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Biomedical subjects

S D Williams

Publications and source records attributed to S D Williams.

At least 19 recordsLinked to original sources
PubMed1999

Late relapse of ovarian dysgerminoma: case report and literature review.

Dysgerminoma of the ovary is a rare tumor. Ovarian dysgerminoma is chemosensitive and potentially curable even when in advanced stage. We report a case of intra-abdominal relapse of stage Ia ovarian dysgerminoma 20 years following initial surgery. The patient was treated with surgical resection followed by a full course of platinum-based chemotherapy. However, she had rapidly progressive disease and eventually died. To date, this is the latest reported case of relapse of ovarian dysgerminoma. This rare situation has been reported in patients with germ cell tumors of the testis, the male counterpart of ovarian germ cell tumors. Testis cancer patients with late relapse are rarely, if ever, curable by chemotherapy. A diagnosis of recurrent dysgerminoma should be considered in patients who have the appropriate findings with a history of dysgerminoma, even if remote. Patients with late recurrences of ovarian germ cell tumors may be less responsive to chemotherapy.

Adult↗
PubMed1999

Phase II trial of gemcitabine in refractory germ cell tumors.

PURPOSE: This phase II study was designed to determine the toxicity and activity of single-agent gemcitabine in heavily pretreated patients with germ cell tumors. PATIENTS AND METHODS: From March 1996 through November 1997, 21 patients were enrolled onto a phase II study of gemcitabine 1,200 mg/m2, given on days 1, 8, and 15 every 4 weeks. One patient was unassessable because he never received any gemcitabine. Thirteen of 20 patients had received three prior regimens, and 13 patients were platinum refractory (progression during or within 4 weeks of platinum treatment). There were five extragonadal cases and two patients with late relapse (relapse beyond 2 years). RESULTS: Gemcitabine was well tolerated. Only one patient had grade 3 or 4 nonhematologic toxicity (grade 3 nausea). Six of 20 patients had grade 3 leukopenia. There were no episodes of granulocytopenic fever, and no patient required platelet transfusion. Three (15%) of 20 patients achieved an objective response, including one complete remission. Three additional patients had a minor radiographic or serologic response. CONCLUSION: Gemcitabine had definite activity in this heavily pretreated germ cell tumor patient population.

Adolescent↗
PubMed1998

Evidence that MutY is a monofunctional glycosylase capable of forming a covalent Schiff base intermediate with substrate DNA.

The Escherichia coli adenine glycosylase MutY is involved in the repair of 7,8-dihydro-8-oxo-2'-deoxyguanosine (OG):A and G:A mispairs in DNA. DNA strand cleavage via beta-elimination (beta-lyase) activity coupled with MutY's removal of misincorporated adenine bases was sought using both qualitative and quantitative methods. The qualitative assays demonstrate formation of a Schiff base intermediate which is characteristic of DNA glycosylases catalyzing a concomitant beta-lyase reaction. Borohydride reduction of the Schiff base results in the formation of a covalent DNA-MutY adduct which is easily detected in SDS-PAGE experiments. However, quantitative activity assays which monitor DNA strand scission accompanying base release suggest MutY behaves as a simple monofunctional glycosylase. Treatment with base effects DNA strand cleavage at apurinic/apyrimidinic (AP) sites arising via simple glycosylase activity. The amount of cleaved DNA in MutY reactions treated with base is much greater than that in non-base treated reactions, indicating that AP site generation by MutY is not associated with a concomitant beta-lyase step. As standards, identical assays were performed with a known monofunctional enzyme (uracil DNA glycosylase) and a known bifunctional glycosylase/lyase (FPG), the results of which were used in comparison with those of the MutY experiments. The apparent inconsistency between the data obtained for MutY by the qualitative and quantitative methods underscores the current debate surrounding the catalytic activity of this enzyme, and a detailed explanation of this controversy is proposed. The work presented here lays ground for the identification of specific active site residues responsible for the chemical mechanism of MutY enzyme catalysis.

Amino Acid Sequence↗
PubMed1998

A phase II trial of paclitaxel in refractory germ cell tumors.

BACKGROUND: A significant percentage of patients with refractory germ cell tumors will not respond to standard salvage regimens. Thus there is a need for new active agents. Paclitaxel has demonstrated activity against a variety of solid tumors in both laboratory and clinical studies. METHODS: Eighteen patients with refractory germ cell tumors who failed initial cisplatin-based chemotherapy and a maximum of 2 salvage regimens were enrolled into a Phase II trial of paclitaxel at a dose of 170 mg/m2 by intravenous infusion over 24 hours every 21 days without growth factor support. The median age of the patients was 32.5 years (range, 18-49 years). The testis was the primary site of tumor for 13 patients (72%) and the tumor was extragonadal in 5 patients (28%). Six patients (33%) were late recurrences. Twelve patients (67%) had > or = 2 metastatic sites. The median number of previous chemotherapy cycles was six (range, four to nine). Three patients (17%) previously had undergone autologous bone marrow transplantation. RESULTS: Two patients (11%) responded to paclitaxel. Major toxicities were Grade 3-4 neutropenia (55% of patients) and Grade 3-4 neurotoxicity (2 patients). Neutropenic fever occurred in 3 patients (17%). CONCLUSIONS: Paclitaxel demonstrated minimal activity in heavily pretreated patients with multiple, poor risk clinical features. These results in part may be due to the unfavorable characteristics of the patients in the current study, specifically the high percentage of patients with late recurrences and extragonadal primary tumors, both of which are known to respond poorly to salvage therapy. Other trials with different patient populations and doses of paclitaxel reported response rates ranging from 13.3%-26%. The role of paclitaxel in the treatment of patients with refractory germ cell tumors remains to be defined in future studies.

Adolescent↗
PubMed1998

Ovarian germ cell tumors: an update.

Ovarian germ cell tumors, while very rare, are important beyond their incidence because they occur in young people and they are highly responsive to appropriate treatment. Since 1991, when this topic was last discussed in Seminars in Oncology, there have been a few important publications specifically devoted to ovarian germ cell tumors. In addition, a number of important studies have added to the knowledge base of chemotherapy in testis cancer. This article reviews and updates progress made in this field.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1997

Activation of myocardial cAMP-dependent protein kinase by lysoplasmenylcholine.

Plasmalogen-specific, calcium-independent phospholipase A2 (iPLA2) is activated during myocardial ischemia. Accordingly, we have assessed the activation of myocardial protein kinases by the iPLA2 product, lysoplasmenylcholine. Lysoplasmenylcholine-activated protein kinase activity from heart cytosol fractionated on a DE-52 column was identified as cAMP-dependent protein kinase (PKA) based on the following: (1) protein kinase activity stimulated by cAMP and lysoplasmenylcholine co-eluted on sequential chromatographic steps; (2) lysoplasmenylcholine-activated protein kinase activity was inhibited by the PKA inhibitor, PKI; and (3) the unprimed PKA form generated from the primed form of PKA was activated by cAMP and lysoplasmenylcholine. These results demonstrate a novel mechanism for PKA activation by lysoplasmenylcholine.

Animals↗
PubMed1996

Intraperitoneal cisplatin plus intravenous cyclophosphamide versus intravenous cisplatin plus intravenous cyclophosphamide for stage III ovarian cancer.

BACKGROUND: Intravenous platinum-based chemotherapy is the standard primary therapy for advanced ovarian cancer. We conducted a phase 3 trial to compare the effects of intraperitoneal and intravenous cisplatin on the survival of women with previously untreated, stage III, epithelial ovarian cancer. METHODS: The patients underwent an initial exploratory laparotomy and resection of all tumor masses larger than 2 cm. Within four weeks after surgery, six courses of intravenous cyclophosphamide (600 mg per square meter of body-surface area per course) plus either intraperitoneal cisplatin (100 mg per square meter) or intravenous cisplatin (100 mg per square meter) were administered at three-week intervals. RESULTS: Of 654 randomized patients, 546 were eligible for the study. The estimated median survival was significantly longer in the group receiving intraperitoneal cisplatin (49 months; 95 percent confidence interval, 42 to 56) than in the group receiving intravenous cisplatin (41 months; 95 percent confidence interval, 34 to 47). The risk of death was lower in the intraperitoneal group than in the intravenous group (hazard ratio, 0.76; 95 percent confidence interval, 0.61 to 0.96; P = 0.02). Moderate-to-severe tinnitus, clinical hearing loss, and neuromuscular toxic effects were significantly more frequent in the intravenous group. CONCLUSIONS: As compared with intravenous cisplatin, intraperitoneal cisplatin significantly improves survival and has significantly fewer toxic effects in patients with stage III ovarian cancer and residual tumor masses of 2 cm or less.

Adult↗
PubMed1995

Practicing with the urban underserved. A qualitative analysis of motivations, incentives, and disincentives.

OBJECTIVE: To investigate the personal characteristics and professional experiences of medical providers working with medically underserved urban populations. DESIGN: Focus groups of primary care providers. SETTING: Public and private clinics in Salt Lake City, Utah, in which the providers had ongoing relationships with medically underserved patients. PARTICIPANTS: Twenty-four providers (11 men and 13 women), including 12 physicians (three family physicians, seven pediatricians, and two psychiatrists), one dentist, three physician assistants, and eight nurse practitioners participated in three focus groups. MAIN OUTCOME MEASURE: Interpretative analysis of verbatim quotations regarding personal beliefs, feelings, and practice experiences. RESULTS: Participants revealed a strong sense of service to humanity and pride in making a difference. They thrive on the challenge of creatively dealing with their patients' complex human needs with limited health care resources. Factors critical to survival in an urban underserved setting include a hardy personality style, flexible but controllable work schedule, and multidisciplinary practice team. The camaraderie and synergy of teams generate personal support and opportunities for continuing professional development. CONCLUSIONS: Increasing the numbers of health care professionals wanting to work with the medically underserved may be facilitated through refining admissions criteria to schools for health care professionals to include values and personality characteristics, emphasizing within curricula the important skills and practice styles necessary to work with underserved patients, and ensuring that underserved practice environments provide support through multidisciplinary teams and structured work hours. These potentially effective approaches could increase success in recruiting and retaining health care professionals to work with medically underserved patients.

Adult↗
PubMed1994

Early salvage therapy for germ cell cancer using high dose chemotherapy with autologous bone marrow support.

BACKGROUND: Patients with relapsed germ cell cancer (GCT) have a poor prognosis when treated solely with conventional chemotherapy; high dose chemotherapy with autologous bone marrow rescue (ABMR) has shown curative potential in patients with relapsed and refractory GCT. This protocol was designed to incorporate high dose therapy with initial salvage therapy. METHODS: Twenty-three patients in the first relapse of GCT received two cycles of conventional dose cisplatin-based therapy (either vinblastine, ifosfamide and cisplatin [VeIP] or cisplatin, vinblastine, and bleomycin) followed by carboplatin (1500-2100 mg/m2) and etoposide (1200-2250 mg/m2) given in divided doses with ABMR. RESULTS: Eighteen of 23 patients completed protocol therapy including high dose therapy. Five of 23 did not undergo high dose therapy due to: insurance refusal (1); patient refusal (1); active infection (1); central nervous system metastasis (1); death on induction therapy (1). Response to two courses of conventional dose induction therapy (N = 23) was complete response (CR), 8; partial response (PR), 12; stable disease (SD), 2; and toxic death, 1. Two of five individuals who did not continue with high dose therapy are alive and progression free after conventional salvage therapy and surgery with at least 24 months of follow-up. Outcome after high dose therapy (N = 18) was CR, 9, PR, 6, SD, 1, and PD, 2. Two patients who were in PR after receiving two cycles of conventional dose therapy were converted to CR using high dose therapy. There was only one treatment-related death in this cohort, a septic death during VeIP induction therapy. There were no transplant related deaths. Of those patients completing high dose therapy, 7 of 18 (39%) survived, progression free with a median follow-up of 26 months, 2 of 18 are alive with active disease, and 9 of 18 died of recurrent disease. CONCLUSIONS: Conventional dose induction therapy followed by consolidation with high dose therapy and ABMR is well tolerated and provides prolonged disease-free survival in some patients with chemosensitive relapsed germ cell cancer.

Adolescent↗
PubMed1994

Second-look laparotomy in ovarian germ cell tumors: the gynecologic oncology group experience.

The Gynecologic Oncology Group (GOG) experience with second-look laparotomy in malignant ovarian germ cell tumors is reviewed. All patients in this study were enrolled prospectively on one of three protocols that employed relatively brief cisplatin-based chemotherapy after initial surgical staging and cyto-reduction. Forty-five surgical procedures were done in patients who received three courses of cisplatin-based adjuvant therapy after complete tumor resection. Findings were no tumor or mature teratoma in 43; 2 patients had immature teratomas. One of the latter patients received further chemotherapy and one did not. Both of these patients and 44 of the total are disease free. Seventy-two patients were treated with similar chemotherapy for advanced incompletely resected tumor. Forty-eight of these patients did not have teratoma elements in their primary tumor. At surgery, 45 patients had no tumor and 3 had persistent endodermal sinus tumor or embryonal carcinoma. All three of the latter patients are dead despite further treatment. Twenty-four patients had teratoma elements in their primary tumor. Of these patients, 16 had mature teratoma at second-look, which in 7 was bulky or progressive. Fourteen of the total 16 and 6 of the 7 with bulky residual tumor remain disease free after surgical resection. Second-look laparotomy is not necessary in patients completely resected initially or in those patients with advanced tumor that does not contain teratoma. However, enough patients with incompletely resected tumor which initially contains elements of teratoma benefit from the procedure to warrant its general use.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1994

Persistent cancer in postchemotherapy retroperitoneal lymph-node dissection: outcome analysis.

Surgery following chemotherapy for treatment of metastatic testis cancer is reserved for partial remissions with localized tumors considered resectable. After primary chemotherapy, about 90% will have teratoma or necrosis and only 10% will have cancer. The concept of two cycles of post operative chemotherapy in this small group with cancer is supported by a 70% long term cure rate. A more difficult group of patients are those who have had not only primary but also salvage chemotherapy for refractory tumor. About 55% of these patients undergoing post (salvage) chemotherapy RPLND surgery have persistent cancer in the resected specimen. There is no data to support the routine use of repeat salvage chemotherapy post operatively. Of 91 patients presenting for surgery post salvage chemotherapy, 53 were considered completely resected and 36 incompletely resected. Of the 53 realistic candidates for cure with complete resections, 25 were given post operative repeat salvage chemotherapy and 28 received none. 9 (36%) receiving more chemotherapy remained NED and 12 (43%) receiving none remained NED. 12 in each group died of disease. Therefore, there is no data to support routine repeat salvage chemotherapy in patients considered completely resected who had already received salvage chemotherapy pre-operatively. Rather the outcome in this cohort depends more on the completeness of its resectability.

Antineoplastic Agents↗
PubMed1994

Clinical and radiological features in three cases of pulmonary involvement from recurrent respiratory papillomatosis.

Clinical case reports of 3 children with recurrent respiratory papillomatosis who developed lung dissemination of the disease are presented. The radiological features of the primary pulmonary disease included papillomata in the distal airway and multiple, nodular lung lesions, both solid and cavitated. Changes secondary to pulmonary papillomatosis included atelectasis, infection and bronchiectasis. Respiratory papillomatosis involving pulmonary parenchyma is associated with a poor prognostic outcome. Early detection of such involvement and aggressive treatment of secondary infection are required to limit parenchymal damage.

Child, Preschool↗
PubMed1994

Incidence of neutropenic fever in patients treated with standard-dose combination chemotherapy for small-cell lung cancer and the cost impact of treatment with granulocyte colony-stimulating factor.

PURPOSE: We sought to determine the incidence of neutropenic fever associated with the use of standard-dose combination chemotherapy for small-cell lung cancer (SCLC) and to use these data as a template to analyze the costs and benefits of the routine use of granulocyte colony-stimulating factor (G-CSF). PATIENTS AND METHODS: We retrospectively reviewed records of 137 consecutive, unselected patients with SCLC treated with combination chemotherapy from January 1987 to March 1992. Admission criteria for neutropenic fever were temperature > or = 38.5 degrees C and an absolute neutrophil count < or = 500/microL. Neutropenic fevers were managed with a 25% dose reduction of the myelosuppressive drugs in subsequent cycles. Charge estimates for hospitalization ($1,244 per day) and G-CSF use ($2,027 per course) were estimated by reviewing charges to patients at Indiana University hospitalized for neutropenic fever or treated with outpatient G-CSF. We imposed assumptions from the Neupogen (filgrastim; Amgen Inc, Thousand Oaks, CA) licensing trial regarding the effectiveness of G-CSF and the Indiana University charge estimates on three models of G-CSF use: (1) preemptive--with all courses of chemotherapy, (2) reactive--with all cycles of chemotherapy following a neutropenic fever, and (3) dose reduction only (no G-CSF)--to derive charge estimates for G-CSF use. RESULTS: Records of 137 patients with SCLC were identified and reviewed. The incidence of neutropenic fever was 12% in the first cycle of chemotherapy, and 18% overall, compared with the placebo- and G-CSF-treated arms of the Neupogen licensing trial, in which the incidence of neutropenic fever was 77% and 40%, respectively. Other therapeutic outcomes, such as neutropenic septic deaths, response rates, and survival, were comparable. We derived the following charge estimates for the three models of G-CSF: (1) preemptive--total charges = $1,287,481; (2) reactive--total charges = $276,154; and (3) dose reduction only--total charges = $192,820. CONCLUSION: The incidence of neutropenic fever with standard-dose chemotherapy for SCLC was 18%. Routine use of G-CSF in SCLC patients treated with standard-dose chemotherapy appears to be expensive and is not associated with an obvious therapeutic benefit or cost savings. We suggest that careful analysis of the incidence of infectious complications, rather than granulocyte nadir and duration, be performed, and that clinical guidelines for the use of these effective, but expensive, products be developed.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1994

Understanding physicians' decisions to practice in rural areas as a basis for developing recruitment and retention strategies.

The shortage of providers in rural areas is threatening the quality and availability of health care in many communities. The causes of the provider shortage are many and varied-from economic to social to personal. Government programs have addressed the issue of provider supply by offering scholarships and loan repayment programs for medical students who then must fulfil service obligations in underserved settings, among which are rural areas. Experience has shown that once providers complete their obligations under these grant programs, retention of providers in rural areas becomes an even more critical issue. Using focus group research, this study explores the practice setting choices of a group of physicians currently practicing in rural areas. The discussion reveals that personal values are one of the primary motivators for choosing to practice in rural settings while lack of availability of career opportunities for spouses and educational opportunities for children are major obstacles. The health care system poses barriers to success for providers in rural settings. The key rewards from rural practice are the ability to become integrated into the local community and the provider/patient relationships that develop in such settings. These findings are used as the basis for proposing recruitment and retention strategies for providers to improve access to medical care by patients in rural areas.

Career Choice↗
PubMed1994

Salvage chemotherapy for recurrent germ cell cancer.

Clinical trials of chemotherapy in germ cell cancer have explored the full range of the relationship of chemotherapy dose and intensity. In good-risk patients, successful efforts have diminished the duration of treatment or number of drugs required to reliably cure the illness. In patients with a poor prognosis, efforts to intensify therapy have been undertaken. In the setting of disease recurrence after primary chemotherapy, the outlook is considerably less hopeful, as only 20% to 30% of patients survive recurrent illness. Current standard treatment in this setting is combination therapy with ifosfamide and cisplatin, given with either etoposide or vinblastine. High-dose chemotherapy with bone marrow or peripheral blood stem cell support can cure a small portion of selected patients with multiple recurrences of germ cell cancer. The impact of earlier treatment with high-dose chemotherapy (either as initial salvage therapy or primary treatment) is less certain. Clinical trials in these settings have not yet demonstrated a definite advantage over less toxic conventional-dose therapies.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1994

Current management of ovarian germ cell tumors.

Ovarian germ cell tumors, although rare, are important because they occur in young individuals and frequently are fulminant if initial treatment is inadequate. These tumors can be broadly divided into dysgerminomas and nondysgerminomatous tumors, although in reality many tumors are of mixed pathology. Surgical staging is important, and when performed by inexperienced surgeons is often inadequate. However, except for localized purely dysgerminomatous tumors, prompt institution of chemotherapy is more appropriate than repeat exploration to establish more precise staging. Tumors other than dysgerminoma are most often treated with etoposide-containing regimens, and recent studies suggest that patients with dysgerminomas also should be treated primarily with chemotherapy.

Antineoplastic Agents↗
PubMed1993

Thymic carcinoma. A distinct clinical entity responsive to chemotherapy.

BACKGROUND: Thymic carcinomas are rare tumors of the anterior mediastinum. These tumors are distinct thymic neoplasms that differ from their more common counterpart, thymoma. As opposed to thymomas, thymic carcinomas are histologically malignant neoplasms with a clinical course that tends to be much more aggressive than that of patients with thymoma. METHODS: Between 1984 and 1990, five patients with thymic carcinoma treated with cisplatin-based combination chemotherapy were seen at Indiana University Hospital. These patients' diagnoses, courses, and treatments were reviewed. RESULTS: Three patients responded (two completely) to cisplatin-based chemotherapy. CONCLUSIONS: This form of chemotherapy merits additional study in such patients, and our experience indicates that at least some will have clinically meaningful responses. The optimum regimen is unclear, but would contain cisplatin and probably should be similar to that used in germ cell tumors.

Adult↗