Effects of hyaluronidase and hydrocortisone on myocardial necrosis after coronary occlusion. In anesthetized open chest dogs, hydrocortisone (50 mg/kg body weight administered 30 minutes after occlusion and 25 mg/kg 12 hours later) substantially reduced the size of myocardial infarcts, as reflected by both myocardial creatine phosphokinase activity and histologic appearance 24 hours later. Similarly, hyaluronidase, which increases diffusion through the extracellular space and presumably facilitates delivery of substrate to ischemic cells, also reduced the extent of myocardial necrosis after coronary occlusion in the dog. In view of the salutary effects of hyaluronidase and the absence of serious side effects, this agent was administered clinically to two groups of patients, who were compared with two groups of untreated control subjects. Hyaluronidase (500 National Formulary units/kg X 8) was shown to result in a significantly more rapid reduction in the magnitude and the extent of precordial S-T segment elevations, and in patients treated within 4 hours a tendency to a lower incidence rate of Q waves and a smaller reduction of R waves.


Beneficial metabolic effects of methylprednisolone sodium succinate in acute myocardial ischemia. The metabolic and hemodynamic effects of methylprednisolone sodium succinate (40 mg/kg body weight) after acute myocardial ischemia were determined in 24 heparinized mongrel dogs. Myocardial ischemia was produced by ligation of the left anterior descending coronary artery. Catheters in the coronary sinus and the vein draining the left anterior descending coronary arterial area were used to collect blood samples from nonischemic and ischemic myocardium. Lactate, pyruvate, glucose, free fatty acids and oxygen were measured in arterial and venous blood from ischemic and nonischemic areas before and 3, 30 and 60 minutes after myocardial ischemia in animals with (Group II) and without (Group I) steroid treatment. In both Groups I and II glucose, lactate, free fatty acids, oxygen and coronary blood flow in nonischemic areas were not significantly changed, whereas glucose uptake in ischemic areas was significantly increased with myocardial ischemia and remained elevated. In Group I lactate uptake in ischemic areas became negative after coronary arterial ligation and remained so; in Group II, it increased after 30 (70%) and 60 (111%) minutes. Free fatty acid uptake in ischemic areas was reduced after myocardial ischemia in Group I, but in Group II it increased after 30 (224%) and 60 minutes (173%), and there was a concomitant increase in oxygen uptake. Pyruvate uptake in nonischemic areas decreased after 60 minutes in Group I, whereas it was reduced after 30 (68%) and 60 minutes (513%) in Group II. The changes were similar in ischemic myocardium. There were no significant changes in hemodynamic indexes. Coronary blood flow in ischemic areas decreased in Group I after myocardial ischemia and further after 30 and 60 minutes, but in Group II it increased after 30 (82%) and 60 minutes (53%). The data indicate that administration of methylprednisolone results in improved collateral blood flow into the infarcted area and a significantly improved metabolic response of ischemic myocardium. The glucocorticoid may also have a direct benefical effect on carbohydrate metabolism and cause the increased pyruvate neccesary to maintain the generation of energy-producing substrates. The results also suggest that methylprednisolone increases cell survival time and results in greater salvage of ischemic myocardium.


Methylprednisolone treatment in acute myocardial infarction. Effect on regional and global myocardial function. The effects of methylprednisolong treatment on acute myocardial ischemia were studied in nine closed chest dogs. After 1 hour of proximal occlusion of the left anterior descending coronary artery, an intravenous bolus injection (50 mg/kg body weight) of methylprednisolone was administered and its effects studied during an additional 2 hours of occlusion. After 2 hours of treatment the following significant mean alterations from levels after 1 hour of occlusion were noted: an increase of 16.7% in heart rate and decreases of 23% in left ventricular end-diastolic pressure, 32% in stroke volume, 14% in cardiac output and 37% in stroke work. Peak systolic pressure, maximal rate of rise of left ventricular pressure (dP/dt), left ventricular end-diastolic volume, systemic vascular resistance and coronary sinus blood flow changed less than 10%. Ejection fraction and regional cardiac wall motion were not improved. Metabolic dysfunction of the coronary-occluded myocardium, revealed by regional lactate as well as potassium derangements, persisted throughout the 2 hour treatment period. Comparison of these results with equivalent data from an untreated series of nine dogs with 3 hours of occlusion demonstrated no improvement in the treated series. Methylprednistone failed to restore regional cardiac metabolic and mechanical function, and treatment was associated with a further rise in S-T segment elevations. Administration of methylprednisolone after 1 hour of proximal left anterior descending coronary occlusion apparently does not reverse cardiac dysfunction in the first 2 hours of treatment.


Influence of vasodilators upon function and metabolism of ischemic myocardium. Although the systemic hemodynamic effects of vasodilators such as nitroprusside, phentolamine and nitrates are well known, relatively little information is available regarding their effects upon the function and metabolism of ischemic myocardium. Experimental and clinical studies indicate that vasodilators improve the mechanical performance of regional ischemic myocardium, probably by simultaneous reduction of peripheral resistance and reduction of the degree of ischemia. The majority of evidence, although still controversial, seems to indicate that myocardial perfusion can also be increased, particularly when coronary collateral vessels are present. Concomitant reduction in preload contributes to reduced oxygen demand, as evidenced by findings of reduced oxygen extraction. Thus, the balance of the oxygen supply and demand may be improved as indicated by decreases in lactate production. In addition, limited evidence in experimental animals and man suggests that vasodilators may also reduce the extent of myocardial injury as measured by S-T segment mapping and the creatine phosphokinase (CPK) release technique. However, these effects are contingent upon the arterial pressure response, and directionally opposite results may be anticipated if hypotension occurs. Since the mechanism of action of vasodilators is reasonably well understood, vasodilator therapy can be administered safely in anticipation of both improvement in total cardiac performance and a decrease in severity of ischemia.


Diastolic retroperfusion of acutely ischemic myocardium. The effectiveness of coronary venous retroperfusion treatment of an ischemic myocardial segment was assessed by measurements of regional and global myocardial function in 16 dogs. The left anterior descending coronary artery was acutely occluded for 75 minutes. After the first 30 minutes of occlusion, diastolic retroperfusion was instituted for 45 minutes by synchronized pumping of arterial blood from the brachial artery into the anterior interventricular coronary vein. Data collected in the preocclusion control period, during occlusion and the subsequent retroperfusion period included simultaneous measurement os ischemic and border zone myocardial forces, epicardial electrocardiographic S-T segments, intracoronary pressure, coronary blood flow and oxygen pressure (PO2) sampled distal to the site of occlusion. Retroperfusion resulted in significant improvement from the level of regional dysfunction observed after 30 minutes of occlusion: Ischemic zone myocardial force increased 106%, epicardial S-T elevation decreased 46%, normalized peripheral left anterior descending coronary arterial flow increased 50% and distal left anterior descending PO2 decreased 44%. These regional improvements were significant when compared with findings in an untreated series of 12 dogs with 75 minutes occlusion of the left anterior descending coronary artery. Diastolic-augmented coronary venous retroperfusion with arterial blood provided significant but not complete restoration of function in the ischemic segment. Therefore, in the earliest phase of acute myocardial infarction, retroperfusion might represent a useful temporary support to an otherwise inaccessible jeopardized zone of the heart. Regional retroperfusion may constitute an effective emergency procedure, particularly when the occlusive lesions are diffuse and other medical or surgical emergency procedures  are inadvisable, unavailable or ineffective.


Effects of heparin in large doses on the extent of myocardial ischemia after acute coronary occlusion in the dog. Heparin in large doses significantly improved epicardial electrocardiographic findings and preserved myocardial tissue and creatine phosphokinase (CPK) after coronary ligation in the dog. Epicardial S-T segment elevation 15 minutes after occlusion was lowered 84% (from 64.5 + 8.5 [standard error of the mean] to 10.4 +/- 3.0 mv) by heparin infusions of 60,000 units. Myocardial creatine phosphokinase depletion was reduced from 39 to 24% at comparable levels of S-T segment elevation. Histologic evidence of necrosis decreased 32%. It is concluded that heparin can reduce the extent of ischemic injury after acute coronary occlusion in the dog. These results may lend insight into the factors responsible for ischemic injury.


Effect of heparin in anticoagulant doses on the electrocardiogram and cardiac enzymes in patients with acute myocardial infarction. A clinical pilot study. The effect of heparin in clinical anticoagulant doses on S-T segment and cardiac enzymes was studied in 18 patients with acute myocardial infarction by electrocardiogram and enzyme evaluation 1 hour and 24 hours after initial heparin infusion. Intestinal mucosa heparin was given by infusion, 10,000 units after the admission electrocardiogram, and 5,000 units every 6 hours. Data in the nine control and nine treated patients were statistically similar on admission. The electrocardiograph findings were improved, but not significantly, 1 hour after administration of heparin. At 24 hours of heparin therapy, the S-T deviations were reduced 64% (from 139 +/- 2.1 [standard error of the mean] to 50.5 +/- 1.2 mm); in control patients S-T deviations were reduced 21% (from 109 +/- 1.8 to 86 +/- 0.9 mm (t=2.9, P less than 0.019). At 24% hours electrocardiographic leads with 2 mm or more deviation were reduced 86% in heparin-treated patients and 28% in control subjects. Cardiac enzymes were comparably elevated at 24 and 48 hours in both groups, with no clear trend. It is concluded that heparin in anticoagulant doses reduces the 12 lead electrocardiographic pattern of injury without discernibly modifying cardiac enzymes. The question of heparin efficacy in acute myocardial ischemic injury, reopened by findings with large dose heparin in therapy in dogs and anticoagulant dose in this study, awaits further expanded investigation.


Comparative study of exercise-induced ventricular arrhythmias in normal subjects and patients with documented coronary artery disease. The incidence, types and patterns of emergence of treadmill exercise induced ventricular arrhythmias were studied in 482 subjects with and without coronary heart disease. All subjects were free of premature ventricular complexes at rest and were classified into groups on the basis of their clinical status. In Group 1A were 141 patients with chest pain and normal coronary arteriograms and in Group IB 144 age-matched subjects free of clinical evidence of heart disease. Group II consisted of 197 patients with chest pain and arteriographically documented coronary artery disease. Patients in Group IA and II exercised to at least 85% of their predicted maximal heart rate or until chest pain occurred. Subjects in Group IB underwent maximal exercise testing. The total incidence of exercise-induced ventricular arrhythmias was 16% in Group IA, 44% in Group IB and 29% in Group II. However, when exercise heart rate at the time of appearance of ventricular arrhythmias was taken into account the incidence of exercise-induced ventricular arrhythmias up to a heart rate of 130/min was 27% in the patients with documented coronary artery disease (Group II) compared with rates of 9 and 6%, respectively, for Groups IA and IB (P less than 0.001). The incidence rates of multifocal ventricular premature complexes, ventricular tachycardia and ventricular premature complexes at a rate of more than 10/min were also significantly greater at submaximal heart rates in the patients with coronary disease. Patients with three vessel coronary artery disease and abnormal left ventricular wall motion had a significantly greater incidence of exercise-induced ventricular arrhythmias. The incidence of exercise-induced ventricular arrhythmias in patients with coronary disease and a positive S-T segment response was not significantly increased.


Prevalence and reproducibility of exercise-induced ventricular arrhythmias during maximal exercise testing in normal men. The occurrence of ventricular arrhythmias at rest or during ordinary daily activities has been implicated as a risk factor for future coronary-related events and sudden death. However, the clerical significance of exercise-induced ventricular arrhythmias remains uncertain. To assess the prevalence and reproducibility of such arrhythmias, two serial maximal treadmill exercise tests were performed in a study population of 543 male Indian State policemen at an average interval of 2.9 years. Four hundred sixty-two subjects were clinically free of evidence of cardiovascular disease, and 81 had evidence of definite or suspected cardiovascular disease. The prevalence of exercise-induced ventricular arrhythmias during the first test was 30% in men aged 25 to 34 years, 32% in those aged 35 to 44 years and 36% in those aged 45 to 54 years. The prevalence rate in these age groups with repeat testing was 36, 38 and 42%, respectively. These differences were not statistically significant. The group with definite or suspected cardiovascular disease had a greater prevalence of exercise-induced ventricular arrhythmias than normal subjects during both tests but the prevalence rate with repeat testing remained constant. The occurrence of exercise-induced ventricular arrhythmias was reproducible in individual subjects during the second test in 55% of 25 to 34 year olds, 58% of 35 to 44 year olds and 62% of 45 to 54 year olds. Thus, individual reproducibility in two consecutive tests was only slightly greater than reproducibility by chance alone. The group with known or suspected cardiovascular disease demonstrated a trend toward greater reproducibility with repeat testing. Exercise-induced ventricular arrhythmias were not reproducible by type or complexity. The marked variability of exercise-induced ventricular arrhythmias during repeat maximal exercise testing in a clinically normal population appears to negate the usefulness of this finding during a single test as a marker of future cardiovascular disease. Nevertheless, subjects whose arrhythmias were reproducible may form a group destined to manifest clinical cardiovascular disease in long-term follow-up studies.


Beneficial effects of nitroglycerin on abnormal ventricular wall motion at rest and during exercise in patient with previous myocardial infarction. The effects of sublingually administered nitroglycerin on segmental left ventricular wall motion determined by videotracking and radiographic left heart size were evaluated at rest and during submaximal hand grip exercise in 10 patients with previous transmural myocardial infarction. After nitroglycerin, diastolic left heart size decreased in the resting state from an average of 49.5 +/- 5.7 (standard deviation) to 47.9 +/- 5.6 mm/m2 body surface area (P less than 0.01) and during handgrip exercise from a mean of 50.7 +/- 590 to 49.1 +/- 4.7 mm/m2 (P less than 0.05). In the resting state, the average maximal velocity of shortening in segments with normal wall motion increased after nitroglycerin from 18.1 +/- 3.0 to 23.5 +/- 5.5 mm/sec (P less than 0.01), whereas during handgrip exercise alone, the velocity of shortening averaged 25.6 +/- 6.9 mm/sec and increased further after nitroglycerin to 30.1 +/- 10.6 mm/sec (P less than 0.05). The effects of nitroglycerin on the average extent of shortening in normal segments were similar. In all 10 patients, there was a decrease in the number of segments with abnormal wall motion. The number of sites with dyssynergy decreased after nitroglycerin from 24 to 15 in the resting state and from 40 to 22 when nitroglycerin was administered before handgrip exercise. Sublingually administered nitroglycerin appears to decrease left heart size, increase the velocity and extent of shortening in normal left ventricular segments and often reduce the extent of left ventricular wall motion abnormalities at rest and during isometric exercise in patients with previous transmural myocardial infarction.


High blood pressure in children: problems and guidelines for evaluation and treatment. Evidence is presented from studies of the authors and of other investigators that primary hypertension is more common in children than was previously thought. Ninety-five percent of 131 asymptomatic children with incidental hypertension were considered to have primary hypertension after investigation for possible causes. The definition of hypertension was based on normal ranges of blood pressure for each age and sex. However, the definition of juvenile hypertension is still unsettled as is the question of treatment. Investigation of the effect of prolonged antihypertensive therapy on growth and development is needed. Primary hypertension in the young makes possible the study of the disease at its inception.


Big renin: identification, chemical properties and clinical implications. Big renin has a greater molecular weight (63,000 versus 43,000) than normal renin, but it shares the characteristic enzymatic and immunologic properties of normal renin. As it exists in the kidney or plasma of a patient, big renin is less active than normal renin, but its enzymatic activity is greatly enhanced by exposure to pH values of 3.0 to 3.6 or by brief incubation with pepsin or trypsin. Use of the terms prorenin and zymogen might be withheld until big renin is shown to exist in normal tissue or plasma and to be converted to normal renin in vivo. To date, big renin has been found in renal tumors and other abnormal kidney tissues as well as in the plasma of patients with renal disorders. The remarkable activation of big renin at pH levels of 3.3 can be used to detect its presence. If a method involving acidification is used to quantitate plasma renin activity of a patient with circulating big renin, the activated plasma renin activity greatly exceeds that measured in plasma maintained at neutral pH. Gel filtration of plasma is used to prove the presence of big renin. When large amounts of big renin are secreted by a renal tumor, hyperfusion may ensue and be cured by removal of the tumor. The secretion of small amounts of big renin does not necessarily result in any physiologic disorder. However, if there is a concomitant diminution or absence of normal renin a state of apparent hyporeninemia exists, as we have observed in diabetic nephropathy; this may be associated with hypoaldosteronism and hyperkalemia. Big renin does not appear to respond to physiologic changes that stimulate or suppress normal plasma renin activity. The finding of big renin may indicate the presence of certain renin-secreting renal tumors or other renal disorders, especially diabetic nephropathy.


Light and electron microscopic observations on hydrocortisone-induced cleft palate in hamsters. Palatal histogenesis in hydrocortisone-treated hamster fetuses was studied by both light and electron microscopy. At an early stage in the hydrocortisone-affected fetuses, when the palatal shelves hung vertically on either side of the tongue, necortic changes could be seen in some of the basal epithelial cells which lay adjacent to the fragmented basal lamina. The normal looking cells lay on an intact basal lamina and were attached to the contiguous necrotic cells by desmosomes. With horizontal reorientation of the palatal shelves and their approach to the midline, cellular necrosis and fragmentation of the basal lamina increased. When compared with normal cells, the hydrocortisone-affected ones were seen to be lighter, to contain fewer ribosomes and no lysosomes. At a later stage, when midline palatal fusion was lacking, the epithelium underwent stratification and keratinization while the necrotic debris was removed by mesenchymal macrophages. It appears that the normal process of protein synthesis is inhibited following hydrocortisone administration and that this, in turn, during palatogenesis, disrupts normal cellular differentiation and the integrity of the basal lamina, which are associated with the production of a cleft palate.


The transmural passage of blood cells into myeloid sinusoids and the entry of platelets into the sinusoidal circulation; a scanning electron microscopic investigation. Scanning electron microscopic observations of rat bone marrow reveal that the sinusoidal wall is continuous and has no permanent patent apertures allowing free communication between the extravascular and intravascular myeloid compartments. Blood cells migrate into the sinusoids by perforating the endothelial cell body. Platelets are derived from long intrasinusoidal "proplatelet" processes which originate from the cell body of extravascularly located megakaryocytes. Proplatelet processes frequently occur in clusters, with the probability that all processes in a cluster arise from a single megakaryocyte. The release of platelets into the circulation may be initiated by local constriction along these processes, at which places either individual platelets or larger segments of proplatelet cytoplasm are pinched off. The larger segments may subsequently undergo further fragmentation into individual platelets.


Movement of entire cell populations during renewal of the rat incisor as shown by radoioautography after labeling with 3H-thymidine. The concept of a continuously differentiating cross-sectional segment. (With an appendix on the development of the periodontal ligament). Renewal of the rat incisor was studied in three dimensions by employing a serial cross-sectioning technique to locate the boundary between labeled and unlabeled cells in the enamel organ and odontoblast layer at various times after a single injection of 3H-thymidine. This boundary, or leading edge of the front of labeling, was graphically illustrated through point-plotting reconstruction of the labial surface of the incisor. At one hour after the injection of 3H-thymidine the front of labeled ameloblasts was located within the presecretory zone related to early predentin secretion. This front formed a "C"-shaped curve stretching across the labial surface of the tooth from the lateral to the mesial cemento-enamel junction. The "C" was open anteriorly and the lateral arm extended almost twice as far incisally as the mesial arm. The edge of the front of labeled odontoblasts was positioned apical to and parallel with this "C"-shaped curve. The morphological appearance of all cells along each respective front was found to be similar. As the fronts of labeled ameloblasts and labeled odontoblasts moved forward with the erupting incisor, the cells along these fronts differentiated simultaneously and subsequently formed enamel and dentin. Throughout this movement the distance between fixed points along the leading edge of the front of labeled ameloblasts, and its positional relationship to the front of labeled odontoblasts, did not change appreciably. This indicated that cells of the tooth were being carried incisally at a uniform speed. It was concluded that renewal in the rat incisor consists of the generation by the bulbous part of the odontogenic organ of epithelial "U"-shaped cross-sectional segments which enclose a core of pulp. As this segment is transported towards the gingival margin, cellular differentiation and subsequent formation of hard tissue is seen to begin at the central labial side of the segment and to progress in a mesial and lateral direction towards the lingual side. In the process, the limits of the enamel organ at the mesial and lateral cemento-enamel junctions are established and the entire circumference of the segment is eventually enclosed by a rim of dentin.


Sugar as a vehicle for iron fortification: further studies. The data presented confirm the advantages of sugar as a vehicle for iron fortification over other vehicles used in the past. The absorption comparison between ferric and ferrous salts added to sugar demonstrated that Fe(III)-EDTA Complex and ferrous sulfate exhibited the highest absorption, while ferric ammonium citrate was poorly absorbed. It was also found that Fe(III)-EDTA reacts slowly with the tannin contained in tea; the color of the tea changes slightly in the first 2 hr after the addition of the fortified sugar. Iron absorption of sugar fortified with ferrous sulfate was tested in seven beverages. The mean absorption ratio from fortified sugar given with beverages to reference dose of iron ascorbate ranged between 0.42 and 0.70, that is, more than 4 times the absorption from fortified sugar when it is administered with a meal containing one or more vegetals. An absorption of between 0.25 and 0.80 mg of iron/soft drink sugar fortified with 3 mg of iron as ferrous sulfate can be expected in subjects with various degrees of iron deficiency. Thus, two soft drinks per day between meals would be enough to meet the iron requirement in more than 95% of menstruating women, even though the daily iron absorption from the diet is about 0.8 to 1.0 mg.


Human protein requirements: the effect of variations in energy intake within the maintenance range. Protein requirement studies in man generally avoid deficient dietary energy intakes because they decrease the efficiency of nitrogen utilization, but the opposite effect of excess dietary energy is usually overlooked. Four young men were fed the 1973 FAO/WHO safe level of egg protein (0.57 g/kg) at several levels of dietary energy. The data indicate that a significant proportion of the population may require excess energy intakes to maintain nitrogen balance at this level of dietary protein. Variations in dietary energy ranging from submaintenance to 15 to 20% above estimated maintenance needs altered net egg protein utilization in three subjects by 2 to 4.5 units/kcal per kg body wt.


A nomograph method for assessing body weight. The ratio of weight/height emerges from varied epidemiological studies as the most generally useful index of relative body mass in adults. The authors present a nomograph to facilitate use of this relationship in clinical situations. While showing the range of weight given as desirable in life insurance studies, the scale expresses relative weight as a continuous variable. This method encourages use of clinical judgment in interpreting "overweight" and "underweight" and in accounting for muscular and skeletal contributions to measured mass.


Nutrition, infant behavior, and maternal characteristics: a pilot study in West Bengal, India. Free activities and mother-child interaction in a standard setting were observed among undernourished and well-nourished children between the ages of 7 and 18 months in West Bengal. The undernourished boys showed less vigor in play activity, less attachment behavior toward the mother, especially in interaction across a distance, and maintained close physical contact with her more frequently than did the well-nourished boys. The mothers of the undernourished boys had lower scores in four of six measures of maternal behavior. Correlations between child and maternal scores revealed a high reciprocity in mother-child interaction for the well-nourished boys, but a lack of reciprocity for the undernourished boys. The developmental quotient and activity scores of the well- and undernourished boys were not different. However, the correlations between these and the maternal scores showed a divergent pattern of relationships for the two nutritional groups.


Pulmonary vascular disease in systemic lupus erythematosus. The pulmonary vascular changes in systemic lupus erythematosus (SLE) have been investigated from 20 autopsies performed at the Mount Sinai Hospiral from 1964 to 1973. Acute lesions included fibrinoid necrosis and vasculitis. Chronic lesions consisted of intimal fibrosis, medial hypertrophy, alteration of elastic laminae, periadventitial fibrosis, and, in one case, aneruysmal dilatation. These changes were found variously in arterioles, arteries and veins. The fibrotic and occlusive vascular lesions may account for the syndrome of "unexplained breathlessness" that occurs in SLE. These lesions may progress in certain individuals to overt pulmonary hypertension; the concept of coexisting primary pulmonary hypertension and SLE should be re-examined.


Glomerulonephritis due to Staphylococcus aureus antigen. Staphylococcus aureus antigen was identified within the glomeruli of a patient with acute bacterial endocarditis and diffuse glomerulonephritis. Routine immunofluorescence had revealed only granular deposits of complement (C3). C3 activator and C4 were not present. Direct immunofluorescence studies with a specific anti-Staphylococcus aureus conjugate were positive. Electron microscopy showed subepithelial and intramembranous electron-dense deposits. Eluates of the kidney did not contain anti-S. aureus antibody. The absence of immunoglobin suggests that the toxic action of S. aureus antigens may activate complement and cause glomerular injury and that immune complexes are not essential for the production of glomerulonephritis in this entity.


Cystosarcoma phyllodes with liposarcomatous stroma. A case of cystosarcoma phyllodes with liposarcomatous stroma is presented. Electron-microscopic study revealed lipid-containing tumor cells admixed with other mesenchymal cells devoid of fat, correlating well with the light-microscopic findings. The literature is briefly reviewed.


Ultrastructural observations on a follicular carcinoma of the thyroid gland. Electron microscopic studies were performed on a follicular carcinoma removed from a 31-year-old woman. The tumor was poorly differentiated and inoperable but distinctly follicular in pattern. Ultrastructurally, the neoplasm had many of the features of papillary carcinoma, follicular adenoma, and anaplastic carcinoma. Due to the presence of secretory granules it even somewhat resembled medullary carcinoma, but the granules were distinctly larger, and the production of amyloid was definitely excluded.


Pancytopenia associated with a granulosa-cell tumor of the ovary. Report of a case. An unusual case of pancytopenia associated with a granulosa-cell tumor of the ovary in a 44-year-old woman is reported. Initially the patient was thought to have the rare, but well recognized, syndrome of hemolytic anemia complicating an ovarian tumor. However, laboratory studies and clinical follow-up ruled out hyperhemolysis and documented a condition of bone-marrow failure. Excision of the massive tumor was followed by hematologic recovery, which has now lasted more than a year and a half.


The detection of CPK1 (BB) in serum. A summary of sixteen cases. CPK1 (BB) was detected in the sera of 16 patients during an 18-month period. Eight of 16 had undergone cardiopulmonary resuscitation for cardiac arrest or ventricular fibrillation. Four of these eight had clinical or EEG evidence of cerebral damage. The brain is the most probable source for CPK1 in these eight cases. Two others had proven brain damage, one a massive cerebral infarct and one a traumatic cerebral hematoma requiring craniotomy. One patient had membranous enterocolitis, suggesting an intestinal source for CPK1. The source for the CPK1 in the other five cases was much less obvious, but was probably the brain.


A new combined thyroid hormone index based on thyroxine, triiodothyronine and resin uptake. A new thyroid hormone index, based on measurements of thyroxine (T4), triiodothyronine (T3) and resin uptake (RT3U), is proposed. In contrast to previous thyroid hormone indices, it incorporates both T3 and T4 measurements. This combined thyroid hormone index appears to have superior predictive value in terms of clinical correlation with thyroid disease.


Measurement of DNA antibodies.

Measurement of DNA antibodies. Modifications of the standard Farr technic for assaying DNA antibodies are presented; these result in improved separation of normals from abnormals, enhanced reproducibility, and simplicity of performance. The use of 0.4 M borate buffer extends the range of the assay, while a 0.1 M buffer aids differentiation when equivocal results are obtained. Centrifugation of vials prior to counting improves the reproducibility by approximately 3%. Polyethylene glycol, at a final concentration of 6 Gm. per 100 ml., can be substituted for ammonium sulfate, with some advantages.


Urinary loss of clotting factors due to hereditary membranous glomerulopathy. Severe plasma deficiencies of clotting factors IX and XII developed in a 59-year-old woman with a nephrotic syndrome secondary to a laminated membranous glomerulopathy. Both these clotting factors were subsequently identified in the patient's urine. Chromatographic analysis of the urine revealed that the bulk of clotting activity attributed to factors IX ann XII was in early eluting gel filtration fractions containing predominately alpha-2 globulin and albumin. The unprecedented finding of two coagulation proteins in the urine is attributed to the marked proteinuria present in this case.


Antithrombin and heparin antithrombin patterns in pre-thrombosis and thrombosis. An antithrombin assay (AA) and an antithrombin assay modified by the addition of heparin (H-AA) were performed using sera from healthy subjects, patients predisposed to thrombosis, and patients with thromboembolic disease. Characteristic AA, and H-AA patterns were found in each group. Normal controls and four of 39 "pill" patients (10%) had normal AA and H-AA findings (Pattern A). Normal AA, with "decreasing" H-AA (Pattern B) was found in sera of 31 of 39 "pill" patients (80%) and three patients who had non-embolic arterial occlusive disease. Low AA and "decreasing" H-AA (Pattern C) occurred in sera of four "pill"-takers (10%) and one patient who had an arterial embolus. Low AA and low H-AA (Pattern D) developed in sera of eight patients with thrombophlebitis and seven patients with pulmonary embolus. It is concluded that the AA and H-AA assays help to identify thrombosis-prone (Pattern C) and thrombotic (Pattern D) individuals for whom antiplatelet (aspirin; dipyridamole) or anticoagulant therapy might be beneficial.


Blood recalcification time. A simple and reliable test to monitor heparin therapy. The applicability of blood recalcification time as a laboratory test to assess and thereby regulate heparin anticoagulation was evaluated. Normal values for blood recalcification time ranged from 65 to 135 seconds, with a mean and standard deviation of 99 and 12 seconds, respectively. Duplicate determinations showed a mean variation of 5%. Blood recalcification times increased as a linear function of increasing heparin concentrations in vitro. Comparison with whole-blood clotting times revealed reasonably good correlation between the two tests. For whole-blood clotting times of 20 to 45 minutes the corresponding blood recalcification times were 142 to 212 seconds. The therapeutic range is often considered to be twice the normal range (130-270 seconds). In-vivo study revealed the peak blood recalcification time in the first sample collected 30 minutes after heparin injection, and a progressive decline thereafter to the pre-injection level during the subsequent 4 hours. The blood recalcification time is a simple, precise and clinically useful test to monitor heparin therapy.


Frontometaphyseal Dysplasia. Evidence for dominant inheritance. A 10-year-old boy with mixed bilateral hearing loss and unusual facies was found to have frontometaphyseal dysplasia. He has prominent supraorbital ridges, height-span disproportion, dental abnormalities, thick clavicles, pectus excavatum, winged scapulae, joint contractures, and generalized muscular underdevelopment. Roentgenograms show supraorbital hyperostosis, antegonial notching of the mandible, flared ilia, contraction of the midpelvis, flattened vertebrae, deformities of the ribs posteriorly, flared metaphyses of the long tubular bones, and greatly widened and elongated metacarpals, metatarsals, and phalanges. His mother has prominent supraorbital ridges, distinct scoliosis, contractures of the fifth fingers, and conductive hearing loss. She also has many of the roentgenographic features of frontometaphyseal dysplasia. Frontometaphyseal dysplasia in a mother and son strongly suggests a dominant mode of inheritance.


A considered approach to sterilization of mentally retarded youth. A protocol of response to families requesting sterilization for retarded youths was developed, utilizing the multidisciplinary approach already structured in a project of sex education and family planning for handicapped juveniles. We operated on 20 patients over a 3 1/2 -year period. Specific criteria for sterilization eligibility were applied, based on medical diagnosis and psychometric and psychosocial maturity evaluation. Long-term follow-up indicates parental satisfaction, improved school attendance for patients after hysterectomy who were previously unable to cope with menstrual hygiene, and no postoperative depression or increase of sexual activity or sexual exploitation.


Acute encephalopathy in siblings. Reye syndrome vs salicylate intoxication. Siblings, aged 9 and 7 years, had simultaneous onset of vomiting, disorientation, ataxia, and coma. Both children had prodromal symptoms of upper respiratory tract infections, and had been treated with large doses of aspirin. Laboratory data showed evidence of hepatocellular dysfunction, with an elevated serum ammonia level in one patient; salicylate levels were 50 and 44 mg/100 ml. The child who died had autopsy evidence of cerebral edema and fatty liver. The difficulty in clinically differentiating Reye syndrome from salicylate intoxication is discussed.


Bronchial adenoma in childhood. Two case reports and review of literature. A review of the literature discloses 56 cases of bronchial adenoma in children under the age of 16 years; we now report two additional cases. The diagnosis of bronchial adenoma in children is often delayed due to erroneous interpretation of the secondary manifestations of pneumonitis, fever, or wheezing. These tumors should be considered potentially malignant, since local invasion and metastasis have been reported in this age group. Treatment is by thoracotomy with total excision of the lesion.


Abnormal collagen in ataxia telangiectasia. Ataxia telangiectasia has been associated with varying clinical and laboratory abnormalities of the cutaneous, immune, neurological, and endocrine systems. Recently, a primary defect in tissue differentiation has been proposed as a probable cause of the disease. The presence of biochemically abnormal collagen in the skin of two siblings with the disease may further support this hypothesis.


Partial DiGeorge syndrome with substantial cell-mediated immunity. Results of studies on two male infants with incomplete expression of the DiGeorge syndrome are analyzed. Both infants demonstrated neonatal tetany with hypoparathyroidism, cardiovascular anomalies, and absence of a thymus shadow on roentgenographic examination. Some degree of cellular immunity was present in both infants, however, including normal in vitro responses to phytohemagglutinin, thus postponing attempts at thymus transplantation. Both infants died suddenly at home, one at age 7 1/2 weeks and the other at age 44 weeks. At autopsy, no thymus was found in one, and a 2x2-mm thymus was detected after extensive search in the other. These cases emphasize the need for repeated monitoring of all immunologic measurements in the partial DiGeorge syndrome, so that early therapeutic intervention can be undertaken.


Colitis associated with oral clindamycin therapy. A clinical study of 16 patients. The clinical, radiologic, and histologic features of 16 patients hospitalized with clindamycin-associated colitis are presented. The findings are tabulated and compared to 33 cases reported in the literature. The majority of patients were caucasian females over 40 years of age. The clinical presentation varied from mild persistent diarrhea to acute surgical abdomen. Proctoscopic examination revealed nonspecific colitis in 9 and pseudomembranous colitis in 7 cases. No specific radiologic or histologic fingings for postanitbiotic colitis were found. Therapy was nonspecific and varied according to the severity of the clinical course. Clinically, there appeared to be some benefit from systemic steroid therapy. 4 of the 16 patients died. None of the recovered patients have had spontaneous relapses off medication during follow-up evaluation. The pathogenic mechanism for postantibiotic colitis secondary to clindamycin remains unknown and does not appear dose related. Clindamycin therapy should be limited to disorders with specific indications.


Clindamycin-associated colitis. Review of the clinical spectrum of 47 cases. A review of 47 cases of clindamycin-associated colitis demonstrates two groups of patients. Group I includes patients who developed diarrhea and colitis while they were still receiving clindamycin and the antibiotic was immediately stopped. Group II includes patients who developed diarrhea and colitis either after a complete course of antibiotics had been given, or while they continued to receive clindamycin. It is in this latter group of patients that significant morbidity and occasional mortality occurs.


Relationship between the changes in gastrin levels and intestinal properties in the starved rat. Intestinal DNA, RNA, and protein content were decreased to a greater extent than was body weight when rats were starved for 3 days. Specific lactase and maltase activity increased with progressively longer periods of starvation. Antral and serum gastrin concentration significantly decreased during the 3 days of starvation. Pentagastrin (250 mug/kg 3 times daily) was injected into a group of rats for the duration of a 3-day starvation period and caused a small but significant increase in the relative intestinal RNA and protein content and decreased lactase and maltase specific activities in comparison with the levels of 3-day starved controls. Pentagastrin thus partially reversed some of the starvation-induced changes toward fed levels. Thus, a deficiency in the trophic hormone gastrin may be partially responsible for the disproportionate changes in intestinal tissue during starvation.


The effect of cholecystokinin-pancreozymin on circulating gastrin levels in man and dog. Perfusion of the jejunum with a mixture of amino acids (MAA) stimulates cholecystokinin-pancreozymin (CCK) release in man. Since gastrin is normally found in the small intestine, studies were conducted to determine if MAA perfusion had an effect on circulating serum gastrin levels in man. In man, endogenous stimulation of CCK had no effect on gastrin release; however, when CCK was given exogenously (10% pure form), serum gastrin levels were significantly increased. In dogs, the 10% pure CCK given exogenously also significantly increased gastrin concentrations, while the pure CCK octapeptide did not. Cross-reactivity between CCK and the gastrin antibody was minimal and could not be shown to be responsible for the serum gastrin elevations. Neither the physiological release of CCK in humans nor exogenous administration of CCK octapeptide in dogs at a dose equivalent to maximal stimulation of pancreatic secretion in humans significantly altered peripheral venous serum levels of immunoreactive gastrin. Therefore, we conclude that the gastrinemic response of exogenous CCK (10% pure) in man and dog is probably due to an impurity in the CCK preparation; when studying the effects of CCK on the gastrointestinal tract, only the pure CCK or the octapeptide should be used.


Identical twins discordant for ulcerative colitis with colon cancer. A 22-year-old patient with a 16-year history of ulcerative colitis who developed multifocal anaplastic colon cancer is presented. His identical twin, proven by blood type, HL-A, and fingerprint analyses, has been completely asymptomatic. This report suggests that ulcerative colitis results from a polygenic predisposition without full penetrance. Subsequent development of colon cancer seems more likely related to the inflammatory disease that an independent genetic determinant.


Acute colitis resembling ulcerative colitis in the hemolytic-uremic syndrome. The case report of a 10-year-old boy, admitted to the hospital after he had experienced 4 days of periumbilical abdominal pain, intermittent vomiting, and diarrhea, is presented. He had proctoscopic and radiologic findings resembling ulcerative colitis. However, further analysis of laboratory data suggested hemolytic-uremic syndrome. Since the patient in the pediatric age group presents with a clinical picture mimicking ulcerative colitis, this hemolytic-uremic syndrome should be included in the differential diagnosis. Examination of a peripheral smear revealing typical findings of microangiogpathic, hemolytic anemia, thrombocytopenia, and a rising blood urea nitrogen value will lead to the diagnosis of hemolytic-uremic syndrome and early appropriate therapy.


An outbreak of nosocomial Proteus rettgeri urinary tract infection. Between December 1, 1971, and November 30, 1972, 11 patients on a single physical rehabilitation ward in a large St. Louis, Missouri, community hospital developed Proteus rettgeri urinary tract infections; P. rettgeri isolates from each patient were indole-negative and resistant in vitro to all antibiotics tested. Infected patients were more likely to have indwelling urinary tract catheters than were matched control patients, and all had previously received systemic antibiotic therapy. Retrospective epidemiologic investigation and microbiologic samplig at the time of the investigation failed to detect a common source of infection. Infected patients appeared to be the major reservoir of the epidemic strain, and indirect-contact transmission of the organism via nursing personnel probably occurred. Data collected from a prospective study suggested that placing catheterized patients in rooms that did not contain other catheterized patients may be an effective control measure.


Hospital-acquired infections. I. Surveillance in a university hospital. A new system of surveillance is described for detecting hospital-aquired infections. Surveillance begins on the ward where a weekly review of the nursing care plan (Kardex) is used to select high risk patients (approximately 65% of the total population) for a subsequent chart review. A nurse-epidemiologist required 16-25 hr per week to perform surveillance and 4 more hr to organize line listings of infected patients. The Kardex review was 82 to 94 percent accurate in detecting nosocomial infections when compared to prospective reviews of the charts of all hospitalized patients. The new surveillance method was more accurate than a system based on weekly chart reviews of all patients receiving systemic antibiotics and/or of all patients with fever (temperature less than or equal to 37.8 C orally). In addition, it was more accurate and offered advantages over a system in which surveillance depended primarily on the bacteriology laboratory. Over a 12-month period 1154 hospital-acquired infections were identified for a 7% annual infection rate. Data from ongoing surveillance are used to record accurate infection rates by service, to define the risk of various hospital procedures, and to monitor for common source outbreaks of infection.


Mortality among rubber workers. I. White male union employees in Akron, Ohio. Mortality among a cohort of 13,571 white male rubber workers in Akron, Ohio is described. Mortality from all causes was 82% of that expected on the basis of death rates for US white males. Excess deaths from cancer (observed/expected numbers) in specific sites among workers in specific work areas include stomach:processing (18/9.9); large intestine: processing (14/10.5); lung: tire curing (20/12.4): bladder: all workers (48/39.5); brain: tire building (7/3.7): lymphatic: tire building (11/7.1): and leukemia: all workers (55/43.0). In general, excess cancer deaths occurred most often among men who started working between ages 35 and 44 and prior to 1935, who worked 25-34 years and were over age 74 at death, and who died after 1954.


Some atherogenic concomitants of menopause: The Framingham Study. Longitudinal assessment of the effect of change in menopausal status on seven biologic concomitants was made in 40- to 51-year-old women from the cohort of 1686 women premenopausal at the initial Framingham examination and subsequently followed for nine biennial examinations. Within this age range, women of any specific age undergoing natural menopause were leaner at the exam prior to menopause than their controls; while women undergoing surgical menopause with bilateral oophorectomy were heavier. Hemoglobin levels rose after menopause. There was a rise in serum cholesterol levels between the premenopausal and menopausal examinations in natural menopause and in surgical menopause with bilateral oophorectomy. This rise was not seen in surgical menopause without bilateral oophorectomy. No significant changes in weight, blood pressure, blood glucose or vital capacity were found to accompany the menopause.


Psychosocial factors and the risk of myocardial infarctions in white women. The relationship of risk of myocardial infarction (tmi) to psychosocial factors was studied retrospectively in 107 white women hospitalized with first MI's and in 218 controls hospitalized for other diseases. Meical records were abstracted and the women were interviewed. Psychosocial factors associated with MI were educational discrepancy, in which the patient ha less education than her husband, householo crowding and late birth order. Eoucational discrepancy was independently associated with MI, but household crowding and birth order seemed to act as risk factors for MI only when certain biological risk factors were also present. The findings indicate that certain psychosocial factors related to risk of MI in white males are also risk factors for MI in white females especially in association with biologic risk factors. Thus the effects of certain psychosocial factors may assume clinical importance only when interacting with an underlying disease state as indicated by the presence of major biologic risk factors.


Life dissatisfactions, job dissatisfaction and illness of married men over time. This study examines the degree to which job and marital satisfaction and participation in leisure activities could predict concurrent and future health status relative to ethnicity, class and occupational factors, and mental health. Data were obtained from a longitudinal study of a random sample of 1034 Manhattan families with at least one child 6 to 18 years of age. The wives in these families were interviewed twice at 5-year intervals. Multiple regression analyses, using variables abstracted from the records of 640 wives of working husbands, indicated that husbands' health status at Time I (R = .33) and Time II, 5 years later (R = .28) was significantly predicted by the Time I assessments on 12 independent variables. The largest single unique contributor, i.e. net of all other independent variables, to concurrent husband's health was job dissatisfaction (partial r = .15), followed by husband's institutionalization for mental illness (r = .14), being Spanish (r = .10), and the factor of Unhappy Marriage (r = .09). This preliminary investigation indicated that uncertain life satisfactions were important predictors for either concurrent or future health status which operated across class, ethnic, occupational and mental health factors. These findings tend to support models which postulate stressful psychosocial conditions as potential etiologic agents in the development of illness.


Previous fetal loss and risk of sudden infant death syndrome in subsequent offspring. The relationships between previous fetal loss (obtained by mother's statement) and certain categories of infant death including probable instances of the sudden infant death syndrome (SIDSp) were examined. The deaths were those occurring among the cohort of live singleton births born in the State of North Carolina, 1960-1967. SIDSp were defined by age (28-364 days), place of death (outside the hospital), and certain ICD code numbers of the 7th Revision (273, 331, 422.2, 491-493, 500-501, 522, 525, 527.2, 762, 795 and 924). Other deaths in the postneonatal period were dichotomized between congenital malformations (ICD 750-759) and all other causes combined. Neonatal deaths were classified as due to either congenital malformations or other causes. For neonatal deaths and for all categories of deaths other than SIDSp in the postneonatal period there was a strong tendency for the standardized mortality ratios (SMR) to increase with increasing history of previous fetal loss. This was true for blacks and whites, and for both mothers under and over 25 years of age. The SMR for SIDSp, on the other hand, suggested an opposite association among blacks and little association among whites. Overall there was a significant difference between the patterns for SIDSp and all other postneonatal causes of death combined.


Investigating possible effects of abestos in city water: surveillance of gastrointestinal cancer incidence in Duluth, Minnesota. The recent discovery of over one million asbestos-like fibers per liter of Duluth tap water and the suggestive evidence of a link between certain gastrointestinal (GI) cancers and work exposure to asbestos fibers in the air prompted this study. GI cancer incidence data were gathered for Duluth in  the same manner as data previously gathered for comparison cities, Minneapolis and St. Paul. Although some differences in GI cancer incidence occurred among the three cities in 1969-1971, there was no consistent pattern of statistically significant differences observed. The number of GI cancers diagnosed in Duluth residents in 1972 was similar to that in each of the previous three years. This study represents the start of ongoing cancer surveillance in Duluth.


Population serum urate levels and their correlates. The Sherbrooke regional study. A natural population has been studied for its serum urate levels and for host factors associated with these levels. Householdhood, ethnicity, drug and alcohol use were found to be negligible behavioral attributes with respect to population serum urate concentrations. Of interest among significant correlates of serum urate are smoking behavior, serum protein, creatinine, calcium and monocyte count. Predominant statistically significant host factors, however, are sex, body weight and age, body weight being linearly related in both sexes and age in females only.


An outbreak of type B hepatitis associated with transfusion of plasma protein fraction. An outbreak of type B hepatitis followed transfusion with a single lot of plasma protein fraction (PPF) at a 1200-bed hospital in June and July 1973. Of 51 recipients of the product, 31 were available as a study population and 19 (61%) had an illness compatible with hepatitis. Epidemiologic and serologic investigations provided firm evidence that this material was the vehicle for transmission of disease to its recipients. Recipients of four other PPF lots from the same manufacturer were studied. Two of these lots were also associated with extremely high clinical hepatitis attack rates (45% and 55%). The other two lots, which had been prepared from donor plasma contributing to the composition of the initially-studied PPF lot, failed to produced clinical illness, although one of these lots was associated with a high prevalence of hepatitis B seropositivity in recipients. Thus, a broad spectrum of clinical and serologic responses was evident in PPF produced from similar donor plasma and pasteurized in the same bulk container. This study is the first to incriminate heat-treated PPF in transmission of type B hepatitis and suggests the need for further studies of the effect of pasteurization cycles on inactivation of hepatitis B virus.


Rabies immunization of red foxes (Vulpes fulva) with vaccine in sausage baits. Foxes were orally vaccinated against rabies with two modified live vaccine viruses, ERA/BHK-21 and PRI strain, in sausage baits. The baits proved acceptable to caged foxes and effectively delivered immunizing doses of vaccine. Antibody profiles on the vaccinated foxes and intramuscular challenge with "street" rabies virus showed the ERA/BHK-21 vaccine to be more effective than the PRI vaccine. The addition of a stabilizer helped maintain virus titers when the baits were subjected to high (35 C) temperature.


Recent trends in violent deaths among young adults in the United States. Those Americans who feel that theirs has become an increasingly violent society have support for that belief in recent mortality statistics. Since 1960, death rates in the United States among young adults from motor vehicle accidents, homicide, and suicide have increased dramatically. As of 1973, homicide and suicide rates have shown no indication of leveling off. Death rates from nonviolent causes among young adults, however, are declining, particularly among nonwhite females.


Looking ahead--the report of the Study Commission on Pharmacy. The findings and recommendations of the Study Commission on Pharmacy are presented. The Commission defined pharmacy as a knowledge system which produces a service. Practitioners in specific areas of pharmacy are considered to possess both common and differentiated knowledge and skills. While pharmacy as a system is viewed as effective and efficient with reference to drug products, it is far from satisfactory with reference to drug knowledge and information. Current forces of change in the health care system and forces of change internal to pharmacy are discussed in relation to their impact on pharmacists for the future. The Commission recommended that pharmacy should move to meet the health care system's unmet needs which involve drugs and drug information. Specific recommendations are summarized regarding educational objectives, the curriculum, the faculty and credentialling. These recommendations call for heavier emphasis in pharmacy education on the behavioral and social sciences, the establishment of a small body of "clinical scientists," and the creation of a National Board of Pharmacy Examiners.


Comparison of methods for detection of particulate matter in large-volume perenterals. The particulate matter content of six commonly used types of large-volume parenteral solutions was evaluated using five methods. The five methods were: (1) visual examination with the naked eye under diffuse light, (2) visual examination with a 2.5 diopter lens under diffuse light, (3) examination with a light scattering apparatus, (4) instrumental examination using the Prototron particle counter, and (5) a membrane filtration and microscopic examination technique. The visual methods (1) and (2) proved to be inadequate because of the insensitivity and high degree of subjectivity. The light-scattering apparatus was reasonably accurate and a considerable improvement over the first two techniques. The Prototron instrument was shown to be capable of predicting whether a solution would pass or fail the recently adopted USP-NF standards for particulate matter content, when compared with the membrane filtration and microscopic examination technique. All of the solutions tested were found to contain very low levels of particulate matter in relation to the USP-NF standard. It is recommended that this recently adopted standard be reevaluated with a view toward increased stringency.


Salary survey of hospital pharmacy residency programs. The original purpose of this survey was to obtain sufficient salary information on residency programs to assist us in evaluating our residents' annual stipend. The data reported are intended to assist other hospital pharmacists and administrators in their efforts to maintain a fair and equitable stipend for residents in hospital pharmacy.


National survey of selected hospital pharmacy practices. The incidence of 10 selected hospital pharmacy programs in short-term hospitals which contained a pharmacy was surveyed. A short questionnaire was mailed to a national sample of 738 hospitals. The 10 programs surveyed were: unit dose drug distribution; pharmacy-prepared i.v. admixtures; pharmacy-controlled drug administration; radiopharmaceutical dispensing; drug usage review; use of computers in the dispensing process; 24-hour pharmacy service; participation in group purchasing; pharmacy operation of central supply; and pharmacists' authority to select the brand or supplier of drugs. In addition, the volume of drug and supply purchases was determined. A large number of pharmacies (41%) belonged to a group purchasing plan, and a high percentage (67%) reported that pharmacists had authority to select the source of supply for all drug orders unless noted otherwise by the prescriber. Less than 10% of the hospitals had both complete unit dose drug distribution and intravenous admixture programs; an additional 10% had implemented such programs partially. Only 17% of the pharmacies in large hospitals were open 24 hours a day. Computer-assisted medication dispensing was used by 13% of the large hospitals and 5% of the small hospitals. Total pharmacy purchases for all short-term hospitals in 1974 was estimated to be 1.5 billion dollars.


Psychotropic drug therapy knowledge of health care practitioners. The psychotropic drug therapy knowledge of eight types of health care practitioners was studied. An examination, dealing with case studies of schizophrenia, depression and mania, was developed. The categories of practitioners were: (1) clinical pharmacists in psychiatric practice, (2) psychiatrists, (3) physicians (nonpsychiatrists), (4) hospital pharmacists in mental health institutions, (5) hospital pharmacists in nonmental health institutions, (6) community pharmacists, (7) nurses in mental health institutions, and (8) nurses in nonmental health institutions. The specific areas of drug knowledge tested were: diagnosis; drug selection; side effects; adverse reactions; monitoring parameters; influence of other disease states; drug-drug interactions; drug-laboratory test interactions; and clinical drug judgment. Clinical pharmacists in psychiatric practice and psychiatrists had the highest scores, and the scores of these two groups were significantly higher than those of the other groups. Nurses practicing in nonmental health institutions had the lowest scores. The results suggested that clinical pharmacists trained in psychotropic drug therapy may be competent to manage this therapy of patients in mental health institutions. Patients receiving this therapy in nonpsychiatric facilities and in ambulatory environments are being served by physicians, nurses and pharmacists whose knowledge of psychotropic drug therapy may be inadequate.


Anaphylactic shock following oral penicillin--report of two cases. Two cases of anaphylactic shock secondary to oral penicillin therapy are presented. The clinical course and treatment of the two patients are discussed. Ways in which physicians and pharmacists may reduce the incidence and severity of anaphylactic reactions to penicillin are reviewed.


Drug treatment of hyperlipidemia.

Drug treatment of hyperlipidemia. The most frequent indication for treatment of hyperlipidemia is for prevention of arteriosclerosis, a suspected but unproved benefit. The cornerstone of treatment of primary hyperlipidemia is diet; drugs may be added to, but do not replace, diet. When a drug is used with any patient, its potential benefits and hazards must be carefully weighed for the given subject. The subjects should be carefully followed and observed for side effects. Plasma lipids should be monitored during the course of treatment. Five drugs have been approved by the U.S. Food and Drug Administration for the treatment of hyperlipidemia: cholestyramine, clofibrate, nicotinic acid, sodium dextrothyroxine and beta-sitosterol. The use, the actions and the side effects of each and of several nonapproved agents are discussed.


Bacteroides fragilis resistant to the administration of clindamycin. The susceptibility of Bacteroides fragilis to the administration of clindamycin, and the efficacy of this agent in Bacteroides infections are well documented. Clindamycin-resistant strains of B. fragilis were isolated from two patients with bacteremia at two institutions. Clinically significant resistance to clindamycin therapy has not been noted previously in B. fragilis infections.


Arteritis of the aged (giant cell arteritis) and fever of unexplained origin. Arteritis of the aged (giant cell arteritis) masquerades as a degenerative, infectious, neoplastic or even functional disorder in the elderly. In the absence of obliterative vascular changes, the diagnosis is often overlooked when too rigid diagnostic criteria are employed. Four elderly women presented with fever of unexplained origin as the initial manifestation of this disease. The temporal arteries were conspicuously normal in all four, and other traditional clinical clues, such as visual disturbances, headache or manifestations of polymyalgia rheumatica were likewise infrequent of entirely absent. Influenza immunization and uncomplicated rectal surgery preceded the onset of illness in two. Anemia and an increased erythrocyte sedimentation rate are important diagnostic features, particularly in the face of spontaneous clinical improvement accompanied by defervescence and disappearance of nonspecific liver dysfunction. Occult intestinal perforation complicated steroid therapy in one case. Significant and sometimes hectic fever may be a common pattern for this arteritis in its earliest stages, when palpably abnormal temporal arteries, obliterative vascular changes and other traditional diagnostic clues are more likely to be absent.


Guillain-Barré syndrome following administration of live measles vaccine. In a 19 month old girl and a 10 month old girl the Guillain-Barre syndrome developed within a week after they received, respectively, live measles-rubella vaccine and live measles vaccine. The older child was immune to the rubella at the time of vaccination, but both girls demonstrated a primary measles antibody response. Serum obtained during the acute and convalescent stages from the younger child was tested for antibodies against the herpes viruses (herpes simplex, Epstein-Barr virus, cytomegalovirus and varicella-zoster) and found to be negative.


Measles virus and Guillain-Barré syndrome during long-term hemodialysis. In a black man, recently receiving long-term hemodialysis, a severe, rapidly progressive polyradiculoneuritis (Guillain-Barre syndrome) developed. Routine virologic study revealed a high antimeasles virus antibody titer (1:1280 by hemagglutination-inhibition) which progressively decreased. There was no clinical evidence of measles. Discussed here is the possible relationship between the Guillain-Barre syndrome and clinically inapparent measles associated with and perhaps modified by the uremic state.


Multiple lentigines syndrome. Case report and review of the literature. The multiple lentigines syndrome is reviewed and a new case is presented. The major features of this syndrome are lentigines and other cutaneous abnormalities, cardiac defects, meurologic defects, cephalofacila dysmorphism, shortness of stature, skeletal anomalies, genitourinary abnormalities, and a family history consistent with an autosomal dominant mode of inheritance. The multiple lentigines syndrome manifests markedly variable expressivity; no single finding is pathognomonic and few patients have all major features. We propose specific criteria for diagnosis.


Comparison of five methods for preparing blood smears. An extensive study was undertaken to compare five methods of blood smear preparation. Three mechanical devices for preparing blood smears were compared to the traditional coverslip and manual wedge methods. A series of five slides was prepared from each sample of blood. One hundred-cell leukocyte differential counts, red cell morphology, and platelet distribution were compared. Differential counts along the axis and margins of each slide failed to reveal any significant distribution difference by method. On the other hand, there were a significantly fewer neutrophils as well as higher lymphocyte counts on the two spinner preparations. Subsequent analysis suggested that spinner preparations create more smudge cells in smears of normal and granulocytic leukemia patients, and significantly fewer smudge cells in smears of lymphocytic leukemia patients. Both spinner methods produced significant increases in erythrocytic target cells, spherocytes, and cells with shifted pallor; and significantly fewer burr cells and ovalocytes, as compared to the reference methods. The mechanical wedge device was most similar to both reference methods. Of the two reference methods, the cumbersome coverslip preparation apparently offers no practical advantage over wedge methods.


The influence of diabetes and hypertension on the results of coronary revascularization. The effects of diabetes and hypertension on the early postoperative course of patients undergoing coronary revascularization were studied by reviewing the records of 177 patients operated upon in 1972. There were 121 nondiabetic, nonhypertensive; 32 hypertensive; ten diabetic; and 14 diabetic-hypertensive patients. The incidence of postoperative low cardiac output, renal insufficiency and arrhythmia was significantly higher in the hypertensive patient. Operative mortality ranged from 0 in diabetic patients, to 0.8 per cent in nondiabetic, nonhypertensives, to 7.1 per cent in diabetic-hypertensives and 12.5 per cent in hypertensive patients, suggesting an increased risk for the hypertensive patient. The one- to two-year follow-up results documented symptomatic improvement in 90.7 per cent of patients with little adverse effect apparent from diabetes or hypertension. Pre- and postoperative coronary angiography was carried out in 103 patients between 1968 and 1973 with a mean elapsed time between operation and postoperative angiogram of 9.3 months. The progression of atherosclerosis was graded on a 0-4 basis in both grafted and ungrafted coronary arteries. While hypertension appeared to contribute to disease progression, the incidence of vein graft and internal mammary artery bypass occlusion was not significantly affected by either diabetes or hypertension. This study has shown that while hypertension contributes to increased morbidity and mortality in the early postoperative period and an increased rate of progression of atherosclerosis, neither diabetes nor hypertension appeared to influence the one- to two-year results of coronary revascularization.


The remote prognosis of eclamptic women. Sixth periodic report. All but three of the 270 women surviving eclampsia at the Margaret Hague Maternity Hospital in the period 1931 through 1951 were traced to 1973-74. Seventy-six have died and 13 were not re-examined. In white women having eclampsia in the first pregnancy carried to viability the remote mortality rate is not increased over that in unselected women; in white women having eclampsia as mulitparas and in all black women the remote mortality rate is from 2 to 5 times the expected numbers. Primiparous eclamptic women are not different from women matched for age, in several epidemiologic studies, in the prevalence of hypertension or in the frequency distributions of systolic and diastolic blood pressures. There is, however, a considerable increase in the prevalence of hypertension among women having had eclampsia as multiparas and that has accounted for their increased remote death rates. The prevalence of diabetes, developing many years after eclampsia is 2.5 times the expected rate in primiparous and about 4 times the expected rate among multiparous eclamptic women. Eclampsia neither is a sign of latent essential hypertension nor causes hypertension. Hypertensive pregnancies following eclampsia indicate the probabilty of later chronic hypertension, but do not cause it.


Case report. Mini-epidemic of thyrotoxicosis occurring in physicians. This report describes the appearance of thyrotoxicosis over the past eight years in three male physicians working in the Division of Endocrinology at The Mount Sinai Hospital. Since no other instances of hyperthyroidism developed among the hospital medical or dental attending staff, to the authors' knowledge, during the years of 1953-1973, this incidence appears to indicate an unusual occurrence. (Information regarding other possible instances of thyrotoxicosis was obtained by questioning all of the physicians in the Division of Endocrinology at The Mount Sinai Hospital, members of the Division of Endocrinology at the other major institutions in the city and, finally, inquiry of the physicians in the Department of Medicine at The Mount Sinai Hospital.)


Production of experimental toxemia in the pregnant rabbit. Experimental toxemia of pregnancy was induced in 51 of 122 rabbits by constriction of the aorta below the renal arteries. The approach was extraperitoneal and dependent on the accuracy in calibrating this stricture between 0.6 and 1.0 mm. Experimental toxemia in the rabbit was characterized by hypertension, proteinuria, weight gain, and reduced weight of the fetus. Blood pressure and blood flow studies distal to the aortic constriction demonstrated a marked diminution of blood supply below the constriction. The light microscopic changes in the kidneys and in the liver were similar to those of human toxemia. The electron microscopic changes consisted of endothelial swelling and subendothelial deposits. In a separate experiment, 22 pregnant rabbits near term had an aortic constriction varying between 0.6 and 1.0 mm. This constriction lasted 4 to 12 days. Glomerular deposits of fibrinogen were demonstrated by immunofluorescence in 20 of 22 animals. The intensity of the immunofluorescence was related to the severity and duration of the aortic stricture.


Case report. Severe hyperuricemia, hypokalemic alkalosis and tubulointersitial nephritis. A patient with severe idiopathic hyperuricemia and hypokalemic alkalosis was followed over a one-year period. A tubulointersitial nephritis consistent with hypokalemic nephropathy was found on biopsy. However, the possibility that the hyperuricemia contributed to the hypokalemia and renal lesion cannot be excluded. Inappropriate urinary loss of potassium could be prevented by administration of spironolactone or triameterene. Six months after initiation of allopurinol therapy with reduction of serum uric acid concentrations to normal concentrations, this potassium wasting was substantially decreased.


Cortisol levels in maternal venous and umbilical cord arterial and venous serum at vaginal delivery. To provide evidence that the high levels of cortisol found in mixed cord serum at spontaneous delivery are derived from the fetus rather than the mother, arterial and venous cord samples were collected separately along with simultaneous maternal venous samples at term. In the group with spontaneous labor, the difference between umbilical arterial levels of cortisol (78.6 +/- 4.1 ng. per milliliter) exceeded venous levels (61.9 +/- 4.1 ng. per milliliter) (P less than 0.0001). In the group with induced labor, the arterial level (58.4 +/- 6.9 ng. per milliliter) did not differ significantly from the venous level (50.6 +/- 5.9 ng. per milliliter) (P greater than 0.05). In four cases where spontaneous rupture of the membranes occurred prior to induction, values were similar to those of the group with spontaneous labor. The arterial levels of the group with spontaneous labor exceeded those of the group with induced labor (P less than 0.02). These differences cannot be related to duration of labor, gestational age, or maternal cortisol concentration, none of which differed between the group with electively induced and spontaneous labor. The present data provide further evidence that a rise in fetal cortisol production independent of the mother precedes and is involved in the mechanism initiating the spontaneous onset of human labor.


Association between maternal bleeding during gestation and congenital anomalies in the offspring. The incidence of maternal bleeding complicating the pregnancies of 326 children examined at the Jerusalem Community Center for Child and Family Development is surveyed. A history of bleeding during pregnancy was more frequent in children with congenital anomalies of the central nervous system (and/or psychomotor retardation) (33 per cent) and in children with congenital anomalies of other systems (29 per cent) than in control children (12 per cent). The implications of these findings are discussed in relation to placental pathophysiology and the pathogenesis of threatened abortion.


Placental aging monitored by gray scale echography. With gray scale ultrasonics echography, it is possible to identify changes in placental anatomy which formerly have been recognized only by examination of the placenta after delivery. By serial examinations these changes can be detected as they occur. The significance of the changes is discussed and an association between the premature appearance of aging of the placenta and a decline in placental function is noted.


Purification of naturally occurring antibody to human placental lactogen by affinity chromatography. Antibodies against human placental lactogen (HPL) were isolated from maternal postpartum sera and nonpregnant female sera by the technique of immunoadsorption (or affinity chromatography). HPL was linked to Sepharose gel by cyanogen bromide activation and the resultant chromatographic resin was used in a repetitive column procedure to absorb and fractionate naturally occurring antibodies to HPL. The antibody to HPL was concentrated after elution from the column with a chaotropic ion, and tested for immunologic acitivity. It was determined to be an IgG molecule, and only radioimmunoelectrophoresis was sensitive enough, among the several tests performed, to show specific anti-HPL activity after treatment.


Outpatient postconceptional fertility control with vaginally administered 15(S) 15-methyl-PGF2alpha-methyl ester. 15(S) 15-methyl-PGF2alpha-methyl ester was administered as vaginal suppositories to terminate very early gestation in 16 outpatients who were thought to be pregnant. All patients received between 2.5 and 5.0 mg. of the prostaglandin compound. Pregnancy was confirmed later in 10 of the women. In these patients vaginal bleeding started 3 to 6 hours after the start of therapy and continued for an average of 8 days. By subjective assessment, the amount of bleeding during this time was equal to or slightly heavier than that of a normal menstruation for each woman. Patients were followed for 2 to 4 weeks with serial measurements of serum progesterone and HCG. There were no failures at early pregnancy interruption. Gastrointestinal side effects rarely were encountered; no serious complications occurred and no curettage had to be performed because of heavy bleeding. The vaginal use of the methyl ester of 15(S) 15-methyl-PGF2alpha for the termination of early pregnancy seems promising as a reliable and parctical outpatient procedure.


Contraceptive knowledge and practice among undergraduates at a Canadian university. A total of 509 undergraduate students aged 17 to 23 years, were tested to assess the adequacy of their knowledge of methods of birth control. A level of adequate knowledge was arbitrarily defined a priori as one standard deviation below the mean score of a random sample of second-year medical students, who were assumed to have more than adequate knowledge on the basis of prior courses in reproductive physiology and human sexuality. Of the undergraduate population sampled, 34 per cent were found to have inadequate knowledge. This population is in need of birth control information. Of nonvirgins in the sample, 20.2 per cent risk unwanted pregnancy, the majority (78.3 per cent) in spite of adequate knowledge. This suggests that lack of motivation, rather than purely lack of information, is an important factor contributing to the unwanted pregnancy rate of the college student population.


Carcinoma in situ of the vagina following treatment for carcinoma of the cervix: a distinctive clinical entity. A series of 10 patients who presented with carcinoma in situ of the vagina following treatment for carcinoma of the cervix were seen in a 3 year period and their clinical and histologic features reviewed. Vaginal lesions developed 1 to 22 years after diagnosis of carcinoma of the cervix was made. In three patients the vaginal lesions progressed to invasion. In the remaining patients repeated biopsies have revealed persistent carcinoma in situ. From this series of 10 patients we conclude that the biologic behavior of vaginal carcinoma in situ following carcinoma of the cervix resembles that of carcinoma in situ of the cervix and that carcinoma of the vagina following carcinoma of the cervix should be considered a separate clinical entity distinctive from primary invasive carcinoma of the vagina.


Vascular injuries in pelvic cancer surgery. Although pelvic cancer surgery is attended by many difficulties, vascular injuries are actually rare. New techniques of isotopic and ultrasound monitoring allow objective assessment of such patients with vascular injury. In venous problems, absolutely precise diagnosis is now possible and in both arterial and venous injury, extra-anatomic reconstructions can be done which return the vascular status of the patient to near normal.


Contraceptive choice and prevalence of cervical dysplasia and carcinoma in situ. Whether use of oral contraceptives is associated with subsequent development of cervical neoplasia is an important public health question. Before evaluating this issue, we must determine if choosing oral contraceptives identifies a woman who is intrinsically at high risk of developing cervical neoplasia. We have examined the demographic and reproductive characteristics as well as cervical premalignant changes manifest by 15- to 44-year-old black women who enrolled in a public family-planning clinic. When compared to IUD acceptors, oral contraceptive acceptors did not have a disproportionately large number of women with traits which predicted for high risk of developing cervical neoplasia. Oral contraceptive acceptors, compared to IUD acceptors, did not have a higher prevalence rate of carcinoma in situ. Oral contraceptive acceptors with no Pap smears prior to initial choice of contraceptive method did have a 1.4-fold higher prevalence rate of cervical dysplasia than IUD acceptors. These results suggest that the deicision to use oral contraceptives, per se, does not identify a group of women at higher risk to develop cervical carcinoma in situ. Such a decision may, however, identify a group with a small increased propensity for developing cervical dysplasia.


The barrel-shaped cervical carcinoma.

The barrel-shaped cervical carcinoma. Twelve patients had barrel-shaped cervical carcinoma among 493 new patients with primary invasive cervical carcinoma, at the Downstate Medical Center, New York from January, 1964 to December, 1972. The incidence of barrel-shaped lesions among invasive carcinoma of the cervix was 2.43%. All 12 patients were treated with external radiation to the whole pelvis followed by two radium applications. In six patients an extrafascial hysterectomy was performed 6 to 12 weeks after radiation. Six patients died and six survived (50%). Six patients survived for over 2 years after therapy with no evidence of recurrence. Of these, four are alive and well for over 5 years. All six patients died within 20 months after therapy. The barrel-shaped cervical carcinoma fared poorly (six deaths among 12 patients or 50%) when compared with the over-all Stage I and Stage II cervical carcinoma (87 deaths among 339 patients or 25.5%).


Effect of estradiol-17beta on blood flow to reproductive and nonreproductive tissues in pregnant ewes. The effect of estradiol-17beta (1 mug per kilogram) on regional blood flow and cardiac output was studied by means of radionuclide-labeled microspheres in 6 nonpregnant and 13 pregnant ewes five to seven days after operation. Estradiol caused vasodilation in myometrium, endometrium, and placental cotyledons throughout pregnancy, but these responses were significantly less than the fifteenfold increase seen in the nonpregnant uterine tissues. Significant vasodilation also occurred in the ovaries, cervix, vagina, uterine tubes, mammary gland, skin, and adrenal glands of pregnant ewes. Cardiac output increased by 14%. No significant change in uterine oxygen consumption was associated with the increase in blood flow to the pregnant uterus.


Cytogenetics of methadone-managed and heroin-addicted pregnant women and their newborn infants. Chromosomal damage was assessed prenatally and at delivery from 99 addicted pregnant women (80 from a methadone maintenance program and 19 heroin addicts) and their 101 off-spring at delivery. About 10% of the 27,907 cells scored showed chromosomal abberations. Chromosome damage was random, affected all chromosomes, and was mainly of the acentric fragment type. The per cent of hypodiploidy was significantly higher than the per cent of hyperdiploidy. In the mothers, no significant differences were found with respect to dosage and duration of methadone treatment and years of heroin abuse. No significant association was found between maternal variables and infant chromosome damage. Infants with low Apgar scores (1 to 6) had cells with significantly higher levels of chromosome damage than infants with higher scores (7 to 10).


Placental morphometric and morphologic alterations in maternal undernutrition. Placentas, mothers, and neonates belonging to different socioeconomic groups were examined for morphometric and gross morphologic changes to assess the effect of maternal undernutrition. The mean maternal caloric intakes for socioeconomic Groups I, II, and IIII + IV are 2,919, 2420, and 1,589 calories per day, respectively, and differences were significant (P less than 0.001). The mean protein intakes were respectively, 76.1, 67.3, and 52.0 Gm. per day for socioeconomic Groups I, II, and III + IV, respectively (p less than 0.001). The birth weight, placental weight, volume, surface area, and number of cotyledon showed significantly decreasing trends (P less then 0.001) with the fall in socioeconomic group and maternal dietary intakes. Placentas of socioeconomic Group I had significantly higher incidence of well-defined cotyledons and central cord attachment. In lower socioeconomic groups and small-for-dates placentas there was significantly higher incidence of hemorrhages. There were no changes in incidences of placental infarcts, calcifications, and degeneration in various socioeconomic groups.


Teratogenic effects of ethyl alcohol administered to pregnant mice. Concern has recently been renewed about detrimental effects of maternal alcoholism on human prenatal development. In light of current interest in maternal alcoholism, data are presented on the effects of ethyl alcohol administration to pregnant mice. Alcohol treatment consisted of intraperitoneal injection of 0.030 ml. per gram of body weight of a 25 per cent (v/v) solution of 95 per cent ethyl alcohol in saline. Following alcohol treatment on both of gestation days 8 and 9 or days 10 and 11 the frequency of fetal death was substantially elevated compared to saline-treated controls. Alcohol treatment on one of gestation days 7, 8, 9, 10, 11, or 12 resulted in significantly increased fetal death following alcohol treatment on day 8. The incidence of congenital anomalies was significantly increased following alcohol treatment only on gestation days 8, 9, or 10. The most frequently observed abnormalities were coloboma of the iris and ectrodactyly affecting the forepaws.


Abnormal coagulation and fibrinolysis in eclampsia. A clinical and laboratory correlation study. This study evaluated the existence of abnormally increased coagulation and fibrinolysis in 33 severely toxemic and eclamptic women by means of a combined hemotologic profile with clinical and morphologic correlations. The dominant findings were: different degrees of thrombocytopenia, abnormal levels of blood fibrinogen, prolonged thrombin time, and positive protamine sulfate test. Altered activated partial thromboplastin time and positive ethanol gelation test were slightly less frequent, and only few cases showed prolonged prothrombin time or early lysis of euglobulins. These abnormalities seemed to be more numerous and more pronounced in the worst cases of the series and their severity seemed to be associated with the age of the patient and the presence of previous underlying disease. These variously handicapped pregnant women exhibited worse hematologic hematologic abnormalities, and provided most of the fatal cases in the series. Finally, the main findings were discussed and commented upon.


Erythrocyte 2,3-diphosphoglycerate in normal and hypertensive gravid women and their newborn infants. Red blood cell 2,3-diphosphoglycerate (2,3-DPG) levels were studied in 227 normal gravid women in all stages of pregnancy, active labor, and early post partum. An increase to peak levels was observed at 19 to 22 weeks followed by a gradual fall toward normal. During labor and early post partum, 2,3-DPG again rose significantly above levels observed at term. Serial 2,3-DPG values through the third trimester, labor, and postpartum period in 11 hypertensive mothers and 20 normal gravid control subjects and their newborn infants were studied. Maternal 2,3-DPG levels were significantly higher in the hypertensive mothers when compared to control mothers at similar gestational stages. However, no difference in 2,3-DPG levels was observed when newborn infants of hypertensive mothers were compared with those of normal control subjects.


Strangulation of umbilical cord by amniotic band. Congenital malformation caused by amniotic bands is an extremely rare entity. A case report of a fetal death caused by constriction of the umbilical cord by an amniotic band which joined both hands is presented.


The effect of methadone on fetal brain function. The effect of methadone on fetal brain function in terms of the electroencephalogram (EEG) was studied in eight short-term fetal sheep experiments by single injections of 5 to 20 mg. of methadone into the fetal circulation. Plasma methadeone concentrations (determined by radioimmunoassay) greater than 0.065 mg. per cent were associated with an immediate brief decrease in carotid blood flow, a rapid decrease in frequency and amplitude in the EEG that occasionally became isoelectric but recovered, and immediate and relatively prolonged bradycardia. Similar cardiovascular observations were obtained with plasma methadone concentrations less than 0.065 mg. per cent, but the EEG changes were either minimal or not observed. These results indicate that uptake of methadone by the fetal brain is rapid and that electrical activity and heart rate are affected.


Effect of oral contraceptives on rhythmic urinary metal excretion. Thirteen women, six of whom were using oral contraceptive agents, between the ages of 23 and 34 years, free from illness, and without a previous clinical history of menstrual abnormality, were studied with chronobiological methods for circadian (about 24 hour) patterns of metal and creatinine excretinine excretion. Circadian rhythms were detected for the excretion of lithium, potassium, iron, sodium, copper, and creatinine. Statistically significant by lower 24 hour excretion (mesors) of lithium, potassium, and iron was detected for the subjects using oral contraceptive agents. Although all women adhered to nearly identical activity-rest (synchronization) schedules, the peak times (acrophases) of the metal excretory rhythms for oral contraceptive users were phase delayed by about two hours.


An investigation of the effects of the intrauterine contraceptive device based on a longitudinal study of a self-selected sample of Barbadian women. The results of longitudinal study of a self-selected sample of 1,790 Barbadian women who accepted the intrauterine contraceptive device (IUD) as their method of contraception are reported. The accumulated experience of 44,000 woman months of IUD use is presented. The demographic, medical, and obstetric data on admission for 2,797 IUD acceptors and 4,296 nonacceptors are contrasted. The reproductive experience of the two groups prior to the insertion of an IUD with respect to live births, stillbirths, and miscarriages is similar while the incidence of ectopic pregnancy is shown to be different. The association between the IUD and the incidence of tubal pregnancy is evaluated, and the literature dealing with this topic is reviewed. Estimates of the relative risk of an ectopic pregnancy in a woman with an IUD in utero are given.


Experience in mass Papanicolaou screening and cytologic observations of teen-age girls. This report is based on a seven-year retrospective analysis of computerized data available from the Chicago Board of Health's Cancer Control Section and its Cytology Laboratory. All patients included were medically indigent. The cytologic specimens were obtained by the VCE technique; all Papanicolaou smears were classified with both the numerical and descriptive systems for abnormal cytology. The study cohort was composed of 33,641 teen-age patients through age 19; 58 (1.7/1,000) had abnormal  cytology (Class III, IV, or V). In Chicago, from 1962 through 1969, approximately 25 per cent of the total patient load were teen-agers under the age of 19 with an extremely low yield of suspect cytology: Class III = 1.6 per month; Class IV = 0.1 per month; Class V = 0.0 per month. The Chicago Board of Health has reduced the number of Papanicolaou smears taken on young women under the age of 19; however, this conceptual approach does not exclude women under age 19 who epidemiologically and/or clinically warrant the implementation of a Papanicolaou smear with the use of Friedell's "biologic age of the cervix" formula.


Association of estrone with the development of endometrial carcinoma. Although few clinicians suspect estrogen as the prime cause of endometrial carcinoma, a retrospective study showed the following among postmenopausal women: 70 per cent of those with endometrial carcinoma and only 23 per cent of matched control subjects used estrogen systemically. Endometrial cancer developed an average of five years earlier in those taking than in those not receiving estrogen. Forty-two per cent of those with endometrial cancer had received estrogen three years or more. Most significantly, conjugated estrogens were used by 89 per cent of postmenopausal cancer patients who had received any estrogenic substance. The increased risk of endometrial cancer for all patients receiving conjugated estrogen (the risk ratio) was 7.4. This risk ratio increased with duration of conjugated estrogen exposure, from 4.6 in patients with less than three years' exposure to 9.2 in patients with three or more years' exposure.


Carbon dioxide hysteroscopy.

Carbon dioxide hysteroscopy. Hysteroscopy was performed on 75 patients undergoing a dilatation and curettage for routine gynecologic problems. For the distetnion of the uterine cavity carbon dioxide was used and found to be an adequate medium to establish a pneumometra. It provided good visualization and was simple and safe to use for the hysteroscopic examination. Arterial blood-gas determinations revealed no change in the POI PCO2, and pH with carbon dioxide insufflation. There were no complications in this series. The advantages and applications of carbon dioxide hysteroscopy are outlined.


Dysplasia and carcinoma in situ of the uterine cervix: prevalence in very young women (under age 22). A one-year study in a health plan population. An increased number of cervical epithelial abnormalities has been observed in women up to and including 21 years of age. The prevalence and incidence of dysplasia in adolescents and young women is increasing at a time when the incidence of cervical carcinoma is decreasing. We studied 247 women under age 22 with "other than negative" cytologic diagnoses identified during a one-year period (1973) in which approximately 27,500 women in this age group were screened. The prevalence rates of "other than negative" cytology and "other than negative" cytology with confirmed histopathologic abnormalities were 9/1,000 and 2.7/1,000, respectively. Repeat smears and/or tissue speciments were obtained in over 70 per cent of these cases. The majority of abnormalities identified were mild or moderate dysplasia; however eight severe dysplasias and three carcinomas in situ were identified. Fifty-nine percent of these women had a history of one or more pregnancies. Our findings emphasize the presence of dysplasia and carcinoma in situ in young women and suggest the need for re-evaluation of the age at which initiation of the Papanicolaou smear should be considered.


Ureterovaginal fistula as a complication of radical pelvic surgery. The main objection to radical hysterectomy and pelvic node dissection as a method of primary treatment for cervical carcinoma is the inherent danger to the ureters that may result in ureterovaginal fistula formation. The purpose of this paper is twofold: (1) to show that with adoption of certain surgical and clinical measures our incidence of fistula formation has been significantly reduced, and (2) to discuss the management of ureterovaginal fistula when it occurs.