Search PubMed⌕ Search

Biomedical subjects

David Adams

Publications and source records attributed to David Adams.

8 recordsLinked to original sources
PubMed2003

4-hydroperoxycyclophosphamide--purged peripheral blood stem cells for autologous transplantation in patients with acute myeloid leukemia.

We have performed a phase I dose escalation of 4-Hydroperoxycyclophosphamide (4HC) purging of autologous peripheral blood progenitor cells (PBPCs) to improve the outcome of autologous transplantation for patients with myeloid leukemia. Peripheral blood stem cells were mobilized after cytosine arabinoside of 2 g/m(2) every 12 hours x 8 doses with etoposide of 40 mg/kg total dose infused over 4 days, followed by growth factor support. The preparative regimen included Busulfan of 1 mg/kg orally every 6 hours x 16 doses, followed by etoposide of 60 mg/kg x 1 day (the patient with chronic myeloid leukemia received cyclophosphamide of 60 mg/kg/d x 2 days in lieu of etoposide). PBPCs purged with 4HC were infused following this induction. Toxicities included grade 3 or 4 skin rashes, stomatitis/mucositis, and delay in time to hematopoietic recovery. The maximum tolerated dose of 4HC used to purge PBPCs in this trial was 20 microg/mL, which resulted in an average of 18 days for white blood cells and 28 days for platelet recovery. With a median follow-up of 2.25 years in surviving patients, the 3-year disease free survival rate is 44% and the overall survival rate is 89%. These data suggest that autologous PBPCs are more sensitive than marrow purged with 4HC, tolerating less intense purging, although a survival advantage may still be seen and should be assessed in larger studies. Approaches to minimize stomatitis and protect normal stem cells from the toxicity of 4HC may improve the tolerance and efficacy of this approach.

Acute Disease↗
PubMed2003

Inflammatory vasculopathy in multifocal diabetic neuropathy.

Besides the common distal symmetrical sensory-motor polyneuropathy (DSP) that is often associated with autonomic dysfunction, diabetic patients may develop multifocal sensory-motor deficits (MDN) secondary to roots, plexus and nerve trunk involvement. Nerve ischaemia has been suggested as a common mechanism for the different patterns of diabetic neuropathies, yet the important clinical differences that exist between DSP and MDN suggest concurrent factors. In order to learn more on the subject, we prospectively studied 22 consecutive diabetic patients with MDN, for which other causes of neuropathy were excluded by appropriate investigations, including biopsy of a recently affected sensory nerve. Three patients had a relapsing course, and the others an unremitting subacute-progressive course. Painful MDN progressed over 2-12 months. The neurological deficit predominated in distal lower limbs which were involved in all patients, unilaterally in seven, bilaterally in the others, with an asynchronous onset in most cases. In addition, a proximal deficit of the lower limbs was present on one side in seven patients, and on both sides in six. Thoracic radiculoneuropathy was present bilaterally in two patients, and unilaterally in one. The ulnar nerve was involved in one patient, and the radial nerve in two. The CSF protein ranged from 0.40 to 3.55 g/l; mean: 0.87 g/l. Electrophysiological testing showed severe, multifocal, axonal nerve lesions in all cases. Asymmetrical axonal lesions were found in all nerve specimens. The mean density of myelinated axons was reduced to 1340 +/- 1070 per mm(2) of endoneurial area versus 8370 +/- 706 myelinated fibres/mm(2) in controls. The mean density of unmyelinated fibres was reduced to 5095 +/- 6875 per mm(2) (extremes: 0-26 600). On teased fibre preparations, 34 +/- 31% of the fibres were at different stages of axonal degeneration (extremes 0-99%); 7 +/- 6% of the fibres showed segmental demyelination or remyelination. Necrotizing vasculitis of perineurial and endoneurial blood vessels were found in six patients. Endoneurial seepage of red cells was present in 11 specimens, and endoneurial haemorrhage in five. Ferric iron deposits that characterize previous bleeding were found in seven patients, including two who had no red cells in the endoneurium. Perivascular mononuclear cell infiltrates were present in the nerve specimens of 21 out of 22 patients, prominently in four patients. In comparison, nerve biopsy specimens of 30 patients with severe distal symmetrical diabetic polyneuropathy showed mild epineurial mononuclear cell infiltrate in one patient and endoneurial seepage of red cells in another. We conclude that MDN is related to pre-capillary blood vessel involvement in elderly diabetic patients with a secondary inflammatory response.

Action Potentials↗
PubMed2002

Long-lived immature dendritic cells mediated by TRANCE-RANK interaction.

Immature dendritic cells (DCs) reside in interstitial tissues (int-DC) or in the epidermis, where they capture antigen and, thereafter, mature and migrate to draining lymph nodes (LNs), where they present processed antigen to T cells. We have identified int-DCs that express both TRANCE (tumor necrosis factor-related activation-induced cytokine) and RANK (receptor activator of NF-kappaB) and have generated these cells from CD34(+) human progenitor cells using macrophage colony-stimulating factor (M-CSF). These CD34(+)-derived int-DCs, which are related to macrophages, are long-lived, but addition of soluble RANK leads to significant reduction of cell viability and Bcl-2 expression. This suggests that constitutive TRANCE-RANK interaction is responsible for CD34(+)-derived int-DC longevity. Conversely, CD1a(+) DCs express only RANK and are short-lived. However, they can be rescued from cell death either by recombinant soluble TRANCE or by CD34(+)-derived int-DCs. CD34(+)-derived int-DCs mature in response to lipopolysaccharide (LPS) plus CD40 ligand (L) and become capable of CCL21/CCL19-mediated chemotaxis and naive T-cell activation. Upon maturation, they lose TRANCE, making them, like CD1a(+) DCs, dependent on exogenous TRANCE for survival. These findings provide evidence that TRANCE and RANK play important roles in the homeostasis of DCs.

CD40 Ligand↗
PubMed1996

Development of a steady-state oral microbial biofilm community using the constant-depth film fermenter.

The complexity of biofilm communities like dental plaque suggests that laboratory model biofilm growth systems may help to understand their structure and function. This study describes the use of a constant-depth film fermenter (CDFF) to investigate biofilm formation by a nine-membered community of oral bacteria. The community was grown to steady state in a chemostat incubated anaerobically. The chemostat output was fed into the CDFF incubated aerobically. Viable counts for each species from the chemostat and the CDFF at steady state showed major differences; however, all nine organisms were present under both conditions. There was evidence of succession during biofilm formation with obligately anaerobic species only establishing after several days. A steady-state biofilm community was achieved which remained stable over time. Electron microscopy showed evidence of spatial differentiation with what appeared to be Neisseria subflava dominant near the upper surface and Fusobacterium nucleatum largely confined to the middle portion.

Bacteria, Anaerobic↗