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Biomedical subjects

T Shea

Publications and source records attributed to T Shea.

30 records · Page 2Linked to original sources

Time to recovery, chronicity, and levels of psychopathology in major depression. A 5-year prospective follow-up of 431 subjects.

The course of illness of 431 subjects with major depression participating in the National Institute of Mental Health Collaborative Depression Study was prospectively observed for 5 years. Twelve percent of the subjects still had not recovered by 5 years. There were decreasing rates of recovery over time. For example, 50% of the subjects recovered within the first 6 months, and then the rate of recovery declined markedly. Instantaneous probabilities of recovery reflect that the longer a patient was ill, the lower his or her chances were of recovering. For patients still depressed, the likelihood of recovery within the next month declined from 15% during the first 3 months of follow-up to 1% to 2% per month during years 3, 4, and 5 of this follow-up. The severity of current psychopathology predicted the probability of subsequent recovery. Subjects with moderately severe depressive symptoms, minor depression, or dysthymia had an 18-fold greater likelihood of beginning recovery within the next week than did subjects who were at full criteria for major depressive disorder. Many subjects who did not recover continued in an episode that looked more like dysthymia than major depressive disorder.

Adolescent↗

Differentiation of Axis I and Axis II disorders.

The revised 3rd edition of the Diagnostic and Statistical Manual of Mental Disorders (American Psychiatric Association, 1987) distinguishes between Axis I and Axis II disorders: Axis II includes personality (and developmental) disorders, and all others are on Axis I. This distinction is often useful, but the reification of Axis I and II constructs through diagnostic criteria sets that demarcate categorically distinct entities is at times problematic. We review the issues of differentiating personality from Axis I disorders, specifically illustrated by schizotypal and schizophrenic disorders, borderline and mood disorders, antisocial and substance use disorders, and avoidant personality from social phobia. The options for addressing their differentiation include adding exclusion criteria, shifting the placement of disorders, deleting overlapping criteria, adding differentiating criteria, and converting to a dimensional format.

Diagnosis, Differential↗

High-dose ifosfamide with mesna uroprotection: a phase I study.

Phase II trials of ifosfamide have been performed with standard doses of 5 to 8 g/m2/course. In this phase I study, 29 patients were treated with a 4-day continuous infusion ifosfamide to determine the maximum-tolerated dose and the nonhematologic dose-limiting toxicity. Autologous bone marrow support was to have been used for the subsequent dose level if granulocytes were more than 500/microL for more than 14 days in two of two to five patients at a given dose level. Doses were escalated from 8 to 18 g/m2 ifosfamide. Mesna was given at an equivalent dose by continuous infusion for 5 days. At the 18 g/m2 dose level, dose-limiting renal insufficiency and a median of 11 days (range, 8 to 18 days) of granulocytopenia (less than 500/microL) were observed. Thus, autologous bone marrow reinfusion ws not used. The duration of myelosuppression, the frequency and severity of mucositis, and renal tubular acidosis were all dose-dependent. Mild to moderate CNS toxicity also appeared to be related to dose; however, severe CNS toxicity (transient confusion, hallucinations, and somnolence) was observed sporadically at both low- and high-dose levels. Transient hematuria (greater than 50 red blood cells [RBCs]/high power field) occurred once but did not affect treatment. There were nine responses (two complete) in 27 heavily pretreated assessable patients including seven responses in 20 patients with advanced refractory sarcoma. Ifosfamide with mesna uroprotection can undergo considerable dose escalation over the usual prescribed doses before nonhematologic dose-limiting toxicity is encountered. Ifosfamide has broad cytotoxicity against solid tumors and may prove to be an important addition to high-dose combination chemotherapy regimens.

Blood↗

High-dose combination alkylating agent preparative regimen with autologous bone marrow support: the Dana-Farber Cancer Institute/Beth Israel Hospital experience.

Fifty-nine patients received 61 courses of cyclophosphamide, cisplatin, and carmustine combined. The phase I study consisted of seven dose escalations. Dose levels 5 and 6 also included the attempted addition of melphalan at 40 and 80 mg/m2. The maximum tolerated dose for the three-drug combination was 5620 mg/m2 of cyclophosphamide, 165 mg/m2 of cisplatin, and 600 mg/m2 of carmustine. The dose-limiting toxic effect was fatal veno-occlusive disease of the liver in two of five patients treated at the highest dose level. Veno-occlusive disease of the liver was fatal in two of 40 patients treated at Dose level 4, the maximum tolerated dose. The median time to recovery of polymorphonuclear leukocyte counts to greater than 500/microliters and platelet counts to transfusion independence greater than 20,000/microliters was 19 and 22 days, respectively, after marrow reinfusion. Other toxic effects observed included postdischarge pulmonary toxicity, which appeared to respond to prednisone therapy. Thus, this combination of alkylating agents can be combined at close to the transplant dose of each individual agent. The response rate was high despite considerable prior treatment in most patients. Of 16 evaluable patients with breast cancer, 15 responded (six complete responses). Of six evaluable patients with sarcoma, six responded (one complete response). While patients with melanoma had had no prior treatment, 11 of 17 patients responded (65%). There are currently three patients who are disease-free. Two patients with melanoma were rendered disease-free by excisional biopsy of the only remaining nodule after good partial response, and a patient with metastatic breast cancer remains disease-free after a complete response at 36+ months.

Adult↗

High-dose combination alkylating agent chemotherapy with autologous bone marrow support for metastatic breast cancer.

Seventeen patients with metastatic breast cancer were treated with a high-dose combination chemotherapy regimen and autologous bone marrow support. Thirteen patients had prior combination chemotherapy. Fifteen patients were treated with a phase II regimen of cyclophosphamide (5.625 g/m2), cisplatin (165 mg/m2), and BCNU (600 mg/m2). Bone marrow harvest and reconstitution were uncomplicated. All patients became profoundly myelosuppressed. Fourteen of 16 evaluable patients (88%) responded, including six complete responses (CRs) (38%). The median time to tumor progression was 5 months. The median survival was 8 months. CRs occurred more frequently in patients with no prior chemotherapy for metastatic disease, inflammatory breast cancer; and patients treated within 3 months of first recurrence. The rate of tumor regression was rapid, with a median of 11 days to partial response (PR) and 12 days to CR. Those patients achieving a PR by day 7 had a greater likelihood (P = .03) of attaining a CR than those patients whose PR occurred later. Three deaths (18%) occurred, all in women with inflammatory breast cancer treated with prior chemotherapy. High-dose combined alkylating agent therapy produced high PR and CR rates in metastatic breast cancer patients, most of whom had failed prior chemotherapy. The rate of tumor regression was rapid. Current efforts are directed at developing a regimen using drugs specifically active in breast cancer, with an intent of combining an effective high-dose regimen with additional modalities of therapy in the treatment of breast cancer.

Adenocarcinoma↗