Etanercept for the treatment of severe childhood psoriasis.
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Adolescent↗
Biomedical subjects
A Mazzotta
Publications and source records attributed to A Mazzotta.
Treatment of erythrodermic psoriasis with etanercept.
BACKGROUND: Severe variants of psoriasis, such as erythrodermic psoriasis, may be associated with serious morbidity and mortality. Current treatment options for erythrodermic psoriasis are limited, unsatisfactory and potentially associated with organ-specific toxicity. Recently, a new class of agents, targeted biological therapies, has emerged. Etanercept is a recombinant human fusion protein acting as a competitive inhibitor of tumour necrosis factor-alpha. The safety and efficacy of etanercept have been widely demonstrated in psoriatic arthritis and moderate to severe plaque-type psoriasis. OBJECTIVES: To assess the efficacy and tolerability of etanercept in the treatment of erythrodermic psoriasis over a period of 24 weeks. METHODS: Ten patients, eight men and two women, were selected to receive etanercept 25 mg subcutaneously twice weekly. The Psoriasis Area and Severity Index (PASI) score, ranging from 0 to 72, was used to assess the severity of disease. RESULTS: Etanercept was well tolerated and led to a significant reduction in the severity of disease over the period of treatment. After 24 weeks, the mean PASI score decreased from 39.1 (baseline) to 5.1. At week 12, five of 10 (50%) patients achieved an improvement of PASI score from baseline exceeding 75%. At week 24, six of 10 patients (60%) achieved or maintained an improvement of PASI score from baseline exceeding 75% while two patients (20%) maintained an improvement of between 50% and 75%. CONCLUSIONS: In this study, etanercept has been demonstrated to be an effective treatment for erythrodermic psoriasis, providing a safe and convenient alternative to current therapies.
Adult↗
Safety and efficacy study on etanercept in patients with plaque psoriasis.
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Adult↗
Angiotensin II activates extracellular signal regulated kinases via protein kinase C and epidermal growth factor receptor in breast cancer cells.
Angiotensin II (Ang II) induces, through AT1, intracellular Ca(2+) increase in both normal and cancerous breast cells in primary culture (Greco et al., 2002 Cell Calcium 2:1-10). We here show that Ang II stimulated, in a dose-dependent manner, the 24 h-proliferation of breast cancer cells in primary culture, induced translocation of protein kinase C (PKC)-alpha, -beta1/2, and delta (but not -epsilon, -eta, -theta, -zeta, and -iota), and phosphorylated extracellular-regulated kinases 1 and 2 (ERK1/2). The proliferative effects of Ang II were blocked by the AT1 antagonist, losartan. Also epidermal growth factor (EGF) had mitogenic effects on serum-starved breast cancer cells since induced cell proliferation after 24 h and phosphorylation of ERK1/2. The Ang II-induced proliferation of breast cancer cells was reduced by (a) Gö6976, an inhibitor of conventional PKC-alpha and -beta1, (b) AG1478, an inhibitor of the tyrosine kinase of the EGF receptor (EGFR), and (c) downregulation of 1,2-diacylglycerol-sensitive PKCs achieved by phorbol 12-myristate 13-acetate (PMA). A complete inhibition of the Ang II-induced cell proliferation was achieved using the inhibitor of the mitogen activated protein kinase kinase (MAPKK or MEK), PD098059, or using Gö6976 together with AG1478. These results indicate that in human primary cultured breast cancer cells AT1 regulates mitogenic signaling pathways by two simultaneous mechanisms, one involving conventional PKCs and the other EGFR transactivation.
Angiotensin II↗
[Optimization of extracorporeal dialytic treatment: on-line hemodiafiltration].
The study evaluates the potential of high ultrafiltration on-line hemodialfiltration (HDF) as a means of achieving the goals of extracorporeal RDT: the removal of small and medium-sized molecules, vascular stability and biocompatibility. The removal of small molecules was correlated with the UF rate and therefore with reinfusate volume. Medium-sized molecules were only removed from high permeability synthetic membranes in HD, but to a greater extent in HDF because of higher absorption. Vascular stability during the dialytic session is improved by convective processes, as is confirmed by a low prevalence of arterial hypertension in HDF patients. This suggests that HDF facilitates the achievement of dry body weight and therefore an improved correction of hydrosaline retention which is the main cause of hypertension in RDT patients. The biocompatibility of the dialytic system depends on the membrane and the dialysate. Synthetic membranes were shown to be much less toxic than cellulosic membranes and ultrapure dialysate was a useful aid to reduce the risk of inflammatory stimuli. On-line HDF associated the value of low-cost sterile dialysate-reinfu sate with a highly efficient and well tolerated technique.
Hemodiafiltration↗
Overdiagnosis of prostate carcinoma by screening: an estimate based on the results of the Florence Screening Pilot Study.
OBJECTIVES: To estimate overdiagnosis (detection of latent carcinomas) as a consequence of screening for prostate cancer. DESIGN: Based on actual screen (first or repeat) detected and interval prostate cancer rates observed in the Florence screening pilot study, a scenario was simulated where males aged 60 years (or 65) had six biennal screens and were followed up for four years. Overdiagnosis was determined as the proportional excess of cancers detected by screening with respect to that expected in its absence. SETTING: City of Florence, Italy, from 1992 through 1995. POPULATION: 2,740 resident males, aged 60 to 74 years. RESULTS: Overdiagnosis was estimated to be 51% (95% confidence limits: 44%-55%) or 93% (85%-101%) for age 60 or 65 at entry. Comparison with other screening experiences obtaining higher detection rates suggests that a more aggressive screening approach could be associated with overdiagnosis estimates as big as 200%-250%. CONCLUSIONS: Screening for prostate cancer is associated with a relevant risk of overdioagnosis. As latent carcinomas can not be presently identified, this would lead to overtreatment in most overdiagnosed cases. The negative consequences of overdiagnosis (knowledge of having a cancer) and of overtreatment (impotence, incontinence, perioperatory death) may be extremely serious. In absence of any scientific evidence of screening benefits (if any) screening should not be recommended as a current practice, but should be limited to prospective controlled studies designed to assess its cost-effectiveness.
Aged↗
[Magnesium hydroxide in idiopathic calcium nephrolithiasis].
BACKGROUND: While in vitro the protective effect of magnesium on calcium oxalate crystallization is well known, its clinical relevance in calcium nephrolithiasis is still debated. Therefore, the clinical and metabolic effects of magnesium hydroxide therapy were evaluated in calcium stone formers. METHODS: Nine patients (7 M, 2 F), selected for a low urinary magnesium excretion (uMg 56 +/- 12 mg/day), were given Mg hydroxide (500 mg/day), with clinical and metabolic controls at 3, 12 and 18 months. RESULTS: Urinary Mg/uCreat increased throughout the study; uOx/uCreat decreased significantly; uCa/uCreat increased but not significantly. The stone recurrence rate decreased from 0.75 to 0.11 stones/year/patient, throughout the study period. The decrease of uOx is considered a more important risk factor in calcium stone patients than a similar uCa change; it may be due to a reduced intestinal Ox absorption, for the formation of insoluble and not absorbed Mg oxalate. CONCLUSION: In conclusion, Mg hydroxide therapy was encouraging in patients with calcium nephrolithiasis and low uMg; nevertheless a longer period of treatment is needed to confirm these data.
Calcium↗
Cost analysis in a population based screening programme for colorectal cancer: comparison of immunochemical and guaiac faecal occult blood testing.
OBJECTIVE: To compare the costs of colorectal cancer (CRC) screening by two faecal occult blood tests (FOBT)-namely, Hemoccult (guaiac based) and reversed passive haemagglutination (RPHA) tests. RPHA was interpreted according to two positivity thresholds (+ or +/-). METHODS: Attenders performed both tests. Subjects with a positive FOBT test were invited to have a complete exploration of the colon. The total costs for every 10,000 screened subjects and costs for each unit of result (screened subject, or patient with adenoma/s or cancer detected) were calculated for both tests. RESULTS: 8353 subjects were enrolled. A total of 2109 repeated screening after two years. RPHA(+ and +/-) showed the highest and RPHA(+) the lowest positivity rate at first screening. The Hemoccult positivity rate was highest at repeat screening. Total costs of screening by RPHA(+ and +/-) were highest as this method had the highest recall rate. Screening by RPHA(+) was the least costly. Costs for each screened subject were highest for RPHA(+ and +/-) and lowest for RPHA(+). Costs for each cancer detected were lowest for RPHA(+) and highest for Hemoccult or RPHA(+ and +/-) in subjects aged > 49 or < 50, respectively. Costs for subjects with detected adenoma/s of > 9 mm were lowest for RPHA(+ and +/-) and highest for Hemoccult. At repeat screening total costs of RPHA(+ and +/-) were lower than at first screening, whereas for each subject with cancer or adenoma/s costs were increased. CONCLUSIONS: Our data confirm that screening by RPHA is more cost effective than by Hemoccult.
Adult↗
Screening by ultrasonography for endometrial carcinoma in postmenopausal breast cancer patients under adjuvant tamoxifen.
Seven-hundred thirty-seven asymptomatic postmenopausal breast cancer patients under long-term adjuvant tamoxifen therapy (average, 50 months) were screened by endometrial ultrasonography. Abnormal endometrial thickness (6 mm or larger) was observed in 209 subjects and was significantly associated with patients' age and duration of tamoxifen therapy. Outpatient endometrial biopsy was recommended in presence of abnormal endometrial thickness: 25 subjects refused biopsy, whereas 76 were not biopsied because of cervical stenosis and were followed-up by repeat sonography. Of 108 biopsied subjects, one case of endometrial carcinoma (as expected in the screened cohort according to age-specific incidence rates provided by the regional cancer registry) and one case of endometrial hyperplasia were histologically confirmed, whereas endometrial atrophy was evident in the remaining cases. No other case of endometrial carcinoma has been recorded so far in the studied cohort according to the local cancer registry and no further change of the endometrium has been observed at sonographic follow-up. The cohort will be followed-up by repeat annual endometrial sonography. Thus far, we did not find evidence of increased prevalence of endometrial pathology (carcinoma or hyperplasia) which may be ascribed to tamoxifen therapy. The apparent increase in endometrial thickness observed at sonography might be explained by tamoxifen-induced changes of endometrial stroma and myometrium, misinterpreted as hyperplasia, while causing no real epithelial disease.
Aging↗
Immunochemical vs guaiac faecal occult blood tests in a population-based screening programme for colorectal cancer.
Two faecal occult blood tests (FOBTs), Hemoccult II (guaiac based) and Hemeselect (immunochemical) were compared in a population screening for colorectal cancer on 24 282 subjects aged 40-70. Hemeselect was interpreted according to a lower (+ and +/-) and a higher (+) positivity threshold. A total of 8008 compliers were enrolled in the study. Positivity rates: Hemoccult = 6.0%, Hemeselect (+ and +/) = 8.2%, Hemeselect (+) = 3.1%. Among FOBT-positive subject complying with the diagnostic work-up, 22 had colorectal cancer (17 Hemeselect-positive (+), four Hemeselect-borderline (+/-), 15 Hemoccult-positive) and 166 subjects had adenomas (62 Hemeselect(+), 56 Hemeselect-borderline (+/-), 79 Hemoccult-positive) were detected. The positive predictive values (PPVs) for cancer were as follows: Hemoccult = 3.7%, Hemeselect (+ and +/-) = 3.8%, Hemeselect (+) = 8.4%. The PPVs for adenoma(s) were: Hemoccult = 19.7%, Hemeselect (+ and +/-) = 21.4%, Hemeselect (+) = 30.5%. The specificity for cancer was: Hemoccult = 94.1%, Hemeselect (+ +/-) = 92%, Hemeselect (+) = 97.1%. Ratios between detection rates of each test and expected incidence of colorectal cancer suggest that Hemoccult anticipates cancer diagnosis by approximately 2 years on average whereas the mean diagnostic anticipation of Hemeselect ranges between 2.5 and 3.2 years. Hemeselect is superior to Hemoccult as it is at least as effective but more efficient and acceptable than guaiac testing. Further evaluation of Hemeselect cost-effectiveness and sensitivity is needed in order to assess the optimal threshold of positivity and screening frequency.
Adult↗
Sensitivity of screening sigmoidoscopy for proximal colorectal tumours.
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Adenoma↗
Comparative analysis of results of guaiac and immunochemical tests for faecal occult blood in colorectal cancer screening in two oncological institutions.
The performances of three faecal occult blood tests, rehydrated Hemoccult (HOR), Hemoccult sensa (HOS) and Hemeselect (HSEL) on 3 days were compared in 1,725 subjects consecutively recruited in two oncological institutions in Milan and Florence. Significant differences between the results were evident as far as HOR positivity rates (7.5% vs 4.0%, respectively) and specificity (94.3% vs 97.5%, respectively) are concerned. Overall positivity rates of HOR, HOS and HSEL were 5.9%, 5.4% and 12%, respectively; significant differences were evident between HSEL and each of the two guaiac tests. Cancer was detected in eight subjects, adenoma/s in 47. Specificity estimates were 95.8%, 90.2% and 90.5% for HOR, HOS and HSEL, respectively; significant differences were evident between HSEL and the other two tests. No significant difference between tests was evident for sensitivity or positive predictive values for cancer or adenomas. In the CSPO (Florence) population (1,223 subjects; five with cancer, 16 with adenoma/s) the performances of 1-day HSEL testing were determined on the basis of the first faecal sample only and compared with 3-day HOR, HOS and HSEL testing. The positivity rates of 1-day HSEL, 3-day HOR, HOS and HSEL testing were 7.0%, 5.0%, 5.5% and 12.9%, respectively. Only 3-day HSEL positivity rate was significantly higher than 1-day HSEL. One-day HSEL specificity (94.9%) was significantly higher than 3-day HSEL (90.0%), whereas no significant difference was seen between 1-day HSEL, HOR (96.5%), and HOS (96.1%) specificity. No significant difference between tests is evident in the CSPO population as far as positive predictive values and sensitivity for cancer and adenomas are concerned.(ABSTRACT TRUNCATED AT 250 WORDS)
Adenoma↗
[Comparison between 2 techniques of screening for prostatic carcinoma. Rectal exploration and transrectal ultrasonography vs. prostate specific antigen].
We report the results of two pilot studies for the early detection of prostatic carcinoma in resident men aged 60-75 years, using combined digital rectal examination (DRE) and transrectal ultrasonography (TRUS) versus prostate-specific antigen (PSA; cutoff: 4 ng/ml) as screening tests. Both screening protocols exhibited high cancer detection rates (DRE + TRUS = 1.82%, PSA = 1.67%), with a high prevalence/incidence ratio (observed/expected ratio: DRE-TRUS = 13.8:1, PSA = 11.3:1) and a diagnostic anticipation of about 6-7 years. Stage (DRE + TRUS: A = 0%, B = 69%, C-D = 31%; PSA:A = 14%, B = 77%, C-D = 9%) and grading distribution (no case with Gleason score < 5) suggests that most screen-detected cancers were clinically assessable but the extent of overdiagnosis of latent carcinomas cannot be estimated. Both screening protocols proved to be cost-effective (biopsy rate: DRE + TRUS = 2.7%, PSA = 2.8%; cost per screened subject: DRE + TRUS = L. 33,750, PSA = L. 30,400; cost per cancer detected: DRE + TRUS = L. 1,854,000, PSA = L. 1,817,500) but screening by PSA was much better accepted (attendance rate: DRE + TRUS = 33.7%, PSA = 66.9%), which makes it the screening test of choice for controlled studies on screening efficacy. This study allows no definitive conclusions to be drawn on screening efficacy but confirms only that screening is feasible at a reasonable cost and yields high diagnostic anticipation. Whether this benefits the screened population is currently debated and needs to be confirmed by controlled studies. Screening may have upsetting negative outcomes such as overdiagnosis, overtreatment, increased treatment-related mortality rates and worsened quality of life, and there is no evidence supporting the recommendation of screening as a routine practice.
Aged↗
[Can malnutrition be prevented in patients on chronic extracorporeal dialysis?].
In the attempt to prevent malnutrition, a seven year longitudinal evaluation was carried out in 24 RDT patients in order to assess the efficacy of the following strategy: 1) Counseling for an adequate physical activity and a high caloric intake limiting dietary restrictions to fluids, salt and fruit. 2) Improvement of anemia by increasing dialysis dose and/or by administering EPO. 3) The use of high UF HDF in order to employ more biocompatible membranes and to improve small and middle molecules removal. Nutritional status was assessed by a biochemical screening and by evaluating the variations of dry body weight (BW), which had to be also confirmed by a normal cardiac volume. Moreover in all patients a 4 consecutive days dietary record was obtained one year before the end of the observation period. During this period the mean dry BW increased significantly except in the two last years, when it remained stable. The increase of BW was associated with a reduced incidence of hypertension, a significant increase of Hb and reduction of BUN and sCr. The remaining biochemical parameters were constantly in the normal range. The dietary record showed a mean caloric-proteic intake similar to that recommended for the general population. These data point out that the above strategy can prevent malnutrition in patients on RDT. It must be confirmed whether the use of more biocompatible membranes and the removal of the middle molecules can play an important role in this setting.
Aged↗
[Arterial pressure in idiopathic calcium nephrolithiasis].
Hypertension and calcium nephrolithiasis show some common features, such as the high prevalence of hypercalciuria and of elevated urinary sodium excretion. 28 patients with idiopathic calcium stone disease and 17 normals were studied: all the subjects were evaluated for the mean arterial pressure, and for the metabolic risk factors for calcium stone disease. The mean arterial pressure proved to be higher in patients with calcium nephrolithiasis than in normals. In normals the mean arterial pressure showed a direct relationship with the urinary calcium, while in the group of stone patients it had a direct relationship with the urinary sodium excretion. The lack of relationship between the mean arterial pressure and calcium excretion, in patients with calcium stones, suggests an impaired tubular calcium handling in such patients.
Blood Pressure↗
Comparison between heparin dose during hemodiafiltration with high flux synthetic membranes.
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Blood Coagulation↗
Testing cervicography and cervicoscopy as screening tests for cervical cancer.
AIMS AND BACKGROUND: Suboptimal sensitivity is currently reported for Pap test in screening for cervical cancer. Colposcopy is known to be more sensitive than cytology but its use as a screening test is not possible due to costs and complexity. Screening by cervicography has been suggested as a compromise being less costly and feasible. The present study evaluates the feasibility of screening by cervicography and cervicoscopy (naked eye examination of the cervix after acetic acid lavage) on a consecutive screening series. METHODS: Cervicography and cervicoscopy were performed by the smear taker in subjects consecutively attending a screening clinic. Women with abnormal cytology (atypia or more severe lesion) and/or abnormal cervicography or cervicoscopy (acetowhite lesion) underwent colposcopic assessment. The three screening methods were compared according to positivity rate, CIN 2-3 detection rate and positive predictive value. RESULTS: 2105 consecutive subjects were screened. Positivity rate was 3.8%, 15.3% or 25.4% for cytology, cervicography or cervicoscopy, respectively, 486 of 555 women attended the assessment phase, 281 directed biopsies were performed and 8 CIN 2-3 lesions were detected. Cytology, cervicography and cervicoscopy, detected 5.5, or 7 of 8 CIN 2-3 lesions, respectively. The positive predictive value was 0% for cytologic atypia, 25% for cytologic SIL, 1.75% for cervicography and 2.05% for cervicoscopy. Detecting one CIN 2-3 lesion at cytology cost $5,543. The cost per each additional cytologically negative CIN 2-3 lesion detected at cervicography or cervicoscopy was $12,947 or $3,916, respectively. CONCLUSIONS: The study confirms the limited sensitivity of cytology for CIN 2-3. The association of cervicography was not cost effective. Cervicoscopy was poorly specific but increased the detection rate of CIN 2-3 at relatively low costs. Cervicoscopy is worth further evaluation as a screening test.
Adolescent↗