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Biomedical subjects

S Nelson

Publications and source records attributed to S Nelson.

At least 127 records · Page 7Linked to original sources
PubMed1997

Phase 1 safety trial of Filgrastim (r-metHuG-CSF) in non-neutropenic patients with severe community-acquired pneumonia.

The objectives of the present study were to: (1) evaluate the safety of Filgrastim therapy in non-neutropenic patients with severe community-acquired pneumonia; (2) determine the absolute neutrophil count (ANC) response to various dosages of Filgrastim in non-neutropenic patients with active infection; and (3) describe the impact of therapy with Filgrastim in combination with antibiotics on selected pneumonia-related clinical parameters. The study design was an open-label, dose-ranging, clinical trial, set in the General Clinical Research Unit of a large, public community hospital. The study population consisted of 30 patients who had presented to the Emergency Department with severe, community-acquired pneumonia. One of five dosages (75, 150, 300, 450 or 600 micrograms day-1) of Filgrastim (r-metHuG-CSF) was given subcutaneously daily for 10 days, until discharge or until the absolute neutrophil count > 75 x 10(9) l(-1), whichever was earlier. Vital signs, pulse oximetry, arterial blood gases, daily complete blood counts with differential, serum chemistries, coagulation profiles, electrocardiograms, chest radiographs, plasma G-CSF concentrations and duration of hospitalization were measured. There was no evidence of Filgrastim-related lung injury or evidence of extra-pulmonary toxicity. There was no apparent dose-response effect of Filgrastim on pneumonia-related clinical variables. Dosages of Filgrastim between 150 and 600 micrograms day-1 had similar effects on increasing the ANC. Filgrastim appeared to be safe in non-neutropenic patients with severe, community-acquired pneumonia when given in dosages of 75-600 micrograms day-1 in combination with appropriate antibiotic therapy. Further study is needed to determine the effect of Filgrastim on morbidity, mortality and duration of symptoms in this patient population.

Adult↗
PubMed1997

Pastoral care and moral government: early nineteenth century nursing and solutions to the Irish question.

This paper re-examines the role of the early nineteenth century nurses, conventionally depicted in nursing histories as the well-meaning but untrained Catholic nursing nuns or, in post-Reformation Europe, servants and fellow patients. It will be argued here that professional and capable nursing had begun to transform the care of the sick poor and to demonstrate its importance to the success of medical/surgical innovation long before Florence Nightingale and her call to Scutari. Moreover, the case is put that the emergence of nineteenth century forms of care for the sick occurred in response to the pressing problems of population management in Ireland, Great Britain and North America. The pastoral concerns of the first Irish nurses, with their expertise in both the spiritual and material domains, provided the prototype for what was to follow: a spiritual form of life that addressed the governmental concerns of its time. Finally, it is argued that given the overt moral imperatives of nineteenth century nurses of all persuasions, the depiction of nursing history as a crossing from the religious to the secular domain is challenged.

Catholicism↗
PubMed1997

Intraportal lipopolysaccharide suppresses pulmonary antibacterial defense mechanisms.

Translocation of enteric bacteria or their components (or both) has been postulated to play a role in precipitating sepsis or the systemic inflammatory response syndrome. To simulate the effects of translocation on pulmonary host defenses, lipopolysaccharide was injected into the portal vein of normal rats that were subsequently challenged by aerosol inoculation with Pseudomonas aeruginosa. Injection of LPS into the portal vein resulted in increased serum tumor necrosis factor (TNF)-alpha levels and reduction in lung clearance of P. aeruginosa after aerosol challenge. There were corresponding reductions in alveolar neutrophil recruitment, diminished alveolar macrophage phagocytosis and superoxide anion (O2-) production, and diminished lung TNF recovered by bronchoalveolar lavage. Furthermore, prior intravenous injection of recombinant TNF-alpha reproduced the defective bacterial clearance, the altered recruitment of airspace neutrophils, and the defective alveolar macrophage phagocytosis. Thus, systemic TNF-alpha is important in altering pulmonary defenses, and this work supports the concept that bacterial translocation may adversely affect host defenses in distant organs.

Animals↗
PubMed1997

Antibody-mediated depletion of tumor necrosis factor-alpha impairs pulmonary host defenses to Legionella pneumophila.

Tumor necrosis factor-alpha (TNF-alpha) has been shown to stimulate the resistance of alveolar macrophages and neutrophils to Legionella pneumophila in vitro. To determine whether endogenous TNF-alpha is necessary for host defense against legionellosis in vivo, anti-TNF-alpha IgG or control IgG was administered to rats exposed to aerosolized L. pneumophila. Treatment with anti-TNF-alpha neutralized >90% of the intrapulmonary TNF-alpha response to infection, resulting in persistent pneumonitis and failure to clear L. pneumophila from the lungs. Depletion of TNF-alpha limited the recruitment of mononuclear cells to the lungs and resulted in a progressive increase in the proportion of alveolar macrophages that were infected; neutrophil recruitment and phagocytosis were not impaired. Both systemic and intrapulmonary IFN-gamma levels were significantly higher in rats depleted of TNF-alpha. These observations indicate that TNF-alpha is required for the prompt resolution of pneumonic legionellosis and point to a direct role for TNF-alpha in the activation of phagocytes.

Animals↗
PubMed1997

Nosocomial acquisition of pertussis diagnosed by polymerase chain reaction.

Awareness is growing of the role of pertussis infection among adolescents and adults, and of the possibility of nosocomial transmission. However, pertussis remains difficult to diagnose. We report a case of nosocomially acquired pertussis in a healthcare worker, diagnosed by polymerase chain reaction. The high sensitivity and rapid turnaround time for this test is useful to confirm the diagnosis when advising a healthcare worker to refrain from working.

Adult↗
PubMed1997

Psychiatric disorder among American Indian adolescents: prevalence in Northern Plains youth.

UNLABELLED: This article presents data on the prevalence of psychiatric disorders among American Indian adolescents, using DSM-III-R criteria. OBJECTIVE: To generate current prevalence data using a structured diagnostic instrument, the Diagnostic Interview Schedule for Children, Version 2.1C (DISC-2.1C). METHODS: Youths from a Northern Plains tribe who had participated in an earlier study comprised the sample. At reinterview, respondents were between 14 and 16 years of age, when Indian adolescents are thought to be at particularly high risk for manifesting emotional disorders. One hundred nine of the original sample of 251 were still in schools on the reservation. Trained indigenous lay interviewers administered the DISC-2.1C to respondents in a private setting within the school. RESULTS: The findings indicate that rates of some psychiatric problems (e.g., disruptive behavior disorders, substance-related disorders, and their comorbidity) are high among these high school students. CONCLUSIONS: These data, as well as national statistics, suggest that, compared with non-Indian populations, a greater percentage of Northern Plains adolescents manifest significant psychiatric symptoms which warrant treatment.

Adolescent↗
PubMed1997

Modulation of the lung host response by granulocyte colony-stimulating factor in rats challenged with intrapulmonary endotoxin.

The effects of granulocyte colony-stimulating factor (G-CSF) on the functional activities of circulating and lung-recruited neutrophils (PMNs) and alveolar macrophages (AMs) were studied in rats to further elucidate the mechanisms underlying G-CSF-enhanced pulmonary host defense. Animals received G-CSF or vehicle twice a day for 2 days, followed by an intratracheal challenge with endotoxin or saline. G-CSF up-regulated CD11b/c expression and mean channel fluorescence intensity of phagocytosis in circulating PMNs. G-CSF also enhanced phagocytic activities, reflected by both the percentage of phagocytosis and mean channel fluorescence intensity in lung-recruited PMNs and AMs in intratracheal endotoxin-challenged rats. The endotoxin-induced increase in pulmonary production of tumor necrosis factor-alpha and cytokine-induced neutrophil chemoattractant was not affected by G-CSF pretreatment. These data demonstrate that G-CSF-enhanced pulmonary recruitment of PMNs is primarily based on the effects of G-CSF on the PMNs themselves, rather than the generation of certain chemotactic stimuli, i.e., cytokine-induced neutrophil chemoattractant and tumor necrosis factor-alpha. The enhanced phagocytic activities of lung-recruited PMNs and AMs also augment pulmonary host defenses in G-CSF-pretreated animals.

Animals↗
PubMed1997

Use of granulocyte colony-stimulating factor in the treatment of acute infectious diseases.

Infectious diseases continue to be a major cause of morbidity and mortality in the United States. Novel strategies directed at amplifying critical components of the host's immune system may be one potential adjuvant therapy. To date, studies with granulocyte colony-stimulating factor (G-CSF) treatment have demonstrated favorable results, decreasing both morbidity and mortality in a variety of infectious disease models in non-neutropenic hosts. The recent completion of two clinical trials has also provided supportive data that G-CSF is effective in patients with serious infections. Most important, G-CSF does not produce any adverse consequences, which were of concern to some because of the capacity of G-CSF to enhance neutrophil production and function. This review focuses on current data suggesting that augmentation of the immune system with G-CSF is a promising new approach to adjuvant therapy in infectious diseases.

Acute Disease↗
PubMed1997

Reading nursing history.

This paper undertakes a reading of nursing history as a constituent discourse. The discursive power of history, with its active mining of the archives of the past to construct a narrative of contemporary force and power, is emphasized. The essay begins with the nineteenth-century and early twentieth-century professional histories that celebrated nursing's evolutionary achievements. It then moves to the sociologically influenced revisions of the 1960s, and the feminist and critical revisions of the 1980s and 1990s. We then turn to recent scholarship and examine the call for nursing history to participate in the theoretical construction of the discipline of nursing. The observation is made that, in the name of relevance, contemporary nursing history appears to be expected to contribute to the development of nursing knowledge, just as early histories contributed to the professionalization of nursing. The teleological assumptions of both nursing history and nursing theory are then argued to set the limits of nursing discourse, with detrimental effect on scholarship.

Female↗
PubMed1997

Detection of Bordetella pertussis in clinical specimens by PCR and a microtiter plate-based DNA hybridization assay.

In order to improve detection of Bordetella pertussis in nasopharyngeal aspirates (NPAs) in our laboratory, a PCR-based assay was optimized, and a study was designed (i) to compare results obtained by PCR to those obtained by culture and (ii) to evaluate a novel microtiter plate-based DNA hybridization assay (PCR-plate) by comparing it to agarose gel electrophoresis (PCR-gel) for detection of the PCR product. DNA for the PCR was extracted with a guanidine thiocyanate buffer and used in a PCR mixture containing primers directed against a reiterated gene sequence in B. pertussis (Q. He, J. Mertsola, H. Soini, M. Skurnik, O. Ruuskanen, and M. K. Viljanen, J. Clin, Microbiol. 31:642-645, 1993). Of 96 NPAs submitted from a targeted study group, 23 were positive by culture, 27 were positive by PCR-gel, and 31 were positive by PCR-plate. All culture-positive specimens were also positive by PCR. Of nine patients with culture-negative-PCR-positive results, six had discharge diagnoses of pertussis. Thus, PCR with plate-based product detection is a sensitive method for the laboratory detection of B. pertussis in NPAs. Additional advantages of the plate assay include rapidity, objectivity in reading results, specificity, and the capability of being adapted to a high-volume, automated system.

Bordetella pertussis↗
PubMed1997

Activation of alveolar macrophages and lung host defenses using transfer of the interferon-gamma gene.

Interferon-gamma (IFN-gamma) is a critical cytokine in pulmonary host defenses against both intracellular and extracellular pathogens. To investigate whether this cytokine could be used therapeutically, we constructed an E1-deleted recombinant adenovirus encoding murine IFN-gamma. After intratracheal inoculation in rats, this vector resulted in prolonged expression of functional cytokine in vivo, as demonstrated by increased alveolar macrophage class II major histocompatibility complex expression, enhanced release of tumor necrosis factor in response to lipopolysaccharide, and enhanced host defenses against Pseudomonas aeruginosa. We postulate that this vector may be useful to study the role of exogenous IFN-gamma in a variety of pulmonary intracellular and extracellular pathogens.

Animals↗
PubMed1997

Increased levels of glutathione S transferases and appearance of novel alpha class isoenzymes in kidneys of mice exposed to mercuric chloride. I. Biochemical and immunohistochemical studies.

Glutathione S transferases (GST) are a family of enzymes that detoxify electrophilic xenobiotics. This enzyme family was examined in kidneys of mice exposed to mercuric chloride, a known nephrotoxin, because GST have been shown to protect cells against toxicant-induced damage and may serve as biomarkers for toxicant exposure. The purpose of this study was to determine the effect of mercuric chloride on GST activity, isoenzyme levels, and cellular localization in the kidney of Swiss Webster mice. The cellular localizations of alpha, mu, and pi class GST in the kidneys of control and mercuric chloride treated mice were studied immunohistochemically. The GST isoenzyme levels were measured by high-performance liquid chromatography. The mice treated with mercuric chloride had (1) increased amounts of GSTA1/A2 protein in kidney homogenates as compared with controls when analyzed by chromatography and electrophoresis; (2) two new isoforms of the alpha isoenzyme in kidney as demonstrated by Western blot, polyacrylamide gel electrophoresis, and high-performance liquid chromatography, and (3) increased reactivity between antibodies, against GSTA1/A2 or GSTM1 isoenzymes, and cells in the proximal and distal renal tubules as shown by immunohistochemical techniques. The authors conclude that the GSTA1/A2 may protect those cells in the proximal and distal tubules of the renal cortex from toxicant effects of mercuric chloride. This would be one general mechanism for cell protection against a wide variety of toxicants including heavy metals and halogenated aromatics.

Animals↗
PubMed1997

Keratinocyte growth factor increases transalveolar sodium reabsorption in normal and injured rat lungs.

Keratinocyte growth factor (KGF) prevents alpha-naphthylthiourea (ANTU)-induced permeability edema ex vivo. To explore the mechanisms in this involved effect, we administered KGF (5 mg/kg, intratracheally) 48 h prior to ANTU (50 mg/kg, intraperitoneally). Several groups were studied: phosphate-buffered saline/dimethylsulfoxide (PBS/DMSO) (vehicles), PBS/ANTU, and KGF/ANTU. At 90 min after ANTU injection the lungs were removed, ventilated, and perfused ex vivo for 180 min. Quantification of fluorescein isothiocyanate (FITC)-labeled dextran in bronchoalveolar lavage fluid (BALF) was used to assess alveolar capillary barrier permeability. KGF attenuated ANTU-induced edema and blockade of sodium transport, with ouabain (10(-3) M) or amiloride (10(-4) M) added ex vivo reversed this effect. FITC-dextran was increased in the PBS/ANTU group as compared with the PBS/DMSO group, indicating permeability edema. In the KGF/ANTU group, there was concentration of BALF FITC-dextran, consistent with permeability edema and increased alveolar fluid export. Albumin space measurements showed similar increases in permeability in the PBS/ANTU and KGF/ANTU groups. Extravascular lung water (measured with radiolabeled erythrocytes) was decreased in the KGF/ANTU group. Following KGF pretreatment, uninjured lungs exported more intratracheal PBS than normal lungs following terbutaline stimulation ex vivo. In conclusion, KGF, through type II alveolar pneumocyte hyperplasia with increased sodium-potassium-adenosine triphosphatase (Na,K-ATPase) activity, attenuated ANTU-induced edema formation by potentiating alveolar fluid clearance.

Absorption↗
PubMed1997

Exacerbation of murine Pneumocystis carinii infection by adenoviral-mediated gene transfer of a TNF inhibitor.

The role of mononuclear phagocytes and their cytokine products in host defense against Pneumocystis carinii (PC) remains unclear. The cytokine tumor necrosis factor (TNF) has been proposed as critical for host defense against this pathogen. To investigate the role of this cytokine in PC infection, we treated immunocompetent mice (CD4+) or mice depleted of CD4 lymphocytes (CD4-) with a recombinant adenovirus encoding a TNF inhibitor gene (AdTNF-R). AdTNF-R treated CD4+ animals displayed delayed clearance of PC after intratracheal inoculation, whereas AdTNF-R treated CD4 animals developed more severe chronic infection. Moreover, AdTNF-R treated CD4- animals, in contrast to control CD4- mice, failed to show any interleukin-6 (IL-6) gene induction in the lung after PC challenge. The results firmly implicate TNF in host defense against PC, and support a role for TNF in orchestrating the intrapulmonary cytokine cascade in PC infection.

Adenoviridae↗
PubMed1997

Hereditary endotheliopathy with retinopathy, nephropathy, and stroke (HERNS).

We describe a Chinese American family with a hereditary syndrome consisting of retinopathy, nephropathy, and stroke, affecting 11 members spanning three generations. Ophthalmologic evaluations revealed macular edema with capillary dropout and perifoveal microangiopathic telangiectases. Several members had renal abnormalities with proteinuria and hematuria. Initial manifestations were visual impairment and renal dysfunction; neurologic deficits occurred in the third or fourth decade of life. Symptoms included migraine-like headache, psychiatric disturbance, dysarthria, hemiparesis, and apraxia. Neuroimaging consistently demonstrated contrast-enhancing subcortical lesions with surrounding edema. Ultrastructural studies showed distinctive multilaminated vascular basement membranes in the brain and in other tissues, including the kidney, stomach, appendix, omentum, and skin. Genetic analysis ruled out linkage to the CADASIL locus on chromosome 19. Distinct from CADASIL, hereditary endotheliopathy with retinopathy, nephropathy, and stroke (HERNS) is an autosomal dominant multi-infarct syndrome with systemic involvement.

Adult↗
PubMed1997

Contribution of craniofacial risk factors in increasing apneic activity among obese and nonobese habitual snorers.

STUDY OBJECTIVE: To determine the role of craniofacial risk factors in increasing apneic activity between nonobese and obese habitual snorers. DESIGN: Cross-sectional. SETTING: Care-seeking volunteers identified through advertisements, and referral-based volunteers from two sleep centers serving the greater Cleveland area. PATIENTS: The study included 142 habitual snorers (mean +/- SD, 45.5 +/- 10.6 years, 68% men; 20% African-Americans) MEASUREMENTS AND RESULTS: Apneic activity was determined using unattended home sleep monitoring to assess the respiratory disturbance index (RDI). Independent variables included body mass index, cranial index, facial index, and 13 anatomic variables (lateral and frontal cephalometric radiographs were used to characterize craniofacial hard and soft tissues). A linear regression model explained approximately 54% and 53% of the variation in RDI (log transformed) scores for the nonobese and obese groups, respectively. The largest predictor of RDI in the nonobese group was tongue length, followed by alignment of the middle cranial fossa, and age. In the obese group, the largest predictor of RDI was hyoid to mandibular plane, followed by tongue length. CONCLUSIONS: Measurements of soft tissues of the oropharynx (especially the tongue) are more closely associated with increased apneic activity. In addition, the hard tissue anatomic limits of the oropharynx may place nonobese individuals in the at-risk group. Therefore, anatomic relationships that are temporally stable may be useful to predict apneic activity in later years.

Adult↗