Biomedical subjects

T Le

Publications and source records attributed to T Le.

At least 91 records · Page 5Linked to original sources

PubMed1998

Reduced growth, abnormal kidney structure, and type 2 (AT2) angiotensin receptor-mediated blood pressure regulation in mice lacking both AT1A and AT1B receptors for angiotensin II.

The classically recognized functions of the renin-angiotensin system are mediated by type 1 (AT1) angiotensin receptors. Whereas man possesses a single AT1 receptor, there are two AT1 receptor isoforms in rodents (AT1A and AT1B) that are products of separate genes (Agtr1a and Agtr1b). We have generated mice lacking AT1B (Agtr1b -/-) and both AT1A and AT1B receptors (Agtr1a -/-Agtr1b -/-). Agtr1b -/- mice are healthy, without an abnormal phenotype. In contrast, Agtr1a -/-Agtr1b -/- mice have diminished growth, vascular thickening within the kidney, and atrophy of the inner renal medulla. This phenotype is virtually identical to that seen in angiotensinogen-deficient (Agt-/-) and angiotensin-converting enzyme-deficient (Ace -/-) mice that are unable to synthesize angiotensin II. Agtr1a -/-Agtr1b -/- mice have no systemic pressor response to infusions of angiotensin II, but they respond normally to another vasoconstrictor, epinephrine. Blood pressure is reduced substantially in the Agtr1a -/- Agtr1b -/- mice and following administration of an angiotensin converting enzyme inhibitor, their blood pressure increases paradoxically. We suggest that this is a result of interruption of AT2-receptor signaling. In summary, our studies suggest that both AT1 receptors promote somatic growth and maintenance of normal kidney structure. The absence of either of the AT1 receptor isoforms alone can be compensated in varying degrees by the other isoform. These studies reaffirm and extend the importance of AT1 receptors to mediate physiological functions of the renin-angiotensin system.

Adrenal Glands↗

PubMed1998

Involvement of genes encoding a K+ channel (ether a go-go) and a Na+ channel (smellblind) in Drosophila olfaction.

We have investigated the roles of the putative cyclic nucleotide-modulated K+ channel subunit encoded by the ether a go-go (eag) gene and a voltage-gated Na+ channel, smellblind (sbl), encoded by the paralytic (para) locus in odorant responsiveness and cell excitability in Drosophila melanogaster. Three independent mutant alleles of eag revealed reduced antennal responsiveness in adult flies to a subset of odorants, all having short aliphatic side chains: ethyl butyrate (EB), propionic acid, 2-butanone and ethyl acetate (manuscript submitted). Loose patch recordings revealed that significantly fewer eag antennal neurons responded to EB compared to control neurons. As expected if Eag were involved in odor transduction, fewer EB-induced inhibitory responses were observed in eag mutants and focal application of high K+ saline to sensillae altered the excitability of the majority of neurons from wild-type, but not eag, antennae. Interestingly, there were fewer excitatory odorant responses dependent on extracellular Ca2+ in eag neurons. In contrast to the involvement of Eag in adult olfactory neuron odorant transduction, we found no evidence that adult sbl and allelic olfactory D (olfD) gene mutants were defective in their behavioral response to a complex attractive odor. Furthermore, electrophysiological analyses of adult sbl and olfD mutants revealed normal electroantennogram responses to a broad range of individual pure odorants and no changes in the excitable properties of olfactory neurons as determined by loose patch recordings.

Animals↗

PubMed1998

Chronic cholestasis in rats induces anhedonia and a loss of social interest.

Central fatigue commonly occurs in patients with primary biliary cirrhosis (PBC) and correlates closely with depression, and cholestatic rats exhibit central fatigue. Therefore, we undertook a series of experiments in both rats with cholestasis caused by bile duct resection (BDR) and sham-resected controls (15 days after surgery) to determine if experimental cholestasis is associated with symptoms of depression that can be modeled in rats, namely anhedonia (loss of pleasure) and the loss of social interest. BDR rats exhibited significant anhedonia compared with sham controls as indicated by a loss in their preference for consuming a saccharin solution, a highly desirable drink for rats. Furthermore, social interest was examined by determining the time BDR or sham rats spent investigating a juvenile rat in an open-field apparatus compared with the time spent on nonsocial behaviors. BDR rats exhibited significantly reduced time spent in social investigation and significantly more time in nonsocial behaviors than did sham rats. Major depression in humans is often associated with elevated circulating glucocorticoid levels and impaired glucocorticoid feedback. Therefore, we measured these parameters in BDR and sham rats and found a striking elevation in circulating glucocorticoid levels in BDR compared with sham animals. However, elevated circulating glucocorticoid levels in BDR rats suppressed normally in response to exogenous dexamethasone, indicating intact glucocorticoid feedback control at the pituitary level in BDR rats. In summary, we have identified behaviors in cholestatic rats that are consistent with those seen in depression.

Animals↗

PubMed1998

Augmented interleukin-1beta-induced depression of locomotor activity in cholestatic rats.

"Sickness behaviors" such as lethargy, fatigue, and malaise occur commonly in patients with cholestatic liver diseases and contribute significantly to the morbidity associated with these diseases. However, the cause of these symptoms is unknown. Interleukin-1beta (IL-1beta) released within the brain has been implicated in the genesis of a number of "sickness behaviors," including malaise and lethargy. Therefore, we investigated whether experimental cholestatic liver disease caused by bile duct resection (BDR) in rats is associated with enhanced central sensitivity to IL-1beta-induced "sickness behaviors." The central infusion of IL-1beta at a dose that produced an insignificant decrease in locomotor activity in control rats produced a striking reduction in locomotor activity in cholestatic rats. The anorectic response to central IL-1beta infusion was similar in cholestatic and noncholestatic animals and did not parallel our locomotor activity findings. Therefore, cholestatic liver injury is characterized by augmented central responsiveness to IL-1beta with respect to a decrease in locomotor activity. These findings may explain, at least in part, the high incidence of symptoms such as fatigue, malaise, and lethargy that occur in cholestatic patients and may open novel future avenues for their treatment.

Animals↗

PubMed1998

Panniculectomy: a useful technique for the obese patient undergoing gynecological surgery.

OBJECTIVES: To establish the safety and efficacy of panniculectomy at the time of surgery for benign and malignant gynecological disease. METHODS: Retrospective review of the course of 57 patients undergoing radical gynecological surgery and panniculectomy between January 1992 and January 1997 at the Mercy Hospital for Women, Melbourne. Data were collected regarding indication for treatment, operative details, and complications of surgery. RESULTS: Of 57 patients in the study, 32 had a primary gynecological malignancy, 11 had benign gynecological disease, 3 had cervical dysplasia, 5 had endometrial hyperplasia, and the remaining 6 had incisional hernia repair. The mean age of patients was 55 years with a mean weight of 101 kg (range 70-145 kg). The mean operative time was 2 h 24 min, and blood transfusion was undertaken in 23 (41%) patients. Four (7.1%) individuals had a minor wound infection and 3 (5.4%) a moderate wound infection. One patient experienced a nonfatal pulmonary embolus and 2 patients experienced a deep vein thrombosis. There were no postoperative deaths. Long term, 6 patients developed an incisional hernia. CONCLUSIONS: Panniculectomy is a useful technique in obese patients. It improves surgical access facilitating radical surgery and is cosmetically pleasing to the patient. It has acceptable morbidity when compared to conventional midline vertical or transverse incisions in comparable populations.

Adipose Tissue↗

PubMed1998

SMN oligomerization defect correlates with spinal muscular atrophy severity.

Spinal muscular atrophy (SMA) is a motor-neuron disorder resulting from anterior-horn-cell death. The autosomal recessive form has a carrier frequency of 1 in 50 and is the most common genetic cause of infant death. SMA is categorized as types I-III, ranging from severe to mild, based upon age of onset and clinical course. Two closely flanking copies of the survival motor neuron (SMN) gene are on chromosome 5q13 (ref. 1). The telomeric SMN (SMN1) copy is homozygously deleted or converted in >95% of SMA patients, while a small number of SMA disease alleles contain missense mutations within the carboxy terminus. We have identified a modular oligomerization domain within exon 6 of SMN1. All previously identified missense mutations map within or immediately adjacent to this domain. Comparison of wild-type to mutant SMN proteins of type I, II and III SMA patients showed a direct correlation between oligomerization and clinical type. Moreover, the most abundant centromeric SMN product, which encodes exons 1-6 but not 7, demonstrated reduced self-association. These findings identify decreased SMN self-association as a biochemical defect in SMA, and imply that disease severity is proportional to the intracellular concentration of oligomerization-competent SMN proteins.

Cyclic AMP Response Element-Binding Protein↗

PubMed1998

In situ hybridization analysis of the expression of human telomerase RNA in normal and pathologic conditions of the skin.

Human telomerase RNA (hTER) expression in skin was examined by in situ hybridization analysis. All newborn foreskins examined (n = 5) expressed hTER in epidermal basal cells at moderate levels. Telomerase RNA was not detectable in most adult specimens from sun protected areas (six of seven), whereas all samples obtained from sun exposed areas (n = 8) showed moderate hTER signals in epidermal basal cells. Telomerase RNA was also detected at moderate to strong levels in basal cells of psoriasis, contact dermatitis, and the proliferative cells of the anagen hair bulb. Basal cell carcinoma samples (14 of 15) had moderate to high hTER expression throughout the entire tumor, whereas squamous cell carcinomas (seven of eight) showed variable intensities of hTER expression but only in the cells at the periphery of tumor nests. All melanomas examined (n = 5) had moderate hTER expression in all tumor cells. The hTER signal intensities in skin tumors did not correlate with the age or sex of the donors, the clinical history of the lesions, or the histologic subtypes. To address whether hTER expression correlated with the proliferative state, sequential sections were stained with anti-Ki-67 antibody, a proliferation marker. In newborn foreskins, squamous cell carcinomas, and basal cell carcinomas, the distributions of hTER and Ki-67 were similar but not always identical. Telomerase RNA was more abundant than Ki-67 in the basal and suprabasal layer of newborn foreskins, suggesting that hTER expression is present both in actively cycling and in resting cells.

Biomarkers↗

PubMed1998

Establishment of drug chests in commune health stations in Vietnam, Bamako Initiative.

In remote areas in Vietnam essential drugs are often not available. Some of the reasons are inadequate resources and failure of distribution. All activities at the health stations are very weak, partly because of inappropriate usage of drugs and lack of fund for buying drugs. The object of the project was to establish sustainable provision of essential drugs for commune health stations in rural areas, to teach the health personnel the importance of essential drugs and to create incentives for the staff and a certain surplus for other health activities. Four District Health Centers (DHC) and 10 Health Stations (HS), 2-4 in each DHC were selected. A pharmacist was made monitor of the project. The health personnel were trained in proper use of drugs, drug prescription, price setting, book keeping and management of pharmacy. Written guidelines were produced. One person was responsible for the drug chest at each HS. After recognizing the aim of the project and signing the contract by which the responsible person was bound, the initial capital was given free. The DHC was responsible for the supervision and advice to the HS. Reporting on prescribed drugs, buying and selling price, profit and fund left took place monthly. Monitoring of recovery of capital, turnover rate, rate of essential drugs and incentives for staff were monitored on forms and quarterly collected by the monitor on his visits. The HS were visited half-yearly by a steering group. All ten HS had been able to establish and maintain the pharmacy and to fully recover or even increase the capital and to create a surplus. Seven out of ten HSs had a turnover rate of more than one. The rate of essential drugs sold was more than 60% in seven pharmacies. The interest rate of 18% on average was used for incentives for staff, to provide drugs for those who cannot pay and for equipment for the HS. The cooperation between the DHC and the HS became closer. Establishment of drug chests seems to be a reasonable strategy of reinforcing primary health. Much attention should be paid on training of staff, monitoring, supervision and integration of health services.

Allied Health Personnel↗

PubMed1998

Point prevalence of secretory otitis media in children in southern Vietnam.

Few reliable data exist on the prevalence of secretory otitis media (SOM) in the Third World. A large epidemiologic cross-sectional study was undertaken in two communes in southern Vietnam to study an urban and a rural community during two different climatic conditions: the dry and rainy seasons. The participants included 3,300 children (6,598 ears) ages 6 months to 10 years. Otolaryngological and medical histories were obtained, and an otolaryngological examination was carried out on 1,669 children in April 1995 (the dry season) and on 1,631 children in December 1995 (the rainy season). Tympanograms were obtained (n = 6,055), 429 of which were type B curves. The overall prevalence of SOM was 7.1%, the highest incidence was at the age of 2 years (with a prevalence of 22%), and there was a significantly higher prevalence of SOM during the rainy season than during the dry season. No significant difference in incidence was found in the urban district as compared to the rural district.

Acoustic Impedance Tests↗

PubMed1997

Effects of retinoid X receptor-selective ligands on proliferation of prostate cancer cells.

BACKGROUND: Management of prostate cancer that either is detectable by prostate specific antigen (PSA) measurements after curative intent or has spread outside of its capsule is a serious problem. Innovative, nontoxic approaches to the disease are required. One approach might be therapy with retinoids. Retinoid activities are mediated by two distinct families of transcription factors: the retinoic acid receptors (RARs) and retinoid X receptors (RXRs), which can induce transcriptional activation through specific DNA sites or by inhibiting the transcription factor AP-1 that usually mediates cellular proliferative signals. The RARs require heterodimerization with RXRs. RXRs can form either heterodimers or homodimers; and the latter can bind to DNA response elements that are distinct from those bound by the RAR/RXR heterodimers. METHODS: A series of novel synthetic retinoids that selectively interact with RXR/RXR homodimers or RAR/RXR heterodimers, or that selectively inhibit AP-1 activity without activating transcription were evaluated for their ability to inhibit clonal growth of three human prostate cancer cell lines (PC-3, DU-145, and LNCaP). RESULTS: Several notable findings were: 1) RXR-selective retinoids, such as SR11246, were able to inhibit the clonal growth of prostate cancer cells. In contrast, SR11246 had little effect on clonal growth of myeloid leukemic cells. 2) RAR-selective retinoids also inhibited clonal growth of prostate cancer cells. 3) The retinoid (SR11238) with potent anti-AP-1 activity had no effect on the clonal growth of prostate cancer cells. CONCLUSIONS: This study shows that both RXR- and RAR-selective retinoids are worthy of further study and may be candidates for future clinical trials in prostate cancer.

Antineoplastic Agents↗

PubMed1997

Regulation of interleukin-10 gene expression: possible mechanisms accounting for its upregulation and for maturational differences in its expression by blood mononuclear cells.

Interleukin-10 (IL-10) downmodulates phagocytic immune responses and accentuates humoral responses. Human neonates exhibit broad immune deficits that parallel actions of IL-10. We postulated that IL-10 production would be diminished in neonatal blood cells. We found that IL-10 production by lipopolysaccharide-stimulated peripheral blood mononuclear cells (PBMNCs) in vitro was greater by adult cells than by term cells and preterm cells. Additional studies were undertaken to identify mechanisms responsible for the developmental differences in IL-10 gene expression. IL-10 transcription was present in freshly isolated adult and neonatal cells in the absence of detectable levels of transcript. Transcription rates were not different between adult and neonatal cells. IL-10 transcripts were approximately 40% more abundant in adult cells than in term cells and were consistent with differences in secreted protein; however, no differences were noted in mRNA stability. IL-10 half-life was 60 minutes for both adult and term PBMNCs. We conclude that up-regulation of IL-10 gene expression in PBMNCs is modulated at the post-transcriptional level, that IL-10 protein production and mRNA content are greater in activated cells from adults compared with those from neonates, and that maturational differences in IL-10 expression are not due to differences in transcription rate or mRNA stability. Maturational differences in IL-10 expression might be due to differences in subpopulations of cytokine-producing cells or differences in nucleo-cytoplasmic transport.

Adult↗

PubMed1997

Utility of magnetic resonance imaging in a patient with anomalous origin of the right coronary artery, acute myocardial infarction, and near-sudden cardiac death.

A 46-year-old female presented with an acute myocardial infarction and cardiac arrest. Coronary angiography revealed an anomalous origin of the right coronary artery coursing between the aorta and pulmonary artery. Magnetic resonance imaging confirmed the life-threatening nature of this anomaly and led to referral for surgical revascularization.

Coronary Angiography↗

PubMed1997

Malignant mixed mesodermal ovarian tumor treatment and prognosis: a 20-year experience.

Mixed mesodermal sarcoma of the ovary is a rare clinical entity. To review the epidemiology, prognostic factors, and treatment results related to primary ovarian sarcoma at our center, a retrospective chart review of all patients referred for ovarian cancer was carried out from 1974 to 1994. Cases with confirmed pathologic diagnosis of primary mixed mesodermal ovarian sarcomas were selected, forming the present study group. Thirty-six charts were identified. The median age at presentation was 67.5 years. Findings at laparotomy demonstrated extraovarian metastasis in 33/35 patients. Total abdominal hysterectomy and bilateral salpingo-oophorectomy +/- omentectomy were performed in 34 patients, with 22 patients left with macroscopic residual disease after surgery. Follow-up adjuvant chemotherapy consisting of cisplatin and doxorubicin was administered to 29/36 patients. Follow-ups ranged from 1 to 11 years with a median of 2 years. As with epithelial ovarian cancer, residual disease after initial surgery is an important prognostic factor. Thirteen patients had a second-look laparotomy. Five patients were positive for disease. Eight patients, one of whom recurred, were histologically negative. The patients with positive second-look findings, as well as all those who recurred clinically, subsequently died within 12 months despite trials with different second-line chemotherapeutic agents. Survival analysis showed a median survival of 3 years among patients treated with combination cytotoxic chemotherapy. Primary ovarian sarcomas make up about 2-3% of all ovarian cancer cases seen in our center. These are often very aggressive tumors with widespread metastasis at the time of presentation, making optimal tumor debulking difficult. The combination of cisplatin and doxorubicin appears to have activity resulting in a survival of 35% at 5 years. Second-look surgery offers little helpful information on the management of these tumors.

Adult↗

PubMed1997

Does debulking surgery improve survival in biologically aggressive ovarian carcinoma?

Aggressive tumor reduction surgery has been widely used in patients with advanced stage epithelial ovarian carcinoma before initiation of cytotoxic chemotherapy. No randomized controlled trial has been carried out to confirm the benefits of such procedures. To examine the role of cytoreductive surgery in the management of stage 2 and 3 patients with epithelial ovarian carcinoma treated with postoperative adjuvant platinum-based chemotherapy, survival analysis was carried out on patients with initial microscopic disease documented on staging laparotomies, patients with large volume of disease at time of exploration and tumor reduced to microscopic residuals, and patients who were suboptimally debulked with more than 2-cm residual disease. Twenty-four, 81, and 191 patients were identified from a computerized data base, respectively. Kaplan-Meier survival estimates showed that 62% with initial microscopic residual are alive with no evidence of disease at 5 years and 56% of patients left with microscopic residuals after tumor reduction are alive and well at 5 years. There was no statistical significant difference between these two groups. The groups are equivalent with respect to known adverse prognostic factors. In contrast, 5-year survival in the suboptimal debulked group was significantly lower at 15%. Debulking surgery to achieve microscopic residual disease improved the prognosis in patients with initial large volume of disease. Survival was similar to survival in patients with microscopic disease at time of exploration. The beneficial effect may be attributed to the removal of chemoresistant clones in bulky tumors. Tumor reduction surgery remains important in the management of advanced stage epithelial ovarian carcinoma.

Aged↗

PubMed1997

Antigen presentation by autoreactive proteolipid protein peptide-specific T cell clones from chronic progressive multiple sclerosis patients: roles of co-stimulatory B7 molecules and IL-12.

To assess the role of T cell antigen (Ag) presentation in multiple sclerosis (MS), proteolipid protein (PLP) peptide reactive CD4+ T cell clones (TCCs) from MS patients and normal subjects were studied. TCCs derived from chronic progressive (CP) MS patients were able to proliferate and secret cytokines in response to PLP peptide stimulation in the absence of professional antigen presenting cells (APCs), suggesting that these T cells can simultaneously present and respond to Ags. However, they did not respond to total PLP protein, suggesting that PLP-peptide TCCs were unable to process and present the whole PLP molecule. The ability of the different TCCs to act as APCs in response to Ag stimulation did not correlate with expression of HLA-class II molecules. However, the degree of expression of B7-1 and B7-2 co-stimulatory molecules showed a significant correlation with APC capacity. Furthermore, a combination of anti-B7-1 and anti-B7-2 mAbs effectively inhibited proliferative responses as well as secretion of IL-10, IFN gamma and TGF beta induced by antigen presenting T cells. By contrast, IL-4 secretion was not affected. Finally, IL-12 significantly enhanced the efficiency of T cell Ag presentation by a pathway independent of Ag processing, suggesting that IL-12 might act as an additional co-stimulatory signal for T cell activation during T-T cell interactions. Together, these observations suggest that Ag presentation by T cells might amplify and perpetuate an autoimmune response previously initiated by professional APCs. These properties may account for progression of MS into a CP phase.

Adult↗

PubMed1997

Semaphorin III can repulse and inhibit adult sensory afferents in vivo.

During development, semaphorins (collapsin, fasciclin) mediate repulsive and inhibitory guidance of neurons. Semaphorin III, a secretable member of this family, is expressed by the ventral spinal cord at the time corresponding to projection of sensory afferents from the dorsal root ganglion (DRG) into the spinal cord. The inhibitory effect of E14 ventral cord is active only on nerve growth factor (NGF)-responsive sensory afferents (small-diameter A-delta and C fibers subserving sensations of temperature and pain). Similarly, COS cells secreting recombinant semaphorin III are able to selectively repel DRG afferents whose growth is stimulated by NGF and not NT-3. However, it is not known whether these molecules can exert a functional role in the fully developed adult peripheral nervous system. In this study, we demonstrated that gene gun transfection and production of semaphorin III in corneal epithelial cells in adult rabbits in vivo can cause repulsion of established A-delta and C fiber trigeminal sensory afferents. In addition, it is shown that, following epithelial wounding and denervation, semaphorin III is able to inhibit collateral nerve sprouts from innervating the reepithelialized tissue. These findings are significant in that they provide direct evidence that small-diameter adult sensory neurons retain the ability to respond to semaphorin III. In addition, the corneal gene gun technique may be generally used to study the in vivo effects of neural growth modulators by quantifying the amount of sensory nerve growth.

Animals↗

PubMed1997

The impact of the quantity of skeletal injury on mortality and pulmonary morbidity.

OBJECTIVE: To determine if the quantity of skeletal injuries (and the timing to fixation) increases the mortality or pulmonary morbidity in patients with and without chest injuries. DESIGN: Retrospective analysis of trauma registry. Statistical analysis with multiple logistic regression and chi(2) analysis. METHODS: Looking specifically at adult patients (> 16 years), skeletal injury was quantified by determining the presence or absence of a fracture in specific body regions (humeri, forearm, femur, tibia, spine, and pelvis) for a maximum of 10 skeletal injuries. The timing of fixation for fractures was categorized as < 24 hours, < 48 hours, < 72 hours, < 5 days, > 5 days, or no fixation. Chest injuries and pulmonary morbidity were based on the accepted list of complications reported in the literature. RESULTS: Three groups were analyzed according to the presence or absence of a chest or skeletal injury: those without skeletal injury (group NSI, n = 59), those without chest injuries (group NCI, n = 108), and those with both skeletal and chest injuries (group B, n = 59) Pulmonary Complications: When all patient groups (NCI, NSI, and B) were pooled, greater chest injury (p < 0.0008), greater skeletal injury (p < 0.02), and delayed fixation (p < 0.04) were associated with increased risk of developing a pulmonary complication. In the group of patients without a chest injury (NCI), this risk was associated with greater head injury (p < 0.005) and greater skeletal injury (p < 0.04), whereas in the group without a skeletal injury (NSI), only chest injury demonstrated significance (p < 0.05). When both skeletal and chest injuries were present, greater head injury (p < 0.03) and fixation time (p < 0.03) increased the risk of developing a pulmonary complication. Mortality: With all patients pooled (NCI, B, and NSI), head injury (p < 0.02), abdominal injury (p < 0.012), and fixation time (p < 0.01) were risk factors. In patients without a chest injury (NCI), none of the indexed variables were associated with mortality. In patients without a skeletal injury (NSI), greater head injury (p < 0.01), greater chest injury (p < 0.01), and greater abdominal injury (p < 0.04) were risk factors for mortality. When both chest and skeletal injuries were present (B), only head injury (p < 0.0003) was associated with mortality. The prevalence of mortality and pulmonary complications were compared between groups NCI, NSI, and B. Group NCI had fewer pulmonary complications (p < 0.004) than the other groups (difference not significant). When examining mortality, group NCI had less mortality than groups NSI and B. CONCLUSION: The combination of skeletal and chest injuries does not seem to amplify the pulmonary morbidity and mortality compared with chest injury alone. The quantity of the skeletal injury and the time to fixation of structures affecting mobilization seem to have an effect on pulmonary morbidity and mortality. Better scientific studies on the effects of skeletal injury and timing to fixation in relation to pulmonary morbidity and mortality are required.

Adult↗

PubMed1997

Hypothalamic nitric oxide synthase is depressed in cholestatic rats.

We examined hypothalamic nitric oxide synthase (NOS) levels and release as well as steady-state mRNA levels in rats with cholestasis due to bile duct resection (BDR) and in sham-resected control rats. BDR rats had a significant reduction in hypothalamic NOS-containing neurons in the hypothalamic paraventricular nucleus as determined by NADPH-diaphorase staining, compared with sham-resected controls. In addition, NOS activity, measured indirectly by determining nitrite release from hypothalamic explants, was significantly lower in BDR rats compared with sham-resected animals. Hypothalamic steady-state NOS mRNA levels [brain constitutive NOS (bNOS)] were determined by semiquantitative reverse transcription-polymerase chain reaction and were found to be increased 1.5-fold in BDR rats compared with sham rats. In summary, BDR rats have diminished hypothalamic NOS levels and activity coupled with enhanced steady-state bNOS mRNA levels, suggesting that depressed hypothalamic NOS protein levels are due to posttranscriptional defects.

Animals↗