Regulation of glycolysis by the hypoxia-inducible factor (HIF): implications for cellular physiology.

Under conditions of hypoxia, most eukaryotic cells can shift their primary metabolic strategy from predominantly mitochondrial respiration towards increased glycolysis to maintain ATP levels. This hypoxia-induced reprogramming of metabolism is key to satisfying cellular energetic requirements during acute hypoxic stress. At a transcriptional level, this metabolic switch can be regulated by several pathways including the hypoxia inducible factor-1α (HIF-1α) which induces an increased expression of glycolytic enzymes. While this increase in glycolytic flux is beneficial for maintaining bioenergetic homeostasis during hypoxia, the pathways mediating this increase can also be exploited by cancer cells to promote tumour survival and growth, an area which has been extensively studied. It has recently become appreciated that increased glycolytic metabolism in hypoxia may also have profound effects on cellular physiology in hypoxic immune and endothelial cells. Therefore, understanding the mechanisms central to mediating this reprogramming are of importance from both physiological and pathophysiological standpoints. In this review, we highlight the role of HIF-1α in the regulation of hypoxic glycolysis and its implications for physiological processes such as angiogenesis and immune cell effector function.

Succinate is an inflammatory signal that induces IL-1ß through HIF-1α.

Macrophages activated by the Gram-negative bacterial product lipopolysaccharide switch their core metabolism from oxidative phosphorylation to glycolysis. Here we show that inhibition of glycolysis with 2-deoxyglucose suppresses lipopolysaccharide-induced interleukin-1ß but not tumour-necrosis factor-α in mouse macrophages. A comprehensive metabolic map of lipopolysaccharide-activated macrophages shows upregulation of glycolytic and downregulation of mitochondrial genes, which correlates directly with the expression profiles of altered metabolites. Lipopolysaccharide strongly increases the levels of the tricarboxylic-acid cycle intermediate succinate. Glutamine-dependent anerplerosis is the principal source of succinate, although the 'GABA (γ-aminobutyric acid) shunt' pathway also has a role. Lipopolysaccharide-induced succinate stabilizes hypoxia-inducible factor-1α, an effect that is inhibited by 2-deoxyglucose, with interleukin-1ß as an important target. Lipopolysaccharide also increases succinylation of several proteins. We therefore identify succinate as a metabolite in innate immune signalling, which enhances interleukin-1ß production during inflammation.

Neutrophil-derived 5'-adenosine monophosphate promotes endothelial barrier function via CD73-mediated conversion to adenosine and endothelial A2B receptor activation.

During episodes of inflammation, polymorphonuclear leukocyte (PMN) transendothelial migration has the potential to disturb vascular barrier function and give rise to intravascular fluid extravasation and edema. However, little is known regarding innate mechanisms that dampen fluid loss during PMN-endothelial interactions. Using an in vitro endothelial paracellular permeability model, we observed a PMN-mediated decrease in endothelial paracellular permeability. A similar decrease was elicited by cell-free supernatants from activated PMN (FMLP 10(-6) M), suggesting the presence of a PMN-derived soluble mediator(s). Biophysical and biochemical analysis of PMN supernatants revealed a role for PMN-derived 5'-adenosine monophosphate (AMP) and its metabolite, adenosine, in modulation of endothelial paracellular permeability. Supernatants from activated PMN contained micromolar concentrations of bioactive 5'-AMP and adenosine. Furthermore, exposure of endothelial monolayers to authentic 5'-AMP and adenosine increased endothelial barrier function more than twofold in both human umbilical vein endothelial cells and human microvascular endothelial cells. 5'-AMP bioactivity required endothelial CD73-mediated conversion of 5'-AMP to adenosine via its 5'-ectonucleotidase activity. Decreased endothelial paracellular permeability occurred through adenosine A2B receptor activation and was accompanied by a parallel increase in intracellular cAMP. We conclude that activated PMN release soluble mediators, such as 5'-AMP and adenosine, that promote endothelial barrier function. During inflammation, this pathway may limit potentially deleterious increases in endothelial paracellular permeability and could serve as a basic mechanism of endothelial resealing during PMN transendothelial migration.

Hypoxia-inducible factor 1-dependent induction of intestinal trefoil factor protects barrier function during hypoxia.

Mucosal organs such as the intestine are supported by a rich and complex underlying vasculature. For this reason, the intestine, and particularly barrier-protective epithelial cells, are susceptible to damage related to diminished blood flow and concomitant tissue hypoxia. We sought to identify compensatory mechanisms that protect epithelial barrier during episodes of intestinal hypoxia. Initial studies examining T84 colonic epithelial cells revealed that barrier function is uniquely resistant to changes elicited by hypoxia. A search for intestinal-specific, barrier-protective factors revealed that the human intestinal trefoil factor (ITF) gene promoter bears a previously unappreciated binding site for hypoxia-inducible factor (HIF)-1. Hypoxia resulted in parallel induction of ITF mRNA and protein. Electrophoretic mobility shift assay analysis using ITF-specific, HIF-1 consensus motifs resulted in a hypoxia-inducible DNA binding activity, and loading cells with antisense oligonucleotides directed against the alpha chain of HIF-1 resulted in a loss of ITF hypoxia inducibility. Moreover, addition of anti-ITF antibody resulted in a loss of barrier function in epithelial cells exposed to hypoxia, and the addition of recombinant human ITF to vascular endothelial cells partially protected endothelial cells from hypoxia-elicited barrier disruption. Extensions of these studies in vivo revealed prominent hypoxia-elicited increases in intestinal permeability in ITF null mice. HIF-1-dependent induction of ITF may provide an adaptive link for maintenance of barrier function during hypoxia.

Synovial tissue hypoxia and inflammation in vivo.

INTRODUCTION: Hypoxia is a microenvironmental feature in the inflamed joint, which promotes survival advantage for cells. The aim of this study was to examine the relationship of partial oxygen pressure in the synovial tissue (tPO(2)) in patients with inflammatory arthritis with macroscopic/microscopic inflammation and local levels of proinflammatory mediators. METHODS: Patients with inflammatory arthritis underwent full clinical assessment and video arthroscopy to quantify macroscopic synovitis and measure synovial tPO(2) under direct visualisation. Cell specific markers (CD3 (T cells), CD68 (macrophages), Ki67 (cell proliferation) and terminal deoxynucleotidyl transferase dUTP nick end labelling (cell apoptosis)) were quantified by immunohistology. In vitro migration was assessed in primary and normal synoviocytes (synovial fibroblast cells (SFCs)) using a wound repair scratch assay. Levels of tumour necrosis factor alpha (TNFalpha), interleukin 1beta (IL1beta), interferon gamma (IFNgamma), IL6, macrophage inflammatory protein 3alpha (MIP3alpha) and IL8 were quantified, in matched serum and synovial fluid, by multiplex cytokine assay and ELISA. RESULTS: The tPO(2) was 22.5 (range 3.2-54.1) mm Hg and correlated inversely with macroscopic synovitis (r=-0.421, p=0.02), sublining CD3 cells (-0.611, p<0.01) and sublining CD68 cells (r=-0.615, p<0.001). No relationship with cell proliferation or apoptosis was found. Primary and normal SFCs exposed to 1% and 3% oxygen (reflecting the median tPO(2) in vivo) induced cell migration. This was coupled with significantly higher levels of synovial fluid tumour necrosis factor alpha (TNFalpha), IL1beta, IFNgamma and MIP3alpha in patients with tPO(2) <20 mm Hg (all p values <0.05). CONCLUSIONS: This is the first study to show a direct in vivo correlation between synovial tPO(2), inflammation and cell migration, thus it is proposed that hypoxia is a possible primary driver of inflammatory processes in the arthritic joint.

Systemic inflammation: a key factor in the pathogenesis of cardiovascular complications in obstructive sleep apnoea syndrome?

Obstructive sleep apnoea syndrome (OSAS) is a highly prevalent disease and is recognised as a major public health burden. Large-scale epidemiological studies have demonstrated an independent relationship between OSAS and various cardiovascular disorders. The pathogenesis of cardiovascular complications in OSAS is not completely understood but a multifactorial aetiology is likely. Inflammatory processes have emerged as critical in the pathogenesis of atherosclerosis at all stages of atheroma formation. Increased levels of various circulating markers of inflammation including tumour necrosis factor alpha (TNFalpha), interleukin 6 (IL6), IL-8 and C-reactive protein (CRP) have been reported as associated with future cardiovascular risk. There is increasing evidence of elevated inflammatory markers in OSAS with a significant fall after effective treatment with continuous positive airway pressure. This evidence is particularly strong for TNFalpha, whereas studies on IL6 and CRP have yielded conflicting results possibly due to the confounding effects of obesity. Cell culture and animal studies have significantly contributed to our understanding of the underlying mechanisms of the association between OSAS and inflammation. Intermittent hypoxia, the hallmark of OSAS, results in activation of pro-inflammatory transcription factors such as nuclear factor kappa B (NF-kappaB) and activator protein (AP)-1. These promote activation of various inflammatory cells, particularly lymphocytes and monocytes, with the downstream consequence of expression of pro-inflammatory mediators that may lead to endothelial dysfunction. This review provides a critical analysis of the current evidence for an association between OSAS, inflammation and cardiovascular disease, discusses basic mechanisms that may be responsible for this association and proposes future research possibilities.

Cardiovascular disease in obstructive sleep apnoea syndrome: the role of intermittent hypoxia and inflammation.

There is increasing evidence that intermittent hypoxia plays a role in the development of cardiovascular risk in obstructive sleep apnoea syndrome (OSAS) through the activation of inflammatory pathways. The development of translational models of intermittent hypoxia has allowed investigation of its role in the activation of inflammatory mechanisms and promotion of cardiovascular disease in OSAS. There are noticeable differences in the response to intermittent hypoxia between body tissues but the hypoxia-sensitive transcription factors hypoxia-inducible factor-1 and nuclear factor-kappaB appear to play a key role in mediating the inflammatory and cardiovascular consequences of OSAS. Expanding our understanding of these pathways, the cross-talk between them and the activation of inflammatory mechanisms by intermittent hypoxia in OSAS will provide new avenues of therapeutic opportunity for the disease.

Systemic inflammation: a key factor in the pathogenesis of cardiovascular complications in obstructive sleep apnoea syndrome?

Obstructive sleep apnoea syndrome (OSAS) is a highly prevalent disease and is recognised as a major public health burden. Large-scale epidemiological studies have demonstrated an independent relationship between OSAS and various cardiovascular disorders. The pathogenesis of cardiovascular complications in OSAS is not completely understood but a multifactorial aetiology is likely. Inflammatory processes have emerged as critical in the pathogenesis of atherosclerosis at all stages of atheroma formation. Increased levels of various circulating markers of inflammation including tumour necrosis factor alpha (TNFalpha), interleukin 6 (IL6), IL-8 and C-reactive protein (CRP) have been reported as associated with future cardiovascular risk. There is increasing evidence of elevated inflammatory markers in OSAS with a significant fall after effective treatment with continuous positive airway pressure. This evidence is particularly strong for TNFalpha, whereas studies on IL6 and CRP have yielded conflicting results possibly due to the confounding effects of obesity. Cell culture and animal studies have significantly contributed to our understanding of the underlying mechanisms of the association between OSAS and inflammation. Intermittent hypoxia, the hallmark of OSAS, results in activation of pro-inflammatory transcription factors such as nuclear factor kappa B (NF-kappaB) and activator protein (AP)-1. These promote activation of various inflammatory cells, particularly lymphocytes and monocytes, with the downstream consequence of expression of pro-inflammatory mediators that may lead to endothelial dysfunction. This review provides a critical analysis of the current evidence for an association between OSAS, inflammation and cardiovascular disease, discusses basic mechanisms that may be responsible for this association and proposes future research possibilities.

Activated endothelial cells elicit paracrine induction of epithelial chloride secretion. 6-Keto-PGF1alpha is an epithelial secretagogue.

Endothelial cells play a central role in the coordination of the inflammatory response. In mucosal tissue, such as the lung and intestine, endothelia are anatomically positioned in close proximity to epithelia, providing the potential for cell-cell crosstalk. Thus, in this study endothelial-epithelial biochemical crosstalk pathways were studied using a human intestinal crypt cell line (T84) grown in noncontact coculture with human umbilical vein endothelia. Exposure of such cocultures to endothelial-specific agonists (LPS) resulted in activation of epithelial electrogenic Cl- secretion and vectorial fluid transport. Subsequent experiments revealed that in response to diverse stimuli (LPS, IL-1alpha, TNF-alpha, hypoxia), endothelia produce and secrete a small, stable epithelial secretagogue into conditioned media supernatants. Further experiments identified this secretagogue as 6-keto-PGF1alpha, a stable hydrolysis product of prostacyclin (PGI2). Results obtained with synthetic prostanoids indicated that 6-keto-PGF1alpha (EC50 = 80 nM) and PGI2 stable analogues (EC50 = 280 nM) activate the same basolaterally polarized, Ca2+-coupled epithelial receptor. In summary, these findings reveal a previously unappreciated 6-keto-PGF1alpha receptor on intestinal epithelia, the ligation of which results in activation of electrogenic Cl- secretion. In addition, these data reveal a novel action for the prostacyclin hydrolysis product 6-keto-PGF1alpha and provide a potential endothelial- epithelial crosstalk pathway in mucosal tissue.

Parallel induction of epithelial surface-associated chemokine and proteoglycan by cellular hypoxia: implications for neutrophil activation.

Neutrophil-induced damage to the protective epithelium has been implicated in mucosal disorders associated with hypoxia, and such damage may be initiated by epithelial-derived chemokines. Because chemokines can bind to membrane proteoglycans, we hypothesized that chemokines may associate with epithelial surfaces and activate polymorphonuclear neutrophils (PMN). Epithelial hypoxia (pO2 20 torr) resulted in a time-dependent induction of interleukin-8 (IL-8) mRNA, soluble protein, as well as surface protein. Such surface IL-8 expression was demonstrated to be dependent on heparinase III expression, and extensions of these experiments indicated that hypoxia induces epithelial perlecan expression in parallel with IL-8. Finally, co-incubation of post-hypoxic epithelia with human PMN induced IL-8-dependent expression of the PMN beta2-integrin CD11b/18. These data indicate that chemokines liberated from epithelia may exist in a surface-bound, bioactive form and that hypoxia may regulate proteoglycan expression.

MRI findings in patients with a history of failed prior microvascular decompression for hemifacial spasm: how to image and where to look.

BACKGROUND AND PURPOSE: A minority of patients who undergo microvascular decompression for hemifacial spasm do not improve after the first operation. We sought to determine the most common locations of unaddressed neurovascular contact in patients with persistent or recurrent hemifacial spasm despite prior microvascular decompression. MATERIALS AND METHODS: Eighteen patients with a history of a microvascular decompression presented with persistent hemifacial spasm. All patients underwent thin-section steady-state free precession MR imaging. Fourteen patients underwent repeat microvascular decompression at our institution. Images were evaluated for the following: the presence of persistent vascular compression of the facial nerve, type of culprit vessel (artery or vein), name of the culprit artery, segment of the nerve in contact with the vessel, and location of the point of contact relative to the existing surgical pledget. The imaging findings were compared with the operative findings. RESULTS: In 12 of the 18 patients (67%), persistent vascular compression was identified by imaging. In 11 of these 12 patients, the culprit vessel was an artery. Compression of the attached segment (along the ventral surface of the pons) was identified in most patients (58%, 7/12). The point of contact was proximal to the surgical pledget in most patients (83%, 10/12). The imaging interpretation was concordant with the surgical results regarding artery versus vein in 86% of cases and regarding the segment of the nerve contacted in 92%. CONCLUSIONS: In patients with persistent hemifacial spasm despite microvascular decompression, the unaddressed vascular compression is typically proximal to the previously placed pledget, usually along the attached segment of the nerve. Re-imaging with high-resolution T2-weighted MR imaging will usually identify the culprit vessel.

Intolerance of uncertainty as a mediator of reductions in worry in a cognitive behavioral treatment program for generalized anxiety disorder.

Growing evidence suggests that intolerance of uncertainty (IU) is a cognitive vulnerability that is a central feature across diverse anxiety disorders, including generalized anxiety disorder (GAD). Although cognitive behavioral therapy (CBT) has been shown to reduce IU, it remains to be established whether or not reductions in IU mediate reductions in worry. This study examined the process of change in IU and worry in a sample of 28 individuals with GAD who completed CBT. Changes in IU and worry, assessed bi-weekly during treatment, were analyzed using multilevel mediation models. Results revealed that change in IU mediated change in worry (ab = -0.20; 95% CI [-.35, -.09]), but change in worry did not mediate change in IU (ab = -0.16; 95% CI [-.06, .12]). Findings indicated that reductions in IU accounted for 59% of the reductions in worry observed over the course of treatment, suggesting that changes in IU are not simply concomitants of changes in worry. Findings support the idea that IU is a critical construct underlying GAD.

Berberine inhibition of electrogenic ion transport in rat colon.

1. The effects of the alkaloid berberine on basal and stimulated ion transport were investigated in voltage-clamped rat colonic epithelia. 2. Berberine (100-500 microM) reduced basal short circuit current (SCC) when applied basolaterally but not when applied apically. 3. SCC responses to mast cell activation by anti-rat IgE were significantly attenuated in the presence of berberine. 4. Berberine, applied to the basolateral bathing solution, also reduced SCC responses to the following agents which stimulate chloride secretion in rat colon: carbachol, forskolin, sodium nitroprusside, dibutyryl cyclic-AMP, heat-stable E. coli enterotoxin, 8-bromo-cyclic GMP and thapsigargin. Calcium mediated ion transport responses appear to be more sensitive to berberine inhibition than those which are cyclic GMP-mediated, which in turn are more sensitive than cyclic AMP-mediated responses. 5. Berberine added apically was without effect upon forskolin-stimulated ion transport. Cytochalasin D treatment of the lumenal surface of rat colon conferred apical-side sensitivity to berberine. 6. Berberine (at concentrations up to 500 microM) was without effect on generation of cyclic AMP by forskolin or on generation of cyclic GMP by sodium nitroprusside in isolated mucosal segments. Protein kinase A activity stimulated by dibutyryl cyclic AMP was unaffected by berberine (at concentrations up to 500 microM). 7. The precise mechanism of action of berberine remains to be elucidated. However, its site of action appears to be distal to second messenger production and may be at a level common to all stimuli of colonic chloride secretion.

Characteristics of trophoblastic tissue derived from in vitro culture of preimplantation embryos of the common marmoset monkey.

The features of trophoblastic tissue derived from the in vitro culture of marmoset monkey embryos have been described. Long-term trophoblast cultures (in excess of three years in one case) were established from the primary trophoblast monolayer of four of 38 embryos; division of one of these embryos produced two long-term cultures. The trophoblast cells retained their ability to synthesize and secrete chorionic gonadotrophin (CG) during maintenance in vitro and were capable of prolonging the luteal phase when transferred to the uterus of marmosets. A characteristic feature of the cultures was the formation of multiple fluid-filled vesicles enclosed by a single layer of cytotrophoblast cells and attached to the culture dish by a small monolayer of syncytiotrophoblast cells. The tissue was propagated by cutting vesicles into small pieces and placing into a fresh culture dish; attempts to subculture using single-cell suspensions were unsuccessful. These cultures provide a convenient source of marmoset CG for purification as well as an in vitro system for studying other secretory products of primate trophoblast.

Soluble CD46 (membrane cofactor protein, MCP) in human reproductive tract fluids.

CD46 (membrane cofactor protein, MCP) is a cell surface complement regulatory protein which may have an additional role in human sperm-egg interaction. A soluble form (sCD46) has also been detected in a number of biological fluids, most notably seminal plasma. The present study has employed a monoclonal antibody-based ELISA to assay sCD46 in reproductive tract fluids in normal and pathological conditions. Large amounts of sCD46 were detected in seminal plasma of both fertile and infertile men (combined mean, 4859 ng/ml). Vasectomized men had lower levels (mean, 2421 ng/ml), indicating contributory sources both before and after the vas deferens ligation site. Pre-colostrum also contained relatively high quantities (mean, 445 ng/ml), whereas breast milk (mean, 117 ng/ml), peritoneal fluid (mean, 154 ng/ml) and follicular fluid (mean, 107 ng/ml), as well as uterine (mean, 208 ng/ml), umbilical (mean, 166 ng/ml) and peripheral (mean, 206 ng/ml) blood plasma, had sCD46 levels within a comparable range. Amniotic fluid had low sCD46 concentrations (mean, 22 ng/ml). In endometriosis, peritoneal fluid levels of sCD46 were significantly raised (mean, 199 mg/ml). These results indicate distinctive fluid compartmentalisation of sCD46 consistent with a biological function in human reproductive tract fluids.

Quality of life and Parkinson's disease.

BACKGROUND: People with Parkinson's disease (PD) have a progressive loss of function eventually leading to severe disability. Although PD would be expected to have a profound impact on an individual's psychosocial health, there is relatively limited research on its psychosocial effect. The purposes of this study were (a) to examine the relationships between physical disability, depression, and control beliefs and quality of life in people with PD and (b) to characterize how these psychosocial variables differ by stage of disease. METHODS: Eighty-six individuals from five stages based on clinical disability, ages 51-87, were interviewed. Established instruments were used to measure physical disability, depression, and control beliefs. Quality of life (QOL) was rated on a 5-point Likert scale. RESULTS: A multivariable regression model including physical disability, stage of disease, depression, mastery, and health locus of control predicted QOL (R2 = 0.48), with mastery as the only significant predictor (p = .0001). There were significant differences by PD stage for all variables (p < .05). CONCLUSIONS: Mastery predicted quality of life in individuals with PD even when depression and physical disability were included in the model. Differences in psychosocial variables by stage of PD suggest that the psychosocial profile of PD patients may change as the disease progresses.

The appearance of a second genotype of Japanese encephalitis virus in the Australasian region.

In mid-January 2000, the reappearance of Japanese encephalitis (JE) virus activity in the Australasian region was first demonstrated by the isolation of JE virus from 3 sentinel pigs on Badu Island in the Torres Strait. Further evidence of JE virus activity was revealed through the isolation of JE virus from Culex gelidus mosquitoes collected on Badu Island and the detection of specific JE virus neutralizing antibodies in 3 pigs from Saint Pauls community on Moa Island. Nucleotide sequencing and phylogenetic analyses of the premembrane and envelope genes were performed which showed that both the pig and mosquito JE virus isolates (TS00 and TS4152, respectively) clustered in genotype I, along with northern Thai, Cambodian, and Korean isolates. All previous Australasian JE virus isolates belong to genotype II, along with Malaysian and Indonesian isolates. Therefore, for the first time, the appearance and transmission of a second genotype of JE virus in the Australasian region has been demonstrated.

U50,488H-induced pressor effect in the ovine foetus is mediated by sympathetic activation and vasopressin.

The purpose of this study was to investigate the mechanism behind the increase in blood pressure observed after intravenous administration of U50,488H (trans-3,4-dichloro-N-[2-(1-pyrrolidinyl)cyclohexyl]benzeneacetamide), a selective Kappa-opioid receptor agonist, to the ovine foetus. Intravenous administration of U50,488H (1.0 mg/kg) to the foetus resulted in an immediate increase in foetal blood pressure which lasted 15 min. Pretreatment with phentolamine (1.0 mg/kg i.v.) completely blocked the immediate (1-4 min) pressor effect of U50,488H, but not the subsequent increase in blood pressure after 5 min. In contrast, pretreatment with the vasopressin antagonist ([beta-mercapto-beta, beta-cyclopentamethylene-propionyl)-O-Me2-Tyr,Arg8]vasopressin, 0.06 mg/kg) did not affect the immediate pressor effect of U50,488H, but completely blocked the latter increase in blood pressure after 4 min. These data suggest that the immediate increase in blood pressure caused by U50,488H was mediated by sympathetic activation which was then further sustained by a release of vasopressin.

Berberine inhibits ion transport in human colonic epithelia.

The effects of berberine on ion transport in both human colonic mucosal epithelia and an intestinal epithelial cell line (T84) were examined. Berberine (concentration range 0-500 microM) reduced both basal and stimulated ion transport responses in human colonic mucosae in a manner which was non-specific for Ca2+ -or cAMP-mediated signals. Similarly, in cultured intestinal epithelial monolayers, berberine inhibited Ca2+ -and cAMP-mediated responses indicating an inhibitory activity directly at the level of the epithelium rather than an indirect effect through other mucosal element(s). Berberine did not alter the rate of generation of cAMP by adenylyl cyclase or the activity of protein kinase A, the effector enzyme of the cAMP pathway. Berberine inhibited carbachol-stimulated 86Rb+ efflux from T84 monolayers. Berberine also inhibited K+ conductance in apically-permeabilised re-sected mucosae. These results indicate i) that berberine exerts an anti-secretory action directly upon epithelial cells and ii) the mechanism of action may be at the level of blockade of K+ channels.

Transport in vitro fertilization--a novel scheme for community-based treatment.

OBJECTIVE: To provide an inexpensive and extensive in vitro fertilization (IVF) service for the Mersey Region, United Kingdom. DESIGN: Twenty-four transport IVF patients treated in two district general hospitals using the central university laboratory as co-ordination point for treatment schedule and embryology. Outcomes were compared with 26 control patients treated in the central unit. SETTING: Royal Liverpool University Hospital, a central IVF unit, and two district general hospitals in the Mersey Region. PATIENTS: Fifty patients under 35 years of age with irreversible tubal damage selected and treated by IVF, half in the central unit and the other half in two district general hospitals. MAIN OUTCOME MEASURES: Pregnancy rate (PR) in the different centers. RESULTS: A PR of 42.3% per cycle in the peripheral hospitals compared with 30.7% per cycle in the central unit. CONCLUSION: Transport IVF is an inexpensive and feasible alternative to standard IVF in a central unit for patients without access to central units.