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J M Heal

Publications and source records attributed to J M Heal.

At least 55 records · Page 3Linked to original sources
PubMed1988

Perioperative blood transfusions and prostate cancer recurrence and survival.

This retrospective clinical study of patients with nonmetastatic prostate cancer demonstrates that patients transfused at the time of initial diagnosis or operation have a higher frequency of recurrence (54 percent) and death due to cancer (19 percent) than patients not receiving blood transfusions (recurrence rate 31 percent, p = 0.005; death rate 10 percent, p = 0.08). This difference is not explained by the transfused patients being older, having a less favorable clinical stage of disease, or less differentiated tumor histology. A multivariate analysis confirmed that the additional risk of dying from prostate cancer was 2.82-fold higher in transfused patients than in those not transfused. As in previous studies, the risk of recurrence may be greater in those receiving whole blood transfusions. Prospective studies of the association between perioperative blood transfusion and cancer recurrence are needed. For the present, prudent clinical practice should include avoidance of whole blood, fresh frozen plasma, and platelet transfusions and greater reliance on autologous blood transfusions.

Humans↗
PubMed1987

Perioperative blood transfusion and solid tumour recurrence.

Evidence regarding the association of blood transfusions with recurrence of solid tumours is largely conflicting. This is perhaps unsurprising given the retrospective nature of the studies performed to date, the complexity of the disease and its treatment, and variations in local transfusion practices. Nonetheless, new data demonstrating that transfusions of whole blood, as opposed to red cell concentrates, are associated with earlier cancer recurrence are most readily explained by a cause and effect relationship. There is a growing literature documenting previously unforeseen immunologic consequences of homologous blood transfusion. These possible clinical consequences include earlier cancer recurrence and increased susceptibility to infection with bacteria and viruses. The questions raised in this review can be answered conclusively only by controlled prospective studies. For the present the prudent clinician will select red blood cells rather than whole blood for transfusion, employ autologous transfusions whenever feasible, and recognize that blood transfusion is a therapy with considerable benefits, but also considerable risks.

Humans↗
PubMed1987

Perioperative blood transfusion and solid tumor recurrence--a review.

Evidence regarding the association of blood transfusions with recurrence of solid tumors is largely conflicting. This is perhaps not surprising given the retrospective nature of the studies, the complexity of the disease and its treatment, and variations in local transfusion practices. Nonetheless, data demonstrating that transfusions of whole blood are associated with earlier cancer recurrence are most readily explained by a cause and effect relationship. There is a growing literature documenting previously unforeseen immunologic consequences of homologous blood transfusion. These possible clinical consequences may include earlier cancer recurrence, and increased susceptibility to infection with bacteria and viruses. The questions raised in this review will likely be answered by further studies. For the present, the prudent clinician will select red blood cells rather than whole blood for transfusion, and recognize that blood transfusion is a therapy with considerable benefits, but also considerable risks.

Acquired Immunodeficiency Syndrome↗
PubMed1987

An evaluation of crossmatching, HLA, and ABO matching for platelet transfusions to refractory patients.

Refractoriness occurs in many patients receiving multiple platelet transfusions. We used a sensitive ELISA assay to assess the utility of crossmatching HLA-A,B matched single donor platelets in 51 consecutive, typical refractory patients. Of the 222 transfusions evaluated at 1 to 4 hours posttransfusion, only 17 of 54 (31%) with positive crossmatches had corrected platelet count increments of greater than or equal to 7,500/microL. In contrast, 95 of 168 (57%) of those with negative crossmatches had such increments (P less than .001). Regardless of the results of the crossmatch, HLA-A,B, and ABO matching had independent influences on transfusion outcome. The median corrected 1- to 4-hour increment for crossmatch negative transfusions was 13,300/microL for A/BU grade matches, 9,700 for BX, and 7,800 for C. Increments were 10,000/microL for ABO-identical transfusions and 5,900 for transfusions of platelets ABO incompatible with the recipient's plasma antibodies. When the donor platelets were ABO compatible, but the donor plasma contained ABO antibodies to the recipient's platelets, the increment was intermediate (8,200/microL). The most important factor in predicting platelet survival was the crossmatch, followed by HLA-A,B and ABO, each having independent predictive value. These data demonstrate that the predictive value of a negative crossmatch may be considerably less than that reported in previous studies with stable, less ill patients. In typical refractory patients, there appear to be mechanisms of platelet destruction that are related to HLA-A,B and ABO but are not detected with current crossmatch methods. We hypothesize that soluble plasma HLA-A,B and ABO antigens contribute to the destruction of donor and sometimes recipient platelets by an immune complex or other "innocent bystander" mechanism. With our crossmatching technique, HLA-A,B and ABO match grades remain relevant to platelet transfusion therapy in some refractory patients.

ABO Blood-Group System↗
PubMed1986

Association between transfusion of whole blood and recurrence of cancer.

Transfusion affects the immune response to renal transplantation and may be associated with recurrence of various human neoplasms. Data from patients with colonic, rectal, cervical, and prostate tumours showed an association between transfusion of any amount of whole blood or larger amounts of red blood cells at the time of surgery and later recurrence of cancer. Recipients of one unit of whole blood had a significantly higher incidence of recurrence (45%) than recipients of a single unit of red cells (12%) (p = 0.03). Recipients of two units of whole blood also had a higher rate of recurrence (52%) than those receiving two units of red cells (23%) (p = 0.03). Recipients of any amount of whole blood had similar recurrence rates (38-52%). Recipients of four or more units of red blood cells had a higher rate of recurrence (55%) than those receiving three or fewer units of red blood cells (20%) (p = 0.005). Mortality due to cancer in patients receiving three or fewer units of red blood cells (2%) was similar to that in patients who did not have transfusions (7%) and significantly lower than that observed in patients receiving three or fewer units of whole blood (20%) (p = 0.003). A proportional hazards risk analysis showed that transfusion of any whole blood or more than three units of red blood cells was significantly associated with earlier recurrence and death due to cancer. These data support an association between transfusion and recurrence of cancer. They also suggest that some factor present in greater amounts in whole blood, such as plasma, may contribute to the increased risk of recurrence in patients who have undergone transfusion. Until the questions raised by retrospective studies of cancer recurrence and transfusion can be answered by prospective interventional trials with washed red blood cells, red blood cells should be transfused to patients with cancer in preference to whole blood when clinically feasible.

Blood Transfusion↗
PubMed1983

The effect of steroids and filtration leukapheresis on circulating hematopoietic progenitor cells.

Filtration leukapheresis (FL) in which donors are pretreated with steroids, induces a rapid neutropenia followed by neutrophilia. To investigate whether these phenomena are associated with changes in circulating progenitor cells (CFU-GM and BFU-E), 5 donors who underwent FL following steroid administration were compared with a control group who received steroids alone. Steroids alone caused an initial reduction in both circulating lymphocytes and committed progenitor cells followed by a rebound above baseline. Among donors undergoing FL, the changes in lymphocyte counts were identical to the steroid controls and the same early suppression of progenitor cells also occurred, but the rebound was blunted. Thus, the neutrophilia that occurs as a result of the FL procedure is not associated with an increase in circulating progenitor cells; and hence, the procedure does not appear to be a useful adjunct for increasing the yield of hematopoietic stem cells from the peripheral blood.

Female↗
PubMed1983

Non-centrifugal plasma collection using cross-flow membrane plasmapheresis.

A prototype of a cross-flow membrane plasmapheresis system was tested for its safety and efficacy in normal donors. 550 ml of plasma can be harvested in less than 1 h. The procedure appears to be safe for the donor. No significant alterations in donor hematological, coagulation, or biochemical values were obtained after the procedure compared to the predonation levels. Changes in the classical and alternate complement pathways were studied serially by analysis of functional hemolytic titers, C3 and C4 levels, and C3 and factor B cleavage products. No firm evidence of complement activation by the polysulfone filtration cell membrane was found.

Adult↗
PubMed1983

Long-term follow-up of donors cytapheresed more than 50 times.

11 volunteers who had donated white blood cells or platelets more than 50 times over a 5- to 9-year period were studied to determine whether any adverse consequences of many cytaphereses could be detected. Among the donors no significant differences were found in 18 hematological and biochemical parameters when compared to a group of age- and sex-matched nondonor controls. Despite extensive cumulative lymphocyte losses sustained by these donors, the ratio of T, B, helper and suppressor cells has been maintained within the normal range. No detrimental effects of multiple cytapheresis on the donors' health has been demonstrated to date.

Adult↗
PubMed1982

Two-dimensional gel electrophoresis method for investigation of human plasma proteins: detection of subtle changes during filtration leukapheresis.

Special problems are associated with analysis of human plasma proteins by standard "high-resolution" two-dimensional gel electrophoresis methods in which isoelectric focusing is followed by electrophoresis in sodium dodecyl sulfate/polyacrylamide gels (SDS-PAGE). Individual plasma proteins are often separated into overlapping groups of multiple spots, and identification of individual spots is further confounded by genetic variation. Analytical recovery of components of high molecular mass is also low or variable. These problems may be reduced or overcome by use of a "low-resolution" method consisting of electrophoresis of native proteins at pH 8.6 in an agarose gel followed by SDS-PAGE without added reducing agent. About 60 proteins can be resolved, most as single spots. About 25 of these proteins have been "mapped," and tentatively identified. We have examined 119 plasma samples taken from six donors who were undergoing filtration leukapheresis and 10 donors who were undergoing centrifugation leukapheresis or plateletpheresis. In all cases, passage of blood through a nylon filter induced a significant increase in a doublet of spots tentatively identified as complement component C3c. This was detected in the effluent from the filter throughout the first 30 min of filtration, and to a lesser extent in the venous blood. These spots were not induced by the centrifugation procedures. One filtration donor also showed increased acute-phase proteins 24 h after the procedure.

Blood Proteins↗
PubMed1978

Biological and biochemical properties of the 2-hydroxyl metabolites of 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea.

The lethal and bone marrow toxicity and antitumor activity of the cis- and trans-2-hydroxylated metabolites of 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea (CCNU) have been correlated with their relative in vitro alkylating and carbamoylating activities. Both the isomers have considerably greater alkylating activity and shorter chemical half-lives than the parent compound and on a molar basis have greater antitumor activity against i.p. L1210 leukemia. However, in terms of molar doses resulting in the death of 10% of normal mice, the cis- and trans-2 isomers were 2- and 3-fold more toxic than was CCNU in normal mice. In comparing the antitumor activity produced by a maximum nonlethal dose for each compound, we found that the trans isomer had activity identical to that of CCNU (413 and 410% increased life span compared to control), and the cis isomer had considerably less (152%). Like chlorozotocin, both isomers possess low carbamoylating activity and increased water solubility, two features that have been considered possible contributors to the bone marrow-sparing character of chlorozotocin. However, in the murine model the human bone marrow colony formation (CFU-C) assay neither hydroxylated metabolite of CCNU was associated with reduced myelotoxicity.

Alkylation↗
PubMedDate not supplied

Harvesting of committed hematopoietic progenitor cells (CFU-GM) by hemapheresis.

In order to investigate collection of committed hematopoietic progenitor cells (CFU-GM) by hemapheresis, four protocols using a discontinuous cell separator (Haemonetics) were evaluated. The combined platelet and granulocytapheresis procedure using hydroxyethyl starch (HES) but no steroids was significantly more efficient (75%) than a standard plateletapheresis (40%, p less than 0.001) or a plateletapheresis modified by either using HES during the collection (49%, p less than 0.05) or pretreating the donors with steroids in an attempt to raise circulating stem cell levels prior to harvesting (46%, p less than 0.001). Donor basal CFU-GM levels were very variable but could be predicted by the circulating lymphocyte levels. In all four protocols, there was a direct correlation between the number of stem cells circulating at the start of the procedure and the final harvest. With this equipment, an appropriate transplant dose of CFU-GM could be provided for a child under 30 kg with less than seven procedures.

Blood Component Removal↗
PubMedDate not supplied

Bacterial proliferation in platelet concentrates.

Growth curves of bacteria in platelet concentrates were studied to determine whether increasing the shelf-life of platelets from 3 to 7 days might have contributed to the increased number of deaths caused by contaminated platelets that have been reported to the FDA since 1980. Platelets inoculated with 10(3) organisms or more showed logarithmic bacterial growth throughout the 7 days of storage or until the platelets became visibly abnormal. With an inoculum of 10(2) organisms or less, proliferation patterns were variable: 20 percent (%) showed uninhibited logarithmic growth and 50 percent (%) remained sterile throughout the 7 days. In another 30 percent (%), bacterial growth was temporarily suppressed for 5 to 6 days before bacteria actively proliferated. These data support the hypothesis that bacterial contamination of platelets not clinically significant at 3 days of storage might become so during the current 7 day shelf life.

Blood Platelets↗
PubMedDate not supplied

Cryopreservation of hematopoietic progenitor cells collected by hemapheresis.

Colony-forming units-granulocyte/monocyte (CFU-GM) harvested from normal donors as a byproduct of plateletapheresis can be cryopreserved successfully with 10 percent dimethyl sulfoxide with the use of standard protocols that have been developed for freezing bone marrow. Short-term storage of CFU-GM in polypropylene vials in the liquid phase of liquid nitrogen yielded a recovery rate of 88 +/- 5 percent (mean +/- SEM). Significant loss of committed progenitor cells was not detected until 1 year after freezing (65 +/- 5%). A comparison of CFU-GM recovery with the polyolefin bag technique (107 +/- 13%) was not statistically different from that obtained with polypropylene vials (78 +/- 7%). Although the freezing bags are more expensive and prone to fracture than the vials, they are easier to handle, store, and thaw in the laboratory, and reinfusion to the patient is more convenient. Cryopreservation of CFU-GM harvested from peripheral blood appears feasible in either of two freezing systems.

Blood Component Removal↗
PubMedDate not supplied

Fatal Salmonella septicemia after platelet transfusion.

A thrombocytopenic, leukopenic patient with multiple myeloma who was given 7 units of platelets died 6 days later from complications of Salmonella heidelberg septicemia. A platelet donor who was asymptomatic at the time of donation had group B Salmonella on stool culture. His clinical history and the results of serologic studies and stool culture were consistent with a mild Salmonella gastroenteritis 5 days before donation. Antibiotic sensitivity patterns and plasmid profiles indicated that the organism (S. heidelberg) isolated from the donor's stool was identical to that isolated from the patient's blood and from the platelet bags. It is believed that low-grade, asymptomatic bacteremia in the donor was the source of infection in the recipient. Food and Drug Administration records contain reports of six septic deaths due to platelet transfusions since 1979, compared with none in the preceding 4 years. Increased use of platelet products and the standard practice of storage at room temperature may contribute to the risk of sepsis after platelet transfusion, particularly in immunocompromised patients.

Antibodies, Bacterial↗