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This article analyses Moses Maimonides' account of the AfterDeath and, more specifically, of olam ha-ba’ (lit.: the world to come), the state of ultimate human happiness and perfection (in contrast to this world). Maimonides is unequivocal about what olam ha-ba’ is not. Contrary to a competing medieval Jewish tradition, it is utterly incorporeal and, contrary to rabbinic tradition, it is not a motivational reward nor compensation for undeserved suffering in a theodicy. Instead, Maimonides gives two positive accounts of the metaphysics of olam ha-ba’. The first is an intellectualist account on which the denizens of olam ha-ba’ are perfected intellects engaged in intellectual apprehension of the deity. The second is sceptical: it denies that humans have any understanding or knowledge (‘ilm, episteme) of olam ha-ba’ and claims that all language used to describe it is purely equivocal or homonymous, although it allows that some immutable thing, whatever it is, survives death. Instead of being a motivational reward or compensation, olam ha-ba’ is the end, that is, final cause or telos, of the best possible human life in this world at which one aims and which one attempts to approximate even if one cannot actually realize it.

This paper analyzes two transformative conceptions of qedushah (holiness) in medieval Jewish thought, Moses Maimonides’s and Moses Nahmanides’s. Maimonides reduces qedushah to the Mosaic commandments which he reconceives as communal institutions to constrain bodily desires and promote intellectualist values and as training for perfected individuals to de-corporealize themselves in imitation of God. Nahmanides argues that Maimonides’s legal reduction of qedushah leads to the absurd conclusion that the perfectly scrupulous law-abiding scoundrel who exploits loopholes in the law is qadosh! He therefore reconceives qedushah as a complement to the Mosaic commandments intended to counter the problem of the scoundrel. Thus qedushah is re-born as a corrective to abuse of the Law. Nahmanides then proposes two ways to achieve this goal: i) by rabbinic enactment of more laws to fill in (loop) holes in the Law and ii) by cultivating a virtue-oriented, non-legal conception of holiness as a character-trait that leads agents to act properly and spontaneously without legislation. For Maimonides the ultimate state of qedushah is the dis-embodied state of the intellect, for Nahmanides it is a state in which the whole person, body and soul, clings to the deity.

The proposal of a semantics for quotations using explanatory notions drawn from philosophical theories of pictures. In Quotations as Pictures, Josef Stern develops a semantics for quotations using explanatory notions drawn from philosophical theories of pictures. He offers the first sustained analysis of the practice of quotation proper, as opposed to mentioning. Unlike other accounts that treat quotation as mentioning, Quotations as Pictures argues that the two practices have independent histories, that they behave differently semantically, that the inverted commas employed in both mentioning and quotation are homonymous, that so-called mixed quotation is nothing but subsentential quotation, and that the major problem of quotation is to explain its dual reference or meaning—its ordinary meaning and its metalinguistic reference to the quoted phrase attributed to the quoted subject. Stern argues that the key to understanding quotation is the idea that quotations are pictures or have a pictorial character. As a phenomenon where linguistic competence meets a nonlinguistic symbolic ability, the pictorial, quotation is a combination of features drawn from the two different symbol systems of language and pictures, which explains the exceptional and sometimes idiosyncratic data about quotation. In light of this analysis of verbal quotation, in the last chapters Stern analyzes scare quotation as a nonliteral expressive use of the inverted commas and explores the possibility of quotation in pictures themselves.

This chapter addresses Saadia’s theodicies in his Doctrines and Beliefs, a treatise of Jewish theology, and his seminal commentary on the Book of Job whose aim, I argue, is not to investigate the theological problem of evil but to give a phenomenology of people’s mental reactions to suffering. On Saadia’s radically naturalistic interpretation of Job, according to which Job’s human adversary Satan challenges his piety—that Job is pious only because he is prosperous—Job is made to suffer to justify his piety. But Job’s reaction to this suffering manifests the ambiguity, isolation, and uncertainty of one who suffers without understanding why.

BACKGROUND Secondary lymphedema is a leading sequela of cancer surgery and radiotherapy. The microsurgical transfer of lymph node flaps (LNFs) to affected limbs can improve the symptoms. The intra-abdominal cavity contains an abundant heterogenic source. The aim of this study is to aid selection among intra-abdominal LNFs. METHODS Eight LNFs were harvested in a microsurgical fashion at five sites in 16 cadavers: gastroepiploic, jejunal, ileal, ileocolic, and appendicular. These flaps were compared regarding size, weight, arterial diameter, and lymph node (LN) count after histologic verification. RESULTS One hundred and sixteen flaps were harvested. The exposed area correlated with the flap weight and volume (r2 = 0.86, r = 0.9). While gastroepiploic LNFs (geLNFs) showed the highest median weight of 99 ml, the jejunal LNFs (jLNFs) had the highest density with 3.8 LNs per 10 ml. The most reliable jLNF was 60 cm from the ligament of Treitz. Three or more LNs were contained in 94% of the jejunal, 88% of the ileal/ileocolic, and 63% of the omental LNs. The ileocolic LNF had the largest arterial diameter of 3 mm, yet the smallest volume. CONCLUSIONS jLNF and ileal LNF provide a reliable, high LN density for simultaneous, smaller recipient sites. geLNFs are more suitable for larger recipient sites.

VHDA prepared at high pressures and temperatures appears to be mainly free of (nano)crystallinity. It is the thermally most stable amorphous solid phase of water at elevated pressures reported so far. Water's no man's land's low temperature boundary is thus shifted to higher temperatures by up to 4 K., The influence of the protocol of preparation on the crystallisation temperature TX of very high-density amorphous ice (VHDA) was studied by varying the annealing pressure (1.1, 1.6 and 1.9 GPa) and temperature (160, 167 and 175 K, respectively). TX increases by up to 4 K in the pressure range of 0.7 to 1.8 GPa for samples annealed at 1.9 GPa compared to samples annealed at 1.1 GPa. Concomitantly, secondary crystallisation channels are suppressed, indicating the absence of structural inhomogeneities. For VHDA prepared at 1.1 GPa and 1.6 GPa our results indicate such inhomogeneities, which we regard to be incompletely amorphized, distorted nanodomains of hexagonal ice that cannot be detected through X-ray diffraction experiments. VHDA prepared at high pressures and temperatures thus represents the amorphous state of water at >0.7 GPa least affected by nanocrystals that has been described so far. We expect the TX obtained for the samples prepared in this manner to be close to the ultimate limit, i.e., we do not consider it possible to raise the low-temperature border to the no-man's land notably further by changing the preparation protocol. An additional, considerable increase in this border will only be possible by working at much shorter time-scales, e.g., by employing fast heating experiments.

Maimonides’ view of the significance of dying for God, I will argue, is his understanding of the phrase that the rabbis appropriated (at least by the Middle Ages) for dying in martyrdom scenarios—namely, “Qiddush HaShem,” literally: “Sanctification of the Name [of God].” For Maimonides, a holy life is no more but also no less than a life constituted by perfect performance of all commandments in the Mosaic Law without exception. Does this ideal allow for—indeed mandate in specific circumstances—transgressing rather than dying, especially when coerced? Or does a truly holy life require nothing less than perfect performance of all commandments allowing for no violations under any circumstances? The view that demands perfect observance of all commandments in all circumstances, I will call “holiness perfectionism.” Maimonides, I shall argue, offers a critique of this view.

An accurate blood-based RAS mutation assay to determine eligibility of metastatic colorectal cancer (mCRC) patients for anti-EGFR therapy would benefit clinical practice by better informing decisions to administer treatment independent of tissue availability. The objective of this study was to determine the level of concordance between plasma and tissue RAS mutation status in patients with mCRC to gauge whether blood-based RAS mutation testing is a viable alternative to standard-of-care RAS tumor testing. RAS testing was performed on plasma samples from newly diagnosed metastatic patients, or from recurrent mCRC patients using the highly sensitive digital PCR technology, BEAMing (beads, emulsions, amplification, and magnetics), and compared with DNA sequencing data of respective FFPE (formalin-fixed paraffin-embedded) tumor samples. Discordant tissue RAS results were re-examined by BEAMing, if possible. The prevalence of RAS mutations detected in plasma (51%) vs. tumor (53%) was similar, in accord with the known prevalence of RAS mutations observed in mCRC patient populations. The positive agreement between plasma and tumor RAS results was 90.4% (47/52), the negative agreement was 93.5% (43/46), and the overall agreement (concordance) was 91.8% (90/98). The high concordance of plasma and tissue results demonstrates that blood-based RAS mutation testing is a viable alternative to tissue-based RAS testing.

In a classic paper, Leon Roth asked »Is there a Jewish Philosophy?« to which he replied No. In this paper, focusing on the case of Medieval Jewish Philosophy, I argue, first, that we cannot characterize Jewish philosophy in terms of the identity, religious or secular, of its philosophers, in terms of a language in which it was written or conducted, in terms of a particular style or school, or in terms of content: as philosophy specifically of Judaism the religion. I then go on to argue that all the medieval Jewish philosophers were doing was Philosophy, although I sketch two different conceptions of what a philosophical interpretation of Judaism and the Jews might be: a Saadyanic model and Maimonides’. However, even though there is no kind of philosophy called »Jewish philosophy« as opposed to simply »Philosophy,« I argue that we can identify (medieval) Jewish philosophy as a philosophical »tradition,« a causally related sequence of philosophers who influence and are influenced by each other and who engage in a distinguishable dialogue or conversation among themselves. In the last part of the paper, I critically discuss various recent arguments that purport to show that there is something paradoxical, self-contradictory, and philosophically illegitimate about the very idea of a Jewish philosophy.

Like many of his fifteenth-century Spanish contemporaries, Arama opposed the Aristotelianism of Maimonides. His philosophical sermons and biblical commentaries attack Jewish Aristotelians on charges of subordinating revelation to reasoning, upholding an eternal universe whose necessity limits God’s power, and excluding miracles and individual providence. Yet while stressing the fallibility of human reason, Arama is no fideist. An eclectic, he values reason and philosophy as ways of deepening the understanding of Scripture through allegorical interpretation. He also develops striking philosophical theories of miracles, providence and the fundamentals of faith.

One of the most influential medieval Jewish thinkers to engage with the philosophical tradition, Nahmanides was also a leading Talmudist, biblical exegete, and a founding figure of the Jewish mystical tradition (Kabbalah) that emerged in thirteenth-century Spain. Generally critical of Aristotle, he was deeply influenced by predecessors such as Moses Maimonides. As the leading rabbi in Catalonia, Nahmanides played a central role in the ‘Maimonidean controversy’ of 1232–3, a dispute that raged over the permissibility of philosophical study. He was also at the centre of the ‘Barcelona disputation’ of 1263, conducted with the apostate Pablo Christiani over the issue of philosophically motivated allegories. Unlike his Provençal contemporaries, Nahmanides wrote neither free-standing philosophical treatises nor commentaries on Graeco-Arabic philosophical texts. Instead, he developed his original metaphysical views in sermons and his highlt influential biblical commentaries treating such topics as miracles, providence and idolatry. The commentaries proved especially influential through their thematic treatments of philosophical questions raised by the biblical text and for their suggestive expositions of mystical and theosophical ideas.

We investigated moderate-temperature oxygen diffusion mechanisms in Sr2ScGaO5 with Brownmillerite structure type. From oxygen isotope 18O−16O exchange experiments we determined that oxygen mobility sets in above 550 °C. Temperature-dependent neutron and X-ray (synchrotron) diffraction experiments allowed us to correlate the oxygen mobility with a subtle phase transition of the orthorhombic room-temperature structure with I2mb space group toward Imma, going along with a disorder of the (GaO4)∞-tetrahedral chains. From lattice dynamical simulations we could clearly evidence that dynamic switching of the (GaO4)∞-tetrahedral chains from its R to L configuration sets in at 600 °C, thus correlating oxygen diffusion with the dynamic disorder. Oxygen ion diffusion pathways are thus constrained along the onedimensional oxygen vacancy channels, which is a different diffusion mechanism compared to that of the isostructural CaFeO2.5, where diffusion of the apical oxygen atoms into the vacant lattice sites are equally involved in the diffusion pathway. The proposed ordered room-temperature structure in I2mb is strongly supported by 17O, 45Sc, and 71Ga NMR measurements, which indicate the presence of crystallographically unique sites and the absence of local disordering effects below the phase transition. The electric field gradient tensor components measured at the nuclear sites are found to be in excellent agreement with calculated values using the WIEN2k program. The oxygen site assignment has been independently confirmed by 17O{45Sc} transfer of adiabatic populations double-resonance experiments.

Background: The high incidence of cholesterol gallstones in patients after proctocolectomy with ileal pouch-anal anastomosis (IPAA) may be due to an increased loss of bile acids. We aimed to evaluate the kinetics of the primary bile acids cholic acid (CA) and chenodeoxycholic acid (CDCA) in these patients. Methods: Pool sizes, synthesis rates, and fractional turnover rates of CA and CDCA were determined by combined capillary gas chromatography/isotope ratio mass spectrometry in serum samples after administration of [13C]CA and [13C]CDCA in 6 patients and 9 healthy volunteers. Results: In patients with IPAA, pool sizes of CA and CDCA were 11.5 (8.2-23.8) and 12.1 (6.7-20.1) µmol/kg, respectively, and were significantly lower than in healthy controls [36.0 (24-47) and 29.0 (21-42) µmol/kg, respectively; p < 0.05, each]. Fractional turnover rates of CA [1.19 (1.06-1.82) vs. 0.31 (0.13-0.54) per day] and CDCA [1.01 (0.50-1.63) vs. 0.23 (0.09-0.36) per day] were increased fourfold in patients with IPAA (p < 0.05, each). Synthesis rates of CDCA [10.2 (5.2-32.9) vs. 6.6 (2.7-10.5) µmol/kg per day, p = 0.05] and CA [15.1 (9.3-39.4) vs. 11.5 (3.1-20.5) µmol/kg per day, n.s.] tended to be higher in patients with IPAA than in controls. Conclusion: The reduced pool size of primary bile acids may contribute to the high incidence of cholesterol gallstones in patients after proctocolectomy and IPAA.

This essay examines the conditions under which the great medieval Jewish rabbinic figure Moses Maimonides (1138–1204) took war to be justified. In particular, it argues that Maimonides did not hold that universal belief in one deity, on the model of a (Christian or Almohad) holy war or religious crusade, is a sufficient condition to justify the pursuit of a war. At most a war is justified if it enables the creation of a monotheistic environment for the Jewish people within their own boundaries or national territory. Among other topics, the essay also analyzes Maimonides' distinction between ‘commanded’ wars and ‘optional wars’, his concept of idolatry, and his account of jus in bellum.

This paper argues first that, contrary to what one would expect, metaphorical interpretations of utterances pass two of Cappelan and Lepore’s Minimalist tests for semantic context-sensitivity. I then propose how, in light of that result, one might analyze metaphors on the model of indexicals and demonstratives, expressions that (even) Minimalists agree are semantically context-dependent. This analysis builds on David Kaplan’s semantics for demonstratives and refines an earlier proposal in (Stern, Metaphor in context, MIT Press, Cambridge, 2000). In the course of this argument, I also discuss some new examples of linguistic phenomena that motivate a semantic structure underlying metaphorical interpretation, phenomena I argue that neither Minimalists nor Contextualists can explain.

All English quotations are from The Guide of the Perplexed, trans. S. Pines (Chicago: University of Chicago Press, 1963). Parenthetical citations are to part, chapter, and page in this edition. For the Arabic text of the Guide, see Dalalat al-Hairin, ed. S. Munk and I. Joel (Jerusalem 1930/31). Henceforth I refer to this edition as the "received" Arabic text of the Guide; the term "received" is not intended to carry any normative weight. In addition to the passages cited and referred to, see Mishneh Torah, Hilkot Yesodei ha-Torah I, 5, 7.

Background and aims: Restorative proctocolectomy with construction of an ileoanal pouch (IPAA) is the surgical treatment of choice for patients with ulcerative colitis (UC) or familial adenomatous polyposis (FAP). This procedure imposes an essential change in function on the terminal ileal mucosa and pouch mucosa. Glutamine is one of the major nutrients for the small-bowel mucosa; it is metabolized into glutamate and subsequently alanine in the human enterocyte. In a prospective clinical trial we compared glutamine distribution in patients with UC to that in patients with FAP before and after restorative proctocolectomy. Methods and patients: Concentrations of glutamine, glutamate, and alanine were measured pre- and postoperatively in the terminal ileal mucosa, pouch mucosa, skeletal muscle and venous blood of patients undergoing IPAA for UC or FAP. Healthy individuals served as controls for skeletal muscle glutamine concentration. Results: After IPAA the glutamine concentration in UC patients was decreased in skeletal muscle. In the mucosa glutamine remained unaltered while glutamate and alanine concentrations increased. In plasma the glutamine concentration increased, the glutamate level fell, and the alanine level increased. In FAP patients the glutamine level was unchanged in skeletal muscle after IPAA. In mucosa the glutamine level did not change, but glutamate and alanine increased. In plasma the glutamine level remained unaltered, glutamate decreased, and alanine increased. Conclusion: Patients with UC or FAP before surgical therapy do not suffer from glutamine depletion. IPAA resulted in changes in the distribution of glutamine and its metabolites in skeletal muscle, plasma, and ileal pouch mucosa, particularly in patients with UC. Further studies should investigate whether characteristics in the glutamine distribution have any impact for the long-term outcome after IPAA.

Accurate staging is essential to plan therapeutic strategies and appropriate surgical treatment in patients with advanced gastrointestinal malignancies. Tremendous efforts have been undertaken to develop more sensitive techniques for the detection of premalignant, early-stage lesions and micrometastases. Despite the improvements in preoperative radiologic imaging, precise assessment of the local, regional, or distant extent of the primary tumor can be a major problem. Even with computed tomography, magnetic resonance tomography, or ultrasound, minimal tumor spread remains undetected. 1 Laparoscopy has emerged as a highly sensitive and specific method of comprehensive abdominal exploration, 2–4 but even with this staging tool an unknown amount of lesions still remain occult. Fluorescence diagnosis, also known as photodynamic diagnosis, is being increasingly used to distinguish healthy from diseased tissue in various medical disciplines. Especially in urology, fluorescence diagnosis has been used to visualize even small, plane tumors of the bladder. The principle of fluorescence diagnosis is based on the accumulation of administered agents, called photosensitizers, in malignant cells. After intravenous, oral, or topical application, the agent concentrates in tumors and remains inactive until exposed to light of a specific wavelength. When light is delivered to the cancer site, either directly or indirectly through a fiberoptic device, it causes fluorescence of the photosensitizers. Whereas earlier generations of photosensitizers, such as Photofrin, were fluorescent at the time of application (exogenous photosensitizers), the photosensitizer aminolevulinic acid (ALA) requires endogenous metabolism before it becomes fluorescent (endogenous photosensitizer). ALA is the natural precursor of the heme pathway. Administration of ALA, either systemically or locally, overloads the last step in the heme biosynthesis pathway of tumor cells because of missing negative feedback mechanisms and reduced enzymatic activities. This results in increased accumulation of ALA’s metabolite protoporphyrin IX. Protoporphyrin IX is a fluorescent agent when stimulated by a defined wavelength within its absorption spectrum. One main emission wavelength is within the visible light spectrum at 635 nm (red light) 5 (Fig. 1). The positive, red fluorescence of protoporphyrin IX is even detectable in macroscopically invisible tumor foci and can indicate lesions that would have been missed under conventional white-light illumination. Detection of fluorescence may be achieved by two distinct technical principles. In an imaging system, a two-dimensional picture of the fluorescence intensity distribution of the examined tissue is captured with a charge-coupled device (CCD) camera and displayed on a monitor. In a point system, the fluorescence signal is measured in a restricted area and spectrometrically evaluated with an optical multichannel analyzer. Figure 1. Typical protoporphyrin IX fluorescence emission spectra of tumor tissue (CC531 colon carcinoma) and surrounding healthy tissue (peritoneal muscle) with its typical peak at 635 nm and a lower secondary emission peak in the far red around 700 ... Fluorescence diagnosis for surgical staging laparoscopy was adopted to achieve better assessment of disseminated intraabdominal tumor spread. 6 This allowed early detection of dysplastic and malignant peritoneal changes caused by metastatic growth of gastrointestinal tumors. The feasibility of this modality in the detection of lesions occult to conventional white-light laparoscopy has been evaluated and confirmed as practicable in an experimental setting. The use of fluorescence laparoscopy increased the visualization of tumors by 17.5% compared with white-light laparoscopy. 6 In the pilot study, photosensitization parameters, such as an ALA concentration of 3.0% and a photosensitization time of 4 hours, were chosen according to data gained in urology. The following experimental study evaluated the variation of these two parameters to achieve optimal diagnostic results in the detection of peritoneal tumors. Both fluorescence detection techniques, the imaging and point system, were applied. Serum samples were investigated for ALA and protoporphyrin IX.

To analyze the association between pre- and perioperative factors and pouch-related septic complications (PRSC) in ulcerative colitis (UC) and in familial adenomatous polyposis (FAP) after ileal pouch-anal anastomosis (IPAA).For patients with UC and FAP, IPAA is the surgical therapy of choice, but in some patients the outcome is compromised by PRSC.A total of 706 consecutive patients (494 UC, 212 FAP) were assessed in a study aimed at identifying subgroups of patients who were at high risk for PRSC. The rate of PRSC was analyzed as a time-dependent function (Kaplan-Meier estimation). Patients with UC and FAP were stratified separately according to associated factors (age, sex, surgeon's experience, temporary ileostomy, colectomy before IPAA, anastomotic tension, and several factors specific for UC).In all, 131 (19.2%) patients had PRSC (23.4% UC, 9.4% FAP). In patients with UC, the estimated 1-year PRSC rate was 15.6% and the estimated 3-year PRSC rate was 24.2%. In patients with FAP, the estimated 1-year and 3-year PRSC rates were 9.2%. The difference between the estimated rates of PRSC was significant (P.001). In the univariate analysis, patients with UC younger than 50 years, with severe proctitis, with preoperative hemoglobin levels less than 10 g/L, or receiving corticoid medication had a significantly higher risk for PRSC (P =.039, P =.037, P =.047, P =.003, respectively). Multivariate analysis showed that patients with UC receiving a systemic prednisolone-equivalent corticoid medication of more than 40 mg/day had a significantly greater risk of developing pouch-related complications than patients with UC receiving 1 to 40 mg/day and patients with UC who were not receiving corticoid medication (RR: 3.78, 2.25, 1, respectively, P.001). Patients with FAP proved to have a significantly higher risk for PRSC in the univariate and multivariate analyses if anastomotic tension had occurred (RR 3.60, P =.0086).Pouch-related septic complications occur as late complications and should therefore be considered in regular, specific long-term follow-up examinations. The authors identified significant risk factors for PRSC specific to patients with UC and FAP; these must be considered for each individual surgical strategy.

Die zweizeitige ileoanale Pouchanlage (IAP) ist Standardverfahren zur kurativen Therapie der familiaren Adenomatosis coli (FAP) sowie der chirurgisch therapiepflichtigen Colitis ulcerosa (CU). Neben den klassischen Komplikationen beeinflusst die Entfernung des Colorectums die Blut- und Volumenhomoostase. Patienten und Methoden: Aus einem Patientenpool von 320 Patienten mit J-Pouchanlage wurden uber einen Beobachtungszeitraum von 2 Jahren Patienten mit hohem facalen Verlustsyndrom ohne fassbare organische Ursache identifiziert. Der Ausschluss einer organischen Ursache erfolgte mittels Pouchoskopie, Pouchographie und ggf. mittels MRT-Untersuchung. Neben Messparameter der Routinediagnostik wurden der Saure-Basen-Haushalt analysiert, eine Urin-pH-Metrie durchgefuhrt sowie mittels Hormonanalysen die adrenale Kompensationsleistung erfasst. Sieben Patienten mit „High-Pouch-Output“-Syndrom konnten identifiziert werden. Das Kontrollkollektiv bildete eine Gruppe aus 14 beschwerdefreien, in der endoskopischen Routinediagnostik unauffalligen IAP-Patienten. Ergebnisse: Die Analyse der Routineparameter ergab bei beiden Patientengruppen keinerlei signifikante Unterschiede. Eine deutlich verminderte Urinnatriumkonzentration 40,5 ± 18,7 mmol/l (Kontrollgruppe 98 ± 43,4 mmol/l) bestand fur die Patientengruppe mit hohen facalen Verlusten. In dieser Gruppe waren mit 42,6 ± 28,9 ng/dl (Kontrollgruppe 13,2 ± 6,8 ng/dl) die Aldosteronspiegel sowie mit 153,7 ± 121,1 ng/dl (Kontrollgruppe 53 ± 23 ng/dl) die 18-OH-Corticosteronspiegel signifikant erhoht. Fur die Glucocorticoide, Corticosteron, Cortisol wurden bei beiden Gruppen keine erhohte Aktivitat festgestellt. Nur 11-Desoxycorticosteron war im Patientenkollektiv mit „High-Pouch-Output“-Syndrom erhoht. Schlussfolgerungen: Unsere Ergebnisse belegen, dass Hormone mit mineralocorticoider Wirkung eine zentrale Rolle bei der Aufrechterhaltung der Blut- und Volumenhomoostase spielen. Die niedrige Incidenz therapiepflichtiger Verlustsyndrome nach Abschluss der ileoanalen Pouchoperation belegt die hervorragende Kompensation des entfernten Colorectums. Mit Aldosteron scheint ferner ein Marker gefunden, der die intestinale Natriumresorptionsproblematik proktocolektomierter Patienten erfasst.

PURPOSE: Inflammation of the ileoanal pouch (pouchitis) is one of the main complications after restorative proctocolectomy, yet its cause remains poorly understood. A standardized definition and diagnostic procedures in pouchitis are lacking. METHOD: We analyzed all cases of pouchitis occurring in a group of 308 patients (210 with ulcerative colitis, 98 with familial adenomatous polyposis) who took part in a prospective long-term follow-up program. The severity of pouchitis was measured using a pouchitis activity score (Heidelberg Pouchitis Activity Score). An algorithm for the classification and management of pouchitis was established which enables the clinician: 1) to determine theseverity of pouchitis, 2) to differentiate betweenprimary pouchitis and pouchitis caused by surgical complications (secondary pouchitis), and 3) to evaluate the course (acute vs. chronic (>3 months)). RESULTS: The median duration of follow-up was 48 (range, 13–119) months. At least one episode of pouchitis was diagnosed in 29 percent of patients with ulcerative colitis and in 2 percent of familial adenomatous polyposis patients. Secondary pouchitis occurred in 6 percent of ulcerative colitis patients and was cured by surgical treatment in 13 (87 percent) of 15 cases. Primary pouchitis was diagnosed in 23 percent of ulcerative colitis patients, including 6 percent of all ulcerative colitis patients with chronic primary pouchitis. The latter showed poor response to medical treatment. In one case multifocal high-grade dysplasia occurred. Histologic examination of the excised pouch identified a carcinoma originating from the ileal mucosa. CONCLUSIONS: Ulcerative colitis patients after restorative proctocolectomy face a high risk of developing pouchitis. The algorithm used in this study was highly efficient in identifying patients with a secondary pouchitis who require surgical treatment and patients with chronic primary pouchitis. For the latter, long-term surveillance seems mandatory because of the risk of malignant transformation of the pouch mucosa.

It is well known that Maimonides rejects the Kalam argument for the existence of God because it assumes the temporal creation of the world, a premise for which he says there is no “cogent demonstration ( burhan qat'i) except among those who do not know the difference between demonstration, dialectics, and sophistic argument.” Moses Maimonides, The Guide of the Perplexed, trans. Shlomo Pines (Chicago: University of Chicago Press, 1963), I:71:180. All references are to this translation; parenthetic in-text references are to part, chapter, and page. By contrast, he claims to establish belief in the existence of God “through a demonstrative method as to which there is no disagreement in any respect” (I:71:182). Taken at his word, Maimonides’ proofs for the existence of the deity, like Aquinas’s five ways, have traditionally been read as models of medieval natural theology: of the power of human reason to independently establish revealed truth. In recent years, however, the same demonstrations have assumed a second kind of significance. For scholars, like myself, who argue that Maimonides holds severe views about the limitations of human knowledge of divine science and metaphysics, these demonstrations are the strongest conceivable counterevidence. The locus classicus for this view is Shlomo Pines, “The Limitations of Human Knowledge According to Al-Farabi, Ibn Bajja, and Maimonides,” in Studies in Medieval Jewish History and Literature, ed. I Twersky, 3 vols. (Cambridge: Harvard University Press, 1979), I:82–109. See also his “Les Limites de la Metaphysique selon Al-Farabi, ibn Bajja et Maimonide; Sources et Antitheses de ces Doctrines chez Alexandre d’Aphrodise et Chez Themistius,” Miscellanea Mediaevalia 13 (1981): 211–25; “Dieu et L’Etre Selon Maimonide: Exegese d’Exode 3,14 et doctrine connexe,” in Celui qui est: Interpretations juives et chretiennes d’Exode 3, 14, ed. A. de Libera et E. Zum Brunn (Paris: Les Editions du Cerf [Collection “Patrimoines”], 1986), 15–24; and “The Relation between Maimonides’ Halakhic and non-Halakhic Works,” in Maimonides and Philosophy, ed., S. Pines and Y. Yovel (Dordrecht: Martinus Nijhoff, 1987). Pines concludes, on the basis of the limitations of the intellect with respect to knowledge of metaphysics, that Maimonides, like Kant, gives priority to the practical over the theoretical. For arguments drawing different ‘skeptical’ conclusions, see my “Maimonides in the Skeptical Tradition,” ms.; “Maimonides on the Growth of Knowledge and the Limitations of the Intellect,” to appear in Tony Levy, ed., Maimonide: Traditions philosophiques et scientifiques medievales arabe, hebraique, latine ; “Logical Syntax as a Key to a Secret of the Guide of the Perplexed, ” (in Heb.), Iyyun 38 (1989): 137–66; “Maimonides on Language and the Science of Language,” in Maimonides and the Sciences, ed., H. Levine and R. Cohen (Dordrecht: Kluwer, 2000), pp. 173–226; and The Matter and Form of Maimonides’ Guide (forthcoming). If Maimonides really held that humans cannot apprehend metaphysical truths about the deity, how could he have demonstrated (or even thought he could demonstrate) the existence of God? If he does demonstrate it, then humans evidently do have knowledge of metaphysics. As one distinguished scholar has recently protested, it is nothing less than “perverse” to interpret Maimonides as “meaning that the existence of God is unknowable when he in fact prides himself on having demonstrated the existence of God in four different ways.” Herbert A. Davidson, “Maimonides on Metaphysical Knowledge,” Maimonidean Studies 3 (1992–1993): 49–103, 86. See also Alfred L. Ivry, “The Logical and Scientific Premises of Maimonides’ Thought,” in Perspectives on Jewish Thought and Mysticism, ed. Alfred L. Ivry, Elliot R. Wolfson, and Allan Arkush (Amsterdam: Harwood Publishers, 1998), pp. 63–97, 70.

The ileo-anal pouch procedure: Complications, quality of life, and long-term results. Restorative proctocolectomy with construction of an ileal pouch-anal anastomosis (IPAA) has evolved as the surgical therapy of choice for patients with ulcerative colitis (UC) and patients with familial adenomatous polyposis (FAP). 662 patients (493 UC, 169 FAP) consecutively received IPAA. Marked differences were observed between UC and FAP patients regarding the rates of overall complications (33.1 % vs. 12.5 %), pouchitis (29 % vs. 2 %), and pouch extirpation (3.2 % vs. 0.6 %). Pouchitis occurred as primary (79 %) and secundary (21 %) form, with acute (67.2 %) or chronic (32.8 %) course. Each form and course required specific therapy. Chronic pouchitis implies the risk of malignant transformation of the pouch mucosa. Quality of life improves significantly after IPAA in patients with UC and is equal to that in normal individuals, in UC and FAP, if postoperative complications are either prevented or under control.

After proctocolectomy with ileal pouch-anal anastomosis (IPAA) patients have increased stool frequency and intermittently use antidiarrheal medication. In addition to other factors, gastrointestinal transit time (MTT) could influence stool frequency. The aim of this study was to investigate how MTT changes after IPAA and to study whether MTT has an influence on daily stool frequency. In a prospective trial MTT was investigated with the lactulose breath test in 12 patients undergoing surgery for chronic ulcerative colitis (CUC) or familial adenomatous polyposis coli (FAPC) at different stages: before proctocolectomy, after IPAA with loop ileostomy, and 3 months and 1 year after ileostomy closure. MTT was also measured in 12 patients with IPAA, 12 patients with subtotal colectomy and ileorectal anastomosis (IRA), and 8 patients with conventional proctocolectomy and Brooke ileostomy (CPC) several years after surgery. Twelve healthy volunteers served as controls. Before IPAA, MTT was prolonged in CUC versus FAPC and controls. After restoration of gut continuity MTT was markedly accelerated. After 1 year MTT was slowed again, though values before proctocolectomy and those in controls were not reached. Several years after surgery MTT was significantly prolonged in IPAA and IRA versus controls. In CPC, MTT could not be determined by lactulose breath test. Stool frequency showed an inverse correlation to MTT in IPAA. In conclusion, this study shows that orocecal and oropouch transit are accelerated in the early postoperative period after (procto)colectomy but prolonged in the long-term course. Adaptation of the small bowel takes longer than 1 year. Impairment of stool frequency may be partly due to this adaptation.

Background and Objectives 5-Aminolevulinic acid (ALA) increases the intracellular accumulation of endogenous protoporphyrin IX in colon cancer. Protoporphyrin IX itself is a potential photosensitizer that can be used for laser light-induced fluorescence diagnosis. The aim of this study was to detect cancer in the rat colon before macroscopic visibility. Study Design/Materials and Methods Multifocal colon carcinomas were induced by weekly subcutaneous injections of 1,2-dimethylhydrazin-dihydrochloride in male Wistar rats. Local photosensitization was performed with an ALA colon lavage. Red fluorescence (635 nm) was induced by green laser-light irradiation with an Ar-Dye Laser (514 nm) in the colon. Fluorescence was observed by the naked eye with a filter at < 515 nm to eliminate the excitation light. Results Twenty-five Wistar rats developed 99 macroscopically visible carcinomas and four macroscopically visible dysplasias. The following laser-light–induced fluorescence diagnosis procedure was able to detect 16 additional carcinomas and 41 additional dysplasias. Conclusions Local ALA application induces a tumor-specific protoporphyrin IX accumulation in the rat colon and is an efficient method for fluorescence detection of invisible dysplasias and early colon cancer in the rat. Lasers Surg. Med. 26:302–307, 2000. © 2000 Wiley-Liss, Inc.

PURPOSE: Restorative proctocolectomy is a standard procedure in the surgical treatment of ulcerative colitis and familial adenomatous polyposis. The radical removal of the colorectum with construction of an ileostomy often results in high stoma losses. These may lead to changes in the electrolyte and acid-base balance and to alterations in renal and suprarenal gland function. METHODS: In this study 33 patients who received an ileoanal pouch before and after proctocolectomy were investigated at different time intervals for electrolyte changes, alteration of the acid-base balance, kidney function, and hormonal changes of the suprarenal glands. Measurements were performed before proctocolectomy, ten days after proctocolectomy with ileal pouch-anal anastomosis under protective loop ileostomy, before ileostomy closure, and 6 to 12 months after ileostomy closure. Neither acute renal failure nor other vital complications were observed. RESULTS: Statistical analysis showed a significant decrease of urine pH to 5.4±0.22 (before ileostomy closure) and metabolic acidosis (pH 7.32±0.04; base excess −1.3±5.6 (before ileostomy closure)). Likewise, we found a decrease in renal clearance to 86 ml/minute (before ileostomy closure) without signs of tubular damage. The most important change during the phase with ileostomy was a functional secondary hyperaldosteronism with aldosterone levels of 63.2±70.8 ng/dl (before ileostomy closure). In comparison with preoperative levels, there was a ten-fold increase in mineralocorticoid adrenal activity. Additionally, during the period with protective ileostomy, the hepatic synthesis of aldosterone-18-glucuronide was only slightly increased, and the cortisol/cortisone ratio was extremely decreased. CONCLUSIONS: These results show that restorative proctocolectomy with ileal pouch-anal anastomosis and protective loop ileostomy significantly influences fluid, electrolyte, and acid-base balance. Functional secondary hyperaldosteronism is of central importance for subsequent renal recompensation. Approximately one-half year after ileostomy closure, the endogenous hormones with mineralocorticoid effects returned to normal levels.

Background: Lymph node metastases and peritoneal carcinosis, occurring as a result of gastrointestinal cancer, reduce the likelihood that conventional therapy will be adequate to remove the cancer. Although diagnostic techniques have greatly improved, it is not always possible to diagnose the entire extent of the metastases. Often, peritoneal micrometastases are not visible and may be missed during laparoscopic or open surgery. Methods: Peritoneal carcinosis was induced in WAG-Rij rats (n = 6), by laparoscopically implanting 1,2-dimethylhydrazine–induced colon carcinoma tumor cells (CC531, 5 × 10 5 ) at multiple sites within the peritoneal cavity. After 12 days of tumor growth, the animals were given δ-aminolevulinic acid (ALA) (5 mL, 3% solution in 0.17 mol/L NaHCO 3 ) by peritoneal lavage. The tumors were visualized laparoscopically using both white and blue light (D-light, Karl Storz, Tuttlingen, Germany). Fluorescence was detected by using a modified CCD camera and a special observation filter incorporated into the laparoscope. Results: Peritoneal carcinoma foci ranging in size from 0.05 to 2.0 cm were clearly visible laparoscopically with conventional white light (n = 142). After blue light excitation, all 142 tumors identified with white light were also identified by fluorescence. There were an additional 30 tumors that could only be identified by blue light–induced fluorescence and were histologically confirmed to be derived from colon carcinoma tumor cells. Conclusions: Peritoneal colonic carcinoma foci were detected laparoscopically after intraperitoneal lavage with δ-aminolevulinic acid (ALA) and excitation with blue light. These experiments demonstrate that fluorescence laparoscopy is an important technique for the staging of gastrointestinal cancer, including colorectal cancer, because of the enhanced ability to detect small cancerous foci. (Surgery 1999;126:469-73)