Impact of food security on glycemic control among low-income primarily Hispanic/Latino children in Los Angeles, California: A cross-sectional study.

Studies examining the impact of food insecurity on metabolic markers are limited, specifically in Hispanic youth. This study was a cross-sectional analysis of 218 3rd-5th grade students (83% Hispanic and 49% male). Anthropometrics, blood glucose, insulin, and lipids via fasting blood draw, dietary intake via Block screener, and a 5-item food security scale were collected. HOMA-Insulin Resistance was calculated. Multivariate analyses of covariance were used to examine differences in glucose and insulin indices, adiposity, metabolic and dietary intake variables between categories of food security. Food secure children had greater glycemic control and decreased insulin resistance compared to food insecure children.

Consumption of artificial sweetened beverages associated with adiposity and increasing HbA1c in Hispanic youth.

Research examining the impact of artificial sweetened beverages (ASBs) on obesity and metabolic diseases in adolescents is limited. The overall goal is to examine the longitudinal effects of ASBs on changes in adiposity and metabolic parameters in Hispanic adolescents. Longitudinal cohort with 98 Hispanics (12-18 years) who were overweight or had obesity with the following data at baseline and 1-year later: anthropometrics, diet (24-h recalls), body composition (DXA), glucose and insulin dynamics (oral glucose tolerance and frequently sampled intravenous glucose tolerance test) and fasting lipids. Repeated measures analyses of covariance assessed changes over time between control (no ASBs at either visit), ASB initiators (no ASBs at baseline/ASBs at 1-year) and chronic ASB consumers (ASBs at both visits). ASB initiators (n = 14) and chronic ASB consumers (n = 9) compared to control (n = 75) had higher total body fat at baseline and 1-year (P = 0.05 for group effect). Chronic ASB consumers had a 6% increase in haemoglobin A1c, 34% increase in energy intake (kcal d-1 ) and 39% increase in carbohydrate intake (g d-1 ) over time, while control and ASB initiators maintained (P < 0.05 for group-by-time interactions). These results do not support promoting ASBs as a strategy for adiposity loss or to improve metabolic health.

Infectious disease associations in advanced stage, indolent lymphoma (follicular and nonfollicular): developing a lymphoma prevention strategy.

BACKGROUND: Eradication of Helicobacter pylori in gastric mucosa-associated lymphoid tumor can result in lymphoma remission. We prospectively identified/treated infections in nonbulky, advanced stage indolent lymphoma (follicular; nonfollicular lymphoma) eligible for observation. MATERIALS AND METHODS: Stool H. pylori, hepatitis C and Borrelia serologies, Borrelia and Chlamydia fixed tissue PCR, Chlamydia peripheral blood mononuclear cell PCR and hydrogen breath test for small bowel bacterial overgrowth (SBBO) were obtained. RESULTS: Fifty-six patients were enrolled. Positive infections: H. pylori (13); hepatitis C (3); SBBO (11). Negative: Borrelia (13); Chlamydophila psittaci (12, except one PCR). Lymphoma responses to antimicrobial therapy: H. pylori [one complete response (CR), 24+ months; one transient near CR]; hepatitis C [two CRs, 18+ and 30+ months; one partial response (PR) but hepatitis C virus persistent]; SBBO (one PR, 30+ months). Patients with associated infections, but without lymphoma CR, have required lymphoma treatment sooner than those without initial infections (treatment-free survival at 23.4 months median follow-up, 40.5% versus 74.7%, P = 0.01), indicating a different biology. CONCLUSION: Infections are common in advanced stage indolent lymphoma (37.5% in our series). Anecdotal lymphoma responses have been seen and three have been durable CRs (18 to 30+ months) with infection eradication alone. The identification and treatment of associated infections may be a first step towards developing a lymphoma prevention strategy.

Organizational manipulation of gonadal hormones and systemic morphine analgesia in female rats: effects of adult ovariectomy and estradiol replacement.

Previous research has indicated the importance of sex in mediating the larger magnitude of mu-opioid receptor agonist-induced analgesia in male relative to female rodents. Whereas manipulations involving the adult activational effects of gonadal hormones minimally alter these analgesic sex differences, manipulations involving neonatal organizational effects of gonadal hormones have previously been shown to profoundly affect morphine analgesia. Thus, adult male rats neonatally castrated on the first day after birth displayed reductions in morphine analgesia relative to sham-operated males, and adult female rats neonatally treated with testosterone propionate on the first day after birth displayed enhancements in morphine analgesia relative to vehicle-treated females. Because neonatal androgenization in female rats produces an anovulatory syndrome that could change their adult hormonal milieu, the present study examined whether adult ovariectomy altered the magnitude of systemic morphine analgesia (1-5 mg/kg) in neonatal androgenized female rats relative to neonatal vehicle-treated female rats as well as gonadal steroid hormone replacement with estradiol benzoate. Intact male rats displayed significantly greater magnitudes and potencies (2- to 2.3-fold leftward shift) of systemic morphine analgesia than female rats treated neonatally with either vehicle (1-5 mg/kg) or testosterone (1.7-5 mg/kg). In turn, neonatal androgenized female rats displayed significantly greater magnitudes of systemic morphine (1, 5 mg/kg) analgesia than vehicle-treated female rats accompanied by a smaller 20% leftward shift in potency. Adult ovariectomy minimally affected morphine analgesia in neonatal vehicle-treated females, while significantly reducing the magnitude (1 mg/kg), but not the potency of morphine analgesia in neonatal androgenized female rats. Estradiol replacement therapy significantly increased the magnitude of morphine analgesia in both groups at some doses, but only changed the potency (20-30%) in females treated neonatally with vehicle. Taken together, these data suggest a limited organizational-activational gonadal hormone interaction in the mediation of systemic morphine analgesia in female rats.

The founder mutation MSH2*1906G-->C is an important cause of hereditary nonpolyposis colorectal cancer in the Ashkenazi Jewish population.

Hereditary nonpolyposis colorectal cancer (HNPCC) is caused by mutations in the mismatch-repair genes. We report here the identification and characterization of a founder mutation in MSH2 in the Ashkenazi Jewish population. We identified a nucleotide substitution, MSH2*1906G-->C, which results in a substitution of proline for alanine at codon 636 in the MSH2 protein. This allele was identified in 15 unrelated Ashkenazi Jewish families with HNPCC, most of which meet the Amsterdam criteria. Genotype analysis of 18 polymorphic loci within and flanking MSH2 suggested a single origin for the mutation. All colorectal cancers tested showed microsatellite instability and absence of MSH2 protein, by immunohistochemical analysis. In an analysis of a population-based incident series of 686 Ashkenazi Jews from Israel who have colorectal cancer, we identified 3 (0.44%) mutation carriers. Persons with a family history of colorectal or endometrial cancer were more likely to carry the mutation than were those without such a family history (P=.042), and those with colorectal cancer who carried the mutation were, on average, younger than affected individuals who did not carry it (P=.033). The mutation was not detected in either 566 unaffected Ashkenazi Jews from Israel or 1,022 control individuals from New York. In hospital-based series, the 1906C allele was identified in 5/463 Ashkenazi Jews with colorectal cancer, in 2/197 with endometrial cancer, and in 0/83 with ovarian cancer. When families identified by family history and in case series are included, 25 apparently unrelated Ashkenazi Jewish families have been found to harbor this mutation. Although this pathogenic mutation is not frequent in the Ashkenazi Jewish population (accounting for 2%-3% of colorectal cancer in those whose age at diagnosis is <60 years), it is highly penetrant and accounts for approximately one-third of HNPCC in Ashkenazi Jewish families that fulfill the Amsterdam criteria.

Making health care safer: a critical analysis of patient safety practices.

OBJECTIVES: Patient safety has received increased attention in recent years, but mostly with a focus on the epidemiology of errors and adverse events, rather than on practices that reduce such events. This project aimed to collect and critically review the existing evidence on practices relevant to improving patient safety. SEARCH STRATEGY AND SELECTION CRITERIA: Patient safety practices were defined as those that reduce the risk of adverse events related to exposure to medical care across a range of diagnoses or conditions. Potential patient safety practices were identified based on preliminary surveys of the literature and expert consultation. This process resulted in the identification of 79 practices for review. The practices focused primarily on hospitalized patients, but some involved nursing home or ambulatory patients. Protocols specified the inclusion criteria for studies and the structure for evaluation of the evidence regarding each practice. Pertinent studies were identified using various bibliographic databases (e.g., MEDLINE, PsycINFO, ABI/INFORM, INSPEC), targeted searches of the Internet, and communication with relevant experts. DATA COLLECTION AND ANALYSIS: Included literature consisted of controlled observational studies, clinical trials and systematic reviews found in the peer-reviewed medical literature, relevant non-health care literature and "gray literature." For most practices, the project team required that the primary outcome consist of a clinical endpoint (i.e., some measure of morbidity or mortality) or a surrogate outcome with a clear connection to patient morbidity or mortality. This criterion was relaxed for some practices drawn from the non-health care literature. The evidence supporting each practice was summarized using a prospectively determined format. The project team then used a predefined consensus technique to rank the practices according to the strength of evidence presented in practice summaries. A separate ranking was developed for research priorities. MAIN RESULTS: Practices with the strongest supporting evidence are generally clinical interventions that decrease the risks associated with hospitalization, critical care, or surgery. Many patient safety practices drawn primarily from nonmedical fields (e.g., use of simulators, bar coding, computerized physician order entry, crew resource management) deserve additional research to elucidate their value in the health care environment. The following 11 practices were rated most highly in terms of strength of the evidence supporting more widespread implementation. Appropriate use of prophylaxis to prevent venous thromboembolism in patients at risk; Use of perioperative beta-blockers in appropriate patients to prevent perioperative morbidity and mortality; Use of maximum sterile barriers while placing central intravenous catheters to prevent infections; Appropriate use of antibiotic prophylaxis in surgical patients to prevent postoperative infections; Asking that patients recall and restate what they have been told during the informed consent process; Continuous aspiration of subglottic secretions (CASS) to prevent ventilator-associated pneumonia; Use of pressure relieving bedding materials to prevent pressure ulcers; Use of real-time ultrasound guidance during central line insertion to prevent complications; Patient self-management for warfarin (Coumadin) to achieve appropriate outpatient anticoagulation and prevent complications; Appropriate provision of nutrition, with a particular emphasis on early enteral nutrition in critically ill and surgical patients; and Use of antibiotic-impregnated central venous catheters to prevent catheter-related infections. CONCLUSIONS: An evidence-based approach can help identify practices that are likely to improve patient safety. Such practices target a diverse array of safety problems. Further research is needed to fill the substantial gaps in the evidentiary base, particularly with regard to the generalizability of patient safety practices heretofore tested only in limited settings and to promising practices drawn from industries outside of health care.

High incidence of severe twin hemodialysis catheter infections in elderly women. Possible roles of insufficient nutrition and social support.

BACKGROUND: Cuffed-tunneled hemodialysis (HD) catheters are recommended as a bridging therapy until peripheral access is available, but their long-term use is controversial. AIM: To evaluate the complications and lifetime of twin-tunneled HD catheters and to identify parameters which could predict their outcome. METHODS: 29 chronic HD patients (19 female and 10 male) were inserted with twin hemodialysis catheters (28 Tesio, 1 Schon Duoflow), followed for up to 9 months or until catheter loss, and evaluated for severe catheter-related complications necessitating catheter removal. Since the most common severe complication was catheter-related infection, we retrospectively examined whether parameters such as age, gender, duration of end-stage renal disease, delivered dose of dialysis, nutrition, diabetes and indices of social support correlate with this outcome. RESULTS: Severe catheter infection requiring catheter removal occurred in 11 patients (10 female). Of these infected female patients, 9 were elderly (> or =67 years) and in 6 of those, catheter infection was fatal (54% of infected cases). At 9 months, severe catheter infection and related patient death rates were 38 and 21%, respectively. Severe catheter infection was significantly related to less social support (p < 0.005), older age, female gender, lower nPCR (all p < 0.05), and tended to be related to shorter end-stage renal disease duration prior to catheter insertion (p = 0.06). CONCLUSION: This study demonstrated that twin HD catheters are associated with a high incidence of severe catheter-related infections which was most significantly related to social-support as well as inadequate nutrition, older age and female gender. Therefore, we suggest early removal of the catheter, enhancement of social support and dietary counseling for the elderly and lonely HD patients using this type of catheter.

Utility of the full root bioprosthesis in surgery for complex aortic valve-ascending aortic disease.

The objective of this study was to demonstrate the use of the full root bioprosthesis (Medtronic Freestyle) in the patient with complex aortic valve-ascending disease. Of 148 patients undergoing stentless aortic valve replacement since 4/98, 22 required concomitant replacement of the entire ascending aorta with a Dacron graft (beveled to include hemi-arch) for either "porcelain" aorta (8) or diffuse aneurysmal dilatation (14): 17/22 had aortic stenosis, 4/22 had aortic insufficiency, and 1 had bioprosthetic degeneration. All patients had right axillary cannulation, circulatory arrest at 18 C, and retrocerebral perfusion through the superior vena cava. Valve sizes included 23 mm (7), 25 mm (2), and 27 mm (13). Average age was 69.5 years, average intensive care unit stay was 64 hours, and average postoperative length of stay was 6.5 days. Although the initial intent was full root replacement, 7 patients had calcified coronary ostia precluding reimplantation. Subcoronary implantation techniques were modified to interdigitate the outflow suture lines between and through islands of calcium buttressed with small pericardial pledgets on the outside of the native aorta. All valves demonstrated either no or trace aortic regurgitation on pre-discharge transesophageal echocardiography, 30-day mortality was 0, and there were no neurologic sequelae. The full root bioprosthesis has great utility in surgery for complex aortic valve-ascending aortic disease. Axillary artery cannulation and retrograde cerebral perfusion provide a reproducible neurologically safe approach in this group of patients at high risk for intraoperative neurologic morbidity.

Effectiveness of erythropoiesis on supervised intradialytic oral iron and vitamin C therapy is correlated with Kt/V and patient weight.

BACKGROUND: Poor compliance to oral medication and diet is common in hemodialysis (HD) patients and limits the ability of oral iron therapy to support erythropoiesis. Intravenous (i.v.) iron may be associated with undesirable and sometimes life-threatening complications. PATIENTS AND METHODS: We hypothesized that intradialytic oral iron therapy can overcome compliance problems and support effective maintenance erythropoiesis, which will keep Hct in the range of 33% to 36% and EPO requirements up to 50 units/week/kg. In a prospective observational study, SC EPO-treated hospital-based HD patients without conditions known to cause EPO resistance, were managed on intradialytic oral administration of iron and vitamin C. The primary endpoints were EPO requirements and resistance to EPO which standardized EPO requirements by the Hct level. Secondary endpoints included parameters that might affect the primary endpoints. Exclusion criteria were refusal to take oral medication, prestudy Hct < 27%, recent i.v. iron therapy or transfusions, bleeding, clinical conditions obligating Hct > 30% and known causes of EPO resistance. Twelve patients completed minimal follow-up period of 9 months. RESULTS: Mean Hct was 34.4% (range: 31.8% - 40.2%). EPO requirements were 61.7 +/- 28.2 units/kg and below 52.5 units/kg in 50% of patients. Patients were classified into equal groups according to resistance to EPO, which was positively correlated (r = 0.71 p < 0.01) with body weight and Kt/V (r = -0.38, p < 0.05). CONCLUSION: In conclusion, intradialytic oral iron therapy can support effective maintenance erythropoiesis in 50% of patients without known causes for EPO resistance. High response to EPO and low EPO requirement are correlated with lower body weight and possibly improved dialysis.

Conformational modulation of human cytochrome P450 2E1 by ethanol and other substrates: a CO flash photolysis study.

The alcohol-inducible cytochrome P450 2E1 is a major human hepatic P450 which metabolizes a broad array of endogenous and exogenous compounds, including ethanol, low-molecular weight toxins, and fatty acids. Several substrates are known to stabilize this P450 and inhibit its cellular degradation. Furthermore, ethanol is a known modulator of P450 2E1 substrate metabolism. We examined the CO binding kinetics of P450 2E1 after laser flash photolysis of the heme-CO bond, to probe the effects of ethanol and other substrates on protein conformation and dynamics. Ethanol had an effect on the two kinetic parameters that describe CO binding: it decreased the rate of CO binding, suggesting a decrease in the protein's conformational flexibility, and increased the photosensitivity, which indicates a local effect in the active site region such as strengthening of the heme-CO bond. Other substrates decreased the CO binding rate to varying degrees. Of particular interest is the effect of arachidonic acid, which abolished photodissociation in the absence of ethanol but had no effect in the presence of ethanol. These results are consistent with a model of P450 2E1 whereby arachidonic acid binds along a long hydrophobic binding pocket and blocks exit of CO from the heme region.

Cutaneous ulcers associated with hydroxyurea therapy in myeloproliferative disorders.

Hydroxyurea (HU) is an established chemotherapeutic agent in the treatment of myeloproliferative disorders (MPD) including chronic myelogenous leukemia (CML), polycythemia vera and essential thrombocythemia (ET). It is well tolerated, has minimal toxicities, and produces hematological response in most patients treated. Side effects of hydroxyurea are few and include myelosuppression, oral ulcers and skin rashes. Cutaneous toxicity is rare. This study aims to describe the occurrence of cutaneous ulcerations attributed to HU therapy in patients with MPD, and familiarize the oncology community with this unusual but disturbing toxicity of HU. Five patients with MPD receiving HU therapy at doses of 0.5 to 4 g/day who developed skin ulceration were reviewed (median age was 53 years). Three patients had Philadelphia positive CML, and two had ET. Cutaneous ulcers developed after a long period of HU therapy (median 36 months, range 7 to 96 months). The time after discontinuation of HU to the healing of the ulcers was 1 to 4 months. Ulcers developed mainly in the lower extremities particularly adjacent to the malleoli, indicating a possible relation to trauma. In conclusion, cutaneous ulceration represents a poorly recognized and rare HU-related side effect. Discontinuation of HU usually leads to slow resolution of the ulcers over several months. The etiology of this rare side effect remains poorly understood.

Screening and surveillance for colorectal cancer.

Colorectal cancer is the second most common cause of cancer death among American men and woman. Currently available screening and surveillance techniques are effective in detecting early-stage colorectal cancer and its premalignant precursor lesion, the adenomatous polyp (adenoma). Removal of adenomas by colonoscopic polypectomy significantly reduces the incidence of colorectal cancer. Appropriate screening and surveillance recommendations should be based on the individual's colorectal cancer risk stratification. High-risk groups, such as patients with hereditary nonpolyposis colorectal cancer (HNPCC) and familial adenomatous polyposis (FAP), should be offered genetic counseling and specialized screening recommendations for colorectal and associated extracolonic malignancies.

Ondansetron with propofol reduces the incidence of emesis in children following tonsillectomy.

PURPOSE: This study tested the hypothesis that the antiemetic effects of a combination of ondansetron and propofol were superior to propofol alone in children undergoing tonsillectomy surgery. METHODS: A prospective, randomized, double-blind, placebo-controlled study design was employed. Young children underwent mask induction with halothane, nitrous oxide and oxygen and then had i.v. access established: older children had i.v. induction with propofol. All patients received 0.3 mg x kg(-1) mivacurium and 2-4 microg x kg(-1) fentanyl i.v. and 30 mg x kg(-1) acetaminophen pr to a maximum dose of 650 mg. Following induction, patients received either 100 microg x kg(-1) ondansetron or placebo. Anaesthesia was maintained with 120-140 microg x kg(-1) x min(-1) propofol, nitrous oxide and oxygen to maintain vital signs within 20% of baseline. After surgery, in all patients the tracheas were extubated in the operating room without use of neuromuscular reversing agents. Episodes of emesis were recorded by PACU nurses for four to six hours. A telephone interview on the following day was also used for data recovery. Groups were compared in relation to age using the Mann-Whitney test, and with respect to sex and number of episodes of vomiting using the Fisher Exact Test. RESULTS: Three of the 45 patients who received ondansetron vomited (6.7%), whereas 10 of the 45 patients who received placebo vomited (22.2%). (P = 0.035) CONCLUSION: Ondansetron in a dose of 100 microg x kg(-1), when combined with propofol for children undergoing tonsillectomy reduced the incidence of postoperative vomiting to very low levels.