Pre-engraftment syndrome after myeloablative dual umbilical cord blood transplantation: risk factors and response to treatment.

High fevers and/or rashes prior to neutrophil engraftment are frequently observed after umbilical cord blood (UCB) transplantation, and the condition is referred to as pre-engraftment syndrome (PES). Few studies have evaluated the risk factors for and treatment response to PES. Therefore, we retrospectively characterized PES in 57 consecutive engrafted patients (≥ 12 years old) who received myeloablative dual UCB transplantation. All patients received TBI (≥ 13.2 Gy)-based myeloablative conditioning. Tacrolimus (n=35) or CYA (n=22) combined with mycophenolate mofetil was used as GVHD prophylaxis. PES was defined as the presence of non-infectious fever (≥ 38.5 °C) and/or rash prior to or on the day of neutrophil engraftment. The incidence (95% confidence interval) of PES was 77% (66-88%). The incidence of PES was significantly higher in patients who received CYA as a GVHD prophylaxis than those who received tacrolimus (P<0.001), and this association was confirmed in the multivariate analysis. The occurrence of PES did not impact OS or tumor relapse, although it may have increased non-relapse mortality (P=0.071). The incidence of acute GHVD or treatment-related mortality was not influenced by the choice to use corticosteroids to treat PES. This study suggests that use of CYA for GVHD prophylaxis increases the risk of PES following dual UCB transplantation.

In vitro and in vivo analysis of B-Myb in basal-like breast cancer.

A defining feature of basal-like breast cancer, a breast cancer subtype with poor clinical prognosis, is the high expression of 'proliferation signature' genes. We identified B-Myb, a MYB family transcription factor that is often amplified and overexpressed in many tumor types, as being highly expressed in the proliferation signature. However, the roles of B-Myb in disease progression, and its mammary-specific transcriptional targets, are poorly understood. Here, we showed that B-Myb expression is a significant predictor of survival and pathological complete response to neoadjuvant chemotherapy in breast cancer patients. We also identified a significant association between the G/G genotype of a nonsynonymous B-Myb germline variant (rs2070235, S427G) and an increased risk of basal-like breast cancer [OR 2.0, 95% CI (1.1-3.8)]. In immortalized, human mammary epithelial cell lines, but not in basal-like tumor lines, cells ectopically expressing wild-type B-Myb or the S427G variant showed increased sensitivity to two DNA topoisomerase IIalpha inhibitors, but not to other chemotherapeutics. In addition, microarray analyses identified many G2/M genes as being induced in B-Myb overexpressing cells. These results confirm that B-Myb is involved in cell cycle control, and that its dysregulation may contribute to increased sensitivity to a specific class of chemotherapeutic agents. These data provide insight into the influence of B-Myb in human breast cancer, which is of potential clinical importance for determining disease risk and for guiding treatment.

A wireless telemetry system for training users of upper limb prostheses.

Telemetry from prosthetic systems is useful in aiding the users and clinical team in setting up and training and monitoring in the use of a prosthesis. The different forms are discussed and a new radio frequency based telemetry system is described. This system uses a computer to display the data and a video mixer to place the information on the same screen as the image of the user so that their actions and control signals can be simultaneously recorded for later study.

Polymorphisms in the DNA repair gene XRCC1 and breast cancer.

X-ray repair cross complementing group 1 (XRCC1) encodes a protein involved in base excision repair. We examined the association of polymorphisms in XRCC1 (codon 194 Arg-->Trp and codon 399 Arg-->Gln) and breast cancer in the Carolina Breast Cancer Study, a population-based case-control study in North Carolina. No association was observed between XRCC1 codon 194 genotype and breast cancer, and odds ratios (ORs) were not modified by smoking or radiation exposure. A positive association for XRCC1 codon 399 Arg/Gln or Gln/Gln genotypes compared with Arg/Arg was found among African Americans (253 cases, 266 controls; OR = 1.7, 95% confidence interval, 1.1-2.4) but not whites (386 cases, 381 controls; OR =1.0, 95% confidence interval, 0.8-1.4). Among African-American women, ORs for the duration of smoking were elevated among women with XRCC1 codon 399 Arg/Arg genotype (trend test; P < 0.001) but not Arg/Gln or Gln/Gln (P = 0.23). There was no difference in OR for smoking according to XRCC1 codon 399 genotype in white women. ORs for occupational exposure to ionizing radiation were stronger for African-American and white women with codon 399 Arg/Arg genotype. High-dose radiation to the chest was more strongly associated with breast cancer among white women with XRCC1 codon 399 Arg/Arg genotype. Our results suggest that XRRC1 codon 399 genotype may influence breast cancer risk, perhaps by modifying the effects of environmental exposures. However, interpretation of our results is limited by incomplete knowledge regarding the biological function of XRCC1 alleles.

Circulating semicarbazide-sensitive amine oxidase is raised both in type I (insulin-dependent), in type II (non-insulin-dependent) diabetes mellitus and even in childhood type I diabetes at first clinical diagnosis.

Plasma semicarbazide-sensitive amine oxidase is raised in patients with Type I (insulin-dependent) diabetes mellitus. It has been suggested that this enzyme is involved in the development of microvascular damage through its ability to convert amines (e.g. methylamine and aminoacetone) into aldehydes, hydrogen peroxide and ammonia. Plasma semicarbazide-sensitive amine oxidase was found to be equally raised both in patients with Type I diabetes (n = 73) and Type II (non-insulin-dependent) diabetes mellitus (n = 88) compared with control subjects (621 +/- 209 and 619 +/- 202 vs 352 +/- 102 mU/l, p < 0.0001) and to correlate in multiple regression analysis with HbA1c. Since the enzyme could protect the islets from the inhibitory effects of methylamine on insulin secretion, we also tested sera of 100 children, collected consecutively at first diagnosis of Type I diabetes, for semicarbazide-sensitive amine oxidase. The activity was greatly increased compared with serum values of 76 control (siblings) children (757 +/- 300 vs 455 +/- 138 mU/l, p < 0.0001), but not associated with HbA1c. Our study confirms the increase of plasma semicarbazide-sensitive amine oxidase in Type I diabetes and extends this finding to Type II diabetes as well as to childhood Type I at first clinical diagnosis. In the last case increased enzyme activities could serve to protect the islets from inhibitory effects of methylamine but cause damage by generation of hydrogen peroxide, aldehydes and ammonia. In the long run the increased enzyme activities could also contribute to vascular damage by direct cytotoxic action on endothelial cells, including increased oxidative stress and glycosylation of proteins.

[No difference in frequency of family practitioner consultation by Turkish, Surinam and Moroccan 0-14-year-old children from Dutch children, but difference in reason for contact]. / Geen verschil in frequentie van huisartsbezoek door Turkse, Surinaamse en Marokkaanse kinderen van 0-14 jaar en door Nederlandse, maar wel in contactredenen.

OBJECTIVE: To determine whether consultation behaviour of Turkish, Surinam and Moroccan children (0-14 years old) with a GP differs from that of a comparable group of Dutch children. DESIGN: Cohort study with comparison of matched groups. SETTING: 103 general practices in the Netherlands. METHODS: Data on 63.753 children collected in the Dutch National Survey were used. 161 GPs registered all contacts between patient and practice during 1 year (in 4 parts of each 3 months). Sociodemographic characteristics of all 103 practice populations were gathered. For each Turkish, Surinam and Moroccan child a Dutch child was selected with similar age, gender, socio-economic status, degree of urbanisation, season of registration and sickness insurance coverage. Consult frequency, number of encounters per episode of care, morbidity presented, duration of encounter and percentages of encounters during evening, night and weekend were registered. RESULTS: There were no significant differences in consult frequency between the three ethnic groups and their Dutch reference group, nor were there any differences in number of encounters during an episode of care. The morbidity presented did vary compared with Dutch children. Turkish children consulted the GP more often for gastrointestinal problems (relative risk (RR): 1,81) and respiratory problems (RR: 1,27), but less often for ear problems (RR: 0,54). Surinam children consulted the GP less often for musculoskeletal problems (RR: 0,65), but more often for respiratory problems (RR: 1,20). Moroccan children consulted the GP less often for ear problems (RR: 0,51). For a larger percentage of ethnic children the duration of encounter was less than ten minutes. CONCLUSION: Turkish, Surinam and Moroccan children do not consult a GP more often than a comparable group of Dutch children. The morbidity presented differed.

Methods for development of building codes and disaster recovery measures

The reduction of the impact of an earthquake disaster involves planning for mitigation of earthquake effects both before and after the seismic event. Building codes provide the basis for implementation of pre-event measures to minimize the impact of an earthquake. Planning can also facilitate recovery after such an event and minimize long term impacts upon society. The paper will suggest methodologies to be used in the development of building codes which can encourage the use of local building practices while developing safer standards for construction. The discussion will focus on the processes used in the United States to formulate building codes and on the application of these processes to formulation of codes appropriate for developing nations. The paper will also explore disaster recovery through the training of personnel to perform post earthquake evaluation of damaged structures to ascertain levels of damage and suitability for occupancy (AU)

Possible effects of kanamycin and incubation in newborn children with low birth weight.

In an acoustico-vestibular follow-up investigation of 91 four- to six-year-old children with birth weight below 2000 g, the same incidence of sensorineural hearing loss (19%) was found in 54 children treated with kanamycin in the neonatal period as in a group of 37 infants not treated with kanamycin. When comparing a group of children treated with both kanamycin and incubator (54 children) with a group treated with incubator only (16 children), no definite signs of synergism between incubator noise and kanamycin were found. However, the 5 cases of moderate or severe hearing loss all belonged to the group treated with both incubator and kanamycin. These 5 children had more severe neonatal complications, especially apnea, cyanotic spells and hyperbilirubinemia, which may increase the severity of the hearing loss. Among 56 incubator treated children with normal hearing (ISO standards) 52% had an audiogram pattern suggesting minor noise-provoked cochlear lesions. Among 18 non-incubator treated children with normal hearing only one child (6%) had a similar pattern. It should be stressed, however, that these children had no clinical symptoms of hearing loss.

A follow-up study of infants who received intra-uterine transfusions because of severe rhesus haemolytic disease.

The developmental characteristics of infants surviving the neonatal period after the performance of prenatal intra-uterine transfusions because of severe rhesus haemolytic disease were studied in 17 of 19 children, using the revised Denver Developmental Screening Test and a physical-neurological examination. The children ranged in age from 5 to 91 months. Two cases are reported as having retared psychomotor development. No cases of cerebral palsy were found. Among the minor abnormalities were squints, abdominal hernia and enamel defects. The results justify the use of intra-uterine transfusions in appropriately selected fetuses when combined with treatment of hyperbilirubinaemia and respiratory distress during the neonatal period.