Management of the side-effects of intravenous bisphosphonates: targeting the serum parathyroid hormone elevation.
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Diphosphonates↗
Biomedical subjects
A Mosca
Publications and source records attributed to A Mosca.
In vitro antimicrobial activity of benzalkonium chloride against clinical isolates of Streptococcus agalactiae.
OBJECTIVES: Despite antibiotic prophylaxis for at-risk mothers during labour and delivery, Streptococcus agalactiae (group B Streptococcus; GBS) still causes substantial morbidity and mortality among newborns. In addition to the well-known side effects of the administration of antibiotics, resistance to drugs recommended for penicillin-allergic pregnant women, such as erythromycin and clindamycin, has increased, thus raising concern about the possibility of inadequate prophylaxis. On this basis we evaluated the antimicrobial activity of benzalkonium chloride against GBS, which has been described as an antimicrobial agent for the topical treatment of vaginal infections. METHODS: A total of 52 GBS from pregnant women have been studied. The capacity of benzalkonium chloride as well as of penicillin, erythromycin, clindamycin, vancomycin, chloramphenicol and tetracycline to inhibit GBS was evaluated using broth macrodilution and microdilution methods, respectively. RESULTS: While all the strains were penicillin- and vancomycin-susceptible, 19.2% were resistant to both erythromycin and clindamycin. In contrast, all GBS isolates were either inhibited or killed by benzalkonium chloride at not only low but also very similar concentrations (MIC90 = 3.12 mg/L). CONCLUSIONS: Benzalkonium chloride might represent an alternative strategy that is useful in reducing vaginal GBS colonization in pregnant women before delivery by topical treatment.
Anti-Infective Agents, Local↗
Predictive factors for skeletal complications in hormone-refractory prostate cancer patients with metastatic bone disease.
Factors predictive of skeletal-related events (SREs) in bone metastatic prostate cancer patients with hormone-refractory disease were investigated. We evaluated the frequency of SREs in 200 hormone-refractory patients consecutively observed at our Institution and followed until death or the last follow-up. Baseline parameters were evaluated in univariate and multivariate analysis as potential predictive factors of SREs. Skeletal-related events were observed in 86 patients (43.0%), 10 of which (5.0%) occurred before the onset of hormone-refractory disease. In univariate analysis, patient performance status (P=0.002), disease extent (DE) in bone (P=0.0001), bone pain (P=0.0001), serum alkaline phosphatase (P=0.0001) and urinary N-telopeptide of type one collagen (P=0.0001) directly correlated with a greater risk to develop SREs, whereas Gleason score at diagnosis, serum PSA, Hb, serum albumin, serum calcium, types of bone lesions and duration of androgen deprivation therapy did not. Both DE in bone (hazard ratio (HR): 1.16, 95% confidence interval (CI): 1.07-1.25, P=0.000) and pain score (HR: 1.13, 95% CI: 1.06-1.20, P=0.000) were independent variables predicting for the onset of SREs in multivariate analysis. In patients with heavy tumour load in bone and great bone pain, the percentage of SREs was almost twice as high as (26 vs 52%, P<0.02) and occurred significantly earlier (P=0.000) than SREs in patients with limited DE in bone and low pain. Bone pain and DE in bone independently predict the occurrence of SREs in bone metastatic prostate cancer patients with hormone-refractory disease. These findings could help physicians in tailoring the skeletal follow-up most appropriate to individual patients and may prove useful for stratifying patients enrolled in bisphosphonate clinical trials.
Aged↗
Independent prognostic role of circulating chromogranin A in prostate cancer patients with hormone-refractory disease.
The presence of neuroendocrine (NE) differentiation in the context of predominantly exocrine prostate cancer may play a key role in androgen-independent tumor growth. The prognostic significance of plasma chromogranin A (CgA) was assessed in a series of consecutive prostate cancer patients with hormone-refractory disease. One hundred and eight patients with newly diagnosed hormone-refractory prostate cancer entered the study. Plasma CgA levels and other biochemical parameters, such as serum prostate specific antigen, serum alkaline phosphatase, serum lactate dehydrogenase, serum albumin and hemoglobin concentration, were measured at baseline (i.e. when hormone refractoriness occurred) and their prognostic role was evaluated together with patient performance status, Gleason score (at diagnosis of prostate cancer) and the presence of visceral metastases. Furthermore, plasma CgA was prospectively evaluated in 50 patients undergoing chemotherapy. At baseline, 45 patients (43.3%) showed elevated CgA values. Plasma CgA negatively correlated with survival, either in univariate analysis (P=0.008) or in multivariate analysis, after adjusting for previously mentioned prognostic parameters (P<0.05). In the patient subset undergoing chemotherapy, median CgA (range) values were 13.3 (3.0-141.0) U/l at baseline, 19.1 (3.0-486.0) U/l after 3 months, 20.8 (3.0-702.0) U/l after 6 months and 39.4 (3.0-414.0) U/l after 9 months (P<0.01). The corresponding supranormal rates were 17/50 (34%), 23/50 (46%), 26/50 (52%) and 34/50 (68%) respectively (P<0.005). Elevated plasma CgA levels are frequently observed in prostate cancer patients with hormone-refractory disease and correlate with poor prognosis. NE differentiation in hormone-refractory patients is a time-dependent phenomenon and is not influenced by conventional antineoplastic treatments.
Aged↗
The neuroendocrine phenotype in prostate cancer: basic and clinical aspects.
Most of the conventional adenocarcinomas of the prostate display focal neuroendocrine (NE) differentiation at diagnosis, usually revealed by immunohistochemistry as solitary or clusters of cells, in the context of predominantly exocrine tumors. Even though the biological and clinical significance of NE differentiation in prostate cancer is still to be elucidated, NE phenotype is emerging as an important factor in the prognosis, evolution and progression of prostate cancer. It seems to be particularly relevant in facilitating prostate cancer progression during the ordinary androgen-suppression therapy (LHRH-analogs +/- anti-androgens). Several mechanisms have been identified: NE cells are androgen receptor negative, therefore they survive to androgen deprivation; NE cells produce peptides, hormones and growth factors which could stimulate proliferation [chromogranin (A-CgA), PTHrp, bombesin, etc.], inhibit apoptosis (Survivin) and stimulate neoangiogenesis [vascular endothelial GF (VEGF)] of the neighbouring exocrine prostate cancer cells. NE differentiation appears to be a dynamic phenomenon. The NE phenotype expression increases during androgen-deprivation therapy and results more elevated in hormone refractory than in hormone sensitive disease. Pre-clinical and clinical studies demonstrated a direct stimulation of NE differentiation by androgen-suppression therapy, resulting in a dramatic increase in the number of cells expressing NE markers. CgA appears to be the most sensitive marker and is most frequently used for detecting NE phenotype either at the tissue level or in the general circulation. Elevated plasma CgA levels are frequently observed in hormone-refractory disease and correlate with poor prognosis. Even in hormone refractory disease, NE differentiation is a time-dependent phenomenon and is not influenced by conventional antineoplastic treatments.
Adenocarcinoma↗
Somatostatin receptors: from basic science to clinical approach. Unlabeled somatostatin analogues-1: Prostate cancer.
Neuroendocrine cells have been found in all the stages of prostate cancer, but their clinical significance is not completely understood. Neuroendocrine cells are androgen receptor- and prostate-specific antigen-negative, do not proliferate, and secrete many neuropeptides, such as chromogranin A. Neuroendocrine differentiation of prostate cancer correlates with an advancing tumour stage, poor prognosis and tumour progression after androgen deprivation. Furthermore, neuroendocrine phenotype is associated with the increased expression of neo-angiogenesis and vascular endothelial growth factor and with an over-expression of survivin, a new anti-apoptosis protein. Chromogranin A is the quantitatively major secretory protein of the vesicles inside neuroendocrine prostate cells and it is the marker most frequently used to detect neuroendocrine features, both in tissues and in general circulation. Tumours displaying neuroendocrine phenotype tend to be more aggressive and resistant to hormone-therapy. Neuroendocrine differentiation seems to be a dynamic phenomenon: in vitro and in vivo data suggest that it can be induced by androgen suppression. Moreover, the differences in the expression of somatostatin receptors between primary and hormone-refractory prostate cancer are likely to be related to the changes in neuroendocrine phenotype during androgen deprivation. Circulating chromogranin A levels seem to be scarcely affected by endocrine- and chemotherapy, while they significantly decreased after treatment with somatostatin analogs.
Cell Differentiation↗
Effect of lercanidipine compared with ramipril on albumin excretion rate in hypertensive Type 2 diabetic patients with microalbuminuria: DIAL study (diabete, ipertensione, albuminuria, lercanidipina).
Microalbuminuria and hypertension are risk factors for diabetic nephropathy in Type 2 diabetic patients. Recent data suggest that blockade of the renin-angiotensin system slows the progression of diabetic nephropathy; in contrast, the results on the renoprotective effect of calcium channel antagonists are conflicting. We evaluated the effectiveness of lercanidipine, in comparison with ramipril, on the reduction in albumin excretion rate (AER) and blood pressure in mild-to-moderate hypertensive patients with Type 2 diabetes and persistent microalbuminuria. A total of 277 patients were enrolled in a multicentric, randomized, double-blind, active-controlled, parallel-group trial; 180 were randomized to receive 10-20 mg/day of lercanidipine or 5-10 mg/day of ramipril and followed up for 9-12 months. The primary outcome was the change in AER from baseline. After 9-12 months of follow-up, a reduction in AER of -17.4+/-65 microg/min (p<0.05) and -19.7+/-52.5 (p<0.05) in the lercanidipine and ramipril group, respectively, was observed, without differences between the groups. A significant reduction in systolic and diastolic blood pressure was observed in both the lercanidipine and ramipril-based treatment groups (p<0.0001 for both). This study demonstrated that treatment with lercanidipine 10-20 mg/day does not worsen albuminuria in microalbuminuric Type 2 diabetic patients with hypertension. Indeed, both lercanidipine and ramipril treatments resulted in a significant reduction in AER without a statistically significant difference between the two groups.
Adult↗
Streptococcus pneumoniae nasopharyngeal colonization in young healthy children: rate of carriage, serotype distribution, and antibiotic resistance.
The nasopharyngeal colonization rate of Streptococcus pneumoniae and its antibiotic susceptibility was determined in a given population of 317 young children (ages 1-7 years) in the area of Bari, Italy. 18.29% of the cultures were positive for S. pneumoniae. 8.62% of the strains were intermediately resistant to penicillin. Erythromycin-(65.51%) and cotrimoxazole-(17.24%) resistance was also observed whereas all the strains resulted uniformely susceptible to cefotaxime and ceftriaxone. The high rate of nasopharyngeal carriage of Streptococcus pneumoniae along with the resistance to antibiotics widely used in the community suggests the importance of epidemiological surveillance as well as the application of new vaccine strategies.
Carrier State↗
[Nasopharyngeal colonization of Streptococcus pneumoniae in healthy children: percentage of carriers, serotypes distribution and antibiotic resistance].
AIM: The nasopharyngeal carriage of Streptococcus pneumoniae is an important risk factor for pneumococcal diseases. Data regarding prevalence and serotype distribution of this pathogen are lacking in our population. METHODS EXPERIMENTAL DESIGN: longitudinal observational cohort study. SETTING: healthy children aged 1-7 years attending day-care centers and schools of a district of a Southern Italy city. MEASURES: the nasopharyngeal colonization rate of Streptococcus pneumoniae as well as its antibiotic susceptibility was determined. RESULTS: Of 317 nasopharyngeal cultures obtained, 18.29% of the cultures were positive for Streptococcus pneumoniae; 60.34% of the isolates were serotypes 19A, 19F, 14, 6B, or 23F; 8.62% of the strains were intermediately resistant to penicillin. Erythromycin-resistance was observed in 65.51% of the micro-organisms isolated and particularly serotypes 19, 14, and 6 were more erythromycin-resistant than organisms of other serotypes. Co-trimoxazole resistance was detected in 17.24% of the strains. All the strains resulted uniformly susceptible to cefotaxime and ceftriaxone. CONCLUSION: The high rate of nasopharyngeal carriage of Streptococcus pneumoniae, along with the resistance to antibiotics widely used in the community, suggests the importance of an epidemiological surveillance as well as the application of new vaccine strategies.
Anti-Bacterial Agents↗
Detection of Mirizzi syndrome with magnetic resonance cholangiopancreatography: laparoscopic or open approach?
Imaging of the gallbladder and biliary tract has changed dramatically in the past 20 years. Magnetic resonancecholangiopancreatography provides a noninvasive alternative to endoscopic retrograde cholangiopancreatography and percutaneous transhepatic cholangiography in the diagnosis of Mirizzi syndrome. In this laparoscopic era, when diagnosis is certain, surgeons must choose between a laparoscopic and a traditional open approach. The authors review their cases of hepatobiliary surgery during the period 1993-2000. Three cases of Mirizzi syndrome (0.4%) were observed among 712 surgical hepatobiliary patients (two type 1 cases and one type 2 case). The authors suggest that with Mirizzi syndrome type 1, laparoscopy together with peroperative cholangiography should be used to resolve anatomic doubts. If clipping of the cystic duct is possible and certain, then laparoscopy may be continued and finished. In the case of cholecystocholedochal fistula (Mirizzi syndrome type 2), when the diagnosis is determined before surgery, the authors believe that laparoscopy is dangerous. Adhesions, inflammation, and anatomy changes may cause injuries to the main bile duct, so an open traditional approach is suggested.
Cholangiopancreatography, Endoscopic Retrograde↗
BCG septicemia after radical cystectomy: a rare postoperative complication following BCG therapy.
It is reported a case of life-threatening septic shock due to BCG septicemia after radical cystectomy in a patient with a previous treatment with BCG therapy. In the absence of response to standard antimicrobial therapy and a negative CT scan, a PCR-based technique detected the presence of BCG bacilli in bloodstream. Immediate antimycobacterial therapy resolved the sepsis, thus suggesting either the awareness of this infection or the prompt antimycobacterial therapy as the key for the appropriate management. Furthermore, isoniazid prophylaxis should be taken into consideration in patients with history of intravesical BCG therapy undergoing cystectomy.
Aged↗
Effects of the somatostatin analog lanreotide on the circulating levels of chromogranin-A, prostate-specific antigen, and insulin-like growth factor-1 in advanced prostate cancer patients.
BACKGROUND: The concept that neuroendocrine cells detected within prostate adenocarcinoma produce paracrine factors, that may exert a proliferative effect on exocrine prostate tumor cells, provides a rationale for the use of somatostatin analogs with the aim to counteract or delay the tumor progression. This study was designed to provide preliminary information on the effect of the administration of a long-acting somatostatin analog, lanreotide, on plasma levels of chromogranin A (CgA). Secondary aims were the evaluation of changes in circulating prostate-specific antigen (PSA) and insulin-like growth factor-1 (IGF-1). METHODS: Lanreotide (Ipstyl 30 mg; Ipsen, Milan, Italy) was administered intramuscularly every 14 days for 2 months to nine heavily pretreated prostate cancer patients with hormone refractory disease. All patients had, at baseline conditions, CgA values above the normal range. Androgen deprivation was maintained during the study period, while other concomitant antineoplastic treatments were not allowed. Serum PSA levels and plasma CgA and IGF-1 values were measured every week. RESULTS: Lanreotide treatment was very well tolerated and no patient experienced major toxicity. Plasma CgA values at baseline: mean 109 U/liter, standard deviation +/- 85 decreased significantly after treatment as follows: 42 U/liter, +/- 17.8; 27.2 U/liter +/- 13.6; 31.4 U/liter, +/- 17.8 and 27.6 U/liter, +/- 17.0; after 7, 14, 21, and 28 days, respectively (P < 0.01, Friedman ANOVA). Serum PSA did not change. Baseline IGF-1 was found to be above the detection limit in four cases, all of them showing a decrease after lanreotide. CONCLUSIONS: Lanreotide administration to prostate cancer patients induces a decrease in plasma CgA and IGF-1 levels, without any influence on serum PSA values. Prostate 47:205-211, 2001.
Adenocarcinoma↗
Potential clinical value of circulating chromogranin A in patients with prostate carcinoma.
BACKGROUND: Neuroendocrine (NE) differentiation of prostate adenocarcinoma has received increasing attention in recent years as a result of possible implications for prognosis and therapy. The presence of NE tumor subpopulation can be gauged non invasively by measuring circulating levels of secretory products, primarily chromogranin A (CgA). METHODS: This article provides a review on published papers evaluating circulating CgA in prostate cancer patients. RESULTS: Circulating CgA levels were found to be higher in prostate cancer patients than in patients with benign or pre-malignant prostatic diseases. In patients with malignancy, they correlated either to the stage of disease or to the condition of hormone refractoriness. CgA levels did not correlate with serum prostate specific antigen (PSA) and were supranormal in the majority of advanced patients with PSA within normality. In hormone refractory cases, elevated CgA was a significant predictor of poor prognosis, independently from serum PSA. CgA values were not substantially affected by either endocrine therapy or chemotherapy. They were found to increase during androgen deprivation in some cases and this trend preceded that of PSA. The administration of a somatostatin analog in hormone refractory cases was able to reduce plasma CgA values consistently. CONCLUSIONS: Present data suggest a potential role of circulating CgA in the management of prostate cancer patients. CgA determination may be useful diagnostically and prognostically and could offer complementary information with respect to PSA. Serial evaluation of circulating CgA could provide information on changes in the NE phenotype expression as a consequence of tumor progression and/or treatment administration.
Androgen Antagonists↗
Relationship between neuroendocrine features and prognostic parameters in human prostate adenocarcinoma.
PURPOSE: The biological behaviour of prostate cancer is highly variable and prediction by the commonly employed prognostic parameters is not sufficient. The concept of neuroendocrine (NE) differentiation in prostate adenocarcinoma has recently received increasing attention due to possible implications for prognosis and therapy. MATERIALS AND METHODS: Core needle biopsies from 142 newly diagnosed patients were immunohistochemically examined for the coexistence of NE differentiation using an antibody against chromogranin A (CgA). Circulating CgA was available in 106 of these patients. RESULTS: NE differentiation was found in 64 (45.1%) tumors. Among them 29 (20.4%) had CgA positive cells scattered or focally distributed in less than 5% per mm3 of tumor tissues, 26 (18.3%) between 5% and 10% and 9 (6.4%) more than 10%, respectively. There was a significant correlation between the extent of NE features and either Gleason score (P < 0.01) or stage of disease. Circulating CgA but not PSA correlated with immunohistochemical CgA (P < 0.03) particularly in metastatic cases. CONCLUSIONS: These data support the concept that NE differentiation in human prostate cancer has a negative prognostic significance. Circulating CgA levels reflect immunohistochemical findings.
Adenocarcinoma↗
Circulating neuroendocrine markers in patients with prostate carcinoma.
BACKGROUND: Circulating neuroendocrine markers were measured in patients with prostate carcinoma (PC), prostatic intraepithelial neoplasia (PIN), and benign prostatic hypertrophy (BPH) with the goal to: 1) evaluate the differences in the expression of these markers in patients with benign, premalignant, and primary or metastatic PC; 2) evaluate their prognostic significance; 3) compare values in patients with hormone-naive and hormone-refractory disease; and 4) assess changes after androgen deprivation or chemotherapy. METHODS: Serum neuron specific enolase (NSE) (immunoradiometric assay) and plasma chromogranin A (CgA) (enzyme-linked immunoadsorbent assay) were evaluated in 141 patients with BPH, 54 patients with PIN, and 159 patients with PC; 119 patients were bearing hormone-naive disease and 40 were bearing hormone-refractory disease. CgA was monitored in 31 patients submitted to androgen deprivation and in 24 patients receiving chemotherapy. RESULTS: Supranormal CgA was observed more frequently in patients with American Urologic Association (AUA) Stage D2 disease (45.5%) compared with those with Stage D1 disease (33.3%), Stage C disease (16.7%), Stage A/B disease (18.8%), PIN (25.9%), and BPH (17.0%) (P < 0.02). Supranormal NSE did not change in any of the patient subgroups. Elevated CgA was observed in 36.0% of patients with metastases who had hormone-naive disease and in 45.0% of patients with hormone-refractory disease (P value not significant). Supranormal NSE and CgA values were predictors for poor prognosis in patients with hormone-refractory disease. Elevated baseline CgA values decreased > 50% in 1 of 12 patients who received luteinizing hormone-releasing hormone analogs and in 2 of 12 patients who underwent chemotherapy. CONCLUSIONS: CgA appears to reflect the neuroendocrine activity of PC better than NSE. Elevated CgA values correlate with poor prognosis and are scarcely influenced by either endocrine therapy or chemotherapy.
Aged↗
Inter-method differences and commutability of control materials for HbA2 measurement.
The intermethod variability of control materials and patient blood samples for the measurement of hemoglobin A2 (HbA2) were compared. A set of 54 blood samples and 10 control materials were analyzed in duplicate by HPLC and microcolumn methods. For each set of methods the distances of the materials from the regression line of patient blood results (expressed as normalized residuals) were calculated. Four out of ten controls had normalized residuals exceeding three standard deviations from the regression line. Moreover, total Hb and Hb derivatives analysis proved that only a minority of the controls could be considered similar to patients' blood samples. Intermethod calibration performed "a posteriori" by the two best performing control materials improved intermethod variability among all the five tested methods. We conclude that the use of high resolution HPLC methods together with appropriate commutable control materials allows for better harmonization of results in the field of diagnosis of hemoglobin disorders in research and clinical practice.
Calibration↗
Prevalence of antibodies to Bartonella henselae in patients with suspected cat scratch disease (CSD) in Italy.
Cat scratch disease (CSD) is a relatively new diagnosed illness with clinical signs of self-limiting regional lymphadenopathy accompanied by symptoms of fever and malaise, to encephalopathy and neuropathy, occurring after a cat scratch or flea bite. Bartonella henselae is now accepted as the etiologic agent of CSD. From January 1994 to September 1998, 412 patients were evaluated for suspect CSD in Italy. Sera were tested for antibodies to B. henselae by a commercially available indirect immunofluorescent assay (IFA), based on B. henselae-infected Vero-cells as the antigen substrate. Of the 412 patients, 26 (6.3%) were considered positive having titers of immunoglobulin G (IgG) to B. henselae of 64 or higher. In these patients CSD was indeed confirmed by either histopathologic examination of lymph nodes biopsy or fourfold raise in antibody titers. Nevertheless, sera were tested by IFA for Afipia felis and one showed a double reactivity to B. henselae and A. felis. Finally, three sera, negative to B. henselae serology, were positive to A. felis. Three hundred and eighty-six patients received alternative diagnoses. One hundred and twenty-five serum samples from control subjects were negative by IFA for either B. henselae or A. felis. Moreover, a cross-reactivity with sera from patients affected by other diseases was not observed. Our study shows that the ascertained cases of CSD are etiologically determined by B. henselae, IFA assay is confirmed as a useful tool in the laboratory diagnosis and, over a 5 years period of study, the incidence of CSD in Italy has been low.
Adolescent↗
Changes in free and free-to-total prostate specific antigen after androgen deprivation or chemotherapy in patients with advanced prostate cancer.
PURPOSE: To provide preliminary data on whether the diagnostic role of serum prostate specific antigen (PSA) in assessing the response to treatment is improved by concomitant free PSA evaluation both markers were evaluated in 42 patients with advanced prostate cancer who received hormonal therapy and 57 with hormone refractory disease who received chemotherapy. MATERIALS AND METHODS: PSA was assessed at baseline and every 3 months during treatment. Free PSA was assessed in stored serum samples obtained at baseline and at maximum PSA decrease. Free PSA was not measurable in 17 patients who received androgen deprivation (40.5%) and 2 who received chemotherapy (3.5%) because it was less than 1.5 ng./ml. RESULTS: Of the 21 patients with greater than 50% PSA decrease after hormonal therapy free-to-total PSA increased in 12 (57.2%) and decreased in 9 (42.9%). Of the 20 patients with PSA response after chemotherapy free-to-total PSA increased in 18 (90.0%) and decreased in 2 (10.0%). Free-to-total PSA increased in 12 of the 20 patients (60.0%) with PSA stabilization after chemotherapy. Patients with an increase in free-to-total PSA after chemotherapy had greater survival compared to those with a decrease or no change (19.8 versus 15.5 months, respectively, p <0.03). CONCLUSIONS: These data suggest that an effective cytotoxic regimen mainly affects the protein bound PSA fraction. The absence of a clear predominant pattern of free-to-total PSA in patients with PSA response to hormonal therapy and the high percentage of hormone sensitive patients in whom free PSA was not assessable at maximum PSA decrease suggest that free PSA evaluation is less useful in prostate cancer patients undergoing androgen deprivation.
Aged↗