A 1000-year-old mystery solved: Unlocking the molecular structure for the medieval blue from Chrozophora tinctoria, also known as folium.

The molecular structure of the medieval watercolor known as folium has finally been solved in the 21st century. The interdisciplinary approach taken was the key to producing extracts that had been prepared following medieval instructions, and shows the blue/purple chromophore as the major dye in Chrozophora tinctoria fruits (shell). A multi-analytical characterization of its structure was made using HPLC-DAD-MS, GC-MS, NMR (1H, 13C, COSY, HSQC, HMBC, INADEQUATE), and computational studies. The results demonstrate that the blue compound corresponds to 6'-hydroxy-4,4'-dimethoxy-1,1'-dimethyl-5'-{[3,4,5-trihydroxy-6-(hydroxymethyl)tetrahydro-2H-pyran-2-yl]oxy}-[3,3'-bipyridine]-2,2',5,6(1H,1'H)-tetraone, a hermidin derivative, which we named chrozophoridin. Experimental data and computational modeling studies show that this mono-glycosylated dimer is represented by two stable isomers (atropisomers). This is an indispensable piece of knowledge for the characterization of this medieval dye in works of art such as medieval manuscript illuminations and for testing its stability and contributes to the preservation of our cultural heritage.

Seroepidemiology of Bovine Herpes Virus-1 Infection in Water Buffaloes from the state of Veracruz, Mexico.

Water buffaloes (Bubalus bubalis) were introduced to Mexico at the end of the last century. In Mexico, buffaloes are commonly pastured together with cattle; however few studies have been done on buffalo herd health in Mexico. We hypothesized that a better knowledge of the epidemiology of infections shared between cattle and buffaloes may improve herd profitability and promote buffalo production in areas unsuitable to cattle farming. This study aimed to determine the prevalence of antibodies against bovine herpes virus - 1 (BoHV1) in water buffaloes raised on six farms from the state of Veracruz, Mexico. Of 368 buffaloes sampled, 217 (59%) were seropositive for BoHV-1. Age was identified as a risk factor for BoHV-1 infection with buffaloes older than 5 years being the most likely to be infected. Animals more than 7 years old had the highest prevalence (86.0%). Females and males had similar seroprevalence rates. Females with history of abortion had higher prevalence of antiBoHV-1 antibodies than those with no record of abortion. Buffaloes and cattle were raised together in only one of the six farms under study. Interaction with cattle was not a risk factor for BoHV-1 seropositivity. This study showed that BoHV-1 is prevalent among buffalo herds in the state of Veracruz, Mexico. Buffaloes appear to play an important role in the epidemiology of BoHV-1 infection in parts of Mexico when there is no apparent risk of interaction with cattle. Animal health programs established to mitigate the burden caused by BoHV-1 must take into consideration buffaloes when this bovid species is part of the agroecosystem shared with cattle.

A multiproxy approach to evaluate biocidal treatments on biodeteriorated majolica glazed tiles.

The Fishing House located on the grounds of the Marquis of Pombal Palace, Oeiras, Portugal, was built in the 18th century. During this epoch, Portuguese gardens, such as the one surrounding the Fishing House, were commonly ornamented with glazed wall tile claddings. Currently, some of these outdoor tile panels are covered with dark colored biofilms, contributing to undesirable aesthetic changes and eventually inducing chemical and physical damage to the tile surfaces. Phylogenetic analyses revealed that the investigated biofilms are mainly composed of green algae, cyanobacteria and dematiaceous fungi. With the aim of mitigating biodeterioration, four different biocides (TiO2 nanoparticles, Biotin® T, Preventol® RI 80 and Albilex Biostat® ) were applied in situ to the glazed wall tiles. Their efficacy was monitored by visual examination, epifluorescence microscopy and DNA-based analysis. Significant changes in the microbial community composition were observed 4 months after treatment with Preventol® RI 80 and Biotin® T. Although the original community was inactivated after these treatments, an early stage of re-colonization was detected 6 months after the biocide application. TiO2 nanoparticles showed promising results due to their self-cleaning effect, causing the detachment of the biofilm from the tile surface, which remained clean 6 and even 24 months after biocide application. © 2013 Society for Applied Microbiology and John Wiley & Sons Ltd.

A blue 4',7-diaminoflavylium cation showing an extended pH range stability.

The introduction of two amine substituents in 4' and 7 positions, leads to the formation of a blue flavylium cation, 7-(N,N'-diethylamino)-2-(9-julolidine)-1-benzopyrilium, which is extremely stable across a wide acidic pH range. The kinetic and thermodynamic constants of the multistate system have been calculated by studying the relaxation kinetics after equilibrium perturbation by addition of base (direct pH jumps) or acid (reverse pH jumps). Except for the cis-chalcone, which is an elusive species, the relative energy levels of the other species could be calculated and a global energy level diagram constructed. The diagram explains that the stability of the diamino compound is due to the high energy level of the hemiketal species, which is difficult to access in acidic medium.

[Pneumomediastinum associated with hyperemesis gravidarum: a case report]. / Neumomediastino secundario a hiperémesis gravídica: reporte de un caso.

Background: The hyperemesis gravidarum is a severe illness of nauseas and vomit that is present in the first trimester of the pregnancy, it has an incidence of 0.3 to 2%, it has been associated to weight loss, electrolytic disturbances, ketonuria, dehydration and in very seldom cases spontaneous pneumomediastinum. Clinical case: A 21 years old female patient, primigest, in the first trimester of gestation, she started her disease with nauseas and vomiting more than 15 times during 6 hours period, odynophagia, dysphonia and pain in the cervical region, loss of 5 kilograms in the last month. The physical examination showed the patient in bad conditions, dehydration, neck with volume increased and emphysema subcutaneus, crakles until torax. Laboratory findings with hypokalemia, leukocytosis, acute kidney failure, and elevation of hepatic enzymes. The initial treatment was with intravenous fluids resuscitation, hydroelectrolytic balance restoration, antiemetic treatment and rest, it was taken TC of neck and torax, and was exclude any laryngeal and esophageal injury and perforation, but it showed air in the mediastinum. Conservative management with favorable evolution and completed resolution in 7 days. Conclusion: It is very important that the medical doctor must keep in mind the different diagnosis of and take an opportune decision in case of present those complications potentially fatal to the mother.

Next-generation-sequencing of recurrent childhood high hyperdiploid acute lymphoblastic leukemia reveals mutations typically associated with high risk patients.

20% of children suffering from high hyperdiploid acute lymphoblastic leukemia develop recurrent disease. The molecular mechanisms are largely unknown. Here, we analyzed the genetic landscape of five patients at relapse, who developed recurrent disease without prior high-risk indication using whole-exome- and whole-genome-sequencing. Oncogenic mutations of RAS pathway genes (NRAS, KRAS, FLT3, n=4) and deactivating mutations of major epigenetic regulators (CREBBP, EP300, each n=2 and ARID4B, EZH2, MACROD2, MLL2, each n=1) were prominent in these cases and virtually absent in non-recurrent cases (n=6) or other pediatric acute lymphoblastic leukemia cases (n=18). In relapse nucleotide variations were detected in cell fate determining transcription factors (GLIS1, AKNA). Structural genomic alterations affected genes regulating B-cell development (IKZF1, PBX1, RUNX1). Eleven novel translocations involved the genes ART4, C12orf60, MACROD2, TBL1XR1, LRRN4, KIAA1467, and ELMO1/MIR1200. Typically, patients harbored only single structural variations, except for one patient who displayed massive rearrangements in the context of a germline tumor suppressor TP53 mutation and a Li-Fraumeni syndrome-like family history. Another patient harbored a germline mutation in the DNA repair factor ATM. In summary, the relapse patients of our cohort were characterized by somatic mutations affecting the RAS pathway, epigenetic and developmental programs and germline mutations in DNA repair pathways.

Genomic inverse PCR for exploration of ligated breakpoints (GIPFEL), a new method to detect translocations in leukemia.

Here we present a novel method "Genomic inverse PCR for exploration of ligated breakpoints" (GIPFEL) that allows the sensitive detection of recurrent chromosomal translocations. This technique utilizes limited amounts of DNA as starting material and relies on PCR based quantification of unique DNA sequences that are created by circular ligation of restricted genomic DNA from translocation bearing cells. Because the complete potential breakpoint region is interrogated, a prior knowledge of the individual, specific interchromosomal fusion site is not required. We validated GIPFEL for the five most common gene fusions associated with childhood leukemia (MLL-AF4, MLL-AF9, MLL-ENL, ETV6-RUNX1, and TCF3-PBX1). A workflow of restriction digest, purification, ligation, removal of linear fragments and precipitation enriching for circular DNA was developed. GIPFEL allowed detection of translocation specific signature sequences down to a 10-4 dilution which is close to the theoretical limit. In a blinded proof-of-principle study utilizing DNA from cell lines and 144 children with B-precursor-ALL associated translocations this method was 100% specific with no false positive results. Sensitivity was 83%, 65%, and 24% for t(4;11), t(9;11) and t(11;19) respectively. Translocation t(12;21) was correctly detected in 64% and t(1;19) in 39% of the cases. In contrast to other methods, the characteristics of GIPFEL make it particularly attractive for prospective studies.

Next-generation-sequencing-spectratyping reveals public T-cell receptor repertoires in pediatric very severe aplastic anemia and identifies a ß chain CDR3 sequence associated with hepatitis-induced pathogenesis.

Current diagnostic approaches that characterize T-cell deficiency by analyzing diversity of T-cell receptor sequences effectuate limited informational gain about the actual restrictiveness. For deeper insight into T-cell receptor repertoires we developed next-generation-sequencing-spectratyping, which employs high coverage Roche/454 sequencing of T-cell receptor (ß)-chain amplicons. For automated analysis of high-throughput-sequencing data, we developed a freely available software, the TCR profiler. Gene usage, length, encoded amino acid sequence and sequence diversity of the complementarity determining region 3 were determined and comprehensively integrated into a novel complexity score. Repertoires of CD8(+) T cells from children with idiopathic or hepatitis-induced very severe aplastic anemia (n=7), children two months after bone marrow transplantation (n=7) and healthy controls (children n=5, adults n=5) were analyzed. Complexity scores clearly distinguished between healthy and diseased, and even between different immune deficiency states. The repertoire of aplastic anemia patients was dominated by public (i.e. present in more than one person) T-cell receptor clonotypes, whereas only 0.2% or 1.9% were public in normal children and adults, respectively. The CDR3 sequence ASSGVGFSGANVLT was highly prevalent in 3 cases of hepatitis-induced anemia (15-32% of all sequences), but was only low expressed in idiopathic aplastic anemia (2-5%, n=4) or healthy controls (<1%). Fifteen high frequent sequences were present exclusively in aplastic anemia patients. Next-generation-sequencing-spectratyping allows in-depth analysis of T-cell receptor repertoires and their restriction in clinical samples. A dominating clonotype was identified in hepatitis-induced anemia that may be associated with disease pathogenesis and several aplastic-anemia-associated, putatively autoreactive clonotypes were sequenced.

Controversies in using urine samples for prostate cancer detection: PSA and PCA3 expression analysis

PURPOSE: Prostate cancer (PCa) is one of the most commonly diagnosed malignancies in the world. Although PSA utilization as a serum marker has improved prostate cancer detection it still presents some limitations, mainly regarding its specificity. The expression of this marker, along with the detection of PCA3 mRNA in urine samples, has been suggested as a new approach for PCa detection. The goal of this work was to evaluate the efficacy of the urinary detection of PCA3 mRNA and PSA mRNA without performing the somewhat embarrassing prostate massage. It was also intended to optimize and implement a methodological protocol for this kind of sampling. MATERIALS AND METHODS: Urine samples from 57 patients with suspected prostate disease were collected, without undergoing prostate massage. Increased serum PSA levels were confirmed by medical records review. RNA was extracted by different methods and a preamplification step was included in order to improve gene detection by Real-Time PCR. RESULTS: An increase in RNA concentration with the use of TriPure Isolation Reagent. Despite this optimization, only 15.8 percent of the cases showed expression of PSA mRNA and only 3.8 percent of prostate cancer patients presented detectable levels of PCA3 mRNA. The use of a preamplification step revealed no improvement in the results obtained. CONCLUSION: This work confirms that prostate massage is important before urine collection for gene expression analysis. Since PSA and PCA3 are prostate specific, it is necessary to promote the passage of cells from prostate to urinary tract, in order to detect these genetic markers in urine samples.

Hospital resource utilization and treatment cost of skeletal-related events in patients with metastatic breast or prostate cancer: estimation for the Portuguese National Health System.

BACKGROUND: Skeletal-related events (SREs) occur frequently in patients with bone metastases as a result of breast (BC) and prostate (PC) cancers. They increase both morbidity and mortality and lead to extensive health-care resource utilization. METHODS: Health care resource utilization by BC/PC patients with at least one SRE during the preceding 12 months was assessed through retrospective chart review. SRE-treatment costs were estimated using the Portuguese Ministry of Health cost database and analyzed using generalized linear models. RESULTS: This study included 152 patients from nine hospitals. The mean (SD) annual SRE-treatment cost per patient was €5963 (€3646) and €5711 (€4347), for BC (n=121) and PC (n=31) patients, respectively. Mean cost per single episode ranged between €1485 (radiotherapy) and €13,203 (spinal cord compression). Early onset of bone metastasis (P = 0.03) and diagnosis of bone metastases at or after the occurrence of the first SRE (P < 0.001) were associated with higher SRE-treatment costs. CONCLUSION: These results reveal the high hospital SRE-treatment costs, highlighting the need for early diagnosis and treatment, and identify key factors determining the economic value of therapies for patients with skeletal metastases.

Controversies in using urine samples for Prostate Cancer detection: PSA and PCA3 expression analysis.

PURPOSE: Prostate cancer (PCa) is one of the most commonly diagnosed malignancies in the world. Although PSA utilization as a serum marker has improved prostate cancer detection it still presents some limitations, mainly regarding its specificity. The expression of this marker, along with the detection of PCA3 mRNA in urine samples, has been suggested as a new approach for PCa detection. The goal of this work was to evaluate the efficacy of the urinary detection of PCA3 mRNA and PSA mRNA without performing the somewhat embarrassing prostate massage. It was also intended to optimize and implement a methodological protocol for this kind of sampling. MATERIALS AND METHODS: Urine samples from 57 patients with suspected prostate disease were collected, without undergoing prostate massage. Increased serum PSA levels were confirmed by medical records review. RNA was extracted by different methods and a preamplification step was included in order to improve gene detection by Real-Time PCR. RESULTS: An increase in RNA concentration with the use of TriPure Isolation Reagent. Despite this optimization, only 15.8% of the cases showed expression of PSA mRNA and only 3.8% of prostate cancer patients presented detectable levels of PCA3 mRNA. The use of a preamplification step revealed no improvement in the results obtained. CONCLUSION: This work confirms that prostate massage is important before urine collection for gene expression analysis. Since PSA and PCA3 are prostate specific, it is necessary to promote the passage of cells from prostate to urinary tract, in order to detect these genetic markers in urine samples.

Combined analysis of EGF+61G>A and TGFB1+869T>C functional polymorphisms in the time to androgen independence and prostate cancer susceptibility.

Proliferative mechanisms involving the epidermal growth factor (EGF) and transforming growth factor beta (TGF-beta(1)) ligands are potential alternative pathways for prostate cancer (PC) progression to androgen independence (AI). Thus, the combined effect of EGF and TGFB1 functional polymorphisms might modulate tumor microenvironment and consequently its development. We studied EGF+61G>A and TGFB1+869T>C functional polymorphisms in 234 patients with PC and 243 healthy individuals. Intermediate- and high-proliferation genetic profile carriers have increased risk for PC (odds ratio (OR)=3.76, P=0.007 and OR=3.98, P=0.004, respectively), when compared with low proliferation individuals. Multivariate analysis showed a significantly lower time to AI in the high proliferation group, compared with the low/intermediate proliferation genetic profile carriers (HR=2.67, P=0.039), after adjustment for age, metastasis and stage. Results suggest that combined analysis of target genetic polymorphisms may contribute to the definition of cancer susceptibility and pharmacogenomic profiles. Combined blockage of key molecules in proliferation signaling pathways could be one of the most promising strategies for androgen-independent prostate cancer.

Feasibility of adequate resectable rectal cancer treatment in a third-level hospital.

PURPOSE: The aim of this study was to determine the feasibility, concerning compliance to protocol and recommended clinical practice guidelines, as well as efficacy results of multidisciplinary treatment (surgery, radiotherapy and chemotherapy) of resectable rectal cancer in a third-level hospital devoid of radiotherapy and clinical oncology units. PATIENTS AND METHODS: A retrospective, single-institution analysis was completed for 45 consecutive patients diagnosed with resectable rectal cancer who entered an officially proposed multidisciplinary treatment protocol from October 1998 to September 2003. Adequacy of patient inclusion, according to clinical stage, was reviewed. Neoadjuvant radiotherapy schedule, surgery procedures and adjuvant chemotherapy indication were assessed. All treatment time intervals were analysed. Finally, efficacy results are discussed and contextualised by comparison with results of clinical trials which support this treatment strategy. RESULTS: According to an independent board review, 3 patients (6.7%) with stage I rectal cancer, 31 patients (68.9%) with stage II and 11 patients (24.4%) with stage III rectal cancer were included. Radiotherapy dosage, volume and schedule were as planned. Median time from diagnosis to start of radiotherapy was 26.36 days (24.26- 28.57; CI 95%). Median duration of radiotherapy was 6.00 days (5.56-6.44; CI 95%). Median time from start of radiotherapy to surgery was 15.67 days (14.47-16.87; CI 95%). Median time from completion of radiotherapy to surgery was 10.67 days (9.53-11.81; CI 95%). Most of the patients underwent low anterior resection [23 patients (51.2%)] and abdominoperineal resection [16 patients (35.6%)]. Correlation between clinical and pathologic staging was as expected. Twenty-nine patients (64.4%) of the 45 that were initially included started adjuvant chemotherapy. A statistically significant relationship between pathologic stage (grouped I-II vs. III) and the use of adjuvant chemotherapy was found (p=0.033; chi-square test). Radiotherapy- and chemotherapy-induced toxicity did not differ from that previously reported. With a median follow-up of 65.46 months, a total of 10 recurrences have been diagnosed, all of them in stage III patients. Overall survival rate at five years was 76% for the complete population included. CONCLUSION: Multidisciplinary treatment of resectable rectal cancer in a third-level hospital is feasible. Although efficacy results are comparable to those previously reported in the literature, further improvements in clinical staging as well as in adjuvant chemotherapy indication are desirable.

Feasibility of adequate resectable rectal cancer treatment in a third-level hospital

PURPOSE: The aim of this study was to determine the feasibility, concerning compliance to protocol and recommended clinical practice guidelines, as well as efficacy results of multidisciplinary treatment (surgery, radiotherapy and chemotherapy) of resectable rectal cancer in a third-level hospital devoid of radiotherapy and clinical oncology units. PATIENTS AND METHODS: A retrospective, single-institution analysis was completed for 45 consecutive patients diagnosed with resectable rectal cancer who entered an officially proposed multidisciplinary treatment protocol from October 1998 to September 2003. Adequacy of patient inclusion, according to clinical stage, was reviewed. Neoadjuvant radiotherapy schedule, surgery procedures and adjuvant chemotherapy indication were assessed. All treatment time intervals were analysed. Finally, efficacy results are discussed and contextualised by comparison with results of clinical trials which support this treatment strategy. RESULTS: According to an independent board review, 3 patients (6.7%) with stage I rectal cancer, 31 patients (68.9%) with stage II and 11 patients (24.4%) with stage III rectal cancer were included. Radiotherapy dosage, volume and schedule were as planned. Median time from diagnosis to start of radiotherapy was 26.36 days (24.26- 28.57; CI 95%). Median duration of radiotherapy was 6.00 days (5.56-6.44; CI 95%). Median time from start of radiotherapy to surgery was 15.67 days (14.47-16.87; CI 95%). Median time from completion of radiotherapy to surgery was 10.67 days (9.53-11.81; CI 95%). Most of the patients underwent low anterior resection [23 patients (51.2%)] and abdominoperineal resection [16 patients (35.6%)]. Correlation between clinical and pathologic staging was as expected. Twenty-nine patients (64.4%) of the 45 that were initially included started adjuvant chemotherapy. A statistically significant relationship between pathologic stage (grouped I-II vs. III) and the use of adjuvant chemotherapy was found (p=0.033; chi-square test). Radiotherapy- and chemotherapy-induced toxicity did not differ from that previously reported. With a median follow-up of 65.46 months, a total of 10 recurrences have been diagnosed, all of them in stage III patients. Overall survival rate at five years was 76% for the complete population included. CONCLUSION: Multidisciplinary treatment of resectable rectal cancer in a third-level hospital is feasible. Although efficacy results are comparable to those previously reported in the literature, further improvements in clinical staging as well as in adjuvant chemotherapy indication are desirable (AU)

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Insecticide residues in stored grains in Sonora, Mexico: quantification and toxicity testing.

Food safety has acquired great attention by food importer and exporters. Food rejection or acceptance across international borders is based on the compliance with international food regulations. Due to the lack of recent data on pesticide residues in Mexican grains, this study focused on detecting and quantifying insecticide residues in stored wheat, corn, chickpeas, and beans, as well as to determine their mutagenic potential. Grains were sampled from primary storage sites in Sonora, Mexico. Malathion, chlorpyrifos, deltamethrin, cypermethrin, 4,4-DDE, 4,4-DDD and 4,4-DDT were analyzed in 135 samples. Grain samples were not mutagenic and most pesticide levels were within regulation limits.

Transferencias del segundo y tercer dedo del pie en tándem para reconstrucción de la mano metacarpiana / Reconstruction of metacarpal hand by combined second and third toe transfer

Introducción. Las amputaciones multidigitales representan un auténtico desafío para el cirujano. En amputaciones proximales al pliegue comisural, el método óptimo de reconstrucción es un colgajo combinado de segundo y tercer dedos del pie. El objetivo de este trabajo es presentar los resultados funcionales conseguidos en cinco pacientes, los cuales recibieron transferencias del segundo y tercer dedo del pie en tándem para rehabilitar mutilaciones graves de la mano. Material y método. Desde 1995 hemos realizado 95 transferencias de dedos del pie a la mano con una supervivencia de 94/95. Cinco pacientes de edades comprendidas entre los 21 y 53 años, que habían sufrido amputaciones de 5 dedos (3 casos) y 4 dedos (2 casos), fueron tratados mediante la transferencia de un colgajo combinado de segundo y tercer dedo en tándem. Todos fueron intervenidos en fase aguda o subaguda. Cuatro de ellos habían sufrido la amputación del pulgar, cuya reconstrucción se realizó mediante trasplante de dedo gordo del pie en los tres casos y con reimplante ectópico del dedo medio (de urgencia) en un caso. La reconstrucción del pulgar primó sobre las otras y se hizo una semana antes que la de los dedos con el colgajo tándem. Resultados. Todos los trasplantes sobrevivieron. El seguimiento mínimo fue de seis meses tras la operación. En todos los casos se consiguió, al menos, una pinza trípode estable. En el pie no hubo casos de entrecruzamiento, dolor permanente en la marcha o déficit funcionales manifiestos. La encuesta sobre la secuela estética objetiva revela que ésta es importante para nosotros, pero no tanto para el enfermo. Todos repetirían y aconsejarían la misma a otros enfermos que se encontrasen en igual situación. Conclusión. La complejidad de la reconstrucción de la mano metacarpiana implica consideraciones en la posición y número de dedos transferidos, en el manejo de la pérdida de sustancia asociada y en la gestión de vasos receptores. La transferencia combinada del segundo y tercer dedo permite la recuperación de la pinza trípode y un alto grado de satisfacción de los pacientes. La secuela, estéticamente mayor, es compensada en nuestra opinión por la mayor estabilidad en la prensión y en la pinza. La intervención es recomendable para pacientes que hayan sufrido amputaciones de tres dedos trifalángicos proximales al pliegue comisural

Introduction. Multidigital amputations are a formidable challenge for the surgeon. In the case of amputations near the digital commissure the best reconstruction can be achieved using a combined flap of the 2nd and 3rd toes. The aim of this study is to present the functional results achieved in 5 patients who underwent combined 2nd and 3rd toe transplants to rehabilitate severely mutilated hands. Materials and methods. Since 1995 we performed 95 toe-to-hand transplants with a survival rate of 94/95. Five patients (ages 21­53 years) that had suffered amputations of 5 fingers (3 cases), and 4 fingers (2 cases), underwent 2nd and 3rd toe flap combined transplants. All were operated on during the acute or subacute phase. Four of the patients that had suffered a thumb amputation underwent reconstruction by means of a big toe transplant in 3 cases and emergency ectopic middle toe reimplantation in 1 case. Thumb reconstruction was considered a priority and performed one week before the toe flap tandem transplants. Results. All the transplants survived. Minimum postoperative followup was 6 months. In all cases at least one stable tripod pincer grasp was achieved. As to the foot, there were no cases of toe crossover, permanent pain during gait or manifest functional impairment. The objective survey on cosmetic sequelae revealed that these were important to us but not so important for the patients. The patients would all choose to undergo the operation again and would advise other patients in the same situation to have this type of surgery. Conclusions. The complexity involved in the reconstruction of a metacarpal hand implies consideration of such issues as the position and number of toes to be transplanted and the management of associated tissue loss and blood supply. The combined transplant of the 2nd and 3rd toes allows recovery of a tripod pincer grasp and results in a high degree of patient satisfaction. The greater cosmetic sequelae are offset, in our opinion, by the greater pincer grasp stability. This type of surgery is recommended for patients that have suffered amputations of three fingers with three phalanges proximal to the commissural fold

Bicalutamide (Casodex) 150 mg plus standard care in early non-metastatic prostate cancer: results from Early Prostate Cancer Trial 24 at a median 7 years' follow-up.

Trial 24, one of three ongoing trials in the Early Prostate Cancer programme, is evaluating the efficacy and tolerability of bicalutamide (Casodex) 150 mg following standard care (radiotherapy, radical prostatectomy or watchful waiting) in patients with early, non-metastatic prostate cancer. At 7 years' median follow-up, addition of bicalutamide significantly improved objective progression-free survival (PFS) for patients with locally advanced disease, reducing the risk of progression by 34% versus standard care alone (hazard ratio 0.66; 95% confidence interval 0.55, 0.79; P<0.001). In localized disease, a significant difference in objective PFS was not found. There was no significant difference in overall survival.

Bicalutamide ('Casodex') 150 mg in addition to standard care in patients with nonmetastatic prostate cancer: updated results from a randomised double-blind phase III study (median follow-up 5.1 y) in the early prostate cancer programme.

Trial 24 is one of three placebo-controlled trials within the ongoing bicalutamide ('Casodex') Early Prostate Cancer (EPC) programme evaluating bicalutamide 150 mg/day in addition to radical prostatectomy, radiotherapy or watchful waiting for T1b-4, any N, M0 prostate cancer. In Trial 24, at 5.1 y median follow-up, the addition of bicalutamide significantly (P < 0.0001) improved objective progression-free survival (PFS) and prostate-specific antigen PFS compared with standard care alone. There was no significant difference in overall survival (P = 0.746). In the context of the whole EPC programme, long-term bicalutamide is not appropriate for localised disease, yet provides advantages in delaying disease progression in patients with locally advanced prostate cancer.