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At least 973 records · Page 54Linked to original sources
PubMed1998

Weekly systemic combination of cisplatin and interferon alpha 2a in diffuse malignant pleural mesothelioma.

The treatment of diffuse malignant pleural mesothelioma (DMPM) remains grim. Neither surgery, radiotherapy nor chemotherapy can be considered as a standard therapy. Immunotherapy with interferon (IFN) in combination with chemotherapy may be an interesting new approach. In 13 consecutive patients with DMPM, we used a weekly combination of cisplatin (CDDP) (60 mg/m2; day 2) and IFN alpha 2a (6 MU/day; days 1-4) in a protocol of two cycles of 4 weeks on/4 weeks off followed by 3 weeks on/3 weeks off. Total treatment duration was thus 25 weeks. In responders, IFN as maintenance monotherapy was continued for a further 6 months. There were nine males and four females with an average age of 65.3 years (range 51-72 years). Eleven had epithelial, one had mixed and one had a sarcomatoid form of DMPM. Five patients were classified as stage II, six as stage III and two as stage IV, as per the International Mesothelioma Interest Group. Thirty-five cycles were administered with a median of three cycles/patient (range 0.75-4). The median total cumulative dose of CDDP was 596 mg/m2 (range 114-861) and that of IFN alpha 2a was 264 MU (range 72-336). Four patients received IFN maintenance therapy, one for 3 months and three for 6 months. One patient had a complete response, four had a partial response, six had a stable disease and the disease progressed in one. One patient was non evaluable for response. All patients were assessable for toxicity. Hematological toxicity was the most frequently observed but was manageable (grade 3 anemia in five patients, grade 3 thrombocytopenia in three patients, grade 3 neutropenia in five patients). Grade 1 renal toxicity was observed in six patients, grade 2-3 asthenia in six patients and an average 5-kg weight loss was noted in nine patients. In conclusion, systemic combination of CDDP and IFN alpha 2a in large doses is effective at the expense of non-negligible toxicity.

Aged↗
PubMed1999

Phase II study of paclitaxel and carboplatin for advanced non-small-cell lung cancer.

A prospective phase II study was conducted to determine the response, toxicity and survival rate of lung cancer patients treated with combination paclitaxel and carboplatin in stage IIIB and IV NSCLC. Eligible patients required measurable and/or evaluable diseases; performance status (ECOG) 0-2; no previous chemotherapy; adequate hepatic, renal and bone marrow function. Paclitaxel was administered at a dose of 200 mg/m2, 3 h infusion, followed by carboplatin at an AUC of 6. Treatment was repeated every 3 weeks for six courses. G-CSF 5 microgram/kg was subcutaneously injected during subsequent courses if there was grade 3-4 leucopenia or granulocytopenia in the previous course. From April 1996 through July 1997, 53 patients were enrolled; all are assessable for toxicity and response. The median age was 56 years (range, 20-77 years). Sixty four percent were male, 64% had adenocarcinoma and 62% had stage IV disease. Two hundred and seventy two courses were administered; 36 patients (68%) completed all six cycles. Two patients achieved a complete response (4%) and 27 patients achieved a partial response (51%), for an overall response rate of 55%. Sixteen patients had stable disease (30%) and 8 patients had progressive disease (15%). The median progression free survival time for all patients, stage IIIB and stage IV patients was 28 weeks (range, 18-37 weeks), 31 weeks (range 21-41 weeks) and 22 weeks (range 16-29 weeks), respectively. The median survival time and 1 year survival rate for all patients was 55 weeks (range, 51-59 weeks) and 55%, respectively. Stage IIIB patients had better median survival time and 1-year survival rate than stage IV patients (75 vs. 46 weeks, P = 0.007; 80% vs. 42%, P = 0.003). Grade 3 and 4 granulocytopenia, anemia and thrombocytopenia were observed in 25, 3, and 1%, respectively, of the 272 courses administered. G-CSF was required in 28% of the 272 courses. There were four episodes of febrile neutropenia (1.5%), three episodes of angina pectoris (1%) and one episode of anaphylaxis (0.4%). Other common toxicities, generally mild, included myalgia, arthralgia, peripheral neuropathy and asthenia. Most toxicities showed cumulative effect. Paclitaxel plus carboplatin is a moderately active regimen in advanced NSCLC. Toxicities of this regimen are well tolerated.

Adenocarcinoma↗
PubMed2000

Second-line treatment with gemcitabine and vinorelbine in non-small-cell lung cancer (NSCLC) cisplatin failures: a pilot study.

PURPOSE: This pilot study was designed to evaluate the efficacy and toxicity of the gemcitabine/vinorelbine combination in non-small-cell lung cancer (NSCLC) patients who had failed cisplatin-based first-line chemotherapy. PATIENTS AND METHODS: Eligible patients had refractory or resistant NSCLC, WHO performance status 0-2, adequate hematologic parameters and normal hepatic, renal and cardiac function. Gemcitabine (1200 mg/m2) was administered on days 1, 8 and 15; vinorelbine (25 mg/m2) was administered on days 1 and 8, every 4 weeks until patients experienced disease progression. RESULTS: From September 1997 to March 1998, 16 patients were enrolled (six: stage IIIB: ten: stage IV). All 16 patients were assessable for toxicity and evaluated for response. One complete (6.25%) response and no partial responses were observed. Median survival was 25 weeks (95% CI 19-30). A median of 3.31 courses per patient was administered, and the median interval between courses was 28 days. The median delivered dose was 664.85 mg/m2 per week of gemcitabine and 10.71 mg/m2 per week of vinorelbine, corresponding to a relative dose intensity of 0.73 and 0.85, respectively. Grade 2/3 thrombocytopenia occurred in 13 (24.52%) of 53 courses administered. Neutropenia Grade 2/3 occurred in 14 courses (26.41%). There were seven (13.20%) episodes of fever related to the drug administration. Mild asthenia was observed in six (37.5%) patients. Other toxicities were mild to moderate. CONCLUSION: These results suggest that this gemcitabine/vinorelbine combination is not an active salvage regimen in patients with refractory NSCLC. The combination merits further evaluation with modified regimens.

Adult↗
PubMedDate not supplied

Isolated glucocorticoid deficiency and ACTH receptor mutations.

Familial isolated glucocorticoid deficiency is a form of potentially lethal hereditary unresponsiveness to ACTH that manifests as primary adrenal insufficiency, usually without mineralocorticoid deficiency. Affected children commonly present with hyperpigmentation, recurrent hypoglycemia, chronic asthenia and failure to thrive within the first 2 years of life. Typically, they have deficient production of cortisol and adrenal androgens in the presence of markedly elevated ACTH levels, while renin and aldosterone levels are usually normal and responsive to activation of the renin-angiotensin axis. Clinical awareness of these syndromes is of considerable prognostic and therapeutic importance. The etiological involvement of the ACTH receptor gene in isolated glucocorticoid deficiency has been recently established in many, but not all, affected families. Several naturally occurring mutations of the ACTH receptor gene have been identified to date and have helped illuminate the mechanisms of ligand binding and signal transduction by this receptor. Discovery of the molecular defect(s) responsible for isolated glucocorticoid deficiency in cases with a normal ACTH receptor gene coding region and for the triple A syndrome (adrenal insufficiency, alacrima, achalasia) will hopefully provide further insight into the mechanisms of adrenocortical function and will increase the prospect of new therapeutic approaches.

Animals↗
PubMed2000

[Clinical features of respiratory tuberculosis and diagnosis delay].

OBJECTIVE: To make a descriptive analysis of the clinical characteristics of patients with pulmonary tuberculosis and find the time of diagnostic delay. DESIGN: Retrospective study. SETTING: Autonomous Community of Navarre. PATIENTS: 317 cases of pulmonary tuberculosis diagnosed between January 1 1993 and June 30 1996. RESULTS: The most commonly observed symptom was coughing (76.8%), followed by expectoration (63.8%) and high temperature (60.3%). The high percentages of high temperature, asthenia, anorexia and weight loss in HIV-infected patients stood out. The mean period of diagnostic delay was 36.9 to 58.5 days, with a median of 15 days. For 76.8% of patients the delay in diagnosis was under a month. CONCLUSIONS: Early diagnosis is essential in tuberculosis control, especially in cases transmitted by bacilli, since these are highly contagious for months.

Adolescent↗
PubMed2000

[Influence of the patient's gender in the management of anxiety/depressive profiles].

OBJECTIVES: To find whether the diagnosis-therapy approach of doctors to people with symptoms of anxiety-depression differs depending on whether the patient is a man or a woman. DESIGN: Crossover, descriptive study through a postal questionnaire, based on clinical cases. SETTING: Primary Care (PC) in Castilla-La Mancha. PARTICIPANTS: PC doctors working in the public domain. MEASUREMENTS AND MAIN RESULTS: We designed two models of questionnaire which only varied in the sex of the patient. Each model consisted of five clinical hypotheses, two on anxiety-depression and three others, whose aim was to mask the first two, on organic pathology. The sample was divided into two halves, with a different model of questionnaire placed in each half. We received back 273 (34.2%) of the 800 questionnaires sent out. Average age was 41, and 70.4% were men. In hypothesis 1, which analysed the therapeutic attitude to a patient with various episodes of atypical "knotting sensation" precordialgia, through ECG, normal examination and analysis, we found that in 77.2% of women, against 58.5% of men, treatment with anxiolytic drugs was prescribed (p < 0.01, chi 2 = 9.97). Psychological support at the consultation was opted for in 52.1% of women against 33.9% of men (p < 0.01, chi 2 = 7.89). However, doctors opted to refer to the cardiologist 9.5% of women against 24.5% of men (p < 0.01, chi 2 = 10.01). In hypothesis 2, doctors were asked about their first diagnosis of a smoking patient with asthenia, anorexia, difficulties in concentration and various months of non-specific sick feelings. 55.7% of women were diagnosed as having an anxiety-depression profile against 34.3% of men (p < 0.01, chi 2 = 13.67). The doctor's sex in hypothesis 2 led to no significant differences. CONCLUSIONS: The approach of primary care doctors to patients with symptoms of anxiety and depression differs with the sex of the patient. We prescribe more anxiolytic drugs, give more psychological support and think more of functional causes when our patient is a woman.

Adult↗
PubMed2005

[Biological and pathological data in a case of yellow fever imported from the Gambia].

A 47-year-old woman developed fever and asthenia 1 week after having traveled to Gambia. Four days after the first symptoms, she was transferred to the intensive care unit. She was in poor general condition, with anuria and jaundice. Liver function tests showed severely disturbed function and the diagnosis of yellow fever infection was made by RT-PCR in this patient who had not been vaccinated. Encephalopathy appeared on day 7 and death occurred on day 8 due to massive gastrointestinal bleeding. At autopsy, extensive panlobular liver necrosis was observed together with the presence of numerous Councilman bodies in the three hepatic zones.

Anuria↗
PubMed2000

[Hereditary hemochromatosis].

INTRODUCTION: Hereditary hemochromatosis is a fairly common disease in the Caucasian population, with a prevalence estimated at between 1.5 to 3/1,000 inhabitants. Over the past few years, its symptomatology has altered; at present, its clinical aspect with diabetes mellitus, cirrhosis, and darker skin pigmentation only constitutes 10% of new cases of this disease. CURRENT KNOWLEDGE AND KEY POINTS: In 1996, the discovery of the C282Y mutation in the HFE gene radically altered the diagnostic approach to hereditary hemochromatosis. At present, any patient admitted with an isolated case of asthenia, or with arthralgia or hypertransaminasemia should be examined via transferrin-saturation testing: if the transferrin saturation coefficient is > 45%, then the presence of the C282Y mutation should be investigated to confirm the diagnosis of hemochromatosis. A liver biopsy is no longer necessary to establish the diagnosis, but this is still useful in cases of possible cirrhosis, which is the main risk factor for hepatocellular carcinoma. Phlebotomy remains the sole recommended treatment, and should be undertaken in a case-specific manner. Family screening should be carried out for all first-degree relatives for every new case that is diagnosed. FUTURE PROSPECTS AND PROJECTS: The discovery of the HFE gene has permitted hereditary hemochromatosis to be easily differentiated from other forms of hepatic iron overload including a new syndrome, dysmotabolic hepatosiderosis. Casos of homozygotic C282Y without hepatic iron overload have been described, but the clinical outcome of some of these cases requires further study, and adds to the controversy on whether systematic population screening should be made available.

Amino Acid Substitution↗
PubMed2001

[Clinical diagnosis of overtraining using blood tests: current knowledge].

PURPOSE: Overtraining results from an imbalance between training load-induced fatigue and organism's recovery abilities. Its etiology is complex and to date there is no useful clinical diagnostic tool. The purpose of this review is to discuss the blood chemistry parameters potentially useful for diagnosing overtraining in athletes. CURRENT KNOWLEDGE AND KEY POINTS: Chronic alterations of the myocyte structure may cause high plasma concentration increases of myoglobin, troponin I and creatine kinase enzyme, resulting in chemical and/or mechanical aggression. Monitoring reactive oxygen species' activity appears to be a good tool for evaluation of the metabolic stress level experienced by skeletal muscles. In energetic metabolism, a succession of chronic glycogen depletions might change the use of amino acids and lipids, inducing transient but severe hypoglycemia during exercise. A higher oxidation of circulating glutamine might cause immunosuppression (lower reactivity to inflammations and cellular traumatisms), inhibiting alarm signals during acute training. A higher branched-chain amino acid oxidation might favor free tryptophan's entry into the cerebral area, enhancing serotonin synthesis. As a consequence, asthenia and a loss of sensitivity to muscular and tendon traumatism might appear. Exercise anemia might also be a worsening factor of the physiological situation of the tired athlete, inducing predisposition to overtraining by the lower inflammation reactivity of depleted hepatic and muscular proteins. FUTURE PROSPECTS AND PROJECTS: Early diagnosis of overtraining diagnosis may be established only from a battery of analyses, which should include the whole of the potential parameters. These remain unpredictable and do not allow systematic determination of new cases. Only a longitudinal study of the physiological situation appears to allow the necessary conditions for detecting overtraining in the early stages of its process for each subject.

Biomarkers↗
PubMed2003

[Severe lactic acidosis in HIV-infected patients treated with nucleosidic reverse transcriptase analogs: a report of 9 cases].

PURPOSE: Symptomatic lactic acidosis requiring intensive care is a rare and severe adverse event related to the mitochondrial toxicity of the nucleoside analog reverse transcriptase inhibitors (NRTIs). METHOD: We retrospectively investigated the clinical and biological features of HIV-infected patients who developed severe lactic acidosis syndrome at the University teaching hospital of Bordeaux and the regional community hospital, during 1996-2000. RESULTS: Nine patients were identified (incidence: 0,9/1000 NRTI treated patient-years), 4 men and 5 women with a median age of 36 years. They had a moderate immunodeficiency (median CD4+ T lymphocyte counts: 197/mm(3)) and only one of them presented a virological failure. The causes of hospital admission were abdominal pain (n = 6), dyspnea (n = 6), asthenia (n = 5), jaundice (n = 4), and vomiting (n = 2). Hepatomegaly was present in 6 patients. Lactic acidosis was found in all cases: median pH: 7.28, bicarbonate: 12 mmol/l, anion gap: 27 mEq/l, plasma lactic acid: 13 mmol/l. Cytolysis (n = 8), cholestasis (n = 6), hepatic failure (n = 4), rhabdomyolysis (n = 4) and pancreatitis (n = 2), were also present. Despite medical intensive care, seven patients died. The only two post-mortem examinations revealed severe hepatic steatosis. Median duration of NRTI therapy was 4 years. At presentation, five patients were receiving lamivudine, five didanosine, four stavudine and three zidovudine. Six patients were coinfected by HCV and/or HBV, four had chronic renal failure and five an immediately preceding infectious disease. CONCLUSION: The prognosis of lactic acidosis is severe. Nucleosid-analog therapy needs clinical and biological monitoring, specially in patients with comorbidities.

Abdominal Pain↗
PubMed1999

[Macrophagic myofasciitis: description and etiopathogenic hypotheses. Study and Research Group on Acquired and Dysimmunity-related Muscular Diseases (GERMMAD) of the French Association against Myopathies (AFM)].

PURPOSE: A new type of inflammatory myopathy of unknown etiology has recently been described in France. The myopathy, called macrophagic myofasciitis, had never been described in the literature. METHODS: In December 1998, 35 cases of macrophagic myofasciitis were reported, showing an increase in its incidence since the description of the first case in 1993. The first 22 cases are described. RESULTS: The 22 patients were each referred with a presumptive diagnosis of either polymyositis (11 patients), polymyalgia rheumatica (5 patients), mitochondrial cytopathy (4 patients), or congenital myopathy or muscle dystrophy (1 patient for each). Clinical symptoms included myalgias (91%), arthralgias (68%), marked asthenia (55%), muscle weakness (45%), and fever (32%). Laboratory findings included elevated CK levels (50%) and a marked increased in the erythrocyte sedimentation rate (37%). Electromyographic recordings showed the existence of myopathy (35%). Muscle biopsy showed a unique pattern characterized by: (i) centripetal infiltration of the epimysium, perimysium and perifascicular endomysium by non epitheloid, cells of the monocyte/macrophage lineage (CD68+, CD1a-, S100-) with both large cytoplasm and PAS-positive content; (ii) absence of necrosis, of both epithelioid and giant cells, and of mitotic figures; (iii) occasional CD8+ T-cells; and, (iiii) minimal myocyte suffering. The disease symptoms were easily distinguishable from those of sarcoid myopathy and fasciitis-panniculitis syndromes. Infectious diseases known to be associated with reactive histiocytosis, including Whipple's disease, Mycobacterium avium intracellulare infection and malakoplakia, could not be documented. Patients' condition improved under corticosteroid therapy, associated or not with non-specific antibiotic therapy. CONCLUSION: A new inflammatory muscle disorder of unknown etiology, characterized by a distinctive pathological pattern of macrophagic myofasciitis, is emerging in France. Diagnosis is based on muscular biopsy. Numerous clinical, epidemiological and etiopathologic studies initiated by the GERMMAD (Groupe d'études et de recherche sur les maladies musculaires acquises) are in progress.

Adult↗
PubMed1999

Course and outcome of tubulointerstitial nephritis and uveitis syndrome.

We report here the clinical features and outcomes of 10 patients, aged 11 to 21 years (median, 13.0), with idiopathic tubulointerstitial nephritis (TIN) and uveitis syndrome (TINU syndrome). The initial symptoms were visual impairment in 7 patients and prolonged fever, anemia, or asthenia in 4 patients. An increase in urinary beta(2)-microglobulin was noticed at the initial checkup in all patients, including 2 patients who showed the normal ranges of 24-hour protein excretion. Creatinine clearance was decreased in 8 patients. TIN was found simultaneously with ocular symptoms in 7 patients and preceded these symptoms in the remaining 3 patients. Percutaneous renal biopsy indicated tubulointerstitial lesions in varying degrees. The histological grade of TIN was correlated with urinary beta(2)-microglobulin levels. Systemic steroid therapy was performed in 7 patients because of the progression of uveitis. The 10 patients were followed-up for 16 to 94 months (median, 31.0 months). In all patients, creatinine clearance recovered to the normal ranges (>/=70 mL/min/1.73 m(2)) mostly within 1 year. Urinary beta(2)-microglobulin excretion gradually declined but was slightly elevated in 4 patients at the latest checkup. Uveitis recurred in all 10 patients, which did not affect the renal status. Our findings indicate that early referral of patients from ophthalmologists and determination of beta(2)-microglobulin in the urine is helpful for the early discovery of TINU syndrome. In children and adolescents with this syndrome, TIN spontaneously resolves and its long-term prognosis is good, but uveitis often relapses. Systemic steroids may be required for uveitis, but not for TIN.

Adolescent↗
PubMed2003

Effects of topiramate in patients with cerebellar tremor.

PURPOSE: To evaluate the safety and potential beneficial effect of topiramate (TPM) as monotherapy or adjunctive therapy to carbamazepine (CBZ) in patients with cerebellar tremor. METHODS: Nine patients with cerebellar tremor participated a 4-week, open-label, prospective-controlled trial. TPM was given as monotherapy (n=7 cases), or in combination with CBZ (n=2 cases), at dosages ranging from 25 mg twice daily to 100 mg twice daily. The severity of tremor was assessed clinically on a 0-4 scale, by tremograms, by the Patients Global Impressions Scale, and by a "free writing" task at baseline and after 4 weeks. RESULTS: TPM was discontinued in four patients due to adverse effects (sedation=2; cognitive impairment=2; increased aggressiveness=2; asthenia=1). During TPM, all patients improved. The mean tremor amplitude, compared with the baseline period, was reduced from 20% to 75%. After TPM, mean clinical scores of postural tremor and kinetic tremor decreased from 2.1+/-0.8 to 0.9+/-0.9 and from 2.1+/-1 to 1.4+/-1 (P<.05), respectively. All patients with head tremor improved. Writing, eating, and drawing were improved with TPM. Four patients chose to keep taking the drug. CONCLUSIONS: Our study indicates that TPM may be useful for the management of cerebellar tremors. A prospective placebo-controlled trial of TPM in this kind of tremor is warranted. TPM dosages should be titrated slowly to avoid the potential side effects of the drug. The range and the frequency of adverse events might limit the clinical usefulness of TPM.

Adult↗
PubMed2002

Sarin: health effects, metabolism, and methods of analysis.

Sarin (O-isopropylmethylphosphonofluoridate) is a highly toxic nerve agent produced for chemical warfare. Sarin is an extremely potent acetylcholinesterase (AchE) inhibitor with high specificity and affinity for the enzyme. Death by sarin is due to anoxia resulting from airway obstruction, weakness of the muscles of respiration, convulsions and respiratory failure. The main clinical symptoms of acute toxicity of sarin are seizures, tremors and hypothermia. Exposure to sarin during incidents in Japan in 1994, 1995 and 1998, and possible exposure to low levels of sarin during the Gulf War, resulted in the deaths and injury of many people in Japan and caused possible long-term health effects on Gulf War veterans. Symptoms related to sarin poisoning in Japan still exist 1-3 years after the incident and include fatigue, asthenia, shoulder stiffness and blurred vision. Sarin produced seizures in rats and pigs. Recent studies showed that long-term exposure to low levels of sarin caused neurophysiological and behavioral alterations. Toxicity from sarin significantly increased following concurrent exposure to other chemicals such as pyridostigmine bromide. Further research to examine effects of sarin on the cellular and the molecular levels, gene transcription, endocrine system as well as its long-term impact is needed.

Acetylcholinesterase↗
PubMed1985

Adrenocortical insufficiency.

Adrenocortical insufficiency causes difficulty in diagnosis and morbidity out of proportion to its rarity, because of the non-specific, multi-system nature of the clinical features. Most of these are due to cortisol deficiency. Prominent features are well-known ones such as weight loss and asthenia, and hypoglycaemia. Less prominent in recent accounts are those due to failure of cellular sodium export and to vasopressin excess, which are frequent and clinically significant. For this reason, the clinical features of isolated ACTH deficiency, isolated glucocorticoid deficiency and Addison's disease overlap greatly. In addition, cortisol deficiency has secondary endocrine effects, e.g. glucocorticoid-reversible hypothyroidism, hyperprolactinaemia and hypercalcaemia. Further overlap between the various steroid insufficiency syndromes occurs because of the association of various organ-specific autoimmune endocrinopathies with Addison's disease. Over 80% of Addison's disease is of the autoimmune type, though almost any systemic destructive process can cause similar steroid insufficiency. Demonstration of adrenal insufficiency requires various combinations of tetracosactrin adrenal stimulation tests, and hypoglycaemia or equivalent tests, if the cause is ACTH deficiency but the correct test can only be chosen to suit a firm clinical diagnosis. The treatment of adrenocortical insufficiency is described.

Addison Disease↗
PubMed1998

Host metabolism: a target in clinical oncology?

The presence of the tumour induces important metabolic changes in the cancer patient which are not merely due to the fact that the tumour acts as a parasite, thus depleting the host of nutrients, but that are mainly the result of both tumoral and humoral mediators. The new metabolic status of the cancer patient may lead to cancer cachexia (a pathological state characterized by weight loss together with anorexia, weakness, anaemia and asthenia) which represents one of the worst effects of malignancy, accounting for nearly a third of cancer deaths. The complications associated with the appearance of the cachectic syndrome affect both the physiological and biochemical balance of the patient and have effects on the efficiency of the anticancer treatment, resulting in a considerably decreased survival time. At the metabolic level, cachexia is associated with loss of skeletal muscle protein together with a depletion of body lipid stores. The present study emphasizes the fact that neutralizing some of the metabolic changes in the patient may be an essential therapeutic strategy in controlling tumour growth and improving survival.

Anorexia↗
PubMed2002

Hypofractionated and accelerated radiotherapy with cytoprotection (HypoARC): a short, safe, and effective postoperative regimen for high-risk breast cancer patients.

PURPOSE: Although the role of radiotherapy (RT) after mastectomy in reducing the local relapse rate is well established, its impact on overall survival is strongly questioned. Up to 70% of patients will not benefit from additional RT, and a "wait and see" policy is often adopted. Establishment of short, still safe, and effective RT regimens would render adjunctive radiotherapy more appealing. We evaluated the toxicity and efficacy of a Hypofractionated and intensively Accelerated RT regimen supported with amifostine Cytoprotection (HypoARC) in a cohort of 72 high-risk breast cancer patients treated with modified mastectomy or conservative surgery and FEC (5-fluorouracil/epirubicin/cyclophosphamide) chemotherapy. PATIENTS AND METHODS: A high dose of amifostine, 1,000 mg, was given as a 5-min i.v. infusion before each of the 12 consecutive fractions of RT (4 x 3.5 Gy/fraction and 8 x 4 Gy/fraction, 1 fraction/day, 5 fractions/week). The breast or chest wall, as well as supraclavicular and axillary area, was included in the RT fields. The follow-up of patients ranged from 18 to 42 months (median, 28 months). Alkaline phosphatase (AF) expression was assessed immunohistochemically in normal and cancerous breast tissues. RESULTS: Ninety-two percent of patients successfully completed the regimen, the only side effects being mild nausea and asthenia. In 7% of patients, amifostine was interrupted because of a rash/fever reaction. A dramatic reduction in acute skin toxicity was noted (p < 0.0001). Acute pneumonitis, as well as late toxicity in breast, chest wall, axillary, and lung tissue, was lower with the HypoARC regimen, although not significantly, than with the standard fractionation regimen used to treat two matched control cohorts. Both HypoARC and standard RT significantly reduce the local relapse rate (p < 0.0001), although the local relapse-free and overall survival times were marginally better for the HypoARC group of patients (p > 0.09). AF showed a mixed nuclear/cytoplasmic pattern of expression in the epithelial, endothelial, and stromal component of the normal breast and benign lesions, whereas an impressive loss of AF expression was noted in in situ and invasive breast cancer and tumoral stroma. CONCLUSIONS: The HypoARC regimen is convenient for both patients and radiotherapy departments. The regimen is well tolerated and shows a significantly better profile in terms of early toxicity; a reduced rate of late sequel may be expected. The local relapse rate is as low as that expected from conventional RT. The absence of AF expression in cancer cells and tumoral stroma is probably a major reason for the selective protection of normal breast tissue by amifostine.

Adult↗
PubMed1996

Hormone replacement therapy: clinical benefits and side-effects.

Beside well-established clinical benefits, the current doses of oestrogens may induce clinical side-effects leading to non-compliance and loss of efficacy. During a normal menstrual cycle the incidence of any cyclic discomfort is consistently reported to be lowest during the mild-follicular phase when plasma E2 remains between 60 and 150 pg/ml. The incidence of pregnancy-like symptoms such as bloating, breast tenderness and mood swings tends to increase in mid-luteal phase when E2 increases upto 150 pg/ml. On the other hand incidence of asthenia, sleep disturbances, depressive mood, headaches and migraines increase during perimenstrual days when E2 drops to 40 pg/ml or below. Accordingly experimental and human studies in castrated animals and postmenopausal women suggest that plasma E2 around 100 pg/ml is optimal for treatment of hot flushes, prevention of bone loss and cardiovascular protection. Due to large interindividual variation in estrogen clearance rate, it is unlikely that any standardized unique dose of oral or non-oral formulations will reproduce the optimal levels in all postmenopausal users. Efforts for individual titration are mandatory to improve compliance and actual efficacy on a long term. Because older postmenopausal women tend to have a better clinical tolerance to low E2 levels, objective markers of efficacy should also be identified when the aim of HRT is the prevention of osteoporosis or vascular diseases. In addition clinical and metabolic side-effects related to added progestins can be substantially reduced by the use of lower dose inducing amenorrhea and by progesterone instead of synthetic steroids.

Adult↗