Use of an intravascular thrombectomy device to treat life-threatening venous thrombosis in a patient with Crohn's disease and G20210A prothrombin gene mutation.
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Biomedical subjects
Publications and source records attributed to M T Harris.
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Mesenchymal stem cells (MSCs) have been used to repair connective tissue defects in several animal models. Compared to "natural healing" controls (no added cells), MSC-collagen gel constructs in rabbit tendon defects significantly improve repair biomechanics. However, ectopic bone forms in 28% of MSC-treated rabbit tendons. To understand the source of bone formation, three studies were performed. In the first study, the hypothesis was tested that MSCs delivered during surgery contribute to bone formation in the in vivo repair site. Adjacent histological sections in the MSC-treated repair tissue were examined for pre-labeled MSCs and for cells showing positive alkaline phosphatase (ALP) activity. Both cells were observed in serial sections in regions of ectopic bone. Contralateral "natural healing" tendons lacked both markers. In the other two studies, the effects of osteogenic supplements and construct geometry (monolayer vs. 3-D) on ALP activity were studied to test three hypotheses: that rabbit MSCs increase ALP activity over time in monolayer culture conditions; that adding osteogenic inducing supplements to the culture medium increases cellular protein in monolayer culture; and that rabbit MSCs increase ALP activity both in monolayer and in 3-D constructs, with and without media supplements. Culture in monolayer under similar conditions to in vivo (as in the first study) did not increase ALP at 2 or 4 weeks. Medium designed to increase osteogenic activity significantly increased cell numbers (cellular protein increased by 260%) but did not affect ALP activity either in monolayer or 3-D constructs (p>0.12). However, MSCs in 3-D constructs exhibited higher ALP activity than cells in monolayer, both in the presence (p<0.045) and absence of supplement (p<0.005). These results suggest that in vitro conditions may critically influence cell differentiation and protein expression. Mechanisms responsible for these effects are currently under investigation.
29Si NMR, small-angle X-ray scattering (SAXS), and dynamic light scattering (DLS) are used to monitor the synthesis of silica nanoparticles from the base-catalyzed hydrolysis of TEOS in methanol and ethanol. The reactions are conducted at a [TEOS] =0.5 M, low concentrations of ammonia ([NH(3)] =0.01-0.1 M), and [H(2)O] =1.1-4.4 M to resolve the initial size of the first nuclei and to follow their structural evolution. It is found that after an induction period where there is a buildup of singly hydrolyzed monomer, the first nuclei are fractal and open in structure. Interestingly, the nuclei are twice as large in ethanol (R(g) approximately 8 nm) as those in methanol (R(g) approximately 4 nm). The data suggest that the difference in primary particle size is possibly caused by a higher supersaturation ratio of the singly hydrolyzed monomer in methanol than in ethanol if it is assumed that the surface energy of the first nuclei is the same in methanol and ethanol. The particle number concentration and the volume fraction of the silica particles are calculated independently from the SAXS, DLS, and 29Si NMR results. Finally, the rate of nucleation is obtained from the particle number concentrations.
BACKGROUND: The use of prosthetic materials in tension-free incisional hernia repairs has diminished reherniation rates markedly; however, infection, intestinal fistulization, and seroma formation have been reported after repairs. Use of the Rives-Stoppa procedure for incisional hernia repair, in which the prosthesis is placed between the rectus abdominis muscle and the posterior sheath, may reduce occurrence of these problems. METHODS AND MATERIALS: Over a 6-year period 57 open abdominal wall incisional hernia repairs were performed using the Rives-Stoppa technique; 15 (26.3%) had previously undergone incisional hernia repair. The prosthetic materials used were polypropylene, expanded polytetrafluoroethylene (ePTFE), and ePTFE with perforations. The prosthesis size ranged from 8x8 cm to 20x28 cm (mean area 199.6 cm(2)). Follow-up consisted of an office visit 12 months postoperatively and at least one subsequent office visit or telephone interview; mean follow-up time was 34.9 months (range 11.7-81.9). RESULTS: There were no hernia recurrences (except in one patient whose prosthesis was removed), gastrointestinal complications, fistulas, or deaths. Seromas occurred postoperatively in seven patients (12.3%). Two patients (3.5%) had wound infections that required removal of the prosthesis. CONCLUSIONS: In this series the Rives-Stoppa technique had excellent long-term results, with minimal morbidity, in patients with large primary or recurrent incisional hernias. The absence of serious complications and hernia recurrences in patients with grafts in place suggests that the Rives-Stoppa procedure is the repair of choice in such patients.
Temozolomide has an evolving role in the treatment of high grade gliomas. Recent studies suggest that temozolomide is well tolerated and efficacious. This study retrospectively analysed the activity and toxicity associated with temozolomide at two Australian centres over a 24 month period. Fifty-six patients with recurrent high grade gliomas were treated with temozolomide. Patients received temozolomide orally at 150-200mg/m(2)daily, days 1-5, every 4 weeks. The median number of treatment cycles was 4 (1-12). Of the 56 patients, 15 (27%) achieved complete or partial response and 18 (32%) achieved minor response or stable disease. There were no episodes of febrile neutropenia and temozolomide was generally well tolerated. In conclusion, temozolomide is an active therapy in patients with recurrent high grade glioma and our results concord with published studies.
An enzymatic method to graft hexyloxyphenol onto the biopolymer chitosan was studied. The method employs tyrosinase to convert the phenol into a reactive o-quinone, which undergoes subsequent nonenzymatic reaction with chitosan. Reactions were conducted under heterogeneous conditions using chitosan films and also under homogeneous conditions using aqueous methanolic mixtures capable of dissolving both hexyloxyphenol and chitosan. Tyrosinase was shown to catalyze the oxidation of hexyloxyphenol in such aqueous methanolic solutions. Chemical evidence for covalent grafting onto chitosan was provided by three independent spectroscopic approaches. Specifically, enzymatic modification resulted in (1) the appearance of broad absorbance in the 350-nm region of the UV/vis spectra for chitosan films; (2) changes in the NH bending and stretching regions of chitosan's IR spectra; and (3) a base-soluble material with (1)H-NMR signals characteristic of both chitosan and the alkyl groups of hexyloxyphenol. Hexyloxyphenol modification resulted in dramatic changes in chitosan's functional properties. On the basis of contact angle measurements, heterogeneous modification of a chitosan film yielded a hydrophobic surface. Homogeneously modified chitosan offered rheological properties characteristic of associating water-soluble polymers.
BACKGROUND: Exposure of male Wistar rats to estradiol-17beta (E(2)) in the presence or absence of dihydrotestosterone propionate (DHT) was previously shown to result in prostate inflammation. The present study examines, for the first time, changes in the expression level of several proinflammatory genes during the course of this experimentally induced prostatitis. METHODS: Adult male Wistar rats were given chronic exposure to E(2) + DHT by capsule implantation or were injected with E(2) for short-term exposure. Semiquantitative RT-PCR was employed to measure changes in proinflammatory transcript levels in the separated lobes of the prostate after various times of exposure to estrogen with or without DHT. RESULTS: We observed an upregulation of IL-1beta, IL-6, MIP-2, and inducible nitric oxide synthase (iNOS) after only 4 days treatment with E(2). After 4 weeks of treatment with E(2) + DHT, a significant increase in transcript levels of IL-4, IL-5, IL-6, MIP-2, eotaxin, and iNOS was detected, while IL-1beta and TNF-alpha transcript levels only increased slightly. No increase in transcript levels for cyclooxygenase-2 (cox-2), IFN-gamma, IL-2, or IL-12 was observed. CONCLUSIONS: Upregulation of proinflammatory transcripts occurred shortly after exposure to E(2) and well before any inflammatory cells were observed in the prostate. The pattern of gene expression resembled a T(H)2-type helper-cell response.
Mesenchymal stem cells (MSCs) were isolated from bone marrow, culture-expanded, and then seeded at 1, 4, and 8 million cells/mL onto collagen gel constructs designed to augment tendon repair in vivo. To investigate the effects of seeding density on the contraction kinetics and cellular morphology, the contraction of the cell/collagen constructs was monitored over time up to 72 h in culture conditions. Constructs seeded at 4 and 8 million cells/mL showed no significant differences in their gross appearance and dimensions throughout the contraction process. By contrast, constructs seeded at 1 million cells/mL initially contracted more slowly and their diameters at 72 h were 62 to 73% larger than those seeded at higher densities. During contraction, MSCs reoriented and elongated significantly with time. Implants prepared at higher seeding densities showed more well aligned and elongated cell nuclei after 72 h of contraction. Changes in nuclear morphology of the MSCs in response to physical constraints provided by the contracted collagen fibrils may trigger differentiation pathways toward the fibroblastic lineage and influence the cell synthetic activity. Controlling the contraction and organization of the cells and matrix will be critical for successfully creating tissue engineered grafts.
PURPOSE: Inflammatory bowel disease surveillance strategies are designed to identify patients at greater than average risk for the development of invasive colonic carcinoma. Colonoscopic detection of mucosal dysplasia is considered the best available surveillance tool. However, the usefulness of dysplasia as a marker for cancer is uncertain. Furthermore, when dysplasia is found some suggest immediate colectomy, whereas others opt for continued surveillance. The aim of this study is to determine whether an association between dysplasia grade and cancer exists in patients with chronic ulcerative colitis, to ascertain the sensitivity, specificity, and positive predictive value of dysplasia as a cancer marker, and to clarify what action to take once dysplasia is discovered. METHODS: The pathology reports of 590 patients who underwent total proctocolectomy or restorative proctocolectomy for chronic ulcerative colitis were reviewed for dysplasia, grade of dysplasia, presence of carcinoma, and tumor stage. One hundred sixty of these patients had undergone colonoscopic examination within the year before surgery. Findings from these studies were also reviewed. RESULTS: Seventy-seven specimens (13.1 percent) contained at least one focus of dysplasia. Invasive cancers were found in 38 specimens (6.4 percent). Cancers were significantly more common among specimens with dysplastic changes (33/77 vs. 5/513; P < 0.001). Specimens with dysplasia of any grade were 36 times more likely to harbor invasive carcinoma. Stage III disease was found in association with indefinite or low-grade dysplasia in 5 of 26 (19.2 percent) of cases. Tumor stage did not correlate with dysplasia grade. Preoperative colonoscopy identified neoplastic changes in 57 (69.5 percent) cases. Dysplasia, cancer or both were missed in 25 cases. Lesions were correctly identified in only 31 (39.7 percent) of cases. Colonoscopically diagnosed dysplasia as a marker for synchronous cancer had a sensitivity of 81 percent and a specificity of 79 percent. The positive predictive value of a finding of preoperative dysplasia of any grade was 50 percent. The positive predictive value of a finding of low-grade dysplasia was 70 percent. CONCLUSIONS: Dysplasia is an unreliable marker for the detection of synchronous carcinoma. However, when dysplasia of any grade is discovered at colonoscopy, the probability of a coexistent carcinoma is relatively high. Colonoscopic evidence of low-grade dysplasia has a higher positive predictive value than either dysplasia associated mass or lesion or high-grade dysplasia. Dysplasia grade does not predict tumor stage. Because advanced cancer can be found in association with dysplastic changes of any grade, confirmed dysplasia of any grade is an indication for colectomy.
Fragments of putative chitin synthase (chs) genes from two filarial species (Brugia malayi and Dirofilaria immitis) were amplified by PCR using degenerate primers. The full genomic and cDNA sequences were obtained for the B. malayi chs gene (Bm-chs-1); the predicted amino acid sequence is highly similar, over a large region, to two CHS sequences of the nematode Caenorhabditis elegans and also to two insect CHS sequences. Bm-chs-1 is abundantly transcribed in B. malayi adult females, independent of their fertilization status, but is also expressed in males and microfilariae. Oocytes and early embryos contain large amounts of Bm-chs-1 transcript by in situ hybridization, but later stage embryos within the maternal uterus show little or no Bm-chs-1 transcript. No specific hybridization could be demonstrated in maternal somatic tissues. Polyclonal antibodies were raised against a peptide expressed from a recombinant cDNA fragment of Bm-chs-1; immunostaining detected CHS protein in oocytes and early to midstage embryos. These studies characterize a gene that is likely to be essential to oogenesis and embryonic development in a parasitic nematode. Because chitin synthesis and eggshell formation begin after fertilization, the presence of CHS protein in early oocytes suggests that the enzyme must be activated as a result of fertilization. These studies also demonstrate that chitin synthesis may not be restricted to eggshell formation in nematodes, as the Bm-chs-1 gene is transcribed in life cycle stages other than adult females.
BACKGROUND: A prosthetic device must be used to repair ventral hernias in patients with insufficient tissue for a tension-free primary closure. Several prosthetic materials have been employed for this purpose, with varying results. We here review a long experience with the use of expanded polytetrafluoroethylene (ePTFE) patches in the open repair of large abdominal wall defects. METHODS: Demographic, operative, follow-up, and histologic data were recorded and analyzed for all patients in a surgical practice who were treated for large abdominal wall defects with open repair using ePTFE patches between November 1983 and March 1996. RESULTS: Ventral hernia repairs using an ePTFE patch were performed in 98 patients. In 48 (49%), the patient had already undergone at least one previous ventral hernia repair. Of the 98 operations, 78 were full-thickness repairs, 11 were Rives-Stoppa procedures, and 9 were onlay operations. Complications included 5 seromas, 3 fistulas related to removal of a previously implanted prosthesis, and 9 infections. In addition, 10 patients developed recurrent hernias not related to explantation of the patch because of infection or fistula. In 3 patients, infections were treated successfully without removal of the patch. There were no complications related to adhesions, erosion of the patch into the viscera, or bowel obstruction. Histologic studies of longterm ePTFE implants showed excellent fibrous tissue ingrowth and minimal foreign body response. CONCLUSIONS: Our long-term clinical experience indicates that prosthetic patches of ePTFE are safe and effective when used in the repair of large abdominal wall defects that cannot be closed primarily. Operative complications were within acceptable limits, as was the reherniation rate.
PURPOSE: This study was undertaken to compare functional results, complications, preoperative durations of disease, and rates of dysplasia and neoplasia between older and younger chronic ulcerative colitis patients undergoing restorative proctocolectomy (RPC) with mucosectomy. METHODS: A total of 392 patients with a preoperative diagnosis of chronic ulcerative colitis underwent elective RPC with mucosection and handsewn ileoanal anastomosis. Pathologic reports were reviewed, with specific reference to findings of dysplasia or cancer. Functional results concerning the number of bowel movements per 24 hour period and the incidence of fecal soilage were obtained by direct or telephone patient interview. FINDINGS: Group I consisted of 326 patients aged 5 to 49 (mean, 30.9) years and 160 women. Group II comprised 66 patients aged 50 to 74 (mean, 56.9) years and 29 women. Duration of disease was significantly longer in the older group (6.2 vs. 15.6 years; P < 0.001). The older group had significantly higher rates of dysplasia (29/326 vs. 19/66; P < 0.0001) and malignancy (14/326 vs. 9/66; P = 0.003). Rates of complication, hospital days following RPC, and total hospital days for all causes were comparable between groups. Perfect day-time continence was observed in 81.6 percent of Group I and 80 percent of Group II patients (213/261 vs. 40/50; P = 0.79). Perfect continence during sleep was observed in 65.1 percent of Group I and 62 percent of Group II patients (170/261 vs. 31/50; P = 0.67). Mean number of bowel movements per 24 hour period for Group I was 6.3 +/- 0.2 and for Group II was 7.4 +/- 0.5. Mean difference, one movement per 24 hours, was not significant (95 percent confidence interval, -0.02 to 2.1; t = 1.95, P = 0.055). CONCLUSIONS: We conclude that patients older than 50 years are suitable candidates for RPC with mucosectomy. Functional results and complication rates are similar to those observed among younger patients. Patients older than 50 years have a significantly higher rate of concurrent dysplasia and malignant degeneration than younger patients, most probably because of a longer duration of disease. RPC with mucosal excision potentially lowers this risk by elimination of all colorectal mucosa.
This study was undertaken to determine preoperative criteria indicating which patients with Crohn's disease are most amenable to minimally invasive intestinal resection. Laparoscopic-assisted intestinal resection was attempted in 25 patients with Crohn's disease. Preoperative assessment of all patients included physical examination and contrast radiography. Laparoscopic intestinal resection was successfully completed in 19 patients. Four patients in whom both palpable mass and fistulous disease were present required conversion to open surgery. One patient found during surgery to have a fistula required conversion, as did one patient who had undergone previous ileocolic resection. In patients treated laparoscopically, oral alimentation, discontinuation of parenteral narcotics, and hospital discharge were possible at an average of 3.4, 4.2, and 6.5 days postsurgery, respectively. Patients operated upon using open techniques stayed in the hospital an average of 8.5 days. Laparoscopic-assisted intestinal resection is beneficial to selected patients with Crohn's disease. The presence of both a fixed mass and fistula on preoperative evaluation is predictive of conversion to open laparotomy and should be considered a relative contraindication. Patients with either a fixed mass or a fistula alone are more amenable to laparoscopic-assisted intestinal resection, while patients with primary uncomplicated Crohn's disease appear to be ideally suited to minimally invasive surgery.
In otherwise healthy individuals, disease caused by the fungus Histoplasma capsulatum manifests itself as a self-limiting pulmonary infection. Dissemination of the organisms may occur in a setting of compromised cellular immunity. Gastrointestinal involvement occurs in many such cases, but rarely it is clinically obvious and the disease seldom comes to the attention of the general surgeon. However, with the increasing incidence of acquired immunodeficiency syndromes, general surgeons are managing more of these patients than in the past. In our report, we describe a patient with acquired immunodeficiency syndrome who presented with gastrointestinal histoplasmosis.
PURPOSE: The inflammatory process associated with Crohn's disease often makes dissection difficult, even in "open" surgery. This study was undertaken to determine if dissection and resection could be performed laparoscopically and whether it would benefit this group of patients. METHODS: Between November 1992 and November 1994, laparoscopic-assisted intestinal resection was attempted in 18 patients with Crohn's disease and was successfully completed in 14. One patient had ileal disease, requiring ileal resection with ileoileal anastomosis. The remainder had disease requiring ileocolic resections. Muscle-splitting incisions averaging 5 cm in length were made to facilitate removal of specimens. RESULTS: Commencement of oral alimentation was possible at an average of 3.6 (range, 1-7) days postoperatively. Discharge occurred at an average of 6.6 (range, 4-9) postoperative days. In comparison, 14 patients operated on by the authors for the same disease in the open manner during the past six months stayed an average of 8.5 (range, 5-14) postoperative days. Postoperative complications were minimal. CONCLUSIONS: On the basis of this initial study, it appears that laparoscopic-assisted intestinal resection can be readily performed in patients with Crohn's disease. In our early experience, we have found that laparoscopic mobilization and resection may be difficult or impossible in patients with large fixed masses, multiple complex fistulas, or recurrent Crohn's disease. Extraction incisions are frequently so large in these patients that they do not derive the same benefits from laparoscopic surgery that are enjoyed by patients without these findings. Most patients having laparoscopic resections eat earlier, may require fewer narcotics, and are able to be discharged from the hospital an average of two days earlier than patients operated on in an open manner. In addition, it appears that laparoscopic-assisted intestinal resection results in a shorter, easier convalescence and an earlier return to full activity.
PURPOSE: Restorative proctocolectomy (RPC) by abdominal colectomy and ileal pouch-anal anastomosis (IPAA) in the setting of chronic ulcerative colitis (CUC) and familial adenomatous polyposis (FAP) has gained widespread popularity among surgeons and patients. Traditionally, temporary loop ileostomy has been established proximal to the ileal pouch in an effort to mitigate the effects of any suture line complications that may occur. This study compares functional results and complications encountered after RPC with mucosectomy with and without temporary ileostomy. METHODS: One hundred forty-three consecutive patients with either CUC or FAP underwent RPC including mucosectomy and ileal "J" reservoir. Proximal loop ileostomy was performed in 69 patients, and ileostomy was omitted in 74. Ileostomy was omitted if the patient was taking no immunosuppressives and less than 20 mg of prednisone daily in the month preceding surgery, the anastomosis was absolutely tension-free, and blood supply to the pouch was excellent. RESULTS: There were no perioperative deaths. There were two instances of pelvic abscess, one in the diverted group and one in the nondiverted group. Occurrence of IPAA suture line dehiscence was not significantly different between the two groups (ileostomy, 4/69 (6 percent), vs. no ileostomy, 6/74 (8 percent); P > 0.05). Comparison of 129 patients with colitis with and without diversion also failed to demonstrate a significant difference with regard to IPAA suture line dehiscence (ileostomy, 4/69 (6 percent) vs. 4/60 (7 percent); P > 0.05). Frequency of bowel movements and continence were the same in both groups and were comparable with results obtained without mucosectomy. Mean hospital stay at time of RPC for the nondiverted group was significantly longer (12 days vs. 10 days; P = 0.0004). Significantly fewer patients without an ileostomy were hospitalized for partial intestinal obstruction (ileostomy, 13/69 (19 percent), vs. no ileostomy, 3/74 (4 percent); P = 0.02), and significantly fewer required enterolysis (ileostomy, 7/69 (10 percent), vs. no ileostomy, 1/74 (1 percent); P = 0.04). On average, patients without an ileostomy spent significantly fewer total days in the hospital (17 vs. 24; P = 0.002). CONCLUSION: Restorative proctocolectomy with mucosectomy and without ileostomy is the procedure of choice for selected patients with FAP and CUC. Septic complications and functional results are similar to those seen in patients managed with a stoma. Anastomotic leakage, when it occurs, can be safely managed in most cases without surgery. RPC without ileostomy results in significantly fewer episodes of intestinal obstruction, fewer instances of re-exploration, and fewer total days in the hospital.
The mesenteric circulation is acutely sensitive to processes that affect the entire body. Such systemic diseases and syndromes are reviewed with particular emphasis on the mechanisms by which they influence the mesenteric vasculature and blood flow.
Campylobacter species are known to cause infectious abortion in domestic animals. In humans, Campylobacter are an important cause of enteritis, an occasional cause of systemic infection and have had a rare association with abortion and perinatal infection. A case history of spontaneous abortion, at 26 weeks' duration, associated with maternal bacteraemia, due to Campylobacter coli is presented. Transmission, pathogenesis, treatment, and the need for further investigation are discussed.