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Biomedical subjects

A Maggioni

Publications and source records attributed to A Maggioni.

At least 19 recordsLinked to original sources

Randomised study of systematic lymphadenectomy in patients with epithelial ovarian cancer macroscopically confined to the pelvis.

No randomised trials have addressed the value of systematic aortic and pelvic lymphadenectomy (SL) in ovarian cancer macroscopically confined to the pelvis. This study was conducted to investigate the role of SL compared with lymph nodes sampling (CONTROL) in the management of early stage ovarian cancer. A total of 268 eligible patients with macroscopically intrapelvic ovarian carcinoma were randomised to SL (N=138) or CONTROL (N=130). The primary objective was to compare the proportion of patients with retroperitoneal nodal involvement between the two groups. Median operating time was longer and more patients required blood transfusions in the SL arm than the CONTROL arm (240 vs 150 min, P<0.001, and 36 vs 22%, P=0.012, respectively). More patients in the SL group had positive nodes at histologic examination than patients on CONTROL (9 vs 22%, P=0.007). Postoperative chemotherapy was delivered in 66% and 51% of patients with negative nodes on CONTROL and SL, respectively (P=0.03). At a median follow-up of 87.8 months, the adjusted risks for progression (hazard ratio [HR]=0.72, 95%CI=0.46-1.21, P=0.16) and death (HR=0.85, 95%CI=0.49-1.47, P=0.56) were lower, but not statistically significant, in the SL than the CONTROL arm. Five-year progression-free survival was 71.3 and 78.3% (difference=7.0%, 95% CI=-3.4-14.3%) and 5-year overall survival was 81.3 and 84.2% (difference=2.9%, 95% CI=-7.0-9.2%) respectively for CONTROL and SL. SL detects a higher proportion of patients with metastatic lymph nodes. This trial may have lacked power to exclude clinically important effects of SL on progression free and overall survival.

Adult↗

Solid-state characterization of a novel chemotherapeutic drug.

We present the results of a thermal, spectroscopic, diffractometric, and microscopic study of a novel DNA intercalator synthesized by Novuspharma S.p.A. (code name BRR 2778, purity by high-performance liquid chromatography: 99.4%). We found that the form that is stable at room temperature contains 1.5 water molecules per unit of formula (or about 4.7% in mass): this water is reversibly lost in two stages below 80 degrees and 90 degrees C in dry and wet nitrogen atmosphere, respectively. The hydrated compound is a pseudo-polymorph and dehydration is accompanied by a structural change that modifies the diffraction pattern without changing the shape of the microcrystals. Annealing above 150 degrees C causes decomposition of the anhydrous form and (above 190 degrees C) amorphization of the solid residue occurs.

Antineoplastic Agents↗

Practical recommendations for the use of ACE inhibitors, beta-blockers and spironolactone in heart failure: putting guidelines into practice.

Surveys of prescribing in both hospitals and primary care have shown delays in translating improved survival data from clinical trials into clinical practice thereby denying patients the benefits of proven treatments, such as the angiotensin converting enzyme inhibitors. This may be due to unfamiliarity with clinical guidelines and concerns about adverse events. Recent trials have shown that substantial improvements in survival are associated with spironolactone and beta-blocker therapy. In order to accelerate the uptake of these treatments, and to ensure that all eligible patients should receive the most appropriate medications, a clear and concise set of clinical recommendations has been prepared by a group of clinicians with practical expertise in the management of heart failure. The objective of these recommendations is to provide practical guidance for non-specialists in order to support the implementation of evidenced-based therapy for heart failure. These practical recommendations are meant to supplement rather than replace existing guidelines.

Adrenergic beta-Antagonists↗

Molecular and genomic analysis of genes encoding surface-anchored proteins from Clostridium difficile.

The gene slpA, encoding the S-layer precursor protein in the virulent Clostridium difficile strains C253 and 79--685, was identified. The precursor protein carries a C-terminal highly conserved anchoring domain, similar to the one found in the Cwp66 adhesin (previously characterized in strain 79--685), an SLH domain, and a variable N-terminal domain mediating cell adherence. The genes encoding the S-layer precursor proteins and the Cwp66 adhesin are present in a genetic locus carrying 17 open reading frames, 11 of which encode a similar two-domain architecture, likely to include surface-anchored proteins.

Amino Acid Sequence↗

[Magnetic resonance imaging in the evaluation of parametrial invasion of carcinoma of the cervix uteri: optimization of the study protocol].

PURPOSE: To determine the efficacy of three different MR sequences in the evaluation of parametrial invasion by early-stage cervical cancer. MATERIAL AND METHODS: Eighteen consecutive patients with cervical cancer clinically assessed as stage IB1 underwent MR imaging examination with the use of the following sequences: FSE T2-weighted, FSE fat-suppressed T2w, and SE fat-suppressed Gadolinium-enhanced T1w. In all cases, the presence or absence of parametrial invasion on both sides per each sequence used was evaluated. Subsequently all the sequences have been considered together for the evaluation of tumor invasion. Gold standard of the study was the histopathologic analysis of the surgical specimens. RESULTS: At histological examination, parametrial invasion by tumor was found in 6 out of 36 parametria evaluated. The accuracy achieved with each of the sequences used was as follows: 94% with FSE T2w; 86% with FSE fat-suppressed T2w; and 67% with SE fat-suppressed Gadolinium-enhanced T1w. The simultaneous evaluation of all 3 sequences obtained an accuracy level similar to that achieved with FSE T2w. The difference between the accuracy of T2w sequences and that of fat-suppressed contrast-enhanced T1w sequences was statistically significant (p<0.01). DISCUSSION AND CONCLUSIONS: Our data suggest that the MR imaging protocol for the evaluation of parametrial tumor invasion could be restricted to FSE T2w sequences. These proved to have the highest negative predictive value (97%) which allows a reliable selection of patients who can be surgically treated.

Adenocarcinoma↗

Physico-chemical characterization of a novel tricyclic beta-lactam antibiotic.

GV118819X, a novel tricyclic beta-lactam antibiotic of GlaxoWellcome, is a racemic mixture of two diastereoisomers, A and B. Of the two diastereoisomers, only A is available as a pure compound. By analyzing mixtures of GV118819X and A, a partial phase diagram is constructed, which indicates the presence of a eutectic when the A fraction is approximately 39%. Moreover, the melting enthalpies of the eutectic mixture and of diastereoisomer B can be estimated. With the exception of the pure A form, all mixtures undergo important modifications in morphology and microstructure as a consequence of thermal treatments, which induce melting/amorphization of the eutectic, and crystallization of the A form. Analyses of the sieved fractions of GV118819X demonstrate that it consists of acicular crystals of different composition, with the larger crystals having a larger A fraction than the smaller ones. Grinding causes melting/amorphization of the eutectic and, following hours-long treatments, the formation of a substantial fraction of submicron particles with unusually low melting temperatures.

Anti-Bacterial Agents↗

The ENACT study: a pan-European survey of acute coronary syndromes. European Network for Acute Coronary Treatment.

AIM: The European Network for Acute Coronary Treatment (ENACT) study was designed to collect prospective information across Europe on the relative frequency, diagnosis and management of the whole spectrum of acute coronary syndromes. METHODS: Cardiologists, who were respondents to mailings sent out to 17 European countries with the target of reaching one centre per million inhabitants, completed a prospective patient record, each physician providing information on 10 consecutive patients with a working diagnosis on admission of acute coronary syndrome, and a questionnaire. RESULTS: A total of 390 responses were received (0.91/10(6)population) with data on 3092 patients in 29 countries. The patient population comprised 1431 (46%) with an initial working diagnosis of unstable angina/non-ST-segment elevation myocardial infarction, 1205 (39%) with myocardial infarction and 445 (14%) with suspected acute coronary syndrome. The ratio of unstable angina to myocardial infarction was 1.2:1 and this was similar across Europe. An initial diagnosis of myocardial infarction was more likely to be confirmed than unstable angina or suspected acute coronary syndrome. There were wide variations in the rates of angiography and percutaneous coronary intervention across Europe. Most unstable angina patients received aspirin, nitrates and heparin (unfractionated heparin 44% intravenous, 16% subcutaneous; low-molecular-weight heparin 50%). Overall, 50% of unstable angina patients and 34% of myocardial infarction patients received low-molecular-weight heparin and 6% and 8% respectively received a glycoprotein IIb/IIIa inhibitor, but there were large inter-country differences. There were also national differences in the use of calcium antagonists, angiotensin-converting enzyme inhibitors and beta-blockers. CONCLUSION: The ENACT study provides robust data, for the first time, on the relative frequency of unstable angina and acute myocardial infarction across Europe. It provides insight into differences in management across Europe and a reference benchmark of current treatment.

Acute Disease↗

Sentinel node biopsy in early vulvar cancer.

Lymph node pathologic status is the most important prognostic factor in vulvar cancer; however, complete inguinofemoral node dissection is associated with significant morbidity. Lymphoscintigraphy associated with gamma-probe guided surgery reliably detects sentinel nodes in melanoma and breast cancer patients. This study evaluates the feasibility of the surgical identification of sentinel groin nodes using lymphoscintigraphy and a gamma-detecting probe in patients with early vulvar cancer. Technetium-99m-labelled colloid human albumin was administered perilesionally in 37 patients with invasive epidermoid vulvar cancer (T1-T2) and lymphoscintigraphy performed the day before surgery. An intraoperative gamma-detecting probe was used to identify sentinel nodes during surgery. A complete inguinofemoral node dissection was then performed. Sentinel nodes were submitted separately to pathologic evaluation. A total of 55 groins were dissected in 37 patients. Localization of the SN was successful in all cases. Eight cases had positive nodes: in all the sentinel node was positive; the sentinel node was the only positive node in five cases. Twenty-nine patients showed negative sentinel nodes: all of them were negative for lymph node metastases. Lymphoscintigraphy and sentinel-node biopsy under gamma-detecting probe guidance proved to be an easy and reliable method for the detection of sentinel node in early vulvar cancer. This technique may represent a true advance in the direction of less aggressive treatments in patients with vulvar cancer.

Adult↗

Comparison of candesartan, enalapril, and their combination in congestive heart failure: randomized evaluation of strategies for left ventricular dysfunction (RESOLVD) pilot study. The RESOLVD Pilot Study Investigators.

BACKGROUND: We investigated the effects of candesartan (an angiotensin II antagonist) alone, enalapril alone, and their combination on exercise tolerance, ventricular function, quality of life (QOL), neurohormone levels, and tolerability in congestive heart failure (CHF). METHODS AND RESULTS: Seven hundred sixty-eight patients in New York Heart Association functional class (NYHA-FC) II to IV with ejection fraction (EF) <0.40 and a 6-minute walk distance (6MWD) <500 m received either candesartan (4, 8, or 16 mg), candesartan (4 or 8 mg) plus 20 mg of enalapril, or 20 mg of enalapril for 43 weeks. There were no differences among groups with regard to 6MWD, NYHA-FC, or QOL. EF increased (P=NS) more with candesartan-plus-enalapril therapy (0.025+/-0.004) than with candesartan alone (0.015+/-0.004) or enalapril alone(0.015+/-0.005). End-diastolic (EDV) and end-systolic (ESV) volumes increased less with combination therapy (EDV 8+/-4 mL; ESV 1+/-4 mL; P<0.01) than with candesartan alone (EDV 27+/-4 mL; ESV 18+/-3 mL) or enalapril alone (EDV 23+/-7 mL; ESV 14+/-6 mL). Blood pressure decreased with combination therapy (6+/-1/4+/-1 mm Hg) compared with candesartan or enalapril alone (P<0.05). Aldosterone decreased (P<0.05) with combination therapy (23.2+/-5.3 pg/mL) at 17 but not 43 weeks compared with candesartan (0.7+/-7.8 pg/mL) or enalapril (-0.8+/-11. 3 pg/mL). Brain natriuretic peptide decreased with combination therapy (5.8+/-2.7 pmol/L; P<0.01) compared with candesartan (4. 4+/-3.8 pmol/L) and enalapril alone (4.0+/-5.0 pmol/L). CONCLUSIONS: Candesartan alone was as effective, safe, and tolerable as enalapril. The combination of candesartan and enalapril was more beneficial for preventing left ventricular remodeling than either candesartan or enalapril alone.

Aged↗

Characterization of surface layer proteins from Clostridium difficile by liquid chromatography/electrospray ionization mass spectrometry.

Surface layers (S-layers) are regularly ordered protein subunits found as the outermost cell envelope component of many bacteria. Most S-layers are composed of a single protein or glycoprotein species with a molecular weight varying between 40 and 200 kDa. Clostridium difficile is the most common cause of antibiotic associated diarrhea (AAD) and pseudomembranous colitis (PMC) in humans. Detection of the S-layer in some C. difficile strains, and preliminary characterization of two glycoproteins, P36 and P47, involved in the composition of the S-layer of one of these strains (C. difficile C253), led us to investigate the most appropriate conditions for purification and chemical characterization of these proteins. This work describes the results obtained when liquid chromatography (LC) coupled to mass spectrometry (MS) using electrospray ionization was applied to the analysis of C. difficile S-layer proteins (SLPs). In this way the molecular weights of the two SLP components, P36 and P47, were detected to be 34,258 +/- 2 and 39,545 +/- 3 Da, respectively. These data deviate from sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) results by 1.85 and 7.5 kDa. To confirm the LC-MS results, an alternative molecular weight analysis was performed: the two S-layer proteins were isolated by semipreparative high performance liquid chromatography (HPLC), concentrated, and analyzed by matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF). The two SLP subunits were digested with protease V8, and the peptide maps were determined by LC-MS using a C18 column. Finally, preliminary results about peptide glycosylation were obtained.

Bacterial Outer Membrane Proteins↗

Effect of lesions of the nucleus basalis magnocellularis and of treatment with posatirelin on cholinergic neurotransmission enzymes in the rat cerebral cortex.

The effect of 4 and 8 weeks of treatment with the thyrotropin releasing hormone (TRH), analogue posatirelin (L-6-ketopiperidine-2-carbonyl-L-leucyl-proline amide), on the changes of cholinergic neurotransmission enzymes, choline acetyltransferase (ChAT) and acetylcholinesterase (AChE), caused by lesions of the nucleus basalis magnocellularis (NBM), was investigated in the rat frontal cortex. ChAT and AChE were demonstrated with immunohistochemical and histochemical techniques, respectively associated with image analysis and microdensitometry. Monolateral and bilateral lesions of NBM area caused a significant loss of ChAT-immunoreactive nerve cell bodies in the NBM, as well as a remarkable decrease of ChAT-immunoreactive fibres and of AChE reactivity in the frontal cortex ipsilateral to the lesion or of both sides, respectively. The number of ChAT-immunoreactive nerve cell bodies in the lesioned NBM was higher in posatirelin-treated rats for 8 weeks in comparison with control NBM-lesioned rats. Moreover, the compound increased the number of ChAT-immunoreactive fibres in the frontal cortex of monolaterally and bilaterally NBM-lesioned rats at 8 weeks after lesion, but was without effect on these fibres in sham-operated rats. The same is true for AChE reactivity, developed in the neuropil of the frontal cortex, which was restored in part by an 8-week treatment with posatirelin in NBM-lesioned rats. These findings suggest that treatment with posatirelin rescues cholinergic neurons of the NBM and cholinergic projections to the cerebral cortex affected by lesioning of the NBM. The functional relevance of these observations and their possible applications should be evaluated in future studies.

Acetylcholinesterase↗

Predischarge two-dimensional echocardiographic evaluation of left ventricular thrombosis after acute myocardial infarction in the GISSI-3 study.

Left ventricular (LV) thrombosis can be found in patients with acute myocardial infarction (AMI). No wide multicenter trial on AMI has provided information about LV thrombosis until now. The protocol of the GISSI-3 study included the search for the presence of LV thrombosis in patients from 200 coronary care units that did not specifically focus on LV thrombosis. We examined the GISSI-3 database results related to 8,326 patients at low to medium risk for LV thrombi in which a predischarge echocardiogram (9 +/- 5 days) was available. LV thrombosis was found in 427 patients (5.1%): 292 of 2,544 patients (11.5%) with anterior AMI and in 135 of 5,782 patients (2.3%) with AMI in other sites (p <0.0001). The incidence of LV thrombosis was higher in patients with ejection fraction < or = 40% (151 of 1,432 [10.5%] vs 276 of 6,894 [4%]; p <0.0001) both in the total population and in the subgroup with anterior AMI (106 of 597 [17.8%] vs 186 of 1,947 [9.6%]; p <0.0001). Multivariate analysis showed that only the Killip class > I and early intravenous beta-blocker administration were independently associated with higher LV thrombosis risk in the subgroup of patients with anterior AMI (odds ratio 1.75, 95% confidence interval 1.28 to 2.39; odds ratio 1.32, 95% confidence interval 1.02 to 1.72, respectively). In patients with anterior AMI, oral beta-blocker therapy given or not given after early intravenous beta-blocker administration does not influence the occurrence of LV thrombosis. The rate of LV thrombosis was similar in patients treated or not treated with nitrates and lisinopril both in the total population and in patients with anterior and nonanterior AMI. In conclusion, in the GISSI-3 population at low to medium risk for LV thrombi, the highest rate of occurrence of LV thrombosis was found among patients with anterior AMI and an ejection fraction < 40%. Killip class > I and the early intravenous beta-blocker administration were the only variables independently associated with a higher predischarge incidence of LV thrombosis after anterior AMI.

Adrenergic beta-Antagonists↗

Intravenous correction of neonatal hypomagnesemia: effect on ionized magnesium.

OBJECTIVES: Neonatal hypomagnesemia is defined as total magnesium (TMg) < or = 0.65 mmol/L (1.6 mg/dl). However, magnesium (Mg) deficiency and sufficiency overlap at serum values of 0.57 to 0.74 mmol/L (1.4 to 1.8 mg/dl). We hypothesized that (1) some infants with TMg < or = 0.65 mmol/L (1.6 mg/dl) have normal ionized Mg values (normal neonatal range 0.40 to 0.56 mmol/L (0.97 to 1.36 mg/dl)); (2) the dose (6.0 mg of elemental Mg/kg) used to correct hypomagnesemia does not lead to elevation of ionized Mg; (3) after intravenous magnesium sulfate infusion, ionized calcium increases in patients with low baseline ionized Mg and decreases in patients with normal baseline ionized Mg. STUDY DESIGN: We recruited 22 neonates with TMg < or = 1.6 mg/dl. They received intravenous sulfate (6 mg elemental Mg/kg) over a 1-hour period. Serum TMg, ionized Mg, and ionized Ca were measured before and after magnesium sulfate infusion. An ion-selective electrode was used to allow direct measurement of ionized Mg and ionized Ca. RESULTS: Thirteen (59%) of 22 neonates with TMg < or = 0.65 mmol/L (1.6 mg/dl) had normal IMg. In 7 (31%) of 22 cases ionized Mg increased slightly above 0.56 mmol/L (1.36 mg/dl); the maximum value was 0.61 mmol/L (1.48 mg/dl). The change in ionized Ca concentrations and the baseline ionized Mg value were inversely correlated (r = -0.79; p < 0.0001). CONCLUSIONS: (1) Measurement of ionized Mg should prevent overdiagnosis and treatment of hypomagnesemia. (2) The dose used in this study is safe. (3) Ionized Mg concentrations are inversely correlated to the response of ionized Ca concentrations to an Mg load.

Calcium↗

Platin-based chemotherapy and salvage surgery in recurrent ovarian cancer following negative second-look laparotomy.

AIM: To evaluate the role of platin-based chemotherapy followed by salvage surgery in patients with recurrent ovarian cancer after negative second-look laparotomy. METHODS: A retrospective chart review was conducted on 38 patients with recurrent ovarian cancer after a pathologic complete response to first-line chemotherapy. After diagnosis of recurrence all patients underwent retreatment with platin-based chemotherapy followed by radical salvage surgery. RESULTS: Recurrent disease was diagnosed at a median interval of 22 months after second-look surgery. All patients had complete surgical debulking with no macroscopic tumor at the completion of the surgical procedure. Eight patients (21%) required an intestinal resection but no colostomy was performed. Two operative deaths occurred (5%). Twenty-two patients (58%) experienced a second recurrence after salvage surgery The median survival time for all patients after diagnosis of recurrent disease was 29 months (range 6-96 months), with nine patients (25%) surviving more than three years. Survival time after diagnosis of recurrence was not significantly related either to known prognostic factors of ovarian cancer or to the length of the clinical remission time. CONCLUSION: Retreatment with platin-based chemotherapy followed by salvage surgery should be offered to recurrent ovarian cancer patients and would appear to prolong survival in a highly selected group of patients.

Adult↗