Calcium homeostasis, bone metabolism and safety aspects during long-term treatment with a GnRH agonist. Thirty-five women with symptomatic fibroids were treated with monthly injections of 3.2 mg microcapsulated D-Trp-6-LHRH for 6 months. During treatment serum 17 beta-oestradiol levels decreased, falling to castration levels associated with a reduction in the volume of the fibroids. In 16 patients a complete calcium homeostasis and bone metabolism work-up was carried out during treatment and subsequently for a 6-month follow-up period. Bone mineral content (BMC) and Compton bone densitometry readings remained unchanged. There were significant increases in serum calcium phosphate and alkaline phosphatase concentrations. A slight although not significant increase was observed in osteocalcin and parathyroid hormone (PTH) serum levels. Serum 1,25(OH)2D3 values decreased significantly after 3 months of treatment. Urinary hydroxyproline/creatinine and calcium/creatinine ratios as well as 24-h urinary calcium values increased significantly during the treatment period but decreased rapidly to pretreatment values after 3 months in the follow-up period. The endocrine changes induced by the GnRH-agonist treatment were associated with reversible biochemical signs of increased bone turnover and no significant changes in bone mass, suggesting that the treatment can be administered safely for a period of 6 months in patients with oestrogen-dependent diseases.


Secretory endometrial protein PP14 in serum from post-menopausal women receiving continuous combined oestradiol-cyproterone acetate: correlation with serum hormone concentrations and bleeding patterns. The secretory endometrial protein PP14 was measured in serum from 49 healthy, early post-menopausal women receiving continuous combined oestradiol valerate/cyproterone acetate (2 mg E2V + 1 mg CPA daily) or placebo over a period of 2 years. In the hormone group, serum PP14 increased from 2.1 micrograms/l to a maximum of 8.1 micrograms/l after 1 month of treatment, then fell after 3 months to 3.8 micrograms/l and remained at that level for the rest of the 2-year period. After the first month, the occurrence of uterine bleeding was associated with significantly increased serum PP14 levels. Bleeding was not correlated with the serum concentration of 17 beta-oestradiol (E2) or CPA, or the CPA/E2 ratio. Serum PP14 was significantly dependent on the serum concentration of E2, but not on that of CPA. The present data confirm that serum PP14 levels reflect the secretory phase of the endometrium and that bleeding during continuous combined hormone replacement therapy is probably caused by a sub-optimal hormonal balance.


Polymeric hydrogel compounds and their application in restorative surgery in cases of portal hypertension. This paper deals with aspects of developing the biologically-compatible polymeric material for filling cavities or deposition of the physiologically-active preparations. Determined is the possibility of using the composite material in one of the complex fields of restorative surgery, i.e. the syndrome of portal hypertension.


Biomechanical substantiation of design features and physicomechanical characteristics of pins made of biocompatible polymers for intraosseous osteosynthesis. This paper suggests a biomechanical model for osteosynthesis of tubular bones with the use of pins made of biocompatible polymers for the substantiation of the basic physicomechanical requirements to jointing elements (pins) with regard to functional loads, design features of pins and physicochemical properties of the materials used. It is shown that the known polymers including the biocompatible ones, do not individually possess the necessary strength characteristics for the production of jointing elements for highly loaded tubular bones. The properties of pins, made of biocompatible polymers, can be increased by optimizing their shapes and modifying the materials.


New equipment for stereophlebography.

New equipment for stereophlebography. Discussed in the present article is the complex of the equipment intended for roentgenodiagnosis of the lower limb varicosity and for use in planning the operations on the vessels. The complex includes the automatic stereocassette, constructed as an attachment to the standard roentgenodiagnostic apparatus, and the stereoscope for analyzing the stereophlebograms visually. The article provides a description of this equipment and methods of its employment.


Medical laser mass spectrometric standardless microanalysis. This paper deals with application of the laser mass spectrometry method for the standardless elementary analysis of the medical and biological samples. Reviewed is process of the laser emission interaction with the target substance and ion formation. Illustrated is the radical possibility of using laser ionization for standardless analysis. The primary criterion of such a possibility is the laser emission power density. The obtained results were used for the non-standard analysis of the medical and biological samples on the EMAL-2 device series-produced in the USSR. The mass spectra of the liver tissue and whole blood without preliminary preparation (liberation from the organic part) are presented. The issues of using this method as regards the sanitary and hygienic, toxicological and diagnostic tasks associated with the change in the microelementary composition of the tissues and biological fluids are substantiated.


Pulse wave sensors with improved noise immunity. Reviewed in this article are the principle of operation and design features of the pulse wave sensors realizing the method of space-oriented differentiation for the noninvasive arterial pressure meters which can measure pressure during the physical tests of a patient. Disclosed are the test results and procedure for checking the pulse wave sensors using the nonstandard means of measurement.


Toxicological aspects of preclinical studies of hemosorbents. The main tendencies in the development of methods for hemo- and lymphosorption are considered. Base toxicological requirements to sorbents have been formulated. Special attention is paid to possible tox effects of sorbents containing carcinogenic admixtures. The importance of choosing appropriate methods sorbents' sterilization or conservation has been emphasized. Results of studies of various sorbents a presented.


Toxicological estimate of polyvinyl chloride containers for preparation and storage of blood, its components, preservatives and infusion solutions. Migration of dioctyl phthalate from the polyvinyl chloride containers (PVC-containers) into blood, its components, preservatives and infusion solutions was studied for the purpose of estimating toxicity of the articles. Dependence of the plasticizer cumulation on the composition of the media found in the containers was discovered. The effect of the storage conditions on the toxicological and hygienic characteristics of the containers and intact condition of the bioproducts housed therein was investigated. Compliance of the polyvinyl chloride containers with the requirements of international standards for estimating toxicity of the polymeric materials and articles of medical purpose was established.


Ultrasonic immersion echomammography: state of the art and prospects. This article discusses the state of the art and the prospects of evolution of ultrasonic immersion mammographs. It is shown that ultrasonic immersion mammography for diagnostics of surface organs has a preference over existing ultrasonic scanning devices of contact type. An immersion mammograph has been developed, a characteristic of which is the use of compact ring multielement antenna with the electronic dynamic focusing block.


Characteristics of MR-tomographers' image and their monitoring. Similar to X-ray computer tomography and taking into account the specificity of obtaining the MR image a range of characteristics is proposed for the control of the MR tomographers' images. On the basis of the literature analysis and our own research requirements are formulated to the range and the errors of the MR image characteristics guaranteeing the required diagnostics reliability level. Proceeding from the requirements to the MR image characteristics the requirements are formulated to test objects for their monitoring, including the MR-contrast media for test objects. The test objects' structures are described, developed in accordance with the formulated requirements.


New medical-purpose absorbent materials based on polyacrylic acid and alpha-cyanoacrylates, their structure and properties. Hydrophylic porous polymers (HPP) obtained by polymerization of the alpha-cyanoacrylates under contact with solution of the polymeric carboxylic acids has the degree of water absorption up to 50.000 percent. Disclosed are the data on the HPP porosity investigation, water absorptions HPP are not toxic, do not exhibit allergenic and irritative actions, admit introduction of the medicine into HPP. The HPP films and sheets were used in the course of the experiment for treatment of purulent wounds. Their high effectiveness expressed in reduction of the adhesion time by 1.5 to 2 times was established.


Cryoultrasonic and cryogenic equipment for medicine. The problem of cryodestruction control in a biological object may be characterized by various decisions. This paper deals with technical solutions based on the use of cryogenic and cryoultrasonic equipment with different technological functions to provide, with an appropriate probability, the required and controlled tissue destruction.


Luminescent screens for general X-ray diagnostics. This article gives the main parameters of amplifying screens manufactured in the USSR: the sensitivity, the resolution, the modulation depth, the noise. The technical level of Soviet screens is compared with the level of those manufactured by certain foreign companies. The measures taken to increase the technical level of today's products and the further evolution directions are discussed. Data are given on screen production in the USSR during the last 5 years and their supposed production up to 2000.


Biosoluble polymeric medicinal films.

Biosoluble polymeric medicinal films. This paper offers a brief review of the issues related to selection of the polymeric matrix base that determines the possibilities of forming medicinal film. Estimated is its efficiency as compared to other polymeric carriers. Also discussed are examples of using medicinal films in certain fields of medicine.


Testing of dielectric properties of biological tissues in microwave range for solving matching problems. Since the employment of microwave energy for defrosting biological tissues and for microwave-aided diagnosis in cryosurgery is very promising, the problem of ensuring the match between the contact antennas (applicators) and the frozen biological object has become a pressing one. It is for this reason that investigations were aimed at the study of the dielectric properties of the dog's muscular and fatty tissues in a temperature range of +20 to -30 degrees C including the phase transition of the samples to the solid state. The investigations were performed in a waveguide device using a short-circuit method. During the investigation possible error was estimated. The experiment provides for the reduction of the error caused by the waveguide linear expansion.


Medical-purpose elastic materials based on siloxane rubbers and items made from them. Vulcanization of the unsaturated siloxane rubbers with silicon hydrides of various structure (organohydrosiloxanes, organohydrosilazanes, organohydrosilanes) was investigated for the purpose of creating biologically-compatible materials with a high complex of medical and engineering properties. The effect of the silicon hydride structure on the vulcanization process and properties of the produced rubbers was identified. The basis sanitary and hygienic indices of rubbers were studied. A wide range of medical-purpose items was manufactured using the developed compounds.


T and B cell responses to chimeric proteins containing heterologous T helper epitopes inserted at different positions. The ability of a T helper (Th) epitope to induce help for B cells recognizing different determinants within a multideterminant antigen was investigated. Chimeric fusion proteins, containing inserts of single or multiple copies of the Th epitope ovalbumin 323-339 (ova) at two different positions, were compared with respect to their ability to induce specific antibody production and ova-specific T cell activation. The antibody responses against B cell determinants at the amino and carboxy terminus, respectively was differently influenced by the molecular positioning of the inserted Th determinant. All ova-containing fusion proteins induced antibody production against the B cell determinant at the amino terminal end irrespective of the positioning of ova. In addition, multiple copies of ova in any position led to increased levels of antibody production against this epitope. In contrast, T cell help for antibody production against the determinant at the carboxy terminus was more effective after insertion of multiple copies of ova in a distal than in an adjacent position. Furthermore a fusion protein, containing four copies of ova effectively elicited T cell help for high levels of antibody production against both examined B cell determinants, showing that activated Th cells recognizing a single epitope could simultaneously provide help for distinct sets of B cells specific for widely separated epitopes within a protein. Immunodominant T cell recognition of ova in all chimeric peptides, independently of its position, was demonstrated by lymph node cell (LNC) proliferation of primed BALB/c mice. The level of ova-specific T cell proliferation was similar, irrespective of which chimeric peptide that had been used for priming, and thus did not reveal any differences in T cell priming efficiencies related to the number of ova copies in the fusion proteins. However, when the peptides were presented to a ova-specific T cell line by A20 B lymphoma cells, a close correlation between IL-2 production by the clonal T cells and the number of ova epitopes in the chimeric peptides was observed. Thus, increased cytokine production by ova-specific T cells may be important for the increased level of in vivo antibody production observed in response to multiple copies of ova in the chimeric antigens.


RHP is antigenically related to factor H and binds to the globular heads of C1q. RHP was purified from normal serum by sequential euglobin precipitation, ion exchange chromatography on DEAE-Sephacel and gel filtration using Sephacryl S-300. RHP reacted with anti-Factor H antibodies in ELISA assays and in Western blots, suggesting that it is antigenically related to Factor H. It bound to intact C1q but not to the collagen-like N-terminal half of the molecule. C1q-specific monoclonal antibody BUS-1, which blocks the binding of C1q to immune complexes, did not block the binding of RHP to C1q. This implies that the binding sites on C1q for IgG and RHP do not overlap.


Cell-to-cell spread of calcium signals mediated by ATP receptors in mast cells. Rat basophilic leukaemia cells, like mast cells from which they are derived, have surface Fc epsilon receptors that trigger secretion of inflammatory mediators when crosslinked. Both GTP-binding proteins and a rise in cytosolic calcium concentration ([Ca2+]i) are implicated in the secretory mechanism. Here we use a video-imaging technique to report that transient rises in [Ca2+]i initiated in an individual cell can spread from cell to cell in a wave-like pattern by means of a secreted intermediate, in the absence of gap-junctional communication. We find that the leukaemia cells, peritoneal mast cells and mucosal mast cells have cell-surface P2-type purinergic receptors that can trigger similar [Ca2+]i transients. We provide evidence that ATP is rapidly released, and that it can amplify [Ca2+]i signals and initial secretory responses during antigen-stimulation of rat basophilic leukaemia cells.


Inhibition of histamine turnover by 8-OH-DPAT, buspirone and 5-hydroxytryptophan in the mouse and rat brain. The effects of 5-hydroxytryptamine (5-HT) receptor agonists on histamine turnover in mouse and rat brains were examined. The histamine turnover rate was estimated from the accumulation of tele-methylhistamine 90 min after i.p. injection of pargyline (65 mg/kg). In whole mouse brains, the histamine turnover was significantly inhibited by the 5-HT1A agonists, 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) (greater than 0.5 mg/kg) and buspirone (greater than 2 mg/kg) injected s.c. 10 min before pargyline treatment. 5-hydroxytryptophan (20 mg/kg) also significantly inhibited histamine turnover. Injections of the 5-HT1B agonist m-trifluoromethylphenylpiperazine (10 and 20 mg/kg) or the 5-HT2 agonist (1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (1, 2 and 5 mg/kg), however, did not affect histamine turnover. The inhibitory effect of 8-OH-DPAT (1 mg/kg) on histamine turnover was significantly antagonized (by 40%) by pindolol (20 mg/kg) and slightly antagonized (by 29%) by spiperone (10 mg/kg), while methysergide (20 mg/kg) and ketanserin (10 mg/kg) demonstrated no antagonistic effects. 8-OH-DPAT (0.3 and 1 mg/kg) also showed an inhibiting effect on histamine turnover in various regions of rat brains. Although the extent of inhibition was slightly larger in the striatum and cerebral cortex, there was no marked regional difference. These results suggest that histaminergic activity in the brain is regulated by 5-HT1A receptors.


Endocrine status in stage II vs. advanced premenopausal and postmenopausal breast cancer patients. Circulating preoperative levels of DHEA-S, androstenedione and SHBG were measured in 40 premenopausal and 49 postmenopausal breast cancer patients, and in 30 and 15 age-matched healthy controls, respectively. Moreover, the levels of LH, FSH, prolactin, estradiol, progesterone, testosterone, DHEA-S, androstenedione and SHBG of Stage II breast cancer patients were compared with advanced patients and also with controls. In premenopausal patients the levels of steroid hormones were significantly low whereas those of peptide hormones were significantly high. On the contrary, in postmenopausal patients, except DHEA-S, all other hormones were significantly elevated in comparison with controls. In premenopausal patients, DHEA-S, androstenedione, estradiol, progesterone, and testosterone decreased as stage advanced with concomitant increase of SHBG, LH, FSH and prolactin when compared with hormone levels of Stage II patients. In postmenopausal advanced breast cancer patients, when compared with Stage II patients, the levels of SHBG, LH, FSH, and prolactin increased significantly, while DHEA-S, androstenedione, estradiol, and progesterone decreased as stage advanced.


Influence of long-term amelioration of anemia and blood pressure control on left ventricular hypertrophy in hemodialyzed patients. The course of left ventricular hypertrophy was investigated in anemic hemodialysis patients treated with recombinant human erythropoietin (r-huEPO). 12 patients, aged 60.8 +/- 9.9 years (mean +/- SD) were treated for 18.8 +/- 2.7 months. Left ventricular size was estimated by echocardiography performed before treatment and at least 12 months after relieving anemia. Patients had signs of left ventricular and/or asymmetric septal hypertrophy when compared with a nonanemic and normotensive control group matched for sex and age. At baseline, hemoglobin (Hb) was 8.6 +/- 0.7 g/dl; interventricular septum thickness (IVST) was 1.75 +/- 0.34 cm, left ventricular posterior wall thickness (LVPWT) 1.32 +/- 0.19 cm, left ventricular muscle mass index (LVMI) 222.7 +/- 41 g/m2 and blood pressure (BP) 146.4 +/- 10/81.6 +/- 6 mm Hg. Hb rose to 11.4 +/- 1.2 g/dl (p less than 0.001); IVST and LVMI decreased to 1.42 +/- 0.35 cm (p less than 0.02) and 155.4 +/- 25.1 g/m2 (p less than 0.001); LVPWT and BP remained unchanged (1.30 +/- 0.26 cm and 146.8 +/- 16.9/81.2 +/- 7.8 mm Hg) at the end of the study. During the observation period, two groups of 5 and 7 patients differed from each other. The group of 5 patients had higher BP values (158.9 +/- 9.8/86.5 +/- 5.3 vs. 140.0 +/- 9.5/79.2 +/- 6.8 mm Hg, p less than 0.01), and the period with Hb values above 10 g/dl was shorter (14.5 +/- 2.4 vs. 17.8 +/- 2.4 months, p less than 0.05). These 5 patients failed to show a significant decrease in IVST and LVMI.(ABSTRACT TRUNCATED AT 250 WORDS)


Response suppression induced with selective 5-HT agonists can be differentially blocked with LY53857 in an animal model of depression. Studies from this laboratory have demonstrated that administration of the selective 5-HT2/1C antagonist LY53857 can block 5-HTP-induced response suppression. To further investigate the serotonergic mechanisms involved in this effect, we decided to test the capacity of LY53857 to block response suppression induced with two selective 5-HT agonists. After a 15 minute baseline period, rats trained to press a lever for milk reinforcement on a VI 1' schedule were given IP injections of 1.0 mg/kg DOI, or 1.0 mg/kg 8-OH-DPAT to induce response suppression. Subsequently, rats were injected with 1.0 mg/kg LY53857 1 hour prior to DOI- or 8-OH-DPAT-induced response suppression. Preinjections with LY53857 resulted in a 100% blockade of DOI-induced response suppression whereas the same dose did not block response suppression induced with 8-OH-DPAT. These results indicate that the 5-HTP-induced response suppression shows some pharmacological similarity to DOI-induced response suppression and may be mediated through 5-HT2 and/or 5-HT1C receptors.


The effects of rubidium, caesium and quinine on 5-HT-mediated behaviour in rat and mouse--3. Quinine. It has been shown that caesium, which shares properties with quinine as a K(+)-channel blocker, enhanced 5-HT-mediated behaviour in both rats and mice. It was therefore of interest to investigate the effects of quinine on 5-HT-mediated behaviour in the rat and mouse. Quinine, dose-dependently (ED50 = 5 mg/kg), produced the 5-HT behavioural syndrome in rats pre-treated with tranylcypromine (TCP) (15 mg/kg, i.p.). p-Chlorophenylalanine (i.p., 300 mg/kg x2) or (-)-propranolol (20 mg/kg, i.p.), pindolol (4 mg/kg, i.p.) and ritanserin (0.4 mg/kg, s.c.), all prevented the behavioural syndrome induced by quinine (72 mg/kg, i.p.) plus TCP. The administration of quinine (72 mg/kg, i.p.) enhanced the 5-HT syndrome elicited by p-chloramphetamine (4 mg/kg, i.p.) and the 5-HT agonists, 8-OH-DPAT (0.5 mg/kg, s.c.), 5-MeODMT (2 mg/kg, i.p.), DOI (8 mg/kg, s.c.) and quipazine (25 mg/kg, i.p.) in rats. Pretreatment with quinine also potentiated the 5-HT2-mediated head-twitch in the mouse but had no effect on the hypothermia in the mouse, induced by 8-OH-DPAT (0.5 mg/kg, s.c.). Quinine also enhanced the rate of synthesis of 5-HT in the brain of the rat. On the basis of these findings, together with those in the preceding two papers, it is suggested that the effects of rubidium, caesium and quinine, to enhance differentially various aspects of 5-HT function are mediated by actions on 5-HT-modulated K(+)-channels. This conclusion is also discussed in relation to the actions of lithium and electroconvulsive shock on 5-HT function in brain and the treatment of manic-depressive disease.


The effects of corticosterone on 5-HT receptor function in rodents. In the mouse, administration of corticosterone-21-acetate (30 mg/kg, s.c. daily) for 3 and 10 days produced an attenuation of the hypothermic response to the 5-HT1A receptor agonist 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT), which was not present after administration for 1 day. A similar effect was observed in the rat after administration of corticosterone-21-acetate (30 mg/kg, s.c. daily) for 10 days. Mice which had been given corticosterone for 10 days displayed the serotonin syndrome when injected with 5-hydroxytryptophan (5-HTP, 100 mg/kg, s.c.), 15 min after injection of carbidopa (25 mg/kg, i.p.). This was not seen in control animals. The serotonin syndrome was also induced in mice using 8-OH-DPAT; this increased in a dose-dependent manner and could be significantly decreased by pre-treatment with 1-(2-methoxyphenyl)-4-(4-phthalimidobutyl)-piperazine (NAN-190 5 mg/kg, i.p., 30 min prior to administration of 8-OH-DPAT), a 5-HT1A receptor antagonist. Administration of corticosterone (30 mg/kg, s.c. daily) did not significantly alter the serotonin syndrome induced in treated mice, compared with controls. Mice pre-treated for 3 or 10 days with corticosterone did not differ from controls in the number of head-twitches induced by 5-HTP and carbidopa or 5-methoxy-N,N-dimethyltryptamine, nor did they differ from controls in their response to the putative 5-HT1B agonist 5-methoxy-3 (1,2,3,6-tetrahydropyridin-4-yl)1-H indole (RU 24969, 3 mg/kg, i.p.).(ABSTRACT TRUNCATED AT 250 WORDS)


A comparative study of the anatomical, radiological and therapeutic features of the lumbar facet joints. An anatomical study of the lumbar apophyseal joints was carried out to facilitate recognition of facet joint lesions, which we now examine routinely by percutaneous arthrography. Special attention was given to the configuration of the different compartments of the joint space and to its relationships with the contents of the intervertebral foramen. The abnormalities seen on lumbar facet joint arthrography are very varied; two major groups should be stressed: synovial fringe hypertrophy and pseudodiverticular synovial ectasia. The percutaneous approach to lumbar facet joint arthrography allows it to be used a therapeutic measure, with injection of anti-inflammatory drugs into the joint space, the beneficial effects of which were confirmed in our series. The precision, efficiency and cost-effectiveness of this outpatient technique justify and should encourage its more widespread application in the diagnosis and treatment of low back pain.


[Value of computerized tomography in the diagnosis of discopathy in the L4-L5-S1 segment]. The aim of this analysis was demonstration of the usefulness of CT in the diagnosis of lumbar discopathy. In 110 patients with backache, CT of the L4-L5-S1 part of the spine was done. The observed abnormalities were analysed, including presence of nucleus pulposus herniation, pathological changes of osseous structures of the spine, width of the vertebral canal and lateral recesses, and presence of other lesions there. Comparing the results of (CT) and myelography with intraoperative observations it was possible to confirm the high usefulness and value of CT in such cases. CT may be an important diagnostic method preoperatively in patients with iodine hypersensitivity and those with vertebral canal stenosis.


[Factors determining the results of surgical treatment of backache syndromes in the lumbar spine]. The therapeutic results were analysed in a group of 509 patients operated on for low back pain syndromes (after previous establishing of indications based on clinical examination and radiological investigations) with over 6 months of follow-up. The therapeutic results were compared with the observed symptoms and signs, neurological findings, age, duration of acute phase of the disease, surgical approach used, changes found during the operation, stability of the spine and type of its surgical immobilization. The therapeutic result depended mainly on the degree of neurological abnormalities before the operation, duration of the acute phase and operative findings as well as spinal stability. The operative approach and stabilization type, although influencing the result, were a consequence of the above factors.


Glucosyltransferase phase variation in Streptococcus gordonii modifies adhesion to saliva-coated hydroxyapatite surfaces in a sucrose-independent manner. Phase variation of Streptococcus gordonii between high (Spp+) and low (Spp-) levels of glucosyltransferase (GTF) activity resulted in the greater adhesion of Spp- strains to saliva-coated hydroxyapatite (S-HA) in a washed-cell adhesion test. Specific GTF mutants did not show this response. Although washed Spp+ cells produced 5-fold or more glucan from sucrose than Spp- cells did under the conditions of the adhesion test, sucrose elevated the adhesion of both phenotypes to hydroxyapatite (HA) equally, but had no effect on adhesion to S-HA. This effect was not sucrose-specific, however, because equimolar amounts of other carbohydrates and NaCl elevated adhesion of both Spp types to levels similar to those seen with sucrose. Adhesion did not correlate with relative changes in cell hydrophobicity. These results suggest that, in addition to changes in GTF activity, other changes relevant to adhesion may occur during Spp phase variation.


Acitretin (Neotigason). A review of pharmacokinetics and teratogenicity and hypothesis on metabolic pathways. Acitretin was introduced as a replacement for etretinate, the ethyl ester of acitretin. Acitretin is eliminated at a much faster rate than etretinate. Although both drugs are teratogens, the replacement was important especially as it allowed for a much shorter post-medication period in which pregnancy should be precluded. Recent findings showed the presence of etretinate in the plasma of acitretin-treated patients. This article gives a review of known metabolic pathways of the retinoids and tries to elucidate the possible conversion of acitretin into etretinate after acitretin ingestion.


Renal contraluminal transport systems for organic anions (paraaminohippurate, PAH) and organic cations (N1-methyl-nicotinamide, NMeN) do not see the degree of substrate ionization. Using the stop-flow peritubular capillary microperfusion method pH dependence of the interaction of different substrates with the contraluminal PAH- and NMeN transporter was investigated. Substrates for both transport systems with pKa values around 7.0 were chosen and the pH of the perfusates was varied between 6.0 and 8.0. The inhibitory potencies (app. Ki values) were determined and the influx into the proximal tubular cells was measured. The app. Ki(NMeN) values of imidazole (pKa 7.03), a substrate for the NMeN-transporter, the app. KiPAH values of the dipeptide tryptophyl-tryptophan (pKa 7.36), a substrate for the PAH-transporter, and the app. Ki,NMeN and Ki,PAH of cimetidine (pKa 6.98) and buspirone (pKa 7.2) which interact with both transport systems, did not vary between perfusate pH 6.0 and 8.0. The same holds for the influx of 3H-cimetidine into proximal tubular cells. The data indicate that both transporters have no preference for the ionized form of their substrates and that the name organic anion and organic cation transporter resides rather on history than on molecular interaction.


Viral hepatitis. Preexposure and postexposure prophylaxis. Rational strategies for preventing viral hepatitis are being developed as the epidemiology of the disease is becoming better defined. A vaccine is available only for hepatitis B. Other prophylactic strategies are based on avoidance of high-risk behavior and use of immune globulin. Universal vaccination for hepatitis B is now recommended.


[Organization of prophylactic mass screening for tuberculosis of the population in the south of the Aral sea cost region]. The results of mass prophylactic screening of the population for tuberculosis in the south of the Aral sea costal region have been generalized with consideration of its geographic and sanitary--epidemiologic conditions. A mixed model of comprehensive prophylactic screenings was used for the first time with integration, for the first time, of the traditional (team) and field-work methods. The obtained results proved the efficiency of this approach: during one year a total of 1,217,400 subjects or 80% of the relevant population were involved in the prophylactic screening for the first time in one region. As a result, the epidemiologic situation related to tuberculosis was revealed and a complex of the therapeutic and health-improvement measures accomplished. The proposed measures have been tested and made the basis of a section in a complex program "Health of the population of the Aral sea costal region up to the 2000th year" which is recently being introduced in other regions of the republic.


[Ecologic significance of M. avium infectiousness of waterside and aquatic birds]. A total of 777 specimens of the river-side and water birds of 36 species belonging to 8 orders were examined for infectivity by the causative agent of tuberculosis M. avium. Examination was carried out in the northern zone of the land along the lower Volga. Infectivity was studied by serologic and bacteriologic tests. Serologic examination showed that 104 out of the 399 birds were AIT-positive (26.0 +/- 2.195%), in bacteriologic examination 73 out of the 378 specimens were infected (19.57 +/- 2.040%). The infectivity parameters of birds determined by both methods had certain characteristic features typical of the examination territory. The character of distribution of the infected birds was determined according to the regions of the examination zone.


Independent deposition of heterogeneous nuclear ribonucleoproteins and small nuclear ribonucleoprotein particles at sites of transcription. The major nuclear ribonucleoproteins (RNPs) involved in pre-mRNA processing are classified in broad terms either as small nuclear RNPs (snRNPs), which are major participants in the splicing reaction, or heterogeneous nuclear RNPs (hnRNPs), which traditionally have been thought to function in general pre-mRNA packaging. We obtained antibodies that recognize these two classes of RNP in Drosophila melanogaster. Using a sequential immunostaining technique to compare directly the distribution of these RNPs on Drosophila polytene chromosomes, we found that the two patterns were very similar qualitatively but not quantitatively, arguing for the independent deposition of the two RNP types and supporting a role for hnRNP proteins, but not snRNPs, in general transcript packaging.


A factor from CD8 cells of human immunodeficiency virus-infected patients suppresses HLA self-restricted T helper cell responses. Defective in vitro T helper cell (Th) function can occur in asymptomatic human immunodeficiency virus (HIV)-seropositive (HIV+) individuals. A characteristic, early finding is the loss of an in vitro response to recall antigens, such as influenza A virus (FLU), despite an intact Th response to alloantigen (ALLO). To determine whether suppressor cells and/or inhibitory factors could contribute to this HIV-associated Th immunodeficiency, coculture studies were performed using peripheral blood leukocytes (PBLs) from monozygotic twins, one of whom was HIV-infected (HIV+) and one of whom was uninfected (HIV-seronegative, HIV-). In vitro Th function was measured as interleukin 2 production or proliferation to FLU and ALLO. Two pairs of twins were repetitively studied. A single HIV+ individual with multiple samples of cryopreserved PBLs over 6 years (including a HIV- specimen) was also studied. PBLs from the HIV+, but not from the HIV-, individuals demonstrated defective in vitro Th function in response to FLU but not to ALLO. PBLs from HIV+ individuals could induce a similar defect in the Th function of syngeneic or autologous HIV- PBLs. This suppression was generated by CD4-depleted, but not by CD8-depleted, PBLs. A suppressive factor from CD8+ cells of HIV+ donors was generated by 24-hr unstimulated cultures of HIV+ PBLs. This factor inhibited FLU but not ALLO responses of autologous, syngeneic, or allogeneic HIV- PBLs. This suppressive effect could not be explained by HIV infection or replication during the culture period. These results demonstrate that selective abrogation of Th function to recall antigens in HIV+ individuals is associated with an inhibitory factor produced by CD8+ T cells.


Alternative splicing generates functionally distinct N-methyl-D-aspartate receptors. We have used expression cloning in Xenopus oocytes to isolate two different cDNAs encoding functional N-methyl-D-aspartate (NMDA) receptor subunits. The two receptors (NMDA-R1A and -R1B) display different pharmacologic properties as a consequence of alternative exon addition within the putative ligand-binding domain. The splicing choice is regulated such that R1B is the predominant form of receptor in the cerebellum, whereas R1A predominates in other brain regions. Expression of either of the subunits alone in oocytes results in an NMDA-evoked inward current with electrophysiologic properties closely resembling those of the NMDA receptors observed in neurons. Thus, the complex properties exhibited by the NMDA receptor in neurons can be generated by the expression of a single receptor subunit.


Cloning and intracellular localization of the U2 small nuclear ribonucleoprotein auxiliary factor small subunit. U2 small nuclear ribonucleoprotein auxiliary factor (U2AF), an essential mammalian splicing factor, is composed of two subunits: a 65-kDa protein (U2AF65), which binds the pre-mRNA polypyrimidine tract and is required for in vitro splicing, and an associated 35-kDa protein (U2AF35). Here we report the isolation of a cDNA encoding U2AF35. U2AF35 contains sequence motifs found in several mammalian pre-mRNA splicing factors. We show directly that U2AF65 and U2AF35 interact with each other and delineate the regions of both proteins that mediate this interaction. Using anti-peptide antibodies against U2AF35, we show that the protein has the intracellular distribution characteristic of U2AF65. Both U2AF65 and U2AF35 are concentrated in a small number of nuclear foci corresponding to coiled bodies, subnuclear organelles first identified by light microscopy in 1903.


Differential response of maize catalases to abscisic acid: Vp1 transcriptional activator is not required for abscisic acid-regulated Cat1 expression. In this paper we describe the distinctive responses of the maize catalases to the plant growth regulator abscisic acid (ABA). We analyzed RNA and enzyme accumulation in excised maize embryos and found that each catalase responded differently to exogenously applied ABA. Levels of Cat1 transcript and enzyme activity rapidly increased. In contrast, levels of Cat2 transcript and protein decreased, while Cat3 transcript levels were not affected. In developing kernels of the ABA-deficient/biosynthetic viviparous mutant vp5, lower levels of Cat1 RNA correlated with lower endogenous ABA levels when compared to measured levels in comparably aged wild-type siblings from the same ear. The maize vp1 mutant line is morphologically insensitive to normal endogenous levels of ABA. Analysis of the response of Cat1 to exogenously applied ABA in mutant and wild-type vp1 sibling embryos suggests that, unlike other ABA-responsive genes analyzed to date, the Vp1 gene product is not essential for the ABA-mediated regulation of Cat1. The significance of these responses to ABA in defining the roles of the various CATs in maize is discussed.


Cardiorenal reflexes do not attenuate the renal effects of infused atriopeptin in conscious dogs. Low-dose infusions of atriopeptin produce only a modest diuresis and natriuresis. However, these infusions also decrease atrial pressures, a change that has been postulated to elicit an antidiuretic and antinatriuretic reflex from cardiac receptors and thereby to attenuate the direct renal effects of atriopeptin. To determine whether the renal effects of intravenously administered atriopeptin might be attenuated by a cardiorenal reflex, we infused alpha-human atrial natriuretic peptide (alpha-hANP) into cardiac-denervated and sham-operated (normal) conscious dogs. Following a control period, alpha-hANP was infused into each dog at 12.5, 25, or 50 ng.kg-1.min-1 for 1 hr. Infusion of alpha-hANP at 50 ng.kg-1.min-1 produced similar decreases in left atrial pressure in both normal and cardiac-denervated dogs (peak changes, -1.6 +/- 0.8 vs -2.4 +/- 0.9 mm Hg, respectively). Increases in urine flow (peak changes, 0.13 +/- 0.05 vs 0.20 +/- 0.06 ml/min) and sodium excretion (peak changes, 56 +/- 22 vs 70 +/- 11 microEq/min) also were not different between groups. The lower doses of alpha-hANP also elicited renal and hemodynamic responses in the cardiac-denervated dogs that did not differ significantly from those in the normal dogs. These data indicate that the diuresis and natriuresis elicited by intravenously administered alpha-hANP are not attenuated by a cardiorenal reflex in conscious dogs.


Progestin and estrogen control of cathepsin D expression and processing in rat uterine luminal epithelium and stroma-myometrium. Progestins increase the activity and rate of synthesis of cathepsin D, a lysosomal aspartyl protease, in the uterine luminal epithelium in ovariectomized rats. Western blot analysis of luminal epithelial proteins determined that the progestin, medroxyprogesterone acetate (MPA) increased the 43-kDa form of cathepsin D by 7-fold in 24 hr, whereas estradiol increased the amount of the same form by only 2-fold. To examine the precursor-product relationship between cathepsin D proteins in the luminal epithelium and stroma-myometrium after progestin or estradiol treatment, uterine proteins were prelabeled by incubation with [35S]methionine in vitro, cathepsin D was isolated by immunoprecipitation, and equal amounts of labeled cathepsin D were subjected to sodium dodecyl sulfate-polyacrylamide gel electrophoresis. After each hormonal treatment in each uterine tissue, a 48-kDa precursor was processed into a 44-kDa cathepsin D product. Endoglycosidase H digestion of [35S]methionine-labeled cathepsin D from the luminal epithelium and stroma-myometrium of medroxyprogesterone-treated rats shifted the molecular masses of the cathepsin D proteins by approximately 5.7 kDa. To examine the contribution of increased mRNA to increased rates of cathepsin D synthesis, we measured levels of cathepsin D mRNA in uterine tissues after progestin and estrogen treatment. Total RNA was isolated from the uterine luminal epithelium and from the stroma-myometrium. Northern blot analysis identified a single 2.2-kb RNA band corresponding to the size expected for cathepsin D mRNA. Medroxyprogesterone increased levels of cathepsin D mRNA in the luminal epithelium (greater than 17-fold) and in the stroma myometrium (3-fold), with maximum increases at 9 hr after treatment. Estradiol also increased cathepsin D mRNA levels in both uterine tissues, but by only 2-fold. No hormonal effects on liver cathepsin D mRNA were observed. Increases in cathepsin D synthesis and activity in uterine tissues in response to progestin and estrogen appear to depend in part upon increased levels of mRNA.


Reinforced responding of the 11-day-old rat pup: synergistic interaction of D1 and D2 dopamine receptors. Reinforced responding of 11-day-old rat pups was assessed after blockade of D1 and D2 dopamine receptors. Initially, rat pups were trained to traverse a straight alley for nipple attachment reward. Rat pups were than injected IP with either the D1 antagonist SCH 23390 (0.01, 0.015, 0.03, or 0.1 mg/kg), the D2 antagonist sulpiride (15 or 50 mg/kg), or a combination of SCH 23390 (0.015 mg/kg) and sulpiride (15 mg/kg). The approach performance of drug-treated pups was then compared to vehicle-treated pups on both reinforcement and extinction trials. Sulpiride (15 mg/kg) did not affect either the extinction or reinforced responding of 11-day-old rat pups. In contrast, SCH 23390-treated pups showed significantly longer response latencies than the vehicle controls in both extinction and reinforcement conditions. Combined treatment with SCH 23390 and sulpiride produced the longest response latencies. Analyses of "best score" and frequency data indicated that the drug-induced decline in responding was due to effects on both reward processes and motor capability. The combined results indicate that D1 and D2 receptors interact complexly to affect reinforced responding.


Influence of dopaminergic and serotonergic neurons on intravenous ethanol self-administration in the rat. Rats implanted with chronic indwelling intravenous catheters and allowed access to a self-administration apparatus learned to self-inject intravenous ethanol. Ethanol concentrations of 0.5, 1.0, and 2.0%, corresponding to a dose/injection of 1, 2, and 4 mg/kg, respectively, were consistently self-injected. Self-injection was not acquired or maintained with ethanol doses of 0.5 or 8 mg/kg/injection. Saline replacement of ethanol reservoirs led to marked increases in lever-pressing response in animals self-injecting 1, 2, and 4 mg/kg ethanol/injection but not with 0.5 or 8 mg/kg/injection. Neurotoxin-induced lesions of dopamine-(DA) containing neurons in nucleus accumbens septi failed to alter the acquisition or maintenance of ethanol self-injection. Pretreatment with haloperidol (0.05 and 0.1 mg/kg, SC) failed to alter hourly or daily self-injection rates. On the other hand, p-chlorophenylalanine pretreatment increased, while fluoxetine (2.5 and 5.0 mg/kg) administration significantly reduced, self-injected intravenous ethanol. These data suggest that ethanol is self-injected by the rat in a narrow dose range and that 5-hydroxytryptamine (5-HT), but not DA-containing neurons, subserves some function in the reinforcing or aversive affects of ethanol.


Domestication alters 5-HT1A receptor binding in rat brain. Serotonin-1A receptor binding density was compared in the brains of wild and domesticated adult male Rattus norvegicus using in vitro receptor autoradiography of [3H]8-hydroxy-2-[n-dipropylamino]tetraline (DPAT). While both groups exhibited similar patterns of labeling, [3H]DPAT binding density was significantly (p less than or equal to 0.05) lower in the median raphe nucleus and greater in superficial entorhinal cortex and rostral dentate gyrus of domesticated compared to wild rats. The results suggest that specific serotonergic circuits from the median raphe nucleus to the entorhinal and hippocampal regions might be involved in regulation of the defensive behaviors that differ profoundly between wild and domesticated rats. The relationship of these putative differences to behavioral disorders such as anxiety and depression in humans is discussed.


The 5-HT1A antagonist (-)-alprenolol fails to modify sleep or zimeldine-induced sleep-waking effects in rats. Sleep and waking in rats were studied for 8 h following administration of a selective 5-hydroxytryptamine (5-HT) reuptake inhibitor (zimeldine), a putative 5-HT1A antagonist (L(-)-alprenolol hydrogene tartrate monohydrate [(-)-alprenolol]) and a combination of (-)-alprenolol and zimeldine. Consistent with earlier findings, zimeldine gave a biphasic effect on sleep and waking. Waking was increased during the first 3 h, followed by a small decrease. Deep slow-wave sleep (SWS-2) showed the opposite trend. An initial decrease in SWS-2 was followed by an increase after around 3 h. Rapid eye movement sleep was markedly suppressed and latencies to sleep increased after zimeldine. (-)-Alprenolol had no effects on the different sleep and waking stages or latencies to sleep. The 5-HT1A antagonist also failed to modify the effects of zimeldine administration. The behavioral syndrome induced by a selective 5-HT1A agonist [8-hydroxy-2-(di-n-propyl-amino)-tetralin (8-OH-DPAT)] was clearly antagonized by administration of (-)-alprenolol, indicating that (-)-alprenolol was an efficient 5-HT1A blocker. The data indicate that the sleep-waking effects of zimeldine cannot easily be explained by stimulation of 5-HT1A receptors.


Ondansetron and arecoline prevent scopolamine-induced cognitive deficits in the marmoset. The cognitive-enhancing potential of the 5-hydroxytryptamine (5-HT) selective 5-HT3 receptor antagonist, ondansetron, was investigated in a model of cognitive impairment induced by the muscarinic receptor antagonist, scopolamine. For this purpose, marmosets were trained in an object discrimination task utilizing the Wisconsin General Test Apparatus. Administration of scopolamine (0.01-0.04 mg/kg, SC) caused a dose-dependent impairment in the acquisition of the object discrimination task in that marmosets required more trials to reach criterion, made more errors, and took longer to choose the objects. Administration of arecoline (0.06-0.1 mg/kg, SC) or 1,2,3,9-tetrahydro-9-methyl-3-[(2-methyl-1H-imidazol- 1-yl)methyl]-4H-carbazol-4-one,HCl.2H2O (ondansetron) (0.1-1 micrograms/kg, SC) prevented the scopolamine-induced impairment in task acquisition in that the performance of marmosets was indistinguishable from that of saline-treated animals and was significantly better than that following scopolamine/saline. From these studies, we conclude that ondansetron prevents impairment in the cognitive performance of marmosets induced by administration of scopolamine.


Sex differences in self-disclosure: a meta-analysis. A meta-analysis of 205 studies involving 23,702 Ss was conducted to determine whether there are sex differences in self-disclosure. Across these studies, women disclosed slightly more than men (d = .18). This effect size was not homogeneous across studies. Several moderator variables were found. Sex of target and the interaction effect of relationship to target and measure of self-disclosure moderated the effect of sex on self-disclosure. Sex differences in self-disclosure were significantly greater to female and same-sex partners than to opposite-sex or male partners. When the target had a relationship with the discloser (i.e., friend, parent, or spouse), women disclosed more than men regardless of whether self-disclosure was measured by self-report or observation. When the target was a stranger, men reported that they disclosed similarly to women; however, studies using observational measures of self-disclosure found that women disclosed more than men.


Gender differences in mate selection preferences: a test of the parental investment model. Evolutionary-related hypotheses about gender differences in mate selection preferences were derived from Triver's parental investment model, which contends that women are more likely than men to seek a mate who possesses nonphysical characteristics that maximize the survival or reproductive prospects of their offspring, and were examined in a meta-analysis of mate selection research (questionnaire studies, analyses of personal advertisements). As predicted, women accorded more weight than men to socioeconomic status, ambitiousness, character, and intelligence, and the largest gender differences were observed for cues to resource acquisition (status, ambitiousness). Also as predicted, gender differences were not found in preferences for characteristics unrelated to progeny survival (sense of humor, "personality"). Where valid comparisons could be made, the findings were generally invariant across generations, cultures, and research paradigms.


MMPI-ER two-point codes of industrially injured Hispanic workers by DSM-III--R diagnosis. The purpose of this study was to describe the MMPI-ER two-point codes of 492 Hispanic adults who had sustained work-related injuries and who had applied for workers' compensation benefits. More specifically, the focus was on whether there are unique MMPI two-point codes for Hispanic workers with three specific types of DSM-III--R diagnoses--adjustment disorder, anxiety disorder, and major depression. Analysis suggests that psychiatric condition or diagnosis may act as a moderator variable in Hispanic persons' MMPI performance, including MMPI two-point codes.


[A case of phlebothrombosis of lower extremity and pulmonary embolism due to progesterone]. A case with lower extremity phlebothrombosis and pulmonary embolism caused by progesterone is reported in this paper. The patient is a 64-year-old woman who had been operated on for right breast cancer 22 years before. It was noticed that there was a relapsing cancer on her right shoulder 6 months before this episode. After effective treatment of 5-FU, she had received 1,200mg of Medroxyprogesterone acetate and 30mg of Tamoxifen daily for 4 months. With the complaint of dyspnea and left leg swelling 4 months after above treatment, she was admitted in our hospital. Laboratory data and angiograms showed venous thrombosis in her left leg and pulmonary embolism. Relapsing cancer had already disappeared by the time she was admitted. After discontinuance of these medicines, her condition had improved. Considering these observations, the patient's phlebothrombosis and embolism seem to have been caused by Medroxyprogesterone acetate.


Estimating genomic distance from DNA sequence location in cell nuclei by a random walk model. The folding of chromatin in interphase cell nuclei was studied by fluorescent in situ sequences chromatin according to a random walk model. This model provides the basis for calculating the spacing of sequences along the linear DNA molecule from interphase distance measurements. An interphase mapping strategy based on this model was tested with 13 probes from a 4-megabase pair (Mbp) region of chromosome 4 containing the Huntington disease locus. The results confirmed the locations of the probes and showed that the remaining gap in the published maps of this region is negligible in size. Interphase distance measurements should facilitate construction of chromosome maps with an average marker density of one per 100 kbp, approximately ten times greater than that achieved by hybridization to metaphase chromosome. achieved by hybridization to metaphase chromosomes.


[Laparoscopic cholecystectomy. The beginning of a new era]. An important breakthrough in the field of general surgery, laparoscopic cholecystectomy (LC) offers significant advantages for patients. Major reasons for the rapid worldwide acceptance of this new surgical procedure is that patients experience reduced postoperative pain, ileus is virtually abolished, and the patient is able to leave the hospital the following day without a major abdominal scar. This appears to respond to patients' desire for less invasive approaches to the treatment of gallstone disease. LC is thus becoming the treatment of choice for symptomatic gallbladder disease. Its rapidly growing popularity is evident in Italy where many centers are offering LC routinely, in alternative to open cholecystectomy. A critical appraisal of this new technology is necessary, in light of recent data from centers presenting results and complications of large series of LCs. Adequate training of surgeons who will perform LC is also becoming a major concern. In this review the authors describe patient evaluation and selection for LC. Effective therapeutic strategies are illustrated, including the central, but nevertheless controversial role of endoscopic retrograde cholangiopancreatography (ERCP) as an approach to common bile duct lithiasis. Currently, LC should be performed in centers with the availability of an endoscopist with expertise in ERCP. Following the success of LC, other minimally invasive techniques will evolve in various surgical specialties. New generations of surgeons will thus have to familiarize with these emerging techniques while maintaining a critical attitude of evaluation.


Threshold phenomena and long-distance activation of transcription by RNA polymerase II. To explore the underlying mechanisms by which genes are regulated in eukaryotes, long-distance transcriptional activation and threshold effects were reconstituted in vitro. Long-range activation of transcription by GAL4-VP16 protein located 1300 base pairs upstream of the RNA start site was dependent on packaging of the template into histone H1-containing chromatin. A transcriptional threshold effect by GAL4-VP16 was observed with repressed chromatin templates but not naked DNA templates. The experimental data with the chromatin templates were similar to the theoretical activation profile that is predicted if the action of each DNA bound protomer of GAL4-VP16 were independent and additive in terms of free energy.


Formation and activation of a cyclin E-cdk2 complex during the G1 phase of the human cell cycle. Human cyclin E, originally identified on the basis of its ability to function as a G1 cyclin in budding yeast, associated with a cell cycle-regulated protein kinase in human cells. The cyclin E-associated kinase activity peaked during G1, before the appearance of cyclin A, and was diminished during exit from the cell cycle after differentiation or serum withdrawal. The major cyclin E-associated kinase in human cells was Cdk2 (cyclin-dependent kinase 2). The abundance of the cyclin E protein and the cyclin E-Cdk2 complex was maximal in G1 cells. These results provide further evidence that in all eukaryotes assembly of a cyclin-Cdk complex is an important step in the biochemical pathway that controls cell proliferation during G1.


[Initial experience with laparoscopic cholecystectomy]. The authors discuss the technique and indications for laparoscopic cholecystectomy. n the course of four and a half months they operated, using this technique, 74 patients, in two patients they had to switch over to open cholecystectomy. They did not perform peroperative biligraphy. Complications occurred twice, once an injured ductus choledochus, once a biliary fistula. The mean period of hospitalization was 4.7 days. Advantages of the procedure are minimal surgical trauma, less intense postoperative pain, a shorter hospitalization period, rapid convalescence.


[Initial experience with laparoscopic cholecystectomy]. The authors present their first experiences with laparoscopic cholecystectomy. They introduced this new operative method in Czechoslovakia. They operated upon 58 patients. The authors discuss about indication, complications and results.


Training, credentialing, and evaluation in laparoscopic surgery. Laparoscopic cholecystectomy has become the procedure of choice for the treatment of gallbladder disease. Many general surgeons have incorporated laparoscopic cholecystectomy into their clinical practices, usually after completing a postgraduate didactic and laboratory animal training course. This additional formal training is both appropriate and necessary because laparoscopic surgery involves techniques different from those of traditional celiotomy, and most surgeons who completed their residencies prior to 1992 have had no laparoscopic training. Because additional formal training for practicing surgeons is necessary at this time, it is appropriate for hospitals to mandate separate granting of operative privileges for laparoscopic surgical procedures. In the near future, when graduates of general surgery residency programs have had training in laparoscopic surgery, separate privileges will no longer be necessary, and laparoscopic procedures should be included in the standard privilege category of biliary tract surgery. Once privileges in laparoscopic surgery are granted, laparoscopic operations, like all surgical procedures, should be monitored by peer review to ensure that they continue to be performed safely and appropriately. Only those laparoscopic procedures that are similar to open operations and have been shown by pilot studies to be safe (e.g., cholecystectomy) should be included currently in a surgeon's laparoscopic privileges. Laparoscopic procedures that are very different from proven open procedures and are investigational (e.g., inguinal herniorrhaphy) should be permitted by the hospital only as part of an experimental protocol monitored by an institutional review board. Only after their safety and efficacy have been established should they become part of standard privilege categories.


Anesthesia for laparoscopic surgery.

Anesthesia for laparoscopic surgery. The anesthesiologist's goals during laparoscopic surgery are hemodynamic and respiratory stability, appropriate muscle relaxation, control of diaphragmatic excursion, intraoperative and postoperative patient analgesia, and a quick postanesthesia recovery. One must also consider that 3% to 5% of all laparoscopic procedures require conversion to an open laparotomy. Whatever the choice of anesthetic technique, it is important to maintain cooperation and communication among the members of the operating room team in order to ensure a successful patient outcome.


Laparoscopic instrumentation, videoimaging, and equipment disinfection and sterilization. Laparoscopic equipment, like the field of laparoscopic surgery, continues to evolve rapidly. This article discusses basic laparoscopic equipment and instruments now being developed as well as the basics of videoimaging. The topic of sterilization and disinfection of laparoscopic equipment is presented in detail.


Diagnostic laparoscopy in nonmalignant disease. Laparoscopy is useful in the management of a wide range of benign conditions. In the elective situation, it may be chosen to evaluate hepatobiliary disorders, abdominal masses, or chronic pain, and is an ideal way to sample tissue. Under the emergency setting, it is another tool for the assessment of trauma patients and may be of value in those patients with abdominal pain, mesenteric ischemia, fever of unknown origin, or gastrointestinal hemorrhage. It is important for the surgeon to be familiar with the technique, correctly prepare the patient, and be aware of the risks and limitations of this diagnostic modality.


Laparoscopic management of acute and chronic cholecystitis. Contrary to earlier predictions, it appears that acute cholecystitis should be considered a relative rather than an absolute contraindication to laparoscopic surgery. The most important parameter in determining the feasibility of attempting laparoscopic cholecystectomy in the setting of acute inflammation appears to be the experience of the surgeon. This also appears to be true when encountering individuals with elements of long-standing chronic cholecystitis. Although laparoscopic intervention in such patients is associated with a greater likelihood of conversion to open laparotomy, the incidence of major biliary and nonbiliary complications appears to be low. In addition, these patients enjoy the same benefits of laparoscopic surgery as those undergoing elective surgery.


[Two years of experience and 119 peritoneal dialysis catheters placed with peritoneoscopy control and Y-TEC system]. In this work we report our 24 months experience in the placement of 119 peritoneal catheters in 105 patients (59 males, 46 females, mean age 60.1 years; range 24-90) using the peritoneoscopic insertion technique. After catheter implantation a dialysis solution leak is encountered in 7.5% of cases, tunnel infection in 4 cases (3.3%) and exit site infection in 12.5% of the catheters. Placement by endoscopic control is considered as a technique able to avoid catheter migration; in our series we reported this complication in 15 cases (12.5%). The easy access to the peritoneal cavity and the atraumatic insertion of the catheter obtained with the Y-TEC procedure reduced the hospitalization period from 25 to 5 days on average. In our experience actuarial survival of catheters is 82.5% at 24 months.


Biliary ductal anatomy and anomalies. The role of intraoperative cholangiography during laparoscopic cholecystectomy. Biliary ductal anomalies of surgical importance can occur in 10% of patients. The short cystic duct draining into the common bile or right hepatic duct and the extreme proximity of the common bile duct in case of spiral or posterior entry of the cystic duct--if not recognized in time--can result in ductal injuries. The new mobile, digitized fluoroscopic units provide a vastly improved image within minutes. In case of an inadvertent ductal injury (extravasation, no contrast material visible in the proximal ductal system) the surgeon can immediately repair the injury. Routine intraoperative cholangiography is strongly recommended during laparoscopic cholecystectomies.


Laparoscopic management of bile duct stones. Although it may seem that laparoscopic cholecystectomy has revolutionized the way we approach the patient with stones in the gallbladder and bile ducts, only a few rules have really changed. Fluoroscopic cholangiography, a requirement for radiologists and gastroenterologists performing percutaneous transhepatic cholangiography and ERCP, is slowly finding its way into the operating room. No longer is a "palpable stone" a common indication for common bile duct exploration. Most importantly, it is not necessary to make an incision into the bile duct to remove the majority of bile duct stones. The transcystic approach will clear the duct in 85% to 90% of all patients, sparing them extra hospitalization, a T-tube, and the risk of creating a bile duct stricture during sutured closure of the choledochotomy.


Alternative methods in the management of bile duct stones. Common bile duct stones may now be dealt with, in most cases, without the need for surgery. To be sure, surgery continues to remain the gold standard for duct clearance and treatment of biliary sepsis. Improvements in endoscopic and radiologic technology and methodology have permitted excellent access to the biliary tree by the transduodenal and transhepatic approaches. In the majority of patients, total duct clearance and excellent drainage can be accomplished, averting sepsis and the need for open surgery.


Laparoscopic herniorrhaphy.

Laparoscopic herniorrhaphy. Laparoscopic inguinal hernia repair could represent an attractive alternative to conventional inguinal herniorrhaphy if it can be shown to result in less perioperative morbidity (primarily postoperative pain) or a decreased long-term recurrence rate. The data addressing either of these concerns will be forthcoming in ensuing years. The variations in the laparoscopic approach to the preperitoneal space and the differences in dissection and fixation techniques outlined in this article reflect the fact that the procedure is still evolving, and there is not yet a consensus on the best laparoscopic herniorrhaphy. It is likely that there will not be one laparoscopic technique applicable to all inguinal hernias. Rather, the patient's body habitus and the type of hernia encountered at laparoscopy will persuade the surgeon to use one of several techniques. Once a consensus is reached among surgeons as to the optimal laparoscopic hernia repair(s), it will be possible to begin gathering data concerning perioperative morbidity and recurrence rates. Only then can the question be answered whether laparoscopic inguinal herniorrhaphy has any advantages over the conventional extraperitoneal operation. A multicenter prospective nonrandomized trial has been initiated by our group in an attempt to determine whether laparoscopic inguinal herniorrhaphy has efficacy. The exact technique employed by the individual centers has not been strictly regulated, but general guidelines have been given. It is hoped that this project will provide information on whether laparoscopic inguinal herniorrhaphy is a useful alternative to conventional repair. Most of the laparoscopic inguinal herniorrhaphy techniques described in this article expose the patients to the inherent risks of initial laparoscopic penetration of the abdomen and the long-term possibility of adhesions to the sites where the peritoneum has been breached. Because these risks are not present in a conventional repair, the laparoscopic technique must have other advantages if it truly is to obtain a place in the armamentarium of general surgeons.


Laparoscopy in malignant disease.

Laparoscopy in malignant disease. The use of laparoscopy in patients with malignant disease is particularly helpful diagnostically and will often impact on future therapy. The indications and complications of this technique in combination with other diagnostic and therapeutic modalities in patients with malignant disease are evaluated and the accuracy of results are compared to laparotomy procedures. Future trends in laparoscopic surgery also are discussed.


Suturing and knot tying in laparoscopy.

Suturing and knot tying in laparoscopy. Laparoscopic surgery is evolving, and its applications are growing to include most abdominal operations. Tissue approximation by means other than mechanical clips or staples will be increasingly important. Laparoscopic surgeons must learn and apply basic suturing and knot-tying skills in this remote, two-dimensional operating theater. The authors advocate practice of these skills using inanimate and animate training models prior to application in the clinical setting.


Laparoscopic repair of duodenal ulcer and gastroesophageal reflux. The low morbidity and early recovery associated with laparoscopic procedures have heralded a new era for many types of surgery. In addition to the initial promising reports for duodenal ulcer disease and gastroesophageal reflux discussed above, there is a growing body of reports of gastric procedures performed laparoscopically, including omentopexy for perforated duodenal ulcer and laparoscopic repair of full-thickness stomach injury. Laws et al recently described the use of transthoracic vagotomy in recurrent peptic ulcer disease for four patients who had previously undergone a gastric drainage procedure. As with any new procedure, laparoscopic techniques for duodenal ulcer and Nissen fundoplication reviewed in this section need to be evaluated further for long-term effectiveness and comparability to existing therapy. At least one controlled multicenter trial is ongoing to compare the long-term results and cost-effectiveness of laparoscopic surgery for duodenal ulcer with those of standard medical therapy, and as surgeons gain more experience with these laparoscopic procedures, it is likely that other similar trials will be initiated.


Laparoscopic management of the acute abdomen, appendix, and small and large bowel. The application of laparoscopy for diagnosis and treatment of the acute abdomen, appendicitis, and in the management of small and large bowel diseases is a natural step for the general surgeon. Acute appendicitis is a common general surgical problem that can be difficult to diagnose. Laparoscopy is an excellent aid in diagnosis and laparoscopic appendectomy can be performed easily. The controversy of incidental appendectomy and recommendations for management are discussed. Small and large bowel diseases and their surgical treatment now can be managed laparoscopically thus decreasing morbidity and mortality. The uses and limitations of these techniques are discussed as well as future trends in treatment.


History of laparoscopic surgery.

History of laparoscopic surgery. Laparoscopic surgery has a long and colorful history. Although most general surgeons, especially in the United States, have discovered this technology only recently with the advent of videolaparoscopy, extensive diagnostic and therapeutic laparoscopy has been accomplished throughout the twentieth century, especially in Europe. Since its origin in 1901 by Kelling to the development of the computer chip television camera in the late 1980s, the history of laparoscopy entails a chronicle of discovery, innovation, and rediscovery. An appreciation for this historical chronicle may actually provide surgeons with a secure foundation as they embark on the new era of videolaparoscopy.


Active and passive modulation of cutaneous red cell flux as measured by laser Doppler anemometry. 1) We have found that the fluctuations in blood motion and blood content in cutaneous microvessels in man can be related to either active vasomotion (an order parameter for this system) or to a passive penetration of arterial (or venous, not shown) pressure waves (the control parameters for the microvascular blood motion). Arterial, respiratory (not shown), neuronal and myogenic rhythms can be clearly differentiated. 2) Spectral analysis of the signal fluctuations of a LDA method (monitoring phasic shifts in blood velocity) in combination with a photoplethysmographic method (monitoring shifts in blood content) can be used to identify the "normal state". In normal human subjects, it is characterized by broad band synergetic liberty (a wide spectrum of rhythmic activities between 0.01 and 5 Hz). The spectrum readily responds to changes in thermoregulatory state and/or myogenic activation by positional changes of the extremity. 3) The spectral analysis of LDA and photoplethysmographic records of the volar finger reveals predominance of active vasoconstriction during heat conserving thermoregulatory reflexes (18 degrees C ambient), predominantly passive reactions are seen at 27 degrees C. At 21-24 degrees C ("thermoregulatory indifference temperature range"), a mixed reaction pattern is seen. 4) Functional or irreversible elimination of the activity of subsystems leads to the elimination of circumscript spectral bands and/or potentiation of others. The functional differentiation of active and passive components can be utilized in the future for differential diagnosis of vascular and nervous disease state on the basis of spectral shifts and/or spectral narrowing.


Transcription mapping of mouse adenovirus type 1 early region 4. Early region 4 (E4) of mouse adenovirus type 1 was analyzed by Northern blotting, cDNA sequencing, and S1 nuclease protection and primer extension assays. The transcription map of this region was dissimilar to the consensus human adenovirus E4 transcription map in which all transcripts have identical 5' and 3'-terminal sequences. Seven classes of mouse adenovirus type 1 mRNAs were identified; all shared the same 3' end. Three classes of unspliced mRNAs differed at their 5' start sites, two classes of spliced transcripts differed in the locations of their splice acceptors, and two classes of spliced messages differed in their splice donors and acceptors. From the structure of the various transcripts, translational products were predicted. In addition to a predicted polypeptide with similarity to the human adenovirus 2 E4 34K protein previously identified (A. O. Ball, C. W. Beard, P. Villegas, and K. R. Spindler, 1991, Virology 180, 257-265), two open reading frames with similarity to human adenovirus 2 E4 open reading frames 2 and 3 were found.


In vitro excision and replication of 5' telomeres of minute virus of mice DNA from cloned palindromic concatemer junctions. HeLa cell extracts containing wild-type copies of the minute virus of mice NS-1 polypeptide produced from a recombinant vaccinia virus vector could support the excision and replication of viral 5' telomeres from cloned concatemer junction fragments. Resolution did not occur if wild-type NS-1 was omitted from the extract or if the substrate DNA contained palindromic sequences without specific viral resolution sites. In the presence of NS-1, [32P]dGTP incorporation into all templates was slightly increased, but if the template contained specific viral resolution sites DNA synthesis was greatly enhanced, and took two distinct forms: (i) generation of a limited number of high-molecular-weight molecules, probably due to a form of rolling-circle replication, and (ii) synthesis of new DNA at the viral telomeres. Resolution of the junction fragment generated two newly synthesized viral telomeres, each of which was covalently associated with NS-1 and contained a duplex copy of the complex palindrome located around the axis of symmetry of the concatemer junction. Cloned junction fragments of 296 bp or more could be resolved efficiently in vitro, and since NS-1 molecules were left covalently attached to the newly resolved termini, the latter could be partially purified by immuno-precipitation with anti-NS-1 serum. Restriction analysis and further fractionation of the precipitated DNA showed that the in vitro resolution sites were in the predicted positions on either side of the axis of symmetry, and that de novo DNA synthesis was associated predominantly with one of the two daughter strands. Telomeres were generated from both arms of the substrate with equal efficiency, and contained the characteristic "flip" and "flop" sequence inversions observed in vivo. Since a high proportion of termini were associated with adjacent viral sequences that retained the bacterial methylation pattern, in vitro resolution was not dependent upon prior DNA replication proceeding through the entire palindromic insert.


[Changes in hypertrophy and diastolic left ventricular function during hypertension therapy]. The authors examined a group of hitherto not treated patients with primary hypertension and hypertrophy of the left ventricle. By means of echocardiography and isometric loading they investigated the effect of treatment on the left ventricular morphology and function. Despite long-term normalization of casual and loading values of the blood pressure the authors did not observe a significant regression of LV hypertrophy. The authors did not find a relationship between the casual blood pressure and weight of the left ventricle with exception of the diastolic pressure after a load. The indicators of diastolic function did not correlate with the weight of the left ventricle but with changes of the end diastolic volume and blood pressure.


Dissociation of cortisol and adrenal androgen secretion in poorly controlled insulin-dependent diabetes mellitus. In acute illness, cortisol secretion increases whereas that of the adrenal androgens, dehydroepiandrosterone and dehydroepiandrosterone sulfate declines. The present study examined if a similar dissociation of cortisol and adrenal androgen secretion occurs in poorly controlled diabetes mellitus. Serum concentrations of cortisol, dehydroepiandrosterone and dehydroepiandrosterone sulfate obtained at 08.00 were compared in 13 post-pubertal diabetics (mean age 18.0 years) in good control (HbA1C less than 8.0%) and 10 post-pubertal diabetics (mean age 17.0 years) in poor control (HbA1C greater than 10.0%). Those in poor control had significantly higher serum cortisol (597 +/- 94 nmol/l vs 479 +/- 208, p less than 0.05), lower dehydroepiandrosterone (13.1 +/- 5.5 nmol/l vs 25.3 +/- 16.9, p less than 0.025) and lower dehydroepiandrosterone sulfate (4.5 +/- 2.4 mumol/l vs 7.0 +/- 3.7, p less than 0.025). The ratios of dehydroepiandrosterone and dehydroepiandrosterone sulfate to cortisol were also significantly lower in those with poor control. It is concluded that poor control of insulin-dependent diabetes mellitus results in a dissociation of cortisol and adrenal androgen secretion.


[Geographic occurrence of retinoblastoma]. The dot mapping technique was used to study the areas of retinoblastoma prevalence in Kazakhstan. A total of 344 retinoblastoma cases were analyzed. The landscape confinement of retinal tumors was taken into consideration. The tumors were more often seen in the children living near water, near the Alatau plain where chemical elements are accumulated, and in large industrial cities polluted by industrial waste products. The data of this study will be used to develop prophylactic measures and for early detection of retinoblastomas in children living in Kazakhstan.


The pituitary-gonadal axis in women with benign or malignant ovarian tumors. The serum levels of follicle-stimulating hormone (FSH), luteinizing hormone (LH), human chorionic gonadotropin (hCG), estradiol, progesterone, androstenedione, testosterone (total and free) and dehydroepiandrosterone sulphate (DHEAS) were investigated prior to surgery in 24 postmenopausal women with benign and 28 postmenopausal women with malignant epithelial ovarian tumors. The serum concentrations of hormones were compared with those of 28 healthy, postmenopausal, age-matched controls. Significantly lower serum FSH levels were demonstrated in women with malignant tumors. No significant differences were found between the groups regarding the serum LH levels. The hCG levels were low in all groups. Regarding progesterone and estradiol levels, low postmenopausal steroid levels were found in all groups examined and no significant differences were demonstrated within the groups. No significant correlations between the levels of estradiol and FSH or progesterone and LH were demonstrated. To exclude a central depression of gonadotropin release mediated by the dopaminergic system we examined the thyroid stimulating hormone (TSH) and prolactin. No differences were found between the groups regarding TSH and prolactin levels. A possible relationship between other hormones/factors produced by the tumor and exerting a negative feedback, either centrally or directly, on the gonadotropin release remains to be investigated. A change in biological activity in the gonadotropins might explain the present findings.


Atrial natriuretic peptide attenuates pressor but enhances natriuretic responses to angiotensin II in pregnant conscious goats. This study was designed to examine the actions of ANP in acute, ANGII-mediated hypertension during pregnancy. Effects on blood pressure, blood volume, and renal Na and K excretion were evaluated in conscious goats (n = 6). ANP (2 micrograms min-1), ANGII (0.5 microgram min-1), or ANGII+ANP (doses the same as for each peptide alone) was infused intravenously for 60 min. The pressor response to ANGII was reduced in pregnant goats. This reduction was seen in systolic, but not in diastolic pressure. ANP decreased pressure by 5-10 mmHg both in pregnancy and in non-pregnancy. When ANGII+ANP was infused, blood pressure initially rose as with ANGII but then declined. ANP suppressed only the elevated systolic pressure. Plasma protein concentration and haematocrit was reduced by ANGII but increased by ANP alone or together with ANGII, thereby implying fluid shift into the vasculature by ANGII and opposite movement by ANP. ANGII increased renal Na excretion to 1500 mumol min-1 in non-pregnancy, but only to half of that in pregnancy. ANP alone caused small natriuresis, but enhanced ANGII-induced natriuresis to near 3000 mumol min-1 in both non-pregnant and pregnant goats. In summary, ANP further attenuated the blunted blood-pressure rise due to ANGII in pregnant goats, and reduced plasma volume, but enhanced renal Na excretion as in non-pregnant goats. This implies that with the present combination ANP and ANGII caused a near maximal natriuretic response that was not modified by the systemic cardiovascular changes occurring in pregnant goats.


Effects of cyclopiazonic acid, an inhibitor of the Ca++ ATPase of sarcoplasmic reticulum, on Ca++ transport, contraction and relaxation in cardiac muscle. Cyclopiazonic acid is a potent inhibitor of cardiac sarcoplasmic reticulum Ca++ ATPase. It scarely affects inotropism but significantly impairs lusitropism suggesting a greater role for cardiac sarcoplasmic reticulum in the control of cardiac relaxation than in the control of cardiac contraction.


Suppression of the Arthus reaction by Y-24180, a potent and specific antagonist of platelet-activating factor. A novel and potent antagonist of platelet-activating factor (PAF), Y-24180 (4-(2-chlorophenyl)-2-[2-(4-isobutylphenyl)ethyl]-6,9-dimethyl-6H- thieno[3,2-f][1,2,4]triazolo[4,3-a][1,4] diazepine) was investigated for the effects on the skin reactions induced by chemical mediators and the Arthus reactions. In the rat dorsal skin, Y-24180 (0.1-10 mg/kg, p.o.) inhibited increase in vascular permeability by the intradermal PAF injection in a dose dependent manner and the inhibitory activity was 60 times more potent than that of WEB 2086. While even at doses as large as 10 mg/kg, p.o., it had no effect on vascular permeability in the rat skin induced by histamine, serotonin, bradykinin and leukotriene D4. On a reversed passive Arthus reaction in rat dorsal skin, Y-24180 (0.1-1 mg/kg, p.o.) markedly inhibited vascular permeability in a dose dependent manner and the inhibitory activity was 15 times more potent than that of WEB 2086. Y-24180 also inhibited the Arthus dermal reaction in rabbits (0.03-0.3 mg/kg, p.o.) and guinea pigs (0.1-1 mg/kg, p.o.). In addition, Y-24180 (0.1-10 mg/kg, p.o.) significantly reduced the exudate volume and the number of infiltrated inflammatory cells in the reversed passive Arthus pleural reaction in rats. Furthermore, in rat passive Arthus pancreatitis, Y-24180 (0.3-10 mg/kg, p.o.) significantly inhibited the dye extravasation from the pancreas. These results provide strong evidence that endogenous PAF plays an important role as a mediator in the type III allergic inflammation.


Dimaprit--induced neurotoxicity.

Dimaprit--induced neurotoxicity. The neurotoxicity of the histamine H2 agonist dimaprit was characterized. Dimaprit (100 micrograms administered into the lateral cerebral ventricle) induced a large area of brain necrosis 1-3 days later which was uniformly lethal. Lower doses caused dose - related effects on survival, gross brain pathology and body weight. Experiments with other H2 agonists and H2 antagonists, together with studies by others demonstrating a similar toxicity of the congener homodimaprit suggest that the neurotoxicity of dimaprit is independent of brain H2 receptors. Although dimaprit is a useful tool for the characterization of H2 receptor responses, the present results show that this agent must be used with caution, if at all, in classifying brain H2-receptor mediated events.


In vitro effects of Etodolac and acetylsalicylic acid on human chondrocyte metabolism. The effects of two nonsteroidal anti-inflammatory drugs (NSAIDs), Etodolac (ETO) and acetylsalicylic acid (ASA), used at pharmacological concentrations, were tested on several metabolic parameters of human chondrocytes cultivated in three-dimensional culture. The results indicated that proteoglycan synthesis was significantly decreased by ASA treatment, whereas Etodolac did not affect this parameter. Neither ASA nor Etodolac modified type-II collagen production. Both NSAIDs were potent inhibitors of PGE2 production, but Etodolac was more efficient at equimolar concentrations. In contrast, collagenolytic activity was unaffected by Etodolac.


[Laparoscopic pelvic lymphadenectomy in patients with localized prostate cancer]. Laparoscopic pelvic lymphadenectomy is a newly developed technique of lymph node dissection in patients with malignancy of the pelvic organs. Three patients with localized prostatic cancer underwent laparoscopic pelvic lymphadenectomy. The patients were 77 years old with stage C disease, 73 with stage B1, and 65 with stage A2. Five to ten lymph nodes were removed from each patient after laparoscopic procedures lasting 220 to 270 minutes. There were no complications during the procedures and their convalescence was uneventful. All lymph nodes were negative by pathological examination and a radical retropubic prostatectomy was done 2 weeks after the lymphadenectomy in two patients. The other patient was treated with external radiotherapy and bilateral orchiectomy. Patients with stage C cancer, a high serum level of prostate specific antigen or a high grade tumor are the best candidates for this less invasive staging procedure. The disadvantage of this procedure is long operation time and complications due to CO2 pneumoperitoneum.


Atrial natriuretic peptide in severe heart failure: response to controlled changes in atrial pressures during intravenous nitroglycerin therapy. Atrial natriuretic peptide (ANP) levels were measured in 17 patients with severe congestive heart failure (New York Heart Association functional class IV), and the response of the peptide was studied during changes in cardiac filling pressures induced by a 24-hour infusion of nitroglycerin. In the control state plasma ANP levels (687 +/- 551 pg/ml) were 10-fold normal. During the administration of nitroglycerin, natriuretic peptide levels decreased (p less than 0.005) with changes matching very closely the decreases in pulmonary arterial wedge and right atrial pressures, a 1% mean decrease in the peptide level for every 1.5 to 2% mean change in atrial filling pressures. In patients with hemodynamic tolerance to constant-dose nitroglycerin infusion, the resulting increase in atrial pressures was accompanied by an appropriate secondary increase in the plasma ANP level. During the 24-hour study period there was a direct linear relationship between both wedge (r = 0.93, p = 0.007) and right atrial (r = 0.93, p = 0.008) pressures and the plasma ANP level, with a zero-pressure ANP intercept near normal (69 pg/ml for wedge, 174 pg/ml for right atrial pressure). The findings were no different in a subgroup of five patients receiving simultaneous treatment with captopril, except that plasma renin activity was higher and the aldosterone level lower than in the control group by a factor of approximately 2.5. The close relationship and tracking of atrial pressure and natriuretic peptide curves suggested that the sensitivity of the atrial stretch response to changes in atrial filling pressures was maintained in severe congestive heart failure.


Cardiomegaly on chest x-ray: prognostic implications from a ten-year cohort study of elderly subjects: a report from the Bronx Longitudinal Aging Study. This report is from a 10-year cohort study of community-dwelling elderly men and women. Mean age at the time of entry into the study was 79 years. Annual chest x-ray studies were performed, and data are presented regarding prevalence, incidence, and prognosis of cardiomegaly. Cardiomegaly was defined as a transverse diameter of the cardiac silhouette greater than or equal to 50% of the transverse diameter of the chest (increased cardiothoracic ratio). At the time of entry into the study 110 subjects (23%) had cardiomegaly. After 10 years, 51% of the subjects with cardiomegaly at baseline died compared with 33% of the subjects without cardiomegaly (mortality rate = 9.1 vs 4.8/100 person-years respectively; p = 0.014). Cardiovascular disease incidence was also higher for those with preexisting cardiomegaly at baseline (rate 9.1 vs 6.1/100 person-years; p = 0.0001). According to the Cox proportional hazards regression analysis, age, cardiomegaly, diabetes, and prior evidence of myocardial infarction were independent predictors for death in this cohort. Similarly, the best predictive variables for cardiovascular disease were age, diabetes, prior evidence of myocardial infarction, and cigarette smoking. Of the 359 subjects without cardiomegaly at baseline, 108 (30%) showed evidence of new cardiomegaly, and their risk of cardiovascular disease was 1.8 times that of subjects whose test results were negative for cardiomegaly throughout the study (p = 0.003). Thus cardiomegaly, as defined by an increased cardiothoracic ratio on x-ray films, irrespective of cause, is associated with a poor prognosis in very elderly men and women.


Measurement of volumetric coronary blood flow with a Doppler catheter: validation in an animal model. Although Doppler catheter recordings are used to determine coronary flow velocity, their accuracy in the estimation of volumetric blood flow has not been validated. To address this issue, Doppler-derived coronary flow was measured in a canine model and compared with that obtained by means of an electromagnetic flowmeter. A carotid artery-to-circumflex coronary artery shunt was created in six dogs with tubing that incorporated an inline electromagnetic flow device. The circumflex artery was occlusively cannulated by means of a rigid metal stent of known internal diameter, which was placed 2 cm into the vessel, and flow was measured in the stent region by means of a 3F Doppler catheter. Analysis of Doppler shift signals was performed by means of a zero-crossing detector (ZCD) and an off-line fast-Fourier transformation (FFT) system. Flow derived from peak FFT velocities corresponded closely to electromagnetic flow (slope 1.09, r = 0.93), whereas mean FFT and ZCD velocities underestimated electromagnetic flow (with slopes of 0.47 and 0.46, respectively) despite a close correlation (r = 0.92, 0.94). Thus FFT analysis of the Doppler signal with determination of peak velocity gives the most accurate representation of flow, whereas measurements based on ZCD mean velocities may significantly underestimate coronary flow.


Effect of gallopamil on electrophysiologic abnormalities and ventricular arrhythmias associated with left ventricular hypertrophy in the feline heart. Left ventricular hypertrophy increases vulnerability to ventricular fibrillation. To determine whether calcium channel blockade protects against ventricular arrhythmia in left ventricular hypertrophy, we studied the effects of gallopamil, a potent and specific calcium channel antagonist, in 37 cats undergoing aortic banding (group 1, n = 28) or a sham procedure (group 2, n = 9). Each cat underwent serial echocardiography and was studied after the development of left ventricular hypertrophy, defined as an increase of at least 30% in left ventricular posterior wall thickness. After baseline electrophysiologic testing, animals received gallopamil (70 micrograms/kg loading dose followed by 2.5 micrograms/kg/min infusion) (n = 19) or a control infusion of saline solution (n = 18), and testing was repeated. There was no significant difference between groups 1 and 2 in baseline excitability thresholds intraventricular conduction times, ventricular effective refractory periods, or monophasic action potential durations. Thresholds for induction of ventricular fibrillation were lower in group 1 than in group 2, and only in group 1 was ventricular fibrillation inducible during programmed stimulation. This altered vulnerability was associated with a significantly greater dispersion of excitability thresholds, ventricular effective refractory periods, and monophasic action potential durations. Gallopamil did not change baseline measurements except for prolonging sinus cycle length and atrioventricular conduction time.(ABSTRACT TRUNCATED AT 250 WORDS)


Assessment of the efficacy and safety of antiarrhythmic therapy for chronic atrial fibrillation: observations on the role of trial design and implications of drug-related mortality. The findings in clinical trials of antiarrhythmic drug efficacy and safety are frequently difficult to compare, since study design often has an important effect on trial outcome. To explore this problem further, we compared three designs--randomized control, nonrandomized control, and uncontrolled--collectively enrolling 2415 patients in 21 trials reporting on the role of quinidine in the prevention of chronic atrial fibrillation. The proportion of patients remaining in sinus rhythm at 3, 6, and 12 months after cardioversion was calculated by means of Kaplan-Meier techniques, and the data were pooled for each trial design. For the randomized control trials the difference in the absolute percentage of patients remaining in sinus rhythm in the quinidine and control groups was 24% at each of the three follow-up intervals. Contrary to findings in the randomized control trials, the magnitude of the treatment benefit in nonrandomized trials was smaller and declined markedly over time. The percentage of patients remaining in sinus rhythm in the uncontrolled trials was intermediate to the percentages in the other two trial designs. When the data from all three trial designs were pooled, the crude mortality rate was 2.0% in quinidine-treated patients and 0.6% in control patients. Sudden cardiac death or ventricular fibrillation was the cause of death in 13 of 19 patients for whom the cause of death was known, highlighting the potential risk of quinidine-induced proarrhythmia. Although quinidine is effective in maintaining sinus rhythm, estimates of the treatment effect vary among trial types.(ABSTRACT TRUNCATED AT 250 WORDS)


Influence of left ventricular hypertrophy and function on the occurrence of ventricular tachycardia in hypertrophic cardiomyopathy. Sixty-nine patients with hypertrophic cardiomyopathy were studied by 2-dimensional and Doppler echocardiography and 72-hour Holter monitoring to examine the relation between the degree of left ventricular (LV) hypertrophy and dysfunction and the occurrence of ventricular tachycardia (VT). Episodes of nonsustained VT were detected in 20 patients (29%). Maximal wall thickness was not different between patients with (22 +/- 5 mm) and without (21 +/- 5 mm) VT. Total hypertrophy score, calculated as the sum of 10 segmental wall thicknesses, was also similar in both groups (157 +/- 22 and 153 +/- 32 mm, respectively; p = not significant). Furthermore, no significant differences were found between the 2 groups in LV end-diastolic dimension (41 +/- 7 vs 40 +/- 6 mm), fractional shortening (33 +/- 7 vs 34 +/- 10%) and left atrial size (40 +/- 10 vs 41 +/- 11 mm). An LV outflow tract gradient was detected in 25% of patients with and 35% without VT (p = not significant). One or more Doppler indexes of diastolic function were abnormal in 70% of patients, but no difference in any of these indexes was found between those with and without VT. In summary, the occurrence of VT in hypertrophic cardiomyopathy is not related to the degree of LV hypertrophy, outflow tract gradient or dysfunction. This finding suggests a dissociation between the arrhythmogenic substrate and echocardiographic features of the disease.


Effects of calcitonin gene-related peptide on cardiac contractility, coronary hemodynamics and myocardial energetics in idiopathic dilated cardiomyopathy. This study was performed to examine the effects of calcitonin gene-related peptide on cardiac function and coronary circulation in patients with heart failure. Synthetic human calcitonin gene-related peptide was infused in the left main coronary artery of 9 patients undergoing cardiac catheterization at different doses corresponding to incremental infusion rates of 15, 50, 150 and 600 pmol.min-1. No hemodynamic change was observed in response to administration of the 2 lowest doses. The 2 highest doses induced an increase in cardiac index and a decrease in systemic arterial pressure. The infusion of 600 pmol.min-1 resulted in a decrease of mean systemic arterial pressure (86.8 +/- 6.5 to 71.8 +/- 4.9 mm Hg; p less than 0.01), and an increase in both cardiac index (2.1 +/- 0.1 to 3.1 +/- 0.17 liters.min-1.m-2; p less than 0.01) and heart rate (87 +/- 3.7 to 101 +/- 6.1 beats.min-1; p less than 0.01). These hemodynamic changes were associated with a significant increase in plasma norepinephrine and epinephrine concentrations. Peak positive first derivative of left ventricular pressure did not change at any infusion rate. Left ventricular end-diastolic pressure decreased at the 2 highest doses associated with a decrease in plasma atrial natriuretic factor concentration (730 +/- 140 to 436 +/- 115 pg.ml-1; p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)