Vaso-vasostomy, a modified technique.

Vaso-vasostomy, a modified technique. A modified technique for vaso-vasostomy is described with the aim to achieve better results in operative recanalization and restoration of fertility after vasectomy. Vaso-vasostomy is a success when the man is able to produce fertile semen. Criteria for a fertile semen are mentioned. Fertile semen was obtained in all 5 patients treated by this modified technique.


Rectal bladder with dorsolateral, intrasphincteric submucosal pul through of the sigmoid colon in adult bladder cancer patients. Five years later. Report on 12 adult bladder tumor patients with cystectomy, rectal bladder and dorsolateral, intrasphincteric pull through of the sigmoid and anal colostomy (Nédélec type). Voluntary control of feces and urine was found satisfactory by most patients although urinary continence at night was not perfect. The long-term prognosis with this form of urinary diversion in patients with bladder cancer was far from satisfactory: 4 patients died of recurrent carcinoma with terminal symptoms of sepsis, but 5 patients died from primary sepsis (and not cancer) from 3 months to 4 years after diversion. It seems that this bad prognosis was due to insufficient separation of urinary and fecal passage in a group of patients, where the upper urinary tract has often already suffered as the result of earlier tumor treatment. Fewer complications might be expected with an intersphincteric pull through and perineal colostomy (Gersuny type).


Selective hypothermic perfusion of the kidney for intrarenal surgery. Clinical experience and physiological consideration of selective hypothermia for conservative renal surgery are described. While surface cooling is satisfactory for relatively short ischaemia times, continuous renal perfusion via catheters offers the best wash-out and a completely bloodless field for lengthy surgical procedures. This is demonstrated by a comparison of three different methods of renal hypothermia in somewhat similar cases. During the last 6 years we have successfully used a continuous perfusion technique by direct introduction of catheters into the renal vessels in 16 selected cases. Advantages and drawbacks of this method are discussed.


Hydrostatic overdistension for contracted tuberculous bladder. A review of 61 cases. When a contracted tuberculous bladder is not improved on anti-tuberculosis drug treatment the bladder capacity can be increase by hydrostatic overdistension, done either cystoscopically if reflux is present, or by using a balloon catheter. Of 61 cases so treated, 40 showed marked improvement and 24 of these needed only one overdistension, and the rest required more than one treatment. Nine cases showed no improvement but no further deterioration and 12 cases had continued deterioration.


The wandering testicular pain.

The wandering testicular pain. A typical syndrome of wandering testicular pain and unilateral hydrocele has been observed in three patients.. It is caused by intravaginal, which seem to arise from testicular and epididymal appendices undergoing gradual necrosis and subsequent calcification during torsion.


Impotence and diabetes mellitus.

Impotence and diabetes mellitus. Impotence is a rather frequent symptom in the diabetic patient. The aetiology of this problem is not clear. Urodynamic and hormonal examinations have been performed in a group of 10 diabetics with impotence in order to evaluate its neurogenic and endocrine factor. The determination of the parameters that effect micturition are dependent on the erector nerve, which at the same time participates in erection, demonstrating the existence of a neuropathy of the erector nerve and shows if it is responsible for the impotence. The hormonal examinations were all normal. The different urodynamic alterations which have been found are tabulated and the importance of a simple determination of voiding time, as a proof in the screening of these patients, is emphasized.


Intermittent self-catheterization, and alternative in the treatment of neurogenic urinary incontinence in women. Preservation of kidney function and management of incontinence are the main goals of urological rehabilitation in patients with neurogenic bladder disturbance. It is also the assumption of social intergration. Whereas in male patients this problem can be mostly solved, if need be, by a urinal, females still rely on pads or operative procedures with the risk of complications and failures. For this group of patients intermittent catheterization and, respectively, intermittent self-catheterization, is in selected cases a helpful and harmless method to achieve this goal. Contrary to operative procedures nothing is destroyed and all possibilities remain open for further and better treatment, hopefully soon available. This report presents our experience and results from 12 female patients with neurogenic urinary incontinence, who were treated with this method between 1972 and 1976.


Calcified bacteria in renal stones: electron-microscopic aspects. In some renal calculi whose structure was studied in thin sections, we have found large numbers of rods of the size and shape of bacteria, included in a material consisting of defective apatite calcium phosphates and organic matter. Electron transmission microscopy showed patterns of partially calcified bacteria. With the scanning electron microscopy we obtained only images of bacterial impressions. In struvite stones bacteria are rarely found in thin sections. Extremely high ammonium alkalinisation does not seem to be compatible with the preservation of bacterial bodies capable of being calcified.


Biliary excretion and enterochepatic recycling of proscillaridin A after oral adminstration to man. A single oral dose of proscillaridin A (1.0-1.5 mg) was given to six patients with T-tube drainage of the common bile duct, and simultaneous samples of bile and plasma were collected at various times during the following 24 hours. Glycoside activity was assayed by the 86Rb-uptake inhibition technique. Peak activities in plasma (mean 0.80 ng/ml) were attained after 0.5-2h, and in bile (mean 6.9 ng/ml) after 1-4h. Subsequently, proscillaridin activity in bile was less than 5 ng/ml for the remainder of the sampling period, and 10-100 times higher than that in plasma. Bile samples treated with beta-glucuronidase and sulphatase showed 100-200 fold increase in glycoside activity. Deconjugation was also produced by treatment with enteric contents. The results suggest that conjugation of unchanged proscillaridin is a major metabolic route. After excretion in the bile, the conjugates may be split in the intestine and reabsorbed as active glycoside.


Proscillaridin activity in portal and peripheral venous blood after oral administration to man. The absorption of proscillaridin A was studied in four patients undergoing catheterization of the portal vein for diagnostic purposes. Proscillaridin 1.5 mg was given as a single oral dose and plasma glycoside activity was analyzed by the 86Rb-uptake inhibition technique. Proscillaridin appeared rapidly in the portal blood, peak activity being found after 15 min in three and after 30 min in one patient. In peripheral blood the peak activity occurred after approximately 35 min. Despite rapid passage across the gut wall, porto-peripheral differences in glycoside activity were small; they were zero after 4h. The mean amount absorbed as active porscillaridin during the first 4h after the dose was calculated to be only 7.1% of the given amount. Late porto-peripheral differences, probably due to enterohepatic recycling, appeared after 6h in three patients; The results suggest that proscillaridin undergoes first pass inactivation in the gut wall. Enterohepatic recirculation may contribute to the amounts of active glycoside that reach the systemic circulation.


Pharmacokinetics of paracetamol (acetaminophen) after intravenous and oral administration. Plasma paracetamol concentrations were measured in 6 volunteers after single intravenous (1000 mg) and oral (500 mg, 1000 mg and 2000 mg) doses of the drug. Paracetamol levels declined multiphasically with a mean clearance after intravenous administration of 352 +/- 40 ml/min. A two-compartment open model appeared to describe the decline adequately. Comparison of the areas under the plasma concentration-time curves (AUC) indicated that oral bioavailability increased from 0.63 +/- 0.02 after 500 mg, to 0.89 +/- 0.04 and 0.87 +/- 0.08 after 1000 mg and 2000 mg, respectively. As a consequence of the incomplete bioavailability of paracetamol, as well as its multicompartmental distribution, accurate estimates of its distribution volume and clearance cannot be obtained if the drug is given orally. However, an estimate of its total plasma clearance may be derived from the AUC after a 500 mg oral dose.


Stimulation of drug metabolism by rifampicin in patients with cirrhosis or cholestasis measured by increased hexobarbital and tolbutamide clearance. Eleven patients with hepatic cirrhosis or cholestasis were treated with rifampicin for 7 to 132 days. Ten patients received hexobarbital (7.32 mg/kg) and five received tolbutamide (20 mg/kg) by i.v. infusion prior to and after rifampicin treatment; plasma concentrations of the two test compounds were determined during and after infusion. The average elimination half-life of hexobarbital had decreased from 624 to 262 min and that of tolbutamide from 292 to 160 min following rifampicin treatment. It was calculated that the metabolic clearance of hexobarbital had increased more than two-fold and that of tolbutamide almost two-fold. The results suggests that rifampicin is able to stimulate hepatic drug metabolism in patients with liver disease. It was apparent in general that the induction did not lead to improvement of hepatocellular function during disease as judged by laboratory findings.


Pharmacokinetics and relative bioavailability of levomepromazine after repeated administration of tablets and syrup. Plasma levels of levomepromazine and its sulphoxide were measured in 8 psychiatric patients after repeated doses of levomepromazine tablets or syrup. The rate and extent of absorption of the drug were similar for the two dosage forms, although the extent of presystemic metabolism appeared to be slightly greater after administration of syrup than of tablets. The biological half-life of levomepromazine ranged from 16.5 h to 77.8 h, and a 13-fold variation was seen in the ratio of the total clearance to the absorbed fraction of the dose (Cl/Fpo). It is postulated that individual variation in the dose required for therapy was due in part to individual variation in the pharmacokinetics of the drug.


Cerebrospinal fluid amine metabolites after combined amitriptyline-triiodothyronine treatment of depressed women. Levels of 5-hydroxyindoleacetic acid and homovanillic acid were measured in cerebrospinal fluid from 33 depressed women with no clinical response to amitriptyline, before and after combination treatment with triiodothyronine. Although the latter showed significant clinical improvement, changes in CSF amine metabolites did not differ significantly from a control group of 16 therapy-resistant depressed women receiving higher doses of amitriptyline. Possible explanations for the mechanism of action of triiodothyronine are discussed.


Effect on maturation of kidney function in newborn infants of repeated administration of water and electrolytes. In newborn infants of various ages, the influence of repeated administration of water and electrolytes on renal excretion of urine, sodium, potassium, free and bound hydrogen ions and on urine osmolarity was studied. In 14- and 21-day-old infants the repeated administration of water and electrolytes was followed by diminution of renal excretion of hydrogen ions and potassium, possibly caused by stimulation of hormonal regulation of ion exchange in the kidney. In animal studies performed with a larger water and electrolyte load, stimulation of renal excretion of sodium was caused by the pretreatment.


Control of immunity in parental and F1 hybrid mouse strains to a spontaneously arising parental tumor. I. Correlation between in vitro and in vivo anti-tumor reactivity in responsive and unresponsive animals. This study has investigated the in vivo and in vitro cellular immunity of the AKR/J, (AKR/J x C57BL/6)F1 and (AKR/J x DBA/2)F1 mouse strains to a spontaneously arising AKR/J tumor. The study concludes that: 1) there is an excellent correlation between the growth of the tumor in vivo, and the ability of spleen cells from the respective strains to generate both primary and secondary cell-mediated cytotoxic responses in vitro; and 2) one F1 host can be considered a responder against this tumor, whereas the other F1 strains studied appears to be genetically nonresponsive. Possible mechanisms relating to the observed patterns of response are discussed.


Lymphokine-induced secretion of plasminogen activator by murine macrophages. Thioglycollate-stimulated macrophages are known to release a plasminogen activator (PA) into the medium. In this study it was investigated whether macrophages could be activated to release PA after exposure to lymphokines. Macrophage monolayers obtained by 24 h culture of proteose peptone-elicited murine exudate cells were incubated with lymphocyte culture supernatants. After 48 h the supernatants were replaced by serum-free medium and the macrophages were incubated for another 24-48 h. These supernatants were assayed for PA as measured by the lysis of 125I-labeled fibrin. The following results were obtained: (a) Supernatants of antigen or mitogen-stimulated spleen cells induced PA secretion by macrophages whereas control supernatants were ineffective. The same was found with supernatants of mitogen-stimulated lymph node cells. (b) PA secretion by macrophages seems to be induced by a rather narrow concentration range of lymphokines. (c) Lymphokine-induced PA secretion by macrophages is enhanced after phagocytosis of latex beads. The results show that PA secretion by activated macrophages can be considered as a parameter of immunoactivation.


Genetic control of contact sensitivity to oxazolone in inbred, H-2 congenic and intra-H-2 recombinant strains of mice. Delayed-type hypersensitivity (DTH) to 2-phenyl-4-ethoxymethylene-5-oxazolone (oxazolone) was found to be under multigenic control in inbred, H-2 congenic and intra-H-2 recombinant strains of mice. A high response was associated with haplotypes H-2d,a,k and low response with haplotype H-2b. DTH to oxazolone was high or intermediate in different F1 hybrids of high and low responder mice. In F2 and backcross generations a higher response was associated with the "dd", than with "bb" phenotype, while intermediate response was found in the heterozygote "db" mice. A study of H-2 recombinant strains suggests that a gene controlling the DTH response maps in the I-B subregion of the H-2 complex. The response was significantly modified by gene(s) which are not linked to the H-2 complex and have not been mapped. Since congenitally athymic nude (nu/nu) mice did not respond to oxazolone, this contact sensitivity is belived to be a T cell-dependent immune response.


Thermoregulatory effects of intraventricularly injected dopamine in the goat. Dopamine (DA) was injected in the third brain ventricle of goats and the thermoregulatory effects were studied under different ambient conditions. The effects depended on dose, ambient conditions and cannula used. In the cold, there was a drop in body temperature, sometimes accompanied by suppression of shivering and by vasodilatation. Both temperature decrease and suppression of shivering were dose-dependent but there was no relation between magnitude of temperature drop and occurrence of shivering suppression. In a thermoneutral environment, there was either a slight vasoconstriction or hypothermia, occasionally accompanied by induction of panting. In the heat, either hypothermia or hyperthermia was observed. Hypothermia was accompanied by an increase in panting. Hyperthermia only occurred when the animals became excited as a result of the injection of DA. It is concluded that DA acts by stimulating the thermoregulatory pathway from heat sensors to heat loss effectors at a locus similar to that for 5-hydroxytryptamine in the thermoregulation model of Bligh et al. (1971).


Central cardiovascular effects of phentolamine in chloralose-anesthetized cats. Phentolamine (50, 100 and 200 microng/min for 30 min) perfused through the cerebroven system of chloralose-anesthetized cats produced dose-related reductions in tricular blood pressure. Evidence is presented which suggests that this hypotensive activity was due to an interaction at central nervous system sites and was not attributable to escape of the compound from the brain. Centrally administered phentolamine was more effective in lowering blood pressure than the i.v. infusion of phentolamine at a dose (25 microng/kg/min for 30 min) which markedly antagonized peripheral alpha-adrenoceptors. In addition, central phentolamine induced bradycardia in contrast to the tachycardia which accompanied i.v. administration. By limiting the perfusion of phentolamine to selected portions of the cerebrospinal fluid spaces a major site of action responsible for the hypotensive activity was located outside the ventricles in an area accessible from the subarachnoid spaces. A second, less important site, anterior to the midbrain adjacent to the ventricular system apparently contributed to the hypotension. Phentolamine, introduced centrally, also impaired reflexogenic bradycardia elicited by pressor doses of norepinephrine. Both the sympathetic withdrawal and the vagal activation which account for this reflex seemed to be antagonized by phentolamine.


On the reduced retention of extravesicular noradrenaline in rabbit atria produced by potassium. The effects of KC1 on the retention of extravesicular (--)-[3H]noradrenaline were investigated. Atria, from reserpine-pretreated rabbits, were exposed to tropolone and pargyline before incubation with (--)-[3H]noradrenaline. After efflux for 50-60 min, exposure of tissues to media containing 65 mM KC1 resulted in increased efflux of (--)-[3H]noradrenaline. This effect was not Ca2+-dependent and was not altered by oxymetazoline, phentolamine, indomethacin or methacholine. The KC1-induced reduction in retention of (-)-[3H]noradrenaline was, however inhibited by cocaine and desipramine, but not by lidocaine. Efflux was not increased by RbCl and CsCl. It is suggested that KCl may have accelerated the efflux of extravesicular (--)-[3H]noradrenaline by increasing a cocaine- and desipramine-sensitive carrier-mediated efflux process.


Adrenergic mechanism in cold stored taenia caecum after rewarming. After cold storage of guinea-pig taenia strips for 4 days at 2 degrees C, structures with specific catecholamine fluorescence were not observed. Upon incubation in Krebs Ringer medium (37 degrees C) the fluorescence in the cold stored tissue reappeared and the density of fluorescence was comparable to that of fresh preparations. The specific fluorescence was affected following reserpine or 6-hydroxydopamine treatment; however, the rewarming process restored fluorescence only in the reserpine-treated tissue. The cold storage treatment (4 and 7 days) also decreased the tissue noradrenaline and dopamine contents and dopamine-beta-hydroxylase activity and inhibited the [3H-noradrenaline release from the tissue, all of which were not restored by the incubation procedure. Moreover, in these cold stored taenia the inhibitory effect to nicotine and perivascular nerve stimulation were not manifested. Therefore, the reappearance of specific fluorescence in the cold stored taenia strips after rewarming does not assure functional recovery of adrenergic nerve activity.


The effects of tiadenol, clofibrate and clofibride on bile composition in the rat. Biliary secretion was studied in normolipidemic rats after a 7 day treatment with the hypolipidemic drugs, tiadenol (bis-(hydroxyethylthio)-1,10-decane), clofibrate and clofibride (chloro-4-phenoxy-2-methyl-2-propionate of dimethylcarbamoyl-3-propyl). All three drugs decreased blood cholesterol and total lipids, increased liver weight and liver catalase content, and decreased biliary excretion of cholesterol. The biliary concentrations of bile salts, phospholipids and cholesterol decreased to a variable extent, in such a way that the ratio of bile salts + phospholipids to cholesterol was increased by the drugs. The bile salt independent fraction was increased. The effects were qualitatively similar for all three drugs tested, but quanitative differences appeared for some of the parameters.


Possible role of endogenous catecholamines in the contractions induced in rabbit aorta by ouabain, sodium depletion and potassium depletion. Effects of ouabain, Na+ depletion and K+ depletion on the tension development of rabbit aorta were studied. Contraction in the strips was induced by ouabain and Na+-free solution substituted with Li+, tris or sucrose. The contractions were rarely seen under alpha-adrenergic blockade, in reserpinized aorta and mechanically denervated aorta. Contractions induced by norepinephrine were potentiated by Na+ depletion, K+ depletion and ouabain. Contractions induced by high K+ solution were also potentiated by Na+ depletion and ouabain. The potentiation in Li+ solution, K+-free solution and with ouabain was not seen under alpha-adrenergic blockade, in reserpinized aorta and denervated aorta although the potentiation by tris and sucrose solutions was still observed. These data suggest that Na+ depletion, K+ depletion and ouabain release endogenous catecholamines which affect the contraction of the vascular smooth muscle of rabbit aorta.


Occurrence of oxalyl-CoA synthetase in Indian pulses. The presence of oxalyl-CoA synthetase was observed in common edible pulses. Excepting in chick pea, the changes in oxalyl-CoA synthetase activity of winter pulses proceeded in stages. The enzyme remained more active in late strains than in early strains of winter pulses. Unlike the activity of the enzyme in winter pulses, that in summer pulses behaved differently.


Nuclease for DNA apurinic sites in chicken liver. Chicken liver crude extract produced acid-soluble diphenylamine-positive material in the presence of depurinated and alkylated DNA, while the formation of such material from normal and single stranded DNA was comparatively low. The maximum acid-soluble material produced was not increased further by alkali, indicating that the enzymatic action is mostly directed towards apurinic sites.


Effects of Ag+ on frog skin: interactions with oxytocin, amiloride and ouabain. Different biological effects of Ag+ (10(-4) M) were found depending on its presence in the outer or the inner solution bathing the frog skin. A marked increase in the electrical conductance and an interference with the action of oxytocin and amiloride were found only when Ag+ was added to the outer solution. Results suggest that Ag+ affects several transport processes, in particular the permeability of the Na entry pathways.


Role of Friend-associated lymphatic leukemia virus in immunization against Friend leukemia complex. Mice inoculated with Friend leukemia complex (FLC) pretreated with concanavalin A are resistant to FLC challenge only when they have become infected with the FLC-associated lymphatic leukemia virus (LLV). In interpreting states of resistance to FLC induced by various immunizing procedures, the possibility that immunity is sustained by an unrecognized LLV infection should always be considered.


Artificial kernels and food bands for raising Sitophilus oryzar (L.) on microscopic concave slides. Artificial kernels and food bands (1 mm thick) stretched on concave microscopic slides proved inviting and very suitable for oviposition and for completing the life cycle of Sitophilus oryzae (L.). This artificial medium contains jelly, wheat flour and corn oil, its moisture content is 18.1%. This is the first time it was possible to breed an insect on artificial media on glass slides.


Synthesis of ecdysone-14C and ecdysterone-14C from cholesterol-14C in cockroaches (Periplaneta americana) without molting glands. The synthesis of molting hormone of cockroaches of which the prothoracic glands had previously been extirpated was investigated after injection of cholesterol-14C. It could be proved by means of radio thin-layer chromatography of extracts that ecdysterone and in small amounts ecdysone are synthesized in Periplaneta americana larvae without prothoracic glands. The results demonstrate that other tissues are also able to perform the molting hormone besides the molting gland itself.


Age-dependent change in the ability of protein synthesis by rat liver microsomes-significance of 2 associated factors. An activator and an inhibitor of polypeptide synthesis were isolated from microsomes of rat liver. The young rat contained a higher level of the activator but a lower level of the inhibitor than the aged rat. The significantly higher ratio of the specific activity of the activator to inhibitor in the young microsomes helps explain the higher capacity for protein synthesis of these microsomes as compared to the microsomes of the aged animal.


Light evoked release of radioactivity from rabbit retinas preloaded with (3H)-GABA. Light flashes evoke an increased release of radioactivity in vitro from rabbit retinas preloaded with (3H)-GABA in vivo. Constant light does not affect the release. No light evoked release can be demonstrated from the glia. Pentobarbitone and AOAA depress the evoked release. The results are consistent with GABA being a retinal neuro-transmitter, most likely in a class of amacrines.


Experimentally induced otitis and audiogenic seizure in the mouse. Audiogenic seizures can be induced in genetically non-susceptible 17-day-old mice (Rb/3 strain) with various results. Priming only induces 9% of seizures, auditory insulation 3,8%, while experimental otitis leads to 79%. The hypothesis concerning disuse supersensitivity subsequent to acoustic deprivation was not confirmed by the experiment. However, modification of acoustic transmission at middle ear level induced by otitis or ear physical damage during the maturation period, exposes the upper nervous centers to intense stimulation to which the reaction is a recruiting response.


Intracellular recordings from Deiters' neurons in response to saccular and oculomotor nucleus stimulations. 2 populations of cells were found in the Deiters' nucleus responsive to direct electrical stimulation of the ipsilateral saccule. Only those Deiters' neurons activated monosynaptically from the saccule could be driven antidromically from the oculomotor nucleus. Such an intracellular study provides strong evidence for a tri-neuronal arc in the sacculo-ocular reflex for vertical eye movements.


Electrically-induced mechanical activity of the isolated guinea-pig sciatic nerve. Influences of calcium and anoxia. The electrically-induced motility of isolated segments of guinea-pig sciatic nerves is reported. This motility was characterized by waves of tensional variations. The removal of Ca2+ from the suspending solution, the addition of EDTA as well as anoxia, resulted in a decrement of tension accompanied by a prolonged duration of the cycles of mechanical activity.


Preparation of fixed antigenic, non-oncogenic and protective neoplastic cells. Transplantable spontaneous mammary adenocarcinoma and sarcoma P 1798 cells were incubated with vibrio cholera neuraminidase (VCN), then fixed cells demonstrated ability to exclude trypan blue dye and to immunized animals and produce cytotoxic sera of high titers. The fixed neuramindase-treated tumor cells became non-oncogenic and protected the host against high doses of fresh untreated homologous tumors.


The role of the subependymal plate in the origin of gliomas induced by ethylnitrosourea in the rat brain. The fine structure of early cell proliferations induced transplacentally by ethylnitrosourea in the rat brain reveals that the cells show features of the undifferentiated cells of the subependymal plate: high nuclear-cytoplasmic ratio, scarity of cell organelles and dominance of free over membrane-bound ribosomes. These findings suggest that most, if not all, gliomas induced by ethylnitrosourea originate from these primitive cells.


Relation between stimulus intensity and neutrophil chemotactic response. The effect of chemotactic peptides which lack chemokinetic activity has been investigated. The neutrophil response is proportional to the logarithm of the stimulus intensity, or alternatively a power function with an exponent of 0.3. Equal responses are obtained for equal ratios between the peptide concentration in the lower compartment and the threshold concentration. The significance of Weber-Fechner's law in leucocyte chemotaxis is discussed.


The influence of long term estrogen treatment on plasma prolactin levels induced by ether anesthesia in ovariectomized rats. 2 methods of continuous estrogen delivery, polyestradiol phosphate injection and implantation of Silastic capsules of estradiol-17 beta, in ovariectomized rats induced increases in plasma prolactin in the afternoon (15.00-17.00) beginning at 1 week and continuing for 4-8 weeks. In addition these methods of estrogen treatment potentiated the ether-induced increase in plasma prolactin in the morning (9.00-11.00) beginning on week 2 and continuing for 3-8 weeks. These results indicate that estrogen activates the mechanisms that cause an afternoon surge in prolactin before potentiating a morning elevation induced by ether anesthesia.


Hypercalcitoninemia in pancreatitis--evidence for immunochemical heterogeneity. Recently in our laboratory we have demonstrated increased immunoreactive calcitonin (iCT) levels in 4 patients with acute pancreatitis and hypocalcemia. The present study consists of 17 additional patients in whom serial determinations for (iCT) were performed. Furthermore, with the use of 2 different antisera directed against human calcitonin we present evidence for immunochemical heterogeneity of this hormone in acute pancreatitis.


The occurrence of 12, 13-epoxytrichothecenes in seeds of safflower infected with Fusarium oxysporum f. sp. carthami. From the seeds of safflower (Carthamus tinctorius Linn.), infected with Fusarium oxysporum f. sp. carthami, 3 toxic compounds have been isolated in quantities sufficient to cause mycotoxicosis on prolonged ingestion. 2 of these have been identified as diacetoxyscirpenol and T-2 toxin, while the third one has also been partially characterized as a 12, 13-epoxytrichothecene. Additionally, the incidence of secondary fusarial infection of healthy seeds due to contamination with the infected ones has been reported for the first time.


The absolute configuration of SU 23397: a novel neuroleptic agent. The absolute configuration of a novel chiral neuroleptic agent SU 23397 (I) was determined by ORD comparison of (+)-5-methoxy dihydro coumarilic acid (VIII), a synthetic precursor of SU 23397 (I), with (+)-dihydro coumarilic acid, whose absolute configuration is known. This assignment was confirmed by oxidative degradation of (+)-5-methoxy dihydro coumarilic acid VIII to D-(+)-malic acid.


Calcite growth under controlled diffusion. The growth of calcite was studied in a gelatin-gel medium under variable environmental conditions by 2 different methods. The results suggest that the organic matrix, the temperature, the diffusion fluctuation depending on ionic concentrations, and the presence of additives exert a fine control on the evolution of single crystals, polycrystalline aggregates, and highly structured concretions of calcite.


On urea formation in marine mammals.

On urea formation in marine mammals. Ornithine carbamoyltransferase (EC 2.1.3.3) has been determined in homogenates of liver of the sei whale (Balaenoptera borealis), the bottle-nose dolphin (porpoise) (Tursiops truncatus) and California sea lion (Zalophus californianus). These marine mammals show levels of this ornithine-urea cycle enzyme which are typical of terrestrial mammals.


Gas chromatographic-mass spectrometric identification of epinine in rat superior cervical ganglia and formation in vivo. Epinine was identified in rat superior cervical ganglia by a gas chromatographic-mass spectrometric method. The deuterated methyl group of i.v. administered labeled methionine was incorporated into epinine at a slow rate, although epinephrine-CD3 was rapidly formed. These results indicate that epinine found in the ganglia is not a precursor of epinephrine.


Phalloidin poisoning of isolated hepatocytes: inhibition of protein synthesis. Phalloidin added to isolated hepatocytes inhibits amino acid incorporation into protein. Inhibition is very strong with 20 micrograms/ml phalloidin and occurs after a lag period of about 30 min. After this period, poisoned hepatocytes also show morphological changes in their plasma membrane.


[Larval development and determinism of nymphal diapause in a Lepidoptera, Actias selene Hbn. (Attacidae) (author's transl)]. Actias selene has been reared under different conditions of lights, photophases and temperatures. The red light (630-670 nm) corresponding to the maximum of absorption of pterobilin and phorcabilin chromoproteins reduces the average length of development from 29 days to 50 days and totally inhibits the nymphal diapause. The results are discussed.


Temperature-dependence of stress-induced hepatic autophagy. In rats, restraint for 48 h elicits hepatic glycogen depletin, autophagy and other ultrastructural changes (e.g. mitochondrial enlargement and rough endoplasmic reticulum disorganization) associated with marked hypothermia. By restoring the body temperature of these animals, all the hepatocytic alterations are abolished.


Effects of sera and liver extracts from partially hepatectomized rats on liver slice DNA synthesis. Sera from partially hepatectomized rats (PH) compared to sera from control rats (C) enhance liver slice DNA synthesis but depress kidney slice DNA synthesis. Alone, liver extracts from PH do not affect DNA synthesis; but adding sera to PH extracts stimulates, suggesting that sera and liver factors from PH may participate in compensatory growth.


Is the renal vasodilatation induced by beta-adrenoceptor stimulants in the dog mediated through dopamine receptor? In chloralose-anaesthetized dogs the renal vasodilator effect of isoprenaline is depressed by blockade of either dopamine or beta-adrenoceptors but the renal vasodilator effect of dopamine is depressed only by blockade of dopamine receptors. This suggests that the vasodilatation induced by beta-stimulants within the canine kidney is due in part to activation of dopamine receptors.


Hormonal manipulation of carrageenin-induced pyresis in rats,. The intensity of the hyperthermic response in rats promoted by subplantar injections of 1 mg of carrageenin is directly related to the irritant properties of the type of carrageenin. The overall pyretic response is more dramatic in female rats than in male rats. Subtle changes in the time-course hyperthermic profiles are seen after hormonal modifications.


Spectral changes resulting from the interaction of some N-alkyl nitrosamines and rat liver microsomes. Dimethyl (DMN) and diethyl nitrosamine (DEN) do not give characteristic spectral changes upon interaction with rat liver microsomes, while dipropyl (DPN) and dibutyl (DBN) nitrosamine cause type I spectral changes. The spectral binding constant is 100 mM for DPN and 1.17 mM for DBN. The maximal spectral change is 3.2 X 10(6) and 1.0 X 10(6) absorbance units per milligram protein for DPN and DBN respectively.


Thymus gland involution induced by lithium chloride. Chronic treatment with lithium chloride produced significant involution of the thymus gland with histological evidence of reduced cellularity due to loss of thymic lymphocytes and a significant reduction in the weight of the gland in normal and adrenalectomized mice. Lithium also increased corticosterone levels in normal mice without changes in adrenal weights. The involution of the thymus gland is most likely due to an effect of lithium on the gland, and it is not mediated by adrenocortical mechanisms or stress.


Red blood cell glycolysis and potassium type in sheep. Based on the observations made on human and dog red blood cells, it was recently proposed that the response of red cell glycolysis to variations in the levels of specific cations in an evolutionary adaptation in response to a specific cellular environment. We have now examined the effect of K+ and Na+ on the activity of pyruvate kinase (PK) in the red blood cells from 2 genetically different types of sheep high potassium (HK) and low potassium (LK). The results indicate that K+ stimulate glucose consumption and the activity of PK in both types of sheep. It thus appears that red cell PK from LK sheep does not fit into the concept of cellular environment and PK activity.


A simplified method for reading hemagglutinations on a flat-bottom microtitration plate in the mouse H-2 assay. Kaliss' method for determining hemagglutination titer of mouse alloantiserum was modified to a simpler form. It became possible to read the hemagglutination directly on a flat-bottom microtitration plate using an inverted type microscope. Sensitivity of the modified method was almost the same as that of the original one. This method seems to be useful especially for the larger scale assay of H-2 specificities.


Species difference in the effects of proteolytic enzymes on red cell membrane. Pronase and alpha-chymotrypsin digested the major glycoprotein in the human and mouse red cell membranes and in SDS gel electrophoresis the glycoprotein disappeared accompanied by the appearance of a new band of lower mol. wt. However in the membranes of sheep, rat and rabbit, no digestion was demonstrated. The effects of pronase on anion permeability were almost identical for human and animal erythrocytes.


Aggregation pheromones in 2 Australian hard ticks, Ixodes holocyclus and Aponomma concolor. The presence of an aggregation pheromone has been demonstrated for the first time in indigenous Australian ticks. Filter paper discs exposed to either Australian paralysis ticks Ixodes holocyclus or echidna ticks Aponomma concolor showed inter-sex or intra-sex attraction for ticks of their own species. Nymphal exuviae of Ap, concolor were highly attractive to adult ticks. Discs were significantly attractive to I. holocyclus at distances up to 80 cm.


The effect of small doses of antidiuretic hormone on renal excretion of sodium and water in saline loaded acutely hypophysectomized rats. Small doses of vasopressin (200 micronU min-1 kg-1) did not influence the loss of ability of acutely hypophysectomized rats to react by natriuresis to the extracellular fluid volume expansion with saline, inspite of restoring their arterial blood pressure to normal. It is concluded that the level of antidiuretic hormone efficient enough to concentrate urine is not a decisive factor in the homeostatic mechanism promoting the 'volume' natriuresis.


Birth control in India: the carrot and the rod? The fall of the Indira Gandhi government seems to validate the prediction made six years ago by demographer Frank Notestein that any attempt by a developing country to force its people to use birth control methods "would be more likely to bring down the government than the birthrate." This author, however, interviewing couples seeking sterilization, contraception and abortion, as well as the doctors, nurses and administrators who provided the service, just weeks before the upset election, found that family planning was very much wanted and needed by the people, and was being provided in an efficient and humane way. Thus, pressing the population panic button was probably not only unnecessary, but a tragic mistake on the part of the Gandhi government.


Guessing and misinformation about pregnancy risk among urban mothers. Only one-third of urban mothers interviewed twice, a year apart, answered correctly both times about when during the menstrual cycle a woman is most likely to become pregnant. Classroom discussions about contraception, attendance at family planning clinics, and discussions with one's mother about contraception are not positively associated with knowledge about pregnancy risk. Those using methods other than the pill or IUD are more knowledgeable about pregnancy risk--perhaps because they have a greater need to know.


Observations of conjointly hospitalized "alcoholic couples" during sobriety and intoxication: implications for theory and therapy. This paper presents clinical data from a research study designed to examine the relation between alcohol consumption and interactional behavior in "alcoholic couples". The central innovative feature of the study was the simultaneous admission to an inpatient setting of up to three couples, one or both members of which was alcoholic. The in-patient experience was part of an intensive, six-week, multiple-couples, group-therapy program. During hospitalization couples were encouraged to reproduce as closely as possible their usual drinking patterns and interactional behavior. Therapists utilized observations of interactional behavior during intoxication and sobriety to formulate central interactional and psychological issues for each couple. The authors utilized these same observations to develop the interactional model of alcoholism in families that is presented in detail in this paper. This model is an extension of earlier work delimiting an interactional theory of alcoholism based on general systems concepts.


Multiple overt incest as family defense against loss. A case report of father-daughter incest is presented that illustrates the way in which overt incest can function as a multi-determined familial defense against separation and loss. The case is further distinguished by: (a) multiple incest and (b) family therapy--an approach infrequently described in the literature on this problem. The authors have adopted the psychodynamic view that incest expresses the collective psychopathology of all the family members as well as their common adaptational capacities. Specifically, we have attempted to demonstrate that separation anxiety was a shared dread in this family and that incest defended against this painful prospect.


A system for tailoring change measures to the individual family. The focus of this project is the problem of evaluating change in families. Prior work has tended to limit itself to anecdotal or self-report data. By and large, the studies that have evaluated a family intervention by observing family interactions have failed to demonstrate change. A major drawback in such studies has been the assumption that the few interaction variables selected (e.g., amount of silent time) have roughly the same salience and meaning for all the families studied. The measurement system described here was developed to fulfill four methodological requirements: (a) to represent the family as a whole; (b) to be sensitive to change; (c) to contain multiple measures; and (d) to be adaptable to the variation among families. The solution to these requirements, presented here, is a system for tailoring measures to individual families.


Interpersonal perception in addict families. A technique called the "Interperception Matrix" was devised to investigate interpersonal perception in eight families in which addicted offspring maintained close parental ties. The addict families were compared with eight matched control families. Several differences were found between the two types of families. In addict families: (a) addicts, their fathers, and their mothers all held the addicts in low regard; (b) addicts were described as very different from their parents; (c) parents and addicts disagreed more in their perception of the addicts; (d) there was a consensus that the addicts' major flaws were passivity and dependence; and (e) the addicts' mothers described themselves as less agreeable and more passive. Addict families and control families were similar in their descriptions of an ideal for the offspring and in generally favorable descriptions of both parents. These results extend and partially validate clinical observations that social perception in addict families serves to perpetuate opiate addiction by undermining addicts' self-esteem. These data, in conjunction with new understandings emerging from the addiction literature, support an approach to addiction therapy based on reframing family perception.


Paradigmatic classification of family therapy theories. This review proposes a method for classifying theories of family therapy in terms of the ideal categories from which they derive. Establishing the relationship between a family-system theory and a more general world view facilitates the identification of unique aspects of theory and lays the groundwork for a theoretically consistent integration of therapy and research.


Architecture: effect of territory, boundary, and orientation on family functioning. Most students of family process and family therapy practitioners have failed to pay sufficient attention to the importance of the physical home environment. The thesis of this paper is that the physical home environment may facilitate or constrain inter- and intrafamily interaction, role relationships, values, and indentities. The paper presents a comprehensive review of the status of current knowledge concerning family interaction and the home environment. We propose a conceptual framework to facilitate discussion of the nature of man-environment relationships and focus attention on those aspects of the physical environment that have been noted as profoundly influencing family life. These are illustrated by three brief vignettes drawn from case studies of families in their home environment.


A mother-child, multiple-family, counseling program: procedures and results. The purpose of this study was to determine the effects of a family counseling program of the following variables: (a) parents' family satisfaction, perceived integration, and family congruence; (b) the number of positive and negative responses communicated among family members; and (c) an undesirable behavior exhibited by one child in the family. The sample consisted of 14 families in the experimental condition and 11 families in the control condition. Mother and one child had responsibility for teaching other family members that principles taught during the multiple-family category sessions. The findings indicated: (a) parents receiving family counseling increased significantly their family-satisfaction and perceived-integration scores as compared to the parents not receiving counseling; (b) families receiving counseling increased significantly the number of positive responses among them compared with the control families; (c) children receiving counseling decreased significantly the frequency of exhibiting a specific undesirable behavior; and (d) no significant differences were found between the groups of families in parents' family-congruence scores and in the number of negative responses communicated among family members.


Structural family therapy for children of divorce: case reports. Structural family therapy techniques for treating families with a parental divorce in which a child is symptomatic are described. The family configurations considered are: mother, child, and maternal grandparents; overprotective mother and child; helpless and mildly neglectful mother; father; new family formation; and couples who divorce and marry new spouses.


The marital system of the hysterical individual. The purpose of the present article is to supplement the considerable body of clinical literature that focuses on hysterical behavior from an individual perspective. Based on findings from a total sample of 16 couples, this paper accomplishes this task in a threefold manner. First, the characteristic type of individual who selects and is selected by the hysterical individual as a life partner is described. Second, the type of relationship these two individuals typically develop, which promotes and reinforces severely maladaptive behavior on the part of both is delineated. Third, a number of specific recommendations regarding psychotherapy for this type of relationship are proffered.


Time-extended family interviewing.

Time-extended family interviewing. This paper presents a family-therapy technique--time-extended family interviewing--in which the therapist extends the traditional one-hour interview to three to seven hours, by plan, at a particular point in the life of a case and for a particular purpose. Extended sessions promote movement in a case for a variety of reasons. Furthermore, the use of such sessions highlights the dimension of time as an important element of good casework practice.


[Bicyclic analogs of piperazine. XII. (1) - Synthesis of 3,8-diazabicyclo/3,2,1/octanes as potential antiparkinson agents]. As a part of research on 3,8-diazabicyclo [3,2,1] octanes, the Authors report on the synthesis of some amides of methyl, phenyl and cyclohexyltropic acid, potentially active as antiparkinson agents. Also reported is the synthesis of some compounds similar to two known drugs, Caramiphene and Cycrimine. These compounds differ from the said drugs in having a 3,8-diazabicyclo [3,2,1] octane as a basic moiety.


DNA receptor sites for the intercalation of nogalamycin. The intercalation of the planar chromophoric moiety of nogalamycin between two base pairs of duplex DNA has been evidenced by means of low-dichroism measurements. The possible presence of specific binding sites for mogalamycin on DNA has been suggested by studies on the denaturation and renaturation of DNA complexed with nogalamycin. A clear evidence was obtained by investigating the interaction of nogalamycin with polydeoxyribonucleotides containing known, regularly repeating sequences, used as model compounds. The results obtained with these polymers and the DNA suggest that the segment containing both purine (A,G) anf pyrimidine (T,C) bases in alternate sequences is the preferential receptor site on the DNA. A decreasing affinity is exhibited by poly d(A--T)-poly d(A--T), poly d(G--C)-poly d(G--C) and poly dG-poly dC segments, in the order. The poly dA-poly dT sequence appears to be closed to the interaction of nogalamycin.


Synthetic analogs of natural prenylated and chromene chalcones. A number of synthetic analogs of the prenylated and chromene chalcones isolated from lonchocarpus neuroscapha (Leguminosae) were obtained by condensation of prenylated acetophenones with substituted benzaldehydes. The antibacterial activity of these products was studied and correlated with their structure.


[On the phytotoxicity of some N 1-phenyl-N 1- alkylureas]. A series of N1-phenyl-N1-alkylureas (E) and a series of N-carbamoyl derivatives of tetrahydroquinoline (D) were prepared and studied for phytotoxicity. The substances studied (Tables I, II, substances i leads to xxvii) were mostly new compounds and were prepared from suitable secondary amines by condensation with alkylating agents. Biological tests involved pre- and post-emergence treatment of five common weeds with doses of 6 kg/ha and lower doses (Tables i, ii). The tetrahydroquinoline derivatives (I leads to VII) proved inactive except for the N-dimethylcarbamoyl derivative (III) which on foliar absorption showed selective phytotoxicity against Vicia sativa L. Most of the members of the N1-phenyl-N1-alkylurea class (VIII leads to XXVII) did not have wide spectrum phytotoxicity. Some compounds have however interesting specificity of action against Vicia sativa L.


Synthesis and antiinflammatory activity of 3-chloro-4-cyclopropylmethoxyphenylacetic acid and its alpha-methyl homologue. The synthesis of 3-chloro-4-cyclopropylmethoxyphenylacetic acid (I) from 3-chloro-4-hydroxyacetophenone (III) by the etherification with cyclopropylmethyl bromide and by the Willgerodt reaction is described. The alpha-methyl homologue (II) was also prepared from 4-benzyloxy-3-chlorophenylacetate (VIII). The antiinflammatory, analgesic and antipyretic activities of the lysine salts of (I) (ISF 2508) and (II) (ISF 2606) were tested in comparison with alclofenac and phenylbutazone. The new ocmpounds compare favourably with the standards; in particular ISF 2508 was selected for further pharmacological studies.


2,6-dialkylpiperazines. VIII (1)-N1-arylalkyl-N4-(2'-pyridyl)-2,6-dimethylpiperazines as adrenolytic and vasodilator agents. A series of cis and trans N1-arylalkyl-N4-(2'-pyridyl)-2'6-dimethylpiperazines were synthetized and tested as adrenolytic and vasodilator agents. The N1-substitution with the 3,4-dimethoxyphenethyl group seems the most promising with regard to pharmacological activity, which was found to reside mainly in the trans isomer (3-II b). The adrenolytic activity of (3-II b) is comparable with that of the related 2-methyl derivative (1-III), while it is higher than that of (IV) in which the piperazine nucleus is C-unsubstituted.


Drug-protein interaction: the binding of cephalosporins to albumins. The binding of some cephalosporin antibiotics, namely cephalothin, cephaloridine and cephalexin, to serum albumins was quantitized using a fluorescence probe technique. The results suggest that these drugs bind to hydrophobic sites on serum albumins. The association constants of the three drugs with bovine serum albumin showed the strongest binding for cephalothin (Ka 1.2 x 10(3) M(1)) and weaker ones for cephaloridine and cephalexin (Ka 0.59 and 0.4 x 10(3) M(-1)). Serum albumin from different species was also investigated, only minor variations in the binding properties being found.


[Synthesis of n-pentanoylmethylenetriphenylphosphorane]. An efficient synthesis of n.pentanoylmethylenetriphenylphosphorane (II), useful intermediate for achievement of prostanoic derivatives, is described. The procedure affords the desired product at a remarkable degree of purity.


Interaction of new derivatives of daunorubicin and adriamycin with DNA. The interaction of a number of new derivatives of the antitumour antibiotics daunorubicin and adriamycin with calf-thymus DNA has been studied by equilibrium dialysis and low-shear viscosimetry. The results are interpreted in terms of structure of the compounds, also by examining molecular stereomodels.


[Non-steroid anti-inflammatory agents. Stereoisomers of 2-(-4-biphenylyl)-3-oxybutyric acid]. The synthesis, diastereoisomeric separation, attribution to erythro and threo series, and resolution of the enantiomers of 2-(4-biphenylyl)-3-oxybutyric acid are described. The four isomers were tested for anti-inflammatory activity: the preliminary results are interesting, particular those for the (--) erythro enantiomer.


On the thermal properties of 2-sulfanilamido-5-methoxypyrimidine. The thermal behavior of 2-sulfanilamido-5-methoxypyrimidine (sulfamethoxydiazine; SMD) polymorphs was investigated and the heat effects associated with solid-solid and solid-liquid transitions are briefly discussed.


[Study on substances with antiblastic activity. LIX - Anthramycin and analogs. VIII : synthesis of derivatives of 4H-pyrrolo/1,2-a/[1,5]benzodiazepine]. Preparation of 4H-pyrrolo[1,2-a][1,5]benzodiazepine derivatives related to the antitumoral antibiotic anthramycin, a derivative of 5H-pyrrolo[2,1-c] [1,4]benzodiazepine, is reported. Reaction between 1-(o-acetamidophenyl)-2-dimethylaminomethylpyrrole iodomethylate and potassium cyanide afforded 4,6-dihydro-5H-pyrrolo[1,2-a][1,5]benzodiazepine-5-one, which was then reduced to 5,6-dihydro-4H-pyrrolo[1,2-a][1,5]benzodiazepine by the action of lithium aluminum hydride. Some 6-acylderivatives of the latter compound are also described. The Vilsmeier-Haack reaction on 6-acetyl-5,6-dihydro-4H-pyrrolo[1,2-a][1,5]benzodiazepine furnished the corresponding 1-formyl derivative which was then condensed with ethyl cyanoacetate to give the related compound with the acrylic moiety.


[Synthesis and antimitotic activity of 3- and 5-halogen substituted bis-(2-aminophenyl)disulfides and corresponding N-alkyl derivatives]. In continuation of previus research on the antimitotic activity of aryldisulfides, the Authors have synthesised 3- and 5-chloro or fluoro substituted bis-(2-aminophenyl)disulfides and some of their 2-N-alkyl derivatives. These compounds were synthesised in order to submit them to biological testing to find any activity caused by halogen substituents on the benzene ring.


[Study on the degradation products of mecinarone]. The isolation and identification of degradation products of mecinarone produced when the drug is exposed to heat, light or a mild oxidant are described. A method for separating these products by low pressure liquid chromatography is presented.


The behaviour of 2-methylene-3,3-dimethylcyclopentane-1-one towards Michael's addition. The employment of malonic acid dimethylester as a blocking group of a dynamic and self isomerising alpha,beta-unsaturated cyclopentanone-exomethylene group is reported.


[Studies on the chiroptical properties of 2,4-dinitrophenyl derivatives of amino compounds of pharmaceutical interest]. Some results on the chiroptical properties of 2,4-dinitrophenylaminoacids reported in the literature, have been re-examined since they were in disagreement with our earlier research. Extension of this research to several sympathomimetic amines, demonstrates that the chiroptical properties of these derivatives show coherent behaviour; as a consequence the absolute configuration of the amino compounds condensed with Sanger reagent can be correlated to the sign of their higher wavelength Cotton effect.


[Chemical and pharmacological research on pyran derivatives. VIII. Synthesis of 2-dialkylamino-7-methoxychromones and derivatives]. 2-Dialkylamino-7-methoxychromones were prepared by reaction of a m-methoxyphenol with N,N-dialkylethoxycarbonylacetamides in the presence of phosphorus oxychloride. Treatment of such compounds with 57% hydriodic acid resulted in the formation of the corresponding 7-hydroxy derivatives. These latter, treated with dialkylamines and formaldehyde, were transformed into the 8-dialkylaminomethyl derivatives. On the other hand the reaction of 2-dialkylamino-7-methoxychromones with morpholine and formaldehyde, in the presence of acetic acid, led to the formation of the corresponding 3-morpholinomethyl derivatives. Pharmacological investigation showed that 2-dialkylamino-7-hydroxy-chromones were without effect, whereas all other compounds tested had a clear, but generally weak, CNS stimulant activity.


[Formation of an azoderivative of phenothiazine]. The reaction of phenothiazine-5-oxide in 2 N HCl with 2,4-dinitrophenylhydrazine gives rise to 3-azo-(2',4'-dinitrophenyl)phenothiazine and phenothiazine. The stoichiometric ratio is two molecules of phenothiazine-5-oxide to one molecule of 2,4-dinitrophenylhydrazine.


Synaptic modulation of endogenous neuronal oscillators. Techniques derived from oscillator theory can be used to describe the activity of molluscan endogenous bursting neurons and some ways in which synaptic inhibition from an interneuron can modulate this pacemaker activity. The effects of exogenous synaptic inputs on the endogenous neuronal oscillator can be described by a phase response curve. On the basis of the phase response curve, more complex interactions (such as synchronization and entrainment) can be predicted.


Reconstructive tubal surgery for midtubal obstruction. With the  currently growing trend toward voluntary sterilization comes an increase in requests for reversal of that procedure. In our study, 14 patients were candidates for tubal reanastomosis. Seven of the patients became pregnant within 17 months after the procedure: three had normal infants (21%), three had ectopic pregnancies (21%), and one was lost to follow-up (7%). We emphasized very careful handling of the tissues and as short an operative period as possible. We did not use corticosteroids or polyethylene or Teflon prosthetic devices, believing them to be neither a substitute for nor an aid to careful surgical techniques involving delicate instruments and small, atraumatic needles.


The concentration of copper in human uterine secretion during four years after insertion of a copper-containing intrauterine device. The contraceptive action of a copper-containing intrauterine device (Cu IUD) is mainly associated with the copper ions released, thus its efficiency varies with the surface area of the copper wire. It is of considerable clinical interest to know the usful life-span of a Cu IUD. Therefore, the concentration of copper in the uterine secretion of women wearing a Cu-7 IUD (Gravigard) with a surface area of the copper wire of 200 sq mm was determined by atomic absorption spectroscopy. No decrease in the concentrations of copper was found in a series of women followed for 4 years after the insertion of a Cu IUD.


Evidence of higher ethynylestradiol blood levels in human hypertensive oral contraceptive users. These studies were designed to investigate the differences in blood plasma levels of ethynylestradiol (EE2) in women who developed hypertension while taking combined estrogen and progesterone oral contraceptives (OCs) and in normotensive OC users. Blood samples were collected in heparinized tubes 10 hours after OC ingestion, the plasma was separated, and EE2 was measured by radioimmunoassay. The results showed significantly higher plasma levels of EE2 in the hypertensive OC users as compared with the levels in normotensive OC users (P less than 0.01). In another study, blood samples from hypertensive and normotensive OC users were obtained for 3 consecutive days at fixed intervals following OC ingestion, and plasma levels of EE2 were measured. The results showed consistently higher EE2 blood levels during this 3-day period in the hypertensive subjects (P less than 0.01). It is postulated that the higher blood levels of EE2 in hypertensive OC users result from either decreased metabolism or excretion of synthetic estrogens.


Acute effects of intravenous infusion of 17beta-estradiol and 17alpha-hydroxyprogesterone on gonadotropin release. The normal midcycle surge of luteinizing hormone (LH), an approximately 10-fold increase, and a smaller surge of follicle-stimulating hormone (FSH) are preceded by peaks in serum estradiol (E2) and 17alpha-hydroxyprogesterone (17-P). The elevation in E2 is thought to be the important trigger mechanism for the LH surge. The possibility that the preovulatory elevation in 17-P may by itself, or combined with E2, be the trigger mechanism was investigated. E2 ans 17-P, alone and combined, were infused to mimic late follicular-phase blood concentrations in postmenopausal women pretreated with E2. This produced 1.6- to 4.6-fold increases in serum LH and lesser increases in serum FSH 24 hours after infusion. Thus, the normal ovulatory surge of gonadotropins could not be reproduced by infusions of 17-P or E2, or both. Infusion with 17-P appeared to stimulate LH release and did not augment or inhibit the effect of E2 on gonadotropin release.


Phenotypic and cytogenetic findings in eighty-two patients with ovarian failure--changing trends. Eighty-two patients with primary ovarian failure were evaluated clinically and cytogenetically. Sex chromosome privations were present in 52 individuals (chromosomally incompetent ovarian failure [CIOF]). A normal chromosomal constitution was present in 30 individuals (chromosomally competent ovarian failure [CCOF]). Limited estrogenic function (menses) occurred in 11.5% of the CIOF group and 40% of the CCOF group. The phenotypic features of each group are detailed in relation to chromosomal constitution, stature, estrogenic ridge function, incidence of dysgenetic tumors,  and cardiovascular renal malformations. The increasing percentage of patients with CCOF due to possible diverse etiologies is noted and discussed.


Spontaneous spermagglutination in ejaculates from men with head-to-head or tail-to-tail spermagglutinating antibodies in serum. Weak or sometimes up to moderate spermagglutination was encountered in ejaculates from a group of men without spermagglutinating antibodies in serum. A similar pattern of spermagglutination was seen in ejaculates from men with head-to head (H-H) spermagglutinating antibodies in serum, even when a high titer (greater than or equal to 1:64) of antibodies was present. In contrast, men with high titers of tail-to-tail (T-T) sperm agglutinating antibodies in serum showed very marked or complete spermagglutination in the ejaculates. The agglutination in ejaculates from men with low titers (less than or equal to 1:32) of T-T spermagglutinating antibodies in serum was much less conspicuous and equaled that in ejaculates from men without such antibodies. This indicates that only a high titer of T-T spermagglutinating antibodies is associated with marked or complete spermagglutination in ejaculates.


Bilateral testicular biopsy in men with varicocele. Fifty-two infertile men with varicoceles were subjected to bilateral testicular biopsy to detect the effect of the varicocele on each testis. The results indicate that varicocele can result in infertility primarily through sloughing of immature cells or through arrest of spermatogenesis at the spermatid or primary spermatocyte stage. The effect is bilateral but is more marked on the varicocele side. However, the presence of a varicocele could not explain the infertility of seven men with normal biopsies and of four men with a normal biopsy on the varicocele side and arrest on the other side.


Demonstration of proacrosin and quantitation of acrosin in ejaculated human spermatozoa. Proacrosin has been isolated from human ejaculated spermatozoa and constitutes at least 90% of the total acrosin present. The total amount of acrosin in milli-international units per million spermatozoa was between 4.4 and 8.9, with a mean of 6.5. This is the first report of the demonstration of proacrosin and the quantitation of total acrosin in human spermatozoa.


Failure of seminal plasma to enter the uterus and oviducts of the rabbit following artificial insemination. Twelve adult does in estrus were artificially inseminated with 1 ml of semen from bucks that had received injections of 3H-thymidine 22 to 32 days previously. The ejaculates contained radioactive seminal plasma and unlabeled sperm. The reproductive tracts of the does were removed at selected intervals after insemination, divided into segments of no more than 300 mg, and processed for scintillation counting. Significant levels of radioactivity were never detected in any uterine or oviductal segment. The technique was capable of detecting as little as 1.5 X 10(-4) ml of semen in a segment. These results demonstrate that seminal plasma is not transported from the vagina into the uterus or oviducts in the rabbit, emphasizing the importance of the motility of spermatozoa in their passage to the site of fertilization.


A clinical evaluation of a new Silastic seminal fluid collection device. A new Silastic seminal fluid collection device has been tested clinically and comparison studies have been made with both the polyethylene sheath and commercial latex condoms. In a series of 100 patients, the Silastic seminal fluid device has been found to be superior to the polyethylene sheath with regard to patient comfort and also has had greater reliability. In comparison with the latex device, the Silastic seminal fluid collection device is nearly as comfortable and has been found to be far more reliable.


[Electrophysiologic study of the connections of the 2d somatosensory area of the cortex with the neo-, paleocortical and striate formations of the brain]. 2nd somatosensory area (C2) was shown to have modulating influence on evoked activity of the 1st somatosensory and visual areas. Electrical stimulation of C2 evoked short latency potentials in the structures of paleocortex (hippocampus) and striatum (putamen, caudate nucleus). Analysis of the data obtained here and elsewhere (19) suggests the important role of C2 in mechanisms of selection, comparison and integration of adequate sensory information under conditions of uncertainty, for the programming of behaviour.


[Age and changes in the levels of biogenic amines in the brains of rats]. No significant change occurs in the total cerebral level of norepinephrine, dopamine, and histamine in rats of 1--36 months age, whereas the serotonin (5-HT) level is increasing. During the maturation period the hypothalamic levels of catecholamines and histamine are increasing. Between 2--36 months of life the hypothalamic norepinephrine level decreases while 5-HT, 5-HIAA, and histamine do not change. Role of the age-related changes of brain biogenic amines in disturbances of neuroendocrine feedback mechanisms is discussed.


[Relationship between oxidative deamination of cerebral seroton in during hibernation and changes in monoamine oxidase activity and temperature]. The highest MAO was found in alert ground squirrels and it became minimum in hibernating animals. The temperature relations of the oxidative serotonin desamination (OSD) in alert ground squirrels was relatively low from 7 to 37 degrees C. At the beginning of hibernation OSD did not differ from that of alert animals at 22--37 degrees C, while at 7--22 degrees C it was significantly lower--about 1.0. In hibernating ground squirrels, high OSD was observed at low and high temperatures in all parts of the brain except hypothalamus. At awaikening OSD remained high.


[Relationship between interaural phase difference and the response of neurons in the frog midbrain hearing center]. Many binaural neurons within the torus semicircularis of the lake frog are cyclically responsive to the interaural phase angles of a sinusoidal stimulus at frequencies up to approximately 1.2 kHz. In the range of small interaural delays, the neurons increase their reactions when the contralateral stimulus leads. The 20 mcsec delay of the contralateral tone can elicit a considerable drop in spike generation probability. The "characteristic" delay occurs outside the range of interaural delays the frog could naturally encounter. Some other neurons responding both to contralateral and ipsilateral stimuli discharge minimally when there is no interaural delay. The variety of discharge patterns can be elicited from a single neuron by alteration of the interaural delay.


[Effect of binocular interaction of rat visual cortex neurons]. In anesthetized rats, out of 135 neurons recorded in binocular area within the striate cortex, 92 (74%) were binocular. 53 of these had well defined, mainly identical receptive fields on the two retinae. The range of relative horizontal and vertical disparity was found to be 5 degrees and 4 degrees respectively. These findings suggest that the visual system of the rat is capable to discover the spatial relationship using mechanisms of binocular fusion, in contrast to data obtained in rabbits.


[Contrast sensitivity in the area of a moving form]. Brightness thresholds of the test stimulus were measured at different distances from a moving contrast contour, the contour's velocity being 0, 5, 20, and 30 grad/sec. The data show a significant extension of the spatial and temporal zones of the contour influence which depends on the contour's velocity. Some neurophysiological correlates of this phenomenon are discussed.


[Slowly-adapting mechanoreceptor units of the guinea pig mammary nipple]. Slowly--adapting mechanoreceptor units of areola and nipple (MAI and MAII) at rest exhibited spontaneous 1--2/sec firing in 6% only. At constant mechanical displacement of the skin surface. MAI had an irregular firing while MAII--regular one. Mean frequency of MAI and MAII APs linearly depended on the amplitude of mechanical stimulus. trepeated stimulation of MAI and MAII reduced number of APs for each successive stimulus. At sinusoidal mechanical stimulation, the smallest AP threshold for MAI and MAII was about 10--15 Hz.


[Response of splenic resistance and capacitance vessels to electrical stimulation of the hypothalamus and reticular formation in cats]. The effect of electrical stimulation of anterior, medial, and posterior hypothalamus and of midbrain RF on the spleen resistance and capacitance vessels was studied in 48 anesthetized cats. The stimulatin of all the structures but the anterior hypothalamus evoked constrictory responses of the resistance vessels and decreased the blood volume in the spleen. Apart from the constriction, the stimulation of the anterior hypothalamus decreased the tonus of both kinds of vessels in some cases. The highest perfusion pressure was observed during the stimulation of anterior hypothalamus while the greatest rise of venous outflow with the briefest latency was found during the stimulation of the midbrain RF.


[Hemodynamic reactions in response to simultaneous nociceptive and amygdalar influences following stimulation and removal of the cervical sympathetic nerves]. In cats, nociceptive stimulation and stimulation of amygdala elicited pressor reaction which was much more obvious at the combination of these stimuli. In sympathectomized animals, these stimuli produced a weaker pressor reaction. Combination of sympathetic nerve stimulation with the nociceptive stimulation and stimulation of amygdaloid complex elicited different reactions depending on the order of stimulation. After sympathectomy, separate stimulations produced a decrease of the blood flow rate; the same was obtained after combination of stimulation of the amygdaloid complex with nociceptive stimuli; however, complex effects also depended on the order of stimuli.


[Effect of acute hypothermia on the lipid composition of the myocardial mitochondria of warm-blooded animals]. In dogs and albino rats, artificial drop of body temperature by 8--10 degrees C elicits change of phospholipid spectre and increases amount of unsaturated fatty acids in lipids of the myocardium mitochondria. Drop of the temperature by 18--20 degrees C decreased amount of polyen fatty acids in dogs but caused no changes in the high amount of unsaturated lipids in rats. Role of of these facts in mitochondrial functions during hypothermia and possible dependence of the animals resistance against low temperature of the degree of membrane lipids reorganization, are discussed.


[Secretion of small intestinal enzymes after section of the pancreatic duct]. In chronic experiments on dogs, soon after ligation of the pancreatic duct, amylase increases in the peripheral blood as well as the total amylase and lipase release in liquid and solid portions of the secret from isolated parts of the small intestine. The alpha--amylase release was shown to depend on the level of the blood amylolytic activity and on secretory activity of small intestine. The alpha--amylase and lipase release is more increased at mechanical rather than at chemical stimulation of the small intestine. After the secretory function of the pancreas is excluded, two stages of compensatory--adaptive changes occur in the secretory activity of small intestine: first the compensation is due to less energy--consuming processes (recretion of the blood enzymes), and further the compensatory mechanisms of the small intestine become involved.


Effect of different daily rate of continuous irradiation upon changes in cfu number. The effect of continuous irradiation upon colony-forming capacity of bone marrow cells was studied in mice exposed continuously for the length of 130 days to ionizing radiation at exposure rates ranging from 1--50R per day. A stabilized state in CFU number was observed between days 30 and 100, its level being related solely to the daily exposure rate. An interpolation of data on CFU found on days 30, 40, 50, 60, 70, 80, 90, and 100 provided an exponential curve which can be characterized by the equation log y = a + bx + cx2. This equation can be applied to prognostic estimation of CFU level during the stabilized state between days 30 and 100 of continuous radiation exposure at rates ranging from 1--50R day.


Grain distribution in autoradiograms of nuclei of synchronized HeLa cells continuously labelled with 3H-thymidine. Changes in distribution of silver grains were evaluated in autoradiograms of nuclei of synchronized HeLa cells that were continuously labelled with 3H-TdR. Synchronization was achieved by repeated blocking with cold thymidine. Three patterns of grain distribution were distinguished: uniform, non-uniform, and a special case of non-uniform distribution, the S.C. clustering. The kinetics of changes in the proportion of individual types of grain distribution indicate that uniform and non-uniform distribution patterns result from 3H-TdR incorporation into DNA replicating during the entire S-phase, whereas DNA responsible for clustered grain distribution takes up 3H-TdR only during the second half of the S-phase. The rate of the increase in grain counts per nucleus of labelled cell and the kinetics of the exhaustion of radioactive precursor from the culture medium suggest that replication of DNA in DNA in the S-phase is not merely a linear function of time.


The outcome of the effect of polyvinylpyrrolidone and chondroitin sulphate in the presence or absence of serum on con A-induced activation in vitro and agglutination of mouse lymphocytes. Activation of mouse lymphocytes with Con A in the presence or absence of serum in the culture medium and the effect of two polymers, PVP and CS, on this stimulation was investigated. The presence of different sera in the culture medium resulted in a different degree of lymphocyte activation and the tested polymers affected it mildly, whereas in serum-free medium they had a strong inhibitory effect. This inhibition was not the outcome  of a toxic effect nor of a reduced mitogen-binding capacity of Con A. In investigating the delayed agglutination of lymphocytes with small doses of Con A in vitro, it was found that PVP had a potentiating effect on agglutination in the presence of serum in the medium and an inhibitory effect in serum-free medium. The differences in the action of the tested polymers on stimulation and agglutination of cells in the presence and absence of serum in the medium in vitro suggest a pronounced effect of the sera on cultured cells. The results are discussed with respect to the effect of culture medium on the properties of the lymphoid cell membranes.


Antitumour and immunosuppressive activity of hydroxyanthraquinones and their glucosides. Both isomeric monohydroxyanthraquinones (1a, b), three dihydroxyanthraquinones (alizarin 1c, chrysazin 1d, and anthraflavin 1e) and corresponding acetylated (2) and free (3) beta-D-glucosides were screened for antitumour and immunosuppressive activity. Furthermore, four O-acetyl and O-benzyl derivatives of alizarin (5a--d) were tested. Antitumour activity was judged by the inhibition of growth of syngeneic tumours in the treated recipients and immunosuppressive activity by the effect on tumour growth or on skin graft survival in pretreated allogeneic recipients; as standard of reference served the activity of certain cancerostatic or immunosuppressive drugs used in clinical practice. 1-Hydroxyanthraquinone (1a), alizarin (1c), chrysazin (1d), acetylated glucoside of 2-hydroxyanthraquinone (2b), 2-benzylalizarin (5c), and 1-acetyl-2-benzylalizarin (5d) were found to exhibit antitumour activity. Distinct immunosuppressive activity was detected in alizarin (1c), acetylated glucoside of 1-hydroxyanthraquinone (2a), acetylated glucoside of 2-hydroxyanthraquinone (2b), acetylated glucoside of chrysazin (2d), 2-acetylalizarin (5a), and 1-acetyl-2-benzylalizarin (5d). The group of hydroxyanthraquinone glucodises (3a--3d) exhibited neither antitumour nor immunosuppressive activity.


[Effect of 8-methoxypsoralen and blacklight on microorganisms in vitro and in experimental trichophytosis in guinea pigs]. The lack of experimental test models causes problems in comparative evaluation of photodynamic effects of 8-MOP and its possible derivatives after irradiation with blacklight or other irradiation sources. In our experiments in vitro, tests with various microorganisms and the in vivo model of experimental dermatophytosis in guinea pigs by Trichophyton mentagrophytes appeared to be suitable. In vivo, 8-MOP was applicated orally and topically in two formulations.


Photo-onycholysis induced by 8-methoxypsoralen. Two patients, who we had under surveillance since 1969, were found to develop photo-onycholysis from orally administered 8-methoxypsoralen and sunlight irradiation. Morphological examination of the nail bed revealed characteristics of a microtrauma. The photosensitizing effect of the drug induced the generation numerous binucleate, tetranucleate and multinucleate epithelial cells as well as numerous binucleate and tetranucleate fibroblasts in the dermis.


Virus-like structures in the skin in the course of chronic lupus erythematosus. Six skin biopsies of one patient, from foci of chronic lupus erythematosus in different stages of development of the disease and from unchanged skin were examined by electron microscope. The aim of the investigations performed was to check the presence of reticulotublar structures in these samples. Reticulotublar structures appeared in numerous quantities in early foci, while in scarred foci, as in structurally unchanged skin, they were, although always present, rare.


Topical parabens: benefits and risks.

Topical parabens: benefits and risks. Parabens are the most frequently used preservative in dermatological medications. Some allergies have been reported to parabens, but these risks must be considered with respect to the benefits of parabens in concentrations used as preservatives in dermatological formulations. Considering the alternatives to parabens in preservat ives and placing perspective on the reported allergies we still find parabens to be a useful preservative with minimal risk to its benefits.


Hodgkin's disease and mycosis fungoides in a married couple. Hodgkin's disease and mycosis fungoides are malignancies in which there is abnormal T lymphocyte proliferation. The authors report the occurrence of Hodgkin's disease and mycosis fungoides in a husband and wife, respectively. This represents another instance of clustering of cases of T lymphocyte malignancies.


Treatment of psoriasis vulgaris with a new retinoic acid derivative Ro 10-9359; An uncontrolled clinical trial. The retinoic acid derivative Ro 10-9359, given orally in maximum daily doses of 100 mg to 15 patients with psoriasis vulgaris, led to clearing of the lesions in 8 patients. The average period of treatment was 9 weeks. In 14 patients side-effects were observed, the most important being palmo-plantar desquamation, shivering, thirst and diffuse hair loss. In 2 patients scaling led to withdrawal. In 6 patients abnormal alkaline phosphatase and glutamic-aspartatic transaminase values, partly transient, developed (glutamicaspartatic transaminase, p less than 0.01).


Diseases sometimes associated with psoriasis. I. Candidosis. Of 5,033 patients who were seen between 1968 and 1975, 407 suffered from psoriasis (Ps) and 245 from candidosis (Cn). Of these, 38 patients (p less than 0.001) had both diseases. In 24 additional families, Ps was found in one member and Cn in another. The relationship of the two diseases is discussed.


Ultrastructural features of psoralen plus black light induced successive changes in psoriatic cell. Based on an ultramicroscopic investigation of the psoralen plus black light-induced photodynamic reaction in the psoriatic cell, there is evidence that the primary reaction takes place in the nuclei, which possess abundant nucleic acid. This initial reaction is manifested by a large vacuole situated in the nucleus. As the vacuole gradually enlarges, the nucleus becomes an annex to the vacuole, while the cytoplasm of the cell succumbs to the necrobiotic process.


Study of the effects of certain drugs on experimental porphyria in rats. The effect of ethanol, phenobarbitone, griseofulvin or chloroquine on 3,4-diethoxycarbonyl-1,4-dihydrocollidine (DDC)-induced porphyria in rats has been studied in experiments lasting up to 40 days. Ethanol, phenobarbitone or griseofulvin given later, in addition to DDC, resulted in a clearly greater porphyrin excretion and liver porphyrin concentration than with DDC alone. Chloroquine at first increased, then decreased porphyrin excretion and liver porphyrin was lowered. No drug without DDC was porphyrogenic.


Nickel content of plasma, urine and hair in contact dermatitis. The nickle (Ni) concentrations of blood plasma, urine and scalp hair do not differ between hypersensitive and non-hypersensitive subjects. Those who are occupationally exposed have about ten times the control content of nickel in the plasma, urine and hair, whether hypersensitive or not. During vacations the Ni contents of their plasmas and urines decrease sharply. Oral administration of only 5 mg Ni (as the sulphate) increases the Ni concentration of plasma and urine to ten times the normal for more than the subsequent 24 h.


Comparisons of various clomipramine (Anafranil) dosage regimes. An open study of four dosage regimes of clomipramine (Anafranil)--10 mg t.d.s., 30 mg o.n., 25 mg t.d.s. and 75 mg o.n.--was performed in patients seen in general practice suffering from depression. The primary purpose of the study was to gather information on steady-state blood levels of unchanged drug and major metabolite. However, clinical assessments were also made on a seventeen symptom depression rating scale initially and after 1,2 and 4 weeks treatment and side-effects were assessed. Seventy patients were admitted to the study; forty-nine completed it. All four treatment groups showed significant improvement. The groups were small and no significant differences emerged between them. The best response of 77% improvement on total score after 4 weeks was obtained in the group of patients receiving 25 mg t.d.s. The patients on 30 mg daily showed a 67% response when this was divided and 65% when given singly. The worst response was obtained in the patients receiving 75 mg single dose (50%). Thirteen of the twenty drop-outs did so because of side-effects. Ten of these were in high dose groups. However, amongst patients who completed the study there was no difference in the side-effects observed in the four groups.


A clinical trial of a 50 mg formulation of clomipramine (Anafranil) with steady-state plasma level measurements. Twenty depressed patients seen in general practice were admitted to an open, uncontrolled pilot trial of a new 50 mg formulation of clomipramine. Treatment was administered for four weeks and clinical progress assessed by the General Health Questionnaire, a new depression rating scale and a new design of a visual analogue scale. Two patients dropped out of the study, one because of side-effects and a second because it was necessary to change the dosage. Of the 18 patients remaining 17 showed significant improvement during the four weeks treatment as assessed by the three clinical measures. Plasma levels of clomipramine and desmethylclomipramine were assayed. Steady-state appeared to be achieved between one and two weeks. Between two and four weeks levels of clomipramine varied between 14 and 136 microng/ml with a mean level of 54-6 microng/ml and of desmethylclomipramine, between 3-5 and 344-3 microng/ml with a mean level of 76-7 microng/ml The 50 mg formulation of clomipramine appeared to produced therapeutic levels in 17 of the 18 patients treated. Because so many patients recovered in spite of individually variable plasma levels no correlations between clinical effect and plasma levels were demonstrable. Side-effects were not generally troublesome and were low in incidence. Correlations between plasma level and side-effects were inexplicably negative but rarely significantly so.


The general practitioner's role in the management of psychiatric illness. Psychiatric illness is of major social and medical importance. At least one fifth of the patients seen by doctors in general practice suffer predominantly from mental illness. Only one in twenty of these patients suffering from psychiatric disorders are referred to the hospital and specialist services. The general practitioner therefore deals with the bulk of psychaitric illnesses which constitutes a problem of considerable magnitude. Psychiatric illnesses may be considered in terms of the distrubance they cause in mental state. The following aspects of mental state are considered: consciousness, memory, mood, thinking, intelligence and personality. Disorders of each of these components of mental state are described and their management discussed.


Biochemistry of the affective disorders. The idea that affective illness might be due to some biochemical malfunction of the patient is not new. A number of features of affective illness lend support to the biological hypothesis of aetiology. The evidence is briefly reviewed in this paper. There are three principal areas of biochemical interest in depression, namely electrolytes, biogenic amines and neuroendocrine abnormalities. Each of these is briefly reviewed.


Antidepressants and pain: a review of the pharmacological data supporting the use of certain tricyclics in chronic pain. There have been reports that tricyclic antidepressants, such as clomipramine (Anafranil), alleviate some forms of chronic pain in man. This paper examines and compares the pharmacological properties of centrally-acting analgesics and the tricyclic antidepressants, to establish a scientific basis for the observed clinical effects of the tricyclics. Opiates and tricyclic antidepressants share a number of pharmacological properties including activity in animal tests for antidepressant and analgesic activity. In doses which alone were not analgesic, clomipramine potentiated whilst maprotiline (Ludiomil) attenuated the analgesic activity of single doses of morphine in laboratory animals. However, when morphine and tricyclic agent were given repeatedly over several days, clomipramine enhanced or accelerated the onset of morphine tolerance, whereas maprotiline delayed tolerance. It is concluded that there is much experimental data to support the belief that tricyclics such as clomipramine may be useful in chronic clinical pain. Where an opiate is being administered chronically (for example in terminal pain) the concomitant administration of maprotiline may delay onset of tolerance.


A comparison of various clomipramine (Anafranil) dosage regimes. This study was a multicentre general practitioner trial comparing four dosage regimes of clomipramine (Anafranil, Geigy Pharmaceuticals): 10 mg t.d.s., 30 mg o.n., 25 mg t.d.s. and 75 mg o.n. This paper concerns the clinical results obtained using a series of twelve visual analogue scales completed independently by doctor and patient. Also side-effects, recorded on a standard list of unwanted effects of tricyclic antidepressants, were studied. Very few statistical differences were found between the dosage regimes, and they were difficult to interpret clinically. It was concluded that although 25 mg t.d.s. was most effective, 30 mg o.n. was probably the best compromise in terms of efficacy and tolerability.


An investigation into the short-term effects of clomipramine (Anafranil) administered in low doses, on weight. Patients treated with four dosage regimes of clomipramine (Anafranil) 10 mg t.d.s., 30 mg o.n., 25 mg t.d.s. and 75 mg o.n. in a clinical trial lasting four weeks were regularly weighed. Due allowance was made for the normality or otherwise of normal weight, appetite and, in women, menstruation. There was no evidence that during the four weeks of this particular study and on these doses of clomipramine patients showed any increase in weight.


Sexual side-effects of clomipramine (Anafranil). An attempt was made to measure the effects of depressive illness and of clomipramine (Anafranil) therapy in doses of 30 mg and 75 mg daily on sexual appetite and performance. A special questionnaire was devised to gather information on sexual habits before illness, during illness and following treatment. It proved difficult to differentiate between the beneficial effects of recovery from depression and the possible adverse drug effects on sexual activity. Two patients dropped out of the study because of supposed sexual side-effects--a male with ejaculatory difficulties and a female with orgasmic impotence. Fifty-four patients completed the sexual questionnaire and a four-week course of clomipramine. There were nineteen males and thirty-five females. Sixty-eight per cent of males and 57% of females had their 'sex life' impaired by depressive illness. Coital rate was decreased and depression interfered with performance and satisfaction. Clomipramine therapy seemed to have advantageous and disadvantageous effects. The advantageous effects were probably associated with improvement in depressive illness. There was evidence that clomipramine had an adverse effect sexually in 26% of males and 14% of females. The effect was dose-related in females.


Comparison between physician and patient completed visual analogue scales. In a multicentre general practitioner trial, in which patients were treated with various dose regimes of clomipramine (Anafranil, Geigy Pharmaceuticals), patients and doctors completed independently of each other a series of visual analogue scales on admission and after one, two and four weeks of treatment. A regression technique is described to deal with the comparison between patient and doctor completed scales. It is suggested that this method is more informative than just giving correlations between ratings. The study shows that for the two target symptoms, depression and anxiety, the agreement between patient and doctor ratings is poor, particularly at the beginning of the study. The 'best' results are obtained for initial sleep, appetite and libido. Some explanations for these findings are offered, and further researches of the visual analogue scale are suggested.


Experiences with some new scales for use in general practice trials. The proper assessment of depression in general practice requires the use of adequate and sensitive measurement of target symptoms. In a pilot trial of a new 50 mg formulation of clomipramine (Anafranil) various new techniques of measurement were explored, namely, the General Health Questionnaire, a series of visual analogue scales with a centre reference point and a new physician rating scale for depression.


Psychotropic drugs and migraine.

Psychotropic drugs and migraine. The incidence and differential diagnosis of migraine is discussed. The use of clomipramine (Anafranil) in the prophylaxis of migraine is considered and the results of a pilot study presented. The problems which arise in the organization of clinical trials of migraine prophylaxis and hypotheses for the possible mode of action of clomipramine and other psychotropic drugs in the prevention of migraine are discussed.


Factors influencing plasma drug concentrations. The usefulness of measuring plasma concentrations of drugs in patients is now well established and permits a greater efficacy and safety of treatment since dosage can be adjusted on an individual basis. In monitoring plasma concentrations one must recognize that a number of factors may influence these levels. For instance, levels may be affected by age, body-weight and size, genetical factors, abnormalities of water and electrolyte balance and complications associated with pathological conditions such as renal and hepatic impairment. Likewise, plasma levels will depend on dosage, time and route of drug administration, the bioavailability of the drug and time of blood sampling. In addition, absorption, distribution, metabolism, excretion and concurrent drug administration may profoundly affect plasma drug concentrations.


Plasma level studies with clomipramine (anafranil). Patients showing symptoms of depressive illness were treated in general practice with one of four clomipramine (Anafranil) dosage regimes (25 mg t.d.s., 75 mg o.n., 10 mg t.d.s. and 30 mg o.n.). Blood was sampled on admission to the study and at days 7, 14 and 28. Plasma analysis revealed that steady-state concentrations of clomipramine and its main metabolite desmethyclomipramine were reached at day 7 of treatment in each of the dosage groups. No apparent relationship between dosage and plasma level of clomipramine was found in this study since there was no significant difference between mean steady-state plasma levels in each of the four dosage regimes. In contrast, plasma concentrations of desmethylclomipramine appeared to be directly related to the dose of clomipramine administered. Intersubject variations in plasma levels of the parent compound within each dosage group ranged from three to fourteen-fold.


Open-field behavior of prenatally irradiated and/or postnatally handled C57BL/6 mice. Mice (C57BL/6) were prenatally irradiated with 60Co and/or handled on postnatal Days 1-10, and subsequently tested in an open field on Days 21, 42, and 63, and in a shuttle box on Days 30 and 60. Another group of mice was treated and tested similarly, but the shuttle box testing was omitted. All animals were cross-fostered at birth. Handling increased open-field activity and decreased defecation whereas irradiation decreased activity and had inconsistent effects on defecation. A comparison of the data from both groups of mice indicated that the shuttle box experience decreased open-field activity, particularly for the irradiated and unhandled animals. Direct and indirect irradiation effects--revealed by the cross-fostering procedure--were both significant and about equal in magnitude, underlining the importance of attending to irradiation effects on maternal as well as on offspring behavior.


Interaction of separation distress with fear in infant dogs. Forty-one Telomian, beagle, and F1 hybrid puppies were tested in the presence and absence of a sound-producing stimulus under 2 social conditions, single and paired, at 6, 7, and 8 weeks of age. The sound stimulus definitely produced fearful reactions, as measured by tail carriage, which were not affected by social condition and accompanying differences in distress vocalization. Nor was distress vocalization significantly altered by the sound stimulus. We conclude that sound-induced fear and separation distress are separate and independent affective states. Social condition and the presence of the sound stimulus produced interactive effects at the behavioral level in that paired animals showed longer latencies to contact and maintained greater distances from the sound stimulus.