Muscle Coat Research Articles

Preventive Diaphragm Plasty after Pneumonectomy on Account of Lung Cancer

Experience is presented of 53 cases of diaphragm plasty of the bronchial stump, tracheobronchial anastomosis, pericardium, and esophagus wall after extended pneumonectomy on account of lung cancer. A pedicled diaphragm flap was used to prevent bronchopleural fistula in 53 patients, as well as heart dislocation after wide resection of the pericardium in 26, and esophagopleural fistula after resection of the muscle coat of the esophagus in 2. In all cases, there was a high risk of these complications. Dehiscence of the bronchial stump or tracheobronchial anastomosis occurred in 9 patients, but due to diaphragm plasty, a bronchopleural fistula formed in only 3. Restoration of the pericardium and the esophageal muscle coat was successful in all cases. Overall morbidity was 22.6%, 30-day mortality was 7.5%, hospital mortality was 11.3%. Causes of death were fulminant pneumonia of the single lung, cerebral hemorrhage, pulmonary embolism, heart failure, early tumor progression, and sepsis, in one case each. The results were compared with those in 49 patients who underwent other methods of bronchial stump or tracheobronchial anastomosis reinforcement. The analysis revealed that the diaphragm flap was highly efficacious as a multipurpose plastic material.

Hypoxic vasoconstriction of partial muscular intra-acinar pulmonary arteries in murine precision cut lung slices

BackgroundAcute alveolar hypoxia causes pulmonary vasoconstriction (HPV) which serves to match lung perfusion to ventilation. The underlying mechanisms are not fully resolved yet. The major vascular segment contributing to HPV, the intra-acinar artery, is mostly located in that part of the lung that cannot be selectively reached by the presently available techniques, e.g. hemodynamic studies of isolated perfused lungs, recordings from dissected proximal arterial segments or analysis of subpleural vessels. The aim of the present study was to establish a model which allows the investigation of HPV and its underlying mechanisms in small intra-acinar arteries.MethodsIntra-acinar arteries of the mouse lung were studied in 200 μm thick precision-cut lung slices (PCLS). The organisation of the muscle coat of these vessels was characterized by α-smooth muscle actin immunohistochemistry. Basic features of intra-acinar HPV were characterized, and then the impact of reactive oxygen species (ROS) scavengers, inhibitors of the respiratory chain and Krebs cycle metabolites was analysed.ResultsIntra-acinar arteries are equipped with a discontinuous spiral of α-smooth muscle actin-immunoreactive cells. They exhibit a monophasic HPV (medium gassed with 1% O2) that started to fade after 40 min and was lost after 80 min. This HPV, but not vasoconstriction induced by the thromboxane analogue U46619, was effectively blocked by nitro blue tetrazolium and diphenyleniodonium, indicating the involvement of ROS and flavoproteins. Inhibition of mitochondrial complexes II (3-nitropropionic acid, thenoyltrifluoroacetone) and III (antimycin A) specifically interfered with HPV, whereas blockade of complex IV (sodium azide) unspecifically inhibited both HPV and U46619-induced constriction. Succinate blocked HPV whereas fumarate had minor effects on vasoconstriction.ConclusionThis study establishes the first model for investigation of basic characteristics of HPV directly in intra-acinar murine pulmonary vessels. The data are consistent with a critical involvement of ROS, flavoproteins, and of mitochondrial complexes II and III in intra-acinar HPV. In view of the lack of specificity of any of the classical inhibitors used in such types of experiments, validation awaits the use of appropriate knockout strains and siRNA interference, for which the present model represents a well-suited approach.

Substance P and Neurokinin 1 receptor - expression is affected in the ileum of mice with mutation in the W locus

The tachykinin substance P (SP) acts on the gut muscle coat via its preferred receptor, neurokinin 1 (NK1r). In the mouse ileum, NK1r-immunoreactivity (NK1r-IR) was detected in neurons, in the interstitial cells of Cajal at the deep muscular plexus (ICC-DMP) and the myoid cells of the villi. SP-IR was detected in neurons and varicose nerve fibers, which were especially numerous at the DMP and closely associated with the ICC-DMP. In mice with a mutation in the W locus (c-kit mutant animals), innervation is suggested to be normal although few studies have actually tested this hypothesis. Indeed, studies demonstrating ICC-DMP integrity are lacking and whether SP- and NK1r-IR are normal in these animals has not been investigated. Our aim was to perform an immunohistochemical study on the ileum of a strain of heterozygous mice with a mutation in the W locus, the We/+ mice, to test this hypothesis. SP-IR nerve fibers were significantly more numerous than in wild type mice; NK1r-IR was clustered on the plasma membrane and also intracytoplasmatic in the neurons, but absent in the ICC-DMP. The richness in SP-IR nerve fibers and the NK1r-IR distribution in the neurons, similar to that of activated cells, might be attempts to compensate for the SP preferred receptor absence at the ICC-DMP. In conclusion, SP content and NK1r expression are noticeably different in c-kit mutants with respect to wild type mice, and probably causing an anomalous tachykininergic control of intestinal motility. Physiological studies on W mutant mice have to take into account that innervation in this animal model is affected by the c-kit mutation.

Gastrointestinal stromal tumours: a regular origin in the muscularis propria, but an extremely diverse gross presentation

Gastrointestinal stromal tumours (GISTs) are thought to arise from the interstitial cells of Cajal (ICCs). ICCs form a network surrounding the myenteric plexus and between-muscle fibres of the muscularis propria of the tubular GI tract. The cell of origin of so-called extra-gastrointestinal stromal tumours (EGISTs) is not known. To study the diversity of gross presentation of GISTs and to critically assess the incidence of EGISTs and their relationship to mural GISTs, a total of 200 neoplasms with typical morphologic and immunohistochemical features of GISTs were reviewed, looking for any degree of association with the muscularis propria of the gut wall. There were 130 gastric (65%), 9 duodenal (4.5%), 48 small intestinal (24%), 9 colorectal (4.5%), 1 appendiceal (0.5%) and 3 unclassifiable GISTs (1.5%). Fourteen cases (7%) were initially submitted as EGISTs (four mesenteric, four omental, one pararectal/prostatic, one pelvic/Douglas, one perivesical, one located between root of mesentery and tail of pancreas, one involving the mesentery, omentum and abdominal wall extensively and one located between liver and stomach). After critical re-evaluation of surgical reports and remote clinical history and a careful search for residual muscular tissue from the gut wall in the tumour pseudocapsule (in some cases supported by desmin immunoreactivity), it was possible to reclassify most of these cases (11/14) as either GISTs with extensive extramural growth resulting in loss of contact to the external muscle coat of the gut (8/14) or as metastases from an inoperable GIST (2/14) or from a previously resected deceptively benign tumour (1/14). EGISTs are probably rarer than previously reported (1.5% or less in this study). We concluded that most so-called EGISTs represent apparent EGISTs that should have arisen from the outermost muscle coat, but have lost their contact to the point of origin due to extensive extramural growth pattern. From a surgical point of view, it is crucial to document and mark any focal attachment or adhesions to the gut wall noticed during surgery for an apparent EGIST. In contrast to most other neoplasms, GISTs should be defined by virtue of any degree of association with the muscularis propria (no matter how minimal), but not by localisation of the bulk of the tumour.

Relationships between neurokinin receptor-expressing interstitial cells of Cajal and tachykininergic nerves in the gut.

The so-called interstitial cells of Cajal (ICC) are distributed throughout the muscle coat of the alimentary tract with characteristic intramual location and species-variations in structure and staining. Several ICC sub-types have been identified: ICC-DMP, ICC-MP, ICC-IM, ICC-SM. Gut motility is regulated by ICC and each sub-type is responsible for the electrical activities typical of each gut region and/or muscle layer. The interstitial position of the ICC between nerve endings contain tachykinins. Three distinct tachykinin receptors (NK1r, NK2r and NK3r) have been demonstrated by molecular biology. Each of them binds with different affinities to a series of tachykinins (SP, NKA and NKB). In the ileum, SP-immunoreactive (SP-IR) nerve fibers form a rich plexus at the deep muscular plexus (DMP), distributed around SP-negative cells, and ICC-DMP intensely express the SP-preffered receptor NK1r; conversely a faint NK1r-IR is detected on the ICC-MP and mainly after receptor internalization was induced by agonists. ICC-IM are never stained in laboratory mammals, while those of the human, antrum are NK1r-IR. RT-PCR conducted on isolated idleal ICC-MP and gastric ICC-IM showed that these cells express NK1r and NK3r. Colonic ICC, except those in humans, do not express NK1r-IR, at least in resting conditions. Outside the gut, NK1r-IR cells were seen in the arterial wall and exocrine pancreas. In the mouse gut only, NK1r-IR is present in non-neuronal cells located within the intestinal villi, so-called myoid cells, which are c-kit-negative and α-smooth muscle actin-positive. Immunohistochemistry and functional studies confirmed that ICC receive input from SP-IR terminals, with differences between ICC sub-types. In the rat, very early after birth, NK1r is expressed by the ICC-DMP and SP by the related nerve varicosities. Studies on pathological conditions are few and those on mutant strains practically absent. It has only been reported that in the inflamed ileum of rats the NK1r-IR ICC-DMP disappear and that at the peak of inflammatory conditions ICC-MP are NK1r-IR. In ileum of mice with a mutation in the W locus, ICC-DMP were seen to express c-kit-IR but not NK1-IR, and SP-IR innervation seems unchanged. In summary, there are distinct ICC populations, each of them under a different tachkininergic control and, likely, having different functions. Further studies are recommended at the aim of understanding ICC involvement in modulating/transmitting tachykininergic inputs.

Morphological and Immunocytochemical Investigations on Mast Cells in Porcine Ureter

Morphological, morphometric, histochemical and immunocytochemical investigations on mast cells, located in the wall of ureter of 8 months aged pigs were performed. Mast cells were found in all three layers of ureteral wall, but their distribution was irregular and the number unequal. It was established that alcian blue (AB)-positive mast cells were significantly more than toluidine blue (TB)-positive mast cells. A statistically significant smaller number of both AB and TB-stained mast cells were observed in the tunica mucosa. The largest number of mast cells was found in the tunica muscularis. In the adventitia, mast cells were higher in number in the main connective tissue than in the connective tissue near the blood vessels. Mast cells stained with TB showed variably expressed gamma-metachromasia, which was best visible in those situated in the lamina propria of the mucosa. The prevailing parts of mast cells, however, were AB-positive after AB-safranin staining. This was mostly found in mast cells of the tunica muscularis and in mast cells of perivascular location in the tunica adventitia. Immunocytochemically, mast cells were found to be positive for histamine and vasoactive intestinal polypeptide in the muscle coat, and to histamine in the adventitia, as well. On the basis of obtained results it was presumed that the mast cells in porcine ureter most probably took part not only in keeping of local homeostasis, but played also an important role of mobility of smooth muscle cells in the middle layer of ureter on one hand, and, on the other, in the adventitial blood vessels.

Relaxin Restores Altered Ileal Spontaneous Contractions in Dystrophic (mdx) Mice

We studied the effects of relaxin on ileal contractility in normal and dystrophic (mdx) mice. Ileal preparations from male normal and mdx mice showed spontaneous myogenic contractions whose amplitude was significantly higher in the latter ones. Relaxin added to the bath medium together with l-arginine depressed the amplitude of the spontaneous contractions in the mdx mice to a level similar to that of the normal mice. The nitric oxide synthase (NOS) inhibitor L-N(G)-nitroarginine reverted this effect. In mdx mice pretreated for 18 hours with relaxin, spontaneous motility was greatly reduced in amplitude, resembling that of the normal mice. Concurrently, iNOS expression in the muscle coat was markedly increased. Therefore, in mdx mice, relaxin can restore an ileal motility pattern similar to that of the normal mice by upregulating endogenous NO biosynthesis.

The Histopathology of Congenital Pouch Colon Associated with Anorectal Agenesis

The colonic pouch excised during surgery in 17 patients with congenital pouch colon associated with anorectal agenesis (CPC) was subjected to detailed histological examination after staining with hematoxylin and eosin. The patients included 11 newborns, 3 infants, and 3 older children. The most frequently observed abnormalities were acute and chronic inflammation of the mucosa and submucosa, focal or generalized thinning of muscle layers, especially of the outer muscle coat, disorganized muscle layers, a decreased number of mature ganglion cells, and neuronal hyperplasia and hypertrophy in nerve plexuses. Ectopic heteroplastic tissues were identified in 2 patients. These findings suggest that the colonic pouch in CPC represents abnormally developed colonic tissue and points to the similarity with segmental dilatation of the colon. The neuromuscular abnormalities explain the physiological characteristics of the colonic pouch, namely weak peristalsis as well as the propensity to undergo marked dilatation even after tubularization.

Intra-abdominal Esophageal Duplication Cyst in an Adult

Esophageal duplication cysts are congenital anomalies of the foregut that are rarely found in the abdomen. An accurate preoperative diagnosis is not always possible, so the definitive diagnosis can be made by histologic examination of the surgical specimen. We experienced a case of Intra-abdominal esophageal duplication cyst in a 52-year-old female, who initially presented with an esophageal submucosal tumor on upper gastrointestinal endoscopy. She did not have any gastrointestinal symptoms. Barium esophagography, chest computed tomography scan and endoscopic ultrasonography demonstrated the cystic lesion in the intra-abdominal esophagus. Transhiatal enucleation of the lesion was performed successfully via the abdominal approach with no postoperative complications. Histologic study showed that the cyst wall contained a two-layered muscle coat and the surface of the lumen was lined by pseudo-ciliated columnar epithelium. The patient has been doing well without any complaints for 3 months of follow-up period.

Distribution and chemical coding of corticotropin-releasing factor-immunoreactive neurons in the guinea pig enteric nervous system

Immunofluorescence was used to study immunoreactivity (IR) for corticotropin-releasing factor (CRF) in the guinea pig enteric nervous system. CRF-IR was expressed in both the myenteric and the submucosal plexuses of all regions of the large and small intestine and the myenteric plexus of the stomach. CRF-IR nerve fibers were present in the myenteric and submucosal plexuses, in the circular muscle coat, and surrounding submucosal arterioles. Most of the CRF-IR fibers persisted in the myenteric and submucosal plexuses after 7 days in organotypic culture. CRF-IR was not coexpressed with tyrosine hydroxylase-IR or calcitonin gene-related peptide-IR fibers. The proportions of CRF-IR cell bodies in the myenteric plexus increased progressively from the stomach (0.6%) to the distal colon (2.8%). Most of the CRF-IR myenteric neurons (95%) had uniaxonal morphology; the remainder had Dogiel type II multipolar morphology. CRF-IR cell bodies in the myenteric plexus of the ileum expressed IR for choline acetyltransferase (56.9%), substance P (55.0%), and nitric oxide synthase (37.9%). CRF-IR never colocalized with IR for calbindin, calretinin, neuropeptide Y, serotonin, or somatostatin in the myenteric plexus. CRF-IR cell bodies were more abundant in the submucosal plexus (29.9-38.0%) than in the myenteric plexus. All CRF-IR neurons in submucosal ganglia expressed vasoactive intestinal peptide-IR and were likely to be secretomotor/vasodilator neurons. CRF-IR neurons did not express IR for the CRF(1) receptor. CRF(1)-IR was expressed in neuronal neighbors of those with CRF-IR. Collective evidence suggests that VIPergic secretomotor neurons might provide synaptic input to neighboring cholinergic neurons.

CGMP‐generating cells in the bladder wall: identification of distinct networks of interstitial cells

To identify cells which might contribute to the complex physiological responses of the guinea-pig bladder, and specifically to describe the distribution and types of cell in the bladder wall of the guinea pig which respond to nitric oxide (NO) with an increase in intracellular cGMP, i.e. putative interstitial cells (ICs). The whole bladder was removed from 11 male guinea pigs killed by cervical dislocation. Sections of the bladder wall, from the dome lateral wall and base, were isolated and incubated separately in Krebs' solution at 36 degrees C, gassed with 95% O(2) and 5% CO(2), and containing 1 mmol/L of the nonspecific phosphodiesterase inhibitor isobutyl-methyl-xanthene. Individual pieces of tissue were then exposed to 100 micromol/L of the NO donor NONOate for 10 min; control tissues remained in Krebs' solution. Tissues were then fixed in 4% paraformaldehyde and processed for immunohistochemistry. cGMP and neuronal NO synthase (nNOS) were subsequently visualized using appropriate primary and secondary antibodies. Cells responding to NO with an increase in cGMP were detected in the dome, lateral wall and base, with positive cells in the thin outer surface of the wall (muscle coat), associated with muscle bundles in an outer layer of muscle, and in a region immediately beneath the urothelium. These cells (not urothelium, smooth muscle or vascular) are described as interstitial cells. Superficial urothelial umbrella cells were apparent and were strongly cGMP-positive. A high density of interstitial cells was associated with muscle bundles on the outer aspects of the wall, while few cells were detected on inner bundles. Thus there appeared to be two distinct types of muscle, inner and outer, with no obvious orientation of the fibres in each layer. Both muscle groups contained fibres expressing nNOS. In the outer muscle layer most of these fibres co-localized with cGMP, suggesting that different populations of nerves innervate each layer. There were more nNOS-positive fibres in the base of the bladder than in the dome. Three populations of cGMP-positive interstitial cells were associated with the outer muscle layer; cells in the outer surface (muscle coat interstitial cells, MC-ICs), cells on the surface of the bundles (superficial, SM-ICs) and cells within the muscle bundles (intramuscular, IM-ICs). The IM-ICs form a network in close apposition to the smooth muscle cells while the SM-ICs may connect adjacent muscle bundles and connect to the MC-ICs. Thus, there is a network linking potentially the muscle cells in the outer muscle bundles. cGMP-positive cells were also detected in the suburothelial layer (suburothelial, SU-ICs) which had a different structure to the cells associated with muscle, had a oval cell bodies with bifurcating processes and appeared to form a complex network; they were prevalent in the base and virtually absent in the dome. There are structures within the bladder wall that can be identified and categorized by the ability of the constituent cells to increase intracellular cGMP in response to NO; these cells have been defined as ICs. Two distinct networks were identified, one associated with the outer muscle layers and another lying immediately beneath the urothelium, predominantly in the base of the bladder. The functions of these cells and networks are unknown; their possible roles in complex motor activity, urothelial signalling and bladder pathophysiology are discussed.

Interstitital cells of Cajal in the human stomach: distribution and relationship with enteric innervation.

Interstitial cells of Cajal (ICC) are distributed throughout the gastrointestinal muscle coat with a region-specific location, and are considered to be pace-maker and/or mediators of neurotransmission. Little is known about their shape, size, distribution and relationships with excitatory and inhibitory nerves in human stomach. With this aim, we labeled the ICC, using c-Kit immunohistochemistry, followed by a quantitative analysis to evaluate the distribution and area occupied by these cells in the circular and longitudinal muscle layers and at the myenteric plexus level in the human fundus, corpus and antrum. Furthermore, by NADPH-d histochemistry and substance P (SP) immunohistochemistry, we labeled and quantified nitric oxide (NO)-producing and SP-containing nerves and evidenced their relationships with the ICC in these three gastric regions. In the fundus, the ICC appeared as bipolar cells and in the corpus and antrum they mainly appeared as multipolar cells, with highly ramified processes. The networks formed by ICC differed in the three gastric regions. The ICC number was significantly higher and cell area smaller in the fundus compared to the corpus and antrum. The area occupied by the ICC was significantly higher at the myenteric plexus level compared with circular and longitudinal muscle layers. Everywhere, NADPH-d-positive nerves were more numerous than SP-positive ones. Both kinds of fibers were closely apposed to the ICC in the corpus and antrum. In conclusion, in the human stomach, the ICC have region-specific shape, size and distribution and in the corpus and antrum have close contact with both inhibitory and excitatory nerves. Presumably, as suggested for laboratory mammals, these differences are in relationship with the motor activities peculiar to each gastric area.

Immunohistochemical Evidence of Vanilloid Receptor 1 in Normal Human Urinary Bladder

Experimental and clinical evidences have shown the importance of the vanilloid receptor 1 (TRPV1) in the lower urinary tract. In humans, this receptor has been detected in nerve endings of primary sensory neurons, smooth muscle and connective tissue cells and in the rat also in the urothelium. The aim of this study is to identify, by immunohistochemistry, the cell types expressing TRPV1 in the human urinary bladder. Specimens, obtained from normal urinary bladder by multiple biopsy and from ureter at the time of radical nefrectomy for renal cell carcinoma, were fixed and frozen. Full-thickness sections were processed for light and fluorescence microscopes. To label the TRPV1, three polyclonal antibodies were used: the anti-capsaicin receptor, the anti-VR1 (N-15) and the anti-VR1 (C-15). Urothelium, smooth muscle cells, mast cells and endothelium were labelled and the labelling was intracytoplasmatic. In the urothelial cells, the labelling was slightly granular. In the bladder urothelium, the superficial cells were more intensely stained than the basal and club-shaped cells. VR1-positive nerve fibers were seen running single and/or in groups in the sub-urothelium and as single varicose fibers in the muscle coat, and VR1-positive nerve endings in the urothelium. The present findings provide the evidence of the presence of TRPV1 on normal human urothelium where it could have important implications in the mechanism of action of intravesical vanilloids (capsaicin and resiniferatoxin).

Nitric oxide and the regulation of large artery stiffness: from physiology to pharmacology.

The association between arterial stiffening and aging is well described and can be observed in almost all populations worldwide. A number of other cardiovascular risk factors including diabetes and cigarette smoking are also associated with increased large artery stiffness, often referred to as “premature arterial stiffening.” It is now apparent that the aortic pulse wave velocity (PWV), a measure of arterial distensibility, predicts outcome in a variety of different populations, including hypertensives,1 diabetics,2 individuals with end-stage renal disease (ESRD),3 and even in older adults.4 Indeed, in some populations, aortic PWV is a better predictor of future events than peripheral blood pressure.4 Moreover, arterial stiffening may be more than just a marker of cardiovascular risk; stiffening may also play a more direct role in the development of atherosclerotic plaques. Thus, arterial stiffness would appear to be a novel therapeutic target for the prevention of excess cardiovascular morbidity and mortality. To exploit such an exciting prospect fully, it is necessary to understand the factors regulating arterial stiffness. Traditionally, the stiffness of a vessel was viewed as simply a function of the structural elements of the vessel wall and distending (mean arterial) pressure. However, the large arteries also have a generous coat of smooth muscle, which can alter the distribution of stresses between the elastic and collagenous fibers of the vessel wall and thus alter arterial stiffness. Because smooth muscle tone is influenced by a number of circulating and local vasoactive mediators, arterial stiffness may be actively regulated, and indeed modifiable, at least in the short-term. The muscular arteries have a rich sympathetic innervation, and catecholamines are known to alter smooth muscle tone. Moreover, removal of the vascular endothelium in animals alters large artery stiffness,5,6 suggesting that endothelial-derived substances regulate arterial stiffness in vivo. However, the endothelium …

The Placenta

The human placenta is a discoid organ that has a hemochorial relationship with the mother. That is to say, the trophoblast that covers the villi is in direct contact with the maternal blood. Transfer of substances has to traverse the syncytiotrophoblast, cytotrophoblast, villous basement membrane, fetal capillary bed, and its endothelium. Although the placenta is the most available tissue, it is the least thoroughly investigated organ, and many aspects of its control still are unknown. Especially deficient is our knowledge of the genetic control of its many functions. The placenta also has a different imprinting pattern (paternal imprinting) from that of the embryo. The prevailing sentiment is that once delivery has occurred, it is a superfluous tissue that only needs to be discarded. There are many reasons, however, that knowledge of placental pathology can aid materially in a better understanding of newborns who have anomalies or neonatal problems. Further, a detailed examination of the placenta at birth can provide a better insight into prenatal life and its possible disturbances than is possible from notes in the history of the patient. The shape of the placenta is extremely variable (Fig. 1), probably due to placental location, its interaction with the endometrium, and uterine shape. The placenta implants anywhere in the uterus, but most commonly, it is in an anterior or posterior location. Much less often it is on the fundus. The shape often can be understood best by considering the history of its implantation. The reason for a specific shape can be derived further from the frequently aberrant shapes of twin placentas where competition for space in the uterus, a phenomenon that has been termed “trophotropism,” can be inferred to have existed. This term was used initially in attempts to explain the placental features in the uncommon event of a placenta …

The pathology of diverticulosis coli.

Left-sided diverticulosis coli is a common condition in western communities, with 30% to 50% of adults over the age of 60 being affected. It predominantly involves the sigmoid colon. The diverticula (pseudodiverticula) are pockets of mucosa bounded by muscularis mucosae and invested with a thin layer of submucosa, that are forced out through weak points in the muscularis propria, the tips ending in the colonic subserosa. The weak points in the muscle coat are the sites of entry of the nutrient vessels of the colonic mucosa. Diverticulosis is attributed to increased colonic intraluminal pressure while straining at stool in individuals who eat low-fiber diets. Muscular hypertrophy, shortening of the bowel, and thickened mucosal folds due to mucosal redundancy are characteristic of this condition. Complications of diverticulosis include bleeding, diverticulitis, peridiverticular abscess, perforation, stricture, and fistula formation. However, most individuals with diverticulosis are asymptomatic, without evidence of complications. Mucosal changes in the diverticula in uncomplicated diverticulosis include an increased lymphoid infiltrate, development of lymphoglandular complexes, mucin depletion, mild cryptitis, architectural distortion, Paneth cell metaplasia, and ulceration. The mucosa of the remainder of the sigmoid colon (ie, the nondiverticular mucosa) is usually normal, but in about 1% of cases it has features that are indistinguishable from ulcerative colitis or from Crohn's disease (segmental colitis associated with diverticular disease, SCAD). Such cases pose a difficult diagnostic challenge as patients with SCAD respond to medical or surgical therapy for diverticular disease, whereas those with ulcerative colitis or Crohn's disease will develop other manifestations of their disease in time and require different treatment. In SCAD, the mucosal changes are confined to the area of diverticulosis; therefore, histologic evaluation of the rectum (which is unaffected by diverticulosis) and more proximal bowel can be helpful in the differential diagnosis.

Regrowth of lymphatic vessels following transection of the muscle coat in the rat small intestine.

Regeneration of lymphatic vessels after transection of the muscle coat in the rat jejunum was studied by histochemical methods. The lymphatic regrowth occurred behind the regeneration of blood vessels. Enzyme histochemistry for 5'-nucleotidase (5'-Nase) demonstrated the manner of lymphatic regrowth, which was essentially attributed to vascular sprouting from preexisting lymphatics, and structural changes of the endothelial cells indicating their high migratory potential. The lymphatic regeneration progressively advanced with vascular maturation throughout the experimental period. The expression of 5'-Nase in the regenerating lymphatics was increased in proportion to their growth. VEGF-C, a highly specific lymphangiogenic factor, was highly expressed in a subpopulation of interstitial cells, being close to the regrowing lymphatics with immunoreactivity of its receptor, VEGFR-3, in the regenerative area. The present findings suggest that transection of the intestinal muscle coat affords a useful experimental model for the investigation of lymphatic regeneration in tissue repair and that the interstitium may play a crucial role in lymphangiogenesis.

Autologous-allotopic ileum mucosa transplantation for small bowel elongation. A morphological study

Since a standard therapy for short bowel syndrome does not yet exist, every search for new surgical methods would be worthwhile. In previous studies we could show that autologous-allotopic ileum mucosa transplantation is feasible. After a modification of our technique a vascularized colon muscle coat lined completely with transplanted ileum mucosa could be engendered. In 12 young beagles autologous ileum mucosa was transplanted in a demucosed vascularized transverse colon segment. The colon coat-ileum mucosa complex was anastomosed with the small bowel immediately after transplantation, 4 weeks later the animals were sacrificed and histology specimens were harvested from the colon coat-ileum mucosa complex, normal ileum and normal colon. After fixation in 2.5% glutaraldehyde the samples were frozen (-40 degrees C) and 14 micro m sections were stained with hemalaun and eosin. The lumen diameter, the mucosa, submucosa and colon muscle coat thickness, as well as the mucosal crypt depth were evaluated. The diameter of the colon coat-ileum mucosa-complex was smaller than the diameter of normal ileum and colon with no significant stenosis. There were no marked differences in thickness of mucosa and depth of the mucosal crypts compared to the controls, but the transplanted mucosa showed a slightly higher rate of shortened villi. The submucosal layer was thicker following transplantation and showed good neovascularization. The circular muscle layer of the transplanted colon coat was up to 178% thicker and the thickness of the transplanted longitudinal muscle layer differed between 58% and 143% in comparison to normal colon. Only a few histologic differences between transplanted and normal ileum mucosa could be observed after autologous-allotopic ileum mucosa transplantation. Therefore a nearly normal function of the colon coat-ileum mucosa complex has to be expected. Long term experiments of the histologic changes as well as further functional studies are on-going in order to finally apply autologous-allotopic ileum mucosa transplantation clinically.

Poor effect of glutamin and human-EGF on autologic-allotopic transplanted ileum mucosa.

After establishing a new method of autologic-allotopic ileum mucosa transplantation as a therapy for short-bowel syndrome, the effects of glutamine and human epithelial growth factor (human EGF) on the transplanted ileum mucosa were evaluated. Ileum mucosa was transplanted in 28 young beagle dogs in a demucosed vascularised transverse colon segment. The ileum mucosa was kept in place with silicone stents in all animals. Eight animals of the control group were irrigated with saline solution. In the second group with 10 animals, 100 mg/kg glutamine were administered daily in the lumen. The 10 animals of the third group were treated with 25 microg/kg human EGF per day subcutaneously and irrigated with saline solution. 4 weeks later, histological specimens were harvested from the colon coat-ileum mucosa complex, the normal ileum and normal colon. Lumen diameter, percentage ileum mucosa uptake as well as mucosa and colon muscle coat thickness were evaluated. In all groups, the diameter of the lumen was larger than 10 mm after fixation, due to the silicone stent. The group with glutamine irrigation showed the largest lumen diameter. A complete mucosa lining of the inner surface of the colon muscle coat was achieved in none of the animals. The highest percentage of ileum mucosa uptake was found in the group with glutamine irrigation. In most animals, the transplanted ileum mucosa was markedly thinner than normal ileum mucosa. Only in the group with glutamine irrigation did we find two animals with nearly normal mucosa thickness. The longitudinal muscle of the transplanted colon coat was thicker in all three groups compared to normal colon. There were no differences in thickness of the circular muscle in all animals compared to normal colon. Silicone stents maintain a lumen after autologic-allotopic ileum mucosa transplantation. However, additional irrigation with glutamine, as well as treatment with human EGF subcutaneously could not provide a complete lining of the colon muscle coat with transplanted ileum mucosa. A modification of the operative procedure is necessary to achieve a colon muscle coat that is completely lined with ileum mucosa before the absorptive capacity of the transplanted colon coat-ileum mucosa complex can be evaluated.

未破裂脳動脈りゅうの治療検討 未破裂脳動脈りゅうの易破裂性の検討

Subarachnoid hemorrhage is the most devastating clinical presentation of intracranial aneurysms, which makes it desirable to treat them before they bleed. Because this apoplectic event leaves most survivors with neurological deficits, we aim to define high-risk criteria for rupture based on our series. We retrospectively analyzed 383 cases of treated unruptured aneurysms between January 1999 and December 2002, sixty-four of whom received coil embolization. Treatment indications were previous SAH, presence of bleb, symptomatic aneurysms, size more than 5 mm, posterior circulation, irregular dome wall and high-amplitude bleb-site pulsatility on 4D-CTA. Intraoperative aneurysm wall resection was performed and histological examination done. The outcome was good in all cases after clipping and coiling; there were no cases of mortality or permanent morbidity. Immunostaining and histopathology verified loss of tunica media muscle coat and elastic lamina at the bleb site with smooth muscle actin and Type IV collagen positivity in 15 cases of aneurysm resection. Screening with 4D-CTA or 3D-CTA are noninvasive methods that can be employed in first degree relative of SAH patients and those with risk factors. Symptomatic aneurysms need treatment as a priority; direct surgery and coiling are recommended in unruptured aneurysms. Prediction of rupture point based on 4D-CTA is confirmed histologically.