Publications

Endoscopic mucosal resection (EMR) is preferred to standard polypectomy for the resection of non-polypoid lesions because these lesions can be technically difficult to capture with a snare; furthermore, without submucosal injection the underlying muscularis propria may be excessively coagulated or even inadvertently resected. Because the resection plane of EMR is in the middle or deeper part of the submucosa, EMR allows the precise depth of the lesion to be evaluated. Although the majority of non-polypoid lesions are adenomatous, non-polypoid colorectal neoplasm has a high association with advanced pathology, irrespective of size. Using EMR, a complete pathologic specimen is obtained, the risk of lymph node metastasis can be accurately assessed based on the depth of invasion, and patients can be suitably managed. Used according to its indications, EMR provides curative resection, and obviates the higher morbidity, mortality, and cost associated with surgical treatment.

BACKGROUND

Methionine-choline-deficient (MCD) diets cause steatohepatitis in rodents and are used to model fatty liver disease in human beings. Recent studies have identified sucrose as a major contributor to MCD-related liver disease through its ability to promote hepatic de novo lipogenesis.

AIMS

To determine whether glucose and fructose, the two constitutents of sucrose, differ in their capacity to provoke steatohepatitis when incorporated individually into MCD formulas.

MATERIALS & METHODS

MCD and control formulas prepared with either glucose or fructose as the sole source of carbohydrate were fed to mice for 21 days. Liver injury was assessed biochemically and histologically together with hepatic gene expression and fatty acid analysis.

RESULTS

Mice fed MCD formulas developed similar degrees of hepatic steatosis whether they contained glucose or fructose. By contrast, mice fed MCD-fructose developed significantly more hepatocellular injury than mice fed MCD-glucose, judged by histology, apoptosis staining and serum alanine aminotransferase. Liver injury in MCD-fructose mice coincided with an exaggerated rise in the ratio of long-chain saturated to unsaturated fatty acids in the liver. Notably, hepatic inflammation was not enhanced in mice fed MCD-fructose, correlating instead with hepatic lipid peroxidation, which was equivalent in the two MCD groups.

DISCUSSION

Fructose is more cytotoxic than glucose when used as the source of carbohydrate in MCD formulas.

CONCLUSION

The data suggest the enhanced cytotoxicity of fructose in the MCD model is related to its ability to stimulate de novo lipogenesis, which yields harmful long-chain saturated fatty acids.

Over the course of infection, the human immunodeficiency virus type 1 (HIV-1) continuously adapts in part to evade the host's neutralizing antibody response. Antibodies often target the HIV envelope proteins that mediate HIV fusion to its cellular targets. HIV virions pseudotyped with primary envelopes have often been used to explore the fusogenic properties of these envelopes. Unfortunately, these pseudotyped virions fuse with greatly reduced efficiency to primary cells. Here, we describe a relatively simple strategy to clone primary envelopes into a provirus and increase the sensitivity of the virion-based fusion assay.

BACKGROUND

Venous thromboembolism (VTE) is common after lung transplantation. Enoxaparin is an approved therapy for VTE and anti-factor Xa level can be used to monitor enoxaparin activity. Some studies have demonstrated elevated anti-factor Xa levels are associated with an increased risk of hemorrhage. Having identified a high incidence of supratherapeutic anti-factor Xa levels in lung transplant recipients, we aimed to elucidate the relationship between enoxaparin dose and anti-factor Xa level in this patient population.

METHODS

We identified post-lung transplantation patients with VTE receiving therapeutic enoxaparin who had anti-factor Xa level measured. Standard enoxaparin dosing was defined as 0.9 to 1.1 mg/kg. After identifying a high incidence of supratherapeutic anti-factor Xa levels, we implemented "non-standard" dosing of 0.8 mg/kg. Multivariate linear regression analysis was used to examine the association between enoxaparin dose and anti-factor Xa level; age, body mass index (BMI) and creatinine clearance were included as covariates.

RESULTS

In the cohort, 18 patients received standard and 8 patients received non-standard enoxaparin dosing. Twelve of 18 patients (67%; 95% confidence interval [CI]: 43% to 91%) receiving standard dosing had supratherapeutic anti-factor Xa levels vs 0 of 8 patients (0%; 95% CI: 0% to 37%) receiving lower non-standard dosing (p = 0.002). Anti-factor Xa levels were significantly different between the two groups; the mean anti-factor Xa level was 1.3 IU/ml (95% CI: 1.06 to 1.53) in the standard group vs 0.79 IU/ml (95% CI: 0.67 to 0.91) in the non-standard group (p = 0.008). After controlling for covariates, for each 0.1-mg/kg increase in enoxaparin, the mean anti-factor Xa level increased by 0.18 IU/ml (95% CI: 0.05 to 0.31; p = 0.011; model r(2) = 0.53).

CONCLUSIONS

Standard dosing of enoxaparin in lung transplant recipients is associated with a high incidence of supratherapeutic anti-Xa levels. Further study will be required to correlate this finding with risk of hemorrhage.

BACKGROUND

Older adults comprise an increasing proportion of the prison and homeless populations. While older age is associated with adverse post-release health events and incarceration is a risk factor for homelessness, the health status and homelessness risk of older pre-release prisoners are unknown. Moreover, most post-release services are geared towards veterans; it is unknown whether the needs of non-veterans differ from those of veterans.

OBJECTIVE

To assess health status and risk of homelessness of older pre-release prisoners, and to compare veterans with non-veterans.

DESIGN/PARTICIPANTS

Cross-sectional study of 360 prisoners (≥ 55 years of age) within 2 years of release from prison using data from the 2004 Survey of Inmates in State and Federal Correctional Facilities.

MAIN MEASURES

Veteran status, health status (based on self-report), and risk of homelessness (homelessness before arrest).

KEY RESULTS

Mean age was 61 years; 93.8% were men and 56.5% were white. Nearly 40% were veterans, of whom 77.2% reported likely VA service eligibility. Veterans were more likely to be white and to have obtained a high school diploma or GED. Overall, 79.1% reported a medical condition and 13.6% reported a serious mental illness. There was little difference in health status between veterans and non-veterans. Although 1 in 12 prisoners reported a risk factor for homelessness, the risk factors did not differ according to veteran status.

CONCLUSIONS

Older pre-release prisoners had a high burden of medical and mental illness and were at risk for post-release homelessness regardless of veteran status. Reentry programs linking pre-release older prisoners to medical and psychiatric services and to homelessness prevention programs are needed for both veterans and non-veterans.

Type 2 immunity is a stereotyped host response to allergens and parasitic helminths that is sustained in large part by the cytokines IL-4 and IL-13. Recent advances have called attention to the contributions by innate cells in initiating adaptive immunity, including a novel lineage-negative population of cells that secretes IL-13 and IL-5 in response to the epithelial cytokines IL-25 and IL-33. Here, we use IL-4 and IL-13 reporter mice to track lineage-negative innate cells that arise during type 2 immunity or in response to IL-25 and IL-33 in vivo. Unexpectedly, lineage-negative IL-25 (and IL-33) responsive cells are widely distributed in tissues of the mouse and are particularly prevalent in mesenteric lymph nodes, spleen, and liver. These cells expand robustly in response to exogenous IL-25 or IL-33 and after infection with the helminth Nippostrongylus brasiliensis, and they are the major innate IL-13-expressing cells under these conditions. Activation of these cells using IL-25 is sufficient for worm clearance, even in the absence of adaptive immunity. Widely dispersed innate type 2 helper cells, which we designate Ih2 cells, play an integral role in type 2 immune responses.