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Biomedical subjects

J J Perry

Publications and source records attributed to J J Perry.

At least 19 recordsLinked to original sources

Quality of life and psychological distress of bone marrow transplant recipients: the 'time trajectory' to recovery over the first year.

The purpose of this study was to measure the trajectory of psychosocial recovery over the first year after bone marrow transplantation (BMT). BMT patients were assessed at baseline (n = 86), hospital discharge (n = 74), 100 days (n = 64) and at 1 year (n = 45). Participants completed the Functional Assessment of Cancer Therapy-Bone Marrow Transplant Scale (FACT-BMT), the Profile of Mood States Total Mood Disturbance Scale (POMS-TMDS), the Medical Outcomes Social Support Survey (MOS-SSS), the Center for Epidemiologic Studies-Depression (CES-D) scale screener, a performance Status Rating Scale (PSR), and an interview questionnaire. The recovery trajectory in this patient population showed three distinct trends. The trajectory for distress was linear and improved over time with approximately 20% of patients continuing to have psychological distress at 1 year. Secondly, the trend for overall quality of life was parabolic, worsening at discharge, then improving at 100 days and at 1 year. However, there were individual areas of deficit at follow-up, eg fatigue, even while overall quality of life mean scores improved. Thirdly, the trend for patient concerns over time was linear and worsening. These recovery trajectories suggest psychosocial interventions before and after BMT that may prepare patients for increasing and worsening concerns even as physical well-being improves.

Adult

High-dose cyclophosphamide, etoposide and carboplatin with autologous bone marrow support for metastatic breast cancer: long-term results.

We report long-term results of high-dose cyclophosphamide, etoposide and carboplatin with ABMT in 20 patients with metastatic breast cancer. Median age of the group was 41 years, ECOG performance status = 0 in 18 patients and 1 in two patients. Twelve patients had received adjuvant chemotherapy. Predominant sites of metastases were lung (eight), chest wall (four), liver (four), bone (three) and lymph nodes (three). Response to pretransplant chemotherapy was complete (CR) in four patients, partial (PR) in 10 patients and stable (SD) in five patients. After high-dose chemotherapy eight patients were in CR, six PR, four SD and one progressive disease. Two patients died of regimen-related toxicities (candidal sepsis and alveolar hemorrhage). With a median follow-up period of 55 months (minimum 48 months), 12 patients have died of recurrent breast cancer, one died of toxicity of salvage chemotherapy, two are alive with disease, two are alive and free of progressive disease. One patient with relapsed disease was lost to follow-up. Median event-free survival is 6 months and median overall survival is 17 months. All three of the long-term disease-free survivors had predominantly nodal disease. Two of these three patients presented with metastatic disease and received high-dose chemotherapy with ABMT as part of initial therapy for breast cancer; two of three attained CR to standard-dose cytoreductive therapy; none received doxorubicin-containing adjuvant chemotherapy.

Adult

Biodegradation of groundwater pollutants by a combined culture of Mycobacterium vaccae and a Rhodococcus sp.

The catabolism of selected groundwater pollutants by a combined culture of Mycobacterium vaccae and a Rhodococcus sp. (strain R-22) was investigated. The M. vaccae-R-22 combined culture was five times more effective in mineralizing benzene than either organism alone. Mycobacterium vaccae oxidized benzene to phenol, and R-22 catabolized the phenol to cellular components and CO2. Benzene did not support growth of M. vaccae, R-22, or the combined culture. Optimization of ratios of the two species indicated that the maximum mineralization of benzene occurred at an initial ratio of 75% M. vaccae to 25% R-22. Cell fractionation of the combined culture after mineralization of [U-14C]benzene indicated that 10% of the benzene carbon was incorporated into cell material, and of this 45% was present in protein and 20% in nucleic acids. This suggested that minimally one species could utilize the products of benzene as a nutrient source. The M. vaccae-R-22 combined culture catabolized ethylbenzene and chlorobenzene without the accumulation of phenolic intermediates, which are inhibitory to M. vaccae's ability to degrade the parent compounds. This study demonstrates that defined mixed cultures may be useful in studying the effects of environmental pollutant degradation on microbial ecosystems and mineralization of these pollutants by the ecosystem.

Benzene

Changes in mutagenicity during crude oil degradation by fungi.

Two fungal strains, Cunninghamella elegans and Penicillium zonatum, that grow with crude oil as a sole carbon source were exposed to three crude oils that exhibit a range of mutagenic activity. At regular time intervals following fungal incubation with the various crude oils, extracts were tested for the presence of mutagenic activity using the spiral Salmonella assay. When the most mutagenic of the oils, Pennsylvania crude oil, was degraded by C. elegans or by P. zonatum, its mutagenicity was significantly reduced; corresponding uninoculated (weathered) controls of Pennsylvania crude remained mutagenic. West Texas Sour crude oil, a moderately mutagenic oil, exhibited little change in mutagenicity when incubated with either C. elegans or P. zonatum. Swanson River Field crude oil from Cook Inlet, Alaska is a slightly mutagenic oil that became more mutagenic when incubated with C. elegans; weathered controls of this oil showed little change in mutagenicity. Mycelial mat weights measured during growth on crude oils increased corresponding to the biodegradation of about 25% of the crude oil.

Biodegradation, Environmental

Octreotide acetate in refractory bone marrow transplant-associated diarrhea.

OBJECTIVE: To evaluate the effectiveness of octreotide acetate in the treatment of refractory bone marrow transplant-associated diarrhea. DESIGN: Case series encompassing 30 months. SETTING: A 12-bed bone marrow transplant unit at a tertiary care medical center. PARTICIPANTS: Twenty-four patients with bone marrow transplant-associated diarrhea who did not improve with supportive or attapulgite therapy. INTERVENTIONS: Patients received subcutaneous octreotide acetate at doses ranging from 50 to 250 micrograms 2 to 3 times daily. Concurrent treatment with antimotility or antisecretory agents did not occur. MAIN OUTCOME MEASURES: The number of bowel movements and stool volumes were recorded daily. Complete response to octreotide therapy was defined as a reduction of both stool output and stool frequency by more than 50% within 72 hours. Partial response was defined as a reduction of either stool output or stool frequency by more than 50% within 72 hours. Treatment failure occurred if neither of the two parameters decreased by 50% within the designated time period. RESULTS: Twenty-eight treatment challenges were initiated in the 24 patients evaluated. Diarrhea completely or partially subsided in 23 of 28 challenges (82.1%) within 72 hours. Stool output decreased from 1143 +/- 595 at baseline to 252 +/- 356 mL/d within 72 hours (p < 0.005). Stool frequency decreased from a baseline of 7.5 +/- 3.4 to 2.7 +/- 2.2 stools per day within 72 hours (p < 0.005). Adverse effects associated with octreotide were pain or burning at the injection site (24.1%), abdominal pain (13.8%), and increased stool output (6.9%). CONCLUSIONS: These data suggest octreotide acetate significantly reduces stool output and frequency in patients with refractory bone marrow transplant-associated diarrhea. Additional research is necessary before this agent can be recommended for routine use in this patient population.

Adolescent

Urinary elimination of cyclophosphamide alkylating metabolites and free thiols following two administration schedules of high-dose cyclophosphamide and mesna.

Twenty patients with a variety of neoplastic diseases were treated with preparative regimens containing high-dose cyclophosphamide (CY) administered as a 2-h infusion (60 mg/kg) for 2 days or by continuous infusion (1500 mg/m2/day) for 4 days. In patients receiving CY by 2-h infusion, the uroprotectant 2-mercaptoethane sulfonate (MESNA) was administered as an intermittent, bolus intravenous infusion (20% of CY dose) every 6 h. In patients receiving continuous infusion CY, MESNA was administrated concomitantly at an equivalent dose to CY by continuous infusion. During the first 24 h of CY administration, urine was collected at 2-h intervals and analyzed for free thiols and CY-alkylating metabolites. In patients receiving CY by short infusion and MESNA by intermittent bolus infusion, urinary concentrations of alkylating metabolites peaked at 4-8 h. During each dose of MESNA, urinary free thiols peaked at 2 h following administration but fell to pre-treatment levels at subsequent intervals. In patients receiving CY by continuous infusion, CY alkylating metabolites increased gradually over the 24-h study period while free thiols remained at a constant level during this period. With bolus administration of CY and intermittent bolus administration of MESNA every 6 h, there are periods where urinary CY-alkylating metabolites are elevated and free thiol concentrations are diminished. During continuous infusion of CY and MESNA, urinary CY alkylating metabolites reached peak concentrations at 18-22 h while the exposure of the bladder to free thiols remained constant. Recommendations are provided to increase the exposure of free thiols in the bladder when MESNA is administered by bolus or continuous infusion.

Adult

Quality of life in breast cancer patients before and after autologous bone marrow transplantation.

The purpose of this study was to compare pre- and posttreatment quality of life (QOL) in breast cancer patients undergoing high-dose chemotherapy with autologous bone marrow transplantation (ABMT). Fifty-two female breast cancer patients were assessed on overall QOL, mood status, and social support before transplantation. After ABMT, 24 patients were assessed on the same measures as well as a measure of depressive symptoms and specific concerns identified in a structured interview. Mean pre- and post-transplant scores on the quality of life measure, mood scores and social support were not significantly different. Eight patients (33%) reported depressive symptoms post-transplantation. In the structured interview, a percentage of patients reported concerns in the following areas: job or work situation (25%); finances (42%); general physical health (50%); general frame of mind (25%); appearance (33%); health or life insurance (37%); personal or intimate physical relations (33%); planning for the future (38%). QOL and mood following ABMT improved slightly and compares favorably with breast cancer patients treated with conventional treatment. However, approximately 30% of patients had problems with sexuality, fatigue and depressive symptoms and may need follow-up psychosocial care in these areas. ABMT may pose no more threat to quality of life than conventional chemotherapy.

Adult

High dose toremifene for estrogen and progesterone receptor negative metastatic breast cancer: a phase II trial of the Cancer and Leukemia Group B (CALGB).

In pre-clinical and limited clinical studies, high doses ( > or = 200 mg/day) of the triphenylethylene derivative toremifene showed activity in estrogen receptor (ER) negative and ER-unknown metastatic breast cancer after progression on tamoxifen, and a mechanism of action independent of hormone receptor binding was speculated. The CALGB conducted a Phase II trial (CALGB 8945) to test the efficacy of high dose toremifene in a population of patients who had hormone receptor-negative, metastatic breast cancer with limited prior chemotherapy exposure, good performance status, and measurable disease. Twenty eligible patients received toremifene at a dose of 400 mg/day orally for 8 weeks. Toxicity was minimal. Nausea was reported by 20% of the patients, lightheadedness by 20%, weight loss by 20%, and hot flashes by 15%. There was no grade 3-4 toxicity. No objective responses were observed, and 5 of 6 patients with stable disease at 8 weeks developed progressive disease at 11 to 33 weeks. High dose toremifene (400 mg/day) is well-tolerated but imparts no detectable activity in hormone receptor-negative, metastatic breast cancer.

Administration, Oral

Catabolism of 2,4,6-trinitrotoluene by Mycobacterium vaccae.

Mycobacterium vaccae strain JOB-5 cometabolized 2,4,6-trinitrotoluene (TNT) in the presence of propane as a carbon and energy source. Two novel oxidized metabolites, as well as several known reduced products, were generated during catabolism of TNT by M. vaccae. During the cometabolic process, there was transient production of a brown chromophore. This compound was identified as 4-amino-2,6-dinitrobenzoic acid. When M. vaccae was incubated with [14C]TNT and propane, 50% of the added radiolabel was incorporated into the cellular lipid fraction. These results suggest that ring cleavage occurred prior to the incorporation of radiolabelled carbon into phosphatidyl-L-serine, phosphatidylethanolamine, cardiolipin, and other polar lipids.

Biotransformation

Biodegradation of trichloroethylene by Mycobacterium vaccae.

Nonproliferating cells of Mycobacterium vaccae that were grown on propane could mineralize limited amounts of trichloroethylene. Intermediates in the biodegradation of trichloroethylene were 2,2,2-trichloroethanol and 2,2,2-trichloroacetaldehyde. Trichloroethanol was completely degraded when added to a nonproliferating cell suspension of Mycobacterium vaccae. Addition of toluene to the reaction mixtures effected a 50% increase in the mineralization of [14C]trichloroethylene.

Biodegradation, Environmental

Lymphomatoid papulosis associated with Ki-1-positive anaplastic large cell lymphoma. A report of two cases and a review of the literature.

BACKGROUND: Lymphomatoid papulosis (LyP) is an uncommon disorder characterized by recurrent papulonodular cutaneous lesions that last from 4 to 5 weeks and often heal with hypopigmented or hyperpigmented scarring. Prognosis is varied, 10%-20% of patients have associated lymphomas: mycosis fungoides, T-cell immunoblastic lymphoma, or Hodgkin's disease, which can precede, occur simultaneously with, or follow the diagnosis of LyP. Anaplastic large cell lymphoma (ALCL) is histologically and phenotypically similar to LyP and also appears as part of this disease spectrum. Recent reports analyzing immunophenotype and T-cell receptor gene rearrangements in patients with both LyP and lymphoma suggest that they are derived from an identical T-cell clone, in the rare cases studied. METHODS: The case histories of two patients with LyP in whom ALCL involving the skin and lymph nodes subsequently developed are presented. RESULTS: Intensive treatment with combination chemotherapy resulted in complete remission of ALCL in both patients, followed by the recurrence of LyP. A spontaneous remission of LyP occurred in the initial patient described, whereas the second patient suffered recurrences of both LyP and ALCL despite therapy. CONCLUSIONS: The case histories presented illustrate the immunophenotypic and morphologic similarities of ALCL and LyP, and the difficulties in distinguishing between them. Both entities can occur in a single patient, as shown by this report, supporting a close relationship between these processes. However, different clinical behavior and response to therapy are apparent, which connote a fundamental difference in the biologies of these neoplastic disorders. A review of the literature concerning the association between these entities is provided.

Aged

Marrow transplantation from hepatitis C virus seropositive donors: transmission rate and clinical course.

Bone marrow transplant recipients are at risk for acquiring hepatitis C infection from the donated marrow. Twelve patients who were hepatitis C virus (HCV) RNA-negative pretransplant received marrow from anti-HCV seropositive donors. HCV RNA was present in the sera of seven of these donors. After transplant, serial serum specimens were obtained from all marrow recipients for determination of HCV RNA and aminotransferase levels. All seven recipients of marrow from HCV RNA-positive donors were HCV RNA-positive after marrow infusion; none cleared virus from the serum. All five recipients of marrow from anti-HCV seropositive, HCV RNA-negative donors remained free of HCV RNA in serum up to day 100. Abnormal serum aminotransferases were common in both HCV RNA-negative and HCV RNA-positive marrow recipients. One HCV-infected recipient developed marked elevation in aminotransferases after immunosuppressive drugs were stopped. We conclude that the presence of HCV RNA in the serum of marrow donors is an accurate predictor of HCV infection in marrow recipients. The acute infection was subclinical in all patients. The long-term risk of chronic hepatitis C virus infection in these patients remains to be determined.

Adult

Dehalogenation by Mycobacterium vaccae JOB-5: role of the propane monooxygenase.

Mycobacterium vaccae JOB-5 has an inducible propane monooxygenase that has been implicated in the catabolism of most major groundwater pollutants including trichloroethylene. Propane-grown cells are also induced for the dehalogenation of 1-chlorobutane and other chloroalkanes. 1-Chlorobutane is oxidized to 2-butanol, indicating that subterminal oxidation of 1-chlorobutane resulted in a concomitant release of the chloride. Nonproliferating suspensions of M. vaccae induced for the propane monooxygenase can dehalogenate a variety of chlorinated hydrocarbons including monochlorinated alcohols, dichlorinated short chain alkanes, and several multiple-substituted compounds including trichloroethylene. The results indicate that M. vaccae JOB-5 has a monooxygenase of broad specificity that can dehalogenate an array of halogenated hydrocarbons.

Biodegradation, Environmental

Management of disseminated disease in the patient with bladder cancer.

Advanced transitional cell carcinoma of the bladder is a chemotherapy-sensitive neoplasm. Several single agents demonstrate substantial activity, and combination chemotherapy produces responses in the majority of patients treated. The benefits and toxicities associated with the most widely used combination regimens are discussed. Other topics reviewed include the use of colony-stimulating factor support for chemotherapy, adjunctive surgical therapy, and newer cytotoxic regimens.

Antineoplastic Agents

Coincidental polycythemia vera and multiple myeloma: case report and review.

Polycythemia vera (PCV) and multiple myeloma are both clonal disorders of hematopoietic stem cells. The simultaneous occurrence of these diseases in an individual patient is rare. A case of synchronous PCV and smoldering myeloma is presented and the literature is reviewed. The issues of clinical importance in this unusual case include the mechanisms of anemia in multiple myeloma, the difficulty in using anemia as a parameter on which to base the initiation of therapy for myeloma, and the risks of treatment-induced leukemia and myelodysplasia.

Aged

Biodegradation and biotransformation of groundwater pollutant mixtures by Mycobacterium vaccae.

Mycobacterium vaccae can catabolize a number of major groundwater pollutants. When added singly, acetone, cyclohexane, styrene, benzene, ethylbenzene, propylbenzene, dioxane, and 1,2-dichloroethylene can be catabolized by M. vaccae. Catabolism of a number of these chemicals was monitored by gas-chromatographic analysis. Gas-chromatographic analysis indicated that the products of benzene degradation are phenol and hydroquinone. The products of chlorobenzene and ethylbenzene degradation are 4-chlorophenol and 4-ethylphenol. The extent that some compounds were catabolized when present as mixtures was also investigated. When toluene and benzene were present concomitantly, toluene was catabolized and benzene oxidation was delayed. Although toluene promoted the degradation of styrene, a lower rate of toluene degradation occurred when styrene was present. Both 4-chlorophenol and 4-ethylphenol had an antagonistic effect on the ability of M. vaccae to degrade other aromatic compounds. Studies with [14C]benzene indicated that M. vaccae can mineralize small amounts of this compound. These results suggest that components in mixtures may have a positive or a negative effect on the rates of biodegradation of other pollutants.

Acetone

Isolated central nervous system relapse of testicular cancer.

Central nervous system involvement with testicular cancer usually occurs with advanced systemic disease. Isolated CNS disease at relapse is rare. We report a patient who developed a solitary brain metastasis with no other systemic disease after having achieved a complete response to frontline therapy. After combined modality therapy for the CNS disease, the patient has remained disease-free for more than 3 years. The literature regarding brain metastases in relapsed testicular cancer is reviewed, including nine cases of isolated brain metastases. The CNS can be a "sanctuary" site for testicular cancer, and in the unusual subset of patients with isolated brain relapse, long-term remission is possible with aggressive therapy.

Adult