Chantal R. Harrison

Evidence for Linkage of Postchallenge Insulin Levels With Intestinal Fatty Acid-Binding Protein (FABP2) in Mexican-Americans

Single genes with large effects may contribute to insulin resistance or influence susceptibility to non-insulin-dependent diabetes mellitus (NIDDM). In the Pima Indians, results from sib-pair analysis have suggested that a gene on chromosome 4q influences both fasting insulin levels and maximal insulin action. We conducted sib-pair and logarithm of odds (LOD)-score linkage analysis to seek evidence for linkage between genes influencing insulin levels and chromosome 4q loci. Analyses were conducted on nondiabetic individuals from 28 different families participating in the San Antonio Family Diabetes Study. All subjects received a 2-h oral glucose tolerance test. Fasting insulin levels were measured in 382 nondiabetic individuals, and 2-h insulin levels were measured in 366 individuals. Initial sib-pair linkage analysis revealed a possible association between 2-h post–glucose challenge insulin levels and the intestinal fatty acid–binding protein (FABP2) locus located in the region of chromosome 4q28–31 (P = 0.006). Subsequent sib-pair linkage analysis of 11 additional chromosome 4q markers supported this hypothesis. We next conducted segregation analyses to estimate allele frequencies and other model parameters for the putative locus influencing 2-h insulin levels. Results of LOD-score linkage analysis indicated possible linkage between the major gene described by the segregation model and FABP2. Using combined segregation and linkage analysis, we obtained a LOD-score of 2.80 at recombination frequency of 0.0 between FABP2 and the putative locus influencing 2-h insulin levels. The maximum likelihood estimate of the allele associated with low insulin levels was 0.21. Individuals having one or two copies of this allele had a mean ln(2-h insulin level) equal to 3.484 (back-transformed mean = 298.4 pmol/1), compared with 4.480 (back-transformed mean = 807.8 pmol/1) for individuals in whom this allele was absent. Approximately 32% of the total phenotypic variance in ln(2-h insulin levels) could be attributed to this locus. These results are consistent with the hypothesis that FABP2, or a tightly linked gene, influences 2-h insulin levels. This gene may be associated with insulin resistance.

Antibodies to Kaposi's Sarcoma—Associated Herpesvirus (Human Herpesvirus 8) in Patients with Multiple Myeloma

Kaposis sarcoma-associated herpesvirus (KSHV) serologic assays were used to detect specific antibodies to KSHV lytic and latent antigens in 27 patients with multiple myeloma, 27 control patients with other cancers, and 50 random blood donors. Antibodies to KSHV recombinant minor capsid antigen orf65 were found in 81% of patients with multiple myeloma, 22% of control patients with other cancers, and 6% of the blood donors. Antibodies to KSHV latent nuclear antigens were found in 52% of patients with multiple myeloma, 26% of control patients with other cancers, and 2% of the blood donors. All of the 11 patients with progressive multiple myeloma were KSHV-seropositive. Antibodies to Epstein-Barr virus nuclear antigen 1 were present in 89% of patients with multiple myeloma, 93% of control patients with other cancers, and 88% of the blood donors. These data support the possible association of KSHV infection with multiple myeloma, particularly with progressive disease.

Severe neonatal alloimmune thrombocytopenia caused by antibodies to human platelet antigen 3a (Baka) detectable only in whole platelet assays

BACKGROUND:  Maternal antibodies that cause neonatal alloimmune thrombocytopenia are commonly identified by solid‐phase assays that detect the causative antibodies on the basis of their reactions with specific PLT glycoproteins. Two cases of severe neonatal alloimmune thrombocytopenia caused by maternal antibodies specific for human PLT antigen 3a (HPA‐3a [Baka]) that failed to give the expected reactions in some solid‐phase assays were recently encountered.

Evidence for a Major Gene for Type II Diabetes and Linkage Analyses With Selected Candidate Genes in Mexican-Americans

We have carried out two independent family studies in low-income Mexican-Americans from San Antonio, Texas. In the first study, probands were ascertained at random without regard to any medical condition (658 examined individuals from 50 families), and in the second study, probands were subjects with type II diabetes identified in a prior epidemiological survey (523 examined individuals from 29 families). Pedigrees ranging in size from 2 to 45 family members (median 11) in the first study and from 2 to 50 family members (median 12) in the second study were examined. Diabetes was diagnosed according to World Health Organization criteria. In both sets of families, segregation analyses revealed support for a major gene with an autosomal dominant mode of inheritance influencing early age of onset of diabetes. Non-Mendelian inheritance was rejected in both data sets. Individuals with the early age of onset allele had a mean age of diabetes onset of 51 years in the first data set and 60 years in the second data set. In the first data set, the major gene accounted for ∼70% of the phenotypic variance in age of onset of diabetes, and there were no residual family effects once the major gene effect was taken into account. In the second data set, the major gene accounted for ∼50% of the phenotypic variance, and residual family effects were statistically significant. Linkage analyses were performed with 11 candidate genes, and tight linkage with diabetes was rejected for Rh blood group, glucose transporter 2, fatty acid–binding protein, tumor necrosis factor β, glucokinase, and lipoprotein lipase. A logarithm of odds (LOD) score of 0.92 at a recombination fraction of 0.05 was observed for insulin receptor substrate 1. This LOD score corresponds to a χ2 of 4.24 (P = 0.039).

Massive Transfusion in Adults:Diagnoses, Survival and Blood Bank Support

Abstract. In a retrospective study covering a 2‐year period (1986–1987), 125 patients received massive blood transfusion. Trauma accounted for only 29% of the cases. The larger nontrauma diagnostic categories were: gastrointestinal hemorrhage, 31%; cardiovascular surgery, 12%, and oncology cases, 9%. The overall survival rate was 60%; survival rates ranged from 38% for patients with hepatic failure to 100% for obstetric cases. Clinically important alloantibodies were present in 4%, and transfusion reactions occurred in 9%. Massive transfusions accounted for a significant proportion of total blood component usage: at least 12% of the yearly total red cell units, 20% of plasma, and 14% of platelets transfused.

Seroprevalence of Kaposi's sarcoma-associated herpesvirus infection among blood donors from Texas

PURPOSE Kaposis sarcoma-associated herpesvirus (KSHV), a gammaherpesvirus recently discovered among AIDS patients with Kaposis sarcoma, is a potential candidate for screening in blood and plasma donors. While a number of studies have assessed KSHV infection among U.S. blood donors, larger-scale population-based studies would be necessary to develop more refined estimates of the magnitude and variation of KSHV infection across different geographic regions of the U.S. blood supply. The goal of the present study, therefore, was to determine the seroprevalence of KSHV infection and to assess demographic correlates of KSHV infection among south Texas blood donors. METHODS KSHV infection was determined using specific serologic assays that measure antibodies to KSHV latent and lytic antigens. RESULTS The overall seroprevalence of KSHV in Texas blood donors (15.0%) is substantially higher than previously reported among blood donor and general population samples in the United States. This high rate of KSHV infection persisted across most of the sociodemographic subgroups under study but was particularly elevated among participants with less than a high school education. The infection rate also increased linearly with age. CONCLUSIONS The elevated infection rate reported in the present study suggests that screening methods to detect KSHV infection in blood donors should be considered. In view of the etiologic role of KSHV for several malignancies, it would be important for future studies to directly assess the risk of KSHV transmission via blood transfusion.

Quantitation of CMV by real‐time PCR in transfusable RBC units

BACKGROUND: CMV is one of the most significant pathogens infecting immunocompromised individuals. CMV is transmissible through transfusion of blood components. The goal of this study was to measure CMV levels in RBC units using a sensitive and quantitative DNA amplification assay.

Autotransfusion of hemothorax blood in trauma patients: Is it the same as fresh whole blood?

BACKGROUND Autotransfusable shed blood has been poorly characterized in trauma and may have similarities to whole blood with additional benefits. METHODS This was a prospective descriptive study of adult patients from whom ≥50 mL of blood was drained within the first 4 hours after chest tube placement. Pleural and venous blood samples were analyzed for coagulation, hematology, and electrolytes. RESULTS Twenty-two subjects were enrolled in 9 months. The following measured coagulation factors of hemothorax were significantly depleted compared with venous blood: international normalized ratio (>9 in contrast to 1.1, P < .001), activated partial thromboplastin time (>180 in contrast to 28.5 seconds, P < .001), and fibrinogen (<50 in contrast to 288 mg/dL, P < .001). The mean hematocrit (26.4 in contrast to 33.9), (P = .003), hemoglobin (9.3 in contrast to 11.8 g/dL, P = .004), and platelet count (53 in contrast to 174 K/μL, P < .001) of hemothorax were significantly lower than venous blood. A hemothorax volume of 726 mL was calculated to be equivalent to 1 U of red blood cells. CONCLUSIONS Hemothorax blood contains significantly decreased coagulation factors and has lower hemoglobin when compared with venous blood.

A small amount can make a difference: a prospective human study of the paradoxical coagulation characteristics of hemothorax

BACKGROUND The evacuated hemothorax has been poorly described because it varies with time, it has been found to be incoagulable, and its potential effect on the coagulation cascade during autotransfusion is largely unknown. METHODS This is a prospective descriptive study of adult patients with traumatic chest injury necessitating tube thoracostomy. Pleural and venous samples were analyzed for coagulation, hematology, and electrolytes at 1 to 4 hours after drainage. Pleural samples were also analyzed for their effect on the coagulation cascade via mixing studies. RESULTS Thirty-four subjects were enrolled with a traumatic hemothorax. The following measured coagulation factors were significantly depleted compared with venous blood: international normalized ratio (>9 vs 1.1) (P < .001) and activated partial thromboplastin time (aPTT) (>180 vs 24.5 seconds) (P < .001). Mixing studies showed a dose-dependent increase in coagulation dilutions through 1:8 (P < .05). CONCLUSIONS An evacuated hemothorax does not vary in composition significantly with time and is incoagulable alone. Mixing studies with hemothorax plasma increased coagulation, raising safety concerns.

Intravascular Hemolytic Transfusion Reaction without Detectable Antibodies: A Case Report and Review of Literature

Abstract. A case of intravascular hemolytic transfusion reaction without detectable antibodies occurring in a 55‐year‐old male is reported. Specificity for the C antigen in the Rh system was demonstrated by technetium‐99m red cell survival studies. A cell‐mediated mechanism of hemolysis was suspected and investigated. Previously reported cases are reviewed and discussed. The entity of intravascular hemolytic transfusion reaction associated with minimal symptoms and no detectable antibodies deserves further investigation.