Seropositive abdominal and thoracic donor organs are largely underutilized.

The aim of this study was to describe the epidemiology and utilization of anti-hepatitis B core protein(+) and anti-hepatitis C virus(+) organ donor referrals in a large organ procurement organization. Between 1995 and 2006, 3,134 deceased organ donor referrals were tested for anti-HBc and anti-HCV using commercial assays. The prevalence of anti-HCV(+) organ donor referrals significantly increased from 3.4% in 1994-1996 to 8.1% in 2003-2005 (P < .001), whereas the prevalence of anti-HBc(+) organ donor referrals remained unchanged at 3%-4% (P = .20). The 112 anti-HBc(+) (3.5%) and 173 anti-HCV(+) (5.5%) organ donor referrals were significantly older and more likely to be noncaucasian than seronegative organ donor referrals (P < .02). The procurement and utilization rates of seropositive thoracic and abdominal donor organs were significantly lower compared with seronegative organ donors (P < .0001). However, liver utilization rates significantly increased from anti-HBc(+) donors over time (21% vs 46%; P = .026), whereas utilization of anti-HCV(+) liver donors remained unchanged over time (5% vs 18%; P = .303). In summary, the proportion of anti-HCV(+) organ donor referrals has significantly increased and the proportion of anti-HBc(+) organ donor referrals has remained stable. Both thoracic and abdominal organs from seropositive donors are largely underutilized.

Warfarin reversal emerging as the major indication for fresh frozen plasma use at a tertiary care hospital.

Because of the increase in the use of warfarin in the population in recent years, reversal of warfarin-related coagulopathy has become common in daily hospital practice. Transfusion of fresh frozen plasma (FFP) is the preferred treatment method for urgent warfarin reversal in the USA. We have undertaken a 1-month audit of FFP usage to ascertain the impact of warfarin use on the consumption of FFP. Sixty percent of the 376 units of FFP that were transfused during the study month were used to reverse warfarin effects. The most common reason to reverse warfarin was bleeding. Thirty-three percent of the units were used for the treatment of other coagulopathies, 7% were used in therapeutic plasmapheresis, and <1% was transfused empirically. One hundred and eighteen patients received FFP during the study month. The study population consisted mostly of elderly patients (65%); however, the warfarin reversing patients consisted disproportionately more of elderly patients (75%) compared with patients receiving FFP for other reasons (46%) (P = 0.0032). Warfarin reversal emerged as the major indication for FFP use in this study. Blood banks of hospitals serving a predominantly elderly patient population should anticipate a higher consumption of FFP. Careful monitoring of warfarin therapy, stringent implementation of the warfarin reversal guidelines, and the introduction of newer products for warfarin reversal would help reduce the consumption of FFP.

Hepatosplenic gamma/delta T-cell lymphoma in immunocompromised patients. Report of two cases and review of literature.

We describe 2 male patients in whom hepatosplenic gamma/delta T-cell lymphoma (HSTL) developed 6 and 10 years after renal transplantation. The onset was abrupt with systemic symptoms, cytopenia, and hepatosplenomegaly. The histologic examination of the spleen (case 1), liver, and bone marrow revealed sinusoidal infiltrates of markedly abnormal lymphocytes. The neoplastic cells in these cases were CD2+, CD3+, CD4-, CD5-, CD7+, CD8+, CD16+, CD56+, beta F1-negative, and TIA-1-negative. Both cases displayed clonal rearrangement of the T-cell receptor (TCR) delta gene and the TCR beta gene. The spleen in case 1 was positive for Epstein-Barr virus genome and showed TCR-gamma gene rearrangement by polymerase chain reaction. Isochromosome 7 [i(7)(q10)] was found in each case. Both patients died within 4 months of diagnosis. HSTL has been reported in only 5 renal transplant recipients. HSTL may be relatively more frequent in immunocompromised patients compared with the general population.

Application of a sensitive and specific reagent for the determination of serum iron to the Bayer DAX48.

We describe a modification of a previously described serum iron procedure applied to the Bayer DAX48 (Bayer Diagnostics, Tarrytown, NY) automated chemistry analyzer. The iron-ligand used in this assay, 2-(5-nitro-2-pyridylazo)-5-(N-propyl-N-sulfopropylamine) phenol (nitro-PAPS), has a molar absorptivity of 94,000 L mol(-1) cm(-1), which is three to four times more sensitive than the more commonly used ligands. The increased sensitivity of the iron-ligand complex facilitates modification of a Ferene S method that requires a smaller sample volume while it maintains the precision of the assay. Because the reagent does not contain ascorbate, the "onboard" stability has been increased to more than 4 weeks. The reagent seems to be quite insensitive to icterus and hemolysis. Furthermore, the interference of turbidity caused by triglycerides, abnormal proteins, or fibrinogen, present in samples from patients undergoing anticoagulant therapy, seems to have been eliminated.

Clinical laboratory investigation of the Sanofi ACCESS CK-MB procedure and comparison to electrophoresis and Abbott IMx.

This evaluation was undertaken to verify the application protocol for the CK-MB assay on the ACCESS Immunoassay Analyzer (Sanofi Diagnostics Pasteur, Chaska, MN). The results show that the ACCESS CK-MB assay total imprecision was 6.8% to 9.1%. Analytical linearity of the ACCESS CK-MB assay was excellent in the range of < 1-214 micrograms/L. A comparison of the ACCESS CK-MB assay with the IMx (Abbott Laboratories, Abbott Park, IL) method shows good correlation r = 0.990 (n = 108). Linear regression analysis yielded Y = 1.36X-0.3, Sx/y = 7.2. ACCESS CK-MB values also correlated well with CK-MB by electrophoresis with r = 0.968 (n = 132). The linear regression equation for this comparison was Y = 1.08X + 1.4, Sx/y = 14.1. The expected non-myocardial infarction range of CK-MB determined by the ACCESS system was 1.3-9.4 micrograms/L (mean = 4.0, n = 58). The ACCESS CK-MB assay would appear to be rapid, precise and clinically useful.

Graft failure in children receiving HLA-mismatched marrow transplants with busulfan-containing regimens.

Identifying risk factors that lead to graft failure may reduce morbidity and mortality after bone marrow transplantation (BMT) for hematologic malignancies. We evaluated engraftment of all patients with acute myelogenous leukemia (AML), chronic myelogenous leukemia (CML) and myelodysplastic syndrome (MDS) receiving an unmanipulated marrow allogeneic BMT at the Detroit Medical Center from 1987 to 1992 using a busulfan, cyclophosphamide +/- cytarabine preparative regimen. Three of 118 patients had graft failure (2.5%; (95% confidence interval (CI) 0.7%, 6.4%). Graft failure was high in patients < or = 15 years with 3 of 12 patients with failure (25.0%) compared with 0 of 106 patients > 15 years (p = 0.002). Failure to engraft was not seen in HLA-identical (related or unrelated) donor transplants (0 of 103) whereas 3 of 15 HLA-mismatched donors failed (p = 0.003). Patient diagnosis, locus of HLA-mismatch, cytarabine in the preparative regimen, marrow cell dose and the relative reactive index (RRI) were not significant factors. Altered busulfan kinetics secondary to young age was probably not a major factor since 8 of 8 HLA-identical donor transplants engrafted in children. These findings demonstrate that patients receiving an unmanipulated marrow graft using busulfan-containing regimens were at a high risk for graft failure only if they were < or = 15 years of age and had an HLA-mismatched donor. More immunosuppressive preparative regimens, possibly including total body irradiation, should be considered to prevent potential graft failure in children.

Association between HLA-DQB1 alleles and risk for cervical cancer in African-American women.

Squamous-cell carcinoma of the cervix and its precursor lesions are associated with human papillomavirus (HPV) infection. Epidemiological studies indicate that HPV infection in itself is not sufficient for cervical-cancer induction, suggesting that other factors contribute to carcinogenesis. We have investigated the potential role of host genetic background as one such factor. We screened a series of squamous-cell carcinomas of the cervix for HLA-class-II DQB1* alleles by the polymerase chain reaction and site-specific oligonucleotide probe hybridization and for HPV type from African-American women using a local, ethnically matched control panel. Statistically significant associations for increase in relative risk for cervical cancer were seen for DQB1*0303 and DQB1*0604. DQB1*0201 and the heterozygote DQB1*0301/*0501 showed a decrease in relative risk for cervical cancer. HPV typing revealed no association between virus type and DQB1 alleles. Our results confirm other studies showing an increase in relative risk for cervical cancer associated with HLA-DQ3 alleles in Caucasians.

Monoclonal antibody to human cartilage cells and its reactivities to chondrocytic tumors.

A murine monoclonal antibody (E10) was made against cultured cartilage cells. The E10 antibody binding is localized to the surface of cultured cartilage cells in suspension and is present in the cytoplasm in paraffin embedded sections. There is no reactivity with cartilage matrix, or with the matrix of cartilaginous tumors. Reactivity is removed by treatment with trypsin and hyaluronidase, but not by treatment with heparinase, neuraminidase, and chondroitinase. Regeneration of E10 antigen after trypsinization takes 48 hours in chondrocytes in tissue culture. SDS-polyacrylamide gel electrophoresis of an E10 immune precipitate of cultured chondrocytes results in two peaks: one at a very high molecular weight and a small fragment at approximately 250 kd. Specificity has been demonstrated by cytofluorometry, immunofluorescence, and immunohistochemistry, in both frozen and paraffin-embedded tissues. Positive reactivity was seen in cultured cartilage cells, chondrocytes in fetal and adult cartilage, chondrosarcomas, and chordomas. Minimal reactivity was found in a chondromyxoid liposarcoma. Acinar cells of salivary and sweat glands and mast cells in various tissues and tumors were also positive. There was no reactivity with other tissues and tumors, including myxoid and mucinous tumors and epithelial tissues.

Phosphatidylglycerol in amniotic fluid. Comparison of an "ultrasensitive" immunologic assay with TLC and enzymatic assay.

Phosphatidylglycerol (PG) in amniotic fluid is recognized as a good indicator of fetal lung maturity and is unaffected by moderate amounts of blood or meconium contamination. A rapid immunologic agglutination assay, Ultrasensitive AmnioStat-FLM (FLM), was compared with two-dimensional thin-layer chromatography (TLC) and an enzymic, colorimetric procedure (E-PG). Eighty amniotic fluid specimens were analyzed. FLM results were reported as high (H), intermediate (I), or low positive (L). TLC was compared with FLM:H (n = 27), mean 0.14 (fraction of total phospholipids); I (n = 7), mean 0.11; L (n = 9), mean 0.03; negative results had no detectable PG by TLC. In 33 cases E-PG was compared with FLM:H (n = 9), mean 7.0 mumol/L; I (n = 5), mean 8.1 mumol/L; L (n = 3), mean 3.0 mumol/L; negative (n = 16), mean 3.2 mumol/L. Records were reviewed in 70 cases. Thirty cases were excluded: sample to delivery time was greater than 72 hours; steroids were given or sepsis was documented. Fetal lung immaturity was clinically present in six cases: respiratory distress syndrome in three cases and transient tachypnea of the newborn (TTN) in three cases. One false positive result was identified (TTN, FLM:H). FLM sensitivity for fetal lung maturity was 85.3%, specificity was 83.3%, and the positive predictive value for fetal lung maturity was 96.7%. FLM is a fast, reliable indicator of fetal lung maturity.

Outcome after posthemorrhagic ventriculomegaly in comparison with mild hemorrhage without ventriculomegaly.

The neurodevelopmental sequelae in 33 low birth weight neonates with moderate or severe hemorrhage and ventriculomegaly (VM group) and in 39 neonates with mild hemorrhage only (non-VM group) were evaluated prospectively. Both groups were comparable in birth weight, gestational age, and socioeconomic status. Ventriculoperitoneal shunts were inserted in 23 of the 33 VM group infants at a mean age of 26 days. Eighty-two shunt revisions were performed, for obstruction (71 revisions) or infection (11 revisions), in 18 of the 23 children. At a mean age of 50 months, 19 of 33 children in the VM group had sequelae; 14 children had moderate or severe neurologic deficits, and 5 children had mild sequelae. In the non-VM group, only 3 of 39 children had deficits, all of which were mild (p less than 0.05). In the VM group, 19 of 33 children had mental developmental delay in comparison with 8 of 39 in the non-VM group (p less than 0.05), and 17 of 33 children in the VM group had motor developmental delay in comparison with 5 of 39 in the non-VM group (p less than 0.01). Within the VM group, the number of children with neurodevelopmental sequelae did not differ significantly among the 23 children with shunts, in comparison with the 10 who did not require shunting. Among the children with shunts, a higher incidence of sequelae occurred when lack of ventricular decompression was noted immediately after shunt insertion (p less than 0.005) and when shunt infections occurred (p less than 0.01). The most important predictor of mental and motor outcome in the group with shunts was lack of ventricular decompression immediately after shunt insertion. We speculate that, in some infants, loss of brain tissue, cerebral atrophy, or both may occur before insertion of the ventriculoperitoneal shunt, even when the shunt is inserted early.

Effects of glucocorticoids on eosinophil colony growth.

The in vivo and in vitro effects of glucocorticoids on eosinophilopoiesis were examined with soft agar cultures of bone marrow and peripheral blood cells. Prednisone, 10 mg four times daily for three days, administered to normal volunteers, caused a significant drop in circulating eosinophil numbers (p less than 0.005) but did not decrease eosinophil colony numbers in cultures of bone marrow or peripheral blood. A patient with peripheral blood eosinophilia demonstrated a larger percentage decrease in mean eosinophil colony numbers (50%) after prednisone than did any normal volunteer. Incubation of bone marrow cells for 1 hour with either high concentrations of hydrocortisone, up to 3.3 X 10(-4) mol/L, or with postinfusion plasma from volunteers administered intravenous hydrocortisone, plasma levels to 1.6 X 10(-5) mol/L, did not decrease the numbers of eosinophil colonies. At a concentration of 3.3 X 10(-6) mol/L of hydrocortisone, there was a slight but statistically significant stimulation of eosinophil colony numbers. In contrast, incubation with high concentrations of dexamethasone, 3.3 X 10(-4) mol/L or 3.3 X 10(-6) mol/L, significantly reduced eosinophil colony numbers. Prednisone caused a significant reduction in plasma levels of Charcot-Leyden crystal protein but not of eosinophil granule major basic protein. The results indicate that soft agar assay of eosinophil colony growth by blood or bone marrow cells cannot be used to model the in vivo eosinopenic effect of glucocorticoids, levels of dexamethasone in excess of levels commonly administered in clinical practice are required to inhibit eosinophilopoiesis in vitro, and patients with peripheral blood eosinophilia may be more susceptible to the eosinopenic effects of glucocorticoids than normal subjects.

Intracranial pressure and cerebral perfusion pressure in near-drowning.

Intracranial pressure (ICP) and cerebral perfusion pressure (CPP) were strictly controlled in 11 pediatric victims of near-drowning. Three outcome groups were defined: complete recovery, persistent vegetative state, and death. In the early postimmersion phase (first 72 h), CPP was consistently above 50 mm Hg in all patients. There were occasional, nonrepetitive, and easily controllable ICP spikes above 15 mm Hg in three patients from each group. Repeated ICP spikes above 15 mm Hg were observed in some patients with adverse outcome only after 72 h. Successful control of ICP and CPP did not ensure intact survival, and sustained late intracranial hypertension is more likely a sign of profound neurologic insult rather than its cause.

Seasonal variation of in vitro lymphocyte proliferative response to ragweed antigen E.

Seasonal variation of symptoms and IgE response to short ragweed (SRW) allergens is well documented. Clinical symptoms generally parallel the rise and fall of the SRW-pollen count, whereas total and specific-IgE levels peak after the SRW-pollen season with a more gradual return to preseason levels. Because IgE synthesis is under T-lymphocyte control, we tested for seasonal variation in T cell-proliferative response to SRW antigen E (AgE) in vitro. Nine untreated SRW-sensitive and five nonallergic individuals were studied on 15 occasions from June 1981 through May 1982. In vitro proliferative index (SI) to AgE, serum total and specific IgE and SRW-pollen counts were measured; all persons studied kept daily symptom diaries. The mean SI was higher for the atopic group on all 15 sampling dates. The cumulative SI and the daily SI were statistically different between groups before, during, and after pollination. The peak SI for the atopic patients occurred almost 1 2/5 wk after the pollination peak, and the peak IgE antibody levels to SRW occurred at 5 2/5 wk after the pollination peak. We conclude that in vitro responsiveness to AgE is a specific response of allergic individuals and that this response demonstrates a significant seasonal component.

Melanosis and hydrocephalus. Report of four cases.

Four cases are presented in which hydrocephalus and extensive pigmented lesions of the body coexisted. A related developmental defect is suggested.