John Bernard Henry

Febrile nonhemolytic transfusion reactions. Management by premedication and cost implications in adult patients.

CONTEXT Febrile nonhemolytic transfusion reactions (FNHTRs) cause unwelcome interruptions during the course of blood product transfusions and necessitate measures to verify the nature of the reaction and to exclude certain dangerous reactions, such as hemolytic and septic phenomena. OBJECTIVE To examine transfusion medicine data to determine the clinical implications of the routine administration of antipyretic medication to adult patients before transfusion for the prevention of FNHTRs. DESIGN A retrospective review was conducted of FNHTR data during 5 years (1998-2002), and a determination was made of the cost of a transfusion complicated by an FNHTR. In addition, a comparative cost analysis was performed using our data and published data on the incidence of FNHTRs. The clinical implications of medication with respect to possible drug-induced adverse effects were assessed, as well as the potential interference with diagnosing other forms of transfusion reactions and the mitigation of the clinical effect of an FNHTR. RESULTS For nearly 120,000 U of transfused blood components, approximately 80% of which were preceded by antipyretic medication during the study period, the overall incidence of FNHTR was found to be 0.09%. Furthermore, there was no evidence of antipyretic-associated complications, nor any evidence that antipyretics prevented the recognition of other more dangerous complications of transfusions. CONCLUSION Our findings indicate that this practice provides significant advantages to the recipient of a transfusion, but does not appear to yield significant cost benefits for the health care provider.

Regional enteritis: evidence for genetic transmission by HLA typing.

Lymphocytes from kindreds containing five sibling pairs affected with regional enteritis were typed to ascertain the association between histocompatibility leukocyte antigens (HLA)-A and -B and regional enteritis. Also, the frequency of HLA antigens in 22 patients with nonfamilial cases of regional enteritis was compared to the frequency in 402 normal blood donors. No HLA haplotype was found in more than one kindred, and no HLA antigen was more prevalent in nonfamilial cases of regional enteritis than in the normal population. In the five affected sibling pairs, four shared both haplotypes (HLA identical), and one shared one haplotype. Only one unaffected sibling shared two haplotypes with an affected proband. The high frequency of HLA identity in affected siblings and the low frequency of identity in unaffected siblings suggest linkage between the histocompatibility locus and the development of regional enteritis. There appears to be a genetic component in kindreds with regional enteritis.

Diagnostic Value of Muramidase

Serum and urinary muramidase assays are of greatest value in diagnosing myelomonocytic and chronic myelocytic leukemia and in evaluating renal tubular damage. Like all known enzymes, muramidase is a protein. The assay of this enzyme is based on its ability to hydrolyze the cell wall of Micrococcus lysodeikticus, the substrate in most turbidimetric assay methods and in the agar-plate method of Osserman.

A New HLA-A1 MutationA Novel, Null Variant Allele

From an unusually informative family of 8 with near identical parental haplotypes (a and c), which differed by a single nucleotide substitution, we identified a new HLA-A1 null variant. While serologic antigen typing initially showed a “blank” allele in maternal haplotype “c” and 2 male offspring, more sophisticated DNA molecular HLA typing subsequently revealed the presence of a novel HLA-A0101 allele. Sequence-based typing showed a point mutation consisting of a nucleotide substitution of a cytosine for a guanine at nucleotide 215 yielding an amino acid change of arginine to proline at codon 48 in exon 2 (R48P). The impact on the HLA and immunogenetics laboratory is the need to not assume that all blanks are homozygous, as well as the need for the availability of high-resolution DNA molecular typing to clarify new alleles and to detect HLA-A null variants.

HLA Antigens and Childhood Acute Lymphocytic Leukaemia

Summary. HLA‐A and ‐B antigens were determined for 94 children with acute lymphocytic leukaemia (ALL) and for 376 normal controls. Sixty‐four of these 94 patients were typed for lymphocyte surface markers and 59 were defined as ‘null cell’ ALL. There was no difference in the distribution of the HLA‐A or ‐B locus antigens between the control group and the entire group of patients with ALL or the ‘null cell’ subgroup. Patients with HLA‐A9 determinants had a significant increase in early, first remission duration compared to patients without HLA‐A9. This was particularly evident in the ‘null cell’ ALL subgroup. In addition, HLA‐A9 appeared to be an independent factor affecting the length of first remission since there was no correlation between known prognostic factors such as patient age, sex or WBC and the presence or absence of the HLA‐A9 antigen. Survival for the first 12–18 months was also greater in the HLA‐A9 group than in the non‐HLA‐A9 population. Thus, the presence of HLA‐A9 appears to be associated with some protective effect among patients with ALL.

Pitfalls of Mass Chemical Screening: First of Two Parts

Chemical screening of large populations has serious limitations that are related to statistical properties of such groups and to commonly used methods. Among the pitfalls are low disease prevalence, extrapolating research data to screening practice, laboratory variation, ill-defined limits, unselected specimens, and screening for unbeatable diseases. Unless these limitations are understood, screening can be useless and costly.

Comprehensive graphic-based display of clinical pathology laboratory data

In this age of ever-increasing demands for and uses of patient data, technologic advancements in the form of electronic patient records permit improved data access and prompt retrieval of higher quality patient care data, with more versatility in display, facilitating the integration of information concerning patients over time and between settings of care, which is in turn more accessible for use by practitioners and provides more efficient and effective decision support in areas of patient care. The graphic display of laboratory data is central to the evolving computerized patient record and needs to be taken into careful consideration along with clinician perception and ease of data interpretation in redesigning the graphic reporting of numeric clinical pathology laboratory data. An ideal system should generate user-friendly, graphic-based comprehensive reports highlighting abnormalities with trends for diagnosis, clinical management, and risk-factor detection.

Clinical Significance of Creatinine Measurements

Determining creatinine clearance is probably the best method available to most physicians for approximating the glomerular filtration rate. However, the methods of measurement used most often are based on the Jaffe reaction, which is not specific for creatinine. Creatinine is formed from creatine in muscle by an irreversible reaction. Clearance rates below 60 ml per minute are considered pathologic. Recent studies indicate that the creatinine level in amniotic fluid may predict fetal maturity.

The Physiology of Pregnancy: Clinical Pathologic Correlations

Pregnancy is a physiologic stress test during which subtle impairment of any organ system is manifested. The hepatic and gastrointestinal systems are the least affected by pregnancy, whereas the endocrine system probably undergoes the greatest stress and presents some of the most confusing test results. Only by being aware of the physiologic changes that accompany pregnancy can the physician make sound clinical judgments regarding both mother and fetus.

Allorecognition of an HLA-A*01 Aberrant Allele by an HLA Identical Family Member Carrying the HLA-A*0101 Allele

We identified and characterized an HLA-A1 aberrant allele (A*0118N) resulting from a novel molecular mechanism; this allele was present in an unusually informative family with a near identical parental HLA haplotype (c d) differing only by one nucleotide substitution in one HLA-A allele, A*0118N, of the maternal HLA haplotype (c) and not of the paternal HLA haplotype (a). Although serologic HLA typing showed a “blank,” DNA molecular HLA typing detected a HLA-A*0118N allele. Sequence based typing identified the substitution of guanine by cytosine at the nucleotide position 215, which resulted in the replacement of arginine by proline at position 48 of the HLA-A1 H chain. The loss of surface protein expression was also found by FACS analysis. Isoelectric-focusing analysis detected a HLA-A H chain with a unique isoelectric-focusing pattern, which does not associate with the L chain (β2-microglobulin). These results suggest that the residue 48-containing interaction site on the α1 domain plays a critical role in the association between HLA class I H chain and β2-microglobulin. Functional studies showed that the T cells of the propositus (HLA haplotypes c d) carrying this null allele recognized its wild-type counterpart, HLA-A*010101, in her HLA-identical son that carries the HLA-A*0101 heterodimer. This is the first example of the generation of cytotoxic T cells in the absence of proliferation of CD4+ T cells (mixed lymphocyte culture) and the description of an aberrant allele, A*0118N, that may behave as a minor histocompatibility Ag, with implications in allorecognition by cytolytic T cells in solid organ and stem cell transplantation.