Autologous bone marrow mononuclear cell implantation therapy is an effective limb salvage strategy for patients with severe peripheral arterial disease.

OBJECTIVE: This study was conducted to determine if intramuscular and intra-arterial stem cell injections delay or prevent major limb amputations, improve ankle-brachial index measurements, relieve rest pain, and improve ulcer healing. METHODS: A prospective case series with interventions occurring between December 2007 and September 2012 and a 3-month minimum follow-up was conducted at an urban tertiary care referral hospital. Patients with severe limb-threatening peripheral arterial disease, without other options for revascularization, were eligible for enrollment. Dual intramuscular and intra-arterial injection of bone marrow mononuclear cells harvested from the iliac crest was performed. Major limb amputation at 3 months was the primary outcome measure. Secondary outcome measures included ankle-brachial index measurements, rest pain, and ulceration healing. Kaplan-Meier survivorship was performed to ascertain overall survivorship of the procedure. RESULTS: No complications related to the procedure were reported. Of 49 patients (56 limbs) enrolled, two patients (two limbs) died, but had not undergone major amputation, and five limbs (8.9%) underwent major amputation within the first 3 months. Three-month follow-up evaluations were conducted on the remaining 49 limbs (42 patients). Median postprocedure revised Rutherford and Fontaine classifications were significantly lower compared with median baseline classifications. After 3 months, seven patients (nine limbs) died but had not undergone major amputation, and seven limbs (14.3%) underwent major amputation. At a mean follow-up of 18.2 months, the remaining 33 limbs (29 patients) had not undergone a major amputation. Freedom from major adverse limb events (MALE) was 91.1% (95% confidence interval, 79.9-96.2) at 3 months and 75.6% (95% confidence interval, 59.4-86.1) at 12 months. CONCLUSIONS: This procedure was designed to improve limb perfusion in an effort to salvage limbs in patients for whom amputation was the only viable treatment option. The results of this analysis indicate that it is an effective strategy for limb salvage for patients with severe peripheral arterial disease.

Quantitative assessment of the yield of osteoblastic connective tissue progenitors in bone marrow aspirate from the iliac crest, tibia, and calcaneus.

BACKGROUND: It is well known that bone marrow aspirate from the iliac crest contains osteoblastic connective tissue progenitor cells. Alternative harvest sites in foot and ankle surgery include the distal aspect of the tibia and the calcaneus. To our knowledge, no previous studies have characterized the quality of bone marrow aspirate obtained from these alternative sites and compared the results with those of aspirate from the iliac crest. The goal of this study was to determine which anatomic location yields the highest number of osteoblastic progenitor cells. METHODS: Forty patients were prospectively enrolled in the study, and separate bone marrow aspirate samples were harvested from the ipsilateral anterior iliac crest, distal tibial metaphysis, and calcaneal body. The aspirate was centrifuged to obtain a concentrate of nucleated cells, which were plated and grown in cell culture. Colonies that stained positive for alkaline phosphatase were counted to estimate the number of osteoblastic progenitor cells in the initial sample. The anatomic locations were compared. Clinical parameters (including sex, age, tobacco use, body mass index, and diabetes) were assessed as possible predictors of osteoblastic progenitor cell yield. RESULTS: Osteoblastic progenitor cells were found at each anatomic location. Bone marrow aspirate collected from the iliac crest had a higher mean concentration of osteoblastic progenitor cells compared with the distal aspect of the tibia or the calcaneus (p < 0.0001). There was no significant difference in concentration between the tibia and the calcaneus (p = 0.063). Age, sex, tobacco use, and diabetes were not predictive of osteoblastic progenitor cell yield. CONCLUSIONS: Osteoblastic progenitor cells are available in the iliac crest, proximal aspect of the tibia, and calcaneus. However, the iliac crest provided the highest yield of osteoblastic progenitor cells. CLINICAL RELEVANCE: The study demonstrated that osteogenic progenitor cells are available in bone marrow aspirate harvested from the tibia or calcaneus as well as the iliac crest. All three sites are easily accessed, with a low risk of adverse events. However, larger volumes of aspirate may be needed from the tibia or calcaneus to approach the yield of cells from the iliac crest.

Short- to mid-term results using autologous bone-marrow mononuclear cell implantation therapy as a limb salvage procedure in patients with severe peripheral arterial disease.

Short- to mid-term results of a prospective study evaluating dual intramuscular and intra-arterial autologous bone-marrow mononuclear cell (BM-MNC) implantation for the treatment of patients with severe peripheral arterial occlusive disease (PAD) in whom amputation was considered the only viable treatment option are presented. Ankle-brachial indices (ABIs), rest pain, and ulcer healing were assessed at 3 months. Success was defined as improvement in ABI measurements; absence of rest pain; absence of ulcers; and absence of major limb amputations. Twenty patients (21 limbs) have been enrolled. Three-month follow-up evaluation accounting included 18 patients (19 limbs). Four (22.2%) major and 2 (11.1%) minor amputations were performed within 3 months postoperatively. With 17 (94.4%) of 18 limbs demonstrating at least one criterion for success and major amputation avoided in 14 (77.8%) of 18 limbs at the 3-month evaluation, this specific BM-MNC implantation technique is an effective limb salvage strategy for patients with severe PAD.

Use of autologous bone marrow mononuclear cell implantation therapy as a limb salvage procedure in patients with severe peripheral arterial disease.

BACKGROUND: Few options other than amputation exist for some patients with peripheral arterial occlusive disease (PAD) and severe anatomical limitations. METHODS: This prospective study presents short-term results of dual intramuscular and intra-arterial autologous bone marrow mononuclear cell (BM-MNC) implantation for the treatment of patients with severe PAD in whom amputation was considered the only viable treatment option. Baseline, two-week, and three-month evaluations were conducted. Ankle brachial indices (ABI) were calculated for both the dorsal pedis and the posterior tibial arteries. Rest pain and ulcer healing also were assessed. Success was defined as meeting the following four criteria: improvement in ABI measurements; relief of rest pain; ulcer healing, if applicable; and absence of major limb amputations. Patients not undergoing major limb amputations continued to be monitored for subsequent procedures. RESULTS: Nine patients for whom limb amputation was recommended underwent this procedure. The study population was comprised of five females and four males, with a mean age of 61.7 years. Eight (88.9%) patients had rest pain. Seven (77.8%) patients also had diabetes. Non-healing ulcers were present in eight (88.9%) cases. After the procedure, non-significant improvements of 0.12 and 0.08 in ABI were observed for the dorsalis pedis and posterior tibial ankle arteries, respectively. Three (33.3%) major amputations subsequently were performed, including a below-knee amputation 4.1 weeks after the BM-MNC implantation and two above-knee amputations at 5.4 and 11.0 weeks after the procedure. The six (66.7%) patients who did not have major amputations demonstrated improvement in symptom severity three months after the procedure, as evidenced by alleviation of rest pain and improvements by at least one level in Rutherford and Fontaine classifications, and have not required amputations at a mean follow-up of 7.8 months. Complete wound healing was achieved within three months in all patients who had ulcers prior to BM-MNC implantation and for whom amputation was not required. This specific BM-MNC implantation technique was fully successful in three (33.3%) patients, as major amputation was avoided and the other applicable criteria were met. Five (55.6%) additional patients demonstrated success in at least one of the four criteria. CONCLUSIONS: With eight (88.9%) of nine patients showing some level of improvement and amputation avoided in six (66.7%) patients, these short-term results indicate the use of BM-MNC implantation as a means of limb salvage therapy for patients with severe PAD shows promise in postponing or avoiding amputation in a patient population currently presented with few alternatives to amputation.

A "large and graceful sinuosity". John Herschel's graphical method.

In 1833 John Herschel published a graphical method for determining the orbits of double stars. He argued that his method, which depended on human judgment rather than mathematical analysis, gave better results than computation, given the uncertainty in the data. Herschel found that astronomy and terrestrial physics were especially suitable for graphical treatment, and he expected that graphs would soon become important in all areas of science. He argued with William Whewell and James D. Forbes over the process of induction, over the application of probability, and over the moral content of science. Graphs entered into all these debates; but because they constituted a method, not a metaphysics, they were acceptable to most practicing scientists and became increasingly popular throughout the nineteenth century.