An interstitial tandem duplication of 9p23-24 coexists with a mutation in the BRCA2 gene in the germ line of three brothers with breast cancer.

Germ-line mutations of the BRCA2 gene account for the majority of families with both male and female breast cancer. However, among independently ascertained families with the same mutation, cases of male breast cancer often appear to cluster in a single family or in a particular branch of one family. This suggests that the risk of male breast cancer conferred by BRCA2 mutations may be modified by other genetic or environmental factors. We report a family in which three brothers with breast cancer carry in their germ line two genetic abnormalities: an insertion A at nucleotide 2041 in exon 10 of BRCA2, which leads to premature termination of the encoded protein at codon 615, and a tandem interstitial duplication involving chromosome bands 9p23-24. We propose that the coexistence of this rare chromosomal abnormality with BRCA2 mutation may be augmenting the risk of male breast cancer conferred by the BRCA2 mutation.

Deletion mapping defines different regions in 1p34.2-pter that may harbor genetic information related to human colorectal cancer.

Cytogenetic and molecular analyses of colorectal cancer cells have revealed deletions at 1p as prominent alterations, suggesting that genetic information on the short arm of chromosome 1 has a role in tumorigenesis. In this study we have used 33 microsatellite markers to fine map deletions at 1p in primary colorectal carcinomas. We found 1p-deletions in 84% of the cases (31/37). High frequencies of loss of heterozygosity (LOH), often the result of small independent interstitial deletions in the same tumor, defined three regions, that may harbor genetic information relevant for colorectal cancer: (i) region A between D1S243 and D1S468 (7cM; 1p36.3); (ii) region B between D1S436 and D1S199 (7cM; 1p35.1-36.31) and (iii) region C between D1S496 and D1S255 (1cM; 1p34.2-35). In addition we identified seven cell lines with LOH at 1p, all of which have deletions that span at least from the distal border of region A to the proximal border of region C.

Secretory type II phospholipase A2 (PLA2G2A) expression status in colorectal carcinoma derived cell lines and in normal colonic mucosa.

There is good evidence now that the secretory type II phospholipase A2 (Pla2g2a) gene represents the Mom1 locus, a genetic modifier of tumor resistance in the multiple intestinal neoplasia (Min) mouse. Previously we have mapped the human homolog PLA2G2A to 1p35-36.1 within a region that is the target of frequent deletions in sporadic colorectal tumors. Here we show 64% loss of heterozygosity (LOH) at the PLA2G2A locus in primary tumors. We studied PLA2G2A expression in both colorectal tumor cell lines and normal mucosa. Most of the lines lacked detectable PLA2G2A transcripts by Northern analysis. Large differences in expression were seen among normal mucosa of different patients with sporadic tumors. We analysed the coding region of PLA2G2A in eight colorectal cancer cell lines with hemizygous deletion at 1p35-36/PLA2G2A, in none we did detect a mutation. Biallelic expression of PLA2G2A was observed in a cell line heterozygous for an exon 3 polymorphism, rendering unlikely that imprinting is a pathway participating in the loss of PLA2G2A function. It remains uncertain if PLA2G2A, in particular its apparent lack of expression in tumor cells, might be a factor in human colorectal tumorigenesis.

Amplification of satellite DNA at 16q11.2 in the germ-line of a patient with breast-cancer.

Cytogenetic analyses of peripheral blood cells of breast cancer patients unveiled in one case a grossly enlarged G-band in one copy of chromosome 16 (16qh+), which scored also strongly positive in C-banding. Fluorescence in situ hybridization with both a total chromosome 16 library and with probe pHuR195 detecting locus D16Z3 further documented the increase of the copy number of the corresponding satellite DNA at 16q-11.2. Slot-blot analyses with pHuR195 revealed an approximately 10-fold amplification compared to a random selection of normal chromosomes 16. The chromosome 16 carrying amplified DNA is passed on to one of 3 children, who shows no obvious anomaly. Previous studies (Kokalj-Vokac N, Alemeida A, Gerbault-Seureau M, Malfoy B, Dutrillaux B: Gene Chromosome Cancer 7: 8-14, 1993) had revealed that satellite DNA in chromosome 16 often participates in interchromosomal recombinations, preferentially with chromosome 1, in breast cancer cells. Although the increased copy number of satellite DNA could represent a polymorphism, it might provide an enlarged target for recombination events and therefore could be a determinant for cancer predisposition.

Intracompartmental pressure during hyperthermic isolated limb perfusion for melanoma and sarcoma.

Side effects of isolated limb perfusion (ILP) include rhabdomyolysis, paresthesia, or nerve palsy. The increase in intracompartmental pressure during ILP is thought to be linked to neuro- and muscular toxicity, and fasciotomy is recommended for protection. In 24 patients, intracompartmental pressure was measured. A flexible 5 F probe was placed into the non-tumour-bearing compartment of the perfused limb. Interstitial fluid pressure was measured using a piezoresistant tip. Compartmental pressure values were continuously recorded during and after ILP. The drugs used were a combination of doxorubicin, cisplatinum and melphalan or rhTNF-alpha combined with melphalan. The median overall compartmental pressure prior to ILP was 13 mmHg (range: 11-21 mmHg); during the heat-up phase the median pressure rose to 28 mmHg. During therapeutic perfusion a further increase could be documented and the maximum pressure measured was 90 mmHg; the median of the pressure maxima of all patients was 34 mmHg. During wash-out, at the end of the perfusion, a clear reduction in compartment pressures could be observed and the median dropped to a value of 27 mmHg. In all patients a continuous decrease in compartmental pressure could be recorded, reaching the pre-ILP values by 48 h post-operatively. A dramatic increase in compartmental pressure during ILP can be observed by continuous monitoring. Because of our observation that during the wash-out phase elevated compartmental pressures return to normal, there is no general indication for a fasciotomy. However, for patients maintaining a peak compartmental pressure above a critical threshold of 35 to 40 mmHg fasciotomy may be indicated.

Expression of CD44 standard and isoforms in human breast cancer xenografts and shedding of soluble forms into serum of nude mice.

Standard CD44 (CD44s) and variant isoforms (CD44v) are expressed on different malignant cells and tissues. Their upregulation has been implicated, in the progression and metastasis of malignomas. In this work we addressed the question of whether these molecules are also expressed on xenografted human breast carcinomas and if certain expression patterns are correlated with biological parameters like tumour size, hormone receptor status, histology, growth rate, chemoresistance and microenvironment. Additionally, we were interested in the shedding of soluble CD44 (sCD44) into the blood circulation of tumour bearing nude mice. The human breast carcinomas MCF-7, MCF-7/ADR, 4296 and MDA-MB435, 4134 and 4151 were transplanted subcutaneously (sc.) or into the mammary fat pad (mfp.) of nude mice. The expression of the CD44s, -v6, and -v9 isoforms was determined at different time points on tissue samples by immunohistochemistry or RT-PCR employing human-specific antibodies or primers, respectively. The serum concentration of CD44s and -v6 was measured by human specific ELISAs. All tumours expressed CD44s. The lowest level was observed in the MCF-7 cancer. The CD44v6 and -v9 sequences and epitopes were distinctly expressed in MCF-7/ADR. MDA-MB435, 4134, 4151 and 4296, while MCF-7 lacked these isoforms. The highest serum concentration of the v6 isoform was detected in mice bearing the tumour 4296 with a high tendency for lymphogenic metastasis. The serum levels of sCD44 were in 5/6 xenografts linearly correlated with the tumour size. Interestingly, there was a remarkable difference between the two sublines MCF-7 and MCF-7/ADR: Both the tissue and serum levels of CD44 isoforms indicated that the development of multidrug resistance is accompanied by an alteration in the expression of membrane proteins discussed to be involved in metastasis. There was no relation of tissue expression with the transplantation site and the hormone receptor status of the tumour lines. CD44s and its variant isoforms are expressed in human xenotransplanted breast cancers in very different levels and patterns. The highest expression in the tumour 4296 is related to lymphogenic metastasis while the absence of isoforms in the model MCF-7 is related to non-metastatic behaviour. CD44 is shed into the serum and can be used for monitoring of tumour growth.

Faculty perceptions of teaching on television: one school's experience.

Videoteleconferencing (or teaching on television) represents a means of growing importance for distant learners to gain greater access to nursing education. Research has identified a number of key issues for nurse educators to consider related to videoteleconferencing: teaching/evaluation strategies, faculty workload, rewards and incentives, and support structures. The authors conducted an evaluation survey using a case study approach aimed at describing the perceptions of a convenience sample of faculty members (n = 17) regarding their recent television experiences. The survey, conducted by means of a mailed questionnaire, examined perceptions centering on sources of support, reception site logistics, rewards teaching strategies, and future directions. Key findings included: overall, respondents perceived television teaching positively; reception site, administrative support, and peer support were important to faculty; additional preparation time was required for television teaching; teaching on television required changes in style and pedagogical strategies; and student-teacher interactions were affected by the medium. Findings have implications for the implementation of videoteleconferencing operations, recruitment of faculty for television teaching, and evaluation of videoteleconferencing operations.

Child psychiatric nursing. Moving into the 21st century.

Changes in health care policy must be made to pave the way for the appropriate treatment and prevention of child and adolescent mental health problems. Nurses can provide the leadership needed to make the changes. Organizations such as the Association for Child and Adolescent Psychiatric Nurses and the Society for Education and Research in Psychiatric/Mental Health Nursing are already making important contributions. Challenges in the arenas of treatment, education, and research are before us in child psychiatric nursing. We are facing these demands, however, and are moving forward into the twenty-first century.

The use of seclusion is not evidence-based practice.

TOPIC: Published articles on the use of seclusion in psychiatric care. PURPOSE: To present the argument that the use of seclusion in the psychiatric care of children is not evidence-based practice. SOURCES: Review of the scientific study literature of the last 30 years on the use of seclusion. CONCLUSIONS: The scientific evidence available illustrates that the use of seclusion with children is not therapeutic and is, in fact, harmful to patients.

Factors in childhood drug and alcohol use: a review of the literature.

TOPIC: Drug and alcohol use in children. PURPOSE: To identify the prevalence of drug and alcohol use in children 12 and younger and the factors associated with this use. SOURCE: A review of the literature. CONCLUSIONS: The identified factors include: a) differences in use between boys and girls; b) influence of family members' drug and alcohol use; c) influence of peers; d) the child's self-esteem; and e) the child's knowledge about drug and alcohol use. Awareness by child psychiatric nurses of the identified factors is crucial to prevent, assess, and treat the problem of drug and alcohol use by children.

Two weeks post-death report by parents of siblings' grieving experience.

Nurses who work with children and families need to be aware of the impact that the death of sibling has on children. Although many children have experienced losses, the loss of a sibling of course has a tremendous affect. Nurses must educate parents and children about death and the affect on the entire family. Siblings should be involved in the communication about the impending death and in the funeral arrangements. Open communication between the dying child, the siblings and the parents is very important. Young children will have different needs than older children because of their difficulty in understanding the finality of death. It is natural for parents to try to protect their children from unpleasant experiences such as death and dying. Research supports the dying process including the funeral. Children and their families need support through out the dying experience including follow up after the actual death. They need to be assured that their feelings and actions are common to others that have suffered a significant loss.