Differences in the metabolism of postprandial lipoproteins after a high-monounsaturated-fat versus a high-carbohydrate diet in patients with type 1 diabetes mellitus.

There is little information comparing the effects of a high-monounsaturated (Mono)-fat versus a high-carbohydrate (CHO) diet in patients with type 1 diabetes mellitus. In the present study, the effects of these diets on a number of metabolic parameters were compared. Seventeen normolipidemic, nonobese patients with type 1 diabetes were provided with the diets for 4 weeks each in a randomized, crossover design. The percentages of Mono fat of the two diets were 25 Mono versus 9 CHO, with a corresponding total fat content of 40% versus 24% and a total CHO content of 45% versus 61%. At the end of each dietary period, parameters of glycemic control, coagulation factors, and fasting and postprandial lipoproteins were assessed. There were no differences in weight, glycemia, insulin dose, fasting lipid profile, or coagulation factors between the two diets. However, the metabolism of postprandial lipoproteins after a fat load differed; viz, after the Mono diet compared with the CHO diet, mean plasma triglyceride levels over 10 hours were higher (P=.0025, by repeated-measures ANOVA). The levels of triglyceride (P=.0045) and retinyl esters (P=.0046) in chylomicrons (Sf>400) and chylomicron remnants (Sf 100 to 400) (P=.0047 and P=.043, respectively), and the total particle number (apolipoprotein B levels) in chylomicron remnants (P=.001) and small, very low density lipoprotein (Sf 20 to 100, P=.016) were also higher. Our data suggest that in patients with type 1 diabetes, a CHO diet might be preferable to a Mono diet, since adherence to the former results in a lower number of circulating postprandial lipoprotein particles that are potentially atherogenic.

Diagnosis and outcome of 100 consecutive patients with extreme granulocytic leukocytosis.

PURPOSE: To determine the clinical features, causes, and prognostic significance of extreme leukocytosis in adults. PATIENTS AND METHODS: Medical records of 100 consecutive patients who presented at the Minneapolis Veterans Affairs Medical Center between March 1993 and January 1994 with more than 25,000 leukocytes/microL blood and with more than 50% granulocytes were reviewed. Demographic, clinical, and outcome information was recorded, and a cause of extreme leukocytosis was sought in each case. RESULTS: Extreme leukocytosis was attributed to infection in 48 cases, advanced malignancy in 13 cases, hemorrhage in 9 cases, glucocorticoids in 8 cases, and other causes in 22 cases. Four patients had previously diagnosed conditions resulting in chronic leukocytosis. Higher leukocyte counts were associated with malignancy (chi2 for trend=12.5, P <0.002). Fever was more common in patients with infection (weighted rate ratio=3.7, 95% Confidence interval [CI]=2.2 to 6.2). Mortality was high overall (31%), and was greater in patients with noninfectious diagnoses compared with infected patients, an association which persisted after stratification by leukocyte count (weighted rate ratio=2.5, 95% CI=1.2 to 4.9). CONCLUSION: Clinicians should be aware that extreme leukocytosis with a predominance of granulocytes is associated with infection in only 48% of cases. The presence of fever increases the likelihood that infection is the cause. Mortality is high, particularly in patients without infection.

Calibration verification of the International Normalized Ratio.

The International Normalized Ratio (INR) system for reporting the prothrombin time (PT) is essentially a calibration activity intended to standardize PT reporting across various reagent/instrument systems. However, complete standardization of PT reporting through the INR has been difficult to achieve for a variety of reasons, including inaccurate assignment of thromboplastin International Sensitivity Indexes (ISIs) and specific (local) reagent/instrument effects. Until now, the individual laboratory has not been able to easily verify the accuracy of its INR. Using standard lyophilized plasmas with INR values assigned against IRP RBT/90 rabbit thromboplastin, the authors present a method that allows a laboratory to locally verify its range of accuracy for the INR. The method is illustrated on a single coagulometer with two thromboplastin lots of differing sensitivity (Pacific Hemostasis Thromboplastin-DS and Thromboplastin-D from rabbit sources, with respective International Sensitivity Indexes of 1.20 and 1.97). In this illustration of the method, the accuracy of Thromboplastin-DS was superior to that of Thromboplastin-D. Interpretation of the data and cautions regarding the use of standard plasmas for calibration verification are discussed. Using this method, a reportable range of accuracy at a given error tolerance can be established locally for INR measurements within a laboratory. Laboratories of any size can apply this method to study the accuracy of their INR reagent/instrument systems, thus performing calibration verification. When used in conjunction with assessments of assay precision, this method can help laboratories to select better reagent/instrument systems and thereby produce more accurate and more clinically meaningful INR results.

Effect of ciprofloxacin on the pharmacokinetics and pharmacodynamics of warfarin.

To determine if ciprofloxacin therapy alters the response to warfarin treatment, 36 adult patients attending three university-affiliated outpatient anticoagulation clinics randomly received a 12-day course of ciprofloxacin (750 mg twice daily) and a 12-day course of placebo; each course was separated by a 2-week washout period. Prothrombin times (PTs), concentrations of S-warfarin and R-warfarin (the isomers of warfarin), and concentrations of clotting factors II and VII were determined three times weekly for 9 weeks. By day 12 of ciprofloxacin therapy, concentrations of S-warfarin remained unchanged compared with those after placebo therapy, but R-warfarin concentrations increased significantly (1.15 times those after placebo therapy; P = .001); concentrations of clotting factors II and VII decreased (0.903 and 0.872 times those after placebo therapy, respectively, P < or = .020). The mean PT ratio after 12 days of ciprofloxacin therapy increased slightly (1.032 times that after placebo therapy; P = .057), but no patient had bleeding or a change in PT that required alteration in warfarin or ciprofloxacin therapy. We conclude that warfarin therapy is not a contraindication to the use of ciprofloxacin.

Prospective, randomized trial of autotransfusion after routine cardiac operations.

To study the effectiveness of autotransfusion of shed mediastinal blood in decreasing the need for homologous blood transfusion in the routine cardiac surgical patient, we prospectively randomized 35 consecutive patients into two groups. The experimental group (n = 18) received autotransfusion for 12 hours after completion of the operative procedure. The control group (n = 17) was treated with standard chest drainage and fluid replacement. Both groups received homologous blood transfusion when the hemoglobin level fell to less than 8.0 g/dL. Student's t test, chi 2 analysis, and multivariate logistic regression analysis were used where appropriate. Packed red blood cells were required postoperatively in 6 of the 17 control and 6 of the 18 autotransfusion patients (p = not significant). Postoperative colloid fluid replacement (excluding autotransfusion fluid) in the autotransfusion group (333 +/- 78 mL; 95% confidence bounds, 168 to 498 mL) was less than in the control group (615 +/- 114 mL; 95% confidence bounds, 372 to 857 mL; p = 0.048). Total homologous blood product exposure tended to be higher in autotransfusion patients (83%) than in control patients (47%) (p = 0.057). Fibrin split products were elevated only in the serum of the autotransfusion patients (p < 0.002). No transfusion-related complications were apparent in either group. Although the sample size is small, autotransfusion of shed mediastinal blood does not appear to decrease the need for homologous blood transfusion in the routine cardiac surgical patient.

Laboratory and clinical evaluation of white blood cell differential counts. Comparison of the Coulter VCS, Technicon H-1, and 800-cell manual method.

Eight hundred-cell manual white blood cell differential count evaluations of Coulter VCS and Technicon H-1 included estimates of accuracy, imprecision, random and systematic errors, clinical relevance, and detection of immature neutrophils. Accuracy was acceptable, except for H-1 testing of monocytes. Instrument imprecision was similar, except for tighter monocyte values as measured by the VCS. Deming regression determined random errors were greater for H-1 monocytes and proportional errors were similar. Constant errors for the VCS were less than the H-1 for neutrophils and monocytes and greater than the H-1 for eosinophils and lymphocytes. H-1 morphologic false-negative rates were twice those for VCS. True-positive and false-negative rates in cases with immature neutrophils were 70.6% and 20.3% for the VCS and 35% and 55.9% for the H-1. The reference false-positive rate was 4.4%. Clinically appropriate VCS flags were generated in distributionally abnormal cases. Predictive values were higher for the VCS.

Factor XI deficiency: genetic and clinical studies of a single kindred.

A four-generation 25-member kindred with Factor XI:C deficiency is reported. Factor XI:C levels in heterozygotes varied from 15 to 58%, suggesting that Factor XI:C values for homozygote determination should be less than 15%. The frequency of bleeding was not correlated with Factor XI:C levels in this range. Individuals with joint pain had significantly lower Factor XI:C levels than members without joint pain and pain occurred more frequently in frequent bleeders. Lod scores showed no close genetic linkage of Factor XI:C deficiency with blood group MNSs (chromosome 4), complement components Bf and C4B (chromosome 6), or blood group P.

Structural features of endotoxin required for stimulation of endothelial cell tissue factor production; exposure of preformed tissue factor after oxidant-mediated endothelial cell injury.

Cultured human umbilical vein endothelial cells synthesize the procoagulant, tissue factor, after exposure to bacterial endotoxin. Wild-type lipopolysaccharide from Escherichia coli 0127:B8 stimulates a five- to 20-fold increase in cellular tissue factor. Similarly, rough or incomplete lipopolysaccharide subunits from mutant bacterial strains, or lipid A prepared by mild acid hydrolysis of whole endotoxin, are also stimulatory. In addition, a lipid A biosynthetic precursor, consisting of a phosphorylated glucosamine disaccharide substituted with four beta-hydroxymyristoyl residues, is stimulatory at nanomolar concentrations. Endothelial cell tissue factor is not detectable on the surface of undisrupted cells, but can activate clotting on the cell surface after oxidant-mediated cell injury. The procoagulant, tissue factor, is synthesized by endothelial cells after stimulation mediated by a moiety contained within the lipid A region of lipopolysaccharide. Exposure of clotting factors at the endothelial cell surface after cell injury suggests a mechanism for the microvascular thrombosis associated with disseminated intravascular coagulation with sepsis.

Budd-Chiari syndrome in a patient with the lupus anticoagulant.

Lupus anticoagulant is an immunoglobulin that interferes with prothrombin conversion to thrombin and is manifested biochemically by prolongation of the partial thromboplastin time. Paradoxically, bleeding is rare in association with this anticoagulant, and deep leg vein thromboses, pulmonary emboli, and cerebrovascular accidents have been described in patients with this clotting inhibitor. This report describes the first case of Budd-Chiari syndrome associated with the lupus anticoagulant. The patient presented with abdominal pain and massive ascites. The Budd-Chiari syndrome was confirmed by liver biopsy and venography. No medical condition known to predispose to an increased thrombotic tendency could be identified, and the presence of the lupus anticoagulant in the patient's plasma may provide an explanation for his hypercoagulability and development of the Budd-Chiari syndrome.

Measurement of canine von Willebrand factor using ristocetin and Polybrene. Diagnosis of canine von Willebrand's disease.

Dogs with VWD provide useful models for the study of the factor VIII complex. However, the study of canine VIIIR:WF has been hampered by the lack of a routine plasma assay for canine RCF, an activity that is usually used as a measure of VIIIR:WF. This study shows that canine plasma can be assayed for RCF with a macroscopic tilt-tube method using formalin-fixed human platelets, ristocetin, and extra canine albumin (5.0 mg/ml) to prevent plasma precipitation. An assay was also developed for canine plasma PBCF, an activity that is closely related to RCF. In 45 normal canine plasmas, VIII:C was not correlated with RCF, PBCF, or VIIIR:AG. However, RCF, PBCF, and VIIIR:AG were well correlated with each other. In 26 canine VWD plasmas, VIII:C was frequently normal, whereas VIIIR:AG, RCF, and PBCF were almost always deficient. The patterns of VIIIR:AG, RCF, and PBCF deficiencies in the canine VWD plasmas suggested that some canine breeds have a "classic" form of VWD whereas other breeds have "variant" forms of disease.

Acquired von Willebrand's disease, platelet-release defect and angiodysplasia.

A previously healthy elderly man with gastrointestinal bleeding was found to have criteria for von Willebrand's disease. The late clinical onset of the disorder and negative family studies suggest that the von Willebrand's disease may be acquired. The findings in the patient were similar to the abnormalities reported in the small number of other patients thought to have acquired von Willebrands disease. An inhibitor of factor VIII could not be demonstrated in this patient. This patient also had platelet aggregation abnormalities that are atypical for patients with congenital or acquired von Willebrand's disease. Vascular abnormalities were also found in this patient and in several other previously described patients with von Willebrand's disease.

IgM pyroglobulinemia with erythrocytosis presenting as hyperviscosity syndrome. I. Clinical features and viscometric studies.

The hyperviscosity syndrome is described in a patient with erythrocytosis and an immunoglobulin M with kappa light chain (IgMK) macroglobulinemia. Viscometric studies were carried out on whole blood and demonstrated the contribution of both the increased hematocrit value and the macroglobulinemia to the whole blood viscosity. Clinical improvement followed phlebotomy and was accompanied by a decrease in whole blood viscosity. Continued treatment with chlorambucil has been associated with a long symptom-free period. The macroglobulin was characterized as a monoclonal IgMK pyroglobulin which retained its thermoprecipitability was reduced to 7S monomers. The presence of IgMK aggregates in the serum may have contributed to the increase in blood viscosity.

Disseminated intravascular coagulation in the urologic patient.

Gram-negative septicemia and metastatic prostatic cancer are frequent causes of disseminated intravascular coagulation. The clinical manifestations of this condition as well as the laboratory data vary considerably, depending on the patient's compensatory mechanisms in relation to the magnitude and duration of the thromboplastin or endotoxin release. Treatment centers primarily on correcting the underlying disorder. Secondly, deficient clotting factors and platelets should be replaced in the appropriate patient. Heparinization is often unnecessary. The use of drugs that inhibit the protective fibrinolytic mechanism is contraindicated in disseminated intravascular coagulation.

Urine concentration and dilution: effect on red cell survival.

Survival time of 51Cr-labeled red cells was determined in dogs subjected to water restriction excreting concentrated urine and again following a 6-week period of ad lib. water intake. During water restriction, RBC survival was reduced to one-seventh of normal. In rats with untreated diabetes insipidus, 51Cr RBC survival was reduced 30% as compared to the pitressin-treated state. It appears that RBC survival may be influenced by osmotic stress associated with the state of urine concentration and dilution.