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High-dose sequential epirubicin and cyclophosphamide with peripheral blood stem cell support for advanced breast cancer: results of a phase II study.

The aim of this study was to evaluate the feasibility of a high-dose intensity and high-dose density multicycle epirubicin and cyclophosphamide regimen with peripheral blood stem cells (PBSC) and haematopoietic growth factor (G-CSF) support in advanced breast cancer patients. From August 1994 to September 1999, 56 breast cancer patients (8 stage IIIB and 48 stage IV) received 205 courses of cyclophosphamide 3 g x m(-2) and epirubicin 100 mg x m(-2) every 14 days. G-CSF 5 microg x kg(-1) x day(-1) was administered from day 3 to neutrophil recovery. 4 courses were planned. PBSC were collected after course 1, and reinfused after courses 3 and 4, with > or = 2 x 10(6) CD34+ PBSC x kg(-1) required for each reinfusion. 48 patients (86%) received all 4 planned courses. Early withdrawal was consecutive to infectious complications (n = 4), severe asthenia (n = 3), haemorrhagic cystitis (n = 1). A median number of 10.8 x 10(6) CD34+ PBSC x kg(-1) (range, 3-80) was harvested with 1 or 2 apheresis in 48 patients (94%). Median relative dose intensity was 91.3% (range, 72-102%). Grade 4 neutrophil toxicity was observed in 100% of patients. Febrile neutropenia was observed in 40% of courses (median duration 2 days). Red blood cells and platelets had to be transfused in 54% and 27% of courses, respectively. There were no toxic deaths. Objective response rate was 69% in stage IV patients (31/45 evaluable pts), with a 16% complete response rate. Their median progression-free and overall survivals were 22.5 and 37 months, respectively. This epirubicine-containing high-dose regimen appeared feasible, albeit with high toxicity. Time-related progression parameters exceed commonly reported ones. Controlled studies of upfront sequential high-dose chemotherapy are still needed to evaluate its real benefit.

Adult↗

Diagnosis and treatment of biliary obstruction caused by portal cavernoma.

While hemorrhagic complications of portal cavernoma are frequent, compression of the bile ducts by portal cavernoma is uncommon and treatment is still a matter for debate. We report here six new cases in order to describe: (a) the clinical, biological, and morphological features of this condition, and (b) the long-term results of a combined endoscopic and surgical treatment. The median age of patients at the time of diagnosis was 36.5 years. The circumstances of diagnosis were acute cholangitis (n=3), asymptomatic biological cholestasis (n=1), pruritus, jaundice and asthenia (n=1) and jaundice alone (n=1). Portal cavernoma and bile duct dilatation were confirmed by abdominal ultrasonography with pulsed color doppler and endoscopic retrograde cholangiography (ERC). Gallstones were found in four patients. Following stenting of the bile duct, there was a good outcome in two patients. In four patients, after failure of prolonged endoscopic treatment, second-line surgical portal-systemic shunting allowed removal of the biliary stent, and no recurrence of disease. In conclusion, biliary involvement in portal cavernoma is now a well-recognized entity, and our results suggest that combined endoscopic and surgical treatment could be required.

Adult↗

Adrenal insufficiency due to primary bilateral adrenal non-Hodgkin's lymphoma.

A case of primary adrenal insufficiency, secondary to primary bilateral adrenal lymphoma is reported. A 50-year-old woman presented with features of primary adrenal insufficiency (darkening of skin, asthenia, anorexia, constipation) for at least 8 months. Clinical examination was unremarkable except for low body mass index and generalized skin and buccal mucosal pigmentation. Routine investigations including complete hemogram, serum chemistry, urine analysis, chest radiograph and electrocardiogram were normal; serum lactate dehydrogenase was moderately elevated. Primary adrenal insufficiency was confirmed on cortisol dynamics (very low basal and peak cortisol) after insulin-induced hypoglycemia. Routinely detected adrenal masses on ultrasonography were confirmed by contrast enhanced CT abdomen. A diagnosis of primary adrenal non- Hodgkin's lymphoma (B-cell) was made after exploratory laprotomy and further staging. The patient was put on combination chemotherapy (CHOP) protocol, but was lost to follow-up after receiving two cycles of treatment. Primary adrenal lymphoma, although a rare entity, needs to be suspected in patients with features of primary adrenal insufficiency who have evidence of bilateral adrenal masses on imaging.

Adrenal Gland Neoplasms↗

Safety database on fluvoxamine: analysis and report.

A review was conducted of the safety and tolerability of fluvoxamine in 54 worldwide marketing studies that enrolled 24,624 patients, the majority of whom were treated with fluvoxamine in uncontrolled studies in depression. In accordance with the general epidemiologic distribution of depressive disorder, female patients and patients aged between 30 and 50 years predominated. The majority of patients were treated for 6 weeks, the most frequent, or modal, total daily dose being 100 mg. Overall, 57.4% of the patients exposed to fluvoxamine did not have any adverse experiences. The greatest proportion of adverse experiences, as defined using COSTART body systems, affected the digestive system (24.1%), the nervous system (23.7%), and the body as a whole (15.3%). The only adverse experience with an incidence greater than 10% was nausea (15.7%); somnolence (6.9%) and asthenia (6.2%) were the next most frequent adverse experiences. Notably, the rates of agitation and anxiety were only 1.4% and 1.3%, respectively. The incidences of adverse experiences generally increased with age and were slightly higher in females than in males. In total, 15.1% of patients discontinued treatment prematurely as a result of adverse experiences, principally nausea, dizziness, vomiting, somnolence, abdominal pain, and headache. The overall incidence of serious adverse events in association with fluvoxamine treatment was 2.5% when U.S. Food and Drug Administration criteria and the most conservative approach, without causality judgments, were used.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

[Diagnosis of local panarteritis nodosa of the uterine cervix].

A 44-year old woman was referred because of metrorrhagia and asthenia. A diagnosis of uterine malignancy was suspected on the basis of the management of the Cervix uteri and an elevated erythrocyte sedimentation rate. Conisation and hysterectomy were performed, and histological examination revealed necrotising vasculitis affecting the Cervix uteri. Corpus uteri, muscle and fat biopsies showed no Periarteritis nodosa lesions. The incidental finding of necrotising arteritis in a surgical uterine specimen, involves further study to exclude systemic disease. The ability to involve any organ in the body makes it possible for specialists in every branch of medicine to be involved in the management and care of these patients.

Adult↗

A controlled trial of riluzole in amyotrophic lateral sclerosis. ALS/Riluzole Study Group.

BACKGROUND: Amyotrophic lateral sclerosis is a progressive motor neuron disease for which there is no adequate treatment. Some research suggests that the excitatory amino acid neurotransmitter glutamate may be involved in the pathogenesis. METHODS: To evaluate the efficacy and safety of the antiglutamate agent riluzole, we conducted a prospective, double-blind, placebo-controlled trial in 155 outpatients with amyotrophic lateral sclerosis. The dose of riluzole was 100 mg per day. Randomization was stratified according to the site of disease onset (the bulbar region or the limbs). The primary end points were survival and rates of change in functional status. The main secondary end point was change in muscle strength. Analyses were undertaken after 12 months of treatment and at the end of the placebo-controlled period (median follow-up, 573 days). RESULTS: After 12 months, 45 of 78 patients (58 percent) in the placebo group were still alive, as compared with 57 of 77 patients (74 percent) in the riluzole group (P = 0.014). For patients with bulbar-onset disease, one-year survival rates were 35 percent (6 of 17) with placebo and 73 percent (11 of 15) with riluzole (P = 0.014), whereas for those with limb-onset disease one-year survival was 64 percent and 74 percent, respectively (P = 0.17). The survival advantage with riluzole was smaller (37 percent [29 of 78] with placebo vs. 49 percent [38 of 77] with riluzole) at the end of the placebo-controlled period, but it remained significant in the overall population (P = 0.046) as well as in the patients with bulbar-onset disease (18 percent [3 of 17] vs. 53 percent [8 of 15], P = 0.013). The deterioration of muscle strength was significantly slower in the riluzole group than in the placebo group (P = 0.028). Adverse reactions to riluzole included asthenia, spasticity, and mild elevations in aminotransferase levels. Twenty-seven patients in the riluzole group withdrew from the study, as compared with 17 in the placebo group. CONCLUSIONS: The antiglutamate agent riluzole appears to slow the progression of amyotrophic lateral sclerosis, and it may improve survival in patients with disease of bulbar onset.

Adult↗

Interferon gamma-1b compared with placebo in metastatic renal-cell carcinoma. Canadian Urologic Oncology Group.

BACKGROUND: Most trials of immunomodulators in metastatic renal-cell carcinoma have been uncontrolled and subject to selection bias. The objective of this blinded, placebo-controlled study was to compare overall response rates, time to disease progression, and survival of patients with metastatic renal-cell carcinoma treated with recombinant human interferon gamma-1b or placebo. METHODS: Patients with biopsy-proved metastatic renal-cell carcinoma were randomly assigned to receive interferon gamma-1b (60 microg per square meter of body-surface area subcutaneously once weekly) or placebo. The primary tumor had been treated by nephrectomy or angioinfarction at least three weeks previously. Patients were evaluated for radiologic evidence of progression, and all responses were independently reviewed by a committee that was unaware of the treatment. RESULTS: A total of 197 patients with metastatic renal-cell carcinoma were enrolled at 17 centers in Canada. One hundred eighty-one patients could be evaluated; of these, 91 were assigned to receive interferon gamma-1b and 90 were given placebo. The groups were well balanced in terms of prognostic factors. Two thirds of all patients had Karnofsky scores of 90 or 100, and more than half had two or more metastatic sites. Grade I and II toxicity, mostly chills, fever, asthenia, or headaches, was reported in 91 percent and 61 percent, respectively, of the patients in the interferon group, as compared with 76 percent and 63 percent in the placebo group. Life-threatening drug-related events were rare, occurring in 1 percent of patients in the interferon group. No significant differences between groups were observed in overall response rates, time to disease progression, or survival. The overall response rate was 4.4 percent (3.3 percent complete response and 1.1 percent partial response) in the interferon group and 6.6 percent (3.3 percent complete response and 3.3 percent partial response) in the placebo group (P=0.54), with a rate of durable complete response of 1 percent in both groups. The median time to disease progression was 1.9 months in both groups (P=0.49), and there was no significant difference in median survival (12.2 months with interferon vs. 15.7 months with placebo, P=0.52). CONCLUSIONS: No difference in outcome was observed in patients with metastatic renal-cell carcinoma who were treated with interferon gamma-1b as compared with placebo. These results emphasize the necessity of testing the efficacy of immunomodulators in randomized studies.

Adjuvants, Immunologic↗

Pegylated interferon-alpha2b: pharmacokinetics, pharmacodynamics, safety, and preliminary efficacy data. Hepatitis C Intervention Therapy Group.

AIMS: The objectives of this study were to assess the safety, pharmacokinetic and pharmacodynamic profiles, and antiviral efficacy of pegylated interferon-alpha2b monotherapy in patients with chronic hepatitis C. METHODS: Fifty-eight patients (38 men, 20 women; age range, 25 to 65 years) with compensated chronic hepatitis C were enrolled in this open-label, randomized, active controlled study. Patients received 0.035 to 2.0 microg/kg pegylated interferon-alpha2b subcutaneously weekly or the active control, interferon-alpha2b 3 million IU subcutaneously three times/week, for 24 weeks. Safety and antiviral efficacy assessments were performed during treatment and in a subsequent 4-week follow-up period. Detailed pharmacokinetic assessments were performed at weeks 1 and 4. RESULTS: Pegylated interferon-alpha2b produced dose-related reductions in white blood cells, neutrophils, and platelets, and dose-related increases in oral temperature, serum neopterin, and serum 2'5'-oligoadenylate synthetase activity, which were qualitatively similar to those produced by nonpegylated interferon-alpha2b. Reported adverse events (flu-like symptoms, asthenia) were qualitatively similar in pegylated interferon-alpha2b- and nonpegylated interferon-alpha2b-treated groups. Dose-related antiviral activity, as measured by loss of detectable serum hepatitis C virus RNA (<100 copies/mL), was noted at the end of treatment and after 4 weeks of follow-up. Both pegylated and nonpegylated interferon-alpha2b were rapidly absorbed, with maximal concentrations occurring approximately 8 to 12 hours after dose administration. Pegylated interferon-alpha2b had sustained maximal serum concentrations for 48 to 72 hours after dose administration, whereas nonpegylated interferon-alpha2b concentrations declined rapidly. Volume of distribution for both compounds was similar (approximately 1 L/kg). Pegylated interferon-alpha2b elimination half-life was approximately 10-fold greater, and mean apparent clearance was one tenth that of nonpegylated interferon-alpha2b. CONCLUSIONS: Pegylated and nonpegylated interferon-alpha2b safety and pharmacodynamic profiles were comparable. Pegylated interferon-alpha2b demonstrated delayed clearance compared with nonpegylated interferon-alpha2b, consistent with once-weekly administration.

Absorption↗

Clinical and histologic response to single-dose treatment of moderate to severe psoriasis with an anti-CD80 monoclonal antibody.

Pathologic T-cell activation is implicated in psoriasis progression. CD80, a costimulatory molecule involved in T-cell activation, likely plays a key role. IDEC-114, an IgG(1) anti-CD80 antibody, was evaluated for safety, pharmacokinetics, and preliminary clinical activity in this open-label, single-dose, dose-escalating study in patients with moderate to severe chronic plaque psoriasis. Twenty-four patients received IDEC-114 (0.05 mg/kg, 0.25 mg/kg, 1 mg/kg, 5 mg/kg, 10 mg/kg, or 15 mg/kg). Psoriasis Area and Severity Index, Physician's Global Psoriasis Assessment, and Psoriasis Severity Scale scores improved in the highest-dose groups. Average plaque thickness and plaque CD3+ and CD8+ T-cell counts decreased in the 10 mg/kg dose group. Adverse events were primarily mild, transient, constitutional symptoms; the most common related events were mild asthenia (29% of patients), chills (25%), and headache (21%). The serum half-life of IDEC-114 was approximately 13 days. A single dose of IDEC-114 appears to be safe and well tolerated and has promising clinical activity in psoriasis.

Adolescent↗

Safety and efficacy of fluoxetine in patients who receive oral contraceptive therapy.

OBJECTIVE: Because many women who receive pharmacologic therapy with antidepressants are also prescribed oral contraceptives, it is important to assess the risk of clinically significant drug interactions. We reviewed the United States fluoxetine clinical trial database, specifically analyzing women ages 18 to 45 years, for differences in safety, antidepressant efficacy, and unplanned pregnancies that were associated with oral contraceptive use. STUDY DESIGN: Data from 17 double-blind, placebo-controlled clinical trials in 1698 women were analyzed retrospectively. A subgroup of women with oral contraceptive use was compared with a subgroup of women with no oral contraceptive use. Differences in treatment-emergent adverse events, unplanned pregnancies, and 17-item Hamilton Depression Scale (HAMD-17) scores were analyzed. RESULTS: The only treatment-emergent adverse events that showed a statistically significantly different odds ratio for oral contraceptive use versus no oral contraceptive use were headache, asthenia, and pain. There was not a statistically significant interaction in the incidence of unintended pregnancies (P =.111) or in the changes from baseline in HAMDD-17 scores. CONCLUSION: There is no clinical evidence that concomitant use of oral contraceptives and fluoxetine affects the safety or efficacy of either agent.

Antidepressive Agents, Second-Generation↗

Oral histoplasmosis in Brazil.

OBJECTIVE: We report 10 cases of histoplasmosis with oral manifestations seen in a teaching hospital in Brazil. STUDY DESIGN: This is a retrospective study of the sociodemographic, clinicopathologic, and treatment data of these cases. RESULTS: Overall, 8 of 10 cases were seropositive for human immunodeficiency virus (HIV), whereas 2 were negative. The predominant oral manifestations found in HIV-seropositive patients were ulcers, oral pain, and odynophagia; both of the HIV-seronegative patients were symptom-free. HIV infection was suspected in 7 cases because of the presence of oral lesions of histoplasmosis. Asthenia, fever, weight loss, lymphadenopathy, and hepatosplenomegaly were found only in HIV-seropositive patients. Radiographs in 3 out of 10 patients suggested pulmonary involvement. Amphotericin B was the antifungal therapy chosen, and clinical remission of oral lesions occurred in an average of 30 days (accumulated doses: 500-1500 mg). Itraconazole was very effective as a follow-up treatment in terms of prevention of recurrence. CONCLUSION: Histoplasmosis only rarely affects HIV-seronegative patients; however, the possibility of hidden immunodepression should be considered when oral manifestations of histoplasmosis are present.

AIDS-Related Opportunistic Infections↗

Direct pull of lateral cricoarytenoid muscle for unilateral vocal cord paralysis.

CONCLUSION: Lateral cricoarytenoid muscle-pull surgery (LCA pull) is a safe and effective method for the treatment of unilateral vocal cord paralysis. OBJECTIVE: To evaluate the results of an improved method of LCA pull for unilateral vocal cord paralysis. MATERIAL AND METHODS: Thirteen patients with unilateral vocal cord paralysis underwent LCA pull between April 2003 and January 2004. A small window was made in the posterior lower part of the thyroid cartilage and 2-3 mm in a cranial direction to the lower edge of the thyroid cartilage. The inner perichondrium was carefully removed to expose the LCA muscle. A 4-0 nylon suture placed through the LCA muscle was pulled to adduct the arytenoid and was tied to the anterior lower part of the thyroid cartilage. All cases were treated by LCA pull alone. In all cases, the maximum phonation time was measured and an auditory evaluation was performed using the grade, roughness, breathiness, asthenia and strain scale. The airflow rate was measured in five cases. RESULTS: Vocal improvement was obtained in 11/13 cases (85%). One of the unimproved cases had cricoarytenoid joint ankylosis. No complications were observed.

Adult↗

Study of human neurovegetative and hematologic effects of environmental low-frequency (50-Hz) electromagnetic fields produced by transformers.

A survey of neurovegetative and hematologic disorders was conducted in a population (n = 13) exposed occupationally to environmental electromagnetic fields; the population was matched with 13 control subjects. The exposed subjects worked at least 8 h/d for 1-5 y in premises located above transformers and high-tension cables, and the subjects were submitted to low-frequency electromagnetic fields (i.e., 50 Hz) of 0.2 microT-6.6 microT. The subjects were matched with respect to socioeconomic category, sex, and age with a control population of subjects that worked in premises outside of the immediate vicinity of transformers or high-tension cables. The exposed population had a significant increase in degree of certain neurovegetative disorders (i.e., physical fatigue, psychical asthenia, lipothymia, decreased libido, melancholy, depressive tendency, and irritability). In addition, the population experienced a significant fall in total lymphocytes and CD4, CD3, and CD2 lymphocytes, as well as a rise in NK cells. Leukopenia and neutropenia were also observed in two persons permanently exposed to doses of 1.2-6.6 microT. The disorders disappeared when exposure stopped, and they reappeared on reexposure.

Adult↗

Macroamylasaemia, IgA hypergammaglobulinaemia and autoimmunity in a patient with Down syndrome and coeliac disease.

The association between macroamylasaemia and coeliac disease in Down syndrome with multiple autoimmune abnormalities has never been reported. A 40-year-old woman with a 15-year history of immunoglobulin A and immunoglobulin M hypergammaglobulinaemia, chronic diarrhoea, persistent mild aspartate aminotransferase (AST) elevation and anaemic syndrome was admitted to hospital because in the previous 3 months she had developed amenorrhoea, dizziness, alopecia, constipation, pallor and asthenia. Biochemical and immunological analyses showed macroamylasaemia. The patient presented clinical and intestinal histopathological features of coeliac disease. Immunological abnormalities included the presence of antigliadin, antiendomysium, antitransglutaminase, antinuclear, antismooth muscle and anti-SSA/Ro antibodies. Macroamylase resulted in a complex of amylase and immunoglobulin A. Later clinical follow-up of a gluten-free diet showed a transitory decrease in seric immunoglobulin A and macroamylase with persistent autoantibodies and AST elevation. An intestinal mucosal immune disorder could lead to coeliac disease and macroamylasaemia in a patient with Down syndrome presenting other immune alterations.

Adult↗

Stereotactic body radiation therapy for primary and metastatic liver tumors: A single institution phase i-ii study.

The feasibility, toxicity and tumor response of stereotactic body radiation therapy (SBRT) for treatment of primary and metastastic liver tumors was investigated. From October 2002 until June 2006, 25 patients not suitable for other local treatments were entered in the study. In total 45 lesions were treated, 34 metastases and 11 hepatocellular carcinoma (HCC). Median follow-up was 12.9 months (range 0.5-31). Median lesion size was 3.2 cm (range 0.5-7.2) and median volume 22.2 cm3 (range 1.1-322). Patients with metastases, HCC without cirrhosis, and HCC < 4 cm with cirrhosis were mostly treated with 3 x 12.5 Gy. Patients with HCC > or =4 cm and cirrhosis received 5 x 5 Gy or 3 x 10 Gy. The prescription isodose was 65%. Acute toxicity was scored following the Common Toxicity Criteria and late toxicity with the SOMA/LENT classification. Local failures were observed in two HCC and two metastases. Local control rates at 1 and 2 years for the whole group were 94% and 82%. Acute toxicity grade > or =3 was seen in four patients; one HCC patient with Child B developed a liver failure together with an infection and died (grade 5), two metastases patients presented elevation of gamma glutamyl transferase (grade 3) and another asthenia (grade 3). Late toxicity was observed in one metastases patient who developed a portal hypertension syndrome with melena (grade 3). SBRT was feasible, with acceptable toxicity and encouraging local control. Optimal dose-fractionation schemes for HCC with cirrhosis have to be found. Extreme caution should be used for patients with Child B because of a high toxicity risk.

Adult↗

A dose escalating study of oxaliplatin and high dose weekly leucovorin and 5-Fluorouracil in patients with advanced solid tumors.

PURPOSE: To determine the dose-limiting toxicities (DLTs) and the maximum tolerated doses (MTD) of L-OHP plus 5-FU and LV in patients with advanced solid malignancies. PATIENTS AND METHODS: Patients received escalated doses of L-OHP (starting dose 50 mg/m2) as a 2-hour IV infusion on Days 1 and 15, and LV (500 mg/m2 as a 2-hour IV infusion) followed by escalated doses of 5FU (starting dose 1,800 mg/m2) as a 22-hour continuous IV infusion on Days 1, 8, 15, 21 every 6 weeks. DLTs were evaluated in the first cycle. RESULTS: Fifty-two patients [median age: 66 years; PS (ECOG) 0-1 in 90 percent] were treated on 12 dose-levels. Five (10 percent) patients had received 2 prior chemotherapy regimens, 24 (46 percent) one, and 23 (44 percent) were chemo-naïve. The DLT was reached at the dose of LOHP 100 mg/m2 and 5FU 2,200 mg/m2. Dose-limiting events were G3 diarrhea, G3 asthenia, G4 neutropenia, and G4 thrombocytopenia. Grade 3 diarrhea was observed in 6 (12 percent) patients and Grade 3 fatigue in 6 (12 percent). One (2 percent) patient developed Grade 4 neutropenia and another (2 percent) Grade 4 thrombocytopenia. CONCLUSION: The MTD were L-OHP 95 mg/m2 on d1 and d15 and 5FU 2,200 mg/m2/week for 4 consecutive weeks every 6 weeks.

Adult↗

Combined chemo-immuno-hormonotherapy of advanced renal cell carcinoma.

Thirty-five patients (pts.) with advanced renal cell carcinoma were treated with a combination of vinblastine (5 mg/m2/IV) plus epirubicin (50 mg/m2/IV) every 3-4 weeks, alpha-2-A-interferon (9 x 10(6) U/IM 3 times in the 1st week, then 18 x 10(6) U/IM 3 times weekly), and medroxyprogesterone acetate (2,000 mg/os/day plus 500 mg IM/week). Thirty-one patients were males and 4 were females with a median age of 63 years (range 35-75) and median performance status of 70% (range 50-90%). We observed nine partial remissions (26%) with median duration of 40 weeks (range 20-232+). Fifteen pts. had no change (43%) while 11 pts. progressed (31%). The main side-effects were: leukopenia (29/35, 83%) with median nadir of 3,100 WBC/mm3 (range 510-3,990) and fever (32/35, 91%). Thrombocytopenia occurred in 4 pts. (11%), anemia in 5 (14%), asthenia in 12 (34%), nausea/vomiting in 12 (34%), alopecia in 8 (23%) and stomatitis in 3 (8.5%). Two patients stopped the therapy with medroxyprogesterone acetate because of muscular cramps. Median survival was 65 weeks (range 6-327+). We conclude that the combination of recombinant alpha 2A-interferon-vinblastine-epirubicin and medroxyprogesterone acetate has modest but definitive activity in patients with advanced renal cell carcinoma.

Adult↗

Between morality and repentance: recapturing "sin" for bioethics.

Distinguishing within "sin" the dimensions of anomia, hamartia, and asthenia makes it possible to analyze in greater detail the contrary manners in which traditional and post-traditional Christianities in this issue of Christian Bioethics endeavor to recapture what was lost when secular bioethics reconstructed the specifically spiritual-context-oriented normative commitments of Christianity in one-dimensionally moral terms. Various post-traditional attempts at securing moral orientation and resources for forgiveness, both of which secular bioethics finds increasingly difficult to provide, are critically reviewed. Their engagement of secular moral concepts and concerns, and even their adoption of an academically philosophical posture and language, is presented as responsible for their failure to adequately preserve what in traditional Christianity would count as prohibited vs. permitted, and advisable vs. non-advisable, or what would allow to resolve "tragic conflicts." The deeper reason for this failure lies in post-traditional Christianity's restricting the Christian life (with its central tension between love and the law) to what can be captured by cognitive categories. As the survey of several traditionally Christian accounts of sin in bioethics makes clear, both moral orientation (along with the resolution of "tragic" conflicts) and the sources of forgiveness are available, once that Christian life is framed in terms of persons' spirit-supported practical involvement in ascesis and liturgy, and once bioethical reflections are situated in the experiential context of such involvement.

Bioethics↗