyte stimulation test exhibited significantly higher specificity (P less than 0.005) than the serologic tests.


Bronchial and intravenous provocation tests with indomethacin in aspirin-sensitive asthmatics.

In an attempt to elucidate the mechanisms involved in analgesic-induced asthma, I performed bronchial and intravenous challenge tests with indomethacin in 5 aspirin-sensitive asthmatics. Bronchial challenge with less than 2 mg of indomethacin elicited bronchoconstriction that developed immediately in most cases, reached its macimum at a mean time of 64 min, and was over within 2 to 4 h. The time sequence of the reaction after intravenous challenge was similar to that after bronchial challenge, except that to obtain a comparable degree of bronchoconstriction it was necessary to administer at least twice the inhaled dose. Inhalation of disodium cromoglycate during bronchoconstriction inhibited the reaction within 8.6 +/- 5.7 min, regardless of the route of challenge. This suggests that sequential mast cell degranulation with liberation of chemical mediators is the mechanism responsible for bronchoconstriction in analgesic-induced asthma.


[Pseudomonas aeruginosa infections in an Oncological Center (author's transl)].

Distribution of Pseudomonas aeruginosa was observed, both in cancerous hospitalized and ambulatorial patients, through Uroculture or by Screening at the time of admission in Hospital. The data have been statistically evaluated according to the specific sectorial activities. The chemiosensitivity of isolated strains was evaluated for eight antibiotics, selected among the most active ones. Minimal Inhibent Concentration (MIC) and Minimal Bactericidal Concentration (MBC) were also evaluated for Gentamicin and Colistin. The results obtained are relevant to the significance of Pseudomonas aeruginosa infection in neoplastic diseases.


[A medium for a simultaneous assay of l-triptophane desaminase, beta-galactosidase, motility and indole production (author's transl)].

The author describes a medium for a simultaneous assay, in a single test-tube, of 1-triptophane desaminase, beta-galactosidase, motility and indole production.


[Antimeningococcal antibodies in healthy mothers and their newborn (author's transl)].

Blood specimen from 180 healthy mothers and their newborn were obtained during the delivery for the evaluation of placental transfer of anti-A, anti-B and anti-C antimeningococcal antibodies. The detection of titration of antibodies were performed by passive haemagglutination. Anti-A antibodies were found in 22%, anti-B in 64%, and anti-C in 30% of the mothers. In the newborns the corresponding proportions were 4.5%, 50% and 28%. For anti-A and anti-B antibodies a moderate positive correlation was found between the titre in mothers and their newborn. For anti-A antibodies, titres were generally low among both mothers and newborn and passive transfer was found in only 20%. For anti-B antibodies, titres were higher among both mothers and their newborn. Titre in newborn was as a rule lower than the corresponding titre of mother. Placental transfer of anti-B antibodies was high (78%). Finally, a strong positive correlation between the titre of mothers and their newborn was found for anti-C antibodies. Titres were usually similar in mothers and newborns and the placental transfer of anti-C antibodies was practically free (93%).


Alpha 1-antitrypsin and total trypsin-inhibitor capacity in acute pancreatitis.

Twenty three patients with acute pancreatitis were studied to assess the serum alpha 1-antitrypsin levels as well as the total trypsin-inhibitor capacity. These parameters were found to be normal or increased, which is not the case with patients with chronic pancreatitis. The value of protease-inhibitor treatment in acute pancreatitis is doubted.


Phosphonopeptides as antibacterial agents: metabolism and pharmacokinetics of alafosfalin in animals and humans.

The metabolism and pharmacokinetics of a synthetic antibacterial phosphonodipeptide, alafosfalin, have been studied in rats, baboons, and human volunteers. The compound was rapidly absorbed from the injection site after subcutaneous and intramuscular administration and gave peak plasma concentrations at 15 to 20 min after dosing. Distribution studies showed that high drug concentrations were produced in inflammatory exudates and most tissues except brain. Alafosfalin was rapidly cleared from the general circulation, mainly by the kidney. Plasma half-lives were 20 min in rats and approximately 1 h in baboons and humans. Alafosfalin was well absorbed after oral administration, but was extensively hydrolyzed to alanine and L-1-aminoethylphosphonic acid before it reached the general circulation. This first-pass metabolism was less marked in humans than in animals. Administration of 200-mg intramuscular and 500-mg oral doses produced concentrations of intact phosphonodipeptide in human plasma and urine which were in excess of the in vitro minimal inhibitory concentrations for many pathogenic organisms. The rate of absorption and elimination of alafosfalin in humans were also very similar to published data on beta-lactam antibiotics. This suggests that the pharmacokinetics can be matched to provide synergistic combinations for clinical use.


Competition of beta-lactam antibiotics for the penicillin-binding proteins of Pseudomonas aeruginosa, Enterobacter cloacae, Klebsiella aerogenes, Proteus rettgeri, and Escherichia coli: comparison with antibacterial activity and effects upon bacterial morphology.

The competition of a number of beta-lactam morphogenic probes for the penicillin-binding proteins (PBPs) of Pseudomonas aeruginosa, Enterobacter cloacae, Klebsiella aerogenes, Proteus rettgeri, and Escherichia coli has been studied. The results indicate that the various gram-negative bacteria have similar, but not identical, PBP patterns and that the individual proteins probably perform similar morphogenic functions as in E. coli K-12. Comparison of the 50% binding concentrations of the compounds for the various PBPs of the five strains with their antibacterial activity indicates that the different antibiotics are excluded to a greater or lesser degree by the outer membrane permeability barrier and that the exclusion is most pronounced in P. aeruginosa.


Comparison of the penicillin-binding proteins of different strains of Neisseria gonorrhoeae.

This study was undertaken to determine if the categorization of Neisseria gonorrhoeae strains into disseminated gonococcal infection (DGI) and non-DGI types was also paralleled by some common characteristic in their penicillin-binding proteins (PBPs). Fluorography of sodium dodecyl sulfate-containing polyacrylamide gels, on which the [14C]penicillin-labeled PBPs had been separated, was used to visualize the PBPs. No common characteristic PBP for genital or DGI strains was observed. Apart from PBPs 1 and 4, which were observed in all cases, there was an apparently random distribution of other PBPs in both types of N. gonorrhoeae. It was concluded from these data that the penicillin susceptibility associated with most DGI strains of N. gonorrhoeae cannot be correlated with any specific changes in their PBP patterns.


Lytic effect of di- or tricarboxylic acids plus sodium dodecyl sulfate against Pseudomonas aeruginosa.

Pseudomonas aeruginosa was rapidly lysed and killed when treated with several multiple-carboxylic acids at 100 micrograms/ml, followed by exposure to sodium dodecyl sulfate at 5 mg/ml.


Aucte intermittent porphyria and epilepsy.

A 14-year-old boy had suffered from intermittent acute hepatic porphyria, myoclonic convulsions and mental retardation (Lennox-Gastaut syndrome). The porphyria was treated by stopping the administration of phenobarbitone and phenytoin. Sodium valproate at a dose of 70 mg/kg per day lessened the severity and frequency of convulsive crises.


The absence of protein--sparing effects utilizing crystalline amino acids in stressed patients.

The protein-sparing effects of the peripheral infusion of crystalline amino acids (PAA) was studied metabolically in selected surgical patients subjected to various degrees of stress. Twenty-one patients (sixteen cancer patients receiving chemotherapy and/or radiotherapy, three with major abdominal traumatic injuries and four with paralytic ileus) were infused with 2 1/24 hours of a solution of 4.2% Travasol amino acids with only 5% glucose as a source of nonprotein calories. One-half of the cancer patients were also allowed ad libitum oral intake of a regular hospital diet or Vivonex-HN. The nutritional status was evaluated by measuring changes in body weight, serum albumin levels and nitrogen balance. Body weight decreased in only the trauma patients. When these solutions were the sole source of nutrients all patients were in negative nitrogen balance and had significant decreases in their serum albumin levels. Serum albumin levels were preserved only when extra sources of calories were provided. The infusion of the crystalline amino acids without adequate levels of nonprotein energy did not conserve protein in these stressed patients.


Proline metabolism in sepsis, cirrhosis and general surgery. The peripheral energy deficit.

Proline metabolism was prospectively evaluated in patients with surgical sepsis, cirrhosis, and elective surgical procedures. Significant correlations were found in the septic patients. Proline levels were an excellent indicator of mortality and correlated positively with lactate levels. Lactate and proline were inversely related to total peripheral resistance and oxygen consumption. In septic patients who expired: the metabolites involved in the hepatic pathways of proline degradation were elevated in proportion to proline; lactate, glutamate and proline were directly related to pyruvate; lactate/pyruvate ratios were constant; proline, glutamate, ammonia, ornithine, lactate and pyruvate levels were inversely proportional to oxygen consumption and total peripheral resistance. The primary defects in sepsis seem to be metabolic; there are very strong correlations in time between physiology and metabolism; the metabolic abnormality seems to be a progressive energy-fuel deficit, possibly from a progressive inhibition of substrate entry into the Krebs cycle.


Chylous ascites following abdominal aortic aneurysmectomy. Management with total parenteral hyperalimentation.

Chylous ascites may follow operative injury to retroperitoneal lymphatics. When possible, early reoperation has been advised. This report describes a patient with chylous ascites following emergency abdominal aortic aneurysmectomy. Because the patient was not a candidate for reoperation, total parenteral hyperalimentation was employed in management. This approach resulted in a successful outcome.


The effects of intraaortic balloon counterpulsation on myocardial infarct size.

The left anterior descending coronary artery was ligated in 6 baboons. Subsequently, 3 animals were supported with long-term (24-hour) intraaortic balloon pumping (IABP), and 3 were on coronary occlusion alone. Animals were studied hemodynamically and with unipolar electrocardiographic mapping acutely and then were studied after a week and killed. A histological measurement of infarct size was made. The use of IABP had no influence on the area of ischemia determined by unipolar mapping or on infarct size measured quantitatively at a week. Similarly, there were no acute hemodynamic differences between the two groups. The only significant difference noted was a reduction in systolic pressure in IABP animals during balloon pumping and a significantly higher left ventricular systolic pressure a week following infarction in animals treated with IABP. The data indicate no significant effect of IABP on altering infarct size in animals with acute coronary ligation in the absence of cardiogenic shock.


[Comparative immunochemical study of the serum proteins of Lacertilia (Reptilia)].

The immunochemical relationships of the serum proteins of Uromastix acanthinurus, Agama mutabilis, Oplurus cuvieri, O. quadrimaculatus, Chamaeleo chamaeleon, Chalcides ocellatus and Lacerta lepida were studied by means of immunoelectrophoresis with an antiserum anti-Uromastix successively absorbed. Homogeneity of the Iguania species was pointed out and they were found more closely related to the Scincid Chalcides ocellatus than to the Lacertid Lacerta lepida. Within the Iguania, the two Agamids are immunologically more closely related to the Chamaeleon than to the two Iguanids.


[Average steady-state plasma levels with slow release quinidine preparations].

Arabogalactane sulphate of quinidine (AGSQ) is a slow release preparation of quinidine. The aim of this study was to compare the plasma levels of quinidine obtained by different preparations of AGSQ (AGSQ I, II and III) and to determine which was best suited to therapeutics. The "in vitro" study showed different amounts of quinidine liberated in 6 hours, 34% with AGSQ I, 58% with AGSQ II and 100% with AGSQ III. The plasma quinidine levels were studied after administration of a dose corresponding to 330 mg quinidine base, morning and evening for 7 consecutive days to 27 hospitalised patients; 7 received AGSQ I, 11 received AGSQ II 5, received AGSQ III and 4 quinidine sulphate. The delay in reaching a steady state was 24 hours for the quinidine sulphate 36 hours for AGSQ I, 48 hours for AGSQ II and 60 hours for AGSQ III. The average plasma level on the 7th day (Cee) was 2.74 +/- 0.71 microgram/ml, 2.62 +/- 0.74 microgram/ml and 3.29 +/- 0.72 microgram/ml respectively. The plasma quinidine levels were maintained between toxic and therapeutic levels (3,5 and 1,7 microgram/ml) only with AGSQ II by suppressing the peak observed 1 hour administration of quinidine sulphate. An excellent correlation (r = 0,984) was observed between the plasma quinidine 6 hours after ingestion and the Cee. A blood test during the steady state, 6 hours after ingestion of the drug, is useful in adjusting the dosage. These results suggest that AGSQ II is the preparation best suited for therapeutic usage although it does not give the best relative bioavailability of the drug.


[Value of potassium canrenoate in the prevention of arrhythmia during the acute phase of myocardial infarction].

This study was based on a series of 486 patients with acute myocardial infarction. All were treated with heparin and nitrite derivatives. 320 patients received 600 mg/24 h Potassium Canrenoate for 5 days (long duration); 90 patients received 1000 mg of Potassium for the first 36 hours only. 76 patients did not receive the drug and served as controls. The biochemical changes due to Potassium Canrenoate are discussed with special emphasis on the serum and intraerythrocytic potassium levels. The antiarrhythmic action of the potassium was assessed directly (the number of ventricular extra systoles decreased significantly) and indirectly (the amount of antiarrhythmic therapy required in association was three times less in patients treated by Potassium Canrenoate). The mortality rate changed from 17 to 12%. The beneficial effect of Potassium Canrenoate is attributed to the maintenance or the restoration normal potassium levels of ischaemic myocardial tissue.


[Constrictive pericarditis and rheumatoid arthritis].

Pericarditis is the commonest cardiac manifestation of rhumatoid arthritis. It is often clinically latent but it may evolve to constriction or less often to tamponade. The case presented is of a 60 year-old woman with a 5 year history of seropositive nodular rhumatoid arthritis in whom bilateral pleural effusions and constrictive pericarditis were observed after sudden termination of corticotherapy. She was treated successfully by pericardectomy. This complication is far from being exceptional (55 cases already reported). It justifies a systematic search for pericarditis in rhumatoid arthritis, especially by echocardiography.


[Embolism in a fragment of the mitral papillary muscle to the left main coronary artery. A rare complication of valve replacement].

A 64-year-old man, who underwent double valve replacement for mitral and aortic incompetence due to infective endocarditis, presented with a coronary embolism of a fragment of mitral papillary muscle in the immediate post-operative period. The diagnosis, suggested by the sudden development of acute myocardial insufficiency during ventricular filling, was confirmed by the absence of clinical or electrical improvement during circulatory assistance and by surgical exploration of the left coronary artery. Complete recovery after embolectomy emphasises the value of the association of circulatory assistance and immediate myocardial revascularisation.


[Identification of the sinus potential in man by endocavitary electrocardiography. Identification criteria, preliminary results].

The potential of the sinus node was recorded in 24 patients by endocavitary electrocardiography using the same equipment as for usual electrophysiological investigation. The sinus node potential is a slow wave which starts progressively, has a rounded peak and precedes the endocavitary atrial activation and the surface P wave, and is relayed at an acute angle to the high amplitude deflection of atrial depolarisation. In some specially selected recordings it is easy to confirm the sinus origin of this slow wave where its preatrial position may be defined by the fixed relation of the S-P interval and by the variability of the T-S interval. Usually it is necessary to use technical manoeuvres (vagal stimulation, premature atrial stimulation) to demonstrate the preatrial behaviour of a potential thought to be of sinus origin. The variability of the sinus potential and the apparent sinoatrial conduction time, is suggestive of a physiological instability of the intrasinus pacemaker. The sinoatrial conduction time measured directly does not seem to exceed 140 ms in normal subjects.


[Outcome of myocardial infarctions complicated by heart conduction disorders in the acute phase].

Of 945 patients hospitalised for myocardial infarction between January 1st 1972 and December 31st 1975, 40 with anterior myocardial infarction (Group I-A) and 53 with posterior myocardial infarction (Group II-A) were complicated by atrioventricular and/or intraventricular arrhythmias. The average follow up period is now of 48 months (range 24 to 78 months). Their outcome was compared to two control groups of 50 anterior myocardial infarctions (Group I-B) and 50 posterior myocardial infarctions (Group II-B) uncomplicated by arrhythmias in the acute phase. The immediate (10%) and secondary (30%) mortality was identical in the two groups II-A and II-B with posterior wall necrosis. The immediate (32%) and secondary (40%) mortality in Group I-A was much higher than in Group I-B (22% and 28% respectively). Sudden death was the most frequent form of demise in all groups (I-A, II-A, II-B) except Group I-B in which heart failure predominated. Death occured earlier in Group I-A than in the control Group II-B. These results pose the problem of the indication of prophylactic permanent pacing to decrease the incidence of sudden death.


[Syncope and transient neurologic deficits of undetermined origin. Clinical and electrophysiological correlations].

A consecutive series of 140 patients who presented either with syncope or transient neurological deficit of undertermined cause underwent electrophysiological investigation. The patients were classified in 3 groups: Group I comprising 55 patients having presented "true syncope"; Group II comprising 42 patients with "false vertigo"; and Group III comprising 43 patients in whom a transient neurological deficit had been observed. Globally, the investigations were positive in 58 patients (41,4%). Paroxysmal atrioventricular block was recorded in 21 cases (15%), sinus node dysfunction in 34 cases (2,1%). Permanent pacing was instituted in 57 patients. The correlation between the results of electrophysiological investigation and the clinical symptomatology showed a highly significant difference between Groups I and II where the results were positive in 57% cases, and Groupe III where 93% of the investigations were negative.


[Painless ST elevation with syncope. Diagnosis by continuous electrocardiography].

The aetiology of syncope in a 53 year old man was discovered on continuous ambulatory electrocardiography. A ventricular arrhythmia associated with ST elevation was recorded. It proved resistant to medical therapy and a double aorto-coronary bypass graft was performed. Post-operative Holter monitoring showed surgery to have been effective.


[Critical study of the morphogenesis of trunco-conal malformations].

Anatomical and angiocardiographic studies have made possible discussion of hypotheses of the development and differentiation of the conus and of the trunco-conal orientation of the septum. Three autopsy specimens and two angiocardiogrammes of intertwined great vessels with transposition and partial distortion of the great vessels were studied. The specimen of intertwined great vessels comprised a muscular sub-aortic infundibulum posterior to and greater than the pulmonary infundibulum. In the case of transposition the opposite situation was encountered with a muscular pulmonary infundibulum posterior to and greater than the sub-aortic infundibulum; the plane of the aortic valves was higher than that of the pulmonary valves. The specimen of partial distortion of the great vessels comprised a muscular sub-aortic infundibulum posterior to and greater than the pulmonary infundibulum with the aortic valve set higher and in fibrous continuity with the mitral valve. It is concluded that the relations of the great vessels between each other and with the ventricles depend on the orientation of the trunco-conal septum and on the process of incorporation of the cone. The presence or absence of a posterior muscular infundibulum is not related to the growth or differential reabsorption of the cone but to a process of cellular differentiation. There was no relation between the level of the valves and their spatial orientation and the length of the infundibulum. The continuity or discontinuity between the aortic and atrio-ventricular valves is not determined by the level of the aortic valves.


Pathogenesis of diarrhoea caused by astrovirus infections in lambs.

Experimental infection of 2-day-old gnotobiotic lambs with lamb astrovirus produced mild diarrhoea after an incubation period of about 48 hours. No other clinical symptoms developed. Infection was studied by immunofluorescent and histological examination of tissues from the lambs. Astroviruses infected only mature villus epithelial cells and subepithelial macrophages in the small intestine, where they produced partial villus atrophy. Infected enterocytes were replaced with cuboidal cells from the crypts, and the lesion gradually healed by 5 days after infection. No serological relationship was detected by immunofluorescence between lamb astrovirus antigen in gut sections and antisera to either calf or human astrovirus.


Measles virus-specified polypeptides in infected cells.

The synthesis of wild-type measles virus-specified polypeptides in Vero cells in pulse-chase experiments, in cells with synchronized protein synthesis by high salt concentration, and in the presence of proteolytic enzyme inhibitors was analyzed by polyacrylamide slab-gel electrophoresis. Six major (L, G, 2, NP, 5 and M) structural polypeptides were identified in infected cells. The results of pulse-chase experiments suggested that most of the structural polypeptides were synthesized at their final length. Polypeptide M was found to be sensitive to trypsin. In TLCK-treated cells its molecular weight was about 1000--2000 daltons higher than in untreated cells. A minor virus-specific polypeptide with a molecular weight of about 23,000 was found as a very faint and diffuse band. In addition, three nonstructural polypeptides with molecular weights of 65,000, 38,000 and 18,000 were also detected. The experiments with proteolytic enzyme inhibitors and with synchronized protein synthesis suggested that the polypeptide with a molecular weight of 65,000 might be a precursor of the structural polypeptide 5.


Fetal infection of the baboon (Papio cynocephalus) with lymphocytic choriomeningitis virus.

Recent observations of LCM-induced fetal damage in humans suggested attempts to develop an animal model for studies on viral congenital malformations. We report herein viral studies on three pregnant baboons (Papio cynocephalus) inoculated subcutaneously with LCM virus strain WE3. The first animal, inoculated in the 9th week of pregnancy, aborted 9 days after a high virus dose. Inoculation of the second baboon during a later stage (23rd week) of pregnancy with a moderate virus dose, resulted in the demonstration of virus in the placenta, amniotic fluid, and cord blood. The infant showed only a slight pleocytosis of the spinal fluid, but no virus shedding and no late sequelae. The third baboon inoculated with a high virus dose during the 21st week of pregnancy delivered an underweight, icteric infant that succumbed on the 6th day. All organs of this animal that were tested contained virus. Microscopic examination of these tissues revealed multifocal necrosis, cerebral glial nodules, meningitis, and bilateral choriovasculitis. These results illustrate that fetal damage observed in the LCM-inoculate baboon resembles that seen in humans following infection with LCM virus.


[Cholinergic and adrenergic innervation of the arteries of the base of the brain in certain lower vertebrates].

The arteries in the encephalon base have been investigated by Koelle's and Falck's methods in Teleostei (Anarhichas lupus, Eleginus navaga, Leuciscus brandti, Pelingas), amphibians (Rana temporaria, Rana semiplicata, Bufo bufo) and in reptiles (Testudo horsfieldi, Trionyx chinensis). Cholin- and adrenergic nerve fibres of the encephalic arteries have been revealed in all the vertebrates studied, but their concentration is far from being equal. In fishes and reptiles neural conductors from scarse plexus with wide loops. Concentration of effector neural fibres only in Bufo bufo exceeds that of fishes. In some cases, the arteries of frogs have equal or less density of cholin- and adrenergic neural conductors as compared with those of Pelingas. Certain individual peculiarities are noted in distribution of the effector neural fibres of the encephalic arteries of the vertebrates. In reptiles, the neural apparatus of the encephalic blood vessels reaches a considerable development; it is definitely differentiated into two plexuses - superficial and deep, having a close interconnection. The development of the effector vascular plexus in vertebrates corresponds to increasing mass of the brain and the vascular diameters. Taking into consideration structural peculiarities of the neural conductors and their concentration, it should be recognized that the role of the neural factor in regulation of the cerebral circulation increases in the following order: fishes - amphibians - reptiles.


[Ileo-colonic lymph nodes in macaques and pavians of different ages].

Quantitative and qualitative alterations occurring in various structural components of the ileocolonic lymph nodes of Papio hamadryas at the age of 3.5 months and 5 years and Macaca rhesus at the age of 5 years were studied by means of mathematical methods. Cellular composition was counted in every histological preparation per 1,000 cells in cortical plateau, in myelin cords, in follicles with light centers and in follicles without light centers. Part (in %) of every cell variety was determined, as well as correlation of different structural components of the lymph nodes. Construcgion and cytoarchitectonics of the ileocolonic lymph nodes were stated to depend on the age of monkeys and their systematic differences.


Cranial neuropathy, myeloradiculopathy, and myositis: complications of Mycoplasma pneumoniae infection.

Polymyositis, transverse myelitis, ascending polyneuritis, bilateral optic neuritis, and hearing loss developed in a patient with high complement-fixing antibody titers to Mycoplasma pneumoniae. Each of her three children had primary atypical pneumonia with isolation of the organism. The neurologic disturbance is thought to represent a postinfectious complication of M pneumoniae infection.


Predominance of oligoclonal IgG type lambda in CSF in aseptic meningitis.

Oligoclonal immunoglobulins (Ig) demonstrble as bands by agarose-gel electrophoresis of CSF were characterized in ten patients with aseptic meningitis. Oligoclonal CSF IgG was found in all patients, IgM was found in two. The oligoclonal Ig was more often of lambda light-chain type than of kappa type. In four patients, oligoclonal Ig bands contained kappa and lambda light chains simultaneously. In two patients, bands consisting of free lambda light chains were found. On repeated investigations more than one year later in three cases, the oligoclonal IgG was of the same light-chain type. The immune response within the CNS in aseptic meningitis seems to be dominated by synthesis of IgG with lambda light chains.


Drawing-induced seizures.

In a review of the literature on triggering mechanisms in reflex epilepsy, we found no reported instance of drawing as the provoking factor. Recently we studied the case of a 17-year-old man with myoclonic seizures. These seizures were most effectively triggered by drawing, although occasionally they occurred spontaneously and could also be evoked by other activities requiring concentration. The results of a neurological examination were normal, and family history was unremarkable. Treatment with primidone and methsuximide has been very effective.


360 degrees prophylactic cryoretinopexy. A clinical and experimental study.

Complications occurred after 360 degrees prophylactic cryoretinopexy in three of six eyes in which fellow eyes had previously developed aphakic retinal detachment. Two of the six prophylactically treated eyes developed retinal detachment in advance of anticipated cataract surgery, and a third developed vitreitis and progressive preretinal membrane formation after uncomplicated cataract extraction. In an experiment study with rhesus monkeys, preretinal membrane formation was produced by administering heavy freezes with 360 degrees cryoretinopexy. Although the quantities of cold were considered excessive for clinical use, the cryoretinopexy used clinically in this series must also be considered excessive. The use of 360 degrees cryoretinopexy in the management of eyes at high risk for retinal detachment must be considered judiciously. Particular caution must be exercised in administering cryoretinopexy to nondetached retinas so as to avoid heavy freezes, which destroy the linear retinal layers.


Long-term observations of proton-irradiated monkey eyes.

Fifteen owl monkeys (30 eyes) that received proton irradiation of discrete areas of the retina and choroid have been observed for 3 1/2 years or more after irradiation. The dose delivered to the retina varied from a single dose of 1,600 to 4,750 proton rads and from 10,250 to 18,250 rads delivered in five fractions over a period of one month. Fundus examination, fluorescein angiography, and light and electron microscopy revealed chorioretinal changes at the area of irradiation. The part of the retina adjacent to the chorioretinal scar showed preservation of normal retinal vascular architecture on trypsin digest studies of the retina and on electron microscopic examination, even 1 mm from the edge of the scar. The results of this study suggest that proton beam irradiation may markedly reduce delayed ocular complications, especially radiation retinopathy, which is common to other forms of radiotherapy in the treatment of intraocular tumors.


Modifications of vestibulo-ocular reflex induced by diazepam: experiments in the macaque.

The vestibulo-ocular reflex in the macaque was tested before and after intravenous administration of diazepam. The drug effect was marked by decrease in gain and increase in time constant of nystagmus in response to a modified Bárány test and by reduction in directional asymmetry of nystagmus. Because the time course of reduction in gain differed from the time course of increase in time constant, diazepam probably has more than one site of action. These results emphasize the complexity of neural processing in the vestibulo-ocular reflex arc.


The failure of prolactin to initiate lactogenesis in the ewe.

Infusion of exogenous prolactin (NIH-P-S11) at 1 mg/h for 10 h into ewes pretreated for 30 days with oestradiol benzoate and progesterone was unable to initiate milk secretion. Similarly primed ewes injected with 10 microgram thyrotrophin releasing hormone also failed to lactate but all ewes injected with dexamethasone (10 mg daily for 5 days) after oestrogen plus progesterone treatment secreted copious quantities of milk. The results suggest that prolactin, itself, is not capable of initiating lactogenesis in the ewe.


Selection for ethanol tolerance in two populations of Drosophila melanogaster segregating alcohol dehydrogenase allozymes.

Selection for ethanol tolerance was equally successful in two populations of D. melanogaster in both of which the frequency of AdhF was 0.5 at the start of the experiment. Increased tolerance to ethanol was not invariably associated with increased frequencies of AdhF. In one population alcohol dehydrogenase (ADH) activity was significantly higher in three of the four selected sublines compared with their controls but there was no difference in activity between the selected and control sublines in the second population. The level of ADH activity in the control and selected lines was significantly correlated with the frequency of AdhF, but not with ethanol tolerance. These results show that adaptation to environmental alcohols in populations of D. melanogaster can be independent of the ADH system.


Measurement of diamine oxidase activity in vaginal fluid -- an aid to diagnosis of ruptured fetal membranes.

Measurement of diamine oxidase (DAO) activity in vaginal fluid as an aid to diagnosis of premature rupture of the fetal membranes was studied. In 76 patients following artificial rupture of the membranes and in 70 patients with known intact membranes, the accuracy was 100%. One hundred and forty-nine patients were admitted to hospital with suspected ruptured membranes; using the criteria outlined in this paper, 51 had ruptured membranes and in 98 the membranes were intact. The overall accuracy was 96%.


A review of 2,003 consecutive amniocenteses performed under ultrasonic control in late pregnancy.

A review of 2003 consecutive amniocenteses performed in late pregnancy under ultrasonic control is presented. No perinatal mortality was encountered. On this evidence the method described is suggested to be the safest available for obtaining liquor in late pregnancy.


Multiplicity of induction patterns of rat liver microsomal mono-oxygenases and other polypeptides produced by administration of various xenobiotics.

Induction of hepatic microsomal mono-oxygenase species after administration of various xenobiotics is a well-documented phenomenon. To examine the number and specific species of rat liver microsomal membrane polypeptides involved in such responses, we have used sodium dodecyl sulphate/polyacrylamide-gel electrophoresis to analyse microsomal fractions from animals treated with a number of important xenobiotics. The following are the principal points to have emerged from this study. 1. A minimum of twelve electrophoretically distinct patterns of induction of haemopolypeptides and other polypeptides could be distinguished after administration, either singly or in certain combinations, of phenobarbital, 3-methylcholanthrene, polychlorinated biphenyls, 2-acetylaminofluorene, safrole (or isosafrole), pregnenolone-16 alpha-carbonitrile and ethanol. The patterns consisted of various permutations of the amounts of eight polypeptides of 47000-56000 mol.wt., of which at least three were haemopolypeptides. The possible identities of these polypeptides, which included species of cytochrome P-450, cytochrome P-448 and epoxide hydratase, are discussed. 2. Agents (3-methylcholanthrene, benzo[a]-pyrene, polychlorinated biphenyls, 2,3,7,8-tetrachlorodibenzo-p-dioxin and beta-naphthoflavone) that result in the induction of cytochrome P-448 caused a marked increase in two polypeptides of 54000 and 56000 mol.wt., whereas safrole and isosafrole induced only the former polypeptide. 3. Administration of 2-acetylaminofluorene resulted in the induction of two polypeptides; evidence is presented that suggests that one of these is a species of epoxide hydratase [cf. Levin, Lu, Thomas, Ryan, Kizer & Griffin (1978) Proc. Natl. Acad. Sci. U.S.A. 75, 3240-3243] ANd that the other may be a novel haemopolypeptide. 4. The overall results emphasize the complexity of the responses exhibited by rat liver microsomal fractions to the administration of xenobiotics.


Aortic atherosclerosis in normal and spontaneously diabetic Macaca nigra.

Aortic atherosclerosis is minimal in normal Macaca nigra; development of atherosclerosis correlates with increasing severity of diabetes mellitus. The extent of aortic involvement (plaque plus sudanophilia) was quantified and compared with metabolic and clinical parameters. Increasing atherosclerosis correlated with decreasing ability to clear glucose in a tolerance test (P less than 0.01), decreasing insulin (P = 0.02), and increasing glucose (P less than 0.01) and triglycerides (P less than 0.01). A diabetic index, established as a summation of several metabolic measurements, correlated with atherosclerosis at P less than 0.001. On the average, involvement of the thoracic aorta was about 3-fold greater than in the abdominal portion; involvement reached over 40% in severely diabetic monkeys. Atherosclerosis development is unique in these monkeys since they consume a natural ration low in fat and cholesterol. Serum cholesterol did not correlate with diabetes or artherosclerosis. Increasing age alone was associated with slight sudanophila, some intima-media thickening, and occasional small lesions. However, only with increasing severity of diabetes was there significant atherosclerosis.


[5-methylthioadenosine phosphorylase from C.acidophila. 2. Identification and characterization of reaction products].

Evidences for a phosphorolitic cleavage of 5'-MTA by a specific enzyme from C. acidophila are reported. Methylthioribose-1-phosphate and adenine have been identified as reaction products, by several analytical procedures.


Effect of glyceryl trinitrate on echocardiographic left ventricular dimensions during exercise in the upright position.

Changes in left ventricular size may be of importance in the development of angina and in its amelioration by glyceryl trinitrate, but left ventricular dimensions have not been measured during exercise in the upright position, the circumstance in which angina most often occurs. To assess changes in left ventricular end-systolic and end-diastolic dimensions, echocardiograms were obtained from 5 normal subjects and 6 patients with angina during rest and exercise upright, both before and after glyceryl trinitrate. The end-systolic dimension was considered an index of regional performance rather than an estimate of overall left ventricular behaviour. During exercise the end-diastolic dimension rose both in the normal subjects and in the patients. The end-systolic dimension fell progressively with exercise in the normal subjects but changed inconsistently in the patients. Glyceryl trinitrate lowered the end-diastolic dimension during exercise below comparable pretreatment values in both groups; the glyceryl trinitrate-induced decrease in end-diastolic dimension in the patients diminished at higher exercise levels. In all normal subjects and in 4 of the 6 patients with normal systolic shortening (= end-diastolic--end-systolic dimension) glyceryl trinitrate caused relatively small changes in the end-systolic dimension and systolic shortening on exercise. In contrast, in the 2 patients with hypokinetic ventricles glyceryl trinitrate conspicuously decreased the end-systolic dimension and increased systolic shortening. Thus, during exercise, in the normal subjects and in the patients with normally functioning left ventricles on echocardiography, glyceryl trinitrate caused a modest fall in the end-diastolic dimension and little change in the end-systolic dimension, but in patients with ventricular hypokinesia it greatly improved regional contractile performance. Alleviation of ischaemic hypokinesia during exercise may be an important part of the benefit of glyceryl trinitrate.


Studies of uptake of the bretylium analogue, iodobenzyltrimethylammonium iodide, by non-primate, monkey and human hearts.

Uptake of (+/-)-[3H]-noradrenaline, [14C]-bretylium and [125I]-o-iodobenzyltrimethylammonium iodide (RIBA) by rat heart was studied by the Langendorff technique. All three compounds showed significant uptake. 2 Corticosterone and 17-beta-oestradiol inhibited the uptake of all three compounds by rat heart, a finding consistent with extraneuronal uptake (uptake2). 3 [131I]-RIBA was injected intravenously into pigs and monkeys (M. speciosus). Myocardial samples taken from pigs killed 1 and 2 h after injection showed significant uptake. No significant uptake was found in myocardial samples of monkeys killed 10 min, 2 h and 24 h, respectively, after injection. 4 Four normal human volunteers received [125I]-RIBA intravenously and the image of the precordial area was followed by means of scintillation camera for the first 4 h after injection. In two of the subjects, the scintigrams were repeated at 22 and 23 h after injection, respectively. No evidence of myocardial uptake was observed. 5 These results suggest the possibility that man and at least one other primate species may differ from lower species with regard to uptake.


Ferritin, a sensitizing substance in the leucocyte migration inhibition test in patients with malignant lymphoma.

The nature of the factor in Hodgkin's disease involved spleen to which many patients with malignant lymphoma react in the leucocyte migration inhibition test has been investigated. Our results suggest that ferritin from Hodgkin's disease involved spleens is antigenically different to that prepared from normal spleen. Isoelectric focusing shows the presence of more acidic 'isoferritins' in ferritin prepared from Hodgkin's disease involved spleen than in that prepared from normal spleen. Further observations using the leucocyte migration inhibition test suggest that sensitization to the abnormal ferritin, acting as an onco-fetal tumour associated substance, may be responsible for the reaction of patients with malignant lymphoma in this test.


Pituitary gonadotrophins and prolactin in patients with endometrial cancer, fibroids or ovarian tumours.

The serum levels of follicle stimulating hormone (FSH), luteinizing hormone (LH) and, prolactin (PRL) were measured before and after gonadotrophin releasing hormone (GnRH) and thyrotrophin releasing hormone (TRH) stimulation in 17 patients with endometrial cancer, in 15 patients with uterine fibroids, in 11 patients with ovarian cystadenomas or cancer and in 14 age-matched controls. The women with fibroids had a low FSH level and a diminished FSH response to GnRH but an excessive PRL response to TRH while the other patient groups did not differ from the controls. The results indicate no relation between pituitary function and endometrial or ovarian tumor.


Immunological activity to different corneal antigens in patients with corneal diseases.

Patients suffering from various corneal diseases and waiting for keratoplasty have been immunologically investigated in order to establish sensitisation to corneal antigens. The presence of lymphocytes sensitised to the soluble from human corneas, bovine corneal epithelium, and bovine corneal stroma, which all possess common antigenicity, could be demonstrated in 30%, 50%, and 23%, respectively, of all patients. In none of these patients could a positive plasma antibody titre to human corneal antigens be detected. The results suggest the dominance of T-lymphocyte activity. No correlation was found between the degree of corneal vascularisation and the presence of sensitised lymphocytes to human corneal antigens. Arrangement of the patients according to diagnosis showed that especially those suffering from herpes simplex virus keratitis reacted positively to human corneal antigens. A possible explanation is given. Lymphocytes of controls showed no or only very low stimulation with the soluble fractions of human corneas or bovine corneal stromas. The soluble fraction of bovine corneal epithelium stimulated the lymphocytes of 6 out of 19 controls. The elimination of the donor corneal epithelium before transplantation may be beneficial in view of the involvement of histocompatibility antigens.


Tyrosyluria in marasmus.

1. Plasma tyrosine and urinary p-hydroxyphenyl lactic acid (PHPLA) and p-hydroxyphenyl acetic acid (PHPAA) were studied in thirty patients with marasmus and twenty normal controls in the same age group. 2. In the control group conventional tyrosyluria was not observed but 30% of the group excreted high levels of PHPAA. In the group with marasmus, plasma tyrosine and urinary PHPLA and PHPAA values were signigificantly higher than the control values. However only 13.3% of the patients were considered to have conventional tyrosyluria and 52.3% were found to excrete high levels of PHPAA. 3. Administration of ascorbic acid resulted in a reduction of PHPLA excretion while it had no effect on PHPAA excretion. 4. It was inferred that (a) tyrosyluria in marasmus is due to the reduced activity of the hepatic enzyme 4-hydroxyphenyl pyruvate: oxygen oxidoreductase (hydroxylating, decarboxylating) (PHPAA-oxidase; EC 1.13.11.27) due to the deficiency of ascorbic acid and (b) high excretion of PHPAA is related to age and nutrition of the child and is unaffected by the administration of ascorbic acid. 5. It was further inferred that urinary excretion of PHPLA is a reliable index of tyrosyluria.


Studies on prolactin. Selective reduction of the disulfide bonds of the ovine hormone.

Methods for selective reduction of the disulfide bonds in ovine prolactin are reported. Cleavage of all three disulfide bonds abolishes biological activity and denatures the hormone. Reduction-carbamidomethylation of one or two of the disulfide bridges does not diminish the biological activities in the pigeon crop-sac and mouse mammary gland bioassays. When compared to the native hormone, monomers of these two partially reduced-carbamidomethylated derivatives also show only modest changes in properties measured by exclusion chromatography, circular dichroism, and immunological cross-reactivities. However, cleavage of cystine-4--11 and cystine-191--199, followed by carbamidomethylation, destroys the biological activity of this derivative in a teleost fish bioassay (Gillichthys urinary bladder). In contrast, reduction of cystine-4--11 actually increased the teleost potency of this derivative compared to the intact hormone. Since teleost prolactin appears to lack a homologue to the cystine-4--11 disulfide bond in the amino-terminal loop of the ovine hormone, selective reduction of this bond in ovine prolactin may produce a derivative whose properties more closely resemble the fish hormone.


Physical-chemical characterization and carbohydrate-binding activity of the A and B subunits of the Bandeiraea simplificolia I isolectins.

Bandeiraea simplicifolia I plant seed isolectins comprise a family of tetrameric alpha-D-galactopyranosyl-binding glycoproteins composed of various combinations of teo different kinds of subunits designated A and B. Subtypes of the A (Aa, Ab, Ac, Ad, and Ae) and B (Ba, Bb, Bc, Bd, and Be) subunits were demotypes varies from seed to seed (e.g., some seeds contain only B subunits, others only A subunits), subtypes Ac and Bc predominate in a natural mixture of the isolectins. Two-dimensional agar gel diffusion studies indicate that, in addition to common structural features, each subunit contains its own distinct antigenic determinants. Although the A and B subunits have closely similar amino acid compositions, they differ markedly in one respect: the B subunit has one methionine residue whereas the A subunit contains no methionine. The neutral carbohydrate content of both subunits is identical. The ability of biopolymers and synthetic glycoproteins to precipitate A4 and B4, as well as the capacity of sugars and oligosaccharides to inhibit precipitate formation, was examined. On the basis of these studies, it is suggested that hydrogen bonding occurs between the hydrogen atoms of the C-3 and C-4 hydroxyl groups of alpha-D-GalNAcp and alpha-D-galp units and the A and B subunits, respectively.