From randomized trial to practice: single institution experience using the GOG 172 i.p. chemotherapy regimen for ovarian cancer.

BACKGROUND: The objective of the study was to evaluate completion rates and toxic effects of an i.p. chemotherapy regimen in a cross-section of nonselected patients with ovarian cancer (OC). PATIENTS AND METHODS: All patients with stage IIIC OC consecutively operated at our institution from January 2006 to December 2007 were prospectively collected and analyzed. RESULTS: Eighty-nine patients with stage IIIC OC optimally debulked were evaluated for this study. An i.p. port was primarily placed in 53 of 89 (60%), and i.p. chemotherapy was recommended in 55 patients. Reasons for not recommending i.p. chemotherapy in patients optimally debulked included postoperative complications (n = 7: 8%), poor nutritional/functional status (n = 5: 6%), and extensive surgery including bowel resection (n = 9: 10%). Thirty-three patients (33/55: 60%) recommended to receive i.p. chemotherapy-initiated i.p. treatment. Fifty-two percent of those beginning i.p. therapy (17/33) received three or more cycles with 36% (12/33) successfully completing six cycles. Reasons for discontinuation included grade 3-4 nephrotoxicity in 3 of 21 (14%), febrile neutropenia/sepsis in 3 of 21 (14%), port infection or malfunction in 8 of 21 (38%). CONCLUSIONS: The i.p. chemotherapy regimen used in a consecutive cohort of patients carries could be completed in only a small percentage of patients. Less toxic regimens with higher acceptability should be considered.

Interregional healthcare: patient stories and chart reviews.

The literature and healthcare provider experiences leave questions about which interventions might best assist patients during interregional healthcare. The research was conducted to gain information on the current reality of interregional healthcare for patients needing tertiary cardiovascular care distant from their home. A purposive sample of patients having a cardiovascular diagnosis who were transferred for procedures or surveillance to a tertiary site were interviewed (n = 17), and their charts were reviewed (n = 27). Six broad themes were extracted from the interviews and chart reviews: healthcare provider behaviors, healthcare system issues, patient education or information, discharge from the hospital, overall reflections on the healthcare experience, and healthcare communication issues. A redesign of interregional healthcare is needed to address the areas of care and expert behaviors by providers, documentation, continuity, communication, education, and rehabilitation/adaption. The advanced practice nurse is well suited to lead these practice changes.

Correlation of nitric oxide synthase expression with changing patterns of axonal projections in the developing visual system.

A precise pattern of connections between the retina and central visual nuclei in the brain is established during development. Activity-dependent presynaptic mechanisms and NMDA receptor-mediated postsynaptic mechanisms are thought to play important roles in this developmental process. A model proposed for production of the newly described neurotransmitter, nitric oxide, involves presynaptic activity and activation of postsynaptic NMDA receptors. If present in the developing visual system, nitric oxide could represent a form of retrograde communication from postsynaptic to presynaptic cells that mediates the formation of the proper pattern of connections. This study used the diaphorase histochemical technique to detect the presence of nitric oxide synthase (NOS), the enzyme responsible for the production of nitric oxide, in the developing chick optic tectum. Results from this study showed that NOS is present in the developing tectum and that its expression coincides temporally with innervation by retinal axons. NOS expression reaches a peak at the time that refinement of the initial pattern of connections is occurring. WGA/HRP labeling of retinal axons confirmed that processes of NOS-positive cells in the tectum extend well into the area of the ingrowing retinal axons. Histochemical results from eyeless chick embryos indicate that NOS expression is dependent on the presence of retinal axons, which suggests that retinal axons synapse on cells that express nitric oxide. Northern blot analysis using a cDNA probe to NOS from rat brain verified the histochemical results. These results are consistent with nitric oxide having a role in development of the proper pattern of connections in the chick retinotectal system.

Purkinje cell protein-2 regulatory regions and transgene expression in cerebellar compartments.

The Purkinje cell protein 2 (Pcp-2) is expressed in cerebellar Purkinje cells and retinal bipolar neurons. To illuminate how Pcp-2 expression is restricted to only two neuronal types and to derive tools to express heterologous genes in these neuronal subpopulations, genomic sequences of the mouse Pcp-2 gene have been cloned and flanking sequences have been evaluated as a source of neuron-specific regulatory elements. An upstream region with homology to other genes expressed in neurons was identified and a hybrid gene containing this sequence was constructed by ligating 0.4 kb of upstream and 0.3 kb of downstream Pcp-2-flanking DNA to lacZ. Transgenic mice bearing this construct exhibited beta-galactosidase in a wide array of neuron types, suggesting that this sequence may play an important role in specifying neuronal expression. Addition of a further 3.1 kb of Pcp-2 upstream sequences restricted expression of beta-galactosidase to a small number of neuron types and most notably to Purkinje cells within parasagitally oriented cerebellar compartments. The presence of elements lying within the 3.1-kb upstream region and acting to specifically restrict Pcp-2 expression is therefore suggested. Moreover, as beta-galactosidase was not expressed in the bipolar cells of these transgenic mice, retinal expression of the endogenous Pcp-2 gene must involve elements in addition to those conferring expression within Purkinje cells.

Morphological patterns in the developing vertebrate retina.

Changes in the morphology of the early optic cup were observed in embryos of two distantly-related vertebrate species, a teleost fish, northern pike (Esox lucius), and chicken (Gallus gallus). A similar morphological pattern was noted to appear in both species shortly after the involution of the optic vesicle and the formation of the inner retinal layer. At a gross level, three notches were observed in the retinal margin at approximately nasal, dorsal, and temporal positions, while in histological sections a sharp constriction was found in the thickness of the dorsal retinal layer. In both species, this dorsal constriction appeared to be continuous with the central or dorsal notch. The time of appearance and configuration of this morphological pattern is intriguingly similar to the specification and polarity of retinal positional markers, and suggest a segmentation hypothesis for the origin of retinal polarity.

cDNA cloning and characterization of three genes uniquely expressed in cerebellum by Purkinje neurons.

The characteristics that distinguish the different neuronal cell types of an organism are believed to be primarily determined by unique patterns of cellular gene expression. The identification of cell-type specific molecules should therefore provide a good basis for understanding the biology of specific neuron types. In this paper, we describe the isolation of cDNA clones corresponding to mRNA uniquely expressed by Purkinje cells in mature mouse cerebellum. Three cDNA clones were selected from a library of normal mouse cerebellar cDNA by virtue of their failure to hybridize to mRNA sequences from the cerebella of Purkinje cell degeneration (pcd) mice. The cDNA clones were shown by in situ and Northern hybridization to correspond with mRNA present in Purkinje cells but absent or at low levels in other cell types of the cerebellum. By sequence analysis, clone PCD29 was determined to encode the calcium-binding protein calbindin-D28K. Clones PCD5 and PCD6 encode previously undescribed proteins of 99 and greater than 500 amino acids, respectively. All 3 PCD clones hybridized to mouse mRNA from sources other than cerebellum; clone PCD5 was found to have the most restricted expression, as it hybridized only to mRNA from cerebellum and eye. To define potential correlations between the PCD clones and mutations in the mouse genome known to affect Purkinje cells, clones PCD5, PCD6, and PCD29 were localized to mouse chromosomes 8, 6, and 4, respectively.