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Biomedical subjects

A Raventos

Publications and source records attributed to A Raventos.

At least 19 recordsLinked to original sources

Low-dose, fractionated radioimmunotherapy for B-cell malignancies using 131I-Lym-1 antibody.

PURPOSE: This trial was conducted to assess the toxicity and efficacy of 131I-Lym-1 in patients with either malignant B-cell non-Hodgkin's lymphoma (NHL) or chronic lymphocytic leukemia (CLL) using low-dose, fractionated radioimmunotherapy (RIT). MATERIALS AND METHODS: Thirty adult patients who had advanced B-cell malignancies (25 NHL and 5 CLL) had progressed despite standard therapy; 12 patients entered the trial with Karnofsky performance status (KPS) of equal to or greater than 60. Patients were treated with a series of intravenous doses of 131I-Lym-1 with a goal of reaching a cumulative dose in each patient of at least 300 mCi. All patients were Lym-1 reactive. Clinical responses and immediate toxicity were evaluable in all 30 patients and delayed toxicity in 26. RESULTS: Toxicity to Lym-1 antibody occurred with 28% of the 176 doses and was transient. Human antimouse antibodies (HAMA) were generated in 30% after a mean of 4 doses, but interrupted therapy in only 10% of the patients. Thrombocytopenia was dose-limiting; there were no deaths due to toxicity. Tumor regression occurred in 25 (83%) of the patients and was great enough, and durable enough, in 17 (57%) to qualify them as responders; 13 NHL patients and 4 CLL patients. Advanced disease often interrupted therapy prematurely. However, 18 patients received at least 180 mCi of 131I-Lym-1; 17 (94%) of these responded to the therapy. CONCLUSION: Although advanced disease often interrupted therapy prematurely, the results from 131I-Lym-1 therapy are clearly promising and warrant additional trials.

Adult↗

Bone bacillary angiomatosis in an HIV-infected patient.

Bacillary angiomatosis (BA) is a recently discovered multisystem bacterial infectious disease seen in the setting of immune suppression due to the human immunodeficiency virus (HIV). A case of an HIV-infected patient with osteolytic bone involvement is reported.

Adult↗

Resistance-related mutations in the HIV-1 protease gene of patients treated for 1 year with the protease inhibitor ritonavir (ABT-538).

OBJECTIVE: To define genotypic and phenotypic resistance patterns following prolonged therapy with the protease inhibitor ritonavir (ABT-538). DESIGN: Seven HIV-1-infected patients, all but one previously treated with dideoxynucleoside analogues (zidovudine, didanosine, zalcitabine), were treated for 1 year with ritonavir. METHODS: Direct solid-phase sequencing of the protease gene starting from plasma derived viral RNA followed by comparison to phenotypic drug resistance data. RESULTS: The most frequent amino-acid substitutions occurring upon administration of the protease inhibitor were V82A/F (substrate binding site), I54V (flap region), A71V and L10I. Additional mutations found in more than one patient were I15V, M36I, I84V and I93L. Mutation L63P was found both in pre- and post-ritonavir samples. Phenotypic drug resistance assays confirmed resistance to ritonavir in post-treatment samples (approximately 170-fold) and showed cross-resistance to indinavir (approximately 30-fold) and partially to saquinavir (approximately fivefold). At 1 year of treatment, one patient without known resistance-associated mutations in the protease gene still showed a substantial rise in CD4 cell count accompanied by a more than 2.4 log decrease in RNA viral load. However, at week 78, mutations R8Q, E34K, R57K, L63P and I84V were detected and the treatment benefit was partially lost. CONCLUSIONS: Long-term treatment with ritonavir is associated with the emergence of multiple mutations in the HIV-1 protease gene. The mutations L10I, I54V, L63P, A71V, V82A/F and I84V correspond to known drug-resistance mutations for ritonavir and other protease inhibitors. Phenotypic resistance to ritonavir was detected in a majority of ritonavir-treated patients at 1 year of treatment. In addition, long-term ritonavir treatment selects for cross-resistance to the protease inhibitors indinavir and saquinavir. This argues against sequential therapy with several protease inhibitors. Delayed resistance in one patient was accompanied with a prolonged increase in CD4 cell count and decrease in viral load suggesting a temporary benefit of treatment.

Amino Acid Sequence↗

A short-term study of the safety, pharmacokinetics, and efficacy of ritonavir, an inhibitor of HIV-1 protease. European-Australian Collaborative Ritonavir Study Group.

BACKGROUND: Reverse-transcriptase inhibitors have only moderate clinical efficacy against the human immunodeficiency virus type 1 (HIV-1). Ritonavir is an inhibitor of HIV-1 protease with potent in vitro anti-HIV properties and good oral bioavailability. METHODS: We evaluated the antiviral activity and safety of ritonavir in a double-blind, randomized, placebo-controlled phase 1 and 2 study of 84 HIV-positive patients with 50 or more CD4+ lymphocytes per cubic millimeter. The patients were randomly assigned to one of four regimens of ritonavir therapy, or to placebo for four weeks and then (by random assignment) to one of the ritonavir regimens. RESULTS: During the first 4 weeks, increases in CD4+ lymphocyte counts and reductions in the log number of copies of HIV-1 RNA per milliliter of plasma were similar among the four dosage groups, but in the three lower-dosage groups there was a return to base-line levels by 16 weeks. After 32 weeks, in the seven patients in the highest-dosage group (600 mg of ritonavir every 12 hours), the median increase from base line in the CD4+ lymphocyte count was 230 cells per cubic millimeter, and the mean decrease in the plasma concentration of HIV-1 RNA (as measured by a branched-DNA assay) was 0.81 log (95 percent confidence interval, 0.40 to 1.22). In a subgroup of 17 patients in the two higher-dosage groups, RNA was also measured with an assay based on the polymerase chain reaction, and after eight weeks of treatment there was a mean maximal decrease in viral RNA of 1.94 log (95 percent confidence interval, 1.37 to 2.51). Adverse events included nausea, circumoral paresthesia, elevated hepatic aminotransferase levels, and elevated triglyceride levels. Ten withdrawals from the study were judged to be related to ritonavir treatment. CONCLUSIONS: In this short-term study, ritonavir was well tolerated and had potent activity against HIV-1, but its clinical benefits remain to be established.

Adult↗

Cytologic study of renal angiomyolipoma by fine-needle aspiration biopsy: report of four cases.

Four cases of renal angiomyolipoma (AML) diagnosed by fine-needle aspiration biopsy (FNAB) are reported. One case was associated with the clinical complex of tuberous sclerosis. The tumors were solitary in two cases and multiple and bilateral in the fourth. The cytologic features of the four cases were similar to those described in the literature: smooth muscle cells intermingled with mature fat cells and blood vessels, together with a lipoidic background. These tumors are currently considered benign although they may present characteristics accepted as criteria of malignancy in other tumors: pleomorphism and atypical smooth muscle cells, vascular invasion, capsular rupture, and lymphatic involvement. We conclude that it is important and possible to establish preoperative cytologic diagnosis, since treatment of these tumors is conservative and obviates aggressive nephrectomy.

Adolescent↗

Pulmonary embolism in patients with upper extremity DVT associated to venous central lines--a prospective study.

We performed a prospective study in 86 consecutive patients with central vein catheter-related deep venous thrombosis (DVT) of the upper extremity, to evaluate the prevalence of pulmonary embolism (PE), and to identify clinical variables that would increase the likelihood of developing PE in an individual patient. Since upper-extremity DVT was established, all patients received intravenous heparin therapy. Then, a ventilation-perfusion lung scan was obtained within 24 h of DVT diagnosis, whether respiratory symptoms were present or not. Six points of clinical information were recorded on entering in the study, and then compared with the scintigraphic findings: age, sex, the underlying disease, the catheter material, the character of the infusate, and the duration of cannulation. Thirteen patients were considered to have PE. Sixty-six patients were finally classified as having a normal lung scan, and 7 patients were excluded from the study (because of indeterminate lung scan 6; because of femoropopliteal thrombosis simultaneously present 1). Two out of the 13 patients with PE subsequently died because of recurrent, massive embolism, despite adequate heparin therapy. PE was more commonly present in patients with polyvinyle chloride or polyethylene catheters (10/38, 26%) as compared to patients with either polyurethane or siliconized catheters (3/41, 7%; p < 0.05, Chi-Square test; Odds Ratio = 4.52, 95% CI 1.01-23.07). We conclude that PE is not a rare event in these patients, and it may be life-threatening even despite adequate heparin therapy.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

A distinctive cytologic pattern for diagnosing tuberculous lymphadenitis in AIDS.

Tuberculous lymphadenitis (TL) is a very common infection in human immunodeficiency virus (HIV)-infected patients. We performed fine-needle aspiration biopsy (FNAB) of enlarged lymph nodes in 57 HIV-infected patients to evaluate its usefulness in this population. We observed three cytologic patterns in 21 patients diagnosed as having TL: granulomatous lymphadenitis (GL) in 4 FNABs, necrotizing granulomatous lymphadenitis (NGL) in 7 FNABs, and necrotizing lymphadenitis (NL) in 12 FNABs. GL and NGL are already well-known and considered to be highly suggestive of TL. Our results support the idea that NL should have the same diagnostic value as GL or NGL. In the group of 12 patients with NL, TL was confirmed in 11 by microbiologic methods (7 by a positive Ziehl-Neelsen stain and 4 by a positive Löwenstein culture) and in the remaining patient by a biopsy that showed NGL with acid-fast bacilli. We conclude that FNAB is a useful, inexpensive, and safe technique for diagnosing TL in HIV-infected patients. The finding of a NL pattern is suggestive enough of TL to start antituberculous treatment.

AIDS-Related Opportunistic Infections↗

Prospects for radiolabeled monoclonal antibodies in metastatic disease.

Many monoclonal antibodies are now available that bind to human cancer cells with varying degrees of specificity. These antibodies can be labeled with various radionuclides, permitting tumor sites in the body to be imaged with scintillation cameras. SPECT, the emission counterpart of x-ray computed tomography, provides both qualitative and quantitative information in three dimensions about antibody distribution. We have detected a metastasis as small as 5 mm in a patient, and the theoretical limit of detection size is less than 1 mm. Tumors that are imaged with radiolabeled antibodies can be effectively treated with the same substance (radioimmunotherapy).

Antibodies, Monoclonal↗

Requirements for a treatment planning system for radioimmunotherapy.

Cancer-seeking antibodies carrying radionuclides can, in theory, be very powerful agents for the radiotherapy of cancer. However, as with all radiotherapy, the undesired dose to critical normal organs is the limiting factor that determines success or failure. The distribution of radiation dose in cancer and noncancer tissue is highly dependent on choices the therapist can make: choices of the antigens to be targeted, choices of the antibodies or antibody fragments to be used, choices of radionuclides, of amounts, of timing, and other electives. New technologies, especially of monoclonal antibody production, make the options myriad. Optimization of this therapy depends on a foreknowledge of the radiation dose distributions to be expected. The necessary data can be acquired by established tracer techniques, in individual patients, for particular treatment selections. These tracer techniques can now be implemented by advanced equipment for quantitative, tomographic radionuclide imaging and strengthened by dynamic modeling of the physiological parameters which govern radionuclide distribution, and hence radiation dose distribution.

Animals↗

Clinical trials of adjuvant radiation therapy for breast cancer.

Years ago, radiation therapists conducted randomized clinical trials which showed that regional irradiation significantly reduces local recurrence of breast cancer but does not often affect life span. No new findings challenge these conclusions. Controlled trials in general have lost some credibility, however, as it has become more widely recognized that they are very vulnerable to fallacious reasoning and to simple human error. There is serious concern that some physicians may be unwisely abandoning well tested treatment methods because of the premature dissemination of early results of some trials. Still, many important questions remain that can only be answered by clinical trials, some including radiation therapy. This paper suggests that randomization schemes be incorporated into "routine" medical practice, although only after the most careful deliberation, in order to hasten fuller understanding of old therapeutic methods as well as new ones.

Breast Neoplasms↗

Critical evaluation of hepatic scintiangiography for neoplastic tumors of the liver.

Dynamic hepatic scintiangiography increases the specificity of diagnosis of space-occupying lesions of the liver seen on hepatic scintigraphy. The purpose of this study was to evaluate and compare critically this procedure with histologic and radiopaque diagnosis in the evaluation of suspected hepatic neoplasms. Ninety-two patients had hepatic scintiangiography, scintigraphy, and histologic certification. In ten of these patients the findings of radiopaque arteriography were compared with those of hepatic scintiangiography. In all ten patients with hepatoma, the scintiangiographic and histologic observations correlated; nine of these ten patients had a "tumor stain." Fifty-one of 59 patients with metastases to the liver had scinitangiograms that showed "tumor stain." In 2 of these 59 patients, scintiangiography revealed tumor vascularity whereas the results of scintigraphy were normal. In two of four patients with metastases and two of six patients with hepatomas, scintiangiograms revealed "tumor stain" that was not evident on radiopaque afteriography. Conclusions from this study are: (A) neoplastic arterialization or "tumor stain" is more readily detected by scintiangiography than by radiopaque arteriography; (B) a normal scintigram and a "tumor stain" on the scintiangiogram in a patient with a known primary neoplasm outside the liver is suggestive of hepatic metastases; and (C) a normal scintigram and scintiangiogram make neoplastic involvement of the liver improbable. Dynamic hepatic scintiangiography is a simple, clinically useful method for increasing the specificity of diagnosis of diagnosis of space-occupying lesions of the liver and should be part of the evaluation for possible neoplastic involvement.

Carcinoma, Hepatocellular↗