Definition of cardiac structures using computerized tomography in isolated arrested and beating canine hearts. Computerized axial tomography of the brain is a revolutionary noninvasive technique that has provided remarkable resolution of intracerebral structures. This study was undertaken to determine the potential of computerized tomography for defining the anatomy of 40 arrested and 9 beating (ejecting left heart preparation) canine hearts. Using an EMI cranial unit, scanning was performed in hearts under in vitro conditions with a lactated Ringer's interface. The tomographic scans obtained were later compared with comparable 8 mm thick sections of the heart. At physiologic levels of hematocrit (range 36 to 45%) external structures were well defined, but because of the lack of a differential between cavitary and myocardial densities, it was not possible to distinguish intracardiac structures. With very small amounts of iodinated contrast material (remotely administered in the case of the beating hearts) or with anemia (hematocrit less than 33%), the right and left ventricular cavities became clearly visible in both horizontal and longitudinal tomographic scans. It was possible to distinguish readily the boundaries of the ventricular and atrial cavities, the papillary muscles, the major trabeculae and the aorta. Rhythmic motion of the beating heart, suspended in its pericardium, did not eliminate structural definition. Thus, computerized tomography provides a new approach to the definition of cardiac structure with a relatively high degree of resolution. These observations point to the potential usefulness of this noninvasive technique for the evluation of both cardiac function and ventricular wall abnormalities.


Symptomatic swallowing-induced paroxysmal supraventricular tachycardia. A 55 year old woman with palpitations during ingestion of food or drink was evaluated with surface, esophageal and dynamic electrocardiographic techniques. Recordings documented the consistent induction of supraventricular tachycardia by swallowing; no definable gastrointestinal or other cardiac abnormality was present. Nine previously reported cases are reviewed, with special reference to the role of vagovagal reflexes in the pathogenesis of this unusual clinical syndrome.


Precocious induction of secretory granules by hormones in convoluted tubules of mouse submandibular glands. Precocious differentiation of convoluted tubules of the submandibular glands of mice was induced by daily injection of thyroxine, insulin, hydrocortisone and 5alpha-dihydrotestosterone from day 4 after birth. This treatment induced enlargement of the tubules and synthesis of secretory granules in the tubules. Treatment with 5alpha-dihydrotestosterone alone had no effect on enlargement of the tubules or synthesis of the granules. These findings suggest that, besides androgenic hormones, these three hormones are also involved in synthesis of granules in developing mice.


The effect of large unilateral cortical lesions on rubrospinal tract sprouting in newborn rats. Many previous reports have demonstrated the development of aberrant neural connections in response to neonatal brain lesions. This investigation was undertaken to study possible alterations, particularly axonal sprouting, in rodent rubrospinal projections after neonatal destruction of the corticospinal tract through frontal cortical ablation. The neonatal ablations were made by aspiration in 1 to 2-day-old rats under hypothermic anesthesia. At three to six months after neonatal surgery, the rubrospinal tracts were ablated bilaterally in these small animals as well as in controls, by stereotaxically transecting the ventral tegmental decussation. Animals were killed two to six days after adult surgery, and rubrospinal projections were demonstrated using the Fink-Heimer degeneration stain. No differences in the pattern of rubrospinal projections were observed between animals with neonatal cortical lesions and controls. In all animals rubrospinal projections were located primarily in Rexed's lamina VI with a slight distribution into lamina V and the dorsal portion of lamina VII. Various hypotheses explaining the lack of rubrospinal sprouting after neonatal cortical lesions are presented, along with possible experiments to test these hypotheses.


Innervation of myocardial microcirculation; terminal autonomic axons associated with capillaries and postcapillary venules in mouse heart. Efferent terminal axons are associated with numerous capillaries and postcapillary venules in both the atria and ventricles of mouse heart. These axons possess ultrastructural characteristics which are typical of peripheral autonomic fibers in other tissues. Many are found near pericytes, in a relationship closely resembling that between terminal axons and smooth muscle cells of larger vessels. To demonstrate adrenergic terminals, mice were pretreated with 5- or 6-hydroxydopamine; examination of these animals' hearts revealed that both adrenergic and cholinergic axons terminate near pericytes and endothelial cells. The results of this study are consistent with the view that there may be a functional innervation of capillaries and postcapillary venules of the mouse heart.


Lysine and tryptophan in cereal-based diets for adult human subjects. A basic diet containing rice, wheat, and corn that furnished 6.0 g of nitrogen per day was consumed by health young adults. Two levels of lysine, 900 and 1800 mg, and three of tryptophan, 260, 390, and 520 mg, were tested. Lysine exerted a significant effect (P less than 0.05) on nitrogen retention but tryptophan did not. When consumed in conjunction with at least twice the reported minimal requirements of other essential amino acids, 900 mg of lysine induced mean daily balances of 0.15 +/- 0.18, 0.19 +/- 0.14, and 0.22 +/- 0.21 g, respectively, in response to the three levels of tryptophan; and 1800 mg of lysine caused retentions of 0.75 +/- 0.14, 0.77 +/- 0.21 and 0.71 +/- 0.15 g. These findings are discussed in relation to fulfillment of protein and amino acid requirements of adult human subjects.


Effect of oral alanine loads on the serum triglycerides of oral contraceptive users and normal subjects. The effect of orally administered L-alanine loads on serum triglycerides, and plasma insulin and glucose, was studied in 23 women using an estrogen-containing oral contraceptive and 13 healthy female controls. Oral contraceptive users had significantly higher fasting serum triglycerides than the controls. Serum triglycerides concentrations udnerwent little changes in the controls after alanine ingestion, whereas the oral contraceptive users showed increases which were maintained throughout the 3-hr sampling period. The two groups had similar elevations in plasma insulin after alanine loading; the glucose concentrations were unchanged. The changes in serum triglycerides may have resulted from increased metabolism of alanine to pyruvate, and its incorporation into lipids under the stimulus of elevated insulin levels.


Disaccharide consumption and malabsorption in Canadian Indians. Twenty-eight Sioux and 29 Saluteaux Indians from a southern and an isolated northern Manitoban community were screened for lactose malabsorption; 55 were also screened for sucrose tolerance. Sixty percent of the subjects were lactose malabsorbers; the incidence increased with age. Lactase deficiency appeared, on the average, between 8 and 15 years of age. About 45% of the subjects were lactose intolerant. Malabsorbers who did not regularly drink milk had the highest symptom scores. The northern subjects consumed significantly more lactose and sucrose than the southern subjects. Two Sioux children were sucrose malabsorbers. It was hypothesized that the significantly greater sucrose consumption by the Saulteaux subjects were responsible for their markedly higher blood glucose curve following the sucrose tolerance tests. Dietary sucrose increases jejunal sucrase activity and the intestinal transport of glucose and fructose. Three of eight children less than 4 years were lactose malabsorbers; hence, medical personnel treating noninjective diarrhea in Indian children should examine for lactase deficiency. It was recommended that vitamin D fortified milk supplements to Indian school children be continued and that the milk be treated so as to reduce abdominal symptoms in the intolerant individuals.


The relationship between frequency of eating and adiposity in adult men and women in the Tecumseh Community Health Study. The relationship between frequency of eating and adiposity was studied in a cross-sectional population of about 1000 men and 1000 women ages 35 to 69. A detailed 24-hr diet recall interview was administered by trained interviewers. Frequency of eating--eight categories--was determined by computer program using reported actual eating times and food consumed. The adiposity variable was an index using two skinfold measurements, height and weight. An analysis of covariance removing the effect of caloric intake showed that frequency of eating was related inversely to the adiposity index for men and women separately with statistical significance at the 1% level.


Level of education, level of income, and level of fatness in adults. Socioeconomic status is systematically related to the level of fatness, and therefore the incidence of obesity, in a total community survey of nearly 5,000 adults. Among males with more than 12 years of schooling, the average thickness of 4 fatfolds is 10% greater, amounting to about 2 kg of total fat, than those with 8 years or less of education. In females, however, the opposite trend is observed, those in the higher educational group averaging 20% thinner fatfolds, or about 5.5 kg total fat, than females in the lower educational group. These findings confirm the need for standards of obesity that take socioeconomic status into account.


A behavioral approach to obesity.

A behavioral approach to obesity. For many individuals, the practice of overeating is crucial in the development and maintenance of the obese state. Behavior theory views excessive eating leading to obesity as an overlearned habit, strongly conditioned to numerous internal and external cues. A number of studies are reviewed that assess the relationship between emotional arousal and food consumption. Obese persons who successfully lost and maintained a weight loss appeared able to reduce the number of inappropriate stimuli they previously responded to with food intake. The specific behavior modification techniques employed to change eating patterns are discussed, and weight loss maintenance follow-up statistics using these procedures are presented.


Immune complex glomerulonephritis in a case of retroperitoneal fibrosis. The nephropathology associated with retroperitoneal fibrosis has been commonly related to compression of the ureters and hydronephrosis. This assumption has been made without the use of immunofluorescent microscopy and electron microscopy. The authors studied renal tissue from a patient with retroperitoneal fibrosis by light microscopy, immunofluorescent microscopy and electron microscopy. In addition to the gross and microscopic changes of obstructive nephropathy, histologic findings of glomerular immune-complex deposition were also present. It is postulated that in some cases of retroperitoneal fibrosis, destruction may be mediated by both obstructive and immunologic processes.


Improved estrogen receptor assay in human mammary cancer. Technics for handling small tissue samples. Studies of various technics that aid in performing estrogen receptor assays on small tissue samples from primary cancers of the breast are reported. It is shown how sufficient protein can be obtained from less than 100 mg of small primary tumor without ultracentrifugation to assay estrogen receptor by a simplified two-point Scatchard plot method. The resulting Kd and maximum binding site values with 36 tumor tissue samples approximated the values obtained with the more laborious, larger tissue sample-demanding six-point Scatchard plot. Target and nontarget tissue controls are easily included in an assay run of four to eight samples. For interpretive purposes the derivation of the characterizing value of the Kd for estrogen receptor is given and compared with nonspecific associating binders.


Determination of baseline values for urinary carcinoembryonic antigen-like substances. Carcinoembryonic antigen-like substances were measured in urine samples from 236 apparently healthy, asymptomatic individuals. Twenty-four-hour collections were submitted by 177 subjects, and random specimens were collected from 59 others. In addition to CEA measurements, bacterial colony counts and cytologic examinations were performed on the latter. Baseline values were established for males and females and data were analyzed for the effects of age, smoking, time of collection, and bacterial colonization. Results indicated that levels of CEA-like substances in the urine could be greatly altered by bacterial conlonization. Lesser effects were noted with age and time of collection. Smoking had no demonstrable effect. These variables should be considered for meaningful interpretation of urinary CEA values of patients suspected of urothelial malignancy.


Analysis and interpretation of the impedance blood coagulation curve. The impedance coagulation curve represents the relationship between the changing impedance of a clotting blood sample and the impedance of a heparinized control sample. The impedance method is independent of the conventional technics for coagulation studies and offers, therefore, new perspective into the study of the coagulation process. The technic provides accurate measures of the whole-blood clotting time and clot retraction time and has higher diagnostic power than current methods for whole-blood clotting time determination. The purpose of this study was to reveal the mechanism of the impedance changes and to explore the curve for additional information relevant to clinical or theoretical problems. It is established that before clotting the curve reflects "lag" and "activation" phases that strongly suggest a "cascade mechanism" of coagulation activation. The mechanisms of other parts of the curve are explained and their possible relevances to the coagulation process are discussed.


Comparative recoveries of chlamydia from urethral specimens using glass vials and plastic microtiter plates. Urethral specimens known to contain Chlamydia were stored at -70 C in transport medium (2SP). For the test, circular glass coverslips were placed in the bottom of each culture vessel (glass shell vials and plastic microtiters plates [5 by 15 cm]) and seeded with McCoy's cells in medium containing 5-iodo-2-deoxyuridine. After 72 hours, cultures were inoculated with the specimens, and after 72 additional hours the monolayers on the coverslips were stained with iodine. Of 43 specimens, Chlamydia was recovered from 29 in glass vials but only from three in plastic plates (P less than .001). Chlamydia isolates could be passed serially only by vial-to-vial transfer; losses of 1,800 inclusion-forming units occurred after one subpassage from plates to either vials or plates. The extents of inactivation at 36 C of Chlamydia suspended in medium and placed in plastic plates and in glass vials were similar after seven hours. A substance toxic for Chlamydia could not be demonstrated in the plastic plates. Any new system for isolating Chlamydia from clinical specimens should be evaluated by comparison with culturing in glass vials.


Current issues in mental health continuing education. Data from two studies are presented and related literature is reviewed in an effort to identify current issues of concern to mental health continuing educators. These issues include: (a) the need to increase the level of participation of mental health professionals in continuing education programs, (b) the lack of stable funding sources, (c) the need to evaluate the consequences of continuing education program participation (d) the role of continuing education in the emerging process of recertification and relicensure, (e) the need for continuing education program content to reflect contemplated changes in the organization and financing of human service delivery systems, (f) the growing interest in multidisciplinary continuing education, and (g) problems in meeting the continuing education demands of a more broadly defined constituency.


Ethical concerns in community mental health. With growing emphasis for ethical behavior of professionals in contemporary American society, those mental health specialists involved in the community must focus on their own behavior. This becomes a difficult task, since it is apparent that current ethical guidelines for community psychologists are not comprehensive enough to be adequately helpful. Nine areas of conflicting values and ethical concerns are considered in an effort to begin formulation of a blueprint for community mental health workers. These areas include community participation, continuity of services, politics, planning, autonomy versus manipulation, overism, minority groups, training, and consultation. Ethical principles generic to each area are put forth as proposed guidelines for professional activities and as propagators of discussion and debate.


Job characteristics, work satisfactions, and task involvement as correlates of service delivery strategies. Three agencies which evidenced different strategies for providing services to retarded clients were examined. Employees of an agency which had implemented a community-oriented strategy demonstrated the highest levels of job satisfaction and task involvement. Significant differences were found on four of eight job-design variables; however, methodological difficulties made interpretation of these differences difficult. The results were viewed as consistent with the hypothesis that different service delivery strategies are associated with differences in jobs, satisfactions, and task involvement.


A simple scorecard for the tentative diagnosis of streptococcal pharyngitis. More than 20,000 acute respiratory illnesses of children were studied by physicians in private practice to derive a nine-factor scorecard designed to estimate the probability that a given child's respiratory illness is caused by beta-hemolytic streptococci. Each factor was assigned a weight on the basis of the percentage of positive cultures from patients exhibiting that factor. The sum of these individual scores gave the total score. The higher a patient's score, the more probable was a streptococcal infection. Thus, depending on the score, a reasonably accurate prediction of the probability of a streptococcal infection can be made. The accuracy of such predictions compared favorably with that of skilled physicians.


Neonatal withdrawal syndrome associated with hydroxyzine hydrochloride. To our knowledge, this is the first report of a neonatal withdrawal syndrome associated with maternal usage of 600 mg daily of hydroxyzine hydrochloride throughout pregnancy. This observation suggests that the use of high doses of this agent in pregnancy should be avoided.


Esophageal ulcers in immunodeficiency with elevated levels of IgM and neutropenia. A 17-year-old boy with immunodeficiency, elevated levels of IgM,and neutropenia developed distal esophageal ulcers and stricture. Although his lower esophageal sphincter pressure was decreased, he had normal acid reflux test results, normal findings from acid clearing studies, and absence of diffuse esophagitis at esophagoscopy. Neutropenia and hypogammaglobulinemia are postulated as pathogenic factors in his esophageal ulcers.


Afibrinogenemia with intracerebral hematoma. Report of a successfully treated case. A patient with congenital afibrinogenemia underwent removal of an intracerebral hematoma following specific therapy with fibrinogen-containing concentrates. We believe the successful neurosurgical intervention in a life-threatening complication of this unusual coagulation disorder to be unique.


Nephrotic syndrome in a Chinese infant.

Nephrotic syndrome in a Chinese infant. A male infant, 4 months and 5 days old, who was born with a large placenta, had had onset of edema on the 17th day of life. Heavy proteinuris, hematuris, striking hypoalbuminemia, and hypercholesterolemia were noted in the first studied specimens on the 31st day of life. Corticosteroid therapy had no effect. The infant died on the 181st day after his birth. Pathological emamination disclosed large, pale kidneys with diffuse proliferative glomerulonephritis and a marked epithelial degenerative change and dilation of proximal convoluted tubules.


Torticollis with hiatus hernia in infancy. Sandifer syndrome. Two infants with torticollis and hiatus hernia (Sandifer Syndrome) are presented. Both infants improved with medical management. Abnormal head and neck positioning is attributed to esophagitis secondary to gastroesophageal reflux, with or without hiatus hernia. Since esophagitis due to reflux is not necessarily accompanied by vomiting, infants with torticollis shoud be studied for gastroesophageal reflux. If present, medical management is usually successful.


Mycobacterium kansasii arthritis of the knee joint. Mycobacterium kansasii infection of the knee joint was diagnosed in  an 11-year-old boy on the basis of skin testing to atypical mycobacteria, and a positive culture from a synovial tissur biopsy. Appropriate antituberculose drugs shoud be institute as sole treatment if no bony destruction is present. Ifthere is no response to chemtherapy, synovectomy should be performed.


Computed tomography in pediatric diagnosis. The use of computed tomography has revolutionized the evaluation of the neurologically ill child. This safe and noninvasive procedure may be done on an outpatient basis, eliminating for many the complications that may occur from invasive neuroradiologic procedures. Computed tomography is of particular value in the assessment of intracranial neoplasms, hydrocephalus, and vascular disease. Further advancements are expected in the technology of computed scanning and in its diagnostic use in the rest of the body.


Dialysis of gallbladder bile. Correlation between rates of exit of bile salts and bilirubin from the dialysis sac. Twenty-six gallbladder bile samples were dialyzed against an infinite dilution of Tris buffer at pH 7.4. Bilirubin moved out of the dialysis sac at a rate slower than that of bile salts. The rates of exit of these two molecules showed a significantly positive correlation with each other and a significantly negative correlation with bile salts concentration. Phospholipids and cholesterol did not move out of the dialysis sac. These data are consistent with the assumption that bile is a mixed micellar solution of bile salts, phospholipids, and cholesterol and suggest an association between bilirubin and the mixed micelle.


Effect of antidiarrheal and antimotility drugs on ileal excreta. Commonly used antimotility and antidiarrheal drugs were administered to six ileostomized subjects to determine whether their normal ileal excreta and that induced by prune juice could be altered. A total of 49 studies were performed, 21 with and 28 without prune juice. Bismuth subgallate was the only drug which significantly reduced the normal ileal excreta (P less than 0.05). Codeine sulfate decreased the ileal excreta in two of three subjects in either type of study. The third subject was a nonresponder to drugs. Deodorized tincture of opium (DTO) and diphenoxylate (Lomotil) were also effective in some subjects. Propantheline, tincture of belladonna, Sorboquel, and Kaopectate did not appear to decrease ileal excreta. Calcium carbonate, on the other hand, increased ileal excreta; fat excretion was also increased.


Manometric asymmetry of the lower-esophageal high-pressure zone. The lower-esophageal high-pressure zones (LEHPZ) of 10 normal subjects, 8 patients with hiatus hernia and one patient with progressive systemic sclerosis (PSS) were investigated using a special 8-lumen recording catheter, and lateral orifices of which were spaced at 45 degree intervals around the circumference of the catheter. While similar pressures were recorded from all orifices within the stomach and esophageal body, pressures within the LEHPZ were found to be related to spatial orifice position. In normal subjects, but not in patients with hiatus hernia, a significnatly higher localized pressure was detected by orifices directed toward the left posterior quadrant of the circumference of the distal esophagus, while a lesser, rather uniform, pressure was recorded from the other three quadrants. From the PSS patient, who had severe gastroesophageal reflux, a LEHPZ was detected only in the left posterior quadrant. The results suggest that the recorded LEHPZ represents the summation of two factors; an intrinsic force possibly due to a physiologic lower-esophageal sphincter and an extrinsic force possibly resulting from compression of the distal esophagus by the lateral margin of the diaphragmatic hiatus.


Effect of motilin on the lower esophageal sphincter of the opossum. We have studied the effect of Yajima's synthetic motilin on the lower esophageal sphincter (LES) of the opossum and compared its potency to that of gastrin and its interaction with secretin. Dose-response curves for the LES were constructed from the intravenous bolus injection of graded doses of motilin and gastrin alone and motilin given against a background infusion of secretin. The smallest dose of motilin that elicited a significant response was 0.05 microng/kg, and the highest response was observed with the highest dose used in this study (1.0 microng/kg). Over a wide dose range, both motilin and gastrin were found to be equally potent in stimulating the LES of the opposum, and secretin caused inhibition of the LES pressure to motilin. Therefore, we conclude that (1) motilin is a potent stimulant of the LES; (2) this response is dose dependent; (3) motilin's potency is similar to that of gastrin; and (4) secretin counteracts the effect of motilin on the LES.


Conjugated dihydroxy bile salt inhibition of glucose influx in rat jejunum in vitro. Effects of bile salts on intestinal transfer differ in diverse animal preparations exposed to various bile acids. Radiolabeled glucose influx into rat jejunum in vitro was studied in buffer and compared to taurodeoxycholate, taurochenodeoxycholate, taurocholate, and deoxycholate. Jejunum was obtained from intact, bile-diverted, and colestipol-treated rats and in similar categories after abdominal x-irradiation. Taurodeoxycholate but not taurocholate inhibited glucose influx only in bile-fistula and colestipol-treated rats. Bile diversion increased and colestipol decreased glucose uptake from buffer. Added inhibitory effects of irradiation and bile salts were seen in bile-fistula animals. These data suggest that normal exposure to bile is chronically inhibiting jejunal glucose transport and that dihydroxy bile salts are responsible for this effect. They do not provide an explanation for the role of bile in the intestinal radiation syndrome.


Acute spontaneously recovering ulcerating colitis (ARUC). Report of 6 cases. Six patients each with an extensive ulcerating colitis are reported. Common features were a febrile nonbloody diarrhea; radiological involvement of the whole colon with superficial ulcerations and preservation of haustra, and integrity of the terminal ileum and rectum; the absence of any specific pathological finding; and, most important, the spontaneous recovery of the lesions in the absence of any treatment except sympatomatic measures. The present follow up after recovery range from 18 months to 5 years. Four cases were young women taking oral contraceptives and two patients were older. These patients with colitis could represent a new entity or could be a particular form of Crohn's disease of the colon, with delayed diagnostic pathological features.


Nonoperative retrieval of an impacted long intestinal tube. A patient with recurrent intestinal obstruction and jejunocutaneous fistula was referred for treatment of the latter condition. Management with total parenteral nutrition was complicatied by bacteremia. Subsequently, a double-lumen tube was passed via an existing gastrostomy for purposes of aspirating above the level of the fistula and infusing appropriate nutrients and fluids distally. A period of marked clinical improvement was followed by increased fistula output and evidence of intestinal obstruction secondary to gaseous distention of a sealed latex terminal balloon which was retrieved only after percutaneous puncture. The unusual complication of prolonged intestinal intubation is discussed with special reference to this nonsurgical method of managing the impacted balloon and tube. Factors affecting balloon distention are discussed and the necessity of venting intestinal balloons reemphasized.


Patient experiences with a child-resistant prescription container. The results of a survey of 100 outpatients' experiences with a child-resistant container are presented. Eighty-three patients experienced difficulty with the container. Forty-six used a tool for opening the container. Forty-three reported accidental spillage of their drugs because of opening difficulties. Thirty-eight handled the container in ways which reduced its child-resistant effectiveness. The presence of children in patients' homes appeared to reduce the incidence of dangerous handling practices. Patients who had initial difficulties tended to continue having trouble and were, largely, the same ones who later mishandled the container. Only eight patients received instruction from a health professional on how to open the container. Early education of patients using child-resistant prescription containers is suggested.


Argyria and cyanotic heart disease.

Argyria and cyanotic heart disease. A case report in which argyria is mistaken for cyanotic heart disease is described. A discussion of argyria, a benign cosmetic condition resulting from either ingestion or the local application of silver salts or colloidal silver, is presented. It is suggested that by obtaining comprehensive drug histories, maintaining patient profiles, and through patient counseling, pharmacists are in a position to identify and advise on known cases of argyria.


Diagnosis and management of the infant with genital ambiguity. Clinical management of a child with ambiguous external genitalia requires physicians to consider the immediate management of the condition, as well as parental reactions. They must also obtain the necessary data upon which to make a diagnosis. This review summarizes the most common disorders causing genital ambiguity and suggests approaches toward delineation.


Is the supine pressor test an adequate means of predicting acute hypertension in pregnancy? The supine pressor test was performed on 207 nulliparous young women between the twenty-eighth and thirty-second weeks of gestation. The supine pressor test predicted pregnancy-induced hypertension in 78 per cent of those women who subsequently developed the condition. Ninety-six per cent of the women who failed to demonstrate a rise in diastolic pressure on position change remained normotensive throughout the remainder of the pregnancy.


Characterization of a microvillous membrane preparation from human placental syncytiotrophoblast: a morphologic, biochemical, and physiologic, study. The syncytiotrophoblast microvillous membrane must play a vital role in many essential functions of the placenta. In order to better understand the functional characteristics of this membrane, we have investigated an isolated membrane preparation by a variety of techniques. Electron microscopic observations showed membranous structures similar to microvilli of intact placental villi in size, shape, and microfilamentous content. Similarities in colloidal iron staining and transferrin localization were also shown. The preparation was enriched in enzymes characteristic of surface membranes and diminished in enzymes characteristic of intracellular organelles. Sialic acid content was also increased. SDS gel electrophoresis revealed the presence of a 45,000 molecular weight band, which may be actin. The preparation transported serine, glycine, and alpha-aminoisobutyric acid by a temperature-dependent, saturable process.


Electron probe microanalysis of the chemical elemental content of human follicular fluid. Follicular fluid samples were obtained by puncturing follicles of ovaries in situ from patients undergoing laparotomy. Sodium, potassium, chloride, magnesium, calcium, phosphorus, and sulfur concentrations measured by electron probe microanalysis were similar to those of blood, with minimal differences. This suggested that culture media in which these electrolytes are added in concentrations similar to those of serum are appropriate for culture of the human oocyte.


Prevention of the abortifacient action of antiprogesterone serum by progesterone. Earlier studies1-4 showed that when rats of 10 days' gestation are passively immunized with antiprogesterone (A-P) globulins the biologically available progesterone (P) unbound by A-P (Pu) not only falls precipitously but also remains low for days, despite the rapid clearance of A-P. This finding suggested that the effective reduction of Pu affects P synthesis, probably through action on the fetoplacental unit. If so, pregnancy should be protected from the effect of A-P by P treatment to prevent the reduction of Pu. The present studies demonstrated that if P treatment was delayed for six hours after the administration of A-P, Pu did not return to physiologic levels, and pregnancy did not continue. However, if P was given three hours after A-P, at the same time, or three hours before A-P, the reduction of Pu was short-lived or prevented, and thus pregnancy was protected.


"Johnny, I Hardly Knew Ye:" toward revision of the theory of male psychosexual development. "The psychology of women," as it now exists, is a shadowy negative of the psychology of men, and can be successfully formulated only if male psychology is reassessed and considerably revised. Male theorists and practitioners have made virtues of the harsh facts of male socialization. These conditions, which have unhappy repercussions in the male ego and in the culture as a whole, are modifiable only if they are identified and understood.


Sexual standards and behavior of the kibbutz adolescent. This paper explores the effects of the past decade's "sexual revolution" on adolescents in the kibbutz. Greater sexual freedom, within the context of a stable and affective relationship, is increasingly finding acceptance among kibbutz youth and their elders. The change in adolescent sexual standards is discussed in relation to broader social and philosophical changes in adult society in general, and kibbutz ideology in particular.


Social impairments four years after an acute depressive episode. Social functioning of 40 depressed women was studied four years following the acute episode, and compared with 40 normal community subjects. Results show that the social impairments of depressed patients persist well beyond the acute episode, particularly in marital and close interpersonal relations. Clinical and public health implications are discussed.


Imaginative play training and perceptual-motor interventions with emotionally-disturbed hospitalized children. This study evaluates fantasy play training and perceptual-motor intervention methods which temporarily increased the imaginative behavior of severely emotionally-disturbed, hospitalized children. Increases in imaginative behavior were accompanied by positive changes in body image and by affective and social gains. Implications for further development and implementation of these methods are discussed.


Interpersonal awareness in children: toward an integration of developmental and clinical child psychology. This paper postulates a five-stage developmental sequence of awareness of interpersonal issues such as trust in friendship and loyalty in peer group relations. Results of research comparing the impersonal and interpersonal awareness of children with poor peer relations is presented in an attempt to clarify the function of social cognition in clinical contexts.


Individual psychotherapy with the institutionalized aged. Contrary to the predisposition of many mental health professionals, this paper contends that insight-oriented, dynamically-based, individual psychotherapy is an effective treatment modality with the institutionalized elderly. Issues such as dependency, transference and countertransference, contrasts to psychotherapy with younger patients, and methodological modifications are discussed, and clinical examples are offered.


Battered women: a study of women who live with violent alcohol-abusing men. This study of women who have repeatedly experienced violence in relationships with alcoholic husbands identifies three distinct types of family of origin. It is suggested that the women carry the conditions of their early family situation into the marriage, and that clinicians' awareness of the background typology may help the women to understand and alter their behavior.


Peer rating by a community mental health team: a positive approach to accountability. A peer rating system was devised in response to a request from members of a community mental health team for a positive method of self-evaluation. Team members rated each other three times at one month intervals. Reliability was high, and factor analysis generated two major dimensions--positive regard and competence--assessed by the rating instrument. Validity data are discussed, and applications of the method suggested.


Role, ritual, and the grynnflnk.

Role, ritual, and the grynnflnk. While cohabitation among middle-class youth has been increasing, there has been little exploration of the influence of this change on the extended kin system. This paper examines the formal recognition of cohabitation, via role change and ritual, and introduces terminology to describe a relationship heretofore unaccounted for in our vocabulary.


The state and territorial public health laboratory: program activities, organization and prospects for the future. During the past two years we have studied the characteristics of state and territorial public health laboratories in an attempt to develop guidelines for considering reorganization of laboratory services in Massachusetts. Only a few recent monographs have dealt with this topic and, to our knowledge, the functional and organizational characteristics of these laboratories have not been reviewed. The state public health laboratory system affords an excellent example of applied laboratory science or technology organized to provide basic public health services. In this paper the programs and organization of the state public health laboratory are reviewed, and a functional basis more responsive to society's current needs is suggested.


Patient education and intrauterine contraception: a study of two package inserts. In July 1975 the Food and Drug Administration proposed a patient information package insert for all women considering use of an intrauterine device. In the same year we also prepared a brochure to be given to women considering use of a specific intrauterine contraceptive, the PROGESTASERT system. To compare these information sources for the patient, we surveyed by mail 253 women who are or had been PROGESTASERT system users. Each woman received either the FDA or our own prepared version. Comprehension of the two inserts was generally comparable, but readers of our insert found its informational content more complete. The survey findings affirmed the desirability of providing the patient with an educational brochure to be read prior to IUD insertion.


[On the inhibition of cholinesterases by pancuronium (author's transl)]. 1. The inhibition by pancuronium of acetylcholinesterase (AChE) and of plasma cholinesterase (ChE) was investigated in vitro regarding a) the sensitivity of both enzymes; b) the mechanism and constants of inhibition; and c) the relationship between the neuromuscular blocking and the anticholinesterase activity of pancuronium. 2. Pancuronium is a reversible inhibitor of both AChE and ChE. The inhibitory potency regarding ChE ([I]50=2.7 X 10(-7) M; Ki=4.2 X 10(-8) M) is highly selective and about 1000-fold higher than compared to AChE ([I]50=2.4 X 10(-4) M; Ki=3.5 X 10(-5) M). 3. The kinetic analysis by means of an Lineweaver-Burk plot and an Arunlakshana-Schild plot displayed a pure competitive mechanism of inhibition. 4. The inhibition of AChE and ChE is thought to be induced by a reversible binding of pancuronium to the anionic subsite of the active center, thus decreasing the formation of the primary enzyme-substrate complex. 5. The clinical administration of pancuronium for muscular relaxation during anaesthesia (0.01-0.08 mg/kg) will result in a concentration of approximately 10(-7)=10(-6) M in the extracellular fluid. Thus, an inhibition of plasma ChE can be expected to occur under clinical conditions, however, probably without practical significance.


[Generalized seizure during induction of neurolept analgesia (author's transl)]. A 49-years old female patient without any history of convulsion developed a generalized convulsion on induction of a neuroleptanalgesia (NLA) for vaginal hysterectomy. The treatment and investigations are described and the possible causes are discussed.


Comparison of the haemostatic and cardiovascular effects of adrenaline and ornithine-8-vasopressin (POR 8) in middle ear operations. The local haemostatic and cardiovascular effects of ornithine-8-vasopressin (POR 8) 5.5 IU and adrenaline 350 microng were compared in middle ear operations in combined and methoxyflurane anaesthesia. The study was double-blind. Adrenaline had statistically significantly better haemostatic properties than POR 8 and the method of anaesthesia did not affect the difference between adrenaline and POR 8. With both methods of anaesthesia adrenaline increased systolic arterial pressure and pulse rate, and transiently increased and then decreased diastolic arterial pressure. In contrast to adrenaline, POR 8 markedly increased diastolic arterial pressure and decreased pulse rate. All the parameters studied, the vasoconstrictors, the methods of anaesthesia as well as the times of measuring statistically significantly affected the changes both in systolic and diastolic arterial pressures. Only the methods of anaesthesia markedly affected the changes in the pulse rate. Transient electrocardiographic changes occurred from 6% to 17% in different groups.


[High spinal anaesthesia following intrathoracic intercostal nerve block. Report of a case (author's transl)]. In a 59-year-old female, anaesthetized with halothane, nitrous oxide/oxygen, intercostal nerve blocks were performed after right lateral thoracotomy. Before closure of the chest four segments were blocked each with 3 ml 0.5% bupivacain (Marcain, Carbostesin) without adrenaline. Three minutes after the last injection, the blood pressure, heart rate, and central venous pressure fell. The postoperative neurological status showed a high spinal anaesthesia. The patient was able to be extubated 90' after the last block and there were no further complications. The possible mechanism of producing spinal anaesthesia after peripheral nerve blocks and the necessary precautions to avoid this complication are discussed.


Annulate lamellae in spontaneous prolactin cell adenomas of the rat pituitary. Electron microscopy of 13 pituitary prolactin cell adenomas, removed at autopsy from untreated female aging Long-Evans rats, revealed the presence of annulate lamellae in 3 tumors. No annulate lamellae were detected in 10 non-tumorous pituitary glands of adult untreated rats. Direct continuity was demonstrated between annulate lamellae and rough-surfaced endoplasmic reticulum, consistent with the assumption that annulate lamellae may originate from and/or transform to endoplasmic reticulum membranes. The results indicate that annulate lamellae are not uncommonly formed in prolactin cell adenomas, i.e. in cells which have a faster growth rate than non-tumorous adenohypophysiocytes.


[Ultrastructural relationships between terminal vegetative nerve fibers, ground substance and differentiations of cell surface (author's transl)]. Ultrastructural findings concerning the terminal vegetative nerve formation indicate a functional coupling via proteoglycans of the extracellular matrix with effector cells. The biological function of proteoglycans in the ground substance and in surface coats of axons and cells are discussed in connection with fusiform varicose swellings along terminal vegetative nerve fibers. These contain accumulated vesicles which probably are active in releasing transmitter substances.


Vagus nerve passing in front of the left lobe of the thyroid gland. An anatomical variant of the left vagus nerve in reported which in its cervical portion passes in front of the carotid artery and the left lobe of the thyroid gland.


[The stress of the human hip joint. VII. The distribution of cartilage thickness in the acetabulum and its functional explanation (author's transl)]. The cartilage thickness of the human acetabulum was examined in 10 objects (material from the dissecting room). Cartilage specimens were taken at identical points of the joint and measured by microscope. The greatest thickness is situated in the outer joint edge, with a maximum in the frontal part of the joint roof; the lowest thickness is found at the inner margin of the facies lunata. These results indicate a higher stressing of the outer joint margin. This could be caused by an eccentric position of the hip joint's resultant force, which is shifted towards the edge. Another possible explanation of these results relates to a swelling of the joint cartilage under functional stress. Such a swelling, which has already been proved, would lead to an incongruence of the ball and socket joint, and so to a stronger stressing of the outer joint edge.


Scanning electron microscope study of the extracellular matrix between presumptive lens and presumptive retina of the chick embryo. The three-dimensional architecture of the intercellular matrix contained in the interspace between the presumptive lens and optic vesicle of the chick embryo was examined by scanning electron microsocpy. The fibrous structure of the basement membranes lining the space was demonstrated. The space was shown to be filled with a dense fibrous meshwork. The reaction of basement membranes and interspace contents to enzymic digestion is described. The functional significance of the arrangement of fibres in the interspace is discussed.


The development of the anterior falcate and lacrimal arteries in the human. Certain arteries of the head were studied in injected human fetuses from 143 to 290 mm C.-R., as well as in the orang-utan and gorilla, and in microscopical sections from 29 to 162 mm C.-R., as well as in an adult. It was found that, during human ontogenesis, an anterior falcate artery supplies the dura mater of the medial part of the frontal bone. It appears at 40 mm and reaches its full development by 115 mm. Normally it becomes reduced and is transformed into the anterior meningeal artery postnatally. It communicates with the meningeal branches of the lacrimal artery. Under pathological conditions that affect the dura mater, the falcate artery may appear postnatally in angiograms.


Isolation and storage of progressively motile human sperm. Human sperm progressively motile and free of seminal debris can routinely be isolated, during a 1.5 hour process, from semen of normal and subfertile men. Serum albumin, in a vertical column, acts to filter sperm based on their swimming abilities of forward progression. The isolated sperm constitute a population that can be inseminated as an aid to male subfertility or, to enhance the chances of sperm survival upon deep-freeze preservation. The latter use resulted in twice the survival rate, based on sperm motility, or random populations of control sperm.


Adult preferences for infantile facial features: an ethological approach. In 1943 Konrad Lorenz postulated that certain infantile cues served as releasers for caretaking behaviour in human adults. This study is an attempt to confirm this hypothesis and to identify relevant cues. The stimuli studied were variations in facial features, and the responses were ratings of the attractiveness of the resultant infant faces. Parametric variations of eye height, eye width, eye height and width, iris size, and vertical variations in feature position (all presented in full-face drawings) were tested for their effect on the ratings, and highly significant preferences for particular stimuli were found. In general these preferences are consistent across a wide variety of environmental factors such as social class and experience with children. These findings are consistent with an ethological interpretation of the data.


Cyproterone acetate: I. Microquantity releasing device of cyproterone acetate and its failure in inducing functional sterility in male rats. Prasad and his coworkers emphasized that microquantities of cyproterone acetate (CPA) when continuously available developed functional sterility in male rats by interfering the epididymal physiology. In our experimental rats either 2 or 3 capsules containing CPA as per the specification of Prasad were implanted subcutaneously and left for 300 and 250 days, respectively. Fertility test was made every month and it was observed that all the experimental animals were able to impregnate female rats throughout the experiment. Excepting the epididymis the weight of testes and other accessory glands did not differ from the controls in the animals which had 2 CPA capsules for 300 days; On the other hand, the animals which received 3 CPA capsules for 250 days showed significant reduction in weight of all the acessory glands including the testes.


Vocalizations of the black-tailed prairie dog, Cynomys ludovicianus. Seven variable vocal displays of Cynomys ludovicianus were studied in a captive colony, and checked through limited field work and literature reports. The form of each display makes available information identifying its user. In addition, since each display correlates probabilistically with a consistent set of activities, it makes available information about the behaviour in which the communicator is, or may become, engaged. At least five different kinds of behaviour can be specified through the use of these displays.


Studies of the correlation of morphological and biochemical parameters in human ejaculate in various andrological diagnoses; 2nd report: biochemical parameters. In this report the authors present the results about biochemical analyses in human ejaculate. The following parameters were determined ATP, ADP, pyruvate, lactate, alpha-ketoglutarate, fructose, myokinase, phosphoglucoseisomerase, phosphoglycerate-kinase, ATPase, acid phosphatase. It was found a relationship between age and fructose content, this was equally for pyruvate, whilst the converse was observed for lactate. No age dependend relationship was observed for the other substrates. For ATP and ADP distinctly higher values can be demonstrated in normozoospermia. A special study of the extent to which the encyme activities in sperm plasma are associated with the respective pH values measured shows that pH values above 7.2 correlate with distinctly lower activities for acid phosphatase, PGI and MK.


Development of song and reinforcing effects of song in female chaffinches. Eight autumn-caught female chaffinches were injected with testosterone in their first spring. They were allowed to perch on a particular perch to produce a playback of a normal, male song. Both the course of their song development and the reinforcing effect of the playback song were comparable to that shown by a group of similarly-treated males.


The significance of asbestos exposure in the diagnosis of mesothelioma: a 28-year experience from a major urban hospital. A continued increase in the incidence of diffuse mesothelioma has been attributed to greater industrial use of asbestos but is also due in part to wider acceptance of this tumor by pathologists. In this retrospective study, the epidemiology, clinical presentation, and pathology of asbestos and non-asbestos-related mesothelioma from a major urban hospital were reviewed. Of the 36 cases of mesothelioma on file, 19 were not associated with exposure to asbestos. Although a retrospective study raises the possibility of inadequate occupational histories, the lack of history of asbestos exposure correlated with postmortem histology by light microscopy. When postmortem material was reviewed, evidence of asbestos exposure was present in all cases of mesothelioma with history of exposure to asbestos, and in no cases in which the patient denied history of asbestos exposure. Using strict histologic and histochemical criteria, the diagnosis of mesothelioma was confirmed in 8 of 9 patients with asbestos-related mesothelioma but in only 4 of 13 cases of non-asbestos-related mesothelioma. The diagnosis of diffuse methelioma is often difficult to make even wtih complete autopsy examinations. It should be entertained only with adherence to strict clinical and pathologic criteria, especially in women with no history to exposure to asbestos dust.


The mucous lining of major bronchi in the rabbit lung. Mucous secretions covering the surface of the trachea and major bronchi of the rabbit lung have been demonstrated with the scanning electron microscope. The surface secretion forms a continuous layer overlying the major airways and shows a complex 3-dimensional arrangement of overlapping sheets and fibrous networks. In the main and lobar bronchi, mucus forms more expanded networks, and in the trachea, mucus forms a smoother, more cohesive layer overlying the epithelial cells. The mucous blanket follows closely the contours of the airway epithelium and is situated at the tips of the cilia.


Lung abscess due to Pseudomonas cepacia. A diabetic patient with pneumonia of unspecified origin developed a lung abscess after therapy with ultrasonic nebulization. The etiologic organism was identified as Pseudomonas cepacia. Investigation determined the source of the organism to be the reservoir of the ultrasonic nebulizer, to which the patient was directly exposed through removal of the bottom of the disposable medication cup. When this organism is isolated a nosocomial source of infection should be suspected.


Chest radiographs during isoniazid therapy. For most tuberculin reactors, chest radiographs are obtained at the beginning of, at various intervals through the course of, and at the end of the year of isoniazid preventive therapy. A study of 1,524 tuberculin reactors was performed to determine the value of chest radiographs obtained after therapy was begun; 1,315 had normal radiographs at the beginning and end of therapy, and 209 had radiographic abnormalities at both times. No significant changes were noted in any of the 1,524 patients' radiographs. Similar results had been reported for 551 tuberculin reactors in an earlier study. This provides a total of 2,075 patients for whom no value could be found in the subsequent radiographs. We found no value in repeating normal chest radiographs of positive reactors if they had completed at least 9 months of the properly recommended 12 months of isoniazid preventive therapy. The lack of value of repeat radiographs, coupled with their fixed cost and the potential risk of unnecessary radiation, dictated our change in policy--we no longer repeat normal chest radiographs in such persons.


[Development and long term prognosis of lupus erythematosus (apropos of 124 cases)]. The authors report their experience of the course of lupus erythematosus. The ten year survival rate in 124 patients was 79.3 %. This good result is attributed to the effective treatment of the disorder using corticosteroids; often associated with ummuno-suppressants in severe cases. However, the side-effects of these drugs remain a source of concern and the ideal treatment for lupus has yet to be discovered.


[Pharyngo-laryngeal cancer and Bazex's acrokeratosis (author's transl)]. The authors describe the case of a 62-year-old man presenting with a differentiated epidermoid carcinoma of the piriform sinus, associated with cutaneous lesions of the Bazex's acrokeratosis type. This case is of interest on account of the unusual lesion of the penis, the gland and the scrotum on the one hand of the lack of parallelism between the development of the cancer and that of the cutaneous syndrome on the other.


[Cutaneo-digital metastasis of a cancer of the buccal floor (author's transl)]. The authors describe the case of a patient with cancer of the buccal floor presenting with an inflammatory tumefaction of the tip of the little finger of the left hand passing for a whitlow. No cure was obtained after two lancings, and X-Rays showed lesion of the bone. Amputation revealed neoplastic tissue similar to that in the buccal floor. This cutaneous-digital metastasis is very rare, especially in cases of O.R.L. tumours.


Cairomycin B, a new antibiotic.

Cairomycin B, a new antibiotic. Cairomycin B is a new cyclic peptide antibiotic that was isolated from Streptomyces As-C-19 obtained from the soil of Cairo. The antibiotic had the following empirical formula: C(10)H(15)N(3)O(3); on acid hydrolysis, it yielded aspartic acid and lysine. Spectral analysis and its chemical characteristics indicated that it was a cyclic peptide. The antibiotic melted at 120 to 121 degrees C and was freely soluble in chloroform, ethyl acetate, and acetone, slightly soluble in alcohols, and rather insoluble in water and petroleum ether. Cairomycin B was mainly active against gram-positive bacteria, with high toxicity to experimental animals and weak serum-binding properties.


Bacteriostatic and bactericidal activities of selected beta-lactam antibiotics studied on agar plates. A novel and time-saving method for assessing bactericidal activities of beta-lactam antibiotics on agar plates is described. Minimal inhibitory concentrations (MICs) were determined by the agar dilution method. A potent beta-lactamase solution was sprayed onto the plates to inactivate the antibiotic. After further incubation at 37 degrees C overnight, the minimal concentration at which no visible growth occurred on the plates was defined as minimal bactericidal concentration (MBC). With undiluted culture as the inoculum, strains of Staphylococcus aureus, Escherichia coli, and Klebsiella pneumoniae showed a marked increase in MBC values compared with the values of MIC. There was a marked decrease in both the MICs and MBCs with diminution of inoculum size. The two concentrations were almost the same when the inoculum size was decreased to a 10(-4) dilution. In contrast, MIC and MBC for enterococci showed no marked decrease with decrease in inoculum size. Although the present study was performed with beta-lactamase-unstable penicillins and cephalosporins, the method can be applicable with any beta-lactam antibiotic if optimal and potent enzymes are available.


Cefoxitin: clinical evaluation in thirty-eight patients. Clinical and bacteriological efficacy, patient tolerance, and toxicity of cefoxitin, a beta-lactamase-resistant cephamycin, were evaluated in 38 patients; 13 had soft tissue infection, 12 had pneumonia, 3 had urinary tract infection, 2 had peritonitis, and 4 had miscellaneous infections. In five patients, infection was clinically evident, though not bacteriologically proven. The latter patients were evaluated with regard to tolerance and toxicity only. Among the 34 infections in 33 patients, 71% were considered clinically cured; 86% of those patients who could be recultured were bacteriologically cured. Phlebitis was noted in 32% of the total group, and eosinophilia was observed in 16%. Unexplained deterioration in renal function occurred in two patients. Mean peak cefoxitin levels in serum were 72 mug/ml 30 min after a 2-g infusion and 32 mug/ml 30 min after a 1-g infusion. Cefoxitin was more active against facultatively and obligately anaerobic gram-negative organisms isolated from these patients than was cephalothin.


Chemotherapy of an experimental Bacteroides fragilis infection in mice. The efficacies of five common antimicrobial agents were determined for a pure Bacteroides fragilis infection in mice. Therapy was begun 4 h after bacterial injection and given every 8 h thereafter for 5 days. Blood levels were determined over an 8-h period for each concentration of antibiotic tested. Clindamycin and tetracycline were the most effective in preventing the formation of abscesses. Chloramphenicol, penicillin G, and cephalothin were not effective in protecting the mice from infection.


Terminal stages in the biosynthesis of tylosin. Tylosin, a macrolide antibiotic, was co-produced with four structurally similar antibiotics in fermentation cultures of Streptomyces fradiae. Macrocin, desmycosin, lactenocin, and relomycin were found to be components of a common pathway that functions in tylosin biosynthesis. Data obtained by the addition of the purified (14)C-labeled antibiotics to cultures of S. fradiae revealed that macrocin and desmycosin were direct precursors of tylosin, whereas lactenocin was an immediate precursor of both macrocin and desmycosin. Incubation of these cultures with [(14)C]tylosin resulted in an equivalent distribution of radioactive label between relomycin and an unidentified component. The kinetics of incorporation of label into the two species were similar, suggesting that both were derived directly from tylosin. A system that supported that methylation of macrocin to tylosin by cell-free extracts of S. fradiae was developed. A proposed scheme defining the terminal stages of tylosin biosynthesis is presented.


Bioavailability of tetracycline and doxycycline in fasted and nonfasted subjects. The influence of various test meals and fluid volumes on the relative bioavailability of commercial formulations of doxycycline hyclate and tetracycline hydrochloride was studied in healthy human volunteers. Serum levels of tetracycline were uniformly reduced by approximately 50% by all test meals, whereas serum levels of doxycycline were reduced by 20%. The reduction of tetracycline serum levels will likely be of clinical significance. The bioavailability of each drug was almost identical from an oral solution and from capsules in fasted subjects. The rate of doxycycline absorption was reduced when capsules were administered with a small volume of water, but the overall efficiency of absorption of both drugs was essentially independent of co-administered fluid volume. The use of 8-h serum data provides a reliable estimate of drug bioavailability for tetracycline and, to a lesser extent, for doxycycline.


Effects of 2-deoxy-D-glucose and 3 deazauridine individually and in combination on the replication of Japanese B encephalitis virus. We have tested the potencies of the competitors of glucose, 2-deoxy-d-glucose, and of uridine, 3-deazauridine, on the inhibition of Japanese B encephalitis virus multiplication in BHK-21 cell cultures. The relative effectiveness of the viral inhibitors were evaluated individually and in combination in relation to cytotoxicity as a measure of the selectivity of inhibition. When the drugs were administered individually, the antiviral activity was masked by the cytotoxic effect on the host. By combining the two drugs, it was possible to inhibit Japanese encephalitis virus production at noncytotoxic concentrations. The effects of 2-deoxy-d-glucose and 3-deazauridine on the growth inhibition of BHK-21 cells in cultures were only additive, while they were clearly synergistic on the inhibition of Japanese encephalitis virus production. Thus, it was possible to achieve an increased antiviral effect without a significant increase in cytotoxicity. Although the precise biochemical mechanism of the antiviral activity of these antimetabolites in combination is not known, our results indicate the potential value of this approach in viral chemotherapy.


Comparative growth rates of selected anaerobic species in four commonly used broth media. Generations times (g(t)) of selected anaerobic species were compared in four culture media commonly used for anaerobic bacteria to evaluate these media for growing inocula for anaerobic antibiotic susceptibility determinations. Twenty-two clinical isolates of Bacteroides fragilis, Fusobacterium spp., Clostridium perfringens, and Clostridium spp. were tested in Schaedler broth, supplemented Lombard-Dowell broth, supplemented thioglycolate broth, and supplemented peptone-yeast extract-glucose broth. Growth curves were performed in an anaerobic chamber; changes in cell density were followed by viable count procedures and, in some cases, turbidometric procedures. The clostridia did not appear to have significantly different g(t) values in different media. The g(t) values for the five clostridial species tested ranged from 18 to 45 min. The fusobacteria also showed no apparent differences in g(t) values in the four media; values ranged from 51 to 60 min. The two subspecies of B. fragilis tested showed no significant differences in g(t) values when compared with each other in the same media. The combined data, however, indicated that the growth rate in Schaedler broth was faster than in the other media (average g(t), 45.1 min), whereas the growth rate in peptone-yeast extract-glucose was slower (average g(t), 58.2 min). The growth rates in supplemented thioglycolate and supplemented Lombard-Dowell broth (average g(t), 53.6 min and average g(t), 51.0 min, respectively) were not significantly different.


Inhibition of initiation, elongation, and termination of eukaryotic protein synthesis by trichothecene fungal toxins. The 12,13-epoxytrichothecenes, specific inhibitors of protein synthesis in eukaryotes, can be subdivided further in terms of their mode of action. In addition to the I-type (initiation inhibitors) and E-types (elongation inhibitors), we found that some E-types apparently exhibit inhibition of chain termination at low concentrations. The nature of substituents on C4 may determine the type of inhibitory activity observed.


Effect of ethambutol on the viable cell count in Mycobacterium smegmatis. Soon after a strain of Mycobacterium smegmatis was exposed to ethambutol (EMB), the number of viable cells increased dramatically above the number in a drug-free control. This rapid rise did not occur when the culture was maintained at 4 degrees C instead of 37 degrees C, when an EMB-resistant mutant was used, when auxotrophs were exposed in medium lacking nutrients essential for growth, nor when the levo form of EMB was used. EMB caused no increase in deoxyribonucleic acid synthesis, nor in septum formation of dividing cells. Treated cells changed morphologically, resulting in a lower surface area-to-volume ratio. Whereas EMB did not eliminate cell clusters, the cluster size decreased markedly as detected by filtration and Coulter counter measurements. We concluded that EMB causes a reduced surface-to-volume ratio, leading to reduced cell cohesion and a consequent reduction in cluster size, reflected in an increase in colony-forming units.


Antimicrobial susceptibilities of Yersinia enterocolitica biotype 4, serotype O:3. Agar dilution antimicrobial susceptibility tests were carried out against recent clinical isolates of Yersinia enterocolitica biotype 4, serotype O:3. Aminoglycosides and co-trimoxazole were the most active drugs. All isolates were resistant to ampicillin, carbenicillin, cloxacillin, and erythromycin.


Stimulation of interferon production in mice and in mouse spleen leukocytes by analogues of BL-20803. Various structural analogues of the interferon inducer BL-20803 exhibited close agreement between ability to stimulate interferon production in the intact mouse and in cultures of spleen adherent leukocytes.


Cerulenin-inhibited cells of Staphylococcus aureus resume growth when supplemented with either a saturated or an unsaturated fatty acid. In the presence of an inhibitory concentration of cerulenin, cells of Staphylococcus aureus can resume growth when supplemented with either a saturated or an unsaturated fatty acid. A requirement for both types of acids for growth could not be demonstrated.


In vitro activity of cinoxacin, ampicillin, and chloramphenicol against Shigella and nontyphoid Salmonella. The in vitro antibacterial activity of cinoxacin was compared with that of ampicillin and chloramphenicol against 26 strains of nontyphoid Salmonella and 44 strains of Shigella. Cinoxacin was found to have a lower minimal inhibitory concentration than ampicillin and chloramphenicol against all Salmonella and Shigella sonnei strains. Cinoxacin had minimal inhibitory concentrations similar to those of chloramphenicol but lower than those of ampicillin against Shigella flexneri and S. boydii strains.


Effect of antibiotics of chemotaxis of human leukocytes. The effect of 20 different antibiotics on chemotaxis by human neutrophils was studied. Human leukocytes incubated with chloramphenicol, rifampin, sodium fusidate, and tetracyclines in vitro showed markedly depressed migration. The mechanisms by which these antibiotics affect leukotaxis are discussed.


R plasmids from Asian strains of Vibrio cholerae. Five R plasmids transferred from Asian strains of Vibrio cholerae all proved to be members of compatibility group C. A non-self-transmissible plasmid, stable in V. cholerae, was mobilized for transfer to Escherichia coli K-12 and found to be unstably inherited in that host. Plasmids of group C and P transferred to a wild V. cholerae strain were stably inherited.


Penetration of cefazolin, cephaloridine, and cefamandole into interstitial fluid in rabbits. We compared the penetration of three cephalosporins into interstitial fluid. Interstitial fluid was obtained in rabbits from Silastic tissue cages. Cefazolin, cephaloridine, and cefamandole were administered by the intramuscular route (30 mg/kg per injection). Peak blood levels and interstitial concentrations were studied after a single injection. Interstitial levels were also compared in a three-injection study (one injection every 12 h) and in a cumulative effect study (six injections), in which the interval between injections was established for each drug on the basis of its common therapeutic use. After a single injection, cephaloridine activity was detected more rapidly and attained higher levels than the other two drugs within the first 4 h. However, 2 h after the third injection, cefazolin levels in tissue fluid were higher than with cephaloridine. Cefamandole consistently gave the lowest interstitial levels. With all three drugs, detectable concentrations were present in interstitial fluid at a time when no detectable antibiotic was found in serum. In the six-injection study, the interstitial levels obtained with cefazolin were significantly higher than those observed with the other drugs. Our data suggest that cefazolin is a drug of choice due to its high extravascular levels.


Netilmicin and gentamicin: comparative pharmacology in humans. Thirteen male subjects received 1 mg of either gentamicin or netilmicin per kg, first intramuscularly and then intravenously. After the intramuscular dose, concentrations of gentamicin in the serum were more variable than those of netilmicin. After the intravenous dose, the distribution phase of netilmicin was twice as rapid as gentamicin. The average half-times of the elimination phase were similar, but there was marked variability among the subjects receiving gentamicin. Serum clearance of netilmicin was more rapid than that of gentamicin and could not be attributed to renal elimination. The data indicate that, after intramuscular administration, netilmicin may produce more predictable blood levels than gentamicin and suggest that the body distribution of netilmicin may differ from that of gentamicin.


Plasmid-medicated aminoglycoside phosphotransferase of broad substrate range that phosphorylates amikacin. A plasmid-mediated aminoglycoside phosphotransferase that phosphorylates amikacin has been detected in clinical isolates of Staphylococcus aureus. This enzyme does not confer detectable amikacin resistance to the strains.


Therapeutic evaluation of minocycline and tetracycline for mixed anaerobic infection in mice. Minocycline has demonstrated greater in vitro activity against anaerobic bacteria than its parent compound, tetracycline. In vivo therapeutic efficacy of the two drugs was tested against a mixed anaerobic infection in a mouse model. Fusobacterium necrophorum plus F. nucleatum injected intraperitoneally produced progressive intrahepatic and occasional extrahepatic abscesses, which were measured at autopsy. Three treatment regimens were tested, single daily doses of antibiotic being administered by oral gavage: four doses begun at 2 or 24 h after challenge and 14 doses begun 3 weeks after challenge when abscesses were well developed. Autopsy was not performed until several weeks after completion of treatment to assess long-term effects. Based on the number of mice without lesions, the median effective dose (ED(50)) in milligrams per kilogram per dose for minocycline was significantly lower than that for tetracycline with each regimen tested. With the 2-h (immediate therapy) regimen and the 24-h-delayed therapy regimen, minocycline was 30 and 6 times, respectively, more effective against hepatic abscesses than tetracycline on a weight basis. With each antibiotic, abscesses outside the liver were more resistant to therapy, although again minocycline was more effective. In the treatment of developed abscesses (3-week-delayed regimen), minocycline was effective (ED(50) <16 mg/kg), whereas tetracycline was ineffective (ED(50) >256 mg/kg). Minocycline has demonstrated greater therapeutic efficacy in vivo than tetracycline in this experimental infection, which is similar, in certain aspects, to human anaerobic infection. These data support further evaluation of the clinical usefulness of minocycline.


Susceptibility of anaerobic bacteria to metronidazole, ornidazole, and tinidazole and routine susceptibility testing by standardized methods. A total of 114 strains of anaerobic bacteria were examined for their susceptibility to metronidazole, ornidazole, and tinidazole by measuring the minimum inhibitory concentration (MIC) and minimum bactericidal concentration in different media. All strains, with the exception of the isolates of Propionibacterium acnes, were inhibited by 3.1 mug each and killed by 6.3 mug each of all three nitroimidazole compounds per ml. No significant differences in MIC values were found among metronidazole, ornidazole, and tinidazole. Only minor differences were detected by comparing MIC values obtained in brain heart infusion agar with and without sheep blood, brucella agar, and Mueller-Hinton agar (both containing blood). When the strains were tested by the modified broth-disk method proposed by the Anaerobe Laboratory of the Virginia Polytechnic Institute (VPI), there was good correlation with the MIC values (97.4% agreement for metronidazole and 94.7% for ornidazole and tinidazole). For routine testing, use of a 30-mug-class disk of either nitroimidazole derivative is proposed for the broth-disk method, resulting in a final concentration of 6 mug/ml in the test tubes, a concentration easily attainable in body fluids. In contrast to the broth-disk method, there was very poor correlation between inhibition zone diameters by the standardized VPI agar diffusion test and MIC values.


Assay of gentamicin in serum by high-pressure liquid chromatography. A procedure is described that uses high-pressure liquid chromatography for assay of gentamicin in serum. The technique involves extraction of gentamicin from serum by using a CM-Sephadex column and analysis by reverse-phase, ion-pair chromatography. Continuous-flow, post-column derivatization with o-phthaladehyde is used to form fluorescent products for detection. The possible scope of this method for analysis of other aminoglycoside antibiotics is illustrated by application to sisomicin and netilmicin.


Macrolide resistance in Staphylococcus aureus: induction of macrolide-resistant protein synthesis. Induction of resistance to macrolide-, lincosamide-, and streptogramin B-type antibiotics in Staphylococcus aureus was studied by monitoring the appearance of erythromycin A (EM)-resistant [(14)C]leucine incorporation. Examination of the induction process revealed saturation kinetics and a time course much like that reported for penicillinase in gram-positive bacteria. Induction kinetics in exponentially growing cells were sigmoidal and appeared to reach a maximum and constant rate when growth reached stationary phase. Since the induction of EM-resistant colony-forming ability was complete within 60 min, ribosome modification cannot be limited to a fraction of the population and must occur in essentially every cell. However, EM-resistant growth was expressed in cells where less than half the [(14)C]leucine-incorporating activity was resistant to EM. This suggests that resistance requires that only a threshold level of ribosome modification be exceeded and that, once exceeded, resistance is dominant to sensitivity.


Macrolide resistance in Staphylococcus aureus: inducers of macrolide resistance. Several macrolide-, lincosamide-, and streptogramin B-type (MLS) antibiotics were tested as inducers of erythromycin A (EM)-resistant [(14)C]leucine incorporation. Only 14-membered-ring macrolides having a glycosidically linked 6-deoxy sugar at the C-3 position of the lactone ring and the structurally dissimilar lincosamide, celesticetin, showed inducer activity. Modifications of EM at the C-4'' position of cladinose can apparently destroy the inducer property but do not affect the inhibitory properties of the antibiotic. The findings clearly show that inducer and inhibitor activities can be dissociated and are consistent with the concept that distinct binding/receptor sites are utilized for inhibition of ribosome function and induction of resistance.


Comparative susceptibility of anaerobic bacteria to ticarcillin, cefoxitin, metronidazole, and related antimicrobial agents. The in vitro antimicrobial activity of two newer agents, ticarcillin and cefoxitin, against 204 recent clinical isolates of anaerobic bacteria was determined by an agar dilution technique, and compared to their related compounds carbenicillin, cephalothin, and penicillin, as well as metronidazole, clindamycin, and chloramphenicol. Ticarcillin was similar to carbenicillin, and cefoxitin was more active than cephalothin. At readily achievable blood concentrations of each antimicrobial agent, ticarcillin was slightly less active than clindamycin against Bacteroides fragilis. Cefoxitin was superior to cephalothin and penicillin against B. fragilis. Penicillin remained highly active against all obligate anaerobes other than B. fragilis. Metronidazole, while highly effective against B. fragilis and Clostridium perfringens, was only intermediately effective against anaerobic gram-positive cocci and relatively inactive against nonsporulating anaerobic gram-positive bacilli. Further evaluation of the clinical efficacy of ticarcillin, carbenicillin, and cefoxitin against anaerobic infections is indicated.


Indirect mouse model for the evaluation of potential antiviral compounds: results with Venezuelan equine encephalomyelitis virus. An indirect mouse model was utilized to evaluate the antiviral activity of several compounds against Venezuelan equine encephalomyelitis (VEE) virus infection in mice. Mice were given various dosages of lysine-stabilized polyriboinosinic acid-polyribocytidylic acid, a tilorone analogue, kethoxal, or mepacrine before and/or shortly after receiving one of several dose levels of attenuated strain TC-83 VEE virus. Twenty-one days later, the same mice were rechallenged intracranially with virulent Trinidad donkey strain VEE virus. Susceptibility to rechallenge was interpreted as evidence of drug effectiveness in completely preventing the initial immunizing virus infection. In contrast, if a drug lacked antiviral effectiveness, the initial attenuated infection stimulated sufficient immunity to protect mice against the virulent rechallenge. Both of the interferon inducers, lysine-stabilized polyriboinosinic acid-polyribocytidylic acid and tilorone analogue 11,567, possessed significant (P < 0.01) antiviral activity based upon this indirect model, whereas mepacrine and kethoxal were inactive. Results using the indirect method were confirmed by using the conventional direct method for evaluating the effectiveness of potentially useful antiviral compounds. The indirect mouse model described should prove useful for studying drug efficacy against certain viruses that are lethal only by intracranial inoculation.


Tobramycin: maternal-fetal pharmacology. To investigate the maternal-fetal transfer of tobramycin (TBM) and its distribution in the fetus, a single dose of 2 mg/kg was administered intramuscularly to 35 pregnant patients (13 first trimester, 22 second trimester) 0.5 to 34 h before hysterectomy. TBM concentration was assayed microbiologically in maternal serum, fetal tissues (placenta, brain, lung, liver, and kidney), and fluids (amniotic, cerebrospinal fluid [CSF], urine, and serum). Mean maternal serum half-life (1.54 h) and mean peak serum concentration of TBM were within ranges reported for nonpregnant adults. In fetal serum, half-life was 5.2 h, and TBM levels did not exceed 0.58 mug/ml. For intervals up to 34 h, the mean TBM concentration in placental tissues was 1.4 mug/g. Concentration differences related to fetal maturation were found for fetal CSF, amniotic fluid, and fetal kidney. No antimicrobial activity was found in the fetal CSF of >16 weeks' gestation. TBM was present predominantly in the second trimester amniotic fluid specimens. Fetal kidney concentrations reached 7.2 mug/g at 34 h after maternal drug administration. Higher TBM concentrations were related to advanced maturation of the fetal kidney. Second trimester fetal urine concentrations for TBM ranged from 0.1 to 3.4 mug/ml, and the fetal urinary half-life was 3.7 h. Knowledge of fetal pharmacology is essential for weighing the fetal benefits or risks of antimicrobial therapy for the infected gravid patient.


Levels of carbenicillin, ticarcillin, cephalothin, cefazolin, cefamandole, gentamicin, tobramycin, and amikacin in human serum and interstitial fluid. The ability of eight antibiotics (carbenicillin, ticarcillin, cefamandole, cephalothin, cefazolin, gentamicin, tobramycin, and amikacin) to enter human interstitial fluid was evaluated by the skin window technique. All of the antibiotics tested, except cefazolin, which has the highest percentage of protein binding, diffused into the interstitial fluid quite well. This study confirms our previous observation on the effect of high-percentage protein binding on diffusion of a drug into the minimally inflamed extravascular space.


Chemotherapy of genital herpes simplex virus type 2 infections of female hamsters. The antiviral activity of 1-beta-d-arabinofuranosylcytosine (ara-C, cytarabine, Cytosar), 5-iodo-2'-deoxyuridine (IdUrd), 9-beta-d-arabinofuranosyladenine (ara-A), and disodium phosphonoacetate (PAA) have been compared in herpes simplex virus type 2 (HSV-2)-infected primary rabbit kidney cells and in female hamsters with genital HSV-2 infection. In vitro, ara-C and IdUrd were more active than ara-A, and PAA was least active. In female hamsters with genital HSV-2 infection, intravaginal treatment with PAA or ara-A was more effective than either ara-C or IdUrd. PAA was more active than ara-A when treatment was initiated early (1 h) after infection. The activity of PAA was greatly reduced if initiation of treatment was delayed for 24 h. Both PAA and ara-A reduced the virus titers of the vagina and protected hamsters from death when the drugs were given by either the intravaginal or subcutaneous route, with intravaginal treatment being more effective.


Bacteriocin production by strains of Bacteroides isolated from human feces and the role of these strains in the bacterial ecology of the colon. Several human fecal isolates of Bacteroides have been found to produce bacteriocins. The bacteriocin-producing strain T1-1 was studied in the most detail. Strain T1-1 belongs to the 0061-1 deoxyribonucleic acid (DNA) homology group of Bacteroides. This homology group phenotypically resembles Bacteroides thetaiotaomicron but has little DNA homology with it. The bacteriocin-producing strains T1-12 and T1-48 belong to the 3452-A DNA homology group. This group has DNA homology with B. thetaiotaomicron and Bacteroides ovatus. The bacteriocin-producing strain T1-42 remains unidentified in that it does not belong to any recognized DNA homology group of the saccharolytic intestinal bacteroides. The extracellular bacteriocin produced by strain T1-1 was specifically bactericidal for other bacteria within the genus Bacteroides. The highest bacteriocin titers (32 to 64) were produced in complex media, with only trace amounts being produced in a defined medium. The bacteriocin appeared to have a high molecular weight (>/=300,000) and was unusual because it was stable from pH 1 to 12 and only a 50% reduction in activity resulted after 15 min at 121 degrees C in an autoclave. It was inactivated by trypsin and Pronase. Strain T1-1 was isolated from all three fecal samples obtained over a 25-week period from an individual who was part of a National Aeronautics and Space Administration mock Skylab flight. Strains T1-12, T1-48, and T1-42 were isolated only from the first fecal sample. Each of these strains was immune to the bacteriocins produced by the others. These strains were found to coexist in the colon with a larger population of non-bacteriocin-producing, bacteriocin-susceptible strains of Bacteroides.


Cefoxitin resistance to beta-lactamase: a major factor for susceptibility of bacteroides fragilis to the antibiotic. Toluene-treated cell suspensions of Bacteroides fragilis were used to screen clinical isolates for the production of beta-lactamase. Approximately one-third of the isolates possessed considerable cephalosporinase activity. A significant correlation was found between beta-lactamase production and resistance to cephalosporin antibiotics. Several isolates were resistant to cefuroxime and cefamandole and produced enzymes capable of hydrolyzing these antibiotics. However, none of the 79 strains tested could hydrolyze the cephamycin derivative, cefoxitin. A large percentage (>90%) of the strains were susceptible to cefoxitin. Therefore, resistance to lactamase hydrolysis is a major factor for the effectiveness of cefoxitin against B. fragilis. Detailed studies of four isolates suggest that two different enzymes may be produced. Both are cephalosporinases but differ with regard to cellular distribution and substrate specificity. Cefoxitin is not a substrate for either enzyme, but it is an excellent competitive inhibitor (K(i) approximately 0.1 muM).


Evaluation of the in vitro antifungal activity of allicin. Allicin was effective in vitro against Candida, Cryptococcus, Trichophyton, Epidermophyton, and Microsporum. The minimal inhibitory concentrations (MICs) of allicin against these organisms were 3.13 to 6.25 mug/ml by the agar dilution method and 1.57 to 6.25 mug/ml by the broth dilution method, using Sabouraud glucose (SG) medium. However decreased activity was demonstrated against Aspergillus. The MIC of allicin against various pathogenic fungi was affected considerably by differences in the experimental conditions, e.g., incubation time, inoculum size, type of medium, and medium pH. The MIC of allicin against Candida, Cryptococcus, and Aspergillus remained constant after more than 3 days of incubation, and that against Dermatophytes remained constant after more than 10 days of incubation. Decreasing the inoculum size increased the susceptibility to allicin. The antifungal activity of allicin was stronger on SG agar medium with a pH of 5.6 than on the same medium with a pH of 6.0 or higher. By microscopical observation, allicin induced morphological abnormalities in hyphae of Trichophyton mentagrophytes Morita. Percent germination of spores of the Morita strain at 24 h in SG agar medium was greatly decreased with an allicin concentration of 3.13 mug/ml, and the lethal dose for the spores was about four times higher than the fungistatic concentration. These results suggest that allicin inhibits both germination of spores and growth of hyphae.


Measurement of polyene antibiotic-mediated erythrocyte damage by release of hemoglobin and radioactive chromium. Polyene antifungal antibiotics produce various degrees of membrane damage in sheep erythrocytes in vitro. Mediocidin, filipin, amphotericin B, and candicidin were found to result in greater damage than nystatin, pimaricin, and amphotericin B methyl ester. The degree of sensitivity of the cells varied by 100-fold for mediocidin verus amphotericin B methyl ester as measured by curves of hemoglobin release versus drug concentration. In erythrocytes prelabeled with radioactive chromium, release of the isotope through polyene-damaged cell membranes was found to occur at lower drug concentrations than measurable hemoglobin release, and the percentage of isotope released at the highest drug dose was consistently greater than the percentage of hemoglobin released. Thus, the isotope assay is a more sensitive indicator of polyene-induced membrane damage in the test system. These significant differences in release of molecules through polyene-induced membrane lesions indicate the complex nature of the binding and further interactions of this class of drugs with the plasma membrane.


Evaluation of the Autobac 1 susceptibility testing system in a clinical diagnostic laboratory. The Autobac 1 system was compared to the disk diffusion and agar dilution methods. Overall, there was good correlation; however, certain antibiotic/bacterial combinations gave unreliable results. In particular, unreliable results were obtained against staphylococci with penicillins, aerobic gram-negative rods with cephalothin, and enterococci with cephalothin and clindamycin.


Mutagenicity and antibacterial activity of hydroxamic acids. Hydroxamic acids demonstrated mutagenic and antibacterial activities. These activities appear to be dependent on the hydroxamic acid function and are probably due to the interaction with deoxyribonucleic acid.


Effects of ionenes on interferon induction by poly(inosinic acid) . poly(cytidylic acid). Depending on the spacing of their positive charges, ionenes, a class of quaternary ammonium polymers, increased the interferon-inducing activity of poly(inosinic acid).poly(cytidylic acid) in mouse L-929 cells, whereas they did not enhance poly(inosinic acid).poly(cytidylic acid) induced interferon production in primary rabbit kidney and human skin fibrolast cells.


Distribution of sodium cefazolin in serum, muscle, bone marrow, and bone of normal rabbits. Cefazolin levels were detected in bone and bone marrow of normal rabbits dosed intramuscularly, even in the absence of detectable levels in serum.


Mycobacterium chelonei infection: successful treatment based on a radiometric susceptibility test. A patient with Mycobacterium chelonei infection was treated with erythromycin stearate and streptomycin. The choice of antibiotics was based on a rapid radiometric susceptibility test developed in our laboratory.


Efficacy of 5,6-dihydro-5-azathymidine against cutaneous herpes simplex virus in hairless mice. 5,6-Dihydro-5-azathymidine, administered subcutaneously, was active both prophylactically and therapeutically against cutaneous herpesvirus infection of hairless mice. Activity was comparable to that obtained with adenine arabinoside.


125I radioimmunoassay of netilmicin.

125I radioimmunoassay of netilmicin. We report a radioimmunoassay for the new semisynthetic aminoglycoside netilmicin with a sensitivity of 480 pg per tube and a correlation coefficient of 0.94 between this radioimmunoassay and a microbioassay for measurement of netilmicin in serum.


Effect of sodium salicylate and indomethacin on methotrexate-serum albumin binding. Approximately 60% of methotrexate in serum is protein bound and this binding occurs primarily to serum albumin. The fraction of methotrexate bound remains relatively constant despite changes in free methotrexate concentrations over the range observed clinically. Indomethacin did not influence methotrexate-albumin binding, but salicylate in therapeutic concentrations produced a 20% to 60% decrease in binding. The clinical significance of these findings for patients requiring concomitant methotrexate and salicylate is discussed.


Betamethasone valerate ointment compared with fluocinonide FAPG. Betamethasone 0.1% as valerate in an ointment base and fluocinonide 0.05% in a fatty alcohol propylene glycol (FAPG) base have been compared in a double-blind trial of 76 patients with either eczema or psoriasis. The results show betamethasone valerate ointment to be significantly (P less than.05) superior to fluocinonide FAPG in the treatment of both these skin conditions. In the light of publications from other studies on betamethasone valerate cream this trial indicates that the ointment base considerably increases the efficacy of betamethasone valerate.


Perfume dermatitis. a study of 20 patients. Patch tests to several screening sets of fragrance materials were performed on 20 perfume-sensitive patients. The most common allergens were found to be a jasmin synthetic (18 of 20 patients), cinnamic alcohol (15 of 20 patients), and hydroxycitronella (9 of 20 patients). More than half of the patients were also contact sensitive to other ingredients of cosmetics and over-the-counter and prescription preparations.


Abnormal vascular reactions in atopic dermatitis. Vascular reactions to mechanical stroking, topical application of nicotinic acid ester, and methacholine chloride were examined in both the normal and abnormal skin of 100 patients with atopic dermatitis and 20 patients with allergic contact dermatitis. White dermographism, nicotinic acid blanching, and delayed blanch with methacholine consistently occurred in areas of skin with eczematous change of patients with atopic dermatitis and those with allergic contact dermatitis. Normal skin of atopic patients did not show the abnormal vascular reactions. It is suggested that white dermographism, nicotinic acid blanching, and delayed blanch with methacholine seen in atopic dermatitis are secondary phenomena that give no definite information concerning the diagnosis of this disease.


Lymphocutaneous nocardiosis due to nocardia brasiliensis. A farmer had chaining lymphocutaneous granuloma on the right hand and arm. Clinically the syndrome seemed typical for sporotrichosis. Bacteriological examination revealed Nocardia brasiliensis as the only etiologic agent. Since 1920, eight similar cases of sporotrichoid nocardiosis have been reported from various parts of the world. To our knowledge, isolation of N brasiliensis has not been reported previously in this geographical area.


Eosinophilic ulcer of the tongue.

Eosinophilic ulcer of the tongue. Two cases of tongue ulcers are presented. Histopathologic examination of biopsy specimens obtained from each case showed marked submucosal and muscular infiltration of polymorphonuclear eosinophils compatible with the diagnosis of eosinophilic ulcer of the tongue. The disease entity appears to be uncommon, yet, it should be recognized as benign since in both instances, healing was spontaneous.


Osler node, Janeway lesions, and splinter hemorrhages. This report documents the occurrence of an Osler node, subungual hemorrhages, and Janeway lesions peripheral to an infected arterial catheter. A brief review of these dermatological manifestations of infection is given and the importance of surgical removal of the involved artery after poor response to medical therapy is stressed.


Modern radiotherapy for malignant epitheliomas. There are exceptional cases of malignant epitheliomas in which radiotherapy is at once or eventually becomes a treatment of last resort. We recount the clinical facts, histologic findings, radiotherapeutic techniques, and results of treatment of seven such cases.


Some research on parapsoriasis and lymphomas. Thirty-five cases of benign parapsoriasis en plaques, 24 cases of prereticulotic poikiloderma (3 of which were in evolution towards polymorphous lymphomas), 15 cases of lymphoma and 10 cases of other various skin proliferative disorders were studied. For various reasons the first two conditions are preferably indicated as type 1 and type 2 parapsoriasis. Attention is drawn to the possibility of finding a dermal fibro-histiocytary proliferative condition, more often in type 2 parapsoriasis than in type 1. Dysprotidemia, signs of a reactive bone marrow condition, and changes of the tryptophan leads to niacin pathway, as signs of various degrees of damage of connective tissue, were found in type 2 parapsoriasis and lymphomas.


Chemical composition and swelling of normal and osteoarthrotic femoral head cartilage. I. Chemical composition. Radiochemical and biochemical methods were used to characterize post-mortem and osteoarthrotic femoral  head cartilage. Fixed charge density measurements were correlated with glycosaminoglycan content as estimated by uronic acid and hexosamine analyses. In post-mortem cartilage water content decreased from a maximum at the surface to a minimum in the deep zones. In the osteoarthrotic specimens water content was greatest in the middle zones. Glycosaminoglycan content increased with depth and in the osteoarthrotic specimens was reduced throughout the depth of the cartilage. With increasing degeneration there was an increase in water content and decrease in glycosaminoglycan content. The difference in the water content profile in osteoarthrotic cartilage was explained in terms of damage to the collagen network. In osteoarthrosis the latter is no longer capable of restraining the swelling pressure produced by the glycosaminoglycans and swelling is greatest in the midzones, where glycosaminoglycan content is highest.