Bronchial asthma: some aspects of pathogenesis and therapy.

The first step in management of bronchial asthma is to exclude other diseases which may present as wheezing dyspena. Once the diagnosis is confirmed beyond a reasonable doubt, therapy can be initiated. Treatment depends on the type, severity, and duration of the disease. Other factors which dictate the choice of drug are the patient's response, metabolism of the drug, and complications of the disease. Theophylline forms the backbone of asthma therapy. Because of the wide variation in half-life of theophylline in different individuals due to variation in rate of metabolism and elimination, serum levels of theophylline should be monitored whenever possible. Newer antiasthmatic drugs, such as cromolyn sodium and inhaled steroids, are playing an increasing role in treatment of selected patients.


Double-blind comparison of verapamil and practolol in the treatment of angina pectoris.

In thirteen patients with coronary insufficiency and angina pectoris the therapeutic effects of verapamil, 80 mg three times/day and practolol, 100 mg three times/day, were compared and tested against placebo in a double-blind cross-over fashion. Verapamil proved to be the most efficient drug as regards attack frequency and glyceryl trinitrate consumption as well as physical working capacity, bringing about a statistically significant increase of the exercise tolerance as compared to placebo after a treatment period of four weeks. Verapamil is a good alternative to beta-blockers in the prophylactic treatment of angina. Possible modes of action of verapamil in angina pectoris are discussed. The study had to be interrupted because of the reports of side effects of practolol, explaining the small number of patients.


Angiokeratoma corporis diffusum: the evolution of a disease entity.

The clinical features, diagnosis management, aetiology and inheritance of angiokeratoma corporis diffusum (Fabry's disease) are discussed and the literature reviewed. The treatment and knowledge generally of this rare condition have not greatly improved in 75 years.


[Epilepsy by looking at patterns].

The author, after pointing out the rare occurence and peculiarities of pattern-sensitive forms of epilepsy, reports the case of a seven-year-old boy with infantile cerebral paresis characterized by symptomatic attacks, who was observed to show absence-like conditions when looking at small-checkered patterns of nylon fabric. Grasping and looking at such fabrics assumed the form of an addiction, with a sense of pleasure being believed to be derived therefrom. Although anticonvulsive therapy resulted in attacks of epilepsy being no longer detectable clinically and by electroencephalography, seizures were still triggered by looking at patterns. Also discussed in this article is the problem of transition from real to psychogenic attacks.


Some factors influencing the effects of temporary mother-infant separation: some experiments with rhesus monkeys.

Some experiments, reported in detail elsewhere, on the effects of mother-infant separation in rhesus monkeys are here reviewed and compared. They involved 4 groups--one in which mothers were removed for 13 days leaving the infant in the social group; one in which infants were removed; one in which mothers and infants were removed and separated; and one in which mothers and infants were removed but not separated. The nature of separation experience had a profound effect on the infant's response: infants left in a familiar environment while their mothers were removed showed marked but brief 'protest' and then profound 'despair', whilst infants removed to a strange cage showed more prolonged 'protest'. A major factor determining the effects of the separation experience in the weeks following reunion is the degree to which the mother-infant relationship has been disturbed by it. The multiplicity of factors affecting the outcome of a separation experience are discussed.


The selection of long-stay hospital patients for hostels: a study of patients selected for an experimental hostel and for local authority hostels.

Chronic in-patients from a sample population of 48 women and 43 men were selected for an experimental hospital-hostel and for local authority hostels. Two-thirds were found suitable for the former but only a sixth for the latter. The problems of selection for and management at the experimental hostel are described, and the overall results discussed in relation to recent proposals for the residential care of chronic patients.


Increase in mouse brain dopamine content by baclofen: effects of apomorphine and neuroleptics.

Baclofen, like gamma-butyrolactone, causes a dose-dependent increase in the concentration of dopamine in the mouse brain without affecting the content of norepinephrine. This increase is antagonized by apomorphine. Haloperidol but not pimozide counteracts this effect of apomorphine and dose-dependently enhances the increase in brain dopamine produced by baclofen. The results suggest that baclofen reduces impulse flow in dopaminergic neurons in a manner similar to that produced by gamma-butyrolactone.


Effects of cigarette smoking on incidental memory.

The effects of cigarette-smoking in an immediate memory task were studied in two groups of 25 female students (habitual smokers) tested either under a control (no smoking) condition or after smoking one cigarette. The memory task, requiring immediate serial recall of eight words, showed no differences between the two groups. Subjects were, however, also tested on recall of the position of words on the screen (each word could appear in any of the four corners). On this measure of incidental recall, the non-smoking group was far superior to the smoking group. This finding is in agreement with results obtained with noise-induced arousal and with the view that attentional selectivity is greater during increased arousal.


The disruption of marijuana intoxication.

Ninety-six males Ss were divided into four drug conditions; coltsfoot, placebo, marijuana low dose, and marijuana high dose. Half of the Ss smoked marijuana while listening to music in a relaxing environment, and half smoked marijuana in the same environment but had two 10-min periods of aversive-noise superimposed over the music. A subjective measure of intoxication demonstrated significant drug and environmental group effects with suppression of self-report of intoxication being especially strong for the marijuana low dose noise group. The usual positive correlation between subjective measures and pulse rate measures of marijuana intoxication was interfered with by the noise effect. Although subjective ratings were suppressed, the noise group demonstrated significantly higher pulse rates than the music group. The results are discussed in terms of the effect of extraneous factors on marijuana intoxication, the significance of dosage in this type of research, and the nature of marijuana intoxication.


Marijuana effects on long-term memory assessment and retrieval.

The ability of 16 college-educated male subjects to recall from long-term memory a series of common facts was tested during intoxication with marijuana extract calibrated to 0.3 mg/kg delta-9-tetrahydrocannabinol and during placebo conditions. The subjects' ability to assess their memory capabilities was then determined by measuring how certain they were about the accuracy of their recall performance and by having them predict their performance on a subsequent recognition test involving the same recall items. Marijuana had no effect on recall or recognition performance. These results do not support the view that marijuana provides access to facts in long-term storage which are inaccessible during non-intoxication. During both marijuana and placebo conditions, subjects could accurately predict their recognition memory performance. Hence, marijuana did not alter the subjects' ability to accurately assess what information resides in long-term memory even though they did not have complete access to that information.


The effect of methylphenidate on test performance in the cognitively impaired aged.

It was hypothesized that a central nervous system stimulant with relatively weak peripheral effects would facilitate test performance in the cognitively impaired aged. Twelve elderly subjects participated in a counter-balanced, crossover comparison of 10 mg methylphenidate, 30 mg methylphenidate and placebo. All treatments were administered double-blind as a single dose of oral medication. Neither dosage of active medication was found to effect psychomotor or psychological test performance, subjective report, heart rate or blood pressure. A subsequent open trial of 45 mg methylphenidate resulted in heart rate, blood pressure and subjective changes in two of eight subjects but no effects on test performance. The results suggest that cognitive performance in the moderately impaired aged is unimproved following administration of methylphenidate, and perhaps similar sympathomimetic amines, below a dosage level associated with clinically significant peripheral effects.


Deanol in the treatment of tardive dyskinesia.

Ten hospitalized chronic psychotic patients with symptoms of tardive dyskinesia were given deanol and placebo, each for 8 weeks following a double-bline, crossover design. No psychotropic agents were administered during the trial. Improvement occurred in all patients during the first treatment phase regardless of which drug the patients received; seven patients were on deanol and three on placebo during this time. The possible reasons for this decrease were discussed. It was concluded that deanol may have contributed to the decline but that its effect on the disorder was not dramatic.


Development and disappearance of subsensitivity to pilocarpine following a single administration of the irreversible anticholinesterase angent, DFP.

The present study examined the possibility that subsensitivity to pilocarpine might occur following a single injection of the irreversible anticholinesterase agent, DFP. In one experiment male Sprague-Dawley rats were trained to drink from experimental drinking chambers for 1/2 h per day. After establishment of baselines, pilocarpine hydrochloride (8 mg/kg) was injected i.p. 5 min before the drinking session. One week later DFP or the arachis oil vehicle (1 mg/kg) was injected intramuscularly and injections of pilocarpine were given at varying times thereafter. The suppression of water intake by this dose of pilocarpine was unaffected by pretreatment with arachis oil, but was markedly attenuated by pretreatment with DFP. This subsensitivity was first observed on the second day but had largely disappeared by the 14th day. DFP was found to have comparable effects on water intake and brain acetylcholinesterase activity when the injections were separated by 20 days. In a second experiment the hypothermic effects of pilocarpine were found to be reduced in rats acutely treated with DFP. These data establish that subsensitivity to pilocarpine occurs following a single administration of DFP. This subsensitivity could reflect a reduced sensitivity of postsynaptic receptors to acetylcholine, which may partially account for the behavioural recovery of the rats while acetylcholinesterase activity is still markedly depressed.


An automated method for studying exploratory and stereotyped behaviour in rats.

A technique is described for studying exploratory as well as stereotyped behaviour in rats using an automated hole-board. Both visual and automated recordings can be employed using the technique. Hole dipping is monitored automatically using an infra-red detector system. Repetitive patterns of hole-dipping are used as parameters of stereotyped behaviour while the more random patterns of hole-dipping are used as parameters of exploration. There was a high significant correlation between the records of hole-dipping behaviour as recorded visually and automatically. There was also a high significant correlation between the measures of repetitiveness/randomness of hole-dipping behaviour from automatic and visual recordings. The pattern and levels of hole-dipping conformed with expectations both as regards changes with time and with increasing doses of dl-amphetamine.


Effects of exposure to lead on social behaviour in the laboratory mouse.

Ethological analysis has been employed to study the behavioural effects produced by exposure of mice to lead salts from infancy. Mother mice of the treated group received 0.1% lead acetate as their sole drinking fluid within 24 h after the birth of their litters and the offspring received this fluid from weaning. At 8 weeks, encounters between pairs of unfamiliar mice from the same treatment group and of the same sex were examined by ethological techniques. The frequency and duration of social and sexual investigation was found to be significantly lower in lead-treated mice of both sexes than in their controls. In lead-treated males, agonistic behaviour was also reduced. These effects were due to a reduction in the frequency of several postural elements within each of the categories. Body weight gain was not affected by treatment with lead at this dose level and there were no signs of hyperactivity. The average lead content of the brains was found to be 2.45 nmol/g in the control group and 4.38 nmol/g in the group given lead acetate.


Scopolamine induced learning failures in man.

Two experiments were performed to determine the locus of the amnestic effects of scopolamine in man. The first experiment involved 24 volunteers receiving one of three doses of scopolamine (5, 8 or 10 microng/kg) or a placebo, intravenously. The subjects were tested for retention of material learned prior to administration of the drug, acquisition of new information, and retention of material learned while under the influence of the drug. Results indicated that scopolamine has its primary effect on the acquisition of new material and less of an effect on the retrieval of information already learned. The second experiment was designed to refine and expand upon the results of the first and involved 18 volunteers receiving eith 5 or 10 microng/kg of scopolamine or a placebo, intravenously. The subjects were given four trials to learn a list of verbal materials, and their recall for that material was measured at various intervals up to 24 h. These results confirmed those of the first experiment in that the predominant influence of the drug was to impair the acquisition of new information. Implications of these results for memory mechanisms are discussed.


Performance differences between addicts and non-addicts.

Methadone addicts and non-addict controls were tested before and after receiving up to 10 mg of methadone on simple visual reaction time tests and on a vigilance type visual attention test. Addicts were faster than controls on pre-drug testing, although there were no pre-drug differences between groups on the attention task. Addicts maintained faster reaction times than controls even when money was offered as an incentive for speed. Additional methadone did not affect addict performance on any of the tasks. Methadone slowed control reaction times in a dose-related fashion. No significant attention decrements were seen after methadone in controls. Visual reaction time differences between addicts and controls cannot be attributed to group differences in motivation or ability to attend. Slowing of reaction time with acute dose of methadone in controls cannot be attributed to the effect of the drug on attention. An hypothesized drug-induced decrease in visual sensitivity with acute dose in controls and a drug-induced increase in visual sensitivity with chronic dose in addicts can account for the presented data.


Lethal effects of physostigmine plus lithium in rats.

The interaction between the reversible cholinesterase inhibitor, physostigmine, and lithium chloride was studied in adult male rats. A combination of lithium plus physostigmine increased lethality more than that caused by either physostigmine or lithium alone. Scopolamine completely reversed this effect. These drug interactions may have clinical significance, since lithium plus cholinesterase inhibitors may be used together in the practice of medicine.


Prenatal alcohol consumption and open-field behaviour in rats: effects of age at time of testing.

Throughout gestation pregnant Wistar rats consumed a nutritious liquid diet containing 35% ethanol-derived calories. Control mothers were fed lab-chow. Subsequently, the offspring of the ethanol-fed mothers displayed significantly greater activity (ambulation) in an open-field test at 28 and at 56 days of age, but not at 112 days of age. No differences in defecation were observed at any age.


Bone scintigraphy as a guide to the diagnosis of osteoid osteoma.

This report describes one case in which bone scintigraphy was helpful in establishing the diagnosis of osteoid osteoma and presents three other cases in which increased accumulation of 99mmTc-EHDP was found at the side of the osteoid osteoma. The study contributes to the observation by others that the osteoid osteoma occurs as a scintigraphic 'hotspot'. It is concluded that the diagnostic delay of the osteoid osteoma can be shortened when bone scintigraphy is performed more often and at an earlier stage in patients with unexplained bone pain or with a clinical history that leads to the suspicion of the presence of an osteoid osteoma.


Bladder diverticula and Menkes' syndrome.

Multiple unusual diverticula of the bladder were observed in 3 of 4 children with Menkes' syndrome. This abnormality of the bladder in children with the kiky hair syndrome has only recently been recognized. The diverticula are best visualized on cystographic studies. The clinical manifestation which led to roentgen evaluation of the urinary tract in the 3 children was urinary tract infection or urine retention. Though the etiology of these diverticula is unknown, evidence is presented to suggest that they are acquired.


Electron therapy of intraorbital tumors.

The authors describe a modification of a previously reported method of treating intraorbital tumors using multiple electron beams. An adjustable metal shield is inserted in the electron tube to protect the lens. The three-dimensional dose distribution was determined by film measurements and the film density measured with an RFA-1 densitometer on line with a computer. The density values were stored in a three-dimensional matrix. Different planes in the matrix can be selected for isodose plotting.


Physical aspects of electron-beam arc therapy.

The effect of different parameters on dose distribution in electron-beam arc therapy was studied in order to develop a technique for routine clinical use. A special diaphragm was designed to facilitate telecentric rotation. Dosimetry was performed with an ion chamber, film, and LiF powder in cylindrical polystyrene phantoms and an Alderson Rando phantom. Dose distributions were evaluated with regard to dose homogeneity, and a method of sharpening the dose fall-off near the ends of the arc was proposed. Criteria for selection of isocenter depth and field size were developed. Methods of dose calculation, calibration, and treatment planning are discussed.


Patterns of care given migrant workers in Utah by private physicians and clinics.

This comparison of the care given migrant workers in Utah by private physicians with that provided  by clinics demonstrates that clinics can provide more services and meet more of their needs. For a population group in need of an organization that can function specifically for them, the clinic offers many advantages. The clinic's role can also be expanded to become a focal point in the community for a comprehensive health care program for the disadvantaged. Although the cost of such a program may exceed the cost of traditional curative care from individual private physicians, the potential gains make it worth attempting. If long-term health is valued above short-term palliation, then the clinic would appear to be the best method of achieving this goal.


Gonorrhea screening in family planning clinics when should it become selctive?

Routine screening of females for gonococcal infection has become common in many clinic settings, particularly in public family planning clinics. The results of such routine screening in one large family planning program operated by the Seattle-King County Department of Public Health was examined. From 1973 to 1975 a trend toward decreasing rates of positivity for gonorrhea was observed. Use of computer information on the population being served by the program and a review of individual patient's charts enabled identification of certain high-yield subpopulations, including blacks, welfare recipients, new patients over age 19, and new patients who were not using any contraception when first screened. The cost of detecting a case of gonorrhea through screening was related to the positivity rate with the demonstration of a very high cost per case found when the positivity rate is less than 1 percent. Consideration should be given to identifying high and low-yield subpopulations for gonorrhea screening in large family planning programs so that, as cost considerations demand, funds now used for routine gonorrhea screening may be used instead for selective screening and provision of family planning services to high-yield groups.


Neurohistological observations on the tongue of the tufted capuchin, Cebus apella Linnaeus, 1758.

Neurohistological observations of the tongues of the adult monkeys Cebus apella are described. It was noted that the Cebus tongue presents few vallate papilae situated mainly in the posterior and lateral parts; fungi and filiforms are spread all over the dorsal surface. Histologically there was evidence that numerous nerve fibres of variable size come from the deep layers of the tongue to the surface structure. In many regions they constitute plexuses, other cross the muscular and glandular layers, going to the epithelial layer of the tongue's mucosa. The vallate and fungiform papillae are supplied with abundant nerve fibres which terminate free and are furnished with many taste buds. The epithelium and surrounding connective tissue is innervated by the fibres with free or ramified endings. The muscular layer shows muscle fibres distributed in all directions and the presence of motor end plates and nerve fibres is evident.


Effects of single and repeated cigarette smoke-exposures on the activities of aryl hydrocarbon hydroxylase, epoxide hydratase and UDP glucuronosyltransferase in rat lung, kidney and small intestinal mucosa.

A single exposure to cigarette smoke for one hour decreased the pulmonary microsomal epoxide hydratase activity in rats. A more rapid decrease was seen after 5 consecutive exposures, one hour daily. Meanwhile, the activity of pulmonary aryl hydrocarbon hydroxylase (AHH) increased several fold. In small intestinal mucosa the activities of AHH and epoxide hydratase were enhanced both by single and repeated cigarette smoke-exposures. In kidney the activity of AHH increased, whereas neither that of epoxide hydratase nor of UDP glucuronosyltransferase changed. In small intestinal mucosa the activity of UDP glucuronosyltransferase increased after repeated smoke-exposures, but in lung no clear change in the UDP glucuronosyltransferase activity was detected.


Modification of superoxide dismutase in rat mammary carcinoma.

In female Sprague Dawley rats, the tissue protein is homogeneously distributed and significantly increased in 7,12-dimethylbenz[a]anthracene-initiated mammary carcinoma. At the centre and margin of the carcinoma, the concentration of superoxide dismutase is 54 +/- 10 and 117 +/- 38 microgram/g, respectively, while in the tumour as a whole it is 104 +/- 32 microgram/g. The latter value is not significantly different from 113 +/- 35 microgram/g, the enzyme concentration in mammary tissue from lactating rats. Exposure of the tumour-bearing rats to hyperoxia does not increase the tumour protein but raises the enzyme concentration at the centre and margin of the carcinoma to 162 +/- 73 and 286 +/- 103 microgram/g, respectively.


The effect of phenylethanolamine n-methyltransferase concentration and species difference on the inhibitory potency of SK&F 64139.

We have found that the potency of SK&F 64139 in inhibiting rabbit adrenal phenylethanolamine N-methyltransferase (PNMT) is a function of protein concentration when high concentrations of the latter are employed. At lower enzyme levels, however, the degree of inhibition produced by the drug becomes independent of PNMT, allowing for the proper calculation of an inhibition constant. The Ki for the compound under these circumstances was 3 nM. Inhibitor dissociation constants within the same order of magnitude were subsequently obtained using the adrenal enzyme obtained from the rat, cow, dog, human and squirrel monkey. These data provide evidence that the PNMT receptor sites for SK&F 64139 do not differ substantially from species to species and suggest the general utility of this drug as an inhibitor of adrenal epinephrine biosynthesis.


The effect of Escherichia coli endotoxin on plasma histaminase activity in the domestic fowl and the involvement of caeruloplasmin.

The injection of four-to nine-week-old fowls with Escherichia coli O111:B4 endotoxin (0-1 and 1-0 mg/kg) produced a two to eight fold rise in the histaminase activity of the plasma 24 h afterwards. In some cases this increase was still detectable after 48 h. This activity was strongly correlated with the p-phenylenediamine oxidase activity of caeruloplasmin. Electrophoretic studies with 7-5 per cent polyacrylamide gels indicated that fowl caeruloplasmin also was histaminase and putrescinase activity and that the release of this protein from the liver by endotoxin is largely responsible for the increase in the activity of the plasma. In untreated fowls this activity was lower than published values for several mammals and does not explain the relative resistance of the fowl to the acute effects of endotoxins and large doses of histamine.


The influence of atropine and cromolyn on human bronchial hyperreactivity to aerosolized prostaglandin F2 alpha.

The mechanism of prostaglandin F2 alpha(PGF2alpha)-induced airway constriction was explored by determining the influence of atropine and cromolyn on the bronchoconstrictive properties of PGF2alpha. Increasing doses of aerosolized PGF2alpha were given (150, 300, 600, 1200 microgram) and the response of subjects was determined by measurements of spirometry, specific airway conductance (SGaw), and closing volumes. In normal subjects, PGF2alpha induced small but significant decreases of SGaw and spirometric parameters (FVC, FEV1), whereas there was no effect on the closing volumes. In contrast, in asthmatics, PGF2 alpha induced large decreases of SGaw and spirometric parameters. Asthmatics experienced severe and prolonged shortness of breath and wheezing, whereas normal controls experienced neither. Neither atropine nor atropine plus cromolyn was capable of preventing or substantially reversing the PGF2alpha-induced symptoms and airway constriction. The data suggest that reflex bronchoconstriction via irritant receptors is not a major mechanism of PGF2alpha-induced airway constriction. Although a minor vagally mediated reflex component may participate in the PGF2alpha-induced bronchoconstriction, it is masked by an overwhelming non-reflex mechanism that is probably a direct constricting effect of airways smooth muscle that is exquisitely sensitive to PGF2alpha.


Increased potassium permeability by calcium in hypochromic red blood cells.

The red blood cell (RBC) content of Na+ and K+ were measured both on fresh cells from normal, heterozygous beta-thalassaemic and iron-deficiency-anaemic subjects, and on the same cells incubated for 24 h, at 37 degrees C, either in presence or in absence of Calcium (Ca2+). Ca2+ did not increase membrane permeability to Na+, but increased the K+ loss, both from normal cells and to a greater degree much more from hypochromic cells. Glucose largely prevented the K+ loss from hypochromic cells incubated either in absence or in presence of Ca2+, probably maintaining an adequate level of ATP during the incubation. EDTA only partially decreased the permeability to K+ in hypochromic cells incubated for 24 h at 37 degrees C, possibly removing Ca2+ bound to the cell membrane. The results suggest that Ca2+ does not represent the primary cause of K+ leak in hypochromic cells, but it is able to enhance a pre-existing peculiar abnormality of the cell membrane when the ATP level slows down.


High-resolution soft x-ray microscopy.

X-ray micrographs of biological materials have been obtained with a resolution better than 100 angstroms by using x-ray resist as the recording medium. A high-resolution scanning electron microscope with a short-focal-length final lens, operating in the "low-loss" mode, is used to make the smallest features in the x-ray replica visible.


An effective immunization of experimental monkeys against a human malaria parasite, Plasmodium falciparum.

This is the first report of successful immunization of experimental monkeys against a human malaria parasite, Plasmodium falciparum. Of the five owl monkeys (Aotus trivirgatus) used in this pilot study, two served as controls and the other three were immunized with P. falciparum antigen consisting primarily of mature segmenters containing fully developed merozoites. Two injections of antigen emulsified with Freund's complete adjuvant were administered intramuscularly 3 weeks apart. Three weeks after the second vaccination, all monkeys were challenged with the homologous strain of P. falciparum. The control monkeys died with high levels of parasitemia within 2 weeks of challenge. The three immunized monkeys survived and showed strong protection against P. falciparum. These results are encouraging for the possible future development of an effective vaccine against human malaria.


Polychlorinated biphenyls: penetration into the deep ocean by zooplankton fecal pellet transport.

High concentrations of polychlorinated biphenyls (PCB's) were found in fecal pellets from natural populations of euphausiids collected in the Ligurian Sea. Since biogenic particulate products, especially fecal pellets, are known to sink rapidly and intact to the ocean bottom, the transport of PCB's by such sinking particles could be an important mechanism which contributes to the penetration of PCB's into the deep sea.


Bacteriophages in live virus vaccines: lack of evidence for effects on the genome of rhesus monkeys.

Four juvenile rhesus monkeys were inoculated with 10(12) plaque-forming units of the bacteriophage phiV1 isolated from live virus vaccines. After phiV1 had been cleared from the blood, DNA's were isolated from the livers and kidneys and analyzed for the presence of bacteriophage by plaque assays, and for the presence of phiV1 DNA by DNA-DNA reassociation kinetics. No evidence was found for persistence of the bacteriophage or for replication of the phage genome in these rhesus monkeys.


Erythrocyte carbonic anhydrase I: inherited deficiency in humans.

The virtually complete absence of erythrocyte carbonic anhydrase I is reported in three members of a family from the Greek island of Icaria. Two members with moderately reduced levels are believed to be heterozygous for the deficiency. There are no obvious hematological or renal consequences of the severe deficiency state.


Temporal control of urate oxidase activity in Drosophila: evidence of an autonomous timer in malpighian tubules.

The appearance of urate oxidase activity in the Malpighian tubules of Drosophlia melanogaster is synchronized with the time of emergence of the imago from the puparium. A developmental clock within the Malpighian tubules specifies the time of appearances of urate oxidase activity.


Visual sensitivity: significant within-species variations in a nonhuman primate.

Among squirrel monkeys (Saimiri sciureus) there are significant sex-related differences in visual sensitivity. As measured behaviorally in an increment-thershold task, a sample of males was found to be substantially less sensitive to long-wavelength (640-nanometer) light than a group of females tested in the same way, although the two groups showed no significant differences in sensitivity to a middle-wavelength (540-nanometer) light. The two group also differed on a test designed to measure the effects of chromatic adaptation.


Diabetes mellitus in adolescents: a comprehensive approach to outpatient care.

A comprehensive approach to care of adolescents with diabetes mellitus requires knowledge of the unique characteristics of juvenile diabetes during this development period, appropriate medical goals, and awareness of the numerous psychologic and social problems encountered. Involvement of other health professionals is frequently needed. Successful adjustment of the adolescent to having diabetes includes absence of "maladaptive" coping mechanisms, realistic future goals, and acceptance of responsibility for self-care.


Massive gastrointestinal bleeding and perforation of a duodenal diverticulum with coexisting pancreatitis.

A case of perforation and bleeding from a diverticulum of the second portion of the duodenum in a patient with recurrent pancreatitis is presented. Upper gastrointestinal roentgenogram revealed an abnormal tract and retroperitoneal air arising from the diverticulum. The fistulous tract communicated with pancreas. Bleeding was due to erosion of the wall of the pancreaticoduodenal artery. Extensive bleeding should suggest involvement of blood vessel.


Clinical considerations of the ratio of myocardial oxygen demand to available supply.

Myocardial oxygen demand is the relationship between the inherent needs of the heart and the available oxygenated blood reaching the myocardial tissue. The system is controlled by two different, yet not wholly uncomplementary, mechanisms. The first, coronary blood flow, appears to be regulated primarily by tissue oxygen tension. The second, the determinants of myocardial oxygen consumption, is controlled more by the heart's mechanical performance than the tissue oxygen tension. Currently available antianginal drugs and physical training affect these two mechanisms and may alter angina pectoris.


Urethritis in white men--a microbiological appraisal.

The incidence of infections with Neisseria gonorrhoeae, Chlamydia trachomatis and mycoplasmas has been assessed in White men with urethritis who were attending a Johannesburg clinic for sexually transmitted diseases. Infection with N. gonorrhoeae was demonstrated in 54% of 212 patients with urethritis. C. trachomatis was isolated from 37% of patients with non-gonococcal urethritis, and from 25% with proven gonococcal infection. Although T-mycoplasmas were isolated significantly more often from patients with urethritis (41%) than from controls (23%) (P less than 0,05) their role in the aetiology of urethritis is uncertain.


Evaluation of surgical therapy by cost-benefit analysis.

Cost-benefit analysis (CBA) is described briefly, emphasizing the contribution this technique can make in justifying health care programs vying with other costly public programs for support. Costs and benefits of two surgical diagnostic techniques are outlined briefly as illustrations of the analysis. The first analyzes routine intraoperative cholangiography indicating the slight benefits that accrue from its use in terms of mortality and hospital expense. A more complicated example is an analysis of a policy of universal annual uterine cervical smears in asymptomatic women for cancer prevention where, granted the assumptions of the model, the costs minus the benefits of the program are estimated to be $565,000/beneficiary/year. The average beneficiary will gain 22 years of life at an average cost/year of about $26,000. The two examples are presented primarily as illustrations of a methodology which is being applied widely in medicine and public policy planning. Second, the marshalling of facts in CBA of a policy of annual uterine smears is of interest to those concerned with the justification of this screening procedure.


Continual catheter administration of an elemental diet in infants and children.

Elemental diet offers a safe, simple, widely applicable technique for providing nutritional support in infants and children, thus protecting them against the hazards of malnutrition. Continual catheter administration of elemental diet provides an avenue of nutritional support free of many of the complications associated with total parenteral nutrition. Although mechanical and metabolic complications were avoided by rigid protocol compliance in our group of over 150 patients, further metabolic studies may suggest minor compositional changes providing a more optimal diet for premature and newborn infants.


Comparative studies of coagulative and fibrinolytic faculties between the Japanese monkey and the human.

In the present study, the coagulative and the fibrinolytic faculties of the Japanese monkey (Macaca fuscata) were investigated and compared with those of the human. Regarding the coagulative faculty, the plasmic fibrinogen level, prothrombin times, and partial thromboplastin times of the Japanese monkey were similar to those of the human, but the antithrombin level in the monkey was higher than that in the human. Regarding the fibrinolytic faculty, the simian plasminogen level was significantly higher than the human, but the simian, plasma clot and the euglobulin clot lysis times were extremely prolonged, which means that the Japanese monkey has a great fibrinolytic potential, but that it is difficult to activate. In addition, the human and simian reactivities of plasminogen to streptokinase were also investigated and compared.


Binding of anti-actin autoantibodies to platelets.

Normal platelets incubated with anti-actin autoantibodies (AAA) (from the serum of patients with chronic aggressive hepatitis) do not show binding of these antibodies as seen by indirect immunofluorescence. AAA serum does not inhibit thrombin-induced clot retraction, despite the binding of the antibodies to platelets in the clot. Similarly, AAA serum does not affect "reversible" or "irreversible" aggregation (induced by ADP, collagen or epinephrine), despite the binding of the antibodies to platelet actin under such circumstances. AAA also bind to platelets when aggregation is inhibited by EDTA. The incubation of "reversibly" aggregated platelet with AAA results in a small but definite binding of AAA to platelets. These findings suggest that during "irreversible" and/or "reversible" aggregation, changes take place at the surface of platelets which expose the antigen at the surface of the cell.


[Chemotherapy of the ovarian carcinoma (author's transl)].

Ovarian carcinomas are highly sensitive to chemotherapy. The alkylating agents were most extensively investigated. With these drugs remissions can be obtained in about 50% of the patients. Some early results seem to show a higher response rate and a longer duration of remission after combination chemotherapy. In ovarian carcinoma it has to be the aim of the chemotherapy to obtain a complete remission. The indications for chemotherapy are not yet well defined. Treatment is definitely indicated in stage IV (FIGO) or in recurrent disease after radiotherapy. This treatment has to be given as a long-term therapy over a long period of time. In stage III and II b disease a combined treatment plan has to be developed by the radio- and chemotherapist. At the present time no data are available which prove or disprove the value of an adjuvant chemotherapy in the early stages of ovarian carcinoma. Remembering the somewhat promising results of adjuvant chemotherapy in breast cancer, it is conceivable that prophylactic chemotherapy will prove to be indicated in early stages of ovarian carcinoma.


On a simple method for routine check of the constancy of radiation quality of bremsstrahlung emitted by therapeutic particle accelerators.

The constancy of radiation quality of therapeutically employed particle accelerators has to be checked at weekly intervals. Any change in radiation quality may have considerable therapeutic effects owing to its influence on dose distribution. It can be recommended to make measurements instead of, or in addition to, the axial reference-point measurement at 5 and 15 cm depth in the phantom, at 5 cm depth in the beam axis and at a reference-point about 1 cm within the geometric edge of the field, for checking the constancy of the radiation quality of bremsstrahlung. Only then, if routine checks carried out for the axial and the lateral reference-point dose ratios do not show any deviations greater than e.g. +/- 2%, radiation quality is deemed to have remained sufficiently constant for radiotherapeutical applications.


[Neurofibroma--neurofibromatosis--neurofibrosarcoma].

The author presents 14 patients with the gradations "neurofibroma--neurofibromatosis-neurofibrosarcoma". The great variability of forms of this disease ist emphasized. Apart from pure soft-tissue tumours, primary and secondary osseous changes were demonstrated in 4 patients. Intra-oral neurofibromas were seen in 5 cases. In 3 of these, the tongue was involved. Suggestions are given for the treatment of this clinical picture.


Adverse reactions to isoniazid on ingestion of fish with a high histamine content.

On eating preparations of a particular variety of fish, the skipjack (bonito), patients with tuberculosis on isoniazid repeatedly developed symptoms very similar to those of histamine poisoning. Skipjack was found to contain probably the highest concentration of histamine reported in fish. Isoniazid is a potent inhibitor of histaminase which normally plays an important role in the metabolism of histamine in the body. It is suggested that the symptoms seen in these patients were, in fact, due to histamine. In these circumstances the high histamine content of skipjack and the interference by isoniazid with the metabolism of the amine presumably play complementary roles in the production of histamine poisoning; each of these factors by itself is apparently inadequate to produce such intoxication. An analysis of the symptoms manifested by 21 patients is presented.


Occult tuberculous infection in children.

Three hundred and fifty New Zealand children with occult tuberculous infection are reviewed. Ninety four had received BCG vaccine previously. Three hundred and forty were admitted to hospital and 3 gastric aspirations were obtained from each child and cultured for tubercle bacilli. Mycobacterium tuberculosis was isolated from 1 or more aspirates in 29 (8.5%) of the children. Excluding those who had received BCG the isolation rate was 10.9%. Mycobacterium bovis was not cultured from any child. X-rays of the chest which were initially normal showed calcification after 2 to 5 years in 73 (20.8%) cases. The 350 children were treated with 2 drugs, during the early years isoniazid and PAS and in the past 3 years isoniazid and rifampicin in standard dosage for either 12 or 18 months. The reasons for treating these children are discussed.


Blood group alloantibodies: an assessment of some laboratory practices.

Over a 20-year period, the number of blood donors and transfusion recipients previously immunized by blood group antigens was determined in a large blood center. During that period, the proportion of patients found to have anti-D declined, while those with other antibodies in the Rh system, as well as in the Kell, Duffy, and Kidd systems, increased sharply. As expected, the rate of sensitization was much lower among blood donors than among recipients. In both groups, sensitized females greatly outnumbered sensitized males. Some of the findings summarized here raise questions about current practices in transfusion laboratories and emphasize the responsibilities of blood bank professionals to donors as well as to patients.


Transurethral fulguration of bladder diverticulum: new procedure.

Transurethral fulguration of bladder diverticulum (TUFD) is a new and simple procedure. Since July, 1975, 17 patients have had TUFD at the time of transurethral resection of the prostate. Cystograms have been obtained from one week to twelve months after surgery. The diverticulum has shrunk in 9 cases and has totally disappeared in 5; follow-up is incomplete in 3 cases.


Bone marrow amyloid in patients with M-component.

Amyloid substance was looked for in bone marrow aspirates of 28 patients presenting an M-component, in association with different illnesses (plasmocytoma, chronic lymphatic leukemia, lymphocytic lymphoma, "benign monoclonal gammapathy" and liver cirrhosis). Amyloid was detected in 12 out of 20 patients with plasmocytoma (60%) and in 3 out of 8 patients with other illnesses (37.5%); it was found in 9 out of 13 cases (69.2%) presenting exclusive light chain production and in 6 out of 15 cases (40%) with a monoclonal complete Ig. Lambda type light chain, either free or Ig-bound, was slightly more often (6 cases out of 10, 60%) associated with amyloidosis than was K (9 cases out of 17, 52.9%). Bone marrow appeared to be more frequently involved than other sites considered elective such as rectal mucosa. Amyloid appeared as an intensively fluorescent substance present intercellularly in areas of variable number and size.


Mitochondrial calcium during liver carcinogenesis due to thioacetamide and 4-dimethylaminoazobenzene.

In a series of experiments the prolonged feeding of rats with thioacetamide and 4-dimethylaminoazobenzene provoked an increase in mitochondrial calcium. It seems likely that this continuous mitochondrial overloading with Ca2+ is related to metabolic and functional changes of the liver cell leading to a neoplastic transformation. The drastic changes in cell membrane permeability of cholangiocarcinoma tumor cells, reflected by an increased concentration of extracellular cations (calcium and sodium), while the intracellular cations tended to decrease, indicate that the mitochondrial function of specification of cell membrane characteristics is possibly impaired by that calcification.


Further studies on the ridge at the internal edge of the cataract incision.

A pathologic and experimental study of the etiology and morphology of the ridge, visible gonioscopically in the region of the internal lips of the cataract incision during and after the cataract operation, is described. The ridge observed clinically cannot be reproduced in human eye-banks eyes but can be reproduced in vivo in the eye of the owl monkey. Histopathology and ultramicroscopic studies of these experimental eyes, together with evidence derived from histopathologic slides of postmortem human eyes, suggest that the ridge is probably the result of immediate edematous swelling of the deeper layers of the corneal stroma after the incision transects corneal endothelium and the Descemet membrane. While internal wound lip malapposition may be a contributing factor to formation of the ridge, it is probably not an essential component. The ridge is not caused by the incision-closing sutures for it is already present prior to suturing of the wound. The role in ridge formation of mechanical stress alterations produced immediately by the incision is considered but is not known.


Trabecular damage due to blunt anterior segment injury and its relationship to traumatic glaucoma.

Gonioscopy, performed within 48 hours of traumatic hyphema, revealed not only angle recession but also a high incidence of damage to the trabecular meshwork and the Schlemm canal. These trabecular lesions tend to scar and become much more difficult to recognize over the ensuing weeks. Large tears into the ciliary body (angle recession) also had a tendency to "close." Using a specially calibrated BB gun hyphema was induced in rhesus monkeys. Trabecular tears were recognized by gonioscopic and histologic examination. Impaired outflow facility developed between 10 and 30 days after injury in the one surviving animal studied to date. In patients developing open-angle glaucoma years after trauma, evidence of past trabecular injury was seen by gonioscopy in addition to the obvious ciliary body tears (angle recession). The "normal" fellow eye had early glaucoma, ocular hypertension, or "high normal" intraocular pressure. The evidence presented supports the hypothesis that traumatic glaucoma is the result of trabecular meshwork injury from the original trauma and the rapid scarring that results, in combination with an underlying predisposition for the development of primary open-angle glaucoma and the passage of time.


The tranfer of Brucella abortus antibodies from dam to calf.

The higher sensitivity of the ABGT (Coombs Test) makes it the most useful test for comparison of total specific immunoglobulins for Brucella abortus in different secretions. Using it in the present study it was found that in 85 cows the mean selective concentration of immunoglobulins in colostrum was six to eight fold, whether the cows were infected or not. In the non-infected group calves acquired mean levels of immunoglobulins of about one third those in colostrum whereas in the infected group this ratio reduced to about one seventh. There were wide individual variations. However, mean values indicate that in both groups the calf acquires a level of antibodies up to twice the level of the dam's pre-partum serum, again with individual wide variations. Titres to the SAT and CFT are also given for all animals.


Relation of lipids to the action of streptomycin on Bacillus subtilis and Escherichia coli and griseofulvin and fungizone on Aspergillus niger.

An attempt was made to reveal the relation between the lipid content and components of B. subtilis and E. coli and the action of streptomycin, and those of A. niger and the action of griseofulvin and fungizone (Amphotericin B). Total lipids were extracted in CO2 atmosphere, dried, and weighed. Lipid components were analyzed by thin-layer chromatography. Complements to the growth medium of A. niger with extracted total lipids and phospholipids were made to verify the obtained results. It has been found that the action of streptomycin and griseofulvin was not correlated with lipids. On the other hand, fungizone action was manifested by the decrease in total lipids, free sterols, sterol esters, and triglycerides. Supplementation studies gave evidence of the role of total lipids and phospholipids in protecting A. niger cells against fungizone. Supplementation of 1 g of phospholipid per litre medium raised the M.I.D. of fungizone from 2.5 up to 25 microgram/ml. It was suggested to keep the fat level controlled at a minimum if it is required to increase fungizone activity.


Effect of media composition on the penicillin production.

The conventional penicillin fermentation medium is composed of corn steep liquor, glucose, lactose, minerals, oil, and precursor. The penicillin activity was not affected, due to the addition of carbonate 0-1% or whale oil 0.5% instead of 1%. Also the omission of cupric, magnesium, manganese, zinc sulphates, and acetic acid did not affect the penicillin activity, while the omission of ammonium nitrate and potassium dihydrogen phosphate decreased the penicillin activity in the medium. The penicillin activity of a medium containing 2% calcium superphosphate was higher than that of the control medium, containing 0.4% potassium dihydrogen phosphate and 1% calcium carbonate. Instead of adding the precursor twice, after 0 and 48 hrs, the addition of phenylacetamide in the amount of 0.2%, at the start, did not affect the activity, while addition of phenylacetic acid (0.2%), at the start, decreased the penicillin activity. The omission of the precursors in the medium decreased the penicillin activity measured microbiologically, however, 6-aminopenicillanic acid content was relatively higher as compared with that of the control medium, containing precursor. These results were confirmed, using iodometric assay and paper chromatographic analysis.


Polyphosphate-glucose phosphotransferase. Purification of Mycobacterium tuberculosis H37Ra enzyme to apparent homogeneity.

1. The enzyme (EC 2.7.1.63) was isolated from glucose-grown M. tuberculosis H37Ra; during the purification procedure, 2-mercaptoethanol, glucose, EDTA and NaCl served as protecting agents. 2. The enzyme was purified about 600-fold. The preparation was homogeneous on polyacrylamide-gel electrophoresis and gave one precipitin line in double immunodiffusion test. Molecular weight of the enzyme determined by Sephadex G-100 filtration was about 118 000. 3. The enzyme preparation showed also glucokinase activity with ATP.


[Anatomy, physiology and pathophysiology of the ankle].

Ankle lesions are problematic because of their frequency its anatomy and physiology are complex, disturbances of its functions are caused by the smallest c change of the anatomic relations. It is not able to put the fracture into line by the settled therapy; so these lesions are very frequent in our operative programme. the most important are the lateral maleolus -- its ligamentary part and the tibiofibular syndesmosis. The special emphasis is given to physiology and pathology of the ankle, the Weber's pathoanatomic classification of the ankle lesions is also given in this article.


Effects of intravenous glucose and aminoacids on gastric secretion.

Five healthy females were submited to parenteral nutrition with aminoacids and glucose solution and the acidity and volume of gastric juice were studied. We could find no difference in the obtained values at the various phases, even after the administration of betazole. From this we can conclude that the infusion of aminoacids and glucose does not alter the pattern of gastric secretion.


The need for fentanyl supplementation of N2O-O2 relaxant anaesthesia in chronic alcoholics.

In order to find out how the need for analgesic supplementation during N2O-O2-relaxant anaesthesia is affected by chronic alcohol consumption, 82 patients with various known alcohol habits were anaesthetized for gastric or biliary surgery. Muscular relaxation was kept constant with the aid of a peripheral neurostimulator, and fentanyl was given in increments of 0.05-0.1 mg for nociceptive symptoms during the anaesthesia. For induction, alcoholics (annual consumption above 151 pure alcohol) needed significantly more thiopental/kg body weight than social drinkers (1--151 annually) or non-alcoholics (less than 11 annually), and excitative symptoms were more frequent in alcoholics. A positive correlation was found between fentanyl supplementation and alcohol consumption (r = 0.41), non-alcoholics requiring on average 3.8 microng/kg/h of fentanyl, as compared with 6.4 microng/kg/h in alcoholics. This correlation was clearer than that found previously under similar conditions by the authors between halothane supplementation and alcohol consumption (r = 0.20). In both studies the correlation was partly due to the higher incidence of gastric surgery among alcoholics, since gastric surgery itself requires more supplementation. An analysis of the different symptoms pointing to the need for fentanyl supplementation revealed that the simultaneous occurrence of several symptoms and the prevalence of motor responses were more common in alcoholics. In one patient halothane had to be used as well. In other patients no special difficulties were observed, and none of the patients reported dreams or recollections. The results suggest that during N2O-O2-relaxant anaesthesia the demand for fentanyl supplementation is increased by about 70% in chronic alcoholics with a mean annual consumption of 311 pure alcohol.


The behaviour of microsomal mono-electron carriers in adult and fetal liver and in placenta throughout pregnancy.

The activities and contents of microsomal mono-electron carriers (NADPH-cytochrome c reductase, NADH-cytochrome b5 reductase, cytochrome P-450 and cytochrome b5) in the liver of 160 pregnant rabbits and their response to phenobarbital (PB) administration were found to be different to that of non pregnant animals and to vary depending on the period of gestation. In fetal liver and in placenta the activities and contents of mixed function oxidase system enzymes are very low and increase from the mid-gestation up to the term of pregnancy. PB has either effect or decreases the enzyme levels. The variations of enzyme content and activity in maternal liver and the different response to PB are related to the hormonal modifications of pregnancy. The behaviour of mono-electron carriers in fetal liver can be related to the process of maturation of this organ. The effect of PB can be due to the interference of the drug with steroid metabolism. The behaviour of mixed function oxidase system enzymes in placenta can be related to the processes of maturation and ageing of organ.


Presence of anti-c in the serum of 42 women giving birth to c positive babies: serological and clinical findings.

During routine ante-natal testing during the period 1953-73 anti-c was found in the serum of 63 women. Twenty-four of them had received blood transfusion previously and of these 22 were multigravidae. In 39 women pregnancies alone were responsible for the immunization. The anti-c titres of the 42 women giving birth to c positive babies showed that the probability of developing haemolytic disease increases with higher titres. But low titres by no means exclude the existence of such disease. Among the 42 c positive babies 32 had a positive direct antiglobulin test. Some of the affected infants had a serious degree of haemolytic disease.


Structural similarities between a protein extracted from normal human tissues and a component of amyloid fibrils.

Comparative immunologic and chemical studies of crude or fractionated amyloid fibrils and materials obtained from corresponding normal tissues have been performed. Materials from the amyloidotic and normal tissues were subjected to identical methods of extraction, chemical treatment and protein fractionation. Antigenic similarities between crude amyloid fibrils and corresponding normal tissue extracts were observed, however, a considerably larger concentration of the latter antigens was needed to obtain immunologic reactivity in double diffusion in gel. Striking similarities were observed when the amino acid composition of a high molecular weight subcomponent of amyloid fibrils was compared with that of normal tissue extracts. Crude, intact amyloid fibrils were highly effective in absorbing Congo-red while the ability to absorb Congo-red was by far less if the high molecular weight subcomponent of amyloid fibrils as well as the corresponding normal tissue extracts were used. The high molecular weight subcomponent of amyloid, which seems to be an integral part of the amyloid fibrils, most probably is a protein derived from normal tissue.


Recent census changes in state hospitals: a look below the surface.

The rate at which long term patients are being discharged from the state hospitals in Connecticut has decreased sharply in recent years. This is only one of several trends that have major implications for program planning and evaluation.


The use of echocardiography in determination of reversible posterior wall asynergy.

Recent studies have indicated that nitroglycerin can be delineate potentially reversible asynergic zones depicted ventriculographically. To assess the ability of the echocardiogram to detect reversible asynergy, posterior wall motion was assessed in 19 patients both echocardiographically and ventriculographically before and after nitroglycerin. Thirteen of the 19 patients demonstrated abnormal posterior wall motion both by echocardiography and ventriculography while six were normal by both techniques. In 4 of the 13 asynergic areas, posterior wall excursion improved following nitroglycerin (from 0.99 +/- .07 to 1.30 +/- .07 cm. by echocarciography (p less than .025) with a corresponding improvement in hemiaxis shortening from 12.0 +/- 6.1 per cent to 29.0 +/- 6.7 per cent (p less than .02). In contrast, in nine patients in whom inferior segment hemiaxis shortening was unchanged following nitroglycerin, posterior wall excursion by echocardiography was similarly not improved (1.01 +/- .03 cm. before and 1.02 +/- .03 cm. after nitroglycerin). The effect of nitroglycerin on posterior wall velocity paralleled changes in posterior excursion. The six patients with initially normal posterior excursion showed no significant change by either echocardiography or ventriculography following nitroglycerin. Thus, the echocardiogram is of considerable value in detecting both the presence and potential for improvement of asynergic posterior wall segments.


Placental transfer of glucose-amino acid complexes present in parenteral solutions.

Intravenous infusion of glucose-amino acid complexes, formed during heat sterilization of mixtures of glucose and amino acids or protein hydrolysates, has been associated with mild dehydration in infants, and with excessive trace metal ion excretion in both infants and adults. When parenteral solutions containing these glucose-amino acid complexes were infused into pregnant rhesus monkeys, the compounds accumlated in the maternal plasma and were transported to the fetal circulation. Although all of the compounds studied crossed the placenta, fetal levels were consistently lower than maternal levels. Amniotic fluid concentrations of these compounds increased progressively with the length of maternal infusion, presumably through fetal urination into the amniotic sac. In animals infused with solutions not heat sterilized, levels of these compounds could not be detected in maternal plasma and urine, fetal plasma and urine, or in amniotic fluid. In view of possible toxicity of the glucose-amino acid complexes, parenteral solutions containing these compounds should probably be avoided in the intravenous nutrition of the pregnant woman.


Studies on the significance of hair root protein and DNA in protein-calorie malnutrition.

Hair root protein and DNA, serum nonessential amino acid/essential amino acid ratio, serum total protein, albumin, globulin and albumin/globulin ratio were estimated in children suffering from portein-calorie malnutrition (PCM) and the values compared to those obtained from healthy children. The data were presented in two ways: 1) classified as early malnutrition, marasmus, marasmic kwashiorkor, or kwasiorkor and the parameters compared 2) all the malnourished children were divided into four groups on the basis of percentage of body weight for age and the parameters compared. There was a progressive decrease in the content of hair root DNA and protein with the severity of PCM with these values decreasing to less than half of the normal values. In all types of PCM the serum albumin decreased significantly and the globulin increased while the total protein was altered only in the more severe stages. Differences in the serum consituents between groups were more pronounced when classified clinically than when grouped as percentage of normal body weight. Since hair root changes are progressive and of greater magnitude than those in the serum, hair root DNA and proteins might be useful chemical criteria in detectinc various stages of PCM, and further to help understand the pathogenesis of the condition.


Fe(III)-EDTA complex as iron fortification.

Fe(III)-EDTA as iron fortification presents several advantages over the other iron salts previously used including ferrous sulfate. This iron compound exchange completely with vegetable food iron in the lumen of the gut but with the characteristics that the absorption from both, extrinsic and intrinsic food iron, is higher than that expected from other iron salfs. The comparison between the iron absorption from Fe(III)-EDTA and ferrous sulfate as iron fortification indicates that the absorption form EDTA is about twice as high than that observed from ferrous sulfate. The data indicates that only 10 to 15 mg of iron as Fe(III)-EDTA as iron fortification would be necessary to prevent iron deficiency anemia in population relying their subsistence of vegetable food only and free of parastic infection producing blood loss.


The CAP blood bank comprehensive survey program--1975.

The 1975 CAP Comprehensive Blood Bank Survey Program showed that the ABO and Rh typings were again at an excellent level of performance. What few errors still occurred were at least partially explained by a study that showed that many of these errors were directly traceable to clerical mistakes; many, in fact, were due to a complete failure to submit an answer. Antibody detection was very good when the antibody was strong, but lower levels of performance were attained when the antibody was weak. Low performance was also achieved with a cold-reacting anti-I, but here the difficulty was found to be more a lack of agreement on terminology of the antibody rather than a failure to demonstrate it. A study was performed to see whether the participants that were late in sending in the answer sheets had a higher error level than those that were not, but no difference was found. Finally, the preliminary results regarding the accuracies of various methods of antibody screening are presented. Although there was a statistically significant difference in the results obtained with the different methods, the study does not involve enough antibodies at this time to be valid, and therefore it will be continued.


A civilian case of fatal meningococcemia due to Neisseria meningitidis, group Y.

The present report is that of a civilian episode of fatal, fulminant group Y meningococcemia in a previously healthy adolescent, who denied prior vaccination against group C meningococcus. The patient suffered abrupt onset of purpura, hypotension and cardiopulmonary arrest. A detailed clinical and pathologic report is included.


Gastric secretory and motility studies in chronic chagasic patients.

In Chagas' disease, the degeneration of the nerve cells of the intramural parasympathetic ganglia of the stomach causes a wide range of motor and secretory disturbances of the organ. To assess and to correlate the alterations of these two gastric functions, electromanometric and secretory studies were performed in 22 chagasic patients and in 12 control individuals. The gastric antrum electromanometric records were carried out in basal conditions and under the stimulation of methacholine chloride (Mecholyl). Gastric secretory studies were carried out in two sessions with a Kay's test: in the first, with the test alone; in the second, associated with bethanechol chloride (Urecholine). The chagasic patients were divided into two groups according to their gastric motor response to methacholine. It was concluded that the parasympathetic denervation in Chagas' disease changes both acid and pepsin secretions in the same direction but that as the disease worsens, the responsiveness of pepsin secretion to cholinergic action tends to disappear earlier than that of acid secretion.


Esophageal intramural pseudodiverticulosis.

Three cases of esophageal intramural pseudodiverticulosis (EIP) are described and the literature reviewed. We conclude that EIP is an inflammatory disease of unknown etiology characterized by dilatation of the esophageal submucosal glandular elements. The classic radiographic picture which is that of collar-button-shaped outpouchings projecting in a perpendicular fashion from the luminal surface is mainly related to dilatation in the glandular ductal system. It is usually diagnosed in the sixth and seventh decades, but all ages may be affected. Dysphagia is a very common but not universal symptom of the disease process. Approximately one third of these patients have diabetes mellitus. Strictures of the esophagus are frequently seen, and varying degrees of esophagitis may be manifest endoscopically. Esophageal motility disturbances are common and may be severe. Candida infestation with and without tissue invasion has been seen in a number of patients and should be searched for in all cases of EIP.


Evidence for preferential X-chromosome inactivation in a family with Fabry disease.

Severe clinical signs of Fabry disease were observed in four of eight heterozygous daughters of a male patient. Activities of alpha-galactosidase A in serum, white blood cells, and hair roots of the manifesting carriers were markedly lower than 50% of normal. These findings are not easy to interpret in terms of random X inactivation alone; several alternative models including nonrandom (preferential) X inactivation are discussed.


Compatibility of common additives in protein hydrolysate/dextrose solutions.

The compatibility of common additives in protein hydrolysate/dextrose solutions was studied. The additives included electrolytes (calcium gluconate, potassium phosphate and magnesium sulfate), vitamins (M.V.I., Solu B Forte, phytonadione, cyanocobalamin and folic acid), insulin and heparin sodium. Various concentrations of the admixtures were observed at intervals throughout a 24-hour period. Combinations which displayed no physical change were subjected to spectrophotometric analysis. Thin-layer chromatography was used to examine those mixtures which displayed a spectral change. The principal incompatibility problems are related to concentrations of calcium gluconate and potassium phosphate. The order of mixing affected the concentration tolerances. The vitamins, insulin, heparin and magnesium, in usual therapeutic concentrations, appeared to be compatible in the protein hydrolysate/dextrose solution.


Culture and treatment results in endometritis following elective abortion.

Endometrial culture and treatment results from 228 patients who developed endometritis following elective abortion were analyzed. The most common organisms isolated were group B beta hemolytic streptococci, Bacteroides, Neisseria gonorrhoeae, E. coli, and Staphylococcus aureus. In general, patients responded to treatment with penicillin or ampicillin, with the addition of an aminoglycoside for these requiring hospitalization. Curettage was an important adjunctive treatment for hospitalized patients and for some outpatients.


The effect of marihuana (delta-9-tetrahydrocannabinol) on the secretion of luteinizing hormone in the ovariectomized rhesus monkey.

Despite the widespread use of marihuana by large numbers of young adults in the reproductive years, little is known about the effects of this drug on reproductive function. information on the effect of the drug on the woman is particularly meager. The rhesus monkey provides an excellent animal model from which to generalize to man. While the primary purpose of the project is to determine the effect of long-term administration on the cycling female monkey, the initial studies were carried out in the ovariectomized monkey with resulting elevated gonadotropin levels under conditions of short-term administration of the drug. Marihuana causes a reversible depression in luteinizing hormone levels in the ovariectomized female rhesus monkey.


Unconjugated estriol and 15alpha-hydroxyestriol in complicated pregnancies.

Simultaneous determinations of unconjugated estriol and 15alpha-hydroxyestriol (E4) levels in maternal serum were studied serially to ascertain the relative usefulness of these estrogens as indicators of fetal welfare. Complicated pregnancies included 16 patients with pre-eclampsia and/or hypertension, six patients with severe Rh-isoimmunization, 12 patients with diabetes mellitus, of which four had vascular disease, three patients with fetal death in utero, and three twin pregnancies. Retrospective analysis failed to indicate a clinically useful role for serum E4 determinations in the evaluation of fetal welfare during high-risk pregnancies.


The lack of specificity of the sheep erythrocyte-T lymphocyte rosetting phenomenon.

One subpopulation of lymphocytes, thymus-derived (T) cells, is identified by its characteristic ability to form spontaneous rosettes with sheep erythrocytes (SRBC). However, the mechanism by which the rosettes form remains unknown. To gain more insight into the specificity of this phenomenon, the ability of SRBC to rosette with cells other thah lymphocytes was studied. All of the cell types utilized in this study (L cells, monkey liver cells, HeLa cells, and human liver, bladder, lung, parathyroid, and dermal fibroblasts), except neoplastic B lymphocytes, rosetted with SRBC. Viability was not a factor in the rosette formation. These findings suggest that the process of T lymphocyte-SRBC rosette formation is not due to a T cell-specific membrane receptor or antigen but may be due to a widely distributed basic substructure of the cell membrane.


Cardiorespiratory effects of Pseudomonas and E. coli endotoxins in the awake dog.

A comparison of the cardiovascular and respiratory effects of Pseudomonas aeruginosa and Escherichia coli endotoxins was investigated in the unanesthetized dog. Animals were anesthetized with halothane for placement of cardiovascular catheters and then allowed to awaken prior to collection of control data and experimentation. One group of 12 animals was given E. coli endotoxin (5 mg/kg), another group of 13 received Pseudomonas endotoxin (8 mg/kg). Variables were collected for 6 h after endotoxin injection. A third group of 13 animals serving as sham animals received no endotoxin. When major cardiovascular variables, such as arterial blood pressure, cardiac output, right atrial pressure, and left ventricular pressure and dP/dt were monitored, it was seen that the basic patterns of response to endotoxins were quite similar, with differences between groups being primarily quantitative. Analysis of respiratory data showed that animals receiving Pseudomonas developed an earlier respiratory response. Nevertheless, blood gas data were similar in the two groups.


Prolonged potentials in gastrointestinal muscles induced by calcium chelation.

When stomach muscles of skate, toad, or frog or intestinal muscle of cat are treated with Ca-free physiological solutions containing 2-5 mM EGTA or EDTA, spontaneous spikes and slow waves disappear reversibly. With continued treatment, depolarization of 25-30 mV from resting potentials of -65 mV occurs and rhythmic prolonged potentials of several seconds duration appear. They show rapid depolarization to near zero and rapid repolarization and they may continue for several hours. The prolonged potentials disappear when Na is replaced by Li, Tris, or choline. They are insensitive to TTX. The EGTA-induced waves are abolished by Mn, Co, La, verapamil, and D 600. After 10-15 min in 5 mM EGTA, voltage-current and abolition of anomalous rectification. It is concluded that when bound Ca is removed by a chelator, nonspecific reduction in resistance occurs and Na ions may enter rhythmically through channels normally used by Ca.


Excitation-contraction coupling in multiunit tracheal smooth muscle during metabolic depletion: induction of rhythmicity.

Multiunit canine tracheal smooth muscle responded to carbachol with graded depolarization and tonic contraction. The same concentration of carbachol, after metabolic depletion by substrate removal, produced rhythmic contractions and action potentials. Similar mechanical effects were also observed with acetylcholine or histamine. These effects were reversed by reintroducing glucose or beta-hydroxybutyrate, but not by 3-O-methylglucose, which is not metabolized; hence, the structural requirements for glucose, per se, or any osmotic effect were ruled out. Sensitivity to extracellular Ca2+ was increased. A Ca2+-influx blocker, D-600, in low concentration (2 X 10(-8) M) abolished the rhythmic contractions without affecting the tonic contraction. Progressive metabolic depletion in presence of carbachol led to fluctuations in membrane potential with a crest of depolarization and appearance of action potentials, each of which resulted in a small contraction. Many of the small contractions partially fused to form the major rhythmic contractions which appeared at a frequency of one per minute. Rhythmicity could not be produced by increasing extracellular K+ concentration (20-120 mM) in presence of atropine (13(-7) M), but instead a tonic contraction occurred. These results suggest changes in excitation-contraction coupling mechanism with agonists like acetylcholine, carbachol, or histamine during substrate deprivation.


Heart rate and oxygen uptake response to angiotensin in the squirrel monkey at 10 degrees C.

Unanesthetized squirrel monkeys exposed to an ambient temperature of 10 degrees C showed elevations in total body oxygen consumption (VO2), systemic arterial blood pressure (BP), and heart rate (hr) above values recorded at 28 degrees C. Further elevation of BP in the cold by intravenous infusion of phenylephrine (5-50 microgram/kg-min) was accompanied by reduction in both VO2 and HR, and the changes in VO2 were proportional to those in HR. When BP was raised by intravenous infusion of angiotensin (0.05-1.0 microgram/kg-min), large elevations in BP were again accompanied by reductions in HR and VO2. However, for equivalent elevations in BP, the depressions in both HR and VO2 were much smaller with angiotensin than they were with phenylephrine. Previous studies in this laboratory have demonstrated that in response to experimental elevation of BP, reflexes originating at the sinoaortic baroreceptors depress not only HR but also VO2. The present results suggest that angiotensin modulates baro-reflexive responses to elevation in BP. The reductions in HR and VO2 that ordinarily occur in response to baroreceptor stimulation may be modified by an action of angiotensin on the central nervous system.


Effects of isoproterenol on adrenergic constriction in vascular smooth muscle.

A series of isolated segments of carotid arteries from Dutch-belted, adult, male rabbits were studied with respect to their response to a beta receptor agonist. Segments of 3-cm length were mounted in a chamber with constant surrounding temperature and pressure and perfused at constant pressure. Inflow pressure, outflow pressure, and flow rate were measured, and values of resistance (R) were calculated. Subsequent to control R, each vessel was exposed to a vasoconstricting concentration of either norepinephrine (NE: 10(-8), 10(-9), 10(-10) M) or potassium (K+: 100mM, 50 mM) followed by three doses of the beta-adrenergic agonist, isoproterenol (IP: 10(-7), 10(-6), 10(-5)M) administered simultaneously with each constrictor. R was not altered by IP during NE infusion but was significantly increased at all levels of IP during both K+ infusions. When the K+ series was repeated with alpha blockade, IP did not alter R. Thus, beta receptors do not appear to be functionally present in the adult rabbit carotid artery.


Prostaglandin and histaminergic mediation of prolonged vasodilation after exercise.

An extended period of recovery of vascular resistance, far outlasting the recovery period of oxygen consumption, follows exercise of dog skeletal muscle when flow is restricted relative to the intensity of the exercise pattern. The duration of this postexercise prolonged vasodilation is graded and is related to the blood flow, duration of muscle stimulation, fatigue of the muscles, and total muscle tension development. To test whether prolonged vasodilation is mediated by prostaglandins or histamine, the prostaglandin synthetase inhibitors indomethacin or meclofenamate and the antihistamine tripelennamine were administered intravenously to anesthetized dogs between two 20-min exercise bouts of the anterior calf muscles at 4 twitches/s. Blood flow was held constant at approximately 20 ml 100 g-1 min-1, typically resulting in a venous O2 content below 2.0 ml/100 ml during exercise. The duration of vascular resistance recovery was evaluated by measuring the time at which vascular resistance returned to 90% (t90) of the recovery level (mean +/- SE). All the drugs caused a significant decline in the t90, but none reduced the recovery time to that following free-flow exercise, where the t90 is less than 1 min and the return of vascular resistance parallels the return of oxygen consumption to control. Thus, prostaglandin and/or histamine release may be at least partially responsible for prolonged vasodilation.


Impotence responsive to glyceryl trinitrate.

The author presents suggestive evidence that glyceryl trinitrate served to treat and diagnose atherosclerotic impotence in a man with psychogenic impotence. The prevalence of atherosclerotic impotence is not known but may be relatively high in older men. Vasodilators may be effective in diagnosing these patients, who do not have clear signs of arterial insufficiency of the lower extremities (e.g., Leriche's syndrome). The author postulates a pharmacological interaction between organic nitrates and imipramine.


[The action of ethylenediaminetetraacetate on the retina. Electronmicroscopic study (author's transl)].

Electron microscopic investigations show that intravitreal application of EDTA causes destruction of the viteous body and damage in all layers of the retina. Therefore, it is concluded that it is useless to try prevention of metallosis of the eye by EDTA.


Electron microscopic studies on zonule. Its origin and fibroblast.

Rabbit fetuses (14, 16, 17, 18, 20, 22, and 24 days in utero) were examined with an electron microscope, and the following results were obtained: 1. At the equatorial region of the lens, developing endothelium of the tunica vasculosa lentis was very similar in morphology to typical fibroblast. 2. Much debris of amorphous material was observed around the endothelium and fibroblast, but in general, zonule-like fine fibrils were seen near the former, whereas short collagen fibrils were observed around the latter amid amorphous material. 3. Topographically, fibroblasts lay apart from the lens equator, and few fibroblasts migrated into the posterior portion. 4. From the above data it was postulated that debris around the tunica vasculosa lentis in the vicinity of the lens equator was presumably the precursor of zonular fibrils and that fibroblasts had almost no relation to zonular formation.


Polyclonal gammopathies associated with chronic diseases in nonhuman primates.

Serum samples collected from clinically healthy rhesus macaques (Macaca mulatta) were compared with serums from animals diagnosed as having malignant lymphoma, atypical tuberculosis, progressive multifocal leukoencephalopathy, or more than 1 of these. Electrophoretic analyses of serum proteins (in grams per deciliter) indicated that mean values in a clinically normal group were as follows--total protein, 8.30; albumin, 4.07; alpha-globulin, 0.85; beta-globulin, 2.23; and gamma-globulin, 1.15. In macaques with malignant lymphoma, mean values were--total protein, 7.60; albumin, 2.72; alpha-globulin, 0.91; beta-globulin, 1.71; and gamma-globulin, 2.23. In macaques with atypical tuberculosis, these values were 8.47, 2.92, 0.84, 2.18, and 2.52, respectively, and those with progressive multifocal leukoencephalopathy, 9.06, 4.01, 6.71, 2.42, and 1.93. Where multiple serum samples were available from 1 macaque for analysis, gamma-globulin values were increased before clinical disease was apparent. Evaluation of serums from macaques may be used as a means of detecting preclinical lymphoproliferative disease.


Quantitation of bovine immunoglobulins: comparison of single radial immunodiffusion, zinc sulfate turbidity, serum electrophoresis, and refractometer methods.

Laboratory methods designed to quantitate serum immunoglobulin were evaluated: single radial immunodiffusion, zinc sulfate turbidity, and serum electrophoresis. Estimation of immunoglobulin concentration in neonatle calves, using total protein measurements, was also evaluated. Single radial immunodiffusion proved useful for quantitation when either class or subclass information was needed. Zinc sulfate turbidity measurements gave accurate results for total immunoglobulin except when hemolysis was present in the sample. A correction factor for hemoglobin that will minimize errors resulting from hemolysis was presented. Serum electrophoresis was also found to be an accurate quantitation method. Large errors were encountered in attempting to estimate immunoglobulin on the basis of total protein.


Studies on Macaca mulatta infected with Rocky Mountain spotted fever.

Acid-base alterations and changes in other selected serum constituents (free fatty acids, triglycerides, cholesterol, copper, cortisol, alpha1-acid glycoprotein, haptoglobin, and albumin) were measured during a study of Rocky Mountain spotted fever in 16 male rhesus macaques. Blood samples were taken from nonanesthetized macaques conditioned to repeated handling. Arterial pH increased and PCO2 decreased during the febrile period. Free fatty acids, triglycerides, copper, cortisol, alpha1-acid glycoprotein, and haptoglobin increased, whereas albumin decreased during the disease. Significant changes were not observed in arterial PO2. Cholesterol remained unchanged. The increase in arterial pH and decrease in PaCO2 indicated that respiratory alkalosis was present in macaques acutely affected with Rocky Mountain spotted fever.


[Gangliosidosis GM1. Clinical, radiologic, biochemical and histological studies in two cases (author's transl)].

Two cases of Gangliosidosis GM1 are presented. They are a child who showed psychomotor backward and generalized osteoporosis, died at 16 months, and a girl studied because of psychomotor backward when she was less than a year. This girl showed radiological vertebrae alterations similar to mucopolysaccharidosis and died when she was 7 years old. The enzymatic determinations in serum and cultured fibroblasts showed beta-galactosidase deficiency in both cases. Important storage of cerebral gangliosides with increase of the percentage of GM1 was also found in both cases. Histological alterations were found in some other organs besides the brain.


A case of an anomalous duodenum, pancreas and biliary tract, with gallstone perforation.

A case of an elongated, anomalous duodenum with intestinal rotation, annular pancreas and disease of the biliary tract with acute jaundice caused by gallstone perforation is presented. The ERCP (endoscopic retrograde cholangiopancreatography) was of great value in the preoperative investigations. Surgical relief of the obstruction of the biliary duct made the patient free of symptoms.


Linkage between alpha-fucosidase and the rhesus blood group.

Family studies show that alphaFUC is closely linked to Rh and confirm that the locus for alpha-L-fucosidase is on chromosome 1.


[Study of the antiviral activity of a poly I : poly-C complex with poly-L-lysine in monkeys].

Antiviral activity of poly-I-poly-C complex with poly-L-lysine was studied on macaco rhesus. The complex bifilamentous polyribonucleotide induced active production of serum interferon and provided pronounced protection of the monkeys infected intracutaneously with the variolovaccine virus (10 LD50 for the monkeys in intracutaneous infection). The effectiveness of the protective effect depended on the scheme and route of the drug administration. The highest prophylactic and therapeutic effect was provided by local administration of the complex in a dose of I mg per I kg of the body weight, the incubation period being increased 2--3 times and the period of the skin affections being decreased approximately 2 times. The results of the studies on the effect of poly-I-poly-C complex with poly-L-lysine were evident of definite prophylactic activity of the drug against experimental vernal encephalitis in the monkeys. The animals not treated with the inductor died on the 16th or 17th day after infection because of the paralysis of the trunc and extremities muscles. The clinical evidences of the disease in the animals treated with the drug were not uniform: from complete health to death.


Beta-lactamases produced by a Pseudomonas aeruginosa strain highly resistant to carbenicillin.

A Pseudomonas aeruginosa strain isolated at Besançon Hospital, France, proved to be highly resistant to carbenicillin and showed a high hydrolytic activity toward this antibiotic. We clearly demonstrated that two beta-lactamases were synthetized: one of them, constitutive, has its enzymatic activity directed mainly toward penicillins, and carbenicillin appears to be its best substrate (higher V(max)); thus, this beta-lactamase is a "carbenicillinase" that differs from the well-known "TEM-like" enzymes. The isoelectric point of this carbenicillinase is 5.30 +/- 0.03. The other one is an inducible cephalosporinase, very similar to the cephalosporinases usually found in these organisms. Its isoelectric point is 8.66 +/- 0.04. These two enzymes have been separated by affinity chromatography and isoelectric focusing. The kinetic constants were measured by computerized microacidimetry.


Activities of various 4-aminoquinolines against infections with chloroquine-resistant strains of Plasmodium falciparum.

The studies reported here stemmed from a personal report by Geiman on the capacity of the 4-aminoquinoline amodiaquin to inhibit in vitro maturation of ring stages of the chloroquine-resistant Monterey strain of Plasmodium falciparum. This observation, confirmed in owl monkeys infected with this strain, led to a comparison of the activities of chloroquine, amodiaquin, amopyroquin, and dichlorquinazine (12,278 RP) against infections with various chloroquine-susceptible and chloroquine-resistant strains. The results showed that: (i) these 4-aminoquinolines were essentially equally active against infections with chloroquine-susceptible strains and (ii) the activities of amodiaquin, amopyroquin, and dichlorquinazine were reduced significantly in the face of chloroquine resistance, but (iii) well-tolerated doses of these compounds would cure infections with strains that fully resisted treatment with maximally tolerated doses of chloroquine. Two other 4-aminoquinolines, SN-8137 and SN-9584, which also exhibited activity against chloroquine-resistant parasites in vitro, displayed curative activity in monkeys infected with a chloroquine-resistant strain. These observations show that there is cross-resistance among the 4-aminoquinolines, confirming earlier findings, but indicate that the dimensions of this phenomenon are sufficiently limited so that some derivatives are therapeutically effective against infections refractory to maximally tolerated doses of chloroquine.


Rapid microbiological assay for chlorhydroxyquinoline that uses a cryogenically stored inoculum.

A rapid microbiological assay for chlorhydroxyquinoline is described. It is a turbidimetric procedure that uses Streptococcus faecalis as the test organism. Results are available within 5 h. Data are presented to show the advantages of using a cryogenically stored inoculum over an inoculum prepared on a daily basis.


Inducible resistance to D-cycloserine in Bacillus subtilis 168.

Resistance to d-cycloserine could be induced in Bacillus subtilis 168 by sublethal concentrations of d-cycloserine. Sensitivity to the antibiotic could be regained by growth in the absence of d-cycloserine. The bactericidal activity of d-cycloserine apparently was not altered by resistant cells, and peptidoglycan synthesis was still inhibited by d-cycloserine in resistant cells. The d-cycloserine resistance apparently resulted from a decreased uptake of the antibiotic. The decrease in d-cycloserine transport could be prevented by simultaneous treatment of the cells with rifampin and d-cycloserine. d-Cycloserine was transported by the same system as glycine in B. subtilis. d-Cycloserine was able to exchange for intracellular glycine in both sensitive and resistant cells, suggesting that d-cycloserine is not excluded from the cell in resistant cultures.


D-Cycloserine-induced alterations in the transport of D-alanine and glycine in Bacillus subtilis 168.

d-Alanine, l-alanine, and glycine transport was investigated in Bacillus subtilis 168 cells that were phenotypically resistant to d-cycloserine. These cells showed enhanced rates of uptake as compared with that observed in sensitive cells. The usual enhancement in d-alanine and glycine transport resulting from treatment of the cells with d-cycloserine could be prevented by the addition of rifampin. Kinetic analyses of the initial rate of glycine transport indicated an increase in the V(max) for transport in resistant cells, with no alteration in the K(m) for glycine. Investigations of the net transport of glycine revealed that resistant cells maintained a higher gradient of glycine than did sensitive cells. Kinetic analyses of the net transport of glycine suggested that a new system for the accumulation of glycine was present in d-cycloserine-resistant cells.


Transfer of beta-lactamase genes of Neisseria gonorrhoeae by conjugation.

Recent isolates of Neisseria gonorrhoeae have been shown to be resistant to penicillin because they produce beta-lactamase. In this study, conjugal transfer of the beta-lactamase gene to a recipient N. gonorrhoeae strain occurred in one of the two strains studied but not in the other. The transconjugant could also conjugally transfer the beta-lactamase gene to an Escherichia coli strain.


Bactericidal activity of macromomycin, a antitumor antibiotic.

Susceptibility testing by the broth dilution method showed that all the gram-positive but only some of the gram-negative bacteria tested were susceptible to the antitumor antibiotic, macromomycin (MCR; NSC 170105). The minimal inhibitory concentration for the susceptible organisms was less than 3 mug/ml. The action of MCR was bactericidal; however, at very high concentrations (50 mug/ml and above) some organisms occasionally escaped death. None of the escaped organisms was resistant to MCR. In combination with other commonly used antibiotics, MCR displayed partial synergy for Pseudomonas aeruginosa (from a minimal inhibitory concentration of >100 to 12.5 mug/ml with 100 mug of chloramphenicol per ml) and for Bacillus pumilus and Staphylococcus aureus (from 1.6 to 0.4 mug/ml and below) with polymyxin B. As with mammalian cells, (125)I-labeled MCR was irreversibly bound to both gram-positive and -negative bacteria. Treatment with trypsin of the (125)I-labeled MCR-exposed cells did not release the bound MCR or reverse its lethal effect. When in solution in a protective buffer at 4 degrees C, MCR was stable for up to 45 days; at 37 degrees C, however, 25% of its bactericidal activity was lost in 72 h. Loss of activity was enhanced 16-fold in the presence of both heated and unheated pooled human sera. Urine had no effect on the activity of MCR.


Five-hour minimal inhibitory concentration test of four antimicrobial agents for Pseudomonas aeruginosa.

A rapid 5-h minimal inhibitory concentration procedure and a minimal bactericidal concentration procedure are described for testing Pseudomonas aeruginosa against gentamicin, tobramycin, amikacin, and carbenicillin. The rapid test results were demonstrated to correlate with the conventional tube dilution procedure.


Rapid penicillinase paper strip test for detection of beta-lactamase-producing Haemophilus influenzae and Neisseria gonorrhoeae.

A modified 1-min iodometric paper strip test for penicillinase activity was developed for detection of beta-lactamase-producing isolates of Haemophilus influenzae and Neisseria gonorrhoeae. The test is simple to perform and uses reagent-impregnated strips that may be stored for 1 year or more prior to use.


Synergy between ticarcillin and tobramycin against Pseudomonas aeruginosa and Enterobacteriaceae in vitro and in vivo.

The antibacterial activities of ticarcillin, carbenicillin, tobramycin, and gentamicin and of combinations of these antibiotics were measured against Pseudomonas aeruginosa and other gram-negative bacilli in vitro and in experimental mouse infections. Synergistic effects were produced by the penicillin/aminoglycoside combinations in growth inhibition tests and in bactericidal tests against many of the bacteria tested. Combinations of ticarcillin + tobramycin were more active in vitro than carbenicillin + gentamicin against P. aeruginosa but were no more active than the latter against other gram-negative bacilli. Ticarcillin + tobramycin and carbenicillin + gentamicin also demonstrated synergistic activities against P. aeruginosa, Escherichia coli, and Enterobacter cloacae in experimental mouse infection models. Thus, the penicillin/aminoglycoside combinations produced greater protective effects than the individual antibiotics against lethal intraperitoneal infections and also were more effective in reducing kidney counts of viable bacteria and kidney abscess formation in experimental pyelonephritis infections. As was the case in vitro, ticarcillin + tobramycin was more effective than carbenicillin + gentamicin against the experimental P. aeruginosa infections. The results of these in vitro and in vivo studies suggest that combined therapy with ticarcillin and tobramycin may be warranted in the treatment of serious infections due to P. aeruginosa and Enterobacteriaceae.


New species of Aspergillus producing sterigmatocystin.

A number of species belonging to the genus Aspergillus were evaluated for their toxicity to ducklings and the ability to produce sterigmatocystin. Three new species capable of producing sterigmatocystin were found, namely, Aspergillus aurantio-brunneus, Aspergillus quadrilineatus, and Aspergillus ustus. All three were toxic to ducklings. The production of sterigmatocystin by Aspergillus rugulosus was confirmed, and the toxicity of Aspergillus stellatus and Aspergillus multicolor is described.


Diluent sensitivity in thermally stressed cells of pseudomonas fluorescens.

Thermally injured cells of Pseudomonas fluorescens were unable to produce colonies on Trypticase soy agar (TSA) after dilution with 0.1% peptone. Nutritional exigency could not be used as the criterion for this injury, since varying the composition of the plating medium had little effect on the number of colonies that developed. The injured cells had no requirement for compounds known to leak out during the heat treatment in order to recover. The cells did not exhibit injury if dilution preceded heat treatment on the plating medium, demonstrating that the heat treatment sensitized the cells to the trauma of dilution. Substitution of 0.1% peptone with growth medium as the diluent largely offset the previously observed drop in TSA count. Little difference in survival was observed when monosodium glutamate or the balance of the defined medium was used as the diluent. The diluent effect was ionic rather than osmotic. The presence of cations was important in maintaining the integrity of the injured cell, and divalent cations enhanced this protective effect. The role of these cations at the level of the cell envelope is discussed.