Microradiographic demonstration of pyelolymphatic backflow in the porcine kidney. Pyelolymphatic backflow occurs when intrapelvic pressure rises acutely. Although peripelvic and hilar lymphatics have occasionally been demonstrated during intravenous urography and retrograde pyelography, the patterns of intrarenal microlymphatic filling have not previously been studied radiographically in multipapillary kidneys. Microradiography was performed after retrograde ureteral injections of barium sulfate suspension in recently excised pig kidneys. Contrast filled the ducts of Bellini and extended in a retrograde fashion as far as the distal convoluted tubules. Intrarenal cortical and corticomedullary microlymphatics, as well as veins, filled following forniceal rupture and interstitial extravasation. These anatomic studies suggest that the renal lymphatics may function as an alternate pathway of drainage of an acutely obstructed kidney.


Diabetic emergencies.

Diabetic emergencies. Diabetic emergencies include diabetic ketoacidosis, insulin-induced hypoglycemia, hyperosmolar coma and lactic acidosis. By determining the blood pressure, observing for evidence of dehydration or sweating and making a rapid qualitative assessment of blood glucose and ketonemia, the physician can usually identify the condition promptly. When adequate facilities are available, continuous intravenous insulin infusion is preferred for treatment of diabetic ketoacidosis. The nonketotic hyperosmolar state should be corrected gradually, not rapidly, in order to avoid cerebral edema.


Echocardiography: pericardial tickening and constrictive pericarditis. To evaluate the relation between mitral valve motion and left ventricular end-diastolic pressure, the PR-AC interval, an index derived from the electrocardiogram and mitral echogram, and the left ventricular endodiastolic pressure were determined simultaneously in 22 patients undergoing diagnostic cardiac catheterization. Intravenous infusion of dextran or administration of nitroglycerin was used to alter left ventricular end-diastolic pressure to determine if there was a predictive relation between this pressure and the PR-AC interval during acute hemodynamic manipulations. There was a weak negative correlation (r = -0.33, P less than 0.01) between this pressure and the PR-AC interval. At rest a PR-AC interval greater than 0.06 second correctly predicted a left ventricular end-diastolic pressure of less than 20 mm Hg in 15 of 16 subjects. However, in four of six subjects with a PR-AC interval of 0.06 second or less, the end-diastolic pressure was less than 20 mm Hg. After interventions that varied left ventricular end-diastolic pressure by a factor of 2, the PR-AC interval changed slightly or not at all. These data suggest that the PR-AC interval is of limited value in predicting abnormal values or serial changes in left ventricular end-diastolic pressure.


Unusual vasomotor coronary arterial responses after nitroglycerin. Angiographic evidence of unusual vasomotor responses occurred in two patients after administration of sublingual nitroglycerin. In these patients, right coronary arterial segments that appeared angiographically normal before the administration of nitroglycerin showed narrowing after nitroglycerin. Adjacent segments in each of these vessels, as well as the other coronary arteries, dilated as expected. Both patients remained asymptomatic. Repeated administration of nitroglycerin did not alter the anglographic appearance of these vessels. No reason for the localized reduction of coronary arterial diameter was apparent. The possibility that nitroglycerin was associated with these unusual changes is an additional argument against the routine administration of nitrates before coronary arteriography.


Urinary excretion of N gamma-methylihistidine (3-methylihistidine): a tool to study metabolic responses in relation to nutrient and hormonal status in health and disease of man. Some of the histidine residues of actin and myosin are methylated after synthesis of these contractile muscle proteins. During breakdown of muscle protein in the course of protein turnover, the product of methylation, N gamma-methylhistidine, is released and quantitatively excreted in the urine both of rat and of man. Since most of the N gamma-methylhistidine in the body occurs in muscle, the rate of its excretion becomes a convenient measure of muscle protein breakdown. Output per kilogram of body weight is highest in the infant, especially when related to creatinine, and is reduced in the elderly as a result of loss of muscle mass with aging. A diet deficient in protein causes the young rat to have a reduced output of methylhistidine (reduced rate of muscle protein breakdown) which increases again during repletion on an adequate diet. Fasting obese human subjects also show a progressive fall in output of this metabolite. Thyroidectomy in rats reduces N gamma-methylhistidine excretion, which is only restored by giving large doses of thyroxine. On the other hand, studies on growing rats show that adrenalectomy and moderate doses of cortecosterone have no appreciable effect on the N gamma-methylhistidine output, which is only elevated by steriod administered in amounts large enough to raise plasma corticosteroid levels several-fold. These various observations show that N gamma-methylhistidine provides a useful tool in the study of muscle protein metabolic responses under a variety of nutritional and hormonal circumstances in the intact human.


Hepatitis B vaccines. On the threshold.

Hepatitis B vaccines. On the threshold. Experimental hepatitis B vaccines have recently been developed and are undergoing preliminary evaluation. These vaccines are unique in that they are prepared from viral antigen purified from the plasmas of human chronic carriers because hepatitis B virus has not been cultivated in vitro. They appear to be safe and antigenic, but care must be exercised in their evaluation because of the potential risks inherent in all vaccines.


Bicarbonate therapy revisited. A study in therapeutic revisionism. In summary, infusion of bicarbonate in the treatment of neonatal acidosis has limited value. Although it may be useful adjunct in the resuscitation of severely depressed and acidotic infants, its efficacy in the management of postasphyxia acidosis or RDS is not supported by any data. The clear risks and disadvantages of such infusions should warn against its current indiscriminate use.


Jaundice and breast-feeding among Alaskan Eskimo newborns. The course, incidence, and severity of neonatal jaundice was studied in 95 Alaskan Eskimo infants. Breast-fed infants had higher bilirubin concentrations than bottle-fed babies. Both groups experienced high bilirubin levels, similar to those previously reported in Navajo and Oriental infants but greater than those observed in whites and blacks. A marked capacity to inhibit hepatic glucuronyl transferase was observed in breast-milk specimens but only partly accounted for the bilirubin differences between breast-fed and bottle-fed Eskimo infants. These data suggest that in some racial groups predisposed to neonatal jaundice, feeding practices significantly alter the course and severity of hyperbilirubinemia.


Antigenic relationships between the typhus and spotted fever groups of rickettsiae. Paired sera from cases of epidemic typhus in Ethiopia and from probable cases of Rocky Mountain spotted fever (RMSF) in the United States were examined by microagglutination (MA) and microimmunofluorescence (micro-IF) tests for antibodies against Rickettsia prowazekii, Rickettsia typhi, Rickettsia canada, Rickettsia rickettsii, Rickettsia conorii and Ricksettsia akari. IgG and IgM antibodies against the various rickettsiae were titrated with specific fluorescein-conjugated anti-IgG and anti-IgM sera. Purified, particulate rickettsial antigens were employed in all tests. A majority of patients acutely ill with epidemic typhus produced both IgG and IgM antibodies against R. prowazekii, R. typhi and R. canada. Concurrently they produced IgG (but seldom IgM) antibodies against members of the spotted fever group. In contrast, patients ill with probably spotted fever, while producing IgG and IgM antibodies against R. rickettsii, R. conorii and R. akari, also produced both IgG and IgM antibodies with about equal frequency against members of the typhus group. It was concluded that a relatively broad antigenic relationship exists between rickettsiae of the typhus and spotted fever groups.


Afterload reduction and cardiac performance. Physiologic basis of systemic vasodilators as a new approach in treatment of congestive heart failure. Digitalis and diuretics constitute conventional therapy of congestive heart failure, but systemic vasodilators offer an innovative approach in acute and chronic heart failure of decreasing increased left ventricular systolic wall tension (ventricular afterload) by reducing aortic impedance and/or by reducing cardiac venous return. Thus, vasodilators increase cardiac output (CO) by diminishing peripheral vascular resistance (PVR) and/or decrease increased left ventricular end-diastolic pressure (LVEDP) (ventricular preload) by diminishing venous tone. Concomitantly, there is reduction of myocardial oxygen demand, thereby reliably reducing angina pectoris in coronary disease, and potentially limiting infarct size and ischemia provided systemic arterial pressure remains normal. The vasodilators produce disparate modifications of cardiac function depending upon their differing alterations of preload versus impedance: nitrates principally cause venodilation (decrease LVEDP); nitroprusside, phentolamine and prazosin produce balanced arterial and venous dilation (decrease LVEDP and increase CO) provided left ventricular filling pressure is maintained at the upper limit of normal; whereas hydralazine predominantly effects arteriolar dilation (increases CO). With depressed CO plus highly increased LVEDP and increased PVR, nitrates also induce some increase of CO by reducing PVR. Combined nitroprusside and dopamine synergistically enhance CO and decrease LVEDP. Mechanical counterpulsation aids nitroprusside in acute myocardial infarction. The 30-minute venodilator action of sublingual nitroglycerin is extended for 4 to 6 hours by cutaneous nitroglycerin ointment, by sublingual and oral isosorbide dintrate, and by oral pentaerythritol tetranitrate and sustained-release nitroglycerin capsules. Ambulatory oral vasodilator therapy is provided by long-acting nitrates (relieve pulmonary congestion); hydralazine (improves fatigue); prazosin alone, combined nitrate-hydralazine combined prazosin-hydralazine (improve both dyspnea and fatigue).


Long-term outpatient vasodilator therapy of congestive heart failure. Consideration of agents at rest and during exercise. Increased left ventricular filling pressure and reduced cardiac output are two major hemodynamic deficits in pump failure. In patients with chronic heart failure, consequences of these hemodynamic deficits and diminished cardiac reserve are manifested initially during stress and eventually at rest. The purpose of therapeutic interventions include reduction of ventricular filling pressure increase in cardiac output and improvement in cardiac reserve. To achieve these goals, the hemodynamic effects of predominantly venodilators (nitrates), predominantly arteriolar dilators (hydralazine) and the combination of nitrates and hydralazine were evaluated in patients with chronic heart failure at rest: left ventricular filling pressure (mm Hg) control 28, nitrates 17, hydralazine 25, nitrates plus hydralazine 18; cardiac output (liters/min/m2) control 2.1, nitrates 2.1, hydralazine 3.2, nitrates plus hydralazine 3.3; mean blood pressure (mm Hg) control 87, nitrates 85, hydralazine 83, nitrates plus hydralazine 85. These data suggest improved left ventricular performance with a combination of nitrates and hydralazine. Exercise hemodynamics improved in some patients, suggesting that such vasodilator therapy may be beneficial in chronic heart failure.


Nitroglycerin and nitrate esters.

Nitroglycerin and nitrate esters. The expanding applications of nitroglycerin and nitrate esters--in congestive heart failure, in the reduction of infarct size in myocardial infarction and in the long-term prophylaxis of angina--have enhanced the clinical importance of these drugs. This article reviews some of the significant recent investigations of the nitrates and makes specific recommendations regarding clinical use.


Platinum nephrotoxicity.

Platinum nephrotoxicity. Platinum coordination complexes have recently been introduced in cancer chemotherapy with considerable success. However, significant nephrotoxicity has emerged as a factor that limits the therapeutic usefulness of these compounds. In this article we review the available knowledge on platinum nephrotoxicity and its prevention that has been derived from both toxicologic studies in animals and clinical trials in human subjects.


Multiple myeloma (light chain disease) with rheumatoid-like amyloid arthropathy and mu-heavy chain fragment in the serum. A 52 year old man presented with multiple myeloma and widespread amyloidosis involving joints, bursae- carpal tunnels, lymph nodes and subcutaneous tissue. Osteolytic bone lesions and pathologic fracture of the neck of the left femur were found. Bone marrow was infiltrated with both plasmacytes and lymphocytes. The majority of plasma cells contained large cytoplasmic vacuoles. Free kappa II type light chains and mu-heavy chain fragment were detected in the serum, and kappa II type Bence Jones protein was found in the urine. The molecular weight of the mu-heavy chain fragment was found to be approximately 50,000 daltons. An immunofluorescence study, using the double labelling technic, showed that the majority of plasmacytes in bone marrow contained both mu and kappa antigenic determinants in the cytoplasm. A review of the 12 previously described patients with mu-heavy chain fragment in the serum showed a variable clinical picture, thus their natural history and therapeutic response are difficult to evaluate at the present time. It seems that mu-heavy chain fragment can be found in a variety of clinical conditions and that mu-heavy chain disease cannot yet be accepted as a separate clinical entity.


Fibrinogen turnover in pregnant rabbits during the first and last thirds of gestation. Although thrombin-mediated fibrinogen derivatives have been observed in normal pregnancy, an increased turnover of fibrinogen has been suspected but has not yet been demonstrated. Fibrinogen turnover was studied in 14 pregnant and 10 nonpregnant female rabbits by use of purified rabbit 125I-labeled fibrinogen. In the last third of gestation the half life of fibrinogen was shortened by 45% and the fractional catabolic rate increased by 44% in comparison to the values for the first third of gestation obtained in the same rabbits. The distribution volume of the injected fibrinogen representing the plasma volume increased by a mean of 18% during gestation. Fibrinogen concentration did not change during gestation. From a comparison of the measured data from the first and last thirds of gestation, it can be calculated that the synthesis rate of fibrinogen increased by about 80%. Furthermore, a positive correlation was found between the number of young per litter and the acceleration of fibrinogen elimination, indicating that a local process of intravascular coagulation in the placenta is responsible for the accelerated turnover of fibrinogen during gestation.


Fetal hyperinsulinism in rhesus isoimmunization. Analyses of peritoneal ascitic fluid obtained prior to intrauterine transfusion show that some babies with severe rhesus isoimmunization develop raised insulin levels up to a month before delivery. The glucose content of fetal ascitic fluid is usually only about 10 mg. per 100 ml. less than the glucose content of maternal plasma and there is no evidence that this relation is influenced by the fetal or maternal insulin level. The electrolyte content of fetal ascitic fluid is very similar to that of maternal plasma, but fluid from babies with hyperinsulinism has an unusually high calcium content.


Maternal-fetal hemorrhage: its incidence and sensitizing effects. Although anti-Rh-immune globulin is highly effective in preventing hemolytic diseases of the newborn, there are some failures. The causes for these failures often are unknown and it has been postulated that some of them are caused by the transfer of maternal Rh-positive red cells into the Rh-negative infant at the time of birth. A study of 107 Rh-negative newborn infants born of Rh-positive mothers has demonstrated that maternal-fetal hemorrhage is rare (approximately 2 per cent) and that Rh antibody produced during the first six months in Rh-negative babies is similarly rare. Routine administration of anti-Rh gamma globulin to Rh-negative neonates is not indicated.


Determination of disaturated lecithin in rhesus monkey amniotic fluid as an index of fetal lung maturity. Although increased concentrations of total lecithin in amniotic fluid allow prenatal assessment of fetal lung maturation, it has become clear that routine use of the L/S index may lead to a substantial number of inaccurate predictions. Since disaturated lecithin (DL) is a more specific marker of pulmonary surfactant than total lecithin, we developed a convenient method for measuring this phospholipid in amniotic fluid, and then evaluated its level in pregnant rhesus monkeys of 120 to 163 days of gestation. The method involves osmic acid destruction of unsaturated lipids, chromatographic isolation of disaturated lecithin, and quantitation by phosphorus assay. It can be performed in approximately 5 hours on 4 ml. of amniotic fluid and yield 67 +/- 3 per cent average recovery of added 14C-dipalmitolyl lecithin. The results of analyzing 36 rhesus amniotic fluid specimens showed the disaturated lecithin  and the disaturated lecithin/sphingomyelin ratio (DL/S) increase sharply after 150 days of gestation, consistent with the pattern of lung maturation in this species. We conclude that disaturated lecithin can be readily quantitated in primate amniotic fluid and that its concentration, the DL/S ratio, and percentage of disaturated lecithin are potentially useful indices of fetal lung maturity for the clinical laboratory.


Pars plana vitrectomy as a primary treatment for acute bacterial endophthalmitis. We successfully treated six patients with culture-proven acute bacterial endophthalmitis by a combination of emergency pars plana vitrectomy and the instillation of intravitreal antibiotics. All six patients regained satisfactory vision.


The effect of complement depletion on bacterial lipopolysaccharide (LPS)-induced hemodynamic and hematologic changes in the Rhesus monkey. Lipopolysaccharide (LPS) isolated from Salmonella minnesota R595 or from Escherichia coli 0111:B4 induces hypotension in rhesus monkeys with normal complement levels. This hypotension is accompanied by decreased total peripheral resistance. The depletion of C3 and terminal complement components by prior intraperitoneal administration of the anticomplementary protein cobra factor did not alter the hemodynamic changes which occur following the rapid injection of 5 mg/kg of R595 LPS, the infusion of 500 microgram/kg of R595 LPS, or the injection of 500 microgram/kg of 0111:B4 LPS. We conclude that the  LPS-induced hemodynamic changes in the subhuman primate are medicated by pathways which do not require the participation of C3. The kinetics and extent of the neutropenia and thrombocytopenia resulting from the injection of 0111:B4 or R595 LPS were not latered by prior depletion of greater than 95% of  the plasma C3.


Calcitonin and histaminase in C-cell hyperplasia and medullary thyroid carcinoma. A light microscopic and immunohistochemical study. The thyroid glands of 13 patients with gross medullary thyroid carcinoma (4 sporadic, 9 familial), 3 patients with clinically occult microscopic carcinoma, and 5 patients with C-cell hyperplasia have been studied using routine light microscopy and immunohistochemical techniques. The morphologic features of the spectrum of C-cell proliferative lesions are reviewed, and the distribution of calcitonin and histaminase in these lesions is compared. Calcitonin production is a property of normal, hyperplastic, and neoplastic C cells, and the hormone is present in the majority of tumor cells in medullary carcinoma. In contrast, histaminase is shown to be present only in some cells in medullary carcinoma and not in normal or hyperplastic C cells. We believe that the presence of histaminase in a C-cell proliferative lesion is an atypical phenomenon and indicative of malignancy.


Hyaline membrane disease. Effect of surfactant prophylaxis on lung morphology in premature primates. Neonatal lung morphology was evaluated in 12 rhesus monkeys delivered by caesarean section 1 month before term and cared for as human premature neonates. In 6 monkeys, 0.20 to 0.27 ml of natural rabbit surfactant (SA) was instilled intratracheally before the first breath; the other 6 served as controls. Histology and morphometry of the controls' lungs revealed changes typical of hyaline membrane disease (HMD) in human premature infants, whereas the SA-treated lungs showed improved alveolar expansion and only minor lesions typical of HMD. Transmission and scanning electron microscopy of the controls' lungs showed extensive necrosis and desquamation of bronchiolar epithelium, with formation of hyaline membranes; Type I alveolar epithelial cells showed lesions similar to those in bronchioles, but immature Type II cells appeared relatively well preserved. In the lungs of SA-treated animals, the epithelial lining of most airways and alveoli was intact. This first demonstration of the beneficial effect of exogenous SA on lung adaptation in premature primates indicates that prophylaxis with SA might prevent HMD in premature human infants.


Antiserums for immunofluorescent enumeration of human T lymphocytes utilizing fluoresceinated staphylococcal protein A. Five lots (100 ml or more) of heterologous antiserums specific for human T lymphocytes were prepared using human or Rhesus monkey thymocytes as immunogens. After appropriate adsorptions, these antiserums reacted by immunofluorescence with 68% of human peripheral blood mononuclear cells and 98% of human thymocytes, with E-rosette--positive cells but not with EAC-rosette--positive cells or five human B-lymphoblastoid-cell lines. Blocking experiments showed that Rhesus monkey thymocytes share thymic antigenic determinant(s) with humans. E-rosette receptors modulated independently from T-cell heteroantigens. Non-E--rosetting neoplastic T cells were identified in several patients with lymphoproliferative malignancies. Applying both the E-rosette assay and the anti-T-cell serum provides a better method of defining the biologic properties of normal and neoplastic T lymphocytes. Standardization of immunofluorescent conjugates for human T- or B-cell enumeration is simplified if large lots of well-characterized antiserums are available.


The fate of intraportally transplanted islets in diabetic rats. A morphologic and immunohistochemical study. Streptozotocin-induced diabetes in the rat can be reversed by the transplantation of isogenic islets of Langerhans from neonatal donors. We studied the morphology of intraportally transplanted islets with the aid of the immunoperoxidase staining technique to identify insulin-, glucagon-, somatostatin-, and pancreatic polypeptide-containing cells at 24 hours, 48 hours, 1 week, 2 weeks, 4 weeks, 39 weeks, and 65 weeks after transplant. Embolized pancreatic tissue, composed of approximately 80% acini and 20% islets, is initially distributed throughout the liver mainly to terminal branches of the portal system. Endothelialization and organization occur rapidly with the smaller fragments and within the first 4 weeks for larger thrombi. Exocrine pancreatic elements largely disappear as islet cells move into the hepatic lobules from the portal spaces. At 65 weeks after transplant, all islet cell types can be identified within large complex islet structures. The results of this study establish the survival and continued function of all known rat pancreatic islet cell types long after transplantation and support the theory that islet transplantation may represent the most physiologic replacement of hormonal deficiencies in the diabetic recipient.


Feeding and metabolic patterns in rats with truncular vagotomy or with transplanted beta-cells. The night- and daytime basal plasma insulin levels and insulin responses to an intravenous glucose load, basal blood glucose levels and rates of glucose uptake, and, finally, the diurnal patterns of blood glucose levels were investigated in normal compared to vagotomized Wistar rats. The same comparisons were made between normal and diabetic Lewis rats recovered after fetal pancreas transplantation in the kidney capsule. In an attempt to clarify the relationship between the metabolic and feeding diurnal patterns, a detailed study of the meal pattern of vagotomized and transplanted rats was performed. It was shown that 1) a truncular vagotomy abolished both the metabolic and feeding diurnal cyclicity; 2) both the metabolic and feeding diurnal rhythms were maintained in case of a selective denervation beta-cells. The relationship between the metabolic and feeding diurnal rhythms and the role of the vagus nerve are discussed.


Glucose inhibition of 45Ca efflux from pancreatic islets. Pancreatic islets were microdissected from ob/ob mice, loaded for 2 h with 45Ca and perfused with calcium-deficient medium. Irrespective of the glucose and calcium concentrations in the loading medium, increased glucose in the perfusion medium resulted in reduced amounts of radioactivity in the perfusate. A glucose inhibition of 45Ca washout was also evident when the specific radioactivity of the islets approached that of the labeling medium, indicating that the effect was not simply due to isotopic dilution. The depression of 45Ca washout diminished after culture of the islets in a serum-free medium and it was absent in islets taken from mice homozygous for the gene diabetes. The glucose effect became less pronounced when 50 micron D-600, an inhibitor of the calcium inward transport, was added to the calcium-deficient perfusion medium and abolished in the presence of 20 mM Ca-EGTA. The inhibition of the 45Ca washout observed is not necessarily due to a direct glucose interaction with the outward calcium transport but may also result from stimulation of the uptake and intracellular trapping of the cation.


Effect of ventricular end-diastolic volume on vectorcardiographic potentials of the pig. The Brody hypothesis proposes that alterations in end-diastolic blood volume will produce changes in the magnitude of cardiac electrical potentials recorded at the body surface. To test this hypothesis, several procedures that affect end-diastolic volume were applied in 28 anesthetized domestic piglets. The pig dipole moment magnitude curve is typified by two peaks, designated M2 and M3, which responded to these procedures. Doubling heart rate by electrical pacing or hemorrhage of 20 ml/kg produced reduction in M2 by 30% and 29%, respectively. M3 rose by 27% and 29%, respectively, under these two conditions. Reduction of end-diastolic volume by partial occlusion of the vena cava produced similar effects. Maneuvers increasing end-diastolic volume produced directionally opposite effects. Temporary aortic coarctation of phenylephrine injection caused an increase in M2 with no change in M3, accompanied an acute elevation of arterial pressure. Thus, the pig electrocardiogram shows changes, attributable to adjustments in end-diastolic volume, consistent with the Brody hypothesis, suggesting potentials for this technique in monitoring changes in end-diastolic volume.


Plasmodium falciparum and Plasmodium vivax infections in the owl monkey (Aotus trivirgatus). I. The courses of untreated infections. This study, the first of three designed to determine the feasibility of using owl monkeys infected with human plasmodia in the search for new, more broadly active antimalarial drugs, dealt with the characteristics of untreated infections with eight strains of Plasmodium falciparum and two strains of P. vivax. Such infections, induced by standardized inocula of these strains in 1,733 monkeys, all Aotus trivirgatus griseimembra, were followed from day of inoculation to death of self-cure. The virulence of the various strains differed strikingly. Incidences of fatal reactions, ranging from 24.4--89.4% and 8.1--45.8%, respectively, in infections with strains of P. falciparum and P. vivax, were closely related to the rate at which parasitemia evolved, the height of parasitemia in the primary attack, and/or the time period over which a high parasite level was sustained. Antemortem symptom complexes and gross tissue and organ reactions in infections with P. falciparum varied with survival time, but within that boundary, were the same for infections with all eight strains of this plasmodium. Morbidity in both fatal and self-limited infections with both plasmodial species was related to height of parasitemia; however, at comparable parasite levels, symptoms exhibited in infections with P. vivax were more severe than in infections with P. falciparum. Overall, the characteristics of infections with these plasmodia in owl monkeys were remarkably similar to those of human infections. With respect to biological features, infections with P. falciparum and P. vivax in this simian host appear to have much to offer in the search for new antimalarial drugs.


Plasmodium falciparum and Plasmodium vivax infections in the owl monkey (Aotus trivirgatus). II. Responses to chloroquine, quinine, and pyrimethamine. The studies described in this report were designed to determine the responses of established infections with eight strains of Plasmodium falciparum and two strains of P. vivax in owl monkeys to treatment with chloroquine, quinine, and pyrimethamine. Responses with these different strains ranged from cure via application of well-tolerated doses of two of the above drugs and refractoriness to treatment with maximally tolerated doses of the third, to complete resistance to maximally tolerated doses of all three compounds. The results of treatment exhibited in infected owl monkeys correlated well in two respects with those reported in humans infected with the same plasmodial species. First, calculated on a milligram per M2 basis, the doses of chloroquine, quinine, or pyrimethamine required for a CD90 response in owl monkeys infected with strains susceptible to these drugs were remarkably similar to the doses required and/or employed for cure of infections with so-called drug-susceptible strains in human patients. Secondly, with few exceptions, the responses to the above drugs in owl monkeys infected with the ten specially selected strains were essentially identical with those exhibited by human volunteers or patients infected with the same strains. Together, these findings and correlations provide strong support for use of owl monkeys infected with appropriate strains of P. falciparum and P. vivax in the search for more broadly effective antimalarial drugs.


Plasmodium falciparum and Plasmodium vivax infections in the owl monkey (Aotus trivirgatus). III. Methods employed in the search for new blood schizonticidal drugs. This report describes, illustrates, and validates the major features of a procedure designed to provide primary assessments of the activities of potential antimalarial drugs against infections with chloroquine-resistant or pyrimethamine-resistant strains of Plasmodium falciparum in owl monkeys of Colombian origin. Studies with 14 specially selected compounds have shown that the test method has the capacity to identify and quantify diverse levels of therapeutic efficacy among agents that differ widely in chemical structure. Extended studies with two of the above compounds indicate that such assessments have an acceptable level of reproducibility. Experiments with two other agents, structurally different from those in the selected group, have shown that the impacts of pyrimethamine resistance (or chloroquine resistance) on the activity of a compound can be readily identified during routine application of the test procedure, as can emergence of parasites resistant to the test agent. The above body of information can usually be acquired in infections with two strains of P. falciparum, one chloroquine-resistant, the other pyrimethamine-resistant, with commitments of no more than 1.5 g of test compound and 12 owl monkeys. These modest requirements have made it possible to utilize human plasmodial infections in the owl monkey in the search for new blood schizonticidal drugs more broadly effective than those currently available.


Effect of falciparum malaria infection on the in vitro mitogen responses of spleen and peripheral blood lymphocytes from owl monkeys. The response of spleen and peripheral blood lymphocytes (PBL) to mitogen stimulation with phytohemagglutinin (PHA), Concanavalin A (ConA), and pokeweed mitogen (PWM) was determined for owl monkeys (Aotus trivirgatus) experimentally infected with the Vietnam-Oak Knoll (FVO) and the Uganda-Palo Alto (FUP) strains of Plasmodium falciparum. PBL from Panamanian Aotus monkeys with less than 25% FVO infection responded normally to mitogen stimulation; however, increased parasitemia of 25--50% resulted in a significant suppression of ConA responsiveness. Colombian Aotus monkeys infected with the PUF strain also developed a suppression to ConA stimulation but with a lower parasitemia (10--25%). When the parasitemia became greater than 50% in these animals, PHA, ConA, and PWM responses were significantly decreased in cultures of PBL. Spleen cells from all acutely infected Aotus monkeys were suppressed to PHA and ConA, but not PWM stimulation. Changes in mitogen responsiveness of experimentally infected Aotus monkeys are similar to those reported for humans with acute falciparum malaria.


Pathology of Bolivian Hemorrhagic fever in the African green monkey. Gross and microscopic pathological findings are presented for an African green monkey model of fatal Bolivian hemorrhagic fever. Six animals were inoculated with 1,000 plaque-forming units of Machupo virus, the etiological agent of Bolivian hemorrhagic fever. Five of the monkeys died within 13 days with signs of fever, anorexia, shock, and hemorrhage. The sixth monkey survived until the 24th day and died with signs of central nervous system disease. Gross lesions in the five monkeys that die in the acute stage included hepatic necrosis, necrotic enteritis, bronchopneumonia, and hemorrhages in the subcutis, lungs, intestine, liver, and lymph nodes. Microscopically, necrosis was consistently seen in liver, intestine, skin, oral cavity, and adrenal cortex. Acute thrombosis was observed in four monkeys, in blood vessels of the intestine, lung and choroid of the brain. Gram-negative bacteria were seen in many tissues, suggesting terminal bacteremia. The sixth monkey was emaciated and had bronchopneumonia, but did not have the necrotic hepatic and enteric lesions observed in the other five monkeys. The significant microscopic lesions in this monkey included encephalomyelitis, ganglionitis, and bronchopneumonia.


Tissue reacting antibodies in a rhesus monkey with long-term Trypanosoma cruzi infection. Immunoglobulins (Igs) reacting against endothelial and vascular structures and striated muscle cells as well as against cells from a peripheral nerve were detected by indirect immunofluorescent test (IIF) in a rhesus monkey infected for 29 yr with Trypanosoma cruzi. Anti-T. cruzi antibodies in this monkey showed a titer of 1:128 in the IIF test and the direct agglutination test. Tissue-reacting Igs were bound in vivo to the tissues, as was established by direct treatment of a biopsy of the deltoid muscle with Ig-labeled antisera. Electron microscopy of this tissue showed that Igs reacted with the plasma membrane of the muscle cells. Neither tissue-reacting Igs nor specific antibodies were detected in three uninfected adult monkeys.


Apparent absence of Sarcocystis and low prevalence of Trichinella in artificially digested diaphragm muscle removed during post-mortem examination at a Sacramento (California) medical center. Diaphragm samples taken from 297 humans at autopsy over a 20-mo period were artificially digested and the digestate was examined for Sarcosystis and Trichinella. No infection with Sarcocystis was found while three infections with Trichinella were discovered.


Further evidence for hypothalamic-pituitary dysfunction in alcoholic men. Reduced plasma levels of testosterone and a high frequency of azoospermia have frequently been reported in alcoholic men. Despite the high grade of gonadal failure present, plasma gonadotropins have ranged from normal to only moderately increased. This has been interpreted as suggesting that a central hypothalamic-pituitary defect also might exist in these men. Clomiphene stimulation studies have been consistent with the hypothesis of a central defect. The present work consists of studies utilizing luteinizing hormone-releasing factor and thyrotropin-releasing factor in an effort to examine the hypothesis of whether this central defect exists and, if so, whether at an anatomic, hypothalamic, or pituitary level.


Accelerated atrioventricular conduction in Fabry's disease: a case report. Three unrelated men with Fabry's disease (angiokeratoma corporis diffusum universale) and accelerated atrioventricular conduction are described. AQn His bundle electrogram in one patient who reported episodes of tachycardia demonstrated a prolonged deflection preceding the ventricular complex. This deflection is thought to represent an abnormal His bundle potential, possible resulting from glycolipid deposition. In the second patient the PR interval decreased from 0.18 to 0.11 second during 10 years, and in the third patient it decreased from 0.12 to 0.10 seconds during 13 years. Accelerated atrioventricular conduction may develop in Fabry's disease.


Catheter infection factors affecting total parenteral nutrition. During the five-year interval from January 1, 1971 to January 1, 1976 118 seriously ill adults received 2916 patient days of TPN therapy with an average infection rate of 7.6%. All patients received the benefit of a well-defined TPN catheter care protocol which emphasized regular (every 48 hours) catheter dressing changes. The lowest risk of infection, 2.7%, was seen in 73 patients who received an amino acid-glucose solution through a silicone elastomer catheter protected by an iodophor dressing. When catheter-related sepsis occurred, Staphlylococcus aureus and Candida albicans were the most common organisms cultured.


Early appearance of abscess after biliary operation. Three patients who had an air shadow and fluid levels within seven days after biliary surgery are discussed. In retrospect, this direct evidence of a postoperative abscess was overlooked because of its early appearance and other sources of fever that coexisted.


Psychologic stress, vasodepressor (vasovagal) syncope, and sudden death. Giving up in the face of emotional arousal and psychologic uncertainty are conditions conducive both to vasodepressor syncope and sudden death. Under such circumstances there may be simultaneous activation of two emergency biologic regulatory systems, flight-fight and conservation-withdrawal. In the healthy person this may result in vasodepressor syncope, benign arrhythmias, or both. In the presence of factors lowering the threshold for conduction disturbances, dangerous arrhythmias and sudden death rather than, or as well as, vasodepressor syncope may result. Although active myocardial damage by itself may provide the necessary and sufficient conditions for lethal arrhythmias, psychic uncertainty must be considered an additional risk factor. The implications of this concept for patient care and prevention of sudden death are a challenge for future research.


Ectopic ossification after hip arthroplasty. The incidence of radiographically visible ectopic ossification around the hip joint was redorded in 145 hip joints of 132 patients treated by endoprosthetic replacement. There were 56 total hip replacements with a McKee-Farrar and 39 with a Brunswik type of endoprosthesis; in a further 50 hips the femoral head was replaced with a Moore or Thompson prosthesis. An identical antero-lateral surgical approach was used in all, without detachment of the greater torchanter. The patients were re-examined 3, 6, and12 months after the operation. The extent of ectopic ossification was graded from 0 to III and correlated with pain and with the function and mobility of the operated hip. Ectopic ossification of varied extent was recorded in 37 % after total hip replacement and in 38 % after replacement of the femoral head. Of these ossifications 95 % were recognizable within 3 months; they did not increase in size, but often in density during the following months. One case of bony ankylosis was noted. Ectopic ossification of slight (grade I) to moderate (grade II) degree did not cause pain or affect the function of the operated hip, but reduced the mobility of the affected hip. The difference in mobility between grade I and grade II was significant (p less than 0.05), and between grade 0 and grade II highly significant (p less than 0.001).


Eighteen years experience in stapedectomy. The case for the small fenestra operation. The postoperative findings in almost 800 stapedectomized ears were analyzed to evaluate the proposition that complication rates in stapedectomy were affected by the size of footplate fenestration. It was concluded that small fenestra stapedectomy (diameter 0.4 mm) provided similar hearing gains to those achieved with standard techniques, that articulation problems occurred to a similar extent as with wire loop prostheses, and that there was a significantly lower incidence of a) fistual and b) immediate and delayed severe sensorineural hearing loss than with any other technique. There was also significantly less deterioration in bone conduction thresholds at 4 kHz after three years postoperatively. The incidence of severe immediate sensorineural loss in large fenestra stapedectomy (half or more of footplate removed) was significantly influenced by factors such as age, preoperative bone conduction thresholds and oval window pathology. A retrospective analysis provided no information which might predict oval window pathology. Additional information gained from the analysis indicated that with all types of stapedectomy, bone conduction did not deteriorate significantly more rapidly in the operated as  compared to the unoperated ear, whereas in unoperated ears, deterioration in bone conduction was significantly greater in ears with mixed hearing losses than when the loss was purely sensorineural. It was concluded that small fenestra stapedectomy was currently the operation of choice because with it, the threat of cochlear dysfunction both immediately, and in the long term, was significantly less.


Deviated nasal septum. Incidence and etiology. Septal deformity is of two kinds, which may occur independently, or together: 1) anterior cartilage deformity of the quadrilateral septal cartilage, caused by direct trauma or pressure at any age; and 2) combined septal deformity involving all the septal components, caused by compression across the maxilla from pressures occurring during pregnancy or parturition. This is part of a facial deformity. The incidence of septal deformity was investigated in 2,380 Caucasian infants at birth, 2,112 adult skulls of five ethnic groups (European, Indian [Asian], Chinese, African and Australian Aborignal), 918 mammals (266 higher and lower apes, 457 other placental mammals and 185 marsupials). The method of nasal testing of infants by passage of special testing struts (6 by 2 mm) is described. Forty-two percent of septa of infants were straight, 27% deviated and 31% kinked. A similar pattern was found in adult skulls, namely 21% straight, 37% deviated and 42% kinked. Anterior cartilage deformity occurred in about 4% of births. The maxillary molding theory of transmitted pressures during pregnancy or partitution, causing septal deformity, is described. The findings show that varying degrees of septal deformity occur at a constant rate at birth and in the adult. These may vary slightly for each ethnic type. Birth molding pressures are a major cause of dental malocclusion. The shape and strength of the skull and the erect posture appear to be major factors, for septal deformity did not occur in the lower animals, but occurred in 37% of the higher apes and also in a skull of a hominid 1,750,000 years old. This concept enables easy recognition at birth, and the carrying out of a rational method of treatment by manipulation and rapid maxillary expansion.


[Hormonal control of thyroxine-binding globulin synthesis and metabolism (author's transl)]. Serum thyroxine-binding globulin (TBG), the major plasma transport protein for thyroid hormones in man, was shown to be altered under the influence of estrogen and in hypothyroidism. In order to study these alterations, we used an animal model. Synthesis of TBG was demonstrated in hepatocytes isolated from adult Rhesus monkeys, and in a monkey hepatocarcinoma continuous cell culture line (NCLP-6-E). When the hepatocytes were obtained from monkeys pretreated with beta-estradiol (E2), a specific 2.5-2.9 fold increase of TBG synthesis and secretion was shown; similar data were obtained with the tumor line. Furthermore, an increased TBG production was shown with these cells when T4 (from 10(-14) to 10(-11) M) was added to the culture medium. The in vitro results were correlated with in vivo data obtained by investigating the metabolism of TBG after iv injection of tracer doses of purified, radiolabelled TBG to normal, E2-treated and thyroidectomized monkeys. The main effect of estrogen administration was a marked increase of the production rate. During hypothyroidism, the catabolism and the production rate of TBG were decreased. In both conditions, there were significant changes in the distribution volume of TBG, the physiologic relevance of which remains to be investigated.


[Thyroid function in protein-caloric malnutrition in infants (author's transl)]. Iodine kinetics and thyroid function were investigated in 68 cases of protein-caloric malnutrition (senegales children). This nutritional state induces an acute and severe alteration of thyroid function, as indicated by the reduced iodine uptake and clearance, a 50% decrease of hormonal secretion rate, and the low levels of total and free T4. T3 concentration is also very low: this may be partly due to a defective conversion of T4 to T3. Despite this state of primary hypothyroidism, no hypersecretion of TSH is observed.


[TSH-response to TRH in active coeliac disease in infants (author's transl)]. In 11 infants of 3-19 months of age with active gluten-induced enteropathy, an exaggerated and sustained response of plasma TSH to TRH was observed as compared to controls. In these same patients, there was a decrease in total and free T4 and T3 concentrations. All these values were statistically different from controls.


[TSH increase after subtotal thyroidectomy for nontoxic goiter (author's transl)]. Eighty-nine patients operated for nontoxic goiter have been followed up. An enhanced TSH response to TRH was observed in 74% of the cases of multinodular goiter, but only in 23% of uninodular goiter. The therapeutic implications of these data are discussed.


Radioimmunoassay for serum myoglobin.

Radioimmunoassay for serum myoglobin. A column flow-through radioimmune assay for serum myoglobin has been developed. The assay uses antibodies to human or rhesus monkey myoglobin coupled to Sepharose by cyanogen bromide activation and myoglobin labeled by the Chloramine-T method. The labeled myoglobin is stable over two to three half-lives. Serum myoglobin levels were elevated when serum was taken up to 12 hours after myocardial infarction and generally elevated up to 24 hours. A continued or repeated elevation of serum myoglobin probably indicates continued myocardial damage or new attacks. In the cases of myocardial infarction, levels up to 1340 ng per ml were found.


[TRH test on 6 patients 47, XYZ (author's transl)]. A T.R.H. test has been made on 6 patients 47,XYY, living in a psychiatric hospital. The results show a thyroid disease with latent hypothyroidism whose origin seems to be hypothalamic, or pituitary or both.


[Effect of different grades of agar-agar on the nature of the test microbe growth inhibition zones in controlling antibiotic activity by means of agar diffusion]. The effect of various agar grades on the size and margin character of the inhibition growth zones in assay of antibiotic activity by the agar diffusion method was studied. It was shown that not all the agar grades could be used in antibiotic activity assay. Depending on the agar type the size of the inhibition growth zones produced by the same antibiotic concentration significantly varied. The variations in the size of the inhibition growth zones depended on the agar ability to bind antibiotics and were mainly defined by the agar purity. The agars with low content of nitrogen admixtures bound the antibiotics to a low extent. The commerical grades of the agars of the South-Sea and Korsakov Plants, the experimental grade of the TINRO agar with additional purification, as well as the agars imported from Argentina and France proved to be most useful for determination of the antibiotic activity by the agar diffusion method.


[Effect of Pseudomonas aeruginosa melanin on antibiotic activity]. The properties of microbial melanines are very diverse. Melanine of P. aeruginosa is little studied. The pigment was isolated from a strain of P. aeruginosa possessing all characteristic properties of the species. Interaction of P. aeruginosa melanine with various antibiotics was determined by the method of serial dilutions in beaf-peptone broth, using Staph. aureus 209 as a test-microbe, which was added to the medium in an amount of 10(6) cells to each tube. It was found that P. aeruginosa melanine differed from DOPA-melanine in a concentration of 1 mg/ml and did not change the activity of penicillin, tetracycline, oleandomycin, kanamycin and gentamicin with respect to Staph. aureus.


[Gonococcal sensitivity to penicillin in women with gonorrhea relapse and reinfection]. Penicillin sensitivity of gonococci isolated from patients with relapses and reinfection of gonorrhea was studied. The results of the study were compared with those of the sensitivity tests in primary patients. The gonococcal strains with decreased sensitivity to penicillin were isolated from 82 per cent of the gonorrhea relapses, 47.8 per cent of the patients with reinfection and 33.2 per cent of the primary patients. The average sensitivity of the gonococcal strains isolated from the patients with relapses was 0.404 U/ml, while that in the primary patients and the patients with reinfection was 0.136 U/ml. Strains sensitive to 0.6--1.2 U/ml predominated among gonococci with decreased sensitivity in the patients with relapses, while in the primary patients and the ones with reinfection the value amounted to 0.1--0.2 U/ml. The penicillin sensitivity of gonococci may be used as a parameter in differential diagnosis of relapses and reinfection of gonorrhea.


Molecular studies and possible relatedness between R plasmids from groups B and D streptococci. Resistance plasmids isolated from Streptococcus agalactiae (group B) and S. faecalis (group D) have been compared in regard to resistance markers, molecular weight, and DNA-DNA homology. Three of them (pIP501, pIP612, and pIP613) have been found to confer identical (or very similar) resistance patterns (erythromycin, lincomycin, and streptogramin B, respectively) and to have similar molecular weights (19.8 x 10(6), 22.7 x 10(6), and 17.6 x 10(6), respectively) and a high level of DNA-DNA homology in hybridization experiments (90 to 100%). These results are compatible with the view that these plasmids may derive from one common ancestor, and/or that they can be transferred between unrelated Streptococcus strains belonging to the same or different groups.


Differences in susceptibilities of virulent strains and avirulent strains of Neisseria gonorrhoeae to antimicrobial agents. Virulent cells (T1 colony type) and avirulent cells (T4 colony type) of Neisseria gonorrhoeae were grown in a defined liquid medium in the presence of different antimicrobial agents. Bacteria of T1 colony type were found to be more resistant than bacteria of T4 colony type to the inhibitory effects of specific concentrations of ampicillin (0.50 mug/ml) and penicillin (0.01 mug/ml). Bacteria of T4 colony type, however, were found to be more resistant to the effects of chloramphenicol (0.40 mug/ml), erythromycin (0.10 mug/ml), spectinomycin (10.00 mug/ml), and tetracycline (0.30 mug/ml). The differences in susceptibilities of these bacteria to the antibiotics investigated were not due to differences in growth rate or to differences in permeability. The data suggest that virulent gonococci and avirulent gonococci have unique properties that affect their susceptibilities to certain antimicrobial agents.


Zinc deficiency and acrodermatitis after intravenous hyperalimentation. During the fourth week of intravenous hyperalimentation (IVH) a vesiculopustular and erythematous eruption developed in the perioral and perineal areas of a 60-year-old woman. During the next ten days, the eruption spread to involve the central portion of the face, periorbital areas, entire perineum, upper portion of the thighs, and feet. She became depressed and agitated. Numerous study results for Candida albicans were negative. Within 48 hours of therapy with 220 mg. of zinc sulfate twice daily, the eruption had resolved to a mild erythema. The pretreatment serum zinc level before treatment was markedly depressed at 36 microgram/dl.


Neurofibromatosis and interstitial lung disease. The literature suggests that 10% to 20% of adult patients with neurofibromatosis have associated interstitial lung disease. Characteristics of such involvement, as present in the case reported herein, include bilateral lower lobe fibrosis and may include bullous and cystic changes in advanced cases. In addition to pulmonary fibrosis, neurofibromatosis may have other intrathoracic associations; including "dumbbell" neurofibromas, intercostal neurofibromas, and intrathoracic meningoceles.


Nebulised sodium cromoglycate in the preschool wheezy child. A double-blind controlled study of 14 preschool children with recurrent wheezing episodes was performed to show the effectiveness of nebulised sodium cromoglycate in inhibiting exercise-induced bronchoconstriction in this age group. All 14 children showed markedly less exercise-induced bronchoconstruction after nebulised sodium cromoglycate, 13 of them to a degree indistinguishable from results obtained in normal healthy children in the same age group. Nebulised water afforded protection from exercise-induced bronchoconstriction in some children. This study gives further evidence that sodium cromoglycate is an effective therapeutic agent in children under the age of 5 years.


I-cell disease.

I-cell disease. A boy with fatal I-cell disease is reported. Defective ganglioside and glycoprotein metabolism is due to deficient neuraminidase activity.


Action of the "nude" gene on pigmentation of the coat in c57 black and c3 mice. The authors have studied pigmentary changes of skin and hair due to the presence of the "nude" gene in pigmented species (C 57 Bl. 6J, C3H). Morphological (histology, electron microscopy) and biochemical (polyacrylamide gel electrophoresis of tyrosinase activities) studies showed that the pigmentary alterations of the "nude" mice were related to hair cycle and hair growth wave pattern. In fact, in the "nude"  mice the hair follicles evolves cyclically similarly to mice of normal coat. In depigmented skin, the hair follicles were in the resting phase and no soluble tyrosinase could be demonstrated.


Polymyositis in Chagas's disease.

Polymyositis in Chagas's disease. Polymyositis marked the clinical onset of Chagas's disease in a patient with rheumatoid arthritis. This is unusual, although clinically unimportant muscle involvement in trypanosomiasis has been described. The plasma cell infiltrate and vascular deposition of IgM and C3 suggest that the humoral immune system may play a role in the pathogenesis of chagasic polymyositis. It is not known whether the rheumatoid diseases predisposed to the polymyositis.


Immunodiffusion studies on synovial fluid from patients with rheumatoid arthritis: the reaction of fibrinogen with a streptococcal extract. Synovial fluids (83.3%) from patients with rheumatoid arthritis gave a positive reaction when examined by immunodiffusion against a Lancefield extract of Group A Type 12 streptococci. None of the patients with osteoarthrosis reacted positively. An antiserum was prepared to the material in synovial fluid reacting with the streptococcal extract. This antiserum reacted positively with all synovial fluids tested including the osteoarthrosis patients. It also reacted with all plasma samples tested but only with a few (18.2%) of serum samples. Immunodiffusion and absorption experiments demonstrated that the material reacting with the streptococcal extract was fibrinogen. Of 12 other streptococci examined only one, a Group C organism, gave a similar positive reaction with synovial fluids.


Transplantation of the liver.

Transplantation of the liver. Liver transplantation has had a long gestation period in being accepted as standard therapy. The main reason for this is the formidable operation to which the patient is subjected and because of this, referral of cases tends to be too late. Increasing confidence in the operation should result in earlier surgery. The low incidence of uncontrollable rejection is an encouraging finding which should, in the future, make the results of grafting for nonmalignant parenchymatous liver disease better than those currently obtained with kidney grafts from cadaver donors. The surgery requires a large team of strongly motivated doctors, nurses and technicians, who must have continuing experience with technically successful orthotopic liver grafts in experimental animals.


[Cerebro-spinal fluid assay (author's transl)]. The Author describes an analytical comparative method between cerebrospinal fluid and serum which allows to calculate some protein indices in CSF and in CSF and blood that are very useful in the diagnosis of the nervous system diseases.


Home parenteral nutrition: results in 34 pediatric patients. Although home parenteral nutrition (HPN) has been used successfully for adult patients, no extensive experience with children has been reported. During the past three years, we have managed 34 patients, ages 1 1/2 months to 20 1/2 years, on a HPN program for periods ranging from 23 to 786 days. Silastic Broviac catheters were inserted into the superior vena cava through the jugular or cephalic veins or into the inferior vena cava through the saphenous vein. The catheters were brought out onto the chest or lower abdominal wall through a subcutaneous tunnel. Solutions were infused over a 10--14-hour period each day, using a volumetric pump system. All patients improved their nutritional status. Twenty-three of 29 on the program for more than two months showed an increase in height. All patients evidenced a significant decrease in symptomatology. All resumed per group activities while on HPN and were able to continue their education or work. At present 24 patients including 15 with Crohn's disease no longer receive HPN. Administration of HPN through a Broviac catheter is a safe, successful technique for maintaining an optimal nutritional status in children with severe digestive disorders, and permits resumption of a more normal daily lifestyle. Following HPN, bowel adaptation and initiation of full oral alimentation become possible in many patients.


Amino acid derangements in patients with sepsis: treatment with branched chain amino acid rich infusions. Sepsis is a major catabolic insult resulting in modifications in carbohydrate and fat energy metabolism, and leading to increased muscle breakdown and nitrogen loss. Insulin resistance, which develops in sepsis, decreases glucose utilization, but plasma insulin levels are sufficiently elevated to prevent lipolysis, resulting in a further energy deficit. The availability of fuels in sepsis is therefore limited, and the body resorts to muscle breakdown, gluconeogenesis, and amino acid oxidation for energy supply. Previous work has not defined, however, the exact alterations in amino acid metabolism. Therefore, the following studies were undertaken. Blood samples were drawn from fifteen patients in whom the diagnosis of sepsis was clinically established; the samples were analyzed for amino acid, beta-hydroxyphenylethanolamines, glucose, insulin and glucagon concentrations. The plasma amino acid pattern observed was characterized by an increase in total amino acid content, due mainly to high levels of the aromatic amino acids (phenylalanine and tyrosine) and the sulfur-containing amino acids (taurine, cystine and methionine). Alanine, aspartic acid, glutamic acid and proline were also elevated, but to a lesser degree. The branched chain amino acids (valine, leucine and isoleucine) were within normal limits, as were glycine, serine, threonine, lysine, histidine and tryptophan. Those patients who did not survive sepsis had higher levels of aromatic and sulfur-containing amino acids as compared to those patients surviving sepsis. On the other hand, those patients surviving sepsis had higher levels of alanine and the branched chain amino acids. In a second group of five patients with overwhelming sepsis accompanied by a state of metabolic encephalopathy, a parenteral nutrition solution consisting of 23% dextrose, and an amino acid formulation enriched with branched chain amino acids was administered. In these five patients, normalization of the plasma amino acid pattern and reversal of encephalopathy was observed. The following sequence of events may be postulated: The septic patient develops insulin resistance in the peripheral tissues, primarily muscle, while the adipose tissue is much less affected. The insulin resistance and the inability to utilize fat leads to increased muscle proteolysis. Muscle breakdown results in release into the blood of enormous amounts of various amino acids; the muscle itself is able to oxidize the branched chain amino acids, supplying the muscles' own energy requirements and alanine for gluconeogenesis. The extensive muscle proteolysis coupled with relative hepatic insufficiency occurring early in sepsis results in the appearance in the plasma of high levels of most of the amino acids present in muscle, particularly the aromatic and the sulfur-containing amino acids. The outcome of patients with sepsis might be positively affected by combined therapy with glucose, insulin and branched chain amino acids.


Pharmacological profile of N-(2,6-DIMETHYLPHENYL)-N-(1-methyl-2pyrrolidinylidene)urea, xilobam, a new centrally acting skeletal muscle relaxant. The pharmacological profile of a new centrally acting skeletal muscle relaxant, xilobam, is described and compared to that of existing skeletal muscle relaxants. The potencyof xilobam, administered intravenously, is approximately ten times that of methocarbamol in the linguomandibular assay in the cat. When evaluated in the strychnin assay in the mouse, the potency of xilobam is approximately seven times that of chlorzoxazone and eleven tomes that of methocarbamol and five times that of metaxalone. In contrast to methocarbamol, xilobam exhibits little or no sedative activity and appears devoid of antianxiety properties. When administered to non-anesthetized dogs, xilobam and other centrally acting muscle relaxants, such as chlorzoxazone and methocarbamol, increased arterial pressure and heart rate. Mydraiasis, vocalization and muscle rigidity were concomitantly observed. These effects appear to be centrally induced. It is concluded that xilobam appears to be a potent centrally acting muscle relaxant which should not be sedating or anxiolytic in man.


[Further study of the in vitro antibiotic resistance of strains of Psedumonas aeruginosa isolated in hospital and extra-hospital environments. Differences in resistance between the 2 groups]. The sensibility of Ps. aeruginosa strains to several antibiotics has been tested in vitro. The strains have been divided into two groups: a group of 162 cases from the Hospital and a group of 42 cases from the outside. Then the percentage of resistance to each antibiotic of the cases in both groups has been calculated, and so has the significance of the differences between the percentages, whenever a difference has been found out. The strains from the Hospital have proved to be significantly more resistant to neomycin, nalidixid acid, chloramphenicol, demetilclortetracyclin, rifampicin, whereas the strains from the outside have shown greater resistance to colimicin and gentamicin. All the other differences between percentages haven't proved to be significant.


[Contrast echocardiology in two dimensions and in real time. 1. Ultrasonic techniques]. An aqueous solution (5% glucose) injected rapidly into a peripheral vein modifies the acoustic homogeneity of the blood not only at the periphery, but also within the cavities of the heart. This ultrasonic contrast technique has taken a new lease of life thanks of two-dimensional echocardiology in real time, which allows the blood to be visualised as it moves. A description is given of the current two-dimensional real time transducers, and the dynamically focal multiscan which has been developed in our laboratories. An analysis is made of the chosen ultrasonic contrast medium (glucose water), of the site and mode of injection, of the recording technique and of the various echocardiological views. Finally, a discussion highlights the limitations of single crystal echocardiography, and the advantages of the two-dimensional technique in real time.


[Contrast echocardiography in two dimensions and in real time. 2. Clinical applications]. The anatomical and functional abnormalities which are the basis of septal defects and valvular incompetence can be visualised directly by two-dimensional contrast echocardiology. Although right-left shunts at atrial or ventricular level can easily be discovered and visualised after injection peripherally, the same is not true of left-right ventricular shunts; these are not detectable. As for left-right shunts (as demonstrated by oxymetry) at the atrial level, these are in a separate category; the passage of ultrasonic contrast medium from right to left is inconstant. This technique also allows the study of abnormal blood flow: tricuspid incompetence, turbulence caused by prosthetic valves, etc.


[Continous electrocardiography recording in coronary insufficiency. Diagnostic value]. The accuracy of continuous 24 hour recordings (Holter's method) in the diagnosis of coronary insufficiency has been studied in 115 patients, by comparison with coronary arteriography. The technique was highly specific, but only fairly sensitive under the conditions of the study, because of the relative inactivity of the patients or the absence symptoms during the recording. It has allowed us to detect certain painfree or relatively painless forms of myocardial ischaemia which may be severe, and to have a clearer understanding of the effect of treatment. Comparison with the exercise electrocardiogram has shown inconsistencies due to the limitations of the two techniques. Holter's method is a particularly simple way of detecting coronary insufficiency, and is most useful when exercise tests are impossible or contraindicated.


[Correction of cardiac malformations after corrected transposition of the great vessels. A series of 18 cases operated on by an open heart technique]. Recent progress in the surgical treatment of malformations after transposition has been dealt with has been made in three directions: 1. By knowledge of the position of the conducting pathways in relation to ventricular septal defects, so that total atrioventricular block, the first complication of this type of surgery, may be avoided; 2. By appreciation of the proximity of the conductive pathways to the elements contributing to pulmonary stenosis, which may contra-indicate direct removal of such stenosis. In such a case, a valved tube must be placed between the sub-pulmonary ventricle and the pulmonary artery; 3. By appreciating the frequency, the difficulty in diagnosis and the grave consequences of failing to recognise lesions of the atrioventricular valves, with the result that their systematic investigation should form part of the operative technique.


[Congenital defects of the aortic system]. The authors give a basic embriological classification of congenital arterial defects. Congenital abnormalities of the arterial system (arising in an embryo of 12 to 30 mm) affect the primary segments, and comprise excessive involution of the antibrachial trunk, of the popliteal artery, of the tibio-peroneal trunk and peroneal artery, abnormal or persistence of the interosseus artery, of the artery of sciatic nerve, and of the peroneal artery, a high axillary origin of the radial or antecubital artery, renal polar arteries arising directly from the aorta, and agenesis of the palmar or plantar arches. In the second generation arteries, they comprise agenesis or hypogenesis of the radial, antecubital or tibial arteries, and gross hypogenesis of the trunk of the renal artery with an immature kidney. Arrested or mal-development in the foetus can give rise to coarctation and stenosis of the thoracic aorta and large vessels, to segmental agenesis with huge collaterals, to imperforate osita, especially in the mesenteric arteries, to sudden variations in diameter of the renal arteries, and to parietal dyplasia and aneurysms in vessels in the residual undifferentiated mesenchymatous tissue, and diffuse dilatation or stenosis. The authors give their experience for a cardiological clinic, adding arterial hypertension and arterioparenchymatous dysplasia of the kidneys, Raynaud's, Takayasbu's and Burger's disease, and intermittent claudication of the lower limbs; they indicate the areas which they are currently studying.


[Cardiac findings in bilharziasis without pulmonary arterial hypertension]. 1. A systematic search was made for cardiac abnormalities (clinical, radiological and ECG) and haemodynamic disorders (catheterisation of the right side of the heart and pulmonary artery) in 37 cases of confirmed biharziasis. It was generally found that:--14 patients (37.8%) had no symptoms;--8 patients (21.6%) had pulmonary hypertension (PH) with the corresponding cardiac signs (these will be reported separately);--15 patients (40.5%) had cardiac signs with no PH; these are studied in this paper. 2. Iatrogenic myocarditis was noted on the ECG. It was found in 3 of the 37 cases (8.1%). This points to the importance of careful monitoring of treatment. There was also ECG evidence of anaemyic myocardial changes in 5 cases of the 37 (13.5%). In 3 of these 5 cases this was found to be due to bleeding. Hypertensive myocardial disease was found in 1 case (2.7%), a patient with renal disease. Myocardial signs were also found in 3 cases because of coexistant disease. 3. Three cases (8.1%) remain in whom there were ECG changes, but without PH and without any other definable cause. These could have been due to bilharzia myocarditis; the authors review the experimental and clinical evidence for such a possibility. The real incidence of this condition remains to be determined. 4. Although there was no such case in this series, the authors suggest that bilharziasis might cause endomyocardial fibrosis (EMCF). 5. The authors put forward the hypothesis that the pulmonary arteritis is a tissue immunological reaction, and also that the myocarditis (and possibly the EMCF) is a manifestation of circulating antibodies.


[An unusual type of mid-ventricular obstruction. A discussion of the findings]. The authors report a case of left-sided mid-ventricular obstruction which was completely different from the usual type of obstructive cardiomyopathy, and had asymetrical hypertrophy of the septum demonstrable both by angiocardiography and macroscopically. Complete clinical and haemodynamic recovery followed left ventricular myectomy with replacement of the mitral valve (one year's follow-up).


[Recurrent supraventricular tachycardia. The efficacy of a radio frequency system inserted into the coronary sinus]. The case is reported of a man of 66 with attacks of recurrent supraventricular tachycardia (SVT) which failed to respond to the standard medical treatment and which, because of their frequency, led to mental disturbances. The electrophysiological features of SVT are discussed, and the possibilities of recording potentials from the SA node. A definitive pacemaker was placed in the coronary sinus, and linked to a simple stimulator working at radio frequency (and activated by the patient himself); this led to an almost immediate reduction in the attacks of SVT.


[The supernormal phase of cardiac conduction. An experimental study in the dog]. The existence of a cardiac phase of supernormal excitability is not fully proved at the cellular level. As far as the whole heart is concerned, the phenomenon of supernormal conduction is still under discussion. Intracardiac conduction has been studied both in the right atrium (13 dogs) and in the right ventricle (14 dogs) by programmed stimulation (extrastimulus technique), while monophasic action potential (MAP) was recorded. The phenomenon of supernormal conduction was noted in 67.7% of cases, starting at 59.0% and ending at 78.0% of the basic cycle, hence occuring shortly after phase 3 of the MAP. In the ventricle, a phase of supernormal conduction was present in 52.4% of cases, starting at 66.1% and ending at 77.9% of the basic cycle. After ajmaline, the supernormal conduction was moved towards the end of the cycle. The mechanism of supernormal conduction, and its implications in the study of arrhythmias are discussed.


[Nitroglycerin in experimental myocardial infarction in the baboon. The effect of reducing the pre-charge and post-charge on regional myocardial function]. A left anterior descending coronary artery occlusion was produced in the sedated state in baboons previously instrumented with a left ventricular micromanometer and ultrasonic crystals measuring segmental myocardial lengths of control, marginal and ischemic regions. 3-8 days after the onset of the ischemia, nitroglycerin (0.4 mg IV) was injected. Following the injection (NG), heart rate increased significantly compared to the control ischemic state (CIS); end diastolic pressure and systolic pressure decreased significantly. In control segments, VCF increased from 0.99 +/- 0.11 circ/s to 1.26 +- 0.11 circ/s (p less than 0.01); in marginal segments VCF increased (CIS: 0.32 +/- 0.07 circ/s; NG: 0.42 +/- 0.09/s; p less than 0.01); in ischemic segments, the bulge observed before the injection persisted after nitroglycerin. Increased performances of control and marginal regions were attributed mainly to afterload reduction although preload reduction tended to decrease this response. The contribution of improved marginal function was small indicating that improvement of active hemodynamic function was largely due to changes in control segments function.


Thiethylperazine; clinical antipsychotic efficacy and correlation with potency in predictive systems. A one-to-one relationship between clinical antipsychotic potency and pharmacologic dopaminergic antagonism is implicit in the dopamine hypothesis of neuroleptic action. Thiethylperazine maleate, a classical antiemetic phenothiazine, displays dopaminergic antagonism in behavioral, neurochemical, and neuroendocrine systems, but is paradoxical insofar as it is thought not to possess clinical neuroleptic activity. In three tests of dopaminergic antagonism--elevation of levels of CSF homovanillic acid in monkeys, striatal dihydroxyphenylacetic acid in rats, and prolactin in man--as well as in a clinical trial of neuroleptic efficacy in schizophrenics, thiethylperazine was fully active and approximately three times as potent as chlorpromazine. Differences in efficacy between this and earlier clinical studies can be accounted for on the basis of dosage.


Delayed hypersensitivy and experimental interstitial pneumonitis. The effects of prior sensitization with killed H37Ra tubercle bacilli on the pulmonary reaction to intravenous (IV) challenge with complete Freund's adjuvant (CFA) have been studied and were compared to reactions in nonsensitized CFA-challenged controls. Rabbits that died within 24 hours of challenge demonstrated acute arteritis prior to granuloma formation. Sensitized rabbits had a greater number of exudative cells in the pulmonary lavage fluid and a larger volume of parenchymal infiltrate than did comparable, nonsensitized controls at two and eight weeks. The exudate and infiltrate were diminished in both sensitized and nonsensitized rabbits at eight weeks. An obliterative, granulomatous arteritis was observed in both sensitized and nonsensitized groups receiving IV CFA and was not affected by the state of sensitivation. Granulomatous and collagenous parenchymal lesions regress in both sensitized and nonsensitized groups between two and eight weeks.


[Immunomorphological transformation of the thyroid gland in autoimmune thyroiditis]. In parallel immunochemical, immunohistochemical, and histopathological studies of blood sera and biopsies of the thyroid gland tissue the autoimmune nature of thyroiditis was proved in 11 female patients. The detected antithyroid autoantibody was classified as complement-dependent immunoglobulin. Immunocytochemical data are presented confirming the histiocytic derivation of macrophages and non-epithelial nature of B- and C-cells. Transformation of colloid and cells ans metabollsm of monoclonal immunoglobulins (IgG, IgA, IgM) permit the judgement on the duration of autoimmune thyroiditis. The diffuse lymphoid variant is typical of the first 5 years, and focal fibrinolymphoid variant-for later peroids of autoimmune thyroiditis.


Breast biopsy. A comparison of outpatient and inpatient experience. Nine hundred ninety-seven breast biopsies that were performed at one hospital over the five-year period from 1971 through 1975 were reviewed because of a changing pattern in the use of breast biopsies on outpatients who were under local anesthesia. In 1971, 17% of all breast biopsies were performed as outpatient procedures; by 1975, the figure was 60%. In 1971, 5% of all malignant neoplasms were diagnosed by the use of biopsies as outpatient procedures and 30% in 1975. Hospital charges for biopsy on an inpatient basis of benign breast disease were 7.2 times higher than for biopsy on an outpatient basis. Interviews of 102 patients clearly suggested that most patients were satisfied with the outpatient breast biopsy experience. Outpatient breast biopsy under local anesthesia is a safe procedure that is more economical in terms of medical cost, surgeons' time, and patients' time away from home and/or job. Preliminary biopsy of malignant lesions using local anesthesia permits more efficient use of diagnostic procedures to stage the extent of disease prior to treatment. Patient acceptance of breast biopsy as an outpatient procedure under local anesthesia was similar to their acceptance of biopsy on an inpatient basis under general anesthesia.


[Interneurons of the motor region of the neocortex]. Interneurons of motor area in the brain cortex have been studied in cats and monkeys. The greatest attention has been paid to pyramidal interneurons, among which six cell types have been described according to their axonal composition. Unlike stellate interneurons, all types of pyramidal interneurons possess less developed axonal collaterals. Interneuronal contacts are situated on dendrites or cell bodies of middle and large long-axonal pyramids. Functional role of cortical interneurons seems to be different. Some of them are of inhibitory nature (basket cells and, perhaps, other types of long-axonal stellate neurons), others are exciting elements. The latter include short-axonal stellate neurons and, perhaps, pyramidal interneurons. While comparing the cortex in cats and monkeys, it is evident that the neocortex in monkeys, especially its lower layers, is rich in pyramidal interneurons.


[Blood supply of the compact and spongy myocardium of fish, amphibia and reptiles]. Coronal arteries were injected with lead carbonate suspension and with Indian ink and cleared preparations 150--300 mkm thick were made in 195 hearts of fish, amphibians and reptiles and studied roentgenographically. It was stated that in Chondrichthyes (shark, skate) and in Chondrostei (beluga, stellate sturgeon, sturgeon), as well as in alligator both compact and spongy myocardium of the cardiac ventricle possess blood vessels. In teleostei, amphibians and reptiles (except alligator) spongy myocardium is avascular and receives its nutrition from the ventricle. In view of the data on the presence of blood vessels in the spongy myocardium in some vertebrates, it is impossible to accept the theory suggested by Grant and Regnier according to which vessels in the heart walls appear only in connection with compactization of the myocardium. Vascularization of the spongy myocardium is closely connected with oxygen saturation of the blood flowing through the heart. When this saturation is not satisfactory, the spongy myocardium has blood vessels. In alligator, vascularization of the spongy myocardium is connected with the fact that the heart has four chambers and there are arterial and venous blood streams.


Artificial organ support strategies in combined renal, circulatory, pulmonary and liver failure. Within recent years we have significantly broadened the indication for the treatment of acute renal failure in intensive care patients, even in the presence of multiple organ failure. This was made possible by: 1. safe heparinization of the extracorporeal circulation while avoiding bleeding tendencies 2. hemofiltration of patients threatened by pulmonary complications early during renal failure and 3. the simultaneous use of various special intensive care measures. By this approach we have succeeded in a number of cases to break the chain of complications leading to multiple organ failure and death.


Elevations of hemopexin levels in neuromuscular disease. Hemopexin, a serum glycoprotein that binds free heme and transports it to hepatic parenchymal cells, has been measured by radial immunodiffusion. We have confirmed elevation of serum hemopexin concentration in Duchenne's muscular dystrophy patients and carries, and demonstrated elevations in dermatomyositis/polymyositis and myasthenia gravis, but not in amyotrophic lateral sclerosis. In monkeys, elevations of hemopexin levels were specifically induced by hematin injections, muscle-crush, or myoglobin injections. Myoglobin leakage is the likely explanation of hemopexin level elevation in Duchenne's dystrophy patients and carriers and in dermatomyositis/polymyositis. In myasthenia gravis there might be a slight myoglobin leakage not heretofore suspected; or, the elevation of hemopexin levels might be a new reflection of a dysimmune state in myasthenia gravis, and perhaps as such is a further incrementing factor in dermatomyositis/polymyositis. Hemopexin, presumably as a longer-phase reactant, is sometimes an index of neuromuscular disease when other data are negative or equivocal.


Proton irradiation of choroidal melanomas. Preliminary results. Choroidal malignant melanomas in nine patients were treated with proton beam irradiation at the Harvard Cyclotron Laboratory, Cambridge, Mass. Each patient received five proton beam treatments in eight to ten days, totalling 4,730 to 8,570 rads at the tumor. No complications occurred during the treatment or follow-up period, which, at the time of this writing, ranges from one to 24 months, with an average of 12 months. No further growth of the tumor has been observed in any patient. Different signs of tumor regression have been noted. Resolution of the serous retinal detachments that accompanied some tumors is the earliest finding. Pigment changes over the surface of the tumor and adjacent pigment epithelium is a usual initial tumor response. Fluorescein angiography initially showed decreased leakage of dye; later, destruction of the tumor's vasculature and elimination of fluorescein leakage became evident. Only large choroidal vessels remained patient. Ultrasonography revealed decreased height of the tumors postirradiation, and the radioactive phosphorus (32P) uptake test, repeated in one patient, turned negative on postirradiation measurements.


Inhibition of adenovirus replication in vitro by trifluridine. At present, there is no effective chemotherapeutic agent available for the treatment of adenoviral keratoconjunctivitis. Recent evidence suggests that trifluridine (3FT) may effectively inhibit the replication of some adenovirus serotypes known to cause keratoconjunctivitis. The ability of 3FT to inhibit two reference strains of adenoviruses, type 8 and type 19, was examined using cell cultures. Two second-passage isolates of adenoviruses, identified as serotype 13, were also tested. Compared with untreated, virusinfected cell cultures, drug-treated cell cultures developed a lesser degree of cytopathic effect following infection with all three serotypes. Virus production was reduced in the drug-treated cell cultures: approximately tenfold for type 8, more than 1,000-fold for type 19, and 5,000-fold for the type 13 isolates.


Formation and utilization of 3-hydroxy-3-methylglutarate in liver mitochondria of starved and streptozotocin-diabetic rats. Kidney and liver mitochondria of rat, rabbit and guinea pig are able to transform 3-hydroxy-3-methylglutarate into acetoacetate, whereas ox liver mitochondria and rat mitochondria of heart, diaphragm and brain do not exhibit such an activity. Starvation and streptozotocin treatment decreases the formation of acetoacetate from 3-hydroxy-3-methylglutarate. Addition of acetoacetate and succinate to the incubation media of mitochondria results in a decrease in the transformation of 3-hydroxy-3-methylglutarate into acetoacetate. A 3-hydroxy-3-methylglutaryl-CoA hydrolase is present in rat liver mitochondria; the activity does not show appreciable changes after starvation or streptozotocin treatment.


Comparative studies on two ferredoxins from the cyanobacterium Nostoc strain MAC. Two ferredoxins were isolated from the cyanobacterium Nostoc strain MAC grown autotrophically in the light or heterotrophically in the dark. In either case approximately three times as much ferredoxin I as ferredoxin II was obtained. Both ferredoxins had absorption maxima at 276, 282 (shoulder), 330, 423 and 465 nm in the oxidized state, and each possessed a single 2 Fe-2S active centre. Their isoelectric points were approx. 3.2. The midpoint redox potentials of the ferredoxins differed markedly; that of ferredoxin I was --350mV and that of ferredoxin II was --445mV, at pH 8.0. The midpoint potential of ferredoxin II was unusual in being pH dependent. Ferredoxin I was most active in supporting NADP+ photoreduction by chloroplasts, whereas ferredoxin II was somewhat more active in pyruvate decarboxylation by the phosphoroclastic system of Clostridum pasteurianum. Though the molecular weights of the ferredoxins determined by ultracentrifugation were the same within experimetnal error, the amino acid compositions showed marked differences. The N-terminal amino acid sequences of ferredoxins I and II were determined by means of an automatic sequencer. There are 11--12 differences between the sequences of the first 32 residues. It appears that the two ferredoxins have evolved separately to fulfil different roles in the organism.


Preparation of chromatin containing ribosomal deoxyribonucleic acid from the macronucleus of Tetrahymena pyriformis. A method is described that enables a chromatin fraction containing ribosomal DNA (DNA containing sequences coding for rRNA) to be prepared from the macronuclei of growing or stationary cultures of Tetrahymena pyriformis. This material is obtained in yields of between 25 and 75% of the theoretical maximum. The DNA in this fraction was identified as ribosomal DNA on the basis of its density and molecular weight, and it appears not to be appreciably contaminated by other DNA. The method relies on the approximate assumption that ribosomal DNA is the smallest species of DNA in chromatin in the nucleus, and avoids the use of mechanical force, or enzyme action, to fractionate chromatin.


Histone composition of a chromatin fraction containing ribosomal deoxyribonucleic acid isolated from the macronucleus of Tetrahymena pyriformis. The histone compositions of a chromatin fraction containing ribosomal DNA and of the remaining macronuclear chromatin of Tetrahymena pyriformis was analysed by gel electrophoresis. These chromatin fractions were used as models for transcriptionally active and inactive chromatin respectively. The extent of histone modification, as indicated by the distribution of histone between differently charged subspecies in acid-urea gels, is not grossly different in the two chromatin fractions. However, histone H1 is present, but may be differently modified in the two chromatin fractions. The histone/DNA ratio in ribosomal chromatin, measured after sodium dodecyl sulphate/polyacrylamide-gel electrophoresis of samples of chromatin, was found to be the same whether chromatin was extracted from growing or stationary organisms, and to be approx. 40% of this ratio in the remaining macronuclear chromatin. The implications of these results for the possible structure of transcriptionally active chromatin are discussed.


The role of zinc in the stabilization of the dimeric form of bacterial alpha-amylase. Bacterial alpha-amylase was shown by equilibrium and velocity-sedimentation studies to be a monomer-dimer equilibrium system in 0.10M-NaCl/0.015M-calcium acetate/0.010M-EDTA, pH7.0; an association constant of 2.4 X 10(3)M-1 is obtained. Studies of the binding of Zn2+ to alpha-amylase in 0.10M-NaCl/0.005M-calcium acetate, pH7.0, yielded binding curves that exhibit dependence on the concentration of alpha-amylase (Zn2+-free) used in the equilibrium-dialysis experiments. Results are described very satisfactorily by a reaction scheme in which Zn2+ binds exclusively to the dimer of the above monomer--dimer system with an association constant of 1.0 X 10(6)M-1. The present results refute the earlier scheme for dimer stabilization by Zn2+ in which the metal ion formed a cross-link between two non polymerizing monomer units.


Characterization of proteins structurally related to human N-acetyl-beta-D-glucosaminidase. Those proteins of human liver that cross-reacted with antibodies raised to apparently homogenous hexosamindases A and B were detected by immunodiffusion. Cross-reacting proteins with high molecular weights (greater than 2000000) and intermediate molecular weights (70000--200000) were present both in the unadsorbed fraction and in the 0.05--0.2M-NaCl eluate obtained by DEAE-cellulose chromatography at pH7.0. The unadsorbed fraction also contained a cross-reacting protein of low molecular weight (10000--70000). The possible structural and functional relationships between hexosaminidase and the cross-reacting proteins are discussed. An apparently cross-reacting protein present in the 0.05M-NaCl eluate from the DEAE-cellulose column was serologically unrelated to hexosaminidase, but it gave a reaction of immunological identify with one of the apparently cross-reacting proteins having the charge and size characteristics of hexosaminidase A. It is suggested that immunochemical methods may provide criteria for the homogeneity of enzyme preparations superior to those of conventional methods.


Purification and properties of glutamate synthase and glutamate dehydrogenase from Bacillus megaterium. Bacillus megaterium N.C.T.C. no. 10342 exhibits glutamate synthetase (EC 2.6.1.53) and glutamate dehydrogenase (EC 1.4.1.4) activities. Concentrations of glutamate synthase were high when the bacteria were grown on 3mM-NH4Cl and low when they were grown on 100mM-NH4Cl, whereas glutamate dehydrogenase concentrations were higher when the bacteria were grown on 100mM-NH4Cl than on 3mM-NH4Cl. Glutamate synthase and glutamate dehydrogenase were purified to homogeneity from B. megaterium grown in 10mM-glucose/10mM-NH4Cl. The purified enzymes had mol.wts. 840000 and 270000 for glutamate synthase and glutamate dehydrogenase respectively. The Km values for substrates with NADPH and coenzyme were (glutamate synthase activity shown first) 9 micron and 360 micron for 2-oxoglutarate, 7.1 micron and 8.7 micron for NADPH, and 0.2 mM for glutamine and 22 mM for NH4Cl, similar values to those of enzymes from Escherichia coli. Glutamate synthase contained NH3-dependent activity (different from authentic glutamate dehydrogenase), which was enhanced 4-fold during treatment at pH 4.6 NH3-dependent activity was generally about 2% of the glutamine-dependent activity. Amidination of glutamate synthase by the bi-functional cross-linking reagent dimethyl suberimidate inactivated glutamine-dependent glutamate synthase activity, but increased NH3-dependent activity. A cross-linked structure of mol.wt. approx 200000 was the main product formed.


[Fetal hydrops (review of 30 cases)].

[Fetal hydrops (review of 30 cases)]. Thirty cases of hydrops fetalis were reviewed in the obstetrics hospital No. 2 of the Social Security, and were treated in the isoimmunization clinic. Important data were obtained from the analysis, the most outstanding was the fact that both the mother with previous pregnancies and incompatible Rh blood transfusions, cause the hemolytic diseases to the unborn product, which usually presents at birth a severe and clear hydrops fetalis. Previous care to delivery was of great help, specially spectrometric and photometric studies of the ammniotic fluid with purpose of following the evolution, and to evaluate the right moment to perform the intrauterine fetal transfusions, which at a certain stage may allow the fetus to grow more without important deterioration of its functions, thus avoiding lung problem in premature fetuses. This is the main reason for high mortality. Although if it is not applied at the right moment the results will be negative and it is frequent that the pregnancy ends in fetal deaths. In general, the high mortality index occurred in the products that showed severe hydrops fetalis, in spite of the fact that pre and post natal care, imply fetal problem. This is due to the prematurity as well as the pathological process to which they are submitted. It is also necessary to insist that in promptness to apply treatment in the neonatal period, will depend the life of these infants. This treatment is the responsibility of a whole specialized group that has the knowledge of the problems, such as obstetricians, pediatricians, biochemists, nurses and social workers, etc.


[Solitary mastocytoma].

[Solitary mastocytoma]. A case is reported of a four--month--old male infant with mastocytoma localized on antero--internal side of left leg. It was a single lesion seen since birth, of tumoral aspect, about 3.5 x 2 x 0.8 cms., light brown color. The pathologic study confirmed the diagnosis. The course was uneventful and disappeared spontaneouly in one year.


[Congenital urethral diverticulum].

[Congenital urethral diverticulum]. It is a rare condition; cases seen more frequently are usually secondary to other diseases or to surgical procedures. In this paper, a case of sacular diverticulum of urethra is reported in a newborn and was made evident by urinary obstruction. Treatment is discussed and review is made of the literature.


[Congenital spondyloepiphyseal dysplasia. Apropos of a case]. The present paper describes a case of spondyloepiphyseal dysplasia congenita (S.D.C.), a heritable bone dysplasia manifested at birth and characterized by short stature and retarded ossification of vertebral bodies, pelvis and extremities. Differential diagnosis which is important for genetic counselling purposes is established between S.D.C. and Morqu's disease, diastrophic dwarfism, metatropic dwarfism, psuedoachondroplasia and hypoachondroplasia.


[Tolerance to vitamin C in malnourished children]. Although the concentration of ascorbic acid in the serum of malnourished children is usually low, the state in which organic reserves of this vitamin were found, were unknown. Based on this information, a tolerance study, before and after a saturation period, was planned. The main idea of the investigation was to find out the organic reserves of this nutriment in infants complaining of severe malnutrition. The study was carried out in 12 malnourished children with ages between 3 to 30 months. After a fasting period of 8 hours, a blood sample was taken and each patient was given 200 mgs. ascorbic acid by intramuscular route; following this, blood samples were obtained every hour on 4 occasions. During the next 5 days they were given 1 g. daily of vitamin C and on the 6th day, the tolerance test was repeated. With the purpose of determining excretion of vitamin C, urine was collected 12 hours previously and 12 hours after each study. The results showed a significant statistical difference in responses obtained with the load of vitamin C before and after the course of the saturation period; this finding allows the statement that the organic tissues of the malnourished child keep a short reserve of this vitamin, although it does not reach the critical levels of 0.3 mg/100 ml when the clinical signs of the specific deficiency to this nutriment appear.