Influence of norethindrone on drug-metabolizing enzymes of female rat liver in various B-vitamin deficiency states.

Ingestion of high levels of thiamin significantly decreased the activity of cytochrome P-450, NADPH cytochrome c reductase, and the metabolism of aniline and ethylmorphine. Apparent VmaxS for ethylmorphine N-demethylase and aniline hydroxylase were decreased by high levels of riboflavin even though NADPH cytochrome c reductase was elevated. High levels of dietary pyridoxine significantly decreased only the Vmax for aniline hydroxylase. Generally, norethindrone produces either no change or slight depression of cytochrome P-450 regardless or diet, whereas the administration of norethindrone produced no change or an increase in activity of c reductase and ethylmorphine N-demethylase. Norethindrone induces aniline hydroxylase in animals fed all diets except those deficient in thiamin and riboflavin. The activities of the four parameters of the drug metabolizing system measured in these studies as well as the effects of norethindrone are clearly affected by the dietary status of the animal.


Some effects of naloxone on behavior in the mouse.

The effect of naloxone on the latency of mice to enter a dark box was determined and the study of Jacob et al. (1974) on the effect of naloxone on hotplate behavior was replicated. Mice took significantly longer to enter a dark box after receiving 10 mg/kg of naloxone than did the saline controls. With the hot-plate technique, at all doses (0.1, 0.3, 1, 3, and 10 mg/kg) except the lowest (0.03 mg/kg), naloxone-treated mice jumped from the hot plate significantly sooner than did the saline controls. No effect of naloxone on paw-lick latency was found. All the data confirm the findings of Jacob et al. (1974). The hotplate results suggest that prolonged exposure to a noxious stimulus may be necessary to activate the endorphin system.


Actions of amphetamine and antagonists on pupil diameter in the chronic sympathectomized dog.

The left superior cervical ganglia were removed from 5 dogs. Beginning 30 days postoperatively, epinephrine (10 microgram/kg/min), norepinephrine (10 microgram/kg/min), and d-amphetamine (1.0 mg/kg) were infused i.v. for 10 min following either vehicle, phenoxybenzamine, pimozide, or haloperidol. Epinephrine and norepinephrine dilated the pupil and retracted the nictitating membrane of the denervated side, whereas amphetamine dilated both pupils and retracted both nictitating membranes. Phenoxybenzamine (4 mg/kg) constricted primarily the pupil of the innervated iris and completely antagonized the effects of the catecholamines on the irides and amphetamine on the nictitating membranes, but only partially antagonized amphetamine-induced mydriasis. Haloperidol (1.0 mg/kg) constricted both pupils, possessed only modest alpha-adrenergic blocking activity, and was as effective as phenoxybenzamine in antagonizing amphetamine-induced mydriasis. Pimozide (0.1 mg/kg) constricted both pupils, had no significant alpha-adrenergic blocking activity, and did not antagonize amphetamine-induced mydriasis. Pimozide and haloperidol, but not phenoxybenzamine, blocked amphetamine-induced stereotyped head bobbing. These results suggest that amphetamine produces mydriasis in the dog through a peripheral sympathetic action and also through a central mechanism involving inhibition of the oculomotor nucleus. However, the role of dopamine is not clear.


Plasma concentrations of perphenazine and its sulphoxide metabolite during continuous oral treatment.

Plasma concentrations of perphenazine (PPZ) (Trilafon) and perphenazinesulphoxide (PPZSO) were estimated during a 2-week period in 16 patients receiving peroral PPZ treatment for various psychotic disorders. The results demonstrated that the average concentration of three plasma samples was a reasonably good expression of the steady-state plasma level despite a great fluctuation in the concentration from sample to sample. Increased doses in three of the patients resulted in disproportionate increases in the plasma levels. Neurological side effects were recorded and their relation to plasma concentrations are discussed.


The insomnia of 'sleeping in a strange place': effects of l-tryptophane.

Forty-two normal human subjects were studied in the sleep laboratory for one night each. Fourteen were given placebo at bedtime, 14 took l-tryptophane 1 g, and 14 took l-tryptophane 3 g. Both tryptophane groups had significantly lower sleep latency than the placebo group. The usually discarded 'first laboratory night' produces a mild situational insomnia in normal persons and thus can be useful in certain sleep studies.


Changes in the rate-increasing effects of d-amphetamine and pentobarbital by response consequences.

Keypecking in one group of pigeons was maintained under schedules in which food was presented only when a specified number of responses was followed by a 30-s pause without a response. d-Amphetamine and pentobarbital increased low rates of responding (and, thus, decreased food presentation) only after initial injections or when, during drug sessions, responses during the 30-s period did not reset the period. When responses during the pause-interval postponed food delivery, the rate-increasing effects of both drugs diminished over succeeding administrations. Thus, immediate effects of response consequences were as influential as the actual presence of a drug in determining the reproducibility of the behavioral effects of that drug. In a second experiment, keypecking in another group of pigeons was maintained under a 10-min fixed-interval schedule of food presentation but suppressed by a 100-response fixed-ratio schedule of shock delivery (punishment). d-Amphetamine and pentobarbital increased low rates of punished responding when shock delivery was eliminated during drug sessions. Pentobarbital, but not d-amphetamine, also increased punished responding when shock delivery was present. Rate-increasing effects of these drugs were determined by not only predrug patterns of responding but also effects of reinforcers and punishers that occurred during exposure to the drug.


Readaptation time after photo stress. Alcohol-induced acute and post-alcohol 'hangover' changes in ocular readaptation time.

The effect of alcohol intake on readaptation time (RAT) after photo stress is studied. Ten healthy subjects were given 0.72 g alcohol per kg body weight to be consumed within 20 min. The tests were made during a total period of 11-12 h. The findings demonstrate that moderate blood alcohol concentrations induce definite changes in RAT. An average RAT-prolongation of 60-70% was seen during the acute phase of intoxication. RAT-prolongation ended before the blood alcohol concentration had reached zero, but did not have the same downward slope. Following a period of reduction, a new prolongation of RAT was observed. The lack of congruence between the RAT-curve and the blood alcohol curve in the acute phase of intoxication and the post-alcohol increase are discussed. It is concluded that the alcohol-induced RAT-changes probably are CNS-effects and that the equipment used constitutes a sensitive method of estimating these effects.


Differential haloperidol effect on two indices of fentanyl-saline discrimination.

Using a discrete-trial, two-lever, food-reward discrimination learning paradigm, we trained rats (n = 6) to discriminate 0.04 mg/kg fentanyl (s.c. t-30') from saline. Stimulus generalization experiments with an adequate dose range (0.01-0.04 mg/kg) of fentanyl revealed that the ED50 value for drug lever selection is 0.02 mg/kg, irrespective of whether the animals were pretreated (s.c., t-60') with either saline or 0.08 mg/kg haloperidol. With increasing doses of the haloperidol-fentanyl combination, the percentage of total responding on the selected lever progressively decreased, and reached the 50% level at the highest drug combination. It is concluded that this percentage is heavily contaminated by factors unrelated to the discrimination condition being studied; these factors seem to invalidate this percentage as a discrimination index under experimental conditions (e.g., behaviorally toxic doses of drugs) where they are likely to operate. The use of response selection as a discrimination index in drug discrimination research is further argued.


A comparative study of different amphetamines on copulatory behavior and stereotype activity in the female rat.

The influence of D- and L-amphetamine, fenfluramine, and p-chloroamphetamine on female copulatory behavior (lordosis response) and the induction of stereotype activity was compared. Lordosis response in the female rat has been shown to be inhibited by increased central nervous serotonergic (5-HT) as well as dopaminergic (DA) activity. A dose-dependent inhibitory effect on the estrogen- + progesterone-induced lordosis response in ovariectomized rats was demonstrated after treatment with the four amphetamines. In contrast, only D- and L-amphetamine induced a stereotype activity, which is considered to be mediated by DA mechanisms. A decrease in DA receptor activity, achieved by pimozide pretreatment, abolished the effect of D-amphetamine on lordosis behavior, but the effect of L-amphetamine was only slightly diminished and the action of fenfluramine and p-chloroamphetamine was unaffected. On the other hand, both L- and D-amphetamine-induced stereotype activity was prevented by pimozide treatment. The data suggest that the D-amphetamine effect on lordosis behavior is mediated by increased DA receptor activity. Although it induces stereotype activity by increased DA activity, L-amphetamine, like fenfluramine and p-chloroamphetamine, inhibits the lordosis response by some other action presumably related to serotonergic mechanisms.


Sleep deprivation deficits and their reversal by d- and l-amphetamine.

Vigilance performance, waking EEG patterns and mood were studied before and after one night of sleep deprivation in normal males. The effects of d-amphetamine 10 mg, l-amphetamine 10 mg and placebo on these measures were compared. Changes were found in all three measures after one night of sleep-deprivation. d-Amphetamine was more powerful than l-amphetamine in reversing sleep deprivation effects on vigilance and on waking EEG.


Comparison of ethanol, pentobarbital, and phenobarbital using drug vs. drug discrimination training.

Rats learned drug vs. drug (D vs. D) or drug vs. no drug (D vs. N) discriminations in a T-maze shock escape task with various doses of pentobarbital, phenobarbital, or ethanol. Dose-effect curves were obtained for each drug using D vs. N training. After D vs. N training with any one of these drugs, rats made D choices during substitution tests with the other two drugs, suggesting drug interchangeability. D vs. D training also showed that pentobarbital and phenobarbital were virtually indistinguishable from one another. However, ethanol was readily discriminated from pentobarbital, showing that the two drugs differed. The results show the utility of D vs. D training as a method for studying drug differences that may be too small to detect with substitution tests.


Tolerance to ethanol: effect of congeners present in bourbon.

Fish were exposed to water and to ethanol or bourbon solutions of the same ethanol concentration (0.1, 0.2, 0.4, 0.6, or 0.8 g/100 ml) during 6 h and then tested in 3.1 g/100 ml ethanol for loss of righting reflex or overturn point. The content of ethanol in the brain at overturn was determined for each fish. Although the ethanol brain levels at overturn of bourbon-exposed fish were higher than those of the ethanol group, no significant differences were observed between the two groups. Moreover, there was a tendency for the bourbon fish to take longer times to overturn than the ethanol fish. These findings indicate that the congeners present in bourbon did not affect significantly the development of tolerance to ethanol in goldfish.


Dose-response effects of taurine on some open-field behaviors in the rat.

In two experiments albino rats were injected i.p. with various doses of taurine and their subsequent behavior in an open-field apparatus was observed. Increasing doses of taurine significantly decreased ambulation levels, increased latency scores, and increased thigmotaxis ('wall-hugging' behavior). In general, 50 mg/kg or more of taurine was required to produce significant changes in the dependent behavioral measures. The open-field behaviors of rearing and defecation were not significantly affected by the drug manipulation. The results of these experiments suggest that taurine may act as modulating or stabilizing agent in the central nervous-motor system rather than as a diffuse inhibitory agent.


Unilateral catecholamine depletion of the corpus striatum and amphetamine-induced turning: an ontogenetic study.

Unilateral intrastriatal microinjections of alpha-methyl-p-tyrosine followed by systemic amphetamine treatment produced turning ipsilateral to the side of the injection in rats from 12 days of age to maturity, but not in rats younger than 12 days. These results are consistent with other findings that indicate rapid development of the striatal dopaminergic system and dopaminergic component  of the amphetamine stereotypy in the second postnatal week.


Alcohol-associated conditioned reinforcement.

Research was conducted to examine the ability of alcohol to impart conditioned reinforcement. Rats were allowed to self-administer solutions of either saline or alcohol (25, 50, and 100 mg/kg/infusion) by the intragastric route. Superimposed on the infusion interval was a buzzer (conditioned reinforcing stimulus). Tests during extinction revealed that conditioned reinforcement had been acquired. Results also indicated that as the paired unit dose was increased, potency of the conditioned reinforcer increased. In a second study, the lever-pressing response, which produced saline infusion and the buzzer, became available only subsequent to 5 sessions of pairing the buzzer with infusions of saline or alcohol. The results indicated that lever pressing increased with increasing unit dosage of alcohol infusions in prior pairings.


Effects of pimozide on the acquisition, maintenance, and extinction of an amphetamine-induced taste aversion.

Different groups of rats were pretreated with the dopamine receptor blocker, pimozide (0.25, 0.5, or 1.0 mg/kg), in an attempt to investigate the role of dopaminergic transmission in the acquisition, maintenance, and extinction of a taste aversion produced by d-amphetamine dulphate (1.0 or 2.0 mg/kg). In the first phase of the experiment, all doses of pimozide attenuated but did not block the acquisition of the aversion produced by 1.0 mg/kg but not by 2.0 mg/kg amphetamine. In Phase II, pimozide pretreatment was suspended to allow the attenuated groups to acquire the aversion and then reintroduced in Phase III. In this phase all groups continued to avoid the taste, indicating a failure of pimozide to affect the maintenance of the avoidance response. When amphetamine treatment was suspended in Phase IV, pimozide accelerated the extinction, especially in those groups that had previously received the 1.0 mg/kg dose of amphetamine. These results are discussed with reference to dopaminergic mechanisms in avoidance learning and a pimozide-mediated reduction in the functional strength of amphetamine as an unconditioned stimulus.


Primate information processing under sodium pentobarbital and chlorpromazine: differential drug effects with tachistoscopically presented discriminative stimuli.

Sodium pentobarbital and chlorpromazine were evaluated for the degree to which they differentially reduce the speed or efficiency with which sensory information can be processed. Rhesus monkeys were tested under comparable doses of sodium pentobarbital and CPZ on a visual discrimination problem with varying durations of tachistoscopically presented stimulus information. When unlimited stimulus information was available, no effects of the two drugs were observed at the doses used, but as the duration of stimulus presentation was progressively decreased, the effects of sodium pentobarbital became more severe, whereas CPZ did not differe from the saline control an any presentation duration. While previously published literature indicates that CPZ impairs performance by intermittantly blocking sensory input or transmission, the present data provide the first direct behavioral confirmation that barbiturates impair performance by retarding the rate at which sensory stimuli can be processed and utilized.


Effect of di-n-propylacetate on the 'binding of GABA to synaptosome-enriched fraction of rat cerebral cortex.

The effect of di-n-propylacetate (DPA) on the 'binding' of gamma-aminobutyric acid (GABA) to a synaptosome-enriched fraction of rat cerebral cortex has been examined using differential centrifugation and double-isotope liquid scintillation spectrometry. DPA at 10(-4) M caused a slight decrease in GABA binding. This effect could explain in part the in vivo anticonvulsant and behavioral effects of this drug when administered to animals in high systemic doses.


Effects of chronic administration of diphenylhydantoin on learning and offspring behavior.

An original parent group of 72 Sprague-Dawley albino rats was subdivided into four treatment groups that were administered 5, 10 or 15 mg/kg diphenylhydantoin and distilled water on days 5 to 55 after birth. At 85 days of age the drug females were bred to naive males to produce an F1 generation. In similar fashion, the F1 females were bred at maturity to produce and F2 generation. Neither offspring group received any drug administrations or experimental treatments. All three groups were tested on avoidance conditioning at 75 days of age for a total of 150 trials. The results of statistical analysis indicated no significant differences in number of correct responses in the parent group, a significant Drug effect in the offspring groups and a significant Dose effect in the F2 generation. This detrimental cross-generational effect on avoidance conditioning, caused by chronic diphenylhydantoin administration, is consistent with previously noted cross-generational effects of trifluoperazine, chlorpromazine, and methylphenidate.


Genetic analysis of the behavioral response to d-amphetamine in mice.

The ambulatory and rearing responses to d-amphetamine were studied in a battery of recombinant inbred strains and in three closely related strains: C57BL/6J, C57Bl/10J, and C57BL/LBy. Differences in the increase of ambulation (stimulation) caused by d-amphetamine were seen between C57BL/6By and the other two C57BL strains. Analysis of F1 and backcross matings suggests a one-gene model. A mutation at the genetic locus that affects the response to d-amphetamine seems to have taken place in the C5BL/6By strain. Strain differences in the decrease of rearing behavior (inhibition) produced by the drug were observed in recombinant inbred strains. Although th of l-dihydroxyphenylalanine (L-dopa) and d,l,5-hydroxytryptophan (d,l,5-HTP) on reserpine-induced amnesia.


The ambulatory and rearing responses to d-amphetamine were studied in a battery of recombinant inbred strains and in three closely related strains: C57BL/6J, C57BL/10J, and C57BL/6By. Differences in the increase of ambulation (stimulation) caused by d-amphetamine were seen between C57BL/6By and the other two C57BL strains. Analysis of F1 and backcross matings suggests a one-gene model. A mutation at the genetic locus that affects the response to d-amphetamine seems to have taken place in the C57BL/6By strain. Strain differences in the decrease of rearing behavior (inhibition) produced by the drug were observed in recombinant inbred strains. Although the genetic analysis is not conclusive, it appears to be compatible with regulation by a single major gene. The two single-gene models reported here (one affecting the stimulatory response and the other the inhibitory response to d-amphetamine) may be useful in the study of neural mechanisms involved in stimulation and inhibition of behavior by d-amphetamine.


The effects of electric shock on responding maintained by cocaine injections in a choice procedure in the rhesus monkey.

A choice procedure was used to determine the ability of electric shock to suppress cocaine-maintained responding in a situation where cocaine was also available on a second lever without shock. In each session rhesus monkeys were allowed to self-inject cocaine five times in the presence of a stimulus. Thirty minutes after the fifth injection a second dose of cocaine could be self-injected five times in the presence of a different stimulus. At the onset of the injection of this dose a 5 or 10 mA electric shock was delivered. Thirty minutes later choice trials began in which both stimuli were present and monkeys could choose one of the two doses of cocaine. Electric shock was delivered at the onset of the injection of one of these alternatives. Initially, both doses of cocaine were 0.1 mg/kg. The dose of cocaine associated with electric shock was systematically increased until it was preferred to the dose not associated with electric shock. The results indicate that although responding maintained by cocaine can be suppressed by punishment, this effect can be attenuated by increasing magnitude of reinforcement.


Movement disorders induced in monkeys by chronic haloperidol treatment.

After several months of treatment, Cebus apella, Cebus albifrons, and Saimiri sciurea monkeys maintained on haloperidol, in doses of 0.5 or 1.0 mg/kg orally 5 days per week, began to display severe movement disorders, typically 1-6 h post-drug. Cebus monkeys exhibited violent, uncontrolled movements that flung the animals about the cage. Such episodes usually lasted only a few minutes, recurring several times during the period following drug ingestion. Writhing and bizarre postures dominated the response in S. sciurea. Cessation of drug treatment produced no distinctive after-effects. When tested as long as 508 days after the last administration, however, Cebus monkeys responded to haloperidol with several episodes of hyperkinesis, even at challenge doses considerably lower than those in the original treatment.


Comparative study of retrograde amnesia in rats on active and passive avoidance tasks and spontaneous recovery of memory.

Naive and pretrained rats were trained in two active avoidance paradigms using a pole-climbing box and in a single-trial passive avoidance task using a T-maze. They were then subjected to amnestic treatments with electroshock, leptazol, pentobarbitone, or ether anesthesia. Single retention tests were given at 20-24, 44-48, or 68-96 h posttreatment. Electroshock and leptazol seizures produced retrograde amnesia in all three paradigms, provided that seizures were maximal and retention was tested before 48 h. Prior treatment with anticonvulsant drugs prevented amnesia. Ether and pentobarbitone anesthesia failed to produce amnesia in all three tasks. A trend of recovery from amnesia was observed in the electroshock and leptazol groups when tested for retention 48-96 h posttreatment. On the other hand, the non-amnesic control, pentobarbitone, and ether groups showed signs of forgetting at these longer intervals. Consolidation failure and/or retrieval block was surmised to be the cause of amnesia; recovery was the possible result of removing the block.


The effect of L-tryptophan administration on the concentration of probenecid in plasma and cerebrospinal fluid in patients.

The administration of large doses of probenecid has been used to study the central nervous system metabolism of catecholamines and indoleamines in patients with affective disease. It has been reported that alterations of the binding of L-tryptophan to plasma albumin binding sites occur during probenecid administration. The present study sought to determine if the administration of large doses of L-tryptophan affected probenecid concentrations in cerebrospinal fluid and/or plasma. The data indicate that during L-tryptophan treatment, plasma probenecid concentrations are reduced but that no significant alterations in cerebrospinal fluid probenecid concentrations occur. This would suggest that the kinetics of the probenecid blockade of transport of acidic biogenic amine metabolites out of cerebrospinal fluid are not altered by L-tryptophan loading.


Uptake inhibition of biogenic amines by newer antidepressant drugs: relevance to the dopamine hypothesis of depression.

The dopamine theory of depression was studied by assessing the effect of antidepressant drugs on uptake of dopamine, noradrenaline, and serotonin in synaptosomes from rat brain. Five newer drugs--butriptyline, maprotiline, trimipramine, iprindole, and mianserine--exhibited rather potent inhibition of 3H-dopamine uptake in corpus striatum, as their IC50 values, which were in the order of 10(-6)-10(-5) M, were only about 50 times higher than for nomifensine (IC50 = 10(-7) M). The five drugs were weak, compared to chlorimipramine, on 14C-serotonin uptake in the whole forebrain, as their IC50 were about 10(-5) M. Butriptyline, trimipramine, and iprindole were very weak uptake inhibitors of 3H-noradrenaline in the occipital cortex. Their IC50 values were about 10(-6) M, which is almost 1000 times higher than for desmethylimipramine. These results are discussed in relation to comprehensive recent literature as further indicating a link between dopamine and depression.


Probenecid in CSF and plasma of rabbits and dogs measured by radioimmunoassay.

Probenecid (P) in CSF of rabbits and dogs was investigated using a new radioimmunoassay technique. In rabbits, under steady-state conditions, CSF/free plasma concentration ratios of P were found to be similar to those reported in man. The ratios were concentration dependent and less than 0.5 suggesting an inhibition of transport of the drug in CNS. Under nonsteady-state conditions, no clear evidence of a transport system was found in dogs.


The effects of amphetamine on maze learning by goldfish.

Goldfish performed a simple left-right discrimination in a Y-maze under the influence of amphetamine. The subjects showed facilitation of learning at a low dose (1.25 mg/l) but not at 2.0 mg/l.


Hypervascular pattern associated with idiopathic focal status epilepticus.

Cerebral angiography in 5 patients in idiopathic focal status epilepticus demonstrated a hypervascular pattern consisting of arteriolar or capillary "blush" with early filling veins and corresponding to the seizure focus; however, there was no evidence of vascular occlusion, neovascularity, or mass effect except for minimal local brain swelling. All showed clearing of neurological deficits; repeat angiograms in 2 patients after arrest of seizure activity returned to normal with complete disappearance of the hypervascular pattern. This reversible but potentially misleading angiographic pattern should be recognized as a benign process.


Supervoltage irradiation in the management of giant cell tumor of bone.

Thirteen patients with giant cell tumor of bone were treated with megavoltage irradiation from 1958 to 1972. Nine cases were believed to be true giant cell tumors of bone. The only patient with recurrence following a geographic miss was salvaged surgically. Curative therapy for giant cell tumor of bone may be 3500 rads in 15 fractions in 3 weeks; it is well tolerated with minimal morbidity. Special care must be used in interpretation of the post-therapy radiologic appearance of these lesions because an initial period of osteolysis lasts many weeks before any radiographic indication of healing by recalcification occurs.


Digital K-edge subtraction radiography.

K-edge subtraction images have been produced using a digital video image processor. Images formed by three filtered x-ray beams are detected by an image intensifier-Plumbicon system, digitilized, and combined in real time to produce bone- and tissue-free K-edge subtraction images of iodinated structures. Preliminary studies of rhesus monkey cranial, spinal, and abdominal structures are compared with those of conventional radiography.


Computed tomography: the cost-benefit dilemma.

Although cost-benefit analysis is used for most systems of health care planning, its use in evaluating CT scanning is not appropriate. The authors suggest that cost-effectiveness is a more reasonable approach to the economic analysis of CT installations. Cost effectiveness attempts to assure that disease is treated with the most effective means available which minimizes the cost of such treatment. This method involves such factors as the impact of CT on the existing health care system, health outcome of patients, and reduction of hospital occupancy.


Differential inhibitory effects of vitamin E and other antioxidants on prostaglandin synthetase, platelet aggregation and lipoxidase.

Prostaglandin biosynthesis from eicosa-8,11,14-trienoic acid in microsomes from the bovine vesicular gland is inhibited by the antioxidants alpha-naphthol. guaiacol, NDGA and propyl gallate. Prostaglandin biosynthesis in this system is not inhibited by the antioxidants BHT, DL-alpha-tocopherol and Trolox C. Arachidonic acid induced platelet aggregation is inhibited by specifically by alpha-naphthol. guaiacol, NDGA and propyl gallate. Both arachidonic acid induced platelet aggregation and ADP induced platelet aggregation are inhibited non-specifically by the antioxidants BHT, DL-alpha-tocopherol and Trolox C. All antioxidants tested in this study inhibit soybean lipoxidase. Thus alpha-naphthol, NDGA and propyl gallate are non-specific inhibitors of both prostaglandin synthetase and soybean lipoxidase while BHT, DL-alpha-tocopherol and Trolox C are specific inhibitors of soybean lipoxidase alone.


Inhibitor(s) of prostaglandin biosynthesis and epidermal injury.

Inhibition of the activity of sheep vesicular gland prostaglandin synthetase (a rare limiting enzyme in the biosynthesis of prostaglandins) was demonstrated in the presence of homogenates prepared from skin lesions characterized histologically by epidermal disruption. These inhibitory effects were not observed in homogenates of skin lesions characterized by a lack of epidermal disruption.


[Natural infection of Calomys musculinus (Rodentia, Cricetidae) by Trypanosoma cruzi].

In the rural area of Las Higueras, Río Cuarto, Córdoba, Argentina, a trypanosoma was isolated from a wild rodent (C. musculinus). The trypanosome was classified as Trypanosoma cruzi because of the following characteristics: morphology as described by Hoare for the Schizotrypanum sub-genus: thin shaped, pointed back end, nucleus placed approximately in the middle of the body, prominent and subterminal kinetoplast and short free flagellum. The size measurements were as follows: total lengh 22.02 +/- 0.40 micron, flagellum lengh 5.93 +/- 0.29 mu, Nuclear mean index (NP/NA) 1,21 +/- 0.07 (Table 1). For some authors, this last value is very important for diagnosis of the parasite. BALB/c albino mice were infected with blood of the captured animal; those mice showed a mild parasitemia and amastigotes nests in cardiac fiber (Fig 2 a y b). The xenodiagnosis performed with nimphs of Triatoma infestans on the laboratory mice was positive. The trypanosome grew very well in blood-agar medium. According with these findings along with the wide geographic distribution and density of C. musculinus in Argentina, one should wonder whether or not this rodent is infested withT. cruzi on its whole distribution range. Passages through T. infestans and laboratory mice produced a virulence enhancement of this strain. With these findings, the question is if this situation should take place in nature, affecting domestic animals in any way. The stated questions and findings should estimulate further research on the role of the wild fauna in the epidemiclogy of Chagas' disease in Argintina.


[An avian strain of Escherichia coli with antigens common to the genus Salmonella].

On a commercial poultry farm, a large percentage (9%) of clinically healthy fowls had positive reaction to the plate test, with commercial polyvalent pullorum antigens. We could not isolate Salmonella from the positive birds. An strain, of Escherichia coli Balcarce (E. coli B) was isolated from the feces of one of the birds. The isolate was identified biochemically and the antigenic study showed correlation with E. coli 044 and the somatic fraction 1, 2, 8, 14 and 23 of the Salmonella genus. The common antigens were studied by agglutination, absorption and crossed immunodiffusion tests, comparing the isolated strain and the different Salmonella serotypes. Four pullorum polyvalent commercial antigens reacted with sera containing somatic agglutinins 1, and with the E. coli B antiserum. These observations confirm the high antigenic correlation between the genus of the Enterobacteriaceae family. It is indicated that for the diagnosis of avian salmonelosis rather than using a single serological tests, the isolation and identification of the etiological agent is required.


[Multiple and familial meningiomatosis. A syndrome bordering on Recklinghausen's neurofibromatosis].

The authors present three cases of multiple, intra-cranial meningiomatosis with contact hyperostosis affecting the grandmother, mother and daughter, in a very stereotypic manner. No other sign of von Recklinghausen's disease was noted, except for two tiny neurofibromas on the left hand in the mother. Only the latter suffered from bilateral deafness, but it was not possible to give definite proof of the presence of an acoustic neuroma in this patient. Anatomical verification in the first case, and surgical intervention in the last, confirmed that it was in fact a meningioma. Thus, a new clinical form of expression of neuro-fibromatosis has been found.


[Detection and titration of antitetanus antibodies using an automated passive hemagglutination method].

An automated reversed passive haemagglutination technique is described, using human erythrocytes sensitized by the chromic chloride method with higly purified tetanus toxoid. Such erythrocytes are agglutinated by the specific antibodies in a Technicon autoanalyzer. Clots are decanted, supernatant is hemolyzed and optical density is measured at 550 millimicron. Assay standards for comparison, ranging from 5 to 25 UI/ml, are prepared from human antitetanus immunoglobulins titrated by toxin neutralisation assay in mice. This method allows to screen donors' sera for presence of high titers of tetanus antibodies (larger than or equal to 5 UI) suitable for preparation of antitetanus immunoglobulins. 4,4% of donors have circulating antitetanus antibody levels corresponding to 5 UI/ml or more, by this method. The specificity of antibodies has been confirmed by the neutralisation assay in mice. The results obtained among 1.000 donors well agree with those of the counter-immuno-electrophoresis technique (C.E.P.). But, when, compared with C.E.P., the haemagglutination assay appears more objective, more quantitative and sensitive, and allows to get not only a rapid screening test but also a precise titration simultaneously.


Recent advances in radiotherapy.

Significant recent achievement in radiotherapy are presented, with brief discussions of brachytherapy, clinical dose-rate effects, ultrafractionation, and total and half-body irradiation. Reports on radiation modifiers, including hyperbaric oxygen, chemical radiosensitizers, and normal tissue protective agents are briefly summarized, while the potential of local and systemic hyperthermia is discussed in greater detail. Recent reports of local tumor control in so-called "radioresistant tumors," such as salivary gland tumors, adenocarcinomas of the breast, prostate and pancreas, malignant melanoma and malignant carcinoid, are summarized. Current status of heavy particle radiotherapy is discussed in detail. Results of initial clinical trials of neutron beam therapy are summarized, and a brief review of proton beam clinical trials and pion beam facilities is included. Recent reports defining the role of combined irradiation and surgery in rectal and breast cancer, and in soft tissue sarcomas, are discussed. Reports of enhanced radiation toxicity seen with concomitant or sequential chemotherapy and radiotherapy are detailed, including CNS toxicity seen with methotrexate and cytosine arabinoside, cardiotoxicity with adriamycin, and pulmonary toxicity with bleomycin. New or improved diagnostic techniques with special relevance to radiotherapy treatment planning, including CT scanning, histerography, internal mammary lymphoscintigraphy, and upper extremity lymphangiography are described.


Immunological investigations of meningococcal disease. III. Brevity of group C acquisition prior to disease occurrence.

A surveillance program to determine group C meningococcal acquisition in military personnel during an epidemic was made. Data from fortnightly nasopharyngeal cultures show that individuals who were admitted with meningococcal disease acquired the organism within a week of disease onset. There were 24 company/platoons in which a single case occurred. Six company/platoons had 2 cases each. While other conditions which could act as predisposing factors were not ruled out, the data here favor acute respiratory disease as a predisposing factor(s) that may cause the increased incidence of meningococcal disease seen in military recruits. The exact mechanism is yet to be defined.


Aeromonas hydrophila septicaemia producing ecthyma gangrenosum in a child with leukaemia.

A 4-year-old girl with leukaemia developed fever and ecthyma gangrenosum. Aeromonas hydrophila was isolated from blood and skin lesions. Ecthyma gangrenosum is often considered pathognomonic of Pseudomonas aeruginosa septicaemia. As is evident from the case reported, it may also result from infection with A. hydrophila, which has different antibiotic sensitivities, and which is now being recognised more frequently as a serious pathogen in immunosuppressed patients.


Urodynamic studies in boys with disorders of the lower urinary tract. III. Urethral diverticula. A pre- and postoperative study.

Eight boys with urethral diverticula underwent urodynamic investigation. According to the findins, the patients were divided into three groups: normal micturition pattern; definite infravesical obstruction; miscellaneous group with varying patterns. Urodynamic investigation proved to be of value for the evaluation of postoperative results. The final results of treatment were good in all patients.


A study of the variable heavy chain (VH) regions in human polyclonal IgM rheumatoid factors.

Ten IgM polyclonal rheumatoid factor (RF) preparations isolated from sera from various patients with rheumatoid arthritis (RA) were investigated with respect to their variable heavy chain (VH) subgroups. They were tested in a haemagglutination inhibition system using red cells sensitized with myeloma proteins with known chemical VH subgroups and anti-VH subgroup specific antisera. Most of the preparations showed a considerable degree of restriction to one VH subgroup. Seven of the IgM-RF preparations were restricted to the VHIII subgroup, two to the VHI subgroup and one to the VHII subgroup. However, a weak reaction in other VH subgroup systems was seen in several instances. Two normal IgM fractions from healthy persons showed no VH subgroup restriction, and showed a rather similar degree of reaction in all the three subgroup systems.


Swine influenza virus vaccine: potentiation of antibody responses in rhesus monkeys.

Polyriboinosinic-polyribocytidylic acid stabilized with poly-L-lysine and carboxymethylcellulose [poly(ICLC)] enhances the antibody response in rhesus monkeys immunized with swine influenza virus subunit vaccine. Monkeys given the vaccine-adjuvant combination had earlier and significantly (P less than .05) higher titers by 14 days compared to those that received vaccine alone. The potentiation of the antibody response of young monkeys given a split-virus vaccine in combination with poly(ICLC) suggests that this vaccine-adjuvant combination may similarly provide a potentially useful alternative approach to the immunization of pediatric and young adult age groups against swine influenza.


Visual input to the visuomotor mechanisms of the monkey's parietal lobe.

A newly identified class of neurons of the parietal cortex, studied in waking monkeys (Macaca mulatta), is activated by visual stimuli, perhaps via the retino-collicular visual pathway. This afferent input is thought to provide the visual cues activating the visuomotor mechanisms of the parietal lobe for the direction of visual attention.


Behavioral history as a determinant of the effects of d-amphetamine on punished behavior.

Food-maintained responding by four squirrel monkeys (Saimiri sciureus) was suppressed by the presentation of electric shock (punishment). Two of these monkeys were experimentally naive and two had a history of responding maintained by both shock-postponement and shock-presentation schedules. In accord with earlier studies, d-amphetamine did not increase punished responding by naive monkeys. However, it did increase punished responding in the others. Subsequently, d-amphetamine also increased punished responding by the initially naive monkeys after they were trained under a shock-postponement schedule. Even though not evident in current behavior, an organism's prior experience can influence the behavioral effects of drugs.


Ovenstone Factor in the management of Rh sensitization.

Several methods have been developed for analyzing amniotic fluid to aid in the management of rhesus isoimmunization. Because all methods attempt to predict the severity of fetal hemolysis based on the original findings of Bevis and on the amount of unconjugated bilirubin in amniotic fluid as measured by its optical density at 450 millimicron, they share two possible sources of error: calculation of exact gestational age and accurately reading bloody or contaminated amniotic fluid. The Ovenstone Factor measures the derivative of the bilirubin curve against wavelength and thereby avoids some of the contaminating pigments at 450 millimicron. This paper compares the predictive accuracy of two methods, Liley versus Ovenstone Factor, in 78 samples of fluid from 46 patients. Predictions were correct in 80% of infants using Ovenstone Factor and 67% using the Liley curve, and incorrect in only 7% and 13%, respectively. The Ovenstone Factor, with its simplicity and high predictive accuracy, is an excellent additional tool in the management of Rh-sensitized pregnancies.


Familial Waldenström's macroglobulinaemia: a case report.

A patient with Waldenström's macroglobulinaemia, whose father died of the same condition, is presented. The literature on familial occurrence of paraproteinaemia is briefly reviewed.


Age differences in health care spending, fiscal year 1976.

Of the $120.4 billion spent by the Nation for personal health care in fiscal year 1976, 29% was spent for those aged 65 or older, 15% for those under age 19, and the remaining 56% for those aged 19-64. The average health bill reached $1,521 for the aged, $547 for the intermediate age group, and $249 for the young. Public funds financed 68% of the health expenses of the aged with Medicare and Medicaid together accounting for 59%. Private sources paid 74% of the health expenses of the young and 70% of the expenses of those aged 19-64. Third-party payments met 65% of the health expenditures of all those under age 65.


Serum hepatic enzyme and bilirubin elevations during parenteral nutrition.

Serial liver enzyme and bilirubin concentrations were measured in 100 patients undergoing total parenteral nutrition. Between the eighth and tenth days, serum glutamic-pyruvic transaminase levels rose to 5.4 times pretotal parenteral nutrition levels; serum glutamic-oxalacetic transaminase, 2.8 times; bilirubin, 2.3 times, and lactic dehydrogenase, 1.5 times. These elevations were transient, lasting four to ten days. Biopsies  of the liver taken during maximal elevations demonstrated marked periportal fatty change. A second elevation of serum glutamic-pyruvic transaminase, serum glutamic-oxalacetic transaminase, alkaline phosphatase and lactic dehydrogenase occurred in one-third to one-half of those patients receiving total parenteral nutrition for longer than a 20 day period. These elevations were more prolonged, and no biopsies were taken. Amino acid solutions contain conversion products of tryptophan, an amino acid that is unstable in the presence of the preservative sodium bisulfite which is added to all commercially available protein solutions. Infusion of these products into rats, either alone or as part of total parenteral nutrition solutions, resulted in periportal fatty change of the livers identical to that seen in our patients receiving total parenteral nutrition. A toxic effect of tryptophan conversion products in total parenteral nutrition solutions is proposed.


Studies on the in vivo cellular reactions of insects: an ultrastructural analysis of nodule formation in Galleria mellonella.

Cellular aggregates or nodules which formed in Galleria mellonella larvae in response to injections of killed Bacillus cereus were examined during their first 24 hr of development. The initial aggregation stage was very rapid, occurring within 1 min, and was brought about by the release of an adhesive flocculent material by granular haemocytes in contact with the bacteria. This material, which subsequently became increasingly electron dense owing to melanin deposition, consolidated and by 5 min ramified all the intercellular spaces. The granular cells degenerated, releasing portions of cytoplasm form their peripheries, and eventurally appeared in the matrix as voids containing loosely flocculent material. No bacterial breakdown was seen, however. From 2-4 hr, plasmatocytes began to encapsulate the necrotic mass, and by 24 hr a complete sheath, composed of three discrete regions of cells, was formed. These findings are discussed in relation to the various proposed mechanisms of nodule and capsule formation.


[Contribution to the radiation therapy of cerebral tumors (author's transl)].

Postoperative radiation therapy chiefly has to be regarded under the aspects of prevention or delay of recurrences. Primary radiation therapy without surgical extirpation of the principal mass of the tumor generally represents a palliative measure. As the radiosensitivity of a cerebral tumor is not exclusively dependent on the histological picture, histology should not influence the indication for radiotherapy. A diagnosis however, based on all clinical means, being reliable to a high degree, is a condition of the radiation therapy of brain tumors without a clear histologic determination. In this paper are reported the results of treatment from 132 intracranial tumors, and compared with data from literature.


[Pendulum irradiation of the middle part of the esophagus with rapid electrons and ultrahard X-rays (author's transl)].

In order to find out whether the moving field irradiation with rapid electrons and ultrahard X-rays of a 42 MeV betatron is suitable for the radiotherapy of the esophagus carcinoma, we took measurements on the Alderson phantom. By both methods--irradiation with rapid electrons as well as mono-axial pendulum irradiatin with ultra-hard X-rays--we did not achieve a satisfactory dose distribution, because lung segments of different sizes or the spinal marrow were reached by a relative dose which was too high. The bisegmental pendulum irradiation is the only one which leads to a dose distribution producing a good concentration in the target volume and sparing the surrounding tissues.


Carcinoma within urethral diverticula.

Because diagnosis of urethral diverticulum is often elusive the presence of a tumor within the diverticular cavity may be overlooked until it has grown beyond the confines of the diverticulum. A search of the medical records from 1940 to 1975 at the University of California Medical Center in San Francisco and Alta Bates Hospital in Berkeley has revealed only 3 cases of carcinoma within a urethral diverticulum. Two are presented here and the third was reported by Hinman in 1960. The paucity of cases in the literature reflects the rarity of such location for the tumor--or, perhaps, rather its evasive diagnostic nature. Undoubtedly, many cases are unreported but the important message for the clinician is that he suspect a urethral diverticulum (with the possibility of underlying neoplasm) in any patient with unexplained persistent irritative symptoms of the lower genitourinary tract.


Comparative effects of chloralose anesthesia and Sernylan analgesia on cerebral blood flow, CO2 responsiveness, and brain metabolism in the baboon.

A comparison was made between the effects of two different anesthetics, alpha-D-gluco-chloralose and 1-1-phenylcyclohexyl piperidine hydrochloride (Sernylan), on cerebral blood flow (CBF), brain metabolism and cerebrovascular CO2 responsiveness in primates. The experiments were carried out on immobilized and artificially ventilated baboons. Anesthesia was induced either with 100/mg/kg chloralose (i.p.) or with 1 mg/kg Sernylan (i.m.). CBF in 8 different brain regions was measured by the intra-arterial 133Xe clearance technique. The CO2 responsiveness of the cerebrovascular bed was tested by a gas mixture containing 5% CO2. Chloralose depressed total as well as regional CBF compared to the effect of Sernylan. A significant shift occurred toward lower CBF values in the grey matter while white matter flow was identical in the two groups. Brain O2 consumption was significantly higher during Sernylan analgesia (3.35 +/- 0.34 ml/100 g/min) than during chloralose anesthesia (2.42 +/- 0.22 ml/100 g/min). There were no differences in glucose uptake, lactate and pyruvate production, or in arterial and cerebral venous blood gases in the two types of anesthesia. The cerebrovascular CO2 sensitivity of the Sernylan-treated baboons was higher than that of the chloralose-anesthetized animals, in both the grey and white matter.


Brain water alterations after unilateral nephrectomy. A study of regional circulatory factors in squirrel monkeys.

White and regional gray matter distributions of water, blood flow, and the protein tracer pertechnetate were measured in five normal squirrel monkeys. A second group of five monkeys, which had undergone unilateral nephrectomy six months previously, were found at the time of study to have blood pressures similar to those of the control animals but increased brain water and altered distribution of blood flow which was increased in white matter. No alteration of capillary permeability to the protein traces attended these changes, which appeared to be influenced by blood pressure. Nephrectomy without hypertension influences brain water content, perhaps because of an effect on cerebral resistance vessels. In hypertensive encephalopathy renal lesions, as well as intraluminal pressure changes, may be related to cerebral edema.


[Intravital effect of DDT and gamma-HCH residues on selected parameters of the nutritive value of porcine lard].

On the basis of FAO/WHO tolerance recommendations, slaughtered pigs were divided into groups with gamma-HCH residues ranging from 0.5 to 2.0 mg per kg and with DDT residues ranging between 0.5 and 5.0 mg per kg in fat. Groups with negative residue findings were formed for control. Some parameters of the biological value of lard were determined in pig back fat. The presence of DDT and gamma-HCH residues did not change the melting and congelation points of lard. The acid number was higher by 31%, the saponification number dropped by 2.6%, the iodine number by 7.6%, the level of palmito-oleic acid by 16%, linoleic acid by 15% and linolenic acid by 40% due to the presence of DDT residues in lard. In the lard containing gamma-HCH residues the acid number increased by 42%, the saponification number decreased by 3.6%, the number of 8.1%, the level of palmito-oleic acid by 14%, linoleic acid by 18% and linolenic acid by 30%. It has been inferred from the results that the presence of DDT and gamma-HCH residues in the organism of a pig reduces the biological value of lard owing to the probable alteration of fat metabolism.


[Therapy of hypodermyiasis in heifers from the economic point of view].

The test set of animals consisted of sixty one- to two-year-old heifers of the Slovak Spotted and Pinzgau breeds kept at three sites. The Hypocid preparation (containing 40% trichlorphon) in the dose of 15 ml per 100 kg of live weight was applied to these cows by the lavage method in the sacrolumbar region of the spine in 1973. Another group, consisting of 58 heifers, was left untreated as controls. In the experimental period extending over 158, 150 and 120 days at different sites (143 days on an average), weight gains and the health condition of the experimental and control animals were checked in monthly intervals. The average extensity of invasion in the control heifers was 79.31% and the intensity of invasion was 14.58%. The extenseffectiveness of Hypocid (EE) was 97.90% and the intenseffectiveness of the preparation (IE) was 99.99%. The results prove a negative effect of hypodermatosis on the weight gains of untreated heifers and high profitability of the therapy: after subtraction of the costs of therapy the savings were 1.74, 3.88 and 2.25 crowns per kg gain per day (2.62 crowns on an average). The veterinary measures gave the following savings per each crown expended: 2,243.55; 3,066.85 and 922.83 crowns (depending on site).


Obliteration of vestibular and cochlear aqueducts in animals.

The right vestibular aqueduct was obliterated in guinea pigs, chinchillas, and monkeys, and the right cochlear aqueduct and both the right vestibular and right cochlear aqueducts were obliterated in guinea pigs and chinchilas. Changes in auditory acuity were monitored by determining averaged temporal-response thresholds, and temporal-bone histologic studies were performed. Obliteration of the vestibular aqueduct or both the vestibular and cochlear aqueducts consistently produced endolymphatic hydrops in guinea pigs. In these animals, the auditory acuity gradually deteriorated. The low tones consistently were depressed more than the high tones. The auditory changes corresponded to the severity of endolymphatic hydrops. On the other hand, no significant histologic or audiometric changes were demonstrated in monkeys after obliteration of the vestibular aqueduct or in chinchillas after obliteration of the vestibular aqueduct or of both the vestibular and cochlear aqueducts. No significant histologic or audiometric changes were demonstrated in guinea pigs and chinchillas after obliteration of the cochlear aqueduct.


[Effectiveness of fenbendazole (Panacur) in cattle invaded by gastrointestinal and pulmonary nematodes].

The effectiveness of the new anthelmintic fenbendazole (Panacur) produced by Hoechst, W. Germany, was tested in cattle naturally invaded by gastro-intestinal and pulmonary nematodes. The single dose of 5.7 mg per kg or 7.5 mg per kg body weight administered either in the form of a 10% suspension or in pellets containing 1.5% of the active substance gave 100% intenseffectiveness and 100% extenseffectiveness in the control of Dictyocaulus viviparus, Haemonchus contortus, Trichostrongylus spp., Ostertagia spp., Oesophagostomum spp. and Cooperia spp. The animals tolerated the administration of both drug forms without showing any undesirable symptoms.


[Nonspecific esterase and naphthol-AS-D-chloroacetate esterase in monocytoid and myeloid cells of healthy cattle and cattle suffering from leukosis].

The reaction to non-specific esterase can be used for the identification of the monocytoid cells of the periphery. A negative reaction is exhibited by neutrophile and eosinophile leucocytes and erythrocytes. Varying results are obtained from lymphocytes, rendering it impossible to use this method in the group of lymphoid cells of the periphery or marrow. In the group of large marrow cells (promonocytes), non-specific esterase gave a very strong reaction; this applies both to the marrow of healthy cattle and cattle suffering from leucosis. For the time being, efforts to use this reaction for the solution of the problem of the differentiation of monocytoid cells and cells of similar size in the myeloid series of the bone marrow have not been successful. In neutrophile leucocytes of the periphery, naphtol-AS-D-chloroacetate esterase gives a less intensive reaction than in humans. For this reason, it is less suitable for the differentiation of these cells. Other cell types (eosinophile leucocytes, monocytes, lymphocytes, erythrocytes as well as their bone-marrow stages) give a negative reaction. In the group of large marrow cells of the myeloid series (promyelocytes and neutrophile myelocytes), naphtol-AS-D-chloracetate esterase shows a more intensive reaction in healthy cattle, as compared with cattle suffering from leucosis.


[Metabolic reactions of calves to the feeding with Laktosan or unpasteurized whole milk].

The acid-base and other metabolic reactions to nutrition with Laktosan produced by two feed plants and with unpasteurized whole milk after transport to a dairy plant were studied in calves up to the ninth week of age. Laktosan feeding reduces the metabolic component of the acid-base balance; the use of a lower-quality Laktosan mixture, containing drum-dried milk, gives a picture of metabolic acidosis lasting about 11 days. The changes are cuased by an increased intensity of dissimilation, by the release of metabolic H+, and, in part, by the loss of bases during diarrhoea. With the use of low-quality Laktosan, the utilization of the nutrients of the feed ration is much lower than the utilization of the nutrients of unpasteurized milk or high-quality Laktosan. The use of high-quality Laktosan causes much lower acid-base changes, far from reaching pathological values. At the same time, the utilization of nutrients is higher than with the use of unpasteurized milk. This milk which cannot be considered microbially or chemically undamaged offers no advantages from the health-condition and economic point of view. The facts, revealed by the study, emphasize the high health and economic importance of the production of calf feed mixtures. At the same time the results show that enither milk nor Laktosan feeding provides enough magnesium for the calves to grow. Other metabolic aspects of different calf nutrition are discussed.


Conservation of hearing in acoustic neurilemmoma excision.

Conservation of hearing in acoustic neurilemmoma surgery is possible by the suboccipital route. The hearing preservation prognosis decreases as the size of the cerebellopontine angle neoplasm increases. Von Recklinghausen disease spells a poor prognosis for hearing. Some hearing was retained in seven of ten patients with preoperative hearing. Three patients retained postoperative hearing levels and speech sound discrimination equal to preoperative levels. One patient had a progressive high-frequency sensorineural hearing loss in the nontumor ear and was fitted with a hearing aid for the postoperative ear; he now has successful binaural hearing function. Gentle technique, microhemostasis, special instrumentation, and well-developed surgical craft are essential for preserving the microstructures necessary for hearing. Furthermore, the suboccipital approach for neurilemmomas less than 2 cm gives good surgical exposure and a reasonable chance to save hearing.


[Effect of potassium-hydrogen interaction in the excretory mechanism of the kidneys on the acid-base and other biochemical values of the blood and urine in calves].

The effect of the competitive relationship between potassium and hydrogen in the excretory mechanism of the kidneys on metabolism was studied in calves. The intraruminal exposure of calves to 5.6 meq potassium chloride (KCl) per kg per day has, in itself, only a slight acidotic effect ascribable to a slight reduction of the excretion of acid by the kidney. The same dose of ammonium chloride (NH4Cl) has a strong acidotic effect combined with a negative influence on weight gain. Both basic types of exposure increase the concentration of inorganic phosphorus and reduce the concentration of chlorine in the blood serum. The addition of 2.8 meq of potassium chloride per kg per day to the basic dose of ammonium chloride increases metabolic acidosis, worsens the health condition (being, at times, hazardeous to life) and leads to weight losses. The same amount of ammonium chloride added to the basic dose of ammonium chloride has a relatively small acidotic action on the blood, evoking only a slight and temporary potassium retention in the serum. The negative action on the weight gains and clinical symptoms are generally weaker than in the other group. The results indicate that the acidotic environment creates in ruminants a very dangerous situation if the organism is excessively exposed to the effect of potassium at the same time.


[Examination of muscular and liver tissues of fish for the presence of aflatoxin B 1].

A method of the determination of aflatoxin B1 in the liver and muscular tissue of carp is described, enabling the capture of 50 ng in one kilogram. Extraction and purification were followed by thin-layer chromatography and by identification by means of ultraviolet light with simultaneous comparison with the standard. The examination was performed with 44 samples coming from healthy table carp from the Pohorelice farm of the State Fisheries National Corporation. None of the 44 the Pohorelice farm of the State Fisheries National Corporation. None of the 44 samples contained aflatoxin residues.


[Pathogenicity of aerobically sporulating microorganisms: Bacillus subtilis].

Bioassays were made on white mice and rats to find the potential pathogenicity of B. subtilis and its metabolites. The peroral and intraperitoneal application of several strains of B. subtilis to white mice did not cause any changes either in the behaviour or health condition of the animals until the first to seventh day after test. B. subtilis cultures or cellular suspensions on the one hand and non-cellular filtrates of cultures represented by the B. subtilis metabolism products on the other hand were given to the animals. No changes in the health condition of the mice and rats were observed when feed artificially infected with B. subtilis was fed. Dissection did not reveal any macroscopic changes on the organs of the abdominal and thoracic cavity. Cultures from the individual body organs (liver, spleen, kidneys, parts of the small and large intestines, stomach) perorally infected with B. subtilis showed the presence of the microbe only in parts of the digestive tracts.


Recurrent convulsions in a thoroughbred foal: management and treatment.

A thoroughbred foal had a convulsive attack 12 hours after birth followed by further convulsions on the 10th, 11th and 12th days after birth. It was treated successfully by medication with primidone, feeding by stomach tube and careful nursing.


[Chemical and serological studies of Brucella abortus 99 bacterial wall fractions].

Mahadevan and Tatum's method was used to isolate four fractions from the bacterial walls of Brucella abortus 99. Determined were the amino acid composition and the purity (by means of the complement fixation test) of these fractions. Infrared spectroscopy was carried out as well. It was found that: 1. The particular fractions differ by their amino acid composition. 2. The fractions are practically pure. 3. The functional groups established confirm previous data of the author on the chemical composition of the wall, and give an idea about the distribution of these groups among the individual fractions. The fractions obtained prove to be the building ingredients of the Brucella abortus 99 bacterial wall.


Plants as hosts for animal viruses.

Theoretical considerations and experimental data on the modification of incompatibility relationships between animal viruses and plants are reviewed. Some cases of interaction between presumably incompatible partners are described, and the possible resistance mechanisms are analysed. The new possibilities of virus--cell interaction are discussed as regards both their theoretical implications and the prospects of their application in research and clinic.


[Effect of fractionation dosage of fast electrons on the cell cycle of ascites tumor NK/Ly].

It was found that irradiation increases the duration of the cell cycle (Tc) and decreases the proliferative pool (Pc) in ascites tumor NK/Ly. In fractionated schedules Tc was dependent on the dosage per fraction, while for Pc no such dependence was noted.


Observations on the number of available C antigen sites on red cells.

The number of available C (rh', Rh 2) antigen sites within the Rh system was estimated using trace-labelled antibody. The results, as available sites per red cell, were as follows: CDe/CDe: 45,700-56,400; Cde/Cde: 42,200; CDe/cDE: 25,500-39,700; CwDe/cde: 21,500-40, 000; Cde/cde: 31,100; CDE/cDE: 8,500-9,800; Cde/cde: 7,200. The average equilibrium constant of the anti-C was 0.5 X 10(7) M-1.


[Thermal inactivation and storage behavior of technologically important enzymes. II. Lipase from Geotrichum candidum and lipoxygenase from soybeans].

The thermal inactivation of lipase out of Geotrichum candidum and of lipoxigenase out of soybeans was investigated in phosphate buffer solution. Comparable to peroxidase, a sharp bend was observed in the inactivation curves of both enzymes. The z-value of 19 degrees C for lipase out of Geotrichum candidum was higher than the values indicated in the pertinent literature for pancreas lipase and milk lipase. The z-value for soy lipoxigenase was found to be 9.8 degrees C.


[Thermal inactivation and storage behavior of technologically important enzymes. III. Effect of reagents added to peroxidase and lipoxygenase].

The influence of milieu factors on the thermal inactivation of peroxidase and lipoxigenase was investigated. Cationogenic, anionogenic, non-ionogenic and amphoteric tensides were more or less effective in inactivating horseradish peroxidase. Most effective in this respect were lecithine and monoglyceride, both capable of swelling in water. In presence of lecithine, peroxidase was inactivated already at 0 degrees C and pH 4.0. Linoleic acid was more efficient in an oxygen stream than in presence of nitrogen, in a stream of nitrogen its influence was comparable to oleic acid. This suggests an additional effect by lipid peroxides which are formed of linoleic acid under the heating process. Tensides prevented the regeneration of the heated peroxidase. In the case of lipoxigenase, the authors investigated the influence of lecithine and various fatty acids on the thermal inactivation at 60 degrees and pH 7.0. Lecithine accelerated the inactivation less distinctly than with peroxidase. The accelerated the inactivation less distinctly than with peroxidase. The accelerating effect of the fatty acids decreased in the order oleic acid, linoleic acid, palmitic acid, myristic acid and stearic acid.


Synergy of vancomycin with penicillins and cephalosporins against pseudomonas, klebsiella, and serratia.

A model of antibiotic synergy based on a molecular mechanism of action which blocked sequential steps in a single metabolic pathway was tested. Twenty-five strains each of Pseudomonas, Klebsiella, and Serratia were tested in vitro against three different two drug combinations of vancomycin, carbenicillin, or cephalothin. Synergy was observed when vancomycin was combined with either carbenicillin or cephalothin against isolates of Pseudomonas or Serratia, whereas the combination of carbenicillin and cephalothin did not result in significant synergy against these isolates. The presence of synergy was not related to the sensitivity or resistance of the isolates to the drugs in the combination. Synergy was also observed with all three antibiotic combinations against Klebsiella isolates which may be related to enzyme inactivation by one of the drugs in the combination. These observations support the hypothetical model of antibiotic synergy based on sequential blocking of one biochemical pathway.


[Left ventricular contraction reserve in coronary heart disease. Evaluation, quantification and prognostic value (author's transl)].

Regional and overall left ventricular contraction reserve was studied in 14 patients with coronary heart disease, in 5 healthy subjects and in 4 patients before and after aorto-coronary bypass surgery. Quantification of overall contraction was based on ventricular volumes and ejection fraction. Regional contraction reserve was calculated with the hemiaxis method and a ventricular score. Contraction reserve under nitroglycerin and in postextrasystolic beats was compared. For routine quantification of contraction reserve the ventricular score is recommended. For research purposes the hemiaxis method is to be preferred. Postextrasystolic beats are better suited for analysis of contraction reserve than are angiograms following administration of nitroglycerin. This is due to the minor expense of the procedure, furthermore, postextrasystolic beats allow better differentiation between contracting and non-contracting areas. Left ventricular contraction reserve is larger in patients with coronary heart disease, angina pectoris and ischemic reactions in the exercise ECG than in control patients. These findings are based on overall and on regional volume parameters.  A quantitatively greater improvement in contraction could be provoked in the anterior wall than in the posterior wall. Regional contraction improved significantly in most cases either in the anterior wall or in the posterior wall; rarely it improved simultaneously in both left ventricular regions. In a few cases contraction deteriorated in one area with a simultaneous improvement in the opposite area. Overall and regional ventricular function, as assessed preoperatively by contraction reserve determinations could not be completely regained in normal beats after successful bypass surgery. Differences in the regional contraction reserve seemed to be mainly due to varying degrees of ischemia and scarring.


[Vitamin A and lipids in serum during long term dialysis program].

The author stated an increased serum level of A-vitamin and triglycerides in non-dialysed and dialysed patients with chronic renal insufficiency. The beta-carotene-serum level was higher only in the group of the non-dialysed patients. Under influence of the haemodialysis a reduction of the triglycerides in the serum developed. A linear correlation between the beta-carotene and the cholesterol serum level in non-dialysed patients and the vitamin A and the triglyceride serum level in patients in the permanent dialysis programme. Finally follows a discussion of the authors on the metabolic sequels of the A-hypervitaminosis in the uraemic syndrome of patients with chronic renal insufficiency.


[Ultraviolet spectrophotomerty studies of serum dialysate from patients with long term intermittent artificial kidney treatment].

In 16 chronically dialysed uraemic patients in the course of altogether 61 treatments with the artificial kidney the UV-absorption spectre of the in-vitro-dialysate of the serum was studied. In uraemia on account of the retention of the metabolic products the UV-absorption spectre of the serum dialysate is extremely increased, a decrease is to be registered after the dialysis. The method discussed is suitable for the control of the effectiveness of haemodialysis and gives a more complex picture concerning the changes during the treatment than the usual laboratory parameters.


[Combined therapy for lung cancer (author's transl)].

During 1963 to 1975, 188 patients were operated following pre-operative irradiation on a betatron with 25 MEV energy. The irradiation was conducted for 2 to 3 weeks from 2 or 3 fields daily. The total focal dose ranged 2500 to 4500 rad. Radical interventions were performed in 159 patients (pneumonectomy in 80, bilobectomy in 13, lobectomy in 60, lobectomy with main bronchus resection in 6). Th lethality rate comprised, 6,7%. Over 3-years survival was achieved in 69.1%, over 5-years survival in 57.3%. Preoperative irradiation on a 25 MEV betatron favours an improvement of the patient's state and produces a favourable effect on the clinical and radiological manifestations of lung cancer. A comparative study of the morphology in the diagnostic biopsy material and in the lung specimens removed following irradiation demonstrated a varying degree of pathomorphism of cancer, down to a complete disappearance of the tumour and radial sclerosis development.


[Quantitative determination of menstrual blood loss using the clinical whole-body counter].

In 20 females the whole-body retention test using 59Fe was carried out for quantitative determination of menstrual blood loss. In hypomenorrhoea blood loss ranged from 10 to 40 ml and in normal menstruation from 70 to 150 ml. Blood losses in excess of 150 ml should be considered as hypermenorrhoea. This method constitutes an extension of diagnostic facilities with respect to confirmation of data given in the history of the patients concerning blood loss at menstruation and with particular problems (e.g. undisclosed cases of anaemia, bleedings with uterus myomatosus or with an indwelling endouterine pessary).


[Studies on the binding capacity of thyroxin-binding globulin (TBC), total thyroxin (T4), free thyroxin index (FT4-I) and the ETR-test in gestosis and placental insufficiency].

Total serum thyroxine (T4), thyroxine binding capacity (TBC), free thyroxine index (FT4-I) and effective thyroxine ratio (ETR) were measured in 53 toxemias of pregnancy and in 5 cases with placental insufficiency. Total serum thyroxine, ETR and FT4-I were found in physiological ranges of the normal pregnancy, the TBC-index was decreased. Between the 19. and 34. week of pregnancy, the decrease of the TBC-index was smaller than after the 34. week of pregnancy.


[Suprapubic puncture of the bladder within the scope of bacteriological urine diagnosis in gynecological-obstetrical patients].

Technology, evidence as well as indications and contraindications of the suprapubic bladder puncture are shown from a gynecological and obstetrical point of view. The bacteriological result of urine obtained by puncture from 476 women has been compared with that obtained subsequently by midstream voiding. It was proved statistically that bladder puncture yielded less positive results than midstream voiding. In 8.4 per cent of the cases there was a positive voided midstream urine culture with pathogenic bacteria while the samples of bladder puncture were sterile, thus 29.2 per cent of the positive voided midstream urine cultures proving to be "false-positive" concerning an infection of the bladder and of the upper urinary tract. The frequency of pathogenic bacteria, "apathogenic" bacteria and mixed cultures is given, divided into conforming and nonconforming culture results of puncture and midstream urines.


[Heterologous transformation in Bacillus subtilis. 1. Transmission of DNA of the R1drd19 plasmid].

Bac. subtilis 168 (BD-25) cells were infected with DNA of plasmide R1drd19 isolated from E. coli strain; transformants resistant to streptomycin (500 microgram/ml) and kanamycin (40 microgram/ml) appeared with the frequency of 2.10(-6). These transformants retained resistance to the mentioned antibiotics stably. A satellite DNA peak was revealed in centrifugation in the density gradient of cesium chloride with ethidium bromide. It was possible to infect cells of Bac. subtilis 168 (BD-25) with plasmide DNA isolated from the transformants. Plasmide transduction with the aid of phages AR9 and PBSI multiplied on the transformant strains was also effected. Physico-chemical analysis of the transformed plasmide DNA was conducted; its molecular weight was determined.


[Certain characteristics of isolation of human myelomic IgG of different subclasses and their distribution according to the allotypes, subclasses and types of light chain].

A combination of the methods of preparative electrophoresis in agar gel and of the ion-exchange chromatography on DE-32 cellulose permitted to obtain 32 immunochemically pure human myelomic IgG. The proteins of the first three subclasses were obtained by elution in the 0.01 phosphate buffer at pH 7.6. IgG4 was eluted with the increase of the gradient to 1 M NaCl in the phosphate buffer. Of the 32 human myelomic IgG 26 represented IgG1,4--IgG2, 1--IgG3, and 1--IgG4. Among the 26 IgG1 11 were of the Gm(a) allotype, and 15 proteins had the Gm(f) determinant; one IgG2 protein was Gm(n+) and 3--Gm(n-). One IgG3 protein was referred to the Gm(b) variant. The majority of the IgG proteins of the subclass I had chi-type of the L-chains, and the chi: lambda ratio constituted 2.71.


[Coexistence of coacervate systems of different chemical composition].

Protein--nucleic acids--carbohydrate drops stabilized at pH 6.0 by the products of oxidative enzymes (polyphenol oxidase and peroxidase) were mixed with unstabilized ones. Using light, luminescent and electron microscopic techniques, a possibility was demonstrated of co-existence of coacervate drops with different chemical composition and formation of colonies from them. Coacervate drops are considered as a primitive form of cooperation of molecules in the course of the origin of the living matter. The results obtained will be used for obtaining more complex coacervate systems by imitation of a chain of catalytic reactions.


[Comparative characteristics of corticosteroid metabolism in lower simians and man].

Corticosteroid metabolism has been investigated in Macaca mulatta, Papio hamadryas, Cercopithecus aethiops, Erithrocebus patas and man. Similar character of corticosteroid metabolism in monkeys and man was found. Significant interspecific differences with respect to quatitative and qualitative parameters of the metabolism of steroid hormones were found. In this respect M. mulatta and P. hamadryas are most similar to man as compared with other monkeys. These two species may be used as an adequate model in studies on human cortico-adrenal system.


[Evaluation of the quality of dry anatoxins in the process of their production].

On the example of production of botulin toxoids of A, B and E types the authors demon strated the expediency of using the agar gel diffuse precipitation test for preliminary assessment of the toxoid activity, instead of a more expensive and complicated antitoxin-binding test.


[Duration and intensity of postvaccinal immunity to plague in experimental animals].

Experiments were conducted on guinea pigs and Papio hamadryas; it was shown that a reduction of the intensity of postvaccinal immunity occurred at various periods after a single vaccination. In inhalation method of immunization in guinea pigs it decreased in 6 months 135 times, in monkeys in one year--133 times. However, at the mentioned periods vaccination provided protection of 50% of the animals from infection with Past. pestis in a dose constitutin 20 to 25 aerosol LD50 for nonimmunized animals. Despite the more pronounced (57--640 times) reduction of the intensity of immunity than in the animals vaccinated by inhalation, in the subcutaneously vaccinated guinea pigs in subcutaneously infected with Past. pestis protection level remained high (resistance index in 3 and 6 months constituted 37.10(6) and 3-3-10(6), respectively).


[Several features of the antigenic structure of Bdellovibrio bacteriovorus].

A method of growing Bdellovibrio bacteriovorus (Bdv) based on the use of the host microbe in the state of reduced vital activity permitted to obtain Bdv cultures which could be used for the preparation specific antisera. Immunochemical analysis of 4 Bdv strains showed them to possess individual antigenic components localized in the alpha 2-globulin zone. Testing 17 Bdv strains isolated from natural water bodies showed 11 of them to form precipitation lines with the antisera to 4 Bdv strains.


[Penetration of vaccinia virus through the mucosa of the small intestine and its dissemination in the body following enteric immunization of monkeys].

The authors studied the penetration of variolo-vaccine virus through the mucosa of the small intestine of Macacus rhesus in enteral immunization, by immunofluorescent and virological methods. Fifteen minutes after the immunization the variolo-vaccine virus was revealed at the surface of the mucosal prismatic epithelium and in the t. mucosa propria within the cytoplasm of cells of the macrophage type. Dissemination of the process with detection of the variolo-vaccine virus in the blood, the lymph nodes, spleen and liver was determined within the range of 1 to 3 hours.


[Morphologic characteristics of spheroid elements in a culture of bacterial L-forms according to scanning electron microscopy findings].

The authors studied stable L-cultures of Proteus valgaris, Bac. subtillis, Staphylococcus aureus, Streptococcus pyogenes of group A, and also unstable cultures of the L-forms of Proteus vulgaris and Proteus vulgaris culture at the stage of spheroplasts. Spheroid cells proved to appear at the stage of spheroplasts, prevailed at the log phase in stable and unstable L-cultures, but were less frequent at the stationary phase. Cross section of L-colonies showed that they were located at the surface. The size of spheroid elements was from 1 to 5 micron; their surface was smooth or slightly wrinkled with numerous protrusions and individual sockets. The spheroid cells were distributed in the colonies freely, in clusters, or were connected to one another by anastomosis. Several methods of reproduction of spheroid cells are described, including equal and unequal binary fission, budding, and formation of elementary bodies within the cell. Morphological connection of spheroid cells with large bodies, filamentous structures and structureless matrix of the L-colony apparently pointed to their origin from the corresponding elements of the L-cultures.


[Role of the vascular component in the pathogenesis of headaches in neurotic patients].

The authors studied the volume velocity of extracranial blood flow by an original method of venous occlusional cranial pletysmography in 40 individuals with headaches of stress and in 30 examinees without headaches in conditions of calmness and in stress influences (cold test, terminal desympathization, counting by mind and a nitroglycerine test). Different types of reactivity of the extracranial vessels in 20 patients with headaches of stress and in 20 examiness of the control group were studied. It was established that the medium figures of the extracranial blood flow in patients with headaches of stress do not differ from the corresponding figures of the normals in the control group. Some stress influences (counting in mind and nitroglycerine tests) in patients with headaches of stress call forth a more frequent increase of the blood flow than in the control group of normals.


[Quantitative analysis of conditional-optimal doses of succilep and trimetin in the treatment of children and adolescents with minor forms of epilepsy].

On the basis of a study of 156 patients the authors with the aid of a computer convened a dispersion analysis of interaction found in the process of treatment by conditional optimal doses of trimetin and succilep with 23 clinical parameters of the disease. It was established that on a statistically significant level the largest dose of trimetin (per 1 kg of body weight) was required in the treatment of myoclonic forms of seizures, with duration less that one year, pathological changes in the craniogram, signs of hypertension and the absence of prenatal noxious factors and pathology in the neurological state. The interaction of optimal doses of succilep with the cliniel characteristics is less expressed than for Trimetin and on a significant level is detected only for two of them: a larger dosage in longer duration of the disease and in the existence of prenatal noxious factors in the past history. It was established that with years the used amount of trimetin adn saccilep (per 1 kg of body weight) declines, while the therapeutical effectiveness does not drop.


A 14-month study of severe non-wound infectious complications in general surgery.

A retrospective study of serious non-wound infectious complications in general surgery during at 14-month period is reported. A prospective study on wound infections in available from the same institution and period. Septicemia, intraabdominal and intrathoracal abscesses and rare cases of osteomyelitis occurred in 1.3% of all treated patients, whereas postoperative wound infection developed in 7.5% of primarily non-infected patients. Mortality was significantly higher among patients with serious infections than in all patients nursed during the same period. Severe postoperative infectious complications was in fact the third most common cause of death and accounted for 14% of the mortality of the clinic. This rate rises to close to 50% when death from incurable disease is excluded. Septicemia carried a significantly higher mortality rate than intraabdominal abscesses. The risk of a serious infection developing was significantly higher in operations on the small or large intestine than after appendectomies or biliary operations. Gram negative bacteria dominated, especially in cases with a fatal outcome. Contributing factors such as malignancy, preoperative infection or macroscopic peroperative wound soiling, were more common in patients where a serious infectious complication developed postoperatively.


Function of the thyroid gland after subtotal resection for hyperthyroidism in relation to remnant size.

The size of the remnant gland after subtotal thyroidectomy varied between 5 and 12 g in 85 hyperthyroid patients. The patients were then examined 6 weeks and 6 months after surgery with estimation of TSH and TRH stimulation test as well as thyroxine and triiodothyronine. A significant correlation between TSH response to TRH and remnant weight was found ( r= 0.94, p less than 0.01). The frequency of raised S-TSH was higher in the group with small remnants compared with those with larger ones. There was only minor correlation between raised S-TSH or high TSH response to TRH and remnant size expressed in per cent of the total thyroid weight (relative remnant size). No significant difference in thyroxine and triiodothyronine was found between the weight groups. Hypothyroidism developed in two patients with small remnants (6 g) and in one patient with a remnant weight of 8 g. Recurrent hyperthyroidism occurred in one patient in the 8-gram weight group. These results indicate that the remnant size may be one factor influencing the outcome of thyroid function after surgery.


Nonspecific esterase activity in 'hairy cells'.

Nonspecific esterase activity using alpha-naphthyl butyrate as substrate was found to be present in hairy cells from patients with hairy cell leukemia. Activity of this enzyme was markedly diminished and in some instances obliterated by sodium fluoride. Since alpha-naphthyl butyrate is believed to be a more specific substrate for monocytic-type nonspecific esterase than alpha-naphthyl acetate, its presence in hairy cells combined with fluoride inhibition which is also characteristic of monocytic nonspecific esterase provides additional evidence of monocytic properties of hairy cells.


Acute promyelocytic leukemia: results of therapy and analysis of 13 cases.

Acute promyelocytic leukemia (APL) was diagnosed in 13 of 84 adult patients (15.4%) with acute myeloid leukemia (AML) first admitted between 1972 and 1976. All patients had clinical and/or laboratory evidence of defibrination syndrome. Four patients died of cerebral hemorrhage within 2 days of admission. Two patients died of generalized infection on days 7, and 16, respectively, after admission. The remaining 7 patients (54%) underwent complete remission (CR) with daunomycin, arabinosyl cytosine, and adriamycin. All patients received massive platelet transfusion, no heparin, and no granulocyte transfusion. CR was more frequent in patients with a very low blast cell count and a fibrinogen level higher than 100 mg/100 ml. Median survival of these seven CR patients with APL is similar (15 months) to that of CR patients with other types of AML treated at the same institution during the same period.


An in vitro demonstration of the ability of human bone marrow stromal elements to sustain granulocytopoiesis.

The ability of human bone marrow particles to produce a microenvironment conducive to granulocytopoiesis was tested by culturing them in vitro without an exogenous source of colony stimulating activity (CSA). Granulocytopoiesis in this system was confirmed by the following observations: (1) presence of mitotic figures in promyelocytes and myelocytes; (2) early disappearance of mature granulocytes, followed by their reemergence after 4 days in culture, and (3) presence of immature granulocytes even after 10-14 days in culture. Although no exogenous source of CSA was added to the culture plates, a probable endogenous source was the dense accumulation of stromal elements in the core of particles; these cells may generate sufficiently high local levels of CSA to stimulate and nurture granulocyte proliferation and maturation.


Regulation of human hemopoietic stem cell proliferation by syngeneic thymus-derived lymphocytes.

Viable T lymphocytes stimulate the proliferation of human syngeneic hemopoietic stem cells, but not influence their differentiation. The biological significance of this activity is discussed and its possible physiological role in the regulation of hemopoiesis is considered.


Sensitization of stabilized fibrin to urea dispersion by undiluted plasma and serum.

Clots obtained from normal native platelet-poor plasma are dispersed by the addition of 5 M urea. Clots from plasma diluted greater than 1/4 and clots from undiluted plasma, thoroughly washed, are not dispersed by urea, but are rendered susceptible to its dispersing action by prior incubation in normal undiluted plasma or serum. The same phenomenon was observed by incubating the otherwise unsoluble clots in normal plasma or serum fractions precipitated at 33% saturation with (NH4)2SO4. The serum fraction does not interfere with the incorporation of putrescine into casein, although it conditions the urea-dispersing action on stable clots.


Binding of deoxyribonucleic acid to the surface of human platelets.

It was demonstrated that washed human platelets can bind minute amounts of 14C-DNA on their surface during short-term incubation. The binding was specific and firm in the described experimental conditions. Washed platelets bound also 14C-DNA anti-DNA antibody complexes, although to a lesser amount than 14C-DNA alone. The possible significance of these findings is briefly discussed.


Metoprolol and the peripheral platelet count.

An acute oral administration of 50 mg metoprolol (a selective beta-1-receptor antagonist) to 18 healthy volunteers induced a significant increase in the peripheral platelet concentration lasting more than 4 h. It is suggested that this increment in the platelet count originates from the exchangeable splenic platelet pool. The mechanism by which metoprolol exerts its effect remains to be established.


Classic hemophilia A in a female.

A 53-year-old woman with a history of recurrent bleeding complications since childhood and a positive family bleeding history, previously diagnosed as von Willebrand's disease, was investigated. She was found to have a markedly reduced level of antihemophilic factor (AHF) activity, a low AHF activity/AHF antigen ratio, normal Ristocetin-induced platelet aggregation and a normal level of von Willebrand factor activity. These findings were consistent with the diagnosis of classic hemophilia A which was confirmed by the results of similar studies in nine of the patient's relatives. The report illustrates the usefulness of newer laboratory methods in the differentiation between classic hemophilia A and von Willebrand's disease which may have important clinical implications.


Incorporation of H3-leucine in the mouse kidney in thrombocytopenia. Attempt to demonstrate thrombopoietin production.

Light and dark field autoradiography of semithin sections prepared 6 h after a treatment with APS showed that the incorporation of H3-leucine into the cells of the convoluted tubules of the kidney was increased in mice. There was no difference in the H3-leucine incorporation in the liver, either in thrombocytopenic or in untreated animals. The increased incorporation of leucine in the kidney in APS-induced thrombocytopenia showed coincidence with increased thrombopoietin production.


Oral contraceptives, anti-thrombin III and fibrinolytic activity in Africans.

A comparison of the effects of progestogen-only and combined progestogen-oestrogen types of oral contraceptives on anti-thrombin III activity and fibrinolysis in African subjects in South Africa is reported. The changes in anti-thrombin III activity are similar to those reported in other races, but the augmentation of fibrinolytic activity is more marked than has been reported elsewhere. The possible significance of these findings is discussed.


Permeability of membrane to potassium in hypochromic red cells with different specific density.

In hypochromic anaemias (heterozygous beta-thalassaemia and iron deficiency anaemia) ligher red cells lose more K+ than heavier ones, following incubation at 37 degrees C for 24 h. Both in the light and heavy fractions two subpopulations of cells with different permeability to K+ can be separated by a new centrifugation after incubation. On the basis of the results, a relationship between K+ permeability and probability of survival in hypochromic cells is suggested.


Red cell metabolism and severe neonatal jaundice in West Malaysia.

A study was carried out of 332 babies suffering from severe neonatal jaundice who were admitted to the General Hospital, Kuala Lumpar, Malaysia. Of the 332 neonates, 51 were premature and 281 were full-term babies, 178 (110 Chinese, 58 Malay, 9 Indian and 1 European-Pakistani) had bilirubin levels of 20 mg% or higher, requiring exchange blood transfusion. Of the Chinese neonates, 23 (20.9%) had G6PD deficiency, 9 (8.2%) had Hb Bart's and 2 (1.8%) had an abnormal haemoglobin, one Hb Q and one fetal variant. Among the Malay infants, 10 (17.2%) had G6PD deficiency, 7 (12.1%) had Hb Bart's and 10 (17.2%) had abnormal haemoglobins (four had Hb E trait, one had Hb K and Bart's in addition to Hb E, three had Hb CoSp with Hb Bart's, one had Hb Q and one Hb Tak). One of the nine Indian neonates had G6PD deficiency and one had Hb S trait. The one European-Pakistani baby was a carrier of Hb D Punjab. In addition to G6PD deficiency, abnormal haemoglobins seem to have contributed to the high incidence of severe neonatal jaundice in Malaysia. The mean activities of GP, GR and GR after stimulation with FAD were higher, while the mean activity of PK and mean level of reduced glutathione were lower than in normal cord bloods. The percent increase of GR after FAD stimulation was significantly lower; fewer in this group had increases above 20% than in normal cord blood. The possible significance of the findings is discussed.


Proportions of mouse erythrocyte rosette-forming lymphocytes, immunoglobulin-bearing cells and E rosettes in patients with lymphoproliferative diseases.

The proportions of mouse erythrocyte rosette-forming (MERF) lymphocytes, immunoglobulin (Ig)-bearing cells and E rosettes were examined in the peripheral blood of patients with lymphoproliferative diseases. The proportion of MERF lymphocytes was considerably increased in chronic lymphocytic leukaemia. The correlation between the proportions of MERF and Ig-bearing cells, characteristic of healthy individuals, is not observed in the lymphoproliferative diseases. It is suggested that in a part of the patients with these diseases, the study of the proportion of MERF cells provides more accurate information on the proportion of lymphocytes of bursal origin than does counting of the Ig-bearing cells.


Atypical B cell dyscrasia with Bence-Jones proteinuria and intracellular retention of gamma-chains.

A case of atypical B cell dyscrasia is described. The patient presented with a history of weakness, bone pain, and bleeding. A K-type paraprotein was found in serum and urine. The histology of bone marrow was that of a malignant lymphoma, but no enlargement of peripheral lymphoid organs was detectable. Peripheral blood lymphocytes were increased in number and included two populations of immature cells, one lymphoid and the other lymphoplasmocytoid. Immunofluorescent staining showed both populations to contain K and gamma chains in their cytoplasm. The clinicopathological heterogeneity suggests a malignant clone of B cells undergoing incomplete maturation, with arrest at different stages of the cell cycle.


Scanning and transmission electron microscopy study on the plasma cells of a patient with multiple myeloma.

The ultrastructural features of the plasma cells of a 32-year-old patient suffering from multiple myeloma are described. The high percentage (90%) of plasma cells in the bone marrow aspirate permitted the examination of an almost homogenous population. The appearance of the plasma cells seen with the transmission electron microscope did not differ from that described in other reports. The surface architecture of the plasma cells, such as revealed by the scanning electron microscope, differed from that of the normal and pathological white blood cells. Of particular interest were the membrane-bound portions of the cytoplasm seen as 'buddings', or round bodies in the vicinity of the plasma cells which contained most probably pathological proteins.