The leukointegrin alpha d/beta 2 (alpha d/CD18): specific changes in surface expression in patients on hemodialysis.

Alpha d/CD18 is a newly discovered leukocyte adhesion molecule with sequence homology to CD11a, b and c of the beta 2 integrin family. Little is known about alpha d expression in vivo, particularly how it compares with the other beta 2 integrins. Previous studies have demonstrated that beta 2 integrin expression, particularly CD11b, is upregulated in vivo during hemodialysis (HD) with complement activating membranes. These changes may contribute to the immunologic abnormalities seen in HD patients. Given the well described changes of beta 2 integrins in these patients, we hypothesized that alpha d expression could also be altered by HD. Using flow cytometry with two specific antibodies to alpha d, alpha d expression in healthy adults (n = 16) was compared on macrophages (MO) > polymorphonuclear cells (PMNs) > lymphocytes (LY). Phorbol ester treatment of leukocytes in vitro significantly increased expression on MO and PMN, but not LY. Chronic HD patients at baseline (n = 15) had elevated (P < 0.05) alpha d mean channel fluorescence (MCF) on MOs, PMNs and LYs compared to normals. PMN alpha d MCF increased at 15 min into HD, but then returned to baseline levels at 180 min. Alpha d MCF for LYs decreased at 180 min, while MOs levels were unchanged. Alpha d expression is increased in chronic renal failure and further regulated by hemodialysis, but with unique characteristics compared to the other beta 2 integrins. Alpha d may be important in abnormal cell-cell contacts in renal failure.

Estimated Blood Loss in Group O as Compared to Non-group O Radical Prostatectomy Patients.

BACKGROUND AND OBJECTIVES: Blood group O individuals have been shown to have lower levels of von Willebrand factor (vWF). It is not known if these differences are associated with an increased bleeding risk. We retrospectively assessed estimated blood loss (EBL) in group O and non-group O men undergoing radical prostatectomy. MATERIALS AND METHODS: All patients undergoing radical retropubic prostatectomy from October 1986 through January 1997 were evaluated for ABO type, EBL in the operating room and red blood cell (RBC) transfusion requirements. RESULTS: Complete data were available for 138 group O and 168 non-group O men. Average intraoperative blood loss was 1996 mLs for all men and there was no significant difference in the EBL or transfusion requirements for group O patients. Substantial blood loss (EBL of at least 3 liters) did occur in 20.3% of group O and 13.1% of non-group O patients (P = 0.12). There were no significant differences between the two groups in the number of autologous, allogeneic or total RBCs transfused either intraoperatively or within 48 hours of surgery. CONCLUSION: There was no difference in blood loss or RBC transfusion requirements between group O and non-group O patients undergoing radical prostatectomy. The lower levels of vWF that have been found in group O individuals do not appear to put group O men at significant risk for greater operative blood loss or transfusion requirements during radical prostatectomy. SUMMARY: Group O men undergoing radical prostatectomy do not have greater estimated blood loss or transfusion requirements as compared to non-group O men.

Monitoring for undertransfusion.

BACKGROUND: Most published reviews and audits of blood and blood component transfusion have focused on the issue of overtransfusion and on the inappropriate use of red cell components. There is growing concern that efforts to curb unnecessary transfusions may result in a trend toward undertransfusion of patients. There is little published information that addresses this issue or the magnitude of this practice. STUDY DESIGN AND METHODS: Undertransfusion was evaluated by examining the transfusion records from a 3-month period for 55 patients who met the study criteria of having either a hemoglobin level < 7 g per dL or a platelet count of < 10 x 10(9) per L. If the identified patient did not receive a transfusion within 24 hours of the reported hemoglobin level or platelet count, the medical record was reviewed by a resident physician. RESULTS: A total of 213 individual hemoglobin levels and platelet counts, representing the 55 patients, met our transfusion criteria. All except 8 of the identified patients received red cells and/or platelet transfusions. Reasons for not transfusing red cells included the patient's response to nutritional support and iron supplementation, refusal of blood, and noncompliance. Reasons for not transfusing platelets included falsely low platelet count because of platelet clumping in vitro, contraindication based on clinical diagnosis (e.g., immune thrombocytopenic purpura), and the patient's death before transfusion. CONCLUSION: Red cell and platelet transfusions were appropriately ordered for all patients who met the transfusion criteria. Undertransfusion is not a problem at this institution according to the criteria established. It is recommended that other institutions expand their blood utilization audits to include investigation for evidence of undertransfusion. Further research regarding the issue of undertransfusion is warranted and could be expanded to include other components.

The Effect of Hemodialysis on the Expression of Platelet Glycoproteins Ib, IIb/IIIa and P-Selectin.

UNLABELLED: To determine the effect of hemodialysis on expression of platelet receptors in patients with chronic renal failure. DESIGN: Blood sampling performed in chronic HD patients prior to the dialysis session, then 15 and 180 minutes into HD. Both dialysis machine inlet and outlet samples were taken at 15 minutes. Control subjects had a single blood sample taken. PATIENTS: Thirteen adult males on chronic hemodialysis and 20 age and sex matched healthy controls. MEASUREMENTS: Flow-cytometric analysis of platelet GP-Ib, GP-IIb/IIIa, and P-selectin. Plasma vWF multimers were analyzed by SDS-polyacrylamide gel electrophoresis and immunoblotting. RESULTS: Mean channel fluorescence (MCF) for GP lb was significantly (P < 0.05) decreased in pre-dialysis patients compared to controls and decreased further 3 hours into the dialysis session compared to the start of the dialysis treatment (P < 0.01). MCF for GP IIb/IIIa between predialysis patients and controls was similar, but decreased after a single dialysis session (P < 0.01). MCF for P-selectin on platelets was similar in patients and controls, but fewer platelets from the patients expressed P-selectin compared to controls (P < 0.05). Qualitative multimeric analysis of the vWF in patients, pre- and post-HD was unchanged. CONCLUSIONS: Alterations in platelet surface expression of GPIb, GPIIb/IIIa, and P-selectin may, partially contribute to the changes in platelet function seen in patients on hemodialysis. It is unlikely that alterations in the surface expression of these receptors alone can adequately account for the complex platelet and hemostatic changes associated with uremia and the HD procedure.

Alterations in soluble and leukocyte surface L-selectin (CD 62L) in hemodialysis patients.

Hemodialysis (HD) patients can develop acute reactions during treatment as well as increased long-term susceptibility to infections and malignancy. Leukocyte-membrane interactions may contribute to these processes. The effects of a single HD session on L-selectin, a leukocyte adhesion molecule for endothelium, were examined. Serum levels of soluble L-selectin were measured in 23 patients by enzyme-linked immunosorbent assay before and after a 3-h dialysis session. There was a statistically significant increase in soluble L-selectin from 1.36 +/- 0.12 (SE) to 1.57 +/- 0.18 micrograms/mL (P < 0.001). An increase in shed L-selectin was observed for the "venous" compared with the "arterial" part of the dialyser (P < 0.01) 15 min into HD. Soluble L-selectin levels were found to remain increased at 3 h after treatment. Leukocyte-bound L-selectin and CD11b was examined by the use of flow cytometry. Neutrophil L-selectin decreased to 69 +/- 7% at 15 min (P < 0.01) and then rebounded to 98 +/- 7% at 180 min. Monocyte and lymphocyte L-selectin did not decrease. Because L-selectin is important for leukocyte attachment to endothelium at sites of inflammation, alterations of shed L-selectin and cell-surface L-selectin levels may play a role in the immunologic consequences of HD treatment.

Salt excretory capacity in natives adapted to moderate high altitude living after acute mobilization to sea level.

The sodium excretory capacity of six normal subjects born and raised at moderately high altitude (2600 m) was evaluated at high altitude (HA), and after acute mobilization to sea level (SL). The ability of these individuals to respond to an acute salt load was evaluated by infusing a volume of 100 ml.m-2 body surface area (BSA) of 5% sodium chloride solution over a 30-min time period in both experimental conditions. HA natives were able to excrete a significantly greater salt load at HA than at SL (41.8% vs. 31.6%, respectively, p < 0.05) in 3 h. No changes in plasma atrial natriuretic factor (ANF) concentration were found in either experimental condition. Despite an increase in serum osmolality, no vasopressin (AVP) response was noted either at HA or SL. No correlation between serum AVP levels and urine c-AMP concentrations was found. The enhanced excretory response to a salt load at HA was not explained by the measured hormonal changes. The lack of AVP response to increased serum osmolality, both at HA and SL, in high altitude adapted subjects is presently unexplainable.

Activated and regulatory T lymphocyte populations in chronic hemodialysis patients.

T lymphocyte activation after leukocyte membrane interaction may play a role in immune dysfunction associated with hemodialysis (HD). Studies of T-lymphocyte activation markers in HD have yielded conflicting results, perhaps due to the use of a limited number of markers and different measurement techniques. We studied the lymphocyte activation markers CD25 (interleukin-2 receptor), CD38, CDw49b (VLA-2), CD71 (transferrin receptor), and HLA-DR, as well as the surface antigens CD3, CD4, CD7, and CD8 by two-color flow cytometry in 23 chronic HD patients before and after a single dialysis session; we also studied 30 normal controls. There was no increase in the percentage of activated T cells in the controls and in the patients pre- and post-HD. Conversely, the percentage of CD3+/CD71+ (transferrin receptor) cells was significantly decreased in the patients pre-HD compared with the controls (3.6% +/- 0.5% [mean +/- SEM] v 5.9% +/- 0.5%; P < 0.005). A single dialysis session did not alter the percentage of activated subsets, but led to significant depletion in the number (x 10(9)/L) of cells that were CD3+ (1.10 +/- 0.10 v 0.97 +/- 0.09; P < 0.05), CD7+ (1.0 +/- 0.09 v 0.85 +/- 0.08; P < 0.0001), and CD8+ (0.50 +/- 0.06 v 0.37 +/- 0.04; P < 0.001), but not CD4+ cells (0.73 +/- 0.08 v 0.69 +/- 0.07; P = NS). These data indicate that the chronic HD patients at baseline "predialysis" do not appear to have an increased percentage of circulating activated T lymphocyte subsets and that the CD3+/CD71+ subset is in fact decreased.(ABSTRACT TRUNCATED AT 250 WORDS)

Salt loading test in a population adapted to moderately high altitude living (3,000 m).

The sodium excretory capacity of normal subjects acutely mobilized from sea level to moderately high altitude was compared to native subjects adapted to high altitude living (3,000 meters). This study was conducted in order to provide insights into hormonal adaptations associated with acute mobilization to a hypoxemic environment and to try to determine how these variables could influence the renal handling of a salt load. A standard amount of 5% NaCl solution at a volume of 100 ml/m2 BSA was infused over a 30-min period to all subjects. Urine collections were obtained periodically over the next 3 h. Subjects adapted to moderately high altitude living were able to excrete a salt load faster than unadapted subjects (57.1 vs. 32.9 mmol.m-2.h-1, respectively). No change in plasma atrial natriuretic factor (ANF) concentration in either group of subjects was observed during the salt administration period. Adapted individuals had significantly higher baseline levels of antidiuretic hormone (ADH). The high altitude natives enhanced excretory response to a salt load was not explained by any observed hormonal changes and their lack of increased ADH release to serum osmolar changes was unexplained.

Effects of hypoxemia at sea level and high altitude on sodium excretion and hormonal levels.

Acute hypoxemia at sea level is associated with decreased aldosterone secretion. This inhibition is thought to be mediated through secretion of atrial natriuretic factor (ANF). The interaction of these two hormones should result in enhanced renal salt excretion during hypoxemic conditions. This hypothesis was tested by administration of a standardized salt load to seven normal subjects during normoxemia at sea level (SL), acute hypoxemia (AH) at sea level, and high altitude (HA) (3,000 m). Urine and venous blood samples were collected and analyzed. A natriuresis and diuresis was observed only under AH conditions. It was accompanied by a decrease in plasma aldosterone levels, but did not correlate with changes in plasma aldosterone levels, ANF, or other hormones. Increased plasma renin activity (PRA) and increased norepinephrine levels were encountered at HA, suggesting sympathetic nervous system activation. No change in anti-diuretic hormone (ADH) levels with increased plasma osmolality was seen at HA. We conclude that excretion of a salt load during normobaric hypoxemia is enhanced by a decrease in plasma aldosterone levels, unrelated to changes in ANF or other hormones. The differences observed in norepinephrine, PRA, and ADH levels during HA versus AH conditions suggest that hypobaria or chronic hypoxemia may influence these hormonal responses.

Blood biochemical characteristics of cattle at sea level and at moderately high altitude (3,000 m).

We investigated the biochemical composition of blood from Holstein cows, native breed (criollas), and cows descended from fighting bulls (Vacas de lidia) raised at an altitude of 3,000 m (moderately high altitude, MHA), and compared the results with those from Holsteins and cows of similar genetic ancestry as the criollas (scrub cows), both raised at sea level (SL), to determine blood biochemical values characteristic of adaptation to high altitude. Only potassium and calcium concentrations were similar among groups. Glucose concentration was lower in MHA cows, with the exception of Vacas de lidia. Serum bicarbonate concentration was lower in MHA cows; this finding can be explained by hyperventilation in the hypoxic environment. Serum magnesium concentration was lower in SL and MHA Holsteins than in other groups. Serum phosphate concentration was lower in scrub cows, MHA Holsteins, and criollas than in other groups. Cholesterol concentrations were lower in SL Holsteins, whereas triglycerides were higher in scrub cows and MHA Vacas de lidia. Concentration of high-density lipoprotein was significantly greater in Vacas de lidia and less in MHA criollas than in the other groups. Uric acid and total protein were higher in MHA groups. Using radioimmunoassay for human proteins, thyroxine-binding globulin was undetectable. Total and free thyroxine and free triiodothyronine were higher in scrub cows, followed by Vacas de lidia; lower values were detected in SL and MHA Holsteins and MHA criollas.

Noninfiltrating angiolipoma of the mediastinum.

A case of mediastinal angiolipoma in a 63-year-old man is described. A computed tomographic scan of the thorax demonstrated a large encapsulated mass with fatty and soft-tissue components near the esophagus. This appearance was considered suggestive of a liposarcoma. However, at surgery a benign noninfiltrating angiolipoma was found and removed. To the authors' knowledge, angiolipomas have not previously been reported to occur within the mediastinum.

Granulomatous myocarditis with unusual histologic features.

A 61-year-old white man was found to have granulomatous myocarditis associated with a carcinoid tumor in the ileum with local lymphatic metastasis, a mixed papillary and follicular carcinoma of the thyroid with regional lymph node metastasis, benign tubular cell adenomas of the kidneys, and chronic pancreatitis.