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Biomedical subjects

W H Wilson

Publications and source records attributed to W H Wilson.

At least 73 records · Page 4Linked to original sources
PubMed1996

Time required for initial improvement during clozapine treatment of refractory schizophrenia.

OBJECTIVE: To characterize better the length of time required for the onset of improvement during clozapine treatment for refractory schizophrenia, the author reanalyzed data from a naturalistic outcome study. METHOD: Medical records of 100 adults sequentially treated with clozapine in a state hospital were reviewed through 18 months. A priori criteria were used to categorize change in a measure of global social functioning. RESULTS: Of 73 patients who met the criteria for at least some improvement during clozapine treatment, 55 demonstrated initial improvement within 6 months, and the remainder demonstrated improvement by month 11. Response at 3 months was significantly correlated with outcome at 18 months. CONCLUSIONS: Gross social improvement as measured in this study is likely to lag behind more sensitive indicators of clinical response. This study supports the notion that initial response to clozapine occurs within the first few months of treatment.

Adult↗
PubMed1995

Treatment of HIV-associated Kaposi's sarcoma with paclitaxel.

We investigated whether paclitaxel was active in AIDS-associated Kaposi's sarcoma. We gave 135 mg/m2 intravenously over 3 hours every 21 days. Follow-up is available on the first 20 patients, most of whom had advanced Kaposi's sarcoma and severe immunocompromise. Neutropenia was the most frequent dose-limiting toxic effect; novel toxic effects included late fevers, rash, and eosinophilia. Creatinine increased in 2 patients and 1 patient had cardiomyopathy. There were 13 partial responses (65%, 95% CI 41-85%). All 5 patients with pulmonary involvement responded. Paclitaxel appears to be active against Kaposi's sarcoma as a single agent. Further studies, including a randomised trial, are warranted.

Acquired Immunodeficiency Syndrome↗
PubMed1995

Separation of basic drugs by packed-column supercritical fluid chromatography. 3. Stimulants.

A wide range of stimulants was rapidly and efficiently separated with symmetrical peak shapes with a tertiary supercritical mobile phase and a cyanopropyl liquid chromatography column. Compared with other drug families studied in this series, the stimulants exhibited a much broader range of retention. Several strong bases, including primary aliphatic amines, were easily eluted with a modified mobile phase. The stimulants were generally more retained than antipsychotic drugs. Compared with antidepressant drugs, a few stimulants behaved similarly, but most were more strongly retained. Modifier concentration proved to be the most effective means for changing both retention and selectivity. An over-the-counter eye drop solution (an aqueous buffer) was analyzed for tetrahydrozoline. The positive results with good peak shapes indicate that packed-column supercritical fluid chromatography is compatible with at least small aqueous samples.

Central Nervous System Stimulants↗
PubMed1995

Modulation of multidrug resistance by dexverapamil in EPOCH-refractory lymphomas.

We conducted a controlled trial of dexverapamil, an inhibitor of Pgp, in 45 Hodgkin's (HD) and 154 Non-Hodgkin's (NHL) lymphomas refractory to EPOCH chemotherapy. A total of 154 patients initially received EPOCH alone and (4.2%) with stable disease over two cycles or progressive disease "crossed over" to receive dexverapamil with EPOCH. Dexverapamil was escalated 8 dose levels, from 240 to 1200 mg/m2 per day. When possible, serial biopsies were obtained to measure MDR-1 expression by quantitative polymerase chain reaction. Median age was 44 years, 67% had stage IV disease, and median (range) prior regimens were 2 (1-12) in NHL and 1 (1-4) in HD. The maximum tolerated dose of dexverapamil was 900 mg/m2/day, and median plasma average concentrations of dexverapamil and nor-dexverapamil were 1.2 and 1.4 microM, respectively. There were 3 complete and 2 partial responses (12%) and 5 minor responses in NHL, and 2 of 10 HD patients achieved partial responses. MDR-1 was measured in 44 biopsies from 19 patients. Pre-therapy, MDR-1 was low (median 2.5 U) but increased (median 12.2 U) at cross-over. Among 6 patients with MDR-1 > 15, 3 responded to dexverapamil whereas only 1/8 patients with MDR-1 < 15 responded. EPOCH and dexverapamil were well tolerated. This study suggests that MDR-1 plays a role in clinical drug resistance of lymphomas, but also suggests that non-MDR-1 mechanisms are present in such patients. Earlier intervention with dexverapamil may be more effective and warrants further study.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1995

beta-Endorphin enhances the replication of neurotropic human immunodeficiency virus in fetal perivascular microglia.

The effect of an endogenous opiate, beta-endorphin, on the replication of HIV was investigated in brain perivascular microglia. Beta-endorphin enhanced the synthesis of p-24 antigen and transactivation of HIV promoter. Dialysed culture supernatants of endorphin-treated microglia re-activated latent HIV infection. These culture supernatants showed elevated levels of interleukin-1 beta, IL-6 and tumor necrosis factor alpha. Sub-optimal concentration of beta-endorphin potentiated GP-120-induced synthesis of these cytokines. Nalaxone reversed beta-endorphin-induced, but not GP-120-induced, cytokine production and enhanced HIV replication. These results suggest that endogenous opiates may contribute to the progression of AIDS dementia complex.

Cytokines↗
PubMed1995

Insight in schizophrenia and mania.

We administered a series of 12 brief vignettes depicting examples of positive, negative, and manic psychopathology in everyday language to 21 patients with schizophrenia and 20 patients with mania. We asked patients to rate, first, how similar they were to the individual depicted in each vignette, and, second, the degree to which the experiences or behaviors depicted in each vignette reflected mental illness. Psychiatrists also rated how similar each patient was to each vignette. At admission, patients with schizophrenia rated themselves as significantly less similar to the positive symptom vignettes than the psychiatrists rated them. Patients with mania did not differ from the psychiatrist in rating their similarity to the vignettes, but they strongly denied that the vignettes reflected mental illness.

Adult↗
PubMed1995

Clozapine treatment in Russia: a review of clinical research.

OBJECTIVE: This paper is intended to help American clinicians and investigators further their understanding of the clinical use of clozapine by reviewing experience with the drug in Russia, where it was introduced 17 years before it became available in the United States. METHODS: Key articles on clozapine from the Russian clinical research literature were reviewed by the first two authors, former Russian clinical investigators. The third author comments briefly about the implications of this work from a contemporary American perspective. FINDINGS AND CONCLUSIONS: The review found that although clozapine was not widely distributed in Russia, it was investigated at several large psychiatric research institutions and hospitals. It was not reserved for neuroleptic-resistant disorders but instead was used with some success as a first-line treatment in acute disorders. Although no controlled clinical trials were conducted, results of long-term outcome studies of treatment-resistant schizophrenia were largely in agreement with those of controlled trials and clinical follow-up studies in the U.S. The studies found short-term gains for previously refractory patients as well as improvements in social functioning that continued for extended periods in some cases. Russian investigators described clozapine as an effective antipsychotic agent that lacked the extrapyramidal side effects of other neuroleptics.

Clinical Trials as Topic↗
PubMed1995

18-month outcome of clozapine treatment for 100 patients in a state psychiatric hospital.

OBJECTIVE: The atypical antipsychotic medication clozapine is an effective treatment for refractory psychosis; however, the efficacy of clozapine when used in public mental health programs has yet to be fully characterized. This study assessed the outcome of clozapine treatment in a state hospital. METHODS: The medical records of the first 100 patients to receive clozapine in a state hospital, from six months before clozapine treatment through 18 months of treatment, were reviewed. RESULTS: The patients had chronic psychotic disorders that had responded poorly to treatment with conventional antipsychotic medication. Eighteen months after beginning clozapine, 45 patients were much improved, and 18 were somewhat improved. All except one of the improved patients were continuing clozapine treatment. Forty patients were living in community settings, 59 remained hospitalized, and one had died of an illness unrelated to clozapine. Violent episodes in the hospital decreased during the first six months of clozapine treatment. Thirteen patients had one or two seizures while taking clozapine, 12 of whom successfully continued clozapine treatment. One patient developed agranulocytosis, and one developed leucopenia; each recovered fully after clozapine treatment was discontinued. CONCLUSIONS: Clozapine was an effective treatment for refractory psychotic disorders when given as a part of routine state hospital treatment.

Activities of Daily Living↗
PubMed1995

Phase II study of paclitaxel in relapsed non-Hodgkin's lymphomas.

PURPOSE: To assess the efficacy and toxicity of paclitaxel administered as a 96-hour infusion to patients with relapsed non-Hodgkin's lymphomas (NHLs). PATIENTS AND METHODS: Eligible patients had relapsed NHL and measurable disease and were considered incurable. Paclitaxel was infused at a dose of 140 mg/m2 every 3 weeks. Premedications to prevent paclitaxel hypersensitivity reactions were not administered and no patients received corticosteroids. Expression of the multidrug resistance (mdr-1) gene was determined in tumor from 17 patients by mRNA quantitative polymerase chain reaction (PCR). RESULTS: Thirty-one patients received a total of 99 cycles of paclitaxel. Two patients were not assessable for response. The median age was 50 years, 71% had stage IV disease, and intermediate/high-grade histology was present in 65% of patients. Patients had received a median of three prior chemotherapy regimens, and 68% of patients had responded to the previous chemotherapy (chemotherapy-sensitive). Of 29 assessable patients, five (17%) achieved a partial response (PR). With a median potential follow-up time of 17 months, the median event-free and overall survival durations were 1.6 and 7.5 months, respectively. No correlation was found between response to paclitaxel and extent of prior treatment or response. The mdr-1 gene was easily detectable in 14 of 17 tumor biopsies, but was low in all but one sample. The most serious toxicity was grade 4 neutropenia, which occurred during 14% of cycles. CONCLUSION: Paclitaxel was well tolerated, but had a low response rate in patients with relapsed NHLs. There was no clear association between response to paclitaxel and extent of our response to prior treatment. Most patients had chemotherapy-sensitive disease, which suggests that the low response rate to paclitaxel was probably not due to general chemotherapy resistance. Paclitaxel provided good palliation in a minority of patients and is a reasonable agent to consider for use in patients who have failed to respond to standard chemotherapy.

Adult↗
PubMed1995

Phase I and pharmacokinetic study of the multidrug resistance modulator dexverapamil with EPOCH chemotherapy.

PURPOSE: Dexverapamil is a competitive inhibitor of the P-glycoprotein (Pgp) efflux pump, a potent mechanism of multidrug resistance (mdr-1) in vitro. We performed a phase I study to determine the maximum-tolerated dose (MTD) and pharmacokinetics of dexverapamil with etoposide, prednisone, vincristine, cyclophosphamide, and doxorubicin (EPOCH) chemotherapy. PATIENTS AND METHODS: Eligible patients had relapsed or refractory lymphoma or sarcoma. Patients initially received EPOCH alone, and those with stable or progressive disease were crossed-over to received dexverapamil on subsequent cycles of EPOCH. Dexverapamil was administered orally for 6 days and escalated over eight dose levels ranging from 240 to 1,200 mg/m2/d. Pharmacokinetics of dexverapamil and its active metabolite, nor-dexverapamil, were obtained in most patients. In seven patients, pharmacokinetics of doxorubicin, doxorubicinol, and etoposide were determined on paired cycles of EPOCH with or without dexverapamil. RESULTS: Sixty-five patients received 130 cycles of dexverapamil/EPOCH chemotherapy. The MTD of dexverapamil was 150 mg/m2 every 4 hours (900 mg/m2/d), and hypotension was the principal dose-limiting toxicity. The dexverapamil area under the curve (AUC) increased proportionally with dexverapamil dose, but significant interpatient variation occurred. At the MTD, the median plasma average concentrations of dexverapamil and nor-dexverapamil were 1.2 and 1.4 mumol/L, respectively. Dexverapamil did not affect the steady-state concentration (Css) of etoposide, but increased the Css of doxorubicin and doxorubicinol nearly twofold. The absolute neutrophil and platelet nadirs were significantly lower on the dexverapamil cycles compared with cycles of EPOCH alone, but other chemotherapy-related toxicities did not change. CONCLUSION: The phase II recommended dose of dexverapamil with EPOCH is 150 mg/m2 every 4 hours. This dose was well tolerated on an outpatient basis and achieved plasma concentrations of dexverapamil and nor-dexverapamil within the effective range for Pgp inhibition in vitro. Although dexverapamil increased the hematopoietic toxicity of EPOCH, it was mild, readily reversible, and offset by EPOCH dose reductions. Dexverapamil should be considered for further study.

Adult↗
PubMed1995

Controlled trial of dexverapamil, a modulator of multidrug resistance, in lymphomas refractory to EPOCH chemotherapy.

PURPOSE: Overexpression of the multidrug resistance gene (mdr-1) is present in up to 60% of relapsed lymphomas. To study its role in lymphomas, we conducted a controlled trial of dexverapamil, an inhibitor of the mdr-1 gene product, P-glycoprotein (Pgp), in lymphomas refractory to etoposide, prednisone, vincristine, cyclophosphamide, and doxorubicin (EPOCH) chemotherapy. PATIENTS AND METHODS: Eligible patients had recurrent Hodgkin's (HD) or non-Hodgkin's lymphomas (NHL) and measurable disease. Patients initially received EPOCH alone and those with stable tumor over two cycles or progressive disease crossed over to receive dexverapamil and EPOCH on subsequent cycles. Dexverapamil was escalated eight dose levels, from 240 to 1,200 mg/m2/d. When possible, serial biopsies were obtained to measure mdr-1 expression by quantitative polymerase chain reaction (PCR). RESULTS: Of 154 patients entered onto the trial, 109 had NHL and 45 had HD. The median age was 44 years, 67% had stage IV disease, and the median number of prior regimens was two (range, one to 12) in NHL and one (range, one to four) in HD. Sixty-four patients (42%) crossed over, of which eight were not assessable. The maximum-tolerated dose of dexverapamil was 900 mg/m2/d. Among 41 NHL patients (excluding mycosis fungoides), there were three complete responses (CRs) and two partial responses (PRs) (12%) and five minor responses (MRs); two of 10 HD patients achieved PRs. The mdr-1 level was measured in 44 biopsies from 19 patients. Pretherapy, mdr-1 was low (median, 2.5 U) but increased (median, 12.2 U) at crossover. Of six patients with mdr-1 levels greater than 15 U, three responded to dexverapamil, while only one of eight patients with mdr-1 levels less than 15 U responded. EPOCH and dexverapamil were well tolerated, but compared with EPOCH alone, produced more hematologic toxicity. CONCLUSION: These results suggest that Pgp plays a role in clinical drug resistance of lymphomas. However, they also suggest that mechanisms other than Pgp are prominent in heavily pretreated patients and that, although Pgp inhibition may be necessary, it is probably insufficient. Earlier intervention with dexverapamil may be more effective and warrants further study.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1995

Measurement of materialism and spiritualism in substance abuse research.

OBJECTIVE: A modified version of an instrument called the Mathew Materialism-Spiritualism Scale (MMSS), originally developed in India, was evaluated for possible use in substance abuse research in the U.S. METHOD: The scale was administered to 62 individuals recovering from substance use, 20 clergy people and 61 general controls. RESULTS: Test-retest reliability for the MMSS was verified by administering it to 18 control subjects on two separate occasions, 7 days apart. The Pearson correlation for the MMSS total scores was 0.83 (p < .0001). Internal consistency was examined with Cronbach's alpha in the entire sample of 143 subjects; the result for the total score was .93. Factor analysis showed a factor structure compatible with the subscales proposed by the developer. Women, in general, obtained higher spirituality scores. Members of the recovering group obtained significantly higher scores on "character" and "mysticism" than the general controls. When general controls were divided into MAST positive and MAST negative individuals, the MAST positive group obtained lower scores than the recovering group for "God," "mysticism" and "character." MAST negative individuals had lower scores on "mysticism" than the recovering group. Christians had higher scores on "God" and "religion" subscales than did nonChristians and agnostics. CONCLUSIONS: The results of this study need confirmation using an improved methodology and larger sample sizes. However, they suggest that the scale may be useful for the study of spirituality in the U.S.

Adult↗
PubMed1994

Separation of drugs by packed column supercritical fluid chromatography. 1. Phenothiazine antipsychotics.

Studies of speed, resolution, and sensitivity indicate packed column supercritical fluid chromatography is a viable technique for the analysis of antipsychotic drugs. Fourteen such drugs (mostly phenothiazines) were studied from a cyanopropyl liquid chromatography packed column with a tertiary mobile phase of carbon dioxide, methanol, and isopropylamine. An arbitrary mix of 10 components was baseline resolved in approximately 11 min. Detection limits were as low as 125 ppb, with a feasible 10-fold decrease. Without the isopropylamine in the mobile phase, none of the solutes eluted. With the additive, all produced symmetrical peaks and high efficiency (i.e., > 80% of theoretical). Changing modifier concentration was the most effective physical parameter for changing retention but had little effect on selectivity. Temperature changes had a modest effect on retention but provided surprisingly large changes in selectivity, with numerous peak reversals occurring over only a 30 degrees C temperature range. In addition, temperature programming was the most effective means to optimize resolution of the 10-component mix. No noticeable loss in efficiency accompanied the temperature programs.

Antipsychotic Agents↗
PubMed1994

Separation of drugs by packed column supercritical fluid chromatography. 2. Antidepressants.

Antidepressants can be rapidly and efficiently separated by packed-column supercritical fluid chromatography with a tertiary mobile phase. Ten antidepressants were nearly baseline resolved in < 6 min without programming. Calculated detection limits with a 5-microL injection volume were as low as 88 ppb. The effects of temperature, pressure, and modifier concentration on retention and selectivity were studied. Changing modifier concentration caused significant changes in selectivity. Several relationships between solute structure and selectivity changes were noted.

Antidepressive Agents↗