Minor components of reduced bovine kappa-casein.

Bovine kappa-casein reduced with 2-mercaptoethanol was fractionated on a DEAE-cellulose column to one nonadsorbed, five major adsorbed and two minor adsorbed fractions. The properties of the nonadsorbed and five major adsorbed fractions were reported in our previous paper (4). In this paper, the characteristics of two minor adsorbed fractions (P-X and P-Y) were reported. Gel electrophoretic patterns of these fractions were similar to kappa-casein. These fractions had the same amino acid composition and the same phosphorus content as the major components. P-X contained one residue each of N-acetylneuraminic acid, galactose and galactosamine, and P-Y two residues each. Furthermore, these fractions showed the stabilizing ability for alpha s1-casein in the presence of calcium ion. These results indicate that P-X and P-Y are minor components of reduced bovine kappa-casein.


Dynamic contributions of the components of binocular vergence.

Experimental results from step stimulation of the two major dynamic components in ocular vergence showed that while fusional covergence dominated a coordinated binocular vergence movement, accomodative convergence always contributes to the dynamic response. A quantitative analysis of component dynamics, both in isolation and during coordinated movements, indicates that these components are additive at least through a portion of the movement. Two alternative hypotheses are presented for the role of accommodative convergence during the period immediately following a binocular vergence movement.


The Mandelbaum effect: evidence for an accommodative bias toward intermediate viewing distances.

Previous research has shown that ocular accommodation tends to correspond to an intermediate distance, the dark focus, in the absence of effective stimulation. The present experiments measured accommodative responses in the presence of two adequate, monocular stimuli superimposed optically at different distances. In Experiment I, observers attempted to maintain a matrix of letters in clear focus as a superimposed mesh screen was varied in distance. In experiment II, observers were instructed to focus the "easier" of two similar grating patterns that were presented over a range of distances with a constant separation of two diopters. The results of both experiments showed an accomodative response bias toward target distances near the observers' dark focus of accommodation. The implications of these findings for the theoretical resting state of accomodation and for practical problems of visual performance are discussed.


Bandwidths of orientation channels in human vision.

The ability of observers to discriminate between stimuli differing in orientation was measured using low contrast, foveally viewed stimuli. Detection and discrimination performance were measured simultaneously. A model is presented which permits bandwidths of orientation-tuned mechanisms to be estimated from the data. In a group of five observers, half-amplitude bandwidths varied from 10 degrees to 20 degrees.


Flicker sensitivity measured with intermittent stimuli: I. Influence of the stimulus duration on the flicker threshold.

Flicker tresholds have been measured with intermittent stimuli as a function of the presentation time of the stimulus. The periods of flickering light were separated by 1-s dark intervals. Under these conditions the flicker threshold depends on the stimulus duration and on the number of cycles in the stimulus. The "De Lange" curves measured in this way can be described by a first-order high-pass filter in combination with a fourth-order low-pass filter.


Flicker sensitivity measured with intermittent stimuli: II. Comparison between temporal gradient detection and the "De Lange" curves.

The threshold gradient for perception of a linear change in luminance with time has been measured as a function of the stimulus duration. These data are compared with the "De Lange" curves representing the flicker sensitivity measured with intermittent presentation of the stimulus as a function of the stimulus duration. For this purpose it is necessary to take into account the fact that a linear luminance gradient, being a relatively low-frequency signal, is affected less by the low-pass filter supposedly situated in the visual system than by a sinusoidal signal (flicker) of the same duration.


Study of eccentric fixation with secondary visual feedback.

Secondary visual feedback (2VFB) is a visual signal derived from continuous measurement of eye position and provides an extra artificial indication of the point of gaze. 2VFB may be eccentrically displaced and subjects are able to visually superimpose 2VFB onto a visual target signal and thus achieve and maintain eccentric fixation. Initial transient patterns of movement depend upon training but even naive subjects can achieve eccentric fixation within the first 40 s of such a task. Individual strategies and idiosyncratic patterns are exaggerations of normal control and fixational eye movements. The variance of maintained fixation increases with eccentricity and appears to be related to visual acuity as well as to precision of ocular motor control.


Psychophysical evidence for global feature processing in visual texture discrimination.

By defining texture as a global feature attained by integration over the image domain, we show that texture discrimination can be predicted for a special class of visual textures (composed of paired dots) as a function of such global features. We derive a psychophysical law based on these global features and show that differences in the variance of orientation, but not of dipole length, result in texture discrimination.


Hierarchical detection structures in vision.

A simple example shows that a hierarchy of visual cells can display different behavior for different stimuli. Stimuli with spatial characteristics similar to the receptive fields of a given level in the hierarchy can display summation behavior revealing the organization of that level; but other stimuli may show the organization of cells at other levels. On the other hand, such behavior may not actually occur in vision because the required nonlinearity between levels is very specific and may not be physiologically realistic.


The possible role of the fibroblast in granuloma-induced bone resorption in the rat.

Granulomas were produced over the calvaria of rats by injection of a mixture of turpentine and peanut oil. The granulomas induced localised areas of bone resorption and these resorptive lesions were examined at the fine structural level. A close association was found between osteoclasts and fibroblasts at resorbing surfaces. Furthermore, fibroblasts but not osteoclasts were observed to engulf and phagocytose bone collagen fibrils. It is suggested that the fibroblast either alone or in collaboration with the osteoclast is involved in the destruction of bone collagen during chronic inflammatory disorder of bone.


Ultimobranchial body cysts in the human foetal thyroid: pathological implications.

In a histological study of 28 human foetal thyroids, ultimobranchial body cysts were found in seven foetuses. Large oval cells were seen adjacent to or within the cysts. There is a morphological resemblance between the cells associated with the ultimobranchial cysts and those of medullary carcinoma of the thyroid gland. This similarity, in humans, substantiates the hypothesis that medullary carcinoma arises from the parafollicular cells, which themselves are known to differentiate from ultimobranchial body tissue.


An experimental assessment of macroscopic enzyme techniques for the autopsy demonstration of myocardial infarction.

Experimental cardiac infarction produced in dogs by coronary artery ligation has been used to investigate the value of macroscopic histochemical enzyme loss in the diagnosis of myocardial infarction at post-mortem. Creative phosphokinase and non-specific dehydrogenase methods gave the best results but became positive only 5-6 hr after infarction. It is concluded that the method is of limited value in autopsy practice.


Chronic diarrhea of childhood and the misuse of elimination diets.

A prospective study was undertaken of 108 children referred for outpatient evaluation of chronic recurrent diarrhea. The majority of the children did not have a serious underlying disorder. Elimination diets (milk free, egg free, wheat free) were widely prescribed for the treatment of chronic diarrhea and were given for longer intervals than originally recommended. Elimination diets sometimes resulted in inadequate caloric intake and failure to thrive. Wheat (gluten)-free diets were prescribed for over one month in 59% of children without a specific diagnosis being made. These findings indicate that elimination diets are frequently misused, and prolonged adherence to elimination diets may result in nutritional damage. The indiscriminate use of wheat-free diets for the treatment of chronic diarrhea may be masking the diagnosis of celiac disease and may account for the low incidence of this disorder in the United States.


Late metabolic acidosis: a reassessment of the definition.

The term "late metabolic acidosis" is generally used to define a population of apparently healthy LBW infants who fail to grow and have a base deficit in excess of 5 mEq/l (CO2TOT less than 21 mM). A relationship between hypobasemia and the lack of appropriate growth was postulated. This conclusion was reached, however, in the absence of adequate information regarding the distribution of acid-base variables in healthy LBW infants. The results of this study demonstrate that the CO2TOT of LBW infants (n = 114) rises between birth and three weeks of life from a mean of 18.6 to 20.3 mM. The frequency distribution of CO2TOT values did not show any significant deviations from normality, and 2 SD included values as low as 14.5 mM. No difference in the rate of growth was detected between "hypobasemic" infants given a solution of bicarbonate calculated to bring their blood CO2TOT to greater than 21 mM and those given similar amounts of isotonic saline solution. The ability of the LBW infants to excrete an ammonium chloride load was not related to their acid-base status and was comparable to that of term infants. It is apparent that the definition of late metabolic acidosis needs to be reconsidered.


Thymus size and its relationship to the respiratory distress syndrome.

Thymic size can be affected by both exogenous and endogenous glucocorticoids. The risk of respiratory distress syndrome is reduced after maternal steroid administration. To find whether fetal lung maturity correlates with size of the thymus, the cardiothymic:thoracic ratio was measured in 167 newborn infants with and without RDS. Mean CT/T was significantly greater (0.40 vs 0.35; P less than 0.001) in those babies with RDS. This relation was independent of gestational age, although an increase in CT/T with advancing gestational age was shown. Prepartum maternal steroid administration did not result in significant involution of the cardiothymic shadow when compared with control infants with and without RDS. The CT/T may be of use in predicting which premature babies are more likely to develop RDS.


A study of attitudes and support systems of inner city adolescent mothers.

Because the simultaneous demands of adolescence and motherhood could result in special infant rearing attitudes and concerns, a prospective pilot study of inner city adolescent mothers was undertaken. A sample of primiparous adolescent mothers was compared with primiparous and multiparous nonadolescent mothers. Data were collected by home interviews at two weeks and three months postpartum. The major hypothesis, that the simultaneous occurrence of adolescence and motherhood would result in special infant rearing attitudes, concerns, and support systems which interfered with mothering, was not fully supported by our findings. Few of the adolescent mothers were married (8%) but of those not married, most (95%) lived in an extended family. Adolescent mothers, when compared with older mothers, were more likely to seek medical advice from their mothers as opposed to health professionals and were more insecure in their maternal self-image if caretaking was shared. Attitudinal differences around feeding were seen, but attitudes about spoiling, perception of the baby's behavior, discipline, caretaking, and enjoyment were the same among groups. Adolescent mothers and their infants provide physicians and other child health professional with a special pediatric family. The differences in available support systems and maternal self-image suggest areas for further investigation.


A longitudinal study of body fatness in childhood and adolescence.

Data from the United States Health Examination Surveys were analyzed to determine changes in body fatness between childhood and adolescence. A national probability sample (2,177 children) was examined in both Cycle II (6 to 11 years) and Cycle III (12 to 17 years) of these surveys and comprised the study cohort. The interval between examinations was three or four years. Adiposity was measured as skinfold thickness and correlations between childhood and adolescent adiposity were explored. High rank-order correlations were found between the two examinations for each race-sex group (P less than 0.001). The relationship between childhood and adolescent fatness was independent of stature, skeletal and sexual maturation, and economic status. Childhood fatness was the most predictive factor for adolescent fatness. This strong relationship indicates that the potentially obese adolescent can be identified during childhood.


Ventilatory functions of normal children and young adults--Mexican-American, white, and black. I. Spirometry.

This is a study of the ventilatory functions of 1,805 normal Mexican-American, white, and black students of six public schools in Houston, Texas, with ages ranging from 7 to 20. A roll-seal piston type spirometer was used. The best performed forced vital capacity curve of each student was selected by the computer program from which the following measurements were extracted: FVC, FEV1, FEV1/FVC ratio, PEFR, and MMEF. Each student also had the peak expiratory flow rate measured by the Wright peak flowmeter to establish normal values with this instrument. Significant differences of lung volume and flow rate exist among the three races, and between male and female subjects. Prediction equations and prediction curves for each race and sex are presented. The results of the present study are compared with those of previously published works.


Separation experiences: a new look at an old topic.

Research findings on the effects of separation are reviewed. Children of working mothers develop as well as those whose mothers remain at home. The effects of day care for very young children depend very much on the quality of care provided. Admission to hospital is stressful for preschool children through separation from the family, lack of opportunity to form new attachments, a strange environment, and disturbed parent-child relationships on return home; recurrent hospital admissions may have long-term sequelae, especially in children under chronic stress. An institutional upbringing need not impair cognitive development, but multiple rotating caretakers are likely to interfere with social development. Broken homes are associated with psychiatric disorder only in so far as they reflect family discord and disharmony. Bereavement is most likely to lead to prolonged grief reactions in older children and adolescents. Forced separations of mother and infant in the neonatal period may damage parent-child relationships. Many mechanisms are involved in these different experiences, and in only a few is the separation itself the main stress.


Lung function in children following repair of tracheoesophageal fistula.

Lung function and bronchial reactivity by methacholine challenge were studied in 24 patients seven to 18 years after repair of type I tracheoesophageal fistula. Only one patient had no abnormalities of the variables tested. Thirteen patients had obstructive airways disease, five had a restrictive defect, and 15 had a positive methacholine challenge. It is postulated that continuing subclinical aspiration of esophageal contents causes lung damage and renders the airways hyperreactive.


Chlamydial infection of mothers and their infants.

In 340 women, cultured prospectively during their pregnancies, the rate of infection with Chlamydia trachomatis was 8.8%. The women with positive cultures tended to be younger and more often single and black than their counterparts with negative cultures. There were no statistically significant clinical differences between the two groups. Eighteen children born to Chlamydia culture-positive women and 16 born to negative women were followed for nine months to examine the potential effects of maternal infection on infant growth, development, and illness. Eleven of 18 study patients had culture or tear antibody evidence of Chlamydia infection, as opposed to one of the control subjects (P = 0.00093). Eight of these 11 had clinical conjunctivitis, and two of the eight developed pneumonia. Growth retardation and developmental abnormalities were not detected in either group. It is concluded that maternal carriage of C. trachomatis is associated with a high incidence of clinical illness in the offspring.


The use of plasma androstenedione in monitoring therapy of patients with congenital adrenal hyperplasia.

Therapy of congenital adrenal hyperplasia tranditionally is monitored by the amount of urinary 17-KS. However, 24-hour urine collections are difficult to obtain and are often unreliable. Measurement of the plasma concentrations of androgens, such as delta or T, would therefore be a more convenient way to determine the efficacy of treatment. Over a period of 2 to 24 months, 23 patients were periodically assessed by clinical examination, bone age, and determinations of plasma delta, plasma T, and 24-hour urinary 17-KS. Plasma T concentration correlated well with clinical control in females and in preadolescent males, but not in infant and pubertal males. By contrast, plasma delta concentration correlated well with clinical control in either sex, regardless of stage of puberty. The present study suggests that monitoring plasma delta concentration is useful in the long-term management of patients with CAH.


Autoantibodies to Tamm-Horsfall protein associated with urinary tract infections in girls.

Girls with various forms of urinary tract infections and a reference material were analyzed for autoantibodies in serum to the Tamm-Horsfall glycoprotein. Such antibodies could be detected in all sera analyzed. In the control subjects cord blood contained very low IgA and IgM anti-TH, which increased significantly up to the age of 8 months. The IgG anti-TH levels in cord blood correlated with maternal levels. After the age of 2 months the IgG anti-TH followed the anti-TH levels of the other immunoglobulin classes. Among the infants aged 2 to 7 months with acute UTI, no anti-TH increases were found. In girls more than one year of age with acute nonobstructive UTI, IgG and IgA anti-TH levels were significantly higher in those with acute pyelonephritis and reflux, with or without parenchymal reduction, than in those with acute pyelonephritis and normal radiologic findings. The latter group had significantly higher levels of IgG and IgA but not IgM anti-TH than did those with acute cystitits. In contrast, girls with renal parenchymal reduction but no signs of infection at the time of testing had significantly depressed anti-TH levels compared to control values.


The neonatal blood count in health and disease. I. Reference values for neutrophilic cells.

Reference ranges for absolute total neutrophils/mm3, absolute immature neutrophils/mm3, and the fraction of immature to total neutrophils (I:T proportion) during the first 28 days of life are developed from 585 peripheral blood counts obtained from 304 normal neonates and 320 counts obtained from 130 neonates with perinatal complications demonstrated to have no statistically significant effect on neutrophil dynamics. Perinatal factors other than bacterial disease which significantly alter neutrophil dynamics include maternal hypertension, maternal fever prior to delivery, hemolytic disease, and periventricular hemorrhage. The predictive value of these reference ranges in identifying bacterial disease in the first week of age varies with the neutrophil factor evaluated and the clinical setting. Neutropenia in the presence of respiratory distress in the first 72 hours had an 84% likelihood of signifying bacterial disease, whereas neutropenia in the presence of asphyxia had a 68% likelihood of signifying bacterial disease. An abnormal I:T proportion had an accuracy of 82% and 61%, respectively, in the same clinical settings. Elevations of either immature or total neutrophils were less specific. Interpretation of abnormal neutrophil factors must include consideration of both infectious and noninfectious perinatal events.


Eosinophilia in premature infants: relationship to weight gain.

Serial eosinophil counts were determined in 38 hospitalized, appropriately grown premature infants whose gestational ages ranged from 27 to 35 weeks. Absolute eosinophilia (greater than 700/mm3) was documented in 76% (29/38). Eosinophilia was mild (700 to 999/mm3) in 9, moderate (1,000 to 2,999/mm3) in 17, and marked (greater than or equal to 3,000/mm3) in 3 patients. The average time of onset was day 19. Peak eosinophilia was usually seen within one week of onset and lasted an average of 16 days. A consistent relationship (r = 0.86) was found between the day of peak eosinophilia (mean = day 27) and the day on which birthweight was regained (mean = day 22). No association was apparent between the occurrence or degree of eosinophilia and gestational age, birth stress, presence of umbilical catheter, parenteral alimentation solution, and time of beginning or type or oral feeds. The data suggest that eosinophilia is strongly associated with the establishment of an anabolic state.


Hyperlipoproteinemia and multifocal neurologic dysfunction in systemic lupus erythematosus.

Two patients with systemic lupus erythematosus, including one with neuropathologic findings, had recurrent multifocal neurologic dysfunction and hyperlipoproteinemia. The lipoprotein disturbances were complex and variable over time. Deficient lipoprotein lipase was found in both patients and appeared to be related temporally to neurologic deterioration. One of these patients had neurologic disease and lipoprotein abnormalities 2 1/2 years before SLE could be documented serologically. These studies suggest that lipoprotein lipase deficiency may be a marker for the endothelial disorder causing cerebral vasculopathy in SLE.


Holt-Oram syndrome.

The autosomal dominant association of upper extremity skeletal defects with congenital heart disease is known as the Holt-Oram syndrome. We reviewed our experience with 39 affected patients of whom 15 were considered new mutations. Wide varieties of skeletal defects and congenital heart disease were observed, and the severity of skeletal involvement did not parallel that of cardiac disease. These patients demonstrate four previously unemphasized points: (1) There is a striking asymmetry of skeletal involvement, with the left side more severely affected. (2) Patients with skeletal defects alone can transmit both skeletal and cardiac defects to their children. (3) Hypoplastic peripheral vessels may be an associated abnormality and can result in difficulty with cardiac catheterization. (4) Electrocardiographic changes of terminal conduction delay in the right anterior chest leads were nor uniformly present in patients with otherwise typical secundum atrial septal defects.


The amniotic band disruption complex: timing of amniotic rupture and variable spectra of consequent defects.

Seventy-nine patients with the amniotic band disruption complex, including 54 infants with multiple system involvement and 25 with affected limbs alone, were evaluated. No two cases of the disorder were exactly alike. Defects varied from simple digital band constrictions to major craniofacial and visceral defects; fetal death may also occur. Amniotic rupture appeared to cause injury through three basic mechanisms: (1) interruption of normal morphogenesis; (2) crowing of fetal parts; and (3) disruption of previously differentiated structure. Comparison of 35 cases in which the timing of amniotic rupture could be estimated suggests that early amniotic rupture results in multiply affected infants who are frequently aborted or stillborn, whereas later rupture results primarily in limb involvement. Our findings indicate that both the spectrum of the developmental pathology and the nature of fetal outcome are determined by the timing of amniotic rupture. Appreciation of the mechanism which explains the disparate appearances of infants with the amniotic band disruption complex will allow more acurate diagnosis and appropriate counseling with respect to the sporadic nature of the disorder.


Primary pulmonary hypoplasia in the neonate.

Infants with primary pulmonary hypoplasia with respiratory distress immediately after birth, but usually elude early diagnosis. They have no other abnormalities, but frequently develop signs and symptoms of the PFC syndrome. Roentgenographically, they show small, clear lungs and are prone to develop complicating pneumothoraces. The clinical, roentgenographic, and pathologic features of eight infants with primary pulmonary hypoplasia are presented.


Indomethacin and renal function in premature infants with persistent patent ductus arteriosus.

Renal function during indomethacin treatment was studied in 12 premature infants with patent ductus arteriosus. Decreases in urinary flow rate, GFR, and CH2O by 56, 27, and 66%, respectively, occurred during Indo therapy. Urinary excretion rates of ions were also reduced: Na by 70%, Cl by 79%, K by 40%. These changes were accompanied by slight decreases in plasma sodium concentration and osmolality. Except for GFR and urinary Na and osmolality, all these functions returned to pretreatment values one to two weeks after stopping the drug.


Patent ductus arteriosus treated with ligation or indomethacin: a follow-up study.

The course and complications of fifty-two infants with patent ductus arteriosus requiring closure were assessed prospectively. Twenty-six infants with a PDA received indomethacin for pharmacologic closure of the PDA, and 26 underwent ligation. The current study analyzes and compares the longitudinal follow-up with respect to somatic growth, neurologic function, psychomotor and mental development, and renal, ophthalmologic, and audiologic function in 21 infants in each group who entered the follow-up. No selective morbidity was attributable to PDA closure with indomethacin when compared to surgically treated infants.


Refractory hypoxemia associated with neonatal pulmonary disease: the use and limitations of tolazoline.

Thirty-nine critically ill infants with pulmonary disease received tolazoline because of severe hypoxemia refractory to administration of 100% O2 and mechanical ventilation. Twenty-seven (69%) of the infants responded with an increase in PaO2 greater than or equal to 20 torr in the first umbilical arterial gas after completion of the initial ten-minute infusion (1 to 2 mg/kg) of the drug. A response was not correlated with survival. The overall survival was 46%, essentially unchanged from our previous report (44%). Infants with hyaline membrane disease had the poorest survival rate (33%). Complications associated with the use of tolazoline occurred in 82% of the infants. A hypotensive reaction, defined as a 25% decrease in mean arterial pressure from the pre-tolazoline level, occurred in 67% of the infants, and more commonly in the infants with RDS (87%). In 11 infants who did not respond to the initial dose of tolazoline, the dose was increased up to 10 mg/kg/hour; only one infant responded, and eight (73%) had a hypotensive reaction.


Direct and indirect pulmonary vascular effects of tolazoline in the newborn lamb.

The pulmonary vascular effects of tolazoline were studied in unsedated newborn lambs during normal oxygenation and hypoxia. Direct and indirect pulmonary vascular responses were analyzed separately. During normal oxygenation, tolazoline (1 mg/kg) given into a branch pulmonary artery increased cardiac output while decreasing systemic and pulmonary resistances. Pulmonary flow distribution did not change, suggesting that the fall in pulmonary resistance was due to an indirect rather than a direct action of the drug. Tolazoline had similar effects on systemic and pulmonary resistances in the hypoxic lamb; however, there was a shift in blood flow toward the injected lung, indicating local pulmonary vasodilation induced by the drug. In either case, tolazoline did not alter the resistance ratio between the injected lung and the systemic circulation. We conclude that tolazoline is a direct pulmonary vasodilator in the hypoxic lamb, but does not appear to lower the pulmonary to systemic resistance ratio.


Low cerebral blood flow: a risk factor in the neonate.

Among 19 infants in whom cerebral blood flow had been determined a few hours after birth, four died during the first days or weeks after birth, all with massive intracranial hemorrhage. The other infants were examined at 9 to 12 1/2 months of age by means of clinical neurologic evaluation, developmental psychologic assessment (Cattell), EEG, and cranial computed tomography. Six of the ten infants who had had CBF of 20 ml/100 gm/minute or less had developed cerebral atrophy as demonstrated at autopsy or by CT scan, none with neonatal flows above 20 had done so. Only one in the low flow group had developed completely normally, whereas abnormal development was found in only a minority of the high flow group. No other neonatal observation had such a clear relationship to later development. It is concluded that CBF of 20 or less during the first hours of life is critical.


Aspirin dosage for infants and children.

The labeled dosage schedule that has long been on pediatric aspirin preparations is at variance with the recommendation in authoritative medical references, studies demonstrating antipyretic effectiveness in children, and the prescribing habits of pediatricians as revealed by a poll conducted by the authors. Aspirin pharmacokinetics are influenced by a number of physiologic factors, as well as by dosage, and complicate the problem of assuring safe and effective pediatric use. Basic pharmacokinetic considerations indicate that the increase in size of individual doses needed to assure therapeutic salicyate blood levels, thereby removing the temptation of parents to administer the drug too often, is made permissible (i.e., safe while effective) by expanding the interdose interval to four hours instead of three. A revised pediatric aspirin disage schedule is presented that better meets the practices of the pediatric community and the needs of consumers.


Comparative effects of naproxen and aspirin on fever in children.

The antipyretic effect of single doses of naproxen, 2.5 mg/kg or 7.5 mg/kg, was compared to that of aspirin, 15 mg/kg, and of a placebo in a double-blind study. Febrile children, hospitalized overnight, were randomly assigned to one of the treatment or placebo groups, and their temperatures were recorded hourly. Naproxen, 7.5 mg/kg, was at least as effective as aspirin in onset of action and reduction of fever, and had a longer duration of action. Each of the three treatments had a significant effect as compared to that of the placebo. There was no difference in the total incidence of side effects among the four groups, but mild gastrointestinal complaints were more common among the patients in the high-dose naproxen group, whereas CNS complaints were more prevalent among the patients in the placebo group.


Hydrocephalus in tuberculous meningitis in children: treatment with acetazolamide and repeated lumbar puncture.

Increased intracranial pressure was found in 36 of 49 children with tuberculous meningitis. Four patients who presented with acute onset died early. Eight patients with obstructive hydrocephalus were treated surgically. In the 24 patients who had communicating hydrocephalus and were treated with acetazolamide and repeated lumbar punctures, treatment was successful in all but two, in whom shunt surgery was needed.


Argentophilic papillae of Schistosomatium douthitti cercariae (Trematoda: Schistosomatidae).

Argentophilic papillae of cercariae of Schistosomatium douthitti were studied by light microscopy. The basic number of body papillae was 56, excluding 20 at the anterior tip. The average number of tail papillae was 18. Average locations and spatial ranges of body papillae indicate a rather constant pattern. Tail papillae showed greater variability in location. Twenty papillae (10 on each side) at the anterior tip of cercariae were associated with gland duct openings. Two types of papillae were recognized with light microscopy--uniciliated bulbs and pits. The papilla pattern of S. douthitti differs from those of other species of schistosomes derived to date, and its constancy supports the usefulness of papillae in systematic studies.


Transintegumental uptake of metabolic substrates in male and female Schistosoma mansoni.

A new method for measuring transintegumental uptake in living schistosomes in vitro has been applied to the study of individual males and females. Uptake of a 14-C labeled test metabolite was compared to that of tritiated water (a highly diffusible reference substance). Use of the short half-life (T 1/2 = 100 min) isotope 113m-Indium, bound to EDTA (ethylene diamine tetra-acetic acid, a nondiffusible reference substance) permitted quantification of the relative amount of 14-C test substance passively adhering to the schistosoma surface. Substraction of this amount provided an estimate of net uptake. D-glucose uptake, as measured by this method, increased with time, approaching equilibrium by two min; a positive correlation between temperature and glucose uptake was also observed. Nondialyzable components in rat, human, horse and fetal calf sera did not enhance glucose uptake. In both male and female schistosomes, minimal uptakes were seen for the nonmetabolizable sugar alcohol mannitol (MW = 182). L-glucose uptake was similarly low, but high uptakes were observed in both sexes for D-glucose. In addition to confirming the stereospecificity of hexose uptake, these studies suggested our technique provides a sensitive method for measurement of both high and low uptake compounds. The uptakes of D-glucose and the L-amino acids--arginine, ornithine, lysine, histidine, phenylalanine and serine--were comparatively higher in female than male schistosomes. Slight elevations in uptake by females were observed for threonine, valine and glycine, but aspartate uptake was slightly higher in males. No dramatic male-female differences were immediately apparent for the uptakes of proline, leucine, isoleucine, tyrosine and glutamate. Schistosomal uptake of L-amino acids that are essential for vertebrates was generally higher than uptake of the nonessential amino acids.


Comparison of carbon and nitrogen content of infected and uninfected snails, Succinea ovalis, and the trematode Leucochloridium variae.

In June, 6.7% of adult Succinea ovalis collected near Urbana, Ohio, were infected with the trematode, Leucochloridium variae. The effects of parasitism were assessed as total organic carbon (equivalent to calorific values) and as total nitrogen. The parasite represents 23.8% of total (parasite + snail tissue) dry tissue weight, 21.4% of total carbon and 19.8% of total nitrogen of infected snails. The higher C : N ratio for parasite tissue indicates a higher proportion of nonproteinaceous compounds (e.g., fats and/or carbohydrates) as compared to host tissue. There is less snail tissue in parasited S. ovalis. The C : N ratios for parasitized and nonparasitized snail tissue suggest identical percentage compositions of proteins, fats, and carbohydrates.


A new species of Breinlia (Breinlia) (nematoda: Filarioidea) from the South Indian flying squirrel Petaurista philippensis (Elliot).

Breinlia (Breinlia) petauristi sp. n. from the abdominal cavity of the flying squirrel, Petaurista philippensis (Elliot), from Kerala, India, is described. Of the 15 recognized species of the subgenus, B. petauristi most closely resembles B. trichosuri in the body size, length of spicules, and number of caudal papillae. The detailed structure of the spicules is, however, markedly different in the 2 worms. This is the third species of Breinlia to be reported from a host other than an Australian marsupial.


Studies on the Onchocerca (nematoda: Filarioidea) found in cattle in the United States. I. Systematics of O. gutturosa and O. lienalis with a description of O. stilesi sp. n.

Onchocerca gutturosa and O. lienalis are redescribed and comparative morphological descriptions provided. In addition, a third species of Onchocerca is described from cattle in the United States. This third species, Onchocerca stilesi sp. n., localizes in the connective tissues around the stifle joint, and can be distinguished morphologically from O. gutterosa and O. lienalis. Onchocerca gutturosa and O. lienalis apparently have widespread distribution in the eastern United States; however O. stilesi has been reported only from Minnesota.


Redescription of Camallanus ancylodirus Ward and Magath 1916 (nematoda: Camallanidae) from freshwater fishes of North America.

Camallanus ancylodirus Ward and Magath 1916 is redescribed, based on examination of syntypes. This species differs from C. oxycephalus Ward and Magath 1916, the only other camallanid described from freshwater fishes of North America, in the size of male worms, number and arrangement of caudal papillae in males, shape of the male caudal end, position of the vulva, and length and shape of the female tail. The host range of C. ancylodirus is not clear from literature reports because the species may have been confused with C. oxycephalus.


Eimeria azul sp. n. (protozoa: Eimeriidae) from the eastern cottontail, Sylvilagus floridanus, in Pennsylvania.

Eimeria azul sp. n. is described from the cottontail rabbit, Sylvilagus floridanus, in central Pennsylvania. The oval oocysts are 19.5--27.0 micrometer by 15.0--19.0 (mean - 22.9 X 16.7 micrometer). The fusiform sporocysts are 7.8--14.0 micrometer by 3.3--6.5 micrometer (mean = 11.8 X 5.8 micrometer). A Stieda Body is present. There is no micropyle, oocyst residuum or polar granule. The sporocyst has a residuum which is variable in appearance. The oocysts are characterized by a blue tint when viewed with an apochromatic objective lens.


The Ornithodoros (Alectorobius) capensis group (Acarina: Ixodoidea: Argasidae) of the palearctic and oriental regions. O. (A.) coniceps identity, bird and mammal hosts, virus infections, and distribution in Europe, Africa, and Asia.

Ornithodoros (Alectorobius) coniceps (Canestrini 1890), which was briefly described from adult specimens from St. Mark's Cathedral, Venice, Italy, has been a confusing taxon. We redescribe and illustrate the adult and immature stages from St. Mark's Cathedral (topotypes) and elsewhere, list criteria to distinguish this species from others in the O. (A.) capensis complex, and provide data for 36 collections, chiefly from nest sites of wild and domestic pigeons in humid, rocky situations, and from a nest of the pallid swift, in Italy, France, Egypt, Kenya, Israel, Jordan, Afghanistan, Ukrainia, and Turkmenia. Other collections of small-sized adults and nymphs, lacking larvae, from pigeon, swallow, and swift nest in Nepal, India, and Sri Lanka, are tentatively assigned to this taxon. This is the only member of the O. (A.) capensis group not associated with marine or wading birds. Humans bitten by O. (A.) coniceps in buildings or caves may suffer from pain, edema, chills, and fever. BAku virus (Reoviridae) has been isolated from this tick in Uzbekistan, but most reports of other viruses and infectious agents are clouded by probable misidentification of O. (A.) maritimus as O. (A. coniceps. Published data on the life cycle and dynamics are reviewed briefly. Previously, this tick has not been reported from the Ethiopian Faunal Region (Kenya).


A malarial parasite of Australian skinks, Plasmodium mackerrasae sp. n.

Plasmodium mackerrasae sp. n. parasitizes the Australian lizards Egernia cunninghami and E. striolata (Sauria: Scincidae). Described from an experimental host, E. whitei, it produces mature schizonts containing 6--12 nuclei arranged peripherally as a rosette, and round to oval gametocytes which are equal to or slightly smaller than host cell nuclei. Both schizonts and gametocytes parasitize all cells in the erythrocyte series. Presence of pigment in both asexual and sexual stages is correlated with maturity of the host cell. Asexual forms contain a single large vacuole, whereas mature gametocytes may show 1--4 vacuoles. Plasmodium mackerrasae resembles most closely P. sasai of Japan and P. tropiduri of tropical America. It differs from P. sasai by lacking fan-shaped schizonts and by having less heavily pigmented gametocytes, and from P. tropiduri by less variability in shape and greater vacuolation of the gametocytes. Host and geographic differences further support its distinction.


Antibody to fibrinogen/fibrin products (Anti-F) in malaria, babesiosis, and trypanosomiasis of rodents.

Antibody to fibrinogen/fibrin related products (Anti-F) was stimulated during the course of Plasmodium chabaudi, Babesia rodhaini, and Trypanosoma lewisi infections in rats. Titers of this autoantibody remained elevated in serum from rats that had recovered from each of the infections. Column chromatographic studies indicated that Anti-F was a 19S globulin, possibly IgM. During acute infections high titers of Anti-F were associated with elevated titers of cold-active hemagglutinin (CAH) and immunoconglutinin (IK) and all were associated with anemia and elevated parasitemia. Titers of Anti-F and IK, but not CAH, remained elevated in serum of recovered rats. The presence of Anti-F indicated that the coagulation system had been activated during each infection to release fibrinogen/fibrin-related products (FRP) to serve as antigen(s) for Anti-F. Since IK is antibody to the third component of fixed complement, it could be assumed that complement fixing antigen-antibody complexes were also present during the acute stage of each infection. The possibility that complexes of FRP and Anti-F could have contributed to anemia in each infection is discussed.


Susceptibility of five strains of mice to Babesia microti of human origin.

One outbred (CF1) and four inbred (BALB/c, C57, CBA and C3H) strains of mice were tested for susceptibility to Babesia microti of human origin. Of these, intact C3H mice developed higher parasitemia than all other intact mice, while BALB/c mice developed the highest parasitemia among splenectomized mice. Susceptibility was not related to H-2 haplotype in any obvious way. Because C3H and BALB/c mice developed relatively high initial peak parasitemias, the parasite was serially passaged in both of these mouse strains in an attempt to increase parasite virulence. After 30 passages in BALB/c and 49 passages in C3H mice over a period of 12 months, maximum parasitemias were 50 times higher than those observed initially. After the peak parasitemias of these two mouse-adapted parasites had stabilized, the relationship between onset and level of maximum parasitemia and number of parasites inoculated was determined. With both C3H- and BALB/c-adapted parasites, as inoculum size increased, the time required to reach maximum parasitemia decreased and the level of maximum parasitemia increased. Studies involving infection of either mouse strain with parasites adapted to the heterologous mouse strain indicated that C3H mice were more susceptible than BALB/c mice to homologous or heterologous parasites. These data suggest that the virulence of B. microti to the mouse can be increased by prolonged passage in this host. Once adaptation to this host species has occurred, virulence appears to be more dependent on the innate susceptibility of the mouse strain than on adaptation of the parasites to a particular strain of mouse.


Trichinella spiralis: an intracellular parasite in the intestinal phase.

Trichinella spiralis has been examined by electron microscopy after fixation in situ in the intestine of mice. The worms lie within the cytoplasm of cells of the intestinal mucosa and may occupy both absorptive and goblet cells. They cause little damage to host cells. A few worms have been seen protruding from tissue by SEM techniques. These unusual observations suggest that the nematodes may be capable of exit and reentry into the epithelium.


The effects of miracidal aging and dilution of snail-conditioned water on responses of miracidia of Megalodiscus temperatus.

Miracidia of Megalodiscus temperatus from newly hatched until 10 hr old were tested for their ability to react to Helisoma trivolvis snail-conditioned water (SCW) by contact with return (CR) to agar blocks and by percentage of miracidia reacting to a point inoculation of SCW as determined by a photographic time exposure method. CR to agar blocks containing 1:50 SCW was greatest during the first 6 hr after hatching but declined  thereafter. The reaction during the first hour to a point inoculation was lower than during the 2nd and 3rd hr. Results were variable from 4 to 10 hr after hatching with the lowest response recorded from 9 to 10 hr. Miracidial responses to dilutions of SCW were assessed by the same two methods. CR to agar blocks containing decreasing concentrations of SCW declined until at a dilution of 1:500 CR was only slightly above the controls. On the other hand, miracidial reactions to point inoculations of SCW as determined by the photographic method were still apparent at a dilution of 1:25,000, when 12% of the miracidia tested reacted. Thus, the photographic time exposure method gives a sensitive means for detecting altered miracidial behavior to various intrinsic and extrinsic factors.


Coccidia of wombats: correction of host-parasite relationships. Eimeria wombati (Gilruth and Bull, 1912) Comb. Nov. and Eimeria ursini Supperer, 1957 from the hairy-nosed wombat and Eimeria arundeli sp. n. from the common wombat.

Coccidial oocysts morphologically consistent with Eimeria ursini Supperer 1957, and E. tasmaniae Supperer 1957 were recovered from the feces of wild and captive hairy-nosed wombats (Lasiorhinus latifrons) in Australia. Eimeria arundeli so. n. was recovered from the feces of wild and captive common wombats (Vombatus ursinus). Eimeria arundeli oocysts are ellipsoidal to slightly ovoid 60.2--67.2 (63.7) X 40.6--47.6 (43.4); micropyle 3 in diameter usually visible; with oocyst wall granular, dark brown and occasionally opaque, 4--7 thick; inner oocyst wall clear, about 1.5 thick; small oocyst residuum present, four sporocysts ovoid 22.4--29.4 (25.8) X 12.6--15.4 (14.1) with protuberant Stieda body; opposite end of sporocyst also often slighly pointed; large granular sporocyst residuum obscuring sporozoites. Gametocytes of E. arundeli sp. n. and of an organism which is consistent with E. tasmaniae, are described developing in the lamina propria of villi in the small intestine. The stages in the hairy-nosed wombat are those described as Ileocystis wombati Gilruth and Bull 1912. It is suggested that the identification of the host of Supperer's E. ursini and E. tasmaniae as V. ursinus was in error and that the allopatric L. latifrons is the natural host. Eimeria tasmaniae Supperer 1957 is suppressed and E. wombati (Gilruth and Bull, 1912) comb. nov. is proposed and redescribed. No schizonts were identified among the endogenous stages, consistent with observations in the literature on other coccidia with similar gametocyte and oocyst structure.


Diclidophora embiotocae sp. n. (Monogenea, Diclidophoridae), a parasite of embiotocid fishes of Oregon.

Diclidophora embiotocae sp. n. is described from adult specimens obtained from the gills of three species of embiotocid fishes from the central coast of Oregon. It differs from all other members of the genus in hosts, geographic location, and in possessing pre- and para-ovarian, as well as post-ovarian testes. Diagnosis of Diclidophora (Yamaguti 1963) is emended.


Bronchogenic cyst.

Two recent patients with bronchogenic cysts, presenting in an atypical manner, stimulated our review of this subject. Twenty patients with bronchogenic cysts have been treated at the Boston Floating Hospital over the past 20 yr. Of these patients, 19 out of 20 were symptomatic, the most common symptom being fever (6 out of 20). Half of our patients had no respiratory symptoms but only one was found to have an asymptomatic mass on chest x-ray. The majority of theses cysts were found within the pulmonary parenchyma, the right lung being affected three times more commonly than the left. These facts are at odds with the reports in the literature. Three were found in the neck. Bronchogenic cysts are generally thought to be small, solitary, and limited in area. However, a significant number in our series (8 out of 20) were large, multiple or multicystic, and involved segments, lobes, multiple lobes, and, on one occasion, an entire lung. The correct pre-operative diagnosis was made in only 30% of the cases. The fact that the diagnosis was often missed led to long delays in treatment resulting in recurrent infectious complications and repeated hospitalizations. The most common cause of error in diagnosis was failure to follow a pneumonia to complete resolution. Despite the frequent delays in diagnosis, surgical treatment was curative in all patients.


Pectus carinatum: results of surgical therapy.

There are a variety of protrusion defects of the anterior chest which are collectively referred to as pectus carinatum. Over a 14-yr period, 13 patients have had surgical correction of pectus carinatum at The Johns Hopkins Hospital. Technique includes costal cartilage resection and a sternal osteotomy. There was no mortality, complications were few and results are good. Repair is recommended for patients in late adolescence due to the cosmetic nature of the procedure, the apparent lack of an associated postural deformity and the good results of operation in this age group.


Tongue lesions in children.

A review of tongue lesions in children showed that there is a great variety requiring operative intervention, often in infancy. While the presenting symptoms may be related to dysphagia and dyspnea, the aim of operative intervention should not only be to salvage life by restoration of breathing and swallowing, but also to leave a tongue capable of adequate speech, taste, sensation, and normal orofacial development. Intimate knowledge of lingual anatomy and function is necessary to allow selection of the ideal procedure and appropriate timing of the therapy. While careful observation and nonoperative approach may be indicated in non-neoplastic macroglossia, early intervention is often necessary in diffuse neoplastic lesions such as lymphangioma, fibromatosis, or fibrolipomatous dysplasia. While malignant tumors are rare in childhood, they do occur and have to ruled out.


Pelvic exsanguination following umbilical artery catheterization in neonates.

Umbilical artery catheterization in 400 newborns was followed by umbilical or hypogastric artery perforation with massive extra- and intraperitoneal bleeding in 7 infants. Common predisposing factors were multiple attempts and insertion against resistance. A characteristic clinical picture developed, including hypotension, abdominal distention, and lower abdominal wall induration and ecchymosis, often extending into the genitalia and upper thighs, with absent femoral pulses. Treatment is immediate transfusion and bilateral umbilical and hypogastric artery ligation. One of seven patients survived.


Mixed gonadal dysgenesis, pathogensis, and management.

Fourteen patients with Mixed Gonadal Dysgenesis who presented as infants or children are discussed. Gonadal asymmetry, and/or sex chromosomal mosaicism, as well as retained Mullerian Ducts characterize the anomaly. The dysgenetic testis may occur as the result of a cascade of development mishaps stemming from abnormalities of H-Y antigen expression or function that lead to abnormal differentiation of the indifferent urogenital ridge and, in turn, to aberrant production of Mullerian inhibiting Substance and testosterone. The latter two cause retention of Mullerian ducts and incomplete masculinization of the external genitalia. Absence of a second X chromosome may lead to the formation of a streak ovary, in which the dysgenetic testis may invoke formation of hilar and medullary cords. Neoplastic transformation, so characteristic of this group of patients, may result from unprotected germ cells and abnormally high and prolonged gonadotropin stimulation. Gonadoblastoma and seminoma-dysgerminomas are the tumors found in the gonads with the risk exceeding 50% as the third decade is approached. Laterality of the gonads in this anomaly remains an enigma. The gonads should be removed at birth if possible and the external genitalia repaired soon thereafter. These patients should be raised as females. The risk of neoplastic transformations must be considered at all stages of management.


Hepatic portocholecystostomy for biliary atresia.

Four infants with biliary atresia had gross obliteration of the common hepatic duct but residual patency of the gallbladder, cystic duct and common bile duct. The patients were treated by hepatic portocholecystostomy utilizing the extant bile ducts for biliary reconstruction. Bile drainage was achieved in all four infants. There was a conspicuous absence of postoperative cholangitis. Subsequent obstruction of the distal ducts in two patients necessitated reoperation and construction of a standard biliointestinal conduit. The other two children are surviving, jaundice-free, 5 1/2 and 5 years after operation with minimal sequelae of biliary atresia. Hepatic portocholecystostomy is a feasible surgical alternative to intestinal reconstruction in patients with biliary atresia in whom the disease is limited to the proximal extrahepatic bile ducts.


Determinants of survival after Kasai's operation for biliary atresia using actuarial analysis.

Survival after Kasai's operation for "noncorrectable" biliary atresia is influenced by (1) age, (2) large bile ducts, and (3) concentration of the bile bilirubin. Critical values are: age less than 10.5 wk, any evidence of a large bile duct, and a bile bilirubin concentration greater than 8.8 mg/100 ml. Using these 3 factors, a predictive model is able to identify a favorable group with an 89% expected 4 yr survival.


Anatomic observations and etiologic and surgical considerations in choledochal cyst.

Twenty-five operative and postoperative cholangiograms in children with choledochal cysts indicated an intimate relationship between these cysts and anomalous pancreatico-biliary ductal junction. In all of these patients the distal main pancreatic duct (MPD) is excluded from the sphinctor of Oddi mechanism and free reflux of pancreatic juice up the biliary tree occurs. This leads to chronic cholangitis, which is presumed to be responsible for the formation of the choledochal cysts. Abrupt and intense exposure of the common bile duct (CBD) to pancreatic reflux may cause perforation and bile peritonitis. Long-standing exposure may induce malignant transformation in the choledochal cyst. Total cyst excision and separation of the biliary system from exposure to pancreatic reflux is suggested as the procedure of choice. Long-term results and metabolic and digestive consequences of this operation are yet to be determined.


Crohn's disease in children and adolescents: is inadequate weight gain a valid indication for surgery?

Seventy children and adolescents hospitalized for Crohn's disease at the University of Michigan Medical Center between 1966 and 1976 are reviewed. Thirty-three of these children were managed medically and 37 underwent a total of 60 operative procedures. There were 33 bowel resections, 7 appendectomies, 4 abscess drainages, 3 bowel bypasses, and 13 miscellaneous operative procedures. The total operative mortality was 1.7%, and there were 10 complications, all of which were successfully managed. Among the 26 children undergoing bowel resections, 22 were below the third percentile for weight preoperatively. Nearly two-thirds of these gained weight to the 35th percentile following resection. The remainder of the children had a variety of growth and symptomatic responses to surgery. Resection aimed at complete removal of diseased bowel can be expected to yield substantial weight gain in children with Crohn's disease.


Liver abscess.

A liver abscess may occur secondary to an umbilical vein catheterization or infection in other parts of the body, and is associated with immune deficiencies, especially chronic granulomatous disease. There are no specific signs and symptoms, but an unexplained fever with upper abdominal tenderness and an enlarged liver were present in all of our cases. A liver-spleen scan is the most useful diagnostic test, demonstrating a filling defect in the liver. A single abscess may be unroofed and drained. When multiple abscesses are found, as many as possible are drained, but long-term specific antibiotic therapy is the most important treatment.


Long-term experience with childhood thyroid carcinoma.

Twenty patients with well-differentiated thyroid carcinoma, 20 yr of age or younger have been treated at Vanderbilt University Hospital. The young patient with thyroid carcinoma frequently presents with far-advanced disease but enjoys an improved survival. Preoperative scintiscanning is useful in the evaluation of patients with childhood thyroid carcinoma. A new noninvasive scan is described and appears to be promising in the preoperative differentiation between benign and malignant thyroid lesions in children and young adults. There is a high instance of nodal metastases, but long-term follow-up would indicate that lobectomy and modified neck dissection are sufficient for most patients. However, total thyroidectomy can be performed safely in those patients with disease in both lobes. Additionalally, frozen section diagnoses were found to be helpful in diagnosing and staging thyroid carcinoma.


Partial gastric wrap-around as an alternative procedure in the treatment of hiatal hernia.

The Allison, Belsey, and Nissen antireflux operations have been widely used over the last 15 yr. A number of problems have followed from these procedures that have prompted us under certain circumstances to seek alternative operations. In the last 2 yr, in selected patients, we have done a partial gastric wrap-around (Dor-Nissen) operation on 16 children from age 2 wk to 13 yr for the following reasons: failed Allison and Nissen repairs, two infants with such a small stomach that only a partial stomach wrap-around was possible, with a Heller cardiomyotomy, and for reflux with or without an accompanying hiatal hernia. All of these Dor-Nissen partial wrap-around operations were technically easy to do and all the postoperative patients have been problem-free both clinically and radiologically. Moreover, the gass bloat syndrome seen with the Nissen fundoplication has not been encountered. We recommended this partial wrap-around antireflux operation as a primary procedure, an alterative to one of the more widely used operations, or when re-operating for recurrence of gastroesophageal reflux.


Nectotizing enterocolitis: is there a place for resection and primary anatomosis?

While most situations of peritonitis, perforation and compromised blood flow in necrotizing enterocolitis are best handled by resection and stoma formation, primary resection and anastomosis should be considered in selected cases. Nine premature infants with NEC underwent bowel resection with primary anastomosis in the face of localized perforation and peritonitis. Eight survived and had no problems when oral alimentation was started. One patient with small bowel involvement underwent two anastomoses rather than a high jejunostomy; the proximal anastomosis leaked and led to the death of the patient.


Prospective application of an index of neonatal necrotizing enterocolitis.

Fifty-five patients were scored 1 to 3 according to the criteria: the character of stools, abdominal findings on palpation, x-ray evidence of pneumatosis intestinalis, the development of pulmonary insufficiency, and the duration of symptoms to positive x-rays. Fifteen patients with scores of less than five were considered to have subclinical NEC with one late death. Twenty-nine of 30 patients with scores of 5-10 responded to medical management with 2 deaths related to recurrent bouts of sepsis without recurrent NEC. Eleven patients required surgery with index scores of 10-14 with 6 deaths occurring uniformly in those patients with scores of 12 or more. Two patients were scored inappropriately low due to the lack of the passage of a stool for analysis. One patient with a score of 4 did not pass a stool but had the other diagnostic criteria for the single false negative of the series. This index correctly determined the severity of NEC of 53 of 55 patients, identified the patients who required surgical intervention and predicted survival.


A comparison of Rorschach developmental level and form-level systems as indicators of psychosis.

Psychotic and nonpsychotic psychiatric inpatients were tested on the Rorschach. "Reality-testing" was measured by four form-level scoring systems designed by Beck, Mayman, Becker, and Wilensky. The psychotic subjects were dichotomized on three diagnostic dimensions: schizophrenia, paranoia, and premorbid social adjustment. No significant differences were found for the Beck system. With the other systems, psychotics showed significantly poorer reality testing than nonpsychotics. No differences were found for the schizophrenic and paranoid dimensions. The Phillips premorbid adjustment score was negatively correlated with all four measures of "reality-testing." The conclusion drawn was that Rorschach measures of "reality testing" are associated with psychotic and poor premorbid functioning, but do not differentiate schizophrenic from nonschizophrenic psychotics or paranoid schizophrenics from nonparanoid schizophrenics.


On the use of symmetry in the Rorschach Test.

Rorschach's justifications for the use of symmetry in his inkblots are evaluated in the light of recent empirical research concerning the perception of symmetry. The role of symmetry in response facilitation, in the production of whole and movement responses, in the creation of similar conditions for left- and right-handers, and as a response determinant, is discussed and re-evaluated.


Discriminative effectiveness of the Senior Apperception Test with impaired and nonimpaired elderly persons.

A means was devised of assessing elderly individuals' responses to the Senior Apperception Test (SAT) that would discriminate emotionally-cognitively impaired from nonimpaired. With a matched sample of known impaired and nonimpaired nursing home residents, SAT protocols were scored on four dimensions, and the best discriminating cut-off scores established. Protocols from a second similar matched sample were tested for discriminative effectiveness of previously established criterion scores. Significant discrimination at .01 or better was obtained for all four dimensions in the predicted direction. False positives and false negatives ranged from 7 to 33%. The best predictor score was Interpersonal-relationships, the poorest was mood. This procedure with the SAT appears to be an effective screening method for impairment, and it provides additional useful clinical information.


Bender-Gestalt emotional indicators and acting-out behavior in young children.

This study was designed to investigate the relationship between 15 emotional indicators on the Bender-Gestalt Test and acting-out behavior in young children. The subjects were 93 children ranging in age from five to 12 years. Each was administered the Bender. A measure of each subject's overt acting-out behavior was then obtained by having teachers rate each student on a Behavioral Rating Scale. Subjects' records were then divided into groups on the basis of both sex and age. Results indicated that neither the total number of Bender indicators nor any of the individual Bender indicators were correlated significantly with total scores on the rating scale. Use of the Bender as a projective device to measure acting-out behavior was seriously questioned.


Hand Test indices of violent and destructive behavior for institutionalized mental retardates.

The Hand Test (Wagner, 1962) and the maladaptive behavior scale of the AAMD Adaptive Behavior Scale (ABS) were administered to 78 institutionalized retardates (46 males and 32 females) in order to investigate the relationship between violent and destructive behavior and two purported indicants of violent and destructive acting-out behavior on the Hand Test, the acting-out-score (AOS and movement-content response (ACT-MOV). Significant correlations between the two Hand Test indices and the number of types of violent and destructive behavior evinced during a three-month period were obtained.


The MMPI as a predictor of early termination from polydrug abuse treatment.

The MMPI protocols obtained upon admission to an inpatient program for treatment of polydrug abuse were studied to determine if they could identify abusers who terminated prematurely from treatment. Individual scale T scores, profile code types and discriminant scores were evaluated for 104 patients who completed treatment ("stayers") and 72 patients who left prematurely ("quitters"). Although quitters and stayers did not differentiate on primary drug of abuse, age, sex, race, or IQ, quitters were less likely to obtain normal limits or neurotic code profiles, Univariate analyses revealed that quitters obtained higher mean elevations on 6 of the 15 scales studied (F, 4/Pd, 6/Pa, 8/Sc, 9/Ma, A). Discriminant scores based on a stepwise discriminant analysis correctly identified 71% of the study sample, representing a 13.7% improvement over base rate prediction. The probable importance of initial level of psychological discomfort and ability to delay gratification, and the need to examine varied treatment modalities for polydrug abusers identified as at risk for premature termination from treatment were explored.


The structure of death anxiety: a factor analytic study.

University students in Canada (n = 255) and Northern Ireland (n = 315), graduate nursing students (n = 124), funeral service students (n = 79), and members of the Unitarian Fellowship (n = 83) completed Templer's Death Anxiety Scale (DAS). The responses of each group were subjected to principal components factor analysis using varimax rotational procedures and the factor scores derived from this analysis were then contrasted using multiple discriminant function analysis. Results indicated that there was more commonality than uniqueness in the factor patterns for these groups. Four common death anxiety patterns were classified as follows: (a) cognitive-affective concerns; (b) concern about physical alterations; (c) concern about the passage of time; and (d) concern about stressors and pain. These factors are consistent with and extend the views expressed in previous research (i.e., Pandy, 1974-75; Pandy & Templer, 1972.


Assertiveness, locus of control and coping behaviors used to diminish tension.

To investigate how coping behaviors may be preconditioned by assertiveness and locus of control, a questionnaire was given to 133 undergraduates of whom 87% reported recent tension attributed mainly to academic pressures. From a list of 22 common coping reactions, the students were asked to check those they use to deal with their tensions. The coping responses were also correlated with scores on an assertiveness inventory (AES) and Rotter's Internal-External Locus of Control (I-E) Scale. Reliance on one's own initiatives and turning to significant others were the responses most frequently reported as reactions to tension while seeking professional help was ranked last. Male students more frequently reported using marijuana or seeking sexual comfort than females, while females more frequently reported dysfunctional reactions such as spending endless hours thinking about the problem. The AES correlated significantly with problem-solving approaches. The IE Scale showed internals more inclined to meditate; externals indicated a greater likelihood to seek professional help, fantasize, or drink alcohol.


Bioavailability of imipramine tablets relative to a stable isotope-labeled internal standard: increasing the power of bioavailability tests.

A new methodology for comparative bioavailability testing is described in which each drug formulation is compared with a stable isotope-labeled variant of the drug that is consumed orally in solution at the same time the tested formulation is ingested. The methodology is used to determine the comparative bioavailabilities of two commercially available brands of imipramine hydrochloride. The power of the new methodology to detect differences between drug formulations, when, in fact, such differences exist, is shown to be superior to that of conventional bioavailability tests.


Disposition of synethetic glucocorticoids. I. Pharmacokinetics of dexamethasone in healthy adults.

The pharmacokinetics of dexamethasone alcohol is described in six male and six female healthy adult volunteers who each received 8 mg of dexamethasone phosphate by bolus intravenous injection. Quantitation of the alcohol was done using a high-performance liquid chromatographic method with improved specificity. Statistical evaluation of the results generated by nonlinear least-squares regression analysis of the plasma concentration-time data shows that the phosphate ester is very rapidly hydrolyzed to the alcohol and a biexponential equation is the simplest polyexponential equation that is consistent with the data. The terminal phase half-life t1/2 beta was significantly greater (P less than 0.05) in males (mean 201.5 min) than in females (mean 142.3 min). They prolonged t1/2 beta in males did not appear to be caused by an impaired capacity to eliminate dexamethasone since the total plasma clearance did not differ between males (mean 24.5 ml/min) and females (mean 242.9 ml/min). There was, however, a high positive correlation between t1/2 beta and Vdss among the 12 adults (r = 0.92, p less than 0.001). There were also significant correlation between Vdss and body weight (r = 0.67, p less than 0.05) and t1/2 beta and body weight (r = 0.80, p less than 0.01). The difference in body weight between the sexes seems to be the main factor contributing to the difference observed in t1/2 beta. An average of only 2.6% of the dose was found unchanged in a 24-hr urine sample, and hence it appears that dexamethasone is primarily eliminated by extrarenal, probably hepatic, mechanisms.


Attenuation of furosemide's diuretic effect by indomethacin: pharmacokinetic evaluation.

The pharmacokinetics and pharmacodynamics of intravenous furosemide, 40 mg, were studied in four normal males in a crossover fashion with and without indomethacin pretreatment. In each study 16 plasma and 10 urine samples were collected over 24 hr. Fluid and electrolyte urinary losses were replaced orally throughout the study. Unchanged furosemide and indomethacin were measured using HPLC; urinary sodium was measured by flame photometry. Pretreatment with indomethacin resulted in increased and prolonged fourosemide plasma levels, increased area under the curve, decreased plasma clearance, decreased renal clearance, increased half-life, no change in volume of distribution, and decreased sodium excretion and urine volume. Analysis of sodium excretion rate with time shows that the inhibiting effect of indomethacin was greater during the first 2 hr than at later times.


Sequential first-pass elimination of a metabolite derived from a precursor.

We examined data from our previous studies in which we not only delivered perfusate containing tracer concentrations of [14C]phenacetin and its metabolite [3H]acetaminophen under constant perfusate flow (10 ml/min/liver) into the rat liver preparation just once, but also recirculated fresh reservoir perfusate containing a tracer dose of [14C]phenacetin through the same rat liver preparation. From the single-pass studies, estimates of fm, the fractional rate of conversion for [14C]phenacetin to form [14C]acetaminophen, and F(M.P), the apparent availability of [14C]acetaminophen, were obtained by determining the concentrations of [14C]acetaminophen in the perfusate before and after incubation with Glusulase. These estimates were fm = 0.871 +/- 0.16 and F(M.P) = 0.43 +/- 0.10. These and the steady-state clearance values of phenacetin (9.1 +/- 0.8 ml/min) and acetaminophen (6.7 +/- 0.7 ml/min) from the single-pass studies were used to predict the concentrations of [14C]acetaminophen in the reservoir perfusate on recirculation of [14C]phenacetin. We found that the sequential first-pass elimination of the metabolite must be considered when the metabolite is highly extracted by the liver. If we had neglected to take this into account, the fractional rate of conversion of a precursor to form a metabolite and the rate of formation of the metabolite would have been underestimated by the factor F(M.P).


Creatinine kinetics in the rabbit.

To evaluate the kinetics of creatinine in the rabbit, two radiotagged creatinine forms were used, with 14C in the amidino group or with it in the carboxyl group. Five animals were injected intravenously with tracer amounts, and plasma samples were taken for 250-300 min; urine and feces samples were taken over longer periods. A chromatographic method was used to separate unchanged creatinine from other components of the samples prior to measurement for chemical and radioactivity content. Equations for the proposed flow model were derived and fitted to specific activity data, and values for transfer constants, production rates, and pool sizes were calculated. Evidence supported the concept that a two-compartment model is required and that production occurs in the peripheral compartment. Evidence also indicated that muscle represented a major part of the peripheral compartment. Small amounts of metabolites, chiefly guanido compounds, were detected when amidino-labeled creatinine was used. Also, small amounts of unchanged creatinine and metabilites were found in the feces.


Divergence in pharmacokinetic parameters of quinidine obtained by specific and nonspecific assay methods.

Previously published estimates of pharmacokinetic characteristics of quinidine can be shown to be dependent on whether the investigators have used analytical methods which are specific for quinidine. Areas under the plasma concentration-time curve and peak plasma concentrations after administration of the drug were higher and clearance values consequently lower in studies utilizing nonspecific assays unable to distinguish quinidine from its metabolities. The error introduced is larger after oral administration as a result of marked first-pass metabolism of quinidine. The absolute oral bioavailabilities from pharmaceutical preparations might therefore be estimated higher in studies with assays including metabolites in the determination. Although the pharmacodynamic response to quinidine is related to the plasma concentration, the therapeutic window of drug concentrations has been defined only using nonspecific assays. In light of the availability of newly developed specific assays, redefinition of the range of therapeutic plasma concentrations is opportune.


Examination of blood clobazam levels and several pupillary measures in humans.

The State-Trait Anxiety Inventory was administered to 15 subjects before initiation of the experiment. Three subgroups of five subjects were defined by computing the unweighted sum of the state and trait anxiety scores. A 40-mg dose of clobazam, a 1.5-benzodiazepine, was administered to each subject and repeated with two additional dosage forms following a 2-week washout period. Blood samples were withdrawn, and blood levels were determined by fluorometric analysis. Additionally, pupillary measures of critical flicker fusion, constriction, and dilation in response to a cognitive task were obtained at 0, 2, 4, and 6 hr. A repeated measures analysis of variance revealed that blood levels were, as expected, statistically different over time and dosage form. The pupillary constriction mirrored the blood levels in statistical patterns. The pupillary measure of cognition related to the anxiety state after the performance effects of the cognitive task were statistically removed. The results suggest that clobazam has less immediate human effect than does diazepam.


Physical characterization of solid iopanoic acid forms.

Three solid forms of iopanoic acid were characterized by X-ray diffraction, differential scanning calorimetry, scanning electron microscopy, thermal microscopy, IR spectroscopy, and dissolution studies. X-ray analysis demonstrated that two solid forms were crystalline and that the third was amorphous. The amorphous form had been reported previously as crystalline. Enthalpies and entropies of transition were calculated using differential scanning calorimetry. A fourth form, a benzene solvate, also was isolated but proved to be too unstable at room temperature to permit conclusive characterization. The amorphous form demonstrated a 10-fold greater intrinsic dissolution rate than the commercially available form (Form I). Form II's intrinsic dissolution rate was 1.5 times greater than that of Form I. In powder dissolution studies, the peak solubilities of the different forms followed the same rank order as their intrinsic dissolution rates. Form II was relatively stable in aqueous saturated solutions, but the amorphous form was rapidly converted to Form I under similar conditions.


Guanabenz degradation products and stability assay.

Guanabenz, [(2,6-dichlorobenzylidene)amino]guanidine, acetate was shown to be the E-isomer. It decomposed to form the Z-isomer, 2,6-dichlorobenzaldehyde, aminoguanidine, and 2,6-dichlorobenzaldehyde semicarbazone. A stability-indicating assay for the intact drug in the presence of all of its decomposition products by the use of UV spectroscopy is presented.


Pharmacokinetic model for procaine in humans during and following intravenous infusion.

A multicompartment pharmacokinetic model is presented to describe procaine distribution in humans during and following intravenous infusion. The model, based on a general perfusion model, relates individual characteristics such as sex, age, weight, height, infusion rate and duration, and hematocrit to general parameters such as drug metabolism, protein binding, ion-trapping effects, and tissue-plasma distribution coefficients to provide an individualized distribution prediction. Experimentally observed kinetics of blood procaine levels collected during intravenous procaine infusion as an adjunct to surgical anesthesia and blood lidocaine levels obtained from the literature compared very well with the model simulation.


Myoinositol uptake by rat hepatocytes in vitro.

Myoinositol uptake by rat hepatocytes in vitro was studied. Adult rat hepatocytes were prepared by digestion of the perfused liver with collagenase. Cell suspensions were incubated with tritium-labeled myoinositol in pH 7.4 Krebs bicarbonate solution containing 1% gelatin at 37 degrees. 14C-Carbon-labeled polyethylene glycol was used as a marker of adherent extracellular fluid volume. Myoinositol uptake was demonstrable after 5 min of incubation, but no intracellular concentration in excess of that in the incubation medium was observed after 60 min of incubation. Uptake saturation over a wide myoinositol concentration range could not be demonstrated. Neither the omission of sodium ions nor the inclusion of ouabain suppressed the distribution ratio significantly. Metabolic inhibitors and lower temperatures also showed no effect. Hexoses, phlorizin or mannitol, exerted no observable effect on myoinositol uptake. The results indicated that myoinositol uptake by rat hepatocytes is probably a passive process.


Binding of mono- and bis-N-substituted benzoquinolinium halides to butyrylcholinesterase: fluorescence measurements.

The dissociation constants (Kdiss) of mono-and bis-N-substituted benzoquinolinium salts from butyrylcholinesterase were determined by the disappearance of the fluorescence of the free ligand. The Kdiss value determined by this method agreed closely with the dissociation constants (KI,s) of the free enzyme obtained by steady-state kinetic studies. The results indicate that the N-substituted benzoquinolinium salts with a strong binding ability to butyrylcholinesterase also are potent inhibitors of the esterolytic properties of the enzyme. Enzyme binding is favored by the coplanar structure and does not require a high concentration of charge on the onium function. The shape of the hydrophobic structures markedly influences binding.


Osmolality of parenteral solutions.

Osmolality-concentration profiles for individual and mixed solute systems are presented. Linear relationships between osmolality and concentration held true in all systems examined at concentrations below 0.2 molal levels. At higher concentrations, linearity existed only in select systems. Deviations from linearity can be greater or less than extrapolated values. In view of the need to determine an osmolarity conversion factor for each parenteral formulation and the many errors possible in the use of these values, adoption of osmolality values for labeling parenteral products rather than osmolarity, as stipulated in USP XIX-NF XIV third supplement, strongly recommended.


Preparation of diastereomeric urethane derivatives of atropine and l-hyoscyamine using (-)-1-phenylethylisocyanate.

Diastereomeric urethane derivatives of atropine (d,l-hyoscyamine) and l-hyoscyamine were prepared by reacting the alkaloids with (-)-1-phenylethylisocyanate. The derivatives, as the picrate ion-pairs, were characterized by their melting points, optical rotations, elemental analyses, and IR, NMR, and UV-visible spectra.


TLC differentiation of butyrophenone and diphenylbutylpiperidine compounds from phenothiazine derivatives.

A procedure is described for TLC detection and differentiation of the butyrophenone-diphenylbutylpiperidine group and phenothiazine derivatives at the microgram level. A two-dimensional TLC method to separate butyrophenone and diphenylbutylpiperidine compounds is reported. A variety of possible detection reagents were examined. The solvent systems and spray reagents described should be useful for the identification of these drugs in various dosage forms.


High-pressure liquid chromatographic analysis of antipyrine in small plasma samples.

A high-pressure liquid chromatographic (HPLC) method was developed for the assay of antipyrine in small (0.1-ml) plasma samples using aminopyrine as the internal standard and a reversed-phase microparticulate column. The assay sensitivity (1 microgram/ml) permits development of a plasma level--time curve using a single rat. The mean (+/- SE) plasma elmination half-life in rats was 1.28 +/- 0.14 hr. A comparison of the spectrophotometric method with the HPLC method yielded a correlation coefficient of 0.98. The HPLC assay for antipyrine is rapid and precise and can be used for hepatic drug metabolism study in a single animal.


Metabolic fate of N6-benzyladenosine and N6-benzyladenosine-5'-phosphate in rats.

The radiolabeled antitumor nucleoside (14C-8)-N6-benzyladenosine and its (14C-8)-5'-phosphate were administered to rats intravenously, and their metabolic fate was studied. Twenty-nine percent of the radioactivity was recovered in the 48-hr urine collection after (14C-8)-N6-benzyladenosine administration. The following metabolites were isolated: unchanged N6-benzyladenosine (20%), adenine (12%), uric acid (5%), and N6-benzyladenine (0.3%). In the case of (14C-8)-N6-benzyladenosine-5'-phosphate, a total of 28% of the radioactivity was recovered in the 48-hr urine collection and the following metabolites were isolated: N6-benzyladenosine (40%), uric acid (12%), adenine (trace), and unidentified urea derivatives (30%). Metabolism of N6-benzyladenosine appears to involve N-debenzylation to some extent, followed by conversion to adenine and uric acid. N6-Benzyladenosine and its 5'-phosphate differ from other adenosine analogs in being retained in significant amounts by the animals.


Improvements of dissolution characteristics and chemical stability of 16,16-dimethyl-trans-delta 2-prostaglandin E1 methyl ester by cyclodextrin complexation.

Inclusion complexation of 16,16-dimethyl-trans-delta 2-prostaglandin E1 methyl ester (I), which is effective in early pregnancy termination, with cyclodextrins in water was ascertained by a solubility study. A solid complex of I-beta-cyclodextrin in a 1:2 molar ratio was obtained, and its dissolution behavior and chemical stability were examined. The results indicated that the complex may have great utility as a rapidly dissolving form of I with prolonged storage time.


Differential pulse polarography of tetracycline: determination of complexing tendencies of tetracycline analogs in the presence of cations.

The complexation tendencies, stoichiometries, and stability constants for tetracycline, minocycline, and demeclocycline with the metallic ions calcium(II), magnesium (II), zinc(II), aluminum(III), iron(II), and iron (III) were evaluated using a polarographic technique. Changes in pulse peak heights for each tetracycline deravative were measured as a function of cation concentration. The method provides an in vitro method of evaluating the selectivity of particular metal ions for different tetracycline analogs.


Photolytic decomposition of indapamide.

Photolytic decomposition of indapamide (I) in nitrogen-flushed methanol yields 3-sulfamoyl-4-chlorobenzamide (II), 2-methylindoline (III), semicarbazide (IV), and 1-(N-formamido)-2-methylindoline (V); in oxygen-flushed methanol, II--V, 1-aminocarboxymethyl-2-methylindoline (VI), 3-sulfamoyl-4-chlorobenzoic acid (VII), methyl-3-sulfamoyl-4-chlorobenzoate (VIII), and 2-(N-acetamido)-benzoic acid (IX) are formed. A comparison is made with thermal decomposition of I.


Improved spectrophotometric determination of glycerol and its comparison with an enzymatic method.

A chemical method for the determination of glycerol was developed and compared to an enzymatic assay for sensitivity and reproducibility. The chemical assay is based on glycerol oxidation to formaldehyde and subsequent reaction with chromotropic acid to yield a colored product. With this method, as little as 5 micrograms of glycerol/ml can be detected. The enzymatic assay is based on enzymatic glycerol phosphorylation followed by glycerol phosphate dehydrogenation by nadide (nicotinamide adenine dinucleotide). The reduced nadide is used to reduce iodonitrotetrazolium violet to its colored formazan product. The enzymatic method can be used to deterine 50 micrograms of glycerol/ml in aqueous samples.


Clearance constants in physiologically based pharmacokinetic models.

The intrinsic clearance of an organ is usually approximated by the apparent clearance from that organ in the development of a physiologically based pharmacokinetic model. In this study, the exact relationship between the two clearances was derived and analyzed. When the extraction ratio of the drug was small (less than 0.05), the approximation was reasonable. However, when the extraction ratio was high (greater than 0.2), serious errors could be made by using the approximation. These errors could be as much as 50% reduction in the estimated extraction ratio and as much as an order-of-magnitude difference in the intrinsic clearance.


In vivo methotrexate transport in murine Lewis lung tumor.

Methotrexate uptake by murine Lewis lung tumor was measured in vivo over a wide dose range. The data were analyzed according to a model previously developed for tissues in which methotrexate uptake is rate limited by transport across the cell membrane. Methotrexate transport in this tumor followed Michaelis-Menten kinetics with a rate constant for permeability (k/K) of 0.012 min-1. The methotrexate binding capacity of dihydrofolate reductase in the tumor was not exceeded at any dose studied. A low membrane permeability in conjunction with a high dihydrofolate reductase level explains the resistance of this tumor to methotrexate.


Effect of enzyme-inducing and enzyme-inhibiting agents on drug absorption. II. Influence in proadifen on 3-O-methylglucose transport in rats.

Studies utilizing the in vitro everted rat jejunum were performed to investigate the effects of proadifen pretreatment and fasting on active and passive intestinal transfer of 3-O-methylglucose. Animals were pretreated 24 hr prior to the experiments with 100 mg of proadifen/kg ip. With mucosal concentrations of 0.1 mM 3-O-methylglucose and 14C-3-O-methylglucose, transfer to the sugar-free serosal buffer after pretreatment with proadifen was 50% greater than controls after a 24-hr fast and 120% greater than controls after a 48-hr fast. Everted intestinal segments obtained from unfasted control animals showed diminished ability to transfer the sugar derivative, with transfer rates approximately 50% less than those of segments obtained from 24-hr fasted control animals. Wet and dry tissue weights for 24- and 48 hr-fasted groups increased following proadifen pretreatment. The results suggest that proadifen enhances 3-O-methylglucose transport across the rat jejunum and also increases intestinal tissue weight.


Bioavailability and dissolution parameters of seven lithium carbonate products.

Seven commercial products and a standard powder of lithium carbonate were administered to healthy human volunteers in a crossover study. An analysis of variance of saliva levels and urinary excretion as well as an analysis of variance of peak concentration and the area under the curve from 0 to 24 hr for the saliva levels showed no significant difference between the powder and products, but a significant difference between subjects. A significant difference was found between the time of peak saliva levels, which was attributed to faster powder absorption. A dissolution study using the USP basket method at 50 and 100 rpm and the Levy beaker at 50 rpm also showed no significant difference between products after the lag time for the capsule dosage forms. With a regression analysis, a significant correlation was found between the saliva levels of the products at 2 hr and dissolution in the USP basket at 50 rpm at 4 min.


Synthesis of substituted 2-aminopyrrole analogs of lidocaine II.

The synthesis and local anesthetic and antiarrhythmic properties of eight substituted 2-diethylaminoacetamido-3-carbamyl-4-methylpyrroles are described. Three compounds showed significant local anesthetic activity by the guinea pig wheal test, and four showed antiarrhythmic activity against chloroform-induced ventricular arrhythmias in mice.


Automated analysis of chlorthalidone.

Chlorthalidone inhibition of the enzymatic hydrolysis rate of p-nitrophenyl acetate by bovine erythrocyte carbonic anhydrase was used as a basis for chlorthalidone determination in plasma and urine. For urinary samples, a completely automated, continuous flow system was developed to extract the samples and perform the enzymatic reaction. Over 100 samples per day could be assayed by one person. The assay had a sensitivity of 0.5 micrograms/ml and thus could determine urinary concentrations after a therapeutic chlorthalidone dose. To determine plasma concentrations after a therapeutic dose, a manual extraction procedure was used in combination with a second continuous flow system for the enzymatic reaction. This system was optimized to detect the lowest chlorthalidone concentration allowed by the enzymatic inhibition constant and could detect 25 ng/ml.


Progestin permeation through polymer membranes IV: Mechanism of steroid permeation and functional group contributions to diffusion through hydrogel films.

Hydrogel films were prepared from hydroxyethyl methacrylate, both with (Film II) and withouth (Film I) 5.25 mole% of ethylene glycol dimethacrylate. Permeation, diffusion, and partition coefficients for progesterone, testosterone, nandrolone, norethindrone, 17 alpha-hydroxyprogesterone, estradiol, and hydrocortisone were determined. A solute permeation model was proposed based on the separation of a domain (B) composed of "bulk-like" water and a doman (A) composed of polymer, interfacial water, and bound water present in the films. The separate contributions from the "pore" and "solution-diffusion" mechanisms to the total permeability were calculated from the model. Steroid permeabilities through Films I and II were analyzed in accordance with this model. Permeation of Film II occurred via the solution-diffusion mechanism. Permeation of Film I occurred predominately by the pore mechanism with a small contribution (approximate 20%) from the solution-diffusion mechanism. The latter contribution was dependent on the solubility of the solute within the A domains of the hydrogel film. Functional group contributions to permeation of Film II were ascribed to either steric or hydrogen bonding effects.


Simple field test for marijuana.

A simple, rapid, sensitive, and specific field test for marijuana and its products is described. The test employs an extracting-eluting ssolvent and an inert adsorbent microcolumn coated with Fast Blue B salt as the reagent. One milligram or less of the suspect material can be tested within 1 min. Of greater than nonmarijuana plant samples tested, only nutmeg and its mace responded similarly to marijuana initially. A differentiation was possible by careful evaluation of the colored microcolumn and the elution behavior of the colored products. The test also provides for a confirmatory step, based on spectrophotometric analysis of the colored eluates. The reagent microcolumn was very stable to environmental factors such as moisture, light, and air.


Metabolic performance and GI function in magnesium-deficient rats.

A quantitative evaluation of the mass balance and GI motor effects of dietary magnesium deficiency in the adult male Sprague-Dawley rat is described. Seventy-seven animals were used. Both sham control and experimental groups were maintained on a commercial stock laboratory diet ad libitum for 30 days, after which the experimental rats were switched for 30 days to magnesium-deficient diet ad libitum, containing a magnesium concentration of 16.2 ppm. Ten rats were used to determine the acetylcholine responsiveness of duodenal muscle segments in vitro. In all cases, the segments from the deficient rats were hyperresponsive to a fixed acetylcholine dose. Forty-six rats were used to determine the average intestinal transit rate, which increased significantly in 30-day magnesium-deficient rats. A final series employed 21 rats who were housed in individual metabolic cages. After 5 days on the deficient diet, the average daily fecal pellet counts and fecal weights were significantly reduced. It is concluded that chronic magnesium deficiency is associated with altered GI motor function in the adult male rat.


Absorption and penetration of dinoprost (prostaglandin F2 alpha) and dinoprost methyl ester into perfused mesenteric circulation in rats.

The absorption of dinoprost (prostaglandin F2 alpha) and its methyl ester in rat jejunum was studied. A 22-cm segment of rat jejunum was cannulated at both ends and connected to an oscillating perfusion pump system. The mesenteric vasculature supplying this isolated segment also was cannulated and perfused with Kreb's bicarbonate buffer with dextran. Solutions of 3H-dinoprost or its methyl ester were introduced into the lumen and oscillated through the segment. The disappearance of radioactivity from the lumen and the appearance of radioactivity in the vascular perfusate were monitored. The metabolite patterns in the vascular perfusate were analyzed by TLC. A lag between the time the drug disappeared from the lumen and the time it appeared in the mesenteric circulation was detected. This lag was longer for the methyl ester than for the free acid, even though the ester disappears from the lumen faster than does the free acid. Upon removal of dinoprost from the gut lumen, a gradual decrease in the amount of drug appearing in the mesenteric circulation could be detected. However, with the ester, a slight increase could be observed for approximately 0.5 hr, followed by a decrease. Metabolism by the gut wall appears to be greater for the ester than for the acid. The results suggest that, although the ester disappears from the lumen more quickly than does the acid, it actually penetrates to the blood at a slower rate and undergoes greater metabolism.


Effects of aspirin on 14C-pirprofen disposition in rats.

The effects of aspirin on 14C-pirprofen disposition in the rat were studied. An oral 60-mg/kg dose of aspirin significantly reduced plasma radioactivity during the 1--8-hr interval after an intravenous 5-mg/kg injection of 14C-pirprofen. The aspirin-treated group had only 69% as much area under the radioactivity curve as the control group. The radioactive material in plasma consisted almost entirely of 14C-pirprofen, as shown by GLC. The plasma clearance of 14C-pirprofen was 7.4 ml/hr for the aspirin-treated group and 5.1 ml/hr for the control group, while the volumes of distribution were 0.32 and 0.20 liter/kg, respectively. The apparent elimination half-life was unchanged at 5.9 hr. 14C-Pirprofen was approximately 98.6% bound to plasma proteins, and the binding decreased to an average of 97.2% in the presence of salicylate. Binding to blood cellular constituents was insignificant. Rats give 14C-pirprofen by intravenous injection without aspirin secreted 36.0--42.8% of the dose radioactivity into bile during 4 hr while a comparable group given 60 mg of aspirin/kg secreted 46.4--70.8%. TLC and GLC demonstrated that the radioactivity in rat bile was 80--90% conjugated 14C-pirprofen. The increased radioactive material secretion into bile was compensated in the intact rat by reabsorption, since the total radioactive material excreted in urine was not changed by aspirin administration.