The Inter-Regional Epidemiological Study of Childhood Cancer (IRESCC): past medical history in children with cancer.

The Inter-Regional Epidemiological Study of Childhood Cancer (IRESCC) collected interview and medical information relating to the child's past medical experiences from parents of 555 children diagnosed with cancer and parents of 1110 unaffected matched controls. No significant associations emerged overall for ante-natal care, place and mode of delivery, length of gestation, birth weight, condition at birth, special care, neonatal procedures or breast-feeding. Few risk factors relating to previous illnesses and medication were found, although increasing numbers of illnesses appeared to be associated with an increased risk of childhood cancer, particularly acute lymphoblastic leukaemia. A highly significant excess of case children had not been immunised (p = 0.005). In general, these results indicate that past medical experiences have little influence on the development of cancer in children.     

Impact of automatic orders to discontinue vancomycin therapy on vancomycin use in an antimicrobial stewardship program.

We examined the possible unintended consequences of a 72-hour automatic order to discontinue vancomycin therapy in an antimicrobial stewardship program (ASP). Of 120 patients, 11 had vancomycin therapy discontinued at 72 hours without a call to the ASP, and 7 experienced a treatment interruption of 6-36 hours. All discontinuation of therapy was considered appropriate, and the 7 treatment interruptions did not have clear clinical consequences. Only one-third of patients had ASP stickers that warned of impending discontinuation of vancomycin therapy placed appropriately in the medical record.     

Characterization of a highly polymorphic marker adjacent to the SLC4A1 gene and of kidney immunostaining in a family with distal renal tubular acidosis.

BACKGROUND: Mutations in the human SLC4A1 (AE1/band 3) gene are associated with hereditary spherocytic anaemia and with distal renal tubular acidosis (dRTA). The molecular diagnosis of AE1 mutations has been complicated by the absence of highly polymorphic genetic markers, and the pathogenic mechanisms of some dRTA-associated AE1 mutations remain unclear. Here, we characterized a polymorphic dinucleotide repeat close to the human AE1 gene and performed an immunocytochemical study of kidney tissue from a patient with inherited dRTA with a defined AE1 mutation. METHODS: One CA repeat region was identified in a phage P1-derived artificial chromosome (PAC) clone containing most of the human AE1 gene and the upstream flanking region. We determined its heterozygosity value in multiple populations by PCR analysis. Genotyping of one family with dominant dRTA identified the AE1 R589H mutation, and family member genotypes were compared with the CA repeat length. AE1 and vH(+)-ATPase polypeptides in kidney tissue from an AE1 R589H patient were examined by immunocytochemistry for the first time. RESULTS: This CA repeat, previously reported as D17S1183, is approximately 90 kb upstream of the AE1 gene and displayed considerable length polymorphism, with small racial differences, and a heterozygosity value of 0.56. The allele-specific length of this repeat confirmed co-segregation of the AE1 R589H mutation with the disease phenotype in a family with dominant dRTA. Immunostaining of the kidney cortex from one affected member with superimposed chronic pyelonephritis revealed vH(+)-ATPase-positive intercalated cells in which AE1 was undetectable, and proximal tubular epithelial cells with apparently enhanced apical vH(+)-ATPase staining. CONCLUSIONS: The highly polymorphic dinucleotide repeat adjacent to the human AE1 gene may be useful for future studies of disease association and haplotype analysis. Intercalated cells persist in the end-stage kidney of a patient with familial autosomal dominant dRTA associated with the AE1 R589H mutation. The absence of detectable AE1 polypeptide in those intercalated cells supports the genetic prediction that the AE1 R589H mutation indeed causes dominant dRTA.     

Spontaneous selective attention in schizophrenia.

A visual word identification task was used to measure the type of selective attention that occurs spontaneously when there are multiple stimuli, all potentially relevant, and insufficient time to process each of them fully. This task presents two words simultaneously, one above the other, for 200 ms, and periodically requires the subject to identify either the upper or the lower word. We tested schizophrenic patients, manic-depressive patients, and normal controls under a baseline divided attention condition with no predictability and then introduced a degree of predictability into the upper location that normally results in selective attention to the lower nonpredictable location. In both the divided attention and the selective attention conditions, the schizophrenic group was just as accurate in identifying words as the other two groups, indicating no deficit in the rate of information processing. However, spontaneous selective attention under conditions of predictability was abnormal in the schizophrenic patients: They paid more attention to the predictable than to the nonpredictable source of information, consequently processing different, not less, information than normal subjects. Abnormal values on a ratio measure of selective attention occurred in 85% of the schizophrenic patients compared with only 30% of the manic-depressives and 20% of the normal subjects.     

The effect of vitamin C nutriture on complement component C1q concentrations in guinea pig plasma

This study shows that guinea pigs fed 100 times the amount of vitamin C needed for growth and for prevention of scurvy have elevated levels of complement component C1q. C1q is a plasma protein rich in hydroxyproline, an amino acid whose biosynthesis requires ascorbate. C1q is essential for host defense against pathogens, both as a component of the classical complement pathway and as an opsonin in the phagocytosis process. We measured C1q in vitamin C-depleted guinea pigs that had been repleted for 4 wks with the following daily doses of ascorbate (mg/100 g body wt): 0.50 (suboptimal), 2.0 (adequate), 10 (ample) and 50 (tissue saturating). We measured C1q in three ways: indirectly by quantifying protein-bound hydroxyproline and directly by hemolytic assay and by immunodiffusion against anti-C1q. Regardless of the method, plasma C1q was 30-50% higher in animals fed tissue-saturating ascorbate than in those fed adequate or suboptimal amounts of the vitamin (p less than 0.05, one-way analysis of variance, least significant difference test). These data confirm and significantly extend earlier work that provided indirect evidence for a relationship between C1q and ascorbate nutriture in the guinea pig. They are consistent with a possible relationship between ascorbate nutriture and host defense.     

In vivo anti-melanoma activities of the Melan-A/MART-1101–115 T CD4+ cell peptide

Malignant melanoma causes significant health problems. The identification of tumour-associated antigens has led to novel approaches to increase T cell mediated anti-tumour immune response. Melan-A/MART-1 has been use as target antigen for several T cell based immunotherapeutic treatments. More recently, the critical role of CD4+ T cells in inducing and maintaining anti-tumour immunity has been increasingly recognized. In order to optimize tumour immunotherapy, greater efforts have been concentrated on the identification of tumour antigens presented by MHC class II molecules to CD4+ T cells. In a publication, Tiwari et al. (2004) [1] have identified by a computational approach the 15-mer amino-acid sequence 101–115 (PPAYEKLSAEQSPPP) of the Melan-A/MART-1 as a good target for a vigorous and safe immunotherapy. Therefore, we have investigated the in vivo anti-tumour activity of this peptide in a murine melanoma model. For the prophylactic treatment, 20 μg or 50 μg peptide was subcutaneously injected in mice once a week during 3 weeks before tumour induction. Treatment with 50 μg peptide significantly affected tumour development. Thus, our preliminary data demonstrate potential in vivo prophylactic activity of the 101–115 peptide-based vaccine to control melanoma growth.