Accuracy of automated three-dimensional ultrasound imaging technique for fetal head biometry.

OBJECTIVES: To evaluate the accuracy of an automated three-dimensional (3D) ultrasound technique for fetal intracranial measurements compared with manual acquisition. METHODS: This was a prospective observational study of patients presenting for routine anatomical survey between 18 + 0 and 22 + 6 weeks' gestation. After providing informed consent, each patient underwent two consecutive ultrasound examinations of the fetal head, one by a sonographer and one by a physician. Each operator obtained manual measurements of the biparietal diameter (BPD), head circumference (HC), transcerebellar diameter (TCD), cisterna magna (CM) and posterior horn of the lateral ventricle (Vp), followed by automated measurements of these structures using an artificial intelligence-based tool, SonoCNS® Fetal Brain. Both operators repeated the automated approach until all five measurements were obtained in a single sweep, up to a maximum of three attempts. The accuracy of automated measurements was compared with that of manual measurements using intraclass correlation coefficients (ICC) by operator type, accounting for patient and ultrasound characteristics. RESULTS: One hundred and forty-three women were enrolled in the study. Median body mass index was 24.0 kg/m2 (interquartile range (IQR), 22.5-26.8 kg/m2 ) and median subcutaneous thickness was 1.6 cm (IQR, 1.3-2.0 cm). Fifteen (10%) patients had at least one prior Cesarean delivery, 17 (12%) had other abdominal surgery and 78 (55%) had an anterior placenta. Successful acquisition of the automated measurements was achieved on the first, second and third attempts in 70%, 22% and 3% of patients, respectively, by sonographers and in 76%, 16% and 3% of cases, respectively, by physicians. The automated algorithm was not able to identify and measure all five structures correctly in six (4%) and seven (5%) patients scanned by the sonographers and physicians, respectively. The ICCs reflected good reliability (0.80-0.88) of the automated compared with the manual approach for BPD and HC and poor to moderate reliability (0.23-0.50) for TCD, CM and Vp. Fetal lie, head position, placental location, maternal subcutaneous thickness and prior Cesarean section were not associated with the success or accuracy of the automated technique. CONCLUSIONS: Automated 3D ultrasound imaging of the fetal head using SonoCNS reliably identified and measured BPD and HC but was less consistent in accurately identifying and measuring TCD, CM and Vp. While these results are encouraging, further optimization of the automated technology is necessary prior to incorporation of the technique into routine sonographic protocols. © 2020 International Society of Ultrasound in Obstetrics and Gynecology.

Serine Metabolism Controls Dental Pulp Stem Cell Aging by Regulating the DNA Methylation of p16.

To investigate the characteristics and molecular events of dental pulp stem cells (DPSCs) for tissue regeneration with aging, we isolated and analyzed the stem cells from human exfoliated deciduous teeth (SHED) and permanent teeth of young (Y-DPSCs) and old (A-DPSCs) adults. Results showed that the stemness and osteogenic differentiation capacity of DPSCs decreased with aging. The RNA sequencing results showed that glycine, serine, and threonine metabolism was one of the most enriched gene clusters among SHED, Y-DPSCs, and A-DPSCs, according to analysis based on the Kyoto Encyclopedia of Genes and Genomes. The expression of serine metabolism-related enzymes phosphoserine aminotransferase 1 (PSAT1) and phosphoglycerate (PHGDH) decreased in A-DPSCs and provided less methyl donor S-adenosylmethionine (SAM) for DNA methylation, leading to the hypomethylation of the senescence marker p16 (CDNK2A). Furthermore, the proliferation and differentiation capacity of Y-DPSCs and SHED decreased after PHGDH siRNA treatment, which reduced the level of SAM. Convincingly, the ratios of PSAT1-, PHGDH-, or proliferating cell nuclear antigen-positive cells in the dental pulp of old permanent teeth were less than those in the dental pulp of deciduous teeth and young permanent teeth. In summary, the stemness and differentiation capacity of DPSCs decreased with aging. The decreased serine metabolism in A-DPSCs upregulated the expression of p16 via attenuating its DNA methylation, resulting in DPSC aging. Our finding indicated that serine metabolism and 1 carbon unit participated in stem cell aging, which provided new direction for stem cell aging study and intervention.

ALK-positive anaplastic large-cell lymphoma with primary bone involvement: A rare case and review of the literature.

Primary bone lymphoma (PBL) is an uncommon type of extranodal lymphoma involvement. An anaplastic large-cell lymphoma (ALCL) is an extremely rare type of PBL, and it remains unclear whether ALCLs that primarily involve the bone exhibit favourable or unfavourable biological behaviour, and whether they are similar to ALCLs in general, or not. We reported a case of ALK-positive ALCL with primary bone involvement, and reviewed the clinicopathological features of 22 previously reported cases. An ALCL with primary bone involvement mostly affects younger patients with a preponderant towards the involvement of axial-bone. The prognosis of an ALCL that primarily involves bone is unfavourable, compared with PBL generally. The ALK-positive ALCLs in PBLs had less decedents than the ALK-negative ALCLs with a statistical non-significance (p=0.198).

Variants of Monteggia Type Injury: Case Reports.

BACKGROUND: Monteggia fracture-dislocation is rare in children. Various reports attest to its rarity, while recording the many variant of this injury. It is, therefore, easy to miss the diagnosis in the absence of proper clinical examination and radiographs. CASE REPORT: This report highlights two rare variants of Monteggia fracture-dislocation seen in children. The first case was a 12-year old girl alleged to have fallen from a 15- feet tall tree and sustaining a combined type III Monteggia injury with ipsilateral Type II Salter-Harris injury of distal end radius with a metaphyseal fracture of the distal third of the ulna. The second case was a 13-year old who had sustained a closed fracture of atypical Type I Monteggia hybrid lesion, in a road traffic accident. CONCLUSION: This report highlights the rare variants of Monteggia fracture dislocation which could have been missed without proper clinical examinations and radiographs.

Single- and double-stranded viral RNA generate distinct cytokine and antiviral responses in human fetal membranes.

There has been growing interest in the role of viral infections and their association with adverse pregnancy outcomes. However, little is known about the impact viral infections have on the fetal membranes (FM). Toll-like receptors (TLR) are thought to play a role in infection-associated inflammation at the maternal-fetal interface. Therefore, the objective of this study was to characterize the cytokine profile and antiviral response in human FMs exposed to viral dsRNA, which activates TLR3, and viral ssRNA, which activates TLR8; and to determine the mechanisms involved. The viral dsRNA analog, Poly(I:C), induced up-regulated secretion of MIP-1α, MIP-1ß, RANTES and TNF-α, and down-regulated interleukin (IL)-2 and VEGF secretion. In contrast, viral ssRNA induced a broader panel of cytokines in the FMs by up-regulating the secretion of IL-1ß, IL-2, IL-6, G-CSF, MCP-1, MIP-1α, MIP-1ß, RANTES, TNF-α and GRO-α. Using inhibitory peptides against TLR adapter proteins, FM secretion of MIP-1ß and RANTES in response to Poly(I:C) was MyD88 dependent; MIP-1α secretion was dependent on MyD88 and TRIF; and TNF-α production was independent of MyD88 and TRIF. Viral ssRNA-induced FM secretion of IL-1ß, IL-2, IL-6, G-CSF, MIP-1α, RANTES and GRO-α was dependent on MyD88 and TRIF; MIP-1ß was dependent upon TRIF, but not MyD88; and TNF-α and MCP-1 secretion was dependent on neither. Poly(I:C), but not ssRNA, induced an FM antiviral response by up-regulating the expression of IFNß, myxovirus-resistance A, 2',5'-oligoadenylate synthetase and apolipoprotein B mRNA-editing enzyme-catalytic polypeptide-like 3G. These findings demonstrate that human FMs respond to two viral signatures by generating distinct inflammatory cytokine/chemokine profiles and antiviral responses through different mechanisms.

Evaluating the cost-effectiveness of prenatal surgery for myelomeningocele: a decision analysis.

OBJECTIVE: To determine whether prenatal myelomeningocele repair is a cost-effective strategy compared to postnatal repair. METHODS: Decision-analysis modeling was used to calculate the cumulative costs, effects and incremental cost-effectiveness ratio of prenatal myelomeningocele repair compared with postnatal repair in singleton gestations with a normal karyotype that were identified with myelomeningocele between T1 and S1. The model accounted for costs and quality-adjusted life years (QALYs) in three populations: (1) myelomeningocele patients; (2) mothers carrying myelomeningocele patients; and (3) possible future siblings of these patients. Sensitivity analysis was performed using one-way, two-way and Monte Carlo simulations. RESULTS: Prenatal myelomeningocele repair saves $ 2 066 778 per 100 cases repaired. Additionally, prenatal surgery results in 98 QALYs gained per 100 repairs with 42 fewer neonates requiring shunts and 21 fewer neonates requiring long-term medical care per 100 repairs. However, these benefits are coupled to 26 additional cases of uterine rupture or dehiscence and one additional case of neurologic deficits in future offspring per 100 repairs. Results were robust in sensitivity analysis. CONCLUSION: Prenatal myelomeningocele repair is cost effective and frequently cost saving compared with postnatal myelomeningocele repair despite the increased likelihood of maternal and future pregnancy complications associated with prenatal surgery.

Universal cervical-length screening to prevent preterm birth: a cost-effectiveness analysis.

OBJECTIVE: To determine whether routine measurement of second-trimester transvaginal cervical length by ultrasound in low-risk singleton pregnancies is a cost-effective strategy. METHODS: We developed a decision analysis model to compare the cost-effectiveness of two strategies for identifying pregnancies at risk for preterm birth: (1) no routine cervical length screening and (2) a single routine transvaginal cervical length measurement at 18-24 weeks' gestation. In our model, women identified as being at increased risk (cervical length < 1.5 cm) for preterm birth would be offered daily vaginal progesterone supplementation. We assumed that vaginal progesterone reduces preterm birth at < 34 weeks' gestation by 45%. We also assumed that a decreased cervical length could result in additional costs (ultrasound scans, inpatient admission) without significantly improved neonatal outcomes. The main outcome measure was incremental cost-effectiveness ratio. RESULTS: Our model predicts that routine cervical-length screening is a dominant strategy when compared to routine care. For every 100,000 women screened, $12,119,947 can be potentially saved (in 2010 US dollars) and 423.9 quality-adjusted life-years could be gained. Additionally, we estimate that 22 cases of neonatal death or long-term neurologic deficits could be prevented per 100,000 women screened. Screening remained cost-effective but was no longer the dominant strategy when cervical-length ultrasound measurement costs exceeded $187 or when vaginal progesterone reduced delivery risk at < 34 weeks by less than 20%. CONCLUSION: In low-risk pregnancies, universal transvaginal cervical length ultrasound screening appears to be a cost-effective strategy under a wide range of clinical circumstances (varied preterm birth rates, predictive values of a shortened cervix and costs).

Malignant myoepithelioma of the humerus with a satellite lesion: a case report and literature review.

We report an extremely rare case of malignant myoepithelioma presenting as a cortical osseous lesion on the humeral shaft with a satellite lesion. A 21-year-old man presented with persistent pain of the right upper arm after local trauma that had occurred 2 months earlier. Radiological examination revealed an expansile osseous tumour based on the cortex of the humeral shaft as well as a satellite lesion. En bloc resection was performed. Microscopic examination with immunohistochemical staining was used to establish a diagnosis of malignant myoepithelioma. Osseous malignant myoepithelioma occurring in long tubular bones rather than in bony structures with salivary tissue is extremely rare. Here, we demonstrate radiological and pathological features of a malignant myoepithelioma that developed in the cortex of the humeral shaft and review previously reported cases.

Germ cell apoptosis induced by experimental cryptorchidism is mediated by multiple molecular pathways in Cynomolgus Macaque.

Experimental cryptorchidism is a common model for examining the expression and function of heat-sensitive spermatogenesis-related genes in testis. Previous studies have shown that germ cells in cryptorchid testis die mainly in an apoptotic way. The molecular mechanism, however, is still unclear. We have established unilateral cryptorchid monkey model (Cynomolgus Macaque) to identify possible molecules involved in the germ cell apoptosis. The degree of germ cell apoptosis, the morphology of the cryptorchid testis, and the changes in the serum concentration of FSH, LH and testosterone after cryptorchid surgery were analyzed. Sertoli cell marker molecule vimentin, the orphan receptor LRH-1, as well as the mitochondria-related protein HSP60 and Bcl-2 were examined. Our results showed that the weight of the cryptorchid testis decreased in a time-dependent manner started from day 7 after the surgery, while the weight of the scrotal testis had no obvious change. HE staining showed that from day 5, some germ cells were detached from the epithelium. A massive degeneration of the seminiferous epithelium characteristic of epithelial structural disorganization and the formation of multinucleated giant cells as well as vacuoles was observed on day 10 and 15. The cryptorchidism induced a marked germ cell apoptosis on day 3 after the operation, reaching a peak level on day 7.

VEGF, bFGF and their receptors at the fetal-maternal interface of the rhesus monkey.

Placental development involves trophoblast outgrowth and a coordinated angiogenesis in the implantation site. In this study, expression of angiogenic factors, vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), VEGF receptors, kinase insert domain-containing region (KDR), and bFGF receptor Flg was characterized at the maternal-embryonic boundary of the rhesus monkey on Day 17, 19, 28 and 34 of pregnancy. Immunohistochemistry and in situ hybridization showed that VEGF mRNA and protein were both strongly expressed in the cytotrophoblast, the blood vessels and certain immunocytes. These sites were also immunopositive for KDR. In addition to the vascular endothelial cells and the vascular smooth muscle cells, the protein and mRNA for bFGF were also detected in cyto/syncytiotrophoblast bilayer, whereas the staining for Flg protein was mainly localized in the cytotrophoblast cells. The staining degree of VEGF and bFGF in the villi gradually decreased with the development of placenta. Strong expression of bFGF, Flg and KDR was also detected in the decidual cells. These data suggest that VEGF and bFGF may be involved in angiogenesis, cytotrophoblast proliferation and migration during early stage of placentation in the rhesus monkey.

Low incidence of genetic alterations of the p16CDKN2a in clear cell chondrosarcoma.

Mutational inactivation of the cyclin-dependent kinase inhibitors (CDKIs) (p16CDKN2a) tumor suppressor gene has been found in a variety of human tumor types. To investigate the involvement of CDKI abnormality in clear cell chondrosarcoma, alterations of CDKIs were examined in clear cell chondrosarcoma tissues using a quantitative DNA/PCR, PCR-SSCP. Two of 38 specimens (5.2%) we analyzed showed abnormally low levels of p16CDKN2a amplification, suggesting that the allelic deletion of the gene might be low frequent event in progression of this tumor. For detection of subtle sequence alterations such as point mutations, we performed SSCP analysis of the entire coding region of the p16CDKN2a gene. No altered SSCP patterns were found in 38 clear cell chondrosarcoma specimens. This study reflects the very low incidence of genetic alterations of the p16CDKN2a gene in clear cell chondrosarcoma. Therefore, we conclude that the alteration of the p16CDKN2a gene is not involved significantly in the development of clear cell chondrosarcoma.

Effects of emitted Qi on in vitro natural killer cell cytotoxic activity.

The present study investigated the effects of Korean Qi-therapy, ChunSoo Energy Healing, on natural killer (NK) cell cytotoxicity in vitro depending on Qi-treatment time and the types of cells treated. NK cell cytotoxicity was assayed by measuring LDH release from tumor target cells (K562 cell lines). NK activity was significantly increased by emitted-Qi treatment of 30 sec duration. Three and 5 minutes of Qi projection created the greatest increase in NK cell activity when mixtures of NK cells and K562 cells were treated (1.81 and 2.12 fold for 4 hr culture; 1.54 and 1.36 for 16 hr culture, respectively). NK cell activity increased significantly in Qi-treated K562 cells alone (1.13 fold, p<0.05) compared to control. These results are consistent with in vivo Qi-therapy on humans and suggests that emitted-Qi has an acute stimulatory effect on NK cell activity. This study provides direct scientific support that Qi as such may positively affect human cellular immunity.

Integration of cytogenetic landmarks into the draft sequence of the human genome.

We have placed 7,600 cytogenetically defined landmarks on the draft sequence of the human genome to help with the characterization of genes altered by gross chromosomal aberrations that cause human disease. The landmarks are large-insert clones mapped to chromosome bands by fluorescence in situ hybridization. Each clone contains a sequence tag that is positioned on the genomic sequence. This genome-wide set of sequence-anchored clones allows structural and functional analyses of the genome. This resource represents the first comprehensive integration of cytogenetic, radiation hybrid, linkage and sequence maps of the human genome; provides an independent validation of the sequence map and framework for contig order and orientation; surveys the genome for large-scale duplications, which are likely to require special attention during sequence assembly; and allows a stringent assessment of sequence differences between the dark and light bands of chromosomes. It also provides insight into large-scale chromatin structure and the evolution of chromosomes and gene families and will accelerate our understanding of the molecular bases of human disease and cancer.

Primary alveolar soft part sarcoma of bone.

AIMS: Alveolar soft part sarcoma is a distinct, rare soft tissue tumour occurring primarily within the skeletal muscles or musculofascial planes in young adults. Primary involvement of bone is extremely rare. We report on six patients with alveolar soft part sarcoma occurring primarily in bone. METHODS AND RESULTS: Thorough clinical and radiographic examinations were done to rule out any other primary site. The patients were four women and two men aged 17-35 years (mean, 24.5 years). The primary site of the tumour was the femur in three patients, the ilium in one and the fibula in two. In one of the patients with fibular involvement, the tibia was also involved by direct extension. Of the long bone lesions, three were centred in the metaphysis and one in the diaphysis. Radiographically, all of the lesions demonstrated an osteolytic pattern of bone destruction with ill-defined margins and a wide zone of transition between the lesion and adjacent normal bone. Microscopically, all tumours showed the typical histological pattern of alveolar soft part sarcoma. Diastase-resistant, periodic acid-Schiff-positive crystalline structures were identified within the cytoplasm and confirmed ultrastructurally. Immunohistochemically, a keratin stain was negative in all cases; there was positive staining for MyoD1 in the cytoplasm but not the nuclei. Distant metastasis developed in four patients; one died. CONCLUSION: Alveolar soft part sarcoma arising in bone is extraordinarily rare but should be considered in the differential diagnosis of metastatic hypernephroma in a young patient.

Langerhans' cell histiocytosis of the spine. Analysis of twenty-three cases.

STUDY DESIGN: Retrospective review of clinical and radiologic data in four major tertiary referral centers. OBJECTIVES: To report clinical and roentgenographic findings, to evaluate the results of various treatment methods, and to propose a protocol for management. SUMMARY OF BACKGROUND DATA: Langerhans' cell histiocytosis of the spine is a rare condition, and therefore, appropriate management is still controversial. METHODS: Clinical and roentgenographic findings of 38 vertebral lesions of 23 children, with average follow-up of 5.4 years, were investigated. This is the most extensive report apparent in the literature to date. The results of treatment were assessed clinically and radiologically. Anterior vertebral body height was measured sequentially to evaluate reconstitution of the vertebral body. RESULTS: The last follow-up examination demonstrated no clinical evidence of disease in all patients, regardless of treatment method. Neurologic deficits developed in four patients, but they completely disappeared. Satisfactory restoration of height was demonstrated in all except five vertebrae: one that had collapsed maximally when the patient was more than 15 years of age and four that had been fused anteriorly or posteriorly. Unsatisfactory results were also seen in a patient with progressive scoliosis and in one with an irregular endplate with disc space narrowing. Both of these complications developed after curettage. CONCLUSIONS: For treatment of single or dual spinal lesions, observation with or without bracing seems to be sufficient. In patients with multifocal lesions, chemotherapy produces good results. For treatment of neurologic deficit, low-dose radiotherapy is favored. Patients who underwent surgery--especially curettage and anterior fusion--had the worst outcome.

Fission yeast rad12+ regulates cell cycle checkpoint control and is homologous to the Bloom's syndrome disease gene.

The human BLM gene is a member of the Escherichia coli recQ helicase family, which includes the Saccharomyces cerevisiae SGS1 and human WRN genes. Defects in BLM are responsible for the human disease Bloom's syndrome, which is characterized in part by genomic instability and a high incidence of cancer. Here we describe the cloning of rad12+, which is the fission yeast homolog of BLM and is identical to the recently reported rhq1+ gene. We showed that rad12 null cells are sensitive to DNA damage induced by UV light and gamma radiation, as well as to the DNA synthesis inhibitor hydroxyurea. Overexpression of the wild-type rad12+ gene also leads to sensitivity to these agents and to defects associated with the loss of the S-phase and G2-phase checkpoint control. We showed genetically and biochemically that rad12+ acts upstream from rad9+, one of the fission yeast G2 checkpoint control genes, in regulating exit from the S-phase checkpoint. The physical chromosome segregation defects seen in rad12 null cells combined with the checkpoint regulation defect seen in the rad12+ overproducer implicate rad12+ as a key coupler of chromosomal integrity with cell cycle progression.

Activation of NF-kappaB mediates the PMA-induced differentiation of K562 cells.

The role of NF-kappaB during the PMA-induced megakaryocytic differentiation of K562 cells was investigated using K562 cells transfected with each or both subunits of NF-kappaB. The NF-kappaB subunit-transfected cells have shown much higher sensitivity to PMA-induced differentiation than their parental cells. This result was consistent with the findings that PMA-stimulated activities of NF-kappaB were markedly increased in the NF-kappaB subunit-transfected cells in comparison with their parental cells and PMA-induced differentiation was enhanced by pretreatment with IkappaB-alpha antisense oligonucleotide in the NF-kappaB subunit-transfected cells. Meanwhile, there were basically no difference in the basal and PMA-stimulated MAP kinase activities among the parental and NF-kappaB subunit-transfected cells, respectively. However, PMA-induced differentiation was blocked by pretreatment with PD98059, a specific inhibitor of MEK, in both parental and NF-kappaB-transfected cells. Therefore, these results suggest that during the PMA-induced megakaryocytic differentiation of K562 cells, NF-kappaB works downstream of MAP kinase, or that activation of both NF-kappaB and MAP kinase pathways is involved.

Molecular cloning of ovine and bovine type I interferon receptor subunits from uteri, and endometrial expression of messenger ribonucleic acid for ovine receptors during the estrous cycle and pregnancy.

Interferon-tau (IFN-tau), a type I IFN structurally related to IFN-alpha, is regarded as the major antiluteolytic factor secreted by the conceptus of ruminant ungulate species before definitive trophoblast attachment and implantation. It mediates its effects by acting on the uterine endometrium, where it blunts the normal pulsatile production of PGF2alpha, presumably as a result of its binding to type I IFN receptors. In this study, we describe the complementary DNAs for the two known subunits, IFNAR1 and IFNAR2, of this receptor isolated from bovine and ovine endometrial complementary DNA libraries by homology cloning. Although there is extensive inferred amino acid sequence similarity between bovine and ovine IFNAR1 (92% identity) and between bovine and ovine IFNAR2 (88% identity), they have diverged extensively from the human receptor subunits (approximately 67% and approximately 58% identity, respectively). Despite these differences in primary structure, the respective subunits from all three species are organized similarly in their extracellular and cytoplasmic regions, and the bovine and ovine subunits have each retained a number of polypeptide motifs implicated in signal transduction. These uterine receptors also appear not to be splice variants. The cloned ovine IFNAR1 subunit, for example, possesses the expected four extracellular SD100 domains of full-length bovine and huIFNAR1, and only the homologs of the so-called long form (huIFNAR2c) of human IFNAR2 have so far been identified. RT-PCR procedures indicate that the messenger RNA for both subunits are found, not only in endometrium, but in all other tissues examined except those ofpreimplantation conceptuses, which presumably cannot respond to the IFN-tau they produce. Quantitative RNase protection assays of ovine endometrial RNA show that the expression of neither subunit changes greatly during the estrous cycle or pregnancy. These data suggest that the type I IFN receptor, which is expressed by the endometrium and binds IFN-tau, is probably not a structurally unusual form.

Varicella zoster infection after bone marrow transplantation: incidence, risk factors and complications.

The cellular immunoincompetence which follows bone marrow transplantation (BMT) allows both primary and reactivation infection with herpes viruses. We report the overall incidence and timing of varicella zoster virus (VZV) infections after BMT, including the clinical course, complications and associated clinical risk features. Of 1186 patients undergoing BMT through 1989, 216 patients developed VZV infection between 4 days and 10.8 years after BMT; 86% of them within the first 18 months. Of all patients transplanted, 15 +/- 3% by 6 months and 52 +/- 14% by 5 years had developed VZV infection. Dermatomal zoster represented 62% of the infections, while 32% had complicated VZV infection--CNS, disseminated or visceral zoster. All serious infections occurred within 7 months of BMT but only two patients died, both from VZV pneumonitis. Allogeneic and autologous recipients had a similar incidence of VZV infection. VZV seropositive patients had more frequent, earlier and often more complicated or disseminated infections. Age > or = 10 years and radiation in the pre-transplant conditioning were significantly and independently associated with higher rates of VZV infection within a multivariate regression model. Using this model, we could define clinical risk groups with distinctly different hazards of VZV infection: age > 10 years, radiation pre-BMT and VZV seropositive patients had a 44% incidence by 3 years versus age < 10 years, no radiation and VZV seronegative had a 0% incidence by 3 years. Acyclovir assigned for prophylaxis of CMV or HSV infection had no effect on the timing or incidence of VZV infection.(ABSTRACT TRUNCATED AT 250 WORDS)