We remember that he lived successively in Spain, in Morocco, and

We remember that he lived successively in Spain, in Morocco, and in Egypt; such migrations were then the lot of many physicians, Jewish ones in particular. Maimonides wrote a glossary of drugs,2 in which he used an impressive number of languages. It is well known that the same medicinal plant often appeared under different names, sometimes even in the same language. An Sorafenib accomplished physician was therefore Inhibitors,research,lifescience,medical supposed to be knowledgeable in these matters. In his commentary on the first aphorism of Hippocrates, Maimonides issues a statement that may seem daring or even impossible to the modern reader. He contends that a student physician

should memorize the huge corpus of theoretical and practical medicine. This does not only necessitate long and tedious work, it means that the physician will have to perform constant revision throughout his medical career. The next stage in Inhibitors,research,lifescience,medical medical education is personal experience of treating the sick,

which includes experience in diagnosis, in prognosis, and in the ways of prescribing drugs and adequate diet. In one of his letters to a former student,3 Maimonides stated that in the evening, after a busy day, he reviewed the writings that dealt with the diseases he had treated during the day. Such a critical review and checking of one’s memory was definitely a requisite way in striving Inhibitors,research,lifescience,medical toward perfection. Incidentally, it is known that Maimonides Inhibitors,research,lifescience,medical regularly reviewed his theological writings, his Mishneh Torah in particular, till late in his life. Let us now turn to Galen (131–201 CE). Most of Galen’s extensive works had been translated into Syriac and Arabic by unain ibn Yisaq and others; some of them only survived in their Arabic translation. A compendium of these writings, known as the Sixteen Books of Galen, was since Byzantine times in wide circulation. In his commentary to Plato’s Timaeus (preserved in its Arabic translation only),5 Galen declares that it is beyond human beings’ capability to achieve perfection in the knowledge and in the expertise of the medical art. This Inhibitors,research,lifescience,medical statement will be adamantly

opposed by Maimonides, as we shall see further. In another work, admittedly not written by Galen himself, entitled On Definitions, we read: “The perfect [Gr. téleios] physician is one who has completed the whole scheme of theoretical and practical studies.” The author does not assert that perfection is beyond Carnitine palmitoyltransferase II human reach. The next sentence reads: “The best [Gr. aristos; Lat. optimus] physician is the one who practices medicine according to the right doctrine [Gr. orthon lógon].” (On the Greek word téleios, and on Ps.-Galen’s Definitiones Medicae, see Reference 6.) There is, however, no detailed definition of “orthodox” medicine. This phrase intended most probably to exclude superstition, magic, and quackery. Galen was, then and there, together with Avicenna and Rhazes, the main source of medical learning, for Maimonides as well as for his contemporaries.

2) As predicted, tissue-culture based technology requires signif

2). As predicted, tissue-culture based technology requires significant capital investment, whereas

egg-derived LAIV requires the least investment. Although eggs can present a Libraries potential barrier to manufacture in resource-poor settings (e.g. importation of eggs and/or maintenance of hen flocks), the affordability of the final product is of prime importance and egg-based production appears to be the cheapest. One parameter not visible in Fig. 2 is how these costs would be affected by Erastin the use of adjuvants as these could multiply the number of pandemic IIV doses by at least 4-fold, for minimal capital investment. One of the WHO grantee manufacturers embarked on a programme for the transfer of an oil-in-water adjuvant technology from the Vaccine Formulation Laboratory in December 2010. LBH589 nmr Supporting selected developing countries to establish or expand pandemic influenza production capacity is not sufficient to ensure that all developing

countries have access to pandemic vaccine. Moreover, it is not possible, nor desirable to establish influenza vaccine production in each and every country. For this reason, WHO grants to manufacturers are contingent upon their agreement to sell at an affordable price 10% of their pandemic vaccine production to United Nations agencies such as WHO and UNICEF, if needed in a pandemic event, for distribution to developing countries without domestic production. Other issues require priority attention if the overall goal is to be achieved. The concomitant training and support for regulatory authorities in developing countries, for example, is needed to ensure that influenza vaccines produced there can be registered and licensed without unnecessary delays. Another issue of concern is the remaining geographical imbalance in global influenza vaccine production capacity, and thus access to pandemic influenza vaccine, particularly in countries in sub-Saharan

Africa. A third call for proposals to establish influenza vaccine production capacity in developing countries will target such regions. In response to growing interest by the global health community in the development all of local production to improve access to medicines, WHO undertook an analysis of vaccine-related technology transfer projects over the last two decades. The analysis identified over 100 such transfers to developing countries (principally to Brazil, China and India), the majority of which resulted in increased local production and use of the vaccine. A consultation held in December 2010 identified the following considerations for technology transfer to developing countries. Firstly, although local production does not necessarily mean lower prices, it should be seen as a strategic investment in health.

Patients with Zollinger-Ellison syndrome does not show an increas

Patients with Zollinger-Ellison syndrome does not show an increased risk of developing CRC despite prolonged and marked plasma

elevation of all forms of gastrin (56). Several studies demonstrated that serum/plasma gastrin levels were not significantly different between subjects with and without colorectal neoplasia, and thus unlikely to play a significant role in colorectal tumorigenesis (57-61). Inhibitors,research,lifescience,medical It is interesting to note that some studies have demonstrated that CRC tumor cells express gastrins that may function as autocrine growth factors (62-66). In that scenario, gastrin secretion by tumor cells is likely the source of hypergastrinemia observed in CRC patients. In support of this notion, several studies demonstrated a fall in serum/plasma gastrin values

in CRC patients following surgical resections of the tumors (48,67,68). While these data may further support a role of hypergastrinemia Inhibitors,research,lifescience,medical in colorectal tumorigenesis, they argue against a direct association with H. pylori infection. Change in colorectal microflora Gastric acid barrier is an important regulator of the population and composition of the intestinal microflora (69-72). Atrophic gastritis secondary to H. pylori Inhibitors,research,lifescience,medical infection is associated with reduced acid production, which permits a greater number and variety of microbial species to enter and colonize the intestinal tract. It has been proposed that shifts in the composition of colorectal microflora resulted from H. pylori atrophic gastritis

may facilitate selective growth of bacteria such as B. fragilis, E. faecalis, Inhibitors,research,lifescience,medical and others that are linked to the development of CRC (14-16,18-20). Supporting this hypothesis are studies showing an increased CRC risk following gastric surgery for benign peptic ulcer disease (73,74). However, other studies failed to confirm the association between gastrectomy and subsequent CRC development Inhibitors,research,lifescience,medical (75-78). Toxin production There are different H. pylori strains, some of which are more virulent and more carcinogenic than the others. For instance, patients infected with H. pylori organisms that express cagA gene are more likely to MI-773 mouse develop gastric cancer than those infected with cagA-negative strains (79,80). Shmuely et al. tested not patients with various malignancies for serum antibodies against H. pylori and CagA protein and found that CagA seropositivity was associated with an increased risk not only for gastric adenocarcinoma but also for colonic adenocarcinoma, when compared with CagA-seronegative controls (81). However, as the authors pointed out, the findings should be interpreted with caution because the tests for H. pylori and CagA were performed at the same time of cancer diagnosis, which raised the question about the temporal relationship between the two conditions. The conclusions of the study were drawn under the assumption that H. pylori infection occurred before CRC development, as for gastric adenocarcinoma.

There was not significant interaction between the family history

There was not significant interaction between the family history and the first delivery at the age of 35 yrs and more or no delivery. However, our study show that the sample size of 300 subjects to investigate

interaction in case control studies is not enough, and that case-only BI 6727 designs might be a better design to examine such an interaction in such a sample size. The independence assumption of the two factors was not established in a study by Ardalan and colleagues,12 Inhibitors,research,lifescience,medical and therefore was removed from the case-only analysis. In agreement with the findings of Yavari et al.4 the present study showed that case-only design had more efficiency than that of the matched case-control designs. The interaction of family history of breast cancer and the history of having live birth was not statistically significant in the case-control design. Since the Inhibitors,research,lifescience,medical independence assumption was not established, the interaction of these two factors in case-only design was

not estimated in the study by Yavari and colleagues,4 or was not reported in Becher et al. studies.11 The present study showed that the confidence interval, standard error and -2log likelihood estimations Inhibitors,research,lifescience,medical in case-only design were smaller than those in case-control analogues. These findings are similar to that of Ardalan and colleagues,12 and is an indication of more efficacy of case-only designs than the case-control ones. The confidence interval, standard error, -2log likelihood and p-value estimations in case-only design were smaller than those in the case-control design. This shows that the case-only design had more efficacy than the case-control one. The confidence interval, standard Inhibitors,research,lifescience,medical error, and -2log likelihood estimations in the case-only design were smaller than those in the case-control design. Such findings are a sign that case-only designs are more efficacious than the case-control design. However, the P value in the case-only design was higher than that

in the case-control design. The reason for not detecting the interaction between the family history of breast cancer and other variables might be the Inhibitors,research,lifescience,medical small sample size of the participants in case-control design study. In case-only studies, the basic assumption of gene-environment independence in non-diseased group should be established. In the studies before 2004, this assumption used to be established DNA ligase using classic statistical tests such as Chi Square, Correlation Coefficient and so on. However, such an approach was also criticized,25 for the lack of ability of the use of GE-OR in control groups to estimate the GE-Or in populations. Gatto et al.17described a modification of the methods. In order to establish the independence assumption, they introduce the standard statistical multivariable techniques, which have resolved the previous shortcoming of the design, and have led to widespread use of the techniques. The studies of Yavari et al.4 and Becher et al.

1; SAS Institute, Cary, NC) Results Patient baseline characteris

1; SAS Institute, Cary, NC). Results Patient baseline characteristics The final cohort for analysis consisted of 13,840 patients, 8710 men (63%), and 5130 women (37%). Their age distribution is as follows: 1,207 (9%) aged 18−44; 1,698 (12%) aged 45−54; 2,701 (20%) aged 55−64; 3,901 (28%) aged 65−74; and 4,333 (31%) aged 75 years and older. The median age was 68 years (range: 18−104). 60% of the MGC cohort were White, 13% African American, 13% Asian, 14 % Hispanic, Inhibitors,research,lifescience,medical and 1% Native American. Tumor characteristics and treatment received are shown in Table 1. Table 1 Overall survival of patients with metastatic gastric cancer by demographic and clinicopathologic

characteristics and treatment, SEER data 1988-2004 Age and ethnicity in MGC 5.5 % of Whites with MGC were between 18-44 years of ages as compared to 10% of African Americans, 11% of Asians, and 19% of Hispanic patients. 36% of White gastric cancer patients were diagnosed over 75 years of Inhibitors,research,lifescience,medical age; 29% of Asian, 27% of AA, and 20% of Hispanic. Tumor location: cardia vs non-cardia The incidence of cardia and non-cardia tumors varied significantly depending on gender and ethnic

background. 30% of men and 14% of women had gastric ca arising from the cardia. The incidence of cardia cancers also varied significantly Selleck MLN8237 across ethnicities. 32% of Whites had cardia Inhibitors,research,lifescience,medical primaries, 13% of AA’s, 11% of Asians, and 14% of Hispanics. Survival analysis The median overall survival (OS) in patients with MGC was only 4 months. The prognostic significance of several clinical and tumor characteristics were limited as the median OS varied little when stratified by sex, race, tumor site, grade/ differentiation, and histology Inhibitors,research,lifescience,medical (Table 1). However, age, use of local treatment, tumor differentiation,

and tumor site were found to have a clinically significant effect. The youngest group of patients had an improved OS when compared to their older counterparts (Table 1), as the median OS for patients 44 years or younger was 6 months compared to Inhibitors,research,lifescience,medical 3 months in patients 75 years or older. Survival was significantly worse in every successive age decile. Patients who had received any treatment had significantly improved survival. Gastrectomy or local surgery had a median OS of 8 months compared to a median OS of 3 months in patients who were not treated with surgery and or radiation [HR = 0.600 (0.561, 0.643)] (Table 1). Similarly, patients receiving radiation treatment had a survival benefit [HR = 0.802 (0.746, 0.862)]. Tumor characteristics had a significant impact on survival. As expected, patients with poorly differentiated tumors had a worse survival than those with moderately or well differentiated tumors [HR 1.19, P < 0.001 (1.139, 1.250)]. We also found that tumors located in the gastric cardia conferred a survival benefit when compared to non-proximal tumors [HR=0.945, P < 0.001 (0.904, 0.989)].

For example, Physiotherapy Ireland is described as providing two

For example, Physiotherapy Ireland is described as providing two or three invited commentaries, five or six research articles, and book reviews, whereas Journal of Physical Therapy Education provides one editorial, four research articles, a position paper, four method/model articles, book reviews and abstracts. The second source of information about content is a showcase of this website free samples:

a couple of full-text articles nominated by each journal’s editor to show examples of that journal’s best material. Subscribers to Journal of Physiotherapy also inhibitors benefit from its membership of the ISPJE because of the support all members receive. The ISPJE convenes face-to-face meetings at WCPT and organises web-based seminars on topical issues in publishing. This helps keep our editorial board aware of other resources (such as the documents published by the Committee on Publication Ethics, COPE, to guide editors in how to deal with research misconduct and other ethical dilemmas in publishing) and new initiatives (such as the new public register

Abiraterone for protocols of systematic reviews known as PROSPERO). The ISPJE informs members about potentially problematic issues that may be on the horizon, allowing us to be proactive in dealing with them. Journal of Physiotherapy also benefits from collaborative advice sharing between journals. The ISPJE seeks to increase its role in encouraging member journals to make more informed and cohesive responses to issues in publishing. For example, the ISPJE has an ongoing mentorship program where larger journals can mentor smaller ones. In addition to the mentorship

program, the ISPJE is planning its first joint editorial on important issues in publishing. These interactions and joint actions can ultimately provide better standards for publishing that hopefully will found be used by all physiotherapy journals in order to promote physiotherapy publications worldwide. In summary, physiotherapists can benefit directly by using the information provided by the ISPJE about the range of journals that are available in our profession. Readers of Journal of Physiotherapy also benefit indirectly from the support we receive from ISPJE to raise the standard of our journal. “
“On May 24, 2012, ‘Habitual physical activity after total knee replacement: analysis in 830 patients and comparison with a sex-and age-matched normative population’ by Kersten RFMR, Stevens M, van Raay JJAM, et al was published online ahead of print in Physical Therapy. In the June 2012 issue of Journal of Physiotherapy, ‘After total knee arthroplasty, many people are not active enough to maintain their health and fitness: an observational study’ by Groen JW, Stevens M, Kersten RFMR, et al was published. These two related articles, both of which reported on the same sample of subjects, were written and published each without recognizing the other.

05 Results Patients and controls were not different regarding de

05. Results Patients and controls were not different regarding demographic characteristics such as ethnicity and gender. Moreover, no differences were observed regarding genotype frequencies across these groups

(Table I). Table I. Genotype distribution and demographic characteristics across schizophrenic patients and healthy controls. *: χ2=0.14, P=0.93; †: χ2=1,45, P=023; ‡: χ2=0.86, P=0.77 We further analyzed the association Inhibitors,research,lifescience,medical Epigenetic inhibitor between the genotype and allele frequencies of the T102C polymorphism and total and factor scores of the BPRS. As shown in Table II, no association was found. Table II. BPRS total scores and factor scores across genotypes in schizophrenic patients. BPRS, Brief Psychiatric Rating Scale. *: F=1.06, P=0.4; †: F=11.32, P=0.2; ‡: F=1.26, P=0.3; ║: F=0.5, P=0.88 The history of a suicide attempt and the suicide attempt characteristics were not associated with genotype,

allele frequencies, nor with psychopathological scores (Table III). Furthermore, Inhibitors,research,lifescience,medical the demographic characteristics were not statistically different between patients with a suicide attempt history (n=42; [32.5%], 23 were male, 19 were female; 28 were of Caucasian descent, 14 of African descent) and without such a history (n=87; [67.5%], Inhibitors,research,lifescience,medical 56 were male, 31 were female; 56 were of Caucasian descent, 31 were of African descent). In both groups the genotype frequencies were in Hardy-Weinberg equilibrium. Table III. Distribution of the 5-HT2A receptor gene 102 TC polymorphism in suicidal and nonsuicidal schizophrenic patients. BPRS, Brief Psychiatric Rating Scale. *: χ2=0.48, P=0.79; †: χ2=0.49, P=0.78; ‡: χ2=2.1, P=0.36; §: … Discussion Two previous meta-analyses had shown an association Inhibitors,research,lifescience,medical between the C allele of the T102C polymorphism and schizophrenia.3,14 However, these meta-analyses yielded relatively slight odds ratios (ORs)

of 1.18 and 1.1, respectively. An important question remains as to whether some characteristics present in schizophrenic patients, such as suicidality, rather than schizophrenia itself, Inhibitors,research,lifescience,medical could be related to the C allele. There is much evidence to support this hypothesis. Adenylyl cyclase First, suicide is the leading cause of premature death in schizophrenic patients15,16 and a substantial percentage of patients with schizophrenic patients also attempt suicide, with estimates of lifetime occurrence ranging from 18% to 55 %.15 Second, a previous study showed an association between the C allele and suicidal thoughts in depressed patients,17 and we may speculate whether this same finding could be observed in schizophrenia. Third, it is also known that the 5-HT2A receptor is, at least indirectly, involved in suicidal behavior in both depressed and schizophrenic patients.6 Finally, it has been shown that the atypical antipsychotic clozapine, which acts on 5-HT2A, could have an antisuicidal action.

The proposed method for simultaneous quantification of amoxicilli

The proposed method for simultaneous quantification of amoxicillin and clavulanic acid in human plasma by LC–MS–MS method happens to be first

of its kind described so far in the literature. This new method will be helpful for carrying out pharmacokinetic study. All authors have none to declare. The authors are indebted to Dr. Nitin Borkar, CEO of VerGo Pharma Research Ltd. and Dr. Sujal Kamble, Head of NVP-BKM120 molecular weight VerGo Clinicals, for their continuous support and encouragement. The authors gratefully acknowledge VerGo Clinicals Lab for providing necessary facilities to carry out this work. “
“Grewia Serrulata DC (Family: Tiliaceae) is a small tree with slender branches, bark dark selleck inhibitor grey, leaves thin sharply serrate, ovate to lanceolate, acuminate. It is a cuisine of the popular edible fruit phalsa. 1 Literature shows the plant to have anti inflammatory activity. 2 Traditionally the root juice is taken as expectorant and wood part is applied for skin diseases. In ayurveda root juice is used for controlling bleeding and bronchitis. Latest common pharmacological findings indicate fruits are used as cardio tonic. 3 It is one of the medicinal plants for diabetic complications used in Pankaj Oudihia’s Herbal Formulations. 4 Some of these ethno medical and reported biological activities may be

due to the antioxidant nature of aerial parts of Grewia serrulata DC. Hence in the present investigation aqueous and ethanol extracts of aerial parts of Grewia serrulata DC (AEGS & EEGS) were screened for the in vitro and in vivo antioxidant study, hypoglycemic effect on normoglycemic and glucose loaded hyperglycemic

rats and on streptozotocin-induced hyperglycemic rats. The aerial parts of Grewia Serrulata DC were collected from Tirumala hills, Tirumala, Chittoor DT, A.P, India. The plant was identified and authenticated by Dr. K. Madhava Chetty, Assistant Professor, Department of Botany, Sri Venkateswara University, Tirupati, A.P, and India. After shade drying the aerial parts of Grewia serrulata DC were then blended in to fine powder with a blender and used for the preparation Carnitine dehydrogenase of aqueous and ethanol extracts. The aqueous extract was prepared by cold maceration process for a period of 72 h with occasional stirring. Then the mixture was filtered and the filtrate was collected and the solvent was removed under reduced pressure. 5 Ethanol extract was prepared by using soxhlet extractor for 18–20 h. The extract obtained, was concentrated and dried under reduced pressure at controlled temperature (40–50 °C). 6 All the chemicals used were of analytical grade. Male inhibitors Wistar Albino rats (180–200 g) were used in the study. Animals were housed individually in polypropylene cages in a ventilated room under ambient temperature of 22 ± 2 °C and 45–65% relative humidity, with a 12 h light followed by 12 h dark.

25,26 The currently much-studied family of noncoding RNAs is the

25,26 The currently much-studied family of noncoding RNAs is the microRNA family. MicroRNAs exert their function through direct binding to mRNA nontranslated regions. This indeed adds an important novel site of post-transcriptional regulation that can lead to important phenotypic changes provoked by discrete mutations in the genome.23,27 Finally, one should ABT-737 mw mention the “jumping gene” domain, consisting of short or less short repeated sequences that are transcribed into RNA and

then retrotranscribed into DNA fragments that Inhibitors,research,lifescience,medical are inserted into the genome.28 Such reinsertions provoke mutations that can have considerable consequences when they take place, as is often the case, in gene expression regulatory domains. Many of these sequences no longer jump, (although Inhibitors,research,lifescience,medical some still do29,30) but they are extremely numerous in primates, and particularly so in humans. Conclusions: social consequences This brief technical survey should convince the reader that the figure of 1.23% for the

difference (in point mutations) between the chimpanzee and the human genomes is in fact meaningless. The consequences of this distance between us and the other primates bears consequences Inhibitors,research,lifescience,medical not only in term of brain morphologies but also for the proper understanding of what makes Homo sapiens unique among primates, in particular when comparing social behaviors. One of the most important consequences of the unique character of the human brain is that

part of our social behavior is epigenetic, and thus geographically and historically contingent. This includes Inhibitors,research,lifescience,medical the laws that rule behavior between humans, but also our relationships with the nonhuman world, including the other living creatures with which, from bacteria to chimpanzees, we share common ancestors.
Psychiatric disorders commonly reflect affective imbalances within the brain. Accordingly, a key question in psychiatric research is the neural nature of emotional feelings. Inhibitors,research,lifescience,medical For instance, in depression research, one of the most important unanswered questions is: Why does depression feel so bad? What is the “psychological pain” that leads people to lose their joy of living? not Exactly the same affective issues confront us when we study addictions. Here we explore the possibility that chronic affective changes may arise from functional changes in basic emotional systems of the brain. For example, diminished arousability of specific positive affective systems along with elevated activation of distinct negative affective networks may be the fundamental source of depressive affect. But what systems are they? Here, arguments for the critical importance of brain systems that integrate the distress and despair of separation-distress (overactivity of basic PANIC/GRIEF networks) and the diminished arousal of SEEKING networks that constitute dysphoria will be presented.

In addition, this technique did not increase operating time and t

In addition, this technique did not increase operating time and the learning curve was less steep as compared with laparoscopic colorectal surgery. A study by Nakagoe et al. suggested that minilaparotomy technique for resection of rectal cancer was an attractive alternative in non-overweight patients (12). Very few studies have compared short and long term outcomes of minilaprotomy

surgery for the treatment of rectal cancer (13). Hence, the oncological adequacy of minilaparotomy approach in rectal cancer remains to be determined. The aim of our study was to assess the long-term clinical and oncological outcome after laparoscopic and minilaparotomy surgery Inhibitors,research,lifescience,medical in patients with rectal cancer. Patients and methods Definition of minilaparotomy The minilaparotomy approach for the resection of rectal cancer is defined as a resection performed through a skin incision ≤7 cm in length. Patients All patients with a rectal cancer with the edge ≤12 cm from the anal verge without other concurrent or Inhibitors,research,lifescience,medical previous malignant disease treated by minilaparotomy and laparoscopic surgery were compared retrospectively. Evaluation included physical examination,

colonoscopy Inhibitors,research,lifescience,medical with biopsy, anorectal ultrasonography, pelvic magnetic resonance and thoracic and abdominal computed tomography (CT). The mobility and the location of the tumor from the anal verge were assessed by digital examination by the surgeon and radiological imaging. Patients were staged using the clinical tumor node metastasis (TNM) classification. Exclusion criteria were patients who refused to consent for Inhibitors,research,lifescience,medical the study, and patients with tumors infiltrating to adjacent organs (cT4). Patients who had associated gastrointestinal diseases that required additional extensive operative intervention or evaluation were excluded. Patients with evidence of synchronous

metastatic disease were also excluded. The choice between minilaparotomy and laparoscopic surgery Inhibitors,research,lifescience,medical was based on a joint decision by the patients and doctors. This study was approved by our local research ethics committee. Written informed consent was obtained from all patients. Preoperative BEZ235 cell line preparation from and neoadjuvant chemoradiotherapy All patients had bowel preparations, including a fluid diet and administration of a polyethylene glycol electrolyte solution, one day before the operation unless there were contraindications against bowel preparation. Intravenous antibiotic prophylaxis was given on induction of anesthesia for the operation. The basic indications for neoadjuvant chemoradiotherapy included rectal cancers (T3) and/or node-positive disease, lack of prior radiation therapy to the pelvis, and age <75 years. Neoadjuvant treatment with chemotherapy and radiation therapy was as follows: 45 Gy in five weeks with concomitant 5-fluorouracil.