[Pseudo-tumoral round atelectasis without known pleural history (apropos of 2 cases)].

The authors recall two cases of round atelectasis without any known pleural past-record. The first showed, on successive X rays, an increase in size of the image. In the second case a pleural effusion occurred after the discovery of a round opacity. They stress the various small radiological signs as a way of including the etiology of a purely mechanical atelectasis among the difficult diagnosis of intraparenchymal round opacities.


[Osteosynthesis of metastatic fractures of bronchial origin. Analysis of a series of 18 cases].

The authors present a series of 18 femoral and humeral metastases of bronchial origin treated by surgery. They study the results and recommend "closed wound" osteosynthesis, underlying the antalgic character of the intervention which does not modify the already limited survival.


[Tracheal compression revealing a cold mediastinal abscess of Pott's disease origin].

The authors report the observation of a cold mediastinal abscess during a dorsal Pott disease, revealed by a tracheal compression. In relation with the unusual localization, they recall the main characteristics of cold chest abscesses, secondary or apparently primitive, deep or superficial, parietal but rarely mediastinal, and discuss as to their origin : bone, rib vertebra or lymph node. Modes of medical, or surgical treatment are envisaged.


[Intrapulmonary solitary round opacities. Diagnosis and therapy].

The authors envisage the practical problems brought by unexpected intraparenchymal single round images seen on X ray. Thirty to 40% of these opacities proved to be malignant; the proportion rising over 50% in patients more than 50 years old. The great majority of these malignant tumours are primitive and the earlier the exeresis, the better the prognosis. The criteria of benignity (age under 35, presence of calcification amidst the opacity) are not always absolute. For fear of overlooking a malignant tumour, exploring thoracotomy is recommended.


[Femoral embolism during cardiothyrosis].

This is a case of a systemic embolism during an auricular fibrillation because of a toxic thyroid adenoma in a 73 years old man with latent coronaropathy. The femoral obstruction and the adenoma were successfully operated. The study of the pathogenic factors of the embolism complications, in spite of the rarity of published cases, suggests an anticoagulant treatment in certain cases : auricular fibrillation with periodic returns to sinusal rhythm, the patient's old age.


[Asbestosis. Apropos of one case].

Having reported a very complete observation of a patient with asbestosis, as well as silicosis, hitherto undiscovered tuberculosis and a pleural mesothelioma, the authors sum up our present knowledge on the consequences of inhaling asbestos dust. Clinical signs are numerous, benign or malignant, the risks of pleural and broncho-pulmonary cancer being greater in people exposed to asbestos. Diagnosis rests mainly on professional anamnesis and on the presence of great quantities of asbestos bodies in the sputum. Any pleural thickening on X ray should always suggest the development of a mesothelioma. As it now gives right to legal compensation, it is recommended to authentify the malignancy of the thickening by surgery.


[Monitoring of cardio-pulmonary parameters in cases of severe multiple injuries (author's transl)].

Haemodynamic parameters were monitored for one week (in greatest detail during the first 24 hours) in 35 severely injured persons who had been admitted for treatment within one hour after the accident and, as judged by the type of injury, had probably lost more than 1 1/2 litres of blood. The estimations included not only blood pressure, heart rate and shock index; but the cardiac index, pulmonary arterial pressure, pulmonary capillary pressure and parameters of oxygen transport were also determined with the aid of Swan-Ganz catheters. The importance of the data as guide-lines for the correct type of intensive therapy and their prognostic significance are discussed. The evidence provided by the cardiac index, pulmonary arterial and capillary pressure and the parameters of oxygen transport are of particular importance in these cases. A list is added of the values of some haemodynamic factors which should be taken into account in the initial treatment of severely injured persons.


[Disturbances of the clotting mechanism in severe cerebro-cranial injuries (author's transl)].

Factors II, V, X, VIII, thrombin time, platelet count and the thrombelastogram were estimated in 58 persons who had suffered cerebrocranial injuries of varying degree of severity. The aim of the investigation was to elucidate whether and to what extent the injury affected these parameters and whether the destruction of brain tissue could be regarded as the sole cause of the impairment of the clotting mechanism. First estimations in cases of cerebrocranial trauma uncomplicated by other injuries and in cases of cerebrocranial trauma complicated by moderately severe other injuries showed changes in factors II, V, X, VII as well as a pathological thrombelastogram, viz.: hypercoagulability. More pronounced changes were observed in cases where the cerebrocranial injuries were associated with severe complicating lesions: factors II, V, VII, X and the platelet count were reduced by 50-70 per cent of their normal values. Subsequent estimations carried out over a period of 15 days showed that the clotting mechanism had returned to nearly normal within 6-10 days. The use of heparin for normalizing disturbances of the clotting mechanism in cerebrocranial injuries is discussed.


[Hygienic problems in intensive care units (author's transl)].

Microbiological tests have established that intensive care units act as a reservoir from which hospital infections spread. The mode of their spread is reviewed. The increased incidence of nosocomial infections to intensive care wards is attributable partly to deficient antisepsis and asepsis and partly to inadequate planning of the building and organization of these wards. Plans for two intensive care wards are put forward which would reduce the risk of contact, smear and air-borne infections. In the planning of these units greater attention than has so far been the case should be paid to preventing the spread of pathogenic micro-organisms.


[The epidemiology of blastomyces infections with special reference to postoperative intensive care wards (author's transl)].

230 strains of Blastomyces were isolated during a nine month's period in the course of routine laboratory examinations of faecal and other specimens. Candida albicans was the most frequently present (151), followed by Candida tropicalis (39) and Torulopsis glabrata (16). During an environmental study in a postoperative intensive care unit 426 swabs were taken. 88 strains of Blastomyces were cultured from 75 swabs. The observations indicate that Candida albicans as a free-living organism lacks favourable conditions for multiplication in sick rooms and wards, and that it does not play the same role in cross-infection as does, e.g., Psudeomonas aeruginosa or strains of Klebsiella. The same apparently also applies to Candida tropicalis and Torulopsis. Measures to prevent infection with yeast-like fungi in hospitals are reviewed.


[Long-term intubation (author's transl)].

Establishment of a clear airway has become increasingly frequent and is of high importance, especially in patients with severe injuries, head injuries or intoxications. Though the endotracheal intubation-technique has been improved and soft intubation-tubes are now available, tracheostomy is not rendered unnecessary. However, its indications have changed and have become restricted. This trend was proved by the own experiences in 841 patients. The presuppositions for nasal long-term intubation are described in details.


[Complications of resuscitative measures with special regard to liver damage (author's transl)].

Dissection material comprising 71 cases (total material evaluated: 3,082 post-mortem examinations) in which resuscitation measures are known to have been carried out in the case history showed 46.5% resuscitation damage, including an incidence of liver ruptures of 8.5% (6 cases), which are given special prominence. In the event of substantial haemascos and temporarily successful resuscitation rupture of the liver has been found to be a significant factor in the advent of death. Liver rupture cannot always be avoided during external cardiac massage even if performed professionally. The fact that the ruptured liver is attributable to resuscitation does not warrant the conclusion that external cardiac massage has been carried out incompetently.


[Prostaglandins. Various clinical, physiological and chemical aspects].

The prostaglandins (PTGs) are compounds derived  of the essential lipids of diet. The name was received by isolation of the prostate, however, subsequent investigations demonstrate its existence in all tissues investigated, in every species of animals studied and in the mariner choral Plexaura homamalla, that is important fountain of PTGs for investigation. For its localization, action's mechanisms and diverse effects in apparatus and systems they promise to be potent therapeutic arms in diverse diseases. The literature relationed to PTGs is extense, there exist excellent reviews about it.


[Visceral multiple angiomatosis. Clinical case and review of the literature].

It is presented a case of a 62-year old male, with an illness of two months duration suggestive of an hepatic abscess; six months prior to admission he had surgery done because of a suspected cholelitiasis. Because of treatment failure and taking into account the result of the hepatic punctures (dark blood) with decreasing size of the liver, it was assumed to be a case of angioma. His intrahospital evolution was poor and died in hypovolemic shock complicated with acute pulmonary edema despite medical efforts. The post mortem study showed: a 13 cm. cavernous hepatic angioma, variable number of mesenteric, intestinal and cerebral angiomas. The surgical specimen of the gallbladder showed also angiomatosis. A brief review of the literature is done and particular emphasis is placed upon the clinical and angiographic studies of value to reach the diagnosis. The present case is similar to those in the literature because of the confusing clinical picture and fatal outcome.


Etorphine and shuttle-box self-stimulation in the rat.

Rats were trained to turn rewarding electrical brain stimulation on and off by crossing back and forth in a shuttle-box. Moderate doses of the narcotic analgesic, etorphine, increased mean ON times while having little effect on OFF times. Tolerance did not develop to the reward enhancement action over five consecutive days of injections. This paradigm seems valuable for exploration of the reinforcing properties of narcotic drugs.


Dose-response effects of alcohol upon rat strains bred for differences in reactivity to alcohol.

Two rat strains, designated LA and MA, selectively bred for differential impairment of motor activity following an injection of alcohol, were tested in stabilmeters and compared over a range of ethanol doses. As expected, increasing doses of ethanol produced progressively greater activity decrements in both strains; however, the same dose of ethanol induced a more pronounced decrement in the MA strain than in LA strain at all doses. At the highest alcohol dose (2.25 g/kg), the LA animals were twice as active as were the MA strain at the 1.5 g/kg dose. This strain difference in impairment was evident within 3 min postinjection and remained throughout the 30 min test session. The results are discussed in terms of differential neural and behavioral toelrance to ethanol in the two strains.


Selective facilitation of memory attributes by strychnine.

In two experiments, the effects of strychnine on the specific memory attributes of prior discrimination training were assessed in terms of subjects' performance under various discrimination reversal conditions. Mice were trained in a discrimination task with two redundant relevant cues. Immediately after their last training trial, subjects were administered an intraperitoneal injection of either strychnine (1.0 mg/kg) or saline. When both training cues were reversed (Experiment 1), strychnine treated subjects were observed to exhibit greater performance decrements than saline-treated subjects upon initial exposure to reversal conditions, suggesting that strychnine had enhanced the memory of a relatively specific stimulus-response association. When subjects were tested under partial cue-reveraal conditions (Experiment 2) strychnine treated animals exhibited treater utilization of one of the redundant relevant stimuli than the other, while saline-treated animals exhibited no preference.


Restraint alters the effects of morphine and heroin on core temperature in the rat.

The importance of restraint in determining the magnitude of alteration in the rat's core temperature (Tc) after the administration of morphine sulphate (M) and heroin hydrochloride (H) was investigated. M, in doses of 5, 15 and 30 mg/kg, or H, in doses of 0.1, 1 and 5 mg/kg was administered IP to either the restrained or free-moving rats as Tc was measured. After the administration of 5 mg/kg of H or 30 mg/kg of M to the restrained rat, a marked hypothermia was observed which reached a maximum mean depth of 3.1 and 4.5 degrees C below the baseline Tc, respectively. Conversely, a mean increase in Tc of 1.5 and 1.9 degrees C occurred following the administration of these same doses of M and H in the unrestrained animal. Furthermore, the hypothermic effect of the highest dose of M was not observed when the third of 3 consecutive injections of M, administered at 48-hr intervals, was administered to the restrained rat. On the other hand, when M was repeatedly administered to the free-moving rat, the hyperthermic response was consistently observed. Pretreatment with naloxone hydrochloride (5 mg/kg IP) effectively blocked the opiate-induced hypothermia in the restrained animal, but a total dose of 10 mg/kg was necessary to completely block the hyperthermic response in the free-moving rat. Although the factor of restraint itself did not alter the rat's Tc, it did dramatically alter the action of M and H on the body temperature of the rat.


Effect of substance P on medial forebrain bundle self-stimulation in rats following intracerebral administration.

The effect of Substance P infused intracerebrally via chronically implanted electrode-cannulae on self-stimulation induced from the same site was studied in rats. Substance P caused a significant depression of self-stimulation at 60 and 120 microgram/rat. Morphine infused into this site also caused significant depression of self-stimulation, but the doses were considerably lower than those of Substance P (5 and 10 microgram/rat). Pretreatment with naloxone, a narcotic antagonist, significantly antagonized the effects of Substance P on self-stimulation. It is proposed that Substance P modulates self-stimulation by the release of an endogenous morphine-like substance, but the possibility of a direct effect of Substance P was not ruled out.


Effect of chlordiazepoxide on the partial reinforcement extinction effect.

Rats were trained to run in a straight alley under conditions of partial or continuous reinforcement. Extinction was slower after partial reinforcement. Chlordiazepoxide, administered during acquisition only, had no effect on acquisition but abolished the partial reinforcement extinction effect. The results support the hypothesis that chlordiazepoxide acts by attenuating the effects of averisive stimuli.


Drug discrimination and generalization in pigeons.

In a three-key operant conditioning situation six pigeons were trained to select the response key which was associated with each of three drug treatment conditions: d-amphetamine (2 mg/kg), pentobarbital (5 mg/kg), and saline. Thus, the drug state served as a discriminative stimulus for food reinforcement. After 20 sessions of discrimination training in each of the three conditions, more than 90% of the responses were correctly emitted in the presence of the appropriate drug or saline stimulus. Acquisition of the discrimination progressed at approximately equal rates for the three treatments. Subsequent to discrimination training, generalization gradients were obtained for several doses of the training drugs and for dose ranges of cocaine, morphine, and methocarbamol. The pigeons responded to morphine by choosing the key paired with pentobarbital during training; further, cocaine administration resulted in choice of the amphetamine key. However, metocarbamol, over the doses used, produced responding more characteristic of saline than of the other training drugs. The data suggest that a three-key operant discrimination procedure using pigeons provides a sensitive method for investigating the stimulus properties of relatively low doses of behaviorally relevant drugs.


Effect of tetraethyl lead and restricted food intake on locomotor activity in the rat.

The effect of tetraethyl lead (TEL) and restricted food intake on spontaneous locomotor activity in male albino rats was investigated. Forty animals were injected intraperitoneally with 4, 7, 10 or 13 mg/kg body weight of TEL in peanut oil, or a peanut oil placebo. Forty additional animals were food yoked to lead treated animals as a control procedure to hold food intake constant between lead treated and lead free animals. A comparison of pre- and posttreatment measures revealed significant decreases in food intake and increases in activity levels at dosages of 7, 10 and 13 mg/kg of TEL. In addition, food intake and activity were significantly correlated in both lead treated and yoked groups. The issue of factors associated with reduced food intake playing a role in observed activity level increases was raised.


Cholinergic mechanisms involved in head-shaking of infant rats.

Central cholinergic mechanisms involved in D-amphetamine induced head-shaking (H-S) were explored in 9-day-old albino rats using anticholinergic, anticholinesterase and cholinomimetic drugs. Scopolamine (5 mg/kg, IP) blocks both spontaneous and D-amphetamine induced H-S. Physostigmine (0.10 mg/kg, IP), but not neostigmine, increases D-amphetamine induced H-S up to 400%. Pilocarpine (1-10 mg/kg, IP) per se induces H-S and strongly potentiates the amphetamine H-S effect. Cholinergic--catecholaminergic interactions in the CNS are discussed in relation to the expression of this motor item.


GABA stimulation and blockade in the hypothalamus and midbrain: effects on feeding and locomotor activity.

Microinjections of the gamma-aminobutyric acid (GABA) antagonist, bicuculline methiodide (BM) (100 ng), into the anterolateral hypothalamus (LH) increased ingestion of sweet milk. A subsequent injection of BM 48 hrs. later produced a type of kindling effect consisting of feeding related automatisms, such as gnawing and biting. The behavioral effects of injections of 100 ng of GABA into the LH were variable. GABA injections into the ventromedial hypothalamus (VMH) reliably increased food intake. GABA injections into the origin of the nigrostriatal dopamine (DA) neurons in the substantia nigra (SN) suppressed it. Similar injections into the origin of the mesolimbic DA cells in the ventral tegmental area (VTA) had no effect on feeding behavior. Following BM injections into the SN, a moderate increase in tilt box activity was observed. A second injection of the GABA blocker 6 days later exaggerated this effect. Short latency extreme hyperactivation was accompanied by unidirectional barrel rolling which persisted until blocked by local injections of GABA.


Endorphin analogs with potent and long-lasting analgesic effects.

The analgesic effects of intracerebroventricular administration of alpha, gamma, and beta-endorphin and their D-Ala2-analogs were examined in the rat using the tail-flick test. Analgesia was produced by all substances. The actions of D-Ala2-alpha and -beta-endorphin were considerably greater than the parent forms, whereas D-Ala2-gamma-endorphin was approximately equivalent to the parent compound. The marked analgesia was dose dependent and prolonged for all analogs. Since these effects were reversed by the opiate antagonist naloxone, it was concluded that opiate receptors mediate the action of these analogs. It is suggested that these analogs may be useful in behavioral tests when a longer duration of action is desirable.


Effects of cocaine and fenfluramine on progressive-ratio performance.

Pigeons obtained food on a progressive-ratio schedule that required 8 additional responses for each successive reinforcement. The number of responses in the final completed ratio of the session was defined as the breaking point. When cocaine was administered (IM, 5 min presession), the breaking point increased and then decreased as a function of increasing doses (0.3-10 mg/kg). In contrast, across the same range of doses of fenfluramine, the breaking point only decreased. At doses of each drug that decreased the breaking point, the high running rate of responding was interrupted by pauses. At doses of cocaine that increased the breaking point, the running rate was also disrupted, but the disruption was characterized by lower, irregular rates rather than pausing. The increases in breaking point observed at 3 mg/kg of cocaine were no longer seen when fenfluramine was administered at the same time.


The pneumatic syringe: a simple apparatus for self-administration of drugs by rats.

Drug solution is delivered by a syringe operated by a pneumatic cylinder. Recommended delivery volumes are from 10 to 200 microliter. A solid-state control unit is described which can operate two syringes (drug injection and flush), has outputs for recording responses and injections, and can be programmed to provide several schedules of reinforcement. All components are readily commercially available.


Technique for assessing visual discrimination learning in mice.

An automated technique for the study of visual discrimination learning in mice has been developed. The technique utilizes a nose-poke as the operant response. The nose-poke response requires no shaping, has a relatively high operant level and can be used to measure preacquisition exploratory behavior. CD-1 mice acquired a simultaneous brightness discrimination readily but a successive brightness discrimination proved more difficult. A 20 sec intertrial interval was optimal for acquisition of the simultaneous discrimination. Reversal learning was slow. This procedure should prove useful in the study of the effects of pharmacologic and toxic agents on learning and performance in both weanlings and adult mice.


Circadian variation in an amphetamine induced motor response.

Significant diurnal variation in occurrence and duration of D-amphetamine induced head-shaking were observed in 9-day-old rats. The lowest values were obtained near noon, and the highest around midnight. These variations should be considered if head-shaking is to be used as a quantitative neuropharmacological test.


Effects of amphetamine and nembutal on social exploration in the Mongolian gerbil.

Male Mongolian gerbils were injected intraperitoneally with amphetamine, nembutal, or saline and placed in a preference chamber one side of which contained a female gerbil. Amphetamine significantly decreased amount of time in contact with the females. Although the amphetamine effect held for both novel and familiar females, it was more marked for novel than for familiar females.


Potentiometric determination of acid-base contaminations in drugs.

A potentiometric method for the determination of impurities in pharmaceuticals with acid-base behaviour is proposed. Based on proton balance condition, appropriate equations for the treatment of the data are derived. The latter in combination with Gran's equations allow the determination of acid-base impurities in pharmaceuticals--weak protolytes. The proposed method is quick, accurate and precise. It is suitable both for technical control and for analyses according to the pharmacopoeias.


Photometric extraction method for determination of cefalotin.

A selective, accurate and precise photometric method for the determination of cefalotin (1) is proposed. The method is based on a preliminary hydrolysis of the antibiotic in a strong sulphuric acid medium at 100  degrees C for 15 min. The 2-thienylacetic acid (2) formed as degradation product is determined photometrically with ninhydrin in strongly acidic solution. In these conditions 2 forms a yellow reaction product, which is extracted with chloroform and the absorbance measured at 423 nm. The reaction is practically specific as none of the initial substances used in the preparation of cefalotin or of its degradation products (except 2) reacts with ninhydrin under these conditions. The only other antibiotic which also gives a coloured product with ninhydrin in this strongly acidic medium is cefalexin. The latter however does not interfere at its coloured product absorbs at 520 nm. The method is simple, fast and with sufficient accuracy and precision (coefficient of variation 0,57--0,88% and relative error 0,41--0,64%).


Kinetics of drug decomposition. Part 50: Graphic method for calculation of zero-order rate constants of sequential reaction of indometacine photodegradation.

Calculation of partial zero-order rate constants for a sequential reaction was presented following indometacine photochemical degradation according to the equation A k1 leads to B k2 leads to C k3 leads to D. When zero-order rate constants k1 not equal to k2 not equal to k3 and absorptivity coefficients a not equal to b not equal to c not equal to d, then individuell zero-order rate constants can be obtained from simple equations: k1 = [A]0/tA, k2 = [A]0/tB, k3 = [A]0/tC, where [A]0 is the initial concentration of a substrate, and tA, tB, tC are the starting times of the steps of the sequential reaction, which can be read from the plots for a relationship A = f(t).


A contribution to the kinetics of dissolution of some modern drugs.

A report is presented on the investigation of some drugs being used in modern therapy from the point of view of dissolution kinetics in aqueous and in aqueous micellar solutions. It has been established that the dissolution (saturation) process, in accordance with previous assumptions, is kinetically of the first order both in aqueous and in aqueous micellar solutions. The rate constants describing these processes are nearly identical for the same drug, hence the saturation rates are nearly identical. The amount of drug dissolved within the unit of time decreases in the case of drotaverine and "RJ-64" in direct proportion to the concentration of the surfanctant, whereas in the case of the other drugs examined an increase occurred. The interpretation of the process for drotaverine and "RJ-64" needs further experimental clarification. The importance of kinetic concepts in pharmaceutical technology is emphasized.


Physical parameters of chlorphenamine maleate suppositories and its release as a function of particle size, concentration and nature of the base.

Suppositories of chlorphenamine maleate were formulated. The influence of particle size and percentage concentration of chlorphenamine maleate on the physical standards of its suppositories as well as the release of the drug from oily base (cacao butter), water-soluble base (carbowax) and emulsifying base (Witepsol) has been investigated.


Long acting methadone formulation. Part 3: Preparation and in vivo evaluation of tablets containing methadone salts and methadone-naloxone combinations.

The preparation and in vivo evaluation of the methadone salts, methadone-o-benzoylbenzoate and methadone-alpha-naphthalenesulfonate, and a number of methadone-naloxone formulations, in the form of three layered slowly eroding tablets, were examined. Male albino rats of the Wistar strain were used as experimental animals and the results indicated that a prolongation of the resistance to pain threshold was attained, though severe side-effects were observed. A number of animals died during these experimental procedures.


Failure of ergotamine to alter the lipolytic effect of somatotropin in dogs.

Hypophysectomized dogs were injected intravenously with bovine somatotropin (GH), and plasma free fatty acid (FFA) concentrations were measured over a period of 2 h. The response consisted of an initial reduction in the concentration of plasma FFA followed by a rebound and a delayed rise above baseline values. When the animals were given a single intravenous injection of ergotamine tartrate 30 min prior to the administration of GH, the biphasic pattern with the sluggish rise in plasma FFA was retained. This finding is contrary to the results of identical experiments conducted by us with dihydroergotamine, which proved to be a potent amplifier of the lipolytic effect of GH. Since the only difference between these two compounds is the presence or absence of the double bond at C9 and C10 of the lysergic acid moiety, it appears that unless this bond is saturated the alkaloid is not capable of functioning as a biological amplifier.


Effect of derivatives of 3-(beta-aminoethyl)-1,2,4-triazole on the histamine H1- and H2-receptors.

Derivatives of 3-(beta-aminoethyl)-1,2,4-triazole similar to histamine have been resynthesized and studied. Four well-known effects of histamine have been considered (the contractions of an isolated guinea pig terminal ileum, dog gastric acid secretion, contractile frequency of an isolated guinea pig right atrium, blood pressure lowering effect in cats). Newly synthesized compounds IEM-813 and IEM-759 exerted some selective effects of H1 and H2-receptors: IEM-813 showed greater affinity for gut-isolated H1-receptors than for stomach and atrium H2-receptors, while IEM-759 mainly influenced H2-receptors. Accordingly, the influence of 1,2,4-triazole analogues on H1- and H2-receptors is subject to structural demands.


Consequence of solubility alteration by salt effect on dissolution enhancement and biological response of a solid dispersion of an experimental antianginal drug.

Improvement of dissolution of a poorly water-soluble experimental antianginal drug has been obtained by solid dispersion preparation. Its solubility decreased with rising chloride ion concentration and biological responses in dogs varied with the gastrointestinal administration site. A correlation seemed to exist between the apparent solubility and the heart rate activity.


Bone mass measurement using a xenon-filled multiwire proportional counter as detector.

The application of a xenon-filled multiwire proportional counter to photon absorptiometry of bone mass is described. Performance characteristics obtained from a prototype system are discussed and future developments indicated.


The early detection of osteoporosis by Compton gamma ray spectroscopy.

The density of the distal end of the radius is one of the parameters used to determine the presence and degree of osteoporosis in patients. In this work the bone density has been determined by measuring the intensity of the Compton scattered photons, since this is proportional to the absolute density of the scatterer, in materials for which Z/A is constant. A collimated beam from a 500 mCi 137Cs source was used and the intensity of the scattered radiation measured at an angle of 90 degrees. The exact point of measurement was determined by a two-dimensional scanning technique. A plastic water phantom was used to calculate the correction needed for absorption and backscatter by the surrounding tissue. Bone density was measured by this method in 50 subjects. A good correlation was found between density of the radius and the degree of morphological change in the vertebrae. In a number of cases a low bone density was discovered without signs of osteoporosis in the spine. These findings were considered indicative of early osteoporotic change, not definable by routine X-ray techniques. This technique may be of value in the follow-up of patients and in controlling the effect of various treatment schedules.


A facility for in vivo measurement of kidney and liver cadmium by neutron capture prompt gamma ray analysis.

An in vivo method for the determination of Cd levels in human kidney and liver has been developed. The method allows detection of absolute quantities of Cd in the left kidney and Cd concentration in the liver. The limit of detection of cadmium is 2.5 mg for the left kidney and 1.8 microgram/g (wet weight) for the liver, for a localized dose of 670 mrem. The effects of patient positioning, organ geometry and liver-kidney interference on the measurement have been investigated using an Alderson phantom.


An intercomparison of computer assisted data processing and display methods in radioisotope scintigraphy using mathematical tumours.

Several computer assisted processing and display methods are evaluated using a series of 100 normal brain scintigrams, 50 of which have had single 'mathematical tumours' superimposed. Using a standard rating system, or in some cases quantitative estimation, LROC curves are generated for each method and compared.


Laser iridectomy.

The laser energy required to achieve an iridectomy in the human eye is calculated as a function of laser beam radius and pulse duration. Two widely different models of the stromal pigment distribution are used in order to embrace the range of coloured irides encountered in practice. The attendant hazards to the cornea, lens and retina are also considered, resulting both from self absorption and also by thermal conduction from the heated iris. These calculations are used to interpret experimental iridectomies attempted over the last ten years and to provide a theoretical foundation for the specialized techniques of iridectomy currently employed. Finally, a new single pulse technique, suggested by these calculations, is formulated and results of preliminary dye laser experiments presented. These results are very encouraging because full-thickness iridectomies were formed in both blue- and brown-eyed rabbits with only 40 mJ of incident laser energy. It was found that the threshold laser energy required for iridectomy was sensibly constant over the visible spectrum for the brown-eyed rabbit. However, for the blue-eyed rabbit the energy had a pronounced minimum in the yellow portion of the spectrum.


Lyoluminescence dosimetry in photon and fast neutron beams.

The lyoluminescence (LL) technique using mannose, a monosaccharide, is described. Dose-response curves for 60Co-gamma-rays (5 rad to 120 krad), fission neutrons, 5.3 MeV and 15 MeV neutrons (100 rad to 20 krad) have been measured. The close tissue-equivalence of mannose makes this material well suited for dosimetric use in low energy X-ray fields for radiotherapy and radiobiology. It also provides a cheap, simple and reproducible dosemeter in industrial applications of radiation (sprouting inhibition of onions and potatoes; control of insect infestation). After correction for the gamma contamination of the neutron beam the LL signal per rad in ICRU muscle tissue from the neutron irradiations has been derived and the relative effectiveness of the LL signal for fast neutrons in mannose has been calculated as 0.34 +/- 0.03 (fission neutrons), 0.63 +/- 0.07 (5.3 MeV neutrons) and 0.74 +/- 0.05 (15 MeV neutrons). These results are compared with data from other systems. It is concluded that mannose can be used as a transfer system in neutron dosimetry, if its variation in sensitivity with neutron energy is taken into account.


Effect of positive external pressure on calf volume and local venous haemodynamics.

The pressure external to the calf was increased suddenly in 11 normal subjects and the resulting change in calf volume (considered to be mainly a change of calf vein blood volume) was followed using a mercury-in-rubber strain gauge. For a small increase of pressure the volume decreased exponentially and increased linearly when the pressure was suddenly released. A simple theory was developed which treats the calf veins as a single volume with a single compliance and a single outflow resistance. Using the theory, the following average results were obtained from measured values: effective venous compliance 1-1%kPa (SD 0.3); effective venous outflow resistance 3.8 s kPa/% (SD 1-3); and total flow into the veins from themicrocirculation 0.054%/s (SD 0.020) (% refers to a change in volume expressed as a percentage of the initial volume of the calf). The significance of the findings is considered with special reference to the occurrence of calf vein thrombosis.


Five-component dielectric dispersion in bovine serum albumin solution.

Dielectric measurements were made on aqueous solutions of native BSA monomers at three concentrations and at about eighty separate frequencies in the range 0.03-800 MHz. All measurements were made at 25 degrees C on solutions of pH = 5.0, this being near the isoelectric point. The analysis shows the presence of a double component beta dispersion at frequencies below 10 MHz plus two delta dispersions with relaxation frequencies of around 15 MHz and 100 MHz. The origin at a molecular level of the beta and the higher frequency delta dispersion can be established with confidence but the remaining delta dispersion cannot be interpreted unambiguously. With the inclusion of the well known gamma dispersion at frequencies in excess of 1 GHz the measurements indicate the existence of five clearly separated dispersion regions. This is one more dispersion than previously suggested in the literature for a protein solution of this nature.


The assessment of late effects on a population exposed to activity released into the environment.

The long term effects resulting from an accidental release of radioactive material are considered. The magnitude of the release is defined in terms of the percentage of total excess cancer mortalities relative to the number that would have been expected in the same population had the accident not occurred. The increased risk is expressed as the change in life expectancy as a function of age at the time of exposure. Loss of life-years per person is calculated for an increase of 0.1, 1, 10 and 100% in cancer deaths and are quoted for ages 1, 10, 20, 30, 40 and 50 years at time of exposure. The variation of the effect with age may be summarised using the ratio of the reduced life expectancy to the reduced life expectancy for a person aged zero at the time of the accident. For the initial external dose, this ratio exhibits a linear decrease up to about age 45 years at the rate of about 2% per year so, for example, the increased risk for a person aged 40 at exposure is 20% of the increased risk of a child just born. Similar estimates are made for a dose which is prolonged over 50 years, to represent doses from internally incorporated radionuclides.


[Syntagmatic typology of phonemes (author's transl)].

Based on the recent developments of the distributional calculus of HARARY and PAPER, a method is proposed to discover the constructional mechanism underlying the phonemic distribution of a language. The phonemes are classified hierarchically and the mutual interdependence of their distributional characteristics is studied. To this end, the technics of correlation and regression are being used. In this way, a 'typology' of phonemes in the sense of HEMPEL and OPPENHEIM is arrived at.


Intonation in discourse analysis. With material from Finnish, English, Alemannic German.

intonation is not additional, but essential to the composition of texts. even pathological (written) texts can be made to sound normal when read with a good intonation; even well-formed (written) texts cannot be put across when read with a poor intonation; loss of intonation, in aphasia, is coupled with inability to handle texts, and inversely. intonation is analysed either as phonological pattern or as a constituent of texts. The lexical meaning of intonations (such as question, statement) is spurious; social tradition makes available certain (spoken) rhetorical topoi for use in standard situations; their use ensures textual meaning. It is not predictable in any given instance.


Tonal distinctions in Cantonese.

The experiment reported here is a perceptual study of the six contrastive tones of Cantonese. The monosyllable  was synthesized, and a large number of closely spaced Fo contours were applied to it. Listeners were asked to identify each synthetic stimulus as one of six Cantonese words which all have the segmental shape  and differ only in tone. The response data were used to compare two impressionistic accounts of the tonal distinctions and determine which reflects actual Fo more accurately. In general, the results accord fairly well with straightforward predictions made from the impressionistic accounts, but there is one major exception. It appears that something in addition to differences in Fo is involved in distinguishing the low-low tone from the other tones.


[Intonational phonology of Basel German (author's transl)].

This paper attempts a new departure both in German dialectology and in phonemic analysis: (i) It is based on an open corpus of spontaneous, colloquial speech. (ii) The segmentals (phonemes and clusters) are integrated into the hierarchy of supra-segmentals (syllable types, shape types, intonation contours). (iii) Phonemic variability is recognized within the dialect. Its major isoglosses are restated in terms of phoneme correlations. (iv) Certain unstressed words do occur in isolation. (v) Vowel length is recognized as redundant, but the difference between the dental /t/ and the alveolar /ţ/ is distinctive. (vi) The inventories of stressed and unstressed vowels differ radically, the unstressed suffixes containing the vowels /i e/ only. (vii) The peripheral status is analyzed of the aspirates (other than /kh/), of the affricates /ţs kchi/, and of the lenis /t s eta/, but none of these phonemes is limited to loanwords. (viii) The fusion is analyzed of adjacent stops in initial k- and ţ-clusters.


Emphasis in Telugu.

The phenomenon of emphasis is studied with regard to the phonetic variation of the vowel and consonant units of the word structure in Telugu, a Dravidian language spoken mainly in South India. The electro-aerometer and the mingograph are used to provide phonetic evidence. The study reveals that different means are used to emphasise words of different structures so that the phonological structure is not disturbed.


English stops after /s/ at medial word-boundary.

Subjects listened to a speech perception test. It consisted of a series of items obtained by tape splicing from one recorded English utterance it's still. The subjects assigned one of four possible English utterance choices to each item. Combined duration of the /s/ friction and closure of the following stop account for their choice between it's dill, it still or it's still. A delay in voice onset of the stop is primarily responsible for items consistently heard as it's till. There is no difference in closure duration between the traditionally fortis and lenis stops following the /s/.


Tenseness in vowels: an ultrasonic study.

Ultrasonic imaging was used to measure the distance from the external neck wall to the anterior pharyngeal wall (APW). Measurements were made in the centre of the vocalic segment of 50 CVC syllables. 5 'tense' and 5 'lax' vowels of Standard American English were used. The APW was shown to position itself according to a combination of tongue height, frontness and 'tenseness' of the vowel, and coarticulation effects of neighbouring consonants. Tense vowels showed APW advancement compared to lax vowels having similar tongue height and frontness. Coarticulation effects depend on voicing and place of articulation. The ultrasonic equipment used is described briefly. Implications for distinctive feature theory are mentioned.


[A photoelectric investigation of velar height during vowel articulation: first applications of the velograph (author's transl)].

Some methodological aspects of the main physiological techniques for investigating the velopharyngeal closure mechanism are discussed. A new instrument for optical registration of velar movement is described. The possibilities and limits arising from its mode of operation are discussed. First results corroborate the relation between velar height and tongue height in vowels, which has been established by cineradiographic research. It is argued that the velograph records relative velar height in the speech continuum with reasonable accuracy. Two ways of calibrating the device are proposed so as to allow the measurement of absolute velar elevation (from rest position).


Andegerebenha vowel phonology.

The most common vowel system in Australian languages and the system ancestral to other Australian vowel systems is the triangular system /i-u-a/, with or without phonemic length. This paper shows that this is not appropriate for Andegerebenha, considers the suitability of a two-vowel system /e-a/, and rejects this in favour of one vowel plus length /a-a-/. The short vowel is greatly influenced in quality by the adjacent consonants; the longer one much less so. The consonant inventory is augmented by the addition of a number of labialised consonants, which embody the rounding of earlier *u. Conversely, the phenome/V/, a velar glide, was introduced when an earlier *w acquired the feature [-round] of adjacent vowels.


Studies on a rat liver subcellular poly A-rich RNA fraction with glutamate dehydrogenase template activity.

A heterogeneous poly A-mRNA fraction was isolated from rat liver microsomes by phenol:chloroform extraction, millipore filtration, and poly U-agarose affinity chromatography. The fractions were characterized by their secondary structures and poly A contents. From translational studies, the isolated fraction was found to have high glutamate dehydrogenase template activity in cell-free systems containing microsomes or polysomes. A spectrophotometric procedure for following enzyme biosynthesis was also developed.


Thallium and cesium in muscle cells compete for the adsorption sites normally occupied by K+.

It was shown that Tl+ can stoichiometrically displace K+ in frog muscle cells. This displacement is independent of the function of cell membrane and postulated pumps and of a macroscopic electric charge or Donnan effect. It follows that Cs+ and Tl+ compete for the adsorption sites normally occupied by K+. On this basis, the association-induction hypothesis predicts that Cs+ and Tl+, like K+, should be primarily localized in the A-band of the muscle myofibrils.


A binding protein from rat nerve.

Leucine has been found to bind competitively to a soluble protein (molecular weight 97,000 daltons) from rat sciatic nerve under certain experimental conditions to form a high molecular weight aggregate (MW greater than 302,000). Kinetic study showed that the equilibrium constant for leucine-binding is 1.33 X 10(4) l/m and the rate constants for binding and unbinding are k1 = 0.424 l/m/sec and k-1 = 3.18 X 10(5) sec-1 respectively. The binding reaction is accompanied by an endothermic enthalpy change of 5,000 cal/mole and the favorable equilibrium appears to be due to the large positive (35.3 eu) entropy of binding. L-Proline, thymidine, and succinic acid were also found to bind, non-competitively with leucine, to proteins in the same fraction. Binding of those compounds and leucine was enhanced by the presence of Mg2+. Rat muscle and plasma proteins did not significantly bind leucine under these experimental conditions. The presence of this binding protein in rat nerve suggests an additional mechanism in the metabolism and in the transport of amino acids for incorporation into a protein structure in nerve.


Desulfuration of l-cysteine through transamination and transsulfuration in rat liver.

Desulfuration of L-cysteine by rat liver via a pathway of transamination followed by transsulfuration was studied using cyanide as a sulfur acceptor. More than a 5-fold increase in formation of thiocyanate from L-cysteine and cyanide was observed in the presence of 2-oxoglutarate and pyruvate. L-Cysteine aminotransferase and 3-mercaptopyruvate sulfurtransferase activities in the same preparations were also determined. It was concluded that L-cysteine was desulfurated through transamination and transsulfuration of the resulting 3-mercaptopyruvate, and that the rate-limiting step appears to be the transamination reaction.


Cooperative interactions in nerve membrane potential and in photosynthesis, evidenced by non-linear Arrhenius plots and critical exponents.

The resting membrane potential of Aplysia nerve and the rate of photosynthesis by intact Chlorella cells have temperature dependences characterized by curved Arrhenius plots, for which the logarithm of the activation energy is a linear function of temperature. Ferromagnetic and ferroelectric systems show similar curves, which suggests that the above two biological systems are governed by cooperative interactions between adjacent molecular sites. Critical exponent analysis suggests the same conclusion.


A relation between myocardial taurine contest and pulmonary wedge pressure in dogs with heart failure.

Myocardial taurine levels were correlated with pulmonary wedge pressure (PWP) in dogs with congestive heart failure (CHF). Heart failure was induced by creating an infrarenal aortocaval fistula. PWP ranged from 6.6 to 28 mm Hg, suggesting a wide range in severity of heart failure in those dogs. Compared to taurine levels of normal dogs, levels of the CHF group were significantly elevated in both left and right ventricles. Linear regression analysis of ventricular taurine content yielded a highly significant direct relation to PWP. The results suggest that myocardial taurine content increases as heart failure becomes more severe.


Oxidative phosphorylation in mitochondria from different fiber types of chicken muscles.

Isolated mitochondria from different types of muscle fibers from chickens 3 to 5 weeks were studied to evaluate the comparative oxidation of various substrates. Pectoralis (alphaW fibers), lateral adductor (betaR fibers), and medial adductor (alphaR fibers) were the muscles used. Oxygen consumption rates, RCR, and ADP/O ratios were measured to study mitochondrial function. Mitochondria from pectoralis muscle utilized pyruvate, succinate, L-glutamate, alpha-glycerophosphate, and beta-hydroxybutyrate. Mitochondria from the other two muscle types utilized all of those substrates except alpha-glycerophosphate. In each muscle type utilization of NADH was minimum and was not coupled with phosphorylation of ADP. Thus, in alphaW muscles oxidation of alpha-glycerophosphate may play an important role in transport of cytoplasmic NADH to the mitochondrial respiratory chain. In alphaR and betaR muscles "shuttle" systems other than alpha-glycerophosphate oxidation, e.g., beta-hydroxybutyrate, may perform that important role.


The growth hormone response to insulin induced hypoglycaemia in alcoholics.

The growth hormone response to insulin induced hypoglycaemia was studied in 7 alcoholic in-patients who had been abstinent for 2-11 days and in 10 normal controls. Blood samples were taken at intervals after the injection of soluble insulin (0-1 U/kg body weight). The growth hormone response was impaired in 4 of the alcoholics and the depression was not related to differences in blood glucose or plasma free fatty acids. The cortisol response was also impaired in the alcoholics. We conclude that alcoholics observed after alcohol withdrawal may have a depression of hypothalamic/pituitary function.


Schizophrenia succeeded by affective illness; catamnestic study and statistical enquiry.

On the basis of data derived from a long-term follow-up of 12 cases and a 2-year follow-up of the International Pilot Study of Schizophrenia it is suggested that some patients with remitting schizophrenic illnesses can subsequently present clear-cut affective disorders. The implications of these findings are discussed.


Spontaneous length of depression and response to ECT.

Electro-convulsive treatment (ECT) was therapeutically ineffective in 27 (20%) of 136 depressed patients. Failure to respond occurred in long-lasting depressions and in patients with a history of long-lasting depressions. In these cases the depression lasted at least 6 months. The hypothesis is proposed that ECT is effective only when given within 6 months of thespontaneous end of the depression. Clinical and nosological implications are discussed.


Mental distress in mothers of pre-school children in inner London.

The level of mental 'distress' was assessed for a sample of mothers with pre-school children in Inner London. Fifty-two per cent of mothers had a moderate or severe distress problem in the 12 months prior to interview. Variables correlating with distress were identified and replicated in a second sample. Social class was not found to be related, and the question of the general relationship between social class and distress is considered.


Psychiatric morbidity and hostility in hypertension.

In a large survey of subjects aged between 35 and 64, no difference was detected in the amount of psychiatric morbidity, determined by response to the General Health Questionnaire, between those with hypertension and those with normal pressure. This finding also obtained if only those subjects ignorant of their own blood pressure level were considered for the same comparison. As a result of administration of a standardized psychiatric interview and a hostility questionnaire to 108 hypertensive and normotensive subjects of a special study, differences in the expression of hostility were demonstrated between the 2 groups. Subjects with hypertension appear to demonstrate more hostility and be less self-critical than a normotensive group. This finding could reflect the effect of recent diagnosis and treatment of hypertension or be associated with the hypertensive state itself.


The contribution of psychological features to the symptoms of treated hypertensive patients.

Twenty-seven symptoms of 859 treated hypertensive patients were evaluated using a self-administered questionnaire and correlated with the depression (DEP), free-floating anxiety (FFA), phobic anxiety (PHO), obsessionality (OBS) and extraversion (HYS) scores of the Middlesex Hospital Questionnaire. The psychological features were associated with 24 of the 27 symptoms, and the extent to which these measurements determined the presence of a symptom was calculated. DEP and FFA were correlated with most of the symptoms, PHO with weak limbs, blurred vision, slow walking pace, nocturia and a lessened interest in sex. HYS was positively associated with the frequency of sexual intercourse in men and negatively with complaints of dyspnoea, tingling in the limbs and a slow walking pace. OBS was only associated with diarrhoea.


Migration, culture and mental health.

The former belief that immigrants always suffer from an excess of mental disorder is no longer valid, and the old rivalry between social selection and social causation hypotheses has lost much of its relevance. The mental health of a migrant group is determined by factors relating to the society of origin, factors relating to the migration itself, and factors operating in the society of resettlement; and all three sets need to be considered if one seeks to reduce or merely to understand the level of mental disorder in any immigrant group. Illustrations from each set of factors are presented, with indications of whether they appear to have general relevance or be related to specific mental disorders.


Previous occupational stability as a predictor of employment after psychiatric rehabilitation.

Several indices of occupational stability are discussed and the importance of controlling for age in assessing occupational stability emphasized. The ability of 6 indices to predict the stable resettlement of psychiatric patients at work after a course of rehabilitation was examined. Though mean job length was a significant predictor, indices based on change of occupation rather than change of job were more successful. Stable resettlement at work was related to how much time people had spent in long jobs but not to how little time they had spent in short jobs. The amount of unemployment during the 2 years before hospital admission predicted return to work immediately after discharge, but did not predict stable resettlement at work.


The rating of symptoms by a psychiatrist and a non-psychiatrist: a study of patients referred from general practice.

A psychologist interviewing patients referred to the psychiatric service of a health centre rated twice as much morbidity, measured by total PSE score, as a psychiatrist interviewing equivalent patients. Scores on the self-rated GHQ showed no difference between the 2 groups. It is suggested that such differences could be avoided by giving careful attention to training interviewers.


Lowered responsiveness and auditory signal detectability during depression.

Ten depressed patients were assessed on an auditory signal detection task; testing was repeated on remission. The patients' clinical state was monitored by means of the Hamilton rating scale and the Beck Depression Inventory. The task was performed under three conditions: 2 button (Yes/No); 1 button (Yes); 1 button (No). The findings indicated lower motor responsiveness during depression, consistent with Seligman's learned helplessness model. The measure of auditory sensitivity was also lowered during depression, possibly attributable to attentional disturbance. It is suggested that the lowered initiation of voluntary responses may be an important factor in the assessment of cognitive functioning during depression; such deficits may be reduced if the task does not permit the omission of a response.


A study of the symptomatology and course of manic illness using a new scale.

Sixteen manic patients were rated fortnightly on the Present State Examination and a new manic rating scale. After 4 weeks of treatment a high proportion of symptoms had decreased significantly, but some symptoms likely to affect social functioning persisted. The group displayed many depressive and anxiety symptoms in addition to recognized manic symptoms.


Deconditioning of exercise-induced asthma.

The majority of asthmatic children develop a significant degree of bronchospasm after a moderate amount of exercise. Etiology of this phenomenon has remained unknown. Pulmonary function tests, measurements of blood gases, and immunological assessments have been essentially normal. This study was designed to investigate the role of conditioning process in the development of exercise-induced bronchospasm (EIB). Fifty asthmatic children, between the ages of 8 and 15, were subjected to a standardized test of exercise. Thirty-six of the children who developed EIB were divided into an experimental and a control group. The experimental procedure was designed as a classical extinction procedure in which the conditioned stimulus (exercise) was presented without the occurrence of conditioned response of EIB. Only the experimental group received isoproterenol inhalation before the exercise to prevent the occurrence of EIB, while the control groups received plain air in a similar manner. The experimental group showed a significant improvement after the extinction procedure. A 6 month follow-up indicated that the majority of the children in the experimental group maintained the gains that were acquired during the experimental procedure.


Psychosocial stimuli and human plasma renin activity.

The effects of several types of acute psychosocial stimuli on plasma renin activity (PRA) were studied in normotensive healthy subjects. Puzzle-solving produced an increase in blood pressure but no significant change in PRA, although two of seven subjects did respond with large increases in PRA. Watching a disturbing movie also raised blood pressure, but did not alter PRA. In contrast, a combination of novelty, fear, and/or anticipation did constitute a significant stimulus for renin secretion; this was evidenced by the fact that naive subjects (who were not told in advance what to expect) had significantly higher PRAs on the first day of the 2-day puzzle-solving study. PRA on this day correlated strongly with anxiety proneness, as did the decrease from day 1 to day 2. We conclude that meaningful psychosocial stimuli can enhance renin secretion in susceptible individuals.


Life event questionnaires for measuring presumptive stress.

Cumulative stress from the impact of life events has become an important variable in psychosomatic and psychological research. This article provides both short and long life events questionnaires that add to incidence information the remoteness or recency in time of a given experience. In the weight assignment system that leads to a single presumptive stress score, events remote in time have less influence than recent events. The reliability of weight assignment was checked in subject groups that differed by sex, age, and status. Women weighted life events as more stressful than did men; other differences in groups were less important. In spite of the sex differential, review of these data suggests use of the same weight assignments for all subgroups rather than differential weighting by sex and age. Reliability was also checked by test and retest methods in contrast to common sense expectation, a disappointingly low level of reliability was found. The implications for investigative use of life events questionnaires are discussed.


Ultradian cardiac rhthms in surgical intensive care unit patients.

Several reports have suggested that heart rate may be regulated by an ultradian biological rhythm with a period of about 90--100 min. Blood pressure and heart rate were collected from 10 Surgical Intensive Care patients at 5-min intervals and analyzed by computer. No 90-min rhthms were found, indicating this rhythm has no significant influence on heart rate or blood pressure in postsurgical patients.


Factors influencing serum potassium in treated hypertension.

A retrospective survey of serum potassium measurements in a blood pressure clinic provided evidence that potassium supplements averaging 24 mmol daily were effective in elevating serum potassium concentration and reducing the incidence of hypokalaemia in diuretic-treated hypertensives. In patients treated with bendrofluazide the serum potassium concentration was related to the dose of diuretic, but not to age, sex, body weight, supine blood pressure or serum creatinine. There was no evidence that drugs other than diuretics or potassium (including beta-adrenergic blockers) had a clinically significant influence on serum potassium. The major part of the variation in serum potassium between patients could not be explained by the variables examined.


Progressive airway obliteration in adults and its association with rheumatoid disease.

Six patients with rapidly progressive airway obliteration in the absence of chronic bronchitis or emphysema are reported. Because this pattern of lung disease is very uncommon and five of the six patients had classical rheumatoid arthritis an association between the two diseases is suggested. The patients presented with rapidly developing breathlessness, and râles and a high-pitched mid-inspiratory squeak were heard over the lung fields. Chest radiographs showed distended lungs but were otherwise normal. Tests of lung fuction showed airflow obstruction, most marked at low lung volumes, with air trapping. The carbon monoxide gas transfer coefficient, maximum static recoil pressure and static compliance were normal. In spite of treatment with antibiotics, bronchodilators and corticosteroids, five died in respiratory failure five to 18 months after first becoming breathless. Post-mortem examination in four patients showed an obliterative bronchiolitis but no mucous gland hypertrophy or significant emphysema.


Bacterial endocarditis in England in the 1970's: a review of 70 patients.

The features of 70 cases of bacterial endocarditis are reported. Streptococcus viridans was the cause in 45 per cent, staphylococci in 27 per cent, and enterococci in 7 per cent. Rheumatic heart disease was the predisposing factor in less than one quarter of patients and in almost half there was no obvious pre-existing cardiac disease. Apart from cardiac murmurs and pyrexia, the classical features of infective endocarditis were uncommon, haematuria being observed in less than one-third. Most patients were over the age of 30, one-third more than 60 years of age and the peak incidence occurred in the seventh decade. The mortality was 34 per cent, being highest in infection caused by Staphylococcus aureus. Adverse prognostic features included cardiac failure, advanced age and peripheral embolization. One-third of infections were caused by bacteria resistant to penicillin.


Aplastic anaemia: a study of prognosis and the effect of androgen therapy.

One hundred and twenty-nine Chinese patients with aplastic anaemia, were studied. In ten it was induced by drugs, one followed hepatitis and the remainder were of unkown cause. Mortality within the first six months was 47.3 per cent. Features associated with poor prognosis included a short duration of symptoms of three months or less, neutropenia of less than 0.5 x 10(9)/l and severe thrombocytopenia. On the other hand, some preservation of erythroid activity of the bone marrow was associated with long survival. Remission occurred in 47 patients and this was associated with androgen therapy in 33. Remission was complete in 18 and partial in 29. In the latter group, persistent thrombocytopenia was the main abnormality and treatment with calusterone led to an increase in platelets although the effect was not sustained after its withdrawal. Hepatotoxicity was seen in 16.0 per cent of patients treated with androgens and this occurred even with non-17alpha-alkylated compounds. It is concluded that androgen therapy was useful and should be started as early as possible after diagnosis. Hepatic intolerance to androgens may be an indication for bone marrow transplantation.


Localised nodular myositis: a clinical and pathological variant of polymyositis.

Three cases of a painful, inflammatory, nodular myopathy in young and middle-aged adult males are described. In two of the cases the nodular process gradually evolved into a diffuse proximal myopathy accompanied by dysphagia, and manifesting the so-called "facioscapulohumeral syndrome". The electromyogram (EMG) in all three cases was "myopathic" in type and in two cases abnormalities consistent with an inflammatory muscle disorder were seen. Muscle biopsy revealed a consistent pattern of intense, predominantly interstitial, pleomorphic infiltration of muscle with scattered foci of muscle fibre destruction and regeneration, which resembled muscle infarcts. It is suggested that this syndrome, whilst readily recognizable from both the clinical and pathological standpoints, is not a nosological entity in its own right but rather an unusual presentation of polymyositis.


[The kaolin-activated recalcification test in the screening of coagulation disorders and in the control of anticoagulant therapy].

The AA. have standardized a method for determining the kaolin activated plasma recalcification time (TRA) and have fixed its normal range between 33 and 60 seconds (average +/- 3 DS) testing 2000 normal subjects. By this method they have been able to demonstrate that TRA is more sensitive than PTT during the haemorrhagic manifestations in thrombocytopenic patients and in monitoring heparin therapy, while it shows a behaviour similar to PTT in detecting coagulation defects. It has also been found that TRA had remarkably increased its values in thrombocytopatic non thrombocytopenic patients, when PTT was normal. TRA does not seem to be useful in coumarin or indanedione therapy, since its values are constantly but not proportionally increased only when prothromsitive than PTT during the haemorrhagic manifestations in thrombocytopenic pabin time is very prolonged. Finally TRA can advantageusly substitute the whole blood clotting time and the non activated recalcification time for its easy performance, remarkable precision and low cost.


[Study of a family with a slow type of bisalbuminemia and of 2 other familial cases].

The AA. illustrate cases of slow type bisalbuminaemia that they happen to observe on three different family one of which, on a family of north italian origin, has been particularly developed. The cases have been studied on the various components of each family living and to be found, on serum and urine, using electrophoretic methods on cellulose acetate and acrylamide gel and also using the immunoelectrophoretic and cromatographic method on serum after hydrolysis. Cases taken in account, together with results of investigation, add up to those already given to the litterature.


[Infrared spectroscopy in the quantitative determination of urinary calculi constituents (author's transl)].

Infrared spectroscopy of urinary calculi can be used for the quantitative determination of the major constituents in mixed stones; the method is simple and consists in area-measurements of specific absorption peaks of the spectrum of each compound. In the area-measurement method the average error is +/- 2,5% in calcium-oxalate-apatite and +/- 2% in ammonium magnesium phosphate-carboapatite mixtures; within these limits the calculus matrix do not affect significantly the value of areas. An investigation of 64 mixed renal stones shows that in 57% of the samples, apatite is present in the nucleus; uric acid and calcium-oxalate are the most frequent superficial compounds, while the external layer of ammonium magnesium phosphate and the mixture uric acid-calcium phosphate are rare events. In calcium-oxalate-apatite and ammonium magnesium phosphate-carboapatite calculi the quantitative composition of the nucleus and the external layer differ significantly. The proposed method of analysis of internal and external structures in renal calculi can be useful for the study of etiology, for the prevention and the treatment of urolithiasis.


[The nephelometric method in the study of the hyperlipoproteinaemia: comparative analysis with chemical and electrophoretic methods (author's transl)].

On 814 subjects the cholesterolemia, the triglyceridemia and serum lipoproteins were determined; also the nephelometric analysis of the serum was conducted. The statistical analysis of the results allowed the following conclusions. 1) Approximately 98% of the pathological results are found in 3 types: type IV (about 49%), IIa (about 40%), IIb (about 11%). 2) The nephelometric determination of the M particles is particularly useful in the distinction between types IIa and IIb, because in type IIb there are pathologically increased values also when the triglycerides are normal or almost normal. There exists a significant correlation between the M particles determined by nephelometric analysis and the triglycerides determined by chemical methods.


[The SGLDH determination with the Jung's method in differential diagnosis of hepatobiliary diseases (author's transl)].

SGLDH activity, determined according to Jung, was studied in different classes of hepato-biliary diseases. The discriminant effectiveness of this test, alone or in association with transaminase determination, was evaluated. The ratio of Schmidt and Schmidt and the ratio of Filippa were also calculated and their effectiveness was estimated. The determination of SGLDH activity, performed with the Jung's method (this method is considered the most sensitive among the clinical methods), was proved to offer no advantages neither alone nor in association with the determinations of the SGOT and SGPT.


[Relations between hepatitis B surface antigen and parasitic diseases: observations in patients with ancylostomiasis and schistosomiasis].

Hepatitis B antigen carriage was studied in Somalia in 155 patients with ancylostomiasis, with urinary schistosomiasis and with leprosy (lepromatosus and tuberculoid type and leprosy with schistosomiasis). The results have showed a significantly (p less than 0,001) higher frequency of HBsAg among the patients with ancylostomiasis (33,33%) and with urinary schistosomiasis (25,92%) than either the leprosy patients (9,67% in the L type and 6,89% in the T type) or the controls (11,11%); in the leprosy patients with schistosomiasis the frequency was 40,0%. The role of some penetrating skin parasites in the epidemiology of hepatitis B was discussed.


[Aggregation of blood platelets: changes in Breddin's method (author's transl)].

The evaluation of the blood platelets aggregation, by means of Breddin's method, is rather long and, moreover, the subjective elements connected with the microscopist's experience, fall on it. The AA. have verified, through sixty cases, a great correlation between this method and change prepared by them, whied avoids the inconveniences before mentioned.


A proposal for revision of the quality factor.

As a result of recent radiobiological research it has become evident that the RBE of neurons can at low absorbed doses reach values that are substantially higher than the values of the quality factor (Q) currently adopted for radiation protection. There is theoretical and observational evidence that such high RBE values are the rule rather than the exception and that they apply to at least one radiation effect on humans. New values as well as different formulations are proposed for the factor that is employed in radiation protection to weight absorbed doses for their biological effectiveness.


Radiosensitivity and recovery of mouse L cells during the cell cycle.

Mouse fibroblasts, subline L-929 F were synchronized by mitotic detachment. The synchronized cell cultures were irradiated with 200 kVp X-rays at different time after mitosis, and age response functions and dose effect curves were determined using the colony test. The cell age in the mitotic cycle was obtained from a computer analysis of flow cytometric DNA histograms. Both intrinsic radiosensitivity 1/D0 and extrapolation number n were found to vary during the cell cycle. The D0 has a maximum value of 176 +/- 1 rad in the middle of G1 phase and minimum of 71 +/- 1 rad at the S/G2 transition, while the extrapolation number is rather constant from the beginning of G1 phase (1.9 +/- 0.1) to the middle of S phase (2.3 +/- 0.1) and reaches a steep maximum of 9.3 +/- 1.1 at S/G2 transition. The values of n in the various phases of cell cycle are compared with the respective values of the recovery factor gamma determined after fractionated irradiation. --Cell survival after a single dose of 616 rad has minima for irradiation at G1/S transition and in early G2 phase; the survival in early G2 being about 40 times smaller than in early G1 phase. Implications for a cell cycle specific therapy are discussed.


Light-induced binding of riboflavin to lysozyme.

The photodynamic inactivation of lysozyme in air saturated H2O and D2O (phosphate buffer 0.05 M, pH 7.0) in the presence of methylene blue and riboflavin has been studied. When H2O was replaced by D2O a great increase in the rate of photoinactivation of lysozyme was observed. This finding, together with the fact that photooxidation is inhibited by singlet oxygen quenchers like NaN3, suggests that these reactions occur via a singlet oxygen mechanism. During the course of the studies of the riboflavin sensitized photoinactivation of lysozyme, it was found that riboflavin is strongly bound to the enzyme as a result of illumination. This finding would explain the higher quantum yield observed when riboflavin is used, although this dye is bleached during irradiation.


The effects of gamma-irradiation on the hydration characteristics of DNA and polynucleotides. III. A comparative NMR study of frozen and liquid solutions.

The effects of gamma-irradiation and changes in the macromolecular structure on the water proton resonance spectra observed in frozen and liwuid solutions have been compared for the DNA and polynucleotide solutions, using H2O or mixed H2O/D2O solvents. The results indicate that in order to obtain information concerning the role of hydration water in mediating the overall radiation damage, the NMR studies must be performed in the frozen state.


Changes of adenine nucleotides content and release reaction of human blood platelets following gamma irradiation.

The aim of this work was to examine the effect of gamma irradiation on the energy metabolism and physiological functions of blood platelets. Blood platelets were irradiated with a 60Co-source in the range of 0.5--8.0 krad. Before and after irradiation, the free nucleotide content of platelets and the ability of platelets to perform their hemostatic functions (the release reaction with thrombin) were determined. The obtained results demonstrated that: 1. ATP, ADP and AMP content reached minimum values at 1.5--2.0 krad. 2. The ability of platelets to perform the release reaction correlates with the ATP level at doses of 1.5--2.0 krad. At higher doses (6.0--8.0) disturbances of the release reaction, indicating damage to the platelet plasma membranes, were observed.


Effects of antibiotics on UV-stimulated tube growth of Pinus silvestris pollen.

Studies were made to investigate the effects of different antibiotics on unirradiated pollen and on pollen with enhanced tube growth, stimulated by low doses of UV-light. The antibiotics mitomycin, chloramphenicol, tetracyclin, penicillin, nystatin and carbony-cyanid phenylhydrazon were not able to suppress tube growth stimulation of pine pollen. The data obtained are discussed in view of the stimulation mechanism of low doses of UVP-light.


Radiation dose to the eyes of patients during petrous bone tomography--a comparative survey.

Some investigation has been made in recent years of radiation dose to the eye during radiological procedures. A comparative survey has been made of eye dose during petrous bone tomography in different departments on different tomographic units and during different types of examination. Doses of up to 4 rad per exposure have been recorded and various methods of reducing the dose have been investigated, the most successful being the use of 1 mm lead eyeshields or examining the patient in the posteroanterior position.


[Anatomical and physiological fundamentals of cerebrospinal fluid production and drainage (author's transl)].

After presenting some incontestable facts of CSF-physiology the actual and quite controversial opinions on ventricular and extraventricular sources of CSF as well as the mechanism of CSF-absorption are discussed. Finally the important role of the CSF sytem in the brain-metabolism is opposed to the well known function of brain support and protection.


[Nuclear medicine diagnostic in hydrocephalus (author's transl)].

Some of the main questions about hydrocephalus, its origin and classification are reviewed. Routine radioisotope studies of the CSF pathways during 11 years has brought many valuable criteria for defining pathological cases. Attention is focused on the various states of balance between production and resorption of the CSF in hydrocephalus in order to find the right time for placing a shunting device. Radioisotope studies can provide clear images, patterns and criteria. In most instances hydrocephalus may be defined whether compensated or not. They also give a true representation of this unsteady dynamic state which constitute hydrocephalus. Dubious or intermediary cases still exist for which only dubious or intermediary cases still exist for which only dubious results are to be expected. The "pattern recognition" problem is emphasized while technical problems, so important they may be, are only summarized. Radioisotope studies still remain the most valuable and informative test for stuying the third circulation in men. The successive imaging of the various cisterns in different planes must be clinically interpreted, and may be repeated in dubious cases according to the clinical status.


[Csf ex vacuo (author's transl)].

CSF ex vacuo is a proposed designation for abnormal collection of CSF replacing brain tissue which has been lost by trauma, infection, hemorrhage etc., or which has not been developed e.g. in aplasia of the temporal lobe. Such collections are known as arachnoid, leptomeningeal or porencephalic cysts. Under certain, however unsufficiently understood, conditions CSF ex vacuo may develop expansive tendencies, most obvious in growing fracture of the skull vault or base. In unexplained recurrent meningitis the presence of a frontobasal CSF collection should be looked for.


[Clinical signs and therapy of intermittent normotensive hydrocephalus (author's transl)].

Ventricular fluid pressure (VFP) has been continuously recorded for several days in a series of 9 patients with Intermittently Normotensive Hydrocephalus. This entity can be diagnosed with a reasonable degree of certainty by this method, due to the occurrence of periodic increases of VFP--mainly of ramp-waves as described in the paper. Thus, the designation Intermittently Normotensive Hydrocephalus appears to be more exact. Therapy by means of CSF-shunting procedures is more successful in cases with clearcut periodic rises in VFP.


[Posttraumatic alterations demonstrated by isotope cisternography (author's transl)].

Survey on the diagnostic value of scintigraphy of the spinal and cranial liquor spaces as demostrated by case reports.


The synthesis of 13-cis-dl-erythro-15,16-dihydroxyprostaglandins.

Both pairs of dl-11-desoxy- and dl-13-cis-erythro-15,16-dihydroxyprostaglandins have been synthesized via 1,4-conjugate additions of an appropriately functionalized cis-vinyl cuprate to the requisite cyclopentenone. These prostaglandin analogs are considerably less potent than PGE2 as gastric secretion inhibitors or as bronchodilators.


Identification of prostaglandin D2 as a major prostaglandin in homogenates of rat brain.

Prostaglandin (PG) E2, D2, F2alpha and thromboxane B2 (TxB2) were determined in homogenates of rat brain by gas-chromatography--mass spectrometry. The level of PGD2 was 735 +/- 19 ng/g, of PGF2alpha 150 +/- 13 ng/g, of TxB2 112 ng/g and of PGE2 86 +/- 8 ng/g. The same relative proportions of cyclooxygenase products were found in incubates of unstimulated sliced rat brain. 14C-PGH2 was converted in high yield into PGD2 by enzyme(s) present in the soluble fraction of the homogenate. These results indicate that PGD2 is the major cyclooxygenase product in the central nervous system of the rat.


Dose dependent inhibition of B-16 melanoma growth in vivo by a synthetic analogue of PGE2.

Daily intratumor administration of 16,16-dimethyl-PGE2-methyl ester in two different dosages inhibited tumor growth in C57Bl/6J mice bearing subcutaneous B-16 melanomas. The larger dose (20 microgram/day/mouse) produced a 68% decrease in tumor volume, a 69% decrease in tumor weight and a 60% decrease in the number of cells in mitotic phase. The smaller dose (10microgram/day/mouse) was one fifth less effective than the 20microgram dose but produced similar changes. Histological examination of tumors revealed no significant differences either in the inflammatory cell population or the amount of necrosis in the control and di-M-PGE2-treated tumors.


Non-specific prostaglandin antagonism by 8-ethoxycarbonyl-5-methyl-10, 11-dihydro-PGA1-ethyl ester (HR 546) on some smooth muscle preparations in vitro.

The ability of 8-ethoxycarbonyl-10, 11 dihydro-A-prostaglandin(HR 546) to antagonise smooth muscle contracting effect of prostaglandins E2 and F2alpha on isolated preparations of rat and hamster stomach fundus, guinea pig ileum and gerbil colon has been studied. HR 546 was found to be a potent, non-specific, probably competitive, prostaglandin antagonist on these four smooth muscle preparations.


Interactions between prostaglandins and calcium: the importance of bell-shaped dose-response curves.

Biological responses to PGs show two basic forms of dose/response relationship, plateau and bell-types. Although bell-shaped dose/response curves are well documented their possible occurrence is almost always ignored in the design and interpretation of experiments on PGs and related substances. This may lead to serious errors, several types of which are described. The ignoring of a well-documented phenomenon may take place because there is no accepted hypothesis which attempts to explain the bell-type curves. A hypothesis is proposed which accounts for both plateau and bell type responses. It is developed primarily with respect to PG-calcium interactions but may be applicable to some PG-cyclic nucleotide interactions as well. The model leads to precise predictions which can be experimentally tested in many systems.


Prostaglandin E2 production by renal inner medullary tissue slices: effect of metabolic inhibitors.

Increasing oxygen from 5 to 95% has previously been shown to increase prostaglandin (PG) production in renal inner medullary slices. The possible role of oxidative phosphorylation in this process was investigated. The oxidative phosphorylation inhibitors, dinitrophenol (DNP), oligomycin, and cyanide were evaluted for their effects on PGE2 production and ATP levels. None of the inhibitors affected PGE2 synthesis, although they lowered ATP levels at the concentrations tested. In contrast, incubation of inner medullary tissue slices with 0% oxygen resulted in decreases both in PGE2 and ATP levels. This suggests that the effect of oxygen on prostaglandin synthesis may be due to substrate limiting effects rather than an effect on oxidative phosphorylation. When 22 mM 2-deoxyglucose was added to the incubation medium or when glucose was omitted, PGE2 levels increased. Sodium fluoride, presumably acting as a glycolytic inhibitor, increased PGE2 levels, with a maximal effect at 10 mM. ATP levels were 37% of control values with 20 mM NaF. This indicates that glucose may inhibit prostaglandin synthesis. These results indicate that oxygen (substrate) availability can limit inner medullary PGE2 production. In view of the low pO2 in the inner medulla, especially during antidiuresis, oxygen can potentially regulate prostaglandin production in this tissue.


Prostaglandin A2 and 35S uptake in connective tissue.

Rats deficient in essential fatty acids (EFA) incorporated lesser amounts of radioactive sulfate into lung, kidney, spleen, heart, costal cartilage, long bone and skull bone than did normal control animals. Administration of prostaglandin A2 stimulated 35S uptake by lung, kidney and aorta while 35S levels in costal cartilage, tibial cap and long bone were strikingly reduced. Comments are presented suggesting that this metabolic mechanism may explain, in part, cartilage and bone resorption in areas of inflammation, such as arthritis, both rheumatoid arthritis and osteoarthritis.


Increased collagen metabolism in granulomata induced in rats deficient in endogenous prostaglandin precursors.

Collagen metabolism was measured (in terms of various hydroxyproline (HP), DNA and protein ratios) in granulomata obtained after s.c. implantation of carrageenan-impregnated and untreated polyether sponges into normal and essential fatty acid deficient (EFAD) rats for 8 and 15 days. Collagen synthesis (HP/protein) in day 8 and 15 untreated granulomata was the same for both normal and EFAD rats, though collagen breakdown (total HP) appeared to be greater in EFAD granulomata on day 15. With carrageenan-impregnated sponges, collagen synthesis in EFAD granulomata was much greater than in normal granulomata on both day 8 and day 15. Ratios of protein and/or HP to DNA (probably indicative of cellular infiltration) were increased in EFAD rats with both sponge types, though this increase was less pronounced with carrageenan-impregnated sponges. It is suggested that endogenous prostaglandin (PG) production (marledly reduced during EFA deficiency) may exert a negative feedback effect on collagen metabolism during proliferative inflammation.


Mechanism of relaxant action of prostaglandin F2alpha on the guinea-pig isolated trachea.

Prostaglandin F2alpha consistently produced a dose-related triphasic response in guinea-pig isolated tracheal chain preparations. The response consisted of an initial transient contraction followed by a transient relaxation, followed by a further contraction. The relaxant action was not due to adrenergic or histaminergic transmission, but might be due to a PG-like material released by the PGF 2alpha-induced contraction.


Synthesis of prostaglandins by the ductus arteriosus of the bovine fetus.

Previous studies demonstrated that prostaglandins are local or tissue hormones which can be released from blood vessel walls. In the present study, we investigated the capacity of bovine ductus arteriosus to synthetize prostaglandins in vitro. After incubation of slices of ductus arteriosus in Krebs' solution with (1-14C) arachidonic acid for 3 hours, more than 40% of the radiolabeled material recovered from the incubating medium were metabolites of arachidonic acid. The major product was indistinguishable from 6 keto-PGF1alpha as determined by its chromatographic motility and resistance to alkaline conversion to PGB. The PGI2 synthetic capacity of the ductus arteriosus, as revealed by the predominance of its major metabolite 6 keto-PGF1alpha, suggests that this metabolic pathway of arachidonic acid may contribute to the hemodynamic changes occurring during fetal life and at birth.


Utility of d4-PGE2 as an internal standard to quantify endogenous levels of PGE1, PGE2, 19OH PGE1 and 19OH PGE2 in human seminal fluid by GC-MS-SIM.

Four prostaglandins-PGE1, PGE2, 19OH PGE1 and 19OH PGE2-were quantified in human seminal fluid by GC-MS-SIM using only the internal standard, d4-PGE2. Methods and calculations were developed to minimize errors inherent in using only one internal standard for quantifying four closely related prostaglandins. Preliminary data concerning the statistical significance of the difference found between PGE and 19OH PGE levels in fertile, azospermic and oligospermic men are reported.


Uterine activity and prostaglandin production following intraamniotic hyperosmolar urea.

The relationship between endogenous prostaglandin (PG) production and uterine activity was studied in hyperosmolar urea induced abortion patients. Polygraphic recordings of intraamniotic pressure were obtained at periodic intervals following intraamniotic injection of 80 gm urea. At 0, 0.25, 1, 4 and 8 hours amniotic fluid and blood samples were obtained for PGE, PGF and 13,14-dihydro-15-keto-prostaglandin of abortion. In eight patients studied, uterine tone was elevated by 0.25 hour although no rhythmic contractions were observed by 1 hour. At 4 hours, amniotic fluid PGF concentration increased significantly (P less than .01) over the pre-injection value and continued to increase at 8 hours. Amniotic fluid PGE, PGFM and all plasma PG's showed no change during the 8 hour period following urea administration. At time of abortion the plasma PGFM concentration was significantly. At time of abortion the injection (238 +/- 54.4 vs. 86.7 +/- 7.3 pg/ml). There was no significant concentrations. In the present study, there is no evidence that increased prostaglandin production precedes urea induced contractions. The possible role of PG's in uterine contractions is discussed.


In vitro response of relaxin-treated rat uterus to prostaglandins and oxytocin.

Paired segments of rat uterus were treated in vitro with relaxin (W1164-3, 150 GPU/mg) until the amplitude of contraction was reduced to at least 50% of the pre-treatment amplitude. Test segments then received 100 ng of either PGE1, PGE2, PGF2alpha or 250 uU of oxytocin. Control segments remained untreated. There was a significant increase in contraction amplitude in response to the spasmogens (P less than 0.05) but no increase was seen in controls.


Termination of early gestation with a vaginal polysiloxane device impregnated with (15S)-15 methyl prostaglandin F2alpha methylester.

An investigation of the abortifacient activity of (15S)-15 methyl prostaglandin F2alpha methyl ester released from a vaginal polysiloxane device was performed in eleven pregnant women of 49 days gestation or less. Bleeding and contractions were induced in all women, but only seven aborted their pregnancies. Five subjects received a vaginal device impregnated with 3 mg of drug and two aborted fetal tissue. Six women were given a vaginal device containing 5 mg of drug and five aborted fetal tissue. Ten of the patients had significant side effects, nausea, emesis, diarrhea and chills. Six women expelled the device prior to the termination of therapy. This prostaglandin analogue, when administered from a vaginal polysiloxane device in early gestation was an effective abortifacient but was accompanied by systemic side effects and a high incidence of expulsion of the device prior to its scheduled removal.


Termination of early pregnancy by ONO-802 (16,16-dimethyl-trans-delta2-PGE1 methyl ester).

ONO-802 was infused into the uterine cavity for the termination of early pregnancy in 45 healthy volunteers. Forty two (93%) of the 45 cases had complete abortions and two had incomplete abortions. Nine (20%) of the 45 volunteers complained of nausea, 7 (16%) vomited and 5 (11%) complained of abdominal pain. Neither diarrhea nor weakness was observed. These results suggest that ONO-802 is more acceptable for the termination of early pregnancy than is PGF2alpha.


Prostaglandins in fetal tracheal and amniotic fluid from late pregnant sheep.

Concentrations of prostaglandin E (PGE), prostaglandin F (PGF) and 13,14-dihydro-15-keto-prostaglandin F (PGFM) have been measured in fetal tracheal and amniotic fluid from chronically catheterized sheep during late pregnancy. Amniotic fluid contained significantly greater concentrations of these prostaglandins than tracheal fluid (p less than 0.01); there was no correlation between the level of prostaglandins found in each fluid. In tracheal fluid concentrations of PGE and PGFM exceeded those of PGF (P less than 0.01) whereas no significant differences were found in amniotic fluid. The levels of prostaglandins in these fluids were similar in ewes bearing hypophysectomized fetuses.


Plasma levels of 15(S)15-methyl PGF2alpha following administration via various routes for induction of abortion.

Plasma levels of 15(S)15-methyl PGF2alpha were measured by gas chromatography - mass spectrometry following intravenous, intramuscular and subcutaneous administration. During intravenous infusion of 1.0 and 2.5 microgram/min of the drug for six hours the plasma levels were relatively constant around 600 and 1200 picog/ml, respectively. At an infusion rate of 5 microgram/min the plasma level continuously increased during the administration. Intramuscular injections of 100-400 microgram of 15(S)15-methyl PGF2alpha gave maximum levels in plasma (700-1700 picog/ml) after 15-20 minutes followed by a gradual decrease during more than three hours. This rapid resorption of drug into plasma could be delayed by addition of 5 microgram epinephrine to the injected solution. Analyses during a series of intramuscular injections demonstrated that a therapeutical plasma level could be maintained by injections at two to three hour intervals.


Prostaglandin and thromboxane production by rat decidual microsomes.

The preparation of a microsomal fraction from the decidual tissue of pregnant rat uteri is described. Incubation of such microsomes with a mixture of radiolabelled and cold arachidonic acid (51 micrometer) plus cofactors resulted in a 30% substrate conversion. Products were resolved into four peaks (A, B, C and D) by thin-layer chromatography. Combined gas-liquid chromatography-mass spectrometry and further thin-layer chromatography identified the products as PGF2 alpha (A); thromboxane B2 (B); a mixture of 6-OXO PGF1 alpha and PGE2 (C); PGD2 and PGE2 (D). PGE2 was the major product.


Synthesis of thromboxane B2 and prostaglandins by bovine gastric mucosal microsomes.

Bovine gastric mucosal microsomes synthesize prostaglandins from arachidonic acid but thromboxane B2 is the principal product. Thromboxane B2 synthesis occurs at an appreciable rate from endogenous precursor but more rapidly with added arachidonate. Nonsteroidal antiinflammatory drugs inhibited synthesis of prostaglandins and thromboxanes with the following decreasing order of potency: indomethacin, fenoprofen, acetylsalicylic acid, phenylbutazone, sulfinpyrazone, and acetaminophen.


PGE2 and PGF2alpha biosynthesis in stimulated and nonstimulated peritoneal preparations containing macrophages.

The biosynthesis of PGE2 and PGF2alpha was measured in intact peritoneal exudate preparations obtained from C. parvum-treated and control C3H mice. Although both the control and stimulated preparations biosynthesized PGF2alpha and PGE2 from [1-14C] arachidonic acid, the stimulated preparations generated more of both prostaglandins than did nonstimulated preparations, probably as a result of increased synthesis within macrophages. Increased transformation of PGE2 into PGF2alpha by PGE2 9-ketoreductase was noted in stimulated preparations when compared to that in control cells. The data suggest that stimulated macrophages are capable of generating increased quantities of PGF2alpha and therefore might function as one source of this substance in resolving inflammatory reactions.