Organ donation after circulatory death: current status and future potential.

The continuing shortage of deceased donor organs for transplantation, and the limited number of potential donors after brain death, has led to a resurgence of interest in donation after circulatory death (DCD). The processes of warm and cold ischemia threaten the viability of DCD organs, but these can be minimized by well-organized DCD pathways and new techniques of in situ organ preservation and ex situ resuscitation and repair post-explantation. Transplantation survival after DCD is comparable to donation after brain death despite higher rates of primary non-function and delayed graft function. Countries with successfully implemented DCD programs have achieved this primarily through the establishment of national ethical, professional and legal frameworks to address both public and professional concerns with all aspects of the DCD pathway. It is unlikely that expanding standard DCD programs will, in isolation, be sufficient to address the worldwide shortage of donor organs for transplantation. It is therefore likely that reliance on extended criteria donors will increase, with the attendant imperative to minimize ischemic injury to candidate organs. Normothermic regional perfusion and ex situ perfusion techniques allow enhanced preservation, assessment, resuscitation and/or repair of damaged organs as a way of improving overall organ quality and preventing the unnecessary discarding of DCD organs. This review will outline exemplar controlled and uncontrolled DCD pathways, highlighting practical and logistical considerations that minimize warm and cold ischemia times while addressing potential ethical concerns. Future perspectives will also be discussed.

Organ donation protocols.

Organ transplantation improves survival and quality of life in patients with end-organ failure. Waiting lists continue to grow across the world despite remarkable advances in the transplantation process, from the creation of public engagement campaigns to the development of critical pathways for the timely identification, referral, approach, and treatment of the potential organ donor. The pathophysiology of dying triggers systemic changes that are intimately related to organ viability. The intensive care management of the potential organ donor optimizes organ function and improves the donation yield, representing a significant step in reducing the mismatch between organ supply and demand. Different beliefs and cultures reflect diverse legislations and donation practices amongst different countries, creating a challenge to standardized practices. Maintaining public trust is necessary for continued progress in organ donation and transplantation, hence the urge for a joint effort in creating uniform protocols that ensure transparent practices within the medical community.

Maternal and neonatal outcomes in obese women who lose weight during pregnancy.

OBJECTIVE: To evaluate neonatal and maternal outcomes in obese pregnant women whose weight gain differed from the Institute of Medicine (IOM) recommendations. STUDY DESIGN: Maternal and neonatal outcomes associated with weight change in pregnancy were retrospectively investigated in women with obesity (body mass index (BMI) ⩾30 kg m(-2); N=10734) who gave birth at 12 hospitals. Using a 1:1:1:1 design (n=778 matched groups), we matched women with obesity who lost, maintained, gained appropriate (IOM recommended) and gained excessive weight during pregnancy by gestational age at delivery, maternal age, race/ethnicity, prepregnancy BMI, chronic hypertension, pregestational diabetes and smoking status. Regression techniques were used to adjust for confounders and compare outcomes across weight change categories. RESULT: Compared with IOM recommendations, weight loss was associated with twofold greater odds of low birth weight infants and a mean decrease in estimated blood loss of 30 ml; excessive weight gain was associated with doubled odds of gestational hypertension or preeclampsia, fourfold greater odds of macrosomia and a mean decrease in 5-min APGAR of 0.09. From lost to excessively gained weight, the odds of cesarean delivery increased 1.4 times and mean infant birth weight increased by 197 g. In contrast, the odds of small-for-gestational age were 1.8 times greater for women who lost than gained excessive weight. CONCLUSION: Weight loss in obese pregnant women is associated with increased risk for low birth weight neonates but significantly decreased or maintained risk for other maternal and neonatal morbidities, as compared with appropriate or excessive weight gain. This study supports re-evaluation of the current IOM guidelines for women with obesity.

Multi-Center Study of Diffusion-Weighted Imaging in Coma After Cardiac Arrest.

BACKGROUND: The ability to predict outcomes in acutely comatose cardiac arrest survivors is limited. Brain diffusion-weighted magnetic resonance imaging (DWI MRI) has been shown in initial studies to be a simple and effective prognostic tool. This study aimed to determine the predictive value of previously defined DWI MRI thresholds in a multi-center cohort. METHODS: DWI MRIs of comatose post-cardiac arrest patients were analyzed in this multi-center retrospective observational study. Poor outcome was defined as failure to regain consciousness within 14 days and/or death during the hospitalization. The apparent diffusion coefficient (ADC) value of each brain voxel was determined. ADC thresholds and brain volumes below each threshold were analyzed for their correlation with outcome. RESULTS: 125 patients were included in the analysis. 33 patients (26%) had a good outcome. An ADC value of less than 650 × 10(-6) mm(2)/s in ≥10% of brain volume was highly specific [91% (95% CI 75-98)] and had a good sensitivity [72% (95% CI 61-80)] for predicting poor outcome. This threshold remained an independent predictor of poor outcome in multivariable analysis (p = 0.002). An ADC value of less than 650 × 10(-6) mm(2)/s in >22% of brain volume was needed to achieve 100% specificity for poor outcome. CONCLUSIONS: In patients who remain comatose after cardiac arrest, quantitative DWI MRI findings correlate with early recovery of consciousness. A DWI MRI threshold of 650 × 10(-6) mm(2)/s in ≥10% of brain volume can differentiate patients with good versus poor outcome, though in this patient population the threshold was not 100% specific for poor outcome.

Efficacy and tolerability of methotrexate therapy for refractory Crohn's disease: a large single-centre experience.

BACKGROUND: Randomised controlled trials demonstrate that methotrexate is effective in inducing remission and preventing relapse of Crohn's disease (CD) as a first-line immunosuppressant, but efficacy data after failure with, or intolerance to, thiopurines are limited. AIMS: To report efficacy of methotrexate in a cohort of refractory CD patients, most of whom had not responded to, or were intolerant of, thiopurines. METHODS: Data were collected for patients receiving methotrexate for active CD. Response to methotrexate induction therapy at 4 months, and sustained clinical benefit at last point of follow-up with maintenance therapy, were assessed via physician's global assessment. Demographic and disease factors predicting response, or sustained clinical benefit, were examined by univariate and multivariate analysis. RESULTS: Sixty-six [38 (54%) female patients, mean age at diagnosis 29.4 years] patients received methotrexate between 2001 and 2010, 61 (92%) of whom received the drug parenterally. Sixty patients had failed, or were intolerant of, thiopurines. Response to therapy at 4 months occurred in 54 (82%) patients. However, sustained clinical benefit occurred in only 19 (29%) patients at last point of follow-up, including six patients who discontinued the drug for family planning reasons. No predictors of response or sustained clinical benefit were identified. Adverse events occurred in 20 (30%) patients. CONCLUSIONS: These data suggest that methotrexate is effective in terms of initial response in Crohn's disease patients who have failed, or are intolerant of, thiopurines. However, efficacy is not sustained in the long term.

Changing pattern of organ donation at a single center: are potential brain dead donors being lost to donation after cardiac death?

Donation after cardiac death (DCD) has proven effective at increasing the availability of organs for transplantation.We performed a retrospective examination of Massachusetts General Hospital (MGH) records of all 201 donors from 1/1/98 to the 11/2008, including 54 DCD, 115 DBD and 32 DCD candidates that did not progress to donation (DCD-dnp). Comparing three time periods, era 1 (01/98-12/02), era 2 (01/03-12/05) and era 3 (01/06-11/08), DCD's comprised 14.8,48.4% and 60% of donors, respectively (p = 0.002). A significant increase in the incidence of cardiovascular/cerebrovascular as cause of death was evident in era 3 versus eras 1 and 2; 74% versus 57.1% (p<0.001),as was a corresponding decrease in the incidence of traumatic death. Interestingly, we noted an increase in utilization of aggressive neurological management over time, especially in the DCD group.We detected significant changes in the make-up of the donor pool over the past decade. That the changes in diagnosis over time did not differ between DCD and DBD groups suggests this difference is not responsible for the increase in DCD rates. Instead, we suggest that changes in clinical practice, especially in management of patients with severe brain injury may account for the increased proportion of DCD.

Costs of care for Crohn's disease following the introduction of infliximab: a single-centre UK experience.

BACKGROUND: Infliximab is effective for induction and maintenance of remission in patients with Crohn's disease. There are few data, however, examining effect of infliximab therapy on management costs of Crohn's disease. AIM: To assess Crohn's disease-related costs of care and resource use in a single-centre cohort of patients with Crohn's disease 12 months pre- and post-infliximab therapy. METHODS: Data on 100 consecutive patients receiving infliximab were collected. Crohn's disease-related resource use was collected 12 months pre- and post-infliximab. National Health Service reference costs were applied to these data and the total Crohn's disease-related health service costs per patient were calculated (£UK). The cost of infliximab therapy was not included in our analysis. RESULTS: Cost savings were demonstrated in all areas of Crohn's disease-related resource use following infliximab therapy. Mean total Crohn's disease-related cost reduction, 12 months following commencement of infliximab therapy, was £2750 per patient. Mean costs at 12 months post-infliximab in responders were lower than in nonresponders (£1656 vs. £3608, P = 0.02). The number of hospitalizations was reduced. Requirements for examination under anaesthesia were also significantly decreased. CONCLUSION: Infliximab use resulted in Crohn's disease-related cost savings and hospital resource use, although this was not sufficient to cover the cost of therapy.

Functional contrast-enhanced CT for evaluation of acute ischemic stroke does not increase the risk of contrast-induced nephropathy.

BACKGROUND AND PURPOSE: Concerns have recently grown regarding the safety of iodinated contrast agents used for CTA and CTP imaging. We tested whether the incidence of AN, defined by a >or=25% increase in the post-contrast scan creatinine level, was higher among patients with ischemic stroke who underwent a functional contrast-enhanced CT protocol compared with those who had no iodinated contrast administration. MATERIALS AND METHODS: The contrast-exposed group consisted of 575 patients with acute ischemic stroke who underwent CTA (n = 313), CTA/CTP (n = 224), or CTA/CTP followed by conventional angiography (n = 38) within 24 hours of stroke onset and were consecutively enrolled in a prospective cohort study. The nonexposed group consisted of 343 patients with ischemic stroke, consecutively admitted to the same institution, who did not receive iodinated contrast material. Patients were stratified by baseline eGFR. In the primary analysis, the Fisher exact test was used to compare the incidence of AN between the contrast-exposed and the nonexposed patients at 24, 48, and 72 hours and on a cumulative basis. A secondary analysis compared the incidence of AN in patients who underwent conventional angiography following CTA/CTP versus patients who underwent CTA/CTP only. RESULTS: The incidence of AN was 5% in the exposed and 10% in the nonexposed group (P = .003). Patients who underwent conventional angiography after contrast CT were at no greater risk of AN than patients who underwent CTA/CTP alone (26 patients, 5%; and 2 patients, 5%, respectively; P = .7). CONCLUSIONS: Administration of a contrast-enhanced CT protocol involving CTA/CTP and conventional angiography in selected patients does not appear to increase the incidence of CIN.

Mycophenolate mofetil therapy for refractory inflammatory bowel disease.

BACKGROUND: Mycophenolate mofetil (MMF) is an immunomodulatory drug, and its use in inflammatory bowel disease has previously been reported. The aim of this study was to review the Leeds Colitis Clinic experience of the safety and efficacy of MMF in treating patients with refractory Crohn's disease (CD) and ulcerative colitis (UC). This is an extension of a previously published study from our center with a longer follow-up period and approximately twice the number of patients. METHODS: A retrospective analysis was performed of the records of all patients treated with MMF for inflammatory bowel disease over a 5-year period. RESULTS: Of 70 patients identified, 67 had previously been treated with azathioprine unsuccessfully. Seventeen of the 70 patients had been successfully maintained in remission with MMF for an average duration of 33 months. Treatment with MMF was discontinued for 53 patients, 17 because of side effects and 36 because they had not responded to the treatment. CONCLUSIONS: In our series, 17 patients (24.3%) had a sustained steroid-free remission with MMF therapy. Nineteen patients (27%) experienced side effects, of which 17 (24.3% of the total group) had to discontinue therapy. An additional 36 (51.4%) required an escalation in medical therapy or surgery because of failure of the MMF therapy. MMF may have a role in the treatment of refractory inflammatory bowel disease, especially in patients who have previously failed standard therapies such as azathioprine.

Distinct N-glycan glycosylation of P-glycoprotein isolated from the human uterine sarcoma cell line MES-SA/Dx5.

The uterine sarcoma human cell line MES-SA/Dx5 overexpresses the MDR1 gene product, P-glycoprotein (Pgp). Pgp is a heavily glycosylated, ATP-dependent drug efflux pump expressed in many human cancers. There are more than 150 known isoforms of Pgp, which complicates the characterization of Pgp glycans because each isoform could present a different glycome. The contribution of these oligosaccharides to the structure and function of Pgp remains unclear. We identified distinct Pgp glycans recognized by the lectins in the digoxigenin (DIG) glycan differentiation kit from Roche Allied Science, all of which were N-glycans. Pgp was isolated using both slab and preparative gel elution. The monoclonal antibody C219 was used to identify the presence of Pgp and Pgp treated with PNGase F on our blots. Pgp isolated from MES-SA/Dx5 cells contains at least two different complex N-glycans--one high mannose tree, detected by GNA, and one branched hybrid oligosaccharide-capped with terminal sialic acids, detected by SNA and MAA. DSA, specific for biantennary oligosaccharides possessing beta(1-4)-N-acetyl-D-glucosamine residues, also recognized the blotted Pgp and is probably detecting the core Galbeta(1-4)-GlcNAc(x) component found in other Pgps.

Effect of a saponin-based surfactant and aging time on ruminal degradability of flaked corn grain dry matter and starch.

The objectives of this study were to investigate the effect of a saponin-based surfactant, Grain Prep surfactant (GP), and hot flake aging time on starch characteristics and ruminal DM and starch degradability of steam-flaked corn grain. In 2 experiments, the moisture content of incoming corn was automatically adjusted using the Grain Prep Auto Delivery System to 19.8% (Exp. 1) and 18.5% (Exp. 2). The application rate of GP was 22 mg/kg (as-is basis). Control corn was treated with water alone. Processed corn in Exp. 2 was stored in insulated containers for 0, 4, 8, or 16 h. Flaked corn samples were incubated in the rumen of lactating dairy cows for 0, 2, 4, 6, 16, or 24 h. In Exp. 1, GP increased, compared with the control, the soluble fraction and effective degradability (ED) of DM by 17.2 and 8.6%, respectively. The ED of cornstarch was increased by 6.7%. In Exp. 2, the concentration of soluble DM and starch were increased by GP by 15 and 24% compared with the control. The ED of DM and starch were also increased by 3 and 4%, respectively. No differences in gelatinization temperatures were observed due to treatment, except that GP-treated grain had a slightly greater mean gelatinization enthalpy in Exp. 2. In a pilot study, DM degradability parameters were not affected by germination of the corn kernels. Aging of the hot flakes for up to 16 h resulted in a quadratic decrease in DM and starch ruminal degradability. The aging process affected starch gelatinization enthalpy values of flaked grain in a manner opposite to that observed for ruminal DM and starch degradation. This phenomenon was most likely explained by increased starch intramolecular associations or crystallinity associated with starch annealing, or both. This study confirmed our previous observations that Grain Prep surfactant increases flaked corn DM and starch degradability in the rumen. Because the rate of degradation was not affected by the surfactant, the increase in degradability was attributed mainly to increases in DM and starch solubility.

The marrow cell continuum: stochastic determinism.

Traditional models of hematopoiesis have been hierarchical in nature. Over the past 10 years, we have developed data indicating that hematopoiesis is regulated in a continuum with deterministic and stochastic components. We have shown that the most primitive stem cells, as represented by lineage negative rhodamine(low) Hoechst(low) murine marrow cells are continuously or intermittently cycling as determined by in vivo BrdU labeling. When marrow stem cells are induced to transit cell cycle by in vitro exposure to cytokines, either IL-3, IL-6, IL-11, and steel factor or thrombopoietin, FLT3 ligand, and steel factor, they progress through cycle in a highly synchronized fashion. We have determined that when the stem cells progress through a cytokine stimulated cell cycle the homing, engraftment, adhesion protein, global gene expression, and hematopoietic differentiation phenotypes all change in a reversible fashion. This has led to the continuum model, in which, with cycle transit, chromatin is continually changing altering open transcription areas and providing a continually changing landscape of transcriptional opportunity. More recently, we have extended the changing differentiation profiles to differentiation into lung cells and found that non-hematopoietic differentiation also shows cycle related reversibly modulation. These observations all together support a continuum model of stem cell regulation in which the phenotype of the marrow stem cells is continually and reversibly changing over time.

Tissue injury in marrow transdifferentiation.

Recent findings indicate that adult BM contains cells that can differentiate into mature, nonhematopoietic cells of multiple tissues including cells of the kidney, lung, liver, skin and GI tract and fibers of heart and skeletal muscle. Recently the number of these observations has substantially increased, but there is a lack of information on the mechanistic issues in stem cell plasticity. In three different models for skin, liver and skeletal muscle plasticity, we have shown that following transplantation of the marrow cells from green fluorescent protein (GFP) transgenic mice, high levels of conversion of marrow cells can be identified. Injury to the tissue was the single most important factor for this phenomenon since the incidence of marrow to other tissue conversions significantly increased after tissue injury was implemented. Our studies also demonstrate the effect of radiation on the extent of marrow conversion.

Treatment of tinea imbricata: a randomized clinical trial using griseofulvin, terbinafine, itraconazole and fluconazole.

BACKGROUND: Griseofulvin has been the mainstay of treatment for tinea imbricata (TI) for decades; however, there have been few reports of efficacy of newer antifungals in the treatment of this condition. Many patients with TI have several obstacles to treatment due to their remote geographical locations and the primitive nature of their societies. OBJECTIVES: The aim of this study was to compare the efficacy of itraconazole, terbinafine and fluconazole with that of griseofulvin after 4 weeks of therapy. METHODS: Patients aged 12-76 years with the clinical diagnosis of TI were randomly assigned to one of four treatment groups: griseofulvin 500 mg twice daily for 4 weeks, terbinafine 250 mg daily for 4 weeks, itraconazole 200 mg twice daily for 1 week or fluconazole 200 mg once weekly for 4 weeks. Disease activity was monitored weekly. Laboratory measurements included monitoring complete blood count and liver function enzymes. Fifty-nine patients were included in the efficacy analysis: 13 in the fluconazole group, 15 in the griseofulvin group, 12 in the terbinafine group and 19 in the itraconazole group. RESULTS: Significant remission was achieved in the terbinafine and griseofulvin groups, lasting up to 8 weeks after cessation of therapy. The fluconazole group experienced no significant remission, and remission was of short duration in the itraconazole group. No adverse events were reported, and non-compliance with medications or follow-up was the only reason for removal from the study. CONCLUSIONS: Griseofulvin and terbinafine are effective in the treatment of TI. The decision of whether to treat at all and which medication to choose depends greatly on the extent of involvement, the social situation, and the availability of resources such as laboratory testing and follow-up.

Effects of moisture, roller setting, and saponin-based surfactant on barley processing, ruminal degradation of barley, and growth performance by feedlot steers.

Two experiments were conducted to study the effects of six processing techniques for barley grain in a 3 x 2 factorial arrangement of grain conditions and roller settings on ruminal degradation of the grain (Exp. 1) and on growth performance by 138 feedlot steers (n = 23 per treatment; Exp. 2). Dry barley (11% moisture, D barley), barley tempered to 20% moisture (M barley), and barley tempered with 60 mL/t of surfactant-based tempering agent (GrainPrep, Agrichem, Inc., Anoka, MN; MS barley), were each rolled at two roller settings selected from preliminary tests. The settings selected for the study were RD, the roller position that had yielded optimally processed D barley, and RMS, the setting that had yielded optimally processed MS barley. Setting RMS was tighter than RD. Barley rolled at the RMS setting was more extensively processed (i.e., had a lower [P < 0.001] processing index, PI), had lighter (P < 0.001) volume weight, thinner (P < 0.001) kernels, and fewer (P < 0.001) whole kernels compared with setting RD. Tempering did not affect (P > 0.05) PI, percentage of whole kernels, or kernel thickness at either roller setting. The processing characteristics of tempered barley were unaffected (P > 0.05) by surfactant. The extent of in situ DM disappearance (ISDMD) was higher (P < 0.01) in grain rolled at setting RMS compared with RD. At both roller settings, tempering reduced (P < 0.05) ISDMD between 4 and 24 h of ruminal incubation. Steers fed RMS-rolled barley had lower (P < 0.001) DMI, slightly lower (P = 0.084) ADG, but increased (P < 0.05) gain:feed (G:F) compared with steers fed RD-rolled barley. Tempering did not affect (P > 0.05) ADG, DMI, or G:F during backgrounding, but improved (P < 0.01) these variables during finishing. Surfactant improved (P < 0.05) G:F but not DMI or ADG. The improvement in G:F was most pronounced when setting RMS was used. The optimal PI values calculated from performance data were numerically greater for the backgrounding diet than for the finishing diet. Steers fed M or MS barley had heavier (P < 0.01) hot carcasses and thicker (P < 0.05) fat cover but lower (P < 0.05) dressing percentages than steers fed D. When the feed barley was rolled at setting RMS, steers fed MS barley produced heavier (P < 0.05) carcasses than those fed M. Tempering with or without surfactant increased performance by feedlot steers compared with not tempering. Diet composition and degree of barley processing mediated this effect.

Tolerance induction by costimulator blockade in 100 cGy treated hosts with varying degrees of genetic disparity.

Long-term multilineage allochimerism can be obtained in H2-mismatched B6.SJL to BALB/c transplants with host irradiation of 100 cGy, donor spleen cell pre-exposure and costimulator blockade with anti-CD40 ligand (CD40L) antibody. We evaluated this allochimerism approach in murine marrow transplants with different degrees of major histocompatibility complexe (MHC) mismatching; these include: (1) H2-mismatched transplant H2Kk to H2Kb, (2) full haplo-identical transplant H2Kbd to H2Kbk, (3) a partial haplo-identical transplant H2Kd to H2Kbd and (4) an MHC class II mismatch. Levels of chimerism increased up to 12 weeks and then stayed relatively stable up to 1 year after transplant. At 18 weeks post-transplant, the H2-mismatched, haplo-identical, partial haplo-identical and class II-mismatch transplants evidenced 17.9+/-4.4, 40.7+/-0.9, 25.1+/-4.19 and 33.7+/-3.5% donor chimerism, respectively. Dropping the anti-CD40 antibody treatment and spleen cells or changing the schedule of antibody to one injection, in haplo-identical or full-mismatched transplants resulted in no donor-derived chimerism. On the other hand, these still resulted in minor chimerism in class II-mismatched transplants. Lineage analysis of peripheral blood at 6 and 12 months post-transplant demonstrated a significant shift toward increased chimeric lymphocytes and decreased chimeric granulocytes in the full H2 as compared with haplo-identical or class II transplants. Transplantation with anti-CD40L antibody eliminated both graft-versus-leukemia and graft-versus-host disease (GVHD) and delayed lymphocyte infusion did not rescue animals from fatal leukemia. In conclusion, under the conditions of our tolerization regimen, a haplo transplant gives higher engraftment levels than a full H2 mismatch, and despite lower engraftment levels, a class II-mismatched transplant can be successfully accomplished with only 100 cGy and no CD40L blockade.

The marrow stem cell: the continuum.

The marrow hematopoietic stem cell is currently being redefined as to all aspects of its phenotype and its total differentiation capacity. This redefinition now includes its plasticity as to production of nonhematopoietic and hematopoietic cell types, the determinants of its in vivo engraftment potential and its expression of stem cell functional characteristics.

Marrow stem cell potential within a continuum.

On the basis of our studies of the fluctuation of the hematopoietic stem cell phenotype with cell cycle trnsit, we hypothesize that the ability of marrow stem cells to convert to nonhematopoietic cells will also vary at different points in the cell cycle. The new biology of stem cells has an impact on many fields including developmental biology and stem cell biology and the clinical potential is enormous.

Microvascular abnormalities in the bulbar conjunctiva of patients with type 2 diabetes mellitus.

OBJECTIVE: To study and quantify microvascular abnormalities objectively in vivo in patients with type 2 diabetes mellitus (T2DM). METHODS: The conjunctival microcirculation in 14 patients with T2DM and in age-matched healthy control subjects without diabetes was videotaped and objectively studied by using computer-assisted intravital microscopy (CAIM), a novel and quantitative real-time technology. RESULTS: Patients with T2DM (N = 14) had significantly (P<0.01) wider conjunctival vessel diameters (71.9 +/- 5.2 mm) than did healthy nondiabetic control subjects (54.0 +/- 4.4 mm). In the study patients, microvascular distribution was significantly (P<0.01) abnormal (36.7 +/- 18.2 versus 45.3 +/- 9.6 cm per unit area, patients versus control subjects), and vessel distribution was uneven on the surface of the bulbar conjunctiva. The arteriole:venule (A:V) ratio in patients with T2DM was extremely variable and differed significantly (P<0.01) from that in the nondiabetic control subjects (A:V approximately 1:2). In addition, a unique sinusoidal (hypertensive) vascular pattern frequently existed in some of the large veins of all study patients with T2DM but in none of the nondiabetic control subjects. CONCLUSION: We identified the presence of microvascular changes (abnormalities) in the conjunctival microcirculation of patients with T2DM. Although all these abnormalities did not appear in the same patient at the same time, the sum total of their presence in each patient correlated significantly with disease severity, as noted in the medical records. The severity of microvascular abnormalities, however, did not correlate with the duration of the disease since diagnosis. CAIM may be a useful objective and quantitative technique for assessing microangiopathy in patients with T2DM. The easy noninvasive accessibility of the conjunctival vessels and the ability to identify and locate the same vessels repeatedly for longitudinal evaluations further emphasize the usefulness of this real-time technology.

Cerebral infarction in conjunction with patent foramen ovale and May-Thurner syndrome.

Stroke patients with paradoxical embolus mandate a search for deep venous thrombosis (DVT) in the lower extremities. Iliac vein compression, or May-Thumer syndrome, places certain patients at risk for development of DVT. The authors present 3 stroke patients with patient foramen ovale and paradoxical cerebral embolism, with demonstrated iliac vein compression as the presumed source of their embolus. May-Thumer syndrome should be considered a potential source of clot, as definitive therapy of this disorder can be curative.