Adaptive capacity in ecosystems.

Understanding the adaptive capacity of ecosystems to cope with change is crucial to management. However, unclear and often confusing definitions of adaptive capacity make application of this concept difficult. In this paper, we revisit definitions of adaptive capacity and operationalize the concept. We define adaptive capacity as the latent potential of an ecosystem to alter resilience in response to change. We present testable hypotheses to evaluate complementary attributes of adaptive capacity that may help further clarify the components and relevance of the concept. Adaptive sampling, inference and modeling can reduce key uncertainties incrementally over time and increase learning about adaptive capacity. Such improvements are needed because uncertainty about global change and its effect on the capacity of ecosystems to adapt to social and ecological change is high.

Prenatal therapy in transient abnormal myelopoiesis: a systematic review.

OBJECTIVE: To systematically review current evidence regarding prenatal diagnosis and management of transient abnormal myelopoiesis (TAM) in fetuses with trisomy 21. A novel case of GATA1-positive TAM, in which following serial in utero blood transfusion clinical improvement and postnatal remission were observed, is included. SEARCH STRATEGY AND DATA COLLECTION: A systematic search of electronic databases (inception to October 2014) and reference lists, hand-searching of journals and expert contact. All confirmed cases of prenatal TAM were included for analysis. Data on study characteristics, design and quality were obtained. RESULTS: Of 73 potentially relevant citations identified, 22 studies were included, describing 39 fetuses. All studies included comprised single case or small cohort studies; overall quality was 'very low'. Fetal/neonatal outcome was poor; 12 stillbirths (30.8%), 4 neonatal deaths (10.2%) and 7 infant deaths (17.9%). In two cases, the pregnancy was terminated (5.1%). TAM was primarily detected in the third trimester (79.4%), and in 14 a retrospective diagnosis was made postpartum. Ultrasound features indicative of TAM included hepatomegaly±splenomegaly (79.5%), hydrops fetalis (30.8%), pericardial effusion (23.1%) and aberrant liquor volume (15.4%). When performed, liver function tests were abnormal in 91.6% of cases. CONCLUSIONS: Prenatal TAM presents a challenging diagnosis, and prognosis is poor, with consistently high mortality. A low threshold to measure haematological and biochemical markers is advised when clinical features typical of TAM are detected in the context of trisomy 21. Larger prospective studies are warranted to accurately ascertain the role of GATA1 analysis and potential value of prenatal therapy.

Providing letters and audiotapes to supplement a prenatal diagnostic consultation: effects on later distress and recall.

OBJECTIVES: Information provided at a mid-trimester fetal scan aims to improve patients' knowledge and minimize anxiety. This randomized controlled trial conducted at the Fetal Medicine Centre at Birmingham Women's Hospital aimed to assess the relative value of providing 1.standard information: a consultation and computer-generated ultrasound report (n = 29); 2.standard information plus a post scan written non-technical letter (n = 29); 3.standard information plus audiotapes of the consultation (n = 29); 4.standard information plus both non-technical letters and audiotapes (n = 30). It also aimed at exploring whether severity of diagnosis (none; mild; moderate-severe) interacted with the type of information provided to affect subsequent anxiety, depression and recall of information. PARTICIPANTS: Women (n = 550) referred with suspected fetal anomalies (without a previous history of anomaly or known psychiatric illness) were sent information regarding this study. One hundred and seventeen women consented and were randomly assigned to one of four information groups. The groups were similar with regard to age, education and marital status. MAIN OUTCOME MEASURES: State anxiety and depression were evaluated with the self-report State-Trait Anxiety Inventory (STAI) and Beck Depression Inventory (BDI) prior to consultation and two weeks post-scan. A structured telephone interview assessed recall of information approximately two weeks later. RESULTS: Two weeks after the initial consultation, women who received an audiotaped recording of the consultation reported significantly less anxiety than the control group (mean STAI 41.44 [95% CI 35.63-47.26] versus 44.92 [39.32-50.52]; difference = 10.70 [3.56-17.83], p < 0.01). Women who received a non-technical letter also reported less anxiety than the control group, an effect that approached significance (mean STAI 39.08 [95% CI 32.85-45.30]; difference = 6.48 [0.21-13.16], p = 0.058). There were no differences between the information groups on depression scores or recall of information. Women with a more severe abnormality reported higher anxiety and depression two weeks post-consultation, and had greater free recall but less cued recall of information. CONCLUSIONS: Provision of additional material (particularly an audiotape) following a prenatal scan appears to minimise anxiety compared with standard practice. Provision of audiotapes and non-technical letters do not appear to affect patient recall.

Calcification in untreated mediastinal Hodgkin's lymphoma.

Calcification is very rarely reported in untreated thoracic lymphoma. However, calcification can occur (although uncommonly) in lymphoma following chemotherapy or radiation, and in areas of scaring or fibrous healing. The authors describe the case of a pregnant woman with a large mediastinal mass that contained calcifications visible on both chest radiography and thoracic computed tomography, which proved to be Hodgkin's lymphoma.

Retroperitoneal suppurative lymphadenitis complicating Staphylococcus aureus acute bacterial endocarditis.

Acute bacterial endocarditis is commonly caused by Staphylococcus aureus. Acute bacterial endocarditis due to S. aureus is often complicated by metastatic infection to distant organs, i.e. the central nervous system, the heart, lungs, kidneys and joints. However, metastatic lymph node involvement has not been reported. This is a case report of S. aureus acute bacterial endocarditis complicated by metastatic suppurative lymphadenitis of retroperitoneal lymph nodes. We believe this is the first reported case of suppurative lymphadenitis of the mesenteric lymph nodes secondary to S. aureus acute bacterial endocarditis.

Design and synthesis of thrombin inhibitors: analogues of MD-805 with reduced stereogenicity and improved potency.

Mitsubishi's MD-805, a potent and selective inhibitor of thrombin which contains four stereogenic centers, has been the starting point for an optimization program. A systematic synthetic study resulted in thrombin inhibitors achiral at P2 and P3 but with a 10-fold increase in potency over the original lead. A number of 4-substituted piperidines were synthesized and examined as replacements for 2-carboxy-4-methylpiperidine at P2; 4-fluoroethylpiperidine (FEP) among others provided inhibitors (e.g. 45g) of increased potency. An enantioselective route was developed to 3(R)-methyl-1,2,3,4-tetrahydroquinolinesulfonyl chloride. Inhibitors containing this enantiomerically pure P3 (42d) had similar potency to the racemic material and provided support, with modeling studies, for the preparation of the gem 3,3-disubstituted compounds. A series of inhibitors containing the novel 3, 3-dimethyl-1,2,3,4-tetrahydroquinolinesulfonyl (DMTHQS) P3 (Table 5) were synthesized and showed a similar activity profile as the monomethyl series. The combination of P3-DMTHQS, P2-FEP, and P1-arginine (45g) had a K(i) of 6 nM (MD-805 K(i) = 85 nM). In animal models of both venous and arterial thrombosis, one inhibitor (42e) was shown to produce a dose-dependent inhibition of thrombus formation that in some situations was superior to that of MD-805.

Ion transport across the cecum in normal and colitic mice.

This study was conducted to determine the ion transport mechanisms in the normal mouse cecum and compare them to an inbred mouse model of colitis. The Ussing chamber-voltage clamp technique was used to monitor the short circuit current (I(sc)). The basal I(sc) in the normal cecum was 82.6 +/- 5.8 microA/cm2. It was not affected by bumetanide, 9-anthracene carboxylate, amiloride, and phenamil or by removal of Cl- ions; but was abolished by the removal of Na+ ions. Flux measurements revealed the presence of neutral NaCl transport. In the colitic cecum, the basal current was significantly higher than the normal cecum. Basal current in the normal cecum was due primarily to Na+ absorption through a Na+ channel, while in the colitic cecum it was due to Cl- ion secretion. cAMP addition in colitic cecum did not increase Cl- secretion, further suggesting that the tissue is already secreting at a maximal rate.

Morphological and functional changes in the colonic epithelial cells in a rabbit model of colitis.

A rabbit model of TNBS-colitis was used to study the effect of intestinal inflammation on epithelial cell function. Epithelial cells were isolated using a non-enzymatic isolation method without any apparent contamination with infiltrating immune cells. The isolated cells were found to be viable using dye exclusion studies, unidirectional Na+ -fluxes, proliferation assays and morphological studies. The cells, however, showed morphological changes that suggested the presence of increased number of secretory vesicles. This increase correlated well with the increase observed in ion and water secretion as measured by the short-circuit current. Finally, in the colitic tissue the number of PGE2 receptors was greatly reduced with no changes observed in the affinity of PGE2 to its receptor. The reduced number of PGE2 receptors might be due to sensitization of the receptor. In conclusion, we have demonstrated that morphologically and functionally normal epithelial cells can be isolated from the rabbit inflamed distal colon.

Effects of purified Clostridium difficile toxin A on rabbit distal colon.

BACKGROUND & AIMS: Antibiotic-associated pseudomembranous colitis in humans is caused by proliferation of Clostridium difficile, which elaborates an enterotoxin toxin A that causes epithelial damage and altered motility in rabbit small intestine. The aim of this study was to assess the effects of toxin A on rabbit distal colonic motility and to relate this to histological damage and inflammatory mediator production. METHODS: Two hundred micrograms per milliliter of toxin A was placed in a distal colonic loop in anesthetized rabbits, and myoelectric activity was recorded for the following 7 hours. The colon was histologically evaluated and assayed for eicosanoid production. The effects of toxin A on longitudinal and circular muscle were also assessed in vitro. RESULTS: Beginning 1 hour after instillation, toxin A caused a significant increase in the number of spike bursts without altering slow wave frequency; this was associated with an increase in mucosal neutrophils and increased production of prostaglandin E2 and leukotrienes B4 and C4/D4/E4. Seven hours after administration of toxin A, mediator levels and myoelectric activity remained increased but significant mucosal damage was now also present. Toxin A did not affect longitudinal or circular muscle in vitro. CONCLUSIONS: C. difficile toxin A caused a significant neutrophil infiltration and an increased myoelectric activity before producing mucosal damage. The myoelectric effect may be indirect, resulting from the production of motility-altering arachidonic acid metabolites.

Morphological factors influencing transepithelial conductance in a rabbit model of ileitis.

BACKGROUND & AIMS: Infection of rabbits with coccidia (Eimeria magna) causes chronic ileal inflammation and diarrhea. Inflamed ileum also shows decreased transmural conductance. The aim of this study was to characterize morphological factors known to affect paracellular permeability that may alter transmural conductance in inflamed ileum. METHODS: Ileal mucosa was mounted in Ussing chambers for study of [3H]mannitol and [3H]inulin fluxes. Light and electron microscopy were used for morphometric studies. Alterations in the zonula occludens of epithelial cells were evaluated in freeze-fracture replicas. RESULTS: Inflamed ileum showed diminished paracellular fluxes. Inoculated rabbits showed marked lymphoplasmocytic infiltration and villus blunting in ileum. Villus linear junctional density was unaffected. However, total villus apical surface area per square centimeter of tissue was reduced in inflamed ileum, causing a diminished total villus linear junctional pathway per square centimeter of apical surface. Villus zonula occludens strand number was reduced in inflamed ileum, whereas the frequency of both villus and crypt lateral surface extrajunctional strands increased. CONCLUSIONS: Chronic inflammation exerts a profound effect on ileal paracellular permeability. Morphological data suggest that this effect may be caused in part by alterations in inflamed ileal mucosal structure and tight junctional organization and density, particularly on villi.

Separation of pure populations of epithelial cells from rabbit distal colon.

A simple method using divalent chelators is described for the isolation of viable populations of surface and crypt cells from rabbit distal colon. Histological studies were performed to monitor colonocyte dissociation and determine contamination by nonepithelial cells. Cell viability was assessed by trypan blue exclusion assay and by 22Na uptake measurements. Electron microscopy was used to determine the integrity of the isolated cells. Alkaline phosphatase and [3H]thymidine uptake were measured to assess the purity of the different cell fractions. Combined fractions 4 and 5 contained the highest percentage of pure surface cells, while fractions 10, 11, and 12 were predominantly crypts. Alkaline phosphatase activity was 13 +/- 3-fold higher in the surface cells than in the crypt cells, while [3H]thymidine uptake was 8 +/- 4-fold higher in the crypt cells than in the surface cells. Amiloride-sensitive and -insensitive 22Na uptake was the same in the surface cells directly after isolation and after 3 h in culture. In this study we demonstrate a method for the preparation of highly enriched fractions of rabbit colon surface and crypt cells that remain viable and functional in short-term culture.

Effects of rotavirus on epithelial transport in rabbit small intestine.

The present study investigated changes in small intestinal epithelial transport in rabbits infected with rotavirus. The crypt depth-villus height ratio was increased in infected ileal tissue as a result of a significant increase in crypt depth and patchy shortening of the villi. Similar villus damage was seen in the jejunum. Despite these histological changes, basal fluid absorption by both the ileum and jejunum of infected animals was unaltered. Values for basal short-circuit current and resistance were similar; however, the increase in short-circuit current evoked by prostaglandin E2 was significantly smaller in rotavirus-infected tissues than in controls. The apparent Vmax for electrogenic glucose and alanine uptake by the jejunum was significantly increased following inoculation with rotavirus. Reduced responsiveness to the secretory effect of prostaglandin E2 and increased nutrient uptake may limit diarrhea that would otherwise be expected to occur as a result of the changes in mucosal architecture. This has important implications on the clinical treatment of rotavirus diarrhea, suggesting that oral rehydration therapy, which depends on the active transport of nutrients, may provide a more effective treatment than the use of cyclooxygenase inhibitors.

Defective stimulation of cyclic AMP by prostaglandin E2 in colonic epithelial cells in colitis.

The present study investigated the effect of vasoactive intestinal peptide and prostaglandin E2 on cyclic adenosine monophosphate levels in isolated colonocytes during experimental colitis. Intra-rectal trinitrobenzenesulfonic acid induced a colitis-like inflammation in the rabbit distal colon. Basal levels of cyclic adenosine monophosphate were similar in control and colitic colonocytes. Levels were increased by prostaglandin E2 and vasoactive intestinal peptide in control cells. Colonocytes from colitic tissue responded to vasoactive intestinal peptide normally, but exhibited an attenuated response to prostaglandin E2. We conclude during colitis the epithelium exhibits a specific alteration in prostaglandin E2 receptor number, affinity or adenylate cyclase coupling.

Defective modulation of colonic secretomotor neurons in a rabbit model of colitis.

The present in vitro study was conducted to investigate possible alterations in the control of colonic electrolyte transport in an experimental model of colitis. Intrarectal administration of trinitrobenzenesulfonic acid induced a colitis-like inflammation in the rabbit distal colon. Responses to amiloride and residual short-circuit current after this treatment were unchanged, suggesting that the absorptive and secretory mechanisms remained intact. Electrical field stimulation and vasoactive intestinal polypeptide, a candidate secretomotor neurotransmitter, both elicited similar responses in control and colitic tissue. This suggests that communication at the neuroepithelial junction was unimpaired. In untreated tissue, the effects of prostaglandin E2 (PGE2) and of acetylcholine were attenuated by tetrodotoxin, suggesting, therefore, that both play a role in the modulation of secretomotor neurons. In addition, PGE2 had an appreciable direct epithelial effect. Responses to both of these agonists were absent in colitis. The effects of N6,2'-O-dibutyryladenosine 3',5'-cyclic monophosphate were unchanged in colitis, suggesting that altered PGE2 responsiveness may involve changes in epithelial receptor number, affinity, or in their ability to mediate an increase in adenosine 3',5'-cyclic monophosphate levels. It is concluded that this rabbit model of colitis exhibits 1) defects in the modulation of secretomotor neurons by acetylcholine and PGE2 and 2) an attenuated epithelial response to PGE2.

In vitro changes in the properties of rabbit colonic muscularis mucosae in colitis.

BACKGROUND: The muscularis mucosae is the muscle layer closet to the site of elevated inflammatory mediator production in inflammatory bowel disease. Thus, it is the first muscle layer subject to their influence. METHODS: Using a rabbit trinitrobenzene sulfonic acid model of colitis, changes in the properties of the muscularis mucosae resulting from the inflammatory process were studied in vitro. RESULTS: Animals developed a mild colitis-like inflammation that was confined to the epithelium, lamina propria, and submucosa. Colitic muscularis mucosae contractile responses to leukotriene D4 and prostaglandins E2 and F2 alpha were significantly attenuated relative to the maximum tissue response to acetylcholine, whereas responses to histamine, substance P, and vasoactive intestinal polypeptide were unchanged. In addition, the stress-generating capacity of the colitic muscularis mucosae was compromised in a stimulus-independent manner and passive tension increased relative to active tension. CONCLUSIONS: The muscularis mucosae undergoes two significant alterations in colitis: (a) a selective desensitization to the effects of arachidonic acid metabolites and (b) an impairment of its excitation-contraction coupling mechanism. A loss of the ability of the muscularis mucosae to cause mucosal movement and alter luminal surface area may be an important early stage in the pathophysiology of inflammatory bowel disease.

Systemic Castleman's disease in association with Evan's syndrome and vitiligo.

Systemic Castleman's disease is a lymphoproliferative disorder which has been associated with autoimmune phenomena. We report a case of the plasma cell variant of Castleman's disease that was associated with autoimmune hemolytic anemia and autoimmune thrombocytopenia (Evan's syndrome), and vitiligo, the association of which has not been previously reported.

Rat atrial natriuretic factor (ANP-III) inhibits phosphate transport in brush border membrane from superficial and juxtamedullary cortex.

Previous studies have shown that administration of synthetic atrial natriuretic factor (ANF, 101-126) decreases sodium-dependent phosphate transport across renal brush border membrane vesicles (BBMV) in rats fed a normal or low phosphate diet. In the present study, infusion of rat ANF (atriopeptin III (ANP-III), 103-126 rat ANF) to rats fed a normal phosphate diet caused natriuretic and phosphaturic effects similar to those of ANF (101-126), but unlike ANF (101-126) did not increase the glomerular filtration rate. The effect of ANP-III infusion on sodium-dependent transport of phosphate was also determined in BBM vesicles isolated from the superficial cortex (BBMV-SC) and juxtamedullary cortex (BBMV-JM). The results indicate that ANP-III decreases phosphate transport across BBMV-SC and BBMV-JM similarly (20-24%). However, it had no effect on sodium-dependent transport of proline in these vesicles. The infusion of ANP-III to rats fed a normal phosphate diet inhibits phosphate uptake both in BBMV-SC and BBMV-JM and causes phosphaturia without increments in glomerular filtration rate.

Thrombotic thrombocytopenic purpura: report of a case with a possible response to high-dose intravenous gamma globulin.

The case history of a 71-year-old woman with three episodes of a microangiopathic hemolytic anemia over a 22-year span is detailed. During the last episode a possible response of her thrombotic thrombocytopenic purpura (TTP)-like syndrome to the administration of intravenous immunoglobulin is documented. In retrospect it became apparent that she only improved in her prior episodes after receiving plasma-containing blood products. Prior case reports of TTP responses to intravenous immunoglobulin are reviewed with specific attention to the dosage used. Since a prospectively randomized series is unlikely to be reported, investigators should be encouraged to report their experience with intravenously administered gamma globulin.