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Biomedical subjects

S Lai

Publications and source records attributed to S Lai.

At least 109 records · Page 6Linked to original sources

Predictors of general quality of life in patients with benign prostate hyperplasia or prostate cancer.

PURPOSE: Studies in disease specific populations have emphasized disease specific quality of life with little study of general quality of life. Furthermore, studies of general quality of life in disease specific populations have mostly examined the importance of disease specific variables, and have generally yielded poor correlations of such variables and general quality of life. We attempted to model the emotional component of general quality of life in patients with prostate disease. MATERIALS AND METHODS: We integrated prospectively collected disease specific and nonspecific clinical and self-reported patient data. We also applied neural network and more conventional statistical tools to examine the relative use of various available analytical methodologies in modeling general quality of life. RESULTS: Neural networks created reasonably good models of the emotional component of general quality of life. Logistic regression analysis also created reasonably good models and, given current computational schemes, allowed for identification of significant inputs in the models more readily than did the feed-forward, back propagation neural networks. All models of general quality of life relied primarily on disease nonspecific inputs, including social support, activities of daily living and coping. CONCLUSIONS: Our observations suggested that efforts to optimize general quality of life in patients with prostate disease must integrate disease nonspecific variables.

Humans↗

Reliability of Spanish translations of select urological quality of life instruments.

PURPOSE: Many patients with urological disease do not speak English. In medical studies restricting patients to those who speak only English undermines efforts to understand disease because restrictions decrease efficiency of patient recruitment, and because language and culture are associated with variable outcomes. In Spanish speaking locations, such as South Florida, studies would suffer severe selection bias if patients were required to speak English. To allow grouping in future studies of English and Spanish speaking patients we examined the English-Spanish reliability of select instruments that measure health related quality of life in patients with urological disease. MATERIALS AND METHODS: We assembled available Spanish versions and translated English versions of questions regarding satisfaction, the American Urological Association symptom index, the University of California, Los Angeles Prostate Cancer Index and a pain inventory. We then examined English-Spanish reliability by asking bilingual men 50 years old or older to complete English and Spanish versions at the same sitting. A convenience sample was recruited from outpatients and volunteers at the Miami Veterans Affairs Medical Center and population based subjects living in largely Hispanic Hialeah, Florida. Reliability estimates were calculated with kappa coefficients for categorical data and intraclass correlation coefficients for quantitative data. RESULTS: A total of 100 subjects a median of 59 years old completed the questionnaire, including 55 born in Puerto Rico or Cuba, while the remainder were born at various sites throughout the Americas and Spain. Reliability estimates showed that kappa = > 0.81 for almost all items. For 2 items relating to health and social interactions reliability was poor, and stratification showed that poor reliability was primarily a feature of subjects in good health who are theoretically socially active. CONCLUSIONS: Almost all items tested have excellent English-Spanish reliability in a mixed sample of bilingual men. Nonreliability of 2 items relating to health and social interactions probably originates from the effect of language on perception, and invalidates English and Spanish grouping of these items. Because the sample represents many dialects of Spanish, the translations tested may be transported to other cities. In studies that use these instruments investigators can reasonably group answers from English and Spanish speaking study subjects or study the effects of acculturation on quality of life.

Hispanic or Latino↗

Variation in prostate cancer survival explained by significant prognostic factors.

PURPOSE: Traditional survival analytical tools do not reveal the ability of significant prognostic factors to predict (that is, explain variation in) survival. We used survival data in patients with prostate cancer to illustrate how the association of factors with survival diverges from their ability to explain variation in survival; bladder cancer was included as a point of general comparison. MATERIALS AND METHODS: We used the 1973 to 1990 records of the Surveillance Epidemiology and End Results program. Multivariate proportional hazards models were used to identify factors that significantly associated with survival. The proportion of variation explained by these factors was estimated with the Schemper method. RESULTS: The dataset included 10,636 patients with prostate cancer and 1,070 with bladder cancer. Median survival was significantly longer in prostate than bladder cancer; other characteristics were similarly distributed. Age, stage and marital status were associated with survival in both cancers (p value range 0.0001 to 0.0009). The total proportion of variation explained was 7.1% and 32.1% for prostate and bladder cancer, respectively. In prostate cancer, age, stage and marital status explained 0.6, 5.5 and 0.4%, of the adjusted proportion of variation explained, respectively, and in bladder cancer, they explained 14.7, 8.9 and 0.6%, respectively. CONCLUSIONS: Proportional hazards models identified but did not reveal the ability of significant prognostic factors to explain variations in survival. The proportion of variation explained analyses illustrate why predicting survival is so difficult, especially in prostate cancer. The prognostic factors used do not possess the ability to explain variation in survival; new prognostic factors must be identified.

Aged↗

[Nonsteroidal anti-inflammatory agents: their topical use in the treatment of xerophthalmia secondary to Sjögren's syndrome].

The authors, in a case-control study, analyzed the topical application of nonsteroidal anti-inflammatory drug (flurbiprofene drops) in patients affected by keratoconjunctivitis sicca in Sjögren's syndrome. The variation of break-up-time values, and xerophthalmia grade were analyzed. A mild increase of mean values of break-up-time (two seconds in the treated group), and a mild decrease of xerophthalmia grade were found.

Administration, Topical↗

Methylation, a major mechanism of p16/CDKN2 gene inactivation in head and neck squamous carcinoma.

We studied 11 head and neck squamous carcinoma (HNSC) cell lines and 46 primary tumors for p16 gene status by protein, mRNA, and DNA genetic/epigenetic analyses to determine the incidence, the mechanism(s), and the potential biological significance of its inactivation. Of the 11 cell lines, only 1 showed intact p16 and 10 lacked its protein and mRNA; DNA analysis of these 10 cell lines showed 2 homozygous deletions, 6 methylations at exon 1 and 2, and 2 with no detectable abnormalities. In primary tumors, 16 (34.7%) of the 46 showed detectable p16 protein and mRNA; of these, 12 had no DNA abnormalities and 4 had only exon 2 methylation. Loss of p16 expression was found in three tumors with concurrent mutation at exon 2 and methylation at exon 2 (two) and both 1 and 2 (one). Of the 30 tumors that lacked p16 protein, 27 also lacked mRNA, 1 had detectable p16 mRNA, and 2 failed RT-PCR amplification. Twenty-two of the thirty tumors showed DNA alterations and eight manifested no abnormalities; DNA alterations comprised 6 homozygous deletions, 2 concurrent mutations and methylation of exon 2, and 13 with methylation at exon 1 and exons 1 and 2 (12 with methylation only and 1 with mutation) at exon 1. Except for patients' gender (P = 0.02), no significant correlation between p16 and clinicopathological factors was observed. We conclude that in HNSC 1) intragenic p16 alterations are infrequent events, 2) methylation of exon 1 constitutes a common mechanism in silencing the p16 gene, 3) p16 inactivation may play an important role in the early development and progression of HNSC, and 4) no association between p16 alterations and conventional clinicopathological factors was noted in this cohort.

Adult↗

Human trophoblast and choriocarcinoma expression of the growth factor pleiotrophin attributable to germ-line insertion of an endogenous retrovirus.

Retroviral elements are found in abundance throughout the human genome but only rarely have alterations of endogenous genes by retroviral insertions been described. Herein we report that a human endogenous retrovirus (HERV) type C is inserted in the human growth factor gene pleiotrophin (PTN) between the 5' untranslated and the coding region. This insert in the human genome expands the region relative to the murine gene. Studies with promoter-reporter constructs show that the HERV insert in the human PTN gene generates an additional promoter with trophoblast-specific activity. Due to this promoter function, fusion transcripts between HERV and the open reading frame of PTN (HERV-PTN) were detected in all normal human trophoblast cell cultures as early as 9 weeks after gestation (n = 7) and in all term placenta tissues (n = 5) but not in other normal adult tissues. Furthermore, only trophoblast-derived choriocarcinoma cell lines expressed HERV-PTN mRNA whereas tumor cell lines derived from the embryoblast (teratocarcinoma) or from other lineages failed to do so. We investigated the significance of HERV-PTN mRNA in a choriocarcinoma model by targeting this transcript with ribozymes and found that the depletion of HERV-PTN mRNA prevents human choriocarcinoma growth, invasion, and angiogenesis in mice. This suggests that the tissue-specific expression of PTN due to the HERV insertion in the human genome supports the highly aggressive growth of human choriocarcinoma and possibly of the human trophoblast.

Amino Acid Sequence↗

The Tat and C2-V3 envelope genes in the molecular epidemiology of human immunodeficiency virus-1.

In this study HIV-1 proviral DNA sequences derived from 201 clones of the C2-V3 env region and the first exon of tat were obtained from six HIV-1-infected heterosexual couples. These molecular data were used to confirm the epidemiological relationships. The ability of the molecular data to draw such conclusions was also tested. A bootstrap parsimony analysis of the C2-V3 sequences showed one couple failed to cluster and only two couples clustered in more than 70% of the replicates. The rapid diversification of the C2-V3 region and the length of time that elapsed since the infection event may have limited the certainty of the conclusions that can be reached to infer epidemiological relatedness from this region. Using data from the tat region, all couples clustered, four of them in more than 80% of bootstrap replicates. A single clone from the tat region did not cluster with others from that patient or with those from that patient's partner, indicating that multiple clones are necessary to firmly establish phylogenetic linkage. Nevertheless, the tat region was much more useful in establishing epidemiological relationships among this group than the commonly used C2-V3.

Amino Acid Sequence↗

Improving the temporal resolution of functional MR imaging using keyhole techniques.

Using a keyhole technique, it is shown that the data acquisition rate of gradient-echo imaging for functional MRI (fMRI) studies can be increased substantially. The resulting enhancement of the temporal resolution of fMRIs was accomplished without modifying the hardware of a conventional MRI system. High spatial resolution fMRI images were first collected with conventional full k-space acquisition and image reconstruction. Using the same data set, simulation reconstruction using the keyhole principle and zero-padding were performed for comparison with the full k-space reconstruction. No significant changes were found for fMRI images generated from the keyhole technique with a data sharing profile of 50% of the k-space. As k-space data sharing profiles increased to 75 and 87.5%, the keyhole fMRI images began to show only modest changes in activation intensity and area compared with the standard images. In contrast, zero-padding fMRI images produced a significant disparity both in activation intensity and area relative to the truly high-resolution fMRI images. The keyhole technique's ability to retain the intensity and area of fMRI information, while substantially reducing acquisition time, makes it a promising method for fMRI studies.

Adult↗

Quantitative assessment of blood inflow effects in functional MRI signals.

Functional MRI (fMRI) signal dependence on changes in blood flow velocities were analyzed for both conventional and echo-planar (EPI) gradient-echo pulse sequences. As the flow velocity increases, the fMRI signal increases monotonically in spoiled gradient-echo sequences, while the fMRI signal may increase or decrease in conventional refocused gradient-echo sequences. A larger flip angle generates a larger inflow contribution to the fMRI signal. For conventional gradient-echo sequences, the inflow contribution to the fMRI images is dominated by the cortical draining veins, while its effect on capillaries is generally small and may be negligible in the spoiled sequences. For EPI gradient-echo sequences, the contribution from inflow effects is relatively small, as compared with the blood oxygen level-dependent (BOLD) contribution, to the fMRI signal, not only for capillaries but also for the cortical draining veins.

Blood Flow Velocity↗

Commutator filter: a novel technique for the identification of structures producing significant susceptibility inhomogeneities and its application to functional MRI.

A robust postprocessing method to detect regions of magnetic field change is presented. High resolution gradient echo data is acquired to create a complex baseline image. From this image, two low resolution images are obtained by applying a low pass filter on the magnitude image and the complex image, respectively. Subtraction of the magnitude of the filtered complex image from the filtered magnitude image gives a new image called a commutator image in which regions of susceptibility-induced field variation are greatly enhanced. Results on phantoms and applications to visualize paramagnetic venous blood vessels in the human brain are presented. The use of this technique on a 3D gradient echo data set represents a new approach to obtain an MR venogram. The application of this method to blood oxygenation level dependent (BOLD) functional brain MR imaging is demonstrated and the important role susceptibility plays in this model is verified.

Algorithms↗

Carcinogenic risks of inorganic arsenic in perspective.

Induction of cancer by inorganic arsenic occurs inconsistently between species and between routes of exposure, and it exhibits different dose-response relationships between different target organs. Inhaled or ingested arsenic causes cancer in humans but not in other species. Inhaled arsenic primarily induces lung cancer, whereas ingested arsenic induces cancer at multiple sites, including the skin and various other organs. Cancer potency appears to vary by route of exposure (ingestion or inhalation) and by organ site, and increases markedly at higher exposures in some instances. To understand what might explain these inconsistencies, we reviewed several hypotheses about the mechanism of cancer induction by arsenic. Arsenic disposition does not provide satisfactory explanations. Induction of cell proliferation by arsenic is a mechanism of carcinogenesis that is biologically plausible and compatible with differential effects for species or differential dose rates for organ sites. The presence of other carcinogens, or risk modifiers, at levels that correlate with arsenic in drinking water supplies, may be a factor in all three inconsistencies: interspecies specificity, organ sensitivity to route of administration, and organ sensitivity to dose rate.

Aged↗

An apparent functional correlation between variations in amino acid residues in HLA-DR4.1 and 4.2 serological subtypes and oligonucleotide characterization.

HLA-DR4 can be subdivided serologically into two specificities, DR4.1 and DR4.2, using well-defined monospecific alloantisera used in the 11th International Histocompatibility Workshop. In this study, a total of 1095 random DR4-positive individuals from several ethnic groups were tested first for serotype DR4.1/4.2 and then for DRB1*04 alleles using polymerase chain reaction (PCR) followed by sequence-specific oligonucleotide probe hybridization (SSOPH). An almost 100% correlation between samples testing positive for DR4.1 and the presence of alanine at position 74 was observed, while samples testing positive for DR4.2 correlated with the presence of glutamic acid at position 74. DRB1*04 alleles 0401, 0402, 0404, 0405, 0408, 0409 and 0410 are aligned in functional groups which coincide with the serological subtype of DR4.1. DRB1*04 alleles 0403, 0406, 0407 and 0411 coincide with subtype DR4.2. Amino acid substitutions at positions 57, 71 and 86 indicate other significant variations between alleles within the serological subgroup of DR4.1 and define five minor subgroups. The serologic and oligonucleotide allelic subgroups are in turn correlated with recognized cellular Dw antigens. While sequence data provide evidence of structural differences, data on cellular antigens support a functional association between these designated groups and their significance in transplantation and GVHD. Testing results are categorized by ethnic group in order to establish frequency data for donor selection criteria.

Amino Acid Sequence↗

Predictors of survival in human immunodeficiency virus type 1-seropositive intravenous drug users.

In an ongoing prospective study of street-recruited intravenous drug users (IDUs) in Miami, Fla., 116 human immunodeficiency virus type 1 (HIV-1)-infected IDUs were monitored for up to 7 years. This provided an opportunity to evaluate baseline immunological parameters as potential predictors of survival among HIV-1-infected IDUs. As expected, HIV-1-infected IDUs who had an advanced stage of the disease (Centers for Disease Control and Prevention classification III or IV); p24 antigenemia; human T-cell leukemia virus type 1/2 seropositivity; low CD4 counts (< or = 200); low hemoglobin (< or = 14), high serum immunoglobulin A (IgA) (> 500 mg/dl), or high serum IgG (> or = 3,500 mg/dl) levels; or low proliferative responses to pokeweed mitogen (< or = 1,500 cpm) and to phytohemagglutinin (< or = 80,000 cpm) at baseline had worse survival rates. Results from multivariate Cox's models of survival showed that the baseline serum IgG level, serum IgA level, and CD4 count independently predict survival in HIV-1-infected IDUs. Cross-validation procedures verified the above-mentioned findings. These findings support the routine consideration of serum immunoglobulin levels in addition to CD4 count, especially in early evaluation of disease stage, as these evaluations may modify application of prophylaxis and treatment for HIV-1-infected IDUs. We recommend consideration of use of serum IgG and IgA as immunological markers for long-range prediction of survival in HIV-1-infected IDUs. These determinations are less onerous and more appropriate for use in field studies and financially less favored settings.

Adult↗

Mortality in prostate cancer.

PURPOSE: We evaluated in patients with prostate cancer whether treatment is associated with in decreased mortality and whether the association of treatment with mortality varies with calendar time. MATERIALS AND METHODS: Using the 146,979 prostate cancer patients from the 1973 to 1990 public use tape of the Surveillance, Epidemiology and End Results program, we performed survival analysis and multivariate proportional hazards modeling to estimate the relative risk of disease specific and overall mortality. RESULTS: In men with prostate cancer, advanced age, black race, high tumor stage and not having treatment were independently associated with disease specific and overall mortality. The relative risk of mortality in treated patients decreased significantly from 1973 to 1990. CONCLUSIONS: The fact that advanced age and black race are associated with disease specific mortality (even when treatment and stage are controlled) is a new observation, which suggests that tumor biology and/or response to treatment is worse in elderly and black men. Overall, the data are consistent with the hypothesis that treatment of prostate cancer is associated with lower disease specific and overall mortality rates. The decreases in relative mortality in treated patients from 1973 to 1990 indirectly support the theory that changes in patterns of care from 1973 to 1990 had a beneficial effect on mortality. This observation implies that future studies should account for calendar time when interpreting outcomes data.

Aged↗

Marriage and mortality in prostate cancer.

PURPOSE: We evaluated the association of marital status and survival in patients with prostate cancer. MATERIALS AND METHODS: Using the 146,979 prostate cancer patients of the 1973 to 1990 public use tape of the Surveillance, Epidemiology and End Results program we performed survival analysis and multivariate proportional hazards modeling to estimate the relative risk of mortality. RESULTS: Married patients had significantly longer median survival than those who were divorced, single, separated or widowed. In models that controlled for age, stage, race and treatment, married patients had a significantly lower risk of mortality than those who were divorced, single, separated or widowed. CONCLUSIONS: Several hypothetical models can explain the association of marital status and mortality in men with prostate cancer. The most attractive model relies on the putative salutary effects of being married on social support and/or mood. A social support and depressed mood model of mortality raises the possibility that in prostate cancer quality of life determines quantity of life. Understanding the relationships among marital status, social support, mood and mortality could open the way to rational strategies for postponing death in men with prostate cancer.

Aged↗

Sequential p53 mutation analysis of pre-invasive and invasive head and neck squamous carcinoma.

Single-stranded conformational polymorphism (SSCP) and direct sequencing were performed on uninvolved mucosa, severe dysplasia and invasive carcinoma samples from 20 patients with head and neck squamous carcinoma. Seven (35%) of the non-invasive lesions and 15 (75%) of the invasive carcinomas manifested p53 mutations. Although the majority of mutations were mis-sense, resulting in single amino acid substitution, a silent mutation encoding for the same amino acid and 2 non-sense mutations encoding a stop codon were also observed. Mutations in invasive carcinoma were mostly in exon 8 and involved codons 296, 288 and 298; non-invasive lesions showed more mutations at exons 5 to 7. Five lesions showed simultaneous mutations in 2 different exons; in 3 both non-invasive and invasive carcinomas showed primary mutation at exons 5 to 7, and invasive carcinoma showed a secondary mutation at exon 8. Different codon mutations in the same exon between dysplastic and the corresponding carcinoma samples were found in 2 cases. p53 alterations were not observed in any of the normal mucosa samples. No apparent association between p53 mutations and conventional clinicopathologic parameters, including DNA content, was found in this cohort. Our study indicates that (i) p53 alteration is an early event in the genesis of a subset of head and neck squamous carcinomas, (ii) normal mucosa within the resected specimens lacked p53 mutation, (iii) sequential mutations of different exons of the p53 gene suggests accumulation of genetic alterations during the neoplastic transformation of these lesions and (iv) the difference in codon mutation of the same exon between dysplastic and corresponding carcinoma suggests an independent clonal development.

Adult↗