Intravascular Compartment Research Articles

Hypertension control with daily dialysis.

Hypertension is present in 60-90% of patients on maintenance hemodialysis (HD) and it is an important cause of cardiovascular (CV) mortality and morbidity. Frequent and prolonged HD has been uniformly shown to control hypertension in end-stage renal disease (ESRD) patients more effectively than conventional HD. The etiology of hypertension is predominantly volume dependent, but in a subset of patients increased renin, sympathetic overactivity, and endothelial dysfunction may play a role. Intradialytic hypotension precludes attainment of dry weight and hence optimal control of hypertension in conventional HD is challenging. Frequent and prolonged dialysis with gentle and persistent ultrafiltration allows time for refilling of the intravascular compartment and permits normalization of extracellular volume. It is also possible that intensive dialysis enables removal of pressor molecules and improves endothelial function. Improved blood pressure control translates into regression of left ventricular hypertrophy in patients on daily HD. Thus prolonged and frequent dialysis permits better control of hypertension via volume and volume-independent mechanisms and also improves cardiac geometry.

Peritoneovenous shunt insertion for intractable ascites: a district general hospital experience.

Ascites often contributes to patient morbidity and discomfort. When refractory to medical management, it has been managed with repeated paracentesis, implantable ports for drainage, or diversion to the urinary bladder. Peritoneovenous shunt insertion has been a technique that was traditionally performed only by surgeons but is now within the realm of interventional radiologists. Its advantage is that protein-rich ascitic fluid is returned to the intravascular compartment. This retrospective study elaborates on the successes and problems encountered during shunt insertion in our first 13 patients. Two patients are well with a functioning shunt at 14 and 32 weeks. In 6 the shunt functioned until the patients' death from the underlying malignancy. Two required revision with variable success and in 2, shunt function could not be salvaged. There was one procedure-related mortality. Radiological insertion of these shunts is feasible and should be considered for selected patients. Options are available for assessment and salvaging of dysfunctional shunts.

Recombinant prolylcarboxypeptidase activates plasma prekallikrein

AbstractThe serine protease prolylcarboxypeptidase (PRCP), isolated from human umbilical vein endothelial cells (HUVECs), is a plasma prekallikrein (PK) activator. PRCP cDNA was cloned in pMT/BIP/V5-HIS-C, transfected into Schneider insect (S2) cells, and purified from serum-free media. Full-length recombinant PRCP (rPRCP) activates PK when bound to high-molecular-weight kininogen (HK). Recombinant PRCP is inhibited by leupeptin, angiotensin II, bradykinin, anti-PRCP, diisopropyl-fluorophosphonate (DFP), phenylmethylsulfonyl fluoride (PMSF), and Z-Pro-Proaldehyde-dimethyl acetate, but not by 1 mM EDTA (ethylenediaminetetraacetic acid), bradykinin 1-5, or angiotensin 1-7. Corn trypsin inhibitor binds to prekallikrein to prevent rPRCP activation, but it does not directly inhibit the active site of either enzyme. Unlike factor XIIa, the ability of rPRCP to activate PK is blocked by angiotensin II, not by neutralizing antibody to factor XIIa. PRCP antigen is detected on HUVEC membranes using flow cytometry and laser scanning confocal microscopy. PRCP antigen does not colocalize with LAMP1 on nonpermeabilized HUVECs, but it partially colocalizes in permeabilized cells. PRCP colocalizes with all the HK receptors, gC1qR, uPAR, and cytokeratin 1 antigen, on nonpermeabilized HUVECs. PRCP activity and antigen expression on cultured HUVECs are blocked by a morpholino antisense oligonucleotide. These investigations indicate that rPRCP is functionally identical to isolated HUVEC PRCP and is a major HUVEC membrane-expressed, PK-activating enzyme detected in the intravascular compartment. (Blood. 2004;103:4554-4561)

Cerebral Neutrophil Recruitment, Histology, and Outcome in Acute Ischemic Stroke

Evidence now exists for a pathogenic role for neutrophils in acute cerebral ischemia. We have studied the patterns and temporal profile of cerebral neutrophil recruitment to areas of acute ischemic stroke (IS) and have attempted to correlate this with neurological status and outcome. Patients with cortical middle cerebral artery (MCA) IS were recruited within 24 hours of clinical onset. Neutrophil recruitment was studied using indium-111 (111In) troponolate-labeled neutrophils, planar imaging, and single-photon emission computed tomography (SPECT). Volume of brain infarction was calculated from concurrent computed tomography (CT). Hematoxylin and eosin sections were obtained postmortem (n=2). Outcome was measured using Barthel, Rankin, and National Institute of Health Stroke (NIHSS) scales. Fifteen patients were studied. Significant 111In-neutrophil recruitment to ipsilateral hemisphere, as measured by asymmetry index (AI), was demonstrated within 24 hours of onset in 9 patients; this response was heterogenous between patients and on repeated measurement attenuated over time. Histologically, recruitment was confirmed within intravascular, intramural, and intraparenchymal compartments. Interindividual heterogeneity in neutrophil response did not correlate with infarct volume or outcome. In an exploratory analysis, neutrophil accumulation appeared to correlate significantly with infarct expansion (Spearman rho=0.66; P=0.03, n=12). Neutrophils recruit to areas of ischemic brain within 24 hours of symptom onset. This recruitment attenuates over time and is confirmed histologically. While neutrophil accumulation may be associated with either the magnitude or the rate of infarct growth, these results require confirmation in future studies.

Crystalloids, colloids, blood, blood products and blood substitutes

Debate continues about the ideal replacement fluid for various clinical scenarios. To select the most appropriate fluid one must understand: • fluid distribution and homeostasis in the body • the pharmacology of the available intravenous solutions • the underlying pathology and its effects on normal physiology. The physiology of fluid replacement is discussed in Anaesthesia and Intensive Care Medicine 2:2: 67-9. Fluid administration initially results in expansion of the intravascular compartment. The extent and persistence of effects depend on whether there is free transfer across the vascular endothelium; the essential difference between crystalloid and colloid solutions.

Timing of neutrophil depletion influences long-term neuroprotection in neonatal rat hypoxic-ischemic brain injury.

In neonatal rats, neutrophils do not accumulate in ischemic brain parenchyma to the extent that they do in adult rodents. They are also confined to the intravascular compartment during the first few hours of recovery. However, neonatal rats rendered neutropenic have less brain swelling after a hypoxic-ischemic (HI) insult. In this study, we used the Rice-Vannucci model of HI brain injury in 7-d-old rats, and we depleted neutrophils before injury in one group and 4-8 h after injury in another group to determine 1) whether neutrophils contribute to cerebral atrophy, 2) whether neutropenia induced within 8 h after recovery from HI is neuroprotective, and 3) whether neutropenia preserved energy metabolites during the HI insult. Brain energy metabolites were measured at 0 h and 6 h of recovery. Brain atrophy was measured morphometrically on brain slices at 2 wk of recovery. In 67 rats, we found that neutropenia induced before the HI insult, but not after HI, reduced brain swelling at 42 h of recovery by about 75% (p < 0.001). In another 60 rats, we found that cerebral atrophy was reduced by 61% provided that neutropenia was induced before HI (p < 0.05). Total adenine nucleotides were better preserved in the neutropenic rats at the end of the HI insult (0 h recovery); p < 0.05. We conclude that neutrophils do contribute to vascular dysfunction either during the HI insult or early hours (<4-8 h) of recovery. Antineutrophil strategies initiated after this time are unlikely to be protective in the neonatal rat.

Inter-dialytic variations in blood volume and total body water in uraemic patients treated by dialysis.

An optimal balance of sodium and water is one of the most important goals of haemodialysis (HD) therapy. However, while inter-dialytic variations in blood volume (BV) have been well described, very little is known about the dynamics of fluid accumulation and distribution in body compartments during the inter-dialysis period. We studied inter-dialysis variations in BV, measured as percent variation of plasma haemoglobin (Hb) concentrations (% triangle up BV) and percent variation of total body water (% triangle up TBW), in 24 uraemic patients treated by standard bicarbonate dialysis. These parameters were determined at the end of the last weekly dialysis (T0), after 24 h (T1), 48 h (T2), and at the beginning of the following dialysis session (T3). At each time point we measured Hb, haematocrit (Hct), serum albumin (sAlb), plasma sodium (Na), plasma potassium (K), blood urea nitrogen (BUN), plasma osmolality (Osm), body weight (BW), systolic blood pressure (SBP), diastolic blood pressure (DBP) and heart rate (HR). All patients were clinically stable and had no evidence of acute blood loss in the 3 weeks before the study. During the inter-dialysis period, there were increases in BUN, K and Osm, but Na did not change. SBP and DBP also did not change. HR tended to decrease, and showed a significant reduction between T0 and T3. TBW increased in a linear fashion whereas BV increased exponentially, showing a slow rise during the first 24 h followed by a greater increase in the following time intervals. This was confirmed by concomitant but opposite percent variations in Hct and sAlb concentrations. Despite the limitations of the current methodology, our data show that the increase in TBW is redistributed during the long inter-dialysis period and this may prevent the effects of a too premature expansion of the intra-vascular compartment. This is especially evident during the first 24 h after HD, during which % triangle up BV is lowest, indicating a preferential distribution of the fluid load towards the extra-vascular space. During the following time intervals, the extra-vascular compartment refills in conjunction with an exponential expansion of BV that reaches its maximum in the last 24 h before HD.

Hypertonic solutions for pediatric patients

To describe the current knowledge and indications for use of hypertonic saline solutions in pediatrics patients. Medline recent review articles and personal files. Basic physiologic principles were reviewed concerning the distribution of fluid inside the intravascular, interstitial and intracellular compartments. We also reviewed the findings concerning the mechanisms responsible for the rapid onset of cardiocirculatory effects and the additional effect of the colloid component. Finally, we present the medical terms used in the context of small-volume resuscitation, the indications for clinical use, the evidence from clinical research (hemorrhagic shock, preclinical trauma care, septic shock, and head trauma), and the disadvantages and potential adverse effects of small-volume resuscitation. Resuscitation by means of hypertonic saline solutions associated or not with colloid solutions is one of the most innovative concepts for primary resuscitation from trauma and shock established in the past decade. Currently, the spectrum of potential indications involves not only prehospital trauma care, but also perioperative and intensive care therapy. However, additional randomized double-blind studies are required with both children and adult patients to confirm the advantages of the method in terms of survival.

The kallikrein-kinin and the renin-angiotensin systems have a multilayered interaction.

Understanding the physiological role of the plasma kallikrein-kinin system (KKS) has been hampered by not knowing how the proteins of this proteolytic system, when assembled in the intravascular compartment, become activated under physiological conditions. Recent studies indicate that the enzyme prolylcarboxypeptidase, an ANG II inactivating enzyme, is a prekallikrein activator. The ability of prolylcarboxypeptidase to act in the KKS and the renin-angiotensin system (RAS) indicates a novel interaction between these two systems. This interaction, along with the roles of angiotensin converting enzyme, cross talk between bradykinin and angiotensin-(1-7) action, and the opposite effects of activation of the ANG II receptors 1 and 2 support a hypothesis that the plasma KKS counterbalances the RAS. This review examines the interaction and cross talk between these two protein systems. This analysis suggests that there is a multilayered interaction between these two systems that are important for a wide array of physiological functions.

Contrast optimization and scan timing for single and multidetector-row computed tomography.

Various complex pharmacokinetic interrelationships affect the use of contrast media for computed tomography (CT) imaging. These include factors related to each patient's unique body habitus and their degree of health, such as their age, gender, height, weight, and cardiovascular status. Of equal importance are factors related to the contrast material injection. The volume, concentration, and rate of injection all affect the degree of enhancement that is achieved with an injection of contrast material. In addition, the injection technique--whether the contrast is infused at a constant injection rate (uniphasic injection) or whether the rate is altered during the injection (multiphasic injection)--also affects the magnitude and duration of contrast enhancement. In body CT imaging, the liver poses unique challenges in managing the use of intravenous contrast material because of its dual blood supply and the need to complete imaging before equilibrium occurs between the intravascular and extravascular compartments. The magnitude of hepatic enhancement that is ultimately achieved is related primarily to the amount of iodinated contrast material that accumulates in the extravascular space within the target organ, independent of the speed of the CT scanner. The key determinant of the onset of the equilibrium phase is the injection duration. Given that a high injection flow rate (4-5 ml/s) is desirable for arterial phase imaging, the injection duration is maintained by using an appropriate contrast volume. Thus, modifications of the total iodine dose are best performed by altering the contrast concentration. Use of a high contrast concentration (400 mg iodine/ml) may be advantageous in heavy patients, or in patients in whom routine imaging is married with a need for high-detail imaging of the vasculature with high resolution CT angiography. The magnitude of arterial enhancement that is achieved is related to both the concentration of contrast and the rate of administration. The speed of the scanner determines its ability to record image data during the most advantageous time period, the peak of arterial enhancement. Thus, rapid imaging is particularly advantageous for optimal contrast use in CT angiography as well as in multiphasic imaging of the parenchymal organs.

Assessment of myocardial blood volume and water exchange: theoretical considerations and in vivo results.

The measured signal response in contrast-enhanced myocardial perfusion imaging has been shown to be affected by the rate of water exchange between the intravascular and extravascular compartments, the effect being particularly significant when intravascular contrast agents are used. In the present study, the T(1) relaxation rates were measured in eight pigs in blood and myocardium using a Look-Locker sequence after repeated injections of the intravascular contrast agent NC100150. The selection of myocardial region of interest was automated based on a minimum chi-square method. The intra- and extravascular water exchange rates and the myocardial blood volume were calculated from the measured relaxation rates by applying a two-compartment water exchange limited model that accounts for biexponential longitudinal relaxation. The following (mean +/- SD) values were obtained for the exchange frequency (f), the extravascular residence time (tau(e)), the intravascular residence time (tau(i)) and blood volume (BV), respectively: f = 1.39 +/- 0.52 s(-1), tau(e) = 708 +/- 264 ms, tau(i) = 107 +/- 63 ms, and BV = 11.2 +/- 2.1 mL/100 g. The mean value of f was found to be about 15% higher if biexponential relaxation was not accounted for, supporting the hypothesis that significant biexponential relaxation in tissues with large blood volume can lead to an overestimation of water exchange rates unless corrected for.

Fluid shifts in anaphylaxis

EDITOR: We read the interesting article of Dr Iannuzzi and colleagues [1] and would like to illustrate the extent of fluid shifts induced by anaphylaxis, the necessity of volume support and catecholamine therapy. A 35-yr-old male (ASA I) presented for elective operation of the paranasal sinuses. Five minutes after induction of anaesthesia with propofol (200 mg), fentanyl (0.3 mg) and rocuronium (40 mg), the patient developed acute hypotension (systolic blood pressure below 40 mmHg), tachycardia (130 beats min−1) and a general grey complexion. Bronchospasm did not occur. H1- and H2-antagonists, methylprednisolone (500 mg) and norepinephrine (titrated 1.2 mg) were given. Two arterial blood samples taken 10 and 25 min after the beginning of this acute phase revealed an elevation of haemoglobin (Hb) concentration from 15 g dL−1 preoperatively to 19 g dL−1 (haematocrit, from 45.0 to 59.4%), an elevation of PaCO2 to 8.7 kPa (PaO2 = 10.1 kPa, SaO2 = 89%) and a decrease of pH to 7.19 with a base excess of −5 mmol L−1. This elevation of Hb concentration and haematocrit occurred because approximately 1.5 L of fluids had left the intravascular compartment (according to the formula of Nadler and colleagues [2]), although 1 L of colloidal and 2 L of crystalloids were given. Epinephrine, the preferred catecholamine in anaphylaxis [3], was not given because of tachycardia. Norepinephrine was the catecholamine of choice for cardiovascular stabilization. Skin prick testing and a leukocyte histamine release test [3] performed 6 weeks later revealed a type I allergy to rocuronium. We want to emphasize that in anaphylaxis massive fluid shifts can occur and must be treated adequately (as was done by Iannuzzi and colleagues [1]). Furthermore, it may be of benefit to use those catecholamines that differ from epinephrine for cardiovascular therapy. J. Dahn K. F. Waschke Department of Anaesthesia and Operative Intensive Care; University Hospital Mannheim; Mannheim, Germany B. A. Stuck K. Hörmann Department of Otorbinolaryngology; Head and Neck Surgery; University Hospital Mannheim; Mannheim, Germany

Thrombin and vascular development: a sticky subject.

Formation of the vasculature is an essential step in embryogenesis. It was observed decades ago that the vasculature and the intravascular blood compartment, which uses the former as a means of transportation, develop in a close spatial and temporal relationship. In this review, we discuss the role of the blood coagulation system as a tool to coordinate angiogenesis. Several mouse models lacking coagulation factors result in impaired thrombin generation and display a phenotype of disturbed cardiovascular development. Similar phenotypes are observed in mouse models of impaired thrombin binding to its cellular receptor, protease-activated receptor-1, or of disrupted signaling via G proteins. Most interestingly, the available data provide evidence that thrombin signaling in vascular development cannot be explained by a model based only on the classic extrinsic and intrinsic coagulation pathways. Because angiogenesis in adults follows the same signaling patterns as angiogenesis in embryos, it is important to learn about these pathways, hoping that they may serve as therapeutic targets in cardiovascular disease.

Use of high concentration contrast media (HCCM): principles and rationale—body CT

Numerous complex pharmacokinetic interrelationships affect the use of contrast media for computed tomography (CT) imaging. The volume, concentration, and rate of injection, all affect the degree of enhancement that is achieved with an injection of contrast material. In addition, the injection technique, whether the contrast is infused with a constant injection rate (uniphasic injection) or whether the rate is altered during the injection (multiphasic injection) also affect the magnitude and duration of contrast enhancement. In body CT imaging, the liver poses unique challenges in managing the use of intravenous contrast material because of its dual blood supply and the need to complete imaging before equilibrium occurs between the intravascular and extravascular compartments. The magnitude of hepatic enhancement that is ultimately achieved is related primarily to the amount of iodinated contrast material that accumulates in the extravascular space within the target organ, independent of the speed of the CT scanner. The key determinant of the onset of the equilibrium phase is the injection duration. Given that a high injection flow rate (4–5 ml/s) is desirable for arterial phase imaging, the injection duration is maintained with use of an appropriate contrast volume. Thus, modifications of total iodine dose are best done with alterations in contrast concentration. The magnitude of arterial enhancement that is achieved is related to both the concentration and rate of contrast administration. The speed of the scanner determines its ability to record image data during the most advantageous time period, the peak of arterial enhancement. Thus, rapid imaging is particularly advantageous for optimal contrast use in CT angiography as well as in multiphasic imaging of the parenchymal organs.

Transvascular and intravascular fluid transport in the rainbow trout: revisiting Starling's forces, the secondary circulation and interstitial compliance.

The kinetics of transvascular fluid transport across fish capillaries and redistribution of fluids between intravascular compartments in intact fish are unknown. Cannulae were placed in the dorsal aorta (DA) and caudal vein (CV) of rainbow trout Oncorhynchus mykiss (mass 0.45-0.85 kg) and the fish spleenectomized. The following day a peristaltic pump was fitted to complete the extracorporeal arterio-venous circulation. Hematocrit (Hct) was monitored in unanesthetized fish either manually, by collecting blood from the extracorporeal loop at 5 min intervals for a period of 1 h (groups 1 and 2), or continuously (instantaneously) with an impedance flow-cell inserted in the aortic cannula (group 3). Fish in group 1 were volume expanded by injecting a volume of saline (0.9 g% NaCl; SI) or trout plasma (PI) equivalent to 40% of the plasma volume. In group 2, 20% or 35% of the blood volume was removed, and in group 3, 35% of the blood volume was removed. Plasma volume (Vp) was calculated from an assumed blood volume of 35 ml kg(-1) and the Hct. Vp declined mono-exponentially after SI with a half-time of 6.8 min and Vp reached a new steady state at 28.1 ml kg(-1); 30% of the injected volume remained in the vasculature. Volume recovery after PI was also mono-exponential, but slower (half-time=15.4 min) than SI, whereas the steady-state Vp (27.3 ml kg(-1)) was similar and 30% of the injected volume remained in the vasculature. Thus the presence of plasma proteins delayed fluid efflux from the vasculature, but did not affect the volume lost. Transvascular fluid filtration coefficients calculated from this data were 5.5 (SI) and 4.5 ml mmHg(-1) kg(-1) min(-1) (PI), and interstitial compliance was 11.8 (SI) and 9.7 ml mmHg(-1) kg(-1) (PI). The rate of volume recovery after 20% or 35% hemorrhage was independent of the hemorrhage volume (half-time=13.3 and 15.1 min, respectively) and similar to the half-time of PI, indicating that protein-rich interstitial fluid is returned to the vasculature. There is a nearly instantaneous change in Hct that occurs during the hemorrhage period; it is dependent on hemorrhage duration and volume and not associated with the subsequent mono-exponential recovery. This initial response is best explained by a rapid fluid shift from a large-volume (approximately 40% of total blood volume), low-hematocrit (less than half of systemic Hct) microcirculation into the higher-hematocrit macrocirculation. These studies are consistent with transcapillary fluid flux across a barrier that is highly permeable to protein, and cannot be explained by fluid shift between primary and secondary circulations, or by transcapilllary flux across a capillary bed that is impermeable to plasma proteins. The results support the hypothesis that whole-body reflection coefficients in trout are very low and that plasma oncotic pressure is not a determinant of transcapillary fluid balance. They also show that both transvascular and intravascular fluid movements are important effectors of central volume homeostasis.

Enhanced green fluorescent protein-transfection of murine colon carcinoma cells: key for early tumor detection and quantification.

Many animal models for metastatic colorectal cancer represent clinical manifestations just inaccurately. We introduce a novel mouse model for metastastatic colorectal cancer. In order to remain close to the clinical disease a syngenic murine colon carcinoma cell line (colon 26 cells) was transfected with enhanced green fluorescent protein (EGFP). The transfected cells maintain the highly malignant attributes of the wild-type cells. Following injection into the portal circulation of Balb/c-mice, liver metastases occur in the same time span. Using the fluorescent attributes of the transfected cells, an approximation of the tumor load in liver tissue can be achieved by fluorescence activated cell sorting (FACS) and fluoroscan analysis. Tumor cell load in liver tissue can be accurately measured by Northern blot and Western blot analysis of liver tissue containing EGFP-transfected colon cancer metastases (1250 cells/mg liver tissue and 1000 cells/mg liver tissue) respectively. Confocal microscopy and intravital microscopy confirmed the growth of tumor metastases, originating from the intravascular compartments. The presented animal model using EGFP-transfected colon 26 cells allows the detecting of tumor growth in vivo and post mortem, as well as an accurate quantification of the tumor load in the liver tissue.

Nitrate tolerance: a unifying hypothesis.

) production, endo-thelial dysfunction, and the neurohormonal activation that followlong-term administration of organic nitrates. In this issue ofCirculation, we will try to integrate these observations withother separate, and, to a certain extent, antagonistic hypothesesthat have been proposed for the development of nitrate toler-ance.

Síndrome de hiperestimulación ovárica: clasificación, fisiopatología y manejo

El síndrome de hiperestimulación ovárica es una complicación iatrogénica de la inducción de la ovulación con gonadotropinas y puede resultar en una grave amenaza para la vida por sus complicaciones; como son: accidente cerebro-vascular debido a trombosis venosa, disfunción hepática, falla renal aguda, complicaciones respiratorias y torsión anexial. El mayor factor predisponente de la forma severa del SHO es el ovario poliquístico.El síndrome se caracteriza por una salida del fluido del espacio intravascular, con acumulación de líquido en espacio peritoneal y pleural, produciéndose hipotensión y una disminución del flujo sanguíneo renal y, por consiguiente, una disminución del volumen urinario. El aumento de la permeabilidad capilar es la hipótesis más aceptada para el inicio de la fisiopatología del evento. El factor de crecimiento endotelial y la presencia de otras citoquinas es crucial en la patogénesis del SHO.La clasificación del síndrome nos permite realizar esquemas de tratamiento lógicos, así tenemos que el SHO leve únicamente amerita reposo e hidratación oral. El SHO moderado se trata conservadoramente con observación ambulatoria, analgésicos, antieméticos, monitorización ecográfica, evaluación de la función renal, hepática, hematocrito y coagulación. El SHO severo, sin cambios anormales del perfil bioquímico, es tratado con aspiración del líquido ascítico, suministro de líquidos endovenosos sobre la base de los cuidados diarios del tratamiento. En caso de SHO con disbalance hidroelectrolítico u otras complicaciones, la paciente debe ser hospitalizada para un manejo apropiado. El manejo quirúrgico se reserva para casos de torsión o ruptura de quiste, o tratamiento de embarazo ectópico.

"Coasting" (withholding gonadotrophins) for preventing ovarian hyperstimulation syndrome.

Ovarian hyperstimulation syndrome (OHSS) is an iatrogenic and potentially life threatening condition resulting from excessive ovarian stimulation. Its reported incidence varies from 1% to 10% of in vitro fertilization (IVF) cycles. The factors leading to this syndrome have not been completely explained. It seems likely that the release of vasoactive substances, secreted by the ovaries under human chorionic gonadotropin (hCG) stimulation plays a key role in triggering this syndrome. The hallmark of this condition, is a massive shift of fluid from the intra-vascular compartment to the third space resulting in profound intra-vascular depletion and hemoconcentration. The objective of this review is to assess the effect of "coasting" (withholding gonadotrophins) as a preventative strategy in the management of OHSS following superovulation in assisted reproduction treatment on the incidence of all clinical grades of OHSS, in comparison with "early unilateral follicular aspiration (EUFA)" or other interventions. Publications in the literature that described randomised controlled trials (RCTs) in which "coasting" was used as a preventative strategy to OHSS were included. The Cochrane Menstrual Disorders and Subfertility Review Group specialised register of controlled trials was searched. In addition, MEDLINE (PUBMED) 1985 to 2002, EMBASE (1985 to 2001), CINHAL (1985 to 2001) and National Research Register were also searched. Randomised controlled trials (RCTs) in which coasting was used as a preventative strategy to OHSS were included. Two reviewers, Mr N.N. Amso (NNA) and Dr A. D'Angelo (ADA) scanned the titles and the abstracts of the reports identified by electronic searching in order to find relevant papers. One reviewer (ADA) obtained copies of the full text articles and made copies for the other reviewer (NNA) in which details of authors, institution, results and discussion were removed in order to assess their eligibility for inclusion. Then, both reviewers extracted data independently using forms designed according to Cochrane guidelines. Disagreements were resolved by discussion. Additional information on the trial methodology or data were requested by writing twice to the corresponding authors directly. The interventions compared were "coasting" versus "early unilateral follicular aspiration (EUFA)" or no "coasting" or other interventions. Statistical analysis was performed in accordance with the Cochrane Menstrual Disorders and Subfertility Group guidelines. This review identified thirteen studies but only one trial met our inclusion criteria. There was no difference in the incidence of moderate and severe OHSS (n=30, OR 0.76, 95% CI 0.18, 3.24)and in the clinical pregnancy rate (n=30, OR 0.75, 95% CI 0.17, 3.33) between the groups. There is a lack of randomised controlled trials for where coasting is compared with no coasting or other interventions such as embryo freezing or intra-venous albumin infusion for prevention of OHSS. There is insufficient evidence to determine if coasting is an effective strategy for preventing OHSS.

Fluid status of terminally ill cancer patients with intestinal obstruction: an exploratory observational study.

Although the dehydration-rehydration problem in end-of-life care is one of the most important issues, clinical indications of hydration therapy have not been clarified because the pathophysiology is poorly understood. To explore the physiological changes of fluid status in terminally ill cancer patients, a prospective observational study was performed. We obtained 9 pairs of blood samplings from hospice inpatients with irreversible bowel obstruction who underwent two or more laboratory examinations during the admission periods. The plasma renin activity (PRA) and brain natriuretic peptide (BNP) were measured, in addition to basic laboratory tests performed as clinically required. A chart review evaluated the degree of fluid retention symptoms. In 7 patients receiving intravenous rehydration of 700-2200 ml/day, the mean PRA level significantly increased from 3.5+/-2.5 ng ml(-1) h(-1) to 11+/-8.2 ng ml(-1) x h(-1) ( P=0.047), and the mean BNP level significantly decreased from 52+/-34 pg/ml to 22+/-14 pg/ml ( P=0.047). Edema, ascites, and pleural effusion/pulmonary edema deteriorated in 5, 3, and 5 patients, respectively. In 2 patients without rehydration therapy, peripheral edema deteriorated with increased PRA levels (0.5 to 20 ng ml(-1) x h(-1), 0.4 to 8.7 ng ml(-1) x h(-1), respectively). In conclusion, intravenous volume depletion with fluid retention symptoms was observed in terminally ill cancer patients with intestinal obstruction both receiving and not receiving intravenous hydration. The pathological mechanism hypothesized is the fluid shift from the intravascular compartment to the interstitial spaces.