Biomedical subjects

C Peña

Publications and source records attributed to C Peña.

At least 19 recordsLinked to original sources

PubMed2006

Physico-chemical characterization of lignins from different sources for use in phenol-formaldehyde resin synthesis.

During the last decades lignin has been investigated as a promising natural alternative to petrochemicals in phenol-formaldehyde (PF) resin production, due to their structural similarity. Physico-chemical characterization of three types of lignin, namely kraft pine lignin (L1), soda-anthraquinone flax lignin (L2), and ethanol-water wild tamarind lignin (L3) has been evaluated to determine which one is the most suitable chemical structure for above purpose. Characterization has been performed using Fourier transform infrared spectroscopy (FT-IR) and proton nuclear magnetic resonance spectrometry ((1)H NMR) to analyse the chemical structure, gel permeation chromatography (GPC) for determining molecular weight (MW) and molecular weight distribution (MWD), differential scanning calorimetry (DSC) to measure the glass transition temperature and thermogravimetric analysis (TGA) to follow the thermal degradation. Both structural and thermal characteristics suggest that kraft pine lignin (L1) would be a better phenol (P) substitute in the synthesis of lignin-phenol-formaldehyde (LPF) resins, as it presents higher amounts of activated free ring positions, higher MW and higher thermal decomposition temperature.

Calorimetry, Differential Scanning↗

PubMed2006

The presence of an intronic deletion in p73 and high levels of ZEB1 alter the TAp73/DeltaTAp73 ratio in colorectal carcinomas.

TAp73 variants largely mimic p53 suppressor activities, while DeltaTAp73 forms act as oncogenes through the inactivation of p53 and TAp73. The present study analysed how TAp73 and DeltaTAp73 levels might be affected by the presence of a 73 bp deletion in a regulatory region of p73. The clinical relevance of this deletion was also examined. ZEB1 can bind to the region repressing p73 transcription in vitro. The relationship between ZEB1 and p73 variant expression levels was studied in the context of this deletion and the levels of the ZEB1 cofactors p300 and CtBP. Tumour and normal tissue from 81 colorectal cancer patients was analysed to evaluate firstly the levels of TAp73, DeltaTAp73 (DeltaEx2p73, DeltaEx2/3p73, and DeltaNp73), ZEB1, p300, and CtBP by quantitative real-time RT-PCR, and secondly the presence of the 73 bp deletion. Tumour characteristics were examined in each patient. Suppressor and oncogenic isoforms of p73 were co-up-regulated in tumour tissues. Overexpression of p73 variants was associated with adverse tumour features. The 73 bp deletion was present in 40% of the patients and was associated with adverse pathological parameters of the tumours and also with TAp73 down-regulation. In those cases harbouring the deletion, the levels of ZEB1 and those of DeltaEx2p73, DeltaEx2/3p73, and DeltaNp73 correlated directly. Variations in the concentration of p300 affected the observed correlations between ZEB1 and the different p73 variants. In conclusion, in colorectal cancer, the 73 bp deletion in the first intron of the p73 gene and different expression levels of ZEB1 and p300 may act in concert to affect the ratio of TAp73/DeltaTAp73 forms, favouring p73 oncogenic variants. In addition, up-regulation of p73 oncogenic isoforms predicts a poor prognosis based on its relationship with advanced tumour stage.

Aged↗

PubMed2006

Risk-factors for acquisition of extended-spectrum beta-lactamase-producing Escherichia coli among hospitalised patients.

Between 1996 and 2002, 103 hospitalised patients yielding one or more clinical isolates of extended-spectrum beta-lactamase-producing Escherichia coli (ESBL-EC) were identified. A significant increase was observed in the incidence of ESBL-EC colonisation or infection during the study period (1.65 episodes/100 000 patient-days in 1996 to 12.6 episodes/100 000 patient-days in 2002; p 0.01). Infection developed in 70 (68%) patients (75 episodes), with surgical site (44%) and urinary tract (17%) infections being the most frequent. Pulsed-field gel electrophoresis showed extensive clonal diversity among the isolates. A case-control study and multivariate analysis identified female gender (OR 2.1; p 0.01), use of a nasogastric tube (OR 3.5; p 0.001) and previous antibiotic therapy (OR 3.9; p < 0.001) as independent variables associated with acquisition of ESBL-EC. The study demonstrated a progressive increase in the number of ESBL-EC isolates in a non-epidemic setting. Most cases of ESBL-EC colonisation or infection occurred in hospitalised patients exposed to invasive procedures and antibiotic pressure.

Adolescent↗

PubMed2006

Manipulation of the acetylation degree of Azotobacter vinelandii alginate by supplementing the culture medium with 3-(N-morpholino)-propane-sulfonic acid.

AIMS: The aim of this study was to characterize the influence of 3-(N-morpholino)-propane-sulfonic acid (MOPS) on alginate production by Azotobacter vinelandii and its chemical composition (particularly its acetylation degree), as well as on the rheological behaviour of alginate-reconstituted solutions. METHODS AND RESULTS: Cultures were grown in 500-ml flasks containing 90 ml of medium supplemented with MOPS in concentrations ranging from 0 to 13.6 mmol l(-1). The acetylation degree of the alginate was significantly influenced by the MOPS concentration, obtaining an alginate with an acetylation degree of 1.4% when 13.6 mmol l(-1) of MOPS was added to the medium. This value was twice as high as that obtained when no MOPS was used. The higher acetylation of the polymer resulted in higher viscosity of alginate solutions, having a more pronounced pseudoplastic behaviour. CONCLUSIONS: MOPS added to the culture medium determines the acetyl content of the alginate and thus, the physico-chemical properties of the polymer. SIGNIFICANCE AND IMPACT OF THE STUDY: These changes in the functional properties of the polymer can be very valuable in specific applications of alginate in the food and pharmaceutical fields.

Acetylation↗

PubMed2005

Endobain E, a brain endogenous factor, is present and modulates NMDA receptor in ischemic conditions.

We have isolated from rat cerebral cortex an endogenous Na(+), K(+)-ATPase inhibitor, termed endobain E, which modulates glutamatergic N-methyl-d-aspartate (NMDA) receptor. This endogenous factor allosterically decreases [(3)H]dizocilpine binding to NMDA receptor, most likely acting as a weak channel blocker. In the present study we investigated whether endobain E is present in the cerebral cortex of rats subjected to ischemia and modulates NMDA receptor exposed to the same conditions. Ischemia-reperfusion was carried out by bilateral occlusion of common carotid arteries followed by a 15-min reperfusion period. Elution profile of brain soluble fraction showed that endobain E is present in cerebral cortex of ischemia-reperfusion rats. On assaying its effect on synaptosomal membrane Na(+), K(+)-ATPase activity and [(3)H]dizocilpine binding to cerebral cortex membranes prepared from animals without treatment, it was found that the endogenous modulator isolated from ischemia-reperfusion rats was able to inhibit both enzyme activity and ligand binding. On the other hand, endobain E prepared from rats without treatment also decreased binding to cerebral cortex or hippocampal membranes obtained from animals exposed to ischemia-reperfusion. Since ischemia decreases tissue pH and NMDA receptor activity varies according to proton concentration, pH influence on endobain E effect was tested. Endobain E ( approximately 80 mg original tissue) decreased [(3)H]dizocilpine binding 25% at pH 7.4 or 8.0 but 90% at pH 6.5. These results demonstrate that endobain E is present and also able to modulate NMDA receptor in the short-term period that follows cerebral ischemia and that its effect depends on proton concentration, suggesting greater NMDA receptor modulation by endobain E at low pH, typical of ischemic tissues.

Animals↗

PubMed2005

Modulation of aspartate release by ascorbic acid and endobain E, an endogenous Na+, K+ -ATPase inhibitor.

The isolation of a soluble brain fraction which behaves as an endogenous ouabain-like substance, termed endobain E, has been described. Endobain E contains two Na+, K+ -ATPase inhibitors, one of them identical to ascorbic acid. Neurotransmitter release in the presence of endobain E and ascorbic acid was studied in non-depolarizing (0 mM KCl) and depolarizing (40 mM KCl) conditions. Synaptosomes were isolated from cerebral cortex of male Wistar rats by differential centrifugation and Percoll gradient. Synaptosomes were preincubated in HEPES-saline buffer with 1 mM D-[3H]aspartate (15 min at 37 degrees C), centrifuged, washed, incubated in the presence of additions (60 s at 37 degrees C) and spun down; radioactivity in the supernatants was quantified. In the presence of 0.5-5.0 mM ascorbic acid, D-[3H]aspartate release was roughly 135-215% or 110-150%, with or without 40 mM KCI, respectively. The endogenous Na+, K+ -ATPase inhibitor endobain E dose-dependently increased neurotransmitter release, with values even higher in the presence of KCl, reaching 11-times control values. In the absence of KCl, addition of 0.5-10.0 mM commercial ouabain enhanced roughly 100% D-[3H]aspartate release; with 40 mM KCl a trend to increase was recorded with the lowest ouabain concentrations to achieve statistically significant difference vs. KCl above 4 mM ouabain. Experiments were performed in the presence of glutamate receptor antagonists. It was observed that MPEP (selective for mGluR5 subtype), failed to decrease endobain E response but reduced 50-60% ouabain effect; LY-367385 (selective for mGluR1 subtype) and dizocilpine (for ionotropic NMDA glutamate receptor) did not reduce endobain E or ouabain effects. These findings lead to suggest that endobain E effect on release is independent of metabotropic or ionotropic glutamate receptors, whereas that of ouabain involves mGluR5 but not mGluR1 receptor subtype. Assays performed at different temperatures indicated that in endobain E effect both exocytosis and transporter reversion are involved. It is concluded that endobain E and ascorbic acid, one of its components, due to their ability to inhibit Na+, K+ -ATPase, may well modulate neurotransmitter release at synapses.

Animals↗

PubMed2005

Thirty day prognosis of patients with acute pulmonary oedema complicating acute coronary syndromes.

OBJECTIVES: To investigate the characteristics of the acute coronary syndromes underlying acute pulmonary oedema and their 30 day prognosis. PATIENTS: 185 consecutive patients with acute coronary syndromes and acute pulmonary oedema admitted to a tertiary care centre. MAIN OUTCOME AND MEASURES: Clinical, ECG, echocardiographic, enzymatic, and angiographic features were prospectively investigated. RESULTS: Non-ST segment elevation myocardial infarction (NSTEMI) was the most frequent cause of acute pulmonary oedema (61%) followed by unstable angina (UA; 21%) and ST segment elevation myocardial infarction (STEMI; 18%). In each group, mean age was > or = 70 years, but NSTEMI patients were the oldest and > or = 65% of patients had chronic hypertension. Moreover, patients with NSTEMI and UA were older and had a higher incidence of diabetes, previous myocardial infarction, and moderate to severe mitral regurgitation but a similarly reduced ejection fraction (NSTEMI, 41%; UA, 39%; and STEMI, 39%) and increased incidence of diastolic dysfunction and rate of multivessel disease (94%, 87%, and 86%, respectively). However, patients with STEMI had a higher creatine kinase MB peak concentration (158 v 76 microg/l in the NSTEMI group, p < 0.001) and 30 day mortality (26% v 9% in the NSTEMI group and 8% in the UA group, p < 0.024). Multivariate analysis identified ejection fraction < 40% and a peak creatine kinase MB concentration > 100 microg/l as the main prognostic markers (p < 0.03). CONCLUSIONS: Acute pulmonary oedema is mostly a complication of elderly hypertensive patients with NSTEMI or UA (82%) and with multivessel disease often associated with mitral regurgitation. On the other hand, the larger infarct size and higher mortality in patients with STEMI with a similarly reduced ejection fraction suggest a more extensive acute systolic loss.

Acute Disease↗

PubMed2004

Phase II trial of cisplatin and capecitabine in patients with squamous cell carcinoma of the head and neck, and correlative study of angiogenic factors.

The combination of cisplatin and capecitabine was evaluated in patients with recurrent or unresectable squamous cell carcinoma of the head and neck (HNSCC), and outcome parameters were correlated with the expression of thymidine phosphorylase (TP), thymidilate syntetase (TS), vascular endothelial growth factor receptor (VEGFR) 1-3, and microvessel density (MVD). Patients with recurrent or unresectable HNSCC were eligible if they had received prior neoadjuvant chemotherapy, concurrent chemo-radiotherapy, or no prior systemic therapy. Patients received cisplatin (75 mg m(-2) day 1), and capecitabine (2000 mg m(-2) day 1-14) every 3 weeks. A total of 41 patients received 194 cycles. In all, 16 complete responses (39%) and 12 partial responses (29%) were documented, for an overall response rate of 68% (95% CI, 53-80%). Grade 3-4 uncomplicated neutropenia was documented in five subjects. Asthenia, anorexia, hand-foot syndrome, and constipation were the most frequent nonhaematologic events. Median progression-free and overall survival were 6.4 and 12.6 months. Cytoplasmic TP expression was more prevalent in patients with a laryngeal location vs other, and in patients with a recurrence vs primary disease. Microvessel density count was higher in patients with recurrent vs primary disease. The combination of cisplatin and capecitabine is effective in recurrent or unresectable HNSCC, and shows a manageable toxicity.

Adult↗

PubMed2004

Staphylococcus aureus nasal carriage in patients on haemodialysis: role of cutaneous colonization.

We performed a prospective study of Staphylococcus aureus nasal carriage in patients on chronic haemodialysis to determine the role of cutaneous colonization in the aetiology of recurrent nasal colonization. From February 2000 to September 2001, 71 patients on chronic haemodialysis in the dialysis unit at a university hospital were screened monthly for S. aureus nasal carriage. Carriers received nasal mupirocin for five days and were tested for nasal and cutaneous carriage two days later and monthly thereafter. Using genotyping results, recurrence was defined as relapse if pretreatment and subsequent nasal isolates were clonally identical; if the isolates were different, it was considered recolonization. Thirty-nine patients (55%) were nasal carriers: 11 initially and 28 during follow-up. Among the mupirocin-treated patients, the eradication of S. aureus nasal carriage rate was 88.5%. Nasal recurrence was documented in 17 patients (43.5%), and S. aureus nasal strains were available for molecular typing in 14 patients with a total of 23 recurrence episodes. On the basis of pulsed-field gel electrophoresis analysis, 16 (70%) recurrence episodes were considered relapses and seven were considered (30%) recolonizations. Among the episodes of relapse, prior cutaneous colonization was detected in only three cases. In haemodialysis patients, the majority of nasal carriage recurrences after mupirocin therapy were due to relapses. Cutaneous colonization does not appear to be relevant in the development of these relapses.

Anti-Bacterial Agents↗

PubMed2004

The effect of endogenous modulator endobain E on NMDA receptor is interfered by Zn2+ but is independent of modulation by spermidine.

A brain endogenous factor, termed endobain E, allosterically decreases [3H]dizocilpine binding to NMDA receptor. Such effect depends on receptor activation by the coagonists glutamate and glycine and is interfered by channel blockers, suggesting its interaction with the inner surface of the associated channel. To further analyze endobain E effect on NMDA receptor, in the current study competitive [3H]dizocilpine binding assays to brain membranes were performed with Zn2+ to block the associated channel, as well as with spermidine (SPD), which exerts positive allosteric modulation of NMDA receptor. Partially or nonadditive effects on [3H]dizocilpine binding were recorded, respectively, in the presence of endobain E at a concentration that inhibits binding 25% plus IC25 Zn2+ or endobain E at a concentration that inhibits binding 50% plus IC50 Zn2+. With an endobain E concentration that decreases 25% ligand binding, SPD potentiated binding over a wide concentration range but failed to modify endobain E effect. Similarly, [3H]dizocilpine binding reduction over a wide endobain E concentration range remained unaltered by high SPD concentrations. Additive effects were observed with endobain E at a concentration that decreases binding 25% plus IC25 SPD site antagonists arcaine or ifenprodil. Zn2+ experiments indicated that endobain E effect is interfered by channel blockade produced by this ion. Although endobain E effect is dependent on NMDA receptor activation by glutamate and glycine, it proves independent of the positive modulation exerted by SPD. Thus the endogenous modulator seems not to interact at NMDA receptor polyamine site, favoring the hypothesis that endobain E binds inside the associated channel.

Animals↗

PubMed2003

A comparative study between a brain Na+,K(+)-ATPase inhibitor (endobain E) and ascorbic acid.

In the search of Na+,K(+)-ATPase modulators, we have reported the isolation by gel filtration and HPLC of a brain fraction, termed endobain E, which highly inhibits Na+,K(+)-ATPase activity. In the present study we compared some properties of endobain E with those of ascorbic acid. Kinetic experiments assaying synaptosomal membrane K(+)-p-nitrophenylphosphatase (K(+)-p-NPPase) activity in the presence of endobain E or ascorbic acid showed that in neither case did enzyme inhibition prove competitive in nature versus K+ or p-NPP concentration. At pH 5.0, endobain E and ascorbic acid maximal UV absorbance was 266 and 258 nm, respectively; alkalinization to pH 14.0 led to absorption drop and shift for endobain E but to absorbance disappearance for ascorbic acid. After cysteine treatment, endobain E absorbance decreased, whereas that of ascorbic acid remained unaltered; iodine treatment led to absorbance drop and shift for endobain E but to absorbance disappearance for ascorbic acid. HPLC analysis of endobain E disclosed the presence of two components: one eluting with retention time and UV spectrum indistinguishable from those of ascorbic acid and a second, as yet unidentified, both exerting Na+,K(+)-ATPase inhibition.

4-Nitrophenylphosphatase↗

PubMed2003

Synthesis and immunogenic properties of phosphopeptides related to the human insulin receptor.

Two phosphoserine tetradecapeptides corresponding to sequences 987-1000 (peptide pSer994) and 1017-1030 (peptide pSer1023/1025) from the human insulin receptor involved in the regulation of its activity were successfully synthesized using Fmoc-based chemistry. Phosphorylation was performed by post-assembly phosphitylation followed by oxidation. The selective phosphorylation of Ser residues was achieved incorporating into the peptide chain the Ser (Trt) derivative and t-Bu blocking groups at sites other than those intended to be phosphorylated. The Trt group was selectively removed with dichloroacetic acid while under this condition t-Bu protecting groups remained unaltered. Following conjugation to keyhole limpet hemocyanin phosphopeptides were used as immunogens to generate sequence-specific phosphoserine antibodies. Peptide pSer994 induced antibodies in New Zealand white rabbits which discriminated between the phosphorylated and nonphosphorylated forms of the peptide, thus representing promising candidates to recognize signaling pathways associated to the regulation of the human insulin receptor.

Amino Acid Sequence↗

PubMed2003

An outbreak of carbapenem-resistant Pseudomonas aeruginosa in a urology ward.

OBJECTIVE: To investigate an outbreak of carbapenem-resistant Pseudomonas aeruginosa (CRPA) in a urology ward. METHODS: Patients infected or colonized with CRPA were prospectively identified by daily laboratory surveillance. Routine infection-control measures were reinforced, disinfection protocols were revised, and a surveillance program was set up, analyzing cross-transmission in the nursing ward and environment cultures from urology wards and the operating theater. CRPA isolates from clinical and environment samples were studied by pulsed-field gel electrophoresis (PFGE), following XbaI and SpeI restriction. RESULTS: From February 1998 to September 2000, 59 adult urology patients were colonized or infected by CRPA. All patients had been operated on prior to identification of the CRPA isolate and 79% of these procedures were performed in the same cystoscopy room. No patients had received prior carbapenem therapy. No cross-transmission was detected, and environment cultures from the urology ward and theater were negative except for five samples collected in the cystoscopy room. PFGE identified a single clone in the isolates from different patients and the environment samples. CONCLUSIONS: The PFGE analysis indicated that the CRPA outbreak resulted from the contamination of the cystoscopy room via an unsealed drain. The outbreak ended when the drain was sealed.

Anti-Bacterial Agents↗

PubMed2002

Metabotropic glutamate receptor involvement in phosphoinositide hydrolysis stimulation by an endogenous Na(+), K(+)-ATPase inhibitor and ouabain in neonatal rat brain.

The mechanism of action of an endogenous Na(+), K(+)-ATPase inhibitor, termed endobain E, on phosphoinositide hydrolysis was studied in neonatal rat brain cortex and compared with that of ouabain. Lack of additivity for endobain E and glutamate paired stimulation on inositol phosphates accumulation suggested that they share at least a common step on inositol phosphate metabolism, as previously advanced for ouabain. In addition, Cd(2+) sensitivity of endobain E and ouabain effects strengthened the involvement of glutamate receptors. The participation of ionotropic glutamate receptors on endobain E- and ouabain-induced phosphoinositide hydrolysis seems untenable, since antagonists dizocilpine and CNQX proved unable to inhibit these effects. However, the endobain E effect was blocked by 2 x 10 (-4) M L-AP3 (an antagonist for group I mGluRs) when at least a 15-min preincubation protocol was employed. Maximal inhibition of endobain E effect (42%) occurred when L-AP3 preincubation was extended to 60 min, as already shown with glutamate, but only a trend to decrease was recorded with ouabain. At variance, the ouabain effect was reduced to 50% employing 5 x 10 (-4) M MCPG (a competitive antagonist for group I mGluRs), whereas no blockade was observed with endobain E or glutamate. In addition, MPEP (a selective mGluR5 antagonist) partially reduced ouabain, endobain E and glutamate responses and the selective mGluR1 antagonist LY367385 showed no activity at all. To sum up, the present findings support the involvement of mGluR5 in both endobain E and ouabain phosphoinositide hydrolysis stimulation in neonatal rat brain, in spite of dissimilar response to tested antagonists.

Animals↗

PubMed2002

Effectiveness factor in biological external convection: study in high viscosity systems.

A study regarding the influence of mixing on the efficiency of alginate and xanthan synthesis was carried out. The effectiveness of these two systems in terms of a dimensionless reaction convection number (N(RC)), which is a function of the power input per unit volume, was analysed and compared with low viscosity systems. The results revealed that a decrease in the power input caused a reduction in the growth rate as well as in production rate. It was observed that the effectiveness factor (eta) both for alginate production and xanthan synthesis resulted weakly dependent on the biomass content. A good correlation between effectiveness and N(RC) was obtained for the two tested models. N(RC) number could be appropriately employed in correlating the effectiveness factor for processes with viscosities from 0.001 to more than 1 kg m(-1) s(-1). Due to the parallelism with the conventional internal diffusion approach (Thiele modulus), the advantages for applying N(RC), in particular to correlate the efficiency in systems limited both for external convection and internal diffusional resistance, are shown.

Alginates↗

PubMed2002

Alginate production by Azotobacter vinelandii mutants altered in poly-beta-hydroxybutyrate and alginate biosynthesis.

Mutant AT268 of Azotobacter vinelandii - showing diminished production of poly-beta-hydroxybutyrate (PHB) due to a mutation in phbR (the gene coding for the transcriptional activator of the phbBAC biosynthetic operon); mutant CNT26, containing a mutation (muc26) that increases the transcription of gene algD (encoding GDP mannose dehydrogenase, the key enzyme in alginate biosynthesis); and mutant DM, carrying both phbR and muc26 mutations - were characterised in terms of alginate production, broth viscosity, and molecular weight of the alginate. All the mutants evaluated produced 25% less alginate with respect to that produced by the wild type. Unexpectedly and with no apparent relation to the phbR and muc26 mutations, mutant DM exhibited the highest molecular weight ever reported for a bacterial alginate (up to 4 x 10(6) Da), with a very low polydispersity index (1.3). Acetyl content in the alginate produced by this strain was low (1.4-2.6%). These characteristics make this mutant a very valuable source for producing alginates with improved properties.

Alginates↗

PubMed2002

Induction chemotherapy with paclitaxel, cisplatin and 5-fluorouracil for squamous cell carcinoma of the head and neck: long-term results of a phase II trial.

BACKGROUND: The aim of this study was to evaluate the efficacy and toxicity of a combination of paclitaxel, cisplatin and 5-fluorouracil (PPF) as induction chemotherapy in patients with locally advanced squamous cell carcinoma of the head and neck (SCCHN). METHODS: Seventy patients with previously untreated stage III-IV SCCHN were included in this phase II trial. Induction treatment consisted of a maximum of three outpatient courses of paclitaxel 175 mg/m(2) as a 3-h infusion on day 1, cisplatin 100 mg/m(2) on day 2, and 5-fluorouracil (5-FU) 500-750 mg/m(2)/day as a 24-h continuous infusion on days 2-6, repeated every 3 weeks. The 5-FU dose was reduced from 750 mg/m(2)/day to 500 mg/m(2)/day due to the excessive toxicity observed in the first 14 patients enrolled. Local treatment consisted of radiotherapy and/or surgery. RESULTS: Two-hundred-and-one cycles were administered to 70 patients. The main toxicities of PPF were neutropenia (grade 4, 14%; febrile neutropenia, 4%), peripheral neuropathy (grade 2-3, 14%) and catheter-associated venous thrombosis (7%). There were three early deaths (two from neutropenic sepsis and one from pulmonary embolism), and 13 patients required hospitalization due to toxicity. Other side effects included mucositis, anorexia, diarrhea, myalgias and alopecia. The overall response rate to PPF was 88%, including 59% complete responses (CR) and 29% partial responses. The CR rates at the primary tumor and neck lymph nodes were 74% and 62%, respectively. With a median follow-up of 51 months (range 40-63 months), the estimated 5-year time-to-disease progression and overall survival rates were 56% and 44%, respectively. CONCLUSIONS: The PPF regimen has major antitumor activity and is associated with manageable toxicity as induction treatment in SCCHN patients. The high complete response rate and favorable long-term outcome justify further evaluation of this chemotherapy combination.

Adult↗

PubMed2001

Effect of short-course, high-dose amoxicillin therapy on resistant pneumococcal carriage: a randomized trial.

CONTEXT: Emerging drug resistance threatens the effectiveness of existing therapies for pneumococcal infections. Modifying the dose and duration of antibiotic therapy may limit the spread of resistant pneumococci. OBJECTIVE: To determine whether short-course, high-dose amoxicillin therapy reduces risk of posttreatment resistant pneumococcal carriage among children with respiratory tract infections. DESIGN AND SETTING: Randomized trial conducted in an outpatient clinic in Santo Domingo, Dominican Republic, October 1999 through July 2000. PARTICIPANTS: Children aged 6 to 59 months who were receiving antibiotic prescriptions for respiratory tract illness (n = 795). INTERVENTIONS: Children were randomly assigned to receive 1 of 2 twice-daily regimens of amoxicillin: 90 mg/kg per day for 5 days (n = 398) or 40 mg/kg per day for 10 days (n = 397). MAIN OUTCOME MEASURES: Penicillin-nonsusceptible Streptococcus pneumoniae carriage, assessed in nasopharyngeal specimens collected at days 0, 5, 10, and 28; baseline risk factors for nonsusceptible pneumococcal carriage; and adherence to regimen, compared between the 2 groups. RESULTS: At the day 28 visit, risk of penicillin-nonsusceptible pneumococcal carriage was significantly lower in the short-course, high-dose group (24%) compared with the standard-course group (32%); relative risk (RR), 0.77; 95% confidence interval (CI), 0.60-0.97; P =.03; risk of trimethoprim-sulfamethoxazole nonsusceptibility was also lower in the short-course, high-dose group (RR, 0.77; 95% CI, 0.58-1.03; P =.08). The protective effect of short-course, high-dose therapy was stronger in households with 3 or more children (RR, 0.72; 95% CI, 0.52-0.98). Adherence to treatment was higher in the short-course, high-dose group (82% vs 74%; P =.02). CONCLUSION: Short-course, high-dose outpatient antibiotic therapy appears promising as an intervention to minimize the impact of antibiotic use on the spread of drug-resistant pneumococci.

Amoxicillin↗