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Biomedical subjects

C B Wilson

Publications and source records attributed to C B Wilson.

At least 109 records · Page 6Linked to original sources
PubMed1996

Transsphenoidal pituitary resection for preoperative diagnosis of prolactin-secreting pituitary adenoma in women: long term follow-up.

The long term efficacy and safety of transsphenoidal resection for preoperative diagnosis of PRL-secreting pituitary adenomas in a large series of women have not been described. Four hundred and nine consecutive women at this university tertiary referral center undergoing transsphenoidal resection for preoperative diagnosis of PRL-secreting pituitary adenoma were followed for a minimum of 4 yr. The objective was to determine the efficacy and morbidity of this procedure and to identify features correlating with the resolution of hyperprolactinemia. Outcome measures included referral, preoperative, surgical, postoperative hospitalization, and long-term follow-up information, including recent PRL concentration. Follow-up was ascertained in 83% of patients who were followed for a mean of 9.2 yr. Recurrence of hyperprolactinemia occurred in 47% of total patients, but in only 16% with a single surgical procedure, histological diagnosis of prolactinoma, and postoperative PRL concentration of 5 ng/mL or less. The best single predictor of cure was postoperative day 1 PRL concentration of 5 ng/mL or less. Eighty-eight percent of women desiring conception conceived within 1 yr. Glucocorticoid-dependent hypopituitarism occurred in 23% of patients undergoing postoperative radiotherapy. There was no operative mortality. Operative morbidity was low. Our experience demonstrates that women undergoing transsphenoidal surgery for diagnosis of PRL-secreting adenoma form a heterogeneous patient population. The best long term results are achieved in the pure prolactinoma group, for whom transsphenoidal resection is generally safe and effective.

Adolescent↗
PubMed1996

Renal response to blood pressure elevation in normal and glomerulonephritic rats.

Concurrent renal disease appears to augment greatly the adverse effects of systemic hypertension on renal function and the development of glomerulosclerosis. This study examined the effects of systemic hypertension and treatment of hypertension in groups of normal non-nephritic rats and rats submitted to 16 wk of glomerulonephritis induced by the administration of anti-glomerular basement membrane antibody. Hypertension was produced by application of a clip to the right renal artery and blood pressure was treated with an angiotensin-converting enzyme (ACE) inhibitor, quinapril. Glomerulosclerosis of two types developed: a diffuse type that is characteristic of anti-glomerular basement membrane glomerulonephritis, and a focal segmental glomerulosclerosis that is characteristic of systemic hypertension. Glomerulonephritis significantly reduced the capacity of ACE inhibitors to decrease systolic blood pressure in awake animals. In addition, glomerulonephritis produced significant effects on plasma angiotensin II concentrations, whereby ACE inhibition no longer lowered plasma angiotensin II levels and in fact produced an increase. Glomerular capillary hydrostatic pressure and hydrostatic pressure gradient correlated with systolic blood pressure and with the incidence of focal glomerulosclerosis in non-nephritic rats. However, in glomerulonephritis, systolic blood pressure no longer correlated with glomerular capillary pressure, and glomerular capillary pressure no longer correlated with the development of glomerulosclerosis, although systolic blood pressure did correlate with the degree of focal segmental glomerulosclerosis. Concurrent glomerulonephritis strongly conditions the effects of superimposed hypertension by altering the relationship between systemic blood pressure and glomerular capillary hydrostatic pressure and by decreasing the response of hypertension to therapy.

Angiotensin II↗
PubMed1996

Radiation response and survival time in patients with glioblastoma multiforme.

The determine the value of radiographically assessed response to radiation therapy as a predictor of survival in patients with glioblastoma multiforme (GBM), the authors studied a cohort of 301 patients who were initially treated according to uniform clinical protocols. All patients had newly diagnosed supratentorial GBM and underwent the maximum safe resection followed by external- beam radiation treatment (60 Gy in standard daily fractions or 70.4 Gy in twice-daily fractions of 160 cGy). The radiation response and survival rates were assessable in 222 patients. The extent of resection and the immediate response to radiation therapy were highly correlated with survival, both in a univariate analysis and after correction for age and Karnofsky performance scale (KPS) score in a multivariate Cox model (p< 0.001 for radiation response and p=0.04 for extent of resection). A subgroup analysis suggested that neuroimaging obtained within 3 days after surgery served as a better baseline for assessment of radiation response than images obtained later. Imaging obtained within 3 days after completion of a course of radiation therapy also provided valid radiation response scores. The impact of the radiographically assessed radiation response on survival time was comparable to that of age or KPS score. This information is easily obtained early in the course of the disease, may be of value for individual patients, and may also have implications for the design and analysis of trials of adjuvant therapy for GBM, including volume-dependent therapies such as radiosurgery or brachytherapy.

Adolescent↗
PubMed1996

Slow-flow vascular malformations of the pons: capillary telangiectasias?

PURPOSE: To report clinical and MR features that suggest telangiectatic vascular malformations of the pons: METHODS: The MR scans and clinical data of 12 patients demonstrating an enhancing pontine lesion with minimal or no signal abnormality on T2-weighted images were reviewed. None of the patients underwent angiography or biopsy. Follow-up scans, available for all patients between 3 weeks and 40 months (range, 11.5 months), were reviewed. RESULTS: The patients presented with a variety of symptoms including headache (n = 4), vertigo (n = 3), gait abnormality (n = 3), and hearing loss (n = 2). Two were referred for biopsy or treatment of presumed pontine glioma. On precontrast MR, 3 of 12 lesions were isointense on both T1- and T2-weighted images. Three of 12 lesions were slightly hypointense on T1-weighted images and 8 of 12 were slightly hyperintense on T2-weighted images. Postgadolinium images showed a discrete focus of enhancement with irregular or brushlike borders. Eight of 12 had an anomalous draining vessel from the lesion to the surface of the pons. None demonstrated mass effect or hemorrhage. Gradient-echo sequences in 7 patients all showed marked T2 shortening, despite the absence of hemorrhage on either T1- or T2-weighted images. None of the follow-up scans showed radiographic or clinical progression. CONCLUSION: The benign clinical course, lack of mass effect, and minimal or no T2 prolongation argue against neoplasm and instead indicate a vascular cause. We suspect the decreased signal on gradient-echo sequences represents elevated intravascular deoxyhemoglobin from stagnant blood flow. The findings are atypical for cavernous angioma or classic venous malformation. Although pathologic confirmation is lacking, the radiographic features are most consistent with capillary telangiectasia or a transitional capillary-venous malformation. Despite the absence of progression or hemorrhage in any of the patients to date, the long-term prognosis currently is unknown. We emphasize the importance of recognizing the nonneoplastic nature of these lesions.

Adolescent↗
PubMed1995

Isolation of virus-neutralizing RNAs from a large pool of random sequences.

RNA and ribonuclease-resistant RNA analogs that bound and neutralized Rous sarcoma virus (RSV) were isolated from a large pool of random sequences by multiple cycles of in vitro selection using infectious viral particles. The selected RNA pool of RSV-binding sequences at a concentration of 0.16 microM completely neutralized the virus. Of 19 sequences cloned from the selected pool, 5 inhibited RSV infection. The selected RNA and RNA analogs were shown to neutralize RSV by interacting with the virus, rather than by adversely affecting the host cells. The selection of the anti-RSV RNA and RNA analogs by intact virions immediately suggests the potential application of this approach to develop RNA and RNA analogs as inhibitors of other viruses such as human immunodeficiency virus.

Antiviral Agents↗
PubMed1995

Medulloblastoma in adults.

PURPOSE: To examine the relationship between extent of disease and outcome in adults with medulloblastoma. METHODS AND MATERIALS: We reviewed the records of all patients over 15 years old with newly diagnosed or recurrent medulloblastoma treated by or referred to the University of California, San Francisco, and recorded demographic characteristics, clinical symptoms, radiographic findings, extent of resection, staging, myelography, computerized tomography (CT) scans or magnetic resonance (MR) images of the spine, histopathological assessment, treatment received, treatment response, recurrence patterns, and survival duration. RESULTS: A total of 47 patients were identified, 26 of whom were designated "poor-risk" because they had < 75% removal of tumor, metastatic disease, or brain-stem or leptomeningeal invasion. All patients had radiation therapy; 32 had adjuvant chemotherapy. Twenty-two patients (47%) died of tumor progression, 19 are progression-free, and 6 are alive with disease. The median survival time was 282 weeks in poor-risk patients and has not been reached in good-risk patients. Overall and disease-free 5-year survival rates differed significantly between the two groups (81% vs. 54%, p = 0.03 and 58% vs. 38%, p = 0.05, respectively). Tumors most often recurred in the posterior fossa. The median survival time from recurrence was 77 weeks (range 44 to 89 weeks). CONCLUSION: These findings are similar to those reported for children. Therefore, staging and treatment in adults should be approached the same way as in children: staging should include cerebrospinal fluid assessment and spinal imaging. Treatment should be based on staging, and should include craniospinal irradiation; additional chemotherapy should probably be reserved for poor-risk patients.

Adolescent↗
PubMed1995

Fetal dose estimates for radiotherapy of brain tumors during pregnancy.

PURPOSE: To determine clinically the fetal dose from irradiation of brain tumors during pregnancy and to quantitate the components of fetal dose using phantom measurements. METHODS AND MATERIALS: Two patients received radiotherapy during pregnancy for malignant brain tumors. Case 1 was treated with opposed lateral blocked 10 x 15 cm fields and case 2 with 6 x 6 cm bicoronal wedged arcs, using 6 MV photons. Fetal dose was measured clinically and confirmed with phantom measurements using thermoluminescent dosimeters (TLDs). Further phantom measurements quantitated the components of scattered dose. RESULTS: For case 1, both clinical and phantom measurements estimated fetal dose to be 0.09% of the tumor dose, corresponding to a total fetal dose of 0.06 Gy for a tumor dose of 68.0 Gy. Phantom measurements estimated that internal scatter contributed 20% of the fetal dose, leakage 20%, collimator scatter 33%, and block scatter 27%. For case 2, clinical and phantom measurements estimated fetal dose to be 0.04% of the tumor dose, corresponding to a total fetal dose of 0.03 Gy for a tumor dose of 78.0 Gy. Leakage contributed 74% of the fetal dose, internal scatter 13%, collimator scatter 9%, and wedge scatter 4%. CONCLUSIONS: When indicated, brain tumors may be irradiated to high dose during pregnancy resulting in fetal exposure < 0.10 Gy, conferring an increased but acceptable risk of leukemia in the child, but no other deleterious effects to the fetus after the fourth week of gestation. For our particular field arrangements and linear accelerators, internal scatter contributed a small component of fetal dose compared to leakage and scatter from the collimators and blocks, and 18 MV photons resulted in a higher estimated fetal dose than 6 MV photons due to increased leakage and collimator scatter. These findings are not universal, but clinical and phantom TLD measurements estimate fetal dose accurately for energies < 10 MV and should be taken for each pregnant patient considered for treatment to confirm and document acceptable dose.

Adult↗
PubMed1995

Radiation therapy and bromodeoxyuridine chemotherapy followed by procarbazine, lomustine, and vincristine for the treatment of anaplastic gliomas.

PURPOSE: To conduct a Phase II study to evaluate the long-term efficacy and safety of radiotherapy combined with intravenous bromodeoxyuridine for patients with anaplastic glioma tumors. METHODS AND MATERIALS: Between 1983 and 1987, study patients received 1.7-1.8 Gy radiation once a day, Monday through Friday, to a total dose of 60 Gy. On the Thursday prior to beginning radiotherapy and for the next 5 weeks (6 weeks total), patients received a continuous 96 h intravenous infusion of bromodeoxyuridine at 0.8 g/m2/24 h; following radiotherapy, patients received procarbazine, lomustine (CCNU), and vincristine (PCV) for 1 year or until tumor progressed. RESULTS: One-hundred thirty eight patients (median age, 43 years) were evaluable for analysis. Estimated 4-year survival for the anaplastic astrocytoma (AA) stratum (n = 116) is 46%. For the astrocytoma (ASTRO) stratum (n = 22), the 6-year survival is estimated at 79%. Estimated 4-year progression-free survival for AAs is 42%, and for ASTROs, 68%. Whole brain irradiation was used in 23% and limited-field irradiation in 77%; patients receiving limited-field irradiation had a better survival rate (p = 0.07). Total tumor resection was performed in 15%, partial resection in 53%, and biopsy only in 32%. For the 81 patients with tumor recurrence, 34 (42%) are known to have received additional treatment(s). For AA, fits of the Cox proportional hazards regression model showed that covariates individually predictive of survival were younger age (p < 0.001), Karnofsky performance score (p = 0.10). Major toxicities were rash during Weeks 1 through 6 requiring dose modification in 14%, Grade > or = III leukopenia in 18%, and Grade > or = III thrombocytopeni in 9%. CONCLUSION: The study suggests that the bromodeoxyuridine-radiotherapy-PCV, compared with other published therapies, can improve progression-free survival, and aggressive treatment of ASTRO patients can lead to substantial increases in survival compared to published survival data.

Adolescent↗
PubMed1995

Imaging metastatic testicular germ cell tumours with 18FDG positron emission tomography: prospects for detection and management.

The aim of this study was to investigate the role of positron emission tomography (PET) with [18F]fluoro-2-deoxyglucose (18FDG) in metastatic testicular germ cell tumours. Twenty-one patients with stage II-IV testicular germ cell tumours were imaged by PET with a multiwire proportional chamber PET system and 18FDG. Avid 18FDG uptake was seen in metastatic disease from primary seminoma and malignant teratoma. Normal tissue uptake was seen in differentiated teratoma or necrotic, fibrotic tissue. 18FDG standard uptake values and tumour to normal tissue ratios were 6.0 +/- 1.4 and 1.7 +/- 0.4 (mean +/- 1SD), respectively, for malignant tissue. Reduction of 18FDG tumour to normal tissue ratios from pre-treatment to on-treatment scans was predictive of response (n = 3). No significant reduction in 18FDG uptake was seen in patients not responding to therapy (n = 2). These results suggest a role for 18FDG PET in the detection and management of metastatic testicular germ cell tumours.

Abdominal Neoplasms↗
PubMed1995

Oxidative stress-inducible protein tyrosine phosphatase in glomerulonephritis.

Previously we found that rat mesangial cells express 3CH134/CL100 protein-tyrosine phosphatase (PTPase) in response to reactive oxygen intermediates (ROIs), and we now extend these studies to glomerulonephritis (GN), where ROI have been demonstrated to play a role. The rat homologue of 3CH134/CL100 was cloned from a rat macrophage cDNA library. The rat 3CH134/CL100 mRNA was strongly induced in the lung, liver, and heart the first day after birth, suggesting that hyperoxic adaption might be involved in the induction of the PTPase mRNA. In anti-glomerular basement membrane (GBM) antibody (Ab) GN in rats, the 3CH134/CL100 PTPase mRNA was expressed in glomeruli as early as 30 minutes after anti-GBM Ab injection. The 3CH134/CL100 mRNA expression was modulated by the ROI scavenger dimethylthiourea (DMTU), indicating that its induction was ROI related. In contrast to the glomerular lesion, PTPase mRNA expression was not induced in experimental tubulointerstitial nephritis. In situ hybridization suggested that mesangial and some infiltrating cells were the major glomerular cell sources of the PTPase mRNA. These results indicate that rat CCH134/CL100 PTPase is actively induced in glomeruli as part of an acute immune injury at least in part related to oxidative stress. PTPase induction in GN and potentially other forms of inflammation may play an important regulatory role in protein kinase signaling pathways.

Animals↗
PubMed1995

Long-term hepatic adenovirus-mediated gene expression in mice following CTLA4Ig administration.

Recombinant adenovirus vectors are efficient at transferring genes into somatic tissues but are limited for use in clinical gene therapy by immunologic factors that result in the rapid loss of gene expression and inhibit secondary gene transfer. This study demonstrates that systemic coadministration of recombinant adenovirus with soluble CTLA4Ig, which is known to block co-stimulatory signals between T cells and antigen presenting cells, leads to persistent adenoviral gene expression in mice without long-term immunosuppression. This form of immunotherapy greatly enhances the likelihood that recombinant adenovirus vectors will be useful for human gene therapy.

Abatacept↗
PubMed1995

Effects of endotoxin in the lungs of neonatal rats: age-dependent impairment of the inflammatory response.

Age-dependent maturation of the intrapulmonary inflammatory responses to bacterial lipopolysaccharide (LPS) was studied because nosocomial gram-negative infections cause morbidity in newborn infants. Escherichia coli LPS or live E. coli were injected into the airways of neonatal or adult rats; intrapulmonary recruitment of leukocytes was measured 6 h later. Neonates showed age- and dose-dependent impairment of intrapulmonary neutrophil recruitment after intratracheal administration of LPS or live E. coli that persisted for the first 28 days of life. Neonatal and adult alveolar macrophages released similar amounts of neutrophil chemotactic activity and tumor necrosis factor in response to incubation with LPS in vitro. Treatment of neonates with intratracheal or systemic interferon-gamma did not augment the response to LPS. Thus, intrapulmonary inflammatory responses to LPS and gram-negative bacteria are impaired early in life and do not approach adult levels until approximately 4 weeks of age.

Aging↗
PubMed1995

Pituitary adenoma as an unsuspected clival tumor.

Pituitary adenomas are common tumors that account for about 10% of intracranial neoplasms. Most arise from the adenohypophysis and are confined to the region of the sella turcica. Other sites may be involved as a result of extension, infiltration, or ectopic location. However, posterior extension or ectopic involvement of the clivus of the sphenoid and occipital bones is rare. Seven patients with destructive clival masses were referred to our institution with presumptive diagnoses of chordomas. In all cases, histologic workup revealed pituitary adenomas. Because they represent a subset of adenomas, the histologic features of the tumors were studied, and the clinical histories of the patients were reviewed. Five of the patients were men, aged 31 to 67 years, and two were women, aged 55 and 67 years. Four patients had extremely high plasma concentrations of prolactin (8,132-22,424 ng/ml, nl < 15). Four tumors resembled usual sellar adenomas; however, three exhibited nuclear pleomorphism, mitotic figures, and other morphologic features, suggesting alternate diagnoses. Three required immunoperoxidase stains in addition to those for pituitary hormones, and three required electron microscopy for diagnosis. Destructive invasion of the clivus by pituitary adenomas is rare, and anaplastic features of some of the tumors may lead to difficult diagnoses.

Adenoma↗
PubMed1995

Positionally independent and exchangeable late budding functions of the Rous sarcoma virus and human immunodeficiency virus Gag proteins.

The Gag proteins of Rous sarcoma virus and human immunodeficiency virus (HIV) each contain a function involved in a late step in budding, defects in which result in the accumulation of these molecules at the plasma membrane. In the Rous sarcoma virus Gag protein (Pr76gag), this assembly domain is associated with a PPPY motif, which is located at an internal position between the MA and CA sequences. This motif is not contained anywhere within the HIV Gag protein (Pr55gag), and the MA sequence is linked directly to CA. Instead, a late assembly function of HIV has been associated with the p6 sequence situated at the C terminus of Gag. Here we demonstrate the remarkable finding that the late assembly domains from these two unrelated Gag proteins are exchangeable between retroviruses and can function in a positionally independent manner.

Alleles↗
PubMed1995

Diminished expression of CD40 ligand by activated neonatal T cells.

CD40 and CD40 ligand (gp39) mediate contact-dependent T-B cell interaction. We determined the expression of CD40 ligand by activated neonatal T cells and the response of neonatal B cells when activated through CD40. Although expression of CD40 ligand peaked simultaneously in both activated adult and neonatal cells, neonatal T cells expressed significantly less CD40 ligand surface protein and mRNA than adult T cells. Activated thymocytes also expressed far less CD40 ligand than adult T cells. Consistent with these results, activated neonatal T cells exhibited less helper function than activated adult T cells. Neonatal T cells primed and restimulated in vitro expressed CD40 ligand in amounts comparable with adult T cells and provided B cell help more effectively. This suggests that the poor expression of CD40 ligand reflects antigenic naiveté rather than an intrinsic defect of neonatal T cells. Neonatal B cells cultured with soluble CD40 ligand (sgp39) and IL-10 produced IgM in amounts comparable with adult cells, but much less IgG and IgA. Nevertheless, neonatal B cells were capable of proliferation and class switching, since sgp39 and IL-4 induced proliferation and IgE production comparable to adult B cells and production of modest amounts of IgG. Together, these results indicate that diminished CD40 ligand expression, along with decreased production of lymphokines, may be responsible, at least in part, for the transient immunodeficiency observed in human neonates.

Adult↗
PubMed1995

Modulation of neutrophil influx in glomerulonephritis in the rat with anti-macrophage inflammatory protein-2 (MIP-2) antibody.

The role of the chemokine, macrophage inflammatory protein-2 (MIP-2), during anti-glomerular basement membrane (GBM) antibody (Ab) glomerulonephritis (GN) was studied. Rat MIP-2 cDNA had been cloned previously. Recombinant rat MIP-2 (rMIP-2) from Escherichia coli exhibited neutrophil chemotactic activity and produced neutrophil influx when injected into the rat bladder wall. By using a riboprobe derived from the cDNA and an anti-rMIP-2 polyclonal Ab, MIP-2 was found to be induced in glomeruli with anti-GBM Ab GN as mRNA by 30 min and protein by 4 h, with both disappearing by 24 h. The expression of MIP-2 correlated with glomerular neutrophil influx. A single dose of the anti-MIP-2 Ab 30 min before anti-GBM Ab was effective in reducing neutrophil influx (40% at 4 h, P < 0.01) and periodic acid-Schiff deposits containing fibrin (54% at 24 h, P < 0.01). The anti-rMIP-2 Ab had no effect on anti-GBM Ab binding (paired-label isotope study). Functional improvement in the glomerular damage was evidenced by a reduction of abnormal proteinuria (P < 0.05). These results suggest that MIP-2 is a major neutrophil chemoattractant contributing to influx of neutrophils in Ab-induced glomerular inflammation in the rat.

Amino Acid Sequence↗