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1.
Clin Exp Dermatol ; 47(2): 404-406, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-34407228

RESUMO

Patients with acne are increasingly using sunbeds as a self treatment despite the harmful effects. Little is known about sunbed use in adult patients with acne under dermatology care. This questionnaire study explored prevalence and behaviours surrounding sunbed use in patients with acne at a UK dermatology centre. Over a quarter (26%) of respondents used sunbeds and of these, 72% used them at least weekly. Respondents using sunbeds were more likely to be older, to be female, to have a longer duration of acne diagnosis and to have previously been offered blue-light therapy by their doctor (P < 0.05 for all) Reasons for use included recommendations from external sources (including the Internet), the perceived greater efficacy compared with physician-prescribed treatments and that light therapy was not offered by their doctor. Nearly half (49%) of respondents were taking isotretinoin at the time of sunbed use, which carries an increased risk for photosensitivity and sunburn in this cohort. Dermatologists have a responsibility to address this gap in public awareness by directly counselling patients at risk of sunbed use, particularly for those concomitantly prescribed oral retinoid therapy.


Assuntos
Acne Vulgar/terapia , Autocuidado/efeitos adversos , Banho de Sol , Acne Vulgar/tratamento farmacológico , Adolescente , Adulto , Feminino , Humanos , Isotretinoína/uso terapêutico , Masculino , Pessoa de Meia-Idade , Inquéritos e Questionários , Raios Ultravioleta/efeitos adversos
3.
Clin Exp Dermatol ; 43(5): 589-591, 2018 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-29460979

RESUMO

Naevus sebaceous (NS) is a congenital cutaneous hamartoma, which typically occurs on the head and neck. Historically, the treatment of choice was excision in infancy because of the potential for malignant transformation; however, recent studies suggest that this risk is < 1% and unlikely in childhood. We sent a questionnaire to UK dermatologists and plastic surgeons to investigate current management practice of NS. We found that almost a third of dermatologists still recommend excision for malignancy prevention, while over 90% of plastic surgeons consider excision, with 64% citing malignancy prevention as the reason. Plastic surgeons most commonly recommended excision in childhood, whereas dermatologists waited until adulthood. We have shown there is significant variation in practice across the UK in the management of naevus NS. It is important that patients across the UK receive the same standard of care, and therefore we advocate the development of evidence-based guidance for treatment of naevus NS.


Assuntos
Dermatologia , Hamartoma/cirurgia , Nevo Sebáceo de Jadassohn/cirurgia , Padrões de Prática Médica/estatística & dados numéricos , Neoplasias Cutâneas/prevenção & controle , Neoplasias Cutâneas/cirurgia , Cirurgia Plástica , Transformação Celular Neoplásica , Criança , Pré-Escolar , Hamartoma/patologia , Humanos , Lactente , Nevo Sebáceo de Jadassohn/patologia , Educação de Pacientes como Assunto , Padrões de Prática Médica/tendências , Autoexame , Inquéritos e Questionários , Reino Unido
4.
Br J Dermatol ; 175(6): 1320-1328, 2016 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-27411377

RESUMO

BACKGROUND: The concurrent impact of repeated low-level summer sunlight exposures on vitamin D production and cutaneous DNA damage, potentially leading to mutagenesis and skin cancer, is unknown. OBJECTIVES: This is an experimental study (i) to determine the dual impact of repeated low-level sunlight exposures on vitamin D status and DNA damage/repair (via both skin and urinary biomarkers) in light-skinned adults; and (ii) to compare outcomes following the same exposures in brown-skinned adults. METHODS: Ten white (phototype II) and six South Asian volunteers (phototype V), aged 23-59 years, received 6 weeks' simulated summer sunlight exposures (95% ultraviolet A/5% ultraviolet B, 1·3 standard erythemal doses three times weekly) wearing summer clothing exposing ~35% body surface area. Assessments made were circulating 25-hydroxyvitamin D [25(OH)D], immunohistochemistry for cyclobutane pyrimidine dimer (CPD)-positive nuclei and urinary biomarkers of direct and oxidative (8-oxo-deoxyguanosine) DNA damage. RESULTS: Serum 25(OH)D rose from mean 36·5 ± 13·0 to 54·3 ± 10·5 nmol L-1 (14·6 ± 5·2 to 21·7 ± 4·2 ng mL-1 ) in phototype II vs. 17·2 ± 6·3 to 25·5 ± 9·5 nmol L-1 (6·9 ± 2·5 to 10·2 ± 3·8 ng mL-1 ) in phototype V (P < 0·05). Phototype II skin showed CPD-positive nuclei immediately postcourse, mean 44% (range 27-84) cleared after 24 h, contrasting with minimal DNA damage and full clearance in phototype V (P < 0·001). The findings did not differ from those following single ultraviolet radiation (UVR) exposure. Urinary CPDs remained below the detection threshold in both groups; 8-oxo-deoxyguanosine was higher in phototype II than V (P = 0·002), but was unaffected by UVR. CONCLUSIONS: Low-dose summer sunlight exposures confer vitamin D sufficiency in light-skinned people concurrently with low-level, nonaccumulating DNA damage. The same exposures produce minimal DNA damage but less vitamin D in brown-skinned people. This informs tailoring of sun-exposure policies.


Assuntos
Dano ao DNA/efeitos da radiação , Estações do Ano , Luz Solar , Vitamina D/biossíntese , 8-Hidroxi-2'-Desoxiguanosina , Adolescente , Adulto , Sudeste Asiático/etnologia , Biomarcadores/sangue , Biomarcadores/urina , Reparo do DNA/fisiologia , Reparo do DNA/efeitos da radiação , Desoxiguanosina/análogos & derivados , Desoxiguanosina/urina , Dieta , Exposição Ambiental , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Dímeros de Pirimidina/urina , Pele/metabolismo , Neoplasias Cutâneas/sangue , Neoplasias Cutâneas/etiologia , Neoplasias Cutâneas/urina , Pigmentação da Pele/efeitos da radiação , Vitamina D/administração & dosagem , Vitamina D/análogos & derivados , Vitamina D/metabolismo , Deficiência de Vitamina D/sangue , Deficiência de Vitamina D/etnologia , Deficiência de Vitamina D/urina , Adulto Jovem
5.
Science ; 345(6197): 644-6, 2014 Aug 08.
Artigo em Inglês | MEDLINE | ID: mdl-25104380

RESUMO

Origami can turn a sheet of paper into complex three-dimensional shapes, and similar folding techniques can produce structures and mechanisms. To demonstrate the application of these techniques to the fabrication of machines, we developed a crawling robot that folds itself. The robot starts as a flat sheet with embedded electronics, and transforms autonomously into a functional machine. To accomplish this, we developed shape-memory composites that fold themselves along embedded hinges. We used these composites to recreate fundamental folded patterns, derived from computational origami, that can be extrapolated to a wide range of geometries and mechanisms. This origami-inspired robot can fold itself in 4 minutes and walk away without human intervention, demonstrating the potential both for complex self-folding machines and autonomous, self-controlled assembly.

6.
Br J Dermatol ; 171(6): 1478-86, 2014 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-25110159

RESUMO

BACKGROUND: Low vitamin D status is prevalent in wintertime in populations at northerly latitudes. Photosensitive patients are advised to practise sun avoidance, but their sunlight exposure levels, photoprotective measures and resulting vitamin D status are unknown. OBJECTIVES: To examine seasonal vitamin D status in photosensitive patients relative to healthy individuals and to assess quantitatively behavioural and demographic contributors. METHODS: This was a longitudinal prospective cohort study (53·5°N) examining year-round 25-hydroxyvitamin D [25(OH)D] levels, sun-exposure behaviour and oral vitamin D intake in photosensitive patients diagnosed at a photoinvestigation unit (n = 53), compared with concurrently assessed healthy adults (n = 109). RESULTS: Photosensitive patients achieved seasonal 25(OH)D variation, but insufficient (< 20 ng mL(-1); 50 nmol L(-1)) and even deficient (< 10 ng mL(-1); 25 nmol L(-1)) levels occurred at the summer peak in 47% and 9% of patients, respectively, rising to 73% and 32% at the winter trough. Adjusting for demographic factors, the mean values were lower than for healthy volunteers by 18% [95% confidence interval (CI) 4-29] in summer (P = 0·02) and 25% (95% CI 7-39) in winter (P = 0·01). Behavioural factors explained 25(OH)D differences between cohorts. Patients demonstrated lower weekend ultraviolet B doses (P < 0·001), smaller skin surface area exposure (P = 0·004) and greater sunscreen use (P < 0·001), while average oral vitamin D intake was low in both groups (photosensitive: 2·94 µg per day). Supplementation and summer surface area exposure predicted summer peak and winter trough 25(OH)D levels. A 1 µg per day increment in supplementary vitamin D raised summer and winter 25(OH)D by 5% (95% CI 3-7) and 9% (95% CI 5-12), respectively (both P < 0·001). CONCLUSIONS: Photosensitive patients are, through their photoprotective measures, at high risk of year-round low vitamin D status. Guidance on oral measures should target this patient group and their physicians.


Assuntos
Transtornos de Fotossensibilidade/sangue , Luz Solar/efeitos adversos , Deficiência de Vitamina D/etiologia , Administração Oral , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Suplementos Nutricionais , Exposição Ambiental/efeitos adversos , Exposição Ambiental/análise , Exposição Ambiental/prevenção & controle , Feminino , Comportamentos Relacionados com a Saúde , Humanos , Masculino , Prontuários Médicos , Pessoa de Meia-Idade , Hormônio Paratireóideo/metabolismo , Transtornos de Fotossensibilidade/complicações , Transtornos de Fotossensibilidade/prevenção & controle , Estudos Prospectivos , Estações do Ano , Protetores Solares/uso terapêutico , Vitamina D/administração & dosagem , Vitamina D/análogos & derivados , Vitamina D/metabolismo , Deficiência de Vitamina D/sangue , Vitaminas/administração & dosagem , Adulto Jovem
7.
Clin Exp Dermatol ; 39(4): 439-42, 2014 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-24758600

RESUMO

BACKGROUND: Vulval allergic contact dermatitis (ACD) may be a primary disorder or may be associated with an underlying vulval dermatosis. Few studies have looked at the incidence of ACD and the allergens responsible for it. AIMS: We report the incidence of vulval ACD and the responsible allergens in 282 patients investigated over a 6-year period in a large teaching hospital. METHODS: We performed a retrospective case notes review of all patients investigated for vulval symptoms in our tertiary referral contact dermatitis investigation unit. A total of 282 patients underwent patch testing. RESULTS: The overall incidence of ACD was 54%. The age range of patients was 14-89 years. Pruritus was the most common presenting symptom. Nickel was the most commonly found allergen, but was usually not relevant. Fragrances and topical antibiotics/anaesthetics were less commonly detected, but were almost always relevant to the presentation. Positive reactions were more commonly found in patients who had long-standing symptoms and/or had used many products in the vulval area. CONCLUSIONS: Vulval ACD affects women of a wide age range, and presents with nonspecific symptoms such as pruritus and/or vulval irritation. Patients may have experienced symptoms for many years before presenting to a dermatologist. The diagnosis of vulval ACD is more common in those who have been exposed to many potential sensitizers.


Assuntos
Alérgenos/efeitos adversos , Dermatite Alérgica de Contato/epidemiologia , Doenças da Vulva/induzido quimicamente , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Dermatite Alérgica de Contato/diagnóstico , Dermatite Alérgica de Contato/etiologia , Fármacos Dermatológicos/efeitos adversos , Feminino , Humanos , Incidência , Pessoa de Meia-Idade , Testes do Emplastro , Estudos Retrospectivos , Doenças da Vulva/diagnóstico , Doenças da Vulva/epidemiologia , Adulto Jovem
8.
Lasers Med Sci ; 29(5): 1745-9, 2014 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-23640036

RESUMO

Naevus of Ota (NO) is a disfiguring pigmentary disorder affecting the face. Q-switched neodymium-doped yttrium aluminium garnet (QS Nd:YAG)-1,064 nm is a standard laser treatment because it causes highly selective destruction of melanin within the aberrant dermal melanocytes. However, not all lesions respond. This study aims to evaluate the efficacy/safety of QS Nd:YAG-1,064 nm and the shorter wavelength QS Alexandrite-755 nm and QS Nd:YAG-532 nm lasers in treating NO. Data were evaluated from 21 patients treated in our laser centre from 2004 to 2012. Lesional skin was irradiated with QS-532 nm/QS-755 nm/QS-1,064 nm, with settings titrated according to responses. All received initial test patches to direct initial wavelength choice, with subsequent treatments at 3-monthly intervals until clearance/lack of further response. Laser modality was switched following repeated test patches if there was no or no sustained improvement. Two thirds of patients had ≥ 90% improvement compared to baseline photographs. In 20% of patients, QS-1,064 nm was most efficacious with 97% mean improvement. The mean improvement was 80% for those in whom QS-755 nm was superior, and 90% for QS-532 nm. Median number of overall laser treatments was 8 (range 4-13). Number of treatments required varied significantly according to lesional colour and site: grey lesions and those on the forehead/temple were most resistant. We confirm successful treatment of NO with QS Nd:YAG-1,064 nm and the shorter wavelength QS-755 nm/QS-532 nm lasers without serious or irreversible side effects. We recommend judicious test patch analysis before treatment and a modality switch if complete clearance is not obtained.


Assuntos
Terapia a Laser , Nevo de Ota/terapia , Adolescente , Adulto , Berílio/efeitos adversos , Demografia , Feminino , Humanos , Terapia a Laser/efeitos adversos , Lasers de Estado Sólido/efeitos adversos , Masculino , Pessoa de Meia-Idade , Nevo de Ota/patologia , Adulto Jovem
9.
Br J Dermatol ; 168(1): 179-85, 2013 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-22860570

RESUMO

BACKGROUND: Voriconazole, a broad-spectrum triazole antifungal agent increasingly used to treat aspergillosis, has been linked with acute photosensitivity and skin carcinogenesis. The action spectrum of the photosensitivity is unknown, while an indirect retinol effect secondary to the antifungal's impact on CYP450 enzymes has been proposed to contribute to the underlying mechanism. OBJECTIVES: To perform a detailed photobiological assessment of the photosensitivity presenting in a series of 12 patients treated with voriconazole. METHODS: Minimal erythemal dose thresholds (MED) to narrow wavebands of ultraviolet (UV) A, UVB and visible light were determined. Provocation testing was performed to broadband UVA (310-400 nm) and to solar-simulated radiation (SSR) (290-400 nm). Patients underwent routine photopatch testing and laboratory investigations including serum vitamin A (retinol). RESULTS: Patients (eight men, four women; median age 54years, range 40-63) experienced moderate-severe cutaneous erythema (n = 12), burning pain (n=5), itching (n=3), scaling (n=5), vesiculation (n=5) and oedema (n=1) following sunlight exposure; increased lentigines (n=4) and actinic cheilitis (n = 4) were also observed. While the majority (n=8) of patients showed normal MED thresholds to monochromator phototesting to UVB, UVA and visible light, a low MED to UVA was observed in four patients. Repeated provocation testing with broadband UVA and SSR provoked an abnormal erythema in eight and 10 patients, respectively. Serum retinol levels were mildly elevated in two patients but normal in the majority. CONCLUSION: UVA sensitivity is the predominant finding in acute voriconazole-induced photosensitivity. We found little evidence of elevated circulating retinol as the causal factor. Patients with voriconazole-induced photosensitivity require education in appropriate UVA protective measures in addition to consideration of skin surveillance for malignant sequelae.


Assuntos
Antifúngicos/efeitos adversos , Aspergilose/tratamento farmacológico , Toxidermias/etiologia , Transtornos de Fotossensibilidade/induzido quimicamente , Pirimidinas/efeitos adversos , Triazóis/efeitos adversos , Adulto , Anticorpos Antinucleares/sangue , Anticorpos Antinucleares/urina , Toxidermias/diagnóstico , Feminino , Humanos , Luz , Masculino , Pessoa de Meia-Idade , Testes do Emplastro , Transtornos de Fotossensibilidade/diagnóstico , Luz Solar/efeitos adversos , Voriconazol
10.
Int J Tuberc Lung Dis ; 14(4): 464-70, 2010 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-20202305

RESUMO

SETTING: The correctional system in the United States is large and growing. The Centers for Disease Control and Prevention recommend baseline and annual testing of employees in correctional facilities for latent tuberculosis infection (LTBI). OBJECTIVE: To describe the extent of and factors associated with LTBI testing practices for jail correctional officers. DESIGN: A national survey of 1760 randomly selected jails was conducted. We used multivariable logistic regression models to examine factors associated with testing officers in a guideline-concordant manner and having a written policy. RESULTS: A total of 1174 (67%) surveys were returned. Only 52% of jails had a written policy on LTBI testing of officers, and 51% screened officers at least annually (guideline concordance). Large jails (OR 2.41, 95%CI 1.67-3.49) and jails in states with a high tuberculosis incidence (OR 1.67, 95%CI 1.17-2.38) and in the Midwest (OR 1.58, 95%CI 1.07-2.33) were more likely to screen in a guideline-concordant manner. CONCLUSION: Screening for LTBI among correctional officers in the United States was inconsistent. Strategies to improve LTBI testing among correctional officers are needed.


Assuntos
Tuberculose Latente/diagnóstico , Programas de Rastreamento/organização & administração , Exposição Ocupacional/estatística & dados numéricos , Saúde Ocupacional/estatística & dados numéricos , Prisões , Centers for Disease Control and Prevention, U.S. , Distribuição de Qui-Quadrado , Fidelidade a Diretrizes , Pesquisas sobre Atenção à Saúde , Humanos , Tuberculose Latente/transmissão , Modelos Logísticos , Razão de Chances , Guias de Prática Clínica como Assunto , Avaliação de Programas e Projetos de Saúde , Inquéritos e Questionários , Estados Unidos , Recursos Humanos
11.
J Phys Condens Matter ; 21(36): 364212, 2009 Sep 09.
Artigo em Inglês | MEDLINE | ID: mdl-21832318

RESUMO

We report on electron paramagnetic resonance (EPR) studies of nitrogen doped diamond that has been (15)N enriched, electron irradiated and annealed. EPR spectra from two new nitrogen containing [Formula: see text] defects are detected and labelled WAR9 and WAR10. We show that the properties of these defects are consistent with them being the ⟨001⟩-nitrogen split interstitial and the ⟨001⟩-nitrogen split interstitial-⟨001⟩-carbon split interstitial pair, respectively. We also provide an explanation for why these defects have previously eluded discovery.

12.
AIDS ; 15(10): 1295-302, 2001 Jul 06.
Artigo em Inglês | MEDLINE | ID: mdl-11426075

RESUMO

BACKGROUND: Human T-lymphotropic virus type II (HTLV-II) is widespread among injecting drug users (IDU) and may contribute to the risk of leukemia/lymphoma, neurodegenerative disease, and perhaps pneumonia, especially with HIV co-infection. METHODS: In 1987--1991, 6570 IDU were tested for HIV and HTLV-II antibodies. In 1998, they were matched to the National Death Index. Numbers of observed deaths of each cause were compared by standardized mortality ratios with the numbers expected, using sex-, race-, age-, and year-specific rates in the general population. Relative risk (RR) associated with each virus, compared to uninfected drug users, was estimated by Poisson modeling. RESULTS: There were 1351 deaths, including 683 (15%) of 4604 participants who enrolled seronegative for both viruses; 328 (47%) of 701 who had HIV but not HTLV-II infection; 220 (21%) of 1033 who had HTLV-II but not HIV infection; and 120 (52%) of 232 who were infected by both viruses. Compared to the general population, mortality for participants with neither virus was increased 4.3-fold [95% confidence interval (CI), 4.0--4.7] and was significantly elevated for virtually every cause of death. With HIV, mortality from medical causes, but not external causes, was increased 3.7-fold (95% CI, 3.3--4.2), particularly with AIDS and related conditions. With HTLV-II, all-cause mortality was reduced (RR, 0.8; 95% CI, 0.7--0.9), with no statistically significant reduction or elevation for any specific cause. A non-significant excess of tuberculosis deaths (RR, 4.6; 95% CI, 0.8--25.2) was noted with HTLV-II, but there was no excess mortality from leukemia/lymphoma, other malignancies, or neurodegenerative disease. CONCLUSIONS: Without HIV or HTLV-II, IDU had profoundly increased mortality from medical and external causes. HIV was specifically associated with death due to AIDS and related conditions. HTLV-II infection was not significantly associated with mortality from any cause, suggesting that it is not a significant human pathogen, even when present with HIV infection.


Assuntos
Causas de Morte , Infecções por HIV/mortalidade , Infecções por HTLV-II/mortalidade , Abuso de Substâncias por Via Intravenosa , Estudos de Coortes , Infecções por HIV/epidemiologia , Soroprevalência de HIV , Humanos , Fatores de Risco , Estados Unidos/epidemiologia
13.
J Clin Oncol ; 19(11): 2937-47, 2001 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-11387367

RESUMO

PURPOSE: To assess the feasibility of administering NSC 655649, a water-soluble, rebeccamycin analog with topoisomerase inhibitory properties, as a brief intravenous (IV) infusion once every 3 weeks and to determine the maximum-tolerated dose (MTD) of NSC 655649, characterize its pharmacokinetic behavior, and seek preliminary evidence of antitumor activity. PATIENTS AND METHODS: Patients with advanced solid malignancies were treated with escalating doses of NSC 655649 administered over 30 to 60 minutes IV once every 3 weeks. An accelerated dose-escalation method was used to guide dose escalation. After three patients were treated at the first dose level, doses were escalated in increments that ranged up to 150% using single patient cohorts until moderate toxicity was observed, when a more conservative dose-escalation scheme was invoked. MTD was defined as the highest dose level at which the incidence of dose-limiting toxicity did not exceed 20%. MTD was determined for both minimally pretreated (MP) and heavily pretreated (HP) patients. Plasma and urine were sampled to characterize the pharmacokinetic and excretory behavior of NSC 655649. RESULTS: Forty-five patients were treated with 130 courses of NSC 655649 at doses ranging from 20 mg/m(2) to 744 mg/m(2). Myelosuppression was the principal toxicity. Severe neutropenia, which was often associated with thrombocytopenia, was unacceptably high in HP and MP patients treated at 572 mg/m(2) and 744 mg/m(2), respectively. Nausea, vomiting, and diarrhea were common but rarely severe. The pharmacokinetics of NSC 655649 were dose dependent and fit a three-compartment model. The clearance and terminal elimination half-lives for NSC 655649 averaged 7.57 (SD = 4.2) L/h/m(2) and 48.85 (SD = 23.65) hours, respectively. Despite a heterogeneous population of MP and HP patients, the magnitude of drug exposure correlated well with the severity of myelosuppression. Antitumor activity was observed in two HP ovarian cancer patients and one patient with a soft tissue sarcoma refractory to etoposide and doxorubicin. CONCLUSION: Recommended phase II doses are 500 mg/m(2) and 572 mg/m(2) IV once every 3 weeks for HP and MP patients, respectively. The absence of severe nonhematologic toxicities, the encouraging antitumor activity in HP patients, and the unique mechanism of antineoplastic activity of NSC 655649 warrant further clinical development.


Assuntos
Aminoglicosídeos , Antibacterianos/farmacocinética , Antineoplásicos/farmacocinética , Neoplasias/tratamento farmacológico , Adulto , Idoso , Antibacterianos/administração & dosagem , Antibacterianos/efeitos adversos , Antineoplásicos/administração & dosagem , Antineoplásicos/efeitos adversos , Carbazóis , Relação Dose-Resposta a Droga , Feminino , Glucosídeos , Humanos , Infusões Intravenosas , Masculino , Pessoa de Meia-Idade , Neutropenia/induzido quimicamente , Trombocitopenia/induzido quimicamente
14.
J Clin Oncol ; 19(9): 2493-503, 2001 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-11331328

RESUMO

PURPOSE: To assess the feasibility, toxicity, pharmacokinetics, and preliminary activity of BMS-184476 administered as a 1-hour intravenous (IV) infusion every 3 weeks. PATIENTS AND METHODS: Patients with advanced solid malignancies were treated with escalating doses of BMS-184476 as a 1-hour IV infusion every 3 weeks without premedication to prevent hypersensitivity reactions (HSR). Plasma sampling and urine collections were performed to characterize the pharmacokinetics and pharmacodynamics of BMS-184474. RESULTS: Thirty-four patients were treated with 78 courses of BMS-184476 at five dose levels ranging from 20 to 80 mg/m2. Dose-limiting toxicity (DLT), consisting of severe neutropenia with fever, severe diarrhea, and/or severe mucositis, was experienced during course 1 by six of nine minimally pretreated patients treated at the 70 and 80 mg/m2 dose level. In contrast, of 15 assessable patients treated at the 60 mg/m2 dose level, which is the maximum-tolerated dose (MTD) of BMS-184476 on this administration schedule, only one heavily pretreated patient developed DLT (grade 4 neutropenia with fever and grade 3 diarrhea). One patient developed a grade 2 HSR during a second course of BMS-184476 at the 40 mg/m2 dose level. A previously untreated patient with an advanced cholangiocarcinoma experienced a partial response, and a patient with an untreated carcinoma of the gastroesophageal junction had a minor response. The pharmacokinetics of BMS-184476 seemed linear in the dose range studied. Mean +/- SD values for clearance, volume of distribution at steady-state, and terminal half-life were 220 +/- 89 mL/min/m2, 402 +/- 231 L/m2, and 40.8 +/- 21.8 hours, respectively. CONCLUSION: The MTD and recommended dose for phase II evaluations of BMS-184476 is 60 mg/m2 as a 1-hour IV infusion every 3 weeks. The results of this study suggest that BMS-184476 may have several advantages compared with paclitaxel in terms of toxicity, pharmacokinetics, pharmaceutics, and administration and warrants further clinical development.


Assuntos
Antineoplásicos Fitogênicos/efeitos adversos , Neoplasias/tratamento farmacológico , Taxoides , Adulto , Idoso , Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/farmacocinética , Medula Óssea/efeitos dos fármacos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Paclitaxel/efeitos adversos , Paclitaxel/análogos & derivados , Solubilidade
15.
J Clin Oncol ; 18(24): 4086-97, 2000 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-11118470

RESUMO

PURPOSE: To evaluate the toxicity and pharmacologic behavior of the novel mushroom-derived cytotoxin irofulven administered as a 5-minute intravenous (IV) infusion daily for 5 days every 4 weeks to patients with advanced solid malignancies. PATIENTS AND METHODS: In this phase I trial, 46 patients were treated with irofulven doses ranging from 1.0 to 17.69 mg/m(2) as a 5-minute IV infusion (two patients received a 1-hour infusion) daily for 5 days every 4 weeks. The modified continual reassessment method was used for dose escalation. Pharmacokinetic studies were performed on days 1 and 5 to characterize the plasma disposition of irofulven. RESULTS: Forty-six patients were treated with 92 courses of irofulven. The dose-limiting toxicities on this schedule were myelosuppression and renal dysfunction. At the 14.15-mg/m(2) dose level, renal dysfunction resembling renal tubular acidosis occurred in four of 10 patients and was ameliorated by prophylactic IV hydration. The 17.69-mg/m(2) dose level was not tolerated because of grade 4 neutropenia and renal toxicity, whereas the 14.15-mg/m(2) dose level was not tolerable with repetitive dosing because of persistent thrombocytopenia. Other common toxicities included mild to moderate nausea, vomiting, facial erythema, and fatigue. One partial response occurred in a patient with advanced, refractory metastatic pancreatic cancer lasting 7 months. Pharmacokinetic studies of irofulven revealed dose-proportional increases in both maximum plasma concentrations and area under the concentration-time curve, while the agent exhibited a rapid elimination half-life of 2 to 10 minutes. CONCLUSION: Given the results of this study, the recommended dose of irofulven is 10.64 mg/m(2) as a 5-minute IV infusion daily for 5 days every 4 weeks. The preliminary antitumor activity documented in a patient with advanced pancreatic cancer and the striking preclinical antitumor effects of irofulven observed on intermittent dosing schedules support further disease-directed evaluations of this agent on the schedule evaluated in this study.


Assuntos
Antineoplásicos Alquilantes/efeitos adversos , Antineoplásicos Alquilantes/farmacocinética , Neoplasias/tratamento farmacológico , Neoplasias/metabolismo , Sesquiterpenos/efeitos adversos , Sesquiterpenos/farmacocinética , Adulto , Idoso , Antineoplásicos Alquilantes/administração & dosagem , Esquema de Medicação , Feminino , Doenças Hematológicas/induzido quimicamente , Humanos , Nefropatias/induzido quimicamente , Masculino , Pessoa de Meia-Idade , Náusea/induzido quimicamente , Sesquiterpenos/administração & dosagem , Vômito/induzido quimicamente
16.
J Clin Oncol ; 18(23): 3974-85, 2000 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-11099327

RESUMO

PURPOSE: To evaluate the maximum-tolerated dose, dose-limiting toxicities (DLTs), and pharmacokinetic profile of vesnarinone given once daily in combination with gemcitabine. PATIENTS AND METHODS: Twenty-six patients were treated with oral vesnarinone once daily on a continuous schedule at doses of 60, 90, 120, 150, and 180 mg in combination with intravenous (IV) gemcitabine at a dose of 1,000 mg/m(2) on days 1, 8, and 15 every 4 weeks. To determine whether biologically relevant concentrations were being achieved, predose concentrations (C(min)) of vesnarinone were obtained weekly. Plasma gemcitabine and 2',2'-difluorodeoxyuridine concentrations were obtained during courses 1 and 2. RESULTS: Twenty-six patients were treated with 92 courses of vesnarinone/gemcitabine. The principal toxicities of the regimen consisted of neutropenia and thrombocytopenia, which were dose-limiting in two of eight heavily pretreated new patients treated at the 90 mg/1,000 mg/m(2) dose level and one of 10 minimally pretreated new patients at the 120 mg/1,000 mg/m(2) dose level. None of three patients treated with 15 courses at the vesnarinone/gemcitabine dose levels of 60 mg/1,000 mg/m(2) experienced DLT. Pharmacokinetic studies of vesnarinone revealed significant interpatient variability at any given dose level. There was evidence of a linear relationship between vesnarinone dose and mean C(min) at dosages of vesnarinone less than 150 mg, with plateauing of mean C(min) values at higher dosages. There was no impact of vesnarinone on gemcitabine concentrations, and the vesnarinone pharmacokinetics did not change with gemcitabine between weeks 1 and 2. Two partial responses occurred in patients with refractory breast and non-small-cell lung carcinoma. CONCLUSION: When combined with gemcitabine, the recommended dose of vesnarinone for phase II evaluations is 90 mg orally once daily with gemcitabine 1,000 mg/m(2) IV on days 1, 8, and 15 every 4 weeks. There is no evidence of pharmacokinetic interaction between vesnarinone and gemcitabine. Further studies of vesnarinone as a single agent or in combination with gemcitabine and other antineoplastic agents are warranted.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/farmacocinética , Neoplasias/tratamento farmacológico , Neoplasias/metabolismo , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Apoptose/efeitos dos fármacos , Diferenciação Celular/efeitos dos fármacos , Desoxicitidina/administração & dosagem , Desoxicitidina/efeitos adversos , Desoxicitidina/análogos & derivados , Desoxicitidina/farmacocinética , Relação Dose-Resposta a Droga , Sinergismo Farmacológico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Náusea/induzido quimicamente , Neoplasias/sangue , Neutropenia/induzido quimicamente , Pirazinas , Quinolinas/administração & dosagem , Quinolinas/efeitos adversos , Quinolinas/farmacocinética , Trombocitopenia/induzido quimicamente , Vômito/induzido quimicamente , Gencitabina
17.
Int J Cancer ; 80(5): 662-6, 1999 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-10048963

RESUMO

Adult T-cell leukemia/lymphoma (ATL), a rare outcome of infection with human T-lymphotropic virus (HTLV-I), is endemic in central Brooklyn, which has a large Caribbean migrant population. Previous studies have suggested that HTLV-I prevalence in central Brooklyn may be similar to that recorded in the Caribbean islands. We established a pilot 1-year surveillance program to identify cases of ATL in 7 of 10 hospitals serving the residents of 18 zip codes of central Brooklyn with a combined population of 1,184,670. Of the 6,198 in-patient beds in the catchment area, approximately 83% were covered. Twelve incident cases of ATL were ascertained, all among persons of Afro-Caribbean descent, indicating an annual incidence in African-Americans in this community of approximately 3.2/100,000 person-years. Unexplained hypercalcemia was the most useful screening method, identifying 3 of 5 patients not referred for possible ATL by a local hematologist. The female:male ratio was 3:1. The age pattern was different from that reported in the Caribbean Basin and closer to the pattern seen in Japan. Our study supports evidence that HTLV-I infection and ATL are endemic in central Brooklyn and suggests that a more intensive surveillance program for this disease coupled with intervention efforts to reduce HTLV-I transmission are warranted.


Assuntos
Leucemia-Linfoma de Células T do Adulto/epidemiologia , Adulto , Idoso , Demografia , Feminino , Anticorpos Anti-HTLV-I/sangue , Humanos , Incidência , Jamaica/etnologia , Leucemia-Linfoma de Células T do Adulto/sangue , Leucemia-Linfoma de Células T do Adulto/imunologia , Masculino , Pessoa de Meia-Idade , Cidade de Nova Iorque/epidemiologia , Projetos Piloto , Vigilância da População , Fatores de Risco , Trinidad e Tobago/etnologia
18.
Proc Soc Exp Biol Med ; 215(3): 248-57, 1997 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-9207860

RESUMO

This paper reports an in-depth approach that identifies ascorbyl-2-sulfate (AS) in gastric, blood, liver, and muscle tissues of Atlantic salmon (Salmo salar). To insure the identify of the AS, the study utilized the latest high-performance liquid chromatography (HPLC) technology plus electron ionization mass spectrometry (EIMS). Just before saltwater adaptation stage, juvenile Atlantic salmon were force-fed AS, ascorbic acid (AA), and a molecular-equivalent combination of the two. After tissue analyses for AA and AS were performed by HPLC separation, the HPLC peaks were identified by EIMS. The data collected in this study indicate that Atlantic salmon can absorb AS through the gastric tissue when forced-fed AA and AS as described. The data also indicate that AS is transported through the blood to the liver. There is evidence to indicate that AS is converted to AA in the livers of these salmon. In addition, the muscle tissue contained a large portion of AA and AS.


Assuntos
Ácido Ascórbico/análogos & derivados , Ácido Ascórbico/farmacocinética , Animais , Ácido Ascórbico/sangue , Cromatografia Líquida de Alta Pressão , Mucosa Gástrica/metabolismo , Fígado/metabolismo , Espectrometria de Massas , Músculos/metabolismo , Salmão , Distribuição Tecidual
19.
Infect Control Hosp Epidemiol ; 18(4): 230-6, 1997 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-9131364

RESUMO

OBJECTIVE: To evaluate the risk of phlebitis associated with chlorhexidine-coated polyurethane catheters in peripheral veins. DESIGN: A randomized, double-blinded trial comparing chlorhexidine-coated polyurethane catheters with uncoated polyurethane catheters. SETTING: A university hospital. PATIENTS: Adult medicine and surgery patients. INTERVENTIONS: Certified registered nurse anesthetists or an infusion team consisting of nurses and physicians inserted the catheters. Catheter insertion sites were scored twice daily for evidence of phlebitis. At the time catheters were removed, a quantitative blood culture was performed, and catheters were sonicated for quantitative culture. RESULTS: Of 221 evaluable catheters, phlebitis developed in 18 (17%) of 105 coated catheters, compared to 27 (23%) of 116 uncoated catheters (relative risk [RR], 0.74; 95% confidence interval [CI95], 0.43-1.26; P = .32). By survival analysis, chlorhexidine-coated catheters had a lower risk of phlebitis during the first 3 days (P = .06), but not when all catheters were considered in both patient groups (P = .31). In the absence of catheter colonization, the incidence of phlebitis was 21% (16/76) and 24% (20/86) for coated and uncoated catheters, respectively (P = .85), whereas in the presence of catheter colonization, the incidence of phlebitis was 14% (1/7) and 80% (4/5) for coated and uncoated catheters, respectively (RR, 0.18; CI95, 0.03-1.15; P = .07). CONCLUSION: The risk of phlebitis in the presence of catheter colonization was 82% lower for chlorhexidine-coated polyurethane catheters compared to otherwise identical uncoated catheters.


Assuntos
Anti-Infecciosos Locais/administração & dosagem , Cateterismo Periférico/efeitos adversos , Cateteres de Demora/microbiologia , Clorexidina/administração & dosagem , Infecção Hospitalar/prevenção & controle , Contaminação de Equipamentos/prevenção & controle , Flebite/prevenção & controle , Adulto , Cateterismo Periférico/métodos , Cateteres de Demora/efeitos adversos , Intervalos de Confiança , Método Duplo-Cego , Feminino , Humanos , Controle de Infecções/métodos , Controle de Infecções/normas , Masculino , Modelos de Riscos Proporcionais , Estudos Prospectivos , Risco , Tamanho da Amostra , Staphylococcus/isolamento & purificação , Análise de Sobrevida
20.
J Acquir Immune Defic Syndr Hum Retrovirol ; 12(5): 519-22, 1996 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-8757431

RESUMO

Forty-one human T-cell lymphotropic virus type I (HTLV-1)-seropositive individuals were identified among 1,012 subjects with stored serum samples from a health and seroepidemiological survey conducted in Barbados in 1972. These 41 subjects plus 79 HTLV-1 seronegative household members were targeted in a follow-up study 20 years later. Sixteen seropositive subjects and 22 seronegative subjects were interviewed, examined, and phlebotomized. There were no changes in HTLV-1 serostatus between the 1972 and follow-up serum samples. Three (19%) of the seropositive subjects had HTLV-1-associated disorders: two with dermatitis and one with "smoldering" adult T-cell leukemia. Neurologic and immunologic function was similar in HTLV-1-seropositive and HTLV-1-seronegative subjects. HTLV-1 antibodies persist over many years, and the risk for seroconversion of household contacts is low.


Assuntos
Anticorpos Anti-HTLV-I/sangue , Infecções por HTLV-I/epidemiologia , Adolescente , Adulto , Barbados/epidemiologia , Dermatite/complicações , Feminino , Seguimentos , Infecções por HTLV-I/complicações , Infecções por HTLV-I/imunologia , Infecções por HTLV-I/fisiopatologia , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Risco
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