Unnamed 11/04/2011

• ScienceDirect - The Lancet : Fabry's disease

  • Fabry's disease
  • X-linked lysosomal storage disorder
  • deficiency in α-galactosidase A.
  • Fabry's disease has been identified in different patient populations who have cardiac, renal, or cerebrovascular disease with no other known causes. Its prevalence in patients with end-stage renal disease who are on haemodialysis ranges between 0·2% and 1·2%; in adult male patients with cryptogenic stroke and male patients with unexplained left ventricular hypertrophy (LVH) or hypertrophic cardiomyopathy it could be as high as 3–4%
  • Deficiency of α-galactosidase A leads to storage of neutral glycosphingolipids, particularly globotriaosylceramid and galactosylceramide,
  • 5–10% of residual enzyme activity seems to be sufficient to prevent clinically significant accumulation of globotriaosylceramid.<!--refPreviewPlaceHolder-->11 JT Clarke, Narrative review: Fabry disease. Ann Intern Med,  146  (2007), pp. 425–433. | | Cited By in Scopus (47)
  • at least partly poor perfusion caused by storage in the vascular endothelium particularly in kidneys, heart, nervous system, and skin alone or in combination with damage from deposits in other cell types
  • Pain and acroparesthesia are believed to be caused by either poor perfusion of the peripheral nerves or lysosomal accumulation of glycosphingolipids in neurons, dorsal root ganglia, and spinal cord,<!--refPreviewPlaceHolder-->¹² which leads to atrophy of the small unmyelinated nerves

  • ---

    
    <!--Comment-->

    
    High-quality image (413K)

    Figure 1. 

    <!--Comment-->Progression of clinical findings in Fabry's disease with age

  • Cardiac disease is associated with accumulation of globotriaosylceramid in all cellular components of the heart, including cardiomyocytes, conduction system cells, valvular fibroblasts, endothelial cells, and vascular smooth-muscle cells
  • patients with Fabry's disease show a prominent thickening of the common carotid artery intima, abnormalities of cerebrovascular autoregulation and vasoreactivity, and dysfunction of cerebral circulation with substantial cerebral hyperperfusion in the posterior cerebral circulation, all of which seem to have a considerable role in the pathophysiology of neurovascular disease.^{<!--refPreviewPlaceHolder-->  [15]  and <!--refPreviewPlaceHolder-->  [16]}
  • Storage in vascular endothelium leads to vascular occlusion, which leads to glomerulosclerosis and eventually to renal failure.^{<!--refPreviewPlaceHolder-->  [17]  and <!--refPreviewPlaceHolder-->  [18]}  Storage in podocytes is well documented, although it is not completely related to the amount of proteinuria.
  • three consecutive age periods.
  • Early symptoms in children include burning pain in the hands and feet, hypohydrosis, nausea, abdominal pain, postprandial diarrhoea, poor growth, and school difficulties
  • fter age 20 years, these symptoms tend to progress and proteinuria often presents in men.
  • . Other affected organ systems also progress, leading to life-threatening cardiac and cerebrovascular manifestations with substantial morbidit
  •   Cardiac death is most frequent in women, and although the most frequent cause of death in men was end-stage renal failure, cardiac and cerebrovascular complications are more prevalent than previously in the present era of transplants and dialysis.
  • Pain is not only the earliest manifestation of Fabry's disease but also one of the most disabling complications
  • The classic cardiac abnormality is hypertrophic cardiomyopathy rather than restrictive.
  • initially by myocardial hypertrophy and as the disease progresses, interstitial abnormalities and replacement myocardial fibrosis become important.

  • Cardiac manifestations in Fabry's disease

    <!--Comment-->

    • •	<!--listPara-->Valvular disease: valves are thickened and distorted, with mild-to-moderate regurgitation. Changes are most frequently found on left heart valves (mitral insufficiency)

    • •	<!--listPara-->Left ventricular hypertrophy (LVH): concentric remodelling in early stages, which progresses later to concentric hypertrophy, septal and posterior wall thickness

    • •	<!--listPara-->Right ventricular hypertrophy: does not seem to have major functional or clinical consequences

    • •	<!--listPara-->Ischaemia: vasospastic or stenotic coronary artery disease leads to myocardial infarction, angina, and chest pain, particularly in patients with LVH

    • •	<!--listPara-->Electrocardiogram abnormalities: voltage criteria for LVH and repolarisation changes. Short PR interval, bundle branch block, atrioventricular conduction delay, and progressive sinus node dysfunction

    • •	<!--listPara-->Arrhythmias: bradycardia, supraventricular tachycardias, atrial fibrillation, atrial flutter, and cardiac sudden death

  • earliest manifestation of abnormal rhythm is bradycardia
  • frequency of stroke in men aged 25–44 years can be 12 times higher than that expected in the general population,
  • Gastrointestinal disturbance is the second most common symptom reported in childhood and tends to persist into adulthood
  • Symptoms include nausea, vomiting, abdominal pain, and diarrhoea, especially associated with meals.^{<!--refPreviewPlaceHolder-->} 
  • Angiokeratomas (characteristic reddish-purple skin lesions, <!--refPreviewPlaceHolder-->figure 2) are commonly seen at presentation when physicians carefully search for them, but are easily overlooked and rarely associated with substantial medical problems. They will develop in about 40% of male adolescents with classic Fabry's disease at a median age of onset of 14–16 years
  • hey tend to increase in number and size with age, and tend to cluster around the umbilicus and swimming trunk regions
  • 
    <!--Comment-->

    
    High-quality image (605K)

    Figure 2. 

    <!--Comment-->Typical angiokeratomas

  • Decreased sweating (hypohidrosis) is another common problem in men, which has been attributed to both a main effect on the sweat glands and to autonomic neuropathy. More than 50% of men and 25% of women have proved to have decreased sweating or heat intolerance, or both, in childhood
  • pohidrosis leads to heat intolerance and decreased ability to exercise, and both tend to worsen with age.^{<!--refPreviewPlaceHolder-->  [2]  and <!--refPreviewPlaceHolder-->  [37]}  It might affect employability and limit young patients from participation in sports or other physical activities. Hyperhidrosis (excessive sweating) has also been described. It is frequently exacerbated by stress, fever, and changes in temperature, and typically affects the palms of the hands and soles of the feet. Hypohidrosis is more frequent than hyperhidrosis is and affects more men than women, although hyperhidrosis is more prevalent in women than in men
  • Distinctive corneal opacities (cornea verticillata and a specific diagnostic sign, which is characterised by one or more lines that irradiate from a point near the centre of the cornea) are seen in most patients
  • 
    <!--Comment-->

    
    High-quality image (181K)

    Figure 3. 

  • Hoigne and others<!--refPreviewPlaceHolder-->⁸¹ reported that the combination of four criteria in patients with LVH at baseline—acroparesthesia or polyneuropathy, anhydrosis, absence of hypertension, and presence of Sokolow criteria for LVH—were useful to distinguish Fabry's disease from other disorders.
  • Pieroni and others<!--refPreviewPlaceHolder-->82 M Pieroni, C Chimenti and F De Cobelli, et al. Fabry's disease cardiomyopathy: echocardiographic detection of endomyocardial glycosphingolipid compartmentalization. J Am Coll Cardiol,  47  (2006), pp. 1663–1671. Article | PDF (440 K) | | | Cited By in Scopus (35)⁸² noted that Fabry's cardiomyopathy could be identified with echocardiography by observation of a hypoechogenic line described as a subendocardial binary appearance, which was absent in controls and those with hypertrophic cardiomyopathy.

  • Gold-standard methods to diagnose Fabry's disease

    <!--Comment-->Men

    <!--Comment-->

    • •	<!--listPara-->α-galactosidase A activity in peripheral leucocytes or plasma if leucocyte analysis is unavailable

    • •	<!--listPara-->α-galactosidase A gene sequencing and identification of disease-causing mutation or testing for all known familial mutations

    • •	<!--listPara-->α-galactosidase A gene sequencing and identification of disease-causing mutation or testing for a known familial mutation (α-galactosidase A activity in peripheral leucocytes is not preferred and plasma levels are unreliable)

    • •	<!--listPara-->α-galactosidase A gene sequencing assessing for a known familial mutation

• Calcium Handling in the Failing Heart and SUMO — Weighing the Evidence — NEJM

  • Calcium Handling in the Failing Heart and SUMO — Weighing the Evidence
  • First, extracellular calcium enters the cell through L-type calcium channel
  • resultant increase in intracellular calcium concentration leads to type 2 ryanodine receptor opening and release of calcium from the sarcoplasmic reticulum
  • reversal of these changes occurs during cardiac relaxation (diastole),
  • emoval occurs by means of calcium extrusion through the sodium–calcium exchanger and reuptake of calcium into the sarcoplasmic reticulum through ryanodine receptor 2 closing and, most important of all, through activation of isoform 2a of sarcoendoplasmic reticulum calcium ATPase (SERCA2a)
  • Reduced expression and activity of SERCA2a have been shown in animal models of heart failure and in cardiomyocytes isolated from hearts explanted from patients undergoing transplantation
  • increasing SERCA2a expression is associated with improved inotropy and lusitropy of isolated cardiomyocytes and with improved cardiac function in experimental models of heart failure.
  • levels and activity of SERCA2a in cardiomyocytes are modulated in parallel with the levels of a cytoplasmic protein, small ubiquitin-like modifier type 1 (SUMO1
  • sumoylation appeared to prolong the lifetime of SERCA2a in the cell as well as increase the intrinsic activity of SERCA2a ATPase.

• Ulcerative Colitis — NEJM

  • When inflammatory bowel disease is identified in a new population, ulcerative colitis invariably precedes Crohn's disease and has a higher incidence
  • Among children, however, ulcerative colitis is less prevalent than Crohn's disease
  • A westernized environment and lifestyle is linked to the appearance of inflammatory bowel disease, which is associated with smoking, diets high in fat and sugar, medication use, stress, and high socioeconomic status.13 Inflammatory bowel disease has also been associated with appendectomy.13 Of these factors, only cigarette smoking and appendectomy are reproducibly linked to ulcerative colitis. Smoking is associated with milder disease, fewer hospitalizations, and a reduced need for medications.14 Removal of an inflamed appendix in early life is associated with a decreased incidence of ulcerative colitis,15 whereas the opposite is true for Crohn's disease.
  • Risk loci for ECM1, HNF4A, CDH1, and LAMB1 implicate dysfunction of the epithelial barrier; an association with DAP suggests a link to apoptosis and autophagy; and associations with PRDM1, IRF5, and NKX2-3 suggest defects in transcriptional regulation. In addition, multiple genes in the interleukin-23 signaling pathway overlap in ulcerative colitis and Crohn's disease (e.g., IL23R, JAK2, STAT3, IL12B, and PTPN2)
  • In both ulcerative colitis and Crohn's disease, epithelial cells have a decreased ability to activate suppressor CD8+ T ce
  • Autoimmunity may play a role in ulcerative colitis. In addition to pANCA, this disease is characterized by circulating IgG1 antibodies against a colonic epithelial antigen that is shared with the skin, eye, joints, and biliary epithelium41; since these are the sites of extraintestinal manifestations in ulcerative colitis, it is possible that cross-reacting antibodies against the colon cause organ-specific damage. Tropomyosin 5, a structural protein, is the putative target autoantigen of the IgG1 antibodies,42 but evidence of classical antibody-mediated autoimmunity in ulcerative colitis is still lacking.
  • In ulcerative colitis, inflammation is characteristically restricted to the mucosal layer, with infiltrates varying in density and composition during active disease or stages of remission
  • Sulfasalazine and 5-aminosalicylates (mesalamine, olsalazine, and balsalazide), given orally, rectally (by means of suppository or enema), or both, represent first-line treatment for ulcerative colitis, with an expected remission rate of about 50%
  • Mild-to-moderate proctitis can be treated with mesalamine suppositories (1 g per day) or enemas (2 to 4 g per day); clinical remission occurs in most patients within 2 weeks, with repeated treatments as needed. If this fails, 5-aminosalicylate enemas (2 to 4 g per day) or glucocorticoid enemas (hydrocortisone at a dose of 100 mg per day, or new preparations such as budesonide or beclomethasone) are a next step.61-63 Patients who do not have a response to rectally administered agents may be given oral glucocorticoids (up to 40 mg of prednisone or its equivalent).
  • Patients with mild-to-moderate ulcerative colitis that is refractory to rectal therapies and to oral 5-aminosalicylate are candidates for oral glucocorticoids or immunosuppressive agents (azathioprine or 6-mercaptopurine);
  • ontinue to require glucocorticoid therapy and for those who do not have a response to it, a good therapeutic option appears to be infliximab
  • Unlike Crohn's disease, ulcerative colitis may respond to probiotic therapy. For example, Escherichia coli strain Nissle 1917 (200 mg per day) is not less effective than 5-aminosalicylate (1.5 g per day) for maintaining remission,80 and the probiotic VSL#3 (3600 billion colony-forming units per day for 8 weeks) in conjunction with 5-aminosalicylate can help induce remission in mild-to-moderate ulcerative colitis

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Unnamed 10/26/2011

• Henoch-Schönlein Purpura Nephritis: Pathophysiology, Treatment, and Future Strategy

  • Because acute HSPN episodes are often triggered by an upper respiratory tract infection (11), the removal of any source of chronic bacterial infection should be theoretically beneficial.

• Section IV/CHAPTER 22/Definitions from Comprehensive Clinical Nephrology

  • IgA Nephropathy and Henoch-Schönlein Nephritis
  • CHAPTER 18 – Primary and Secondary (Non-Genetic) Causes of Focal and Segmental Glomerulosclerosis
  • C3 is codeposited in up to 90% of cases
  • Serum IgA levels are increased in one third of patients with IgAN and HSP
  • 40% to 50% of cases, the clinical presentation is episodic macroscopic hematuria, most frequently in the second and third decades of life.
  • HSP is most prevalent in the first decade of life but may occur at any age. A palpable purpuric rash, which may be recurrent, occurs on extensor surfaces
  • C5b-9 is found with properdin but not C4, indicating alternative complement pathway activation.
  • ynpharyngitic hematuria
  • Two distinct patterns of injury are seen in AKI. There may be tubular occlusion by red cells with acute tubular epithelial injury in macrohematuria-associated AKI (Fig. 22.7). Alternatively, glomerular injury may be the cause of AKI with necrotizing GN and cellular crescent formation. Such crescentic IgAN may develop on a histologic background of established chronic renal injury due to IgAN or may be the first presentation of IgAN.
  • There is good evidence that circulating
  • mesangial pIgA1 comes from the mucosal immune system. In IgAN, however, pIgA1 production is downregulated in the mucosa and upregulated in the bone marrow. Moreover, the pIgA response to systemic immunization with common antigens is increased, whereas the response to mucosal immunization is impaired
  • IgA1 in IgAN and HS nephritis has abnormal O-linked hinge-region sugars with reduced galactosylation because of altered IgA production in lymphocytes of patients with IgAN
  • Complement deposits are usually C3 and properdin without C1q and C4.
  • Asymptomatic urine testing identifies 30% to 40% of patients with IgAN in most reported series
  • n a few unwitting experiments, cadaver kidneys with IgA deposits have been transplanted into recipients without IgAN. In all cases, the IgA rapidly disappeared, supporting the concept that abnormalities in IgAN lie in the IgA immune system and not in the kidney.
  • . The renal prognosis is worse in adults than in children. In adults, up to 40% will have CKD or ESRD 15 years after biopsy.
  • IgA antineutrophil cytoplasmic antibodies (IgA-ANCA) have been proposed as a marker of the systemic features that differentiate HSP from IgAN. Circulating IgA-ANCA has been described in HSP, although findings are not consistent. IgA-ANCA is not found in IgAN.

• ScienceDirect - American Journal of Kidney Diseases : Human Cytomegalovirus and Kidney Transplantation: A Clinician's Update

  • Human Cytomegalovirus and Kidney Transplantation: A Clinician's Update
  • detection of viral replication by phosphoprotein 65 antigenemia or CMV DNA polymerase chain reaction

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Technology in (Medical) Education: A 50 dollar Smart Board?

Technology in (Medical) Education: A 50 dollar Smart Board?: "While reading a recent article in Edutopia ' Why integrate technology into the curriculum? The reasons are many. ' I found a post by Chris w..."

Targeted inhibition of complement activation prevents features of preeclampsia in mice

Targeted inhibition of complement activation prevents features of preeclampsia in mice: "

Targeted inhibition of complement activation prevents features of preeclampsia in mice

Kidney International 79,
331 (February (1) 2011). doi:10.1038/ki.2010.393

Authors: Xiaoping Qing, Patricia B Redecha, Melissa A Burmeister, Stephen Tomlinson, Vivette D D'Agati, Robin L Davisson
& Jane E Salmon

"

Angiotensin II: breathtaking in the renal medulla

Angiotensin II: breathtaking in the renal medulla: "

Angiotensin II: breathtaking in the renal medulla

Kidney International 79,
269 (February (1) 2011). doi:10.1038/ki.2010.434

Author: Volker H Haase

"

Serum Iron Markers Are Inadequate for Guiding Iron Repletion in Chronic Kidney Disease

Serum Iron Markers Are Inadequate for Guiding Iron Repletion in Chronic Kidney Disease: "Background and objectives

Iron (Fe) overload may complicate parenteral Fe therapy used to enhance the efficacy of erythropoietic-stimulating agents in the treatment of anemia of chronic kidney disease. However, serum Fe markers are influenced by inflammation or malignancy and may not accurately reflect the amount of body Fe.

Design, setting, participants, & measurements

We studied the relationship between parenteral Fe therapy, conventional serum Fe markers, and liver iron concentration (LIC) measured using magnetic resonance R2 relaxometry (FerriScan) in 25 Fe-deficient predialysis chronic kidney disease patients before and 2 and 12 weeks after single high-dose intravenous Fe and in 15 chronic hemodialysis patients with elevated serum ferritin (>500 µg/L).

Results

In predialysis patients, there was strong dose dependency between the administered Fe dose and changes in LIC at weeks 2 and 12; however, no dose dependency between Fe dose and changes in ferritin or transferrin saturation (TSAT) were observed. In hemodialysis patients, LIC correlated with the cumulative Fe dose and duration of dialysis but not with current ferritin or TSAT. The cumulative Fe dose remained a significant independent predictor of LIC in a multiple regression model. Two dialysis patients who received >6 g parenteral Fe had substantially elevated LIC >130 µmol/g, which is associated with hemochromatosis.

Conclusions

In Fe-deficient predialysis patients, intravenous Fe therapy is associated with increases in LIC unrelated to changes in conventional Fe markers. In hemodialysis patients, TSAT and ferritin are poor indicators of body Fe load, and some patients have LICs similar to those found in hemochromatosis.

"

Beyond genetics: epigenetic code in chronic kidney disease

Beyond genetics: epigenetic code in chronic kidney disease: "

Beyond genetics: epigenetic code in chronic kidney disease

Kidney International 79,
23 (January (1) 2011). doi:10.1038/ki.2010.335

Authors: Rama S Dwivedi, James G Herman, Timothy A McCaffrey
& Dominic S C Raj

The best succinct review of epigenetics

Theory of gastric CO(2) ventilation and its control during respiratory acidosis: implications for central chemosensitivity, pH regulation, and diseases causing chronic CO(2) retention Gastric CO(2) ventilation during respiratory acidosis.

Theory of gastric CO(2) ventilation and its control during respiratory acidosis: implications for central chemosensitivity, pH regulation, and diseases causing chronic CO(2) retention Gastric CO(2) ventilation during respiratory acidosis.: "

Theory of gastric CO(2) ventilation and its control during respiratory acidosis: implications for central chemosensitivity, pH regulation, and diseases causing chronic CO(2) retention Gastric CO(2) ventilation during respiratory acidosis.

Respir Physiol Neurobiol. 2010 Dec 6;

Authors: Dean JB

The theory of gastric CO(2) ventilation describes a previously unrecognized reflex mechanism controlled by neurons in the caudal solitary complex (cSC) for non-alveolar elimination of systemic CO(2) during respiratory acidosis. Neurons in the cSC, which is a site of CO(2) chemosensitivity for cardiorespiratory control, also control various gastroesophageal reflexes that remove CO(2) from blood. CO(2) is consumed in the production of gastric acid and bicarbonate in the gastric epithelium and then reconstituted as CO(2) in the stomach lumen from the reaction between H(+) and HCO(3)(-). Respiratory acidosis and gastric CO(2) distension induce cSC/vagovagal mediated transient relaxations of the lower esophageal sphincter to vent gastric CO(2) upwards by bulk flow along an abdominal-to-esophageal (= intrapleural) pressure gradient the magnitude of which increases during abdominal (gastric) compression caused by increased contractions of respiratory muscles. Esophageal distension induces cSC/nucleus ambiguus/vagovagal reflex relaxation of the upper esophageal sphincter and CO(2) is vented into the pharynx and mixed with pulmonary gas during expiration or, alternatively, during eructation. It is proposed that gastric CO(2) ventilation provides explanations for 1) the postprandial increase in expired CO(2) and 2) the negative P(blood-expired)(CO)difference that occurs during increased metabolic CO(2) production. Furthermore, it is postulated that gastric CO(2) ventilation and alveolar CO(2) ventilation are coordinated under dual control by CO(2) chemosensitive neurons in the cSC. This new theory, therefore, presupposes a level of neural control and coordination between two previously presumed dissimilar organ systems and supports the notion that different sites of CO(2) chemosensitivity address different aspects of whole body pH regulation. Consequently, not all sites of central chemosensitivity are equal regarding the mechanism(s) activated for CO(2) elimination. A distributed CO(2) chemosensitive network-at least nine different areas in the CNS, including the cSC, have been reported to date-may reflect the complexity and dynamic nature of the fundamental neural circuitry required to achieve CO(2)/pH regulation across multiple organ systems under various states of arousal, oxygenation, pH status, and redox state. Moreover, coordination of respiratory and digestive control networks through the cSC could also account for the frequent co-expression of pulmonary diseases that cause chronic respiratory acidosis (and overstimulation of cSC neurons) with peptic ulcer disease or gastroesophageal reflux disease.

PMID: 21144912 [PubMed - as supplied by publisher]

"

Evolutionary biology: Genomic hourglass

Evolutionary biology: Genomic hourglass: "

Evolutionary biology: Genomic hourglass

Nature 468, 7325 (2010). doi:10.1038/468768a

Authors: Benjamin Prud'homme & Nicolas Gompel

Comparative genomics studies reveal molecular signatures of the controversial 'phylotypic' stage — a time when embryos of members of an animal phylum all look more alike than at other embryonic stages. See Letters p.811 & p.815

"

Developmental biology: Placenta key to fetal growth rate

Developmental biology: Placenta key to fetal growth rate: "

Developmental biology: Placenta key to fetal growth rate

Nature 468, 7324 (2010). doi:10.1038/468603d

Gestation period varies widely in the mammalian world, with some species developing twice as fast as others in the womb. This is largely because of differences in the arrangement of fetal and maternal tissues in the placenta.Isabella Capellini at Durham University, UK, and her

"

Developmental biology: Placenta key to fetal growth rate

Developmental biology: Placenta key to fetal growth rate: "

Developmental biology: Placenta key to fetal growth rate

Nature 468, 7324 (2010). doi:10.1038/468603d

Gestation period varies widely in the mammalian world, with some species developing twice as fast as others in the womb. This is largely because of differences in the arrangement of fetal and maternal tissues in the placenta.Isabella Capellini at Durham University, UK, and her

"

Placental microRNA expression in pregnancies complicated by preeclampsia.

Placental microRNA expression in pregnancies complicated by preeclampsia.: "

Placental microRNA expression in pregnancies complicated by preeclampsia.

Am J Obstet Gynecol. 2010 Nov 18;

Authors: Enquobahrie DA, Abetew DF, Sorensen TK, Willoughby D, Chidambaram K, Williams MA

OBJECTIVE:: The role of posttranscription regulation in preeclampsia is largely unknown. We investigated preeclampsia-related placental microRNA (miRNA) expression using microarray and confirmatory quantitative real-time polymerase chain reaction experiments. STUDY DESIGN:: Placental expressions of characterized and novel miRNAs (1295 probes) were measured in samples collected from 20 preeclampsia cases and 20 controls. Differential expression was evaluated using Student t test and fold change analyses. In pathway analysis, we examined functions/functional relationships of targets of differentially expressed miRNAs. RESULTS:: Eight miRNAs were differentially expressed (1 up-regulated and 7 down-regulated) among preeclampsia cases compared with controls. These included previously identified candidates (miR-210, miR-1, and a miRNA in the 14q32.31 cluster region) and others that are novel (miR-584 and miR-34c-5p). These miRNAs target genes that participate in organ/system development (cardiovascular and reproductive system), immunologic dysfunction, cell adhesion, cell cycle, and signaling. CONCLUSION:: Expression of miRNAs that target genes in diverse pathophysiological processes is altered in the setting of preeclampsia.

PMID: 21093846 [PubMed - as supplied by publisher]

"

The "Great Obstetrical Syndromes" are associated with disorders of deep placentation.

The "Great Obstetrical Syndromes" are associated with disorders of deep placentation.: "

The 'Great Obstetrical Syndromes' are associated with disorders of deep placentation.

Am J Obstet Gynecol. 2010 Nov 20;

Authors: Brosens I, Pijnenborg R, Vercruysse L, Romero R

Defective deep placentation has been associated with a spectrum of complications of pregnancy including preeclampsia, intrauterine growth restriction, preterm labor, preterm premature rupture of membranes, late spontaneous abortion, and abruptio placentae. The disease of the placental vascular bed that underpins these complications is commonly investigated with targeted biopsies. In this review, we critically evaluate the biopsy technique to summarize the salient types of defective deep placentation, and propose criteria for the classification of defective deep placentation into 3 types based on the degree of restriction of remodeling and the presence of obstructive lesions in the myometrial segment of the spiral arteries.

PMID: 21094932 [PubMed - as supplied by publisher]

"

D2-40/podoplanin expression in the human placenta.

D2-40/podoplanin expression in the human placenta.: "

D2-40/podoplanin expression in the human placenta.

Placenta. 2010 Nov 20;

Authors: Wang Y, Sun J, Gu Y, Zhao S, Groome LJ, Alexander JS

Placental tissue expresses many lymphatic markers. The current study was undertaken to examine if D2-40/podoplanin, a lymphatic endothelial marker, was expressed in the human placenta, and how it is altered developmentally and pathologically. We examined D2-40/podoplanin and VEGFR-3 expressions in placentas from normotensive pregnancies at different gestational ages and in placentas from women with clinically defined preeclampsia. D2-40 expression in systemic lymphatic vessel endothelium served as a positive control. Protein expression for D2-40, VEGFR-3, and β-actin was determined by Western blot in placentas from normotensive (n = 6) and preeclamptic (n = 5) pregnancies. Our results show that D2-40/podoplanin was strongly expressed in the placenta, mainly as a network plexus pattern in the villous stroma throughout gestation. CD31 was limited to villous core fetal vessel endothelium and VEGFR-3 was found in both villous core fetal vessel endothelium and trophoblasts. D2-40/podoplanin expression was significantly decreased, and VEGFR-3 significantly increased in preeclamptic placental tissues compared to normotensive placental controls. Placental villous stroma is a reticular-like structure, and the localization of D2-40 to the stroma suggests that a lymphatic-like conductive network may exist in the human placenta. D2-40/podoplanin is an O-linked sialoglycoprotein. Although little is known regarding biological functions of sialylated glycoproteins within the placenta, placental D2-40/podoplanin may support fetal vessel angiogenesis during placenta development and reduced D2-40/podoplanin expression in preeclamptic placenta may contribute to altered interstitial fluid homeostasis and impaired angiogenesis in this pregnancy disorder.

PMID: 21095001 [PubMed - as supplied by publisher]

"

Maternal Cardiac Dysfunction and Remodeling in Women With Preeclampsia at Term.

Maternal Cardiac Dysfunction and Remodeling in Women With Preeclampsia at Term.: "

Maternal Cardiac Dysfunction and Remodeling in Women With Preeclampsia at Term.

Hypertension. 2010 Nov 22;

Authors: Melchiorre K, Sutherland GR, Baltabaeva A, Liberati M, Thilaganathan B

Preeclampsia is a disease associated with significant cardiovascular morbidity during pregnancy and in later life. This study was designed to evaluate cardiac function and remodeling in preeclampsia occurring at term. This was a prospective case-control study of 50 term preeclampsia and 50 normal pregnancies assessed by echocardiography and tissue Doppler analysis. Global diastolic dysfunction was observed more frequently in preeclampsia versus control pregnancies (40% versus 14%, P=0.007). Increased cardiac work and left ventricular mass indices suggest that left ventricular remodeling was an adaptive response to maintain myocardial contractility with preeclampsia at term. Approximately 20% of patients with preeclampsia at term have more evident myocardial damage. Diastolic dysfunction usually precedes systolic dysfunction in the evolution of ischemic or hypertensive cardiac diseases and is of prognostic value in the prediction of long-term cardiovascular morbidity. The study findings also have significant implications for the acute medical management of preeclampsia.

PMID: 21098311 [PubMed - as supplied by publisher]

"

The Role of Embryonic Origin in Preeclampsia: A Comparison of Autologous In Vitro Fertilization and Ovum Donor Pregnancies.

The Role of Embryonic Origin in Preeclampsia: A Comparison of Autologous In Vitro Fertilization and Ovum Donor Pregnancies.: "

The Role of Embryonic Origin in Preeclampsia: A Comparison of Autologous In Vitro Fertilization and Ovum Donor Pregnancies.

Obstet Gynecol. 2010 Dec;116(6):1387-1392

Authors: Klatsky PC, Delaney SS, Caughey AB, Tran ND, Schattman GL, Rosenwaks Z

OBJECTIVE:: To compare the risk of gestational hypertension and preeclampsia in pregnancies conceived through standard in vitro fertilization (IVF) using autologous oocytes with pregnancies conceived using donated oocytes. METHODS:: We conducted a retrospective, matched cohort study of women undergoing IVF using autologous compared with donor oocytes between 1998 and 2005. Women with live births resulting from oocyte donor pregnancies were matched for age and plurality (singleton or twin) with women undergoing autologous IVF. Primary outcomes were the incidence of preeclampsia or gestational hypertension (with and without proteinuria) in the third trimester. Data on preterm delivery, low birth weight, and embryo cryopreservation were also recorded. RESULTS:: Outcome data were available for 158 pregnancies, including 77 ovum-donor recipient pregnancies and 81 pregnancies using autologous oocytes. There were no differences in age, parity, and gestational type between the two cohorts. The incidence of gestational hypertension and preeclampsia was significantly higher in ovum-donor recipients compared with women undergoing autologous IVF (24.7% compared with 7.4%, P<.01, and 16.9% compared with 4.9%, P=.02, respectively). Ovum-donor recipients were more likely than women undergoing autologous IVF to deliver prematurely (34% compared with 19%). This association remained after controlling for multiple gestation (odds ratio 2.6, 95% confidence interval 1.04-6.3). Sixteen pregnancies from cryopreserved embryos were more likely to have hypertensive disorders of pregnancy (odds ratio 5.0, 95% confidence interval 1.2-20.5). CONCLUSION:: Pregnancies derived from donor oocytes and cryopreserved-thawed embryos may be at a higher risk for hypertensive disorders of pregnancy. These findings inform future research and help counsel women using assisted reproductive technology. LEVEL OF EVIDENCE:: II.

PMID: 21099607 [PubMed - as supplied by publisher]

"

Combination of loop diuretics with thiazide-type diuretics in heart failure.

Combination of loop diuretics with thiazide-type diuretics in heart failure.: "

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J Am Coll Cardiol. 2010 Nov 2;56(19):1527-34

Authors: Jentzer JC, DeWald TA, Hernandez AF

Volume overload is an important clinical target in heart failure management, typically addressed using loop diuretics. An important and challenging subset of heart failure patients exhibit fluid overload despite significant doses of loop diuretics. One approach to overcome loop diuretic resistance is the addition of a thiazide-type diuretic to produce diuretic synergy via 'sequential nephron blockade,' first described more than 40 years ago. Although potentially able to induce diuresis in patients otherwise resistant to high doses of loop diuretics, this strategy has not been subjected to large-scale clinical trials to establish safety and clinical efficacy. We summarize the existing literature evaluating the combination of loop and thiazide diuretics in patients with heart failure in order to describe the possible benefits and hazards associated with this therapy. Combination diuretic therapy using any of several thiazide-type diuretics can more than double daily urine sodium excretion to induce weight loss and edema resolution, at the risk of inducing severe hypokalemia in addition to hyponatremia, hypotension, and worsening renal function. We provide considerations about prudent use of this therapy and review potential misconceptions about this long-used diuretic approach. Finally, we seek to highlight the need for pragmatic clinical trials for this commonly used therapy.

PMID: 21029871 [PubMed - in process]

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Minocycline Protects against Neurologic Complications of Rapid Correction of Hyponatremia.

Minocycline Protects against Neurologic Complications of Rapid Correction of Hyponatremia.: "

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Minocycline Protects against Neurologic Complications of Rapid Correction of Hyponatremia.

J Am Soc Nephrol. 2010 Nov 4;

Authors: Gankam-Kengne F, Soupart A, Pochet R, Brion JP, Decaux G

Osmotic demyelination syndrome is a devastating neurologic condition that occurs after rapid correction of serum sodium in patients with hyponatremia. Pathologic features of this injury include a well-demarcated region of myelin loss, a breakdown of the blood-brain barrier, and infiltration of microglia. The semisynthetic tetracycline minocycline is protective in some animal models of central nervous system injury, including demyelination, suggesting that it may also protect against demyelination resulting from rapid correction of chronic hyponatremia. Using a rat model of osmotic demyelination syndrome, we found that treatment with minocycline significantly decreases brain demyelination, alleviates neurologic manifestations, and reduces mortality associated with rapid correction of hyponatremia. Mechanistically, minocycline decreased the permeability of the blood-brain barrier, inhibited microglial activation, decreased both the expression of IL1α and protein nitrosylation, and reduced the loss of GFAP immunoreactivity. In conclusion, minocycline modifies the course of osmotic demyelination in rats, suggesting its possible therapeutic use in the setting of inadvertent rapid correction of chronic hyponatremia in humans.

PMID: 21051736 [PubMed - as supplied by publisher]

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Managing Overly Rapid Correction of Chronic Hyponatremia: An Ounce of Prevention or a Pound of Cure?

Managing Overly Rapid Correction of Chronic Hyponatremia: An Ounce of Prevention or a Pound of Cure?: "

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Managing Overly Rapid Correction of Chronic Hyponatremia: An Ounce of Prevention or a Pound of Cure?

J Am Soc Nephrol. 2010 Nov 11;

Authors: Kamel KS, Halperin ML

PMID: 21071525 [PubMed - as supplied by publisher]

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Hereditary renal tubular disorders.

Hereditary renal tubular disorders.: "

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Hereditary renal tubular disorders.

Semin Nephrol. 2009 Jul;29(4):399-411

Authors: Chadha V, Alon US

The multiple and complex functions of the renal tubule in regulating water, electrolyte, and mineral homeostasis make it prone to numerous genetic abnormalities resulting in malfunction. The phenotypic expression depends on the mode of interference with the normal physiology of the segment affected, and whether the abnormality is caused by loss of function or, less commonly, gain of function. In this review we address the current knowledge about the association between the genetics and clinical manifestations and treatment of representative disorders affecting the length of the nephron.

PMID: 19615561 [PubMed - indexed for MEDLINE]

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