Recombinant human interleukin-11 stimulates multilineage hematopoietic recovery in mice after a myelosuppressive regimen of sublethal irradiation and carboplatin

Interleukin-11 (IL-11) is a novel multifunctional hematopoietic cytokine capable of stimulating cells of the myeloid, lymphoid, erythroid, and megakaryocytic lineages in vitro. We have tested the pleiotropic properties of this cytokine on the hematopoietic recovery of mice after a combined regimen of sublethal irradiation and carboplatin administration. This regimen results in severe myelosuppression, characterized by a prolonged period of thrombocytopenia and severe anemia. Administration of recombinant human IL-11 (rhIL-11; 250 micrograms/kg/d) had multilineage effects on bone marrow and spleen hematopoietic activity, increasing the number of megakaryocyte, erythroid, granulocyte, and macrophage progenitors compared with the vehicle-treated controls. This was reflected in the peripheral circulation by a reduction of both the platelet and hematocrit nadirs and a significantly reduced period of thrombocytopenia and anemia in the rhIL-11-treated mice. The results from this study support the broad spectrum of biologic activities that have been attributed to rhIL-11 in vitro and suggest that this cytokine may be an effective agent in the treatment of myelosuppression associated with cancer chemotherapy and bone marrow transplantation.     

X-linked chronic granulomatous disease: correction of NADPH oxidase defect by retrovirus-mediated expression of gp91-phox

Chronic granulomatous disease (CGD) is an inherited immunodeficiency resulting from the inability of an individual's phagocytes to produce superoxide anions because of defective NADPH oxidase. The disease may be treated by bone marrow transplantation and as such is a candidate for somatic gene therapy. Two thirds of patients have defects in an X- linked gene (X-CGD) encoding gp91-phox, the large subunit of the membrane cytochrome b-245 component of NADPH oxidase. Epstein-Barr virus-transformed B-cell lines from patients with CGD provide a model system for the disease. We have used retrovirus-mediated expression of gp91-phox to reconstitute functionally NADPH oxidase activity in B-cell lines from three unrelated patients with X-CGD. The protein is glycosylated and membrane associated, and the reconstituted oxidase is appropriately activated via protein kinase C. The kinetics of superoxide production by such reconstituted cells is similar to that of normal B-cell lines. These data show the potential of gene therapy for this disease.     

Practice parameters for the identification and testing of patients at risk for dominantly inherited colorectal cancer--supporting documentation

It should be recognized that these guidelines should not be deemed inclusive of all proper methods of care or exclusive of methods of care reasonably directed to obtaining the same results. The ultimate judgment regarding the propriety of any specific procedure must be made by the physician in light of all of the circumstances presented by the individual patient. Prepared By The Standards Task Force The American Society of Colon and Rectal Surgeons     

Attenuated Familial Adenomatous Polyposis

PURPOSE: Familial adenomatous polyposis is a well-described, autosomal dominant, inherited syndrome characterized by diffuse polyposis of the colon and rectum as well as various upper gastrointestinal and extraintestinal manifestations. A subset of patients present with fewer colorectal polyps, later age of onset of polyps and cancer, and a predilection toward involvement of the proximal colon. This variant of familial adenomatous polyposis is known as attenuated familial adenomatous polyposis. The purpose of this review is to summarize current knowledge regarding this poorly understood entity and propose guidelines for diagnosis, surveillance, and surgical management. METHODS: The MEDLINE database was searched from 1985 onward using the keywords, attenuated familial adenomatous polyposis, AFAP, adenomatous polyposis coli gene, and APC gene. Additional articles were identified through the reference sections of retrieved papers. All papers that pertained to attenuated familial adenomatous polyposis or mutations in the APC gene producing an attenuated phenotype were included. RESULTS: Attenuated familial adenomatous polyposis is transmitted in an autosomal dominant fashion. Several distinct mutations within the APC gene have been associated with an attenuated phenotype, but variability of disease expression within kindreds possessing identical mutations makes classification difficult. Polyps are diagnosed at a mean age of 44 years, with cancer diagnosed at a mean of 56 years of age. Frequent involvement of the proximal colon necessitates the use of colonoscopy for surveillance, and infrequent involvement of the rectum supports the role of a total abdominal colectomy and ileorectal anastomosis. CONCLUSIONS: Although currently recognized as a distinct clinical entity, attenuated familial adenomatous polyposis may be part of a spectrum of disease that includes familial adenomatous polyposis and is caused by different mutations within the APC gene. Because of its unique characteristics, yet apparent overlap with familial adenomatous polyposis and hereditary nonpolyposis colorectal cancer, increased awareness of attenuated familial adenomatous polyposis should improve diagnosis, surveillance, and treatment strategies in this unique subset of familial polyposis syndromes.     

Intussusception of the vermiform appendix: preoperative colonoscopic diagnosis of two cases and review of the literature

Intussusception of the appendix is an uncommon condition, and the diagnosis is rarely made preoperatively. Making an accurate diagnosis before laparotomy is important in providing the optimal treatment for the patient. We present the clinical and endoscopic features of two cases of intussusception of the appendix and review the literature. Diagnosis was made preoperatively by colonoscopy in these cases and an elective appendectomy was performed. Appendiceal intussusception should be considered in the differential diagnosis of abdominal pain. Colonoscopy can be a valuable tool in establishing this diagnosis and in selecting the appropriate management Accepted: 18 April 2000     

Outcome of ileorectal anastomosis for Crohn's colitis

One hundred thirty-one patients underwent ileorectal anastomosis (IRA) for Crohn's colitis. Preoperatively, 84 patients (63 percent) were found to have mild or moderate proctitis and 47 (37 percent) had rectal sparing. Sixty-eight (52 percent) had associated small bowel disease, and 20 (15 percent) had perianal disease. Sixty-five IRAs were performed at the time of subtotal colectomy, while 56 were done after previous surgery. Anastomotic leaks occurred in four patients. There were no operative deaths. Thirteen patients (10 percent) with protecting stomas never underwent closure. Among the remaining 118 patients with functioning IRAs, 30 (23 percent) required later proctectomy and 16 (13 percent) required proximal diversion, with the mean period with a functioning IRA in these 46 patients being 4.1 years (range, 6.2 months–12.7 years). An additional 13 patients required preanastomotic resection and neo-IRA, and 11 required proximal small bowel resection. The mean duration of function of all 118 IRAs was 9.2 years. At the time of review, after a mean follow-up of 9.5 years, 72 patients (61 percent) retained a functioning IRA, with 44 being free of disease, while 28 were being treated with steroids or antidiarrheal medication. The mean stool frequency was 4.7 per day. In patients with Crohn's colitis, IRA should be considered as an alternative to proctocolectomy if the rectum is not severely diseased and sphincter function is not compromised.Read at the meeting of The American Society of Colon and Rectal Surgeons, Boston, Massachusetts, May 12 to 17, 1991.     

Exome Sequencing Reveals RAG1 Mutations in a Child with Autoimmunity and Sterile Chronic Multifocal Osteomyelitis Evolving into Disseminated Granulomatous Disease

We describe a boy who developed autoinflammatory (chronic sterile multifocal osteomyelitis) and autoimmune (autoimmune cytopenias; vitiligo) phenotypes who subsequently developed disseminated granulomatous disease. Whole exome sequencing revealed homozygous RAG1 mutations thus expanding the spectrum of combined immunodeficiency with autoimmunity and granuloma that can occur with RAG deficiency.