Introduction of a partial shift system for house officers in a teaching hospital. (1) To introduce a partial shift system to reduce the hours of work of preregistration house surgeons to an average of 64 a week to comply with the New Deal for junior doctors; (2) to test linking the partial shift concept to an existing structure of "on call" firms. Formal assessment after three months of a pilot partial shift system for eight house surgeons on three firms instituted on 1 November 1991, followed by questionnaire and interview evaluation at three and six months of a revised system implemented on 1 February 1992. Department of general surgery at St Bartholomew's Hospital, London. 24 house surgeons attached to three surgical firms. In eight weeks each house surgeon worked one week (five shifts) of night duty, one week of "cover" (afternoon and evening) duty, and six weeks of normal daytime hours. Each weekday a house surgeon from the firm on call worked an extended daytime on call shift until 10 pm. Weekend duties were split between two house surgeons from the firm on call. A computer generated graphical display of the rota was used to facilitate leave planning. Average working hours were reduced to below 64 per week, including prospective cover, without detriment to patient care and educational standards. Within the shift system individual house surgeons could be on call with their own firm by day and at weekends. Opinions were equally divided among junior staff as to their preference for either on call or partial shift systems. The principles of this partial shift system are generally applicable and the model can readily be adopted by district general hospitals.


Comparison of enalapril and nifedipine in treating non-insulin dependent diabetes associated with hypertension: one year analysis. To compare the efficacy, safety, and tolerance of enalapril and nifedipine in hypertensive patients with non-insulin dependent diabetes. One year double blind follow up of patients randomly allocated to either enalapril or nifedipine with matching placebos for the alternative drug. Metabolic Investigation Unit, Hong Kong. 102 patients were randomised: 52 to nifedipine and 50 to enalapril. At baseline 44 patients had normoalbuminuria, 36 microalbuminuria, and 22 macroalbuminuria. Blood pressure, albuminuria, and parameters of renal function and glycaemic control. In patients who completed one year's treatment the median dose required by the nifedipine group (n = 49) was 60 mg/day; seven (14%) required additional diuretics. Of 41 patients given enalapril, 37 required the maximum dose (40 mg/day) and 27 (76%) required diuretics. At one year mean arterial blood pressures were similar in both groups. Albuminuria fell by 54% in the enalapril group and 11% in the nifedipine group (p = 0.006). Fractional albumin clearance ratio fell by 47% in the enalapril group and increased by 3% in the nifedipine group (p = 0.009). Creatinine clearance fell similarly in both groups but plasma creatinine concentration was increased by 20% in the enalapril group versus 8% in the nifedipine group (p = 0.001). Patients taking enalapril often required diuretics to control blood pressure. Enalapril reduced proteinuria significantly more than nifedipine in the microalbuminuric and macroalbuminuric patients but increased plasma creatinine concentrations. Longer follow up is required to clarify the importance of enalapril's antiproteinuric effect.


Pet birds as an independent risk factor for lung cancer: case-control study. To test the hypothesis that exposure to pet birds increases risk of developing lung cancer. Case-control study. Computerised interviews were used to assess previous exposure to pets and other risk factors for lung cancer. Three major hospitals treating respiratory disease in former West Berlin. All people newly diagnosed as having primary malignant neoplasm of the trachea, bronchi, or lung who were 65 or younger and control subjects matched for age and sex from the general population of former West Berlin. 279 cases and 635 controls qualified for the study; 239 cases and 429 controls participated. Odds ratio of developing lung cancer according to whether or not pet birds were kept and the duration of keeping pet birds. In addition to the risk of lung cancer imposed by smoking, passive smoking, and occupational exposure to carcinogens, an increased relative risk of 2.14 (95% confidence interval 1.35 to 3.40) was found among people exposed to pet birds. The adjusted odds ratio for exposures longer than 10 years was 3.19 (1.48 to 8.21). Avian exposure seems to carry a risk of lung cancer. Until the pathogenesis is understood, long term exposure to pet birds in living areas should be avoided, especially among people at high risk of developing lung cancer.


Avian exposure and bronchogenic carcinoma. To investigate the association between bird keeping and risk of lung cancer. Case-control study asking detailed questions on exposure to domestic birds and other pets, smoking, and various demographic and potentially confounding variables. District general hospital; current admissions interviewed in hospital or recent admissions interviewed at home. 143 patients with lung cancer, 143 controls with heart disease, and 143 controls with orthopaedic conditions individually matched for age, sex, date of admission, and current or past admission. Odds ratios for lung cancer in relation to various aspects of bird keeping, after adjustment for smoking and other relevant confounding variables. Risk of lung cancer was not significantly associated with household exposure to pet birds at any time or at various specific periods in life, or to keeping large numbers of birds. For specific types of birds no association was seen for living in households with budgerigars or canaries but risk was significantly associated with keeping pigeons (odds ratio 3.53, 95% confidence interval 1.56 to 7.98). This remained significant after regression analysis to account for confounding variables (3.9, 1.2 to 12.62) in both sexes and all age groups. Bird keeping may confer some risk of lung cancer but the relation is not as strong as previously reported.


The TAPS project. 16: Difficult to place, long term psychiatric patients: risk factors for failure to resettle long stay patients in community facilities. To identify patients who could not be resettled in the community as part of the closure plans of two psychiatric hospitals and to determine their numbers and risk factors for failure. Prospective study of the closure of Friern and Claybury psychiatric hospitals. The first third (369) of long stay psychiatric patients to be resettled. Reasons for patients being readmitted to hospital and not leaving the patients' service needs. 22--6% of both hospitals' long stay patients--were not successfully resettled in the community. Eighteen continuing care places per 100,000 of catchment area population seem to be required for this group. Patients whose placements were unsuccessful were usually readmitted because of a deterioration of their mental state and aggressive behaviour, both of which persisted and necessitated their continuing stay in hospital, often in a locked ward. Risk factors associated with failure were a high level of psychosis; a diagnosis of paranoid psychosis; incontinence; and being male. But having a social network, especially a large one, seemed to aid successful placement in the community. Rehabilitation efforts should be focused on the characteristics of these patients that put them at risk of failing to succeed in community placements.


The TAPS project. 17: Readmission to hospital for long term psychiatric patients after discharge to the community. To identify risk factors which increase the likelihood of readmission for long stay psychiatric patients after discharge from hospital. Follow up for five years of all long stay patients discharged from two large psychiatric hospitals to compare patients readmitted and not readmitted. Friern and Claybury Hospitals in north London and their surrounding catchment areas. Most patients were discharged to staffed or unstaffed group homes. 357 psychiatric patients who had been in hospital for over one year, of whom 118 were "new" long stay and 239 "old" long stay patients. Readmission to hospital and length of subsequent stay. Of all discharged patients 97 (27%) were readmitted at some time during the follow up period, 57 (16%) in the first year after discharge, and 31 (9%) then remained in hospital for over a year. The best explanatory factors for readmission were: male sex, younger age group, high number of previous admissions, higher levels of symptomatic and social behavioural disturbance, a diagnosis of manic-depressive psychosis, and living in a non-staffed group home. During the closure of psychiatric hospitals, facilities need to be preserved for acute relapses among long term, and especially younger, discharged patients. Staffed group homes may help prevent relapse and reduce the number of admission beds required.


[A comparative study of the psychotropic activity of different salts of homopantothenic acid]. Psychotropic activity of different salts of homopantothenic acid was studied. In homopantothenic acid derivatives, the substitution of calcium ions by sodium and magnesium ions gives rise to a decrease of the sedative and potentiation of the stimulating properties.


[Changes in the narrow-band components of the EEG spectrum under the action of nootropic drugs]. Patients with asthenic disorders were examined for EEG reactions to the administration of some nootropics. The significance of the narrow bands of the post-drug EEG spectrum was revealed. According to these data, the detailed EEG profiles of the nootropics under study were obtained. Analysis of these EEG profiles discovered the common and specific characteristics of different nootropics.


[The prolonged use of calcium antagonists in myocardial infarct in rats: their effect on hemodynamics and the contractile function and morphology of the heart muscle]. Experiments on rats with myocardial infarction induced by occlusion of the left coronary artery were made to explore the influence of calcium antagonists injected intraperitoneally for a long time (daily, for 21 days) on hemodynamics, contractile function and morphology of the heart muscle. It has been shown that verapamil (0.5 mg/kg), diltiazem (2 mg/kg) and nimodipine (20 micrograms/kg) do not exert under those conditions any noticeable effect on pump and contractile heart functions. Administration of verapamil in a doze of 2 mg/kg enhanced heart failure. The drugs under study normalized the response of contractile heart function to volumetric load, which is related to a considerable measure to the acceleration of reparative processes in the myocardium.


[The characteristics of the action of mildronate (dihydrate 3-(2,2,2-trimethylhydrazine)propionate) on the red blood parameters in heart failure]. Mildronat potentiates the therapeutic effect of the combined treatment of heart failure, which includes the use of nitro drugs. It also decreases the level of methemoglobin in the patients' blood and improves the phosphate balance, especially that of 2,3-diphosphoglycerate to control oxygen transport by hemoglobin, which is of paramount importance in hypoxia caused by coronary heart disease.


[The cytotoxicity of strophanthin G and digoxin]. Cytotoxicity of strophanthin G and digoxin was studied in experiments on lymphoid cells and carcinoma of cervix uteri cells. The glycosides inhibited the growth of three strains of cultured tumor cells tested. It has been found that highly toxic doses of the drugs produced no changes in the cell multiplication of normal human fibroblasts.


[The effect of grofollon on the induction of sex maturation in female rats]. The authors provide the results of experimental studies carried out in immature female rats given the gonadotropin grofollon to stimulate puberty. Grofollon was administered in doses of 20, 30 or 50 units. It was dissolved in a physiological solution or prolongon. The effect of grofollon was found to depend on the dose and type of the solvent. The earliest response (in 6 hours) to grofollon administration was marked by an increase of plasma estradiol. 24 hours after the hormonal treatment there was a rise of the mass of the ovaries and uterus, in particular. The vagina opened on the 3d day. The dissolution of grofollon in prolongon was discovered to enhance the drug efficacy.


[The effect of L-carnitine and acetyl-L-carnitine on blood serum lipid peroxidation in vitro]. In the action mode of carnitine derivatives, the leading role is played by lipid transport inside the cell. Bearing in mind the important role of lipid peroxidation in lipid metabolism in the body and broad-range indications for use of carnitine derivatives in medical practice, it was decided to investigate the influence of carnitine derivatives on lipid peroxidation (LPO) in vitro to have a better understanding of the action mode of these drugs, as carnitine, according to the reported data, may affect certain LPO parameters in vivo.


[The effect of isonitrozine on gas homeostasis]. The action of the cholinesterase reactivator isonitrosine on gas homeostasis was studied in experiments on intact dogs. It has been found that oxygen consumption and CO2 release by tissues were enhanced within the period from 15 min to 6 days following isonitrosine administration. Simultaneously, oxygen return by the blood was improved. Such action of isonitrosine was unrelated to its effect on the cholinesterase activity of red blood cells.


[The effect of verapamil and nifedipine on cholesterol esterification and accumulation in macrophages]. Administration of verapamil and nifedipine in doses of 10-75 microM into the culture of mouse peritoneal macrophages incubated in a non-lipid medium with acetylated low density lipoproteins (50 g protein/ml) decreased the incorporation of 14C oleate into cholesterol esters by 50-90%, increased the content of intracellular free cholesterol by 19-79% and did not influence the content of total cholesterol in macrophages. Administration of verapamil and nifedipine in doses of 25 and 50 microM in the culture of macrophages previously enriched with cholesterol reduced the rate of cholesterol esterification by 22-62%. After combined administration of verapamil and nifedipine in doses of 25 microM into the medium the rate of cholesterol esterification in macrophages fell by 72.4%.


[The effect of protease tissue inhibitor on the activity of pancreatic proteolytic enzymes in in-vitro experiments]. The authors provide the data on in vitro experimental studies into the pharmacological properties of protease inhibitor obtained from bovine pancreas. It is shown that the preparation exerts an inhibitory action on pancreatic proteolytic enzymes such as trypsin, kallikrein, and elastase, drastically reduces the total proteolytic activity in pancreatic tissue homogenates. Comparison with the protease inhibitor gordox has demonstrated the inhibitory effect of both preparations to be practically similar.


[The mechanism of the antioxidant action of D-penicillamine]. The mechanism of the antioxidative effect of D-penicillamine was studied under the conditions of NADPH- and CCl4-dependent lipid peroxidation in microsomes of rat liver and adrenalin autooxidation reaction. The antioxidative action of the drug was shown to be due to both its chelating properties and direct anti-radical influence. The chelating effect was more pronounced and depended on the concentration of ferric ions in the medium.


[The antioxidizing activity of malonic acid derivatives]. Nine newly synthesized malonic acid derivatives were shown to have antioxidizing activity which makes up from 30 to 60% of the antioxidizing activity of ionol and vitamin E in vitro and does not yield to the activity of the latter substances in vivo. It is suggested that malonic acid derivatives may influence the antioxidizing enzymes--catalase, glucose-6-phosphate dehydrogenase and superoxide dismutase.


[The effect of clofelin on the carotid sinus and cardiopulmonary baroreceptor reflexes in man]. A study was made of the influence of clophilin on the vasomotor component of the sinocarotid and cardiopulmonary baroreflexes of man. Clophilin was shown to intensify the cardiochronotropic component of the sinocarotid reflex, thereby suppressing blood pressure fall, evoked by activation of carotid sinus mechanoreceptors, and producing no effect on vasoconstriction induced by a decrease of pressure in the right atrium. It is concluded that the mechanism of the hypotensive effect of clophilin is not related to modulation of the baroreceptor reflexes from the regions of high and low pressures.


[The correction of the hepatotoxicity of antitubercular preparations with tocopherol acetate and riboxin]. It has been established in experiments on white rats that prolonged (for 2 weeks) intoxication with antituberculous drugs (isoniazid plus rifampicin plus pyrazinamide) results in cytolytic liver injury. This manifests by hyperaminotransferasemia, initiation of lipid peroxidation, suppression of the antioxidant system and bile production. Daily injections of tocopherol acetate (15 mg/kg) and riboxine (100 mg/kg) together with administration of antituberculous drugs reduce their hepatotoxicity. The combined use of these hepatoprotectors and antioxidants provides a dramatic increase of their efficacy in durable intoxication with antituberculous drugs.


[An analysis of acute poisonings with drugs]. Analysis of acute drug poisonings was made using materials available at the Saint Petersburg Toxicological Center for the period of 10 years. The indicated poisonings became two times more frequent and in 1989 accounted for 76% of the total number of intoxications. Poisonings with tranquilizers ranked first in frequency, then followed antihistamine drugs, neuroleptics and hypnotics. There was an increase in the percentage of hemiton poisonings, which turned out lethal in 1.6-3% of cases. In most cases, the drugs were taken to commit suicide, more rarely they were used to have or to potentiate the effects of alcoholic euphoria. Among women, poisonings were encountered three times more often than among men.


[The selectivity and protective properties of m-cholinolytics in dichlorodivinylphosphate poisoning]. The activity of selective and nonselective muscarinic antagonists was examined in different experimental models. According to the results obtained, the protective effect of muscarinic antagonists during acute dichlordivinyl phosphate (DDVP) poisoning depends on the M1-subtype cholinoreceptor blockade. Meanwhile the efficiency of muscarinic antagonists in inhibition of tremor reaction induced by arecoline administration is associated with interaction between the drugs and the M2-subtype. The blocking of presynaptic M2-cholinoreceptors is likely to cause the decrease of protective potency of muscarinic antagonists in acute DDVP poisoning.


[An experimental validation of the combined use of dimephosphon with nonsteroidal anti-inflammatory preparations]. The effects of dimephosphon combined with nonsteroidal anti-inflammatory drugs were studied in rats and mice with experimental inflammation. The influence of dimephosphon on ulcerogenic activity of these drugs was also investigated. The dependence of the combinations efficiency on the scheme of dimephosphon administration was established. Synergism in anti-inflammatory activity between dimephosphon and ortophen (sodium diclofenac), indomethacin, and acetylsalicylic acid was shown. The possibility of decreasing the ulcerogenic effects of the drugs by dimephosphon was established. The effects of dimephosphon combinations are discussed as the basis for their use in clinical practice.


[The pharmacokinetics of the prolonged-action beta-adrenoblocker nadolol in hypertension patients after a single administration]. The pharmacokinetics of the beta-adrenoceptor blocker nadolol was studied in 30 patients suffering from mild hypertension given a single 80 mg dose of the drug. It has been shown that distribution of the pharmacokinetic parameters in this sample can be assumed normal. Their averages are similar to the reported data on healthy subjects. The mean retention time of nadolol in the body was estimated for the first time. The absorption of the drug was shown to be slow, which together with a low degree of bioavailability, may be associated with its low lipophility. A close correlation was demonstrated between the half-life and the mean absorption time estimates computed from blood serum and nadolol excretion with urine. The conclusion is made that glomerular filtration plays the key role in the drug elimination.


[An experimental study of the hepatoprotective properties of phytoecdysteroids and nerobol in carbon tetrachloride-induced liver lesion]. The phytoecdisteroids ecdisterone, turkesterone and cyasterone were administered in a dose of 5 mg/kg per os to rats with hepatitis induced by subcutaneous injections of CCl4. Similarly to the anabolic drug nerobol (10 mg/kg), the above agents not only interfere with the manifestation of the hepatic action of CCl4 (in this case the effect of the phytoecdisteroids is more remarkable) but also favour a more rapid normalization, as compared to the control, of functional and metabolic disorders in the liver. The phytoecdisteroids and nerobol noticeably stimulate the recovery of bile secretion, the synthesis of bilirubin and bile acids, cholesterol excretion.


[The experimental treatment of cyanide poisoning with a methemoglobin solution]. The stroma-free methemoglobin solution proved to be an effective antidote against acute cyanide poisoning in experiment. The poisoning was induced by intraperitoneal administration to rats of cyanide solutions in doses of 5, 10 and 15 mg/kg. Methemoglobin solutions were injected intravenously in doses of 2 and 4 g/kg. All the rats given methemoglobin solution after the administration of cyanide survived. Spectrophotometry of rat urine demonstrated rapid excretion of methemoglobin cyanide.


[A spectral analysis of the effect of adapromine on brain bioelectrical activity]. A study was made of the influence of adapromine on bioelectrical activity of the brain, sensorimotor cortex, dorsal hippocamp and lateral hypothalamus in freely moving wakeful rats. Adapromine was established to evoke a decrease of the amplitude of the dominant peak and dominant theta-activity in power spectra of the EEG in the cortex and hippocamp, with an increase of rapid wave activity in the beta 2 range in the right cortex and hippocamp. These changes attained maximum after 1 to 1.5 hour and lasted up to 4-5 hours after adapromine administration. These changes can be viewed as activation of the cortex and hippocamp, which may attest to the presence of antidepressive and psychostimulant effects in the action spectrum of adapromine. The specific influence of adapromine on catecholaminergic processes of the brain may lie at the basis of the above effects.


[The mechanisms of the ethomersol correction of postischemic hypoperfusion]. In rat experiments during brain ischemia (30-min carotid artery occlusion), ethomersol administered intraperitoneally in a dose of 50 mg/kg before occlusion or at the end of ischemia eliminated postischemic hypoperfusion. The effect of the drug was due to its spasmolytic and antiaggregatory activities. An analysis of the vasodilating action of ethomersol revealed its capacity to block potential-dependent calcium channels and partially intracellular calcium mobilization when the adrenergic and serotoninergic receptors were activated. The antiaggregatory activity of the drug appeared as inhibited platelet aggregation, which was induced by ADP, serotonin, arachidonic acid, thrombin, and as enhanced antiaggregatory activity of the vascular wall.


[The effect of GABA-ergic agents on the blood electrolyte balance in acute craniocerebral trauma]. A study was made of the balance of potassium and sodium ions in red blood cells and blood plasma of rats with acute craniocerebral injury seen over time. It has been established that phenibut (50 mg/kg) and sodium hydroxybutyrate (0.2 g/kg) prevent electrolytic changes in blood at different periods of injury. The K+/Na+ ratio of red blood cells can be used as an objective indicator to characterize the time course of changes in craniocerebral injury and to evaluate the efficiency of its pharmacological correction.


[A comparative evaluation of the cardioprotective and antianginal actions of energy-providing agents]. The limitation of a myocardial necrotic area by some energy-yielding compounds in rat coronary occlusion and their capacity to elevate the ischemia threshold in conscious rabbits were studied. Sodium malate, ascorbic acid and phosphoenolpyruvate were demonstrated to reduce the sizes of necrotic areas and increase the ischemia threshold, whereas cytochrome C and fructose-1,6-diphosphate were effective solely in limiting the infection area. It was concluded that the preventive antianginal effect of energy-yielding and electron-accepting compounds depended on their capacity to accumulate in intact cardiomyocytes.


[The antihypoxic and radioprotective properties of selective adenosine receptor agonists]. The selective A1- and A2-receptor agonists L-PIA (ED50 = 0.55-0.78 mmole/kg) and NEGA (D50 = 0.05-0.1 mmole/kg) possess high antihypoxic and radioprotective effects. A2-subtype receptors may be involved in the antihypoxic and radioprotective effects of adenosine analogs.


[The efficacy of hepatoprotectors and cytochrome P-450 inducers in correcting the functional activity of the hepatocyte microsomal system in an acute lesion of the liver in prepuberty]. Intragastric CCl4 inhibited the activity of and lowered the levels of the major components of the hepatic monoohygenase enzyme system in one-month rats. Benzonal was found to be more effective in correcting the impaired monooxygenase enzyme system of hepatic cells in immature rats with acute hepatitis than silibor, phytin and zyxorin.


[The mechanism of action of the bioflavonoid lespeflan and the antihypoxant TB-4 on nitrogen metabolism in animals with acute kidney failure]. The changes in the levels of urea and creatinine caused by the new native preparation lespeflanum and the antihypoxant TB-4 were studied in animal experiments. The agents tested produced a significant hypoazotemic effect in acute renal failure. Lespeflanum showed diuretic and natriuretic effects in healthy animals, elevated plasma aldosterone levels and decreased hepatic arginase activity. There was a normalization of thioldisulfide metabolism in patients treated with lespeflanum and TB-4. The hypoazotemic effect of lespeflanum was due both to its anabolic and anticatabolic effects. Lespeflanum is recommended for wide clinical application to treat patients with chronic renal failure.


[The effect of clofelin on uterine contractile activity (experimental and clinical research)]. Pregnant rat experiments have revealed a pronounced and prolonged naloxone-irreversible depriming effect of clofelin, 0.05 and 0.5 mg/kg, on the frequency and amplitude of myometrial biopotentials, which was eliminated with phenoxybenzamine. In clinical testing, clofelin in therapeutical doses showed a marked tocolytic effect in threatened abortion at 18-34-week gestation. The agent in the same doses normalized blood pressure in hypertensive pregnants, without having a negative action on the fetus.


[The effect of hepatoprotectors on the functional activity of rat hepatocyte mitochondria in in-vitro and in-vivo systems]. In in vitro experiments essential, flacumin, and silibor inhibited the respiratory activity of isolated mitochondria and failed to affect the respiration of hepatocytes in rats at condition 4 by Chance. Essential uncoupled mitochondrial oxidative phosphorylation in the in vitro system. The hepatoprotectors used in ethanol-induced abnormality restored the activity of mitochondrial oxidative phosphorylation of hepatocytes to its level in intact animals.


[The enhanced efficacy of the pharmacological regulation of the processes of blood cell activation and interaction in the flow by polymer additives decreasing the hydrodynamic resistance of the blood]. The increase of blood cell auto- and interactivation and the decrease of aspirin antiaggregant effect were demonstrated under hemodynamic conditions of a stenotic zone in a model maximally approached to the real blood circulation. The lowering of platelet activation, of the release of active agents from platelets, and of platelet-leukocyte interactivation was attained under the conditions of the flow modified by the drag-reducing polymer solution. The recovery of aspirin antiaggregant activity and aspirin-induced reduction of the total platelet release of platelet- and leukocyte-activating agents were demonstrated under the influence of the polymer.


[The possible participation of the GABA metabolic system in the mechanisms of the protective action of L-aspartate in hypoxia in an enclosed space]. L-Aspartate given intradermally in a dose of 100 mg.kg-1 to mice 2-3 minutes before placement to a hypoxic chamber was shown to prolong the mean animal lifespan by 38% and to delay hypoxic convulsions by 38-40%. The agent was ascertained to maintain the higher glutamate decarboxylase (GD) activity and GABA levels in the brain during hypoxia and prevent GD activity and GABA levels from their drastic diminution when hypoxic convulsions occurred.


[The antithromboxane activity of alpha- and omega-modified carbocyclic analogs of PGH1]. In in vitro experiments on a model of arachidonate- and thrombin-induced platelet aggregation, analogues of PG endoperoxides displayed an antiaggregatory effect or stimulated spontaneous platelet aggregation in the whole blood of man and rabbits, but a slight antiaggregatory effect in the rabbit intact organism. The presence of the hydroxyl group instead of the routine alkyl omega-chain produced an antiaggregatory effect due to TxA2 receptor blockade.


[The action of carnitine-series preparations in experimental alloxan diabetes mellitus]. The study was undertaken to examine the effects of l-carnitine and acetyl-l-carnitine in rats and mice with experimental alloxan diabetes. The findings suggest that acetyl-l-carnitine is more effective against diabetes in increasing glucose tolerance, restoring the impaired response of glucagon to glucose, showing glycogen-sparing action than is l-carnitine.


[A comparative study of the activity of antihypoxic agents in hemic hypoxia]. Amino derivatives of ortho-benzoquinone (OBQ) were demonstrated to have a protective action in acute toxic hemic hypoxia induced by sodium nitrite given to laboratory animals. This action of OBQ was due to its capacity to activate the recovery of blood oxygen transport function by accelerating the restoration of methemoglobin and determined by their electron-acceptor properties, lipophilicity and NADP-dependent methemoglobin reductase affinity.


[The pharmacological regulation of inflammation: the current problems and developmental outlook]. The papers summarizes the latest data on the pathogenesis of an inflammation reaction, with emphasis on the mechanism of action of antiinflammatory agents, including the drug regulation of the arachidonic acid cascade, and on the mechanisms of unassociated action on prostaglandins. It also discusses the prospects for using the existing antiphlogistics and the main trends in designing the new approaches to the pharmacological regulation of inflammation.


[The influence of modulators of enzyme activity on the pharmacological effect of thiopental sodium and ketamine and on the pharmacokinetics of thiopental sodium]. The rat experiments studied the impact of inductors and inhibitors of enzymatic activity of xenobiotic metabolism on the pharmacological activity of sodium thiopental and ketamine and on the pharmacokinetics of sodium thiopental. Cocarboxylase, cobalt chloride and cimetidine enhanced the pharmacological action of sodium thiopental, but failed to exert any action on the effect of ketamine. The preparations of vitamin K, particularly vikasol and menadione sodium bisulfite, and phenobarbital attenuated the effects of these anesthetics, but tocopherol unchanged it. Phenobarbital and vikasol accelerated blood elimination of sodium thiopental, whereas cimetidine and cocarboxylase slowed down this process.


[The interaction of the immune system and the liver mono-oxygenase system]. The effect of different immunostimulants (prodigiosan, levamisole, T-activin, sodium diethyl dithiocarbamate, sodium nucleinate, lithium chloride, muramil dipeptide, B-activin) and mixed hepatic function oxidase inhibitors (cimetidine, chloramphenicol) or inducers (phenobarbital, flumecinol, rifampicin) on immune reactivity (macrophage function, humoral and cellular responses) and hepatic microsomal function (hexobarbital sleeping-time) was studied in non-inbred and BALB/c male mice. There was a high correlation between the ability of immunostimulants to depress hexobarbital metabolism and their ability to enhance macrophage activity (carbon clearance test), but not humoral and cellular immunity. No reciprocal changes occurred in immune reactivity after positive or negative pharmacological modulation of hepatic drug metabolizing enzyme activity.


[The radioprotective and antioxidant properties of solubilized alpha-tocopherol acetate]. A single intravenous administration of solubilized alpha-tocopherol acetate in a dose of 1 mg/kg to CBA x C57Bl x F1 male mice 3 and 24 hours before radiation was demonstrated to increase 30-day survival rates in the animals. Oily alpha-tocopherol acetate had the identical effects when the agent was intramuscularly given in a dose of 10 mg/kg. There was a rise in peripheral leukocyte counts 0.5 hour after solubilized alpha-tocopherol acetate administration. The antioxidative activity of the solubilized agent was 3.3 times as high as that the routine agent when attacking Tween 80. The higher radioprotective activity of solubilized alpha-tocopherol acetate is accounted for by its enhanced bioavailability, antioxidative activity and effects on the factors of nonspecific body's resistance.


Ultrasonic study of processed milk cream and vegetable oils. Food systems are complex and inhomogeneous in nature. Ultrasonic propagation velocity in the food systems, in this case processed milk cream and vegetable oils, is studied. Ultrasonic properties of the food systems are similar to those of complex biological tissues. The presence of vegetable oil as an adulterant in the processed milk cream is detected with the help of a double-probe-through-transmission ultrasonic technique. The present study helps to maintain quality control of various food systems, particularly with regard to their adulteration, if any.


High frequency pressure propagation in viscoelastic tubes: a new experimental approach. A new method for estimating the high-frequency characteristics of wave propagation (phase velocity and attenuation per wavelength) in hydraulic lines is presented in this work. It consists of measuring the ratio of pressure amplitudes at two distinct sections of an occluded tube at different frequencies, and minimizing the difference between the experimental pattern and the theoretical one predicted on the basis of the transmission line theory. In this work the method is used for estimating the high frequency propagation characteristics of two different latex tubes. The values obtained are then compared with those provided by the more traditional three-point pressure method. The results of our trials demonstrate that the new method furnishes reliable estimations of the asymptotic values of phase velocity and attenuation per wavelength, provided the frequencies used during the experiment are sufficiently high. Moreover, the method turns out quite robust as to the influence of noise and possible measurement errors. For this reason it seems particularly suitable for studying wave propagation under difficult experimental conditions, such as those met with when measurements are performed on blood vessels in vivo. Finally, some discrepancies between our experimental results and the predictions of the transmission line theory are pointed out, and their possible origin examined.


A study of fracture and inelastic behavior of bioactive glass-ceramics and glasses. The fracture and inelastic behavior of A-W glass-ceramics, phosphate glasses, silicate glasses, and borate glasses were determined in simulated body fluid (SBF), kerosene, and water. By using the stable crack growth technique, an inelastic behavior was observed on the diagram of load versus load-point displacement. From these studies, it was suggested that the inelastic behavior of bioactive glass-ceramics was produced by the plastic deformation of glassy phase on the grain boundary.


Computer simulation on creep of amalgam in Class I cavity. The creep behavior of amalgam in Class I cavity was simulated by an axi-symmetric elastic creep finite element method. In this procedure, the stress and time dependencies of the creep strain of amalgam were incorporated. Exponents of stress and time dependencies were postulated as 2.0 and 1.0, respectively. Amalgam with 1.0% of creep value (tested by American Dental Association Specification No. 1) were selected for the material to calculate. Simulation was conducted for the occlusal force of 40, 100, and 150 N, respectively, on the caps of enamel and vertical direction to the axis of the tooth. Results show that creep strain of amalgam in the cavity did not increase linearly with time because the amalgam deformed to become stress-free and creep rate was a function of the stress. It was concluded that elastic deformation of the crown with no filling material in its cavity is an important factor in determining the creep strain and the gap between the cavity and the restorative material.


[The polymorphism of pachycarpine oxidation]. The ratio of urinary excretory pachycarpine to its oxidized metabolites, 2- and 5-dehydropachycarpines (metabolic ratio) was determined in a selective group of 81 unrelated cardiac patients from a Moscow Caucasian population given pachycarpine in a dose of 25 g. The metabolic ratio distribution was shown to be bimodal. Ninety five per cent of the patients had the metabolic ratio lower than 28 while 4 (5%) patients higher than 70. In 25 patients of the group, the pachycarpine metabolic ratio was evaluated after quinidine, 50 mg. Twenty-two patients with a relatively low metabolic ratio showed a dramatic (several times) increase, while in 3 patients with the prior metabolic ratio higher than 70, the effect of quinidine was insignificant. The findings suggest that pachycarpine oxidation is genetically polymorphic and similar to the polymorphism of sparteine/debrisoquine oxidation. Pachycarpine may be used as a marker in phenotyping the population.


[The inhibiting effect of 8-Cl-adenosine-3',5'-cyclophosphate on the growth of melanoma B-16 in mice]. A site-selective analogue of the cyclic adenosine monophosphate 8-chloro-adenosine-3',5'-cyclophosphate was studied for its effects on the growth of transplanted murine melanoma B-16. When the agent was given to the mice, a substantial effect on the growth of the tumor was produced by a number of factors, which included the route of administration, concentration of the agent, the time and duration of therapy. Intraperitoneal injections of the agent in a dose of 20 mg/kg/day which were made during three consecutive days, beginning from day 5 after tumor transplantation caused a 58% decrease in tumor growth as compared to the controls. An examination of tumour biopsy specimen revealed that after a course of the injections there was a significant suppression of the activity of cAMP-dependent protein kinase, type I, and a drastic increase in that of cAMP-dependent protein kinase, type II.


Literature survey on biomedical applications of thermography. Thermography is a noninvasive technique through which temperatures are monitored and recorded, thereby allowing visualization of heat flow. There are three types of thermography: liquid crystal thermography (LCT), infrared thermography (IRT) and microwave thermography (MWT). This paper presents a survey of the literature pertinent to the biomedical applications of these types of thermography. The noninvasive and high resolution characteristics of the thermographic systems make them valuable diagnostic as well as therapeutic aids. Typical research areas include detection of blood flow, diagnosis of joint inflammation and cancer, thermal modeling of various body parts, and use in reproductive problems. The survey discloses that thermography has found applications in various fields in medicine, veterinary medicine, pharmacy, and dentistry.


[The pharmacological correction of recurrent immediate-type allergic reactions]. The effect of drugs on the early and late phases of repeated allergic reactions (RAR) was studied in experiments on rabbits. The action of the drugs was estimated by the number of challenge doses of antigen, endured by survived and dead rabbits, percentage of the animals' death, and by the place of each group on the lethality scale. Diphenhydramine, ouabain and their combinations, silver nitrate (20 mg/kg) and DOCA enhanced whereas histamine, unithiol, cholesterol, and silver nitrate (20 and 0.2 mg/kg) decreased allergization in the period of RAR. The characteristic features of the action of the drugs on RAR were revealed and compared to the first allergic reaction. Qualitative and quantitative differences were shown in the action of different drug doses and combinations on RAR. The authors provide evidence for the possibility of treating allergic diseases by drug administration in a quiet period.


[The role of ketone bodies in the development of postalcoholic-intoxication heart damage in rats]. Experiments on rats subjected to forced alcoholization for 5.5 days were made to measure the content of ethanol, acetaldehyde and ketone bodies in the blood during intoxication and 2 days after ethanol withdrawal and to estimate the intensity of postintoxication disorders in heart activity on the third day after alcoholization withdrawal. A positive correlation was discovered between depression of left ventricular contractility and the blood content of acetaldehyde and ketone bodies. The magnitude of the threshold of heart fibrillation did not correlate well with the concentration of ethanol during alcoholization. However, it agreed well with ethanol concentration in the postintoxication period. Additional administration to the animals of beta-hydroxybutyrate or caprylic acid in the postintoxication period intensified heart contractility depression. The conclusion is drawn that elimination of ketosis in ethanol withdrawal as well as a progressive taking out of alcoholic patients from dipsomania can prevent the development or attenuate the intensity of postintoxication heart injury.


Comparison of the electrochemical properties of various orthopedic porous metals. The electrochemical properties of various porous metal coatings used in reconstructive orthopedic prosthetics were examined. Potentiodynamic corrosion testing was used to evaluate the behavior of the following porous metals; CSTi on Cast CoCr, CSTi on Ti-6Al-4V, CoCr beads on Cast CoCr, CoCr beads on Ti-6Al-4V, CP Ti beads on Cast CoCr, and CP Ti beads on Ti-6Al-4V. Analysis of the resultant corrosion scans showed that these materials behave similarly to one another. No corrosion-related anomalies were noted.


[A comparative pharmacological evaluation of sea buckthorn, rose and plantain oils in experimental eye burns]. Hippophae, Rosa and plantain oils have been shown to produce and essential therapeutic action on chemical burns of rabbit eye. The effect was attained in the phases of trophic disturbances and epithelialization.


Flexibilized gelatin film-based artificial skin model: I. Preparation and properties of the films. A method was developed to prepare a simple, flexibilized gelatin film-based artificial skin model. The films are tough, adhere to open wounds spontaneously, are permeable to body fluids, and can release incorporated bioactive compounds over 4-5 days.


[A morphological assessment of the efficacy of benzofurocaine in experimental burns]. Studies of the effect of benzophurocaine on the morphological structure of the skin and viscera in animals with burn disease have shown the drug to have a protective action. The latter one manifested itself in a considerable reduction of injuries to the viscera and in a more rapid recovery of the disordered structure and function.


Flexibilized gelatin film-based artificial skin model: II. Release kinetics of incorporated bioactive molecules. Any delivery system for bioactive molecules should have the ability to release the compound in question in a reproducible and predictable way over a certain period. For artificial skin models that are designed to enhance healing by the use of growth factors, this requirement poses another problem: the design of a delivery method that can provide a realistic assessment of the release kinetics. This means that the design should "mimic" conditions encountered in an open wound, i.e., only a certain part of the film can face the wound, from which it can absorb wound fluid that will dissolve the incorporated bioactive molecule and bring it to the open wound. Such a system has been developed and the release of 125I-labelled insulin, incorporated into flexibilized gelatin films, has been determined. The details of this study follow.


An experimental study on biomechanical properties of hepatic tissue using a new measuring method. Hepatic tissue is an important internal organ for life. In this paper, we combined the moire method (an optical method) and indentation technique to investigate biomechanical response of hepatic tissue. To examine this measuring technique, we first measured the biomechanical properties of the block of pig's hepatic tissue using this method. The experimental result indicated that the pig's hepatic tissue was obviously a viscoelastic material. We closely analyzed the change of curves for force relaxation, creep, and nonlinear deformation of the block of pig's liver. Meanwhile, we also compared the changes in the biomechanical parameters of normal and cirrhosis hepatic tissue of humans.


Sonomicrometric studies on the effects of long-term pumping of cardiac assist device on the bulk and regional mechanics of the normal left ventricle in goat. Pneumatically driven, diaphragm type left ventricular assist devices (LVADs) were implanted into 2 goats with normal hearts for approximately 1 month to study the effects of long-term pumping of LVAD on the cardiac mechanics. One sham-operated goat was used to obtain control data. Diameters and myocardial segment lengths of the left ventricle were measured with an ultrasonic displacement meter to calculate the bulk mechanical work (BMW) and regional myocardial mechanical work (RMW), respectively. The LVAD was pumped in the 2:1 drive mode (one counterpulsated pumping in every two cardiac cycles), and was temporarily driven in the 1:1 mode (one pumping in every cardiac cycle) or stopped to obtain the data under these conditions. During the second half of the post-operative period while the animal condition was stable, the BMW in the 2:1 and 1:1 modes were approximately 59% and 72% of that observed under the temporary pump-off condition (0.22 W/(100 g)), respectively. The RMW in the 2:1 and 1:1 modes were 69% and 74% of that obtained during pump-off (6.2 mW/cm3), respectively. The myocyte diameter in the subendocardial layer was reduced by unloading effect of 1-month pumping, whereas those in middle and subepicardial layer showed little change.


Wave propagation in the silicon tube: comparison of the two-point and three-point pressure methods. The values of the propagation coefficient measured on a silicon rubber tube in the frequency range 1-15 Hz were compared, using four different equations. The first formula is based on three simultaneous pressure measurements performed at equidistant points; the remaining three equations are original, and make use of only two of the three pressure measurements together with a no-flow condition at the terminal tube section. The results of our trials demonstrate that the experimental phase velocity, obtained with all equations, settles at a value about 25% in excess of the theoretical one computed with a classic linear mathematical model. This result may be explained by an increase in the dynamical Young modulus with respect to that measured in static conditions. However, the three-point method introduces great errors in the results in the frequency range 11-14 Hz where the spectrum of the second signal becomes minimum. In all cases, the experimental value of attenuation per wavelength at mid-high frequencies is greater than the theoretical one valid for a purely elastic tube. The attenuation values obtained with the two-point method can be explained by introducing a small contribution of wall viscoelasticity (2-3 degrees) into the linear model. Attenuation per wavelength computed with the three-point methods turns out about threefold that computed with each of the two-point formulas. This result supports the idea that the accuracy of the three-point method may be insufficient to achieve correct estimation of wave attenuation, especially when the distance between transducers is small compared to wavelength.


Greater incidence of electrocardiographic left ventricular hypertrophy in black men than in white men in Evans County, Georgia. Population-based studies of black populations in the United States and Puerto Rico have reported higher prevalences of electrocardiographic left ventricular hypertrophy compared to white or lighter-skinned populations residing in the same areas. This study examines the incidence and correlates of electrocardiographic left ventricular hypertrophy in a population-based, biracial cohort of 435 white and 163 black men from the Evans County, Georgia, Heart Study, who were examined at entry in 1960 and reexamined in 1967. Only men over 35 years of age who were free of cardiovascular disease and had normal electrocardiograms at entry were eligible. Black men had a nearly fourfold greater incidence of electrocardiographic left ventricular hypertrophy compared to white men (13.5% vs 3.7%, respectively; incidence ratio 3.7; 95% CI 3.2-4.4). After statistically adjusting for age, systolic blood pressure, weight, and the change in weight and blood pressure, black men had a threefold greater incidence of electrocardiographic left ventricular hypertrophy compared to white men (logistic odds ratio 3.0; 95% CI 1.6-6.1). In summary, black men showed a significantly greater risk of developing electrocardiographic left ventricular hypertrophy at 7-year follow-up in Evans County compared to their white counterparts. This elevated risk could not be explained by the independent or joint effects of risks factors for electrocardiographic left ventricular hypertrophy.


Differences in neonatal mortality by race, income, and prenatal care. To determine the extent to which the social and physical environment affects the association between prenatal care and black pregnancy outcome in Chicago, we performed a stratified analysis of 1982-1983 Illinois vital records and 1980 United States census income data. Median family income of the mother's census tract was used as the ecologic variable. In very-low-income census tracts (less than $10,000 per year), 40% of blacks and 47% of whites received adequate prenatal care. There was no racial disparity in the percentage of low-birth-weight infants attributed to inadequate prenatal care among poor mothers. For mothers who resided in moderate-income areas ($20,001 to $30,000 per year), 50% of blacks and 67% of whites received adequate prenatal care. Although adequate (compared to inadequate) prenatal care was associated with improved birthweight distribution independent of community income, only in moderate-income areas was it related to black neonatal survival. For term black infants who received adequate prenatal care, residence in impoverished areas was associated with a nearly fourfold greater neonatal mortality rate (deaths per 1000 live births): 5/1000 vs 1/1000; RR = 3.8 (1.3-11.0). We conclude that place of residence is an important risk factor for black neonatal mortality.


Renin-angiotensin-aldosterone system and thromboxane A2/prostacyclin in normotensive and hypertensive black Zimbabweans. Fourteen normotensive and 14 hypertensive black men with mild essential low-renin hypertension were examined during two protocols producing sodium depletion (less than 40 mmol sodium diet per day) for 5 days, followed by sodium loading (300 mmol sodium diet per day) for another 5 days. Changes in plasma renin activity, urinary aldosterone excretion, and excretion rates of stable breakdown products of thromboxane A2 (thromboxane B2) and prostacyclin (6-keto PGF1 alpha) were simultaneously assessed by radioimmunoassay. On the basis of low-renin status and paradoxically normal aldosterone excretion in both normotensives and hypertensives, thromboxane B2 excretion was increased by 14% (not significant); 6-keto PGF1 alpha was significantly decreased by 47% in the hypertensives compared to the normotensives. As a result, thromboxane B2/6-keto PGF1 alpha ratio was significantly increased from 1.29 +/- 0.10 in the normotensives to 2.78 +/- 0.12 in the hypertensive patients. The same ratio increased significantly after sodium loading in both groups, but more distinctly in the hypertensives (40%). Prostacyclin is a vasodilator, a natriuretic, and a potent inhibitor of platelet aggregation. Thromboxane A2 has opposite effects. The impaired prostacyclin biosynthesis we found in the hypertensive patients could account for the increased vascular resistance and some complications typical for hypertensive state.


Distributions of hemostatic variables in blacks and whites: population reference values from the Atherosclerosis Risk in Communities (ARIC) Study. The Atherosclerosis Risk in Communities Study measured hemostatic variables in nearly 16,000 men and women, aged 45 to 64 years, from four US communities. This report, based on the first 12,681 participants, presents distributions of fibrinogen concentration, factor VII activity, factor VIII activity, von Willebrand factor antigen, protein C antigen, antithrombin III activity, and activated partial thromboplastin time. Many of the hemostatic variables differed between blacks and whites, and by sex and age. For example, compared to whites, blacks had higher mean values of fibrinogen, factor VIII, von Willebrand factor, and antithrombin III, and lower mean values of protein C. Some seasonal fluctuations in hemostatic variables were noted; most notably, mean values of factor VII were lowest and protein C were highest in subjects examined in the summer compared to those examined during the other seasons. These results provide population-based reference values on blacks and whites for those interested in the relation of hemostasis to disease.


Race, stage of disease, and survival with cervical cancer. Significant disparities in survival with cervical cancer were observed according to social and disease characteristics of 3711 patients from Connecticut from 1984 through 1988. Women with advanced disease were 25 times more likely to die during a 4-year follow-up than those diagnosed with carcinoma in situ. Elevated risk of death was also noted for blacks (OR = 1.73; 95% CI = 1.2-2.5) and for women diagnosed after the age of 52 years (OR = 33.4; 95% CI = 16.5-69.9). Persons living in census tracts with large proportions of high school graduates or with high median incomes experienced decreased risk (OR = 0.66; 95% CI = 0.45-0.98 and OR = 0.65; 95% CI = 0.44-0.95, respectively). Multivariate logistic regression analysis found the effects of stage of disease on vital status to be reduced by approximately 50% when adjusted for other factors, reflecting the sizable effect of a woman's background on those variables. Nonwhite and older women were at significantly greater risk of being diagnosed with invasive disease.


Ethnic variations in the chronic pain experience. Although ethnic identity has been found to have an important influence on experimental and acute pain intensity and response, little work has been directed to understanding how ethnicity affects the chronic pain experience. We report the results of a quantitative study of 372 chronic pain patients, in six ethnic groups, who were under treatment at a multidisciplinary pain management center in New England. The study used questionnaires and standardized instruments for assessing pain intensity to determine whether ethnic background was significantly related to interethnic or intraethnic group variation in pain intensity and response when other significant medical, sociodemographic, and psychological variables were controlled. In this study population, the most frequent statistically significant intergroup differences in pain intensity and in behavioral, psychological, and attitudinal responses to pain are related to differences in ethnic identity and psychological coping style according to locus of control. In addition, in this population, ethnic identity is a predictor of locus-of-control coping style. The major statistically significant intragroup differences in pain intensity and response are related to differences in generation, degree of heritage consistency, and locus-of-control style. We suggest that treatment programs for multiethnic populations should include a thorough cultural assessment and that providers need to be aware of the potential effect of ethnic background on chronic pain patients' communications, concerns, and coping styles related to the chronic pain experience.


The effect of ethnic origin on the rate of spontaneous late mid-trimester abortion. The effect of ethnic origin on perinatal outcome is well recognized. An effect on the rate of spontaneous abortion has not been previously documented, to our knowledge. We report the results of a retrospective survey of late mid-trimester abortions (20 to 26 weeks gestation) at Dudley Road Hospital, Birmingham, England. The aims of the study were to document the rate of spontaneous late mid-trimester abortion by ethnic origin and to define any differences in these groups, both medically and as a result of histological examination of the abortus, that might account for observed differences. Over an 18-month period, during which 6508 infants beyond 26 weeks gestation were delivered, 30 late mid-trimester spontaneous abortions occurred (13 black, 10 white, 7 Asian). Abortion rates per 1000 deliveries were 12.9 for blacks, 3.6 for whites, and 2.7 for Asians. The differences between ethnic groups were statistically significant (chi 2 = 17.4; P = .0002). The black women experiencing spontaneous mid-trimester abortion were of higher mean parity and were more likely to have undergone a previous therapeutic termination. Review of pathology reports revealed more cases of chorioamnionitis and fetal pneumonia in this group. Although these results should be interpreted with caution, a relationship clearly exists between ethnic origin and late mid-trimester loss. Further study is warranted to establish the cause.


The molecular genetics of Down syndrome. Major advances have occurred in the understanding of the genetics of DS since the discovery a little more than 30 years ago that it resulted from an extra copy of HSA-21. It has been learned that only a small region of HSA-21 is required in triplicate to produce at least some of the DS phenotype. Future work will clarify which regions are responsible for particular phenotypes of interest. The mechanisms by which extra genetic material leads to phenotypic abnormalities in DS and other aneuploidies appear to be complex. Although gene dosage effects are operative for many loci, they do not appear to be strictly operative for all genes. A more thorough understanding of the effects of aneuploidy on gene expression is needed. To understand adequately the mechanisms by which extra genetic material leads to particular phenotypic features will require the use of animal models. The trisomy 16 mouse, as well as new transgenic and partial trisomic mouse lines currently being developed, may be of particular help in this endeavor.


Preoperative evaluation of the patient for regional anesthesia. The preoperative evaluation of the surgical patient is important for optimizing the anesthetic management. The evaluation process for the regional anesthesia candidate is reviewed. Patient selection, a review of organ systems, and the impact of medications and selected diseases are also discussed.


Complications of continuous spinal anesthesia. The increased use of continuous spinal anesthesia (CSA) in recent years has resulted in research efforts directed at reducing the complications associated with the technique. Complications of CSA are categorized as general, the same as those associated with single-shot spinal anesthesia, and specific, those associated solely with CSA. General complications include infection, backache, hematoma, and neurological sequelae. Specific complications are all related to catheter use. The risk of developing the neurological complication of postdural puncture headache (PDPH) led to the use of microcatheters designed specifically for CSA. While the incidence of PDPH decreased with the use of microcatheters, the risk of developing the more serious complication of cauda equina syndrome increased, resulting in a Safety Alert being issued by the Food and Drug Administration.


Epidural blockade: a multifaceted anesthesia tool. The search for an optimal analgesic and route of administration continues. The development of the epidural route of administration of local anesthetic solutions and opioids approaches this ideal. In this article, the author details why epidural blockade is a multifaceted anesthetic technique useful in obstetrics, surgery, and pain therapy.


Beneficial effects of the combined techniques of caudal and general anesthesia in the pediatric patient: two case reports. The practice of combining a caudal anesthetic with a general anesthetic is frequently used in the management of pediatric patients. The principal advantage is improved postoperative pain management. Additionally, the perioperative reduction of inhalation agents as well as narcotic and non-narcotic analgesics provides a faster, more pleasant recovery from anesthesia that may result in a shorter hospital stay. The addition of caudally administered narcotics provides superior postoperative pain management in the pediatric patient requiring prolonged hospitalization. This article examines this combined technique in two pediatric patients: one, an ambulatory patient, the second, a patient requiring a postoperative intensive care admission.


Use of the peripheral nerve stimulator and standard, unsheathed needles in performing regional nerve blocks. Although the use of peripheral nerve stimulators and unsheathed needles in performing nerve blocks has been previously described, there has been a growing emphasis on the use of specific, expensive equipment to ensure success. The availability of equipment designed for use in peripheral nerve blocks, insulated needles and nerve stimulators, will help promote the use of these techniques, but the expense of purchasing this specialized equipment may contribute to a decline in performance of certain types of blocks. This article reviews the use of standard equipment, available in most anesthesia departments, for performing peripheral nerve blocks successfully.


Sedation and analgesia techniques for regional anesthesia. The use of adjuvant drugs for regional anesthesia may be indicated for a variety of reasons. Some general patient considerations, indications for the commonly used sedatives and analgesics, and administration techniques for these agents for patients having regional anesthesia are discussed.


[Epidemiology of endemic non-venereal treponematoses]. The occurring resurgence of endemic treponematoses warrant the renewal of WHO mass campaigns. These various infections, pinta, yaws, bejel and endemic syphilis, are due to a treponema apparently identical to the venereal syphilis one. These different treponematoses do act upon epidemiology of venereal syphilis. The recent outbreak of treponematoses justify the current researches in the development of a treponemal vaccine.


Elucidation of kidney function by micropuncture: an historical perspective. An understanding of the fundamental mechanisms of kidney function awaited the advent of micropuncture techniques. The initial micropuncture study by Wearn and Richards in 1924 presented the first direct evidence that the initial step in urine formation was the process of ultrafiltration at the glomerulus and that certain solutes were reabsorbed in the renal tubules. Subsequent micropuncture studies and the development by Burg and colleagues for in vitro perfusion of surviving tubular segments have provided an enormous amount of information about glomerular function and the transport characteristics of all nephron segments in the normal and diseased kidney.


[Importance of diets and their effect on fetal development: function and structure of the endocrine pancreas following protein deficiency during intrauterine life]. When an isocaloric low protein diet (8% versus 20%) is administrated to rats during gestation, the fetus or the neonate has a lower body weight and the structure and function of the endocrine pancreas is altered: islet cell proliferation, islet size and islet vascularisation are reduced when compared with a control group. If these fetal islets are cultured during 7 days in vitro, they secrete less insulin than normal islets in response to an AA challenge. When these newborns are fed with a low protein diet until adult age and analyzed at 70 days, the same alterations of the endocrine pancreas persist: the in vitro insulin secretion of the isolated islets in response to AA is dramatically depressed although their response to glucose is normal. However in vivo glucose and insulin levels in response to oral glucose challenge are abnormal. In addition, permanent functional alterations seem to persist when induced in utero. A normal diet (20% protein) given from birth to adulthood does not restore a normal insulin response in vivo to an oral glucose challenge.


[Refractory diarrhea in infants: experimental basis of current therapeutic perspectives]. Intractable diarrhoea is a severe condition of early infancy producing prolonged food intolerance, massive watery diarrhoea and malnutrition. Although the etiology remains unknown in more than half of the cases, a basic physiopathological mechanism appears to be a variable inhibition of the maturation and differentiation of the crypt cell resulting in immature villus cells. Among the known nutritional and hormonal factors that control maturation of the enterocytes, polyamines (spermine, spermidine) emerge as the most trophic substances potentially useful for humans. Clinical studies are warranted to determine whether semi-elemental diets enriched in polyamines would provide some benefit for patients with intractable diarrhoea or with an adapted bowel after extensive enterectomy.


Rheumatoid arthritis and depression: an overview. Clearly, the determinants of depression in RA are complex and multifaceted. As with the disease itself, there is no simple cure for the depression that often accompanies it. Knowledge in this area is growing rapidly, however. Increasingly effective interventions are being developed to help those having difficulty adjusting to RA. As our understanding of the determinants of depression in RA increases, these therapies will continue to evolve. Ultimately, they may provide the long-term benefits desired by clinicians and patients alike.


Clinical monitoring of neuromuscular function. With the advent of shorter-acting non-depolarizing neuromuscular blocking drugs, the use of nerve stimulation as a means of monitoring the neuromuscular junction has become more widespread. This article describes the patterns of nerve stimulation and modes of monitoring muscular response in current clinical use. These patterns and modes are compared and their clinical relevance is discussed.


Surgical management of Graves' ophthalmopathy. While most patients with Graves' ophthalmopathy have minor or largely cosmetic problems, severe ocular morbidity can occur and lead to blindness or eye loss. In this article the role of surgery in the management of Graves' ophthalmopathy is reviewed.


Illness and insight.

Illness and insight. The term insight, when applied to illness, encompasses a patient's awareness and the personal significance of his/her disease, and the need for treatment. Insight is shaped by cultural, psychological and neurological factors. It affects attitudes to compliance and screening, levels of distress and may influence prognosis.


Computers in respiratory medicine.

Computers in respiratory medicine. Information ranging from patient symptoms to bed state is essential for the efficient functioning of clinical services. Computers have a central role in organizing this information and this review illustrates the impact of their introduction on clinical hospital departments.


Management of pregnancy in women with HIV infection. HIV infection is a common medical problem in pregnancy in many parts of the world. Management involves supportive multiagency care, easy and effective communication, an awareness and understanding of other issues (which may be more important to the mother than her HIV infection), and specialists with both experience and an up-do-date knowledge base.


Localization of interleukin-1 alpha, type 1 interleukin-1 receptor and interleukin-1 receptor antagonist in the synovial membrane and cartilage/pannus junction in rheumatoid arthritis. Using monoclonal antibodies and immunohistochemical techniques we have investigated the presence and distribution of interleukin-1 alpha (IL-1 alpha), type 1 IL-1 receptor (IL-1R1) and of interleukin-1 receptor antagonist (IL-1ra) in synovial tissue from 18 rheumatoid arthritis (RA) and eight osteoarthritis (OA) patients and in eight normal synovial tissue samples. IL-1 alpha and IL-1R1 were found in all of the samples examined. In RA, there were a large number of synovial cells expressing IL-1 alpha and IL-1R1, with 85 and 90% positive cells in the lining layer, 45 and 80% in the interaggregate area, and 90% of the vascular endothelial cells. In the lymphoid aggregates, 20% of the cells contained IL-1 alpha and 70% expressed IL-1R1. IL-1 alpha and IL-1R1 expressing cells showed a similar distribution in OA synovial membrane, but there was a smaller number of positive cells in the deeper area; and the staining intensity was lower. In contrast to IL-1 alpha and IL-1R1, IL-1ra was found only in 10/18 RA, 5/8 OA and 2/8 normal tissue samples. IL-1ra was detected in 35% of RA and 45% OA lining layer cells; 25% RA and 35% OA vascular endothelium; 10% RA and 15% OA interstitial cells and 30% cells in RA lymphoid aggregate. The staining intensity in both RA and OA tissues was comparably low. The presence of IL-1ra in RA and OA tissues was confirmed by Northern blot analysis for IL-1ra mRNA.(ABSTRACT TRUNCATED AT 250 WORDS)


How to prepare for your foreign fellow.

How to prepare for your foreign fellow. Visiting fellows on a 1-year sabbatical can take months to settle in and organize their personal lives. Some forward planning, a general information pack containing useful addresses and an introduction to relevant people can speed their integration.


Clinical manifestations and anti-(U1)snRNP antibodies: a prospective study of 29 anti-RNP antibody positive patients. Twenty-nine anti-RNP positive patients were followed prospectively with a mean observation time of 65 months (29-120 months). The clinical course was correlated to the presence of IgM and IgG anti-(U1)snRNP antibodies as revealed by immunoblotting from sequentially obtained sera. There was a striking dissociation between the fluctuating course, with the appearance of new manifestations followed by remissions, and the stability of the anti-snRNP antibody specificities where an appearance or a disappearance of anti-snRNP specificities was a rare phenomenon. The main epitope recognized by the IgG antibodies was the 70 kDa protein and of the IgM antibodies the B/B' proteins. No shift from the IgM to the IgG isotype was observed. The presence of IgG anti-70 kDa and IgM anti-B/B' antibodies was highly associated with presence of arthralgias, Raynaud's phenomenon and arthritis. Further, an association was noted between the combined presence of IgG anti-70 kDa, anti-A and anti-C antibodies and IgM anti-B/B' and puffy hands, myositis, pulmonary fibrosis and sclerodactyly, i.e. all manifestations of mixed connective tissue disease (MCTD). On the contrary, serositis as often seen in SLE was correlated to the presence of IgG anti-B/B' antibodies. Thus the longitudinal analysis of the correlation between anti-snRNP antibody specificities and clinical manifestations support the concept of MCTD as a distinct entity.


Postmenopausal screening for osteopenia. Dual energy X-ray absorptiometry (DXA) measurements of bone mineral density (BMD) in the lumbar spine and femoral neck have been performed in 1000 consecutive women aged between 40 and 60 years referred for screening for osteopenia. A detailed history was taken from each woman that included relevant lifestyle parameters and known risk factors for osteoporosis. After exclusions, e.g. because of fractures, corticosteroid or prolonged HRT use, 627 women (mean age 53 years) were considered suitable for further analysis. The mean BMD in the lumbar spine (L1-L4) was 0.946 g/cm2 and in the femoral neck was 0.767 g/cm2. Significant correlations were found between BMD and years after the menopause and weight (range r = 0.20-0.24). However, these parameters are not reliable enough predictors of BMD to be of value in clinical practice. If osteopenia is to be the basis for initiating prophylactic measures against bone loss, then a threshold BMD must be chosen below which treatment will be advised. Since the correlation coefficient between spinal and femoral neck BMD measurements was only 0.64, assessment of any individual requires consideration of both sites. There is as yet no consensus as to the number of women who may require to be treated and we have provided BMD values that identify a range of population sizes (the lowest 20, 30, 40 and 50 percentiles). It should be noted that there was a 16% loss of BMD in the spine and 14% in the femoral neck during the first 5 years after the menopause.(ABSTRACT TRUNCATED AT 250 WORDS)


A longitudinal study of pulmonary function in patients with rheumatoid arthritis treated with gold and D-penicillamine. Sixty-two patients with classical or definite RA who were considered suitable for disease-modifying drug therapy were entered into a prospective longitudinal study to determine the long-term effects of commonly used drugs such as gold, D-penicillamine and azathioprine on pulmonary function. Each patient had an assessment of pulmonary function, including spirometry, static lung volumes and diffusion tests, before starting drug therapy and at 6-monthly intervals during treatment. In those patients where drug therapy was discontinued, pulmonary functions were performed at withdrawal and 1 year later. Forty-six per cent of the patients in the 'gold group' and 21% in the 'penicillamine group' had developed a restrictive defect after 2 years. There was a significant reduction in vital capacity and transfer factor for carbon monoxide (P < 0.001) in both groups. A significant improvement in pulmonary function was found in the gold-treated patients (P < 0.05) a year after treatment was discontinued. This study shows that a significant proportion of rheumatoid patients on second-line drugs such as gold and penicillamine develop chronic progressive pulmonary damage indistinguishable from fibrosing alveolitis or 'rheumatoid lung'. Its recognition is important as the condition is asymptomatic, slowly progressive and appears to be reversible on withdrawal of the drug therapy in the majority of the patients.


Idiopathic inflammatory myopathy: clinicopathological observations in the Indian population. The present study attempts to investigate the pathological basis of the two clinically different forms of idiopathic inflammatory myopathy (IIM) namely, polymyositis (PM) and dermatomyositis (DM). Clinicopathological analysis of 73 cases showed that muscle fibre necrosis and regeneration were more frequent in PM than in DM, the latter being significantly so (P < 0.05). On the other hand, vasculitis was more associated with DM while perifascicular atrophy of the muscle fibres was confined to it. Vasculitis was present in eight cases. Its incidence in patients with myositis with systemic connective tissue disease (4/9) was significantly more than in other PM and DM patients (P < 0.01). An equally significant higher frequency of perimysial inflammatory infiltrate was also seen in the former as compared to the latter. Interestingly, idiopathic DM affected men as often as women and juvenile IIM affected boys more frequently than girls. A female predilection was noted in the remaining groups of IIM. These observations indicate that there may be some basic immunopathogenetic differences between polymyositis and dermatomyositis as well as between idiopathic PM/DM and that associated with systemic connective tissue diseases. Though the number of patients studied is small, the absence of female predilection in idiopathic DM and juvenile IIM may be peculiar to the IIM in the tropics.


A study to compare the efficacy of two methods of skin preparation prior to joint injection. This paper compares two methods of skin preparation in terms of their effectiveness in rendering the skin sterile, ease of use, and their cost.


New treatments for cystic fibrosis.

New treatments for cystic fibrosis. The cornerstones of CF medical treatment remain optimised nutrition, antibiotics and chest physiotherapy. There are however a number of promising new approaches which may add considerably to these traditional treatments. The most fundamental prospective new treatment is gene therapy which is still a long way off but could, in theory, provide a virtual cure for the disease. Less visionary but potentially as important is drug therapy aimed at the basic defect in airway ion transport. Both of these approaches are best suited to patients with early or even pre-symptomatic disease. In contrast, a third group of new treatments may prove useful in patients with established lung damage; these include a variety of anti-inflammatory drugs and DNase. This chapter will discuss each of these new treatments as well as exploring the difficult issue of assessing new treatments in pre-symptomatic disease.


Screening for cystic fibrosis.

Screening for cystic fibrosis. Neonatal screening for cystic fibrosis (CF) reduces short-term morbidity but its long term effects remain to be demonstrated. The best available method is the assay of immunoreactive trypsin in dried blood spots, and specificity can be improved by adding direct or indirect genetic analysis. Pregnancies known to be at risk of CF can also be screened by molecular methods, and affected pregnancies terminated. The application of genetic testing to whole communities, to detect unknown heterozygotes, raises many questions which require consideration by society and the health professions. The development of effective treatment of the basic abnormality of cell function in CF would enhance the need for neonatal screening, and possibly reduce the requirement for abortion.


Cystic fibrosis: nutrition.

Cystic fibrosis: nutrition. There has been renewed interest in examining the multiple causes of undernutrition and growth failure in cystic fibrosis. It is now recognized that undernutrition is caused by unfavourable energy balance rather than an inherent component of the disease. Furthermore, there appears to be a direct association between the degree of undernutrition and the severity of pulmonary disease, which in turn affects overall prognosis. Energy imbalance may be caused by three main factors: increased energy loss because of nutrient maldigestion; reduced energy intake due to an improper diet and/or anorexia from respiratory disease, abdominal symptoms or clinical depression and increased energy expenditure with advanced lung disease. Most patients are capable of compensating for these factors; provided energy intake is sufficient, normal growth velocity and nutritional status is maintained. However, in a minority of older patients, when advanced lung disease supervenes, energy expenditure rises resulting in an energy deficit. Undernutrition, with loss of energy stores and lean tissue may in turn contribute to progressive deterioration of lung function. When this occurs, long-term invasive methods of nutritional support can restore energy balance.


Cystic fibrosis: gastrointestinal complications. An individual who has cystic fibrosis (CF) may suffer from gastrointestinal problems related to inadequately controlled intestinal absorption secondary to the pancreatic insufficiency. These include neonatal meconium ileus, distal intestinal obstruction syndrome (DIOS), constipation and acquired megacolon, rectal prolapse and rarely pancreatitis. If the intestinal malabsorption is well controlled with an effective pancreatic enzyme preparation, DIOS, constipation and rectal prolapse are infrequent. Persisting gastrointestinal symptoms should be investigated thoroughly to exclude other disorders not directly related to the cystic fibrosis; these include cows' milk intolerance, coeliac disease, giardiasis, Crohn's disease and intra-abdominal malignancy. Both appendicitis and intussusception may cause difficult diagnostic problems particularly in patients who may also have distal ileal obstruction syndrome.


Cystic fibrosis: bile secretion.

Cystic fibrosis: bile secretion. Bile is an isotonic aqueous solution of bile acids, cholesterol, phospholipids, bile pigments and inorganic electrolytes. It is secreted by the hepatocytes into the bile canaliculi and modified in the bile ductules or ducts. The three main processes identified in the generation of bile flow are: 1. Active transport of bile acids from blood into bile canaliculi. This is responsible of the bile acid-dependent canalicular bile flow. Coupling between water flow and bile acid secretion is probably effected mainly through an osmotic mechanism. There is evidence that water flows (at least in part) through the interhepatocytic junctions. The bile acid-dependent flow accounts for 30 to 60% of spontaneous basal bile flow. 2. A canalicular, bile acid-independent secretion, probably due to transport into bile of organic solutes (glutathione) and inorganic electrolytes. This fraction of bile flow is stimulated by phenobarbital. It represents 30 to 60% of basal bile flow. Normal canalicular bile flow also depends on the integrity of intracellular cytoskeletal organelles, mostly microfilaments. 3. Reabsorption and secretion of fluid and inorganic electrolytes by the ductules and ducts. Secretion chiefly occurs in response to secretin and represents 30% of basal bile flow. Although several ion transport systems have been identified on the biliary epithelial cells (in particular a Na+/H+ exchange, a Na+:HCO3- symport and a CI-/HCO3- exchange), the cellular mechanism of secretion is not known. Abnormalities of bile duct function may account for the liver disease of cystic fibrosis, but these abnormalities have not been characterized.


Liver and biliary problems in cystic fibrosis. There have been striking advances in the management of complications of cirrhosis in the 50 years since biliary cirrhosis was recognised as a feature occurring in a minority of patients with cystic fibrosis. Many questions remain unanswered with regard to its pathogenesis, its effect on other systems, morbidity and mortality and to its optimum management. Factors which may initiate liver disease and/or cause progressive biliary fibrosis leading to biliary cirrhosis in some cystic fibrosis patients are being defined but much is still poorly understood and further research is required. Clinical and pathological studies confirm that cirrhosis is frequently asymptomatic and only slowly progressive, with the prevalence rising with age. In a recent large epidemiological study, however, it was found that the age related prevalence fell in patients over the age of 20 years although deaths from liver disease were rare. Does the presence of liver disease cause premature respiratory death in teenagers? Current treatments control variceal bleeding, the important sequel for most patients with biliary cirrhosis, with less morbidity and mortality than in the past but require reappraisal as newer techniques become available. Endoscopic radiologically controlled methods are emerging as an important adjunct to the surgical control of biliary complications which cause symptoms in up to 4%. Ursodeoxycholic acid improves liver function tests but its effect on hepatic fibrosis and portal hypertension will only be demonstrated by large scale prospective controlled trials. Should liver transplantation have a larger role in management? In this chapter we have attempted to summarise the current state of knowledge and to assess the efficacy of present management.


Immunology of cystic fibrosis.

Immunology of cystic fibrosis. The combination of all the immunological abnormalities described in CF appear to have a final common pathway through effects on neutrophils. Potent neutrophil chemotactic factors are produced as a result of antibody-antigen interactions leading to complement activation and the generation of C5a and the many cytokines released as a result of cellular immune responses leading to neutrophil influx and activation. In addition, the product of bacterial metabolism fMLP also produces neutrophil chemotaxis. The activated neutrophils release a range of proteases and oxygen radicals which directly damage tissues. It can, therefore, be hypothesised that the excessive immune response is directly contributing to the tissue damage. Indeed, it is even possible that this is the principal cause of the lung function defect without invoking any direct influence of the infecting organisms. This, of course, has major implications for approaches to therapy. Currently the main focus is on suppression of the organisms. However, modulation of the immune response is an attractive alternative approach.


Lung transplantation for cystic fibrosis. Significant progress has been made since the first successful human heart-lung transplantation (HLT) for pulmonary vascular disease performed in 1981. The refinement of surgical techniques, use of cyclosporin as the main immunosuppressant, technique of distant organ procurement to expand the donor organ pool, and improved diagnosis and management of pulmonary infection and rejection have all contributed to this accomplishment. This has inevitably coincided with the extension of this procedure to other groups of patients with end stage heart and lung disease. Initially, HLT was offered to patients with cardiac disease associated with pulmonary hypertension. Because of the success, consideration was given to transplantation for parenchymal pulmonary diseases, initially pulmonary fibrosis and emphysema, and then suppurative lung disease such as in cystic fibrosis (CF). However, the application of HLT to patients with CF lagged behind because of concern related to the risk of sepsis, the systemic nature of the disease, malnourishment, and fear of recurrence of the epithelial CF defect in the transplanted lungs.


Reduction of glutamate release and protection against ischemic brain damage by BW 1003C87. BW 1003C87, 5-(2,3,5-trichlorophenyl)-2,4-diaminopyrimidine ethane sulphonic acid, has been tested for its in vitro and in vivo effects on glutamate release in rat brain tissue, and for its cerebro-protective action in two rodent models of cerebral ischemia. In rat brain slices the release of glutamate evoked by veratrine is inhibited by BW 1003C87 (IC50 = 1.6 microM). In anaesthetised rats with microdialysis probes implanted in the dorsal hippocampus the increase in extracellular glutamate evoked by veratrine is markedly reduced by co-infusion of BW 1003C87, 100 microM. In anaesthetised rats with microdialysis probes implanted in the cortex and the caudate nucleus ipsilateral to a middle cerebral artery (MCA) occlusion the increase in dialysate glutamate concentration seen in the first 2 h following MCA occlusion is markedly attenuated by the prior administration of BW 1003C87, 20 mg/kg i.v. In rats subjected to 10 min of bilateral common carotid artery occlusion the loss of CA1 pyramidal neurons (assessed 7 days later) is reduced by administration of BW 1003C87 (20 mg/kg i.v., at the time of ischemia and 4 h later). The volume of cortex showing infarction 72 h after unilateral MCA occlusion is reduced by treatment with BW 1003C87 (20 mg/kg, i.v., beginning 5 min after occlusion). Inhibition of glutamate release may provide a therapeutic approach in cerebral ischemia as well as in epilepsy.


Neurons in the hypothalamic paraventricular nucleus mediate the serotonergic stimulation of renin secretion. The aim of the present study was to resolve which hypothalamic nucleus is necessary for the serotonergic control of renin secretion. RU 24969 is considered a serotonin (5-HT1A/5-HT1B) agonist, while p-chloroamphetamine is a 5-HT releaser. Both drugs reliably elevate plasma levels of renin when injected peripherally. Previous studies suggest that serotonergic neurons, projecting to the hypothalamus, mediate the effect of p-chloroamphetamine on renin secretion. Discrete cell-selective lesions were made with ibotenic acid in three hypothalamic sites: the paraventricular, the dorsomedial or the ventromedial nuclei. Two weeks after surgery rats were injected with RU 24969 (5 mg/kg, i.p.) or p-chloroamphetamine (8 mg/kg, i.p.). The renin response to both RU 24969 and p-chloroamphetamine was significantly reduced in rats with histologically verified paraventricular lesions compared to vehicle treated controls. In contrast, the renin response to p-chloroamphetamine remained unchanged in rats with either dorsomedial or ventromedial hypothalamic lesions. Thus, these results are consistent with the hypothesis that 5-HT receptors located on cell bodies in the paraventricular nucleus mediate the renin response to a serotonin agonist and releaser. Furthermore, they confirm previous studies that suggest that 5-HT neurons regulate renin secretion through central receptors.


Potentiation of cyanide neurotoxicity by blockade of ATP-sensitive potassium channels. Exposure of primary hippocampal cultures to NaCN (2 mM) or glyburide (5 microM) alone for 3 h did not produce a rise in extracellular lactic dehydrogenase (LDH) activity. Coincubation with NaCN and glyburide produced a significant efflux of LDH from the neurons. Diazoxide or D-2-amino-5-phosphovalerate (APV) partially reversed the release of LDH by the combination of NaCN and glyburide. These observations indicate ATP-sensitive potassium channels (KATP) are activated by nonlethal concentrations of cyanide and their blockade with glyburide unmasks cyanide's toxicity. The cytotoxicity of cyanide appears to result from a combination of processes resulting in altered ion handling and excitotoxicity.


Accumulation of amyloid precursor protein in damaged neuronal processes and microglia following intracerebral administration of aluminum salts. Alzheimer's disease is characterized by neurofibrillary tangles and amyloid deposits, with the latter probably occurring because of abnormal accumulation and/or processing of amyloid precursor protein (APP). Aluminum salts are known to be neurotoxic and to be capable of inducing neurofibrillary tangles. We explored the effects of intraventricular or intrastriatal injections of AlCl3 on the immunodistribution of APP in rat brain. There was a striking and long-lasting accumulation of APP in affected neurites, as well as in activated microglia/macrophages. Abnormal neurites also showed argentophilic changes, neurofilament accumulation, and Alz50 immunoreactivity. However, no extracellular amyloid fibrils were seen. The results, taken together with previous studies on colchicine, are consistent with the hypothesis that interruption of axoplasmic flow can lead to both APP accumulation and cytoskeletal changes.


Ketamine blocks the induction of LTP at the lateral entorhinal cortex-dentate gyrus synapses. In many regions NMDA receptor activation is required for the synaptic induction of long-term potentiation (LTP). This role for NMDA receptors is controversial at the synapses formed between the cells of the lateral entorhinal cortex (LEC) and the dentate gyrus (DG). Using anesthetized rats, the present study shows that ketamine reversibly blocks the induction of LTP at the LEC-DG synapses, thus favoring a role for NMDA receptors in the induction of LTP there. Ketamine also reversibly blocks the induction of the small translaminar depression of the medial EC response or of the LEC response by conditioning the other system while the test system is inactive.


Amyloid precursor protein accumulates in regions of neurodegeneration following focal cerebral ischemia in the rat. The distribution of beta-amyloid precursor protein (APP) was examined immunocytochemically in rats subjected to focal cerebral ischemia by permanent occlusion of the middle cerebral artery. At 4 and 7 days post-occlusion, APP immunoreactivity was preferentially localized within axonal swellings, dystrophic neurites and neuronal perikarya all along the periphery of the infarct. Immunolabeling was observed with antibodies generated against N-terminal, midregion, and C-terminal domains of APP. No immunoreactivity was observed with antisera directed against beta-amyloid protein (beta A4) itself. This pathological accumulation of APP is consistent with alterations of APP recently described in other models of neurodegeneration and implies a role for this protein in the response to CNS injury.


Hypotension preferentially induces c-fos immunoreactivity in supraoptic vasopressin neurons. Immunoreactivity to Fos protein (Fos-IR) was detected in rat hypothalamic neurons within 1 h of onset of hemorrhage by withdrawing 4-5 ml of blood, which lowered the arterial blood pressure to 50-70 mm Hg. About 70% of vasopressin (AVP)-containing neurons in the supraoptic nucleus (SON) and 20% in the paraventricular nucleus (PVN) expressed Fos-IR. In contrast, 5% of oxytocin (OXY)-containing neurons in the SON and < 1% in PVN were Fos-IR. Intravenous infusion of the vasodilating agent, nitroprusside, which lowered the blood pressure to levels comparable to that attained by hemorrhage, induced Fos-IR in greater than 65% of AVP-containing neurons in the SON, while relatively few AVP neurons in the PVN were Fos positive. These results suggest that hemorrhage or hypotension preferentially induces c-fos expression in supraoptic AVP-containing neurons.


Age-related changes of motor evoked potentials in healthy humans: non-invasive evaluation of central and peripheral motor tracts excitability and conductivity. A comparative analysis of the corticospinal tract nervous propagation and excitability threshold was carried out in young (25 subjects, age range 16-35 years) and in elderly (40 subjects, 51-86 years) populations of healthy volunteers. Motor evoked potentials (MEPs) were recorded from the hand and foot muscles following transcranial magnetic stimulation (TCS) during complete relaxation and active contraction of the target muscles. Threshold intensities corresponded to the stimulator's output eliciting liminal MEPs in about 50% of stimuli during relaxation. It was found that threshold values of magnetic TCS were significantly higher in the elderly (44 +/- 6.4% vs 39 +/- 3.5% for the hand; 66 +/- 10.1% vs 56 +/- 6.7% for the foot; P < 0.001) than in the young subjects. Moreover, this index progressively increased with age (P < 0.001), whilst the propagation time along the central motor tracts did not parallel such an age-related trend.


Stimulation of cholecystokinin (CCK) release from superfused rat hypothalamo-neurohypophyseal complexes by interleukin-1 (IL-1). This in vitro study examined the effects of interleukin-1 (IL-1) and interferon-gamma (Ifn-gamma) on the release of cholecysto-kinin (CCK) from superfused hypothalamo-neurohypophyseal complexes (HNC) of rats. An increase of CCK from HNC was elicited in a dose-dependent manner by recombinant human IL-1 alpha and -1 beta in concentrations of 0.1-10 nM. In contrast, the release of CCK from HNC was not affected by recombinant human Ifn-gamma at any dose tested (0.1, 1 and 10 nM). The increased release of CCK elicited by IL-1 was calcium-dependent, as was that induced by potassium (60 mM), but it was biphasic and had a different time course and a lower magnitude than those induced by potassium and veratridine. These results suggest that IL-1 activates pituitary-adrenal axis by stimulating CCK neurons in the hypothalamus and/or neurohypophysis to release CCK, since CCK has been implicated in the regulation of adrenocorticotropin release.