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Biomedical subjects

R Doria

Publications and source records attributed to R Doria.

16 recordsLinked to original sources

Efficacy of the combination ampicillin plus ceftriaxone in the treatment of a case of enterococcal endocarditis due to Enterococcus faecalis highly resistant to gentamicin: efficacy of the "ex vivo" synergism method.

The case of a patient with highly gentamicin-resistant Enterococcus faecalis endocarditis treated with an ampicillin + ceftriaxone combination is described. We have designed a method to evaluate synergism between the antibacterial activity of patient's serum taken during a given antibiotic regimen (ampicillin) to which another antibiotic (ceftriaxone) is added in vitro. In this patient the two-drug combination was able to stop the bacteremia and prevent the infection of the prosthetic valve.

Aged↗

[Prion diseases].

The prion diseases or transmissible spongiform encephalopathies (TSE) constitute a group of hereditary or acquired neurodegenerative disorders. The Authors evaluate the etiopathogenetic background, the clinical features and the current concerns with special attention to bovine spongiform encephalopathy and new variant Creutzfeldt Jacob disease.

Creutzfeldt-Jakob Syndrome↗

Cyclophosphamide, cytosine arabinoside and TBI as a conditioning regimen for allogeneic bone marrow transplantation in patients with leukemia.

This is a prospective study designed to determine the toxicity, efficacy and antileukemic effect of high-dose cytosine arabinoside (ara-C), cyclophosphamide and total body irradiation (TBI) as a myeloablative regimen prior to allogeneic bone marrow transplantation for patients with hematologic malignancies. Fifty-eight patients with hematologic malignancies were treated with cyclophosphamide, high-dose ara-C and total body irradiation (TBI) followed by allogeneic bone marrow transplantation. Fifty patients had good prognosis disease and eight had poor prognosis disease. Cyclosporine and short-course methotrexate were used for graft-versus-host disease (GVHD) prophylaxis. The conditioning regimen consisted of ara-C 3000 mg/m2 twice a day x six doses on days -7, -6, and -5; cyclophosphamide 1800 mg/m2 on days -4 and -3; and TBI 1400 cGy midline dose at 5 cGy/min in eight total fractions administered twice a day on days -4, -3, -2, and -1. The bone marrow was infused on day 0 (zero). Toxicity related to the conditioning regimen was comparable to that reported with other conditioning regimens, except for diarrhea which appears to be more frequent. The actuarial survival at 1 year was 69% (58-82) and at 5 years was 54% (42-69) with the numbers in parentheses representing the 95% confidence interval of the Kaplan-Meier estimate. After a median follow-up of 28 months, 31 of 58 (53%) patients are alive without evidence of disease. Only four of the 58 patients (7%) have relapsed. Cyclophosphamide, ara-C and TBI is a safe and effective myeloablative regimen for patients with leukemia. The overall relapse rate in our study was 7% with a median follow-up of 28 months and appears to be lower than relapse rates reported in other series. This is probably due to the added antileukemic effect of ara-C. This regimen should be compared with other myeloablative regimens in a controlled study.

Adolescent↗

Second solid tumors in patients with Hodgkin's disease cured after radiation or chemotherapy plus adjuvant low-dose radiation.

PURPOSE: Late solid tumors (STs) are a significant cause of morbidity and mortality in long-term survivors of Hodgkin's disease. To investigate the carcinogenic potential of two different therapeutic approaches, we measured the relative risk (RR) of STs in patients with early-stage disease cured after primary full-dose (approximately 40 Gy) radiation therapy (RT) and in patients with advanced disease who were treated with chemotherapy followed by low-dose (15 to 30 Gy) involved-field radiation (CMT). PATIENTS AND METHODS: Because therapy-induced STs generally begin after a latency period of 5 to 10 years, we restricted our analysis to patients treated before 1986 who achieved durable remissions. Patients who required salvage chemotherapy or who died of Hodgkin's disease were excluded from analysis. The RR of STs was calculated by dividing the observed number of cases by the expected number in a matched population from the Connecticut Tumor Registry. The actuarial incidence of STs was also measured. RESULTS: A total of 197 patients formed the RT group and 116 the CMT group. The median follow-up period in the RT group was 12.8 years, versus 13.5 years in the CMT group. The overall RR of STs in the CMT group was 1.5 (95% confidence interval [CI], 0.6 to 3.5; P = .122). There were no cases of lung or breast cancer. In the RT group, the overall RR of STs was 3.3 (95% CI, 2.0 to 5.3; P < .001). There were seven cases of lung cancer (RR = 10.8; 95% CI, 5.3 to 22.2; P < .001) and two cases of breast cancer (RR = 2; 95% CI, 0.6 to 7.4; P = .07). All six benign tumors occurred in the RT group. CONCLUSION: In patients cured by initial treatment for Hodgkin's disease, RT was associated with a statistically significant increase in STs, particularly lung cancer. CMT was not associated with a significant increase in STs. These data may have important implications for the design of newer therapies for early-stage Hodgkin's disease.

Actuarial Analysis↗

Primary gastrointestinal lymphomas.

Recent evidence suggests that a significant proportion of primary gastrointestinal lymphomas are driven by exogenous agents/antigens. In the stomach, Helicobacter pylori appears to be responsible for most cases of low-grade lymphomas (MALToma), whereas an infectious etiology is suspected in immunoproliferative small intestine disease (IPSID). Similarly, enteropathy-associated T-cell lymphomas appear to result from a disordered response to gluten, although this profile remains controversial. Accordingly, although traditional antineoplastic treatments, such as surgery and radiation, are still important for the treatment of primary GI lymphomas, antibiotics may be the first line of therapy for low-grade gastric MALToma, and they are often used alone or in combination with chemotherapy for IPSID. In patients with celiac sprue, a gluten-free diet appears to markedly reduce the risk for lymphoma. An important caveat for the treatment of gastric lymphomas is that only low-grade gastric MALTomas have consistently responded to antibiotics. Treatment of high-grade gastric lymphoma is evolving. Although surgery was once considered central to diagnosis, staging, and treatment of gastric lymphoma, most patients can now have a diagnosis established by endoscopic biopsy and are candidates for chemotherapy and adjuvant radiation. The risks of fatal hemorrhage and perforation have probably been vastly overestimated and appear to be equal or less than the mortality associated with surgery. In addition, the long-term effects of gastric resection on quality of life have been almost completely ignored. Systemic lymphomas involve the GI tract far more often than is clinically apparent. In most cases, treatment should not be affected.

Celiac Disease↗

Prognostic significance of DNA aneuploidy in diffuse malignant mesothelioma.

DNA ploidy of pepsin digested preparations of 48 paraffin-embedded specimens from 19 patients with histologically confirmed malignant mesothelioma was determined by laser flow cytometry. Eight of the 19 tumors (42%) were diploid and 11 (58%) were aneuploid. Of the aneuploid tumors, only one showed multiploidy. The median survival time of the patients with diploid tumors was 19, 16, and 14 months from the onset of symptoms, diagnosis, and treatment, respectively. The median survival in patients with aneuploid tumors was 8, 7, and 7 months from the onset of first symptoms, diagnosis, and treatment. Thus, patients with diploid tumors lived longer than patients with aneuploid tumors. These results suggest that DNA ploidy analysis may be of prognostic value in malignant mesothelioma.

Adult↗

Second solid malignancies after combined modality therapy for Hodgkin's disease.

PURPOSE: To determine the actuarial incidence (AI) and relative risk (RR) of second solid malignancies (SSM; solid tumors and non-Hodgkin's lymphoma) in patients with Hodgkin's disease who were treated with chemotherapy and adjuvant, low-dose radiation (combined modality therapy; CMT). PATIENTS AND METHODS: From 1969 to 1983, 102 patients with previously untreated advanced Hodgkin's disease (group A) and 81 patients with recurrent disease after radiation (group B) were treated with CMT. Patients were observed for the development of solid tumors (ST) and non-Hodgkin's lymphoma (NHL), and the AI and RR were calculated. RESULTS: Nearly half of the patients entering remission were observed for greater than 15 years. At 20 years, the AI for SSM was 12% in group A versus 41% in group B (P = .009). The overall RR for developing a ST in group A was 1.88 (not significant) versus 8.84 in group B (95% confidence interval, 5.3 to 15.4). The difference in the RR between groups A and B was significant (P < .001). The RR for developing NHL was significantly increased in both groups, but the difference between groups was not significant. CONCLUSION: Previously untreated patients with advanced disease who were treated with CMT (group A) had a modest but not significant increase in the RR of ST; however, patients treated with CMT for recurrent disease (group B) had a highly significant increase in the RR of ST. Possible explanations for the increase in ST in group B include more cumulative radiation or a greater carcinogenic effect of chemotherapy in previously irradiated patients, but it also is possible that the increase is due to a longer follow-up time.

Adolescent↗

Thyroid lymphoma. The case for combined modality therapy.

BACKGROUND: Radiation therapy with or without surgery is generally considered standard treatment for lymphoma of the thyroid. Because of the small number of cases, the role of chemotherapy or combined modality treatment is difficult to determine. METHODS: The published literature was analyzed, supplemented by a series from Yale, for the incidence of local and distant relapse after radiation therapy, chemotherapy, or combined modality treatment for Stage I-II thyroid lymphoma. Patients with advanced disease or in whom radiation was probably inadequate were excluded. Only patients receiving an anthracyline-based regimen were considered in the group with chemotherapy. Patients receiving single agents or non-anthracycline-based regimens were excluded from analysis or, if they also received radiation, were included in the group that received radiation only. RESULTS: Including a series from Yale, a total of 211 patients with Stage IE and IIE thyroid lymphoma were identified. Distant and overall relapse rate were significantly lower in the group that received combined modality treatment. Local relapse was also less, but the difference was not statistically significant. In a small number of patients with disease confined to the neck, the results with radiation were similar to combined modality treatment if the mediastinum was included in the treatment port. CONCLUSION: Although mucosa-associated lymphoma tissue lymphomas are thought to have a low distant recurrence rate and are therefore often treated with local therapy alone, a review of the published literature suggests that 30% of thyroid lymphomas with clinically localized disease will have a distant relapse. The addition of chemotherapy to radiation significantly lowered distant and overall recurrence.

Aged↗

New strategies are needed in diffuse malignant mesothelioma.

BACKGROUND: Medical records of 50 patients with malignant mesothelioma were reviewed to determine the clinical features and factors influencing survival. METHODS: Charts of all patients whose conditions were diagnosed as malignant mesothelioma were abstracted and analyzed by statistical software. RESULTS: The male-to-female ratio was 4:1. The age distribution was younger than 45 years of age, 10%; 45-54 years of age, 12%; 55-64 years of age, 37%; 65-74 years of age, 33%; and 75 years of age or older, 8%. Both mean and median ages were 58 years. Among the 32 patients in whom asbestos exposure was recorded, 24 had documented exposure. The sites were pleura, 73%; peritoneum, 20%; and both, 6%. The histologic types were epithelial, 51%; sarcomatous, 10%; mixed, 15%; and not specified, 24%. The stage at presentation was Stage I, 37%; II, 39%; III, 12%; IV, 6%; and unknown, 6%. The common symptoms in pleural disease were dyspnea and pain; in peritoneal disease, abdominal distension and pain were common. The median time from first symptom to diagnosis was 3 months (range, 0-23 months). The median survival after the appearance of symptoms, the diagnosis, and the treatment were 13, 10, and 8 months, respectively. CONCLUSIONS: The survival was independent of age, sex, and smoking behavior. It was longer in patients with earlier-stage disease, a good performance status, a longer duration of symptoms, an absence of pain, and who were treated with combined surgery and chemotherapy. Chemotherapy using anthracyclines yielded more remissions (9 of 21) than that using nonanthracyclines (0 of 13). The remission rate after primary chemotherapy with anthracyclines (7 of 16) may be higher than in recurrent tumor (2 of 14). In future trials, stratification into primary chemotherapy and chemotherapy of recurrent cancer is suggested. There is a need for multitechnique trials incorporating primary chemotherapy.

Adult↗

New-onset ventricular tachycardia during pregnancy.

During evaluation for palpitations, presyncope, or syncope, seven pregnant women had documented ventricular tachycardia. Before pregnancy none had a history of significant cardiac disease or symptomatic arrhythmia. The tachycardia rate ranged from 117 to 250 beats/min and lasted up to 65 seconds. Arrhythmia evaluation in five of the patients suggested catecholamine-sensitive ventricular tachycardia. This diagnosis was supported by either a positive relation to exercise or isoproterenol infusion, suppression of arrhythmia by beta-blockade or sleep, and lack of induction of arrhythmia by programmed electrical stimulation of the heart. The arrhythmias resolved in one patient soon after evaluation and in one other patient after 2 months of controlling therapy. Five other patients continued to receive therapy throughout pregnancy. Delivery was accomplished in all patients without significant maternal or neonatal complications.

Echocardiography↗

Purification and characterization of a gamma crystallin from mouse lenses.

A gamma-crystallin has been purified by a two-step column chromatography from an extract of water soluble lens proteins from (101/ E1xC3H /E1)F1 mice. About 17% of the water soluble lens protein in normal mice is represented by this gamma-crystallin. The protein has been shown to be absent in cataractous lenses of Nop /+ mice after isoelectric focusing of water soluble lens proteins. It has a MW of 20,000. Amino acid analysis reveals the occurrence of eight cystein residues, which is considered to be high compared to other crystallins. The protein might play an important role in cataractogenesis.

Amino Acids↗

Combined modality therapy in previously untreated patients with advanced Hodgkin's disease: A 24-year follow-up study.

PURPOSE: To describe the long-term results of treatment with chemotherapy plus adjuvant low-dose, involved-field radiation therapy (CMT) in patients with advanced Hodgkin's disease. Data on disease-free and failure-free survival, second malignancies, and the results of salvage therapy are presented. PATIENTS AND METHODS: From 1969 to 1989, CMT was administered to 186 patients with previously untreated stage IIB, III, and IV Hodgkin's disease. Chemotherapy included MVVPP (47%), MOPP (25%), MOPP/ABVD (26%) and ABVD (2%). After 6 months of chemotherapy, patients received radiation to all involved sites with the exception of the bone marrow. RESULTS: The failure-free survival for all patients was 63% at 5 years, 56% at 10 years, and 40% at 23.5 years, respectively. Significantly worse results were observed in patients older than 40 years and those with stage IV disease. The overall survival of 45 patients after recurrence was 39% at 10 years, but was only 21% if the initial complete remission lasted less than 1 year. Thus far, 21 of 165 patients (12.7%) who achieved complete remission have developed a second malignancy, and 16 have died. CONCLUSIONS: In comparison with comparable chemotherapy programs, chemotherapy plus radiation therapy may improve disease-free survival; however, the results of treatment in patients older than age 40 or with stage IV disease are still poor. Although patients with initial remissions lasting longer than 1 year can have durable second remissions, the long-term disease-free survival is poor and in the current series the majority of failures were due to recurrent Hodgkin's disease.

Adolescent↗