Biomedical subjects

W Grove

Publications and source records attributed to W Grove.

At least 19 recordsLinked to original sources

PubMed2006

Gemcitabine plus CI-994 offers no advantage over gemcitabine alone in the treatment of patients with advanced pancreatic cancer: results of a phase II randomized, double-blind, placebo-controlled, multicenter study.

BACKGROUND: CI-994, an oral histone deacetylase inhibitor, has antineoplastic activity and synergism with gemcitabine preclinically. This randomized phase II trial explored whether CI-994 plus gemcitabine improves overall survival, objective response, duration of response, time to treatment failure and change in quality of life (QoL) or pain compared with gemcitabine alone. PATIENTS AND METHODS: A total of 174 patients received CG (CI-994 6 mg/m(2)/day days 1-21 plus gemcitabine 1000 mg/m(2) days 1, 8 and 15 each 28-day cycle) or PG (placebo plus gemcitabine 1000 mg/m(2) days 1, 8 and 15 of each 28-day cycle days 1-21). RESULTS: Median survival was 194 days (CG) versus 214 days (PG) (P = 0.908). The objective response rate with CG was 12% versus 14% with PG when investigator-assessed and 1% versus 6%, respectively, when assessed centrally. Time to treatment failure did not differ between the two arms (P = 0.304). QoL scores at 2 months were worse with CG than with PG. Pain response rates were similar between the two groups. There was an increased incidence of neutropenia and thrombocytopenia with CG. CONCLUSIONS: Adding CI-994 to gemcitabine in advanced pancreatic carcinoma does not improve overall survival, response rate or time to progression; CG produced decreased QoL and increased hematological toxicity and appears inferior to single-agent gemcitabine.

Adenocarcinoma↗

PubMed2000

Fluorescence in situ hybridization identifies inversion 16 masked by t(10;16)(q24;q22), t(7;16)(q21;q22), and t(2;16)(q37;q22) in three cases of AML-M4Eo.

Bone marrow or peripheral blood from three patients had a t(10;16)(q24;q22), t(7;16) (q21;p13.1), and t(2;16)q37;q22), respectively. In all cases, fluorescence in situ hybridization confirmed an inv(16) masked by the translocation. The three patients were diagnosed with acute myelomonocytic leukemia and increased eosinophils. Because inv(16) has a favorable prognosis, identification of masked inv(16) will promote improved management of these cases. Therefore, all cases that have atypical rearrangement of chromosome 16 should be investigated for a possible inversion.

Adult↗

PubMed1999

A phase II trial of CI-958 in patients with hormone-refractory prostate cancer.

PURPOSE: To assess the antitumor activity of the benzothiopyranoindazole CI-958 ¿5-[(2-aminomethyl)amino]-2-[2-(diethylamino)ethyl]-2H- [l]benzothiopyrano[4,3,2-cd]-indazol-8-ol trihydrochloride¿ in hormone-resistant prostate carcinoma, using an intravenous dose of 700 mg/m(2) every 3 weeks. PATIENTS AND METHODS: Patients eligible for this study had advanced prostate carcinoma that had failed hormonal treatment. Changes in an initially elevated prostate-specific antigen (PSA) level and regression of objectively measurable disease were used as response criteria. RESULTS: All 33 patients enrolled were evaluated. Of 30 with elevated PSA levels, 6 had a >50% decline maintained for >30 days; response durations ranged from 105 to 623 days. Eleven patients had objectively measurable disease; two had partial responses (lasting 316 and 461 days) consisting of shrinkage of retroperitoneal nodes and of masses surrounding the rectum and bladder. The survival of all responding patients ranged from 366 days to 709 days and the median survival of all patients was 12 months (range 1-23 + months). Neutropenia was common, but thrombocytopenia was not. Nonhematologic side effects included nausea, vomiting, anorexia, asthenia, and chills, but were usually mild. The drug caused phlebitis when given into peripheral veins and central venous administration is recommended. No consistent reductions in cardiac function were documented by sequential assessment of left ventricular ejection fractions. CONCLUSIONS: CI-958 has modest but definite antitumor activity in hormone-resistant prostate carcinoma. Its toxicities include neutropenia, nausea, vomiting, anorexia, asthenia, chills and phlebitis.

Adult↗

PubMed1999

The Iowa Personality Disorder Screen: development and preliminary validation of a brief screening interview.

The length and expense of comprehensive personality disorder interviews makes them unwieldy for routine use. A brief but sensitive screen could eliminate administration of longer instruments in many instances. We describe the development of the Iowa Personality Disorder Screen (IPDS)--a mini-structured interview which can be completed in less than 5 minutes. Retrospective analyses using 1,203 SIDP-R interviews suggested that the IPDS items should provide good sensitivity and specificity. We present results from a prospective validation study, using a mixed group of 52 nonpsychotic inpatients and outpatients who were diagnosed using the SIDP-IV. Blind administration of the IPDS yielded excellent sensitivity (92%) and good specificity (79%), using a subset of five screening items. Addition of two more items leads to an estimated sensitivity of 79% and specificity of 86%. The IPDS shows promise as a quick personality disorder screen for use in research settings or standard clinical interviews.

Adult↗

PubMed1998

Phase II study of i.v. CI-980 in patients with advanced platinum refractory epithelial ovarian carcinoma.

CI-980 is a synthetic mitotic inhibitor that binds to tubulin at the colchicine site, inhibiting the polymerization of microtubules and arresting cellular division in metaphase. Myelosuppression and neurotoxicity were dose-limiting in phase I studies. Sixteen patients with stage III and IV platinum-refractory ovarian cancer received 4.5 mg/m2/day of CI-980 as a continuous i.v. infusion for 72 h, repeated every 3 weeks. Eleven patients had progression and four patients had stable disease. One patient (6%; 95% CI 0-25%) achieved a partial response after 9 months of treatment which lasted for 27 months. The overall median survival was 7 months. Grade 4 granulocytopenia occurred in five patients, with two episodes of neutropenic fever. Neurological toxicity was mild with 12 episodes of transient subclinical recent memory loss documented in four patients by specialized neuropsychological evaluations. One patient each had hallucinations and mild truncal ataxia, and four patients had mild, reversible neurosensory toxicity. One episode of severe hypoxemia and dyspnea occurred in a patient with chronic obstructive pulmonary disease. CI-980 has minimal activity and is tolerable in a population of heavily pretreated patients with platinum refractory ovarian cancer.

Adult↗

PubMed1998

The cooccurrence of DSM-III-R personality disorders.

The distinction between personality disorder diagnoses is often unclear because of the frequent cooccurrence of one or more of the diagnoses. To date, studies using sample sizes large enough to evaluate the rates of cooccurrence in the less prevalent personality disorders have not been conducted. The Structured Interview for Diagnosis of Personality-Revised, a semistructured instrument designed to yield reliable personality disorder diagnoses, was used to evaluate 1116 subjects for the presence of DSM-III-R personality disorder diagnoses. Cooccurrence rates and odds ratios were calculated for each pair of diagnoses. There was a high degree of cooccurrence between the cluster A personality disorders, between the cluster C personality disorders, and between narcissistic, borderline, and histrionic disorders. In addition, there was also a high frequency of avoidant personality disorders within the cluster A personality disorder diagnoses. Possible explanations for the high degree of cooccurrence and the potential implications for the DSM-IV personality disorder diagnoses are discussed.

Adult↗

PubMed1997

Phase II trial of intravenous CI-980 (NSC 370147) in patients with metastatic colorectal carcinoma. Model for prospective evaluation of neurotoxicity.

CI-980 (NSC 370147)--a synthetic mitotic inhibitor that binds to tubulin at the colchicine binding site--has significant activity against a broad spectrum of tumor models and greater in vitro cytotoxicity when given over > 24 hours than 4 hours or less. Phase I studies demonstrated central nervous system (CNS) toxicity to be dose-limiting when CI-980 was administered as a 24-hour infusion. When a 72-hour infusion was given, CNS toxicity was reduced and granulocytopenia became the dose-limiting toxicity. In this phase II study, CI-980, 4.5 mg/m2, was administered as a 24-hour continuous intravenous infusion for 3 consecutive days and repeated every 21 days. Fourteen patients who had measurable metastatic colorectal cancer were entered in the trial. Eight patients had received one prior chemotherapy regimen for metastatic disease. Patients were prospectively monitored by neurologic examinations and neuropsychologic assessment of cognitive functioning. No complete or partial responses were observed. Grade 4 granulocytopenia was the dose-limiting toxicity. Reversible declines in recent memory function were noted in all patients. After each course of CI-980, there were also transient non-significant declines in motor coordination, compared with the preinfusion assessment. At the stated dose and schedule, CI-980 lacks activity in metastatic colorectal carcinoma. The agent's toxicity profile (granulocytopenia and CNS effects) was comparable with previously described effects of this agent.

Adenocarcinoma↗

PubMed1997

Neurotoxicity of CI-980, a novel mitotic inhibitor.

CI-980 is a chemotherapeutic agent currently in Phase II trials that arrests cellular division by binding to tubulin. It is structurally and functionally similar to colchicine, a potent nonreversible neurotoxin, and is able to cross the blood-brain barrier. In Phase I studies, neurotoxicity was noted. The neurotoxicity of CI-980 was prospectively evaluated in two Phase II studies by neurological evaluation, quantitative sensory testing, and neuropsychological assessment of cognitive functioning. The results revealed a significant but reversible decline in recent memory functioning after each course of CI-980, with no effect on overall mental status or neurological function. Sixty-seven percent of patients performed in the impaired range on the memory test after their first infusion, whereas only one exhibited a decline on a brief cognitive screen. The results are consistent with the known effects of colchicine on the brain. Colchicine selectively blocks choline acetyltransferase in the hippocampus and basal forebrain, the area of the brain responsible for memory consolidation. Although the effect of CI-980 was reversible at the dose and schedule used, this study suggests that careful monitoring of cognitive function in patients receiving this agent should be performed if dose or schedule parameters are changed. In addition, this study demonstrates the feasibility of incorporating neuropsychological assessment in clinical trials of new anticancer agents having potential neurotoxic side effects.

Adult↗

PubMed1995

Ten-year follow-up of anorexia nervosa: clinical course and outcome.

The clinical course and outcome of anorexia nervosa are presented in a 10-year follow-up study of 76 severely ill females with anorexia nervosa who met specific diagnostic criteria and had participated in a well-documented hospital treatment study. Information was obtained on 100% of the subjects. A comprehensive assessment was made in 93% of the living subjects in specific categories of weight, eating and weight control behaviours, menstrual function, anorexic attitudes, and psychological, sexual, social and vocational adjustment. Five subjects had died, which gives a crude mortality rate of 6.6%. Standardized mortality rates demonstrated an almost 13-fold increase in mortality in the anorexia nervosa subjects. Only eighteen (23.7%) were fully recovered. Sixty-four per cent developed binge-eating at some time during their illness, 57% at least weekly. Twenty-nine (41%) were still bulimic at follow-up. The high frequency and chronicity of the bulimic symptoms plus the high rate of weight relapse (42% during the first year after hospital treatment) suggest that intensive intervention is needed to help anorexics restore and maintain their weight within a normal range and to decrease abnormal eating and weight control behaviours.

Adolescent↗

PubMed1993

Serum complements. Inappropriate use in patients with suspected rheumatic disease.

BACKGROUND: The diagnostic value of serum complement testing is well established in inherited complement deficiencies and glomerulonephritis. Their utility is less certain in diagnosing rheumatic diseases. We noted that complement tests were frequently ordered for patients who were referred to our rheumatology clinic. We sought to determine the clinical rationale for ordering complement tests in our hospital and the effect of the test results in patients with rheumatic diseases. METHODS: We conducted a retrospective medical chart review of patients who had serum complement tests ordered at our hospital. We determined whether the test was ordered as a diagnostic tool in a patient with a suspected rheumatic disease. In these cases, we attempted to correlate the results of the complement tests with the patient's eventual diagnosis. RESULTS: We obtained the medical charts of 130 patients who had 307 complement assays (C3, C4, or total hemolytic complement) performed between October 1988 and July 1989. The tests were ordered for diagnostic reasons in 68% of the patients; 54% of these were ordered by nonspecialists. The complement tests were ordered on 28 patients with suspected rheumatic diseases. The three patients with hypocomplementemia did not have a connective tissue disease. The 10 patients who eventually were diagnosed as having rheumatic disease all had normal serum complement levels. Additionally, we found that 77% of patients had more than one complement assay ordered. The test results were discordant in only 24% of these cases. CONCLUSION: Complement screening is not a useful diagnostic test in most patients with suspected rheumatic disease. Despite their lack of established diagnostic value, these tests were frequently performed in our hospital. Judicious use of complement testing would provide substantial cost savings without a loss of clinically relevant information. When the complement testing is clinically indicated, clinicians should consider using a single C3 assay initially rather than multiple assays unless a hereditary deficiency is suspected.

Adolescent↗

PubMed1991

Phase II study of the amsacrine analogue CI-921 (NSC 343499) in non-small cell lung cancer.

CI-921 (NSC 343499; 9-[[2-methoxy-4-[(methylsulphonyl)amino]phenyl]amino] -N,5-dimethyl- 4-acridinecarboxamide) is a topoisomerase II poison with high experimental antitumour activity. It was administered by 15 min infusion to 16 evaluable patients with non-small cell lung cancer (NSCLC) (7 with no prior treatment, 9 patients in relapse following surgery/radiotherapy) at a dose (648 mg/m2 divided over 3 days, repeated every 3 weeks) determined by phase I trial. Patients had a median performance status of 1 (WHO), and median age of 61 years. The histology comprised squamous carcinoma (11), adenocarcinoma (1), mixed histology (2), bronchio-alveolar carcinoma (1) and large cell undifferentiated carcinoma (1). Neutropenia grade greater than or equal to 3 was seen in 15 patients, infections with recovery in 3, and grand mal seizures in 1 patient. Grade less than or equal to 2 nausea and vomiting occurred in 66% courses and phlebitis in the infusion arm in 37%. 1 patient with squamous cell carcinoma achieved a partial response lasting 5 months. Further testing in this and other tumour types using multiple daily schedules is warranted.

Adult↗

PubMed1990

Treatment of metastatic malignant melanoma with trimetrexate: a phase II study.

Trimetrexate glucuronate, a nonclassical antifolate, was administered to 14 patients with recurrent and progressive metastatic malignant melanoma. Thirteen patients were evaluable for response and toxicity. Five patients had received prior treatment consisting of immunotherapy (one patient), immunotherapy plus radiotherapy (one patient), radiotherapy (one patient), chemotherapy (one patient), or radiotherapy and chemotherapy (one patient). The starting dose of trimetrexate was 8 mg/m2 given as an intravenous bolus daily for 5 consecutive days of a 21-day cycle. Subsequent cycles of therapy were escalated by 25% based on individual patient tolerance. A median of two courses of trimetrexate was administered (range 1-4). No patient demonstrated a measurable objective response to this treatment regimen. Trimetrexate was well-tolerated; toxicity was mild and consisted primarily of myelosuppression or nausea and vomiting. At the dose level and schedule used in this study, trimetrexate was not effective for the treatment of disseminated malignant melanoma.

Adult↗

PubMed1990

3-Deazaguanine: report of a phase I trial and drug-related cardiac toxicity.

3-Deazaguanine (Dezaguanine), a purine antimetabolite, was evaluated in a phase I trial in 42 patients with advanced solid tumors. Dezaguanine was given as a weekly intravenous infusion for three consecutive weeks of a four-week cycle. The dose ranged from 30 to 2000 mg/m2; no consistent dose-limiting hematologic or gastrointestinal toxicity was observed. Some patients reported brief episodes of burning at the infusion site or transient facial flushing immediately following the administration of dezaguanine. Three patients experienced cardiac toxicity. Two patients, at doses of 1130 and 2000 mg/m2 respectively, developed congestive heart failure. In one case the heart failure was fatal; the second patient recovered within 8 weeks. The third patient had a progressive fall in left ventricular ejection fraction but did not develop clinical evidence of heart failure before his death from progressive cancer two months later. Postmortem cardiac pathology in the two patients who died early following therapy revealed nonspecific interstitial fibrosis without inflammatory cell infiltrates. The myocardium of the third patient, who died 20 months after receiving dezaguanine, was normal. Electron microscopic analysis of myocardium from the first patient did not show myofibrillar loss or mitochondrial disorganization characteristic of anthracycline cardiomyopathy. Due to the probable cardiotoxicity of dezaguanine in this study and the lack of objective antitumor response, further development of this agent has been discontinued.

Adult↗

PubMed1989

Bipolar affective disorder and high achievement: a familial association.

The authors studied 442 probands with nonbipolar major depression, 64 with bipolar II disorder, and 88 with bipolar I disorder. Although the proband groups did not differ in occupational or educational achievement, the first-degree relatives of probands with bipolar disorders had significantly higher mean levels of achievement than did those of probands with nonbipolar disorder. This pattern applied whether or not the relatives themselves had bipolar illness. The authors conclude that the socioeconomic advantage previously associated with affective disorder in general may be limited to the bipolar forms.

Achievement↗

PubMed1988

Phase I trial of the amsacrine analogue 9-[( 2-methoxy-4-[(methylsulfonyl)amino]-phenyl]amino)-N,5-dimethyl-4- acridinecarboxamide (CI-921).

CI-921, an analogue of amsacrine with superior activity against in vivo and in vitro experimental tumor models, has been studied in 16 patients with solid tumors refractory to chemotherapy or for which conventional therapy does not exist. Thirty-nine cycles were given and doses escalated from 39 to 810 mg/m2. This total dose was divided over 3 consecutive days and administered by 15-min infusion each day, repeated three times weekly. Neutropenia (Eastern Cooperative Oncology Group) Grade greater than or equal to 3 occurred at Day 8 (range, 7-13) in 10/13 courses at 648 mg/m2 and in 2/2 courses at 810 mg/m2 with recovery in 10 (range, 4-20) days. At 810 mg/m2 Grade 2 mucositis and phlebitis were noted. Mild nausea and venous irritation occurred in some patients at doses greater than or equal to 288 mg/m2. No objective response was seen. Pharmacokinetics were evaluated following 65 infusions on Days 1 and 3 with plasma concentrations of CI-921 measured by high performance liquid chromatography. Peak plasma concentrations ranged from 3.36 to 85.6 mumol/liter and were significantly correlated with dose. Mean (range) model-independent pharmacokinetic parameters were: distribution half-life, 0.46 h (0.24-1.08); elimination half-life, 2.63 h (1.08-4.98); mean residence time, 2.0 h (1.05-3.35); plasma clearance, 158 ml/h/kg (95-290); and steady-state volume of distribution, 319 ml/kg (219-614) with no significant difference between Day 1 and 3. Toxicity as defined by absolute granulocyte count nadir was significantly correlated with dose, area under concentration-time curve, and peak plasma concentration. The recommended dose for Phase II studies in this schedule is 648 mg/m2 (216 mg/m2 daily for 3 days) repeated every three weeks.

Adult↗

PubMed1988

Trimetrexate and cyclophosphamide for metastatic inoperable nonsmall cell lung cancer.

To determine the maximum tolerated dose (MTD) of trimetrexate glucuronate in combination with cyclophosphamide in patients with metastatic or inoperable nonsmall cell lung cancer (NSCLC), trimetrexate in dosages ranging from 3 to 13.5 mg/m2/day was administered intravenously (IV) to 27 patients for 5 days in combination with cyclophosphamide, 600 mg/m2, on day 1. Patients received between one and six courses of treatment at 3 week intervals, 69 treatment courses in all. Hematological toxicity was mainly mild anemia (81%), leukopenia (67%), and thrombocytopenia (52%). Nonhematological toxicity included nausea and vomiting (67%), mucositis (30%), and urticaria or rash (22%). The incidences of leukopenia and mucositis were dose related. The MTD of trimetrexate in combination with cyclophosphamide was 7.5 mg/m2/day. The dosage chosen for the Phase 2 study, based only on the hematological dose limiting toxicity, was 10.5 mg/m2/day. Of 31 patients with previously untreated metastatic or inoperable NSCLC who have entered in the Phase 2 study, 22 are evaluable for clinical efficacy (World Health Organization criteria, 1979). Treatment was discontinued in four patients because of toxicity. One patient refused further therapy. Four patients are too early to evaluate. Five patients had confirmed partial responses (23%), 12 patients achieved stable disease (54%), and five patients had progressive disease. Results suggest that trimetrexate 10.5 mg/m2/day in combination with cyclophosphamide is active against previously untreated NSCLC. Dose limiting toxicity was mucositis and myelosuppression. An 11 item linear analogue scale assessing quality of life during treatment indicated this combination was well accepted by patients and did not compromise quality of life. The Phase 2 study is continuing.

Adult↗

PubMed1986

Immigration and major affective disorder.

We studied bipolar (ever manic; n = 297) primary unipolar (never secondary; n = 328), and secondary unipolar (n = 241) RDC major affective disorder patients in the NIMH--CRB Collaborative Study of the Psychobiology of Depression--Clinical. We examined rates of immigration, for patients and their parents, in these three diagnostic groups. Primary patients had a twofold increase in the odds in favor of immigration, compared to secondary patients. The difference persisted when proband age was statistically controlled, and could not be accounted for by any difference in sex ratios between groups. Previous findings of an increased rate of immigration in bipolar patients could not be replicated.

Age Factors↗

PubMed1983

Assessment of the quality of life of patients with advanced cancer.

Four methods of assessment of the quality of life were compared in 100 patients with advanced cancer. All showed highly significant correlations with each other. In particular, a single-item linear analogue self-assessment (LASA) which indicated the patients' general feeling of well-being showed a highly significant correlation with multiple item measures of the quality of life (interviewer-administered and self-administered versions of a 5-item quality of life index, and a 21-item LASA). The LASA indicating well-being was compared in a further 30 patients with a similar single-item LASA in which the term 'quality of life' was used. This comparison again showed a highly significant correlation. It is concluded that a single-item LASA asking the direct question "How would you rate your quality of life today?" is a valid and reliable indicator of the quality of life of patients with cancer.

Adult↗