Jennings Cd

A Comparison of the Lipid-Lowering and Intestinal Morphological Effects of Cholestyramine, Chitosan, and Oat Gum in Rats

Abstract Cholestyramine, chitosan, and oat gum are lipid-lowering compounds. Cholestyramine use in humans may contribute to colonic adenocarcinoma; chitosan and oat gum are being studied in the rat to determine their potential for human use. To compare these compounds, we fed three groups of 10 male Sprague-Dawley rats one of the substances at 5% of diet with 1% cholesterol and 0.2% cholic acid; two other groups were fed cellulose with and without 1% cholesterol and 0.2% cholic acid. All groups had similar food intake and weight gains. Cholesterol feeding increased total liver lipids almost 3-fold and liver cholesterol concentration almost 10-fold. Cholestyramine, oat gum, and chitosan all significantly lowered liver cholesterol with cholestyramine feeding yielding levels identical to the noncholesterol-fed basal group. Chitosan and oat gum lowered liver cholesterol moderately. Cholestyramine and chitosan both significantly lowered serum cholesterol compared to the cellulose group. Oat gum was less effective. Hemoglobin and serum iron were similar in all groups except the oat gum group, which had decreased serum iron. Histological examination of small and large bowel with morphometry revealed statistically significant increases in both proximal and distal small bowel and distal large bowel mucosal thickness in the cholestyramine-fed group. No changes were noted in the proximal large bowel. Neither chitosan nor oat gum produced mucosal change other than an increase in the distal small bowel with the oat gum diet. Chitosan may have lipid-lowering effects similar to those of cholestyramine without the deleterious changes in intestinal mucosa.

Surface Replacement Arthroplasty of the Proximal Interphalangeal Joint Using the PIP-SRA Implant: Results, Complications, and Revisions

PURPOSE To evaluate the subjective and objective results of surface replacement arthroplasty (SRA) for arthritis of the proximal interphalangeal (PIP) joint using the PIP-SRA implant. Emphasis is placed on causes of complications, failures, and techniques used for revision. METHODS This is a retrospective review of 43 surface replacement PIP joint arthroplasties performed in 25 patients using the PIP-SRA implant. Subjective results were obtained through a mailed questionnaire. Pre- and postoperative ranges of motion were obtained for PIP joints and DIP joints. X-rays were evaluated for signs of subsidence, periprosthetic radiolucency, loosening, or stress-shielding. Joints requiring revision were separately analyzed. RESULTS The average follow-up time was 37 months (range, 12 to 72 months). The average active PIP joint arc of motion went from 57 degrees before surgery to 58 degrees after surgery, excluding 2 joints that were salvaged with arthrodesis. The average active DIP joint arc of motion went from 36 degrees before surgery to 24 degrees after surgery, excluding arthrodeses. Satisfaction rating revealed 26 very satisfactory (60%), 12 fairly satisfactory (28%), and 5 not satisfactory (12%). Thirty-three patients rated their joint pain better, 3 joints were unchanged, and 7 were worse. Eleven (26%) arthroplasties failed, requiring major revision (arthrodesis or replacement of 1 or both components) for pain. Ten of 11 revisions were due to loosening associated with the lack of cement. Revision procedures produced satisfactory results in 8 of 11 joints. CONCLUSIONS Surface replacement arthroplasty of the PIP joint holds promise for the future. It offers motion and stability for the index finger unattainable with silicone arthroplasty. Our results do not differ notably from those of other series using this implant, except that failures due to loosening in our study were almost exclusively associated with the lack of cement. Therefore, we recommend using cement with the PIP-SRA implant in every case until superior long-term results can be demonstrated using uncemented components. Proximal interphalangeal joint arthroplasty is an exacting procedure no matter what technique or implant is used, and no one technique has yet been proven superior to all others. TYPE OF STUDY/LEVEL OF EVIDENCE Therapeutic IV.

Induction of a syngeneic graft-versus-host disease-like syndrome in DBA/2 mice.

Syngeneic graft-versus-host disease has been shown to occur in syngeneic rat radiation chimeras after treatment with a short course of CsA. However, data concerning this model have been controversial in murine systems. We have successfully induced a GVHD-like syndrome in syngeneic mouse radiation chimeras treated transiently with CsA. Lethally irradiated (950 rads) DBA/2 mice were reconstituted with syngeneic bone marrow and treated daily, i.p. with 15 mg/kg CsA in olive oil for 21 days. Within 1 week after discontinuing CsA, animals developed clinical signs of GVHD including runting, hunched posture, and severe diarrhea. This disease was fatal for greater than 80% of treated animals within 4 weeks after cessation of CsA. Furthermore, the induction of syngeneic GVHD did not appear to be linked to a particular MHC haplotype. Histologically, there was pronounced lymphoid atrophy of the spleen and thymus. Sections of large intestine showed an acute inflammatory process involving the mucosal layer ranging from single-cell destruction to complete mucosal ulceration. This murine model of GVHD should provide new opportunities for studying the development and regulation of autoimmune processes.

Enhancement or Modulation of the Vector Competence of Ochlerotatus vigilax (Diptera: Culicidae) for Ross River Virus by Temperature

Abstract Two different doses of Ross River virus (RR) were fed to Ochlerotatus vigilax (Skuse), the primary coastal vector in Australia; and blood engorged females were held at different temperatures up to 35 d. After ingesting 104.3 CCID50/mosquito, mosquitoes reared at 18 and 25°C (and held at the same temperature) had higher body remnant and head and salivary gland titers than those held at 32°C, although infection rates were comparable. At 18, 25, and 32°C, respectively, virus was first detected in the salivary glands on days 3, 2, and 3. Based on a previously demonstrated 98.7% concordance between salivary gland infection and transmission, the extrinsic incubation periods were estimated as 5, 4, and 3 d, respectively, for these three temperatures. When Oc. vigilax reared at 18, 25, or 32°C were fed a lower dosage of 103.3 CCID50 RR/mosquito, and assayed after 7 d extrinsic incubation at these (or combinations of these) temperatures, infection rates and titers were similar. However, by 14 d, infection rates and titers of those reared and held at 18 and 32°C were significantly higher and lower, respectively. However, this process was reversible when the moderate 25°C was involved, and intermediate infection rates and titers resulted. These data indicate that for the strains of RR and Oc. vigilax used, rearing temperature is unimportant to vector competence in the field, and that ambient temperature variations will modulate or enhance detectable infection rates only after 7 d extrinsic incubation. Because of the short duration of extrinsic incubation, however, this will do little to influence RR epidemiology, because by this time some Oc. vigilax could be seeking their third blood meal, the latter two being infectious.

Acute graft-versus-host-like disease induced by transplantation of human activated natural killer cells into SCID mice.

Whereas T lymphocytes are essential for the initiation of acute graft-versus-host disease (aGVHD), it is not at all clear whether they or other cells or noncellular factors actually mediate the characteristic lesions. This report describes the in vivo effects of human NK cells, T cells, and cytokines on the induction of aGVHD in 4 Gy sublethally irradiated C.B-17 scid/scid (SCID) mice. Human NK and T lymphocytes were obtained separately by antibody-and complement-mediated negative selection from the peripheral blood of normal donors and expanded in medium containing rIL-2 and irradiated autologous feeder cells. The characteristics of the two groups of cells were analyzed before injection into SCID mice. Cytofluorometric phenotyping demonstrated that 70–95% of NK-enriched cells expressed CDS-, CD16+, CD56+, and CD8-dim+; ninety-seven per cent of T cells expressed CDS+, TCR-α/β+, CD4+, or CD8-bright+. Analysis of K562 and Daudi cultured target cell lines demonstrated 40–50% higher cytotoxicity by NK-enriched cells as compared with activated T lymphocytes. TNF-α cytokine production was greatly increased in activated NK cells (250 pg/ml) as compared with T cells (25 pg/ml) and fresh PBMC (12.5 pg/ml). IFN-γ was increased in both NK and T cells. After i.v. injection of 1–5 ± 107 cells into irradiated SCID mice, minor to severe skin lesions, diarrhea, and weight loss occurred in NK-but not the T cell-injected animals. In NK-injected animals, thinning and focal loss of epithelium with pyknotic nuclear change and degeneration and loss of skin appendages were observed. Single cell necrosis, crypt abscess formation, and loss of glandular epithelium developed in the colon of NK but not in T cell-injected animals. These findings are very similar to allogeneic aGVHD in SCID mice injected with C57BL/6 mouse splenocytes. Immunohistological staining with anti-human CD56, CD3, TNF-α, and IFN-γ antibodies demonstrated CD56+ cells in association with TNF-α and IFN-γ secretion in the bowel of NK-injected animals. CD3+ cells were not found in the same tissues. These findings were not observed in T cell-injected and control mice. In summary, aGVHD-like lesions were induced by transplantation of xenogeneic human activated NK cells into SCID mice. We hypothesize that cytokines released from human NK cells play a central role in the pathogenesis of clinical aGVHD.

Role of natural killer cells in the pathogenesis of human acute graft-versus-host disease.

Clinical acute graft-versus-host disease (aGVHD) was correlated with alterations in PBL phenotype and skin immunohistology in 52 patients transplanted with HLA-identical bone marrow. Concurrent with the emergence of aGVHD, there was a profound decrease in absolute number of CD3- T cells and an increase in CD3-CD16+, CD56* (a subset of which coexpress CD8+ “dim”) NK cells in the PBL. CD4+ T and CD20+ B lymphocytes failed to recover within 90 days in the patients with grades II-IV aGVHD. Ex vivo partial T cell depletion, in itself, did not significantly impair T cell recovery as compared to that in non-T-depleted recipients unless aGVHD occurred. Although leukocytic cellular infiltration in the skin was generally sparse, CD16+ NK lymphocytes were significantly increased in grades II—IV aGVHD. By contrast, there was no significant increase in CD3+, CD4+, or CD8+ lymphocytes in these lesions as compared to skin biopsies obtained from BMT patients without aGVHD or from normal skin. Taken together, these findings suggest that NK cells may be important in the pathogenesis of human aGVHD.

Population structure and dispersal of the saltmarsh mosquito Aedes vigilax in Queensland, Australia

Population genetics of the mosquito Aedes vigilax (Skuse) (Diptera: Culicidae), a major vector of arboviruses (e.g. Barmah Forest, Ross River), were investigated to obtain an indirect estimate of mosquito dispersal characteristics in typical habitats of Aedes vigilax in south‐east Queensland: on the off‐shore islands of Moreton Bay and on the mainland where disjunct breeding populations of Ae. vigilax are distributed along intertidal marsh. Six allozyme loci were assessed for genetic differentiation between samples from 11 localities. Significant larval variation between some breeding sites was attributed to site‐specific selection. Non‐significant genetic differentiation was found among collections of adult mosquitoes caught in light traps throughout the study area (exceeding 60 × 27 km), indicating widespread dispersal. As distances of ≤ 9 km over water did not appear to act as effective barriers to Ae. vigilax dispersal, localized control activities applied to Ae. vigilax breeding sites are unlikely to be effective against the vagile adult population. Therefore, the contiguous shires programme of broad acre control is endorsed to prevent the spread of arboviruses carried by Ae. vigilax

Dissemination barriers to Ross River virus in Aedes vigilax and the effects of larval nutrition on their expression

Effects of larval nutrition on vector competence of the mosquito Aedes vigilax (Skuse) (Diptera: Culicidae) from Townsville, north Queensland, for Ross River virus (RR) were examined. Larvae were reared on three different diets to create three significantly different size classes of adult mosquito. These were fed on serial dilutions of RR and then sampled on alternate days so the progression of the virus through the mosquito could be examined. No differences of vector competence could be attributed to larval nutrition. Barriers to infection and the correlation between infection rate, viral titre and transmission of RR by Ae. vigilax were also examined. The mesenteronal barrier was the only infection barrier expressed. No correlation between viral titre and transmission was detected, but a strong correlation was found between salivary gland infection and transmission rate. From this it was possible to estimate that 98.7 ± 1.3% of Ae. vigilax with infected salivary glands transmit RR.

A pilot study of new approaches to teaching anatomy and pathology

PurposeMinimally Invasive Surgery (MIS) has impacted patient care as well as medical training. New medical education opportunities have emerged with MIS. In this pilot study we explore the role of live, interactive MIS to augment and strengthen specific segments of the undergraduate medical curriculum.MethodsLaparoscopic cholecystectomy (LC) was selected to demonstrate upper abdominal anatomy and pathology. Second year medical students (n=100) in the course of their GI pathology classes attended live LC telesurgery— the telesurgery student group (TSG). Because of technical difficulties, a second class of medical students (n = 90) was shown the tape of the MIS procedure one year later instead of the live surgery—the videotape surgery group (VSG). Background clinical information was provided by the program director and the durgeon. During the live and taped LC broadcast living anatomy was demonstrated and a diseased gallbladder was resected. TSG students were able to ask questions of the program director and the surgeon and vice versa using telesurgery technology. After the procedure, the surgeon met with the students for further discussion. VSG students were able to ask questions of the program director during and after the program. Both groups of students completed a pre- and posttest using remote audience responders. Students’ responses from the two groups were compared for selected test and evaluation items.ResultsPre-test (Cronbach’s alpha =.10) and post-test (Cronbach’s alpha =.28) data were obtained from 73 students in the TSG and.22 and.54 respectively from 69 students in the VSG. A significant increase in laparoscopic anatomy knowledge was observed from pretest to posttest for the VSG (31–55%) and from the TSG (30–61%). The majority of VSG students (68%) indicated the method used to teach was outstanding, and 87% indicated that the program was outstanding in keeping their interest. This is contrasted with only 24% of the TSG group responding that the teaching method was outstanding, and 41% indicated that the program was outstanding in keeping their interest.ConclusionsMedical students can productively be exposed to surgical methods and living anatomy using telesurgery. The high regard the TSG students had for this program suggests that it can be used effectively to teach and inspire medical students. The positive results have encouraged us to have a backup instructional method such as a tape of the MIS procedure, it apparently does not have the positive impact of live surgery.

Rejection of an MHC class II negative tumor following induction of murine syngeneic graft-versus-host disease

Cyclosporin A (CsA) has been used clinically to induce graft-versus-host disease following autologous bone marrow transplantation in an attempt to destroy residual leukemia cells and reduce relapse. To analyze the antitumor potential of murine syngeneic graft-versus-host disease (SGVHD), C3H/HeN mice were lethally irradiated, reconstituted with T cell-depleted syngeneic bone marrow (ATBM) and treated with CsA for 21 days. Graft-versus-leukemia activity was assessed by challenging groups of olive oil-treated control ATBM (OO-ATBM) and CsA-treated (CsA-ATBM) mice 1 week after CsA therapy with graded doses of the syngeneic 38C13 B cell lymphoma. Following CsA treatment, up to 70% of CsA-ATBM developed SGVHD and more than 70% of the animals injected with 500 38C13 cells exhibited long-term survival (MST >80 days). In contrast, none of the OO-ATBM control mice developed SGVHD, and more than 75% of these mice died following injection of 500 38C13 tumor cells (MST = 34 days). Long-term survivors were not resistant to tumor challenge suggesting that tumor-specific immunity did not develop. Finally, class II negative 38C13 cells cultured in IL-4 or IL-10 were not inducible for MHC class II molecules, demonstrating that class II-independent antitumor mechanisms exist in SGVHD mice.