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Biomedical subjects

A Kohn

Publications and source records attributed to A Kohn.

At least 19 recordsLinked to original sources

Infliximab and newly diagnosed neoplasia in Crohn's disease: a multicentre matched pair study.

BACKGROUND AND AIMS: The widespread use of anti-tumour necrosis factor alpha antibody (Infliximab) in Crohn's disease (CD) raises concerns about a possible cancer risk in the long term. In a matched pair study, we assessed whether Infliximab is associated with an increased risk of neoplasia. METHODS: In a multicentre matched pair study, 404 CD patients treated with Infliximab (CD-IFX) were matched with 404 CD patients who had never received Infliximab (CD-C). Cases and controls were matched for sex, age (+/-5 years), site of CD, age at diagnosis (+/-5 years), immunosuppressant use, and follow up. New diagnoses of neoplasia from April 1999 to October 2004 were recorded. RESULTS: Among the 404 CD-IFX, neoplasia was diagnosed in nine patients (2.22%) while among the 404 CD-C, seven patients developed neoplasia (1.73%) (odds ratio 1.33 (95% confidence interval 0.46-3.84); p=0.40). The survival curve adjusted for patient year of follow up showed no differences between CD-IFX and CD-C (p=0.90; log rank test). In the CD-IFX group, there was one cholangiocarcinoma, three breast cancers, one skin cancer, one leukaemia, one laryngeal cancer, and two anal carcinomas. Among the 7/404 (1.73%) CD-C, there were three intestinal adenocarcinomas (two caecum, one rectum), one basalioma, one spinalioma, one non-Hodgkin's lymphoma, and one breast cancer. Age at diagnosis of neoplasia did not differ between groups (CD-IFX v CD-C: median 50 (range 40-70 years) v 45 (27-72); p=0.50). CONCLUSION: In our multicentre matched pair study, the frequency of a new diagnosis of neoplasia in CD patients treated with Infliximab was comparable with CD patients who had never received Infliximab.

Adolescent↗

Infliximab in the treatment of Crohn's disease: predictors of response in an Italian multicentric open study.

BACKGROUND: Almost 20% of patients with active Crohn's disease are refractory to conventional therapy. Infliximab is a treatment of proven efficacy in this group of patients and it is not clear which variables predict a good response. AIMS.: To evaluate the role of infliximab looking at the predictors of response in a large series of patients with Crohn's disease. PATIENTS AND METHODS: Five hundred and seventy-three patients with luminal refractory Crohn's disease (Crohn's Disease Activity Index (CDAI)>220-400) (312 patients) or with fistulising disease (190 patients) or both of them (71 patients) were treated with a dose of 5 mg/kg in 12 Italian referral centres. The primary endpoints of the study were clinical response and clinical remission for luminal refractory and fistulising disease. We evaluated at univariable and multivariable analysis the following variables: number of infusions, sex, age at diagnosis, smoking habit, site of disease, previous surgery, extraintestinal manifestations and concomitant therapies, and type of fistulas. RESULTS: Patients with luminal refractory disease: 322 patients (84.1%) had a clinical response and 228 (59.5%) reached clinical remission. Patients with fistulising disease: 187 patients (72%) had a reduction of 50% of the number of fistulas and in 107 (41%) a total closure of fistulas was observed. For luminal disease, single infusion (OR 0.49, 95% CI 0.28-0.86) and previous surgery (OR 0.53, 95% CI 0.30-0.93) predicted a worse response for fistulising disease. Other fistulas responded worse than perianal fistulas (OR 0.57, 95% CI 0.303-1.097). CONCLUSION: In Crohn's disease infliximab is effective in luminal refractory and in fistulising disease. A single infusion and previous surgery predicted a worse response in luminal disease whereas perianal fistulas predicted a better response than other type of fistulas.

Adult↗

Ultrastructure of the tegument of Metamicrocotyla macracantha (Alexander, 1954) Koratha, 1955 (Monogenea, Microcotylidae).

The ultrastructure of the body tegument of Metamicrocotyla macracantha (Alexander, 1954) Koratha, 1955, parasite of Mugil liza from Brazil, was studied by transmission electron microscopy. The body tegument is composed of an external syncytial layer, musculature, and an inner layer containing tegumental cells. The syncytium consists of a matrix containing three types of body inclusions and mitochondria. The musculature is constituted of several layers of longitudinal and circular muscle fibers. The tegumental cells present a well-developed nucleus, cytoplasm filled with ribosomes, rough endoplasmatic reticulum and mitochondria, and characteristic organelles of tegumental cells.

Animals↗

A new species of Nasicola Yamaguti, 1968 (Monogenea: Capsalidae) from the nasal cavities of Thunnnus obesus and a redescription of N. klawei (Stunkard, 1962) from T. albacares off Brazil.

Two species of Nasicola Yamaguti, 1968 are described from the nasal cavities of tunas ( Thunnus spp.) from off the coast of Brazil: N. brasiliensis n. sp. from T. obesus (Lowe) and the type-species, N. klawei (Stunkard, 1962), from T. albacares (Bonn.). The new species is differentiated from N. klawei on the basis of the large number of testes and from N. hogansi Wheeler & Beverley-Burton, 1986 by its greater body-size, proportionately smaller haptor and smaller number of marginal spines. The host-specificity of Nasicola spp. is commented upon.

Animals↗

Infliximab in refractory pouchitis complicated by fistulae following ileo-anal pouch for ulcerative colitis.

AIM: To determine the efficacy of infliximab in the treatment of chronic refractory pouchitis complicated by fistulae following ileal pouch-anal anastomosis for ulcerative colitis. METHODS: This open study included seven patients (four females, three males) with chronic refractory pouchitis complicated by fistulae. Pouchitis was diagnosed by clinical, endoscopic and histological criteria. The sites of the fistulae were as follows: pouch-bladder in one, vaginal in three, perianal in two, and both vaginal and perianal in one. Extra-intestinal manifestations (erythema nodosum, arthralgia) were present in four patients. Crohn's disease was carefully excluded in all patients after re-evaluation of the history, re-examination of the original proctocolectomy specimen and examination of the proximal small bowel. All patients had been treated with antibiotics and three with steroids. Patients received infliximab, 5 mg/kg, at 0, 2 and 6 weeks. Azathioprine (2.5 mg/kg) was also started for all patients as bridge therapy. Clinical response was classified as complete, partial or no response. Fistulae closure was classified as complete (cessation of fistulae drainage and total closure of all fistulae), partial (a reduction in the number, size, drainage or discomfort associated with fistulae) or no closure. The pouchitis disease activity index and quality of life were also used as outcome measures. RESULTS: Clinically, all patients improved. At the 10-week follow-up, six of the seven patients had a complete clinical response, and five had complete fistulae closure. At the 10-week follow-up, the median pouchitis disease activity index decreased from 12 (baseline) (range, 10-15) to 5 (range, 3-8); the median quality of life decreased from 37 points (range, 33-40) to 14 (range, 9-18). Erythema nodosum and arthralgia showed complete remission soon after the first infusion of infliximab. CONCLUSIONS: These preliminary results indicate that infliximab may be recommended for the treatment of refractory pouchitis complicated by fistulae following ileal pouch-anal anastomosis for ulcerative colitis.

Adult↗

Some Digenea parasites of tunny from the coast of Rio de Janeiro State, Brazil.

Rhipidocotyle pentagonum (Ozaki, 1924) is reported for the first time in South America parasitizing Auxis thazard and in a new host Katsuwonus pelamis. Tergestia laticollis (Rudolphi, 1819) is reported for the first time in South America and in Thunnus albacares, representing a new host record. Copiatestes filiferus (Leuckart, in Sars, 1885) is recorded for the first time in Brazil and in Thunnus albacares, another new host record. Tetrochetus coryphaenae (Yamaguti, 1934) is presented for the first time in Brazil parasitizing Thunnus albacares.

Animals↗

On some trematodes parasites of fishes from Paraná River.

Crassicutis cichlasomae Manter, 1936 is redescribed for the first time in South America and from a new host: Geophagus brasiliensis (Cichlidae). Iheringtrema iheringi Travassos, 1948 is redescribed for the first time since its original description from Pseudopimelodus zungaro (Pimelodidae); and new host records are referred to Genarchella genarchella Travassos et al., 1928, and to Parspina argentinensis (Szidat, 1954). Other reported species are: Microrchis oligovitellum Lunaschi, 1987, Neocladocystis intestinalis (Vaz, 1932), Pseudosellacotyla lutzi (Freitas, 1941), Thometrema overstreeti (Brooks et al., 1979) and Zonocotyle bicaecata Travassos, 1948. Original figures and measurements are presented.

Animals↗

Anti-tumour necrosis factor alpha (infliximab) in the treatment of severe ulcerative colitis: result of an open study on 13 patients.

BACKGROUND: Conventional treatment options for patients with severe steroid-refractory ulcerative colitis include intravenous cyclosporine, which is frequently burdened by toxicity, or colectomy. Preliminary data suggest a benefit from anti-tumour necrosis factor alpha (Infliximab) therapy in patients with steroid refractory ulcerative colitis. AIM: To evaluate the efficacy of Infliximab in the treatment of severe ulcerative colitis refractory to conventional therapy PATIENTS AND METHODS: A series of 13 patients with severe ulcerative colitis, refractory to therapy with methyl-prednisolone, 60 mg daily for seven or more days, were treated with a single intravenous infusion of Infliximab 5 mg/kg. RESULTS AND CONCLUSIONS: Of these 13 patients, 10 (77%) had a clinical response to therapy defined by a clinical activity index 10 on two consecutive days. In 2 patients (15%) total colectomy was necessary on account of clinical worsening whilst one patient refused surgery and was lost to follow-up. All patients who responded showed very rapid clinical improvement, within 2 to 3 days of infusion. Infusion with Infliximab produced no significant adverse events. The mean time of follow-up was 10.1 months (range 5-12; during this time, 9 out of 10 patients (90%) maintained clinical remission and were able to discontinue corticosteroid therapy. Infliximab appears to be an effective agent for inducing long-standing remission in refractory patients with severe ulcerative colitis.

Adolescent↗

Ultrastructure of the tegument of Saccocoelioides godoyi.

The tegument of adult Saccocoelioides godoyi Kohn & Froes, 1986 (Digenea: Haploporidae), specimens of which were collected from the intestine of the freshwater fish, Leporinus friderici (Bloch, 1794) (Anostomidae) from the reservoir of Itaipu Hydroelectric Power Station, Parana State, Brazil, was studied by transmission electron microscopy. The tegument comprises an external anucleate layer, covered by a surface plasma membrane and associated glycocalyx. The surface layer is bound by the basal plasma membrane and contains spines, two types of inclusion bodies and mitochondria. Tegumental cell bodies are located beneath the surface musculature and contain a single nucleus, cytoplasm with rough endoplasmic reticulum, mitochondria, ribosomes, and inclusion bodies similar to those found in the external layer. Cytoplasmic strands connect the cell bodies to the external surface layer, suggesting that the inclusion bodies are produced in these cells and pass up into the syncytium, as is known for other digeneans from experimental evidence.

Animals↗

Ultrastructure of spermatogenesis and sperm development in Saccocoelioides godoyi Kohn & Froes, 1986 (Digenea, Haploporidae).

Ultrastructural observations of spermatogenesis and sperm development of Saccocoelioides godoyi, an intestinal parasite of Leporinus friderici (Bloch, 1794) are described. The irregular-shaped spermatogonia form a peripheral layer, and show a prominent nucleus. Spermatocytes are larger than spermatogonia, and in the early stage present synaptonemal complex. Spermatids show nuclei smaller than the spermatocytes. Spermiogenesis is characterized by outgrowth of the zone of differentiation, presenting basal bodies, separated by an intercentriolar body. At the end of this process, the spermatozoa are released into the residual cytoplasmic mass. The spermatozoa of S. godoyi are elongate, similar to the pattern described for other Digenea, showing nuclei, mitochondria and two axonemes with the 9+1 configuration. The peripheral cortical microtubules on the dorsal and ventral faces are laterally interrupted.

Animals↗

Scanning and transmission electron microscopy of the tegument of Paranaella luquei Kohn, Baptista-Farias & Cohen, 2000 (Microcotylidae, Monogenea), parasite of a Brazilian catfish, Hypostomus regani.

The surface topography and ultrastructure of the tegument of Paranaella luquei Kohn, Baptista-Farias & Cohen, 2000, a microcotylid monogenean parasite from the gills of Hypostomus regani (Ihering, 1905) (Loricariidae) was studied by scanning (SEM) and transmission electron microscopy (TEM). By SEM, it was observed that the tegument presents transversal ridges, forming folds in the ventral and dorsal surfaces and microvillous-like tegumental projections in the anterior and median regions of body. These projections were also observed by TEM. The tegument is made up of a syncytium delimited by apical and basal plasma membranes, containing inclusion bodies and mitochondria, connected to the nucleated region by means of cytoplasmatic processes. The tegumental cells present a well developed nucleus and cytoplasm containing inclusion bodies, similar to those found on the external layer, mitochondria, rough endoplasmatic reticulum and free ribossomes.

Animals↗

Spermatogenesis and spermiogenesis in Didymocystis wedli Ariola, 1902 (Didymozoidae, Digenea).

The ultrastructure of the male reproductive system of Didymocystis wedli was studied for the first time, demonstrating spermiogenesis and spermatogenesis at different cell stages. The spermatozoa morphology was compared with that of other Digenea species. It was observed that the different cells of the spermatogenesis process follow the classic pattern reported for the majority of the parasitic platyhelminthes. During spermiogenesis, rootlet fibers, electrondense bodies and median cytoplasmic process were not observed. The mature spermatozoa of D. wedli were filiform, presenting nucleus, mitochondrion and two 9+1 axonemes, with a biflagellate distal extremity.

Animals↗

Leukocyte integrin expression in patients undergoing cardiopulmonary bypass.

BACKGROUND: The recruitment of leukocytes to vascular endothelium is controlled by adhesion events mediated through the beta2 integrins, whereas the response of extravasated leukocytes within the tissues is controlled through the beta1 integrins. Although cardiopulmonary bypass (CPB) has been shown to be associated with a systemic inflammatory response and elevated levels of beta2 integrins on leukocytes, its effect on the beta1 integrins is not known. This study investigated the effect of the protease inhibitor aprotinin on the expression of the beta1 and beta2 integrins on circulating leukocytes in patients undergoing CPB. METHODS: Patients undergoing primary elective coronary artery bypass grafting were randomized into full-dose aprotinin or placebo groups. Blood samples were obtained at nine time points preoperatively, intraoperatively, and up to 6 days postoperatively. The surface expression of the beta1 integrins VLA-1, -3, -4, -5, and -6 and of the beta2 integrins CD11a/CD18, CD11b/CD18, and CD11c/CD18 was measured by flow cytometry on gated neutrophil and monocyte subpopulations in whole blood. RESULTS: Expression of the beta1 integrins was not significantly altered during the study period and, therefore, aprotinin had no effect on the expression of these molecules. Of the beta2 integrins, CD11b/CD18 expression was significantly increased on neutrophils at 15 minutes after onset of CPB in the placebo group (p < 0.01) but not in the aprotinin group. CONCLUSIONS: This study showed that expression of the beta1 integrins on neutrophils and monocytes did not alter during the first 6 days after CPB. Expression of the beta2 integrin CD11b/CD18 increased significantly on neutrophils during CPB in control patients but not in patients treated with full-dose aprotinin.

Aprotinin↗

Functional neocortical microcircuitry demonstrated with intrinsic signal optical imaging in vitro.

Intrinsic signal optical imaging was used to record the changes in light transmittance evoked by electrical stimulation in slices prepared from sensorimotor cortex of young adult rats. The spatial characteristics of the optical signal evoked by stimulation of layer II/III, IV, V, or VI were clearly different. Layer IV and V stimulation elicited a radially-oriented region of increased light transmittance which was "hourglass" shaped: its tangential extent was greatest in layers II/III and layer V, and least in layer IV. Layer VI stimulation also elicited a radially-oriented signal but the tangential extent of this signal was the same across layers II-VI--that is, it was column-shaped. Upper layer stimulation produced a signal whose tangential extent was much greater in the upper layers than its radial extent to the deeper layers. The spatial form of the stimulus-evoked intrinsic signal was not dependent on the cytoarchitectonic area in which it was elicited. The tangential and radial distribution of the signal evoked by stimulation of different layers appears to reflect the connectivity of cortex, particularly the horizontal connectivity present in layers II/III, V, and VI, and the interlaminar connections that exist between layers II/III and V and from layers VI to IV. The spatial characteristics of the intrinsic signal were independent of the strength of stimulation used. The idea that inhibitory mechanisms restrict the tangential extent of the signal was evaluated in experiments in which the intrinsic signal was recorded before and after the addition of 10 microM bicuculline methiodide. In all slices studied in this way (n = 12), bicuculline methiodide drastically increased the tangential extent of the signal. In 4/12 slices, the tangential spread of the signal was asymmetric with respect to the stimulus site. Asymmetric spread of the signal occurred for both layer V and layer VI stimulation and, in 2/4 of those cases, could be attributed to a cytoarchitectonic border whose presence appeared to restrict the spread of the signal across the border. Although increasing stimulation strength did not change the spatial characteristics of the radially-oriented signal evoked by layer V or VI stimulation, at maximal stimulus intensity the signal evoked from these layers was often accompanied by a band of decreased light transmittance in the most superficial layers (layers I and II). It is concluded that in vitro intrinsic optical signal imaging allows one to image a response attributable to activation of local subsets of cortical connections. In addition, the opposite effects of high-intensity deep layer stimulation on the superficial layers vs layers III-VI of the same column raise the possibility that the most superficial layers may respond differently to repetitive input drive than the rest of the cortical column.

Animals↗

Paranaella luquei gen. et sp. n. (Monogenea: Microcotylidae), a new parasite of Brazilian catfishes.

Paranaella, a new microcotyline monotypic genus, is erected to accommodate Paranaella liquei sp. n., parasite of gill filaments from Hypostomus sp., Hypostomus regani (Ihering) and Rhinelepis aspera Spix et Agassiz (Loricariidae) from the Parani River, Brazil. The new genus is most closely related to Microcotyle Van Beneden et Hesse, 1863, Diplostamenides Unnithan. 1971 and Solostamenides Unnithan, 1971. From Microcotyle it differs mainly by having the genital atrium formed by a muscular ring with a concentric row of numerous elongate and straight spines; from Diplostamenides it can be distinguished by the unarmed and not differentiated cirrus and from Solostamenides it differs by the single vaginal pore and absence of larval hooks.

Animals↗

Molecular studies define the primary structure of alpha1-antichymotrypsin (ACT) protease inhibitor in Alzheimer's disease brains. Comparison of act in hippocampus and liver.

An alpha1-antichymotrypsin-like serpin has been implicated in Alzheimer's disease (AD) based on immunochemical detection of alpha1-antichymotrypsin (ACT) in amyloid plaques from the hippocampus of AD brains. The presence of neuroendocrine isoforms of ACTs and reported variations in human liver ACT cDNA sequences raise the question of the molecular identity of ACT in brain. In this study, direct reverse transcription-polymerase chain reaction and cDNA sequencing indicate that the hippocampus ACT possesses the reactive site loop that is characteristic of serpins, with Leu as the predicted P1 residue interacting with putative chymotrypsin-like target proteases. The deduced primary sequence of the human hippocampus ACT possesses more than 90% homology with reported primary sequences for the human liver ACT. Moreover, identical ACT primary sequences deduced from the cDNAs were demonstrated in the hippocampus of control and AD brains. Northern blots showed that ACT mRNA expression in hippocampus was 900 times lower than that in liver. Also, hippocampus and liver ACT proteins demonstrated differential sensitivities to deglycosylation. Overall, reverse transcription-polymerase chain reaction combined with cDNA and primary sequence analyses have defined the molecular identity of human hippocampus ACT in control and AD brains. The determined reactive site loop domain of hippocampus ACT will allow prediction of potential target proteases inhibited by ACT in AD.

Alzheimer Disease↗