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Biomedical subjects

C B Wilson

Publications and source records attributed to C B Wilson.

At least 73 records · Page 4Linked to original sources
PubMed1998

Gamma interferon production by cytotoxic T lymphocytes is required for resolution of Chlamydia trachomatis infection.

In this study, we used mice in which the gene for gamma interferon (IFN-gamma) has been disrupted (IFN-gamma-/- mice) to study the role of this cytokine in the resolution of Chlamydia trachomatis infection. We show that IFN-gamma-/- mice are impaired in the ability to clear infection with C. trachomatis compared to IFN-gamma+/+ control mice. Activated CD8(+) cytotoxic T lymphocytes (CTL) secrete IFN-gamma in response to intracellular infection, and we have shown previously that a Chlamydia-specific CTL line can reduce C. trachomatis infection when adoptively transferred into infected mice. In the present study, we found that when these IFN-gamma+/+ CTL lines are transferred into Chlamydia-infected IFN-gamma-/- mice, the transferred CTL cannot overcome the immune defect seen in the IFN-gamma-/- mice. We also show that Chlamydia-specific CTL can be cultured from IFN-gamma-deficient mice infected with C. trachomatis; however, the adoptive transfer of IFN-gamma-/- CTL into infected IFN-gamma+/+ mice does not reduce the level of infection. These results suggest that IFN-gamma production by CTL is not sufficient to overcome the defect that IFN-gamma-/- mice have in the resolution of Chlamydia infection, yet IFN-gamma production by CTL is required for the protective effect seen upon adoptive transfer of CTL into IFN-gamma+/+ mice.

3T3 Cells↗
PubMed1998

Successful readministration of adeno-associated virus vectors to the mouse lung requires transient immunosuppression during the initial exposure.

The airway is an important target for gene transfer to treat cystic fibrosis and other diseases that affect the lung. We previously found that marker gene expression did not persist in the bronchial epithelium following adeno-associated virus (AAV) vector administration to the rabbit lung. In an attempt to promote continued expression, we tested repeat vector administration, but no additional transduction was observed, and the block to transduction correlated with the appearance of neutralizing antibodies to the viral capsid. Here we show that mice exhibit a similar response but that treatment with anti-CD40 ligand antibody (MR1) and a soluble CTLA4-immunoglobulin fusion protein (CTLA4Ig) at the time of primary AAV vector exposure allowed successful repeat transduction and prevented production of neutralizing antibodies. We also tested the possibility that an immune response caused the loss of marker-positive cells in the epithelial population in rabbits by evaluating AAV vector expression in immunocompetent and immunodeficient mice. In contrast to results in rabbits, marker protein expression persisted in the lung in both groups of mice. AAV vector transduction occurred in alveolar cells, airway epithelial cells, and smooth muscle cells, and vector expression persisted for at least 8 months. Although data on persistence of AAV vector expression in the human lung are not available, it is likely that repeat transduction will be necessary either due to loss of expression or to the need for repeat administration to deliver effective amounts of AAV vectors. Results presented here indicate that transient immunosuppression will allow such repeat vector treatment of the lung.

Abatacept↗
PubMed1998

Transient inhibition of CD28 and CD40 ligand interactions prolongs adenovirus-mediated transgene expression in the lung and facilitates expression after secondary vector administration.

Recombinant adenovirus vectors have been used to transfer genes to the lungs in animal models, but the extent and duration of primary transgene expression and the ability to achieve expression after repeated vector administration have been limited by the development of antigen-specific immunity to the vector and, in some cases, to vector-transduced foreign proteins. To determine if focused modulation of the immune response could overcome some of these limitations, costimulatory interactions between T cells and B cells/antigen-presenting cells were transiently blocked around the time of vector administration. Systemic treatment at the time of primary-vector administration with a monoclonal antibody (MR1) against murine CD40 ligand, combined with recombinant murine CTLA4Ig and intratracheal coadministration of an adenovirus vector transducing the expression of murine CTLA4Ig, prolonged adenovirus-transduced beta-galactosidase expression in the airways for up to 28 days and resulted in persistent alveolar expression for >90 days (the duration of the experiment). Consistent with these results, this treatment regimen reduced local inflammation and markedly reduced the T-cell and T-cell-dependent antibody response to the vector. A secondary adenovirus vector, administered >90 days after the last systemic dose of MR1 and muCTLA4Ig, resulted in alkaline phosphatase expression at levels comparable to those seen with primary-vector administration. Expression of the secondary transgene persisted in the alveoli (but not in the airways) for up to 24 days (the longest period of observation) at levels similar to those observed on days 3 to 4. These results indicate that transient inhibition of costimulatory molecule interactions substantially enhanced gene transfer to the alveoli but was much less effective in the airways. This suggests that there are differences in the efficiency or nature of mechanisms limiting transgene expression in the airways and in the alveoli.

Abatacept↗
PubMed1998

The locus of tumor necrosis factor-alpha action in lung inflammation.

The pulmonary host response to infection and inflammation appears, at least in part, to be compartmentalized from the systemic host response. Tumor necrosis factor-alpha (TNF-alpha) has been implicated in lung inflammation and injury, but its site(s) of action has not been clearly defined. To investigate this, transgenic mice (surfactant apoprotein C promotor/soluble TNF receptor type II-Fc fusion protein ([SPCTNFRIIFc] mice) were generated in which TNF-alpha was selectively antagonized in the distal lung through tissue-specific expression of sTNFRIIFc, a soluble TNF inhibitor. The lung inflammatory response in these mice to pulmonary challenge with Micropolyspora faeni antigen or lipopolysaccharide (LPS) was compared with the response of wild-type mice, wild-type mice treated with recombinant sTNFRIIFc intravenously, and type I TNF-receptor knockout mice. Recruitment of polymorphonuclear leukocytes (PMN) to the lung after challenge with M. faeni antigen was essentially abolished in the TNFRI knockout mice and markedly reduced in the SPCTNFRIIFc mice. Wild-type mice given sTNFRIIFc intravenously in amounts resulting in lung concentrations similar to those in SPCTNFRIIFc mice also showed significantly reduced lung PMN recruitment, whereas those given doses that achieved such concentrations in the blood but low levels in the lung did not. In contrast, PMN recruitment to the lung following aerosol challenge with LPS was reduced significantly in the TNFRI knockout mice and in mice given high-dose sTNFRIIFc intravenously, but was not reduced significantly in SPCTNFRIIFc mice. Thus, inhibition of PMN recruitment in response to M. faeni antigen correlated largely with the extent of intrapulmonary inhibition of TNF-alpha, whereas the response to LPS correlated best with the extent of extrapulmonary inhibition of TNF-alpha. These studies indicate that TNF-alpha may act at different loci to mediate lung inflammation, with the site of action depending in part on the nature of the inflammatory stimulus, and that SPCTNFRIIFc mice provide a tool by which the locus of TNF action can be addressed.

Administration, Intranasal↗
PubMed1998

Systemic markers of inflammation in stable bronchiectasis.

Patients with bronchiectasis have an active local and systemic inflammatory response during infective exacerbations. Systemic markers of inflammation were investigated during a stable phase of their illness, because continued inflammation could affect their general health and be involved in disease progression. The relationship between levels of various systemic markers of inflammation and extent of disease on computed tomographic scan, lung function, sputum bacteriology and health related quality of life (HRQoL) was investigated in 87 noncystic fibrosis bronchiectasis patients. Several markers were elevated and correlated with the extent of disease and poor lung function. The total white cell count, neutrophil count and erythrocyte sedimentation rate correlated with both disease measures. Sputum bacteriology did not correlate with inflammation markers and patients with positive and negative cultures were similar. C-reactive protein and total white cell count correlated with some components of a disease-specific HRQoL questionnaire. In conclusion, patients with bronchiectasis in a stable phase have raised systemic markers of inflammation. Some markers, particularly the neutrophil count, correlate with disease severity. This result is in keeping with the hypothesis that the level of inflammation determines disease progression and health status.

Adult↗
PubMed1998

Transsphenoidal microsurgery for growth hormone-secreting pituitary adenomas: initial outcome and long-term results.

Treatment of acromegaly has long been recognized as necessary to relieve symptoms, halt progression of deformities, and decompress the sella turcica. More recently, treatment strategies have focused on decreasing GH levels to a point at which mortality rates normalize, thereby redefining previous concepts of a cure. No surgical series to date has investigated the long-term effect of treatment on mortality rates. We retrospectively reviewed 254 consecutive patients with acromegaly who underwent transsphenoidal microsurgery of GH-secreting adenomas between 1974-1992. Seventy-six percent of these patients had basal GH levels <5 ng/mL within 30 days of surgery, and 24% had persistent disease. Multivariate analysis revealed that higher stage, grade, and preoperative GH levels were all predictive of persistence (P < 0.01). Long-term follow-up was obtained on 129 of the patients in initial remission. Of these, 9 (7%) had disease recurrence and 120 remained in remission. The incidence of major postoperative complications was 8% (2% permanent diabetes insipidus, 2% cerebrospinal fluid leaks requiring surgery, 2% meningitis, and 2% hypopituitarism), with no mortality. In contrast to the 2.4- to 4.8-fold increased mortality among untreated acromegalics, the mortality rate among patients with posttherapy GH levels <5 ng/mL was equivalent to that of age- and sex-matched controls. Aggressive therapy to normalize GH levels should therefore be instituted at diagnosis.

Acromegaly↗
PubMed1998

Expression and localization of cyclooxygenase isoforms and cytosolic phospholipase A2 in anti-Thy-1 glomerulonephritis.

Glomerular expression of the major rate-limiting enzymes for prostanoid synthesis, cyclooxygenase isoforms (COX-1 and COX-2) and cytosolic phospholipase A2 (cPLA2), was investigated in anti-Thy-1 nephritis in rats. Ribonuclease protection assay demonstrated minimal COX-1 mRNA expression in glomeruli of control rat kidneys and a gradual increase of expression from day 1 to day 10 after administration of monoclonal anti-rat Thy-1 antibody. On the other hand, COX-2 mRNA expression, also minimal in the normal glomeruli, was enhanced in a biphasic pattern with two peaks at 1 h and day 10. Expression of cPLA2 mRNA, which was undetectable in normal glomeruli, was induced on day 1 and increased gradually in a pattern similar to that of COX-1 mRNA expression. Immunofluorescence microscopy, using antibodies against COX isoforms, showed that both COX-1 and COX-2 were negligible or faintly detectable in the glomeruli of control rat kidneys. In contrast, the immunofluorescence for COX-1 was intensified on days 4 and 10 along the glomerular capillary walls probably in glomerular epithelial and/or endothelial cells, whereas COX-2 staining was exclusively enhanced in the glomerular epithelial cells at 1 h and day 10 during the course of anti-Thy-1 nephritis. These findings indicate that prostanoids generated through induction of COX-1, COX-2, and cPLA2 are implicated in the mediation of the mesangial cell injury model. In particular, the upregulation of COX-2 expression in glomerular epithelial cells in the selective mesangial cell injury model suggests an intercellular interaction between mesangial cells, and glomerular epithelial cells.

Animals↗
PubMed1997

Delayed infection after elective spinal instrumentation and fusion. A retrospective analysis of eight cases.

STUDY DESIGN: A retrospective analysis of eight cases of delayed spinal infection after elective posterior or combined anterior and posterior spinal instrumentation and fusion. OBJECTIVES: These cases are reviewed to identify risk factors for delayed spinal infection after elective instrumentation and to describe the treatment of this complication. SUMMARY OF BACKGROUND DATA: Delayed spinal infection after elective spinal instrumentation and fusion is uncommon. This diagnosis is frequently difficult. METHODS: Five cases seen in the senior author's practice and three referral cases are reviewed. RESULTS: Of these eight cases, the organisms were Staphylococcus epidermidis in six cases, Propionibacterium acnes in one cases, and in the final patient, all intraoperative cultures were negative. Clinical presentations were variable; however, all patients reported back pain. Seven patients had elevated erythrocyte sedimentation rates, averaging 57 mm/hour. Only two had elevated white blood cell counts. No distant foci of infection were identified in any patient. Five-patients were found to have at least one pseudarthrosis. All patients were treated with debridement, instrumentation removal, and primary wound closure over drains followed by a minimum 6-week course of culture-directed postoperative antibiotics. At an average follow-up of 18 months, no patient has evidence of infection. CONCLUSIONS: The diagnosis of delayed infection after elective spinal instrumentation and fusion requires a high index of suspicion. These infections may have been caused by intraoperative inoculation. All patients were successfully treated with debridement, instrumentation removal, and culture-directed postoperative antibiotics.

Adolescent↗
PubMed1997

Age and the risk of anaplasia in magnetic resonance-nonenhancing supratentorial cerebral tumors.

BACKGROUND: It is often assumed that a cerebral lesion that is nonenhancing on a magnetic resonance imaging study with gadolinium contrast is a low grade tumor. Some physicians recommend observation rather than biopsy for such lesions. METHODS: The authors prospectively evaluated the incidence of anaplastic tumor histology in a consecutive series of patients who presented to a neuro-oncology service with a nonenhancing mass of the cerebral hemisphere. RESULTS: During a 5-month period, the authors evaluated 31 patients who had a nonenhancing lesion in the cerebral hemisphere on initial magnetic resonance images. Thirty patients underwent stereotactic biopsy (27%) or open resection (73%). The median patient age was 36 years (range, 6-63 years). There was no mortality or permanent neurologic morbidity from surgery. Twenty-eight patients had pathologic confirmation of diagnosis while their lesions were still nonenhancing. Of these patients, 9 (32%) had Grade 3 lesions (anaplastic astrocytoma or oligoastrocytoma), 13 (43%) had Grade 2 lesions (astrocytoma, oligodendroglioma, or oligoastrocytoma), and 2 (7%) had Grade 1 lesions (dysembryoplastic neuroepithelial tumors). Two additional patients (ages 33 and 59 years) who developed enhancement within their lesions during preoperative periods of observation had glioblastomas at surgery. Logistic regression was used to relate patient age to the risk of anaplasia in a nonenhancing cerebral mass lesion. Older age predicted a significantly higher risk of anaplasia (P = 0.025). The model predicted that nonenhancing cerebral masses in patients older than 44 years were more likely to be anaplastic tumors than low grade tumors. There was no "safe" age below which low grade histology could be confidently assumed. CONCLUSIONS: Magnetic resonance-nonenhancing cerebral lesions may be histologically anaplastic, even in young patients. The risk of anaplasia in magnetic resonance-nonenhancing lesions increases significantly with patient age.

Adolescent↗
PubMed1997

Inhibition of constitutive nitric oxide synthase (NOS) by nitric oxide generated by inducible NOS after lipopolysaccharide administration provokes renal dysfunction in rats.

Excess NO generation plays a major role in the hypotension and systemic vasodilatation characteristic of sepsis. Yet the kidney response to sepsis is characterized by vasoconstriction resulting in renal dysfunction. We have examined the roles of inducible nitric oxide synthase (iNOS) and endothelial NOS (eNOS) on the renal effects of lipopolysaccharide administration by comparing the effects of specific iNOS inhibition, -N6-(1-iminoethyl)lysine (L-NIL), and 2,4-diamino6-hydroxy-pyrimidine vs. nonspecific NOS inhibitors (nitro- -arginine-methylester). cGMP responses to carbamylcholine (CCh) (stimulated, basal) and sodium nitroprusside in isolated glomeruli were used as indices of eNOS and guanylate cyclase (GC) activity, respectively. LPS significantly decreased blood pressure and GFR (112+/-4 vs. 83+/-4 mmHg; 2.66+/-0.29 vs. 0. 96+/-0.22 ml/min, P < 0.05) and inhibited the cGMP response to CCh. GC activity was reciprocally increased. L-NIL and 2, 4-diamino-6-hydroxy-pyrimidine administration prevented the decrease in GFR (2.71+/-0.28 and 3.16+/-0.18 ml/min, respectively), restored the normal response to CCh, and GC activity was normalized. In vitro application of L-NIL also restored CCh responses in LPS glomeruli. Neuronal NOS inhibitors verified that CCh responses reflected eNOS activity. L-NAME, a nonspecific inhibitor, worsened GFR (0.41+/-0.15 ml/min), a reduction that was functional and not related to glomerular thrombosis, and eliminated the CCh response. No differences were observed in eNOS mRNA expression among the experimental groups. Selective iNOS inhibition prevents reductions in GFR, whereas nonselective inhibition of NOS further decreases GFR. These findings suggest that the decrease in GFR after LPS is due to local inhibition of eNOS by iNOS, possibly via NO autoinhibition.

Animals↗
PubMed1997

Crucial role of CD8-positive lymphocytes in glomerular expression of ICAM-1 and cytokines in crescentic glomerulonephritis of WKY rats.

CD8-positive lymphocytes (CD8+ lym) and ICAM-1/LFA-1 interaction have been implicated in the glomerular accumulation of monocytes/macrophages (Mo/Mphi) and crescent formation in antiglomerular basement membrane (anti-GBM) glomerulonephritis of WKY rats. In the present study, the role of CD8+ lym in the expression of ICAM-1 and inflammatory cytokines as well as in the accumulation of Mo/Mphi in the glomeruli was examined by RNase protection assay and immunofluorescence microscopy. ICAM-1 expression was apparent at 1 h and markedly enhanced at day 3 in glomeruli after an anti-GBM Ab injection in parallel with glomerular accumulation of Mo/Mphi. Expression of mRNA for IL-1beta, TNF-alpha, and IFN-gamma, known to enhance ICAM-1 expression, and MIP-1alpha, MIP-1beta, and MCP-1, known to activate leukocyte integrins or to act as chemokines, were also induced in the glomeruli at a mRNA level in a profile similar to that of ICAM-1 expression. By depleting the CD8+ lym in the circulation, the increased glomerular expression of ICAM-1 and the cytokines, except IL-1beta, and the Mo/Mphi accumulation were suppressed, indicating a crucial role of CD8+ lym in the accumulation of Mo/Mphi through stimulation of ICAM-1 and induction of cytokines.

Animals↗
PubMed1997

Transient immunomodulation with anti-CD40 ligand antibody and CTLA4Ig enhances persistence and secondary adenovirus-mediated gene transfer into mouse liver.

Although recombinant adenovirus vectors offer a very efficient means by which to transfer genetic information into cells in vivo, antigen-dependent immunity limits the duration of gene expression and prevents retreatment. Recombinant murine CTLA4Ig and anti-CD40 ligand antibody block costimulatory interactions between T cells and antigen presenting cells. We previously reported that murine CTLA4Ig prolongs adenoviral-mediated gene transfer, but does not allow for secondary expression after readministration of the vector. In studies described here, when anti-CD40 ligand and recombinant murine CTLA4Ig were coadministered around the time of primary vector administration (i) prolonged adenovirus-mediated gene expression (length of experiment up to 1 year) from the livers of >90% of treated mice was observed, and (ii) secondary adenovirus-mediated gene transfer was achieved in >50% of the mice even after the immunosuppressive effects of these agents were no longer present. Nearly two-thirds of these mice had persistent secondary gene expression lasting for at least 200-300 days. Neither agent alone allowed transduction after secondary vector administration. Treated mice had decreased immune responses to the vector as shown by markedly decreased production of neutralizing antibodies, diminished spleen proliferation responses and IFN-gamma production in vitro, and reduced T cell infiltrates in the liver. These results suggest that it may be possible to obtain persistence as well as secondary adenoviral-mediated gene transfer with transient immunosuppressive therapies.

Abatacept↗
PubMed1997

Characterization of cytokine and iNOS mRNA expression in situ during the course of experimental autoimmune myocarditis in rats.

Ribonuclease protection assay was used to demonstrate mRNA expression of several cytokines as well as inducible NO synthase (iNOS), constitutive endothelial NO synthase (cNOS) and perforin in the myocardium during the course of experimental autoimmune myocarditis (EAM) in rats. Interleukin 2 (IL-2) appeared in the initial inflammatory phase (day 14), subsided in the maximum inflammatory phase (day 19) and disappeared by the recovery phase (day 25). mRNA of IL-3 beta, interferon gamma INF-gamma and tumor necrosis factor alpha (TNF-alpha) were detected only in the maximum inflammatory phase and iNOS also appeared for several days at this time. In contrast. IL-10 mRNA was detected after the maximum inflammatory stage and persisted into the recovery phase (days 25-36). Although transforming growth factor beta 1 (TGF-beta 1) could be detected in all phases, the expression was markedly enhanced in the maximum inflammatory phase and gradually diminished (around day 36) to basal levels. Perforin mRNA was not detected at any point in the disease. Besides macrophages and CD4 T cells, a number of neutrophils were found in the myocardium especially at peak inflammatory stage. We suggest that antigen (Ag) primed Ag presenting cells or macrophages interact with T cells (Th1) to produce IL-2 and subsequent IFN-gamma, which further activates macrophages in the myocardium. Consequently, TNF-alpha and iNOS may inflict tissue damage to myocardium. It is also suggested that TGF-beta) and one representative Th2 cytokine, IL-10, help inhibit inflammation. These findings suggest that Th1 and Th2 cytokines are produced at different stages of EAM and modulate the inflammation and the course of EAM.

Animals↗
PubMed1997

Heterologous expression of adenovirus E3-gp19K in an E1a-deleted adenovirus vector inhibits MHC I expression in vitro, but does not prolong transgene expression in vivo.

An E1a-deleted adenovirus vector constitutively expressing native adenovirus E3-gp19K (Ad.RSV-gp19K) was constructed in order to determine whether or not E3-gp19K mediated interference with antigen presentation would result in prolonged transgene expression in vivo. Cultured fibroblasts infected with Ad.RSV-gp19K produced a native size gp19K protein and had decreased cell surface levels of MHC I as shown by immunoprecipitation and flow cytometry. The congenic mouse strains Balb/b (H-2b MHC I with high gp19K affinity), Balb/k (H-2k MHC I with no gp19K affinity), and Balb/c (H-2d MHC I with moderate gp19K affinity) were chosen for in vivo experiments because of their range of gp19K affinities. Following transduction of mice form each strain with Ad.RSV-gp19K and AD/RSV-hAAT (a reporter adenovirus), or Ad/RSV-cFIX (control adenovirus) and Ad/RSV-hAAT, the level and duration of serum hAAT protein were unrelated to gp19K protein expression. Evaluation of MHC I abundance on hepatocytes following in vivo transduction demonstrated that recombinant adenovirus rapidly increased the abundance of surface MHC I molecules on hepatocytes, and surface MHC I molecules were reduced earlier and to a greater extent following wild-type adenovirus infection compared with hepatocytes transduced with control or Ad.RSV-gp19K recombinant adenovirus. This difference in surface MHC I down-regulation may be related to the different promoters (RSV-LTR versus the native E3 promoter) and will be an important consideration in the development of newer generation adenovirus vectors designed to evade host immune responses.

Adenoviridae↗
PubMed1997

Constitutive expression of murine CTLA4Ig from a recombinant adenovirus vector results in prolonged transgene expression.

The administration of soluble muCTLA4Ig around the time of adenovirus vector mediated gene transfer into murine hepatocytes has been shown to markedly prolong transgene expression, diminish the formation of adenovirus neutralizing antibody, decrease T cell proliferative response and infiltration into the liver without causing irreversible systemic immunosuppression. In this study, an E1/E3-deleted adenovirus vector constitutively expressing murine CTLA4Ig (Ad.RSV-muCTLA4Ig) was constructed in order to determine if production of muCTLA4Ig from within transduced cells (i.e. hepatocytes) would provide a more specific/localized interference with the CD28/B7-1 and B7-2 signaling pathways, and thus result in prolonged transgene expression in vivo at nonimmunosuppressive serum concentrations. In contrast to C3H mice receiving a control adenovirus, transduction with 6 x 10(9) p.f.u. of Ad.RSV-muCTLA4Ig and a reporter adenovirus (2 x 10(9) p.f.u. of Ad.PGK-hAAT) resulted in prolonged reporter gene expression, reduced anti-adenovirus and anti-hAAT antibody production, and attenuated T cell proliferation and IFN-gamma production in response to adenoviral vector. Mice given a constant total amount of adenovirus with diminishing amounts of Ad.RSV-muCTLA4Ig and a constant amount of reporter virus (2 x 10(9) p.f.u. of Ad.PGK-hAAT) demonstrated prolonged reporter gene expression and decreased anti-adenovirus and anti-hAAT antibody production only when high serum levels of muCTLA4Ig were produced. Taken together, these findings suggest that a certain threshold of muCTLA4Ig must be achieved to alter the immune responses and prolong transgene expression from adenoviral vectors.

Abatacept↗
PubMed1997

Venous bleeding during transsphenoidal surgery: its association with pre- and intraoperative factors and with cavernous sinus and central venous pressures.

Venous bleeding during transsphenoidal surgery for resection of pituitary tumors is a common problem that interferes with the performance of the surgical procedure. In this study, data were collected prospectively from 50 patients to determine whether there were pre- or intraoperative factors (e.g., patient demographics, type and grade of pituitary tumor, intraoperative hemodynamics) associated with venous bleeding which might be used to predict its occurrence. In addition, central venous pressure (CVP), and cavernous sinus pressure (CSP) were measured in 13 patients to evaluate the relationship of these pressures to each other and to the severity of venous bleeding. During resection of the pituitary tumor, the severity of venous bleeding was graded as minimal, moderate, or severe, the latter two grades requiring therapeutic intervention. Moderate bleeding requiring intervention occurred in 15 of the 50 patients, and resolved in all cases. Moderate bleeding was not related to CSP or CVP, and no specific associated factor was observed. CSP was not correlated with CVP, and was higher than that predicted from the CVP and the position of the patient or the hydrostatic gravitational pressure gradient. These results suggest that it is not possible to predict in advance which patients will have problems with venous bleeding, but that simple therapeutic maneuvers are effective.

Adult↗
PubMed1997

Validation of the St. George's Respiratory Questionnaire in bronchiectasis.

There is no disease-specific instrument available for health status assessment in bronchiectasis. We examined the stability, validity and responsiveness of a measure designed for asthma and COPD, the St. George's Respiratory Questionnaire (SGRQ), in this condition. One hundred and eleven patients were studied on 2 separate d 6 mo apart. On both days each patient completed the SGRQ and measures of general and disease-specific health, mood, and fatigue. They also performed a shuttle walking test and comprehensive lung function tests. Repeatability was tested over 2 wk in 23 patients. The intraclass correlation (ri) for the SGRQ Total score was 0.97. The SGRQ component scores correlated well with relevant markers of disease activity. Examples include: SGRQ Symptoms score versus MRC Wheeze score, r = 0.634, p < 0.0001; Activity score versus shuttle walking test, r = -0.659, p < 0.0001; and impacts score versus physical fatigue, r = 0.610, p < 0.0001. Changes in the SGRQ Total score from entry to follow-up also correlated with changes in other measures of the patients' health. There were significant differences in the SGRQ total score between patients who improved and those who deteriorated over the 6 mo in respect to wheeze (F = 5.6, p < 0.01) and breathlessness (F = 6.05, p < 0.01). We conclude that the SGRQ reflects impaired health in bronchiectasis patients.

Adult↗