Nurse practitioner-led multidisciplinary teams to improve chronic illness care: The unique strengths of nurse practitioners applied to shared medical appointments/group visits

Purpose: To describe the roles of nurse practitioners (NPs) in a novel model of healthcare delivery for patients with chronic disease: shared medical appointments (SMAs)/group visits based on the chronic care model (CCM). To map the specific skills of NPs to the six elements of the CCM: self-management, decision support, delivery system design, clinical information systems, community resources, and organizational support.
Data sources: Case studies of three disease-specific multidisciplinary SMAs (diabetes, heart failure, and hypertension) in which NPs played a leadership role.
Conclusions: NPs have multiple roles in development, implementation, and sustainability of SMAs as quality improvement interventions. Although the specific skills of NPs map out all six elements of the CCM, in our context, they had the greatest role in self-management, decision support, and delivery system design.
Implications for practice: With the increasing numbers of patients with chronic illnesses, healthcare systems are increasingly challenged to provide necessary care and empower patients to participate in that care. NPs can play a key role in helping to meet these challenges.     

Mechanisms of disease: oxidative stress and inflammation in the pathogenesis of hypertension

Animal studies have shown that oxidative stress and renal tubulointerstitial inflammation are associated with, and have major roles in, the pathogenesis of hypertension. This view is supported by the observations that alleviation of oxidative stress and renal tubulointerstitial inflammation reduce arterial pressure in animal models. Conversely, hypertension has been shown to cause oxidative stress and inflammation in renal and cardiovascular tissues in experimental animals. Taken together, these observations indicate that oxidative stress, inflammation and arterial hypertension participate in a self-perpetuating cycle which, if not interrupted, can lead to progressive cardiovascular disease and renal complications. These events usually occur in an insidious and asymptomatic manner over an extended period following the onset of hypertension. Severe target organ injury can, however, occasionally occur precipitously in the course of malignant or accelerated hypertension. Given the high degree of heterogeneity of hypertensive disorders, the factor(s) initiating the vicious cycle described vary considerably in different forms of hypertension. For instance, oxidative stress in the kidney and vascular tissue is the primary mediator in the pathogenesis of angiotensin-induced, and perhaps lead-induced, hypertension. By contrast, increased arterial pressure is probably the initiating trigger in salt-sensitive hypertension. Although the initiating factor might vary between hypertensive disorders, according to the proposed model, the three components of the cycle eventually coalesce in all forms of hypertension.     

Involvement of endothelium and endothelin-1 in lead-induced smooth muscle cell dysfunction in rats

Lead exposure induces dysfunction of the cyclic guanosine monophosphate-dependent vasodilator system through downregulation of soluble guanylate cyclase (sGC) expression. The endothelium not only releases vasodilators but also vasoconstrictors such as endothelin-1 (ET-1). Our aim was to explore the role of the vascular endothelium and ET-1 as possible mediators of lead-induced downregulation of sGC. Isolated aortic segments from Wistar Kyoto rats were incubated in the presence or absence of lead (1 parts per million) for 24 h. Endothelium was mechanically removed in some of the aorta segments. As reported previously, lead exposure induced downregulation of sGC protein expression in the intact aortic segments. However, lead exposure failed to significantly modify sGC-beta1 subunit expression in the endothelium-denuded aortic segments. Incubation with a selective ETA-type receptor inhibitor, BQ-123 (10(-6) mol/l), restored sGC protein expression in lead-exposed intact aortic segments. As it has also been previously observed, incubation in lead-containing medium resulted in the upregulation of cyclooxygenase-2 (COX-2) in the intact aortic segments. Denudation of endothelium partially abrogated this effect of lead. Incubation with BQ-123 prevented the lead-induced upregulation COX-2 in the intact aortic segments. However, neither ET-1 content nor ETA-type receptor expression were modified by lead exposure of the aortic segments. As conclusion, the endothelium through the activation of ETA-type receptors mediates the downregulation of sGC expression by lead in the vascular wall.     

AT-1 receptor blockade prevents proteinuria, renal failure, hyperlipidemia, and glomerulosclerosis in the Imai rat

BACKGROUND: The Imai rat is a model of spontaneous focal glomerulosclerosis which leads to nephrotic syndrome, hyperlipidemia, hypertension, and progressive renal failure. We evaluated the effects of angiotensin II receptor type 1 (AT-1)blockade, and compared the results with the effects of the administration of hypolipidemic treatment with a 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor. All treatments were started at 10 weeks of age when the rats were already proteinuric and continued for 6 months when rats were sacrificed. METHODS: The following groups (N= 6 each) were studied: (1) control Sprague-Dawley rats, 34 weeks old; (2) Imai group that received vehicle; (3) Imai + angiotensin II receptor blockade (ARB) group that received olmesartan (10 mg/kg/day by gastric gavage); (4) Imai + prava group, that received pravastatin (20 mg/kg/day by gastric gavage); and (5) Imai + ARB + prava group that received both ARB and pravastatin. Lipid profile, renal function, and structure were assessed at 6 months. RESULTS: As expected, the untreated Imai rats exhibited heavy proteinuria, hypoalbuminemia, hypertension, renal insufficiency, marked glomerulosclerosis, tubulointerstitial inflammation, and profound hyperlipidemia. Pravastatin treatment alone led to a significant, but partial improvement of hyperlipidemia and renal disease. The ARB treatment alone or in combination with pravastatin resulted in normalization of the blood pressure, urinary protein excretion, plasma cholesterol, triglycerides, low-density lipoproteins (LDLs), very low-density lipoproteins (VLDLs), and albumin concentrations and renal function. Significant glomerulosclerosis was prevented and tubulointerstitial injury and immune cell infiltration were reduced by long-term AT-1 blockade. CONCLUSION: The study revealed that long-term AT-1 blockade corrects proteinuria, hyperlipidemia, and nephropathy in this model of spontaneous glomerulosclerosis.     

Up-regulation of kidney NAD(P)H oxidase and calcineurin in SHR: reversal by lifelong antioxidant supplementation

BACKGROUND: Spontaneously hypertensive rats (SHR) are born normotensive and develop hypertension (HTN) later in life (age 4 to 5 weeks). HTN in SHR is associated with and caused in part, by oxidative stress and renal interstitial inflammation. This study tested the hypothesis that lifelong antioxidant supplementation beginning at prenatal period may delay the onset and reduce the severity of HTN in SHR. The study further sought to explore the effect of diet modification on renal tissue NAD(P)H oxidase and calcineurin abundance. METHODS: Pregnant SHR and their offspring were fed either an antioxidant-fortified diet (a chow containing alpha-tocopherol 5000 IU/kg, ascorbic acid 500 ppm, selenium 2.76 ppm, and zinc 350 ppm) or regular diet (alpha-tocopherol 40 IU/kg, selenium 0.2 ppm, and zinc 70 ppm). Animals were observed for 24 weeks. Wistar-Kyoto rats fed either a regular or antioxidant diet served as control. RESULTS: Onset of HTN was delayed and severity of HTN was reduced in antioxidant-treated compared with untreated SHR. Markers of oxidative stress (i.e., plasma hydrogen peroxide, renal tissue malondialdehyde, and nitrotyrosine abundance) were elevated in untreated but not in antioxidant-treated SHR. gp91phox and p22phox subunits of NAD(P)H oxidase were markedly elevated in the renal cortex of untreated SHR and partially restored in the treated SHR. Similarly, renal calcineurin Aalpha and B subunits were elevated in untreated SHR and were partially restored in the treated SHR. Antioxidant therapy had no effect on the measured parameters in the WKY control. CONCLUSION: Lifelong consumption of antioxidant-rich diet ameliorates HTN and oxidative stress in SHR. This is associated with the reduction of superoxide-generating enzyme, NAD(P)H oxidase, and immunoregulatory factor calcineurin. Antioxidant-rich diet appears to attenuate oxidative stress, not only by fortifying antioxidant defense capacity but also by lowering NAD(P)H oxidase, which is a major source of reactive oxygen species.     

Oxidative stress in uremia: nature, mechanisms, and potential consequences

Oxidative stress has emerged as a constant feature of chronic renal failure (CRF). The presence of oxidative stress in CRF is evidenced by an overabundance of lipid, carbohydrate, and protein oxidation products in the plasma and tissues of uremic patients and animals. We recently have shown that oxidative stress in CRF animals is associated with and, in part, owing to up-regulation of superoxide-producing enzyme, nicotinamide-adenine dinucleotide phosphate (NAD(P)H) oxidase, and down-regulation of superoxide dismutase (SOD). The functional significance of these findings was confirmed by favorable response to administration of the cell-permeable SOD-mimetic agent, tempol, in CRF rats. Oxidative stress in CRF plays an important role in the pathogenesis of the associated hypertension (oxidation of NO and arachidonic acid and vascular remodeling), cardiovascular disease (oxidation of lipoproteins, atherogenesis), neurologic disorders (nitration of brain proteins, oxidation of myelin), anemia (reduction of erythrocyte lifespan), inflammation (nuclear factor kappa B activation), fibrosis, apoptosis, and accelerated aging. The CRF-induced oxidative stress is aggravated by diabetes, uncontrolled hypertension, and autoimmune diseases, which independently increase production of reactive oxygen intermediates, and frequently are associated with CRF. In addition, dialysis treatment (blood interaction with dialyzer membrane and dialysate impurities), acute and chronic infections (blood access infection, hepatitis, and so forth), and excessive parenteral iron administration intensify CRF-associated oxidative stress and its adverse consequences in patients with end-stage renal disease. The problem is compounded by limited intake of fresh fruits and vegetables (K(+) restriction), which contain numerous natural phytochemicals and antioxidant vitamins.     

Effective portal insulin delivery with enzyme-protected capsules in pancreatectomized pigs.

1. Plasma concentrations of insulin, C-peptide, glucagon and glucose were measured in surgically pancreatectomized pigs given insulin into the colon directly and in enteric peptidase-resistant (methacrylic acid copolymer-encapsulated) form. 2. Following introduction of insulin-containing capsules, plasma insulin concentration rose from 2.7 +/- 0.1 microU/ml to 110.9 +/- 51.9 microU/ml in the portal vein, and from 2.6 +/- 0.1 microU/ml to 26.9 +/- 7.3 microU/ml in the systemic circulation. Corresponding portal and systemic values after direct (non-encapsulated) insulin instillation were 28.2 +/- 15.9 microU/ml to 44.8 +/- 13.0 microU/ml and 7.5 +/- 2.6 microU/ml to 15.2 +/- 2.5 microU/ml respectively. Insulin concentrations peaked at 75 min in the group as a whole and between 60-90 min in individual animals. Absorption was most pronounced in pigs given aprotinin (a trypsin inhibitor) with insulin. 3. Plasma portal vein glucose concentrations fell from 76.2 +/- 8.9 mg/dl to 31.1 +/- 3.2 mg/dl 150 min after encapsulated insulin administration. Corresponding systemic glucose levels were 84.5 +/- 11.0 mg/dl and 37.0 +/- 1.4 mg/dl. 4. Colonic administration of insulin in methacrylic acid coated capsules results in peak portal and systemic insulin levels 60-90 min after administration. Co-administration of aprotinin enhances the fraction of insulin absorbed.     

3-D components of a biological neural network visualized in computer generated imagery. I. Macular receptive field organization

Computer-assisted, 3-dimensional reconstructions of macular receptive fields and of their linkages into a neural network have revealed new information about macular functional organization. Both type I and type II hair cells are included in the receptive fields. The fields are rounded, oblong, or elongated, but gradations between categories are common. Cell polarizations are divergent. Morphologically, each calyx of oblong and elongated fields appears to be an information processing site. Intrinsic modulation of information processing is extensive and varies with the kind of field. Each reconstructed field differs in detail from every other, suggesting that an element of randomness is introduced developmentally and contributes to endorgan adaptability.