Percutaneous insertion of the Kimray-Greenfield filter: technical considerations and problems

Kimray-Greenfield filters were inserted percutaneously into the inferior vena cava (IVC) in 57 patients. Thirty-six were placed from the right femoral vein, 14 from the left femoral vein, and seven from the right internal jugular vein. There were no deaths or major complications and only six minor complications. Inferior vena cavography was done before filter insertion in all cases. Cavography is vital to determine feasibility of filter insertion, route of insertion, and filter location; pertinent findings include caval size, presence or absence of clot in the IVC or iliac veins, and position of the renal veins. The guide wire provided with the standard filter introduction set has a tendency to catch on the filter as the wire is withdrawn. A stiff wire with a straight, tapered, floppy tip was substituted. The femoral approach is preferred when it is feasible. Though there was only one known occurrence of femoral vein thrombosis at the filter insertion site, other cases may have occurred and may not have been detected. If the frequency of this complication proves to be significant, the preferred route for filter insertion may have to be reconsidered.     

Value of chest radiography in excluding traumatic aortic rupture

A retrospective review of chest radiographs from 205 patients with blunt chest trauma who also underwent aortography was performed. Forty-one of the 205 had aortographically proved aortic rupture. Discriminant analysis of 16 radiographic signs indicated that the most discriminating signs were loss of the aorticopulmonary window, abnormality of the aortic arch, rightward tracheal shift, and widening of the left paraspinal line without associated fracture. No single or combination of radiographic signs demonstrated sufficient sensitivity to indicate all cases of traumatic aortic rupture on plain chest radiographs without the performance of a large number of aortographically negative studies. The bedside anteroposterior "erect" view of the chest proved far more valuable than the supine view in detecting true-negative studies. Despite significant reader variability in the interpretation of the various radiographic signs, in general the analysis confirmed the role of chest radiography in this clinical situation, but suggests that its most beneficial use is in excluding the diagnosis and eliminating unwarranted aortography rather than in predicting aortic rupture.     

Characterisation of renal chloride channel, CLCN5, mutations in hypercalciuric nephrolithiasis (kidney stones) disorders

Mutations of the renal-specific chloride channel (CLCN5) gene, which is located on chromosome Xp11.22, are associated with hypercalciuric nephrolithiasis (kidney stones) in the Northern European and Japanese populations. CLCN5 encodes a 746 amino acid channel (CLC-5) that has approximately 12 transmembrane domains, and heterologous expression of wild-type CLC-5 in Xenopus oocytes has yielded outwardly rectifying chloride currents that were markedly reduced or abolished by these mutations. In order to assess further the structural and functional relationships of this recently cloned chloride channel, additional CLCN5 mutations have been identified in five unrelated families with this disorder. Three of these mutations were missense (G57V, G512R and E527D), one was a nonsense (R648Stop) and one was an insertion (30:H insertion). In addition, two of the mutations (30:H insertion and E527D) were demonstrated to be de novo, and the G57V and E527D mutations were identified in families of Afro-American and Indian origin, respectively. The G57V and 30:H insertion mutations represent the first CLCN5 mutations to be identified in the N-terminus region, and the R648Stop mutation, which has been observed previously in an unrelated family, suggests that this codon may be particularly prone to mutations. Heterologous expression of the mutations resulted in a marked reduction or abolition of the chloride currents, thereby establishing their functional importance. These results help to elucidate further the structure-function relationships of this renal chloride channel.      

Expression of CYP1B1 but not CYP1A1 by primary cultured human mammary stromal fibroblasts constitutively and in response to dioxin exposure: role of the Ah receptor

The expression of CYP1B1 in human mammary fibroblasts (HMFs) was characterized as a potential modulator of their individual function as well as effects on adjacent mammary epithelia. We have used these characteristics to explore the diversity of fibroblast cells isolated from reduction mammoplasty patients and from different breast locations in breast cancer patients (tumors, peripheral to tumor and skin). These parameters have also been used to examine differences between two donors. The results have shown that while none of these HMFs expressed a detectable CYP1A1 protein basally or in response to TCDD, they all expressed CYP1B1 constitutively at similar levels (0.5-0.9 pmol/mg microsomal proteins) and they were induced by TCDD (up to 5-fold) consistent with mediation by the Ah receptor (AhR). DMBA metabolism by HMFs exhibited high proportions of 5,6-, 10,11- and 3,4-dihydrodiols, a profile that is typical of human CYP1B1 regioselectivity. RT-PCR followed by Southern blot analyses demonstrated that CYP1B1 mRNA expression in HMFs parallels levels of respective microsomal proteins. The AhR is expressed in these HMFs as two cytosolic forms (approximately 106 and 104 kDa) and a substantial proportion of the 104 kDa form was localized to the nucleus even prior to TCDD treatment. In all HMFs isolated directly from collagenase digested breast tissues the AhR is expressed at levels 10-fold lower than in breast epithelial cells. However, HMFs that were isolated after serial passaging of mammary epithelial cultures had shown much higher levels of the AhR expression and more dramatic TCDD-induced down-regulation (>80% in 24 h) associated with more efficient nuclear translocation. These differences suggested the presence of two functionally distinct subtypes of HMFs: interstitial stromal fibroblasts that are readily released by collagenase digestion of breast tissues, and lobular stromal fibroblasts which are more tightly associated with the breast epithelia.      

Effect of promoter and intron 2 polymorphisms on murine lung K-ras gene expression

Differences in tumor formation among inbred mouse strains with high (A/J) and low (C3H) susceptibility for lung cancer have been linked to a repetitive element within the second intron of the K-ras gene. The purpose of this investigation was to determine whether differences within the K-ras gene promoter region or the intron 2 polymorphism affect K-ras gene expression in lung tumors and target alveolar type II cells isolated from A/J and C3H mice. Ribonuclease protection assays were performed using RNA isolated from 4-(methylnitrosamino)-1-(3- pyridyl)-1-butanone (NNK)-induced lung tumors from each mouse strain and alveolar type II cells isolated from A/J and C3H mice. An 838 bp fragment of the murine K-ras gene promoter region was amplified by PCR, cloned and sequenced from both mouse strains. Promoter regions from both mouse strains were inserted into a luciferase reporter gene vector, with and without the second intron polymorphism, and transfected into sensitive, intermediate and resistant lung tumor cell lines. No significant differences in K-ras gene promoter activity was found between the two strains using these specific reporter gene constructs. Consistent with these results, levels of K-ras expression did not differ between alveolar type II cells, whole lung or tumors induced by NNK in A/J or C3H mice. Moreover, in lung tumor cell lines derived from mice with differing susceptibility for lung cancer, K-ras expression did not correlate with the growth rate of tumors induced in nude mice from these cell lines. These results indicate that factors involved in modulating the rapid clonal expansion of the mutated K-ras allele from A/J mice are not directly linked to expression of this gene. Other genetic changes or losses in conjunction with hypothesized modifier loci, such as the Par1 locus, must play a significant role in establishing the phenotypic strain differences for lung tumor formation.      

Infant survival in Norway and Sweden 1985–88

In recent years, considerable attention has been attached to the disquieting fact that infant survival is much lower in Norway than in Sweden. In the present study, comprising all live single births in Norway and Sweden during 1985–88, the observed infant mortality was 1.5 times higher in Norway than in Sweden. The largest difference between Norway and Sweden was found in infants of young mothers with high birth order. Thus for the second births of mothers aged less than 20 years the observed mortality ratio of Norway to Sweden was 1.8. The infant mortality ratio decreased with increasing maternal age for all birth orders, and for the second births of mothers aged 35 years or more the mortality ratio was 1.0. The higher infant mortality in Norway was evident throughout the first year of life, with the highest mortality ratio observed at 6–8 months of life. Adjustment for maternal age, birth order and geographical region did not alter the observed infant mortality ratios. In both countries, the highest risk was found among infants of young mothers, This suggests a need for a more extensive preventive health care system directed at young mothers during their pregnancy and the infancy period.     

Children of alcoholics. Predictors for psychopathology and addiction

Children of alcoholics have a higher risk of psychopathology and alcoholism. Therefore, in 1993 the Amsterdam Institute for Addiction Research initiated a study on vulnerability markers and risk factors in children of alcoholics, aimed at identifying predictors for the development of psychopathology and addiction in children of alcoholics. This article provides a summary of the background, rationales and aims of the study. With more specific and sensitive biological vulnerability markers that indicate risk status, more effective preventive interventions might become available. The biochemical part of the study aims at answering the question whether adenylate cyclase is a vulnerability marker for alcoholism. The psychophysiological part is directed at event-related potentials during task performance to clarify the nature of the brain and cognitive functions that may underlie or relate to vulnerability to alcoholism. The third part, the psychological component, aims at possible psychological mechanisms of enhanced risk of addition in children of alcoholics as well as the relationship with childhood psychopathology.     

Accelerated schedule of hepatitis B vaccination in high-risk youth

Objective : To perform a feasibility and immunogenicity study of an accelerated schedule of hepatitis B immunization for high-risk youth.
Methodology : High-risk adolescents attending a youth health centre and nearby youth refuges were immunized with Engerix-B recombinant vaccine, 20 μg intramuscularly, at 0,2 and 6 weeks. Serology was performed prior to immunization and 3 months after the third dose.
Results : Forty-two subjects (27 female) aged 13-20 years entered the study. Two (4.8%), already hepatitis B virus (HBV) seropositive, were excluded. Thirty-six of 40 subjects had one or more risk factors for HBV. Participants were often elusive, needing multiple attempts to establish contact. Twenty (50%) of the 40 completed three immunizations and all 14 studied developed anti-hepatitis B surface titres of > 100mlU/mL (geometric mean titre 630 mIU/mL, 95% confidence intervals 309-1290).
Conclusion : High-risk youth can be immunized against hepatitis B successfully using an accelerated schedule, but compliance is difficult.     

Early-life nutritional and environmental determinants of thymic size in infants born in rural Bangladesh

Aim:  The aim was to assess the impact of nutritional status and environmental exposures on infant thymic development in the rural Matlab region of Bangladesh.
Methods:  In a cohort of N_max 2094 infants born during a randomized study of combined interventions to improve maternal and infant health, thymic volume (thymic index, TI) was assessed by ultrasonography at birth and at 8, 24 and 52 weeks of age. Data on birth weight, infant anthropometry and feeding status were also collected.
Results:  At all ages, TI was positively associated with infant weight and strongly associated with the month of measurement. Longer duration of exclusive breastfeeding resulted in a larger TI at 52 weeks. TI at birth and at 8 weeks correlated positively with birth weight, but by 24 and 52 weeks and when adjusted for infant weight this effect was no longer present. Thymic size was not affected by pre-natal maternal supplementation or by socioeconomic status but was correlated to arsenic exposure during pregnancy.
Conclusion:  In this population of rural Bangladeshi infants, thymic development is influenced by both nutritional and environmental exposures early in life. The long-term functional implications of these findings warrant further investigation.