Circulating anti-pericyte autoantibodies are present in Type 2 diabetic patients and are associated with non-proliferative retinopathy

AIMS/HYPOTHESIS: This study aims to determine the prevalence of anti-pericyte autoantibodies in Type 2 diabetes and to characterize these autoantibodies as new markers of disease activity in diabetic retinopathy. METHODS: A total of 299 patients with Type 2 diabetes participated in this study. Retinopathy was assessed by 7-field stereo fundus photography and was graded according to the ETDRS scale. Serum anti-pericyte autoantibodies were detected by immunofluorescence on tissue cultured bovine retinal pericytes. RESULTS: The prevalence of anti-pericyte autoantibodies in Type 2 diabetic patients was 54% and was approximately equal in men and women. The prevalence was approximately 55% with retinopathy at grades from 10 to 53. At grades above 53 the prevalence declined to 23% ( p<0.0001). The highest prevalence by duration of diabetes, 70%, was found at 0 to 5 years and the lowest, 25% at more than 25 years duration ( p<0.0001). CONCLUSION/INTERPRETATION: Anti-pericyte autoantibodies are present at high prevalence in Type 2 diabetes. Their presence during earlier stages of retinopathy could be due to a reaction with antigens expressed by "activated" pericytes. The decline in antibody prevalence in advanced retinopathy could mark pericyte loss and progression to an angiogenic retinal milieu.     

Vascular proliferation and vascular endothelial growth factor expression in the rhesus macaque endometrium

The relationship between vascular endothelial growth factor (VEGF) expression and the pattern of vascular proliferation in the rhesus macaque endometrium has not been studied. In this report, we used in situ hybridization to evaluate VEGF, VEGF receptor type 1 and VEGF receptor type 2 mRNA expression during hormonally regulated menstrual cycles in ovariectomized macaques. Proliferating endothelial cells were identified by a double immunocytochemistry procedure that detected Ki-67 antigen and von Willebrand factor in the same endothelial cells. One and 2 d after progesterone withdrawal (premenstrual), VEGF mRNA was up-regulated in the glands and stroma of the superficial endometrial zones, a finding that supports our previous suggestion that VEGF may play a role in the menstrual induction cascade. During the postmenstrual repair phase, the healing surface epithelium showed a further, dramatic increase in expression of VEGF mRNA, accompanied by strong increases in signals for VEGF receptor types 1 and 2 in multiple profiles of small blood vessels immediately below the surface epithelium. This finding implicates VEGF in the early angiogenic processes associated with endometrial healing and regeneration. Vascular endothelial proliferation persisted throughout the cycle in the upper endometrial zones and showed a dramatic estrogen- dependent peak during the midproliferative phase. This proliferative peak coincided with a peak in VEGF expression in the endometrial stroma. Endothelial proliferation was also significantly correlated with the degree of stromal VEGF expression during the proliferative and secretory stages of the cycle. These results implicate VEGF of stromal origin in endometrial vascular proliferation.     

Myocardial infarction as a presentation of clinical in-stent restenosis.

BACKGROUND: In-stent restenosis is considered to be a gradual and progressive condition and there is scant data on myocardial infarction (MI) as a clinical presentation. METHODS AND RESULTS: Of 2,462 consecutive patients who underwent percutaneous coronary intervention between June 2001 and December 2002, clinical in-stent restenosis occurred in 212 (8.6%), who were classified into 3 groups: ST elevation MI (STEMI), non-ST elevation MI (NSTEMI) and non-MI. Of the 212 patients presenting with clinical in-stent restenosis, 22 (10.4%) had MI (creatine kinase (CK)>or=2xbaseline with elevated CKMB). The remaining 190 (89.6%) patients had stable angina or evidence of ischemia by stress test without elevation of cardiac enzymes. Median interval between previous intervention and presentation for clinical in-stent restenosis was shorter for patients with MI than for non-MI patients (STEMI, 90 days; NSTEMI, 79 days; non-MI, 125 days; p=0.07). Diffuse in-stent restenosis was more frequent in MI patients than in non-MI patients (72.7% vs 56.3%; p<0.005). Renal failure was more prevalent in patients with MI than in those without MI (31.8% vs 6.3%, p=0.001). Compared with the non-MI group, patients with MI were more likely to have acute coronary syndromes at the time of index procedure (81.8% vs 56.8%, p=0.02). CONCLUSION: Clinical in-stent restenosis can frequently present as MI and such patients are more likely to have an aggressive angiographic pattern of restenosis. Renal failure and acute coronary syndromes at the initial procedure are associated with MI.     

Phylogenetic and Pathotypic Characterization of Newcastle Disease Viruses Circulating in West Africa and Efficacy of a Current Vaccine

Newcastle disease (ND) is a deadly avian disease worldwide. In Africa, ND is enzootic and causes large economic losses, but little is known about the Newcastle disease virus (NDV) strains circulating in African countries. In this study, 27 NDV isolates collected from apparently healthy chickens in live-bird markets of the West African countries Benin and Togo in 2009 were characterized. All isolates had polybasic fusion (F)-protein cleavage sites and were shown to be highly virulent in standard pathogenicity assays. Infection of 2-week-old chickens with two of the isolates resulted in 100% mortality within 4 days. Phylogenetic analysis of the 27 isolates based on a partial F-protein gene sequence identified three clusters: one containing all the isolates from Togo and one from Benin (cluster 2), one containing most isolates from Benin (cluster 3), and an outlier isolate from Benin (cluster 1). All the three clusters are related to genotype VII strains of NDV. In addition, the cluster of viruses from Togo contained a recently identified 6-nucleotide insert between the hemagglutinin-neuraminidase (HN) and large polymerase (L) genes in a complete genome of an NDV isolate from this geographical region. Multiple strains that include this novel element suggest local emergence of a new genome length class. These results reveal genetic diversity within and among local NDV populations in Africa. Sequence analysis showed that the F and HN proteins of six West African isolates share 83.2 to 86.6% and 86.5 to 87.9% identities, respectively, with vaccine strain LaSota, indicative of considerable diversity. A vaccine efficacy study showed that the LaSota vaccine protected birds from morbidity and mortality but did not prevent shedding of West African challenge viruses.     

The prevalence of Eustachian tube dysfunction symptoms in patients with chronic rhinosinusitis

Background

While Eustachian tube dysfunction (ETD) is a known comorbidity of chronic rhinosinusitis (CRS), the prevalence of ETD symptoms in the CRS population is poorly understood. We sought to determine the cross‐sectional prevalence of ETD in patients with CRS using the validated Eustachian Tube Dysfunction Questionnaire (ETDQ‐7) and to correlate ETDQ‐7 scores with 22‐item Sino‐Nasal Outcome Test (SNOT‐22) scores, endoscopy scores, and computed tomography (CT) scores.

Methods

A total of 101 patients with confirmed CRS completed the ETDQ‐7 and SNOT‐22 at their initial visit to our rhinology clinic. Lund‐Mackay CT and Lund‐Kennedy endoscopy scores were also obtained. Spearman's correlation coefficient (ρ) was calculated.

Results

Among the 101 patients, 49 patients (48.5%) had an ETDQ‐7 score of ≥14.5, signifying clinically significant ETD. The mean ± standard deviation (SD) ETDQ‐7 score of the entire cohort was 17.8 ± 10.1. There was a moderately strong correlation between ETDQ‐7 and the SNOT‐22 ear subdomain (ρ = 0.691, p < 0.001). The correlation coefficient between ETDQ‐7 and total SNOT‐22 scores was ρ = 0.491 (p < 0.001), indicating moderate correlation. ETDQ‐7 scores were poorly correlated to objective measures of sinonasal disease, including Lund‐Mackay CT score (ρ = ?0.055, p = 0.594) and Lund‐Kennedy endoscopy score (ρ = ?0.099, p = 0.334).

Conclusion

Symptoms of ETD are highly prevalent among patients with CRS as documented by patient‐reported outcome measures. The correlation between ETDQ‐7 scores and SNOT‐22 ear subdomain scores is moderately strong, while the correlation between ETDQ‐7 scores and SNOT‐22 scores is moderate. ETD severity does not correlate with CT score or nasal endoscopy score.

     

Existence of a pool of T-lymphocyte colony-forming cells (T-CFC) in human bone marrow and their place in the differentiation of the T- lymphocyte lineage

The existence and characteristics of bone marrow T-cell progenitors have not yet been established in man. Several pieces of evidence such as the reconstitution of certain immunodeficiencies by bone marrow graft suggest that T-cell precursors are present in the bone marrow. We report the growth of T-cell colonies from bone marrow populations using PHA-stimulated lymphocyte-conditioned medium containing T-cell growth factor (TCGF). Rosetting experiments and complement-dependent cytotoxicity assays with monoclonal antibodies indicate that the bone marrow T colony-forming cells (T-CFC) are E- OKT 3- and la+, i.e., immature progenitors. The colonies derived from these cells have the phenotype of mature T cells: E + OKT 3 + la- with either helper (OKT 4+) and suppressor (OKT 8 +) antigens. These results suggest that a thymic microenvironment may not be necessary for the in vitro proliferation and differentiation of the T-cell lineage in adult humans. These methodologies may permit direct investigation of early phenomena concerning the T-cell lineage, such as the acquisition of self-tolerance, the formation of a repertoire of specificities, and the HLA restriction phenomena that we believe takes place before the thymic maturation.     

Antilymphocyte globulin, cyclosporin, and granulocyte colony- stimulating factor in patients with acquired severe aplastic anemia (SAA): a pilot study of the EBMT SAA Working Party

Patients with severe aplastic anemia (SAA) and a neutrophil (PMN) count of less than 0.5 x 10(9)/L are exposed to a high risk of early mortality when treated with antilymphocyte globulin (ALG) and steroids, with the major problem being infectious complications. The addition of human recombinant granulocyte colony-stimulating factor (rhG-CSF) to ALG may reduce early mortality by improving neutrophil counts in the short term. To test the feasibility of this approach, the SAA Working Party of the European Group for Blood and Marrow Transplantation (EBMT) designed a pilot study that included rhG-CSF (5 micrograms/kg/d, days 1 through 90), horse ALG (HALG; 15 mg/kg/d, days 1 through 5), methylprednisolone (2 mg/kg/d, days 1 through 5, then tapering the dose), and cyclosporin A (CyA; 5 mg/kg/d orally, days 1 through 180). Patients with newly diagnosed acquired SAA (untreated) and with neutrophil counts of < or = 0.5 x 10(9)/L were eligible. Forty consecutive patients entered this study and are evaluable with a minimum follow up of 120 days: the median age was 16 years (range, 2 to 72 years), the interval from diagnosis to treatment was 24 days, and the median PMN count was 0.19 x 10(9)/L. Twenty-one patients had hemorrhages, and 19 were infected at the time of treatment. Overall, treatment was well tolerated: the median maximum PMN count during rhG- CSF administration was 12 x 10(9)/L (range, 0.4 x 10(9)/L to 44 x 10(9)/L). There were three early deaths (8%) due to infection. Four patients (10%) showed no recovery, whereas 33 patients (82%) had trilineage hematologic reconstitution and became transfusion- independent at a median interval of 115 days from treatment. Median follow up for surviving patients is 428 days (range, 122 to 1,005). Actuarial survival is 92%: 86% and 100% for patients with PMN counts less than 0.2 x 10(9)/L or between 0.2 x 10(9)/L and 0.5 x 10(9)/L, respectively. This study suggests that the addition of rhG-CSF to ALG and CyA is well tolerated, is associated with a low risk of mortality, and offers a good chance of hematologic response. This protocol would appear to be an interesting alternative treatment for SAA patients with a low PMN count who lack an HLA-identical sibling.     

Familial hypercholesterolemia presenting with multiple nodules of the hands and elbow

Familial hypercholesterolemia (FH) is a common but commonly missed diagnosis. Tendon xanthomas are a physical sign strongly suggestive of FH. Physicians must identify tendon xanthomas, apply validated clinical scoring such as the Dutch Lipid Clinic Network criteria and offer cascade screening. This approach will increase recognition of FH.