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Biomedical subjects

D C Dale

Publications and source records attributed to D C Dale.

At least 109 records · Page 6Linked to original sources
PubMed1981

Restructuring an internal medicine residency program to meet regional and national needs for general internists.

The Department of Medicine at the University of Washington has reorganized its residency program to increase the emphasis on general internal medicine and primary care. New teaching services in community hospitals have been established, clinical training sites in Montana, Idaho and Eastern Washington opened, and primary care residency tracks begun. Current data indicate that a major shift in the career plans of our new residents also has occurred. Whereas a decade ago approximately two thirds of our residents were becoming subspecialists, almost two thirds of our 1979 and 1980 program graduates are headed towards careers as general internists. Many will practice in the region's smaller cities and towns. The program serves as a model for the development of a regional program for graduate training in internal medicine.

Academic Medical Centers↗
PubMed1981

Human cyclic neutropenia: clinical review and long-term follow-up of patients.

Human cyclic neutropenia is a distinctive disorder of unknown cause characterized by regularly recurrent episodes of profound neutropenia, which have a periodicity of about 3 weeks. This periodicity remains constant and is remarkably consistent among patients. Although blood elements other than neutrophils are nt depleted, essentially all patients experience a cycling of monocyte counts with monocyte cycles of the same length as but reciprocal to neutrophil cycles. Cycling of platelet and reticulocyte numbers also may occur. Patients experience a clinical syndrome of recurrent illness characterized by malaise, fever, aphthous stomatitis, and cervical adenopathy. Incidental infections may occur with neutropenia but respond readily to antibiotics. The clinical course is benign compared with others conditions in which similar degrees of neutropenia occur. The only life-threatening complication encountered during long-term follow-up of patients was the occurrence of spontaneous peritonitis, segmental bowel necrosis, and septicemia which required surgical intervention. Most patients develop the disease in childhood, but a significant number of patients develop the disease in adulthood as an apparently acquired condition. The disease occurs equally in both sexes and is familial in some. Studies of marrow morphology, myelopoiesis, and neotrophil kinetics have shown that cyclic neutropenia is primarily a disease of abnormally regulated neutrophil production. The judicious use of antibiotics, careful oral and dental care, and patient education are the mainstays of management. Alternate-day corticosteroids have been used successfully to abate the recurrent signs and symptoms, and in one patient the disease was gradually corrected by alternate day prednisolone. Human cyclic neutropenia is of special investigative interest because clarification of this disease may contribute greatly to an understanding of the normal control of myelopoiesis.

Agranulocytosis↗
PubMed1981

Neutrophil-endothelial cell interactions on endothelial monolayers grown on micropore filters.

We have developed a technique for growing endothelial monolayers on micropore filters. These monolayers demonstrate confluence by phase and electron microscopy and provide a functional barrier to passage of radiolabeled albumin. Neutrophils readily penetrate the monolayer in response to chemotaxin, whereas there is little movement in the absence of chemotaxin. This system offers unique advantages over available chemotaxis assays and may have wider applications in the study of endothelial function.

Blood Vessels↗
PubMed1980

The cost effectiveness of therapeutic and prophylactic leukocyte transfusion.

We analyzed the cost effectiveness of leukocyte transfusion in preventing death from infection during intensive chemotherapy for acute leukemia. Effectiveness was estimated with an odds-ratio analysis based on published results of controlled studies of therapeutic and prophylactic leukocyte transfusion. Cost estimates were based on blood-bank charges throughout the country. Calculations of effectiveness suggest that leukocyte transfusion might prevent 50 to 75% of early deaths from infection. Therapeutic transfusion would add approximately 10.9% to the hospital bill of the average bill of the average leukemic patient and cost $17.7 million annually nationwide. Prophylactic transfusion would add 35.2% to the hospital bill and cost $57.8 million annually. Mean cost-effectiveness ratios were $14,982 per life-year for therapeutic transfusion and $35,020 to $50,029 per life-year for prophylactic transfusion. The cost per additional life-year achieved with prophylactic rather than therapeutic leukocyte transfusion was $85,291. These data suggest that leukocyte transfusion is an extremely expensive technologic procedure.

Acute Disease↗
PubMed1980

Lithium therapy of canine cyclic hematopoiesis.

Treatment of cyclic hematopoiesis in the grey collie dog with lithium carbonate eliminated the recurrent neutropenia and normalized the other blood cell counts. These findings suggest that human cyclic hematopoiesis may be successfully treated with lithium. The effects of lithium on the monocytes, platelets, and reticulocytes, as well as the neutrophils, suggest that lithium operates on basic regulatory mechanisms affecting the most primitive hematopoietic precursor cells.

Animals↗
PubMed1980

Distribution of granulocytopoietic committed stem cells in mice with tumor induced neutrophilia.

The skeletal distribution of granulocytopoietic committed stem cells (CFUc) was studied in mice bearing a granulocytosis inducing tumor. The total number of CFUc per mouse was estimated and compared with control mice. In both the axial skeleton (vertebrae, skull, tail) and new areas of marrow development in the peripheral skeleton (radii and ulnae), there was an increased incidence of CFUc, while central appendicular long bones (humeri, femora and tibias) CFUc were unchanged. The study indicated that the total number of CFUc in tumor bearing mice increased, additional data supporting the previous observation and the granulocytosis in this animal model is due to an increase in cell production. The study also indicated that inferences about total CFUc numbers of granulocyte production based on CFUc assay from a single long bone should be interpreted with caution.

Animals↗
PubMed1979

Cyclic hematopoiesis. Effects of endotoxin on colony-forming cells and colony-stimulating activity in grey collie dogs.

Cyclic changes in blood neutrophil counts of grey collie dogs with cyclic hematopoiesis can be eliminated by daily endotoxin injections. Studies were performed to determine the mechanism whereby endotoxin alters this disease. Bone marrow granulocyte-macrophage progenitor cells (colony-forming cells [CFUc]) showed cyclic variation in the untreated grey collie, which was eliminated by chronic endotoxin treatment (Salmonella typhosa lipopolysaccharide W, 5 microgram/kg per day). Similar cyclic variation in blood CFUc was eliminated by this treatment. Tritiated thymidine suicide of the marrow colony-forming cells failed to show cyclic changes to explain the marked swing in CFUc numbers in untreated grey collies. The thymidine suicide rates were not significantly changed by chronic endotoxin treatment. Similarly, serum colony-stimulating activity did not show cyclic variation with the cyclic neutrophil counts in untreated grey collies and was not altered by chronic endotoxin treatment. We suggest that endotoxin eliminates neutrophil cycling in cyclic hematopoiesis by a direct effect on the flux of pluripotent stem cells into the committed stem cell compartment and that this occurs independent of changes in serum colony-stimulating activity.

Animals↗
PubMed1979

Neutropenia, inflammation, and the kinetics of transfused neutrophils in rabbits.

A rabbit model was used to study the effects of neutropenia and inflammation on the intravascular distribution, survival, and tissue accumulation of transfused neutrophils. Donor blood labeled with [(3)H]thymidine was infused into normal or neutropenic (vinblastine treated) animals. Inflammation was created by subcutaneous implantation of polyvinyl sponges, some with added endotoxin. Initial circulating neutrophil pool recovery, survival, and inflammatory site accumulation of labeled neutrophils were measured. Neutropenia was associated with a relative increase in the marginal pool size, manifested by a diminished initial circulating pool (CNP) recovery of transfused cells. The CNP recovery was directly proportional to recipient neutrophil count. Neutropenia had no effect on the intravascular survival of transfused cells and was accompanied by only a modest decrease in the inflammatory site recovery of the transfused neutrophils (10.4+/-5.4 vs. 14.4+/-4.0% in normals). Inflammation in the form of subcutaneous polyvinyl sponges was accompanied by an increase in margination with initial CNP recoveries of 24.3+/-4.7 and 27.6+/-8.8% at zero and 4 h after implantation respectively (normal, 38.2+/-9.9%). Transit through the CNP was hastened by inflammation with a t((1/2)) of 2.02+/-0.72 h (normal, 3.2+/-1.0 h). Addition of endotoxin to the sponges further perturbed cell kinetics. CNP recoveries were considerably lower and half-lifes were initially shorter and subsequently uninterpretable in studies done after endotoxin sponge insertion. Inflammatory site accumulation was markedly diminished to 7.4+/-1.9% of injected neutrophil label in the endotoxin sponge animals, suggesting that many of the transfused cells were functionally unavailable rather than marginated. These studies demonstrate that neutropenia and inflammation with or without endotoxin markedly alter the kinetics of transfused neutrophils and that CNP recovery of transfused cells is not necessarily predictive of their inflammatory site accumulation.

Agranulocytosis↗
PubMed1979

Neutrophil kinetics in chronic neutropenia.

Quantitative studies of bone marrow neutrophil pool sizes and production rates and of blood neutrophil kinetics were performed in 16 patients with chronic neutropenia without splenomegaly. Marrow netrophil cellularity was determined from a ferrokinetic estimate of marrow normoblasts and from neutrophil-erythroid ratios determined from marrow sections. Postmitotic pool turnover was derived from the postmitotic pool size and transit time, the latter determined from 3H-thymidine neutrophil emergence time. Blood neutrophil kinetics were studied with 32P-diisopropylfluoophosphate-labeled autologous neutrophils. Mitotic pool size was basal or below basal in 12 of the 16 patients. The turnover of the post-mitotic neutrophils was subbasal in 6, basal in 7, and above basal in 3 patients. Blood neutrophil turnover was within the normal range in 8 patients and decreased in 8. The degree of ineffective granulocytopoiesis was assessed by comparing the relative size of the mitotic pool, postmitotic pool turnover, and blood turnover. On this basis, 13 of the 16 patients showed appreciable degrees of ineffective granulocytopoiesis. Ineffective neutrophil production occurred both early and late in neutrophil development. These studies indicate that most patients with chronic neutropenia without splenomegaly lack a proliferative marrow response to the neutropenia and suggest that ineffective granulocytopoiesis is a common feature of this disorder.

Adult↗
PubMed1979

Blood kinetics and in vivo chemotaxis of transfused neutrophils: effect of colllection method, donor corticosteroid treatment, and short-term storage.

To evaluate effect of collection technique and short-term storage on in vivo cell function, neutrophils were collected from 53 normal subjects by phlebotomy (PB), intermittent flow centrifugation (IFC), or filtration leukopheresis (FL), stored 0 or 1 day, labeled with 32P-diisopropylfluorophosphate, reinfused into the donor, and blood kinetics and/or skin chamber accumulation of labeled cells measured. The blood kinetics of unstored PB and IFC cells were similar; the kinetics of unstored FL cells were markedly abnormal. The percent of infused neutrophils localizing to the skin chamber was 0.1, 0.06, and 0.006 for unstored PB, IFC, and FL cells, respectively. One-day storage substantially decreased chamber accumulation of infused neutrophils. Donor steroid pretreatment had no effect on chamber results. Thus, in vivo chemotactic ability of IFC neutrophils is slightly impaired, whereas that of FL cells is severely impaired. One-day storage of either cell concentrate causes further cell damage.

Adrenal Cortex Hormones↗
PubMed1978

Correction of human cyclic neutropenia with prednisolone.

A 70-year-old woman with cyclic neutropenia was treated with 16 mg of etiocholanolone and 25 mg of prednisolone intramuscularly every other day. During 14 weeks' treatment amplitude of cyclic fluctuations in neutrophil counts gradually decreased, but pretreatment cycles returned promptly after treatment was stopped. Prednisolone alone every other day (25 mg) reproduced this result, and by 23 weeks, neutrophil counts became stable at about 1500 per cubic millimeter. tcycling of monocytes, platelets and reticulocytes was also eliminated, as were symptoms that had accompanied neutropenic periods. In addition, bone-marrow neutrophil precursors and neutrophil marrow reserves were stabilized. The patient was subsequently maintained satisfactorily with oral prednisolone, 20 mg every other day. These studies demonstrate that the discontinuous myeloid maturation that occurs in cyclic neutropenia can be corrected with prednisolone every other day.

Aged↗
PubMed1978

Managing infections in immunosuppressed patients.

Various infections are associated with depressed host defenses. Systemic antibiotic therapy is not useful prophylactically but should be instituted immediately in patients with known bacterial infections and in febrile patients with neutropenia. Meticulous patient care and attention to collection and evaluation of microbiologic data are the keys to early detection of infection. Nonbacterial opportunistic infections should be considered in patients with prolonged fever or fever and pulmonary infiltrates. Some ancillary measures, such as patient isolation and reconstitution of the immune system, may help in prevention or treatment of infections in immunosuppressed patients.

Anti-Bacterial Agents↗
PubMed1978

Neutrophil transfusion: effect of storage and of collection method of neutrophil blood kinetics.

The kinetics in blood of autologous neutrophils collected by phlebotomy, filtration leukapheresis (FL), or intermittent-flow centrifugation (IFC), labeled with 32P-diisopropylfluorophosphate, and stored at 4 degrees C for up to 2 days were measured in 41 normal subjects. Mean initial recovery for unstored IFC cells was 34.0%, compared to 7.9% for unstored FL cells. Blood half-lives were 4.1 and 2.7 hr for unstored IFC and FL cells, respectively. With neutrophils collected by phlebotomy and stored in whole blood for 1-2 days, posttransfusion recoveries and blood half-times were significantly decreased. Storage of both IFC and FL preparations resulted in only moderate kinetic abnormalities in comparison to the unstored cells. These studies indicate that the ability of unstored IFC cells to circulate is basically normal, whereas that of unstored FL cells is significantly impaired. The data further suggest that these neutrophil concentrates might be stored for 1-2 days prior to transfusion.

Blood Preservation↗