Combination of interventional pulmonology techniques (Nd:YAG laser resection and brachytherapy) with external beam radiotherapy in the treatment of lung cancer patients with Karnofsky Index < or =50.

PURPOSE: To compare Nd: YAG laser resection with Nd: YAG laser plus brachytherapy and external beam radiotherapy (EBRT) in the palliation of malignant central airway obstruction symptoms due to lung cancer. PATIENTS AND METHODS: In this prospective non-randomized study we evaluated the effects of Nd:YAG laser photoresection alone vs. Nd:YAG laser resection in combination with brachytherapy and EBRT on cough, dyspnoea, thoracic pain, haemoptysis, body weight loss, atelectasis, postobstructive pneumonia, endoscopic findings, disease-free period and survival rate in lung cancer patients. Only patients with Karnofsky index (KI) < or =50 were included. Sixty-four patients were divided into 2 groups: group I patients ( = 20) were treated only with Nd: YAG laser, and group II patients (n = 44) were treated with Nd: YAG laser followed by brachytherapy and EBRT. RESULTS: Group I patients showed statistically significant improvement in all investigated parameters but cough. Group II patients achieved significant improvement in all investigated parameters. Comparative statistical analysis between the 2 groups revealed statistically significant improvement in group II with regard to dyspnoea, haemoptysis, KI and atelectasis. No significant improvement in group II was seen when other investigated parameters were considered. Disease-free period and survival rate were significantly longer in group II (p< or =0.0005). CONCLUSION: The combination of interventional pulmonology procedures with standard modalities is the best option for the treatment of selected lung cancer patients.

[Overweight and obesity prevalence in children and adolescents from a private school in Recife] / Prevalência de sobrepeso e obesidade em crianças e adolescentes de uma escola da rede privada de Recife.

OBJECTIVES: To determine the prevalence of overweight and obesity in students from a private school in Recife; compare the prevalence rates of overweight and obesity in boys and girls and in different age groups (children and adolescents) and verify the correlation between body mass index and triceps skinfold thickness in this population. METHODS: Cross-sectional study with 762 students (332 children and 430 adolescents) from a middle/upper class school in Recife, in 1999. Overweight was defined as body mass index equal or above the 85th percentile for age and gender. Obesity was defined as body mass index and triceps skinfold thickness equal or above the 85th percentile. RESULTS: The prevalence rates were 26.2% (95%CI = 23 to 29%) for overweight, and 8.5% (CI95% = 6.5 to 10.5%) for obesity. Overweight was more prevalent among children (34.3%) than among adolescents (20.0%) (P<0.001). Obesity was more frequent among children (14.2%) than among adolescents (4.2%) (P<0.001). The prevalence of overweight in boys (34.6%) was higher than in girls (20.6%) (P<0.001). The prevalence of obesity was also higher in boys (14.7%) than in girls (4.4%) (P<0.001). The correlation coefficient between body mass index and triceps skinfold thickness was equal to 0.64 (95%CI = 0.60 to 0.68). CONCLUSIONS: The prevalence of overweight in our study population was as high as that found in industrialized countries; obesity, however, was less frequent.

[Anatomic variations of the coronary arteries]. / Contribuição ao estudo das variações anatômicas das artérias coronárias.

PURPOSE: To study the coronary arteries and their main branches showing the aspects of source, trajectory and anastomoses of these vessels at the subepicardial level. METHODS: The study was carried out on 110 adult human hearts, of both sexes, fixed in 10% formaldehyde solution. The pericardium was removed to expose the coronary arteries and their branches at the subepicardial level. RESULTS: In 38.18% of the cases the left coronary artery presented a trifurcation into anterior interventricular, circunflex and left marginal branches (35.70%) and into anterior interventricular, circunflex and lateral branches (64.30%). In 60% of the hearts examined, the left coronary artery presented a bifurcation into anterior interventricular and circunflex branches. In 1.82% of the cases these two branches arise directly from the aorta. An anastomosis, at the subepicardial level, between the anterior and posterior interventricular branches was observed in 56.36% of the hearts. In 88.18% the posterior interventricular branch arised from the right coronary artery, whereas in 11.82% this vessel arises from the circunflex branch. Anastomoses between the right coronary artery and the circunflex branch were found in 10% of the hearts (crux cordis). The dominance of the right coronary artery was present in 69.09% of the cases, of the left coronary artery in 11.82% and in 19.09% of the hearts had balanced distribution. CONCLUSION: The coronary arteries and their main branches present a great quantity of variations with regard to source, trajectory and anastomoses. This knowledge is important for the interpretation of coronary angiography and surgical myocardial revascularization.

Possible involvement of the chromosome region 10q24----q26 in early stages of melanocytic neoplasia.

A recent report described a translocation involving 10q24 in a compound nevus. We have examined our series of melanocytic tumors ranging from common nevi to metastatic melanomas with the following results. In 24 nevi (congenital or common acquired), no karyotypically abnormal clones were found. Two of 10 dysplastic nevi had abnormal clones: one had an unidentified marker chromosome, the other had a t(9;10)(p24;q24) translocation. Of the three complex primary melanomas studied (lesions with both radial and vertical growth phase present), one had a t(10;?)(q26;?) and one showed a loss of chromosome 10. Among 51 advanced melanomas (primary and metastatic), all but one had multiple alterations, and 18 of these had lost one or more copies of chromosome 10. The one invasive melanoma without multiple abnormalities had a complex three-way rearrangement: 46,XY,t(5;6;10) with breakpoints on chromosome 10 at both q23 and q25. These data support the view that the terminal region of 10q may harbor one or more genes involved in the early stages of melanocytic neoplasia.

A t(1;19) chromosome translocation in three cases of human malignant melanoma.

Abnormalities of chromosome 1, including trisomy for all or a portion of the long arm, have been frequently reported in many cancers. Anomalies of chromosome 19 are far less common, although a t(1;19)(q23;p13) translocation has been reported in association with pre-B-cell leukemia. We have observed a t(1;19)(q12;p13) translocation in three cases of advanced melanoma, with the translocation chromosome representing an extra dose of 1q in each instance. The breakpoint on 1q was within the centromeric heterochromatin, proximal to the site in pre-B-cell leukemia, but the breakpoint on 19p appeared identical. The gene for human insulin receptor has recently been mapped to this region of chromosome 19 (p13.2-13.3). This gene shares structural and sequence homologies with the epidermal growth factor receptor (erb-B oncogene) and members of the src family of oncogenes, suggesting that alterations in the insulin receptor, resulting from chromosomal translocation, could lead to a role in tumorigenesis. The present findings may permit this possibility to be examined in a neoplasm of neuroectodermal origin.

Karyotypic evolution in human malignant melanoma.

Chromosome studies were performed on direct preparations, early passage cultures, and cell lines derived from melanocytic lesions of 37 patients. There were six congenital or common acquired nevi, six dysplastic nevi, one early primary melanoma (radial growth phase), three complex melanomas (RGP with foci of vertical growth phase), six advanced primary melanomas (VGP), and 26 metastases. The karyotype was normal in the six common nevi. A chromosomally abnormal clone with a single karyotypic alteration was found in two dysplastic nevi. All melanomas had clones with multiple cytogenetic changes. Nonrandom abnormalities involving translocations or deletions in the short arm of chromosome #1, either arm of chromosome #6, and/or extra copies of the short arm of chromosome #7 were present in all melanomas. These were not obviously associated with a particular stage of disease, except that the only nonrandom alteration in the early (RGP) melanoma involved chromosome #6. In four cases, cytogenetic data were available on both a primary melanoma and its metastases. In each instance there were common alterations (demonstrating the clonality of the disease), as well as additional changes in the metastases. Our findings indicate that demonstrable somatic genetic abnormalities increase in severity with clinical progression of melanocytic disease, but additional data are required to establish the significance of specific karyotypic changes (and the involved genes) in the clinical evolution of these disorders.

Characteristics of cultured human melanocytes isolated from different stages of tumor progression.

Normal melanocytes and melanocytes of normal nevi, primary melanoma in the radial (RGP) and vertical (VGP) growth phases, and metastatic melanoma exhibited and maintained phenotypic differences when grown in tissue culture or in experimental animals. Only metastatic and VGP primary melanoma cells were tumorigenic in athymic nude mice and had nonrandom chromosomal abnormalities involving chromosomes 1, 6, and 7. The colony-forming efficiency in soft agar was also highest in these two cell types. A cell line of RGP primary melanoma had characteristics of both benign and malignant cells: nevus-like morphology; nontumorigenicity in nude mice; but karyotypic abnormality of chromosome 6. It also had a ganglioside pattern similar to that of normal melanocytes but not melanomas, i.e., a high GM3 ganglioside content compared to the amounts of GM2, GD2, and GD3 gangliosides. Binding of monoclonal antibodies secreted by hybridomas generated by immunization of mice with VGP primary and metastatic melanoma was highest with cells and supernatants of cultures from advanced melanoma and least with nevus cells. There was no binding to normal melanocytes except with the monoclonal antibodies specific for nerve growth factor receptor or 9-O-acetyl-GD3 ganglioside. On the other hand, monoclonal anti-nevus antibodies bound to melanocytes, nevus cells, and RGP primary melanoma cells but not to VGP primary or metastatic melanoma cells. Cultured human melanocytic cells appear to be a unique model for the study of tumor progression.

N-myc amplification in multiple homogeneously staining regions in two human neuroblastomas.

Molecular characterization of two human neuroblastoma cell lines has revealed that both contain multiple homogeneously staining regions (HSRs), each representing a chromosome site of N-myc amplification. The newly established cell line CHP-382/JK had two cytogenetically distinct populations with several identical chromosomal abnormalities, indicating a common progenitor cell. Each population had one HSR, one on chromosome 5 at q31-34 and the other on chromosome 2 at q31-32. Chromosomal in situ hybridization with the N-myc probe pNb-1 demonstrated that both HSRs contained amplified copies of N-myc. Southern blot analysis confirmed amplification of N-myc sequences in genomic DNA of CHP-382/JK. Chromosomal features of CHP-382/JK shared with other neuroblastoma cell lines were the deletion of 1p and the presence of extra 17q material. In addition, the cells were highly reactive to monoclonal antibody PI 153/3 used to identify human neuroblastoma. CHP-382/JK cells were further characterized as neuronal cells by the expression of neurotoxin-responsive Na+ channels. Another neuroblastoma cell line, CHP-134, contained a single cell population with three HSRs, one in the short arm of each chromosome 7 and one in the long arm of a chromosome 6. All three HSRs contained amplified copies of N-myc as shown by in situ hybridization with the N-myc probe pNb-1. One of the 7p HSRs was acquired during culture of CHP-134 cells, whereas the 2q HSR of CHP-382/JK was lost. Such findings highlight the continued process of N-myc amplification and transposition in vitro. To our knowledge, amplification of N-myc in multiple HSRs has not been documented previously in neuroblastoma cell lines.

Expression of the receptor for epidermal growth factor correlates with increased dosage of chromosome 7 in malignant melanoma.

Epidermal growth factor (EGF) receptor is expressed selectively by human melanoma cells which show the presence of an extra copy of chromosome 7. None of the cells of benign pigmented lesions (nevi) or radial growth phase (nonmetastatic) primary melanoma expressed EGF receptor and none of these cells showed an extra copy of chromosome 7. The results indicate that a single extra dose of a gene (for EGF receptor) may provide a selective advantage to cells in the late stages of tumorigenesis.

Primary melanoma cells of the vertical growth phase: similarities to metastatic cells.

Three primary and 16 metastatic melanoma cell lines were established from primary and metastatic lesions of 4 patients with malignant melanoma. Comparison of metastatic melanoma cells with cells of the vertical growth phase (VGP) or late primary melanoma from the same individual revealed, generally, a shorter population-doubling time, growth to a higher cell density, higher tyrosinase activity, and more pigmentation in metastatic cells. Conversely, primary and metastatic melanoma cells had similar morphology, plating efficiency, and tumorigenicity in nude mice. Karyotypic analysis revealed clonality and nonrandom abnormalities in chromosomes 1, 6, and 7 in cells of the primary and metastatic lesions of the 3 patients studied. Few differences were found in the expression of melanoma-associated antigens on short-term and long-term cultured cells by tests with monoclonal antibodies in mixed hemadsorption assays, flow cytometry, and radioimmunoassays. Our results indicate that cells cultured from the VGP but not from the radial growth phase of primary melanoma are similar to metastatic melanoma cells.

Human neuroblastomas and abnormalities of chromosomes 1 and 17.

Structural rearrangements of chromosome 1p have been reported previously as a frequent finding in human neuroblastomas. In a review of karyotypes from 35 neuroblastomas (including 29 published cases and 6 unpublished tumors and cell lines), it was found that, in addition to the abnormalities of chromosome 1p (found in approximately 70% of cases), abnormalities involving only 2 other chromosome segments occurred with significant frequency (in 20% or more of cases) in this cancer. These abnormalities involved trisomies for the long arms of chromosomes 1 and 17. In addition, two novel cytogenetic aberrations, homogeneously staining regions and double minutes, were identified in two-thirds of the cases. It is postulated that the gene change(s) produced by the abnormalities of chromosome 1p in neuroblastoma play a primary role in the development of this cancer. The gene changes produced by the abnormalities of chromosomes 1q and 17q and by the homogeneously staining regions and double minutes are presumed to contribute to tumor progression.

Cytogenetics of human malignant melanoma and premalignant lesions.

Chromosome studies were done on direct preparations, early passage cultures, and/or cell lines derived from melanocytic lesions of 17 patients. There were 5 nevi (3 dysplastic); 1 early primary melanoma (radial growth phase); 1 advanced primary melanoma (vertical growth phase) with multiple metastases; and 10 metastatic lesions. The 5 nevi had normal karyotypes, while each of the tumors had a predominantly abnormal karyotype. The early melanoma was pseudodiploid, including a 6p;22 translocation. Ten of the 11 advanced melanomas had one or more aberrations involving chromosome #1, with 9 having deletions or translocations of lp that involved the proximal segment 1p12----1p22 9 times in 8 lesions. Six advanced tumors had additional material involving 7q, including extra #7s (4 cases) and 7q+ (2 cases). Nine melanomas, including the early tumor, had alterations in chromosome #6. Three had additional copies of 6p (as iso6p or t6p); the others showed no consistent pattern. In one advanced tumor, the primary lesion and 5 metastases (removed seriatim over an 18-month period) had nearly identical karyotypes, indicating the clonal nature of the neoplasm. The nonrandom cytogenetic changes suggest that genes important in melanoma carcinogenesis are located on the proximal portion of 1p, on 7q, and on chromosome #6. More data on early lesions are needed to identify the relation of these various cytogenetic changes to the different stages of malignant melanoma development.

The 13p HSR in a human neuroblastoma cell line does not contain rRNA genes.

We have studied a human neuroblastoma cell line containing a homogeneously staining region (HSR) on the short (p) arm of chromosome #13. The HSRs are believed to represent sites of gene amplification, containing multiple copies of one or a small number of genes. The 18S and 28S ribosomal RNA genes are the only structural genes so far assigned to the p arms of the human acrocentric chromosomes, which include number #13. Using two recombinant DNA probes specific for sequences in the 18S/28S ribosomal RNA (rRNA) gene complex for in situ hybridization, we have been able to establish that the 13pHSR in this line does not contain rRNA genes.

Phenotypic characteristics of cells derived from precursors of human melanoma.

Of 66 specimens from benign melanocytic nevi, including common acquired and congenital nevi, Spitz tumors (epithelioid cell nevi), and melanocytic nevi with dysplasia, 57 could be grown in tissue culture. The cultured cells were identified as melanocytes by the presence of premelanosomes and melanosomes. Cells from 28 of 32 nevus cultures grew in an anchorage-independent way in soft agar with a colony-forming efficiency between 0.001 and 1%. Clones derived from single cells and soft agar-selected colonies showed marked phenotypic heterogeneity, but all had a limited life span and did not undergo transformation in culture. These cells were nontumorigenic in nude mice. Cultured nevus cells expressed antigens present on melanoma but absent on normal fibroblasts and/or melanocytes as tested with monoclonal anti-melanoma antibodies. The anti-melanoma antibodies bound equally well to dysplastic, congenital, and common acquired nevi. Antigens are released by nevus cells similar to melanoma cells.

Homogeneously staining regions and double minutes in a human cell line: chromatin organization and DNA content.

Homogeneously staining regions (HSR) and double minutes, two novel chromosome abnormalities, are believed to represent sites of gene amplification. The basic organization of chromatin in an HSR in a human neuroblastoma cell line was shown, by electron microscopy, to be similar to that in a normal chromosome. Double minutes from another human neuroblastoma cell line were found, by dry mass determination, to contain an average of 1.41 X 10(-14) g DNA. This quantity corresponds to 6.38 X 10(3) kilobase DNA per double minute.

Homogeneously staining regions and tumorigenicity.

A homogeneously staining region (HSR), a chromosome abnormality associated with gene amplification, was found to increase in length coincident with an enhancement in tumorigenicity when cells from a human retinoblastoma cell line were serially passaged in athymic (nu/nu) mice.

Abnormalities of chromosome 1p in human neuroblastoma tumors and cell lines.

Specific constitutional chromosome rearrangements have been described in a small number of individuals with two solid childhood tumors, retinoblastoma and Wilms' tumor. On the basis of these observations, a causal relationship between these chromosome abnormalities and tumorigenesis has been postulated. Though a specific constitutional chromosome abnormality has yet to be reported in association with neuroblastoma, another childhood tumor, we now confirm the involvement of a particular chromosome segment in structural abnormalities in cells from this tumor. Deletions or rearrangements of chromosome 1p were found in preparations from four of six neuroblastomas from individuals with normal constitutional karyotypes and in three of four permanent neuroblastoma cell lines. Structural abnormalities resulting in the loss or rearrangement of material from 1p (with the most frequent break point being 1p32 and with all rearrangements involving the apparent loss or rearrangement of material distal to 1p31, always including 1p34 to 1pter), represent the single most common class of chromosome aberrations in neuroblastoma. This suggests that the distal portion of 1p contains at least one gene involved in the development of neuroblastoma.

Abnormalities of chromosome #13 in retinoblastomas from individuals with normal constitutional karyotypes.

Constitutional chromosome abnormalities have been associated with retinoblastoma, Wilm's tumor, and a familial form of renal carcinoma. For each tumor type, the particular chromosome segment involved in the observed rearrangements is different: in retinoblastoma, that segment is band q14 on chromosome #13. We now present evidence that in retinoblastoma, structural abnormalities involving the particular chromosome segment identified in the constitutional cases can also occur in the tumors of individuals with normal constitutional karyotypes. Six cases with retinoblastoma in one or both eyes were analyzed; deletions/rearrangements involving 13q14 were found in the tumor cell karyotypes of five of the six. These observations suggest that changes in a gene or genes at a common site (13q14) play a role in tumorigenesis in all forms of retinoblastoma, sporadic as well as heritable.

Homogeneously staining regions in direct preparations from human neuroblastomas.

Previous descriptions of homogeneously staining regions in human neuroblastomas have been in karyotypes obtained from established cell lines. We now report homogeneously staining regions in direct preparations from two human neuroblastomas. In one of the cases, the homogeneously staining region identified in the primary tumor was also found in metastases to bone marrow and pleural fluid. The homogeneously staining region is, therefore, not an artifact of growth in vitro.