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.     

A comparison of nutritional intake, functional status and muscle strength between elderly day hospital and day centre attenders in South London

Two sample groups of elderly were compared from a population living in South London. One group attended a local day centre (a socially orientated establishment), and the other attended a local day hospital (a therapeutically orientated establishment).
The aim of the study was to compare nutritional intake, functional status and muscle strength between these two groups.
The mean nutritional intakes of the day hospital and day centre attenders were similar. Intake of macronutrients, with the exception of fibre, met Recommended Daily Allowances (RDAs) in both groups. In take of folic acid, vitamin D and zinc fell below recommendations in both groups.
Low intake of folic acid was improved by supplementation, and some individual blood levels of folate reflected this. Blood folate levels were generally within normal limits. Low intake of vitamin D was improved by supplementation, but blood levels were generally normal anyway. There was, however, a tendency for the more dependent day hospital patients to have lower vitamin D levels. This group also had less sunshine exposure.
Communal dining, whether in the setting of day hospital or day centre, may have been an essential means of bolstering nutritional intake for many 'at risk' elderly.
There were significant differences in functional status and muscle strength in favour of the day centre group and these indicate that anthropometric indices rather than nutritional or biochemical indices were the most reliable markers of disease and disability in this study.
The effect of fortifying local meals-on-wheels was also highlighted, and suggests that this may be one means of preventing nutritional deficiencies in the vulnerable, house-bound elderly.
Alcohol intake was reported as being modest. However, discrepancies were noted on review of biochemical indices known to be influenced by alcohol intake.     

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.     

Tioman virus, a novel paramyxovirus isolated from fruit bats in Malaysia

A search for the natural host of Nipah virus has led to the isolation of a previously unknown member of the family Paramyxoviridae. Tioman virus (TiV) was isolated from the urine of fruit bats (Pteropus hypomelanus) found on the island of the same name off the eastern coast of peninsular Malaysia. An electron microscopic study of TiV-infected cells revealed spherical and pleomorphic-enveloped viral particles (100--500 nm in size) with a single fringe of embedded peplomers. Virus morphogenesis occurred at the plasma membrane of infected cells and morphological features of negative-stained ribonucleoprotein complexes were compatible with that of viruses in the family Paramyxoviridae. Serological studies revealed no cross-reactivity with antibodies against a number of known Paramyxoviridae members except for the newly described Menangle virus (MenV), isolated in Australia in 1997. Failure of PCR amplification using MenV-specific primers suggested that this new virus is related to but different from MenV. For molecular characterization of the virus, a cDNA subtraction strategy was employed to isolate virus-specific cDNA from virus-infected cells. Complete gene sequences for the nucleocapsid protein (N) and phosphoprotein (P/V) have been determined and recombinant N and V proteins produced in baculovirus. The recombinant N and V proteins reacted with porcine anti-MenV sera in Western blot, confirming the serological cross-reactivity observed during initial virus characterization. The lack of a C protein-coding region in the P/V gene, the creation of P mRNA by insertion of 2-G residues, and the results of phylogenetic analyses all indicated that TiV is a novel member of the genus Rubulavirus.     

Cyclic AMP levels in purified rat adrenal zonae fasciculata and reticularis cells and the effect of adrenocorticotrophic hormone

Cyclic AMP levels were measured in combined cells and supernatant fraction from incubations of dispersed rat adrenal zona fasciculata and zona reticularis cell preparations purified by unit gravity sedimentation. These measurements were correlated with deoxycorticosterone (DOC) and corticosterone outputs from the cells in the presence or absence of ACTH. Similar measurements of cyclic AMP outputs were made for unpurified dispersed, decapsulated rat adrenal cell preparations and they were found to correspond to previously reported measurements made by other workers on such preparations. The response of the purest zona reticularis cells to ACTH in terms of cyclic AMP output was 28-fold lower than that of the purest zona fasciculata cells (compared with a fivefold lower DOC output and a 20-fold lower corticosterone output) and the response to ACTH of the mixed-cell preparations was related to the number of zona fasciculata cells in the preparation, i.e. the greater the proportion of zona fasciculata cells in the preparation the greater the response in terms of both outputs of cyclic AMP and of either of the two steroids measured. This correlation is in accordance with the theory that cyclic AMP may be the secondary messenger for both zona fasciculata and zona reticularis cells of the rat adrenal cortex in mediating the response to an ACTH stimulus.     

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.     

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.