Diagnosis of breast cancer: clinical and preclinical.

While a tentative diagnosis of lesion type can be made fairly accurately on the basis of a patient's history, combined with a thorough examination, and the use of diagnostic aids, biopsy and histologic examination remain the only absolute means of determining whether a lesion is benign, premalignant, or malignant.


Prevention of mental disorders: recent advances in theory and practice.

This paper begins by reviewing the current status of primary prevention. Basic concepts and definitions are introduced, and the existing knowledge base is examined. Recent advances in how primary prevention is viewed are described, and some general issues not yet resolved are identified. In particular, the importance of the growing shift of interest from predisposing factors in emotional disorders to precipitating factors, and the shift from the search for disorder-specific causes to the search for general, nonspecific causes is underlined.


The microcomputer as a community mental health public information tool.

A discussion of the role of public information programs in community mental health is followed by a review of various traditional public information techniques. A microcomputer system is described as a tool for public information. A field study of the system is reported in which the results indicate the system's success in creating interest in mental health information and assessing consumer awareness of mental health services and principles. The computer's capability for teaching this information is not substantiated, but appears promising.


Prediction of multiple visits by a community mental health center's psychiatric emergency home visiting team.

Ten psychosocial characteristics of 442 patients treated by a psychiatric-emergency home visiting team were studied to determine whether or not those variables were related to further calls for emergency home visits. Changes in the patients' clinical conditions between first and second visits were also assessed. There were no significant changes between first and second visits, and only the display of bizarre behavior during the first visit was positively related to the number of subsequent visits. The implications of these findings for psychiatric-emergency team crisis intervention are discussed.


Map survey strategy for locating areas with mental health problems.

As part of a community survey of mental health needs, respondents were asked to pinpoint areas high in need on a map of the catchment area. Knowledgeable personnel in agencies dealing with community problems were surveyed. Results indicated that map surveys can be useful in locating high-need census tracts, as evidenced by convergence with an independent service-utilization-based index of mental health need. However, respondents did not differentiate between need areas in terms of ratings on specific community problems.


Affective training for teachers of psychotic children.

A group inservice training program for teachers of psychotic children is described. Special emphasis is given to the teacher's emotional needs in dealing with these very difficult children. The training is designed to enhance mutual support and the acceptance of feelings associated with working with psychotic children. Teachers who worked alone or without the benefit of a supportive team responded most enthusiastically to the group training. All teachers felt their emotional needs for support, self-confidence, and acceptance were important factors in their functioning with their students and that the training met those needs.


Crisis intervention in the court room: the case of the night prosecutor.

Often the cases seen in a municipal court or a mental health center's crisis department are identical. The concepts used to describe these common cases and the resultant agency actions taken differ drastically between the legal and mental health arenas. This paper presents a working model that combines mental health and legal concepts and personnel to deal effectively with this overlapping body of problems. The model provides for crisis intervention for the clients, preventive education for young attorneys, and system change in the criminal justice system.


Sensitization capacity of ethylenediamine in the guinea pig and induction of unresponsiveness.

The sensitization capacity of ethylenediamine was examined by the guinea pig maximization test and compared with dinitrochlorobenzene. Ethylenediamine was found to be a potent sensitizer. An attempt at oral induction of unresponsiveness (tolerance) was unsuccessful with ethylenediamine and DNCB and the same negative result was obtained with intravenous injection of ethylenediamine. Only by the intravenous injection of dinitrobenzene sulfonic acid was unresponsiveness successfully established in 90% of the guinea pigs.


Brilliant Lake Red R as a cause of pigmented contact dermatitis.

Twenty-three patients suffering from pigmented contact dermatitis caused by cosmetics containing Brilliant Lake Red R were observed. Commercial samples of Brilliant Lake Red R proved to contain many ethyl acetate extractable impurities; 1-phenylazo-2-naphthol and azobenzene were isolated and identified. To determine the responsible allergens, five patients were examined by patch tests with purified samples of azo-dyes and the unidentified fractions of ethyl acetate extractable impurities. Three out of five showed weaker reactions to purified samples of Brilliant Lake Red R and the other two showed equal reactions compared to the commercial product. 1-Phenylazo-2-naphthol was found to be a strong allergen in all cases but none showed a positive reaction to azobenzene. Some unidentified fractions also gave positive results. Patch tests were performed with 4-phenylazo-1-naphthol, 4-phenylazo-1-naphthol-2-carboxylic acid, and 2,4-bis(phenylazo)-1-naphthol, as structurally related compounds derived from 1-naphthol. All gave negative and they were not detected in the ethyl acetate extractable impurities by thin-layer chromatography.


Evaluation of hand cleansers.

The effect of three industrial hand cleansers on transepidermal water loss (TWL) was evaluated in groups of healthy volunteers. After 2 weeks, subjects using Baracaide averaged 47% less TWL than those using Swarfega and 35% less than with Go-Jo. In a second study in printers, the use of Baracaide decreased TWL by 20% after 2 weeks. Because it contains no volatile solvents, Baracaide may be less injurious to the barrier layer.


Nickel concentration of blood, urine and sweat after oral administration.

Healthy volunteers without nickel hypersensitivity were given 5.6 mg nickel orally. The nickel concentration was assayed in urine, serum and sauna-provocated sweat from hands and trunk before and after nickel ingestion. The nickel concentration in serum increased in all subjects, and in most cases in urine, but not decisively in sweat.


Allergy to rubber condom urinals and medical adhesives in male spinal injury patients.

In the National Spinal Injuries Unit at Stoke Mandeville Hospital, rubber condom urinals, kept on the penis with a medical adhesive, are used for incontinent male patients where possible. However, contact allergy to rubber condoms and/or the adhesives is a common problem and can cause considerable morbidity in paralysed patients. This paper investigates the rubber chemicals and adhesives most commonly implicated in causing contact allergy. The survey was divided into two parts: 1. Patch testing symptomatic inpatients 2. A questionnaire sent to new patients from January 1974 to ascertain the overall incidence of contact allergy. It was found that allergy to mercaptobenzthiazole (MBT)- and thiuram-containing condoms was relatively common and that latex/petroleum tube medical adhesives most commonly caused adhesive allergy. It is suggested that a condom made of the least allergenic rubber and an adhesive causing the least number of allergic reactions should be used from the outset for paralysed patients requiring a condom urinal.


Skin sensitizing properties of arylalcanoic acids and their analogues.

While participating in a clinical trial of suprofen, a new antiphlogistic agent, a 32-year-old atopic woman developed a severe contact dermatitis reaction of the hands to this substance. To check for cross-reactivity patterns, patch tests were performed with similar arylalcanoic acid derivatives. Positive reactions were obtained for ibuprofen, ketoprofen, fenoprofen, naproxen, alclofenac, and metiazinic acid, which are all antiphlogistic and anti-inflammatory agents for systemic use, and chlorambucil, which is an antineoplastic agent. The antigenic determinant seems to correspond to a very well-defined structure: the carboxyl group (-COOH) has to be separated from the aryl structure by at least one C atom (substituted or not). Furthermore, the aryl group must be substituted with different chemical groups but not in the orthopositions.


An investigation of the pharmacokinetics of ethynylestradiol in women using radioimmunoassay.

A radioimmunoassay for ethynylestradiol (EE) which is applicable to plasma samples obtained from women, who have taken a combination type oral contraceptive, has been developed and fully validated. Plasma concentration of EE rise to a peak of 128 pg/ml following the oral administration of 50 microgram EE. Following the intravenous administration of the same dose of EE, plasma concentrations of the steroid declined biexponentially, the two half-lives being 0.83 and 6.75 hours. Comparison of the results of the intravenous and oral administration of the steroid suggested that its oral bioavailability is 42%. Although EE thus has a lower bioavailability than norethindrone, the pharmacokinetics of the two steroids, as reflected by half-lives, plasma clearance and volume of distribution, are very similar. The occurrence of a secondary peak in plasma at around 12 hours after dosing gave strong evidence that EE undergoes enterohepatic circulation in women; an event that may have considerable clinical significance.


Low risk of pelvic inflammatory disease in young never-pregnant women using Gravigard.

The present four-center investigation involves 516 never-pregnant women in whom a copper-7-intrauterine device (Cu-7-IUD) was inserted. Out of these patients 173 were teenagers at the time of insertion. A "small-sized" Cu-7-IUD (Cu-7-Nullip) - designed for nulliparous women - was randomely used instead of the commercially available Cu-7-IUD (GravigardR) in 76 - 44 of whom were teenagers - out of the 516 women. The incidence of pelvic inflammatory disease (PID) of 9,080 woman-months was reviewed. In the present study the incidence of PID varied from one center to another between 0.9  and 1.4 per cent/year in women wearing Cu-IUDs. When comparing these figures with the estimated incidence (1.2%) in the population of fertile-aged women, it was concluded that the risk for PID was not increased in never-pregnant women using Cu-IUDs, including teenagers as well as women of 20 years of age or more. No difference in the incidence of PID was observed between the GravigardR and the Cu-7 Nullip.


Induction of aryl hydrocarbon hydroxylase by lymphocytes from women taking oral contraceptives.

The peripheral blood lymphocytes (PBL) from two female subjects were assayed for AHH induction 40 days prior to and 30 days during ingestion of progesterone and estrogen analogues as oral contraceptives. Three habitual users of oral contraceptives were also studied. No in vitro inhibition of AHH induction was observed as a consequence of the use of these hormone analogues. Values obtained for enzyme activity suggest a slight increase in AHH induction resulting from the use of oral contraceptives. Further studies with larger numbers of subjects are required before the apparent increase in enzyme inducibility can be considered significant.


A prospective, randomized study of oral contraceptives: the effect of study design on reported rates of symptoms.

A study was undertaken to assess the effects of the study design (frequency and method of inquiry about the side effects) on the reporting of oral contraceptive (OC)-associated side effects. The study found that the one-contact-per-cycle schedule yielded consistently lower rates of side effects than the two-contact-per-cycle schedule. Also, asking subjects about the occurrence of specific symptoms led to the reporting of higher rates of side effects than those obtained by general inquiry. The study suggests that differences in the reported rates of side effects may be due in part to the manner in which the data were collected.


Embryo lethality of Stryphnodendron polliphyllum M. in rats.

To study the effect of Stryphnodendron polliphyllum M. upon implantation, the seeds and empty pods of this plant were given to pregnant rats, on the 5th and 6th days of gestation. The animals were sacrificed on the 14th day of pregnancy and implantation and resorption indices were studied. The results show definite embryo lethality when pregnant animals were given only the seed of this plant.


The Mark-7 intrauterine sound - an accurate determinant of uterine axial length.

The axial uterine length of 60 nulliparous patients has been measured using a standard Galabin sound and a new flexible disposable sound (Mark-7). In 47 patients the values obtained with the plastic sound were between 0.25 cm to 0.5 cm greater than the values obtained with the metal sound. The flexible plastic sound values are probably larger because this sound is able to follow uterine axial curvature. The element of parallax error which is inherent in using metal sounds is avoided by use of a sliding half-collar at the distal end of the instrument, which can be moved against the cervix allowing fixed measurement. This instrument should be a useful adjunct to intrauterine device research and usage where the relationship of uterine length to device performance is being considered.


Termination of pregnancy in rabbit and mouse by Trichosanthin.

The effects of a single intraperitoneal injection of Trichosanthin in 6-, 10-, 17- or 22-day pregnant rabbit (2 mg/rabbit) or in 11-day pregnant mouse (50 micrograms/mouse) were studied. Trichosanthin induced abortion in 100% of the 17- or 22-day pregnant rabbits within 48-72 hours and decreased circulating progesterone (delta 4P)concentrations with 24 hrs. On the other hand, the same dose failed to terminate pregnancy in 6- or 10-day pregnant rabbits and caused no significant changes in circulating delta 4P levels. Exogenous delta 4P or prolactin + human chorionic gonadotropin given twice daily failed to reverse the Trichosanthin-induced termination of pregnancy. However, this resulted in a delay of fetal expulsion. It is concluded that Trichosanthin-induced termination of pregnancy is not solely a result of luteolysis but is likely to be due to its toxic effects on placenta, embryo or both. A dose of 50 microgram Trichosanthin given to 11-day pregnant mice resulted in a termination of pregnancy within 96 hours and also a significant decrease in delta 4P levels in 24 hrs. The ratio of delta 4P to 20 alpha-dihydroprogesterone was also decreased steadily after Trichosanthin administration.


Effects of age at vasectomy on corticosterone production by the rat testes.

The ability of the testicular interstitium to assume a certain degree of adrenocortical-like activity, and the concomitant changes in adreno-gonadal status, 100 days post-vasectomy, were investigated in rats (50 and 150 days of age, at start). The transformation of 11-deoxycorticosterone (1,2-H3) to corticosterone (1,2-H3), by the testicular homogenates, was used as an index of 11 beta-steroid hydroxylase activity in the Leydig cells. The extent of ascorbic acid depletion in the adrenals and testes, and the plasma and testicular levels of corticosterone, were assayed, to examine the adreno-testicular participation in corticosteroidogenesis. Vasectomy in younger rats, as compared to older rats, resulted in a significant increase in the transformation of deoxycorticosterone to corticosterone, and higher plasma corticosterone levels. It appears that vasectomy, at a younger age, is capable of inducing adrenocortical-like activity in the testicular interstitium.


IUD compared with oral contraception in nulliparae.

172 nulliparae attending a Swedish family planning clinic were studied. Doctors and midwives with various experiences gave the contraceptive method. Continuation rate at 12 months was 58 per cent for IUD and 86 per cent for OC. The expulsion rate in the IUD group was 11 per cent and in 30 per cent of IUD users the device was removed because of adverse effects. 10 per cent of the IUD group and 5 per cent of the OC group discontinued their method without introducing another one, thereby risking an unwanted pregnancy.


Influence of an end inspiratory pause on pulmonary ventilation, gas distribution, and lung perfusion during artificial ventilation.

Using a constant tidal volume and ventilatory frequency, anesthetized piglets were ventilated with a new tidal volume ventilator. A short inspiratory time without a pause (10% of breathing cycle) was compared with a longer inspiratory time with a pause (33%) both with and without bronchial obstruction. Mechanics of ventilation, pulmonary ventilation, gas exchange, gas distribution, and lung perfusion were measured. The longer inspiratory time with a pause resulted in lower peak airway and end inspiratory pressures and a higher total compliance. Dead space/tidal volume ratio was reduced and the RQ was increased. While the cranial pulmonary fields were less well ventilated, the right caudal field was better ventilated. In the presence of bronchial obstruction, better alveolar ventilation was achieved when an end inspiratory pause was added. The results emphasize the importance of static end inspiratory tracheal conditions although the tidal volumes were kept unchanged.


Effect of respiratory acidosis on plasma and CSF free amino acids.

Acid-base data and levels of selected cerebrospinal fluid (CSF) free amino acids were analyzed in a series of 8 patients in acute respiratory failure. In these patients, there were increased CSF concentrations of methionine, phenylalanine, tyrosine, histidine, alpha-amino-N-butyric acid, glutamic acid, glutamine, glycine, alanine, and ammonia, while arginine decreased. Phenylalanine, tryosine, and alanine were correlated with CSF PCO2; and alpha-amino-N-butyric acid to the buffer capacity of CO2 and pH. The data suggest the hypothesis that there are two metabolic phases for ammonia removal from brain tissue, that could explain some of these pathhophysiological conditions.


Hyperventilation in tricyclic antidepressant poisoning.

A patient with severe tricyclic antidepressant poisoning who showed recurrent ventricular fibrillation and wide QRS complexes on the ECG, failed to respond to intravenous physostigmine and lidocaine. Deliberate artificial hyperventilation was immediately effective in preventing further arrhythmia and in decreasing the width of the QRS complexes. Hyperventilation, a neglected treatment, may be immediately effective in the treatment of severe tricyclic antidepressant poisoning.


New endotracheal tube adaptor reducing cardiopulmonary effects of suctioning.

The continuous recordings of arterial oxygen saturation (SaO2) and beat-to-beat heart rate before, during, and after tracheobronchial suctioning were studied in eight preterm infants with severe RDS receiving mechanical ventilation. Two suctioning procedures were alternatively performed in each infant; In procedure A, disconnection of the ventilator and preoxygenation preceded suctioning; in procedure B, a special suction adaptor was used without ventilatory interruption or preoxygenation; 128 suctionings were performed with each procedure and the changes in heart rate (HR) and SaO2 during suctioning were compared. Although in both procedures, HR and SaO2 decreased during suctioning, the degree of bradycardia and arterial blood oxygen desaturation were significantly smaller in magnitude and shorter in duration during procedure B. These data indicate advantages of the suction adaptor in minimizing bradycardia and hypoxia from airway suction.


External ventricular drainage. A technical note.

The disadvantages of external ventricular drainage are the threat of sepsis and the nuisance of dislodging a precarious system in routine care. The experience of the authors with nearly 200 cases using a long ventricular catheter demonstrates that a subgaleal tunnel can be easily made for the ventricular catheter using a sharp trocar. The resulting system is secured by the tunnel, easily dressed, and has a minimal likelihood of sepsis. Although external drainage has been maintained for longer than 3 weeks in some cases, the average duration is 6 days; and in the last 68 cases, there has been no incidence of sepsis and but one case of patient removal of the catheter. The device has been used for both monitoring, as well as ventricular decompression in a broad range of patients.


A physiological approach to hemidiaphragm paralysis.

The occurrence of unilateral phrenic nerve injury with the resultant hemidiaphragm paralysis or paresis can cause significant respiratory distress or respiratory failure in infants and children. An early bedside diagnosis of this problem will allow appropriate therapy and prevent needless diagnostic procedures. With the patient in the lateral decubitus position and the paralyzed side up, accentuated paradoxical inspiratory inward epigastric motion ipsilateral to the paralyzed hemidiaphragm can be seen. With the paralyzed hemidiaphragm down, abdominal motion appears to be normal as if the paralyzed hemidiaphragm were plicated. Thus, ventilation may be improved by changing body position as well as instituting ventilatory support while the potential for phrenic nerve recovery is evaluated.


Problems of dose-response studies in chemical carcinogenesis with special reference to N-nitroso compounds.

Dose-response studies in chemical carcinogenesis are a valuable method for evaluating the risk involved by a certain carcinogen. This article deals with the methods that are presently applied for dose-response studies. It is emphasized that there are many possible mistakes that are already hidden in the method itself; a critical approach is made to the indicative value of dose-response studies. It is also emphasized that the conclusions which may be drawn from dose-response studies can always only be extrapolative but never mathematically calculable. Finally, some practical examples for dose-response studies with n-nitroso compounds are described.


Psoralen and sunlight for psoriasis in the Southwest.

The treatment of psoriasis with psoralen and direct sunlight has been reported as successful but unpredictable because of its dependence on prevailing weather conditions which are subject to marked daily and seasonal variations. A study carried out in a locale nearly ideal because of its reliable year-round sunshine produced complete remission of all exposed plaques in twelve consecutive patients.


Pigmented skin lesions in black newborn infants.

Three findings from a study of one hundred black newborn infants examined for pigmented lesions are presented herein: significantly higher incidence than in prior neonatal examinations, a frequent clinical pattern of grouped macules, and an unusual histologic distribution of nevus cell theques. Fifty-one percent of the infants had congenital pigmented lesions. Biopsy specimens of thirty-two lesions were obtained, twenty-six showing histologic changes of lentigo, four melanocytic nevi (nevus-cell nevi), and two ephelides. Three of the four nevi were less than 1.5 cm in diameter and all were of the predominantly junctional type. Clinical appearance was not a consistent guide for classification in the newborn.


Chondrodermatitis nodularis chronica helicis. A review with emphasis on steroid therapy.

Chondrodermatitis nodularis chronica helicis, a disease involving the ear helix of middle-aged to elderly persons is described herein. The clinical, histologic, and therapeutic aspects of this entity are discussed with special emphasis on treatment with intralesional steroids. Several etiologic and pathogenetic mechanisms are also mentioned.


Levamisole and agrandulocytosis.

Levamisole, originally developed as an anthelmintic, is used in the treatment of many disorders. Severe side-effects have been noted by some investigators, and a case is presented herein of levamisole-induced agranulocytosis.


Drug-induced toxic epidermal necrolysis in children. Report of two cases.

Two cases of toxic epidermal necrolysis occurring in children are presented herein. In both, multiple drugs were administered before the onset of the skin eruption. Cultures for staphylococcus were negative. Histopathologic examination of the first case revealed separations at the dermal-epidermal junction. While more commonly due to staphylococcal exfoliatoxin, a drug must be ruled out as the cause of toxic epidermal necrolysis in children.


Structural organization of chromosomes of the Indian muntjac (Muntiacus muntjak).

The identification, morphology, and banding pattern of the chromosomes of the Indian muntjac (Muntiacus muntjak) are described. A diagrammatic representation of the banding pattern as revealed by various techniques is presented following the nomenclature suggested by Paris Conference (1971) for human chromosomes. The Y2 chromosome and the neck of the X chromosome are late replicating based on observations made with the use of a bromodeoxuridine plus Giemsa technique. Most of the G-bands are early replicating, contrary to earlier findings based on autoradiography.


Conservation of whole arms during chromosomal divergence of phyllotine rodents.

The assumption of simple fusion in a group showing a constant number of chromosome arms was tested by comparison of the G-band patterns of chromosomes of three Phyllotis species. The karyotypes, each of which has 40 chromosome arms, have a 2n of 38, 38, and 40 and are made up of mostly metacentric chromosomes. Operational concepts describing the amount of matching in G-band patterns are proposed, separating chromosomes or arms into those with total correspondence, partial correspondence, or unique cases. Seven chromosomes and 21 arms out of the total were identical in the three species, denoting a conservation of whole-arm band sequences in this group. A greater number of identical arms than of identical chromosomes were observed, giving some support to the simple fusion hypothesis. An unexpected chromosomal divergence was detected, including chromosomal variation in the C-banded sex chromosomes.


Regional mapping of the gene for human UDPGal 4-epimerase on chromosome 1 in mouse-human hybrids.

Somatic cell hybrids between mouse and human cells containing two different reciprocal translocations involving human chromosome 1, 46,X,t(1;X)(q12;q26) and 47,XX,+21,t(1;17)(p32;p13), were studied for the expression of human uridine diphosphate galactose 4-epimerase (UDPGal 4-epimerase, E.C. 5.1.3.2) by starch-gel electrophoresis. Analysis of the hybrid clones for the expression of the enzyme and the presence of the translocation chromosome 1 has permitted the assignment of the gene for human UDPGal 4-epimerase to the pter yields p32 region of chromosome 1.


Cytogenetic characteristics of 26 polyethylene glycol-induced human-hamster hybrid cell lines.

A cytological analysis of 26 polyethylene glycol (PEG) induced human/hamster hybrid lines has shown that such lines are similar to inactivated Sendai virus (ISV) induced hybrids in respect to stability, retention of specific chromosomes, and cell selection. The evolution of stable hybrid cell lines carrying variable human chromosome complements depends upon a balance being established between the retained human and hamster genomes. This balance is a result of random loss of human and hamster chromosomes followed by selection of the fittest stem lines. A major mechanism ofchromosome loss may be fragmentation and elimination of acentric fragments. Twelve of the 26 lines had stabilized by the 30th passage, an incidence similar to that found with ISV-induced hybrids studied in this laboratory. Thus, PEG may be considered to be an ideal chemical for inducing somatic cell hybrids for genetic analysis.


Determination of bronchodilation in the clinical pulmonary function laboratory. Role of changes in static lung volumes.

Improved airway resistance following bronchodilator inhalation is not always accompanied by improvement in forced expiratory flow. We studied 241 patients with airways obstruction to learn whether changes in static lung volumes (vital capacity and function residual capacity measured by body plethysmography [FRCB]) would reveal bronchodilation not demonstrated by expiratory flow rates (the ratio of forced vital capacity at one second to the total forced vital capacity [FEV1/FVC]), and the forced expiratory flow for the midportion of the forced vital capacity (FEF25--75%). A significant fall in Raw occurred in 129 patients, 46 of whom had a significant increase in vital capacity (mean of + 465 ml +/- 43, P less than 0.001) and a fall in FRCB (mean of -763 ml +/- 78 P less than 0.001) with no change in FEV1/FVC% of FEF25--75%. We interpret these data to indicate that improvement in static lung volumes can reflect bronchodilation in the absence of improved expiratory flow.


Resting ventilatory pattern, mouth occlusion pressure, and the effects of aminophylline in asthma and chronic airways obstruction.

Patients with obstruction of the airways can maintain normocapnia either by increasing the central inspiratory neuromuscular output or by altering the central timing of each breath. This point and the effects of administration of aminophylline on ventilatory regulation were studied in six normal subjects, seven asthmatic patients, and eight patients with unresponsive chronic obstruction of the airways. Spirometric and body plethysmographic values, the ventilatory pattern, and the mouth occlusion pressure did not differ between the two groups of patients. The results indicate that in these patients, normocapnia is maintained at rest by increased central inspiratory neuromuscular output; central respiratory timing is not altered. Intravenous administration of aminophylline (5.6 mg/kg of body weight) increased alveolar ventilation in all three groups, without increasing the uptake of oxygen. In normal subjects, there was no significant effect on ventilatory regulation or drive. In asthmatic patients the central timing of each breath was altered, with no significant effect on central inspiratory output. In unresponsive obstruction of the airways, the central inspiratory output increased transiently, with no effect on central timing.


Complications of pulmonary artery catheterization in the care of critically ill patients. A prospective study.

In order to evaluate the incidence and the significance of complications resulting from the use of flow--directed, balloon--tipped catheters to monitor critically ill patients, we made a prospective study of 116 pulmonary artery catheterizations. Indications for catheterization included shock, pulmonary edema, or hemodynamic instability following surgery. Arrhythmias, including premature atrial or ventricular depolarizations, ventricular tachycardia, and transient right--bundle branch block occurred during 90 of the 116 insertion procedures, but were unassociated with morbidity or mortality. In two cases (1.7 percent) staphylococcal bacteremia probably originated from the catheter. In addition, the pulmonary artery catheter led to two cases (1.7 percent) of subclavian vein thrombosis. Postmortem examinations revealed perforations of the pulmonic valve in one case. We conclude that although significant complications may result from pulmonary arterial catheterization and monitoring of critically ill patients, the incidence is low.


Distribution of ventilation in normal children.

Measurements of closing volume and the distribution fo ventilation by both single-breath (SBN2) and multiple-breath nitrogen washout methods were obtained in 376 healthy boys and girls, ages 6 to 18 years. A closing volume could be demonstrated in 39 percent of the subjects, and closing volume expressed as percentage of vital capacity did not change with height. Closing capacity expressed as percentage of total lung capacity showed a slight decrease with height. The slope of phase III of the SBN2 curve decreased with height. Single compartment N2 washout curves were observed in 72 percent of the subjects, and the incidence of single compartment curves increased with age. In those subjects with two compartment N2 washout curves, the relative compartmental ventilation became more even with increasing height. Our observations suggest that parallel units among peripheral airways grow at different rates.


Dynamic prognostic profile for acute myocardial infarction.

A prognostic profile for patients with acute myocardial infarction (AMI) treated in a coronary care unit has been constructed by applying a modified sequential statistical analysis. The profile represents a dynamic system which enables the physician to predict hospital prognosis simply and rapidly on the basis of daily changing clinical and laboratory parameters. The procedure was tested prospectively on a population of AMI patients and was found to be a reliable prognostic tool. Comparing this scale with that of popular prognostic indices, it was found that prediction was more accurate with this technique.


Echocardiographic assessment of mitral stenosis by the left atrial emptying index.

Echocardiograms were performed in 35 patients prospectively with mitral stenosis to determine the usefulness of the left atrial emptying index (AEI) in estimating mitral valve orifice area (MVOA). Twnety-five control patients without evidence of cardiac disease had an AEI of 0.91 +/- 0.01. In the mitral stenosis group, the mean AEI was 0.47 +/- 0.09, with Gorlin and Gorlin calculated MVOAs of 1.44 +/- 0.56. There was close correlation between the AEI and MVOA (r = 0.93). The AEI did not correlate well with the left atrial size (r = 0.10), or the EF slope of the mitral valve (r = 0.20). The AEI was useful in separating patients with mitral stenosis into mild, moderate, and severe groups. Twelve out of 12 patients with severe mitral stenosis (MVOA less than or equal to 1.0 sq cm) had an AEI of less than or equal to 0.42. Ten out of 13 patients with moderate mitral stenosis (MVOA of 1.1--1.5 sq cm) had an AEI of 0.43 to 0.51. Eight out of ten patients with mild mitral stenosis (MVOA greater than or equal to 1.6 sq cm) had an AEI of greater than or equal to 0.52. The overall predictive value of the AEI in subclassifying the severity of mitral stenosis was 86 percent. In conclusion, the AEI appears to be a sensitive index in estimating MVOA in mitral stenosis.


Pulmonary functional in patients with gastroesophageal reflux.

Gastroesophageal reflux has been suggested to play a causal role in a variety of chronic pulmonary disorders. This hypothesis has been supported by the increased incidence of reflux in patients with idiopathic pulmonary disorders and by the anecdotal reports of symptomatic improvement following surgical correction of the reflux. In an effort to determine whether patients with reflux as a group demonstrated a significant degree of pulmonary dysfunction, 100 patients with reflux were compared with another group of 100 control patients, matched for age and sex and without demonstrable reflux. Standard pulmonary function studies were used for this comparison. No difference could be detected between the two groups, which suggested that the isolated findings of reflux in patients with pulmonary disorders should not be considered etiologic by virtue of the association alone. Alternate explanations for the relationship are given.


Lung sound terminology in case reports.

Terms used to describe lung sounds in published case reports were tabulated, including qualifying adjectives. Seven journals were reviewed, and a total of 663 case reports were included. From the frequency of usage and similarity of qualifying adjectives it appears that "rales" and "crepitations" are equivalent terms. Many authors feel the need to qualify "rales": sixteen descriptive adjectives were encountered. Some authors distinguish between "rhonchus" and "wheeze," but the terms, for most, appear to mean the same thing. It is evident that current usage varies widely, even in the terminology of the basic categories of sounds.


Subxiphoid two-dimensional echocardiographic detection of tricuspid valve prolapse.

A patient with click and late systolic murmur syndrome originating in the right side of the heart is described. Prolapse of the anterior tricuspid leaflet was demonstrated by subxiphoid two-dimensional echocardiography alone. Neither of the mitral leaflets showed any evidence of prolapse on the echocardiogram. The prolapsed anterior tricuspid leaflet and mild regurgitation were confirmed by right heart cineangiogram.


Asbestos fibers in laryngeal tissues. Findings in two patients with asbestosis associated with laryngeal tumors.

Significant concentrations of asbestos fibers have been found in samples of laryngeal tissue from two patients with past exposure to asbestos and associated asbestosis. In one case, there was a polyp on a vocal cord and in the other one a laryngeal carcinoma. These findings could provide an indication of a local carcinogenic effect of asbestos fibers in laryngeal tissue.


Esophageal compression in association with silicosis and Mycobacterium intracellulare.

An enameler with dysphagia was found to have extrinsic compression of the esophagus by enlarged mediastinal lymph nodes. Scalene lymph node biopsy revealed silicosis, and tissue cultures grew Mycobacterium intracellulare. We believe our patient is the first reported to have dysphagia due to silicotic adenopathy complicated by an atypical mycobacteriosis.


Spontaneous return of patency in a completely occluded coronary artery.

We observed a 56-year=old man in whom an occluded right coronary artery was observed to be widely patent on a subsequent angiogram 40 months later. This "regression," which occurred without a change in his risk factors, shows that manipulation of risk factors can be proven to be a cause of regression only in controlled studies.


The foster family in a systems theory perspective.

Viewing the foster family as a social system provides another tangent from which to understand it, and adds credibility to familiar problems.


A grass-roots model for needs assessment in Hispanic communities.

A design for research to provide data on demographic and socioeconomic needs for service to a Hispanic community can be useful for agencies serving other minority groups.


Prevention in child welfare: a framework for management and practice.

Development of preventive programs in child welfare has been handicapped by the necessity to serve those in immediate need. A framework defining the role, objectives and techniques of prevention is based on a different perspective for service.


Behavioral contracting: theory and design.

An agreement binding a worker and a client, or members of a family, to change specific, measurable behaviors is an effective way to achieve mutual benefits.


Depression in adolescents: a developmental view.

Recent advances in the understanding of adolescent development have provided a frameword for perceptive treatment of certain patterns of adolescent depression.


An adolescent services plan to incorporate status offenders into the child welfare system.

A model plan is presented for adolescent services that would facilitate the current trend to shift troubled but nondelinquent youngsters from the juvenile justice system into the child welfare system.


The family stress consultation team: an Illinois approach to protective services.

An experimental, multidisciplinary approach to the handling of child abuse and neglect cases has proved particularly effective.


The status offender controversy: charges and study evidence.

Critics of public policy on status offenders urge that PINS statutes be abolished as racially discriminatory in its target population, as bureaucratically coercive in its labeling of normal children, as undemocratic in lacking the "will and consent" of those whom it presumably serves, and unnecessary in that the social welfare marketplace provides a better service alternative. This report of a study on PINS intake cases in Manhattan finds that the data do not support the charges.


They can go home again!

A pilot project demonstrates that a carefully designed program encompassing training of foster parents, use of volunteers, community support and full commitment by foster care workers can produce permanent homes for youngsters.


Assisting the status offender.

System change has not kept pace with the accumulating evidence that subjecting the status offender to judicial sanctions is both unfair and unhelpful. Principal arguments for change are presented here, as well as the principal arguments of those opposing removal of the status offender from court jurisdiction.


[Clavicular pseudarthroses in childhood].

Pseudarthrosis of the clavicula in childhood is rare. Beside the congenital forms, especially dysplasia of the skeleton, the cause of acquired pseudarthrosis is often the complete or partial lack of immobilization and poorly performed or not indicated osteosynthesis. Basically firm osteosynthesis with small DC-plates is the therapy indicated, but because of atrophic or short fragments, great defects, or if the relevant parts of the skeleton are too short, a compromise is often necessary, especially for the sake of strength. The autologeous spongiosaplastic, corticospongio bone parts, which strengthen the osteosynthesis procedure, if involved, are basic to undisturbed healing.


[Indication for vascular reconstructive operations in radical tumor surgery].

First experiences concerning reconstructive vascular surgery in malignant tumor surgery are presented. In order to improve total tumor excision, the resection of great veins or nutritive arteries may become necessary. In some cases the reconstruction of vascular defects together with tumor resection may be indicated. Only in the case of younger patients vascular reconstruction of essential vessels seems to be indicated.


[Gastric bypass in the surgical treatment of extreme adiposity].

The gastric bypass is an effective surgical procedure for the treatment of extreme obesity. A small gastric reservoir and a narrow anastomosis are combined (to limit the possibility of food intake). In patients with a mean weight of 94% above the Broca value the normal weight is reached 18 months after the operation. Failure to lose weight can be caused by technical errors during the procedure or by a continuous food intake by the patients. Surgical complications are rare. The operative lethality is less than 1%, and anastomotic ulcers occur in 2% of cases. There is no reason to expect metabolic derangements as after jejunoileal bypass.


Chromosome breakage and rejoining of sister chromatids in Bloom's syndrome.

The occurrence of chromosome breaks and reunion of sister chromatids in lymphocytes of two patients with Bloom's syndrome has been compared with those found in X-rayed and control cells. The distribution of breaks in BS is non-random both between and within chromosomes, the centric regions of certain chromosomes being preferentially involved. The following working hypotheses are put forward: When chromosome breaks in human lymphocytes occur in G0-G1, practically no sister chromatid reunion (SCR) takes place, whereas ends created by an S-G2 break show a considerable tendency to SCR. We propose further that chromosome aberrations in BS mainly result from breaks in S-G2, including possible U-type rejoining of sister chromatid exchanges. Fragments extra to an intact chromosome complement result from a chromatid break or an asymmetrical chromatid translocation in a previous mitosis.


Characterization of human chromosomal unit fibers.

A structural component of mitotic chromosomes that partially explains the compaction of DNA within mitotic chromosomes is suggested on the basis of the occurrence of long, regular cylindrical structures in preparations of isolated human chromosomes. These structures, "unit fibers", of a rather constant diameter of about 4,000 A have been postulated to be formed by coiling of the 250-300 A solenoid chromatin fiber that itself is formed by coiling of the 100 A string of nucleosome fiber. The human chromatid would thus be composed by a hierarchy of helices with contraction ratios for DNA at each level of coiling of 7 (string of nucleosomes), 5 (solenoid) and 40 (4,000 A "unit fiber" or "super-solenoid") which results in an overall contraction ratio for DNA in the "unit fiber" structures of about 1,400, which is approximately 5-fold less than the final contraction of DNA in intact chromatids of condensed metaphase chromosomes. The present report concerns more detailed studies with respect to the dimensions and cytochemical properties of the "unit fiber" structures observed in preparations of isolated human mitotic chromosomes that provide direct and indirect evidence in support of their "super-solenoid" structure and relate to known properties of human mitotic chromosomes.


Detection and location of three simple sequence DNAs in polytene chromosomes from virilis group species of Drosophila.

In vitro synthesized RNAs complementary to the three satellite DNAs of Drosophila virilis have been used in a series of in situ hybridization experiments with polytene chromosomes from virilis group species. Gall and Atherton (1974) demonstrated that each of the satellites of D. virilis is comprised of many repeats of a distinct, seven base pair long, simple sequence. With few exceptions, copies of each of these simple sequences are detected in the chromocenters of all virilis group species. This is true even in species which do not possess satellite DNAs at buoyant densities corresponding to those of the satellite DNAs of D. virilis. Small quantities of the three simple sequences are also detected in euchromatic arms of several different species. The same euchromatic location may contain detectable copies of one, two, or all three simple sequence DNAs. The amounts of simple sequences at each location in the euchromatin may vary between species, between different stocks of the same species, and even between individuals of the same stock. The simple sequences located in the euchromatin appear to undergo DNA replication during formation of polytene chromosomes unlike those in heterochromatin. The locations of the euchromatic sequences are not the results of single chromosomal inversion events involving heterochromatic and euchromatic breakpoints.


In vivo effects of gamma-irradiation on the functional architecture of the lampbrush chromosomes in Pleurodeles (Amphibia, Urodela).

In vivo irradiation of ovaries of Pleurodeles poireti by gamma-rays leads to structural rearrangement of lampbrush chromosomes in late vitellogenic oocytes (stages V and VI). The loops collapse into the chromomeres and the axes condense. Doses between 200 and 2,000 rads have been tested. We observed that such changes were dependent on the irradiation dose though the chronological order of the events was irrespective of the dose. The maximum effect was attained about 10 h after irradiation. The alterations are totally reversible. Over a period of 3 days chromosomes gradually relax regenerate loops and recover their normal appearance. In mid vitellogenic oocytes (stages III and IV) lampbrush chromosomes do not undergo radiation induced alterations. It seems that only full-grown oocytes are competent to respond to the ionizing-flow.


Association of the extra chromosome of tertiary trisomic male mice with the sex chromosomes during first meiotic prophase, and its significance for impairment of spermatogenesis.

Pachytene nuclei were studied in five tertiary trisomic male mice of Ts(1(13))70H and two of Ts(5(12))31H, with special attention given to the sex vesicles. Silver stained air dried cells analysed by light microscopy were used mainly, but in addition one sample of surface spread, ethanolic phosphotungstic acid stained nuclei was analysed by electron microscopy. With both techniques and both karyotypes, the extra chromosome (or the greater part of it) almost consistently aggregated with the sex chromosomes. Thereby, the chromatin structure of the extra chromosome as judged by a fine granular appearance resembled that of the sex chromosomes. The animals used ranged from almost azospermic to fertile oligospermic. This variation was not reflected in the position and morphology of the chromosomes 1(13) and 5(12). -Using the whole mount spreading EM technique within a Ts(1(13))70H tertiary trisomic, both 13;13;1(13) trivalents and 1(13) univalents were observed. The 13;13;1(13) trivalents showed a variety of morphologies, ranging from a situation showing classical partner exchange to complete synapsis between the two 13 homologues with the 1(13) telomeric region adhering. The latter configuration is thought not to lead to chiasma formation.


Chromosome movement and spindle birefringence in locally heated cells: interaction versus local control.

A microheater was used to produce a temperature gradient within the mitotic spindle of living cells. The slope of the temperature gradient was estimated from thermal conductivity calculations and confirmed by measurements of spindle birefringence and by experiments on striated muscle. When the microheater was placed at one spindle pole or at one group of kinetochores, the gradient was steep enough to cause a large difference in birefringence between the two half-spindles, but the velocity of chromosome movement in anaphase was nearly the same in the warmer and cooler half-spindles. When the heater was shifted from the pole toward the interzone, the average velocity of chromosome movement increased approximately two-fold but was, again, nearly uniform in the two half-spindles. The rate of spindle elongation was especially sensitive to the site of heating, increasing ten-fold when the heater was shifted from the pole to the interzone. Regardless of heater position, the rate of chromosome movement was determined largely by the temperature of the coolest spindle region--chromosomes in the  warmer half-spindle moved more slowly than expected from estimates of the temperature in that region. Since the microheater produces a substantial temperature gradient within the spindle, the near uniformity of chromosome velocity in both half-spindles must be due to some biological property of the spindle. Two very different explanations for the results are considered the most likely. According to one explanation, the near uniformity of velocity in both half-spindles is determined by the structure of the interpolar spindle, while changes in velocity involve force producers located both in the half-spindles and in the interzone. On the other explanation, the velocity is nearly the same in both half-spindles because the force producers are located exclusively in the interzone (Margolis et al., 1978).


Genome structure and divergence of nucleotide sequences in echinodermata.

The arrangement of repetitive and single-copy DNA sequences has been studied in DNA of some species of Echinodermata--sea urchin, starfishes and sea-cucumber. Comparison of the reassociation kinetics of short and long DNA fragments indicates that the pattern of DNA sequence organization of all these species is similar to the so-called "Xenopus pattern" characteristic of the genomes of most animals and plants. However, substantional variations have been found in the amount of repetitive nucleotide sequences in DNA of different species and in the length of DNA regions containing adjacent single-copy and repetitive sequences. Measurements of the size of S1-nuclease resistant reassociated repetitive DNA sequences show a variability of ratios between long and short repetitive DNA sequences of different species.--The degree of divergence of short and long repetitive DNA sequences and single-copy DNA was studied by molecular hybridization of the sea urchin Strongylocentrotus intermedius 3H-DNA with the DNA of other species and by determination of the thermostability of the hybridized molecules so obtained. All three fractions of S. intermedius DNA contain sequences homologous to DNA of the other echinoderm species studied. The results obtained suggest that short repetitive DNA sequences are those which have been most highly conserved throughout the evolution of Echinodermata. A new hypothesis is proposed to explain the nature of the evolutionary changes in DNA sequence interspersion patterns.


Electron microscopy of the spindle in locally heated cells.

Individual living cells in metaphase were exposed to a steep temperature gradient by placing a microheater near one spindle pole. The cells were then fixed and the spindle was examined by electron microscopy. The structure of the warmer half-spindle differed from the cooler half-spindle in several ways. Kinetochore microtubules were nearly parallel in the warmer half-spindle but were divergent in the cooler. The total length of microtubules in the warmer half-spindle was 52 per cent greater and the number of kinetochore microtubules per kinetochore averaged 16 per cent higher than in the cooler half-spindle. The warmer half-spindle was longer than the cooler. These observations clearly demonstrate a locally enhanced assembly of microtubules in the warmer half-spindle. The electron microscope study makes still clearer the unusual character of chromosome movement in the differentially heated cells: the structure of the warmer half-spindle is hard to distinguish from that in normal cells, yet chromosome movement there is far slower than normal (Nicklas, 1979).


Sister chromatid exchange in murine alveolar macrophages, regenerating liver and bone marrow cells--a simultaneous multicellular in vivo assay.

Differential labeling of sister chromatids was achieved simultaneously in murine alveolar macrophages, regenerating liver, and bone marrow cells of partially hepatectomized mice as well as in alveolar macrophages and bone marrow cells of nonhepatectomized mice. The mean frequency of SCE/cell +/-S.D. and the percentage of second division cells for each cell type were determined. No significant differences in mean frequencies of SCE/cell were observed among the cell types or between hepatectomized (alveolar macrophages--3.6+/-2.2, bone marrow--3.4+/-2.2; regenerating liver--3.6+/-2.4) and nonhepatectomized (alveolar macrophages--3.4+/-1.9; bone marrow--2.9+/-1.8). Although the percentage of second division cells was dependent upon cell type, no significant differences were apparent between hepatectomized (alveolar macrophages--57+/-8%; bone marrow--37+/-6%; regenerating liver--65+/-6%) and nonhepatectomized mice )alveolar macrophages--53+/-6%; bone marrow--36+/-4%). Comparisons between BrdU treated and nontreated nonhepatectomized mice revealed no significant alteration in mitotic yields.


The formation of ribonucleoprotein droplets in Chironomus salivary gland nuclei.

The appearance of RNP droplets associated with specific regions of polytene chromosomes from Chironomus larvae has been studied, systematically by light microscopy using glutarladehyde fixation and lactic acid squashing of the salivary gland. During the fourth larval instar the highest frequency of nuclei which contained droplets (over 50%) was observed in late prepupae. Several treatments (heat and cold shock, cycloheximide) were found to stimulate the formation of a large number of droplets whose features under the light and electron microscopes seemed to be identical to those observed in untreated larvae. Droplets could be observed either in a free state in the nuclear sap or grouped around specific regions of the chromosome such as some Balbiani rings and puffs. Kinetic studies suggest that droplets first appear in a free state and later group themselves on specific chromosome regions. Transcriptional activity seems to be essential for the process of droplet accumulation in the chromosome, since it does not take place if RNA synthesis is inhibited. Cytochemical tests showed striking similarities between the staining reactions of droplets and those of the fibrillar component of the nucleolus. These observations indicate that droplets probably originate from, or share a common component with, nucleolar material and that this component has a preferential affinity for some active chromosomal loci, where it accumulates.


The development of resistance to methotrexate in a mouse melanoma cell line. I. Characterisation of the dihydrofolate reductases and chromosomes in sensitive and resistant cells.

PG19T3 mouse melanoma cells were selected for resistance to methotrexate. Nine sub-lines that are resistant to concentrations of methotrexate ranging from 1.27 x 10(-7) M, to 1 x 10(-4) M methotrexate were selected and characterised in terms of their content of dihydrofolate reductase activity and their chromosomes. The intracellular level of dihydrofolate reductase activity increases with increasing resistance such that at the highest level of resistance PG19T3:MTXR10(-4)M cells contain approximately 1,000 fold more enzyme activity than the parental PG19T3 cells. It is shown that the enhanced activity is due to an increase in the amount of the enzyme rather than any structural change to the enzyme in resistant cells. Comparisons of pH activity profiles, profiles under different activating conditions and titrations with methotrexate suggest that the sensitive and resistant cells contain identical dihydrofolate reductases. Analysis of the chromosomes of resistant cells shows the presence of up to 5 large marker chromosomes which contain homogeneously staining regions after G-banding. These same regions stain intensely after C-banding and fluoresce brightly after staining with Hoechst 33258. The size of homogeneously staining regions increases throughout the process of selection. For one marker chromosome this increase may have been mediated via a ring chromosome.


Two transcripts of an individual Balbiani ring from the salivary gland cells of Acricotopus lucidus (Diptera, Chironomidae).

The polytene chromosomes in main lobe cells of the Acricotopus salivary gland carry two large Balbiani rings (BR1, BR2), which BR1 exhibits the higher incorporation rate of tritiated nucleosides. The size of BR1 varies in conjunction with a subterminal inversion which includes the BR1 site. BR1 in both the homozygous and heterozygous inverted arrangement (BR1A and BR1B, respectively) is consistently smaller than in the homozygous standard arrangement (BR1C). The RNA content of BR1A and BR1C (3.1 and 6.7 pg, respectively) corresponds well with their relative size.--Using the method of micromanipulation of squashed salivary gland chromosomes the RNA transcripts of BR1A and BR1C have been extracted from microdissected Balbiani rings and fractionated by electrophoresis on 1% agarose gels. In BR1A one RNA fraction with a molecular weight of about 40 x 10(6) D is transcribed. The gel electrophoretic pattern of BR1C is characterized by an additional RNA fraction of 5 x 10(6) D. The main part of BR1 RNA is bound to oligo(dT)-cellulose suggesting the adenylation at the chromosome of Balbiani ring RNA.--In the profile of poly(A)-containing cytoplasmic RNA obtained after in vivo labelling two peaks can be detected which correspond in size to the BR1 RNA. These putative BR1 transcripts accumulate to a high concentration in the cytoplasm and show a relatively low stability during in vivo chase experiments.


Chromomeres and puffing in experimentally induced polytene chromosomes of Calliphora erythrocephala.

In the most advanced types of meroistic ovaries the synthesis of RNA for the growing oocyte in each follicle is taken over by nurse cells, i.e., sister cells of the definite egg cell. In calliphora, the highly polyploid nurse cells (NC) develop a polytene karyotype under conditions of strict brother-sister inbreeding and using a controlled selection technique. A comparison of the polytene NC-chromosomes with those from the pupal bristle forming cells reveals an unexpected discrepancy: while both chromosome complements exhibit a constant banding pattern it is not possible to homologize the two tissue specific patterns by identifying homologous band-sequences. Puffing in NC likewise turns out to be unusual in its extent as well as in that is remains constant during long periods of oogenesis. In a more detailed discussion an interpretation and evaluation of these findings will be attempted.


In vivo sister chromatid exchange in cells of various organs of the mouse.

In vivo sister chromatid exchange (SCE) in mouse cells derived from various organs was studied by infusing BrdU from the tail vein. It was found that at BrdU concentrations ranging from 2.2-13.5 micrograms/g/h, the SCE frequency in bone marrow cells seemed to stay at a constant level (1.5-2/cell/two cell cycles) whereas it started to rise as the BrdU dose exceeded this dose range. When BrdU within this dose range was infused continuously from the tail vein for appropriate hours to label chromosomes in various organs, the average SCE frequencies per cell were found to be 1.64 in bone marrow cells, 1.82 in spermatogonia, 1.99 in splenic cells, 2.89 in intestinal cells and 3.69 in cells from adjuvant stimulated lymph nodes. It is suggested that the spontaneous level of the in vivo SCE frequency might be about 1.5-2/cell/two cell cycles in the mouse. In cells derived from intestine and adjuvant stimulated lymph node, some unknown factors might work as a inducer of SCEs resulting in a significant increase in the SCE frequency in these organs.


Preferential occurrence of sister chromatid exchanges at heterochromatin-euchromatin junctions in the wallaby and hamster chromosomes.

Chromosomes of two mammalian species, the white-throated wallaby and the rat-like hamster, possessed large amounts of constitutive heterochromatin which is detectable as C bands. By making use of this character the frequency of sister chromatid exchanges (SCEs) was determined for the C band and the euchromatic regions of the chromosome. In both species, the distribution of SCEs in the euchromatin of chromosomes was found to be proportional to its metaphase length, while the number of SCEs localized in the C band regions was clearly fewer than expected on the basis of the relative length of those regions at metaphase. Many SCE's were, however, detected at the junctions between the euchromatin and the C band heterochromatin. All of these findings were consistent with previous observations on the Indian muntjac and the kangaroo rat chromosomes.


The rate of fork movement during DNA replication in mammalian cells.

DNA fiber autoradiography was used to measure the rate of replication fork progression along replication units in human diploid cells. The rate in different replication units differs very significantly and lies within the range 0.1 to 1.2 micrograms/min. However, no significant changes were found in the rate of fork movement along single replication units operating during long intervals of S phase. Moreover, the fork progression rate is constant in many replication units of human cells.


Satellite DNA properties of the germ line limited DNA and the organization of the somatic genomes in the nematodes Ascaris suum and Parascaris equorum.

During the early cleavage divisions in some Ascarids, parts of the chromosomes are eliminated from the somatic blastomeres ("chromatin diminution", Boveri, 1887) while the chromosomes in the germ line cells maintain their integrity. To characterize the germ line and soma genome, DNA was isolated from gametes and embryonic somatic cells of two Ascarid species, Parascaris equorum var. univalens and Ascaris suum. It was shown that the germ line limited DNAs of these species have the same density and almost identical reassociation kinetics: in CsCl the predominant component of the germ line limited DNA of P. equorum and A. suum has the buoyant density of 1.697 g/cm3, while soma DNA of both species bands at 1.700 g/cm3. In P. equorum there is a small additional germ line limited satellite DNA component with the density of 1.690 g/cm3, identical to that of mitochondrial DNA of both organisms. Comparison of the reassociation kinetics of germ line and soma DNA demonstrates for both species that the eliminated DNA sequences are highly repetitive. In contrast to these similarities between the germ line limited DNAs of P. equorum and A. suum the analysis of their base composition revealed differences (40% guanine plus cytosine in P. equorum and 36% in A. suum). The only very fast reassociating DNA sequences which we could isolate from soma DNA was demonstrated to be foldback DNA. The reassociation kinetics of total A. suum soma DNA was investigated by hydroxylapatite chromatography. Least squares analysis of the data revealed about 10% of intermediate repetitive DNA sequences. Their interspersion between single copy DNA sequences was analyzed by comparing the reassociation kinetics of DNA fragments 0.35 and 7.2 kilobases long. Thus the DNA sequence arrangement of Ascaris does not follow the short period interspersion pattern observed in most organism.


An enteric-coated pancreatic enzyme preparation that works.

A new enteric-coated pancreatic enzyme preparation (microspheres) was compared with traditional enzyme tablets in six subjects with severe exocrine pancreatic insufficiency. The microspheres were found to be as effective as traditional enzyme supplements. In most patients in balance studies, the lowest fecal fat values were obtained with microsphere therapy in spite of a smaller amount of lipase administered (6015 vs 10,800-43,200 lipase units per meal). In contrast to enteric-coated tablets, microspheres can be recommended in the treatment of pancreatic steatorrhea.


Acute right-sided hemorrhagic colitis associated with oral administration of ampicillin.

Among 56 cases who presented to Kanto-Teishin Hospital complaining of bloody diarrhea or considerable hematochezia of acute onset, 8 cases (14.3%) were considered due to colitis associated with oral ampicillin therapy. The bloody diarrhea, often with abdominal cramps, began 2-7 days after starting the treatment. The dosage of ampicillin taken ranged from 2.0 to 4.5 g. Early total colonoscopy and biopsy revealed marked mucosal hemorrhage with minimal or no inflammatory changes mainly in the right colon. Rectum and sigmoid colon are completely normal except in one case. Symptoms rapidly resolved after the endoscopy. At follow-up colonoscopy, performed 4-12 days later, the mucosal changes had cleared completely. There was no evidence to support a hypersensitivity reaction of the colonic mucosa to ampicillin. We believe that right-sided hemorrhagic colitis is one of the common forms of colitis associated with ampicillin. Its differentiation from other kinds of acute colitis and the importance of early total colonoscopy are discussed.


Role of defunctionalized bowel in jejunoileal bypass-induced liver disease in rats.

The pathogenesis of jejunoileal bypass-induced liver disease was investigated in the rat model. Male Sprague-Dawley rats were subjected to 90% jejunoileal bypass and compared to rats having undergone 90% jejunoileal resection, to ad libitum and pair-fed controls and to weight-matched (underfed) controls. After 8 weeks the animals were killed and selected analyses performed. Several indications of liver dysfunction were observed in the bypass rats including hepatomegaly, hypotriglyceridemia, hypoproteinemia, elevated SGOT levels, and markedly decreased levels of cytochrome P-450. All of these abnormalities with the exception of elevated SGOT levels and decreased serum proteins were not observed to the same degree in animals in which the defunctionalized bowel was resected. Rats which were underfed (weight matched) did not develop any of the abnormalities of liver injury demonstrated in the bypass rats. Multiple factors appear to be responsible for the production of bypass-induced liver disease, but the defunctionalized bowel plays an important role.


Perforation of peptic ulcers related to fiberoptic endoscopy.

Three cases of perforation of peptic ulcers related to either fiberoptic endoscopy or esophageal dilation are presented. A correct preoperative diagnosis can be made by recognising the onset of acute abdominal symptoms and signs after an uneventful fiberoptic examination or dilation of stricture in patients with preexisting ulcer symptoms. The complication is especially likely to occur in peptic ulcer disease coexisting with esophageal stricture, possible due to air trapping in the stomach.


Protein digestion and absorption in the blind loop syndrome.

Protein digestion and absorption was studied in rats with 6-week-old surgically constructed self-filling intestinal blind loops and steatorrhea, ie, blind-loop animals and controls were fed a 14C-labeled protein meal containing a nonabsorbable marker, 51CrCl3, and sacrificed 1 or 2 hr later. Intestinal contents were analyzed for 14C, 51Cr, protein, trypsin, and the products of digestion. At 1 hr, 14C absorption was greater in controls, but at 2 hr there was no difference in absorption between the two groups. Marker studies showed that blind-loop filling resulted in a delay of the progression of intestinal contents distally. Intraluminal trypsin and porteolysis were similar in the two groups. Endogenous protein was greater in the blind-loop animals. The early stages of the blind-loop syndrome may be characterized by delayed protein absorption secondary to blind-loop filling, which is compensated for by the distal gut resulting in an absence of overall protein malabsorption.


Effects of alcohol on the pyloric sphincter.

The effects of an intoxicating dose of alcohol (79 g of 100 proof alcohol) on pyloric sphincter function were studied in 12 normal subjects using an infused manometric system. Alcohol had no effect on resting pyloric sphincter pressure. Intraduodenal administration of olive oil and hypertonic amino acids increased pyloric sphincter pressure significantly to 10.8 +/- 1.4 and 10.2 +/- 2.0 mm Hg, respectively. These responses were not affected by the administration of alcohol. In contrast, alcohol decreased the pyloric pressure response to duodenal acidification from 12.0 +/- 2.1 to 8.0 +/- 1.3 mm Hg (P less than 0.05). These results suggest that an intoxicating dose of alcohol may interfere with the normal function of the pyloric sphincter.


Aortoduodenal fistula: endoscopic diagnosis.

Aortoduodenal fistula has been reported as a complication in up to 4% of aortic aneurysm repairs, presenting as gastrointestinal bleeding of varying severity. Mortality of patients not operated on approaches 100%, and preoperative diagnosis is extremely difficult. In this report five cases are described in which the diagnosis was established endoscopically, and the literature regarding the pathophysiology and natural history of this entity is reviewed.


Esophageal emptying in achalasia quantitated by a radioisotope technique.

Delayed esophageal emptying of a radiolabeled meal distinguished symptomatic achalasia patients from asymptomatic controls. Esophageal emptying of the isotope meal significantly improved in ten achalasia patients after pneumatic dilation, and in one patient after surgical myotomy. The emptying curve in some patients after treatment simulated that of control subjects. Quantitation of esophageal emptying by a radiolabeled meal is a physiologic test that may be useful in evaluating results of therapy for achalasia.


Acute colitis and bacteremia due to Campylobacter fetus.

An acute febrile illness with dysentery and colitis developed in a 26-year-old man following a wilderness outing. Campylobacter fetus ssp. jejuni was subsequently grown on blood cultures drawn during the acute illness and 9 days later when the patient was asymptomatic. Proctosigmoidoscopic and histopathologic evidence of acute colitis was present on admission and resolved on follow-up examination. Campylobacter fetus spp. jejuni infection should be considered in the etiology of acute infectious colitis.


Upper esophageal web due to a ring formed by a squamocolumnar junction with ectopic gastric mucosa (another explanation of the Paterson-Kelly, Plummer-Vinson syndrome).

A patient is presented with Barrett's esophagus (lower esophagus lined with columnar epithelium) who also has a band of columnar epithelium in the upper esophagus separated from that below by normal squamous epithelium in the midesophagus. The upper most squamocolumnar junction coincided with or formed a mucosal ring as seen at endoscopy. This ring, which was first seen on barium swallow, has the radiographic appearance of that associated with the Paterson-Kelly syndrome. This patient's unique findings may provide further insight into the etiology of upper esophageal webs or rings (Paterson-Kelly syndrome).


Gallstones in a retroperitoneal abscess: a late complication of perforation of the gallbladder.

The case of a 72-year-old female with a retroperitoneal abscess which contained cholesterol gallstones is presented. The pathogenesis of this unusual complication of gallbladder disease is discussed.


Plasma insulin and C-peptide levels during continuous subcutaneous insulin infusion.

A study was performed to estimate the absorption kinetics of insulin infused subcutaneously. Four insulin-dependent diabetic subjects had their insulin pumped through a subcutaneously implanted fine polyethylene catheter at a constant rate of 5.0 +/- 0.3 ml/h but at two different insulin concentrations: 218 mU/ml between meals, and 2400 mU/ml at the start of breakfast, lunch, and dinner (lasting 20, 30, and 30 min, respectively). The amount (40 U/day) and distribution of insulin delivered was identical in the four patients in order to facilitate comparison between the subjects. No attempt was made to normalize their blood glucose during the study period. A study of the kinetics of insulin absorption was made by assaying plasma insulin levels; lack of plasma anti-insulin antibodies was verified; plasma C-peptide levels were measured and were far below values observed in the fed state in nondiabetic patients. The mean maximum insulin level reached after switching from low to high concentration insulin was observed 87 +/- 2 min after breakfast, 117 +/- 22 min after lunch, and 125 +/- 20 min after dinner. Differences observed are not significant. These values are similar to those observed after subcutaneous injection of 40 U/ml Regular insulin as a single bolus. After switching from high to low concentration, plasma insulin levels did not return to their basal values before the third or fourth hour. Subcutaneous insulin infusion could be a safe and easy way of insulin administration in an open-loop system; however, this method does not seem to be suitable for a closed-loop system.


Use of an artificial pancreas as a tool to determine subcutaneous insulin doses in juvenile diabetes.

The present study was undertaken to examine the feasibility of determining the most appropriate subcutaneous insulin treatment in unstable diabetes on the basis of the circadian hormonal profile delivered by an artificial pancreas. The metabolic control of 11 brittle diabetic subjects, as assessed by the M value and the MAGE index (used as indexes of blood glucose control and of glycemic fluctuations, respectively), was compared during a 5-day period before and after a 24-h connection to the artificial pancreas. The usual insulin treatment was continued to that day. Examination of the insulin pattern revealed by the artificial pancreas suggested that a valid scheme for subsequent treatment should consist of two daily injections of a mixture of short-acting and intermediate-acting insulins, which was administered to the patients beginning with the injection given after the artificial pancreas onwards. The new insulin regimen was characterized by a total daily dose that increased from 0.93 +/- 0.10 to 1.20 +/- 0.10 U/kg body weight (mean +/- SEM; P less than 0.005) as well as by a higher proportion of the dose given as regular insulin (37.1 +/- 6.9% before vs. 56.0 +/- 2.1% after; P less than 0.05). These changes led to a better control of blood glucose in 10 patients, as evidenced by a decrease of both the M value and the mean of all blood glucose levels. The mean MAGE index was not decreased, however, by the new insulin program, thereby suggesting that the lability of the disease remained unabated. These results indicate that subcutaneous treatment consisting of two daily injections of regular and intermediate-acting insulins and comprising 50 to 60% of the former could improve the metabolic control in unstable diabetes. The artifical pancreas provided a rapid and simple means to determine the appropriate doses for each type of insulin.


Ambulatory diabetes management by a pulse of subcutaneous insulin delivered by a portable pump: preliminary report.

Two teenage patients, who had severe psychosocial problems that complicated their diabetes management, were treated for one month (14-year-old girl) and two months (16-year-old boy) by frequent pulses of insulin injected subcutaneously by a portable, programmed pump. Additional pulses were manually adjusted by the patient before eating. Both patients experienced improved sense of well-being, marked reduction in urine volume and in glycosuria, and reduced glycemic excursions and average levels. The boy had accelerated linear growth and a decreas in HbA1 percentage. Despite marked clinical improvement, permitting return to school, the girl was impelled to interrupt pump administration after two weeks. Both patients continue to use the device voluntarily; a smaller unit, however, that doesn't have the conspicuous external controls, would likely be readily acceptable to most young patients.


Insulin-resistant diabetes with insulin receptor autoantibodies in a male patient without acanghosis nigricans.

A 51-yr-old, nonobese, male patient presented with hyperglycemia and a recent 40-pound weight loss. Severe insulin resistance was documented in studies in which high amounts of insulin were infused using the Biostator GCIIS. Diabetic control was finally achieved with subcutaneous injections of 470 U of insulin per day. Positive laboratory findings included a mild pancytopenia, elevated erythrocyte sedimentation rate, decreased C3 and properdin, and increased IgA. Antinuclear or other autoantibodies were not present. Insulin antibody levels were within the range usually present in insulin-treated diabetic patients. Acanthosis nigricans was not present. Incubation of the patient's serum with IM-9 lymphoblastoid cells revealed that an insulin receptor antibody was present in a serum dilution of 1:80. Insulin-resistant diabetes mediated by insulin receptor antibodies may present in patients with immunologic findings but without overt dermatologic stigmata.


Standard parameters of diabetic control: are they reliable?

To evaluate the reliability of the tradional methods to assess short-term control of diabetes, 25 children with insulin-dependent diabetes were studied with a 24-h glucose profile in addition to the traditional assessment techniques. Patient compliance was elminated as much as possible from the experimental design. The correlation of the routine methods with the 24-h glucose profile was excellent, and a scoring system for control was empirically derived. The single method of assessment that correlated best with the overall control score was the traditional daily urine test. In 6 of the 25 subjects studied, relative hypoglycemia was observed, occurring asymptomatically at night, and was followed by a hyperglycemic rebound. Traditional assessment techniques did not detect this event. Five additional patients had symptomatic daytime hypoglycemia. We conclude that the traditional daily urine tests are adquate indicators of day-to-day control in most diabetic patients, given adquate compliance. Our data also suggest that asymptomatic nocturnal hypoglycemia occurs frequently in children with diabetes, although clinical proof is difficult in the absence of a 24-h glucose profile.


A multidisciplinary, comprehensive, ambulatory treatment scheme for diabetes mellitus in children.

A study has been carried out on 262 children with juvenile diabetes and their parents, treated up to 10 yr on an ambulatory basis by a multidisciplinary team composed of pediatric endocrinologist, nurse, dietitian, psychologist, and social worker. Comparison of the findings with those of a study performed before inception of the Counselling Center for Juvenile Diabetics revealed the following positive influences: the degree of control attained was both higher and sustained with greater regularity; there were fewer complications with no episodes of coma, brittle diabetes, or severe ketoacidosis and almost no need for hospitalization; the attitude of the affected child, his parents, and his teachers was found to be considerably improved; there was better understanding of the nature of the disease and its requirements; the child's motivation to maintain the diabetic regimen was greater and conflicts within the family circle were markedly reduced; the child's self-concept was much higher; and both scholastic achievements and social adjustment were greater. We concluded that psychological stability is a basic factor in the control of diabetes, and the value of the multidisciplinary approach in the treatment of this chronic disease is indicated.


Feasibility of improved blood glucose control in patients with insulin-dependent diabetes mellitus.

An attempt was made to improve the control of blood glucose in patients with insulin-dependent diabetes mellitus. Ten patients were studied over a period exceeding 8 mo in the outpatient department. Each patient was taught to monitor his or her own blood glucose concentration and was enrolled in an exercise program. In addition, they were taught to calibrate insulin, food, and exercise in terms of the response of the blood glucose. After 3 mo of study, there was a significant decrease in hemoglobin A1c (Hb A1c) values from a mean concentration of 10.3 to 7.6%. Hb A1c values correlated well with mean blood glucose levels (r = 0.86). Dietary analysis revealed that the patients selected a diet consisting of 25% protein, 44% fat, and 31% carbohydrate, but there was a wide range in caloric distribution. There was no correlation between blood glucose control as measured by Hb A1c and caloric distribution. Systolic blood pressures decreased greater than 10 mm Hg. Serum alkaline phosphatase also decreased in each patient as control of blood glucose improved. Three of the patients with abnormalities of nerve conduction measurement at the beginning of the study had a complete return to normal at 8 mo. An outpatient program such as this may be cost effective through the avoidance of diabetes-related hospitalizations and may provide a mechanism whereby larger studies can be designed to define further the relationship of glycemia to the sequelae of diabetes.


Glucosuria in children with diabetes: advantages of the 2-drop Clinitest method.

In order to assess the actual and theoretical limitations of using the traditional urinary glucose determinations as an indicator of plasma glucose concentration, we have measured plasma and urine glucose concentrations in 37 children with diabetes mellitus. A constant blood withdrawal system enabled an accurate estimate of the glucose concentration presented to the renal glomerulus over the 30-min period of blood collection and urine formation. The theoretical range of plasma glucose over which the 5-Drop and 2-Drop Clinitest methods are sensitive is 32 mg/dl and 81 mg/dl, respectively. This suggests that the 2-Drop method is the procedure of chioce for most insulin-dependent diabetic patients. Nevertheless, the extremely wide range of plasma glucose corresponding to a given urinary glucose measurement limits the precision with which any single urine test can be interpreted.


Fiber and diabetes.

Plant fibers have important influences on gastrointestinal physiology and the absorption of many nutrients. Certain fibers delay the absorption of carbohydrates and result in less postprandial hyperglycemia. Because the intake of plant fibers lowers plasma glucose concentrations and decreases glycosuria, high-fiber foods may be useful in the management of diabetes mellitus. Consumption of selected fibers and fiber-rich foods lowers serum cholesterol values and may lower triglyceride concentrations. Plant fiber intake may lead to mineral depletion or vitamin deficiency, but this has not been observed in several long-term studies. Further work is required to delineate the therapeutic utility of plant fibers in the diet of persons with diabetes and to assess the undesirable effects of fiber intake. In our opinion, persons with diabetes who are eating very low-fiber diets would benefit from an increase in plant fiber intake from whole grains, legumes, and vegetables.


Factors in the survival of patients with insulin-requiring diabetes for 50 years.

Ninety-seven diabetic patients who had taken insulin for 50 yr and longer were surveyed by questionnaire to identify factors that might explain their unusual longevity. The analysis suggested that the long survival of this group was related to the following: maintenance of normal or near normal body weight, regular contact with a personal physician, periodic blood glucose determinations, frequent urine testing, regular exercise, and longevity of the parents and grandparents. The results support the conclusion that careful management of diabetes favors longevity.


Community screening programs for diabetes?

Considerable uncertainty and disagreement now prevail concerning the utility and priority of community screening programs for diabetes. A large majority of diabetologists believe that substantial benefits attend the early discovery of diabetes. Official statements of the American Diabetes Association support the view that mitigation of hyperglycemia lowers risk of morbidity. Much recent evidence indicates that aggressive early treatment often improves beta-cell function, thereby diminishing the severity of diabetes. Even so, some diabetologists and public health specialists question the practical benefits of community screening programs. Indeed, there is considerable evidence that, as previously performed, results sometimes have not justified costs. This article suggests that, when well designed, community screening is stil justified in some circumstances. To a considerable degree, failures of the past are correctable. The American Diabetes Association should neither approve nor disapprove community screening indisciminately. Affiliate organizations and health departments should be free to examine available evidence and local circumstances and, then, to decide whether to undertake screening programs. More care is needed in planning, executing, and critically evaluating these programs, but there is impressive and mounting evidence supporting the potential utility of the early discovery of diabetes.


Salvage of extremities with ischemic necrosis in diabetic patients by infrapopliteal arterial bypass.

Initial and long-term limb salvage can be achieved by infrapopliteal bypass in diabetic patients with ischemic necrosis of the distal extremity. Mortality is low in all groups, and mortality of subsequent amputation apparently is not affected by the previous bypass. An adequate arteriogram and consideration of distal bypass are frequently indicated in the diabetic patients in whom ischemic necrosis is present. Limb salvage may be feasible even in those diabetic patients in whom popliteal artery is not patent on preoperative arteriogram by bypasses to anterior tibial, posterior tibial, or peroneal artery.


Comparison of the metabolic response to a glucose tolerance test and a standardized test meal and the response to serial test meals in normal healthy subjects.

The plasma glucose and insulin response to a standardized meal test breakfast was compared with the time-honored glucose tolerance test in the same normal healthy subjects. The amplitude of glycemic excursion and between-subject variation was less with the more physiologic standardized test meal than with that seen with the glucose tolerance test. The glucose tolerance test's prime function is to amplify any glucose intolerance, thus aiding diagnosis, whereas a standardized meal gives a more clinically relevant metabolic status. The administration of serial test meals during the same day in a smaller group of normal subjects indicated, as seen previously with repeated glucose tolerance tests, a diminishing carbohydrate tolerance during the day.


Accelerated insulin degradation: an alternate mechanism for insulin resistance.

We have examined insulin and glucagon degrading activities of muscle and fat tissues in 11 subjects (4 lean controls, 3 insulin-resistant obese subjects, 2 non-insulin-dependent diabetic subjects, and 2 insulin-treated diabetic subjects) and correlated degrading activity with (1) basal insulin level and (2) state of insulin resistance. We found hyperinsulinemia and insulin resistance to be significantly correlated with accelerated insulin and glucagon degrading activity. Weight reduction in an insulin-resistant obese patients results in parallel reduction in both basal insulin level and insulin-glucagon degrading activity. These data are consistent with the hypothesis that an alternative mechanism for insulin resistance may be an accelerated insulin degradation at the level of target tissues.


Some social factors related to control of diabetes mellitus in adult Jamaican patients.

A population of 103 adult diabetic patients was interviewed at the Outpatient Clinic for diabetic patients of the University Hospital of the West Indies to examine the effects of severity of the illness and social variables, such as facilities at home, education attained, employment status, informal medication, and understanding of the illness in relation to its control. Patients were classified as severe if there were clinical evidence of vascular or neurologic complications of diabetes and as mild if there were no complications. Control of diabetes was regarded as good if the patients were free from or had less than 2+ glycosuria and as poor if they had had 2+ or more glycosuria during the six months before the study. We found that the quality of control was mainly determined by the severity of the disease. In the mild diabetic, proper diabetic control was not influenced by any social variable examined. In the severe diabetic the quality of control was associated with social amenities, educational status, employment status, and understanding of the disease.


Reuse of disposable syringe-needle units in the diabetic patient.

A comparison was made between reuse of plastic disposable needle-syringe units and glass syringes with daily new needles in diabetic patients who take daily insulin injections. Parameters studied were incidence of infection, clarity of syringe readings, ability to use syringe, and sharpness of needle. The plastic disposable units could be reused with safety and patient satisfaction by most patients for at least 3 days. Considerable cost benefit could accrue if disposable units were used more than one time for insulin injections.


Evaluation of a portable insulin infusion pump for outpatient management of brittle diabetes.

Three "brittle" diabetic patients were given constant subcutaneous insulin infusion with a portable battery-driven pump, and their plasma glucose and hemoglobin A1 were measured at frequent intervals during inpatient or outpatient periods. Mean plasma glucose decreased significantly in all inhospital patients and remained significantly less than before pump therapy in two of three as outpatients during the 8--12 wk of follow-ups; however, complete normalization of glucose metabolism was not accomplished in any. All three demonstrated a progressive decline in hemoglobin A1 levels to normal or near-normal values. The need for long-term studies of open loop infusion systems in a research setting before their adaptation to routine care is emphasized.


Parental attitudes toward children with a chronic medical disorder: special reference to diabetes mellitus.

Children who suffer from chronic medical disorders requiring continuous therapy create threatening situations for parents, which are often acute at diagnosis and may continue over the years. Many parental reactions and consequent emotional interactions with the children are common to all medical handicaps, but also vary with the nature of the particular disease and its treatment. Attitudes of parents to the diagnosis of a chronic handicap or medical disorder will always include some apprehension. This is usually more acute in mothers than in fathers, both by their nature and position of authority in the care of the child in most homes. Some anxiety is normal at diagnosis of a chronic ongoing illness in a child and may even help in making the mother more aware of the extra responsibility that has been thrust on her and give her the desire to manage the treatment well.


Effect of alpha- and beta-blockers on ethanol metabolism.

The acute administration of propranolol or phentolamine resulted in a small (16-19%) but significant reduction in the rate of ethanol disappearance in vivo in the naive Wistar rat. A reduction of essentially similar magnitude was also observed in ethanol-treated rats and pair-fed (sucrose) control animals, following the administration of these blockers.


The adaptive increase in ethanol metabolism due to pretreatment with ethanol: a rapid phenomenon.

Simple models were developed to study changes in oxygen uptake in perfused rat liver and increases in ethanol metabolism in vivo. Results obtained 2.5 hours following a large dose of ethanol were quantitatively similar to those seen after 24 hours or 5 weeks. The rapidity of the increase indicated that SIAM represents an activation rather than an adaptation. Pathways responsible for the swift increase in alcohol metabolism (SIAM) in the perfused rat liver were investigated through the use of ouabain and were found to be related to diminished glycolysis and another unidentified pathway. Investigation of pathways responsible for the increase in ethanol metabolism in vivo following ethanol treatment implicated the alcohol dehydrogenase pathway as that mainly responsible for the adaptive increase, although a catalase-H2O2-dependent component was also involved. The rate of NADH reoxidation generally appeared to be the rate-limiting step. In addition, the genetic aspect of SIAM was indicated through selective breeding resulting in F1 generations of non-SIAM and SIAM rats.


Characterization of brain acetaldehyde oxidizing systems in the mouse.

C57BL mice were treated (75 or 100 mg/kg) with pargyline or Lilly 51641 90 min prior to sacrifice. Liver and brain subcellular fractionation revealed that pretreatment with these drugs resulted in a significant inhibition of aldehyde dehydrogenase (ALDH) in liver cytosol and mitochondria, while brain ALDH in these same fractions was unaffected. Administration of pargyline or Lilly 51641 prior to ethanol treatment (3.0 g/kg) resulted in a significant elevation of blood acetaldehyde. Significant increases in brain acetaldehyde concentrations were not observed until blood acetaldehyde levels surpassed 200 nmol/ml. When mice were injected with ethanol (3.0 g/kg) and acetaldehyde (200 mg/kg), a similar relationship between blood and brain acetaldehyde concentrations was observed. Data presented in the present study indicate that there are very efficient enzymatic mechanisms responsible for acetaldehyde oxidation in brain and that at blood acetaldehyde concentratins normally occurring after ethanol ingestion, brain acetaldehyde levels would be extremely low.


Mechanisms of ethanol tolerance at a cholinergic nerve terminal.

In vitro rat phrenic nerve-diaphragm preparations illustrated a concentration-dependent increase in the spontaneous release (miniature end-plate potentials, MEPPs) of acetylcholine following acute administration of ethanol. In phrenic nerve terminals from rats subjected to long-term ethanol treatmet, ethanol in vitro was significantly less effective in increasing the frequency of MEPPs. The capacity of ethanol administration to change membrane viscosity and alter sequestration of intracellular Ca2+ is discussed as a possible explanation for the observed effects.


Adaptation to ethanol-induced fluidization of brain lipid bilayers.

We have shown that ethanol is less able to fluidize reconstituted membranes prepared from lipid extracts of tolerant mice synaptosomal membranes than those prepared from controls. The effects of ethanol on membrane fluidity were assessed by fluorescence polarization technique. Acute in vivo administration of ethanol did not alter ethanol-induced fluidization of the bilayers. These results suggest that changes in the lipid composition of membranes can account, at least in part, for tissue adaptation to ethanol-induced membrane fluidization. We also discuss the use of reconstituted membranes as a tool both to analyze the significance of changes in membrane composition for the development of tolerance and to refine our concepts concerning the relation between membrane fluidity and anesthetic activity.


Physical dependence on ethanol: its relation to tolerance.

The homeostat hypothesis of drug addiction states that tolerance and physical dependence may both represent adaptive processes, the body's responses to drugs that change the internal milieu. This conceptual framework inextricably links physical dependence with functional tolerance. Dependence may arise by multiple mechanisms, so that different signs, such as body temperature or CNS excitability, may show different degrees of dependence or may have different time courses. Tolerance may be similarly diverse. It is difficult to test whether tolerance and dependence have the same time course because it is hard to find exactly equivalent signs for such a test. The discrepant data from different laboratories on the rate of recovery from physical dependence may be due to the use of different withdrawal signs as indices. Dissociation of tolerance and dependence has been reported in mice treated with 6-hydroxydopamine, where dependence develops without evidence of tolerance. Conversely, tolerance without expression of dependence is seen in experiments on membranes and synapses in vitro. Changes in lipid composition of cell membranes may explain some kinds of tolerance.