Autologous peripheral blood CD133+ cell implantation for limb salvage in patients with critical limb ischemia.

We report the safety and feasibility of autologous CD133+ cell implantation into the lower extremity muscles of patients with critical limb ischemia, whose only other option was limb amputation. Nine patients participated in the study: seven patients suffering from arteriosclerosis obliterans, one with thromboangiitis obliterans (Buerger's disease) and one with thromboembolic disorder. Autologous PBSC were collected after the administration of G-CSF (10 mcg/kg/day).

Hamartomatous polyposis syndromes.

Hamartomatous polyposis syndromes are a diverse group of inherited conditions grouped together because they exhibit hamartomatous rather than epithelial polyp histology. Each syndrome exhibits characteristic polyp histology, gastrointestinal polyp distribution, gastrointestinal cancer risks, extra-intestinal benign findings and often extra-intestinal cancer risks. Identifying individuals at risk for these syndromes and accurately defining the precise diagnosis are necessary for planning surveillance and management in order to prevent the benign and malignant complications.

Invitation to the dance: lessons from Susan Sontag's death.

The standard model for end-of-life decision-making gives roles to two parties--the physician, who explains the medical options, and the patient, who selects from among those options. The model can be harmful not only for individuals but also for the state, if the patient's right to control her own choices is understood as a positive right of access to whatever is available.

C-peptide levels and insulin independence following autologous nonmyeloablative hematopoietic stem cell transplantation in newly diagnosed type 1 diabetes mellitus.

Context: In 2007, the effects of the autologous nonmyeloablative hematopoietic stem cell transplantation (HSCT) in 15 patients with type 1 diabetes mellitus (DM) were reported. Most patients became insulin free with normal levels of glycated hemoglobin A(1c) (HbA(1c)) during a mean 18.8-month follow-up.

Autologous non-myeloablative haemopoietic stem cell transplantation in relapsing-remitting multiple sclerosis: a phase I/II study.

Background: Autologous non-myeloablative haemopoietic stem cell transplantation is a method to deliver intense immune suppression. We evaluated the safety and clinical outcome of autologous non-myeloablative haemopoietic stem cell transplantation in patients with relapsing-remitting multiple sclerosis (MS) who had not responded to treatment with interferon beta.

Methods: Eligible patients had relapsing-remitting MS, attended Northwestern Memorial Hospital, and despite treatment with interferon beta had had two corticosteroid-treated relapses within the previous 12 months, or one relapse and gadolinium-enhancing lesions seen on MRI and separate from the relapse.

Autologous hematopoietic stem cell transplantation for type 1 diabetes.

In this review, we present (1) the scientific basis for the use of high-dose immunosuppression followed by autologous peripheral blood hematopoietic stem cell transplantation for newly diagnosed type 1 diabetes (T1D); (2) an update of the clinical and laboratory outcome of 20 patients transplanted at the University Hospital of the Ribeirão Preto Medical School, University of São Paulo, Brazil, and followed up to January/2008, including 4 relapses among 19 patients without previous ketoacidosis; (3) a commentary on criticisms to our article that appeared in four articles from the scientific literature; and (4) a discussion of the prospectives for cellular therapy for T1D.

Inheritance of Colorectal Cancer.

Inheritance is involved in up to one third of colon cancer cases. Highly penetrant inherited syndromes account for approximately 3%, while more common, but less penetrant inherited factors play a role in the remainder. Approaches to recognizing each of these categories and syndromes, using genetic testing for diagnosis where indicated, and accomplishing proper cancer screening and surveillance will be outlined in this review.

Common familial colorectal cancer linked to chromosome 7q31: a genome-wide analysis.

Present investigations suggest that approximately 30% of colorectal cancer cases arise on the basis of inherited factors. We hypothesize that the majority of inherited factors are moderately penetrant genes, common in the population. We use an affected sibling pair approach to identify genetic regions that are coinherited by siblings with colorectal cancer.

Hematopoietic stem cell transplantation for systemic lupus erythematosus, the antiphospholipid syndrome and bullous skin diseases.

Systemic lupus erythematosus (SLE) is considered the paradigm of autoimmune diseases (AD), and the murine models are known to be curable by means of allogeneic hematopoietic stem cell transplantation (HSCT). However autologous transplantations were predominantly utilized in the clinic, starting from 1996, and by now well over 150 very severe patients have been transplanted worldwide. Transplant-related mortality (TRM) in 153 cases was 7%, with a wide center effect (from 0-2% to 13%).

Colonic adenoma risk in familial colorectal cancer--a study of six extended kindreds.

Objectives: Most colorectal cancers (CRCs) arise from adenomatous polyps, but the effects of CRC family history on adenoma risk are not well known. This issue is clinically relevant since several medical societies currently recommend earlier and more rigorous colorectal screening for individuals with a strong family history of CRC.

Methods: Colonoscopies were performed in 236 first-, second-, and third-degree relatives of 40 index CRC cases from six large kindreds selected from a large population database.

Reversal of new-onset type 1 diabetes in mice by syngeneic bone marrow transplantation.

Autologous hematopoietic stem cell transplantation (HSCT) has recently been performed as a novel strategy to treat patients with new-onset type 1 diabetes (T1D). However, the mechanism of autologous HSCT-induced remission of diabetes remains unknown. In order to help clarify the mechanism of remission-induction following autologous HSCT in patients with T1D, mice treated with multiple low doses of streptozotocin to induce diabetes were used as both donors (n=20) and recipients (n=20).

Walking to school: frequency and predictors among primary school children in Dunedin, New Zealand.

Aim: To estimate the frequency of walking to school among primary school children and examine associated factors.

Method: In-class survey of Years 1-6 children attending Dunedin primary schools, November 2004, and a take home, written questionnaire for parents and caregivers.

Results: On study day, 34.

The use of stem cells in the treatment of inoperable limb ischemia.

Autologous stem cell-based therapy offers many advantages over other nonsurgical treatments of peripheral arterial disease. Transplant stem cells are a renewable source of multiple cytokines and growth factors. Autologous adult stem cells are not rejected and do not form teratomas.

Postpolypectomy colonoscopy surveillance guidelines: predictive accuracy for advanced adenoma at 4 years.

Background: Lack of confidence in postpolypectomy surveillance guidelines may be a factor in the observed low adherence rates among providers.

Objective: To assess the 2006 postpolypectomy colonoscopy surveillance guidelines, which recommend 3-year follow-up colonoscopy for individuals with high-risk adenomas (defined as > or =3 adenomas or any advanced adenomas) and 5- to 10-year follow-up for patients with 2 or fewer nonadvanced adenomas, who are considered to be at low risk.

Design: Analysis of prospective data from the Polyp Prevention Trial.

Resolution of SLE-related soft-tissue calcification following haematopoietic stem cell transplantation.

Background: Calciphylaxis and calcinosis can both cause severe morbidity and mortality in patients with systemic lupus erythematosus (SLE). Haematopoietic stem cell transplantation (HSCT) has been successfully used to treat patients with refractory SLE. It was hypothesized that in calciphylaxis and calcinosis, ongoing inflammatory activity contributes to the calcium deposition in the media of small arteries, as well as perivascular and periarticular tissues.

Clinical applications of blood-derived and marrow-derived stem cells for nonmalignant diseases.

Context: Stem cell therapy is rapidly developing and has generated excitement and promise as well as confusion and at times contradictory results in the lay and scientific literature. Many types of stem cells show great promise, but clinical application has lagged due to ethical concerns or difficulties in harvesting or safely and efficiently expanding sufficient quantities. In contrast, clinical indications for blood-derived (from peripheral or umbilical cord blood) and bone marrow-derived stem cells, which can be easily and safely harvested, are rapidly increasing.

Hematopoietic stem cell transplantation for autoimmune diseases: what have we learned?

Numerous individuals and institutions throughout the world have contributed to the development of hematopoietic stem cell transplantation (HSCT) for autoimmune diseases. In this review, we will summarize what we have learned at our own institution (Northwestern University), and how it has guided our therapy. An emphasis will be placed on both the scientific basis for the development of autologous hematopoietic stem cell transplantation and a summary of the data in a variety of human diseases.

American founder mutation for attenuated familial adenomatous polyposis.

Background & Aims: Specific mutations in the adenomatous polyposis coli (APC) gene can lead to an attenuated form of familial adenomatous polyposis (AFAP). Although AFAP mutation carriers have a 69% risk of colorectal cancer by age 80, clinical recognition remains a challenge in some cases because they present with few colonic adenomas and are difficult to distinguish clinically from patients with sporadic polyps.

Methods: Family relationships were established using family history reports, the Utah Population Database, and the public records of the Mormon Church.

Gonadal mosaicism and familial adenomatous polyposis.

De novo mutations in the adenomatous polyposis coli (APC) gene are estimated to constitute approximately 25% of familial adenomatous polyposis (FAP) cases. A small percentage of these arise in the mosaic form, affecting only a subset of cells in the affected individual. A family is described here whereby an unaffected mother with no detectible mutation in APC, transmitted the identical APC c.

Hematopoietic mixed chimerism derived from allogeneic embryonic stem cells prevents autoimmune diabetes mellitus in NOD mice.

Embryonic stem cell (ESC)-derived hematopoietic stem cells (HSC), unlike HSC harvested from the blood or marrow, are not contaminated by lymphocytes. We therefore evaluated whether ESC-derived HSC could produce islet cell tolerance, a phenomenon termed graft versus autoimmunity (GVA), without causing the usual allogeneic hematopoietic stem cell transplant complication, graft-versus-host disease (GVHD). Herein, we demonstrate that ESC-derived HSC may be used to prevent autoimmune diabetes mellitus in NOD mice without GVHD or other adverse side effects.

Can we identify the high-risk patients to be screened? A genetic approach.

Our understanding of the mechanisms that lead to colorectal cancer expands each year. Patients with a genetic predisposition to colorectal cancer have significantly increased risks for developing this malignancy over their lifetime. These risks can approach an 80 to nearly 100% likelihood of colorectal malignancy with some of the known cancer predisposition syndromes [Burt and Neklason: Gastroenterology 2005;128:1696-1716 and Rowley: Annu Rev Med 2005;56:539-554].

Autologous non-myeloablative haematopoietic stem cell transplantation for refractory systemic vasculitis.

Objective: For patients with systemic vasculitis (SV) refractory to conventional therapy, new treatment strategies aimed at aggressive induction of remission and relapse prevention are being sought. We herein report our single-centre experience in treating four patients with refractory SV employing non-myeloablative autologous haematopoietic stem cell transplantation (HSCT).

Methods: Four patients with refractory SV (two with neurovascular Behcet disease, one with neurovascular Sjögren syndrome, and one with Wegener granulomatosis) were involved in an Institutional Review Board (IRB) and US Food and Drug Administration (FDA) approved phase I clinical trial of high dose chemotherapy and autologous HSCT.