Long term results of a phase II trial of Induction Chemotherapy with Uracil-Ftegafur (UFT), Vinorelbine and Cisplatin (UFTVP) followed by Radiotherapy concomitant with UFT and Carboplatin (RT/UFTJ) in Non-Resectable Locally Advanced (Stage IV-B) Squamous Cell Head and Neck Carcinoma

Purpose. To evaluate the response of advanced squamous cell head and neck carcinoma to a combination of induction chemotherapy and radiotherapy. Methods. We present long-term results of a phase II trial of Induction Chemotherapy with UFT 200 mg/m² p.o. days 1 to 21, Vinorelbine 25 mg/m² i.v. days 1 and 8 and Cisplatin 100 mg/m² i.v. day 1 (UFTVP) each 21 days for 4 courses, followed by Radiotherapy concomitant with UFT 100 mg/m² p.o. daily and Carboplatin AUC = 0.5 i.v. weekly (RT/UFTJ) in patients (pts) with Non-Resectable Locally Advanced (Stage IV-B) Squamous Cell Head and Neck Carcinoma (IV-B-SCHNC). Primary endpoint was Complete Response to induction UFTVP and secondary endpoints were Disease Free Status Rate after locoregional treatment and long-term Overall Survival. Between 1994 and 1997, 32 pts were included. Results. Complete Response to Induction UFTVP was 59% (95% CI: 48%-70%). Main toxicity of UFTVP was G 3,4 neutropenia (94% of pts; 25% developed febrile neutropenia and 1 of this pts dead). After Induction Chemotherapy with UFTVP, 30 pts received radiotherapy and 25 of them received cocomitant Carboplatin and UFT (RT/UFTJ): main toxicity was mucositis (G3-4: 72%) and one patient died during RT/UFTJ because pneumonia. Twenty-five pts (78%) were alive and disease free at the end of the whole treatment. Actuarial 5 year Overall survival is 32%. Conclusion. Although toxicity is important, this approach has interesting activity and deserves further investigation. In the January issue of Clin Transl Oncol the following article was published with a wrong reference: Fernando Rivera, María E Vega-Villegas, Marta F. López-Brea, Almudena García-Casta?o, Ana de Juan, Francisco Javier Ramos, Antonio Collado, Piedad Galdós, Antonio Rubio, Adolfo del Valle, Julio Rama, Marta Mayorga and Jaime Sanz-Ortiz Long term results of a phase II trial of Induction Chemotherapy with Uracil-Ftegafur (UFT), Vinorelbine and Cisplatin (UFTVP) followed by Radiotherapy concomitant with UFT and Carboplatin (RT/UFTJ) in Non-Resectable Locally Advanced (Stage IV-B) Squamous Cell Head and Neck Carcinoma and Peripheral Blood Stem Cell Support (PBSCS) with Febrile Neutropenia Clin Transl Oncol. 2007 Jan;9:40-47 DOI 10.1007/s12094-007-0008-5 The correct reference should be as follows: Fernando Rivera, María E Vega-Villegas, Marta F. López-Brea, Almudena García-Casta?o, Ana de Juan, Francisco Javier Ramos, Antonio Collado, Piedad Galdós, Antonio Rubio, Adolfo del Valle, Julio Rama, Marta Mayorga and Jaime Sanz-Ortiz Long term results of a phase II trial of Induction Chemotherapy with Uracil-Ftegafur (UFT), Vinorelbine and Cisplatin (UFTVP) followed by Radiotherapy concomitant with UFT and Carboplatin (RT/UFTJ) in Non-Resectable Locally Advanced (Stage IV-B) Squamous Cell Head and Neck Carcinoma Clin Transl Oncol. 2007 Jan;9:40-47The original article can be found online at     

Aqueous and hydroalcoholic extracts of Black Maca (Lepidium meyenii) improve scopolamine-induced memory impairment in mice.

Lepidium meyenii Walp. (Brassicaceae), known as Maca, is a Peruvian hypocotyl growing exclusively between 4,000 and 4,500 m altitude in the central Peruvian Andes, particularly in Junin plateau. Previously, Black variety of Maca showed to be more beneficial than other varieties of Maca on learning and memory in ovariectomized mice on the water finding test. The present study aimed to test two different doses of aqueous (0.50 and 2.00 g/kg) and hydroalcoholic (0.25 and 1.00 g/kg) extracts of Black Maca administered for 35 days on memory impairment induced by scopolamine (1mg/kg body weight i.p.) in male mice. Memory and learning were evaluated using the water Morris maze and the step-down avoidance test. Brain acetylcholinesterase (AChE) and monoamine oxidase (MAO) activities in brain were also determined. Both extracts of Black Maca significantly ameliorated the scopolamine-induced memory impairment as measured in both the water Morris maze and the step-down avoidance tests. Black Maca extracts inhibited AChE activity, whereas MAO activity was not affected. These results indicate that Black Maca improves scopolamine-induced memory deficits.     

Flat Serrated Adenomas and Flat Tubular Adenomas of the Colorectal Mucosa: Differences in the Pattern of Cell Proliferation

In the present work we have investigated the cell proliferation pattern of flat serrated adenomas and flat tubular adenomas. For this purpose tissue sections from 23 consecutive flat serrated adenomas and 22 consecutive flat tubular adenomas of the colorcctal mucosa were challenged with MID1, a monoclonal antibody directed against a proliferation-related antigen. The results (including semi-quantitative studies) demonstrated that, whereas flat serrated adenomas had a high cell proliferation at the lower part of the crypts, flat tubular adenomas had a high cell proliferation in the upper part of the crypts. In serrated adenomas with invasive adenocarcinoma, high cell proliferation was demonstrated both at the lower portion of the crypts and in the subjacent submucosa. This suggests that the cells of the lower portion of the crypts in serrated adenomas are truely neoplastic, with the capacity to evolve into invasive growth. The difference in cell proliferation betweeen the two types of flat lesions reported here is a new argument in favor of the classification of flat serrated adenomas as a novel and independent type of neoplastic change of the colorectal mucosa.     

Fiberoptic intraparenchymal brain pressure monitoring with the Camino V420 monitor: reflections on our experience in 163 severely head-injured patients

To assess the safety and accuracy of the Camino intraparenchymal sensor, we prospectively evaluated hemorrhagic complications, zero-drift, infection, and system malfunction in 163 patients monitored after a severe head injury. Mean duration of intracranial pressure (ICP) monitoring was 5 +/- 2.2 days (range: 12 h to 11 days). Of the 141 patients with a control CT scan, four showed a 1-2-cc collection of blood at the catheter's end. When removed, the sensors underread the true ICP value (negative zero-drift) in 80 of the 126 sensors evaluated (63.5%). Fourteen sensors showed no zero-drift, and 32 sensors overread the true ICP value (positive zero-drift) (median: -1 mm Hg; interquartile range: -4 to +1 mm Hg). No significant relationship was found between zero-drift, the surgeon who implanted the sensor, intracranial hypertension, or duration of ICP monitoring. No clinical infections could be attributed to the devices. Sixteen patients (9.8%) required more than one ICP sensor due to malfunctioning of the system. In conclusion, continuous ICP monitoring using the Camino intraparenchymal sensor has a low complication rate. However, this sensor may underread the real ICP values in a high number of patients. The lack of correlation between duration of ICP monitoring and zero-drift suggests that, contrary to the recommendations of other reports, the intraparenchymatous Camino sensor can provide reliable readings after the fifth day of use.     

Importance of entero-salivary recirculation in paracetamol pharmacokinetics

The contribution of an entero-salivary recirculation (salivary secretion-swallowed-reabsorption of drug from the gastrointestinal tract) to the values of the pharmacokinetic parameters of paracetamol was studied in a two-way crossover design. Five healthy volunteers took a tablet of Paracetamol (500 mg) in two occasions separated by a washout period. The difference between the two treatments consisted of saliva that was allowed or not to be swallowed during the 4 h of study. No statistically significant differences were found in the values of the pharmacokinetic parameters between treatments. The half-life time calculated from salivary levels was similar to the values previously reported by other authors. The percent of the oral dose excreted in saliva during 4 h of study was very low (0.1%). Secondary peaks appeared in 8 of 10 profiles. The lack of influence of salivary secretion on the pharmacokinetic parameters of Paracetamol and the low percent secreted in this fluid suggests that entero-salivary recirculation is a possible physiological phenomenon undergoing after oral administration, but it is not one of the principal phenomenon that defines the pharmacokinetic of the drug. We confirm that working with salivary samples in pharmacokinetic studies of paracetamol is a useful tool.     

Naltrexone improves outcome of a controlled drinking program

Naltrexone is widely used in therapeutic programs with abstinence as a goal. However, it has been used in only a few studies aimed at reducing alcohol consumption. The purpose of this study was to evaluate the efficacy of naltrexone as an adjunct in controlled drinking programs. This was an open randomized study of 12 weeks duration that compared two therapeutic strategies: use of naltrexone in a controlled drinking program (NTX+CD) and the controlled drinking program alone (CD), without NTX. Each group comprised 30 male patients with mild alcohol dependence. During treatment, there were no differences between groups in drinking behavior, though the NTX+CD group showed significantly less craving. In the 12-month follow-up period, the NTX+CD group showed significantly fewer drinking days and heavy drinking days and less craving than the CD group. The results of this study suggest a role for naltrexone in controlled drinking programs.     

Home-based treatment,rates of ambulatory follow-up,and psychiatric rehospitalization in a medicaid managed care population

This study reports on the effect of home-based mental health treatment following psychiatric hospitalization on ambulatory follow-up rates and readmission rates in a Medicaid managed care population. Logistic regression models were used to predict the odds of ambulatory treatment after hospitalization and to predict rehospitalization. A consumer who received in-home treatment was 22 times more likely to follow-through with aftercare treatment of more than one visit than were those who did not receive in-home treatment. However, in-home treatment, age, gender, and previous hospitalization did not significantly predict the odds of rehospitalization. While home-based services did not reduce the incidence of rehospitalization, providing services within the home has the potential to increase attendance in aftercare services by Medicaid managed care recipients.     

4-Substituted D-glutamic acid analogues: the first potent inhibitors of glutamate racemase (MurI) enzyme with antibacterial activity

The first potent inhibitors of glutamate racemase (MurI) enzyme that show whole cell antibacterial activity are described. Optically pure 4-substituted D-glutamic acid analogues with (2R,4S) stereochemistry and bearing aryl-, heteroaryl-, cinnamyl-, or biaryl-methyl substituents represent a novel class of glutamate racemase inhibitors. Exploration of the D-Glu core led to the identification of lead compounds (-)-8 and 10. 2-Naphthylmethyl derivative 10 was found to be a potent competitive inhibitor of glutamate racemase activity (K(i) = 16 nM, circular dichroism assay; IC(50) = 0.1 microg/mL high-performance liquid chromatography (HPLC) assay). Thorough structure-activity relationship (SAR) studies led to benzothienyl derivatives such as 69 and 74 with increased potency (IC(50) = 0.036 and 0.01 microg/mL, respectively, HPLC assay). These compounds showed potent whole cell antibacterial activity against S. pneumoniae PN-R6, and good correlation with the enzyme assay. Compounds 69, 74 and biaryl derivative 52 showed efficacy in an in vivo murine thigh infection model against Streptococcus pneumoniae. Data described herein suggest that glutamate racemase may be a viable target for developing new antibacterial agents.