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Biomedical subjects

M Orlando

Publications and source records attributed to M Orlando.

At least 19 recordsLinked to original sources
PubMed2004

Pemphigus serum and captopril induce heat shock protein 70 and inducible nitric oxide synthase overexpression, triggering apoptosis in human keratinocytes.

BACKGROUND: Captopril is an angiotensin-converting enzyme inhibitor with sulphydryl groups in its chemical structure. It is commonly used as an antihypertensive drug. The occurrence of pemphigus vulgaris has repeatedly been reported in patients receiving captopril. The capacity of captopril and pemphigus serum to induce acantholysis, in vivo or in vitro, has been demonstrated experimentally. OBJECTIVES: To show that captopril and pemphigus serum, acting by a biochemical and immunological mechanism, respectively, trigger apoptosis. METHODS: Human keratinocyte cells were treated with 15 mmol L-1 captopril or with pemphigus serum. DNA was extracted and the terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end labelling method was used to detect apoptosis. RESULTS: DNA fragmentation occurred after 72 h of treatment. Increased expression of p53, c-myc and inducible nitric oxide (NO) synthase (iNOS) mRNA were observed by polymerase chain reaction (PCR) in the treated cells compared with the untreated ones. The increase in iNOS gene expression was associated with overproduction of NO. Moreover, the addition of 1 mmol L-1N-monomethyl-L-arginine, a structural analogue of arginine, reduced nitrite levels by about 70% in cells treated with captopril or pemphigus serum. Western blot analysis revealed an overexpression of heat shock protein 70 (hsp70) in cells treated with captopril or pemphigus serum. Finally, total inhibition of the keratinocyte transglutaminase gene was shown by PCR analysis in the same samples, compared with control cells. CONCLUSIONS: These data demonstrate the involvement of apoptosis in keratinocytes treated with captopril or pemphigus serum, with induction of the iNOS gene and hsp70 in the cascade of events leading to programmed cell death.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed2004

3-O-methylfunicone, a secondary metabolite produced by Penicillium pinophilum, induces growth arrest and apoptosis in HeLa cells.

3-O-Methylfunicone (OMF) is a secondary metabolite produced by the soil fungus Penicillium pinophilum which has cytostatic properties. The aim of this study was to investigate the mechanisms by which such properties are exerted, with special reference to any anti-proliferative and apoptotic potential, on HeLa cells. OMF treatment caused about 44% inhibition of cell growth after 24 h, and modifications in the tubulin fibre organization. In addition, a significant increase in p21 mRNA expression and a decrease in cyclin D1 and Cdk4 mRNA expression resulted at the same time. Apoptosis induction was demonstrated by the annexin V assay, cytofluorimetric analysis of the DNA content of the sub-G1 fraction and DNA laddering. Taken together, our data showed that the compound inhibits proliferation of HeLa cells by several mechanisms, such as disruption of tubulin fibres, cell cycle arrest and apoptosis induction. The capacity of the compound to affect the cell cycle and to modulate apoptosis is indicative of a potential for the development of a new agent for cancer chemotherapy.

Annexin A5↗
PubMed2004

Child and family safety device affordability by country income level: an 18 country comparison.

OBJECTIVE: To compare availability, urban price, and affordability of child/family safety devices between 18 economically diverse countries. DESIGN: Descriptive: urban price surveys by local safety organisations or shoppers. SETTING: Retail stores and internet vendors. MAIN OUTCOME MEASURES: Prices expressed in US dollars, and affordability measured by hours of factory work needed to buy a child safety seat, a belt-positioning booster seat, a child bicycle helmet, and a smoke alarm. RESULTS: Prices of child and family safety devices varied widely between countries but the variation for child safety seats and bicycle helmets did not relate strongly to country income. Safety devices were expensive, often prohibitively so, in lower income countries. Far more hours of factory work were required to earn a child safety device in lower income than middle income, and middle income than higher income, countries. A bicycle helmet, for example, cost 10 hours of factory work in lower income countries but less than an hour in higher income countries. Smoke alarms and booster seats were not available in many lower income countries. CONCLUSIONS: Bicycles and two-axle motor vehicles were numerous in lower and middle income countries, but corresponding child safety devices were often unaffordable and sometimes not readily available. The apparent market distortions and their causes merit investigation. Advocacy, social marketing, local device production, lowering of tariffs, and mandatory use legislation might stimulate market growth. Arguably, a moral obligation exists to offer subsidies that give all children a fair chance of surviving to adulthood.

Child↗
PubMed2001

Pretreatment with paclitaxel enhances apo-2 ligand/tumor necrosis factor-related apoptosis-inducing ligand-induced apoptosis of prostate cancer cells by inducing death receptors 4 and 5 protein levels.

We have demonstrated that Apo-2 ligand (Apo-2L)/tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) induces apoptosis of human prostate cancer PC-3, DU145, and LNCaP cells in a dose-dependent manner, with PC-3 cells displaying the greatest sensitivity to Apo-2L/TRAIL. Susceptibility of the prostate cancer cell types to Apo-2L/TRAIL-induced apoptosis did not appear to correlate with the levels of the Apo-2L/TRAIL receptors death receptor (DR) 4 (TRAIL receptor 1) or DR5 (TRAIL receptor 2), decoy receptor (DcR) 1 and DcR2, Flame-1, or the inhibitors of apoptosis proteins family of proteins. Apo-2L/TRAIL-induced apoptosis of PC-3 cells was associated with the processing of caspase-8, caspase-10, and the proapoptotic Bid protein, resulting in the cytosolic accumulation of cytochrome c as well as the processing of procaspase-9 and procaspase-3. Cotreatment with the caspase-8 inhibitor z-IETD-fmk or DR4:Fc significantly inhibited Apo-2L/TRAIL-induced apoptosis. Treatment with paclitaxel or taxotere increased DR4 and/or DR5 protein levels (up to 8-fold) without affecting the protein levels of DcR1 and DcR2, Apo-2L/TRAIL, Fas, or Fas ligand. Up-regulation of DR4 and DR5 was not preceded by the induction of their mRNA levels but was inhibited by cotreatment with cycloheximide. Importantly, sequential treatment of PC-3, DU145, and LNCaP cells with paclitaxel followed by Apo-2L/TRAIL induced significantly more apoptosis than Apo-2L/TRAIL treatment alone (P < 0.01). This was also associated with greater processing of procaspase-8 and Bid, as well as greater cytosolic accumulation of cytochrome c and the processing of caspase-3. These findings indicate that up-regulation of DR4 and DR5 protein levels by treatment with paclitaxel enhances subsequent Apo-2L/TRAIL-induced apoptosis of human prostate cancer cells.

Antineoplastic Agents, Phytogenic↗
PubMed2001

Psychiatric disorders and drug use among human immunodeficiency virus-infected adults in the United States.

BACKGROUND: There have been no previous nationally representative estimates of the prevalence of mental disorders and drug use among adults receiving care for human immunodeficiency virus (HIV) disease in the United States. It is also not known which clinical and sociodemographic factors are associated with these disorders. SUBJECTS AND METHODS: We enrolled a nationally representative probability sample of 2864 adults receiving care for HIV in the United States in 1996. Participants were administered a brief structured psychiatric instrument that screened for psychiatric disorders (major depression, dysthymia, generalized anxiety disorders, and panic attacks) and drug use during the previous 12 months. Sociodemographic and clinical factors associated with screening positive for any psychiatric disorder and drug dependence were examined in multivariate logistic regression analyses. RESULTS: Nearly half of the sample screened positive for a psychiatric disorder, nearly 40% reported using an illicit drug other than marijuana, and more than 12% screened positive for drug dependence during the previous 12 months. Factors independently associated with screening positive for a psychiatric disorder included number of HIV-related symptoms, illicit drug use, drug dependence, heavy alcohol use, and being unemployed or disabled. Factors independently associated with screening positive for drug dependence included having many HIV-related symptoms, being younger, being heterosexual, having frequent heavy alcohol use, and screening positive for a psychiatric disorder. CONCLUSIONS: Many people infected with HIV may also have psychiatric and/or drug dependence disorders. Clinicians may need to actively identify those at risk and work with policymakers to ensure the availability of appropriate care for these treatable disorders.

Adolescent↗
PubMed2001

ADHD treatment in a behavioral health care carve-out: medications, providers, and service utilization.

Children's mental health services are increasingly being managed by managed behavioral health organizations (MBHOs) through carve-outs. Little information is available, however, about services and interventions being received by children whose mental health benefits are carved out. Using claims data, this study explores the treatment of children with a common child psychiatric disorder, attention deficit hyperactivity disorder (ADHD). Children being treated for ADHD see a variety of provider combinations. Children diagnosed with comorbid mood or anxiety disorders are more likely to see a psychiatrist than a primary care physician or therapist, and they are more likely to be in treatment with both a psychiatrist and a therapist than with just one mental health professional. After controlling for severity indicators, costs were significantly lower for patients being treated by just a psychiatrist than for patients seeing both a psychiatrist and therapist. This finding raises the possibility that attempts to save money by "splitting treatment" may not be cost-effective.

Attention Deficit Disorder with Hyperactivity↗
PubMed2001

Malassezia furfur invasiveness in a keratinocyte cell line (HaCat): effects on cytoskeleton and on adhesion molecule and cytokine expression.

The lipophilic yeast Malassezia furfur is a member of the cutaneous microbiota, also associated with several chronic diseases such as pityriasis versicolor, folliculitis, seborrhoeic dermatitis, and some forms of atopic dermatitis, psoriasis and confluent and reticulate papillomatosis. In this study we determined the immunomodulatory and invasive capacity of M. furfur in a human keratinocyte cell culture, HaCat. At a yeast cell to HaCat ratio of 30:1, M. furfur penetration was only 30% with poor phagolysosome fusion and with cytoskeleton modification. Transglutaminase I gene expression was also inhibited, supporting the hypothesis that M. furfur causes an initial break in the barrier function of the epidermis. Moreover, we demonstrated that M. furfur modulates proinflammatory and immunomodulatory cytokine synthesis by downregulating IL-1alpha and by inhibiting IL-6 and TNF-alpha and by upregulating IL-10 and TGF-beta1. The suppressed inflammatory response induced by M. furfur may play a role in chronic disease.

Cell Division↗
PubMed2001

The temporal relationship between emotional distress and cigarette smoking during adolescence and young adulthood.

Empirical evidence regarding the causal nature of the relationship between emotional distress and tobacco use in male and female adolescents provides support for both the distress-to-use and the use-to-distress hypotheses. Using a cross-lagged model with 3 waves of data from 2,961 adolescents followed into young adulthood, the authors tested the hypothesis that this relationship changes over time. As hypothesized, emotional distress in Grade 10 was associated with increased smoking in Grade 12 for both boys and girls. Smoking in Grade 12 was in turn associated with increased emotional distress in young adulthood. The addition of 3 third factors (rebelliousness, deviance, and family problems) to the model did not alter the results. Results suggest that the relationship between tobacco use and emotional distress is a dynamic one in which distress initially leads to use but then becomes exacerbated by it over time.

Adolescent↗
PubMed2001

Gemcitabine in ovarian cancer.

Newer agents and combinations are needed in order to improve current results in the treatment of ovarian cancer. Gemcitabine (Gemzar; Eli Lilly and Company, Indianapolis, IN) is a novel agent with a unique mechanism of action that has shown consistent activity as a single-agent in platinum-resistant ovarian cancer, with remission rates of nearly 20% and a favorable toxicity profile. Because of these benefits and its shown clinical and preclinical synergism with platinum analogues, gemcitabine has been combined with carboplatin as a rational approach for the treatment of ovarian cancer patients. The combination has been studied in phase I and II trials aimed at determining the optimal schedule and potential activity. Triplets including paclitaxel are also feasible. Further combinations of gemcitabine and other agents are being actively studied in both treated and untreated patients with ovarian cancer in order to establish its role in the management of this disease. Semin Oncol 28 (suppl 10):62-69.

Antimetabolites, Antineoplastic↗
PubMed2001

Are better ratings of the patient-provider relationship associated with higher quality care for depression?

BACKGROUND: The interpersonal patient-provider relationship (PPR) is an essential part of health care quality, particularly for patients with depression, yet little is known neither about how to measure this relationship nor about its association with quality of care. OBJECTIVES: To evaluate properties of patient rating measures, understand the relation between 2 types of ratings, and determine the association of ratings with quality depression care. SETTING AND PARTICIPANTS: 1,104 patients with current depressive symptoms and lifetime or 12-month disorder identified through screening 27,332 consecutive primary care visitors in 6 managed care organizations participating in Partners in Care (PIC). DESIGN: Cross-sectional analysis of 18-month data (collected in 1998) after the start of PIC depression quality improvement (QI) interventions (in which clinics were randomized to 1 of 2 QI interventions or usual care). MEASURES: Patient ratings of the interpersonal relationship with the primary care provider and satisfaction with health care, and quality of depression care indicators. ANALYSIS: Factor analysis and multitrait scaling to evaluate the psychometric properties of multiitem constructs and analysis of covariance to evaluate associations between patient ratings and quality. RESULTS: Patient ratings had high internal consistency and met criteria for discriminant validity tapping unique aspects of care. Patients receiving quality care, especially for medication use, had significantly higher ratings of the interpersonal relationship (by 22% to 27% of a SD) and were more satisfied (by 26% to 34% of a SD) than patients who did not receive quality care. CONCLUSIONS: Ratings of the interpersonal relationship and satisfaction measure distinct aspects of care and are positively associated with quality care for depression.

Adult↗
PubMed2000

Low-dose continuous oral fosfestrol is highly active in 'hormone-refractory' prostate cancer.

BACKGROUND: Although not clearly defined, 'hormone refractory' prostate cancer implies disease progression after orchiectomy +/- antiandrogens. Patients in this setting are usually offered chemotherapy protocols which often lead to significant toxicity and expense. In search of a well-tolerated, active, third-line treatment, we have attempted to prolong hormonal maneuvers by using low-dose estrogen therapy. DESIGN: Thirty-eight patients with evidence of disease progression (as indicated by 2 consecutively rising PSA determinations) after > or = 2 hormonal treatments (including surgical or chemical orchiectomy and a median of 3 prior treatment lines) received fosfestrol 100 mg t.i.d. per os in a continuous schedule until the appearance of progressive disease or excessive toxicity. Response was assessed by serial PSA levels. Complete response (CR) was defined as normalisation and partial response (PR) as a > or = 50 decrease of PSA levels for longer than one month. The median duration of prior treatment was 20 months and the median PSA at fosfestrol start was 126 ng/ml (range 8-12,800); symptoms (pain) were present in 73% of patients. RESULTS: CR + PR were observed in 79% (95% confidence interval: 66%-92%). The median time to progression was seven months. Pain remained stable or improved in 34% and 53%, respectively, of symptomatic patients with PSA response. Toxicity included worsening of gynecomastia, peripheral edema, and deep vein thrombosis (8%). No treatment-related deaths occurred. Uni- and multivariate analyses failed to identify predictive factors for response. PSA response was associated with significantly longer survival (13 vs. 7 months, P < 0.05 by Mantel-Haentzel). CONCLUSIONS: FOSF produces high rates of PSA-determined and symptomatic response in 'hormone-refractory' prostate cancer. Toxicity and ease of administration compare favorably with those reported for CHT regimens used in this setting. The role of estrogens in prostate cancer should be redefined.

Administration, Oral↗
PubMed2000

Summed-score linking using item response theory: application to depression measurement.

An item response theory (IRT) approach to test linking based on summed scores is presented and demonstrated by calibrating a modified 23-item version of the Center for Epidemiologic Studies Depression Scale (CES-D) to the standard 20-item CES-D. Data are from the Depression Patient Outcomes Research Team, II, which used a modified CES-D to measure risk for depression. Responses (N = 1,120) to items on both the original and modified versions were calibrated simultaneously using F. Samejima's (1969, 1997) graded IRT model. The 2 scales were linked on the basis of derived summed-score-to-IRT-score translation tables. The established cut score of 16 on the standard CES-D corresponded most closely to a summed score of 20 on the modified version. The IRT summed-score approach to test linking is a straightforward, valid, and practical method that can be applied in a variety of situations.

Depression↗
PubMed2000

Identifying a short functional disability screen for older persons.

BACKGROUND: Disability in instrumental activities of daily living (IADLs) or activities of daily living (ADLs) is an indicator of health risk. The inclusion of these items in population screens may be limited by variation in item performance across gender and age groups. Further, identification of shortened lists may encourage inclusion of these items in screens. METHODS: We applied item response theory (IRT) methods to assess the responses of 9865 community-dwelling elders in the 1993 Medicare Current Beneficiary Survey to 11 IADL/ADL items. Items were classified as "receive help/not receive help" for the overall population and stratified by age and gender. We assessed the same IADL/ADL items using responses classified as "difficulty/no difficulty." After eliminating items that performed poorly, we performed all-subsets analyses to identify abbreviated sets of items that would select the highest proportion of persons with IADL/ADL disability. RESULTS: Responses classified in receive help format showed consistency by gender and age group. Changing the response classification to difficulty/no difficulty influenced the reported order and relationship of IADL/ADL items. Receipt of help for any one of five items--shopping, doing light housework, walking, bathing, or managing finances--identified 93% of individuals receiving help with any IADL/ADL. A slightly different set of five items--walking, shopping, transferring, doing light housework, or bathing--identified 91% of persons reporting difficulty with any IADL or ADL. CONCLUSIONS: The relationship of IADL and ADL items to the underlying construct of disability was similar for men and women. The relationship was also similar for oldest-old and younger-old individuals. This study also identified abbreviated lists of disability items that can be used to efficiently screen community-dwelling elders for the presence of IADL/ADL disability.

Activities of Daily Living↗
PubMed2000

New York State universal newborn hearing screening demonstration project: inpatient outcome measures.

OBJECTIVE: To evaluate the feasibility of universal newborn hearing screening by examining inpatient outcome measures from 8 hospitals located in geographically diverse areas of New York State over a 3-yr period. DESIGN: Funding was provided by the New York State Department of Health to implement predischarge hearing screening programs in the neonatal intensive care units (NICUs) and well-baby nurseries (WBNs) of eight hospitals. Various screening protocols including transient evoked otoacoustic emissions alone or in combination with conventional auditory brain stem response or screening auditory brain stem response were implemented by each site. Measured outcomes included rate of misses, refusals, and fails. Results were analyzed as a function of year of operation, nursery type, and geographic location. RESULTS: Six out of eight hospitals successfully implemented universal hearing screening during the first year, and the remaining 2 hospitals implemented programs during the second year of the project. Over a period of 3 yr, 69,761 newborns were screened at the eight hospitals representing 96.9% of all live births. The overall fail rate (4.04%) combined with the miss rate (2.61%) resulted in 6.63% of infants referred for outpatient follow-up. Mean data indicated that inpatient outcome measures improved with year of operation, with most individual hospitals also showing improvements. Both fail and miss rates were higher in the NICU than in the WBN and for hospitals located in New York City than in other regions of the state. CONCLUSIONS: Inpatient outcome measures of a universal newborn hearing screening project, which involved multiple centers across geographically diverse regions of New York State, were acceptable in terms of successfully screening a high percentage of live births and attaining low refer rates for outpatient screening. This study adds to the growing body of literature supporting the feasibility of screening all newborns before hospital discharge.

Acoustic Stimulation↗
PubMed2000

The New York State universal newborn hearing screening demonstration project: outpatient outcome measures.

OBJECTIVE: To investigate outpatient outcome measures of a multi-center, state-wide, universal newborn hearing screening project. DESIGN: Eight hospitals participated in a 3-yr, funded project. Each hospital designed its own protocol using common criteria for judging whether an infant passed a hearing screening. Infants were tested in the hospital, and those either failing the in-hospital screening or who were not tested in the hospital (missed) were asked to return 4 to 6 wk after hospital discharge for outpatient rescreening. Those infants failing the outpatient rescreening were referred for diagnostic auditory brain stem response testing. Each hospital used its own audiological equipment and criteria to determine whether a particular infant had a hearing loss. All data were collected and analyzed for individual hospitals, as well as totaled across all hospitals. Data were analyzed in terms of year of program operation, nursery type, and geographic region. RESULTS: Seventy-two percent of infants who failed the in-hospital screening returned for outpatient testing. The percentage of in-hospital fails returning for retesting was significantly higher than the percentage of in-hospital misses returning for retesting. The percentage of infants returning for retesting increased with successive years of program operation. Some differences were noted in the percentage of infants returning for retesting among hospitals and geographic regions of the state. Some differences in outpatient outcome measures also were noted between infants originally born into the neonatal intensive care unit (NICU) and the well-baby nursery (WBN). The percentage of infants from the NICU who returned for retesting was slightly higher than that for infants from the WBN. The percentage of infants from the WBN passing the outpatient rescreening was higher than that for the NICU infants. The overall prevalence of hearing loss was 1.96/1000, with that in the NICU being 8/1000 and that in the WBN being 0.9/1000. Positive predictive value for permanent hearing loss based on inpatient screening was approximately 4% and based on outpatient rescreening was approximately 22%. CONCLUSIONS: Several outpatient outcome measures changed with successive years of program operation, suggesting that programs improve over time. Also, some outpatient outcome measures differ between NICU and WBN populations. The differences noted across regions of the state in the percentage of infants returning for outpatient retesting require further research to determine whether differences are due to demographic and/or procedural differences.

Ambulatory Care↗
PubMed2000

The New York State universal newborn hearing screening demonstration project: ages of hearing loss identification, hearing aid fitting, and enrollment in early intervention.

OBJECTIVE: To determine the ages of hearing loss identification, hearing aid fitting, and enrollment in early intervention through a multi-center, state-wide universal newborn hearing screening project. DESIGN: Universal newborn hearing screening was conducted at eight hospitals across New York State. All infants who did not bilaterally pass hearing screening before discharge were recalled for outpatient retesting. Inpatient screening and outpatient rescreening were done with transient evoked otoacoustic emissions and/or auditory brain stem response testing. Diagnostic testing was performed with age appropriate tests, auditory brain stem response and/or visual reinforcement audiometry. Infants diagnosed with permanent hearing loss were considered for hearing aids and early intervention. Ages of hearing loss identification, hearing aid fitting, and enrollment in early intervention were investigated regarding nursery type, risk status, unilateral versus bilateral hearing loss, loss type, loss severity, and state regions. RESULTS: The prevalence of infants diagnosed with permanent hearing loss was 2.0/1000 (85 of 43,311). Of the 85 infants with hearing loss, 61% were from neonatal intensive care units (NICUs) and 67% were at risk for hearing loss. Of the 36 infants fitted with hearing aids, 58% were from NICUs and 78% were at risk for hearing loss. The median age at identification and enrollment in early intervention was 3 mo. Median age at hearing aid fitting was 7.5 mo. Median ages at identification were less for infants from the well-baby nurseries (WBNs) than for the NICU infants and for infants with severe/profound than for infants with mild/moderate hearing loss, but were similar for not-at-risk and at-risk infants. Median ages at hearing aid fitting were less for well babies than for NICU infants, for not-at-risk infants than for at-risk infants, and for infants with severe/ profound hearing loss than for infants with mild/ moderate hearing loss. However, median ages at early intervention enrollment were similar for nursery types, risk status, and severity of hearing loss. CONCLUSIONS: Early ages of hearing loss identification, hearing aid fitting, and enrollment in early intervention can be achieved for infants from NICUs and WBNs and for infants at risk and not at risk for hearing loss in a large multi-center universal newborn hearing screening program.

Age Factors↗