Measuring advanced practice nursing outcomes.

The measurement of outcomes has become an important component of evaluating health care. Although it is clear that measuring outcomes is necessary to establish the effectiveness of advanced practicing nursing, which outcome measures to use and how to conduct an effective outcomes assessment remain unclear. The purpose of this article is to present an overview of advanced practice nursing outcomes research, review outcome measures important to advanced practice nurses (APNs), and discuss sources of outcome measures and instruments that can be used by APNs to establish the effectiveness of the role.

Specificity of treatment effects for learning disabilities in a boy prenatally exposed to dilantin.

The present case study provides evidence that a specific deficit can be improved by a treatment specific intervention in a boy who was prenatally exposed to Dilantin and presented with a learning disability. After implementation of a focused intervention for reading, standardized test scores revealed that the child demonstrated a dramatic improvement in reading performance, but remained consistent in other academic areas. This indicated that his reading improvement was the direct effect of specific training in reading, but did not generalize to other content areas. This finding is significant because it provides support for treatment specificity in contrast to treatment generalizability.

Overexpression of the focal adhesion kinase (p125FAK) in invasive human tumors.

The focal adhesion kinase (FAK) gene encodes a tyrosine kinase (p125FAK) thought to be involved in signal transduction pathways used in cell adhesion, motility, and anchorage-independent growth. Because alterations in these cellular processes occur in tumor invasion and metastasis, we studied the protein expression of FAK in a variety of human tumors and found that in the 119 samples studied, increased levels of p125FAK correlated with the invasive potential of a tumor. By comparing FAK expression in tumors with normal tissue from the same patient, we found that p125FAK was significantly elevated in 17 (100%) of 17 invasive and metastatic colonic lesions and in 22 (88%) of 25 invasive and metastatic breast tumors. Additional studies of FAK expression in 13 high grade sarcomas showed high levels in all samples compared to benign, noninvasive mesenchymal specimens. Furthermore, FAK protein levels were elevated in preinvasive lesions, such as large (> 2 cm) colonic villous adenomas, whereas noninvasive, yet hypercellular, neoplastic tissues such as parathyroid and hepatocellular adenomas did not overexpress FAK. These data provide evidence that both epithelial and mesenchymal tumor progression are accompanied by increased p125FAK expression and suggest that the level of FAK expression might be a marker for the invasive potential of a tumor.

Receptor tyrosine kinases expressed in metastatic colon cancer.

Using a PCR-based cloning technique, we have isolated a series of DNA fragments coding for tyrosine kinases that are expressed in a metastatic human colon tumor, and have subsequently analyzed their expression pattern at the protein level in human tumors. We identified both the alpha and the beta forms of the platelet-derived growth factor receptor (PDGFR), axl and 8 other genes, including 3 cytoplasmic tyrosine kinases. To study their expression in human colon cancer, we performed Western blots of matched sets of normal tissues and of carcinomas from the same patient. These revealed that the alpha-PDGFR migrates predominantly as a 200-kDa band in 8/8 normal tissues, and as a 170-kDa band in 17/17 malignant tissues, as well as in colonic polyps, suggesting that expression of an isoform of this receptor may be a marker for the progression of colon cancer. Additional studies showed that the Axl receptor tyrosine kinase was expressed at 10-fold higher levels in a peritoneal metastatic nodule than in other normal and malignant tissues. Immunohistochemistry revealed Axl over-expression specifically in the malignant cells of the tumor. This indicates that over-expression and possibly a differential processing event of tyrosine kinase receptors may be involved in colon cancer, and that they are potential markers for the progression of this disease.

Molecular mechanisms involved in tumorigenesis and their surgical implications.

Our understanding of normal and malignant cell growth has rapidly advanced in the last two decades as new technologies have accelerated the ability to resolve the underlying molecular mechanisms. The speed and complexity of this advance, as well as the inadequate and confused nomenclature of molecular oncology, has made this field difficult to follow. Nevertheless, many future therapies will be targeted to a genomic level and clinicians will be called upon to communicate with basic scientists in implementing them. To facilitate the surgeon's part in this dialogue, we present a broad review of the molecular genetics of cancer. The selected bibliography contains many review articles by leading researchers in this field. Particular emphasis has been placed on the themes that are emerging, such as oncogenic mechanisms, tumor suppressor genes, signal transduction, the multistage concept of carcinogenesis, and molecular diagnostics and therapies.

Chronic lung disease is the leading risk factor correlating with the failure (wrap disruption) of antireflux procedures in children.

Recurrent gastroesophageal reflux (GER) after antireflux procedures (ARP) has been correlated with significant neurological impairment (NI). Other major risk factors for recurrent GER have not been extensively characterized. The authors reviewed their experience with ARPs in children to better characterize the risk factors for recurrent GER and identify successful management strategies for these patients. The charts of 281 consecutively treated children who had an ARP at our institution (1985 to 1992) were reviewed. The neurological status of each child was assessed as normal or impaired (cerebral palsy, seizures, mental retardation, spasticity), and other medical diagnoses such as chronic pulmonary disorders (eg, interstitial disease, cystic fibrosis, bronchopulmonary dysplasia, asthma, etc), and congenital malformations and syndromes were identified. The average follow-up period was 3 years (range, 1 to 7.5 years). Patients with symptoms of recurrent GER were evaluated with an upper gastrointestinal study. Patients with a radiologically intact fundoplication and suspected GER were further evaluated with a 24-hour pH probe. Statistical analyses were performed using the Fisher's Exact Test. Of the 281 patients who underwent ARP, 39 had documented recurrent GER (average, 16 months after surgery). Twenty-five (64%) of these children had chronic pulmonary disease (CPD). Thirty-two percent of all children with CPD had recurrent GER after ARP, versus 7% of those without CPD (P < .0001). For children with NI and CPD there was an increased risk (P < .0001) of failure when compared with the risk in the normal subgroup (children without CPD or NI) who underwent ARP.(ABSTRACT TRUNCATED AT 250 WORDS)

Expression of growth factor receptors, the focal adhesion kinase, and other tyrosine kinases in human soft tissue tumors.

BACKGROUND: The tyrosine kinases are a family of genes that includes many growth factor receptors and protooncogenes. They appear to have a role in many cancers, but have not been systematically studied in the pathogenesis and progression of human sarcomas. METHODS: To characterize the protein tyrosine kinases that are expressed in human sarcomas, we used a polymerase chain reaction (PCR)-based method to construct kinase-specific cDNA libraries from low-grade and high-grade primary tumors. Thereafter, individual tyrosine kinase gene expression was assessed in a panel of sarcoma cell lines and primary tumors using Northern blotting and PCR. RESULTS: We identified 19 species of tyrosine kinase genes, including many growth factor receptors, the human homolog of the focal adhesion kinase (FAK) gene, and a novel trk-related kinase designated HGK2. Messenger RNA expression analyses showed relative overexpression of the two forms of the platelet-derived growth factor receptors (PDGFRs) with expression of the alpha form restricted to a subgroup of high-grad and metastatic sarcomas. We were unable to demonstrate coexpression of the PDGF isoforms in primary tumors that overexpressed the receptors, suggesting that a PDGF/PDGFR autocrine pathway may not be a central mechanism in the malignant transformation of sarcomas in vivo. FAK expression was observed in a variety of sarcomas, with increased levels in several high-grade and metastatic leiomyosarcomas. CONCLUSIONS: When grouped together by histologic cell type and grade, the expression data of the 19 kinases in primary tumors described a greater degree of heterogeneity than is generally appreciated by clinicopathologic classification schemes. This diversity suggests that sarcomas, even those that appear to be clinically similar, arise through a variety of molecular pathways involving tyrosine kinases.

Expression of focal adhesion kinase gene and invasive cancer.

The focal adhesion kinase (FAK) gene produces a tyrosine kinase that localises to contact points between cells and extracellular matrix. It is believed to be an important signal molecule in cell adhesion. We have isolated a human homologue of the FAK gene from primary sarcomas and looked for FAK mRNA in 49 human tissue samples, including paired normal and neoplastic samples. We found increased levels of FAK in 1 of 8 adenomatous tissues, in 17 of 20 invasive tumours, and in all 15 metastatic tumours. There was no detectable FAK mRNA in 6 normal tissue samples. These observations suggest that FAK overexpression may accompany changes in signal pathways involved in tumour cell invasion.

Pertussis: the return of a bad penny.

We describe two related cases of pertussis infection ("whooping cough"). This disease entity was almost completely eradicated through successful mass immunization programs. In the past decade it has demonstrated a steady rise in incidence. The epidemiology, clinical manifestations, treatment, and current vaccines for pertussis infection are reviewed.

Novel protein kinases expressed in human breast cancer.

The family of protein kinases includes many oncogenes and growth-factor receptors, as well as genes that are involved in cell-cycle regulation. We have identified protein kinases expressed in a human breast-cancer cell line, 600PEI, and a primary human breast carcinoma, using PCR cloning techniques based on consensus sequences in the kinase domain. Twenty-five different protein kinases were isolated, including 3 novel putative tyrosine kinases (designated TK1, TK2, and TK5), and 2 novel putative cell-cycle-associated serine/threonine kinases (designated STK1 and STK2). TK1 is a new member of the src family of kinases that is expressed predominantly in epithelial cells. TK2 is homologous to the receptor kinase, HEK, and TK5 appears to be another member of the JAK family of kinases. The novel serine/threonine kinases, designated STK1 and STK2, were homologous to the human cdc2 and the Aspergillus nimA genes. We subsequently analyzed the levels of expression of all of these protein kinases in a panel of human breast carcinomas, using PCR-based methods. This analysis revealed different expression profiles in different primary breast carcinomas and, therefore, may determine new molecular sub-sets of human breast cancer.

Long term results of percutaneous catheter drainage of pancreatic pseudocysts.

Percutaneous catheter drainage (PCD) has become an established and often preferred alternative to surgical treatment in the management of pancreatic pseudocysts. However, the long term results of percutaneous drainage of pancreatic pseudocysts remain uncertain. In an effort to determine the long term outcome of this therapy, 42 patients undergoing PCD of a pancreatic pseudocyst were analyzed retrospectively. Forty-two pancreatic pseudocysts were drained percutaneously in 42 patients. Sixty-seven percutaneous drainage procedures were performed--22 patients underwent one, 15 had two and five patients required three procedures. Percutaneous drainage was considered not to be effective when the pseudocyst persisted or when it recurred after initial resolution. Twenty-three pseudocysts were infected at the time of drainage and 19 were not infected. In 30 patients, the cause of the pseudocyst was alcoholic pancreatitis. There were no deaths related to the procedures and seven complications occurred, including hemorrhage, pancreatic fistula and empyema. Mean follow-up evaluation time of the patients was ten months. In nine patients, the pseudocyst was successfully drained and resolved. There were 33 treatment failures, among which 26 pseudocysts failed to resolve and seven recurred after initial resolution. Eventually, 25 patients underwent a surgical procedure, 20 for persistent pseudocyst and five for recurrence. Using contingency table analysis, the size of the pseudocyst, amount of fluid drained, amylase concentration in the aspirate, presence of infection, number of drainage procedures performed and duration of catheter drainage had no influence on the likelihood of success in long term pseudocyst resolution after PCD. Pseudocysts not related to alcoholic pancreatitis seemed to be less likely (p < 0.05) to resolve with percutaneous drainage than those caused by alcohol. PCD is a safe and valuable procedure in the acute management of patients with pancreatic pseudocyst. However, the current data suggest that despite early success with percutaneous drainage, the lack of resolution and recurrence rate of pancreatic pseudocyst is high. Therefore, it should not be considered as the definitive form of therapy in most patients. Close surveillance of patients undergoing percutaneous drainage and communication between surgeons and radiologists are critical in the management of pancreatic pseudocysts.

Effects of dietary linoleic acid on blood pressure and renal function in subtotally nephrectomized rats.

The effect of a high linoleic acid diet on blood pressure, renal function, and urinary prostaglandin excretion was studied in rats with decreased renal mass. Subtotally nephrectomized (5/6 nephrectomy) male rats received either a 15% linoleic acid (high linoleic acid, HLA) diet containing 20% safflower oil or a 0.28% linoleic acid (low linoleic acid, LLA) diet containing 20% coconut oil. Sham-operated rats were also placed on either HLA or LLA diet. The subtotal nephrectomized rats developed similar degrees of hypertension during the first 3 weeks after subtotal nephrectomy. However, 4 weeks after subtotal nephrectomy, the rats on HLA diet had significantly lower blood pressure than the rats on LLA diet [HLA 152 +/- 3 (mean +/- SE) mm Hg versus LLA 171 +/- 3 mm Hg]. This difference persisted until termination of the experiment at 7 weeks after subtotal nephrectomy (HLA 159 +/- 7 mm Hg versus LLA 192 +/- 6 mm Hg). The GFR measured 7 weeks after subtotal nephrectomy was significantly lower in both of the subtotally nephrectomized groups. However, the HLA subtotal nephrectomized rats had significantly higher GFR than the LLA-treated rats (HLA 0.23 +/- 0.05 ml/min 100 g versus LLA 0.12 +/- 0.02 ml/min/100 g, P less than 0.05). There was no difference in the GFR or blood pressure in the sham-operated rats treated with HLA or LLA diet. PGE2 excretion was lower in the two groups of subnephrectomized rats, but there was no difference between the HLA and LLA treated rats. Urinary 6-ketoPGF1 alpha was not decreased by subtotal nephrectomy and there was no difference between the dietary groups. However, TXB2 excretion was higher in the groups with subtotal nephrectomy, but there was no difference between the two dietary groups. In conclusion, the HLA diet attenuates the rise in blood pressure after subtotal nephrectomy in the rat and preserves renal function. There was no difference in urinary excretion of PGE2, 6-keto-PFG1 alpha, or thromboxane B2 between the two dietary groups.

22-Carbon polyenoic acids. Incorporation into platelet phospholipids and the synthesis of these acids from 20-carbon polyenoic acid precursors by intact platelets.

The types of unsaturated fatty acids found in platelet phospholipids must be regulated by a series of controls which include specificity for activation and acylation as well as modification of circulating fatty acids by platelets prior to incubation into phospholipids. In this study we show that washed human platelets not only incorporate [1-14C]6,9,12-18:3, [1-14C]6,9,12,15-18:4, [1-14C]5,8,11-20:3, [1-14C]5,8,11,14-20:4, and [1-14C]5,8,11,14,17-20:5 into their phospholipids but also chain elongate each of these acids with subsequent acylation of the chain elongated products into phospholipids. Platelets incubated alone with 1-14C-labeled 5,8,11-20:3, 5,8,11,14-20:4, 5,8,11,14,17-20:5, 7,10,13,16,19-22:5, or 4,7,10,13,16,19-22:6 incorporated each of these acids into individual phosphoglycerides with phosphatidylinositol having the highest specific activity followed by phosphatidylcholine with phosphatidylserine approximately equal to phosphatidylethanolamine. The incorporation specificity of 4,7,10,13,16,19-22:6 was atypical since it was a relatively poor substrate for acylation into all phospholipids except phosphatidylethanolamine. The 20-carbon acids were better substrates for incorporation into phospholipids than were the 22-carbon compounds. Simultaneous incubation of 10 microM [1-14C]5,8,11,14-20:4 with increasing levels (5 to 15 microM) of each of the above five other 1-14C-labeled acids showed a concentration-dependent increase in the amount of the second fatty acid incorporated into platelet phospholipids. Dietary fat modification thus has the potential of increasing the plasma pool of 22-carbon acids for incorporation into platelets. In addition the activation of 20-carbon eicosanoid precursors by the high affinity platelet activating enzyme (Wilson, D. B., Prescott, S. M. and Majerus, P. W. (1982) J. Biol. Chem. 257, 3510-3515) will yield an acyl-CoA for both acylation and chain elongation followed by subsequent incorporation of 22-carbon acids into phosphoglycerides.

Arachidonic acid, 5,8,11-eicosatrienoic acid and 5,8,11,14, 17-eicosapentaenoic acid. Dietary manipulation of the levels of these acids in rat liver and platelet phospholipids and their incorporation into human platelet lipids.

Rats were fed diets in which the sole source of fat was either ethyl oleate, linoleate, linolenate or an equal mixture of ethyl linoleate and linolenate. The fatty acid composition of individual phospholipids from platelets and liver was compared to define how total body metabolism regulates which unsaturated fatty acids are produced and incorporated into platelet lipids for potential release and conversion to eicosanoids. The level of 20:4(n-6) in all phospholipids was not markedly altered by feeding linoleate versus that found in chow-fed controls. In oleate fed rats, the 20:3(n-9)/20:4(n-6) ratio varied from 0.5 in liver PE to 4.1 for liver PI, while ratios of 1.0, 1.1, 0.7 and 1.3 were found respectively for platelet PE, PC, PS and PI. Platelet PE contained a component tentatively identified as 22:3(n-9), which is consistent with the finding that this lipid contains significant amounts of 22:4(n-6) and 22:5(n-3) when rats received respectively linoleate or linolenate. Rats fed linolenate have a tight coupling between the regulation of unsaturated fatty acid biosynthesis and the selective acylation of 20:5(n-3) into all lipids. The 20:5(n-3)/20:4(n-6) ratio, however, varied between lipids. In liver PE, PC, PS and PI it was respectively 4.3, 4.9, 3.8 and 0.4, while in the analogous platelet lipids it was 3.0, 4.0, 0.9 and 0.6. Feeding linolenate did not markedly elevate the levels of 22:5(n-3) or 22:6(n-3) in platelet PI, but the combined amounts of 22:5(n-3) and 22:6(n-3) in liver PI were 21.2%, versus 2.9% in chow-fed controls. When the diet contained linoleate and linolenate, there was selective conversion of 18:2(n-6) to 20:4(n-6) and its acylation into lipids versus analogous metabolism of 18:3(n-3) to 20:5(n-3) and its subsequent incorporation. Again, the 20:5(n-3)/20:4(n-6) ratio was lowest for platelet PI and PS and liver PI. Washed human platelets readily incorporated 20:3(n-9), 20:4(n-6) and 20:5(n-3) into phospholipids. With each substrate, PI had the highest specific activity; this effect was most pronounced with 20:3(n-9). These incorporation studies are consistent with the feeding studies which show that oleate is converted to 20:3(n-9) and incorporated into PI more readily than the analogous metabolism of 18:3(n-3) to 20:5(n-3) and its acylation into PI, which is an important source of unsaturated fatty acids for prostaglandin biosynthesis.