ARH missense polymorphisms and plasma cholesterol levels.

Mutations in a putative low-density lipoprotein (LDL) receptor adaptor protein called ARH have been recently described in patients with autosomal recessive hypercholesterolemia (ARH). ARH plays a tissue-specific role in determination of LDL receptor function. In the ARH gene three mismatched polymorphisms have been detected: Pro202Ser, Pro202His and Arg238Trp. These are of putative interest in plasma cholesterol level determination. To evaluate the effect of polymorphisms on plasma cholesterol levels, all polymorphisms were analyzed by PCR and restriction enzyme analysis by MnII, HpyCH4IV and SacII in 100 Caucasian males with high (>90%, 6.29 +/- 0.89 mmol/l), and 100 males with low (<10%, 3.60 +/- 0.57 mmol/l), total plasma cholesterol levels. No significant differences were observed in frequencies of ARH genotypes or alleles between these two extreme groups. These results suggest that ARH polymorphisms are unlikely to be important genetic determinants of plasma cholesterol levels.     

Heligmosomoides polygyrus inhibits established colitis in IL-10-deficient mice

Inflammatory bowel disease (IBD) is prevalent in industrialized countries, but rare in less-developed countries. Helminths, common in less-developed countries, may induce immunoregulatory circuits protective against IBD. IL-10(-/-) mice given piroxicam develop severe and persistent colitis. Lamina propria mononuclear cells from colitic IL-10(-/-) mice released IFN-gamma and IL-12. The ongoing piroxicam-induced colitis could be partially blocked with anti-IL-12 monoclonal antibody suggesting that the inflammation was at least partly IL-12 dependent. Colonization of piroxicam-treated colitic IL-10(-/-) mice with Heligmosomoides polygyrus (an intestinal helminth) suppressed established inflammation and inhibited mucosal IL-12 and IFN-gamma production. H. polygyrus augmented mucosal IL-13, but not IL-4 or IL-5 production. Transfer of mesenteric lymph node (MLN) T cells from IL-10(-/-) animals harboring H. polygyrus into colitic IL-10(-/-) recipients inhibited colitis. MLN T cells from worm-free mice did not. Foxp3 (scurfin) drives regulatory T cell function. H. polygyrus enhanced Foxp3 mRNA expression in MLN T cells that had regulatory activity. This suggests that H. polygyrus inhibits ongoing IL-10(-/-) colitis in part through blocking mucosal Th1 cytokine production. Resolution of inflammation is associated with increased IL-13 production and can be adoptively transferred by MLN T cells.     

Hereditary multiple and isolated sporadic exostoses in the same kindred: identification of the causative gene (EXT2) and detection of a new mutation, nt112delAT, that distinguishes the two phenotypes

Hereditary multiple exostoses (HME) is a well known autosomal dominant hereditary orthopedic disorder. Isolated exostoses, on the other hand, occur as sporadic events or as secondary post-traumatic sequel. The occurrence of solitary exostoses in individuals from pedigrees affected with HME may distort conclusions about carrier status and/or diagnosis. Both conditions are potentially malignant and both are associated with genetic alterations in either EXT1 or EXT2 genes. In this study, we present a seven-generation family from western Sweden consisting of 170 blood relatives, 38 of whom had multiple cartilaginous exostoses, while 8 had isolated exostoses. Linkage analysis aimed to discern one of the known EXT genes demonstrated linkage of the HME phenotype to the EXT2 gene. Subsequent mutation analysis revealed a novel mutation, nt112delAT, in this gene. All carriers of the detected mutation had multiple exostoses, indicating full penetrance. None of the pedigree members with isolated exostoses were carriers of the detected mutation. Two of the mutation carriers developed chondrosarcoma yielding a 5.2% risk of malignant development for this mutation. The detection of this mutation has enabled us to provide appropriate genetic counseling concerning this complex situation.     

High Prevalence of Physical Frailty Among Community-Dwelling Malnourished Older Adults–A Systematic Review and Meta-Analysis

Background

Malnutrition and frailty are two geriatric syndromes that significantly affect independent living and health in community-dwelling older adults. Although the pathophysiology of malnutrition and physical frailty share common pathways, it is unknown to what extent these syndromes overlap and how they relate to each other.

Survival and quality of life after minimally invasive esophagectomy: a single-surgeon experience

Background

Reports on quality of life (QOL) after minimally invasive esophagectomy (MIE) have been limited. This report compares perioperative outcomes, survival, and QOL after MIEs with open transthoracic esophagectomy (TTE) and open transhiatal esophagectomy (THE).

Methods

After institutional review board approval, retrospective review of a prospectively maintained database identified patients who underwent esophageal resection for esophageal cancer at Creighton University between August 2003 and August 2010. Patients with preoperative stage 4 disease, emergent procedures, laparoscopic transhiatal esophagectomies, or esophagojeujunostomies were excluded from the study. The study patients were categorized as having undergone open TTE, open THE, or MIE. Overall survival (OS) was the interval between diagnosis and death or follow-up assessment. Disease-free survival (DFS) was the interval between surgery and recurrence, death, or follow-up assessment. For the patients who survived at least 1?year after surgery, QOL was assessed using European Organization for Research and Treatment of Cancer (EORTC-QLQ, version 3.0) and esophageal module (EORTC-QLQ OES 18) questionnaires.

Results

The study criteria were satisfied by 104 patients. Lymph node harvest with MIE (median = 20) was similar to that with open TTEs (median = 19) and significantly higher (P?P?Conclusions MIEs offer a safe and viable alternative to open esophagectomies because they reduce the need and volume of intraoperative blood product transfusion and postoperative respiratory complications without compromising oncological clearance, survival, and QOL.     

The predictive value of transcutaneous oxygen tension measurement in diabetic lower extremity ulcers treated with hyperbaric oxygen therapy: a retrospective analysis of 1144 patients

The objective of this retrospective analysis was to determine the reliability of transcutaneous oxygen tension measurement (TcPO2) in predicting outcomes of diabetics who underwent hyperbaric oxygen therapy for lower extremity wounds. Six hyperbaric facilities provided TcPO2 data under several possible conditions: breathing air, breathing oxygen at sea level, and breathing oxygen in the chamber. Overall, 75.6% of the patients improved after hyperbaric oxygen therapy. Baseline sea-level air TcPO2 identified the degree of tissue hypoxia but had little statistical relationship with outcome prediction because some patients healed after hyperbaric oxygen therapy despite very low prehyperbaric TcPO2 values. Breathing oxygen at sea level was unreliable for predicting failure, but 68% reliable for predicting success after hyperbaric oxygen therapy. TcPO2 measured in chamber provides the best single discriminator between success and failure of hyperbaric oxygen therapy using a cutoff score of 200 mmHg. The reliability of in-chamber TcPO2 as an isolated measure was 74% with a positive predictive value of 58%. Better results can be obtained by combining information about sea-level air and in-chamber oxygen. A sea-level air TcPO2 < 15 mmHg combined with an in-chamber TcPO2 < 400 mmHg predicts failure of hyperbaric oxygen therapy with a reliability of 75.8% and a positive predictive value of 73.3%.     

Vitamin K epoxide reductase expression and prostate cancer risk

Purpose

Increasing evidence has demonstrated that men taking the anticoagulant warfarin have a lower risk of developing prostate cancer. This phenomenon is not observed in other cancers. We sought to determine if the target of warfarin, vitamin K epoxide reductase (VKOR), is expressed in benign and cancerous prostate tissues and if a functional single nucleotide polymorphism (SNP) in the VKOR gene is associated with prostate cancer risk.

Cost of a ventilator-associated pneumonia in a shock trauma intensive care unit

BACKGROUND: Nosocomial pneumonia and especially ventilator-associated pneumonia (VAP) are costly complications for the hospitalized patient. Nosocomial pneumonia has been estimated to cost $5,000 per episode, but the specific cost for a VAP has not been well estimated. As part of a successful performance improvement program in decreasing VAP from 10 VAPs/100 ICU admissions to 2.5 VAPs/100 ICU admissions, we examined the costs associated with VAP. METHODS: From January 1, 2002, through September 30, 2003, Shock Trauma Intensive Care Unit patients and charts were reviewed concurrently by an infection control practitioner for development of VAP as defined by National Nosocomial Infection Surveillance (NNIS) guidelines. Costs were obtained from the hospital's cost accounting software Transition Systems version 3.1.01 (TSI). All patients requiring greater than one day of mechanical ventilation were evaluated. Seventy patients with VAP and 70 patients without VAP were matched according to age and Injury Severity Score. Differences were compared using Kruskal-Wallis and two sample T-tests. Significance was considered for p < 0.05. RESULTS: The ICU cost difference was significant (p < 0.05) between the case-controlled patients with VAP ($82,195) and those without VAP ($25,037). There was also a significant increase in ICU length of stay (21.6 versus 6.4 days) and the number of ventilator days (17.7 versus 5.8; both, p < 0.05). Mortality was not different in the case-controlled population. A substantial portion of the increased cost of a VAP was from the increase in ICU length of stay ($1,861/day). Pharmacy, respiratory and "other" also accounted for the increases when cost distribution was analyzed. This translates into a cost avoidance of approximately $428,685 per 100 admissions to the ICU. CONCLUSIONS: Ventilator-associated pneumonia not only leads to a significant increase in ventilator days and ICU length of stay, but adds substantially to hospital costs. In our ICU, an episode of VAP costs $57,000 per occurrence.