Dietary management of presumptive protein-losing enteropathy in Yorkshire terriers.

OBJECTIVES: To describe the clinical outcome of dietary management of Yorkshire terriers with protein-losing enteropathy without immunosuppressive/anti-inflammatory medications. METHODS: Records were searched for Yorkshire terriers with hypoalbuminaemia and a clinical diagnosis of protein-losing enteropathy that were managed with diet and without immunosuppressive/anti-inflammatory medications. Serum albumin changes were compared using a one-way repeated measures ANOVA. Canine chronic enteropathy clinical activity index scores were compared using a Wilcoxon signed-rank test. RESULTS: Eleven cases were identified. Clinical signs were variable including: diarrhoea, respiratory signs, vomiting, lethargy and weight loss. Diets fed included home cooked (n=5); Royal Canin Gastrointestinal Low Fat (n=4); Hill's Prescription Diet i/d Low Fat (n=1); or Purina HA Hypoallergenic (n=1). Clinical signs resolved completely in eight dogs, partially resolved in two dogs and failed to respond in one dog. In dogs that responded, albumin significantly improved from baseline (mean 14·9 g/L, sd ±3·7), at 2 to 4 weeks (mean 24·2 g/L, sd ±5·5, P=0·01), and at 3 to 4 months (mean 27·0 g/dL, sd ±5·9, P=0·01). CLINICAL SIGNIFICANCE: These results indicate that dietary management of protein-losing enteropathy is a potential management strategy in Yorkshire terriers. Randomised clinical trials in Yorkshire terriers with protein-losing enteropathy are necessary to compare success rate, survival and quality of life with dietary management versus combined dietary and immunosuppressive/anti-inflammatory therapy.

Glycoprotein IIb/IIIa inhibitors use and outcome after percutaneous coronary intervention for non-ST elevation myocardial infarction.

AIMS: We investigate the effect of glycoprotein IIb/IIIa (GP IIb/IIIa) inhibitors on long-term outcomes following percutaneous coronary intervention (PCI) after non-ST elevation myocardial infarction (NSTEMI). Meta-analyses indicate that these agents are associated with improved short-term outcomes. However, many trials were undertaken before the routine use of P2Y12 inhibitors. Recent studies yield conflicting results and registry data have suggested that GP IIb/IIIa inhibitors may cause more bleeding than what trials indicate. METHODS AND RESULTS: This retrospective observational study involves 3047 patients receiving dual-antiplatelet therapy who underwent PCI for NSTEMI. Primary outcome was all-cause mortality. Major adverse cardiac events (MACE) were a secondary outcome. Mean follow-up was 4.6 years. Patients treated with GP IIb/IIIa inhibitors were younger with fewer comorbidities. Although the unadjusted Kaplan-Meier analysis suggested that GP IIb/IIIa inhibitor use was associated with improved outcomes, multivariate analysis (including propensity scoring) showed no benefit for either survival (P = 0.136) or MACE (P = 0.614). GP IIb/IIIa inhibitor use was associated with an increased risk of major bleeding (P = 0.021). CONCLUSION: Although GP IIb/IIIa inhibitor use appeared to improve outcomes after PCI for NSTEMI, patients who received GP IIb/IIIa inhibitors tended to be at lower risk. After multivariate adjustment we observed no improvement in MACE or survival and an increased risk of major bleeding.

Pretreatment with intravenous ascorbic acid preserves endothelial function during acute hyperglycaemia (R1).

1. Acute hyperglycaemia may impair endothelial function. Ascorbic acid (AA), administered intra-arterially, has been reported to improve endothelium-dependent vasodilatation during a forearm hyperglycaemic clamp. Using a randomized, double-blind, placebo-controlled, cross-over study, we investigated the potential for intravenous ascorbic acid to modify the endothelial response to acute systemic hyperglycaemia in humans. 2. Nine healthy male volunteers were recruited from the hospital staff. Endothelial function was determined by measuring the forearm blood flow responses to intrabrachial infusions of endothelium-dependent (ED) and endothelium-independent (EID) vasodilators. The endothelial function index (EFI) was derived from the ratio of ED and EID vasodilatation. Haemodynamic and endothelial function measurements were performed at baseline and then repeated 2 h after a systemic hyperglycaemic clamp (14 mmol/L). The subjects, studied on two separate occasions, were randomized to placebo or 2 g intravenous ascorbic acid prior to the initiation of hyperglycaemia. 3. After systemic hyperglycaemia with placebo pretreatment, the EFI fell from 1.08 +/- 0.21 to 0.74 +/- 0.13 (difference (95% confidence interval): 0.34 (0.20, 0.47); P < 0.001). When subjects were pretreated with ascorbic acid, the EFI was not affected by hyperglycaemia (1.11 +/- 0.21 to 1.12 +/- 0.17; P = 0.938). This difference between placebo and ascorbic acid was significant (P < 0.001). Plasma ascorbate concentrations decreased during hyperglycaemia and correlated directly with the reduction in the EFI (r = 0.798; P < 0.001). 4. Pretreatment with an intravenous bolus of ascorbic acid can prevent endothelial dysfunction during acute systemic hyperglycaemia. Therefore, ascorbic acid may have potential therapeutic use in clinical situations where acute hyperglycaemia may be a complication.

Protective effects of ascorbic acid on arterial hemodynamics during acute hyperglycemia.

Mortality increases when acute coronary syndromes are complicated by stress-induced hyperglycemia. Early pulse wave reflection can augment central aortic systolic blood pressure and increase left ventricular strain. Altered pulse wave reflection may contribute to the increase in cardiac risk during acute hyperglycemia. Chronic ascorbic acid (AA) supplementation has recently been shown to reduce pulse wave reflection in diabetes. We investigated the in vivo effects of acute hyperglycemia, with and without AA pretreatment, on pulse wave reflection and arterial hemodynamics. Healthy male volunteers were studied. Peripheral blood pressure (BP) was measured at the brachial artery, and the SphygmoCor pulse wave analysis system was used to derive central BP, the aortic augmentation index (AIx; measure of systemic arterial stiffness), and the time to pulse wave refection (Tr; measure of aortic distensibility) from noninvasively obtained radial artery pulse pressure (PP) waveforms. Hemodynamics were recorded at baseline and then every 30 min during a 120-min systemic hyperglycemic clamp (14 mmol/l). The subjects, studied on two separate occasions, were randomized in a double-blind, crossover manner to placebo or 2 g intravenous AA before the initiation of hyperglycemia. During hyperglycemia, AIx increased and Tr decreased. Hyperglycemia did not change peripheral PP but did magnify central aortic PP and diminished the normal physiological amplification of PP from the aorta to the periphery. Pulse wave reflection, as assessed from peripheral pulse wave analysis, is enhanced during acute hyperglycemia. Pretreatment with AA prevented the hyperglycemia-induced hemodynamic changes. By protecting hemodynamics during acute hyperglycemia, AA may have therapeutic use.

Asthma care in community health centers: a study by the southeast regional clinicians' network.

Federally funded community health centers (CHCs) were surveyed to assess their ability to serve low-income asthma patients in the southeastern United States. Data were collected on CHC clinicians, pharmacy services, and patient characteristics. Twenty-six (74%) of 35 participating CHCs provided data on 83 distinct clinic sites in eight states, representing 898,977 billable patient visits to 318,920 people during the one-year study period. Participating CHCs provided 23% of all CHC patient visits in Region IV in 1995. Sixty-two percent of patients had a family income below poverty level. Almost 75% of the patients were uninsured or receiving Medicaid. Asthma was the diagnosis code for 2.04% of all medical encounters. Twenty-nine percent of sites were unable to provide medications for uninsured asthma patients, while 66% could provide drug samples. Thirty-three percent of CHCs had in-house pharmacies and 33% offered pharmacy vouchers. Eighty-two percent could provide beta-agonist inhalers, 54% could provide steroid inhalers, and 17% could provide peak flow meters. Federally funded CHCs provide care to many asthma patients from the highest risk segments of the population, but often do not have the resources needed to follow current clinical guidelines.

The role of the nutritional support dietitian in Europe.

UNLABELLED: The European Community now supports the potential for professionals to practice in any of the member states subject to recognized local standards of education and practice being achieved. However, there is no agreed role for the nutritional support dietitian. This leads to an inconsistent and, sometimes, fragmented approach to the nutritional management of patients throughout Europe. There is a need to develop a common dietetic approach to nutritional support in order to raise awareness and rationalize standards. This will help to optimize care to individual patients by fostering good practice, developing effective communication and encouraging research. BACKGROUND: The role of the clinical dietitian varies widely throughout Europe - it tends to be more highly developed in some countries than in others, which is a cause for concern among dietitians in ESPEN. This appears to be caused by several factors including education, clinical awareness of the benefits of dietetic support and access to adequate financial resources. The intention of this paper is to focus on the key aspects of the role of the dietitian working in nutritional support. The educational requirements of such a dietitian are outlined and these could be used as a preliminary guide for institutions responsible for delivering undergraduate dietetic programmes. The overall intention is to identify minimum educational standards for practice in this field throughout Europe. However, these should be viewed as a baseline from which to proceed. They should also be perceived as a quality standard for facilitating professional development, sharing clinical practice and enhancing patient outcomes. This paper does not address issues of resource allocation. RECOMMENDATIONS: a) There should be agreement about the key functions of the dietitian working in nutritional support; b) There should be a common standard at first degree level for all dietitians; c) There should be an identified programme of post-graduate study (both clinical and academic) leading to specialization in nutritional support; d) There should be an innovative approach to providing clinical support for emerging specialists; e) ESPEN should investigate the potential for developing an accredited and integrated European dietetic standard in nutritional support.

Suicide among young Australians, 1964-1993: an interstate comparison of metropolitan and rural trends.

OBJECTIVES: (i) To compare suicide rates in 15-24 year old men and women; and (ii) for 15-24 year old men, to investigate differences in suicide rates between metropolitan and rural area, and changes in method-specific suicide rates and, in particular, firearm and hanging suicide rates in rural and metropolitan areas. DESIGN: Retrospective analysis of Australian Bureau of Statistics (ABS) suicide data (1964-1993). SETTING: All Australian States. SUBJECTS: Young women and men aged 15-24 years who died by suicide. RESULTS: Male youth suicide rates rose substantially over the 30 years in all Australian States, whereas female rates did not increase. Increases in suicide rates in young men in small rural towns consistently exceeded those in metropolitan areas in all Australian States. Metropolitan rates in 1964 were higher than those in small rural towns, but by 1993 the position was reversed. Medium-sized cities were the only areas where there was no consistent interstate trend. Differences were noted in suicide base rates in different States. High car exhaust suicide rates were noted in Western Australia, and high firearm suicide rates in Tasmania and Queensland. The ratio of firearm suicide rates in small rural areas to those in metropolitan areas rose in all mainland States, but the same ratio for hanging suicide rates changed little. CONCLUSIONS: All Australian States reflect national suicide trend in relation to sex and residential area. In some States, particular suicide methods predominate. A decreasing trend in overall firearm suicide rates in young men in all States from 1984 to 1993 conceals substantial increases in firearm suicide rates in small rural areas in all mainland States over the 30-year period. This, together with the marked rate ratio difference in firearm suicides between metropolitan and small rural areas, suggests that particular risk factors for suicide are operating in small rural areas. The fact that hanging rate ratios changed little suggests that more general factors in male youth suicide are also operating in all areas. A better understanding of similarities and differences in health risks faced by metropolitan and rural youth is required.

The sequence NPFXD defines a new class of endocytosis signal in Saccharomyces cerevisiae.

The yeast membrane protein Kex2p uses a tyrosine-containing motif within the cytoplasmic domain for localization to a late Golgi compartment. Because Golgi membrane proteins mislocalized to the plasma membrane in yeast can undergo endocytosis, we examined whether the Golgi localization sequence or other sequences in the Kex2p cytoplasmic domain mediate endocytosis. To assess endocytic function, the Kex2p cytoplasmic domain was fused to an endocytosis-defective form of the alpha-factor receptor. Ste2p. Like intact Ste2p, the chimeric protein, Stex22p, undergoes rapid endocytosis that is dependent on clathrin and End3p. Uptake of Stex22p does not require the Kex2p Golgi localization motif. Instead, the sequence NPFSD, located 37 amino acids from the COOH terminus, is essential for Stex22p endocytosis. Internalization was abolished when the N, P, or F residues were converted to alanine and severely impaired upon conversion of D to A. NPFSD restored uptake when added to the COOH terminus of an endocytosis-defective Ste2p chimera lacking lysine-based endocytosis signals present in wild-type Ste2p. An NPF sequence is present in the cytoplasmic domain of the a-factor receptor, Ste3p. Mutation of this sequence prevented pheromone-stimulated endocytosis of a truncated form of Ste3p. Our results identify NPFSD as a clathrin-dependent endocytosis signal that is distinct from the aromatic amino acid-containing Golgi localization motif and lysine-based, ubiquitin-dependent endocytosis signals in yeast.

Effects of alternating current iontophoresis on drug delivery.

OBJECTIVE: The duration of direct current (DC) iontophoresis is limited to 10- to 15-minute periods because of electrochemical burns from hydrogen and hydroxide ions generated by the DC current. A new iontophoretic device, the Lectro Patch, uses a low-frequency alternating current (AC). AC current is theorized to generate H+ ions during one phase and OH- when the current reverses polarity, thus possibly neutralizing pH changes and avoiding burns. This study examined this possibility and evaluated drug delivery with AC iontophoresis, using hydroxocobalamin. DESIGN: A known amount of hydroxocobalamin dissolved in 6mL of water was loaded in Lectro Patches, two of which were then taped on the forearms of 10 patient volunteers. One patch was activated to deliver drug by AC iontophoresis. The second patch was not activated and served as a control for delivery by diffusion. Trials were run for 2 and 4 hours, with both 1,000 micrograms/mL and 2,000 micrograms/mL concentrations. SETTING: Study was conducted with inpatients in an extended care setting using volunteers. MAIN OUTCOME MEASURES: Amounts of hydroxocobalamin remaining in the Lectro Patches after iontophoresis were assayed by spectrophotometry. Data were analyzed by ANOVA. RESULTS: No burns occurred. Significantly greater losses occurred with 4 hours of iontophoresis than with 2 hours (p < 0.05). There was no significant effect of changing the concentration of hydroxocobalamin. CONCLUSIONS: AC iontophoresis avoids electrochemical burns; charged drugs can be delivered by AC iontophoresis; and delivery of drug increases with duration of application.

Pocket computers: a new aid to nutritional support.

A program has been written to run on a pocket computer (Sharp PC-1500) that can be used at the bedside to predict the nutritional requirements of patients with a wide range of clinical conditions. The predictions of the program showed good correlation with measured values for energy and nitrogen requirements. The program was used, with good results, in the management of over 100 patients needing nutritional support. The calculation of nutritional requirements for each patient individually facilitates more appropriate treatment and may also produce financial savings when compared with administration of a standard feeding regimen to all patients.

Pertussis in infants diagnosed by an ambulatory unit: an illness that still persists.

Two instances of pertussis in infants are reported which were diagnosed in an outpatient clinic. Factors regarding the diagnosis and possible prevention or reduction of the severity of this illness are discussed.

Clinical and cell surface marker characterization of the early phase of chronic lymphocytic leukemia.

The immunologic surface markers on lymphocytes and clinical characteristics of 35 patients with established (stages 0-4) CLL with absolute lymphocyte counts greater than 15,000/cu mm were compared to those of a group of 25 patients with CLL in an early or preleukemic phase (counts of less than 15,000/cu mm). We found a monoclonal B cell proliferation in most cases in the latter group, in spite of the paucity of clinical and laboratory findings. Furthermore, early CLL can readily be distinguished from benign lymphocytosis by surface marker criteria. In untreated CLL, surface marker characteristics are stable with time and predominantly reflect expansion of clones expressing only B cell markers; however, small increase of blood T cells are often seen. Surface markers are a simple and clinically useful tool for definding and characterizing the preleukemic phase of CLL and its ultimate progression to established CLL.