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Biomedical subjects

D Bowen

Publications and source records attributed to D Bowen.

At least 55 records · Page 3Linked to original sources

Hemostasis at skin graft donor sites: evaluation of topical agents.

Blood loss from split-thickness skin graft donor sites may be significant. Various topical agents have been used to decrease this blood loss, including thrombin and epinephrine solutions of varying concentrations. We describe a K-Y jelly/epinephrine mixture that serves both as a lubricant for the dermatome and as a hemostatic agent. This mixture, in comparison with other topical agents, produces rapid hemostasis and offers the advantages of easy use, ready availability, and low cost. The blood loss savings based on this hemostatic technique is quantifiable and significant.

Administration, Topical↗

Responsiveness to stem cell factor (SCF) of peripheral blood colony-forming cells from patients with myelodysplastic syndromes (MDS).

We have previously reported that serum stem factor (SCF) levels are significantly lower in patients with myelodysplastic syndrome (MDS) than normal controls. We have now studied the effects of adding SCF to cultures of blood mononuclear cells from patients with MDS and normal subjects. Three of 17 patients with MDS showed marked increases in erythroid colony numbers with SCF + erythropoietin compared to interleukin-3 + erythropoietin. In two cases (1RA and 1ISA) the erythroid colony numbers became normal. The same RA patient also showed a marked increase in myeloid colony numbers, which were undetectable with granulocyte-macrophage colony-stimulating factor alone, but within the normal range when SCF was added. A fourth patient (ISA) showed a 4.7-fold increase in myeloid colonies with SCF, but no erythroid response. The normal subjects showed a trend towards increased numbers of myeloid colonies with SCF; erythroid colonies did not increase. A correlation was found between the MDS patients' haemoglobin levels and erythroid colony numbers with and without SCF, but there was no correlation between erythroid or myeloid colonies in the presence of SCF and their serum SCF level.

Adult↗

Clinical relevance of positive breast periprosthetic cultures without overt infection.

The true incidence of positive breast periprosthetic cultures in the absence of overt infection is not clearly established. We retrospectively reviewed data from 389 implants that were removed for reasons other than clinical infection. Many of these patients presented with a variety of musculoskeletal ailments. Others had symptomatic capsular contracture as the presenting complaint. In a few a known implant rupture was the reason for explantation. We identified a positive culture rate of 23.5 percent from capsule tissue. Most of these organisms were coagulase-negative staphylococci and anaerobic diphtheroids, but fungi and other organisms (generally felt to be more pathogenic than the less virulent coagulase-negative staphylococci) also were cultured. In an attempt to identify the clinical relevance of these positive cultures, we statistically evaluated the culture results for associations with capsular contracture, implant rupture, type of implant, and location of implant. Of these, the only statistically significant correlation was between positive culture result and symptomatic capsular contracture (Baker class IV).

Adult↗

What is ineffective erythropoiesis in myelodysplastic syndromes?

The anaemia of MDS is multifactorial with intramedullary ineffective erythropoiesis resulting from an imbalance between erythroid proliferation, differentiation and apoptosis in favour of initial hypercellularity with high cell death through to a lower cellularity, lower death state with the eventual evolution of the leukaemic clone in many patients. The fundamental molecular abnormality(ies) in MDS, which produce the milieu for the heterogeneous molecular insults described (e.g., oncogene mutations) remains elusive. Many questions such as why MDS red cells are macrocytic and what are the precise cellular and molecular mechanisms of ineffective erythropoiesis remain unanswered but future study of the erythroid lineage should provide molecular clues to the earliest abnormalities in the pathogenesis of MDS.

Cell Death↗

A review of 198 patients (389 implants) who had breast implants removed.

Because of the large number of women now returning to their plastic surgeons with concerns about their breast implants many years after surgery, we are afforded an ideal opportunity to evaluate these patients over the long-term. This study reviewed 198 patients (389 implants) who underwent explantation by two surgeons over a 2-year period, correlating prosthesis type, location, and length of time since implantation with two adverse endpoints, implant rupture and symptomatic capsular contracture. Significant findings included a relatively high rate of implant rupture in patients whose implants had been in place over 20 years, an increased incidence of both symptomatic capsular contracture and implant rupture in single lumen gel implants and a positive correlation between severity of capsular contracture and implant rupture.

Adult↗

Capsular compliance: a measure of a "hard" prosthesis.

Capsular contracture prevents a natural "feel" to an augmented breast and is frequently a source of patient and physician dissatisfaction postoperatively. The degree of hardness of a breast is difficult to quantitate. We have developed a rodent model that measures the pressure rise in a capsule in response to increasing intraluminal volume, generating a pressure-volume curve. The curve's break point determines the volume contained within the capsule and the slope of the steep part of the curve to the right of the break point determines capsule resistance to stretch and deformation. In a group of 14 rats, resistance to distension increased progressively over a 14-week period whereas capsule surface area, break point volume, and resting intraluminal pressure remained relatively constant. This model allows the assessment of changes in capsule contracture over time without having to kill the animal.

Animals↗

Effectiveness and cost-effectiveness of employer-issued back belts in areas of high risk for back injury.

Back belts have gained popularity under the assumption that their use will reduce low back injuries and thereby decrease the costs. This study sought to examine that hypothesis. A retrospective survey instrument was administered to 1316 workers who perform lifting activities at Tinker Air Force Base, Midwest City, Oklahoma, to identify belt use, lifting requirements, injury, and treatment history. Analysis was also performed on costs applicable to providing the belts, treatment of injury, and lost or limited duty work days. Results show an odds ratio of 1.01 (confidence interval 1.01, 1.02) and P value of .0005 of low back injury with the number and weight of lifts performed in an 8-hour period as well as an odds ratio of 5.56 (confidence interval 3.35, 9.26) with prior history of injury. A protective effect, odds ratio of .65, P value of .019 is noted between lifting and attendance at a back training program. Use of a back belt appears to be marginally effective (odds ratio .60, P value .0508) in reducing injuries when controlling for other related factors. Cost analysis over all diagnoses of low back injury shows less intensive treatment and lower cost per injury for workers injured without a belt versus those injured while wearing a belt. It appears that predictors of low back injury are those expected based on risk assumed (amount of time spent performing lifts, history of injury) and that training programs are effective in prevention of problems. Data suggest that back belts appear to be minimally effective in preventing injury.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Effect of all transretinoic acid in newly diagnosed acute promyelocytic leukemia. Results of a multicenter randomized trial. European APL 91 Group.

We designed a multicenter randomized trial comparing chemotherapy with daunorubicin-Ara C (chemotherapy group) and all transretinoic acid (ATRA) combined to the same chemotherapy (ATRA group) in newly diagnosed APL patients aged 65 years or less. The major endpoint of the study was event-free survival (EFS) ("events" being defined as failure to achieve complete remission [CR], occurrence of relapse, or death in CR). Early termination of the trial was decided after the first interim analysis, as EFS was significantly higher in the ATRA group. At the time, 101 patients had been randomized (54 in the ATRA group and 47 in the chemotherapy group). In the ATRA group, 49 (91%) patients achieved CR, 5 (9%) had early death, and 0 had resistant leukemia, compared with 38 (81%), 4 (8%), and 5 (10%) patients, respectively, in the chemotherapy group. The difference in CR rate between the two groups was not significant. The duration of coagulopathy was significantly reduced in the ATRA group, compared with the chemotherapy group. In the ATRA group, six patients relapsed after 7 to 15.5 months. In the chemotherapy group, 12 patients relapsed after 1 to 16 months, and 2 died in CR. Kaplan-Meier EFS was estimated at 79% +/- 7% and 50% +/- 9% at 12 months, respectively, in the ATRA and the chemotherapy group (P = .001). Kaplan-Meier estimate of relapse was 19% +/- 8% and 40% +/- 12% at 12 months (P = .005). In conclusion, ATRA followed by chemotherapy increases EFS in newly diagnosed APL. These results strongly suggest that ATRA should be incorporated in the front line therapy of newly diagnosed APL.

Adolescent↗

Serum stem cell factor concentration in patients with myelodysplastic syndromes.

Stem cell factor (SCF) is characterized by its capacity to synergize dramatically with other haemopoietic growth factors in in vitro erythroid, myeloid, and lymphoid progenitor culture systems. We have measured serum SCF concentrations by enzyme immunoassay in 85 patients with myelodysplasia (MDS). Serum samples were taken in 1988-89 and in 1991-92 and stored at -20 degrees C. Mean serum SCF concentration in the MDS patients was 2.81 ng/ml (range 0.6-8.0). This was significantly lower (P = 0.0001) than the values for 234 normal subjects; mean 3.30 ng/ml (range 1.3-8.0). No significant relationship between SCF concentration and peripheral blood counts, bone marrow parameters, red cell transfusion status, survival or FAB subtype was found, although a trend of decreasing SCF concentration from refractory anaemia through sideroblastic anaemia and chronic myelomonocytic leukaemia to refractory anaemia with excess blasts was seen. The reduced SCF serum concentration in some patients with myelodysplasia suggests a rationale for therapy with recombinant SCF in these patients.

Adult↗

A muscle cell variant defective in glycosaminoglycan biosynthesis forms nerve-induced but not spontaneous clusters of the acetylcholine receptor and the 43 kDa protein.

Myotubes of the C2 mouse muscle cell line form clusters of ACh receptors (AChRs) at apparently random sites along their length when cultured alone, and near sites of nerve-muscle contact when cocultured with neurons. We find in aneural cultures that myotubes of a C2 variant, S27, which is defective in glycosaminoglycan synthesis, express the AChR on their surface, but do not form clusters. S27 cells in aneural cultures also express the 43 kDa protein but do not cluster it. The altered distribution of laminin and collagen IV on the surface of S27 myotubes suggests that the basal lamina is abnormal. Neither the addition of exogenous proteoglycans or conditioned medium from wild-type C2 cells, nor the growth of S27 cells on substrates rich in basal lamina elements caused clusters to appear on S27 myotubes in aneural cultures. When cultured with primary neurons, however, S27 myotubes formed large clusters of the AChR near sites of neurite contact. The clusters were coincident with patches of the 43 kDa protein. Prelabeling experiments indicate that at least some AChRs in the clusters arise through aggregation. Although Torpedo agrin induces AChR clusters on C2 myotubes, it does not do so on S27 cells. Our experiments suggest that the spontaneous formation of clusters of AChRs and the 43 kDa protein in aneural cultures of myotubes depends upon the normal synthesis of muscle proteoglycans, and that nerve-induced clustering does not. Thus, there appear to be multiple mechanisms for the formation of AChR clusters.

Agrin↗

Increased circulating colony-stimulating factor-1 in patients with preleukemia, leukemia, and lymphoid malignancies.

Recently, several malignant cell types have been reported to express colony-stimulating factor-1 (CSF-1) transcripts; however, the clinical significance of CSF-1 in malignancy has not been investigated. Using a CSF-1 radioimmunoassay, we surveyed concentrations of biologically active CSF-1 in the peripheral blood of 316 patients with malignant and premalignant hematologic disorders; 75 had a myelodysplastic syndrome (MDS), 12 acute myelogenous leukemia (AML), 7 chronic myelogenous leukemia, 21 chronic lymphocytic leukemia (CLL), 106 non-Hodgkin's lymphoma (NHL; of low-, intermediate- and high-grade malignancy), 46 Hodgkin's disease (HD), 46 multiple myeloma (MM), and 3 monoclonal gammopathy of undetermined significance. Controls were 64 healthy subjects. The CSF-1 concentration was correlated with the type of disease, status of the disease, treatment status, and hematologic parameters. CSF-1 concentration was significantly elevated in 83.5% of the patients with active disease, and for each active disease group it was significantly greater (P less than .0001) than in the control. Thus, the high circulating CSF-1 concentration was not associated with a particular malignant phenotype or MDS subtype, but did correlate with the disease activity of both NHL and HD, and the tumor burden in MM, AML, and CLL. There was no correlation of the CSF-1 level with total counts of monocytes or neutrophils in patients with MDS or other malignancies. The cellular basis for the elevated circulating CSF-1 was not investigated. However, the results are consistent with the possibility that the premalignant or malignant cells themselves produce CSF-1 or regulate its production by normal cells.

Biomarkers, Tumor↗

The treatment of anaemia in the myelodysplastic syndromes with recombinant human erythropoietin.

Recombinant human erythropoietin was administered subcutaneously to 10 patients with myelodysplasia (MDS) who had haemoglobin concentrations less than 10 g/dl, in an attempt to relieve their anaemia. Doses of 60 units/kg/d rising to 90 units/kg/d were given over a maximum period of 16 weeks. Two out of 10 patients showed a steady rise in haemoglobin concentration during treatment. One patient with refractory anaemia had a sustained rise from 9.9 g/dl to 11.3 g/dl, and one patient with refractory anaemia with excess blasts (RAEB) had a rise from 9.5 g/dl to 11.4 g/dl but then relapsed with the development of an iron deficient state. Serum concentrations of immunoreactive EPO varied considerably between patients, but both responders had relatively low baseline levels. Both responders were also new diagnoses and had received no red cell transfusions. The criteria for response to recombinant human erythropoietin therapy, as well as the indications for therapy remain to be clarified.

Adult↗

Comparison of a modified thiazole orange technique with a fully automated analyser for reticulocyte counting.

Two independent methods for quantitating reticulocyte counts were compared. One used a modified thiazole orange technique and a flow cytometer (Becton Dickinson FACS); the other was a fully automated whole blood analyser (Sysmex R1000). Both methods gave comparable results with a coefficient of variation of less than 5%. Samples measured using the R1000 showed a negligible decrease in the reticulocyte count over five days at room temperature, although there was evidence of continuing intracellular maturation: with thiazole orange there was an apparent increase. A practical reference range of 20-70 x 10(9)/l was established from 89 normal subjects. The close correlation between the two independent estimates indicates the validity of the quantitation of the reticulocyte count and shows that automation allows significant changes within and below the normal range to be detected with a degree of reliability which was not previously possible.

Benzothiazoles↗

Effect of central cholinergic stimulation on regional cerebral blood flow in Alzheimer's disease.

Patients with Alzheimer disease (AD) had reduced regional cerebral blood flow (rCBF) in the posterior parietotemporal region compared with controls, as determined with technetium-99m hexamethyl propyleneamine oxime and single photon emission tomography. Central cholinergic stimulation with physostigmine produced a focal increase in rCBF in the posterior parietotemporal region in the patients with AD but not in controls.

Aged↗

The clearance of a single i.v. bolus of recombinant human erythropoietin from the serum of patients with myelodysplastic syndromes and its effects on erythropoiesis.

The serum erythropoietin (EPO) concentration in patients with myelodysplasia (MDS) varies widely at similar hemoglobin concentrations, although the reasons for this variation are unclear. We have studied the pharmacokinetics of an i.v. bolus of recombinant human EPO in ten subjects with myelodysplasia. Basal serum EPO concentration varied from 210 to 5984 mU/ml. Plasma half-time clearance (t1/2) varied from 3.9 to 20.0 h. A significant positive correlation was found between t1/2 and basal EPO concentration. An increase in immature peripheral blood reticulocytes was found on days 1 and 2 after EPO treatment; this may represent either an effect on hemopoiesis or on reticulocyte release from the bone marrow.

Aged↗