Basal osteotomy of the first metatarsal bone in hallux valgus: experiences with the use of AO plate. In young patients with hallux valgus, osteotomy with excision of the exostosis is frequently indicated. The basal, laterally based wedge osteotomy, is relatively seldom used. However this operation may produce a considerable reduction of the metatarsus primus varus. We modified the method by adding a small AO plate to ensure stabilization. The series consisted of 36 patients, in whom 52 feet were operated on. Pain was the most frequent indication for seeking treatment. A followup was performed an average of 1.5 years postoperatively. The subjective results were good in 41 cases, fair in nine, and poor in one. Objectively the results were good in 42 cases and fair in nine. The mean period of work was seven weeks. The metatarsus varus angle was reduced from 14.8 degrees to 9.3 degrees and the hallux valgus angle from 33.2 degrees to 17.7 degrees. The distance between the first and second metatarsal bones was reduced from 13. 7 mm to 10.2 mm. A good functional and cosmetic result was achieved in most of the cases.


[Lysosomal and cytoplasmic enzymatic activity under the experimental action of carbon disulfide]. Activity of lysosomal enzymes and content of carbohydrate containing biopolymers (glycosaminoglycans, glycoproteins) were altered in various tissues (liver, kidney, brain, aorta) of experimental animals intoxicated with carbon disulfide. Possible role of the impairments observed, related to neurotropic and hepatotoxic effects, is discussed. Subsequent development of atherogenic and embryotoxic effects of carbon disulfide--one of contaminators of surroundings--are considered.


[Determination of hexokinase isoenzymes in different tissues]. A modified method is described for estimation of hexokinase isoenzymes by polyacrylamide gel electrophoresis. The best conditions for detection of hexokinase activity were developed using immobilization of glucose-6-phosphate dehydrogenas: in gel, utilization of riboflavin as a catalyst of polymerization and stabilization by glucose. The method is simple, highly reproducible, comparatively rapid and economically reasonable.


Effect of cholesterol-lowering diet on mortality from coronary heart disease and other causes. International statistics indicate that there is a close correlation between the consumption of saturated fats (dairy fats and meat fats) and the mortality from coronary heart disease (CHD), and this conception has been confirmed by many epidemiological studies. Such studies alone, however, cannot prove the existence of a cause-and-effect relationship between these two variables; dietary intervention trials are needed. The Finnish Mental Hospital Study was such a trial, conducted in two hospitals near Helsinki in 1959--1971. Practically total replacement of dairy fats by vegetable oils in the diets of these hospitals was followed by a substantial reduction in the mortality of men from CHD. Total mortality also appeared to be reduced. As to the causes of death other than CHD, none was significantly influenced by dietary change. This was also true for malignant neoplasms. To alleviate the burden of CHD on public health, many investigators have recommended important changes in the quantity and quality of dietary fats.


[Catalytic properties and isoenzyme composition of hexokinase in thyroid gland normal and neoplastic tissue]. Catalytic properties and isoenzyme composition of hexokinase were studied in extracts of normal thyroid, thyroid benign adenoma and thyroid carcinoma tissues from 23 patients. It was shown that the "cancer" hexokinase was several times more active and had lower Km (glucose) as compared with the enzyme from normal thyroid and benign tumor. Gel electrophoretic study revealed five hexokinase isoenzymes in both normal thyroid and its benign tumor. The hexokinase isoenzyme pattern in thyroid carcinoma was characterized by the "deletion" or distinctly decreased ratio of the "slowest" component. Studies on catalytic properties and isoenzyme composition of hexokinase are important as an additional test for the differentiation between benign and malignant tumors.


Spontaneous course of ST-segment elevation in acute anterior myocardial infarction. The spontaneous course of ST-segment elevation (sigmaST) in 24 patients with acute anterior myocardial infarction (AMI) was studied by precordial ST-segment mapping, which was recorded at 2-hour intervals during the first 48 hours after admission. Change of sigmaST between two registrations was expressed as mV/hr, and was compared with clinical and hemodynamic parameters, course of MB-CK curve, calculated infarct mass and arrhythmias. After an initial rapid increase, there was a decrease of sigmaST, which reaches a plateau-like curve approximately 12 hours after the onset of chest pain. A second new increase of sigmaST exceeding a value of 0.6 mV/hr correlates well with extension of necrosis, verified by re-elevation of MB-CK. During the first 2 days, extension of necrosis could be detected in 50% of our patients. As new ischemic episodes and extension of necrosis in AMI occur frequently and are promptly indicated by an increase of sigmaST, the physician should, while monitoring therapeutic interventions, concentrate on such a second increase rather than on a decrease of sigmaST (which may occur spontaneously), as has been suggested in most previous reports.


Enzymatic indices of myocardial necrosis: influence on short- and long-term prognosis after myocardial infarction. The prognostic effect of the peak level of serum creatine kinase (CK) and aspartate transaminase (AST), estimated daily for 3--5 days after acute myocardial infarction, was studied in 560 patients who survived the first day in hospital. In a subgroup of 54 patients, peak enzyme levels correlated well with the cumulated CK release (r = 0.90 with peak CK, r = 0.74 with peak AST), thus reflecting the extent of myocardial necrosis. Total mortality within a year after infarction was not significantly different in the lower three quintiles of peak serum enzyme level, but increased from 15.5% to 27.9% (p less than 0.001) when peak CK level exceeded eight times the upper limit of normal (8 X N) and form 13.1% to 34.8% (p less than 0.001) when peak AST level exceeded five time the upper limit of normal (5 X N). The effect of high enzyme levels was more marked in patients with a prior history of myocardial infarction; mortality increased from 14.7% for first infarctions to 18.2% for recurrent infarctions, with peak CK greater than 8 X N, and from 27.0% for first infarctions to 38.0% for recurrent infarctions with peak CK greater than 8 X N. Early mortality was more significantly affected (p less than 0.0001) than late mortality (p less than 0.05). In hospital survivors, late deaths from cardiac decompensation were three times (p less than 0.05) more frequent in the high enzyme group as in the low enzyme group, but the number of sudden deaths was unaffected. These findings have important implications for studies of reduction of myocardial infarct size.


Metabolism and proliferation of L929 mouse fibroblasts cultured in the presence of sodium fluoride. L 929 mouse fibroblasts were cultured as monolayers with different amounts of sodium fluoride, corresponding to those used therapeutically. Proliferation of the cells was inhibited in the logarithmic phase of cell growth. There was no change in the protein concentration in the cells, but the concentration of hydroxyproline containing substances in the cells increased while that of hexuronic acid containing substances decreased. The changes in proliferation and in the concentrations of hydroxyproline containing substances and hexuronic acid containing substances were statistically significant. Although the findings cannot be explained in detail it can be concluded that at therapeutic concentrations sodium fluoride has a definite action in contact with the fibroblast, the typical connective tissue cell. This dose dependant action corroborates clinical experience.


Cross-sectional echocardiographic diagnosis of coronary artery aneurysms in patients with the mucocutaneous lymph node syndrome. Real-time cross-sectional echocardiographic studies revealed the presence of coronary artery aneurysms in five patients with mucocutaneous lymph node syndrome. These lesions appeared as circular echo-free spaces with clearly-defined borders in sites corresponding to angiographically proven aneurysms. In 15 normal subjects who were studied only by noninvasive methods, and in 17 who had normal coronary arteriograms (including eight with the mucocutaneous lymph node syndrome), we found no similar echo findings. The aneurysms were in both right and left coronary arteries in three patients, and were confined to the left side in two. The mucocutaneous lymph node syndrome is an increasingly common condition in Japan which may be fatal due to myocardial infarction occurring in a setting of coronary aneurysm with thrombosis. Therefore, the ability to demonstrate coronary aneurysms noninvasively is of prognostic and potentially therapeutic value in this inadequately understood syndrome.


[Experimental infection of an invertebrate cell line with a mollicute-like procaryote inducing the "lethargy of coleoptera" (author's transl)]. In vitro multiplication of a pathogenic intravacuolar mollicute-like procaryote from Melolontha melolontha L. was experimentally obtained in an insect cell line. The elongated and pleomorphic forms observed in the insect-host are reproduced in cell cultures. A third peculiar giant form is missing, showing that it does not play any role in the multiplication of the germ. The intrinsic potentialities of the germ are maintained during the successive passages, as proved by reinfection of the insect and by immunology. The original syndrome including the giant form is reproduced in the insect. The immunserum prepared from the wild germ isolated by density gradient is positive with the in vitro mollicute. The germs are intravacuolar, both in the cultured cells and in the insect host. Clearly the microorganism multiplies within the vacuoles. A cytopathogenic effect is noticed in the cultured cells overcrowed with germs. The germs become extracellular when they are released in the culture medium by disaggregation of the cell membranes. It seems that this work shows the first model of an intravacuolar mollicute-like procaryote experimentally multiplied in cultivated cells.


Factors contributing to altered left ventricular diastolic properties during angina pectoris. Mechanisms involved in the altered left ventricular (LV) diastolic properties during angina were studied in 26 patients with coronary artery disease. Angina was induced by rapid atrial pacing and measurements were made at rest and during angina in the immediate post-pacing period. No changes occurred in heart rate (71 +/- 3 to 73 +/- 3 beats/min, NS) or right ventricular (RV) end-diastolic pressure (10 +/- 1 to 11 +/- 1 mm Hg, NS), while significant increases occurred in LV end-diastolic pressure (17 +/- 1 to 30 +/- 1 mm Hg, p less than 0.01), aortic diastolic pressure (74 +/- 3 to 80 +/- 3 mm Hg, p less than 0.01), coronary sinus blood flow (133 +/- 15 to 212 +/- 32 ml/min, p less than 0.01), and the time constant (T) of LV pressure fall in early diastole (43 +/- 2 to 58 +/- 4 msec, p less than 0.01). Despite the rise in arterial pressure, a significant fall was observed in peak negative dP/dt (1961 +/- 106 to 1751 +/- 80 mm Hg/sec, p less than 0.01). Changes in RV end-diastolic pressure do not explain the increased LV end-diastolic pressure during angina. Increased aortic pressure and coronary blood flow may contribute, but the simultaneous fall in peak negative dP/dt and rise in T suggest that impaired ventricular relaxation is an important factor contributing to the previously demonstrated alteration in LV diastolic properties during angina pectoris.


Intraoperative recording of specialized atrioventricular conduction tissue electrograms in 47 patients. Intraoperative mapping of the specialized atrioventricular conduction system was performed in 47 patients during cardiac surgery. Specialized conduction tissue electrograms were identified in 37, and atrioventricular conduction preserved in 92%. Specialized conduction tissue was identified in 27 patients with atrioventricular canal defect: complete heart block was avoided in 25. Conduction tissue was located in six of 12 patients with complex transpositions; atrioventricular conduction was preserved in all six. Other lesions in which the technique was useful were Ebstein's anomaly and single atrium. Limitations to the technique are 1) deep hypothermia and circulatory arrest; 2) interruption in atrioventricular conduction during mapping; 3) inadequate exposure and access to probable sites of conduction tissue; 4) variation of size and spatial relations of individual malformations; and 5) limited time for identification of unusually located conduction tissue. Indications for use of this technique include patients with both forms of atrioventricular canal, complex transpositions, atrioventricular discordance, single ventricle and single atrium.


Epicardial activation of the intact human heart without conduction defect. To describe the epicardial ventricular activation sequence in the intact human heart, we obtained epicardial maps from 11 patients with normal QRS undergoing open heart surgery. Epicardial breakthrough (EBT), defined as the emergence of a radially propagating epicardial wavefront, occurred in three to five sites in each patient, and was earliest in the anterior right ventricle, 7--25 msec (mean 17 msec) after the onset of the QRS in all patients. Subsequent EBT occurred in the inferior right ventricle (10 sites in 10 patients), in the anterolateral left ventricle (13 sites in 10 patients), and the inferior left ventricle (eight sites in seven patients). Latest epicardial activation (LEA), defined as the latest site of recordable epicardial activity, occurred in the basal segments in all patients, anteriorly in the right ventricle in five patients, and inferiorly in six patients, four on the right and two on the left. LEA occurred 63--96 msec (mean 77 msec) after the onset of the QRS, and was recorded within 20 msec of the end of the QRS in all patients. Sequence of epicardial activation reflected a fusion process among the wavefronts. This descriptive and quantitative data should provide a suitable basis for comparison of abnormal ventricular activation sequences in patients undergoing surgery for preexcitation or ventricular tachycardia.


Dilatation of the ductus arteriosus by prostaglandin E1 in aortic arch abnormalities. Infants with aortic arch interruption of juxtaductal coarctation of the aorta may depend on patency of the ductus arteriosus to provide adequate lower body perfusion. In many such infants the ductus arteriosus constricts after birth, resulting in severe heart failure, poor systemic perfusion and acidemia. We infused prostaglandin E1 (PGE1) at a rate of 0.05--0.1 microgram/kg/min into seven infants with aortic arch interruption and eight infants with coarctation. In one infant in each group the ductus arteriosus was already closed and did not reopen. In one infant with coarctation an adequate trial was not accomplished, and in another adequate pressure measurements were not obtained. Of the remaining 11, the ductus arteriosus was effectively dilated by PGE1 in 10 infants. This was evidenced by an increase in descending aortic blood pressures and a reduction in the pressure difference between the main pulmonary artery and descending aorta in six infants with aortic arch interruption and between ascending and descending aorta in four infants with coarctation. Lower body perfusion improved and left ventricular failure was improved. The infant who did not respond was 5 months old. There were no complications.


Anatomy of aortic atresia. Cases presenting with a ventricular septal defect. The anatomy of 58 specimens of aortic outflow tract atresia was studied. All cases had situs solitus and levocardia, 37 had atrioventricular (AV) concordance, two had common inlet to a right ventricle and 19 had mitral atresia. The great arteries were normally interrelated in all cases. Fifty-one cases had an intact ventricular septum, while seven presented with a ventricular septal defect (VSD). Of the seven with VSD, in two it was associated with a common AV orifice draining exclusively into the right ventricle in the presence of a rudimentary left ventricular chamber. In one case a small VSD accompanied combined mitral and aortic atresia. In the other four cases the left ventricles and mitral valves were fairly normal in size; the VSD was subpulmonary in three cases, due to infundibuloventricular malalignment, and perimembranous in one. These last four cases are of particular interest since they could be amenable to surgical correction. Possible approaches to surgical treatment and morphologic features pertinent to them are described and discussed.


Morphological development of the pulmonary vascular bed in experimental pulmonic stenosis. The main pulmonary trunk was banded in four fetal sheep at 63--69 days of gestation. The fetuses were killed after they had developed progressive pulmonary stenosis at 98, 123, 134 and 135 days of gestation. The right lung of each animal was perfused with glutaraldehyde and serial sections followed microscopically. The medial width/external diameter ratios for fifth generation resistance vessels were significantly less (0.13) than those from six normal control lungs (0.16, p less than 0.001). In addition, the number of resistance vessels per cm2 lung tissue in the lungs of the animals with experimental pulmonic stenosis was less than in normal controls. The altered in utero hemodynamics with severe pulmonic stenosis results in thin-walled pulmonary arterial vessels. This may be caused by an increased blood oxygen tension of the blood perfusing the pulmonary circulation via reversed flow through the ductus arteriosus, or altered pulmonary arterial pressure characteristics in the pulmonary vessels distal to the obstructed pulmonary trunk.


Diagnostic value of visualization of the right ventricle using thallium-201 myocardial imaging. The diagnostic significance of visualizing the right ventricle on thallium-201 myocardial perfusion scans (T-scan) at rest was studied in 53 patients. In 33 patients the right ventricle was visualized clearly on the T-scan (group A). Hemodynamic evidence of right ventricular hypertension with systolic pressure greater than or equal to 30 mmHg was present in 28 of 33 (85%) of these patients. Right ventricular volume overload with left-to-right shunt greater than 2:1 was present in three patients. Other tests were diagnostic for right ventricular enlargement and or pulmonary hypertension as follows: chest x-ray (58%), echocardiogram (36%) and electrocardiogram (15%). In an unselected group of 20 patients (group B) where resting T-scan did not show visualization of the right ventricle, the right ventricular systolic pressure was less than 30 mm Hg in all. The other noninvasive tests did not reveal presence of right ventricular hypertrophy or enlargement. T-scan appears to be a useful and sensitive test in detecting right ventricular pressure or volume overload compared with other noninvasive tests. This may be useful in detection of patients with right ventricular hypertrophy or enlargement secondary to pulmonary hypertension or other causes.


Catecholamines in coronary sinus and peripheral plasma during pacing-induced angina in man. We measured aortic and coronary sinus dopamine (DA), epinephrine (E), and norepinephrine (NE) in eight patients with cardiac ischemia (I) and eight control subjects (C). Samples were taken at rest (73 +/- 3 beats/min in C and 68 +/- 3 beats/min in I) and during coronary sinus pacing to peak rates (144 +/- 4 beats/min in C and 136 +/- 6 beats/min in I). Arterial NE was higher in the ischemic patients at rest (254 +/- 25 pg/ml in C and 324 +/- 21 in I; p less than 0.05). There were no differences in arterial E and DA. Neither pacing nor angina affected peripheral catecholamine concentrations. Resting myocardial NE flux was similar for both groups. With pacing, coronary sinus flow and net myocardial NE release increased significantly in both groups. The maximum relative increase in net myocardial NE release was less in the ischemic patients than in the controls (575 +/- 145% in C and 255 +/- 40% in I; p less than 0.05). Thus, angina induced by pacing does not augment peripheral sympathetic activity. Furthermore, pacing-induced angina appears to be associated with a decrease in cardiac sympathetic tone compared with that found in paced controls.


Myocardial release of lactate, inosine and hypoxanthine during atrial pacing and exercise-induced angina. The coronary venous efflux of lactate, inosine and hypoxanthine during pacing-induced angina has been compared with myocardial extraction of the catabolites during exercise-induced angina. Inosine and hypoxanthine were analyzed by enzyme assay after separation by column chromatography. Myocardial lactate extraction at rest (15 +/- 9%, mean +/- SD) was converted to production levels (-34 +/- 26%) during pacing-induced angina (p less than 0.0005) and increased (24 +/- 13%) during exercise (p less than 0.05). The arterial values at rest (850 +/- 330 mumol/1) were unchanged during pacing and increased five-fold during exercise (4380 +/- 1860 mumol/1). The mean myocardial inosine extraction at rest (33 +/- 10%) was transformed to release values (-41 +/- 30%) during pacing (p less than 0.0005) as well as during exercise (-20 +/- 27%) (p less than 0.0005). The hypoxanthine extraction at rest (25 +/- 11%) decreased during pacing (-7.8 +/- 29%) (p less than 0.0025) and exercise (10 +/- 25%) (NS). The slight increase of arterial inosine and hypoxanthine values was not significant. Myocardially produced lactate, a sensitive marker of pacing-induced ischemia, was obscured by elevated arterial concentrations during exercise. However, inosine significantly correlated with lactate during pacing, and was useful in detecting ischemic myocardial energy deficiency during exercise-induced angina.


Effects of maximal exercise stress on left ventricular function in patients with coronary artery disease using first pass radionuclide angiocardiography: a rapid, noninvasive technique for determining ejection fraction and segmental wall motion. Angiographically determined changes in segmental wall motion (SWM) and ejection fraction (EF) are sensitive indices of left ventricular (LV) function. To compare the effects of exercise on LV function, first pass radionuclide angiocardiography was used before and during maximal upright bicycle stress in patients with nonsignificantly stenosed coronary arteries, and in those with greater than 75% stenosis. Gamma camera acquisitions were made in the 30 degree RAO projection using a 20 mCi I.V. bolus of 99mTc-pertechnetate. In the control group (seven normals, one nonsignificant (CAD) the EF significantly increased between rest and exercise (0.65 +/- 0.03 to 0.81 +/- 0.03 (mean +/- SEM), p less than 0.005). In this group SWM measured over the two anterior and two inferoposterior segments uniformly increased. In the 11 patients with a history of angina and significant coronary artery obstruction, the EF did not change in three and significantly decreased in the remaining eight (0.57 +/- 0.04 to 0.45 +/- 0.03, p less than 0.005). In all 11 patients SWM either decreased or did not increase in the areas supplied by the significantly stenosed coronary arteries. Upright maximal stress angiocardiography appears to be well-suited for diagnosing ischemic heart disease and localizing the area of ischemic dysfunction.


Diabetes and cardiovascular risk factors: the Framingham study. The impact of cardiovascular disease was compared in non-diabetics and diabetics in the Framingham cohort. In the first 20 years of the study about 6% of the women and 8% of the men were diagnosed as diabetics. The incidence of cardiovascular disease among diabetic men was twice that among non-diabetic men. Among diabetic women the incidence of cardiovascular disease was three times that among non-diabetic women. Judging from a comparison of standardized coefficients for the regression of incidence of cardiovascular disease on specified risk factors, there is no indication that the relationship of risk factors to the subsequent development of cardiovascular disease is different for diabetics and non-diabetics. This study suggests that the role of diabetes as a cardiovascular risk factor does not derive from an altered ability to contend with known risk factors.


The effects of ergonovine maleate on coronary arterial size. Changes in coronary arterial size due to ergonovine maleate are described and quantitated in 90 patients--18 with typical angina pectoris, 56 with atypical chest pain, nine with variant angina pectoris, and seven heart transplant (allograft) recipients. We observed two angiographic changes in the diameter of coronary arteries: 1) spasm, which was characterized by occlusion or marked (greater than 85%) focal or diffuse vessel narrowing, or 2) relatively mild and diffuse vessel narrowing, which was interpreted as the normal pharmacologic response to the drug. Serial bolus injections of 0.05 mg, 0.10 mg and 0.25 mg of ergonovine maleate produced diffuse narrowing of the diameter of coronary arteries of 10 +/- 1.5%, 16 +/- 1.4% and 20 +/- 1.3% (mean +/- SEM), respectively, in the 72 patients with anginal syndromes who did not develop coronary spasm. The degree of coronary arterial narrowing was the same in heart transplant recipients and in patients with normally innervated hearts who did not develop coronary spasm. We believe the normal pharmacologic response to ergonovine maleate was due to a direct vasoconstrictor action of the drug; this action was independent of neural control extrinsic to the heart.


Relationship of cardiothoracic ratio and plain film heart volume to late survival. We assessed the prognostic value of cardiothoracic ratio and plain film heart volume in relation to other clinical, exercise, hemodynamic and quantitative angiographic variables. Both cardiothoracic ratio and plain film heart volume are highly sensitive, but nonspecific, indicators of abnormal left ventricular end-diastolic volume and ejection fraction. Both variables are univariately important predictors of survival in cohorts of medically and surgically treated heart disease patients. Plain film heart volume significantly adds to the multivariate prediction of prognosis obtained from groups of clinical, exercise, hemodynamic and quantitative angiographic variables. These measurements from the routine chest roentgenogram are sensitive detectors of abnormal left ventricular function or volume and important predictors of long-term survival. The fact that they contribute prognostic information in addition to left ventricular volume and ejection fraction suggests that other cardiac chamber volumes are of prognostic importance.


Effect of filming projection and interobserver variability on angiographic biplane left ventricular volume determination. Although biplane right anterior oblique-left anterior oblique (RAO/LAO) quantitative left ventricular (LV) angiography is commonly performed, justification of LV volume calculation using the area length method (originally formulated from anteroposterior-lateral (AP/LAT) angiograms) has been limited. To assess whether RAO/LAO and AP/LAT LV volumes are similar when computed by the area length method formula, we performed biplane cine LV angiography in both RAO/LAO and AP/LAT projections in random sequence in 21 patients and four LV models of known volume. LV silhouettes were drawn independently by two trained observers. Calculated angiographic volume of the models correlated almost exactly with their true volume (r = 0.999), establishing the absolute accuracy of this system. Rotation of the LV models through 90 degrees of obliquity at 10 degree increments demonstrated a mean change from true volume of only -5.4 +/- 0.7% (p less than 0.001). In the patient studies, rotation to the 30 degree RAO/60 degree LAO position was associated with significant changes in magnitude of biplane areas and long axes, but area length volume estimates were unchanged. Excellent correlation was found between area length calculated AP/LAT and RAO/LAO volumes with r = 0.90, 0.97, and 0.91 for end-diastolic volume (EDV), end-systolic volume (ESV) and ejection fraction (EF), respectively. Furthermore, interobserver agreement in volume assessment was excellent, with r = 0.98, 0.99, and 0.94 between observers for EDV, ESV, and EF, respectively. Interobserver and inter-method variability for estimates of LV volume and EF ranged from 5--10%. We conclude that when using RAO/LAO LV angiography, volume calculation by the area length method is justified.


Malignant potential of chronic ulcerative colitis. Preliminary report. Prior studies confirm the increased incidence of carcinoma of the colon in chronic ulcerative colitis. The authors reviewed clinical and histologic data retrospectively in 23 patients with colon carcinoma and chronic ulcerative colitis. Twenty-two of these patients had dysplasia of colonic epithelium remote from the cancer. The authors prospectively reviewed clinical data and rectal and colonoscopic biopsy specimens on 36 patients with chronic ulcerative colitis, 12 with Crohn's colitis, and 12 with miscellaneous disorders. Eight patients with chronic ulcerative colitis had dysplasia; 6 have had colectomy, and 2 of these had carcinoma. No patient without chronic ulcerative colitis had dysplasia. Patients with chronic ulcerative colitis should have periodic rectal and colonoscopic biopsies, and those with moderate to marked dysplasia require colectomy because of the increased risk of colon carcinoma.


Effect of short-term therapy with propylthiouracil in patients with alcoholic liver disease. The effect of propylthiouracil (PTU; 300 mg/day) on alcoholic liver disease was evaluated in 133 patients in a short-term randomized double-blind trial. Severity of the disease was assessed by a composite clinical and laboratory index (CCLI). A normalization rate (NR) representing the rate of improvement in CCLI was calculated. Patients with alcoholic hepatitis, with and without cirrhosis, showed a significantly higher NR on PTU (43.6 +/- 4.6) than on placebo (19.8 +/- 3.3; P less than 0.001). A similar effect was observed in patients with abnormal prothrombin (no biopsy): NR was 32.9 +/- 6.9 on PTU and 2.6 +/- 3.7 on placebo (P less than 0.005). The effect of PTU on each clinical and laboratory component of the CCLI was also compared in these two groups. In 38 patients with alcoholic hepatitis and in 25 with abnormal prothrombin, those on PTU showed a greater improvement in 15 of 15 items (P less than 0.001) and 14 of 15 (P less than 0.01), respectively. When patients were divided according to the severity of the disease into those in the lower and upper halves of the CCLI range (81 and 52 patients, respectively), PTU was shown to have a significant effect only in the latter: The NR was 41.4 +/- 3.8 on PTU and 22.5 +/- 4.2 on placebo (P less than 0.005). PTU was ineffective in patients with inactive cirrhosis.


Thyroid hormones in alcoholic liver disease. Effect of treatment with 6-n-propylthiouracil. The relationship between alcoholic liver disease and circulating thyroid hormones was investigated in 124 hospitalized patients treated with placebo or propylthiouracil (PTU) for a maximum of 46 days in a double-blind study. Serum triiodothyronine (T3) levels on admission were significantly (P less than 10(-6) and inversely correlated with the severity of alcoholic liver disease. After hospitalization, changes in T3-levels in patients with low admission T3 significantly correlated (P less than 0.001) with the degree of spontaneous improvement of liver function (placebo group). Treatment with 300 mg of PTU daily (Orrego et al. Gastroenterology 76:105--115, 1979) markedly increased the rate of improvement in severely ill patients with low T3 on admission. In this group, serum T3-levels were also increased after PTU, but this increase did not correlate with the change in the patient's condition. It is suggested that the known inhibitory effect of PTU on peripheral deiodination of T4 to T3 is marked by a more marked improvement in liver function in this group. PTU treatment in this group reduced the free T4-index and increased TSH levels markedly (16%; P less than 0.02) toward levels found in hypothyroidism. PTU did not improve the condition of mildly ill patients with normal admission T3-levels, nor did it alter free T4-index or serum TSH levels in these patients. Serum T3-levels provide a sensitive indicator of the severity of alcoholic liver disease and of its response to conventional treatment. Serum T3-levels also distinguish between a group of patients, in whom low-dose PTU administration results in a beneficial effect, and another group, in whom no therapeutic effect of PTU is observed.


Intracranial pressure in pigs with surgically induced acute liver failure. Cerebral edema has now been noted to occur frequently in patients dying of fulminant hepatic failure. In the present study, intracranial pressure was monitored in an animal model of acute liver failure. Acute liver failure was induced surgically by hepatic devascularization. Serial monitoring of the electroencephalogram revealed progressive slowing of the frequency with decreasing amplitude. Elevation of the blood ammonia was also observed from baseline values of 64 +/- 12 SE to 744 +/- 97 mumol/liter. Monitoring of the intracranial pressure with a subdural pressure transducer demonstrated a progressive and reproducible rise from 12.8 +/- 2.5 mm Hg immediately after the operation to a mean value of 51.6 +/- 11.8 mm Hg just before death 6--12 hr later. At autopsy, the brains of the test animals were found to be swollen with flattened cortical gyri. In the control animals, intracranial pressure rose slightly but returned toward normal levels (8.0 +/- 2.5 mm Hg) 8 hr after laparotomy and remained normal until their death. There was a statistically significant difference between intracranial pressure levels of the test animals and those of the controls (P less than 0.01). Intravenous methylprednisolone (2.0 g initially followed by 0.5 g every 2 hr) administered immediately before and after hepatic devascularization prevented rises in intracranial pressure but had no effect when given 4 hr after operation. The early and progressive increase in intracranial pressure was an unexpected finding, and an assessment of such a sequence in patients with fulminant hepatic failure is currently in progress.


Prevention of effects of ethanol on amino acid concentrations in plasma and tissues by hepatic lipotropic factors in rats. The authors' previous studies have shown that hepatic steatosis of chronic ethanol ingestion in rats can be prevented by adding pyruvate, dihydroxyacetone, and riboflavin to their diet. In this study, the authors investigated the effect of chronic ethanol ingestion, with or without addition of the above metabolites to the diet, on protein and amino acid concentrations in tissues. Rats (120 g) were divided into three groups and fed isocalorically one of the fellowing diets for 30 days: control diet (28% fat, 15% protein, and 57% carbohydrate), ethanol diet (28% fat, 15% protein, 23% carbohydrate, and 24% ethanol), and metabolite diet (ethanol diet plus pyruvate, dihydroxyacetone, and riboflavin). Chronic ethanol ingestion reduced growth of muscle and intestinal mucosa without affecting that of liver and kidney. Among the 15 amino acids measured, chronic ethanol ingestion had the most consistent effect on plasma and tissue concentrations of leucine, alanine and alpha-amino-n-butyrate. The concentration of leucine was increased in muscle, liver, and plasma; that of alpha-amino-n-butyrate was increased in muscle and plasma, whereas that of alanine was decreased in plasma and liver. Addition of pyruvate, dihydroxyacetone, and riboflavin to the ethanol diet either totally or partially prevented ethanol-induced changes in plasma and tissue concentrations of amino acids despite similarity in plasma ethanol levels. Although these metabolites prevented the inhibition of the growth of intestinal mucosa, they were ineffective in blunting the effect of ehtanol on the skeletal muscle. This latter observation suggests that the mechanism of ethanol-induced inhibition of tissue growth is not the same for these tissues.


Antibodies to ribosomes in chronic active hepatitis. A recently developed Farr-type radioimmunoassay for the detection of antibodies to tritium-labeled HeLa cell cytoplasmic ribosomes was evaluated as a serologic test in a variety of liver diseases. Ribosomal antibodies were detected in the sera of 31.4% of 70 patients with chronic active hepatitis (CAH) and primary biliary cirrhosis compared with only 4.2% of patients with chronic persistent hepatitis, acute viral hepatitis, alcoholic liver disease, and miscellaneous liver diseases (X2 = 17.89, P less than 0.001). The level of ribosomal binding activity was also significantly higher in sera of patients with CAH and primary biliary cirrhosis (15.4% vs 6.5%; t = 5.61, P less than 0.001). The antibodies were observed almost exclusively in HBsAg-negative CAH with autoimmune features and infrequently at lower titer in HBsAg-positive CAH or CAH without HBsAg or autoantibodies. Inhibition experiments with purified ribosomal RNA suggested that the ribosomal antibodies are in part reactive with ribosomal RNA. Ribosomal antibodies appear to represent another example of the exaggerated immune response associated with CAH and primary biliary cirrhosis.


Synchronous oscillations in the basal secretion of pancreatic-polypeptide and gastric acid. Depression by cholinergic blockade of pancreatic-polypeptide concentrations in plasma. The effect of cholinergic blockade on the concentrations of pancreatic-polypeptide (PP) in plasma was studied in 19 patients with duodenal ulcer (DU) and 16 control subjects. PP concentrations increased with age both in control subjects and in DU patients. In the DU patients atropine or benzilonium, an antimuscarinic agent with minimal cerebral actions, reduced PP concentrations from 47 (8-220) to 28 (7-53) pmol/liter, n = 18, median and total range. In the control subjects atropine suppressed the PP concentrations from 17 (0-257) to 11 (0-41) pmol/liter, n = 15. Cholinergic blockade had only a minor effect in 1 patient and 1 control, both with high PP concentrations. Both in the DU patients and in the control group the suppression by the cholinergic blockade was most marked in subjects with elevated PP concentrations. Spontaneous acid and PP secretion were measured simultaneously in 25 DU patients. No correlation was found between median acid secretion and median concentrations of PP. However, in the individual patient a positive covariation was found between fluctuations in spontaneous acid secretion and fluctuations in PP concentration. P less than 0.005. We conclude that plasma concentrations of PP in the basal state are suppressible by cholinergic blockade and that PP concentrations fluctuate synchronously with the spontaneous secretion of gastric acid. These results suggest that PP concentrations in plasma before and after cholinergic blockade may possibly serve as indicator of abdominal vagal tone.


Alterations of hepatic triglyceride in patients before and after jejunoileal bypass for morbid obesity. The effect of obesity and jejunoileal bypass on the amount and composition of hepatic lipid and the relationship of adipose tissue fatty acids, body weight, and rate of weight reduction to hepatic triglyceride (TG) were investigated in 16 patients before and at various times after jejunoileal bypass. Liver and adipose tissue biopsy sections were taken at surgery and at various times thereafter. Hepatic lipid was measured and the composition of triglyceride fatty acids (TGFA) compared with that of adipose tissue. Liver TG increased by an average of 2.5-fold during the period of rapid weight loss and decreased during the period of stable weight, but remained above control values. There was no relationship between concentration of liver TG and body weight or rate of weight reduction. The hepatic TGFA composition at surgery and during the period of stable weight resembled that of adipose tissue. During the period of rapid weight loss the composition of hepatic TGFA was markedly different, showing an increase in palmitic (16:0, P less than 0.01), palmitoleic (16:1, P less than 0.05), and oleic acids (18:1, P less than 0.05) and a decrease in linoleic acid (18:2, P less than 0.001). These changes could not be accounted for by a preferential absorption or mobilization of 16:0, 16:1, and 18:1, or by an increased utilization of 18:2 by the liver. It is proposed that an increased conversion of carbohydrate to fat occurs during the period of rapid weight loss when a relative excess of carbohydrate to amino acids results from an imbalance in the intestinal absorption of carbohydrate and protein.


Ingested marihuana-filled balloons.

Ingested marihuana-filled balloons. Three cases of ingestion of balloons containing marihuana are reported. In 2 patients, balloons caused intestinal obstruction. In another patient, there were symptoms of drug overdose when the contents of the balloon spilled into the intestinal tract. Pure marihuana in the gastrointestinal tract has not been reported to cause death by intoxication; however, it may be mixed with more potent substances, especially cocaine. The ingested drug or drugs should be identified as soon as possible to avoid lethal intoxication if a balloon ruptures. A balloon containing drugs will usually pass spontaneously through an uncompromised gastrointestinal tract. Nonoperative management seems appropriate if the substance has been determined to be only marihuana.


Idiopathic hemochromatosis in a young female. A case study and review of the syndrome in young people. Idiopathic hemochromatosis (iH) is typically a disease of older males. The case presented here describes a 26-yr-old woman with problems presenting heart failure, insulin-dependent diabetes, hepatomegaly, and secondary amenorrhea. The diagnosis was established by serum iron and transferrin saturation measurements, liver biopsy, and bone marrow examination for iron. Twenty grams of iron were removed by phlebotomy over 30 mo, and the patient's symptoms improved. A review of the literature pertinent to people with symptomatic onset of IH before age 30 yr revealed 52 young people in addition to this case. In contrast to IH patients older than 30, there was an almost equal ratio between the sexes, a greater frequency of cardiomyopathy and hypogonadism, and a lower frequency of diabetes mellitus and hepatic involvement. An autosomal recessive mode of inheritance appears to be most likely in this young group.


Determinants of diarrhea in viral enteritis. The role of ion transport and epithelial changes in the ileum in transmissible gastroenteritis in piglets. To understand mechanisms of viral diarrhea further, we studied ileal ion transport in vitro in relation to mucosal changes and epithelial differentiation in transmissible gastroenteritis in piglets, an invasive viral enteritis thought to involve mainly proximal intestine. In infected pigs, at the height of diarrhea, short-circuited ileal epithelium failed actively to transport Na+ and Cl-, and there was a defect of glucose-mediated Na+ transport. The Cl- secretory response to theophylline remained intact. Conductance measurements indicate that paracellular permeability may be reduced and transcellular transport may be altered. A mucosal lesion was observed at the time of the transport changes, characterized by villus blunting, crypt hyperplasia, and immature crypt-type enterocytes on the villus epithelium, deficient in disaccharidase and (Na+, K+)ATPase activity but rich in thymidine kinase. Consideration of the major determinants of diarrhea in this invasive enteritis must take into account not only altered mucosal function and differentiation but also the extent of intestinal involvement, including the ileum, a major site of fluid absorption in the intestine.


Crohn's disease in the Jewish population of Tel-Aviv-Yafo. Epidemiologic and clinical aspects. A survey of the incidence and prevalence of Crohn's disease in the Jewish population of Tel-Aviv-Yafo was carried out from 1970 to 1976. The annual incidence rate was 1.28, and the prevalence was 12.31 per 10(5) population. The prevalence of 16.69 per 10(5) population among Ashkenazi jews was significantly higher than that found in "non-Ashkenazi" Jews, 4.19 per 10(5) population. Even so, Crohn's disease is significantly less common in Tel-Aviv than outside Israel, according to most recently published surveys. Similarly, the complication, surgery, and mortality rate are less marked than those reported from other studies. These figures confirm the authors' impression that inflammatory bowel disease in general is less common and possible less severe in Tel-Aviv than in the United State and Western Europe. The strikingly higher prevalence in the Ashkenazi community, especially in the Israeli-born population, suggests a hereditary predisposition. The apparent differences among Askhenazi Jews in various parts of the world may relate to environmental factors.


In vivo absorption and phosphorylation of pyridoxine . HCl in rat jejunum. The absorption and phosphorylation of 3H-pyridoxine . HCl were studied in vivo in isolated loops of rat jejunum. Uptake was rapid and linear over the concentration range of 0.2-1 mM; tissue content of absorbed vitamin was saturable and consisted primarily of phosphorylated forms of vitamin B6. Phosphorylation was saturable with a Km of 11.6 micronM and a Vmax of 1.65 nmol/5 min/g wet tissue. Inhibition of phosphorylation changed neither the t 1/2 of 3H-pyridoxine . HCl disappearance from the lumen nor the calculated uptake after either 5-min or 30-min absorption periods. Inhibition of phosphorylation, however, significantly decreased the t 1/2 for transmural absorption and significantly increased the calculated transmural absorption after a 5-min absorption period. These studies indicate that (a) pyridoxine absorption, over the concentration range tested, is nonsaturable and consistent with passive diffusion; (b) jejunal phosphorylation of pyridoxine occurs in vivo, is saturable, and results in saturation of tissue content of the absorbed vitamin; and (c) phosphorylation has no significant effect on the uptake of pyridoxine but significantly delays the transmural absorption of a finite amount of the vitamin.


Effect of aspirin and acid on human jejunal mucosa. An ultrastructural study. To determine the effects of aspirin and hydrochloric acid on human jejunal mucosa, three obese patients with a small intestinal bypass that opened on the abdominal wall as a mucous fistula were studied. An 80-mM solution of HCl, a 40-mM suspension of aspirin (equivalent to two tablets in a glass of water), and a combination suspension of 40 mM aspirin plus 40 mM HCl damaged a mean +/- SE of 26 +/- 13% (P less than 0.05), 24 +/- 5% (P less than 0.05), and 29 +/- 5% (P less than 0.05) of jejunal villi, respectively, 5 min after administration. By 60 min after instillation, considerable recovery had occurred. Scanning electron microscopy revealed focal villous tip erosion and erythrocyte extrusion after all test solutions. In conclusion, aspirin, 40 mM, physiologic concentration of hydrochloric acid, and the combination of acid plus aspirin are each capable of damaging human small intestinal mucosa on direct contact.


Interaction of calcium, magnesium, and gastrin on gastric acid secretion. A dose response study of the effect on gastric acid secretion of synthetic human gastrin-17 (SHG) in doses of 50, 200, and 500 ng/kg/hr was performed in 8 healthy volunteers. The study was repeated on separate days during i.v. infusion of magnesium sulphate (0.4 meq Mg2+/kg/hr), of calcium gluconate (0.1 meq Ca2+/kg/hr) and of magnesium sulphate plus calcium gluconate. Magnesium infusion resulted in an increase in the dose of SHG required for one-half maximal secretion (D50), whereas infusion of calcium decreased D50. The difference in D50 of SHG when administered in combination with magnesium and with calcium was significant. Combined infusion of SHG, magnesium, and calcium resulted in the same D50 of SHG as found when SHG was infused alone. The calculated maximal acid response was almost identical in the four experiments except for a minor but nonsignificant decrease during calcium infusion. The results indicate an interaction of calcium, magnesium, and gastrin on parietal cell function and extend the observations of others in intact humans as well as in isolated gastric mucosa.


Triolein breath test: a sensitive and specific test for fat malabsorption. In order to develop a simple and accurate screening test for steatorrhea, the authors compared quantitative stool fat excretion with breath excretion of 14CO2 after the ingestion of 14C-labeled trioctanoin, tripalmitin, or triolein. The study group included 24 nonobese subjects without steatorrhea but with diarrhea secondary to irritable bowel syndrome and 40 subjects with steatorrhea. The triolein breath test provided the most reliable discrimination, with 100% sensitivity and 96% specificity. The trioctanoin and tripalmitin breath tests were sensitive, but lacked specificity (69% and 58% false-positive results, respectively). Three of the 12 obese patients with irritable bowel syndrome had false-positive triolein breath results. In detecting steatorrhea, the triolein breath test was moderately superior to the measurement of serum carotene and to qualitative stool fat. Thus, the triolein breath test appears to be a sensitive, specific, noninvasive, and relatively simple screening test for the detection of steatorrhea.


Gastric secretory and humoral responses to anticipated feeding in five men. It is believed that humans anticipate appetizing meals by increasing vagally mediated gastric acid secretion. Studies were conducted on 5 normal male volunteers to characterize further the secretory response to anticipated meals. Plasma gastrin and glucose levels were monitored to assess the possibility that these humoral factors participated in the observed secretory changes. Subjects were not fed for 22 hr and were intubated at 10 AM. Basal gastric collections were begun, and at 1 PM on different days, subjects either (a) selected meals of choice prepared in their presence for 1 hr before nasogastric tube withdrawal and meal ingestion or (b) were not food-teased or fed. Gastric collections were obtained every 10 min during the "test" hour (1-2 PM) during both (a) and (b) studies and titrated for gastric acid. Blood samples for plasma glucose and RIA gastrin were obtained during basal and test hours every 10 min. Pentagastrin-stimulated maximal acid output studies were conducted on all subjects on separate days. Results showed a progressive and statistically significant rise in gastric acid secretion when an appetizing, self-selected meal was anticipated. The magnitude of this rise was 55% of the mean pentagastrin-induced acid response. This acid response did not correlate with changes in plasma glucose or gastrin. The study demonstrated that pure psychic stimulation may be as effective an acid stimulant as sham feeding.


Effect of amino acids on purified rat intestinal brush-border membrane aminooligopeptidase. When a hexapeptide, Leu-Trp-Met-Arg-Phe-Ala, or a pentoapeptide, Leu-Trp-Met-Arg-Phe, was incubated in vitro with a purified aminooligopeptidase from rat small intestinal mucosa, the respective C-terminal dipeptides, Phe-Ala and Arg-Phe, were observed to be resistant to hydrolysis. The resistance of these C-terminal dipeptides to hydrolysis was found to be due mainly to the accumulation of inhibitory hydrophobic amino acids liberated in the incubation mixture. The hydrolysis of various peptides by the brush-border membrane peptidase is inhibited to a varying extent by the hydrophobic amino acids L-tryptophan, L-methionine, L-isoleucine, L-leucine, L-tyrosine, and L-phenylalanine, but not the D-form of these amino acids. The inhibition of the hydrolysis of three dipeptides by hydrophobic amino acids showed these amino acids to be competitive inhibitors (same Vmax, the maximal velocity of the enzyme reaction; different Km, the substrate concentration at which the enzyme reaction is half maximal) of one of the dipeptides while exhibiting a mode of inhibition that was not competitive (different Vmax, different Km) with either of the other two dipeptides. These data indicate that the effect of amino acids on the hydrolytic rate of the brush-border membrane aminooligopeptidases must be considered in studies of intestinal hydrolysis and absorption of peptides.


Jejunal secretion in response to a duodenal mixed nutrient perfusion. A multilumen balloon tube constructed to separate duodenal and jejunal perfusion segments was placed in the proximal small bowel of 6 healthy volunteers. The effect of nutrient mixture in the duodenum on net jejunal water and electrolyte flux was then determined. The duodenum was perfused with a balanced electrolyte solution before and after the nutrient perfusion. Net water flux in the perfused jejunum changed from absorption 27.0 +/- 6.0 microliter/min/cm, (mean +/- SEM) to secretion 7.7 +/- 7.3 microliter/min/cm (P less than 0.025) during nutrient perfusion. There was also net chloride secretion and decreased net absorption of Na, K, and HCO3 (P less than 0.05). The jejunal absorption of water and electrolytes before and after the duodenal nutrient perfusion was the same. Results indicate that intestinal secretion may occur under physiologic conditions at sites remote to the application of food in humans.


Disease caused by a marine Vibrio. Clinical characteristics and epidemiology. We studied the clinical characteristics and epidemiology of disease associated with a rare, unnamed halophilic lactose-fermenting Vibrio species in 39 persons from whom the organism had been isolated. Two distinct clinical presentations were seen. In the first, the illness began with septicemia, often within 24 hours after raw oysters had been eaten; 18 of 24 such patients had pre-existing hepatic disease, and 11 of the 24 died. In the second, there was a wound infection after exposure to seawater or an injury incurred during the handling of crabs; none of these persons had pre-existing hepatic disease, and one of 15 died. Most cases (85 per cent) occurred during relatively warm months (May to October) in men (90 per cent) 40 or more years of age (95 per cent). This Vibrio species is a pathogen and should be considered in the differential diagnosis of septicemia with secondary skin lesions and of wound infections after exposure to seawater.


Iron absorption in the thalassemia syndromes and its inhibition by tea. To determine the hemoglobin concentration at which iron absorption is minimal, five subjects with thalassemia major and one with thalassemia intermedia underwent a series of iron-absorption studies. The effect of tea as an inhibitor of non-heme iron absorption was also tested. Iron absorption increased as the hemoglobin concentration decreased, although iron absorption was much higher at any given hemoglobin level in the subject with thalassemia intermedia. In the subjects with thalassemia major, iron absorption averaged 10 per cent at hemoglobin concentrations between 9 and 10 and 2.7 per cent between 11 and 13 g per deciliter. The percentage of iron absorbed could be accurately predicted from the nucleated red-cell count (r = 0.91, P less than 0.001). Tea produced a 41 to 95 per cent inhibition of iron absorption. Since patients with thalassemia intermedia may absorb a large percentage of dietary iron, inhibitors of iron absorption, such as tea, may be useful in their management.


[Concentration of bilirubin in the neonatal stage in relation to the use of contraceptives]. The present study was carried out with the purpose of determining whether the use of contraceptives by the mothers constitutes an important factor in the elevation of unconjugated bilirubin in breast fed newborns. One hundred mothers of full term healthy newborns with adequate weights for their gestational ages were asked on this point. Twenty-four hours after birth, breast feeding was initiated and at 72 hours, the level of bilirubins was investigated. The results showed a significant difference in favor of the total bilirubin concentration and its indirect fraction in the 45 infants from mothers who had taken contraceptives.


[Perinatal mortality in the Hospital Juarez, S.S.A]. A retrospective analysis on perinatal mortality was carried out at "Hospital Juárez" in México City, between June 1975 and May 1976. The collected data shows a gross perinatal mortality rate of 89.7 per one thousand live borns with a late fetal mortality rate of 33.1 and early mortality rate of 56.6. A prospective study was planned in order to record the perinatal mortality rate between June the first 1976, to May 31, 1977 showing a perinatal mortality rate of 60.8, with a late fetal mortality rate of 25.4  and early neonatal mortality rate of 35.4. The significant decrease in the rate of perinatal mortality could be the result of an accurate perinatal clinical history, specifically designed for such purpose, allowing a better supervision of the pregnant mother, the fetus and the newborn, which permitted to disclose many diagnoses that otherwise would not be obtained and this also contributted to the establishment of better opportunities for treatment. Besides the establishment of routine practices in the handling of newborns, the better relationships between pediatrician and obstetrician and the redistribution of medical and nursing personnel in critical areas, allowed a better perinatal attention. The relationships between perinatal mortality with maternal age and number of pregnancies and the relationships between neonatal mortality with birth weight and gestational age are presented. The factors that have favored the high rates of perinatal mortality in this hospital are also reviewed and corrective measures are proposed.


[Arterial pressure in the newborn infant]. With routine techniques of auscultation and palpation and with the introduction, as useful in the newborn, of the retrograde filling technique, blood pressures were measured in 100 healthy newborns at Hermosillo, Son. Normality limits are established and are reported and illustrated graphically.


[Sarcoma botryoides of the vagina].

[Sarcoma botryoides of the vagina]. The present work includes the review of eight cases of sarcoma botryoides of the vagina, seen at the Hospital Infantil de Mexico, between 1943 and 1972. It is proved that it is an uncommon tumor, which appears between the first and five years of age. The more frequent symptoms were the vaginal hemorrhage, abdominal mass and the visualization of the tumor in the vaginal introit. The evolution was fatal in the 100% of the cases, between 6 and 12 months after the first consultation, whether the treatment given was surgical, with X-rays or chemical agents. The biopsy was definitive in all cases, to corroborate the clinic diagnosis and the cystoscopy, cystogram, vaginoscopy, excretory urography and venocavography were important aids for the diagnosis. The preliminary diagnosis must be done by the general pediatrician in the presence of suggestive symptoms of sarcoma botryoides of the vagina and the radical treatment must be done immediately to obtain some possibility of life.


[Fulminant hepatitis in children. Treatment by exchange transfusion]. Fulminant hepatitis is a potentially fatal clinical form of viral hepatitis. The experience at the Infectious Disease Hospital of the I.M.S.S. in Mexico City is presented. Twenty-two children with encephalopathy, grade III or IV managed with exchange transfusion were included. Results between these patients and a similar control group treated conservatively were compared. The mortality rates for the exchange transfusion and the control group were 91 and 100% respectively. A review of the literature revaled great differences in results obtained by several other authors. We conclude that well controled, prospective studies should be done, before the true efficiency of exchange transfusion can be properly evaluated.


[The potentially infected newborn infant]. In order to establish relationship between premature rupture of membranes (RPM) and neonatal infection, together with the importance of other factors during this process, 50 newborns with history of RPM were studied. In a control group and in groups of newborns with less than and more than 24 hours of plain RPM, related to clinically healthy and vigorous infants, no case of infection was found. On the other hand, 30% and 60% respectively of infections were found in groups less than and more than 24 hours of RPM, but with the presence of other contaminating factors that impair immunological response of the newborn, such as: acute maternal infection, prolonged delivery, unexpected birth, pediatric reanimation procedures, organic immaturity, fetal suffering, immediatie neonatal depression and intercurrent pathology. There were two deaths: a case with RPM of 5 hours and another one with 38 hours, but both with high rating due to the presence and intensity of "aggravating factors" mentioned having internal action mechanism that apparently of restrains to the perpetuation of the hypoxia-acidosis cycle. A provisional sheet is presented to evaluate such "aggravating factors" considering that an RPM associated to them represents a high risk of neonatal infection. In cases of clinically healthy newborns with plain RPM, we advice only to watch over them for 3--5 day, but no antimicrobial treatment at all.


[Simultaneous maternal and infant care or rooming-in care in the General Hospital of Mexico of the S.S.A]. This paper presents the preliminary results of a prospective study undertaken at the Neonatal Unit of the Hospital General de México, S.S.A. (Méx.) conducted to evaluate the possibilities offered by the rooming-in system in this hospital. In both groups, having 250 patients, most of them eutrophic, it was noticed that none of the babies assisted by their mothers showed severe infections, as compared to four babies that showed clinical data compatible with septicemia; these babies were assisted in the nursery in a traditional way, but three of them died. Many of the aspects about the rooming-in system are reviewed, concerning the mothers as well as the babies, and it is finally determined that it is a practical, accessible system that optimizes resources and seems to offer immediate benefits to the mothers as well as to the babies.


[The pediatrician and social aspects of child health]. Accepted that it is through each pediatrician that pediatrics reaches every child, it is necessary to establish the circumstances which hinder the perception of social factors of disease on account of the actual importance of these factors. The author thinks that our perception of special factors is distorted by circumstances which act on the recruitment, during the medical education, the residency and along the professional life. The following circumstances are remarked: a reedificant scientific technology, the constraints of a manipulated consumption of sofisticated medical resources, a centralization of care in complex hospitals and a medical education which does not prepare for primary and community Medicine. The author recommends the pediatrician to recognize, with the help of an autoreflexive criticism, his failures to perceive clearly the social component of health and disease.


[Etiology of suppurative otitis media in pediatrics]. A study on the etiology of bacterial infectious processes of the middle ear in children was carried out in 50 patients with ages between 3 months and 12 years at two of the children's hospitals depending from the Federal District Department. Male infants were found to be preferably affected. In 46% of cases, Staphylococcus aureus was found; also, gram-negative germs appeared in 26%. Comments are made on the possible causes of the variants this report presents in relation with the literature on the etiology of otitis media in pediatrics. Stress is placed on the necessity to support antimicrobial treatment with cultures to determine the etiology of the process.


[Esophageal and tracheal compression caused by vascular ring]. Eight infants with anomalous vessels of the aortic arch were submitted to surgical operation of the structures interfering with tracheal and esophageal function. Four patients had an aberrant right subclavian artery; three had a double aortic arch with a left ligamentum arteriosum. None had congenital heart disease. One had a tracheoesophageal fistula and a short esophagus. Esophagograms and aortograms were performed in all. Tracheal and esophageal compression was relieved in the four boys and the four girls. All are alive and in good condition.


[Disseminated intravascular coagulation in children under 1 year of age]. In this paper, comparison is made of the clinical with the anatomicopathological diagnosis of DIC. The review of the postmortem studies covered from March 1975 to March 1976 at Hospital de Pediatrïa, C.M.N., and the following were the conclusions: Only in 40 of the cases, the clinical diagnosis of DIC was made. DIC was seen more frequently in the neonatal stage. The anatomicopathological diagnostic criterion is emphasized. Hemorrhages and thromboses predominated in lungs. Paracoagulation tests were not useful.


[Embryoclinical correlation ofmaxillofacial abnormalities]. Most publications on maxillofacial malformation are based on their topography and terminology. The list of authors is endless in most cases there are only minor variants. Thus, we are attempting to establish the embryoclinical correlation of maxillofacial malformations produced by changes in the structures of the cephalic pole of the embryo. For such systematization we have considered the following items: 1. Changes in the frontal structure. 2. Changes in upper maxillary structures. 3. Changes in the lower maxillary or mandibular structures. 4. Pathologic associations. In each of these buttons, the structures produced or correlated with them are subsequently analyzed, the same as basic changes and clinical syndromes produced by them and resulting in an embryoclinical systematization.


[Bilateral thrombosis of the renal vein. Report of a case]. A newborn baby with bilateral renal vein thrombosis is presented; diagnosis was made on clinical and radiological basis; she died with severe complications such as pulmonary hemorrhage and disseminated intravascular coagulation. It is emphasized that the bilateral form is rare and prognosis is variable depending upon clinical evolution.


[Congenital malignant neoplasms].

[Congenital malignant neoplasms]. In order to determine the proportion of congenital neoplasias, a study of 1 076 malignant neoplasias was carried out at the Pathology Department of the Hospital Infantil de Mexico. As unquestionably congenital malignant neoplasias were considered those detected since birth and as possibly congenital, those identified during the first year of life of the patient. As a whole, in this series of neoplasias, approximately one case was found of the sum of the congenital group and the possibly congenital, to 4.5 of the total series. However the proportion of the group of congenital malignant neoplasias and that of possibly congenital varied for each type of neoplasias in particular. Excluding malignant neoplasias of hematopoietic tissues, retinoblastoma, nephroblastoma and neuroblastoma were the malignant neoplasias most frequently found.


[New classification of bone dysplasias based on histogenetic changes]. Several attempts have been made to classify constitutional diseases of ossification. The one from the Roman group is at present the most accepted. Based on histogenetic concepts and on conventional microscopic studies of our casuistics, we are proposing a new systematization of bone dysplasias considering the mechanisms that lead to the transformation of primitive bone tissue into adult bone tissue. Changes in bone histogenesis may take place at the following levels: 1. In the bones of connective ossification. 2. In the chondrocytic fertile cartilage. 3. In the bony trabeculae. 4. In the periosteum and endosteum. 5. In the bony fibrose tissue. Based on such changes, we classify bone dysplasias into: 1. Connective-dysplasias. 2. Chondro-dysplasias. 3. Trabecular-dysplasias. 4. Periosteo-endosteo-dysplasias. 5. Fibro-dysplasias. 6. Mixed types.


[Meningitis caused by Candida in a premature infant]. A case of Candida meningitis in a premature infant treated with amphotericin B IV for 41 days, resulted in negative CSF cultures after 5 days of therapy. Amphotericin B was also given intraventricularly for 21 days; purulent meningitis was a complication from this kind of therapy. Psychometric evaluation showed a mental age of 3 months in a chronological age of 7 months. Only one premature infant has been reported in the literature with intraventricular amphotericin B treatment. A review of Candida meningitis diagnosed before death in infants less than 1 year of age and a discussion of the modern therapy is presented.


[Marfan's syndrome].

[Marfan's syndrome]. A family with Marfan's syndrome is reported showing as outstanding features, demonstration of the hereditary character of the entity through the genealogical tree. The classical clinical characteristics of the disease are: long face, arachnodactyly, decreased subcutaneous tissue, muscular hypoplasia, somatometric values above normal percentiles for Mexicans, weight and perimeters of arm and leg showing low mass and height, upper and lower segments above percentil 50 and ocular disorders like bilateral ectopia lentis, spherical and small lens, iridodonesis and myopia.


[Scleroderma in children].

[Scleroderma in children]. Fifteen children, ten with localized forms of scleroderma and five with progressive systemic sclerosis (PSS), were reviewed. Age of onset was 2 to 11 years. Mean follow-up was 3.4 years. Localized forms were: "en coup de sabre" in two cases, lineal scleroderma of extremities in five, morphoea in one, and combined lesions in two patients. None of them had systemic symptoms, although two had transient arthritis. Affected skin became atrophic in three cases, "En coup de sabre" lesions were removed surgically in two cases, and there were not recurrences. The other patients continued the same or worse. All five patients with PSS showed extracutaneous symptoms. Three of them with acrosclerosis, Raynaud's phenomenon and dysphagia. One patient died because of pulmonary fibrosis in less than a year. Disease remained unchanged in the other patients. The course of disease does not seems to be affected by treatment with several drugs (asiaticoside, colchicine, diphenyldantoin).


[Congenital gastric teratoma in a premature newborn infant]. The third published case of gastric teratoma from Mexico, is reported. A premature newborn male infant was operated on at the age of 37 days. A 250 g. mass was excised from the anterior gastric wall together with a third of the stomach. After a 5 year follow-up the patient is asymptomatic. The characteristics of 48 additional cases collected from world literature are described. A general review of germ-cell tumors in the stomach, is also exposed.


[Frequency of malnutrition in a group of female students for 12 to 20 years of age]. A study on the state of nutrition was caried out in a group of 882 female students 12 to 20 years old attending public schools in Mexico City. Five somatometric variables were considered: weight and height in relation to age; weight in relation to height; perimeters of arm and leg. According to the weight in terms of age, 46% of cases fell within limits of normality (M +/- 1 D.S. of mentioned patterns); according to the perimeter of leg, this took place in 49% of the total and according to the perimeter of the arm, in 36%. Weight in relation to height was normal in 53% of cases and height in relation to age, in 62%. Frequency of subnormal cases was 47% for weight/age; 41% for perimeter of leg; 56% for perimeter of arm; 28% for weight/height and 33% for height/age. That of cases above M + 1 D.S. was, respectively of 7, 10, 7, 19 and 5% of the whole. Cases with overweight in relation to height, became more frequent as age increased, coincidentally also with greater frequency of cases with deficient perimeter of leg. According to perimeter of leg, 13% of these girl students might he considered affected of second degree malnutrition, this situation prevailed from 13 to 18 years of age, but was not true in the 12--year--old group. Out of all variables studied, perimeter of the leg was considered the most useful index to determine the state of nutrition. Weight in relation to height was used to judge the degree of adaptation (homeorrhesis). However, it is apparently more adequate to make an interpretation of the information obtained from the integration of the five variables considered.


[Idiopathic nephrotic syndrome with diffuse mesangial proliferation]. The clinicopathologic correlation of 18 cases of idiopathic nephrotic syndrome (INS) with diffuse mesangial proliferation (MP), (over 3 cells per intercapillary space) showed clinical characteristics similar to INS with minimal glomerular lesions (MGL) in relation to age at onset, sex, period of evolution, intensity of proteinuria, hypercholesterolemia, hypoalbuminemia and edema. However, there was a greater incidence of cases with arterial hypertension, hematuria, azotemic retention and positive glomerular immunofluorescence. Out of the 18 cases, 10 were corticosensitive (group I) and 8 were corticoresistant (group II). Patients of I followed a similar course as those with MGL, while most cases of group II showed proteinuria through observation periods up to 5 years. No differences were found in the initial clinical presentation between these 2 groups. The only item with prognostic value was the intensity of the mesangial proliferation which in group I was of 3 to 5 cells per intercapillary space, while in group II, in the spaces of some glomeruli, there were up to 10 mesangial cells present. These findings suggest the convenience to practice renal biopsy before initiating treatment in children with INS and arterial hypertension, hematuria and/or azotemic retention in order to identify this group of patients that appears to be different from that with MGL.


Identification of dihydropteridine reductase in human platelets. Normal human platelets were shown to contain the enzyme dihydropteridine reductase. The enzyme was not found in a variety of other cells of hematogenous origin. Partial purification and kinetic and physical data indicated that the platelet enzyme is similar to that previously characterized from liver. Dihydropteridine reductase is important for the regeneration of tetrahydrobiopterin, a required cofactor in hydroxylation reactions involved in biogenic amine formation. The presence of the enzyme may indicate that some synthesis de novo of serotonin and/or catecholamines occurs in platelets, as opposed to a purely storage and transport function. In addition, screening for hyperphenylalaninemia due to dihydropteridine reductase deficiency may become feasible by assaying platelets for enzyme activity.


Hemoglobin E trait reexamined: a cause of microcytosis and erythrocytosis. The current Indochinese resettlement program in the United States has resulted in an increase in the number of persons with hemoglobin E trait. American physicians should be aware of the hematologic expressions of this innocuous condition. The hematologic manifestations of 21 persons with hemoglobin E trait were evaluated. The subjects were of Tai-dam, Vietnamese, Chinese, Laotian, and European origin. These studies showed uniform hematologic manifestations in hemoglobin E trait, characterized by slight microcytosis, by morphologic features resembling those of thalassemia minor, and often by increased erythrocyte count. Hemoglobin instability also was confirmed.


[Idiopathic dilatation of the choledochus]. In order to modernize some clinical characteristics, their classification, the differential diagnosis and treatment, a review of 18 cases of idiopathic dilatation of the choledochus, seen at the Hospital Infantil de Mexico between 1965 and 1977 was carried on.


[Pyelonephritis in children].

[Pyelonephritis in children]. Fifty cases with pyelonephritis were found among 1314 histopathologic studies performed at Children's Hospital of Cordoba, Argentine from 1967 to 1976. Twenty-six had urologic abnormalities. Most of them were males over two years old. Eleven had unilateral pyelonephritis. Twenty-four had clinical and pathological signs of septicemia or infection. No sex difference was found and most of them were infants under two years of age. All patients had bilateral pyelonephritis. Twenty-four patients showed positive urine culture before death. They also showed clinical features, urinary concentration inability and pyelographic changes that suggest pyelonephritis. Our conclusions are that pyelonephritis is not common among children, and appeares only associated with systemic infection or urologic abnormalities. Clinical signs, urinary examination and intravenous pyelography are useful in the diagnosis of pyelonephritis.


[Results of combined therapy in rhabdomyosarcoma in children]. In a study of rhabdomyosarcoma in children, 16 cases were treated and followed since 1971. Eight patients were staged I and II A and presented a mean survival time of 52 and 21 months respectively, whereas the remaining 8 patients were staged II B and III with a mean survival time of 20 and 9 months respectively. Of the 16 patients treated, 10 (62.5%) continue survival with an overall median survival time of 25 months. It is suggested that an early diagnosis and combined treatment including surgery, radiotherapy and chemotherapy with vincristine, cyclophosphamide and actinomicin and possibly adriamycin as a fourth drug, will give patients in underdeveloped countries, similar survivals and relief as those observed in developed countries. It is apparent that a multidisciplinary medical team is more important than the magnitud of economical resources.


[Meningococcal meningitis in Costa Rica, 1970--1973. Epidemiological study]. A retrospective hospital chart review of meningococcal meningitis cases in Costa Rica revealed a large number of cases confirmed in the laboratory by Gram-stained smear and/or culture of spinal fluid. A large percentage of the isolates studied were serogroup C and all of these were sulfonamide resistant. The age-specific attack rates were high in the preschool children with the highest attack rate in children 3 to 5 months of age. Case fatality ratios were 14% overall, with the low fatality rates in individuals 10 to 29 years of age. The outbreak of serogroup C meningitis in 1970--1971 was relatively brief, country-wide, and not predominantly a urban outbreak. The few secondary cases observed occurred within the first 2 weeks of the primary case.


Nuclear RNA sequences coding for alpha and beta globins in erythroid cells: evidence for multiple intermediate molecules. The poly (A)-containing nuclear RNA from dimethylsulfoxide-induced Friend leukemia cells was fractionated by acrylamide gel electrophoresis in denaturing conditions and analyzed for alpha and beta globin RNA sequences. The results indicate that nuclear RNA contains one species of large-size RNA (0.6 X 10(6) daltons), which is the putative precursor for beta globin mRNA only. In addition, it was shown by electrophoretic analysis that the complex of RNA molecules not resolved by sucrose gradient centrifugation (11S) comprises sequences of decreasing size (0.34, 0.28, and 0.26 X 10(6) daltons), which might be the precursors of alpha and beta globin mRNA.


[Diagnostic significance of hematuria in pediatrics]. Hematuria is the presence of more than 5 RBC's in repeated urinary sediments. Erythrocyturia may be present as an isolated finding or it may be associated to other clinical findings that may lead to the etiology of the hematuria. Its origin may be renal or extrarenal. In the neonate, meatal or urethral bleeding, polycystic kidney or hydronephrosis must be considered. In the infant, hematuria may be due to vascular disease, renal vein thrombosis, as well as to urinary tract infection, urinary tract obstruction or acute tubular interstitial nephritis due to drug ingestion. Primary and secondary glomerulopathies, urinary tract infection and urolithiasis are the most frequent causes of hematuria in pre-school or school-age children. The diagnostic approach emphasizes the importance of the clinical history, familial background and the circumstances of presentation. RBC casts and proteinuria may suggest the presence of a glomerulopathy. Leukocyturia is more frequent in urinary tract infections and requires urine cultures and intravenous pyelogram. In cases of isolated hematuria, blood clotting test, P. T., P.T.T., platelet count and RBC's morphology may be required to rule out hematological disorders. The intravenous pyelogram, voiding cystogram, and occasionally cystoscopy will help to rule out urological abnormalities. If the previous results were negative, the renal biopsy will help to distinguish IgA mesangiopathy, Alport's syndrome or essential hematuria; this last diagnosis resulting by exclusion.


Local development of mast cells from bone marrow-derived precursors in the skin of mice. A mechanism to control development of mast cells was investigated in mice. Although mast cells in the skin of normal C57BL/6 mice were still of host type 290 days after irradiation and injection of bone marrow cells from beige (Chediak-Higashi syndrome, C57BL/6 bgJ/bgJ) mice, donor-type mast cells with giant granules appeared after painting of methylcholanthrene on the dorsal skin. Since donor-type mast cells appeared only at the painted portion of the skin, with an increase in the labeling index of such donor-type mast cells with 3H-thymidine, proliferation and differentiation of bone marrow-derived precursors of mast cells seem to be controlled locally. Although the morphologic feature of marrow-derived precursors was not identified, the finding that all fibroblasts cultured from the methylcholanthrene-treated skin were of host type may exclude the possibility that fibroblasts are the precursors of mast cells.


[Rehabilitation prognosis in the patient with bilateral cortipathy due to prematurity]. Thirty cases of bilateral corticopathy due to prematurity were studied at the Instituto Nacional de la Comunicación Humana. Taking into account all predisposing features, it is concluded that with adequate preventive measures, it is possible to avoid this pathology and thus obtain a favorable rehabilitation prognosis.


[Idiopathic membranous glomerulonephritis]. The only case of idiopathic membranous glomerulonephritis seen out of 106 nephropathic patients biopsied in the two last years at the C. H. 20 de Noviembre, I.S.S.S.T.E., is reported. Twenty-six showed nephrotic syndrome not associated to systemic disease, including the present case, which gave us an incidence of 3.8% of this entity. We were impressed by the low frequency of this disease, so we made a statistical epidemiological analysis localizing it geographically based on the available medical literature. On comparing the results of these studies we confirmed that this disease is significantly low in our environment.


Effects of local anesthetics on human platelets: filopodial suppression and endogenous proteolysis. Agents that affect platelet shape may be useful in understanding the mechanism of shape change; for this reason the effects of local anesthetics are worthy of further study. Local anesthetics cause platelets to retract filopodia. At short time intervals (up to about 30 min) and low concentrations of the drugs, the filopodia are reextended when the platelets are gel filtered with eluant free of anesthetic. At longer time intervals (1-2 hr) or higher drug concentrations, the retraction becomes irreversible. When the polypeptide composition of the total platelet lysate was examined on SDS gels, proteolysis of two high molecular weight bands was seen when the suppression became irreversible. These polypeptides, estimated as 250,000 and 230,000 daltons, were major components of a precipitate that formed when platelets were lysed at low ionic strength and were also enriched in a "cytoskeletal" preparation made by lysing platelets attached to glass beads and analyzing the adherent residue. Electron micrographs of platelets lysed on surfaces showed an intermeshed network of filaments to be a major component of the residue. The results suggest that the proteins comprised of these bands may be part of the cytoskeletal system and that their integrity may be necessary for the platelet to reextend filopodia following suppression.


Acquired coagulation inhibitor delaying fibrinopeptide release. A 14-yr-old girl Down syndrome developed a unique type of circulating inhibitor causing a mild bleeding tendency and interfering strongly with coagulation tests, including reptilase time, and with the reaction of purified fibrinogen and thrombin. The concentration of all coagulation factors was normal. The inhibitor had no direct effect on thrombin activity or on the aggregation of fibrin monomer in plasma. Chromatography on DEAE-cellulose and neutralization by immune sera revealed that the inhibitor was an immunoglobulin of IgG class with both kappa and lambda determinants. Isolated inhibitor delayed the release of fibrinopeptide A from a normal fibrinogen reacting with thrombin and retarded the onset of visible clotting, but had no effect on the the final degree of clottability. The clinical and laboratory features of this patient resemble those of patients with congenital dysfibrinogenemia associated with abnormal fibrinopeptide release.


Morphological differentiation of mechanically dissociated fetal rat brain in aggregating cell cultures. Rotation-mediated aggregating cell cultures of mechanically dissociated fetal rat brains (15-16 days) were morphologically characterized at 4, 19, 26 and 40 days in vitro. The dissociated cells coalesced into spherical aggregates which increased in diameter from 340 micrometer at 4 days to 430 micrometer at 40 days. Cells within the aggregates developed from an undifferentiated state at 4 days to a population of morphologically mature neurons, astrocytes and oligodendrocytes (26 days in vitro) before degenerating. Synaptic contacts and myelinated axons appeared as the cells differentiated. Neurons tended to occur in clusters that were located in central regions of the aggregates, whereas astrocytes were more concentrated in the periphery. Synapses and myelinated axons were more abundant in central portions of the aggregates. The amount of myelin formed within the aggregates was less than in organotypic cultures or in vivo. These results show that the morphological differentiation of mechanically dissociated aggregates resembles the development of rat CNS in vitro. The ease with which large amounts of aggregates can be prepared provides an in vitro system which can be analyzed biochemically without the use of micro-methods. This advantage is particularly useful for multidisciplinary investigations in developmental neurobiology.


Catecholaminergic depressant effects on bulbar respiratory mechanisms. On the basis of histochemical and pharmacological studies, catecholamines have been implicated in central mechanisms controlling respiration. This hypothesis was tested in iontophoretic studies on neurones located in bulbar respiratory centres. Adrenaline and noradrenaline had a predominantly depressant effect on respiratory as well as on closely situated non-respiratory units. These depressions were mimicked by the application of isoproterenol and clonidine; acetylcholine and serotonin had inconsistent effects on these neurones. In control experiments, microinjections, using a Hamilton syringe, were made in the area of bulbar respiratory centres: noradrenaline, but not serotonin, depressed the central respiratory activity reflected in the phrenic nerve discharge. These results suggest that specific adrenergic and noradrenergic depressant mechanisms could affect both respiratory and other physiological centres at the bulbar level.


Brain metabolism and specific transport at the blood-brain barrier after portocaval anastomosis in the rat. The rapid metabolism of [1-14C]butyrate and [2-14C]pyruvate in the brain was studied after intracarotid injection in control rats and rats given an end-to-side portocaval anastomosis (PCA). At 10 or 50 sec after injection there was a 40-50% lowering of the total amount of radioactivity in the brain of operated rats for both compounds. The percentage distribution of label in various metabolic fractions, e.g. amino acids, was unaltered by PCA. The results from the metabolic studies focused on an impaired transport of short chain monocarboxylic acids between blood and brain in rats with a PCA. The brain uptake index (BUI) of acetate, butyrate, pyruvate and glucose was determined by rapid intracarotid injection of the 14C test compound plus 3H2O as a reference marker. At 3 weeks after PCA, transport of all 3 monocarboxylic acids into brain was reduced by 40-50%. The reduction in [2-14C]pyruvate uptake was absent at one week, but thereafter, up to 50 weeks after operation, was consistently present. Eadie-Hofstee analysis of influx at varying substrate concentrations indicated a reduction in Vmax values of pyruvate and butyrate uptake without changes in Km. The calculated influx rate of glucose in operated rats was reduced in direct proportion to the lowering of plasma glucose. Portocaval anastomosis in the rat induces selective changes on substrates that are transported across the blood-brain barrier via a facilitated transport process.


Net uptake of aspartate by a high-affinity rat cortical synaptosomal transport system. Reuptake of neuroactive amino acids by high affinity transport systems (Km approximately 10 micrometer) is thought to terminate the action of these substances. Since homoexchange can complicate the interpretation of uptake experiments, it is necessary to demonstrate net inward transport of neuroactive amino acids before uptake can be considered as a likely mechanism for transmitter inactivation. When rat cortical synaptosomes are incubated with 10 micrometer [14C]L-aspartate, net (chemical) and apparent (radioactive) uptake into the synaptosomal fractions are equivalent. Although there is net aspartate uptake into the synaptosome fraction, aspartate exchange can be demonstrated in a variety of conditions. Net uptake exhibits the characteristics of high-affinity transport systems including Na+-and temperature-dependence. Furthermore, KCl (or RbCl)--1 micrometer--are required for net uptake but not radioactive or apparent uptake. LiCl, NH4Cl, CsCl, and choline chloride fail to support net uptake. Ouabain (0.1 micrometer) inhibits net uptake to a greater extent than apparent uptake. Although glutamate inhibits aspartate uptake (and vice versa), the net uptake of the combination is greater than that of each alone. The demonstration of net uptake of aspartate by a high-affinity system is consonant with the idea that this system may play a role in its inactivation in the synaptic region.


The effects of variations in conductivity and geometrical parameters on the electrocardiogram, using an eccentric spheres model. The effects of variations in the volume conductor properties of the torso on the electrocardiogram were studied by means of a theoretical eccentric spheres model. The model includes a blood cavity, cardiac muscle layer, pericardium, lung region, skeletal muscle layer, and subcutaneous fat. The source of the field is a double-layer spherical cap located within the myocardium. The following effects regarding the electrocardiogram (ECG) potentials were determined: (1) blood augments the potential, but less than predicted by simpler published models; (2) in anemia, high potentials are expected, whereas in polycythemia, voltages are reduced; (3) abnormally low lung conductivity (emphysema) causes low surface potentials whose magnitude is controlled by the low conductivity skeletal muscle layer; (4) low voltages result both from low and high pericardial conductivities; (5) the surface potential increases with increasing myocardial conductivity; (6) low skeletal muscle conductivity (Pompe's disease) causes high surface potentials; (7) obesity lowers the potential only slightly; (8) a thick myocardium, protruding into the lung region, slightly augments the potential; (9) an increase in the thickness of the myocardium at the expense of the blood cavity causes a decrease in potential; (10) the potential increases with increasing heart size; and (11) the location of the heart within the torso has a very significant effect on the surface potential distribution.


An analysis of the effects of acetylcholine on conduction and refractoriness in the rabbit sinus node. The effects of acetylcholine (ACh) on sinus node automaticity, atrio-sinus conduction, and refractoriness were studied in 41 isolated rabbit right atrial preparations. Average control rate was 126 beats/min, and ACh 5 x 10(-8) M, 5 x 10(-7) M, and 5 x 10(-6) M significantly decreased heart rate by 7, 15, and 43%, respectively (P less than 0.01, 0.001, and 0.001). Atrio-sinus conduction time at a pacing cycle length of 400 msec did not significantly change during exposure to ACh 5 x 10(-8) and 5 x 10(-7) M. However, the mean effective refractory period (ERP) of the sinus node, at a pacing cycle length of 400 msec, increased from 183 +/- 16 msec to 210 +/- 24 msec during exposure to ACh 5 x 10(-7) M (P less than 0.025). The change in ERP followed the change in action potential duration. In contrast to the lack of effect of ACh 5 x 10(-7) M on atrio-sinus conduction time, ACh 5 x 10(-6) M caused 2:1 atrio-sinus block in 8 of 10 experiments. The site of block was identified using multiple microelectrode impalements, and occurred between the perinodal fibers bordering on the edge of the sinus node and the pacemaker area in the sinus node proper. When the pacing cycle length was increased and 1:1 atrio-sinus conduciton was present, conduction time did not significantly differ from control. At this longer pacing cycle length the mean ERP of the sinus node was 380 msec greater than control and lasted well after repolarization was completed. Thus, atrio-sinus block during exposure to ACh 5 x 10(-6) M resulted from a marked prolongation of refractoriness.


The relationship between atrioventricular nodal refractoriness and the functional refractory period in the dog. We studied the relationship between the atrioventricular nodal functional refractory period (FRP) and refractoriness by mathematical analysis and by measurement during antegrade Wenckebach cycles in 16 dogs. The FRP relates directly to the conduction time of the control beat, and inversely to the coordinates of the point on the A'-H' vs. A-A refractory curve where the slope is -1. The FRP can vary without any change in refractoriness as measured by the effective refractory period (ERP) or the refractory curve. In 16 dogs the ERP and the FRP were measured during 4:3 Wenckebach cycles. Because of changes in the control conduction times, the FRP declined and did not reflect the progressive increase in refractoriness recorded during Wenckebach cycles. The FRP is a complex parameter and does not reliably measure refractoriness.


The effects of nifedipine on acute experimental myocardial ischemia and infarction in dogs. We studied 25 anesthetized and thoracotamized dogs before and during 5 hours of acute regional myocardial ischemia. Krypton-81m (81mKr) was infused constantly into the aortic sinuses. The myocardial equilibrium of this tracer was used to image and assess the distribution of regional myocardial perfusion using a gamma camera and digital computer. The epicardial ECG was recorded, S-T segment elevation and the loss of R and appearance of Q waves were measured, and the plasma activity of creatine kinase (CK) was determined in aortic and coronary venous blood throughout these experiments. Ten dogs underwent left anterior descending coronary artery (LAD) narrowing for 5 hours and received no drugs. Five dogs received nifedipine 13 microgram/kg, and another five received 1.0 microgram/kg intravenously 30 minutes after LAD narrowing. Those dogs receiving nifedipine, 13 microgram/kg, showed a 30% fall in aortic pressure, a 12% rise in heart rate, and an extension of regional ischemia. The ECG showed an extension of infarct size, and CK release into the coronary vein appeared earlier than in the controls. Dogs receiving nifedipine, 1 microgram/kg, showed a 12% fall in blood pressure, no rise in heart rate, an improvement in regional perfusion, and ECG signs that suggested limitation of infarct size. There also was delayed release of coronary venous CK. The effects of nifedipine on the natural history of regional myocardial perfusion, the electrocardiogram, and enzyme release from the heart were dose related and cannot be generalized. These observations warrant further clinical investigation to improve the use of this agent in man.