Clinical variables and their relation to visual outcome after vitrectomy in eyes with diabetic retinal traction detachment

Background To analyse vitrectomy results in diabetic eyes with retinal traction detachment and to investigate which variables are associated with a worse visual outcome.Methods Forty-four diabetic eyes (33 patients) with central retinal traction detachment were analyzed retrospectively.Results After a median follow-up of 10 months, median visual acuity significantly improved from 20/800 to 20/160 (P=0.02), despite the fact that the majority of patients had a long-standing macular traction detachment (median 120 days). Twenty-two eyes (50%) achieved a visual acuity of >20/200. The retina was finally reattached in 38 eyes (86.3%). Univariate analysis showed that patients with type 2 diabetes, age older than 50 years, preoperative visual acuity <20/200, iris neovascularisation and macular detachment of >30 days had a significantly worse final visual outcome. After multiple logistic regression analysis, age and iris neovascularisation were the strongest predictors of a worse visual outcome; if both were present, the chance of a obtaining a visual outcome of <20/200 was almost 90%.Conclusions Age and iris neovascularisation were the strongest predictors for a low visual outcome. In a review of vitrectomy studies in eyes with severe diabetic traction detachment in the past 2 decades, we found a trend towards higher anatomic success rates, while visual outcome only slightly improved. The current study confirmed the importance of ophthalmic variables, but also indicates the importance of evaluating systemic variables in larger series in order to predict which eyes may truly benefit from vitrectomy.The authors have not received any financial support. The authors have no proprietary interest related to this article.     

Simultaneous detection of apoptosis and proliferation in colorectal carcinoma by multiparameter flow cytometry allows separation of high and low-turnover tumors with distinct clinical outcome

BACKGROUND: Dukes C colorectal carcinoma is treated with adjuvant chemotherapy. Adjuvant treatment is not standard for patients with Dukes B tumors, even though about 20% of patients within this tumor stage die of recurrent disease. The authors investigated whether a novel method of simultaneous detection of apoptosis and proliferation would improve the assessment of prognosis in colorectal carcinoma patients, with the ultimate goal of accurately identifying patients eligible for adjuvant therapy. METHODS: A multiparameter flow cytometric assay with heat pretreatment was performed on 278 paraffin-embedded colorectal adenocarcinomas. After immunochemical isolation of tumor cells, apoptosis and proliferation were assessed simultaneously by immunostaining for the M30 antibody and by quantitative DNA analysis, respectively. Patients were followed for more than 10 years. RESULTS: The mean values of apoptosis (apoptotic fraction [AF], i.e., the percentage of M30-positive cells) and proliferation (S-phase fraction [SPF]) were 11.1% and 13.1%, respectively. The AF and SPF values were correlated positively (P = 0.01) and both increased with advancing tumor stage (P = 0.02). Combining AF and SPF, patients with tumors with a high turnover (i.e., both AF and SPF values were greater than the mean) had an overall survival rate of 13%, whereas patients with low-turnover tumors (i.e., both AF and SPF values were less than the mean) had an overall survival rate of 89% (P < 0.001 by log rank test). Moreover, within Dukes B and C stages, patients with high-turnover tumors had a poorer survival than patients with low-turnover tumors (P < 0.001 for both stages). CONCLUSIONS: The simultaneous detection of apoptosis and proliferation in archival material allows separation of high and low-turnover colorectal adenocarcinomas and improves the assessment of prognosis. This technique could be used to stratify patients for adjuvant chemotherapy.     

Immunotherapy through TCR gene transfer

The antigen specificity of T lymphocytes is dictated solely by the T cell receptor (TCR) alpha and beta chains. Consequently, genetic transfer of TCR chains may be an appealing strategy with which to impose a desirable virus- or tumor-antigen specificity onto cytotoxic or helper T cell populations. We describe here the genetic introduction of a virus-specific TCR into peripheral T cells in a mouse model system. These experiments showed that T cells redirected by TCR gene transfer expanded upon viral infection of mice and efficiently homed to effector sites. In this setting, TCR gene transfer was not associated with any significant autoimmune pathology. In addition, small numbers of TCR-transduced T cells promoted the rejection of antigen-expressing tumors in vivo. These data suggest that the redirection of T cells by TCR gene transfer is a viable strategy for the rapid induction of virus- or tumor-specific immunity.     

Peripheral arterial disease: comparison of color duplex US and contrast-enhanced MR angiography for diagnosis

PURPOSE: To prospectively compare the diagnostic accuracies of color duplex ultrasonography (US) and contrast material-enhanced magnetic resonance (MR) angiography and to assess interobserver agreement regarding contrast-enhanced MR angiographic findings in patients suspected of having peripheral arterial disease (PAD). MATERIALS AND METHODS: The institutional review board approved the study, and all patients provided signed informed consent. Two hundred ninety-five patients referred for diagnostic and preinterventional work-up of PAD with duplex US also underwent gadolinium-enhanced MR angiography. Data sets were reviewed for presence or absence of 50% or greater luminal reduction, which indicated hemodynamically significant stenosis, and to determine interobserver agreement. At duplex US, a peak systolic velocity ratio of 2.5 or greater indicated significant stenosis. Primary outcome measures were differences between duplex US and contrast-enhanced MR angiography in sensitivity and specificity for detection of significant stenosis, as assessed with the McNemar test, and interobserver agreement between the two contrast-enhanced MR angiogram readings, expressed as quadratic weighted kappa values. Intraarterial digital subtraction angiography (DSA) was the reference standard. RESULTS: Two hundred forty-nine patients had at least one hemodynamically significant stenotic lesion at contrast-enhanced MR angiography, duplex US, or both examinations. One hundred fifty-two patients underwent intraarterial DSA. The quadratic weighted kappa for agreement regarding the presence of 50% or greater stenosis at contrast-enhanced MR angiography was 0.89 (95% confidence interval [CI]: 0.87, 0.91). Sensitivity of duplex US was 76% (95% CI: 69%, 82%); specificity, 93% (95% CI: 91%, 95%); and accuracy, 89%. Sensitivity and specificity of contrast-enhanced MR angiography were 84% (95% CI: 78%, 89%) and 97% (95% CI: 95%, 98%), respectively; accuracy was 94%. Sensitivity (P = .002) and specificity (P = .03) of contrast-enhanced MR angiography were significantly higher. CONCLUSION: Results of this prospective comparison between contrast-enhanced MR angiography and duplex US provide evidence that contrast-enhanced MR angiography is more sensitive and specific for diagnosis and preinterventional work-up of PAD.     

The relationship between hypertension and anxiety or depression in Hong Kong Chinese

BACKGROUND:

Psychosocial stress can be the cause or the consequence of hypertension.

OBJECTIVE:

To study the association between hypertension and anxiety or depression in adults from Hong Kong, China.

SUBJECTS AND METHODS:

Patients with diagnosed hypertension (n=197) were recruited to complete the Hospital Anxiety and Depression Scale (HADS) questionnaire. The control group comprised 182 normotensive subjects recruited using random telephone numbers.

RESULTS:

The score in the anxiety subscale (HADS-A) of the HADS correlated with age (r= −0.23, P<0.001) and sex (r=0.11, P=0.042), and was found to be higher in women. The score in the depression subscale (HADS-D) correlated with age (r=0.17, P=0.003) and hypertension (r=0.12, P=0.039), but not with sex (r=0.02, P=0.68). When the control subjects were matched for sex and age with the subjects with hypertension, the mean HADS-A score was 5.51±0.41 in 113 hypertensive subjects and 4.38±0.39 in 113 normotensive subjects (P=0.047). The mean HADS-D score was 5.56±0.39 in the hypertensive and 4.76±0.32 in the normotensive subjects (P=0.11). Multiple regression analysis using data from both groups indicated that the HADS-A score was related to the HADS-D score (β=0.49, P<0.001), age (β= −0.25, P<0.001) and sex (β=0.12, P=0.01) (R²=0.28), whereas the HADS-D score was related to the HADS-A score (β=0.48, P<0.001), age (β=0.30, P<0.001), positive smoking status (β=0.13, P=0.004) and lack of exercise habit (β=0.12, P=0.008) (R²=0.31). Hypertension was related to waist circumference, history of parental hypertension and age (R²=0.38, P<0.001). Anxiety and depression scores were rejected as independent variables.

CONCLUSIONS:

Hypertension was associated with anxiety but not depression; however, age, history of parental hypertension and central obesity appeared to have a stronger association with hypertension in adults from Hong Kong.     

Denaturing interaction between sickle hemoglobin and phosphatidylserine liposomes

It is hypothesized that abnormal interaction between sickle hemoglobin (HbS) and erythrocyte membrane lipid might promote deposition of denatured hemoglobin (hemichrome) on the membrane. We compared the interaction of HbS and normal HbA with large unilamellar phosphatidylserine (PS) liposomes under low salt/pH conditions. Admixture of oxyHb and dioleoyl-PS resulted in loss of absorbance at 412 nm, the apparent first order rate constant for which was .25 +/- 0.02 hour-1 for HbA and .85 +/- 0.18 hour-1 for HbS. This was ascribable largely to formation of metHb and hemichromes and was accompanied by some actual transfer of heme from hemoglobin to lipid phase. By comparison, admixture of oxyHb with liposomes made from bovine brain PS having unsaturated acyl chains promoted even faster absorbance loss if the starting liposomal material contained detectable peroxidation by-product. In such cases, actual heme destruction developed with accompanying liberation of free iron and promotion of lipidperoxidation. Fluorescence quenching experiments indicate that hemoglobin/lipid interaction is characterized by very rapid initial electrostatic interaction, followed by development of irreversible changes. Similar changes still occur under conditions of physiologic salt/pH, but they develop much more slowly. The 3.4-fold faster oxidation of HbS versus HbA on lipid observed here represents an additional augmentation of the disparity in oxidation rates for hemoglobins in solution (1.7-fold faster for HbS than for HbA) observed previously. The accelerated promotion of Hb denaturation resulting from lipid contact may help explain deposits of hemichrome on sickle red blood cell membranes, particularly because these cells are in double jeopardy by virtue of having both the mutant HbS and abnormal amounts of peroxidized membrane lipid.     

Long-term bone marrow culture in persons with Fanconi anemia and bone marrow failure

Fanconi anemia is an autosomal recessive disease characterized by a high risk of developing bone marrow (BM) failure and acute myelogenous leukemia. We studied growth of hematopoietic progenitor cells in long- term BM culture (LTBMC) in 8 persons with Fanconi anemia and BM failure. Although LTBMC were initiated with very few BM cells, an adherent layer formed in cultures from 7 persons. In these cultures, the number of nonadherent cells increased for 10 to 15 days. Cell growth continued until cultures were terminated at day 35 to 40. During the first 2 weeks of culture, most nonadherent cells were differentiated myeloid cells. By days 35 to 40, the adherent layer contained cells able to initiate secondary LTBMCs. These data indicate that hematopoietic precursors cells able to proliferate and differentiate in vitro are present in the BM of persons with Fanconi anemia and BM failure. They suggest that mechanisms other than absent precursor cells are responsible for BM failure in Fanconi anemia.     

T-cell death by apoptosis in vertically human immunodeficiency virus- infected children coincides with expansion of CD8+/interleukin-2 receptor-/HLA-DR+ T cells: sign of a possible role for herpes viruses as cofactors?

One mechanism proposed to play a role in T-cell depletion in human immunodeficiency virus (HIV) infection is apoptosis (activation-induced cell death). We assessed whether apoptosis is related to activation of T cells in vivo and its possible triggers. DNA was extracted from peripheral blood mononuclear cells (PBMC) taken from 16 vertically HIV- infected children and 9 HIV-negative children born to HIV-positive mothers (controls) and tested by agarose gel electrophoresis for the presence of DNA fragments specific for apoptosis. Signs of apoptosis were found on in vitro culture of PBMC from 12 of 16 HIV-infected children, but not in PBMC from the nine controls. Eleven of the 12 HIV- infected children with apoptosis showed an elevated (> 15%) proportion of CD3+/HLA-DR+ cells. This was due to an increased proportion of CD8+/HLA-DR+ cells, as shown in 7 of 7 further tested patients. In none of the probands an increased (> 5%) proportion of IL-2 receptor expressing CD3+ cells was found. T cells undergoing apoptosis were preferentially of the CD8+ phenotype. Expansion of circulating CD8+/interleukin-2 receptor (IL-2R)-/HLA-DR+ T cells is known to occur during active infection with herpes viruses. To investigate the possible role of herpes viral coinfections for apoptosis in HIV infection, we focused on Epstein-Barr virus (EBV) as an example for a herpes virus usually acquired during childhood. In 10 of 12 patients with apoptosis, we found increased levels of EBV genome in PBMC and/or tissues, indicating active EBV replication. By contrast, no increased burden of EBV was found in the four HIV-infected patients without apoptosis or in the controls. Our data indicate that in children the occurrence of apoptosis in HIV infection is closely related to activation of CD8+ T cells. Furthermore, primoinfection with or reactivation of herpes viruses, such as EBV, may substantially contribute to such T-cell activation and the ensuing apoptosis. Additional studies are warranted to evaluate the contribution of herpes virus-triggered apoptosis to the T-cell loss leading to the acquired immunodeficiency syndrome.     

Vasoactive intestinal peptide and pituitary adenylate cyclase- activating polypeptides (PACAP27) and PACAP38) protect CD4+CD8+ thymocytes from glucocorticoid-induced apoptosis

In the present study, the effects of vasoactive intestinal peptide (VIP) and the pituitary adenylate cyclase-activating polypeptides, PACAP27 and PACAP38, in a concentration range from 10(-13) to 10(-6) mol/L were studied in vitro on the spontaneous and dexamethasone (DEX)- induced apoptosis in rat thymocytes. The results show that VIP and both PACAPs inhibit significantly and in a similar way the DNA fragmentation characteristic of glucocorticoid-induced apoptosis and increase the cell survival of thymocytes, with a maximal effect observed at 10(-8) to 10(-9) mol/L. This study showed the ability of the VIP-receptor (VIP- R) antagonist [N-Ac-Tyr1,D-Phe2]-GRF(1-29) amide to partially reverse the inhibitory effect of VIP and both PACAPs on DEX-induced apoptosis, providing evidence for a specific VIP1-R-mediated response and supporting the involvement of a single receptor for the three neuropeptides. Phenotypic analysis showed that VIP, PACAP27, and PACAP38 protect predominantly CD4+CD8+ thymocytes from glucocorticoid- induced apoptosis. These findings suggest that these neuropeptides could be involved in intrathymic T-cell maturation.