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Biomedical subjects

S Fine

Publications and source records attributed to S Fine.

At least 19 recordsLinked to original sources

Paraphilias: a double-blind crossover comparison of clomipramine versus desipramine.

A relationship has been suggested between clinical presentation of paraphilias and obsessive-compulsive disorder (OCD) with respect to the unwanted repetitive nature and insight into the irrationality of the paraphiliac behavior. This has led to speculation that paraphiliac disorders might belong to an "obsessive compulsive spectrum." To address this issue, and because of the striking selective benefit of serotonin reuptake blocking antidepressants (such as clomipramine) in the treatment of OCD, 15 paraphiliacs entered a double-blind crossover comparison of clomipramine vs. desipramine preceded by a 2-week single-blind placebo period. Four subjects responded to placebo and were dropped from the study. Three others failed to complete the study. Although the study is limited by the small number of patients and the heterogeneity of the paraphilias, the observed benefit from both tricyclics (over the initial placebo) encourages further study. For the 8 subjects completing the protocol, there was no preferential response to the more specific serotonin reuptake inhibitor suggesting a difference in underlying pathophysiology between paraphilia and OCD.

Adult

Complications of whole abdominal and pelvic radiotherapy following chemotherapy for advanced ovarian cancer.

We examined the records of 105 patients with advanced ovarian cancer who had been treated with cisplatin combination chemotherapy followed by abdominopelvic radiotherapy. The purpose was to define the morbidity of this approach, and identify those factors predictive of toxicity. Acute toxicity resulting in delay or failure to complete treatment was most commonly due to myelosuppression. Nine of 105 patients (8.6%) required surgery for bowel obstruction that was not due to recurrent disease, 3 had an episode of bowel obstruction that settled conservatively, and a further 5 underwent surgery for obstruction due to recurrent tumor. The presence of both a dose of abdominopelvic radiotherapy over 2250 cGy, as well as a second-look laparotomy prior to radiotherapy, was associated with an increased risk of serious bowel complications. The increased frequency of late bowel morbidity seen in the combined modality group is likely explained by the presence of these two factors, rather than the exposure to chemotherapeutic agents per se. These observations are supported by the published literature.

Abdomen

Prognostic factors in patients with metastatic colorectal cancer receiving 5-fluorouracil and folinic acid.

We have reported that 5-fluorouracil (5-FU) and folinic acid increased response rate and survival in patients with metastatic colorectal cancer. Now we have analysed prognostic factors for response, toxicity, survival and time to progression. The variables used for survival and response were treatment centre, treatment, age, sex, Eastern Cooperative Oncology Group (ECOG) performance status (PS), site of disease, previous radiotherapy, site of primary, disease-free interval, initial alkaline phosphatase (AP), albumin (A), lactate dehydrogenase (LDH) and aspartate aminotransferase (SGOT). The significant independent variables for survival were PS of 2 or more, initial albumin and SGOT, and treatment received, in order of importance. The relative risk of death when patients received 5-FU/folinic acid was 60% of that of patients receiving 5-FU alone. The variables predictive of response were treatment and PS. The variables used for analysis of toxicity were age, treatment centre, treatment, sex, tumour response, PS, number of courses, SGOT, AP and albumin. Treatment was found to be predictive of toxicity. Thus, baseline albumin and SGOT, and 5-FU/folinic acid treatment are significant determinants of survival, 5-FU/folinic acid and PS of 2 or more are major determinants of response and no clinical parameter could be identified as a predictor of toxicity.

Adult

Superiority of granisetron to dexamethasone plus prochlorperazine in the prevention of chemotherapy-induced emesis.

Trials of selective 5-hydroxytryptamine3 receptor antagonists have shown excellent antiemetic activity for chemotherapy containing cisplatin when compared with high-dose metoclopramide. There is little information about the efficacy of these new agents for chemotherapy other than for high-dose cisplatin. We performed a double-blind, randomized trial comparing a single dose of the 5-hydroxytryptamine3 receptor antagonist granisetron (BRL 43694A) as a single intravenous dose with dexamethasone plus prochlorperazine in 152 patients receiving their first course of moderately emetogenic chemotherapy (mainly doxorubicin- and cyclophosphamide-containing combinations). During the first 24 hours, there was a statistically significant advantage for the granisetron group in terms of the prevention of both nausea and emesis. There was no difference in the frequency of reported adverse events. We conclude that granisetron is more effective than dexamethasone plus prochlorperazine in patients who are receiving moderately emetogenic cytotoxic agents.

Antiemetics

Outcome of patients with unfavorable optimally cytoreduced ovarian cancer treated with chemotherapy and whole abdominal radiation.

There is a subgroup of patients with Stage II or III ovarian cancer whose survival is poor despite optimal cytoreduction of tumor and abdominopelvic radiation. This study examined whether the survival of these patients, who have tumor with unfavorable histopathological characteristics and/or small residual disease, could be improved by giving chemotherapy before radiation. Forty-four out of fifty-one eligible patients, seen between 1981 and 1985, with Stage II or III disease were entered into the study. Following six courses of cisplatin-based chemotherapy, 33 (75%) received abdominopelvic radiotherapy. Survival was compared to that of 48 eligible matched control patients, treated with radiation between 1978 and 1981. The median follow-up is 6.6 years. The median survival was extended from 2.4 to 5.7 years (P = 0.13), and 42.6% of patients receiving combined therapy were free of relapse at 5 years, compared to 21.6% (P = 0.03) in the historical control group, treated with abdominopelvic irradiation alone. Only 2 of 44 patients in the combined group required surgery for bowel obstruction, as did 1 of 48 in the control group. Tolerance and toxicity of the combined approach were acceptable. Although we cannot be certain that the entire benefit we observed was not attributable to the chemotherapy alone, there is evidence that the radiotherapy may have been additive. Chemotherapy followed by abdominopelvic radiotherapy seems a reasonable management policy in these patients.

Antineoplastic Combined Chemotherapy Protocols

Patients' willingness to enter clinical trials: measuring the association with perceived benefit and preference for decision participation.

Patients who agree and those who refuse clinical trial entry may differ in attitudes towards decision control and the benefits associated with the trial arms. These differences, if they exist, have implications for the process of obtaining informed consent and for the generalization of the results of a clinical trial. This paper describes the development and initial application of methods designed to detect such differences. Developmental work involved creating an inventory of instruments designed to determine patients' attitudes towards participating in treatment decision making, permitting random selection of treatment, and undertaking the risks and benefits associated with the various treatments in a trial. Initial application involved modifying these instruments in terms of an actual chemotherapeutic trial for colonic adenocarcinoma, seeking responses to these measures from 60 non-eligible colorectal cancer patients, then determining whether those who would agree to trial entry differed systematically on these measures from those who indicated that they would refuse such a trial. Twenty-five of the respondents reported that, if faced with the actual decision, they would agree to trial entry: 35 would refuse. Refusers demanded more participation in decision making (Chi-square; P = 0.01) and a greater increment in treatment benefit (t-test; P = 0.0001). Twenty-two of the 35 refusers reported aversion to randomization as their primary reason for trial refusal. Since their particular content can be modified, these measures may be applicable to all clinical trials. They could be used to study the reasons patients accept or refuse trial entry and to determine if agreer-refuser attitude differences undermine the generalizability of a trials results.

Clinical Trials as Topic

Group therapy for adolescent depressive disorder: a comparison of social skills and therapeutic support.

Two forms of short-term group therapy for depressed adolescents are compared. Adolescents were assigned to either a social skills training or therapeutic support group. Treatment outcome was based on self-report and semistructured clinical interviews for depression, measures of self-concept, and cognitive distortions. After treatment, adolescents in the therapeutic support groups showed significantly greater reductions in clinical depression and significant increases in self-concept compared with those in the social skills training group. These group differences were no longer evident at 9-month follow-up, as adolescents in the therapeutic support groups maintained their improvement, and adolescents in the social skills training groups caught up.

Adolescent

The value of plain radiography in establishing the diagnosis of gastric lesions.

Appreciation for the diagnostic value of plain (noncontrast) radiography of the gastrointestinal tract appears to have diminished with the advent of more sophisticated imaging techniques. A case in which scrutiny of the gastric air pattern on plain abdominal films suggested the underlying presence of Zollinger-Ellison syndrome emphasizes the potential diagnostic value of plain radiography of the abdomen for gastric disorders.

Female

Social problem-solving in depressed, conduct-disordered, and normal adolescents.

Although past theory and research implicate social problem-solving deficits in both depression and aggressive disorders, research examining carefully diagnosed groups of adolescent depressed and conduct-disordered groups had not previously been conducted. In the current study three groups of adolescents (major depression, conduct-disordered, and normal) were studied using two social problem-solving measures. Both the Means-Ends Problem-Solving task (MEPS) and the Social Situations Analysis measure (SSA) failed to show social problem-solving problem deficits in the depressed group relative to their normal age peers, but did provide corroborative evidence for social problem-solving deficits in the conduct-disordered sample. Relative to the other two groups, the conduct-disordered adolescents were found to generate fewer means to a social end, to anticipate fewer obstacles in the pursuit of solutions to interpersonal situations, and to generate fewer assertive behavioral solutions to difficult social situations. The results are discussed in relation to other work with depressed and aggressive youth, and directions for future research are given.

Adolescent

Four psychoanalytic perspectives: a study of differences in interpretive interventions.

This research study was designed to test two main hypotheses: (1) there are detectable differences in interpretive style among classical, Kleinian, Kohutian, and Kernbergian analysts; and (2) the nature of these differences can be discerned and described. The methodology consists of three phases of data collection. The statistical findings are presented, along with clinical examples, followed by a discussion of their implications.

Adult

A mandatory clinical clerkship in child psychiatry: a description and evaluation.

We describe a mandatory clinical clerkship in which students spend one day a week for six weeks assessing and treating a child and family and participate in seminars on common child psychiatric syndromes and their treatments. In two of three settings, two students were assigned to each child and family and in the third setting, one student was assigned. We assessed their satisfaction by a mailed survey and found each student seemed to be satisfied with his/her own experience. The administrative advantages of having two students for each family are outlined. Also a rank order of preference of seminar content was assessed. Seminars on depression, conduct disorders, attention deficit disorders and family assessment were most appreciated.

Attitude of Health Personnel

Phase I/II trial of granisetron: a novel 5-hydroxytryptamine antagonist for the prevention of chemotherapy-induced nausea and vomiting.

A new class of antiemetic agents, the 5-hydroxytryptamine (5-HT3) antagonists, have been shown to possess potent antiemetic properties in the ferret model. We conducted a phase I/II trial of the 5-HT3 antagonist BRL43694 (granisetron) in 24 chemotherapy-naïve patients who were receiving any combination of doxorubicin and/or cisplatin. The first 12 patients received 40 micrograms/kg and the second 12 received 80 micrograms/kg of granisetron intravenously before beginning chemotherapy. Nausea was assessed by a patient-completed visual analogue scale and episodes of retching recorded by the patient and an independent observer. Fifty-two percent of the 22 evaluable patients had no retching or vomiting and 32% had no nausea during the first 24 hours after chemotherapy. Pharmacokinetic measurements were performed. The disposition of granisetron was best described using a two-compartment model. The area under the plasma concentration curve (AUC) was 277 +/- 226 ng.h/mL and 359 +/- 282 ng.h/mL at 40 and 80 micrograms/kg, respectively. The total body clearance was 0.319 +/- 0.315 L/kg/hr and 0.483 +/- 0.504 L/kg/hr at the 40 and 80 micrograms/kg doses. Wide interpatient variation in model independent parameters was observed. There was no suggestion of dose-dependent efficacy at the two dose levels studied. We conclude that granisetron shows promise as a well-tolerated and effective antiemetic. Randomized trials comparing this drug with standard regimens are currently underway.

Antiemetics

Comparison of antiestrogen and progestogen therapy for initial treatment and consequences of their combination for second-line treatment of recurrent breast cancer.

A randomized clinical trial involving postmenopausal patients with estrogen receptor positive recurrent breast cancer is reported. Of 168 patients entered, 156 were evaluable, of whom 79 received oral tamoxifen citrate 10 mg twice daily and 77 oral megestrol acetate 40 mg four times a day. Partial response (PR) plus complete response (CR) rates (both arms, 34%) and time-to-disease progression were similar in both arms. Side effects and toxicity were minimal with both regimens, although more patients who received tamoxifen complained of hot flushes (33% v 11%) and more patients who received megestrol acetate had a 10% or greater weight gain at 6 months from baseline (51% v 19%). On progression of disease, 73 patients who had achieved a CR, PR, or stable response received the alternative hormonal treatment in addition to the original hormonal therapy. Ten of 40 patients (25%) who began treatment with megestrol acetate had a further CR or PR; none of 33 patients originally receiving tamoxifen had a response when megestrol acetate was added. Similarly, patients who received tamoxifen as an addition to their original megestrol acetate treatment also had a significantly longer time to second progression than did those in the comparative arm. It was concluded that as initial hormonal therapy for relapsed patients, either tamoxifen or megestrol acetate can be used with confidence. However, it is suggested that tamoxifen and megestrol acetate should not be used in combination, except for those few occasions when tamoxifen is added as second-line therapy following a completed megestrol acetate response, and the megestrol acetate is continued for its palliative effects on appetite and weight gain. Possible mechanisms behind these results are discussed.

Breast Neoplasms

Short-term group therapy with depressed adolescent outpatients.

A selected review of the literature about short-term therapy and social skills as they may apply to depressed adolescents is presented. Two forms of group therapy are described. These are social skills and a traditional discussion group format. Some of the difficulties in establishing and evaluating a group therapy program are outlined.

Adolescent

Active drug placebo trial of methylphenidate--a clinical service for children with an attention deficit disorder.

A clinical trial of methylphenidate/placebo on 39 patients is described. Fifteen of 20 parents not keen to give their child methylphenidate did give it, after the trial had shown it was effective. Five out of 19 parents keen to give their child methylphenidate were persuaded not to after it was shown that it was ineffective. Some of the difficulties with the trial are described for example, parents confusing the days the drug is to be given, parents and teachers not filling in the questionnaires and the resistance of certain professionals to giving medication. Patients seem to be more accepting of recommendations to give medication or not, after a medication/placebo trial demonstrated efficacy or lack of efficacy.

Attention Deficit Disorder with Hyperactivity