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PubMed1997

Role of nitric oxide in mucosal blood flow response and the healing of HCl-induced lesions in the rat stomach.

The role of nitric oxide (NO) in the gastric mucosal blood flow response and the healing of HCl-induced gastric lesions was investigated in rats. After 18 h fasting rats were given 0.6 N HCl p.o. for the induction of gastric lesions, and 1 h later they were fed normally. After induction of gastric lesions, they were repeatedly administered the NO synthase inhibitors NG-nitro-L-arginine methyl ester (L-NAME 5-20 mg/kg p.o. twice daily) or aminoguanidine (20 mg/kg s.c. once daily) for 7 days. Gastric lesions caused by HCl healed almost completely within 5 days with granulation and to an extent with re-epithelialization. Repeated administration of L-NAME but not aminoguanidine significantly delayed the healing of gastric lesions in a dose-dependent manner. The damaged mucosa secreted less acid, but showed a marked rise in H+ permeability, resulting in luminal acid loss accompanied by an increase of mucosal blood flow. Aminoguanidine did not significantly affect any of these functional changes observed in the stomach after damage by HCl, whereas L-NAME treatment slightly reversed the decreased acid response, increased the luminal H+ loss, and totally inhibited the mucosal hyperemic response associated with luminal acid loss in the damaged mucosa. In addition, the deleterious influences of L-NAME on the mucosal blood flow response and the healing of gastric lesions were significantly antagonized by co-administration of L-arginine but not of D-arginine (500 mg/kg x 2, i.p.). Luminal output of NO2-/NO3- was significantly increased in pylorus-ligated stomachs in control rats on days 3 and 5 after damage, and such increases in gastric NO output were completely attenuated by L-NAME treatment. These results suggest that endogenous NO may contribute to the healing of acute gastric injury by mediating the mucosal hyperemic responses associated with acid back-diffusion and by facilitating acid disposal in the damaged mucosa. NO mediating such responses and participating in the healing aspect of gastric lesions may be produced by the constitutive type of NO synthase.

Animals↗
PubMed2004

Regulation of vascular tone by S-nitroso-myoglobin.

Myoglobin (Mb) is a haem protein present in skeletal, cardiac and smooth muscle where it facilitates the transfer of O(2) from the extracellular matrix to the cell cytosol in a cycle termed 'facilitated O(2)-diffusion'. In addition, we showed recently that recombinant human Mb binds endothelium-derived relaxant factor - nitric oxide ((.-)NO) - via formation of both nitrosyl-haem iron and S-nitroso-myoglobin (S-NO-Mb). S-NO-Mb represents a novel form of endothelium-derived relaxant factor (EDRF) that may be important in maintaining optimal (.-)NO concentrations in the human vasculature. In this study we aim to show that: (i) S-nitrosation of oxygenated ferrous myoglobin (oxyMb) can compete with the rapid oxidation of (.-)NO by oxyMb; and (ii) S-NO-Mb retains characteristics of physiological EDRF.

Animals↗
PubMed1997

The Drosophila sugarless gene modulates Wingless signaling and encodes an enzyme involved in polysaccharide biosynthesis.

We have identified and characterized a Drosophila gene, which we have named sugarless, that encodes a homologue of vertebrate UDP-glucose dehydrogenase. This enzyme is essential for the biosynthesis of various proteoglycans, and we find that in the absence of both maternal and zygotic activities of this gene, mutant embryos develop with segment polarity phenotypes reminiscent to loss of either Wingless or Hedgehog signaling. To analyze the function of Sugarless in cell-cell interaction processes, we have focused our analysis on its requirement for Wingless signaling in different tissues. We report that sugarless mutations impair signaling by Wingless, suggesting that proteoglycans contribute to the reception of Wingless. We demonstrate that overexpression of Wingless can bypass the requirement for sugarless, suggesting that proteoglycans modulate signaling by Wingless, possibly by limiting its diffusion and thereby facilitating the binding of Wingless to its receptor. We discuss the possibility that tissue-specific regulation of proteoglycans may be involved in regulating both Wingless short- or long-range effects.

Amino Acid Sequence↗
PubMed2004

Myoglobin: an essential hemoprotein in striated muscle.

Myoglobin is a cytoplasmic hemoprotein, expressed solely in cardiac myocytes and oxidative skeletal muscle fibers, that reversibly binds O2 by its heme residue, a porphyrin ring:iron ion complex. Since the initial discovery of its structure over 40 years ago, wide-ranging work by many investigators has added importantly to our understanding of its function and regulation. Functionally, myoglobin is well accepted as an O2-storage protein in muscle, capable of releasing O2 during periods of hypoxia or anoxia. Myoglobin is also thought to buffer intracellular O2 concentration when muscle activity increases and to facilitate intracellular O2 diffusion by providing a parallel path that augments simple diffusion of dissolved O2. The use of gene targeting and other molecular biological techniques has revealed important new insights into the developmental and environmental regulation of myoglobin and provided additional functions for this hemoprotein such as scavenging nitric oxide and reactive O2 species. These recent findings, coupled with additional emerging technologies and the discovery of other tissue globins, provide a framework for addressing new questions about myoglobin and readdressing old ones.

Animals↗
PubMed1988

[Acute effects of topical application of methyl N-trimethyl-gamma-aminobutyrate chloride on cutaneous microcirculation in the healthy male rabbit].

Effects of acetylcholine (ACh) and its reversed carboxy analogue, methyl N-trimethyl-gamma-aminobutyrate chloride (MTB), induced either by topical application to the skin surface around a transparent round table chamber (REC) that had been previously installed to the ear lobe or by intravenous injection on the micro- and macrocirculations were studied in the healthy male rabbit. The effects of both drugs on the cutaneous microcirculation within the REC were observed vital-microscopically under conscious conditions and the microcirculatory events were visualized with a microscope-closed TV system and microphotoelectric plethysmography. The results were as follows: (1) Topical application of 1% MTB cream caused an enhanced perfusion of rhythmic microvascular blood due to vasomotion for a period of 30 min or longer, while ACh did so to a much less extent, if any. On the other hand, no appreciable change developed in any systemic hemodynamic parameters. (2) Intravenous administration of MTB or ACh caused a very transient dilator effect on micro-and macrocirculatory blood vessels according to its cholinergic stimulation, which could be blocked by atropinization. Almost the same efficacy on vasomotion was observed for each drug. (3) These findings indicate that the topical application of MTB to the skin surface may cause a physiologically acceptable vasodilation accompanied by vasomotion, and it would facilitate the oxygen diffusion by the follicular circulation.

Acetylcholine↗
PubMed1977

The ontogeny of swimming behavior in the scyphozoan, Aurelia aurita. I. Electrophysiological analysis.

1. Electrical correlates of behavioral activity were observed in the lip and tentacles of the polyp, but none were detected during column contraction. The tentacles are the most electrically active tissue, and the potentials are conducted along the length of the tentacle, but conduction to other parts of the animal were not observed. 2. Although the tentacles of the polyp and the rhopalia of the medusa are probably homologous, the development of pacemaker activity during strobilation is not a smooth transition from tentacle contraction potentials (TCPs) to marginal ganglion potentials (MGPs). This result indicates that each pacemaker activity develops de novo. 3. Two types of behavior were observed in the polyp: local responses, and coordinated activity which involved integrated responses in several body parts. The coordinated responses indicate that neurological coordination can take place in the polyp. Furthermore, feeding and spasm in the ephyra are similar to feeding and the protective response in the polyp. This similarity suggests that both coordinated responses in the polyp are coordinated by interneural facilitation in the diffuse nerve net (DNN) as in the ephyra. 4. Swimming in the ephyra is a medusoid behavior but feeding and spasm are coordinated by the DNN and are polypoid responses. Therefore, the ephyra is a mixture of polypoid and medusoid behaviors. As the ephyra matures into an adult medusa both polypoid responses are lost, but the DNN remains to modulate pacemaker output and control marginal tentacle contractions. As development proceeds from polyp, to ephyra, to medusa, each subsequent stage acquires some new behavior while retaining some aspect from the previous stage.

Animals↗
PubMed1993

Freeze-fracture electron microscopic and osmotic water permeability studies of epidermal lipid liposomes derived from stratum corneum lipids of porcine epidermis.

Freeze-fracture electron microscopic studies revealed that the liposomal membrane morphology was intact before and after osmotic treatment. This finding suggested that water leakage from the liposomes was not due to fusion of two or more lipid vesicles, but rather to the osmotic salt effect. A stop-flow spectrophotometric study revealed that epidermal lipid liposomes derived from stratum corneum lipids of porcine skin underwent increases of the absorbances with decreases of volume of the vesicles. The initial rate at which the changes in optical density occurs is a measure of the water permeability through the liposomes. The reciprocal of the changes in the absorbance at the equilibrium at different salt osmotic shocks showed a linear dependence on the reciprocal of the osmotic pressure gradient, indicating that epidermal lipid liposomes are an ideal osmometer. The present investigation reports that lignoceric acid is a potent water barrier. Present findings suggest that the initial rate of water penetration decreased in the liposomes made from 30-45% (wt% ratio) of cholesterol and ceramides. Oleic acid as drug penetration enhancer facilitated the water diffusion of the stratum corneum lipid liposomes by a fluidizing effect on the liposomal membranes. Furthermore, ceramides are important in the water barrier properties of the skin. The permeability of water depends upon the amount (wt%) and the type of lipid of the membrane.

Animals↗
PubMed2006

Gefitinib accumulation in glioblastoma tissue.

Therapeutic agents for brain tumors confront multiple physical and metabolic hurdles. These include the blood brain barrier (BBB), vascular and interstitial barriers, clearing by MDR1 and other ABC transporter proteins, and drug catabolism. Here, we report an accumulation of gefitinib in glioblastoma (GBM) tissue to over a dozen times plasma levels, and propose that some mechanisms converge to achieve such accumulation: (1) small molecular size of gefitinib facilitates access by diffusion; (2) its high water solubility enables thermodynamic retention inside malignant cells; and (3) low CYP3A4 activity in GBM tissue, the main enzyme for gefitinib catabolism, prevents metabolic elimination. Our data confirm the capacity of gefitinib to accumulate in solid human tumors in vivo.

Antineoplastic Agents↗
PubMed2001

[The Revista Médica de Chile in a science library in the Internet].

Medical journals published in non-English languages face a handicap: their worldwide readership and citation are reduced in comparison to journals published in English. This handicap is worse for small journals edited in developing countries, regardless of whether they publish original research articles including abstracts in English. To facilitate the international diffusion of selected Chilean scientific journals, the "Comisión Nacional de Investigación Científica y Tecnológica" enforced the program "SciELO Chile" with a web site in Internet (www.scielo.cl) including the full text of articles published in recent issues. Revista Médica de Chile is the first Chilean medical journal that appears in this web site, sponsored by the National Library of Medicine, Washington D.C. We expect that this web site will give a favorable input to authors of articles published in our journal.

Bibliometrics↗
PubMed2002

Biological staining: mechanisms and theory.

New staining techniques continue to be introduced, and older ones continue to be used and improved. Several factors control specificity, selectivity and visibility of the end product in any procedure using dyes, fluorochromes, inorganic reagents or histochemical reactions applied to sections or similar preparations. Local concentration of the tissue target often determines the intensity of the observed color, as does the fine structure within the object being stained, which may facilitate or impede diffusion of dyes and other reagents. Several contributions to affinity control the specificity of staining. These include electrical forces, which result in accumulation of dye ions in regions of oppositely charged tissue polyions. Weaker short-range attractions (hydrogen bonding, van der Waals forces or hydrophobic bonding, depending on the solvent) hold dyes ions and histochemical end products in contact with their macromolecular substrates. Nonionic forces can also increase visibility of stained sites by causing aggregation of dye molecules. Covalent bonds between dye and tissue result in the strongest binding, such as in methods using Schiff's reagent and possibly also some mordant dyes. The rate at which a reagent gains access to or is removed from targets in a section or other specimen affect what is stained, especially when more then one dye is used, together or sequentially. Rate-controlled staining is greatly influenced by the presence and type of embedding medium, such as a resin, that infiltrates the tissue. The rates of chemical reactions are major determinants of outcome in many histochemical techniques. Selective staining of different organelles within living cells is accomplished mainly with fluorochromes and is controlled by mechanisms different from those that apply to fixed tissues. Quantitative structure-activity relations (QSAR) of such reagents can be derived from such molecular properties as hydrophilic-hydrophobic balance, extent of conjugated bond systems, acid-base properties and ionic charge. The QSAR correlates with staining of endoplasmic reticulum, lysosomes, mitochondria, DNA, or the plasma membranes of living cells.

Animals↗
PubMed1992

[Functional morphology of resistant pulmonary vessels and capillaries in individual and species adaptation to high altitude].

Morphological and structural rearrangement of resistant pulmonary vessels and alveolar capillaries was assessed in lowland animals (rabbits) during high-altitude adaptation, in aboriginal high-altitude species (yaks, mountain goats) and on native highlanders. Structural adaptive developments in pulmonary vessels and capillaries of high-altitude animals contribute to maximal facilitation of gas diffusion. Similar adaptive changes in pulmonary resistant vessels and capillaries of laboratory animals and in native highlanders are associated with pathological alterations manifest in the elevation of pulmonary vascular resistance, right ventricular hypertrophy, increases in the thickness of the basal membrane of the air-blood barrier. In all the subjects studied the process of high-altitude adaptation is associated with hypertrophy of pulmonary endothelium. The intensification of pulmonary endothelium. The intensification of pulmonary endothelium metabolic activity may be directed at regulation of vascular tone.

Adaptation, Physiological↗
PubMed1976

Inhibition of de novo pyrimidine nucleotide and DNA synthesis and growth of cultured Novikoff rat hepatoma cells and other cell lines by pyrazofurin (NSC 143095).

Pyrazofurin (PYF), a C-riboside, inhibited the replication of cultured Novikoff rat hepatoma cells, HeLa cells, and mouse L-cells at concentrations as low as 0.1 to 10 muM, but Novikoff cells were more sensitive than the cells of the other two cell lines. Inhibition of cell replication was completely prevented by the presence of 0.1 to 1 mM uridine in the medium, and partly by the presence of other pyrimidine, but not purine nucleosides. A 2- to 4-hr treatment of the cells with 10 muM PYF resulted in a 2-fold increase in the rate of incorporation of uridine into the acid-soluble pool and nucleic acids, while the rate of incorporation of adenosine into RNA was reduced about 85%. The incorporation of adenosine and deoxyuridine into DNA were reduced about 85 and 50%, respectively. The results are consistent with the view that PYF inhibits the de novo synthesis of pyrimidine nucleosides. The inhibition of cell replication seems to be due mainly to an inhibition of DNA rather than RNA synthesis, resulting from a rapid depletion of the pyrimidine deoxynucleotide pool, since addition of thymidine and deoxycytidine reversed the inhibition of DNA synthesis and cell replication by PYF. PYF must enter the cells to exert its toxicity since the toxicity of PYF was reduced 70 to 80% by the presence of 8 muM Persantin, a potent inhibitor of the facilitated and simple diffusion of various substrates, in the medium. If PYF is incorporated via normal nucleoside salvage pathways, its affinity for the nucleoside transport system(s) and kinases, must be low since, even at a concentration of 1 mM, it had only a slight effect on the initial rates of incorporation of various nucleosides into the nucleotide pool.

Adenosine↗
PubMed1990

Recent studies on the biological actions of vitamin D on intestinal transport and the electrophysiology of peripheral nerve and cardiac muscle.

Vitamin D, with parathyroid hormone and calcitonin, is an essential factor in the homeostatic regulation of systemic calcium in most vertebrate species. Targets for this aspect of vitamin D action, through its biologically active metabolites, are primarily the intestine, kidney and bone. Each of these tissues or organs are stimulated by 1,25(OH)2D3 to increase the transport calcium into the extracellular fluid compartment when plasma calcium levels are below normal and/or when there is a greater need for calcium to meet the requirements of physiological processes, such as growth, gestation and lactation. During such periods, the efficiency of the absorption of calcium from the intestine increases, the resorption of calcium salts from bone is stimulated, and the efficiency of the reabsorption of filtered calcium by the renal tubule is increased. In addition to the homeostatic function of vitamin D, there is an increasing amount of evidence that vitamin D has important effects on tissues and organs other than those concerned with calcium homeostasis. With regard to the intestinal epithelial system, the genomic effect of 1,25(OH)2D3 was shown several years ago when the de novo synthesis of a specific vitamin D-induced calcium-binding protein (CaBP, calbindin-D) was demonstrated. In our view, this appears to be an essential factor in the well-documented enhancement of calcium absorption by vitamin D. The function of calbindin-D, a high affinity calcium-binding protein, in the absorptive process is not precisely known but currently considered to act as an intracellular facilitator of the diffusion of calcium from the microvillar pole of the enterocyte to the basal-lateral membrane. There is evidence that vitamin D influences another step in the absorptive process. This step appears to be associated with the entrance of luminal calcium into the enterocyte, the first step in the transepithelial transport process. This response appears to occur relatively early (1 h or less) after 1,25(OH)2D3 is given to vitamin D-deficient animals, whereas the de novo synthesis of transport proteins has a much longer lag time (about 4 h). The in vitro absorption studies of Nemere et al (1984) and the in vivo experiments of our group (Wasserman et al, 1982) accentuate this point. However, the more rapid reaction, i.e., the possible modification of the permeability properties of the brush border membrane, does not result in a substantive increase in overall calcium absorption unless the enterocyte had been "primed" by previous exposure to vitamin D. The "priming" reaction might represent the synthesis of CaBP or some other intracellular component.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1990

Circulating neuroactive peptides and the blood-brain and blood-cerebrospinal fluid barriers.

Interactions of radiolabelled circulating neuroactive peptides: enkephalin-leucine (Enk-Leu), delta sleep inducing peptide (DSIP), thyrotropin-releasing hormone (TRH) and vasopressin-arginine (VP-Arg) with the blood-brain and blood-cerebrospinal fluid barriers were studied by mean of: 1. a vascular perfusion technique in the guinea-pig using multiple-time brain uptake analysis, 2. a vascular perfusion technique of the in situ isolated choroid plexus from sheep using single-circulation paired-tracer dilution or steady-state analysis. It has been demonstrated that Enk-Leu, DSIP and VP-Arg were taken up intact at the luminal side of the blood-brain barrier and blood-tissue interface of the blood-cerebrospinal fluid barrier by a saturable mechanism. On the other hand, a non-saturable mechanism as well as possible enzymatic degradation were shown during TRH interactions with either the blood-brain or blood-cerebrospinal fluid barriers. It is concluded that both, facilitated and simple diffusion, govern circulating neuroactive peptide uptake into the central nervous system.

Animals↗
PubMed1988

[Effect of hyaluronidase on the end-plate miniature currents and potentials in the frog].

The effect of 0.1% hyaluronidase on miniature end-plate potentials and currents (MEPP and MEPC) was studied in the frog cutaneous-pectoris muscle. The action of hyaluronidase on armin-pretreated muscles caused a decrease in the amplitude, duration of half-decay time and rising phase of MEPPs and MEPCs. The positive correlation between the amplitude and half-decay time of MEPPs and MEPCs was diminished. Hyaluronidase treatment of preparations with active acetylcholinesterase caused the half-life time of MEPCs to increase without any changes in the amplitude and rising phase of MEPCs. It is suggested that enzymatic destruction of a part of the glycocalix of cells forming the neuromuscular junction and of a part of the extracellular matrix results in a weakening of the nonspecific acetylcholine binding, thus facilitating the acetylcholine diffusion into the synaptic cleft.

Animals↗
PubMed1977

Transport of amino acids and nucleic acid precursors in malarial parasites.

In vitro studies have shown that exogenously supplied amino acids are transferred into the malaria-infected cell, where they are incorporated into proteins. Most amino acids appear to enter the cell by facilitated or simple diffusion; however, the high distribution ratios seen in Plasmodium knowlesi-infected cells are difficult to explain on this basis. The changes (leakiness) observed in amino acid transport in P. lophurae infected cells are probably the result of ATP depletion in the host cell as well as the elaboration of plasmodial substances. Depletion of isoleucine, methionine, and cysteine from the medium strikingly depresses the in vitro growth of P. knowlesi. The degree of amino acid incorporation into the malaria-infected cell is not correlated with the amount of a particular amino acid in the host cell haemoglobin, the decline of that amino acid in the plasma of infected animals, or the ratio of free amino acids of the erythrocyte to those of the plasma. In erythrocyte-"free" P. lophurae, carrier-mediated transport is apparently limited to a small number of amino acids; all others seem to enter by simple diffusion.Malaria-infected erythrocytes transport exogenously supplied purines at substantially higher rates than uninfected red cells. The preferred purines are adenosine, hypoxanthine, and inosine. The only pyrimidine incorporated is orotic acid. Thymidine, cytidine, and uridine do not readily enter the red cell, and incorporation does not take place because the parasites lack the appropriate enzyme for conversion to nucleotides. Erythrocyte-"free" P. berghei and P. lophurae take up purines and orotic acid. It has been suggested that in vivo the preferred purines are hypoxanthine and inosine, and that the transport locus for erythrocytes is specific for 6-oxopurines. Similar results of purine incorporation are reported for the insect stages of P. cynomolgi and P. berghei, although transport studies have not been carried out.

Amino Acids↗
PubMed1993

From bench to bedside: research and testing of Internet resources and connections in community hospital libraries.

Access to information becomes more valuable with the continuing proliferation of medical knowledge and the increasing economic pressure being experienced by health care organizations. This is particularly so for community hospitals in rural or isolated areas, where the economic pressures are at least as great as in urban areas and where access to information is often inadequate. These conditions have implications for the quality of patient care and for economic viability. In response to this, the National Library of Medicine, the University of Washington, and seven community hospitals in five Pacific Northwest states have joined forces in a broad-scale technology diffusion project to facilitate the application of research work to clinical care. There are three components to the project: 1) a pilot connections component to extend Internet access to the community hospitals, 2) a research component to test the performance of a client/server model for network access to anatomical text and images, and 3) a clinical component to develop a registry of DNA diagnostic laboratories facilitating the provision of genetic information to clinicians. The pilot connections component is described and preliminary findings are reported.

Computer Communication Networks↗
PubMed1997

Report of the Canadian Hypertension Society Consensus Conference: 1. Definitions, evaluation and classification of hypertensive disorders in pregnancy.

OBJECTIVES: To provide Canadian physicians with a standard definition of hypertension in pregnancy, recommendations for laboratory investigations and tests for the assessment and management of hypertensive disorders in pregnancy, and a classification of such disorders. OPTIONS: To improve or not improve Canadian uniformity and standardization in the investigation and classification of hypertensive disorders in pregnancy. OUTCOMES: 1) Accuracy, reliability and practicality of diagnostic clinical criteria for hypertensive disorders in pregnancy. 2) Laboratory tests useful to determine severity and prognosis of disorders as measured by maternal and neonatal adverse outcomes. 3) A classification of disorders for use by Canadian physicians to facilitate uniformity and diffusion of research through a common language. EVIDENCE: Articles on hypertensive disorders in pregnancy published from 1966 to 1996, retrieved through MEDLINE search, related to definitions, tests, diagnostic criteria and classification, as well as documents on diagnosis and classification from authorities in the United States, Europe and Australia and from special interest groups. VALUES: High priority was given to the principle of preventing adverse maternal and neonatal outcomes through the provision of diagnostic criteria for severity and prognosis and through dissemination of reliable and pertinent information and research results using a common language. BENEFITS, HARMS AND COST: Higher degree of vigilance in diagnosing hypertensive disorders in pregnancy, allowing for earlier assessment and intervention, and more efficient dissemination of comparative information through common language. No harm or added cost is perceived at this time. RECOMMENDATIONS: (1) A diastolic blood pressure of 90 mm Hg or more should be the criterion for a diagnosis of hypertension in pregnancy and should trigger investigation and management. Except for very high diastolic readings (110 mm Hg or more), all diastolic readings of 90 mm Hg or more should be confirmed after 4 hours. (2) A regularly calibrated mercury sphygmomanometer, with an appropriate-sized cuff, is the instrument of choice. A rest period of 10 minutes should be allowed before taking the blood pressure. The woman should be sitting upright and the cuff positioned at the level of the heart. (3) Both Korotkoff phase IV and V sounds should be recorded, but the phase IV sound should be used for initiating clinical investigation and management. (4) A urine protein level of more than 0.3 g/d should be the criterion for a diagnosis of proteinuria; 24-hour urine collection should be the standard method for determining proteinuria. (5) Edema and weight gain should not be used as diagnostic criteria. (6) Hypertensive disorders diagnosed during pregnancy should be classified as pre-existing hypertension; gestational hypertension with or without proteinuria; pre-existing hypertension with superimposed gestational hypertension with proteinuria; and unclassifiable antenatally but final classification 42 days after delivery. VALIDATION: Except for expert opinions and reviews solicited for this project, these recommendations need to be field tested and validated in Canada. Guidelines endorsed by the Canadian Hypertension Society and the Society of Obstetricians and Gynaecologists of Canada.

Blood Pressure Determination↗