Biomedical subjects

I Hernandez

Publications and source records attributed to I Hernandez.

At least 19 recordsLinked to original sources

PubMed2006

Plasma fibrinogen gamma' chain content in the thrombotic microangiopathy syndrome.

BACKGROUND: Human fibrinogen gamma chain variants, termed gamma' chains, contain a unique 20-residue sequence after gamma chain residue 407 that ends at gamma'427, and is designated gamma'(427L). Full-length (FL) gamma'(427L) chains are constituents of a fibrin-dependent thrombin inhibitory system known as antithrombin I, whereas a gamma' chain processed in vivo, termed gamma'(423P), lacks the C-terminal tetrapeptide EDDL, and does not bind thrombin. Together, the gamma'(423P) and gamma'(427L) chains comprise the total plasma fibrinogen gamma' chain content. OBJECTIVES: Lowered plasma gamma' chain content (i.e. gamma' chain-containing fibrinogen/total fibrinogen ratio) has been shown to correlate with susceptibility to venous thrombosis, thus prompting this study on the total and FL gamma' chain content in 45 subjects with thrombotic microangiopathy (TMA), a disorder characterized by microvascular thrombosis. METHODS: We measured by enzyme-linked immunosorbent assay the total gamma' chain-containing fibrinogen/total fibrinogen (Total gamma'-fgn/Total fgn) ratio and the FL gamma' chain-containing fibrinogen/total fibrinogen (FL gamma'-fgn/Total fgn) ratio in these plasmas and in healthy subjects (n = 87). RESULTS: In healthy subjects, the mean Total gamma'-fgn/Total fgn ratio was 0.127, whereas the FL gamma'-fgn/Total fgn ratio was somewhat lower at 0.099 (P < 0.0001), a difference reflecting the presence of gamma'(423P) chains. In TMA plasmas, both the Total gamma'-fgn and FL gamma'-fgn/Total fgn ratios (0.099 and 0.084, respectively) were lower than those of their healthy subject counterparts (P < 0.0001). CONCLUSIONS: These findings in TMA suggest that reductions in the gamma' chain content indicate reduced antithrombin I activity that may contribute to microvascular thrombosis in TMA.

ADAM Proteins↗

PubMed2004

The ultrastructure of fibrinogen-420 and the fibrin-420 clot.

Fibrinogen-420 is a minor subclass of human fibrinogen that is so named because of its higher molecular weight compared to fibrinogen-340, the predominant form of circulating fibrinogen. Each of the two Aalpha chains of fibrinogen-340 is replaced in fibrinogen-420 by an Aalpha isoform termed alphaE. Such chains contain a globular C-terminal extension, alphaEC, that is homologous with the C-terminal regions of Bbeta and gamma chains in the fibrin D domain. The alphaEC domain lacks a functional fibrin polymerization pocket like those found in the D domain, but it does contain a binding site for beta2 integrins. Electron microscopy of fibrinogen-340 molecules showed the major core fibrinogen domains, D-E-D, plus globular portions of the C-terminal alphaC domains. Fibrinogen-420 molecules had two additional globular domains that were attributable to alphaEC. Turbidity measurements of thrombin-cleaved fibrinogen-420 revealed a reduced rate of fibrin polymerization and a lower maximum turbidity. Thromboelastographic measurements also showed a reduced rate of fibrin-420 polymerization (amplitude development) compared with fibrin-340. Nevertheless, the final amplitude (MA) and the calculated elastic modulus (G) for fibrin-420 were greater than those for fibrin-340. These results suggested a greater degree of fibrin-420 branching and thinner matrix fibers, and such structures were found in SEM images. In addition, fibrin-420 fibers were irregular and often showed nodular structures protruding from the fiber surface. These nodularities represented alphaEC domains, and possibly alphaC domains as well. TEM images of negatively shadowed fibrin-420 networks showed irregular fiber borders, but the fibers possessed the same 22.5-nm periodicity that characterizes all fibrin fibers. From this result, we conclude that fibrin-420 fiber assembly occurs through the same D-E interactions that drive the assembly of all fibrin fibrils, and therefore that the staggered overlapping molecular packing arrangement is the same in both types of fibrin. The alphaEC domains are arrayed on fiber surfaces, and in this location, they would very likely slow lateral fibril association, causing thinner, more branched fibers to form. However, their location on the fiber surface would facilitate cellular interactions through the integrin receptor binding site.

Blood Coagulation↗

PubMed2004

Evidence that catalytically-inactivated thrombin forms non-covalently linked dimers that bridge between fibrin/fibrinogen fibers and enhance fibrin polymerization.

Phe-pro-arg-chloromethyl ketone-inhibited alpha-thrombin [FPR alpha-thr] retains its fibrinogen recognition site (exosite 1), augments fibrin/fibrinogen [fibrin(ogen)] polymerization, and increases the incorporation of fibrin into clots. There are two 'low-affinity' thrombin-binding sites in each central E domain of fibrin, plus a non-substrate 'high affinity' gamma' chain thrombin-binding site on heterodimeric 'fibrin(ogen) 2' molecules (gamma(A), gamma'). 'Fibrin(ogen) 1' (gamma(A), gamma(A)) containing only low-affinity thrombin-binding sites, showed concentration-dependent FPR alpha-thr enhancement of polymerization, thus indicating that low-affinity sites are sufficient for enhancing polymerization. FPR gamma-thr, whose exosite 1 is non-functional, did not enhance polymerization of either fibrin(ogen)s 1 or 2 and DNA aptamer HD-1, which binds specifically to exosite 1, blocked FPR alpha-thr enhanced polymerization of both types of fibrin(ogen) (1>2). These results showed that exosite 1 is the critical element in thrombin that mediates enhanced fibrin polymerization. Des B beta 1-42 fibrin(ogen) 1, containing defective 'low-affinity' binding sites, was subdued in its FPR alpha-thr-mediated reactivity, whereas des B beta 1-42 fibrin(ogen) 2 (gamma(A), gamma') was more reactive. Thus, the gamma' chain thrombin-binding site contributes to enhanced FPR alpha-thr mediated polymerization and acts through a site on thrombin that is different from exosite 1, possibly exosite 2. Overall, the results suggest that during fibrin clot formation, catalytically-inactivated FPR alpha-thr molecules form non-covalently linked thrombin dimers, which serve to enhance fibrin polymerization by bridging between fibrin(ogen) molecules, mainly through their low affinity sites.

Amino Acid Chloromethyl Ketones↗

PubMed2003

The inducible isoform of CREM (inducible cAMP early repressor, ICER) is a repressor of CYP19 rat ovarian promoter.

The synthesis of estradiol by the granulosa cells is a prominent event in ovarian physiology and depends on the expression of P450(AROM). FSH induces the expression of P450(AROM) in granulosa cells as a result of the presence in the ovarian promoter of a CRE (cAMP response element)-like sequence (CLS). In rodents, LH downregulates aromatase expression during luteinization by an as yet undescribed mechanism. In granulosa cells, LH increases the expression of the inducible cAMP early repressor (ICER), an isoform of CREM (cAMP-responsive element modulator) that represses cAMP-induced transcription. The possibility that ICER represses the activity of the aromatase ovarian promoter, thus being part of the mechanism underlying the effects of LH was investigated. We have found that: (1) nuclear proteins from forskolin-stimulated granulosa cells were specifically bound to an oligonucleotide containing the CLS sequence of the CYP19 ovarian promoter and one out of the two protein-DNA complexes formed was supershifted by an anti-CREM antibody; (2) in granulosa cells, forskolin-induced increases in P450(AROM) promoter luciferase reporter gene activity were prevented by the transient overexpression of ICER; (3) similar results were obtained in 8-Br-cAMP-stimulated R2C cells, a Leydig tumor cell line routinely used for the study of P450(AROM) promoter activity; (4) both ICER mRNA levels and P450(AROM) promoter-driven luciferase activity were elevated 6 and 12 h after stimulation of R2C cells with 8-Br-cAMP and were decreased 24 and 48 h later; (5) in an R2C polyclonal line overexpressing ICER, the promoter activity at early stages of stimulation was completely attenuated, while 24 and 48 h downregulation was prevented in another R2C line stably transfected with an antisense ICER construct. These results suggest that ICER represses CYP19 ovarian promoter and that LH-induced expression of ICER may serve to downregulate P450(AROM) transcription in granulosa cells during luteinization.

Animals↗

PubMed2001

Effect of short pulsed nonablative infrared laser irradiation on vascular cells in vitro and neointimal hyperplasia in a rabbit balloon injury model.

BACKGROUND: Neointimal hyperplasia after PTCA is an important component of restenosis. METHODS AND RESULTS: Cultures of rabbit endothelial cells and smooth muscle cells (SMCs) were irradiated with different doses of nonablative infrared (1064-nm) radiation. Normalized viability index detected with nondestructive Alamar Blue assay and direct cell count were studied. Our experiments demonstrated dose-dependent cytostatic or cytotoxic effects of laser irradiation. We also evaluated the long-term effect of endoluminal nonablative infrared laser irradiation on neointimal hyperplasia in a rabbit balloon injury model. PTCA of both iliac arteries of 23 New Zealand White rabbits was performed. One iliac artery was subjected to intra-arterial subablative infrared irradiation via a diffuse tip fiber. The contralateral vessel served as control. The diet was supplemented with 0.25% cholesterol and 2% peanut oil for 10 days before and 60 days after PTCA. Morphometry after 60 days showed that intimal areas were 0.76+/-0.18 and 1.85+/-0.30 mm(2) in the laser and control arteries, respectively (P=2.2x10(-11)). CONCLUSIONS: We conclude that nonablative infrared laser inhibited neointimal hyperplasia after PTCA in cholesterol-fed rabbits for up to 60 days.

Angioplasty, Balloon, Coronary↗

PubMed2001

Effect of angiotensin-converting enzyme inhibitor on renal function in ovarian hyperstimulation syndrome in the rabbit.

OBJECTIVE: To investigate renal function and whether captopril prevents alterations in the handling of sodium and water in the ovarian hyperstimulation syndrome (OHSS) in the rabbit. DESIGN: Experimental study SETTING: Physiology laboratory. ANIMAL(S): Six female New Zealand white rabbits were used as controls, and 13 were hyperstimulated with gonadotropins. INTERVENTION(S): Saline or captopril. MAIN OUTCOME MEASURE(S): Renal excretory and hemodynamic variables. RESULT(S): The 3% extracellular volume expansion in OHSS animals induced a significant elevation in mean arterial pressure by 27%, although increments in natriuresis and diuresis were similar to those observed in controls. The OHSS group had impaired pressure-natriuresis sensitivity compared with controls (0.36 +/- 0.07 microEq/min/g of Na excreted per mm Hg vs. 1.74 +/- 0.45 microEq/min/g of Na excreted per mm Hg; P<.05. Captopril significantly reduced mean arterial pressure (P<.05) and shifted the pressure-natriuresis response to the left by 0.85 +/- 0.17 microEq/min/g of Na excreted per mm Hg (P<.05). CONCLUSION(S): In OHSS in the rabbit model, pressure-natriuresis sensitivity is impaired. Angiotensin II may play a significant role in this phenomenon, since angiotensin-converting enzyme inhibition normalized the pressure-natriuresis relationship.

Angiotensin-Converting Enzyme Inhibitors↗

PubMed2001

Disintegration and reorganization of fibrin networks during tissue-type plasminogen activator-induced clot lysis.

In this study, we investigated tissue-type plasminogen activator (tPA)-induced lysis of glutamic acid (glu)-plasminogen-containing or lysine (lys)-plasminogen-containing thrombin-induced fibrin clots. We measured clot development and plasmin-mediated clot disintegration by thromboelastography, and used scanning electron microscopy (SEM) to document the structural changes taking place during clot formation and lysis. These events occurred in three overlapping stages, which were initiated by the addition of thrombin, resulting first in fibrin polymerization and clot network organization (Stage I). Autolytic plasmin cleavage of glu-plasminogen at lys-77 generates lys-plasminogen, exposing lysine binding sites in its kringle domains. The presence of lys-plasminogen within the thrombin-induced fibrin clot enhanced network reorganization to form thicker fibers as well as globular complexes containing fibrin and lys-plasminogen having a greater level of turbidity and a higher elastic modulus (G) than occurred with thrombin alone. Lys-plasminogen or glu-plasminogen that had been incorporated into the fibrin clot was activated to plasmin by tPA admixed with the thrombin, and led directly to clot disintegration (Stage II) concomitant with fibrin network reorganization. The onset of Stage III (clot dissolution) was signaled by a sustained secondary rise in turbidity that was due to the combined effects of lys-plasminogen presence or its conversion from glu-plasminogen, plus clot network reorganization. SEM images documented dynamic structural changes in the lysing fibrin network and showed that the secondary turbidity rise was due to extensive reorganization of severed fibrils and fibers to form wide, occasionally branched fibers. These degraded structures contributed little, if anything, to the structural integrity of the residual clot, and eventually collapsed completely during the course of progressive clot dissolution. These results provide new perspectives on the major structural events that occur in the fibrin clot matrix during fibrinolysis.

Fibrin↗

PubMed2000

Distribution of protein kinase Mzeta and the complete protein kinase C isoform family in rat brain.

Protein kinase C (PKC) is a multigene family of at least ten isoforms, nine of which are expressed in brain (alpha, betaI, betaII, gamma, delta, straightepsilon, eta, zeta, iota/lambda). Our previous studies have shown that many of these PKCs participate in synaptic plasticity in the CA1 region of the hippocampus. Multiple isoforms are transiently activated in the induction phase of long-term potentiation (LTP). In contrast, a single species, zeta, is persistently activated during the maintenance phase of LTP through the formation of an independent, constitutively active catalytic domain, protein kinase Mzeta (PKMzeta). In this study, we used immunoblot and immunocytochemical techniques with isoform-specific antisera to examine the distribution of the complete family of PKC isozymes and PKMzeta in rat brain. Each form of PKC showed a widespread distribution in the brain with a distinct regional pattern of high and low levels of expression. PKMzeta, the predominant form of PKM in brain, had high levels in hippocampus, frontal and occipital cortex, striatum, and hypothalamus. In the hippocampus, each isoform was expressed in a characteristic pattern, with zeta prominent in the CA1 stratum radiatum. These results suggest that the compartmentalization of PKC isoforms in neurons may contribute to their function, with the location of PKMzeta prominent in areas notable for long-term synaptic plasticity.

Animals↗

PubMed2000

Isolation and characterization of mouse probasin: An androgen-regulated protein specifically expressed in the differentiated prostate.

BACKGROUND: The development and growth of the prostate gland is regulated, in part, by a variety of steroid and polypeptide growth-factor hormones. As a consequence of hormone action, the prostate gland will produce a number of tissue-restricted gene products. Characterization of the regulation, expression, and function of genes encoding prostate-specific proteins is critical to our understanding of prostate biology. Probasin is a prostate-specific gene originally isolated from the rat and has been exploited as a marker of prostate differentiation and to elucidate androgen action. Furthermore, a number of transgenic mouse models of prostate cancer have been established based on the regulatory elements derived from the rat probasin gene. In this report, we describe the isolation and characterization of the mouse probasin ortholog to further facilitate studies related to hormone action in the prostate and the generation and characterization of novel autochthonous models of prostate cancer. METHODS: Mouse probasin cDNA was isolated from a phage library, and the DNA sequence was determined. The predicted protein sequence was used to generate specific oligonucleotide primers and antibodies. Probasin protein and RNA expression were examined by immunobloting, immunohistochemistry, and RT-PCR, in normal mouse prostate tissue and tumor tissues derived from the autochthonous "transgenic adenocarcinoma of the mouse prostate" (TRAMP) model. Regulation of probasin expression in response to surgical castration and hormone supplementation was also characterized. RESULTS: Several points of evolutionary sequence conservation were identified between mouse and rat probasin, especially in the 3' untranslated region. Specific polyclonal antibodies were generated to peptide fragments, and the temporal and spatial pattern of probasin expression was examined. The expression of probasin was primarily localized to the apical membrane of differentiated secretory epithelium. Probasin mRNA and protein were absent from the poorly differentiated tissue of TRAMP tumors. Probasin was found to be androgen-regulated. In contrast to data from studies on rat probasin, no postcastration rebound of mouse probasin mRNA was observed. CONCLUSIONS: Probasin is a marker of differentiation and androgen action in the mouse prostate, and strong sequence conservation between mouse and rat probasin supports an essential role for this gene in the biology of the prostate gland. Isolation and characterization of mouse probasin will facilitate further development and analysis of autochthonous mouse models of prostate cancer.

Amino Acid Sequence↗

PubMed2000

Abnormalities in 5-HT2A receptor mRNA expression in frontal cortex of chronic elderly schizophrenics with varying histories of neuroleptic treatment.

Alterations in the 5-HT2A receptor gene expression in the prefrontal cortex have been suggested to play a role in the pathophysiology and pharmacotherapy of schizophrenia. This study measured mRNA encoding 5-HT2A receptor in the left superior frontal gyrus from chronic elderly schizophrenics (n = 21) with varying neuroleptic-free intervals before death (72 hr to more than 5 years), and normal drug-free elderly controls (n = 14). Levels of 5-HT2A mRNA in schizophrenics correlated significantly and inversely with neuroleptic-free interval before death (r = -0.77; P < 0.0001). In schizophrenics who had been receiving neuroleptic until time of death, levels of 5-HT2A mRNA were similar to controls or greater. In schizophrenics who had been free of neuroleptic for more than six months levels of 5-HT2A mRNA were significantly lower than in controls. These results confirm previous findings of decreased expression of the 5-HT2A receptor gene in the frontal cortex of some schizophrenics and suggest that regulation of this gene may be involved in the therapeutic actions of typical neuroleptics.

Aged↗

PubMed2000

Biodesign of a skeletal muscle flap as a model for cardiac assistance.

In using autologous muscles for cardiac assistance, it is crucial to reduce ischemia-reperfusion injury in the surgically traumatized skeletal muscle. In adult sheep, we developed a simple model of surgically designed 2 latissimus dorsi muscle leaflets by modifying the vascular supply to these leaflets. Three pockets with graded injury were established, and muscle morphology and vascular remodeling were monitored in 3 experimental groups: muscle leaflets without any treatment (Group 1, n = 6) that served as controls; muscle leaflets integrated with a fibrin interlayer (Group 2, n = 6); and leaflets integrated with fibrin and entrapped pyrrolostatin (Group 3, n = 6). We applied the fibrinogen and thrombin solutions, which polymerize to form a three-dimensional meshwork joining the tissues, creating a provisional matrix for angiogenesis, and acting as a delivery depot for agents aimed at minimizing ischemia-reperfusion lesion formation. After 2 months, the muscle leaflets biointegrated with the fibrin interface showed none of the signs of necrosis or ischemia-reperfusion lesions seen in the controls. Although no angiogenic factors were incorporated, the fibrin interlayer rapidly (<2 weeks) became a densely vascularized tissue replete with a voluminous capillary network. In contrast, controls showed poor bonding between the tissues, muscle fiber deterioration, and a compromised vascular network. Muscle structure was best preserved and angiogenesis was greatest when pyrrolostatin, a free radical scavenger, was added to the fibrin meshwork to reduce damage caused by overproduction of free radicals. This newly designed model will be useful to study many current approaches in cardiovascular biology, from pharmaceuticals to gene therapy, which might prove advantageous in muscle-designed cardiac assistance.

Animals↗

PubMed2000

Factor analysis of the Neuropsychological Screening Battery for Hispanics (NeSBHIS).

The Neuropsychological Screening Battery for Hispanics (NeSBHIS; Pontón et al., 1996) was developed to provide clinicians and researchers with appropriate tests and norms to assess the Latino population. However, the construct validity of the NeSBHIS is unclear, and its clinical utility is untested. This study provides data on the construct validity of this battery via factor analytic methodology. Five factors were identified: (a) a language factor, which included the Controlled Oral Word Association Test, the Pontón-Satz Boston Naming Test, and the Escala de Inteligencia Wechsler para Adultos (EIWA; Wechsler, Green, & Martinez, 1968) Digit Span; (b) a verbal learning factor, which included all the World Health Organization--University of California, Los Angeles Auditory Verbal Learning Test scores (Trials V, VII, and VIII); (c) an attentional-mental control factor, which included the EIWA Digit Symbol, Color Trails 1 and 2, and the EIWA Block Design; (d) a visuospatial factor, made up of the Rey-Osterrieth Complex Figure Test Copy and Memory and the Raven's Standard Progressive Matrices total score; and (e) a psychomotor factor, the Pin Test. This was a stable factor structure, suggesting that the NeSBHIS has a robust construct validity.

Adolescent↗

PubMed2000

Phase I trial of all-trans retinoic acid in patients with treated head and neck squamous carcinoma.

Although retinoids show promise for prevention of second primary upper aerodigestive tract tumors, the optimum retinoid, dose, and schedule are unknown. All-trans retinoic acid (ATRA) has greater affinity for retinoic acid receptors and may be more active than other retinoids but has a shorter plasma half life and may up-regulate its own metabolism. We defined the maximum long-term tolerable dose, dosing frequency, pharmacokinetics, and toxicity of ATRA in patients with treated squamous cell carcinoma of the head and neck (SCCHN). Twenty-one patients were randomized to 45, 90, or 150 mg/m2 ATRA either once daily, or as divided doses every 8 h, for 1 year. Pharmacokinetics were assessed periodically. Fourteen men and seven women with previous SCCHN of initial stage I-IV were treated. Grade > or =3 toxicities (reversible) included headache and hypertriglyceridemia in 5 and 6 patients each, mucositis in 2 patients, and hyperbilirubinemia, elevated alkaline phosphatase, colitis, lipasemia, xerostomia, eczema, and arthritis in 1 patient each. The 150-mg/m2 dose was not tolerable. Doses were reduced for grade > or =3 toxicity in seven of eight patients at 90 mg/m2 daily. Three of nine patients at 45 mg/m2/day required dose reduction, two at the once-daily dose. Day 1 ATRA area under the plasma concentration versus time curve (AUC) increased with dose, and after 1-2 months of continued dosing, the AUC declined in 7 of 13 patients (54%) studied. ATRA AUC did not correlate with toxicity severity or frequency. Fifteen mg/m2/day every 8 h is a tolerable dose for 1 year in patients with treated SCCHN. ATRA pharmacokinetics did not correlate with toxicity.

Adult↗

PubMed1999

Differential effects of octreotide treatment and transsphenoidal surgery on growth hormone-binding protein levels in patients with acromegaly.

OBJECT: The high-affinity growth hormone-binding protein (GHBP) represents the extracellular portion of the growth hormone (GH) receptor, and its serum levels are a reflection of the tissue receptor status. Levels of GHBP are decreased in patients with active acromegaly, probably because of downregulation of GH receptors. However, there are no studies of patients with acromegaly in which the effects of medical (that is, administration of somatostatin analogs) and surgical therapy on GHBP levels have been compared. That is the task the authors set out to accomplish in this study. METHODS: The authors studied seven patients in whom acromegaly had been recently diagnosed. They examined these patients at baseline, 2 months after octreotide treatment (subcutaneous administration of 100 microg octreotide three times per day), and 1 month after transsphenoidal surgery. Growth hormone-binding activity was measured, as well as the following biochemical markers of the somatotropic axis: GH suppression induced by oral administration of glucose, insulin-like growth factor-I (IGF-I), and insulin-like growth factor-binding protein-3 (IGFBP3). Although octreotide treatment induced a decrease in the levels of GH, IGF-I, and IGFBP3, as well as an increase in the level of GHBP, these biochemical markers did not reach normal levels. On the other hand, after transsphenoidal surgery, GHBP levels became normal, particularly in those patients in whom serum GH could be suppressed to an undetectable level after glucose loading. CONCLUSIONS: The authors conclude that persistently low GHBP levels in patients with acromegaly are normalized by successful pituitary surgery and correlate well with disease activity.

Acromegaly↗

PubMed1999

The efficacy and cost effectiveness of new antiemetic guidelines.

PURPOSE/OBJECTIVES: To develop antiemetic guidelines to improve efficacy, optimize nursing and pharmacy time, increase compliance, and enhance cost savings. DESIGN: Prospective, descriptive survey. SETTING: Outpatient oncology clinic in a large metropolitan city in the mid-Atlantic United States. SAMPLE: 90 patients were evaluated for the study; 52 patients met the eligibility criteria. METHODS: A standard antiemetic form was developed containing the emetogenic classification of the chemotherapeutic drugs and the recommended antiemetic regimen. A patient diary and visual analog scale measured patient satisfaction with the regimen-measured outcomes. MAIN RESEARCH VARIABLES: Episodes of nausea and vomiting, classification of chemotherapeutic drugs, and patient satisfaction. FINDINGS: Seventy-nine percent of patients receiving highly emetogenic chemotherapy demonstrated complete protection from nausea and vomiting during the first 24 hours post-therapy. All the patients receiving moderately and mildly emetogenic regimens achieved complete protection. Patients who received cisplatin-containing regimens and were on the delayed regimen of antiemetics demonstrated complete protection on days two through seven. The mean overall score for patient satisfaction with the regimen was 89 mm on a 100 mm visual analog scale. CONCLUSIONS: The new oral antiemetic regimen compared favorably with published data, was well-tolerated, and resulted in lower pharmacy and nursing costs, with a cost saving potential of $20,000 per year. IMPLICATIONS FOR NURSING PRACTICE: Oncology nurses must be able to implement state-of-the-art knowledge of chemotherapy, antiemetics, and nonpharmacologic interventions to effectively manage the care of patients receiving chemotherapy. This must be performed to achieve cost effectiveness as well as useful clinical outcomes.

Adult↗

PubMed1998

Role of nitric oxide on the central hemodynamic response to acute volume expansion in the pregnant rat.

OBJECTIVES: Our hypothesis was that during pregnancy nitric oxide acts as mediator in the hemodynamic response to volume expansion. STUDY DESIGN: The study was performed on 12 rats on days 19 to 20 of pregnancy. Six rats were injected intravenously with hexamethonium bromide plus the inhibitor of nitric oxide synthase L-nitro-arginine methyl ester. For a control group, six rats were injected with hexamethonium bromide plus the L-nitro-arginine methyl ester vehicle. A volume expansion (1.2% body weight) was performed in both groups by intravenous infusion of bovine albumin (6%) solution. RESULTS: In the control group volume expansion induced a hyperdynamic circulation characterized by increased cardiac output, decreased total vascular resistance, and no change in arterial pressure; however, in the study group volume expansion induced a pressor response without hyperdynamic circulation. CONCLUSION: During pregnancy volume expansion induces a hyperdynamic circulatory state possibly mediated by nitric oxide release. A defect in the release of nitric oxide may be responsible for an inadequate hemodynamic response to volume expansion.

Animals↗

PubMed1997

Unbalanced 15;22 translocation in a patient with manifestations of DiGeorge and velocardiofacial syndrome.

We report on an 8-year-old girl with an unbalanced 15;22 translocation and manifestations of DiGeorge syndrome (DGS), velocardiofacial syndrome (VCFS), and other abnormalities. The main manifestations of our patient were feeding difficulties, respiratory infections, short stature, peculiar face with hypertelorism, prominent nose, abnormal ears, microstomia and crowded teeth, short broad neck and shield chest with pectus deformity and widely spaced nipples with abnormal fat distribution, heart defect, scoliosis, asymmetric limb development, abnormal hands and feet, and hyperchromic skin patches. Cytogenetic studies demonstrated a 45,XX,der(15)t(15;22)(p11.2;q11.2), -22 karyotype. Fluorescence in situ hybridization (FISH) studies confirmed loss of the proximal DiGeorge chromosomal region (DGCR). This case adds to the diversity of clinical abnormalities caused by deletions within 22q11.2.

Abnormalities, Multiple↗

PubMed1997

Progesterone metabolites and bile acids in serum of patients with intrahepatic cholestasis of pregnancy: effect of ursodeoxycholic acid therapy.

The concentrations in serum of sulfated metabolites of progesterone are known to be elevated in patients with intrahepatic cholestasis of pregnancy (ICP). The profiles of these metabolites and conjugated bile acids were analyzed in serum from 11 patients with ICP before and during administration of ursodeoxycholic acid (UDCA) (8 patients) or placebo (3 patients). The clinical condition of 7 of the patients given UDCA improved markedly, and 1 patient given placebo had a spontaneous remission of the disease. The total concentration of conjugated bile acids in the 11 patients was 25 +/- 6 micromol/L (mean +/- SEM) and decreased to 6.3 +/- 3.5 micromol/L in the 7 patients responding to treatment with UDCA. The level of 7alpha-hydroxy-4-cholesten-3-one was significantly lower (7.2 +/- 2.2 ng/mL) in patients with ICP than in healthy pregnancy (18 +/- 4.6 ng/mL) (P < .05). The concentrations of 5alpha-pregnane-3alpha,20alpha-diol mono- and disulfates decreased by 52% +/- 7.9% and 68% +/- 5.5%, respectively, in the patients responding to treatment. Similar decreases were observed for the mono- and disulfates of 5alpha-pregnane-3alpha,20alpha,21-triol and 5beta-pregnane-3alpha,20alpha-diol. The disulfate of 5alpha-pregnane-3beta,20alpha-diol showed a smaller decrease, while glucuronidated steroids were not affected. The 3alpha-/3beta-hydroxysteroid ratio and di-/monosulfate ratio decreased significantly during UDCA. The magnitudes of the changes of bile acid and steroid concentrations during UDCA were not correlated to each other. The results suggest that UDCA stimulates the biliary excretion of steroids with a 3alpha-sulfoxy group and disulfates. This effect seems to be independent of the effect on bile acid excretion, indicating the use of different transport proteins. The possibility of an effect of UDCA on the formation of the steroid sulfates cannot be excluded.

Bile Acids and Salts↗