Hemodynamic effect of dobutamine in patients with severe heart failure.

Dobutamine, a derivative of dopamine, was infused at a rate of 10 mug/kg per min in 15 patients with severe congestive heart failure. Cardiac output increased from an average of 3.1 to 5.6 liters/min (P less than 0.001) with no change in mean arterial pressure (93.3 to 98.2 mm Hg) and only a slight increase in heart rate (98.5 to 105.2 beats/min) (P less than 0.02). Pulmonary wedge pressure was decreased from an average of 27.4 to 21.1 mm Hg (P less than 0.001). In seven patients a dose of 5 mug/kg per min also produced a significant increase in cardiac output but the effect was less than with the 10 mug/kg per min dose. No side effects were observed during the infusion. Dobutamine therefore is a potent inotropic drug with limited chronotropic and peripheral vascular effects and deserves therapeutic trial in the short-term management of low output heart failure.


Effects of isosorbide dinitrate on the response to atrial pacing in coronary heart disease.

To study the efficacy of isosorbide dinitrate in prevention of myocardial ischemia, 20 patients with angiographically proved coronary artery disease underwent atrial pacing (mean rate 138/min) before (P1), 10 minutes after (P2) and 65 minutes after (P3) sublingual administration of 5 mg of isosorbide dinitrate. The symptomatic, hemodynamic and metabolic responses were evaluated at rest and during each pacing period. Angina occurred in all subjects during P1. Angina did not recur or was less severe in 17 of 19 patients during P2 and in 19 of 20 patients during P3. Resting left ventricular end-diastolic pressure for the group was normal at 11 plus or minus 4 mm Hg (mean plus or minus standard deviation). On interruption of pacing at 4.5 minutes during P1, average end-diastolic pressure during sinus rhythm was abnormal (18 plus or minus 6 mm Hg). After administration of isosorbide dinitrate mean left ventricular end-diastolic pressure was significantly decreased at rest and remained normal when pacing was interrupted during P2 and P3. Brachial arterial pressure, cardiac index, tension-time index, left ventricular stroke work index and maximal rate of rise of left ventricular pressure were all diminished at rest before and during P2 and P3. S-T segment depression was less during P2 and P3 than during P1. Before isosorbide dinitrate was given, resting myocardial lactate extraction was 15 plus or minus 11 percent during P1 lactate extraction decreased to minus2 plus or minus 25 percent. Lactate extraction was significantly greater during P2 and P3 than during P1. This study demonstrates that sublingual administration of 5 mg of isosorbide dinitrate has a significant protective effect against pacing-induced myocardial ischemia at 10 and 65 minutes after administration.


Mitochondrial function, oxygen extraction, epicardial S-T segment changes and tritiated digoxin distribution after reperfusion of ischemic myocardium.

This study examines the effect of 2 hours of reperfusion on transiently ischemic myocardium in pigs. Indexes of myocardial viability measured were mitochondrial function, oxygen extraction, epicardial S-T segment change and distribution of tritiated digoxin. Results were as follows: (1) Mitochondrial function was markedly impaired in the reperfused area after 60 minutes or more of coronary occlusion. The defect would seem to be a block in electron flow near site I, which can be partially bypassed with succinate. (2) An apparent inability of the reperfused myocardium to extract oxygen did not improve with 2  hours of reperfusion. (3) Epicardial S-T segment mapping suggested that necrosis occurred during reperfusion. (4) There was an altered distribution of tritiated digoxin in the reperfused area. The results show that reperfusion for 2 hours did not improve myocardial viability after 60 minutes or more of ischemia.


Contractile and biochemical effects of coronary reperfusion after extended periods of coronary occlusion.

The effects of coronary reperfusion on recovery of regional myocardial contractility and high energy pegmental changes in myocardial contractility were measured by means of a strain gauge-tipped, two-pronged catheter probe that measures myocardial fiber shortening. The curves of contraction are sensitive to the effects of ischemia. Coronary occlusion resulted in a rapid replacement of fiber shortening by passive fiber lengthening. If coronary occlusion was released and blood flow restored within 45 minutes, myocardial contractility returned promptly; adenosine triphosphate and creatine phosphate values were restored to normal. With coronary occlusion of 1 hour or longer, contractility failed to return in the immediate postperfusion period, but delayed return was recorded after 2 weeks of reperfusion. The extent of such recovery varied with the duration of preceding occlusion. Thus, reperfusion after 1 hour of occlusion was followed by return of fiber shortening over the entire reperfused region. With 2 hours of occlusion, recovery occurred over 75 percent of the reperfused myocardium. With 3 hours of occlusion followed by reperfusion, recovery of contractility was only partial, comprising approximately 60 percent of the reperfused region. High energy phosphate content of the reperfused myocardium showed a similar pattern of recovery. With occlusion of longer duration, reperfusion failed to restore contractility to any significant extent. These findings indicate that reperfusion after coronary occlusion of 1 to 3 hours may restore contractility over a period of 2 weeks, but the extent of such recovery diminishes with the increase in the duration of occlusion.


Maximal revascularization (reperfusion) in intact conscious dogs after 2 to 5 hours of coronary occlusion.

Acute infarction was produced in intact conscious dogs by inflating a previously implanted balloon cuff around the left anterior descending coronary artery was occluded in 26 control dogs and reperfused by deflating the balloon cuff after 2 hours of occlusion in 19 dogs (group II) and after 5 hours in 11 dogs (group III). Serial studies were performed and repeated after 48 hours and 7 days. All three groups revealed hemodynamic and metabolic deterioration with coronary occlusion and infarct production. Immediately after reperfusion, arrhythmias developed in groups II and III and persistent ventricular tachycardia was present 2 to 3 hours after reperfusion in 74 percent of animals in group II and 82 percent of those in group III compared with 6 percent and 13 percent incidence rates at corresponding times in control dogs. Q waves developed in 83 percent of animals in group II and 100 percent of those in group III but in only 12 and 27 percent of control animals at corresponding times. Hemodynamic deterioration was accelerated in the postreperfusion period in both groups II and III. Angiographic assessment revealed improvement in 42 percent of dogs in group II, but in none of those in group III after reperfusion. Myocardial oxygen extraction diminished to subnormal levels after reperfusion, indicating either reactive hyperemia or shunting effect. Mortality was not significantly influenced by reperfusion. Infarct size was more than 15 percent of ventricular mass in 92 percent of control dogs and in 100 percent of dogs in group III, but in only 50 percent of those in group II. The data indicate that reperfusion in conscious dogs representing early, noninvasive maximal revascularization under ideal circumstances fails to prevent deterioration or death; instead it hastens the development of arrhythmias and myocardial injury. Reperfusion, although deleterious in the first hours, can reduce infarct size if performed after 2 hours, but not after 5 hours, of occlusion.


Histological and three dimensional organization of the odontogenic organ in the lower incisor of 100 gram rats.

A three dimensional reconstruction of the epithelial tissue at the apical end of the lower rat incisor was made from serial 1 mum thick cross sections. This tissue formed an elongated structure, called the odontogenic organ, which was composed of a bulbous and a "U"-shaped part. Both parts were joined to one another at the posterior aspect of the apical foramen. The bulbous part of the odontogenic organ was situated at the lingual side of the "U"-shaped part and protruded anteriorly over the pulp. It was formed by cells of the outer dental epithelium and stellate reticulum whose organization suggested that the bulbous part was important in the production of cells for renewal of all the epithelia of the incisor. The "U"-shaped part of the odontogenic organ was apparently derived from the bulbous part and delineated the pulp by forming the lateral, mesial and labial sidewalls around the apical foramen. It was composed of all the epithelial cell types recognizable as precursors to (a) cells of the enamel organ which form the enamel, and (b) Hertwig's epithelial root sheath, a part of the odontogenic organ which induces the formation of dentin on the lingual aspect of the incisor.


Histological and three dimensional organization of the odontogenic organ in the upper incisor of 100 gm rats: comparison with the lower incisor.

The epithelial tissue forming the posterior aspect of the apical foramen in the upper incisor of the rat was reconstructed from 1 mum thick serial cross sections. Like the lower incisor, this portion of the odontogenic organ in the upper incisor was composed of a bulbous and a "U"-shaped part. However, the bulbous part was considerably blunter and the "U"-shaped part much larger in circumference in comparison to the lower incisor. Although no differences were found between the upper and lower incisor regarding the contents and the basic organization of cells within each part of the odontogenic organ, specific differences were found within the bulbous part in the upper incisor. There was a more definitive boundary between the outer dental epithelium and stellate reticulum, a more intimate relationship of cell streams to the stellate reticulum, and a noticeable lack of swirling of cells as part of the streams. These features suggest that the activity inside the bulbous part is less intense in the upper incisor than it is in the lower incisor. In addition, the relationships between the bulbous part, the "U"-shaped part and the root sheath part of the odontogenic organ and the enamel organ were described for the upper incisor.


Fetal monkey absorption of 55Fe from amniotic fluid.

A single dose of 0.5 mCi radioiron (55Fe) was injected directly into the amniotic cavity of each of four pregnant monkeys near term. At 6 or 24 hours after 55Fe adminstration, samples of fetal jejunum, ileum, blood, spleen, liver, lung and fetal membranes were taken for radioautography and scintillation counts. Counts were also made on corresponding maternal tissues. Intestinal radioiron levels and localization indicated that fetuses swallowed and absorbed 55Fe within 6 to 24 hours after injection. Silver grains over the meconium bodies of fetal ileum suggested that intestinal epithelium retained at least some of the absorbed radioiron. However, elevated 55Fe levels in fetal blood and hematopoietic organs indicated that transport of radioiron to the circulation had occurred, presumably through fetal intestine, extraembryonic membranes and/or fetal lungs. Transfer of 55Fe across the placenta from fetus to mother occurred at a slow rate, i.e., samples of maternal organs obtained at 24 hours gave low counts.


Presence of cells combining features of two different cell types in the colonic crypts and pyloric glands of the mouse.

A small number of epithelial cells which combine features of two cell types were observed in the descending colon and pyloric stomach of the mouse. In the descending colon, where the base of the crypts is mainly composed of poorly differentiated "vacuolated" cells, a few of these cells contain, besides the characteristic "vacuoles," mucous globules identical to those in mucous cells or, less frequently, dense granules such as are found in entero-endocrine cells. Because there is evidence that the poorly differentiated vacuolated cells give rise to the other cells of the epithelium, those which also contain mucous globules or dense granules are likely to be differentiating into mucous cells or entero-endocrine cells respectively. In the pyloric stomach, where the glands are mainly composed of mucous cells, some of which are poorly differentiated, a few of the latter exhibit, besides the mucous globules, entero-endocrine type granules or features of caveolated cells. It is likely that the poorly differentiated mucous cells give rise to the other gland cells; and, therefore, those mucous-containing cells which also display dense granules or caveolated cell features are taken to be differentiating into entero-endocrine or caveolated cells respectively. Most of the cells containing two kinds of secretory materials are believed to be stem cells which initially contain a few vacuoles (colon) or mucous globules (pylorus) but are differentiating into a cell containing a different type of secretion. Rare observations of two kinds of secretory materials in a mature cell suggest that the transitional period may be prolonged, perhaps indefinitely.


Phagocytosis of degenerating germ cells by follicle cells in fetal guinea pig ovaries.

Virus-like particles (80 mmu to 100 mmu in diameter) occur in the endoplasmic reticulum of germ cells in the ovaries of fetal guinea pigs, and are confined to this population of cells. Using these particles as a marker, the phagocytosis of degenerating germ cells by somatic cells in the cortex of the ovary was traced.


Ultrastructural observations at pineal gland capillaries in four rodent species.

The fine structure of the capillaries of the pineal glands of the rat, mouse, chinchilla, and ground squirrel were investigated. The pineal endothelial cells in the rat, mouse and ground squirrel were often composed of attenuated cytoplasmic portions which contained numerous fenestrations, in contrast to pineal capillaries in the chinchilla which were lined by thick non-fenestrated endothelial cells. Marked morphological differences were also apparent in terms of the types of vesicles within the cytoplasm and abutting on the cell surface of pineal endothelial cells from the various species investigated. The interendothelial junctions exhibited remarkable species differences with the chinchilla pineal possessing typical tight endothelial junctions while those in the rat, mouse and ground squirrel lacked such endothelial cell associations. Generally, capillary lining cells in the chinchilla pineal resembled similar cells within the brain, while endothelial cells in pineal glands of rat, mouse and ground squirrel were more typical of those found in other endocrine organs. Species differences in the structure of the pineal capillaries may represent physiological differences as well.


Morphogenesis of rat lingual filiform papillae.

The morphogenesis of filiform papillae on rat tongue was investigated with the electron microscope. Tongue rudiments were first seen on the 12th day of gestation. At 15-17 days, dermal papillae had formed and were arranged in hexagonal array on the dorsal lingual surface. Capping each dermal papilla was a two-layered epithelium that protruded slightly above the lingual surface, thus forming the early filiform papilla. In the next stage of development, at 18-19 days of gestation, the epithelium lining the papilla had differentiated into two cell populations, one producing hard keratin, the other producing soft keratin. Some of the keratinized epithelial cells assumed a position at an acute angle to the tongue surface and extended deep into the epithelium. In the next stage, 20-21 days, a cleft appeared within these angularly oriented cells. This resulted in the division of the epithelium into keraatin-lined individual filiform papillae. Finally, the individual papillae increased in size to the adult form.


A fine structural study of the development of the chick flexor digital tendon: a model for synovial sheathed tendon healing.

The development of the synovial sheathed flexor digital tendon in the chick was studied by light and electron microscopy in 12-day embryos to 22-day post-hatched chickens. Areas of specialized connective tissue differentiation were identified in this complex structure consisting of a lubricated synovial sheath, elastic vincula and fibrocartilaginous adaptations on the surface of the tendon. The presence of some of these specialized adaptations may be related to the specific types of mechanical forces and stresses applied to the developing connective tissue system. This model system appears to be appropriate for the experimental study of tendon injuries related to the human hand.


Ultrastructural observations on the maturation of the placental labyrinth of the golden hamster (days 10 to 16 of gestation).

Morphogenesis of the labyrinthine part of the chorioallantoic placenta of the golden hamster between day 10 of gestation and term (day 16) was studied by light and electron microscopy. During this period the labyrinth increases greatly in both size and complexity. Trabeculae of the labyrinth, thin partitions composed of trophoblastic tissue and fetal capillaries which delimit the maternal blood spaces, apparently proliferate both by appositional and interstitial growth. From the time of its formation (day 9 of gestation) until term the labyrinth is hemotrichorial in organization (i.e. three layers of trophoblast separate maternal blood from fetal capillaries). Both the inner and intermediate layers of trophoblast (layers III and II, respectively) are syncytial. The outer trophoblastic layer (III), which is in direct contact with maternal blood, remains cellular, although many of its component cells grow to giant cell dimensions ("labyrinthine giant cells"). Between the tenth and fourteenth days of gestation the anatomical barrier to diffusion between maternal and fetal blood is progressively reduced. This is accomplished both by gradual attenuation of the trophoblastic layers and fetal capillary endothelium and by the formation of discontinuities (gaps) in layer I, and diaphragmed fenestrae in fetal capillary endothelium. The labyrinthine placental barrier is fully developed and probably attains maximal functional efficiency by the fourteenth day of gestation. Late in the fifteenth day of gestation, a few hours before parturition, distinct degenerative changes are apparent in the trophoblastic layers and fetal capillaries of the trabeculae. The factors responsible for initiation these degenerative changes and the onset of parturition are still controversial.


Effects of fetal decapitation on the structure and function of Leydig cells in rhesus monkeys (Macaca mulatta).

Fetal decapitation in utero has enabled us to study the role of fetal pituitary hormones in the development of the fetal testis. Testes from males decapitated near 80 days of gestational life and later delivered at 150 days were smaller than normal and about one-tenth the normal weight. The size of the seminiferous tubules was similar in both groups; however, the number of Leydig cells seemed reduced. In addition, the Leydig cells of the experimental group contained smaller mitochondria with reduced tubular cristae, fewer lipid droplets, and reduced agranular endoplasmic reticulum. Androgen production was inhibited. Measured by radioimmunoassay, the testosterone level in the umbilical vein was 329 +/- 82 pg/ml in six decapitates fetuses, 412 +/- 62 pg/ml in ten normal fetuses. The level in the umbilical artery was 328 +/- 56 pg/ml in five decapitated fetuses, 658 +/- 140 pg/ml in normal fetuses. These studies suggest that chronic deprivation of fetal pituitary hormones inhibits the growth and development of the testis in general and of the Leydig cells in particular.


Cell population dynamics of periodontal ligament stimulated with parathyroid extract.

Young adult rats were injected with parathyroid extract (PTE). Periodontal ligament (PDL) adjacent to a previously resorbing alveolar bone surface was divided into four zones number I to IV, from bone to cementum. Zones I and IV were within 25 mmu of the bone and cementum surfaces, respectively, while a line bisecting the center of the PDL separated Zones II and III. A net increase of about 16 total nuclei in all zones was observed during the first five hours after PTE administration. Since local mitosis accounted for no more than two nuclei, approximately 14 cells apparently migrated into the area. Over the first five hours Zones I and II combined showed a 21-cell increase, being apparently the sole recipients of cells migrating into the field (14) plus approximately seven more from Zone III, which lost cells during the time period. The concurrent histological observation in Zone II, of increased intravascular monocytes and perivascular macrophages during the first five hours, suggests cells are migrating into Zone II via vascular channels. The data suggest two sources for increased PDL cellularity associated with stimulated osteoclast histogenesis: (1) local PDL cellular proliferation and (2) influx of migrating cells (probably through vascular channels) during first five hours after PTE.


The dual origin of vaginal epithelium.

The absence of the cranial three-fifths of the vaginae of male mice carrying the gene, Testicular Feminization, provides strong support for the view that vaginal epithelium is of dual origin, the cranial three-fifths being of Mullerian in origin and the caudal two-fifths being derived from the urogenital sinus.


Midbodies and beaded threads.

When the dorsal surface of the young chick embryo is examined by SEM, long threads are visible, each of which appears to connect pairs of cells; these cells may be separated from each other by several intervening cells. Many of the threads possess a bead-like structure about half way along their length. When sections of the beads are examined by TEM they are found to resemble midbodies. Furthermore, the threads possess longitudinally arranged structures within them, which are probably the remnants of the microtubules which were part of a mitotic spindle. It is concluded that each bead is a midbody and that each beaded thread is the remains of a telophase bridge connecting two daughter cells which were incompletely separated after mitosis had taken place. The possible function of the beaded threads is considered.


Platelet plug formation in an extracorporeal unit.

Platelet plugs were formed in an extracorporeal unit from flowing venous blood and studied by electron microscopy. The unit consisted of a stainless steel needle threaded into a section of silicone rubber tubing that was constricted to form a slit-like stenosis equivalent in cross-sectional area to an arteriole 100 mu in diameter. Blood was allowed to flow at a steady pressure from an antecubital vein through a collection line and the attached unit until bleeding was stopped by the formation of a platelet plug at the stenosis. Electron microscopy of the plugs showed closely packed aggregated platelets. No fibrin was detected. The formation of a stable plug in the absence of fibrin was considered a measure of the capacity of platelets in hemostasis and thrombosis to aggregate and resist the force of the blood current.


Statistical comparison of the fibrometer and the Electra 600 for prothrombin time determination.

Determinations of prothrombin time with the semiautomatic fibrometer and with a more automated machine (Electra 600) were compared in regard to reproducibility, accuracy, and speed. Prothrombin times determined for replicate samples with the two machines showed a correlation coefficient of 0.98, but the Electra 600 sensed the clot 0.5 seconds before the fibrometer. The overall coefficients of variation for multiple tests in the normal therapeutic and elevated ranges of prothrombin time were 3.5% for the fibrometer and 2.0% for the Electra 600. The average technician working time was 60% shorter with the fully automated machine than with fibrometer. It is concluded that the automated machine was more accurate and more rapid in determining prothrombin time.


Alpha-methyldopa-induced immune thrombocytopenia. Report of case.

The clinical and laboratory features of a case of alphamethyldopa-induced thrombocytopenia are described. This is the second reported case in which the presence of alpha-methyldopa-induced platelet antibodies have been demonstrated.


Bacterial interference by Streptococcus salivarius.

A strain of streptococcus salivarius, recognized in a throat culture because of its inhibition of the growth of a species of Corynebacterium, was studied in vitro to determine its antagonistic effects agains various other bacteria. It was found to be inhibitory to anaerobic Gram-positive cocci, streptococci belonging to Lancefields groups A, C, F, and G, and Corynebacterium diphtheriae, C. hofmanii, and C. xerosis.


Gravity delivery of laboratory specimens.

A feasible method for the safe transport by gravity of clinical laboratory specimens has been developed. In this method, specimens are delivered inside containers that closely fit the conduit in which they descend. By maintaining either end of the conduit closed, the containers descend at a  constant speed that can be maintained at less than 120 cm. per sec. over a wide range of operating conditions of practical interest. The speed will increase with increasing container weight, but decrease with increasing length or diameter, or both. Heavier payloads can be accomodated at the same safe, slow speeds by increasing the size of the conduit. The system can be fabricated from standard, commercially available metal or plastic conduit.


Impersonal medical care. Role of the pathologist in its evolution.

An evaluation of the change in the former close relationship between the patient and his physician, and the contribution of the pathologist to its development, is presented. The effect of these changes on the interest in and care of the patient by all in the hospital in this changing medical scene is decried; the patient loses much. The problem of impersonal care now involves all hospital care and all fields of medicine. The decline of interest in the autopsy and the formalization of this denigration of the autopsy by the Accreditation Commission has done harm to pathology and the care of the patient; the autopsy is still an important quality control of such care. Further, this change in the medical scene has promoted the development of the employee status of the doctor, with its further loss of independence, individual interest, and personalized care by all in the hospital, even the physician, and inevitably has led to his loss of the protection of due process. Seven recommendations are offered to recapture the old one-to-one doctor-patient arrangement, to yield a combination of tender loving and scientific care for the patient. An active effort must be made to reverse the influence of some of the forces working to the disadvantage of doctor and patient in the changing medical scene.


Anterior pituitary component in benign cystic ovarian teratomas. Report of three cases.

This paper documents three cases of benign cystic ovarian teratoma in which elements of adenohypophysis was recognized as one of the tissue components. Such findings have been recorded but not unequivocally documented in any of the previous reports of benign  cystic teratomas. One of the tumors in this series also contained neuroglial tissue closely associated with the adenohypophyseal elements. The possibility that  these neural elements might represent neurohypophysis is briefly discussed.


The effects of polyanions on NBT Reductions hexose monophosphate shunt activity, and ultrastructure of polymorphonuclear leukocytes.

Heparin causes enhanced nitroblue tetrazolium  (NBT) reduction by polymorphonuclear leukocytes (PMN's). To determine the mechanism of this stimulation, samples of 1 to 3 x 10(7) PMN's were incubated  with various concentrations of heparin, chondroitin sulfate A (CSA), and chondroitin sulfate B (CSB), with and without NBT. The effect of the polyanions (PA) on PMN hexose monophosphate shunt (HMPS) activity was determined by the production of 14CO2 from glucose-1-14C by the leukocytes. NBT reduction was evaluated histochemically and spectrophotometrically at 515 mmu. Samples of PMN's in heparin and heparin-NBT mixtures were examined by electron microscopy after various incubation periods. Increased NBT reductions by PMN's was found when leukocytes were incubated with heparin, CSA, and CSB, but these compounds had no effect on the HMPS activity of PMN's unless NBT was added. Electron microscopy of samples that contained heparin-NBT revealed an insoluble complex that was phagocytosed by the leukocytes. The stimulation of PMN oxidative metabolism and NBT reduction that follows incubation with PA-NBT appears to be directly related to ingestion of this particulate complex by the leukocytes.


The significance of small erythrocytes.

Small erythrocytes (mean corpuscular volume less than 80 mu-3 by the Coulter Model S) were found in 222 (2.75%) of 8,086 consecutive patients admitted to a large suburban general hospital. Forty-five (20.3%) of these 222 patients had laboratory findings consistent with thalassemia. Seventy-six (31.2%) were found to be iron deficient. Patients whose hemoglobin values were below 9.0 Gm. per 100 ml. were more likely to be iron deficient. The hemoglobin A2 values were significantly lower in iron-deficient than in non-iron-deficient patients. Although the mean corpuscular volume is much lower and the erythrocyte count is higher in thalassemia than in iron deficiency, hematologic values obtainable from the Counlter S (such as MCV, erythrocyte count, and hemoglobin) alone are not valuable in differentiating thalassemia from iron deficiency.


Origin and composition of Cabot rings in pernicious anemia.

Cytochemical studies were performed on erythrocytes containing Cabot rings from the peripheral blood of two patients with severe untreated pernicious anemia. These studies demonstrated that the Cabot ring contained arginine-rich histone and non-hemoglobin iron. Structures that may represent precursors of Cabot rings were found in stippled late intermediate marrow megaloblasts. The Cabot ring may result in part from abnormalities in metabolism of both iron and arginine-rich histone that are known to occur in pernicious anemia.


Rapid citrate-agar electrophoresis in routine screening for hemoglobinopathies using a simple hemolysate.

A system for rapid hemoglobin electrophoresis on both cellulose acetate and citrate-agar combined with a simple solubility test for sickling variants is described. By use of a saponin hemolysate of once-washed erythrocytes, all three tests can be performed at one time so that an accurate result of the hemoglobin phenotype can be provided expeditiously. A technic for rapid hemoglobin electrophoresis on citrate-agar, using standard equipment is described in detail.


Diphenylhydantoin and fragility of erythrocytes in normal subjects and in patients with hereditary spherocytic anemia.

To study the effects of diphenylhydantoin (Dilantin, DPH) on membrane function, DPH was incubated with erythrocytes from normal individuals and from patients with congenital spherocytic hemolytic anemia and osmotic fragility measured. The resulting curves show that DPH reduces the osmotic fragility of normal and spherocytic erythrocytes. In the presence of ouabain, DPH still had a protective effect on erythrocytes even though ouabain alone increases hemolysis of erythrocytes at certain saline concentrations. This study shows that erythrocyte fragility can be manipulated in vitro and provides a basis for studies in vivo.


The activated plasma recalcification time. A Measurement encompassing the activated partial thromboplastin time and platelet function, with improved detection of bleeders.

A study of 300 patients is presented to demonstrate the effectiveness of the activated plasma recalcification time (APRT) as a measure of the intrinsic pathway and platelet function in the detection of bleeders. The activated partial thromboplastin time (APTT) and platelet count were determined in all patients having both normal and abnormal APRT's and the results correlated with overt bleeding tendencies. Abnormality of the APTT is closely paralleled by abnormality of the APRT, independent of the platelet count. When the APTT is normal, an abnormal APRT will characterize clinical bleeders with greater frequency than will the platelet count. The value of the APRT is greatest when done in concert with other standard coagulation measurements, as it both reinforces and expands their diagnostic capability.


Detection of mild factor VIII Deficiency by thrombokinetics.

The maximal rate of change in optical density (Vmax-deltaOD)of plasma clots forming in the activated partial thromboplastin time test (APTT) may be significantly influenced by reductions in factor VIII activity insufficient to also cause a distinctly abnormal timed clotting endpoint. Analysis of relationships between Vmax-deltaOD of clotting plasma in the APTT, prothrombin time, and thrombin time tests provides a basis for increasing the screening value of the APTT in suggesting intrinsic system abnormalities. Three illustrative case reports support the added benefit of thrombokinetics in the detection of mild factor VIII deficiency in hemophilia A and in von Willebrand's disease.


In-situ and microinvasive adenocarcinoma of the uterine cervix. A clinical, cytologic and histologic study of 14 cases. Am J Clin Pathol 64: 155-70, 1975. The clinicopathologic features of 14 cases of in-situ and microinvasive adenocarcinoma of the cervix, encountered during the period 1961-1974, form the basis of this report. Seven cases represent examples of in-situ and seven, microinvasive adenocarcinoma. Severe dysplasia and carcinoma in-situ of the squamous epithelium were coincidental finds in 12 patiients. Papanicolaou smears were abnormal in all 14 patients. In nine, malignant glandular cells were identified. Five smears contained both malignant squamous and glandular cells. The mean age of the 14 patients was 38.4 years. Thirteen patients had borne one to six children. Two were pregnant at the time of diagnosis, and four were on birth control medication. Thirteen of the patients underwent conization biopsy. Hysterectomy in one form or another was curative in all. The relatively infrequent occurrence of in-situ adenocarcinoma is probably due to the low incidence of cervical adenocarcinoma and to the fact that the lesion is focal and easily overlooked. Five of the cases in the present series were a chance finding in a review of 200 consecutive cone biopsies of the cervix. The resemblance of the in-situ lesions to carcinoma and the presence of morphologically similar glandular tissue adjacent to foci of microinvasion suggests that the in-situ lesion is the precursor of invasive adenocarcinoma of the cerivs.


Adenomyomatosis of endometrium and endocervix-a hamartoma.

A 44-year-old woman was found to have a sessile lesion replacing most of her endometrium and endocervical mucosa, consisting of an intimate admixture of endometrial glands, endometrial stroma, and smooth muscle. On the basis of a previous curettage, it was concluded that the lesion had been present for at least seven years. The lesion is considered to be related to the pedunculated adenomyomatous polyp. The possibilities that it may represent adenomyosis, neoplasm, or hamartoma are discussed, and the latter is considered to be the most likely possibility. The presence of smooth muscle distinguishes the present case from the recently described and probably closely related entities of papillary adenofibroma, benign müllerian tumor, and müllerian adenosarcoma.


Diagnostic reliability of needle biopsy of the parietal pleura. A review of 272 biopsies.

The clinical charts and histologic preparations from 245 patients who had pleural biopsies to evaluate pleural effusions of unknown etiology were reviewed. This represents an experience with 272 biopsies, as some patients underwent multiple biopsies. In 57 per cent of the cases of suspected or proven granulomatous disease involving the pleura, the pleural biopsy was positive. Similarly, in 48 per cent of the cases of suspected or proven pleural involvement by carcinoma, tumor was identified in the biopsy specimen. Only two false-positive diagnoses (one of granulomatous pleuritis and one of neoplastic disease) were made. The other 35 histologic diagnoses of granulomatous inflammation and 43 histologic diagnoses of carcinoma were verified. In this study, the authors found that the major limiting factor in establishing a diagnosis is the accuracy in random sampling of the parietal pleural surface. Thus, a negative pleural biopsy should not give the clinician a false sense of security.


Cellulose acetate electrophoresis of creatine phosphokinase isoenzymes in the diagnosis of myocardial infarction.

A method for rapid separation and visualization of creatine phosphokinase (EC 2.7.3.2 ATP: creatine phosphotransferase) isoenzymes on cellulose acetate has been developed. The technic uses the Beckman microzone electrophoresis system, and is applicable to other cellulose acetate systems. Incubation is with a commercially available substrate solution, and the isoenzyme bands are visualized by fluorescence using a long-wavelength ultraviolet light. An intermediate migrating isoenzyme band (CPK-MB) was detected in sera of 67 of 68 patients with myocardial infarction, and was not present in patients with other disorders that might clinically be confused with myocardial infarction.


A proposed fluorimetric determination of unsaturated iron-binding capacity.

A completely new method for the analysis of uncombined iron-binding capacity (UIBC) in human serum is proposed. The method is based on the discovery by C. K. Luk that the fluorescence of terbium ion (Tb-3+) is enhanced enormously when it binds to an empty Fe-3+ binding site of transferrin. Tb-3+ cannot displace Fe-3+ from an occupied binding site on transferrin. The analytic procedure is to dilute the serum (in order to lower its ultraviolet absorbance), add a solution of Tb-3+, excite with ultraviolet radiation, and measure the intensity of the resulting green fluorescence. With proper calibration this intensity is a measure of UIBC. Analyses of 65 serum samples previously measured at a hospital laboratory show no obvious difficulty with the method. Its absolute accuracy has not been probed in detail.


A proposed blind routine quality control system for multichannel analyzers.

A blind quality control system using a special type of commercial reference serum is described. As packaged, the product contains six pools of analyzed reference sera with vials identified by coded numbers. The test constituents in the pools cover the range of multichannel analyzers in a random manner, i.e., each pool contains constituents in the low, normal and elevated ranges. As specific pools are not identified, and the analyst is unaware of the expected values for each constituent, results collected for quality control purposes are unbiased, i.e., free of conscious or unconscious editing. Data analysis in the proposed system is by least-squares technics. During an eight-week period, performance was studied using the standard error of the estimate to evaluate precision and the slope of the regression line to evaluate accuracy on the SMA and Mark X instruments. As an empirical comparison, the data are expressed as relative errors and precision and accuracy of analyzer performance evaluated as mean and standard deviation. The proposed regression analysis-based technic has the advantage of simultaneously evaluating linearity, as well as checking accuracy and precision over the total dynamic range of the instrument by use of a series of related serum pools.


The baton dialyzer.

Macromolecular solutions (such as radioactive materials, sterile solutions, infectious materials) requiring special handling precautions for dialysis may be safely and easily handled using a baton-shaped dialysis device.


Eosinophilia and plasmacytosis of the bone marrow in Hodgkin's disease.

Eosinophilia and plasmacytosis of the bone marrow were found in a group of patients with newly diagnosed Hodgkin's disease. An attempt was made to correlate these cytologic findings with other modalities used in the staging of patients with Hodgkin's disease and believed to have prognostic importance, such as age, sex, histologic type of Hodgkin's disease, presence or absence of bone marrow involvement, and pathologic stage. Statistical analyses of these finding s indicated that eosinophilia and plasmacytosis occur frequently but to date appear to be nonspecific findings. Whether the occurrence of eosinophilia and plasmacytosis is related to an immune response in unknown.


Delayed hemolytic transfusion reaction with four antibodies undetected by pretransfusion tests.

A case of delayed hemolytic transfusion reaction in a 43-year-old patient is presented. Pretransfusion tests revealed no antibody, but tests performed when the reaction occurred demonstrated four. Ten months and 15 months later, when the patient's serum was again tested, the antibodies were undetectable. The significance of such antibodies is discussed.


A permanent record of antibiotic susceptibility results (disk method) using a Xerox photocopying machine.

A simple way to produce permanent antibiotic disk susceptibility and radioimmunodiffusion assay records with the aid of a photocopy machine and a flat mirror is described. Advantages and limitations of the procedure are discussed.


Triage abilities of nurse practitioner vs pediatrician.

The ability of ediatric nurse practitioners (PNPs) to perform triage functions for ill children in a busy pediatric outpatient service was compared to that of a group of pediatricians. One hundred thirteen children were seen separately on arrival by a PNP and by a pediatrician. The PNPs' evaluations agreed with the pediatricians' 84% of the time. Only two significant differences were shown: PNPs were more diligent in recording patient problems, while pediatricians were better able to anticipate the need for roentgenograms and laboratory studies. The results indicate that valuable physician time may be conserved by using the PNP to perform triage in large pediatric outpatient services.


Sexual abuse of children. An epidemiologic study.

An epidemiologic study of sexual abuse of children was made by reviewing Minneapolis Police Department records. Children were involved in 33% of all cases reported. Eighty-five percent of cases involved exposure or indecent liberties. Half of the cases occurred in the summer; half of the cases occurred from 2 to 6 PM. The mean age of victims was 10.7 years, and 88% were girls. All reported offenders were men; their "mean estimated age" was 28 years. The method of study did not allow determination of social relationships between victims and the offenders. Little information regarding the magnitude of the problems of medical, psychological, and social sequelae of sexual abuse of children is available in the literature.


High fever. Experience in private practice.

Experience with confirmed high fever, 40 C (104 F) or more, in a private practice during 14 years is presented. The records of 1,500 patients covering 8,000 patient years disclosed only 108 confirmed episodes of high fever. Eleven diagnostic categories included 149 diagnoses. Fourteen of 43 roentgenographic examinations yielded positive findings, including two cases of pneumonia not detected on physical examination. Two of six stool cultures yielded specific enteric pathogens. Convulsions occurred in 12 of the 108 episodes of high fever, and recurred only once in one child. There were no deaths in this series of children with high fevers. Only one diagnosis, pneumonia, was significantly more frequent in confirmed high fever than in unconfirmed high fever. Lastly, the ability of a group of mothers to read thermometers set at three different temperatures proved to be surprisingly good.


Single umbilical artery. Correlation of clinical status and umbilical cord histology.

Although numerous reports are available concerning infants who have single umbilical artery, there are no studies that correlate the incidence of congenital malformations or prognosis of such infants with the presence or absence of an atrophied artery in their associated umbilical cords. For this reason, we studied 48 infants who have single umbilical artery. No significant differences were detected in congenital malformations or neonatal mortality between infants with atrophy of one of their arteries and infants with arterial aplasia.


Hemophilic pseudotumor. Diagnosis, treatment, and complications.

Patients with hemophilia are living longer as a result of improved therapeutic measures. Associated with this longevity is the increased occurrence of complications affecting the osseous system. One of the more serious bone complications is the hemophilic pseudotumor or hemophilic cyst. We studied its diagnosis, treatment, and complications, and report a case of an early hemophilic cyst occurring in a new location, the proximal part of the left clavicle. The increased incidence of this complication should alert the clinician to the possibility of these lesions appearing in previously unreported sites and demonstrating atypical roentgenographic features. Early recognition and treatment is essential if optimal therapeutic results are to be obtained.


Fatal pulmonary involvement in dermatomyositis.

A 12-year-old boy with classic dermatomyositis developed a rapidly progressive pulmonary process that led to his death a month later. Physiologically, there was interference with the oxygenation of the blood even when 100% oxygen was delivered to the lungs under pressure. Microscopic examination of the lungs disclosed diffuse interstitial pulmonary fibrosis. We conclude that these pulmonary changes were a component of the basic disease.


Cardiac neoplasm, tachyarrhythmia, and anasarca in an infant.

An infant had supraventricular tachycardia and massive anasarca at birth. The supraventricular tachycardia and congestive heart failure were minimally responsive to medical therapy. At 1 month of age, a diagnosis of atrial and ventricular septal defect was made by cardiac catheterization. At 5 months of age, at an operation for pulmonary banding, a peculiar neoplasm of the right atrium was noted. On clamping and resection of the neoplasm, the supraventricular tachyarrhythmia reverted to normal sinus mechanism. The neoplasm, by light and electron microscopy, was thought to be a conduction system hamartoma and was thought to have caused the arrhythmia. A review of the literature showed that no such lesions had been reported previously.


Layering of contrast material in oral cholecystography.

Serial erect roentgenograms of the gallbladder during oral cholecystography were taken in 50 patients before and after a fatty meal. In the presence of good opacification, layering of opaque and nonopaque bile was noted in most cases 2 hours after the fatty meal. The degree of layering was related to the extent of gallbladder contraction produced by the fatty meal and the degree to which the gallbladder refilled by the inflow of nonopaque liver bile. The layering phenomenon thus appears to be a manifestation of a normally functioning gallbladder and occurs when the gallbladder refills with fresh nonopaque bile.


Lower esophageal sphincter responses to enteric hormones in two patients with Zollinger-Ellison syndrome.

The effect of exogenous glucagon and secretin on resting lower esophageal sphincter (LES) tone during endogenous hypergastrinemia was studied in 2 patients with proven Zollinger-Ellison Syndrome (ZES). Intravenous glucagon and in one patient secretin, in dosages which decrease LES pressure in normals during LES stimulation by exogenous gastrin, caused a decrease in resting LES pressure in the ZES patients. This drop in LES tone occurred both during concomitant serum gastrin rise caused by secretin and serum gastrin decline caused by glucagon. This finding suggests that the action of secretin on LES pressure may be independent on endogenous gastrin, while the glucagon effect on LES tone may be mediated through gastrin.


Pigment vs cholesterol cholelithiasis: clinical and epidemiological aspects.

This prospective study demonstrated that among 92 consecutive patients who underwent cholecystectomy for gallstones at an urban university hospital, 27% had pigment stones and 73% had cholesterol stones. Age, sex, and weight, but not race, were significant determinants of stone type. The mean hemoglobin, direct and total serum bilirubin, and fasting glucose concentrations were similar for each group. The presence of alcoholism, diabetes, thyroid disease, or heterozygous hemoglobinopathy did not influence stone type. The average patient with pigment stones is a lean man or woman 63 years old; in contrast the composite patient with cholesterol stones is a modestly overweight woman 43 years old.


Multiple lipomas of the stomach and duodenum.

A patient complaining of epigastric distress was found to have multiple gastroduodenal lipomas. Although the roentgenologic findings were both bizzare and initially confusing, close scrutinization of the abnormalities suggested a correct diagnosis.


Absorption of intact protein by colonic epithelial cells of the rat.

Colonic absorption of intact protein was examined in adult rats using histological and ultrastructural procedures. Horseradish peroxidase was introduced into ligated colonic loops and retained therein for 5, 10, 20, or 30 minutes prior to excision of the loops, and their processing for microscopy. Morphological evaluation revealed evidence of peroxidase absorption via pinocytosis. Tracer particles were observed adherent to the mucosal border, in apical pinocytotic vesicles, in vesicles adjacent to and fusing with lateral and basal cell membranes, in extracellular spaces throughout the mucosa, in lymphatic channels of the submucosa and occasionally in blood capillaries of mucosal and submucosal regions. The significance of these findings is discussed in light of the frequent presence of dietary and/or microbial macromolecules in the luminal milieu of the large intestine. It is suggested that pinocytotic uptake and subsequent vesicular transport and exocytosis of intact protein may occur in the colon of some species, and that such a phenomenon may be responsible for penetration of the mucosal barrier by macromolecular antigens or toxins.


A new technique of endoscopic esophageal biopsy using multipurpose biopsy tube in the diagnosis of reflux esophagitis.

A very easily performed new technique of simultaneous introduction of Rubin's multipurpose biopsy tube and gastrofiberscope in the diagnosis of reflux esophagitis is described. This technique will obviate the need of taking multiple biopsies and adds the advantage of direct observation of abnormal mucosa. As the biopsy is obtained under direct vision, there is no need of x-ray or manometric localization and one can avoid inadvertently biopsying a varix or a friable ulcer.


Fiberoptic endoscopic diagnosis and treatment of a congenital esophageal diaphragm.

A 9-month-old infant suffering from dysphagia to solids presented with esophageal bolus obstruction. Using an adult fiberoptic esophagoscope, a congenital web was found at the junction of the middle and distal thirds of the esophagus. Previous direct rigid esophagoscopy and roentgenologic examination had not visualized the web. The web was successfully ruptured and dilated by inserting a guide wire under fiberscopic control and then inserting metal olives, followed later by blind mercury bougienage. This report illustrates the use of adult fiberoptic instruments for diagnosis and treatment in pediatric patients.


Metastatic malignant melanoma of the esophagus.

The occurrence of secondary deposits in the esophagus from cutaneous melanoma has rarely been reported in medical literature. Since esophageal deposits may present as dysphagia, it is important that the clinical picture be defined. Such a case is presented, and the typical radiological appearance described. Surgical treatment for secondary melanoma deposits may be dictated by the need for palliation of symptoms, but the long-term results are poor.


Cholangitis complicating congenital hepatic fibrosis.

A patient with cholangitis complicating congenital hepatic fibrosis is presented. In contrast to most other reported cases, many of whom have been treated surgically, this patient had a benign course. The likelihood that this complication of congenital hepatic fibrosis will respond to appropriate conservative therapy suggests that more aggressive forms of treatment should be reserved for those patients who fail to respond to medical management.


Adenocarcinoma of the jejunum associated with nontropical sprue.

A patient with a thirty-year history of celiac disease, developed malabsorption and ultimately intestinal obstruction. He failed to respond to a strict gluten-free diet, steroids, and antibiotics. Postmorten examination revealed primary adenocarcinoma of the small bowel. The relationship between adenocarcinoma of the jejunum and celiac disease is reviewed.


The diagnosis of necrotizing pancreatic lesions by means of duodenoscopic pancreatography.

Direct demonstration of intrapancreatic abscesses and pseudocysts can be made by means of duodenoscopic retrograde pancreatography. The most important findings are escape of contrast medium from the duct system into a cavity and its visualization, the tryptic perforation of one or more ducts and the concomitant deformity which may be general or limited to the vicinity of the lesion. The differential diagnosis of pancreatic abscess and carcinoma with penetration of contrast medium in the tumor tissue is supported by the fact that the contours of a necrotic cavity are rather well defined, whereas in carcinoma the extraductal opacification is diffuse. As a rule in a necrotic lesion the ductal system is distorted locally or the whole excretory duct system may be involved. In carcinoma the ductal system generally appears normal distally to the tumor. Accurate demonstration of the necrotic lesion, the assessment as to its localization and size are of decisive importance for indication and choice of the surgical procedure.


Arrythmias and ischemic changes of the heart induced by gastric endoscopic procedures.

Changes in the heart rate, blood pressure, ECG, occurring at the time of endoscopy of the stomach were studied in a group of 59 cases of cardiovascular disease and in a control group of 27 cases. With regard to arrythmias appearing at the time of endoscopy of the stomach, ventricular and atrial premature beats were the most numerous. Atrial fibrillation, as well as ventricular bigeminy were encountered. Two cases of atrial fibrillation continued even after the end of the examination. ST-T changes during endoscopy were found most frequently in the ischemic heart disease group and the valvular heart disease group. There were three cases in which severe ST depression made it necessary to stop the examination. The cardiovascular changes generally occurred at the beginning of the endoscopy examination. Two milligrams of propranolol i.v. seemed to be effective in preventing changes of heart rate.


Abnormal liver function and elevated hemoglobins in heroin addicts.

Reports dealing with medical problems of heroin dependency contain conflicting data regarding hemoglobin concentration. Medical evaluation of a large group of asymptomatic heroin users undergoing screening for participation in a methadone maintenance treatment program revealed a significant number of patients with elevated hemoglobin levels. The presence of increased hemoglobin concentrations in the addict population was highly correlated with the presence of abnormalities in liver function. In a preliminary serial study, a diminution of elevated hemoglobin values toward normal was observed in heroin users undergoing methadone maintenance therapy. These findings suggest the presence of deranged mechanisms responsible for the regulation of plasma volume and/or erythropiesis which may have pathophysiologic consequences of importance in the medical management of the heroin addict.


Endoscopic polypectomy of a symptomatic antral polyp.

After the introduction of fiberoptic endoscopy and its fully accepted use as an instrument of great diagnostic ability, we are now in an era where the same instrument is providing us with a route for a mode of therapy. Colonic polypectomies are now being performed by a majority of the endoscopists. There have only been three instances reported in the literature, however, where the polypectomies have been performed for the removal of symptomatic polyps in the stomach and duodenum. This communication describes the removal of such a pedunculated distal antral polyp which not only caused intermittent pyloric obstruction but also a moderately severe iron deficiency anemia in an 82-year old female. The benign procedure of endoscopic polypectomy, which took only 25 minutes to perform, was a means of total cure for this patient. To the best of our knowledge, this case represents the second reported one from this country of the endoscopic polypectomy of a symptomatic benign gastric polyp.


Lung cancer and air pollution in southcentral Los Angeles County.

An increased rate of lung cancer has been consistently observed from 1968-1972 among males in southcentral Los Angeles. This excess risk occurs across several social classes and occupational categories. No differential excess of oral cavity, pancreatic, laryngeal and bladder cancer was observed in the same area, lessening the possibility that regional variations in smoking habits accounted for the excess lung cancer. Air sampling has indicated an excess of certain polynuclear aromatic hydrocarbons (PAH) in southcentral Los Angeles. There was a correlation between the geographic distribution of lung cancer cases and the general location of industries which have emitted these PAH. A case-controlled study of smoking, occupational and residential history in the southcentral area is underway.


Cuff bladder size in a blood pressure survey of children.

To investigate whether cuff bladder dimensions relative to the length and circumference of the upper arm affect the outcome of epidemiologic blood pressure surveys, multiple observers took multiple measurements on each of 92 grade school children from Franklinton and 351 children from Bogalusa, Louisiana. For the present study, the broad, hard surrounding cuff of the Physiometrics blood pressure recorder using a transducer embedded in the ample cuff bladder gave "true readings." Baumanometer readings were performed using standard cuff sizes selected according to currently recommended criteria. "Excess pressure reading" equal to mean Baumanometer reading minus mean true reading. "Deficient cuff bladder length" equal to percentage of upperarm circumference not covered by the rubber bladder. Pearson correlation coefficients for the two groups of children supported the hypothesis (at the 5% level of significance) that deficient cuff bladder length is associated with excess pressure reading. The relevant correlation coefficients for the two groups of children were 0.18 and 0.31 (systolic pressure) and 0.24 and 0.19 (diastolic pressure). In addition to sufficient cuff width, the complete surrounding of the entire arm circumference by the rubber bladder is recommended for epidemiologic studies of children.


Spherulin and coccidioidin: cross-reactions in dermal sensitivity to histoplasmin and paracoccidioidin.

Until recently coccidioidin has been the only antigenic preparation available for detecting delayed dermal sensitivity induced by an experience with Coccidioides immitis. It is prepared from autolysates of the mycelial phase (saprophytic) of the fungus. A more sensitive reagent, spherulin, was developed in 1969 from the spherule phase (parasitic) of the organism. Use of spherulin showed that coccidioidin failed to detect approximately 30% of individuals specifically sensitive to C. immitis. However the potential of spherulin to detect cross-sensitivity induced by Histoplasma capsulatum was unknown. This information was considered to be germane because of the capacity of coccidioidin to detect a histoplasmal experience. Accordingly, both reagents as well as paracoccidioidin were compared simultaneously in 365 Columbian soldiers from areas endemic for histoplasmosis but not for coccidioidomycosis. At standard strength both preparations detected nonspecific responses in 0.8% to 3% of the histoplasmin negative and positive subgroups, respectively. At 10-times standard strength both preparations cross-detected histoplasmin sensitivity comparably; 5.1% to 7.1% of histoplasmin-positive subjects reacted with the coccidioidal antigens. No pattern of cross-reactivity was observed between paracoccidioidin sensitivity and sensitivity to the coccidioidal antigens.


Reye's syndrome: epidemiologic and viral studies, 1963-1974.

Fifty-eight children with Reye's syndrome (RS) confirmed by liver biopsy were treated at the University of Cincinnati between 1963 and 1974. Cases were clustered in the winter and spring with the peak in February and March. These coincided with the occurrence of influenza and, numerically, were associated more closely with influenza B than with influenza A. Six of the 58 cases were associated with chickenpox. Twenty-six children with RS were seen from 1963 to 1971, before the beginning of a systematic epidemiologic and virologic study. Viral infection was documented in either the patient or a contact in only 19% of those studied. Between 1971 and 1973, after the study was initiated, 16 cases of RS were diagnosed and viral infection was confirmed in 56% of these. In 1974, an epidemic of RS occurred during an influenza B epidemic and viral infection was found in either the patient or a contact in 81% of 16 cases. This study demonstrates that an association with viral infection can be proven in the majority of cases of RS when an intensive investigation is undertaken. During this study no significant environmental toxic exposures could be idenified. Most children had taken aspirin and other medications, and seven children had a history of excessive aspirin ingestion.


Measles (rubeola) susceptibility among elementary schoolchildren.

Measles (rubeola) immunity among 479 elementary schoolchildren from suburban Minneapolis was serologically surveyed in December 1971. Of the 479 children, 25 (5.2%) had hemagglutination-inhibition (HI) titers less than 2. These children were considered susceptible to measles. For the 233 immunized children with no measles history, 13 (5.6%) had rubeola HI titers less than 2 while 5 (5.1%) of the 98 youngsters with a history of clinical measles had rubeola HI titers less than 2. Of the 454 immune children, 73 (16%) had measles HI titers between 2 and 8. These findings confirm durable immunity and a low rate of vaccine failure following live attenuated measles vaccination but demonstrate the importance of testing sera beginning at a dilution of 2 in order to detect children with low antibody levels. This survey also suggests that maternal antibody interferes with the active immune response in youngsters immunized when less than 1 year of age because this group of children had significantly lower geometric mean titers and significantly more susceptibles than the children immunized when greater than or minus 2 years.


Smallpox epidemic in a Brazilian community.

The most severe outbreak of smallpox in Brazil in 1969 took place in the municipio of Utinga, Bahia. Of 507 cases, 246 occurred in residents of the urban area of the municipio. This paper describes the findings of the detailed study of the urban area outbreak. An inverse relationship between age and susceptibility was evident; fully 91% of the children less than 5 years of age as well as 75% of the school-age children had no history of smallpox and had never been vaccinated. The overall attack rate was 11% with nearly three-fourths of the cases in children under 15 years of age. Only 4 of the 246 patients had a vaccination scar, and the estimate of vaccine efficacy was 94%. The continued occurrence of cases after the initial vaccination containment measures prompted detailed studies during 2 follow-up visits to the community which demonstrated that 1) transmission of smallpox may continue in a pocket of susceptibles although the overall immune status of a community is high following containment measures, and 2) clinical illness may have been aborted in those affected individuals who were only in their second to fourth day of incubation at the time of vaccination.


The epidemiology of St. Louis encephalitis in Dallas, Texas, 1966.

An epidemic of St. Louis encephalitis (SLE) occurred in Dallas, Texas, in the summer of 1966. A total of 545 suspected cases within Dallas city and county were reported, of which 145 were laboratory-confirmed as SLE virus infection. The greatest concentration of cases occurred in lower socioeconomic areas of the central part of the city in black populations. The attack rate and mortality rate increased markedly with age. The overall attack rate was 15.2 per 100,000, with a case fatality rate of 9.7%. During the course of the epidemic, most of the county was sprayed aerially with an ultra-low volume (ULV), high-concentration malathion mist. The effects of this treatment cannot be adequately assessed from the human epidemiologic aspect alone, but the spraying clearly reduced the number and infection rate of the vector mosquitoes.


The epidemiology of St. Louis encephalitis in Corpus Christi, Texas, 1966.

In the summer of 1966, an epidemic of St. Louis encephalitis occurred in Corpus Christi, Texas, coincident with one occurring in Dallas about 563 km to the north. Among the 76 cases confirmed in Corpus Christi, there were two deaths; the attack rate was 41.0 per 100,000. In contrast with a concurrent outbreak in Dallas and the 1964 outbreak in Houston, attack rates were much higher in populations of the upper socioeconomic districts. This distribution may have resulted from the combined effects of an unusual concentration of vector mosquito breeding sites in storm sewers in the upper socioeconomic districts and a higher degree of residual immunity in the residents of the lower socioeconomic areas.


The present status of vaccination against coccidioidomycosis in man.

Vaccines of killed whole cells of Coccidioides immitis have been injected intramuscularly in 97 human subjects to determine the safety and tolerable dose of vaccine and certain immunologic responses. Seventy-eight individuals received the whole killed spherule preparation; 18 received killed mycelial vaccine. The maximum tolerable dose of spherule vaccine was approximately 5 mg. Systemic effects were slight though in two prior coccidioidin reactors a moderate febrile illness and sbustantial antibody production followed vaccination with killed spherules. The vaccines irregularly induced antibody or delayed hypersensitivity to coccidioidin or spherule antigen. Greater antigenic mass perhaps as a soluble preparation may be needed for consistent immunologic stimulation though the spherule vaccine may be protective despite absence of detectable antibody or sensitivity to coccidioidin.


Host factors in the susceptibility of rheumatic patients to streptococcal infections.

In children and adolescents who each had at least one previous episode of rheumatic fever and who were not maintaining effective anti-streptococcal prophylaxis, the attack rates of subsequent streptococcal infections declined with advancing age, but were unaffected by gender, cardiac status, or multiplicity of antecedent rheumatic episodes. The rate of rheumatic recurrence per streptococcal infection fell with advancing age, but rose with increasing amounts of cardiac damage and with multiplicity of previous rheumatic attacks. The results suggest that the underlying clinical features of the host have a greater effect on the rheumatogenicity of an acquired streptococcal infection than on the ability to avoid the infection.


Prevalence and incidence data in the assessment of the risk of coronary heart disease.

Estimates of risk of coronary heart disease (CHD) derived from two prevalence survey examinations and from a 7- to 9-year incidence study were compared using data from the Evans County Cardiovascular study. Four risk factors were studied: sex, blood pressure, age and serum cholesterol; relative risks and morbidity ratios were used as estimators of the risk of CHD. Considerable agreement was found between the estimates of risk derived from the incidence and prevalence data.


Driving of motor vehicles as a risk factor for acute herniated lumbar intervertebral disc.

In a case-control study of the epidemiology of acute herniated lumbar intervertebral disc in the New Haven, Connecticut, area, it was found that driving of motor vehicles was associated with an increased risk for developing this disease. It was estimated that men who spend half or more of their time on their job driving a motor vehicle are about three times as likely to develop an acute herniated lumbar disc as those who do not hold such jobs. Persons of either sex who said that they drove a car (either away from work or at work) were more likely to develop an acute herniated lumbar disc than those who did not drive at all. These associations between driving and acute herniated lumbar disc could not be attributed to any confounding variables considered in this study.


Some epidemiologic features of motorcycle collision injuries. I. Introduction, methods and factors associated with incidence.

Using official police reports and hospital admission and emergency room medical records, 1273 persons with confirmed medically treated motorcycle injury were identified in Sacramento County, California, during 1970. Less than 39% of all injured motorcyclists were identified in this study using only official police reports. The annual incidence rate was highest for 18-year-old male drivers. In addition to age of driver, risk of injury was associated with drivers of short stature (less than 173 cm) operating an intermediate or larger size motorcycle. Risk of injury was higher for drivers with training than for those without training or those who operated their motorcycles frequently regardless of type of use. Risk of injury was not related to make of motorcycle but was related to engine size. Two-thirds of the injury-producing collisions involved a motorcycle and a second motor vehicle. Motorcycle collisions occurred most fre  quently during the afternoon and early evening hours and during the summer months, but peaks in incidence of collisions occurred during weeks which included a holiday.


Some epidemiologic features of motorcycle collision injuries. II. Factors associated with severity of injuries.

Male drivers sustained relatively more serious motorcycle collision injuries than did male passengers, female drivers, or female passengers. For male drivers, severity of injury was related to age. The relative frequency of serious head injury was highest for drivers not wearing helmets who were involved in collisions at low or high speeds. Severity of injury was related to speed at the time of collision but not in all types of collisions. Factors associated with the incidence of collisions were not identical to those related to the severity of the injury sustained.


Cancer of the colon: socioeconomic variables in a community.

Carcinoma of the colon was studied in Omaha-Douglas County, Nebraska (population 345,000). A total of 154 cases of colon cancer were diagnosed in 1964 (44.7/100,000). The frequency distribution of these patients in specific census tracts of this community was determined. Statistical analysis of the data showed a greater frequency of colon cancer in patients living in census tracts with higher average income. Colon cancer appears to be nonrandomly distributed with respect to the income and socioeconomic status of its victims, suggesting that hypotheses consistent with environmental variables--particularly those characterizing extremely high versus extremely low socioeconomic groups, including occupation, diet and other life patterns--should be pursued. All of these data have implications for cancer epidemiology, cancer control, and carcinogenesis.


Frequency of marriage and live birth among survivors prenatally exposed to the atomic bomb.

Frequency of marriage and birth as of January 1973 was determined for persons exposed in utero to the atomic bombs in 1945 and for controls. The marriage rate was lower in persons heavily exposed in utero than in the non-exposed or lightly exposed. This difference is attributed partly to the lesser marriageability of persons with mental retardation who are significantly more numerous among the heavily exposed, and partly to unmeasured variables, possibly including social discrimination against survivors of the atomic bomb. No consistent relation was observed between radiation exposure and three reproductive indices: childless marriages, number of births, and interval between marriage and first birth.


Tucson epidemiologic study of obstructive lung diseases. I: Methodology and prevalence of disease.

Using a multistage stratified cluster sample of Anglo-white Tucson households (based on the 1970 Census block statistics), this longitudinal study enrolled 1655 households. The study sample of 3805 individuals thus selected representatively covered the household structures, including the age and sex subgroupings, of the Tucson Anglo-white population. The estimated prevalence rates had a very low standard error of estimate both overall and in the age- and sex-specific categories, indicating a good selection and sufficient numbers in all age-sex specific subgroups. As anticipated, prevalence rates of diagnosed respiratory and other chronic diseases were higher than those found nationally. Despite much higher rates of diagnosed pulmonary diseases within the age-sex populations over the age of 40, the results of this study are within the ranges of other surveys in terms of prevalence of many common chronic respiratory symptoms. Reasons for this apparent discrepancy are so far undertermined.


Tucson epidemiologic study of obstructive lung diseases. II: Effects of in-migration factors on the prevalence of obstructive lung diseases.

The effects of in-migration factors on respiratory symptoms, chronic health problems, and lung function were examined in the stratified Tucson population as part of a longitudinal epidemiologic study of obstructive lung diseases. Migration to the area specifically for health reasons explained part of the high prevalences of disease found in the study. But natives still had higher rates of disease than those found generally in the United States, especially for asthma and allergic rhinitis; It was found that previous urban residence was related to the prevalence of several conditions, even when controlling for age, sex, and smoking habits. However, the trends were not always clear and the differences were not great enough to explain the Tucson population's much higher rates of these conditions than reported nationally or in similar studies elsewhere.


Twinning rates among women at the end of their reproductive span and their relation to age at menopause;.

A review of studies on twinning has shown that dizygotic (DZ) twinning rates among women from general populations characteristically peak at ages 35-39, then decline sharply. Analysis of genealogical data from the Archives of the Mormon Church indicates that women who are dizygous twins themselves or the sibs of dizygous twins have a higher twinning rate among their offspring than do women from the general population. The dizygotic twinning rates of women who are twins or the sibs of twins classified by maternal age also peak at ages 35-39 but remain high at ages 40-44, then decline. It is well known that Negro women have high DZ twinning rates; a less well knwon finding is that the DZ twinning rates of Negro women also remain high after age 39. It has been suggested that high DZ twinning rates at later maternal ages may be related to a delayed age at menopause; However, published reports on age at natural menopause and analysis of our data from contemporary white US women indicate the contrary; Women who have borne unlike-sexed (DZ) twins and Negro women have a lower age at natural menopause then do white women from general populations, and a lower age in comparison with women who have borne like-sexed twins.


Tuberculin sensitivity in a high-risk canine population.

An epidemiologic study of tuberculosis in dogs exposed to humans with recently reported tuberculosis was undertaken in Philadelphia between July 1966 and June 1968. A total of 29 dogs meeting the criteria for inclusion in the high-risk population were studied by history, physical examination, intradermal tuberculin tests, and radiographic and bacteriologic examination. Ten of the 29 dogs showed positive responses to US Department of Agriculture (USDA) standard mammalian tuberculin. Positive tuberculin tests to second strength PPD were demonstrated in five of the 10 responders to USDA mammalian tuberculin. No physical, radiographic or bacteriologic evidence of tuberculosis was found in any of the high-risk animals examined. In a comparison group of 70 dogs without knwon exposure to tuberculosis, two positive responses to USDA tuberculin were demonstrated and none to PPD.


Heterogeneity for adenosine deaminase deficiency: Expression of the enzyme in cultured skin fibroblasts and amniotic fluid cells.

Adenosine deaminase (ADA) could be quantitated and the isozyme pattern characterized in cultured amniotic fluid cells. In 20 amniotic fluid cell cultures the mean specific activity was 14.3 U/g protein  +/- 6.7 (SD) and compared favorably with values of 14.6 U/g protein +/- 6.8 (SD) observed in 26 cultures of skin fibroblasts. In cultures of skin fibroblasts established from two obligate heterozygotes for ADA deficiency, the specific activity of ADA was 7.0 and 7.7 U/g protein. The ADA isozyme pattern that existed in cultures of amniotic fluid cells was the same as that observed in cultured skin fibroblasts. This identification of the same apparent enzyme may permit the prenatal diagnosis of that form of combined immunodeficiency disease caused by ADA deficiency. Residual enzyme activity of less than 1% and 10% of the mean of normal fibroblasts could be measured in cultured fibroblasts from two unrelated children with ADA deficiency and combined immunodeficiency disease. The tissue-specific enzyme from cultured skin fibroblasts from the child with 10% residual activity had a faster electrophoretic mobility and greater heat stability than normal ADA. This enzymatic evidence indicates that at least two mutant alleles exist at the locus for ADA which predispose to combined immunodeficiency disease when present in the homozygous state.


The 47,XYY male, Y chromosome, and tooth size.

Permanent teeth of 12 individuals with a 47,XYY  chromosome constitution have been examined. The tooth sizes of 47,XYY males were found to be larger than those of control males and females. In many instances the differences were statistically significant. Using these results, it was possible to conclude that a factor or factors which influence excess growth of 47,XYY males probably are in effect during prenatal life, but without doubt must be in effect very early in postnatal life. The time period needed for the achievement of final excess growth is relatively short, in the case of first permanent molars probably only from 2 1/2 to 3 1/2 years. On the basis of the finding that the Y chromosome apparently carries genes affecting tooth sizes in normal males [1], it was suggested that gene products of the extra Y chromosome could cause the observed size difference between normal and 47,XYY males. The nature of the influence of one versus two Y chromosomes on growth was discussed in terms of the possible influence of the Y chromosome on the cell divisions within the developing tooth germ.


Unique phenotypic expression of glucosephosphate isomerase deficiency.

Studies of a Mexican kindred present evidence for a unique phenotype of erythrocyte glucosephosphate isomerase, GPI Valle Hermoso. The proband was apparently the homozygous recipient of a mutant autosomal allele governing production of an isozyme characterized by decreased activity, marked thermal instability, normal kinetics and pH optimum, and normal starch gel electrophoretic patterns. Unlike previously known cases, leukocyte and plasma GPI activities were unimpaired. This suggested that the structural alteration primarily induced enzyme instability without drastically curtailing catalytic effectiveness, thereby allowing compensation by cells capable of continued protein synthesis. Age-related losses of GPI, however, were not evident by density-gradient fractionation of affected erythrocytes.


A developmental study of girls with trisomy X.

Development of 11 girls (ages 2-10 years) with 47,XXX karyotype identified in a newborn survey is compared with eight girls having a mosaic sex chromatin pattern and with the normal siblings of each group. Delay in early motor development and speech, a mild intellectual deficit, and disturbance in interpersonal relationships occurred in one-third of the index cases, a higher frequency than in the comparison groups. two-thirds were considered normal and adequately adjusted. No consistent phenotype was found.


Hemoglobin Koya Dora: high frequency of a chain termination mutant.

Approximately 10% of the members of the Koya Dora tribe from Andhra Pradesh (India) carry an alpha chain hemoglobin variant, Hb Koya Dora (Hb KD), usually in amounts of 0.5%-2% of total hemoglobin. In four presumed homozygotes for Hb KD, up to 10% of the abnormal hemoglobin was present. The alpha chain of Hb KD was found to be elongated by at least 16 residues, possibly as a result of a mutation of the normal alpha chain termination codon UAA TO UCA, coding for serine. A pedigree in which two individuals possess Hb KD as well as the alpha chain variant Hb Rampa and normal Hb A proves the existence of two alpha chain loci in this population. Hb DK resembles the previously described Hb Constant Spring [6, 7] in many aspects, probably also in its alpha thalassemia-like expression.


Polydactyly in the American Indian.

Polydactyly has an incidence in the American Indian twice that of Caucasians. A minimum estimate of this incidence is 2.40 per 1,000 live births. Preaxial type 1 has an incidence three to four times that reported for Caucasians or Negroes. The overall sex ratio in Indians is distorted with more males affected than females. The preaxial type 1 anomaly has a strong predilection for the hands and always is unilateral in contrast to postaxial type B where more than one-half are bilateral. The evidence to date, consisting of varying incidences of specific types of polydactyly among American whites, Negroes, and Indians in varying enviroments, suggests different gene-frequencies for polydactyly in each population. The incidence in Indians with 50% Caucasian admixture suggests that the factors controlling polydactyly are in large part genetically determined. Family studies and twin studies reported elsewhere offer no clear-cut genetic model which explains the highly variable gene frequencies.


Human X-autosome translocations: differential inactivation of the X chromosome in a kindred with an X-9 translocation.

A kindred with an X-autosome translocation and differential inactivation of the X chromosome is described. The phenotypically normal mother has a reciprocal translocation [46,X,rcp(X;9) (q11;q32)] while the daughter's karyotype is unbalanced [46,X,--X,+der(9),rcp(X;9) (q11;q32)mat], indicating adjacent-two type of segregation in the mother. In the mother's cells the normal X is late replicating, while in the daughter's cells almost the entire der(9) is late replicating, indicating the presence of autosomal inactivation. The daughter's abnormal phenotype can be explained by her sex chromosomal complement and the absence of effective trisomy 9. At this stage there is no simple explanation to account for all types of inactivation patterns encountered in the 14 balanced and 15 unbalanced cases of X-autosome translocations reported to date. Selection of X inactivation is not an inherent characteristic of the X chromosome per se, and it is not dependent on the direction of chromosomal exchange, as was suggested previously. Correlation of the phenotypic and cytogenetic features of these patients suggests a pattern of X and autosomal inactivation consistent with the least amount of genotypic and phenotypic imbalance in most cases. The data are most consistent with random X inactivation followed by selection of the most viable cell line.


A genetic electrophoretic variant of human hair alpha polypeptides.

The structural proteins of hair were solubilized by reduction of disulfide bonds in 6 M urea at alkaline pH. Following conversion of the proteins to the S-carboxy-methyl derivatives, disc electrophoresis was done in 6 M urea at pH 8.3. In about 5% of the individuals studied, a variation in the normal electrophoretic pattern was observed, and this was true of hair from different body sites. An autosomal dominant mode of inheritance was found in the four families investigated. The variant pattern was not associated with any detectable change in the color, shape, stree-strain characteristics, X-ray diffraction pattern, or amino acid composition of the hair. A similar variant pattern was also observed in nail. The most likely hypothesis is that there is a polymorphism of one of the alpha polypeptides, although a mutation of a rate-determining gene cannot be excluded.


Probable genetic linkage between a locus for human urinary pepsinogen and the HL-A loci.

The genetic basis of familial variation in the relative intensities of human urinary pepsinogen isozymes is not completely clear from family studies. An investigation of the linkage relationships of pepsinogen isozyme 5, considering only segregation for the presence or absence of Pg 5, yields a peak lod score of 4.1 at theta = .1 for linkage with HL-A1 or HL-A2. Added to data from segregation interpreted according to a scheme proposed for the inheritance of intensity differences in Pg 5, the peak lod score becomes 3.0 at theta = .2. Data derived from the segregation of pepsinogen isozyme 4, possibly determined by an allele to that controlling the presence or absence of Pg 5, further reduces the total lod score at theta = .2 to 2.9. The results indicate probable linkage between a locus for urinary pepsinogen and the HL-A loci, but are insufficient to permit any conclusion concerning possible heterogeneity in the linkage relationships of Pg 4 and Pg 5 to HL-A.


Genetic studies in relation to Kuru. VI. Evaluation of increased liability to Kuru in Gc Ab-Ab individuals.

The validity of the reported association between GcAb and kuru is analyzed. Phenotypes with one or more GcAb genes have an increased incidence of the disease at the expense of Gc 1-1 and Gc 2-2. Incidence ratios of kuru associated with various phenotypes examined over the linguistic groups studied indicate that only Gc Ab-Ab persons have a significantly greater chance of dying of kuru. The association X2 for the incidence ratio for those phenotypes possessing only one GcAb gene is significant, but there is significant heterogeneity between groups studied. Those of the Gc Ab-Ab phenotype are six times as likely to contract kuru as the baseline group. Criticisms of this analysis include difficulties defining an adequate control group in such heterogeneous populations, errors in determination of Gc phenotypes, inclusion of persons incubating kuru in the control groups, and questions of validity of statistical tests in isolated inbred populations.


Analysis of family resemblance. V. Height and weight in northeastern Brazil.

Sib correlations for height and weight decrease with absolute age difference. Parent-child correlations increase with age of child, with greater resemblance to the mother than the father. Estimates of the relative variance due to common environment are greater, and heritability estimates less, than for earlier studies. Heritability is less for adults than children. There is no significant major locus for height or weight.


Genetics of acheiropodia (the handless and footless families of Brazil). VI. Formal genetic analysis.

A genetic analysis is presented of data from 22 Brazilian sibships with cases of acheiropodia (the handless and footless families of Brazil). Segregation  analysis performed using a 16K CDC 3100 computer showed a segregation frequency of .245 +/- .040, which is close to the expected value of .25. No sporadic cases were detected. The ascertainment of the probands was through multiple incomplete selection (pi = .55 +/- .07). The data are consistent with the hypothesis of an extremely rare autosomal recessive gene as the etiological factor in acheiropodia. Prevalence is estimated as 29 +/- 4, which is the same as the number of high risk cases; gene frequency equals .0009 +/- .0005, and the incidence at birth is 4 times 10(-6) by the indirect method or 7 times 10(-6) by the direct method. The frequency of heterozygotes at birth is assumed to be 0.18% (450 times the frequency of affected). Population size is approximately 10 million, and the number of founders on a unique-mutation hypothesis is estimated as about 500. All these estimates are first approximations and must be accepted with caution.


Anomalous inheritance of Ss in a Caucasian family.

An unusual allele at the Ss locus with no S or s antigenic representation was found in 3 generations of a Caucasian family. Traveling with N, this genetic determinant was detected because of an apparent maternal exclusion.


Quality of pharmaceutical care in hospitals.

The objective of this study was to measure the quality of pharmaceutical services provided to hospital inpatients. Using Donabedian's model, normative standards from the Joint Commission on Accreditation of Hospitals and the American Society of Hospital Pharmacists were used to develop a personal interview schedule to access the structure and process components of pharmaceutical services. To determine the effect of bed size, rural vs. urban, and presence of a full- or part-time pharmacist on the quality of pharmaceutical services, three samples of short-term hospitals were drawn: a random sample of Mississippi hospitals with less than 100 beds; all Mississippi hospitals of 100 or more beds; and a sample of hospitals in Philadelphia, Pennsylvania. In each of the 112 hospitals a personal interview was conducted with either the chief pharmacist or the administrator responsible for the pharmaceutical service. The responses to the items were then tabulated and a structure and a process score were obtained for each hospital. The following conclusions can be made: (1) The quality of the "structural" components is positively related to the bed size and not to whether the hospital is located in a rural or urban setting; (2) the quality of the "process" components is related to both the bed size and the location of the hospital--hospitals having 100 or more beds or located in an urban area have a higher process quality than those having less than 100 beds or located in a rural area; and (3) hospitals employing a full-time pharmacist have a higher quality of care than those who do not.


Mass reconstitution of neutral cephalothin sodium using tandem sequence filling.

A procedure is described for reconstituting and packaging neutral cephalothin sodium in large numbers of underfilled minibags for i.v. bolus administration. A special rack to hold six 20-g Keflin vials was designed for the procedure which employs an automatic pipetting device in a laminar air flow hood. A reconstitution deck and needle holder are used in the admixing stage. The minibags are frozen and later thawed prior to dispensing. The average labor and material cost (excluding drug and minibag) ranges from $0.195 to $0.124 per minibag depending on batch size. The 20-g neutral cephalothin sodium vial improves speed of reconstitution and does not require transfer into an intermediate container during the packaging cycle.


Fat emulsion vehicle for intravenous administration of an aqueous insoluble drug.

Formulation of a sterile preparation for the parenteral administration of a water insoluble drug is described. Methyl CCNU was first dissolved in absolute alcohol and slowly added to a fat emulsion, Intralipid. The preparation was found to be stable for eight hours at room temperature and seven days under refrigeration. After administration of the preparation to approximately 100 patients, no significant side effects were attributed to the fat emulsion.


Room temperature stability of drug products labeled for refrigerated storage.

The stability at room temperature of many pharmaceutical products labeled for storage under refrigeration is presented. The data were obtained through a survey of manufacturers. It is observed that many drug products labeled for refrigerated storage are stable at room temperature for extended periods.


Hospital radiopharmacy training program.

Training of radiopharmacists, including self-study and a hospital short-term course, is discussed. A systematic approach for self-study is suggested. The 30-day hospital training program described includes both didactic material and on-the-job experience.


Pharmacist's role in management of hypertensive patients in an ambulatory care clinic.

A program involving a pharmacist in the management of ambulatory hypertensive patients is discussed. A hypertension monitoring protocol was developed by a physician and a pharmacist. The protocol provided for initial patient assessment and treatment by the physician, counseling and education of the patient by the pharmacist, patient follow-up by the pharmacist every one to two months and follow-up by the physician every four to six months. In the first four months of the program, 28 of 75 newly diagnosed hypertensive patients were referred by the physician to the pharmacist for follow-up.


Pharmacist and physician evaluation of drug information sources.

A survey was conducted to compare how pharmacists and physicians in Tennessee rated six sources of drug information (journals, textbooks, physicians, pharmacists, the Physicians' Desk Reference and detail men) in nine different categories. A one-page questionnaire was mailed to a 10% random sample of pharmacists and physicians. The physicians rated professional journals and the PDR consistently good and rated the pharmacist poor as a source of drug information. Pharmacists rated textbooks good and rated physicians poor for some categories of information. Both groups found the available information in certain categories to be inadequate.


Patient profile card used in clinical pharmacy services.

The patient profile card used in the provision of clinical pharmacy services at the University of Iowa Hospitals and Clinics is discussed. The desirable aspects of the profile card are its (1) completeness, (2) flexibility, (3) portability and (4) documentation of service. Its current applications and possible additional applications in patient monitoring are described.


Bradycardia-hypotension syndrome in acute myocardial infarction. Reappraisal of the overdrive effects of atropine.

Sixty-eight (17 per cent) of 380 patients with acute myocardial infarction had the bradycardia-hypotension syndrome (ventricular rate below 60/min and systolic blood pressure less than 100 mm Hg) during the first 24 hours of admission to a large general hospital. In 61 of the 68 patients, the administration of atropine significantly increased the heart rate (from 46 plus or minus 14 to 79 plus or minus 12/min) (p less than 0.01) and systolic blood pressure (from 70 plus or minus 15 to 105 plus or minus 13 mm Hg) (p less than 0.001). In 26 of the 68 patients, ventricular premature complexes decreased from 9.4 plus or minus 3/min to 2.4 plus or minus 0.7/min (p less than 0.001) after the administration of atropine. It is concluded that the bradycardia-hypotension syndrome is not an uncommon complication following acute myocardial infarction and that selected doses of atropine may have a beneficial effect without significant complications.


Negative influences of ascites on the cardiac function of cirrhotic patients.

Right and left ventricular function was evaluated in 21 men with cirrhosis and tense ascites during staged removal of ascitic fluid. During paracentesis it was observed (1) that there was a significant increase in cardiac output, stroke volume, right and left ventricular stroke work and mean rate of systolic ejection; (2) that up to a certain stage of drainage (about 5,000 ml), there was a relationship between the amount of fluid removed and the intraabdominal and right atrial pressures and (3) that there was a direct relationship between improvement of cardiac function and normalization of right atrial pressure. It is believed that the increased intra-abdominal hydrostatic pressure acting upon the diaphragm affects the intrathoracic pressure to such an extent that the transmural filling pressure of the heart is reduced, and the mean pressure and respiratory pulsations of the right atrium increased, all of which impede venous return. Improved cardiac function during paracentesis appears to be due to an augmented filling of the heart and to a larger venous return.


Coagulopathy in Ruptured or Dissecting Aortic Aneurysms.

A consumption coagulopathy was demonstrated in each of four patients with either ruptured aneurysm of the aorta or a dissecting aortic aneurysm. The most prominent features of this disorder were (1) a prolonged prothrombine time due to a decrease of one or more clotting factors, and (2) formation of fibrin and fibrinogen degradation products. Recognition of this coagulation disorder could be a valuable diagnostic tool to differentiate a ruptured or dissecting aortic aneurysm from other conditions with a similar acute onset. The coagulation disorder could be due to liberation of coagulant material from the aortic wall into the circulation or to an accumulation of clotting factors at the site of the lesion, secondary to the local exposition of tissue factors from the torn arterial wall. The probability of the latter mechanism is suggested by the local increase of radioactivity after the injection of 125I-fibrinogen.