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Biomedical subjects

W H Wilson

Publications and source records attributed to W H Wilson.

At least 55 records · Page 3Linked to original sources
PubMed1997

Effect of nitrous oxide on cerebral blood velocity while reclining and standing.

Cerebral blood velocity (CBV) (measured with transcranial Doppler, TCD) and other physiological and rating scale indices were measured before, during, and after inhaling a mixture of 40% nitrous oxide/oxygen and 40% nitrogen/oxygen, given during two separate visits in 7 normal male volunteers. During nitrous oxide/oxygen but not nitrogen/oxygen inhalation, CBV and euphoria increased significantly with minimal changes in other physiological indices except an increase in pulse rate after nitrous oxide/oxygen. In another 7 male volunteers, similar measurements were obtained while lying down and standing up during nitrous oxide/oxygen mixture and nitrogen/oxygen mixture inhalations, given during two separate visits. Nitrous oxide/oxygen inhalation produced significant CBV increase, which showed nonsignificant decrease of no clinical significance during standing up. There were no significant postural changes in blood pressure. Standing up during nitrous oxide/oxygen inhalation was associated with significant though mild dizziness.

Administration, Inhalation↗
PubMed1997

Cerebral vasodilation and vasoconstriction associated with acute anxiety.

A randomized, between-groups, repeated measures design was used to evaluate changes in cerebral blood flow (CBF), rating scales, and physiologic indices under resting conditions, during 5% CO2 inhalation in combination with epinephrine or saline infusions, in generalized anxiety disorder patients and controls. Subjects were divided into those with decreased anxiety and mild and more severe anxiety increase. The first group was found to have most pronounced CBF increase during CO2 inhalation, with the second group showing less marked increase, and the last group the least increase. In animals, sympathetic activation limits hypercapnic cerebral vasodilation. Thus, the restricted hypercapnic cerebral vasodilation during severe anxiety may be mediated through cervical sympathetic fibers, which innervate cerebral vessels.

Acute Disease↗
PubMed1997

Relationship of p53, bcl-2, and tumor proliferation to clinical drug resistance in non-Hodgkin's lymphomas.

Although the cause(s) of clinical drug resistance in non-Hodgkin's lymphomas (NHL) is unknown, in vitro studies suggest that abnormalities of the p53 gene, bcl-2 overexpression, and low tumor proliferation rates may increase chemotherapy resistance. We analyzed tumor tissue from 75 patients with relapsed/refractory NHL (Working Formulation A through H) for p53 mutation/overexpression (abnormality), bcl-2 expression, and tumor proliferation and correlated them with multiple clinical characteristics, response to therapy, disease-free survival, and overall survival (OS). All tumor biopsy specimens were obtained within 6 weeks of treatment with EPOCH (infusional etoposide, vincristine, and doxorubicin and bolus prednisone and cyclophosphamide) chemotherapy. Overall, 16 (21%) tumors had a p53 abnormality. Of 13 tumors with overexpression, mutations were confirmed by sequence analysis in 11, and, in 44 tumors without overexpression, 3 showed mutations. A multivariate analysis showed that tumors with a p53 abnormality were more likely to be drug resistant than tumors with normal p53 (56% v 17%; P2 = .008) and to have a shorter median progression-free survival (PFS; 2.1 v 8.2 months; P2 = .008) and OS (11.7 v 21.5 months; P2 = .038), respectively. The presence of a p53 abnormality did not correlate with any clinical characteristic, bcl-2 expression, or tumor proliferation. A significant correlation was found between low tumor proliferation and drug resistance in a univariate (P2 < .006) but not multivariate analysis. Patients with tumor proliferation of less than 80% were significantly more likely to have no response to therapy (31% v 6%) or to fail to achieve a complete response (16% v 44%) and tended to have shorter PFS and OS than did patients with higher proliferation. No significant association was found between bcl-2 expression and drug resistance, PFS or OS, although patients with intermediate-grade histologies and high bcl-2 expression tended to be drug resistant as compared with low level expressors (P2 < .065). Of interest was the finding of a significant association between high bcl-2 and low tumor proliferation (P2 = .0045). In studies that have found an association between high bcl-2 expression and short PFS, bcl-2 may have been a surrogate for low tumor proliferation. Further studies are warranted to examine this question. These results suggest that p53 mutation and low tumor proliferation, but not bcl-2, may be important causes of clinical drug resistance in NHL.

Cell Division↗
PubMed1997

Psychomotor effects of the anxiolytic abecarnil: a comparison with lorazepam.

Abecarnil is a metabolically stable beta-carboline that binds with high affinity and selectivity to central benzodiazepine receptors. The effects on cognitive and psychomotor skills of abecarnil (ZK 112-119), 2.5 mg and 5.0 mg, were compared with lorazepam 2.0 mg and placebo. Twenty-four healthy, young males participated in a double-blind, four-way Latin square design and performed batteries of behavioral tests at predrug and at 20, 40, 60, 80, 100, 120, 180, 240, 360 and 480 min after drug administration. Abecarnil 5.0 mg and lorazepam 2.0 mg displayed similar impairment profiles in tests of cognitive functions including memory encoding. Abecarnil 2.5 mg was substantially less impairing than lorazepam. Impairment levels of the abecarnil and lorazepam treatments peaked at 2-3 h after oral administration. The two abecarnil doses showed dose-dependent effects on the cognitive and psychomotor tasks. All three drug treatments were well tolerated by the subjects, with no one terminating early due to adverse events. The incidence of reported adverse events for abecarnil was dose-dependent. The most frequent, statistically significant adverse effects were drowsiness, lack of concentration and visual disturbance for abecarnil 5.0 mg; and lack of concentration and dizziness for lorazepam 2.0 mg. There were no significant differences in adverse incidence rates between abecarnil 2.5 mg and placebo.

Adult↗
PubMed1997

Marijuana intoxication and brain activation in marijuana smokers.

OBJECTIVE AND METHOD: The acute effects of delta9 tetrahydrocannabinol (THC) on cerebral blood flow (CBF) were studied in human subjects. Regional CBF was measured with 15O-water and Positron Emission Tomography (PET) in 32 volunteers with a history of exposure to marijuana. Scans were performed before and after intravenous (I.V.) infusion of either of two doses of THC or a placebo, given under double blind conditions. RESULTS: THC but not placebo increased CBF especially in the frontal regions bilaterally, insula and cingulate gyrus and sub-cortical regions with somewhat greater effects in the right hemisphere. While most regions showed significant change at 60 minutes for the lower dose group, the higher dose group had significant change at 30 and 60 minutes. There was a highly significant change in the anterior/posterior ratio for the two THC groups reflecting minimal change in occipital flow but significant increases in frontal flow. Self ratings of THC intoxication showed significant effects, and regression analysis indicated it correlated most markedly with the right frontal region. CONCLUSION: Behavioral manifestations of marijuana intoxication may be associated with increased functional activity of the brain especially the frontal cortex, insula and cingulate gyrus.

Adult↗
PubMed1997

An immunological approach to detect phosphate stress in populations and single cells of photosynthetic picoplankton.

In the marine cyanobacterium Synechococcus sp. strain WH7803, PstS is a 32-kDa cell wall-associated phosphate-binding protein specifically synthesized under conditions of restricted inorganic phosphate (P1) availability (D. J. Scanlan, N. H. Mann, and N. G. Carr, Mol. Microbiol. 10:181-191, 1993). We have assessed its use as a potential diagnostic marker for the P status of photosynthetic picoplankton. Expression of PstS in Synechococcus sp. strain WH7803 was observed when the P1 concentration fell below 50 nM, demonstrating that the protein is induced at concentrations of P1 typical of oligotrophic conditions. PstS expression could be specifically detected by use of standard Western blotting (immunoblotting) techniques in natural mesocosm samples under conditions in which the N/P ratio was artificially manipulated to force P depletion. In addition, we have developed an immunofluorescence assay that can detect PstS expression in single Synechococcus cells both in laboratory cultures and natural samples. We show that antibodies raised against PstS cross-react with P-depleted Prochlorococcus cells, extending the use of these antibodies to both major groups of prokaryotic photosynthetic picoplankton. Furthermore, DNA sequencing of a Prochlorococcus pstS homolog demonstrated high amino acid sequence identity (77%) with the marine Synechococcus sp. strain WH7803 protein, including those residues in Escherichia coli PstS known to be directly involved in phosphate binding.

Carrier Proteins↗
PubMed1997

Alternating MOPP and ABVD chemotherapy plus mantle-field radiation therapy in patients with massive mediastinal Hodgkin's disease.

PURPOSE: To evaluate the efficacy and toxicity of mechlorethamine, vincristine, procarbazine, and prednisone (MOPP)/doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) chemotherapy plus mantle-field radiation therapy in the treatment of patients with massive mediastinal Hodgkin's disease of any stage. PATIENTS AND METHODS: Eighty patients presented with Hodgkin's disease and a mediastinal mass greater than one third the greatest chest diameter on chest radiograph. Patients were staged and treated with MOPP alternated with ABVD chemotherapy for a total of six cycles. Patients then received 10 Gy mantle-field radiation therapy delivered to the original extent of disease followed by 25 to 35 Gy to the residual abnormalities. RESULTS: The complete response (CR) rate was 89%. With a median follow-up duration of 10 years, disease-free survival of the complete responders is 78% at 15 years and overall survival is 75% at 15 years. For patients with stage I or II disease, disease-free survival was 76% at 15 years and overall survival was 79%; for those with stage III or IV disease, disease-free survival was 82% at 15 years and overall survival was 64%. Age, stage, sex, B symptoms, number of extranodal sites, lactate dehydrogenase (LDH) levels, erythrocyte sedimentation rate, and platelet count did not influence treatment outcome. Treatment-related pneumonitis was noted in 16% of patients (fatal in one), mainly in those older than age 35 years who received total doses of radiation therapy greater than 42 Gy. Fertility is more often preserved with MOPP/ABVD therapy than with MOPP chemotherapy and there appears to be less pulmonary and cardiac disease than with ABVD chemotherapy. Two patients have developed second solid tumors within radiation ports and one relapsed patient developed acute leukemia after MOPP salvage therapy. CONCLUSION: MOPP/ABVD followed by mantle-field radiation therapy is an effective treatment for all stages of Hodgkin's disease that present with a large mediastinal mass. Our data suggest that the large mediastinal mass is a more dominant determinant of prognosis than Ann Arbor stage or other clinical prognostic factors.

Adolescent↗
PubMed1997

Paclitaxel by 96-hour continuous infusion in combination with cisplatin: a phase I trial in patients with advanced lung cancer.

PURPOSE: To determine the maximum-tolerated dose (MTD) of paclitaxel administered by 96-hour continuous infusion in combination with cisplatin, to determine if the addition of granulocyte colony-stimulating factor (G-CSF) permits significant paclitaxel dose escalation, and to assess the toxicity and preliminary activity of this combination in patients with advanced lung cancer. PATIENTS AND METHODS: Fifty patients with untreated lung cancer were enrolled: 42 had advanced non-small-cell lung cancer (NSCLC) and eight had extensive-stage small-cell lung cancer (SCLC). Patients received paclitaxel doses of 100 to 180 mg/m2/96 hours and cisplatin doses of 60 to 80 mg/m2 as a single 30-minute bolus injection at the end of the paclitaxel infusion. RESULTS: Two of six patients experienced dose-limiting neutropenia at a dose of paclitaxel 140 mg/m2/96 hours and cisplatin 80 mg/m2. With G-CSF support, one of three patients experienced both dose-limiting mucositis and fatal neutropenic sepsis at a dose of paclitaxel 180 mg/m2/96 hours and cisplatin 80 mg/m2. Significant peripheral neuropathy developed in five patients and occurred after six or more cycles of therapy. Thirty-three of 42 patients with NSCLC had measurable disease; the objective response rate was 55%, with two complete responses and 16 partial responses. For all 42 patients with NSCLC, the median time to progression and median survival duration were 5 months and 10 months, respectively. The actuarial 1-year survival rate was 41%. Of eight SCLC patients, four responded to therapy, and the median survival duration for all SCLC patients was 11 months. CONCLUSION: The MTD without G-CSF is paclitaxel 120 mg/m2/96 hours and cisplatin 80 mg/m2, and the MTD with G-CSF is paclitaxel 160 mg/m2/96 hours and cisplatin 80 mg/m2. Infusional paclitaxel with cisplatin is well tolerated and active in patients with advanced NSCLC.

Adult↗
PubMed1997

Lymphomatoid granulomatosis: pathogenesis, pathology and clinical implications.

Lymphomatoid granulomatosis (LG) exhibits many similarities both clinically and pathologically to angiocentric T/NK cell lymphoma and was until recently considered to be part of the same disease spectrum. However, recent data indicate that LG is an EBV positive B cell proliferation associated with an exuberant T cell reaction. LG presents in extranodal sites, most commonly the lung (Katzenstein and Peiper, 1990). Other frequent sites of involvement include kidney, skin, central nervous system and liver. The pattern of necrosis in both LG and T/NK cell lymphoma is very similar, emphasizing the probable importance of EBV in mediating the vascular damage. Recent studies implicate the chemokines IP-10 and Mig in the pathogenesis of the vascular damage. Although the predominant infiltrating cells are T cells, the T cell receptor genes are not clonally rearranged. However, by VDJ polymerase chain reaction, approximately 60% of cases contain clonal rearrangements. EBV sequences can be localized to B cells and are clonal in most cases. Most patients with LG when carefully evaluated clinically have defects in cytotoxic T cell function and reduced levels of CD8+ T cells. LG is also common in many immunodeficiency states, such as AIDS, Wiskott-Aldrich syndrome and post-transplantation immunodeficiency. Thus, in many respects, LG resembles an EBV driven lymphoproliferative disorder. Some cases of LG regress spontaneously, but most patients require therapy. Treatment approaches have included cyclophosphamide and prednisone, aggressive combination chemotherapy and interferon alpha 2b, because of its antiviral, antiproliferative and immunomodulatory effects.

Diagnosis, Differential↗
PubMed1996

A study of the potential confounding effects of diet, caffeine, nicotine and lorazepam on the stability of plasma and urinary homovanillic acid levels in patients with schizophrenia.

Ten men inpatients who met DSM-III-R criteria for schizophrenia participated. On five occasions at least one week apart, each subject had an intravenous line placed at 0730 after an overnight fast. On each occasion blood samples were drawn at 0800 and hourly thereafter through 1200 noon for measurement of plasma homovanillic acid (HVA). Total four-hour urine collections were obtained for measurement of urinary HVA. Subjects received five experimental conditions, in randomized sequence: no intervention, smoking one cigarette per hour, drinking one caffeinated cola per hour, lorazepam 2 mg IV push, or a high monoamine meal. Baseline (0800) plasma HVA measures showed only minor intrinsic variability. The average standard deviation in baseline plasma HVA over five occasions of measurement was low relative to the changes in HVA produced during treatment with antipsychotic medications. The high monoamine meal significantly elevated plasma HVA, with a similar trend for urinary HVA. Neither caffeine, nicotine, nor lorazepam significantly affected plasma or urinary HVA.

Adult↗
PubMed1996

Acute changes in cranial blood flow after cocaine hydrochloride.

Cerebral blood flow (CBF) was measured with the 133Xenon inhalation technique and forehead skin flow with laser Doppler, before and twice after 0.3 milligram/kilogram of cocaine hydrochloride and a placebo given intravenously to six cocaine abusers, during two visits, separated by a minimum of one week. After cocaine, subjects showed significant increases in intoxication and tension. Systolic blood pressure and pulse rate also increased significantly after the drug but not after the placebo. CBF, with and without correction for end-tidal CO2, showed increases in left and right hemisphere after cocaine. The CBF increase was maximal in frontal, central and parietal regions. CBF changes correlated only with changes in a rated level of intoxication. Forehead skin flow did not change after cocaine or placebo. In habitual cocaine abusers, 0.3 mg/kg of cocaine, given intravenously produced increased CBF and no changes in forehead skin flow.

Adult↗
PubMed1996

Association of lymphomatoid granulomatosis with Epstein-Barr viral infection of B lymphocytes and response to interferon-alpha 2b.

Lymphomatoid granulomatosis (LyG) is an angiodestructive lymphoproliferative disorder (LPD) often involving the lungs. Its etiology is uncertain, but a number of previous studies had suggested it is a T-cell LPD associated with Epstein-Barr virus (EBV). Because of the similarity between LYG and nasal angiocentric lymphoma, the term angiocentric immunoproliferative lesion was proposed for both entities. Optimal therapy is unknown, but chemotherapy is often used. We studied four patients with LYG over a 5-year period. Biopsy samples were analyzed by immunohistochemistry, EBV in situ hybridization, and for Ig heavy-chain (IgH) gene rearrangements, Clinically, we assessed EBV serology, lymphocyte subsets, and the efficacy of interferon-alpha2b (IFN-alpha2b), All biopsy samples showed an exuberant T-cell infiltrate with scattered atypical large B cells. Double labeling showed EBV in the B cells but not T cells. Clonal IgH gene rearrangements were detected in 2 of 3 patients studied, 1 of whom had three distinct clones, and light-chain restriction showed two clones in an additional patient. All patients had positive EBV serologies. and markedly abnormal lymphocyte subsets. With IFN, 3 patients are alive and disease free at 36, 43, and 60 months; 1 patient achieved a partial response for 16 months but discontinued therapy and died with lymphoma. These results indicate that LYG is a T-cell-rich EBV-associated B-cell LPD in which the infiltrating T cells are numerous but reactive. IgH gene rearrangements may be polyclonal, monoclonal, or oligoclonal. Its association with immune defects suggests it is related to posttransplant LPD. However, LYG and nasal angiocentric lymphoma are distinct entities and should no longer be included together under the term angiocentric immunoproliferative lesion. IFN is effective therapy and should be studied further.

Adjuvants, Immunologic↗
PubMed1996

Clinical reversal of multidrug resistance.

Reversal of drug resistance offers the hope of increasing the efficacy of conventional chemotherapy. We tested dexverapamil as a P-glycoprotein antagonist in combination with EPOCH chemotherapy in refractory non-Hodgkin's lymphoma. In a cross-over design, dexverapamil was added to EPOCH after disease stabilization or progression occurred. Objective responses were observed in 10 of 41 assessable patients. Biopsies for mdr-1 were obtained before EPOCH treatment and at the time of cross-over to dexverapamil. Levels of mdr-1 were low before EPOCH, but increased four-fold or more in 42% of patients in whom serial samples were obtained. Pharmacokinetic analysis revealed median peak concentrations of dexverapamil and its metabolite, nor-dexverapamil, of 1.66 mumol/l and 1.58 mumol/l, respectively. Since both are comparable antagonists, a median peak total reversing concentration of 3.24 mumol/l was achieved. Pharmacokinetic analysis of doxorubicin and etoposide levels confirmed a delay in the clearance of doxorubicin ranging from 5% to 24%; no change in the pharmacokinetics of etoposide was observed. This study provides sufficient rationale for testing dexverapamil in a randomized clinical trial.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1996

A characteristic eruption associated with ifosfamide, carboplatin, and etoposide chemotherapy after pretreatment with recombinant interleukin-1 alpha.

BACKGROUND: Patients who received recombinant interleukin-1 alpha (IL-1 alpha) before chemotherapy followed by autologous bone marrow transplantation had a characteristic intertriginous cutaneous eruption that has not previously been described. OBJECTIVE: Our aim was to document these skin changes and to determine whether IL-1 alpha as a sole agent caused recognizable changes in the skin. METHODS: A prospective study of the skin changes in eight patients was performed. We characterized the clinical, histologic, and immunohistochemical features of the patient's skin after IL-1 alpha infusions and after chemotherapy. RESULTS: No specific clinical or histologic changes were seen immediately after IL-1 alpha infusions. Immunohistochemical studies showed significant upregulation of endothelial leukocyte adhesion molecule-1 (ELAM-1) expression. Within 1 day of the initiation of chemotherapy (ifosfamide, carboplatin, and etoposide), a cutaneous eruption consisting of mucositis and varying degrees of erythema progressing to painful erosions in body folds and under adhesive tape developed in all patients. Histologic features were consistent with a chemotherapeutic effect on the epidermis as well as eccrine and apocrine glands. Expression of keratinocyte intercellular adhesion molecule-1 and HLA-DR as well as of ELAM-1 on dermal endothelial cells was increased. The perivascular lymphocytic infiltrate consisted mainly of CD4+ T cells. CONCLUSION: High-dose chemotherapy with ifosfamide, carboplatin, and etoposide resulted in a characteristic cutaneous eruption that is consistent with a toxic reaction to chemotherapeutic agents. Its accentuation in skin folds and under taped areas suggests that eccrine excretion of the drugs or a toxic metabolite is an important contributing factor. IL-1 alpha may induce the expression of ELAM-1 but does not cause a cutaneous eruption.

Adult↗
PubMed1996

Response of patients with treatment-refractory schizophrenia to clozapine within three serum level ranges.

OBJECTIVE: This study sought to determine the relationships between serum clozapine levels and therapeutic response. METHOD: Fifty-six inpatients who met the DSM-III-R criteria for chronic schizophrenia and who had not responded to extended treatment with classical antipsychotics were randomly assigned to 12 weeks of double-blind treatment with clozapine at one of three serum level ranges: low (50-150 ng/ml), medium (200-300 ng/ml), or high (350-450 ng/ml). Baseline clinical assessments were completed before the patients' regular antipsychotic and anticholinergic drugs were discontinued. During clozapine treatment, serum levels were ascertained weekly to allow adjustment of clozapine doses so as to maintain each patient near the midpoint of his or her assigned serum level range. Clinical assessments were completed after 6 and 12 weeks of treatment. RESULTS: The analyses of the results of treatment supported the superior efficacy of the 200-300 ng/ml and 350-450 ng/ml serum clozapine level ranges over the 50-150 ng/ml range, with no advantage for 350-450 ng/ml over 200-300 ng/ml. Sleepiness increased with increasing serum levels. CONCLUSIONS: Serum clozapine levels per unit of daily dose were at the lower end of the range noted in previous reports, possibly reflecting the current study's dosing schedules of twice or three times a day, the 11- to 13-hour postdose sampling time, and the moderate doses given. Serum clozapine levels, if interpreted in relation to daily clozapine dosing schedules, postdose sampling time, and total daily dose, may help to guide dosing to provide adequate opportunities for therapeutic response and to limit certain side effects of clozapine treatment.

Clozapine↗