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1.
Cureus ; 16(2): e54358, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38500892

RESUMO

INTRODUCTION: Unstable sacral fractures with pelvic fractures are challenging to both surgeons and patients, particularly in the immediate post-injury phase and later when definitive fixation is undertaken. Percutaneous iliosacral screw fixation is widely regarded as the gold standard treatment for unstable sacral fractures without spinopelvic dissociation. Closed reduction and percutaneous fixation using iliosacral screws for sacral fractures provide early stabilisation without the need for extensive surgical exposure, thereby mitigating major complications associated with open surgical procedures. A new technique for stabilising unstable sacral fractures is the minimally invasive ilioilial fixator, also called a transiliac internal fixator (TIIF), which has gained more attention for its ability to address challenges associated with sacroiliac screw fixation. The objective of this study is to compare the functional, radiological, and surgical outcomes between the percutaneous iliosacral screw and the ilioilial fixator. METHODS: A total of 51 patients with sacral fracture injuries sustained between August 2019 and November 2021 were included in this study, with 25 patients in Group A and 26 patients in Group B. Patient randomization was done using computer-generated randomization facilitated by Random Allocation Software (Mahmood Saghaei, Isfahan, Iran). All patients underwent the chosen intervention within 10 days of the trauma. Patients had follow-up at two weeks, six weeks, and 12 months post-treatment. The results of fixation were evaluated radiologically based on the Matta and Tornetta grading system and clinically using the Majeed pelvic scoring system. Complications were detected in both groups during follow-up visits. RESULTS: The study found no statistically significant differences between the two patient groups in terms of final clinical assessment (p=0.79), radiological assessment (p=0.78), or the need for another operation (p=1.0). Moreover, there were no statistically significant differences between the groups with respect to complication rates (p=0.63) or the time of union (p=0.14). No differences were noted in terms of intraoperative blood loss (p=0.93) or operative time (p=0.34) but for longer incision length in the ilioilial fixator group (p<0.001) and an increased risk of intraoperative radiation exposure in the iliosacral screw group (p<00.1). DISCUSSION: Although the iliosacral screw is considered a gold standard for unstable sacral fracture, a TIIF is a good alternative with a very satisfactory outcome. CONCLUSION: Although the iliosacral screw still remains the gold standard for the management of sacral fractures, the ilioilial fixator emerges as a good alternative with comparable functional and radiological outcomes.

2.
Theriogenology ; 77(7): 1438-41, 2012 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-22284220

RESUMO

The combined thickness of the uterus and placenta (CTUP) is one of the characteristics that can be used to assess fetal development and/or placental function in bovine. The current study was designed to establish reference values for the CTUP throughout pregnancy in normal pregnant buffalo-cows. The CTUP at the intracotyledonary space was measured monthly from the second month until full term using electronic calipers of the ultrasound machine. The CTUP increased monthly from 2.5 mm at the second month to 12 mm at the full term. During the last trimester, the monthly increase in the CTUP was higher than that recorded during the first and second trimesters. The result of the current study can be used as normal values for future studies of CTUP in pathologically pregnant buffalo-cows.


Assuntos
Búfalos/anatomia & histologia , Placenta/diagnóstico por imagem , Prenhez , Útero/diagnóstico por imagem , Animais , Búfalos/crescimento & desenvolvimento , Feminino , Gravidez , Valores de Referência , Fatores de Tempo , Ultrassonografia Pré-Natal/métodos , Ultrassonografia Pré-Natal/veterinária
3.
J Eur Acad Dermatol Venereol ; 23(4): 406-9, 2009 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-19175705

RESUMO

BACKGROUND: In psoriasis, keratinocyte hyperplasia may be explained by imbalance of growth factors responsible for epidermal proliferation and altered metabolism of their receptors. Transforming growth factor-beta 1 (TGF-beta1) implications in the pathogenesis of psoriasis can be attributed to several mechanisms besides keratinocyte cell cycle inhibition. OBJECTIVES: To evaluate the relation between serum and tissue levels of TGF-beta1 in psoriasis and their correlation with disease parameters. PATIENTS AND METHODS: Serum and punch biopsy of involved and non-involved skin of 22 patients with psoriasis vulgaris and 10 controls were collected for quantification of TGF-beta1 by enzyme-linked immunosorbent assay kit. RESULTS: Serum level of TGF-beta1 in psoriatic patients was higher than controls in a statistically non-significant manner. Correlations between serum level of TGF-beta1 and extent of the disease (P = 0.007) and Psoriasis Area and Severity Index (PASI) score (P = 0.005) were observed. Mean tissue levels of TGF-beta1 were highest in psoriatic lesions in contrast to normal skin of psoriatic patients and healthy controls, but not statistically significant. Correlation between tissue levels of TGF-beta1 in non-involved skin and extent of the disease (P = 0.007) and PASI score (P = 0.013) was detected. Correlation was detected between levels of TGF-beta1 in psoriatic plaques and serum of patients (P = 0.035), but not between levels of TGF-beta1 in non-involved skin and serum. CONCLUSIONS: Tissue expression of TGF-beta1 in psoriasis may be affected by the stage of development of the lesion. The direct relation between TGF-beta1 in psoriatic plaques and serum imply that the mechanisms for TGF-beta1 production and release in both these compartments may be related.


Assuntos
Psoríase/metabolismo , Fator de Crescimento Transformador beta1/metabolismo , Adulto , Biópsia , Estudos de Casos e Controles , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Psoríase/sangue , Psoríase/patologia , Fator de Crescimento Transformador beta1/sangue
4.
Graefes Arch Clin Exp Ophthalmol ; 245(3): 448-50, 2007 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-16775720

RESUMO

PURPOSE: To report the unexpected finding of a primary retinal B-cell lymphoma in a patient with previous breast carcinoma and subsequent lymphoma of the stomach. METHODS: Histopathologic and immunohistochemical findings in the enucleated eye are described in conjunction with clinical features and investigations. RESULTS: An 80-year-old woman with previous breast cancer presented with moderate loss of vision associated with vitreous opacities, circumpapillary retinal haemorrhages, and attenuated retinal vessels in her left eye. Treatment with systemic steroids and oral immunosuppressive drugs was initiated on suspicion of carcinoma-associated retinopathy. Two years later, the patient was diagnosed with MALT lymphoma of the stomach. Unfortunately, the ocular symptoms did not improve, and the patient developed neovascular glaucoma, for which the eye was eventually enucleated. Histopathology and immunohistochemistry as well as a molecular analysis revealed a primary B-cell lymphoma of the retina. CONCLUSION: Non-Hodgkin B-cell lymphoma of the retina should be considered as a differential diagnosis in cases of non-specific retinopathies even in the presence of other primary neoplastic co-morbidities.


Assuntos
Linfoma de Zona Marginal Tipo Células B/patologia , Linfoma de Células B/patologia , Segunda Neoplasia Primária/patologia , Neoplasias da Retina/patologia , Neoplasias Gástricas/patologia , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/metabolismo , Neoplasias da Mama/patologia , Feminino , Glucocorticoides/uso terapêutico , Humanos , Imuno-Histoquímica , Imunossupressores/uso terapêutico , Linfoma de Células B/metabolismo , Linfoma de Zona Marginal Tipo Células B/metabolismo , Proteínas de Neoplasias/metabolismo , Segunda Neoplasia Primária/metabolismo , Neoplasias da Retina/metabolismo , Neoplasias Gástricas/metabolismo
5.
J Med Liban ; 54(3): 164-7, 2006.
Artigo em Inglês | MEDLINE | ID: mdl-17190135

RESUMO

PURPOSE: To present a unilateral central visual field defect in a patient with psoriatic arthritis treated with Methotrexate and folic acid supplement, probably induced by toxic posterior optic neuropathy. The scotoma incompletely resolved after cessation of Methotrexate (MTX) therapy. METHODS: Serial fundoscopic, perimetric and electrophysiological examination as well as comprehensive neurological investigation including lumbar puncture, carotid sonography, electroneurography, and MRI of the brain. RESULTS: A female patient with psoriatic arthritis on long-standing Methotrexate (MTX 15 mg IM/once a week) therapy suffered first from an acute attack of central visual field defect in her right eye and later on from two subsequent deteriorations of her scotoma within one year. A demyelinating retrobulbar optic neuritis was excluded through repeated comprehensive neurological investigations and unresponsiveness to systemic corticosteroid therapy. A MTX-induced posterior optic neuropathy was suspected and the patient experienced improvement of her visual field defects only six weeks after discontinuing MTX therapy. Further improvement was observed through follow-up perimetric examinations half a year after cessation. CONCLUSIONS: Central scotoma with unremarkable optic disc can occur after long-standing treatment with MTX and despite folic acid supplementary therapy. This is most probably due to posterior optic neuropathy. Early cessation of the drug or change to another antimetabolite therapy can stop the deterioration of the visual field changes and even improve them. The exact pathomechanism is still unclear and the involvement of only one eye requires more investigation. MTX-induced posterior optic neuropathy should be included in the differential diagnosis of toxic optic neuropathy. This is getting more frequent than before because of the nowadays standard use of MTX in treatment of many autoimmune collagen diseases.


Assuntos
Antirreumáticos/efeitos adversos , Metotrexato/efeitos adversos , Doenças do Nervo Óptico/induzido quimicamente , Campos Visuais/efeitos dos fármacos , Antirreumáticos/administração & dosagem , Artrite Psoriásica/tratamento farmacológico , Feminino , Humanos , Metotrexato/administração & dosagem , Pessoa de Meia-Idade
6.
Graefes Arch Clin Exp Ophthalmol ; 244(7): 883-4, 2006 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-16328427

RESUMO

PURPOSE: We report a case of periocular subcutaneous macrofilariasis as an initial sign of a systemic Loa loa infection. METHODS: Thorough history, eye examination and surgical intervention. Parasitological and serological analysis. RESULTS: A periocular adult Loa loa worm was extracted from the left upper eyelid in an African student living in Germany after presenting to our department with intermittent attacks of painful lid swelling. Four weeks later he presented with Calabar swellings in his arms without serological evidence of microfilaria and was treated with diethylcarbamazine. CONCLUSION: Due to increasing migration of populations to Europe rare manifestations of ocular loiasis are becoming more common. Intermittent painful eyelid swelling in patients who visited or have lived in Africa should always raise the suspicion of systemic loiasis.


Assuntos
Infecções Oculares Parasitárias/diagnóstico , Doenças Palpebrais/diagnóstico , Loa/isolamento & purificação , Loíase/diagnóstico , Dermatopatias Parasitárias/diagnóstico , Adulto , África/etnologia , Animais , Dietilcarbamazina/uso terapêutico , Infecções Oculares Parasitárias/tratamento farmacológico , Infecções Oculares Parasitárias/cirurgia , Doenças Palpebrais/tratamento farmacológico , Doenças Palpebrais/cirurgia , Feminino , Filaricidas/uso terapêutico , Alemanha/epidemiologia , Humanos , Loíase/tratamento farmacológico , Loíase/cirurgia , Masculino , Dermatopatias Parasitárias/cirurgia
7.
Acta Ophthalmol Scand ; 83(6): 739-45, 2005 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-16396654

RESUMO

PURPOSE: To compile and appraise the accounts of the miracles of vision in the New Testament. METHODS: We carried out a critical analysis of the compilation of ocular miracles using past medical knowledge and historical reconstruction based on the accounts of the apostles and of various historians living in the first three centuries ad. RESULTS: Three blind adult male beggars residing on three different street locations were described. Two had previously had good vision that had declined over a long time and the third had been born blind. The manifestations of the ocular diseases in these cases were meagre, precluding any precise diagnosis. The healing methodology did not rely on physical examination, detailed history, or the use of medicines. Jesus' tools consisted of spitting, touching, praying and the use of words. Visual outcome reported as a complete cure was realized in all three incidents. CONCLUSIONS: The accounts of miracles in the Gospels appear to be historically reliable, yet subject to different interpretations: faith in the miracle (the Christian perspective); sorcery (the Jewish perspective); mythology (the atheist perspective), and scientifically possible human action by a charismatic, compassionate, knowledgeable man (the scientific perspective: psychotherapy or suggestion).


Assuntos
Bíblia , Cegueira/história , Cura pela Fé/história , Pessoas Famosas , Medicina na Literatura , Religião e Medicina , Cegueira/terapia , Cristianismo/história , História Antiga , Humanos , Oftalmologia/história
9.
Graefes Arch Clin Exp Ophthalmol ; 242(5): 428-31, 2004 May.
Artigo em Inglês | MEDLINE | ID: mdl-14735367

RESUMO

PURPOSE: To present a complication of repeated Valsalva maneuver. METHODS: Case report with serial intravenous fluorescein angiography and comprehensive workup for coagulopathies. RESULTS: After playing strenuous musical pieces, a solo trombonist suffered within 1 year three attacks of visual loss in the right eye; he had two attacks of inferior hemi-central retinal vein occlusion 2 months apart, followed by central retinal vein occlusion 10 months later. Final best spectacle-corrected visual acuity was 6/60. He ended his professional career, and no further attacks occurred in the following 10 years. CONCLUSION: Retinal vein occlusion with irreversible visual loss can occur after playing a strenuous piece of music on a high-resistance instrument.


Assuntos
Música , Oclusão da Veia Retiniana/etiologia , Manobra de Valsalva , Angiofluoresceinografia , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva , Oclusão da Veia Retiniana/diagnóstico , Acuidade Visual
10.
East Mediterr Health J ; 9(4): 689-701, 2003 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-15748066

RESUMO

Treatment failure is a serious problem facing some national tuberculosis (TB) control programmes. Irregularity of treatment is a factor that can lead to treatment failure. A case-control study was carried out in TB centres in Egypt during April 2001-December 2002 aimed at investigating the predictors of treatment failure. We interviewed 119 people with treatment failure and an equal number of cured cases (controls) and their families regarding sociodemographic characteristics, information about TB, information about drugs, treatment compliance, family support and patient-family interaction. Significant risk factors for treatment failure were non-compliance to treatment, deficient health education to the patient, poor patient knowledge regarding the disease and diabetes mellitus as co-morbid condition.


Assuntos
Antituberculosos/uso terapêutico , Terapia Diretamente Observada , Tuberculose/tratamento farmacológico , Adulto , Estudos de Casos e Controles , Comorbidade , Complicações do Diabetes/complicações , Complicações do Diabetes/epidemiologia , Terapia Diretamente Observada/métodos , Terapia Diretamente Observada/psicologia , Escolaridade , Egito/epidemiologia , Família/psicologia , Feminino , Conhecimentos, Atitudes e Prática em Saúde , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Cooperação do Paciente/psicologia , Educação de Pacientes como Assunto/normas , Valor Preditivo dos Testes , Avaliação de Programas e Projetos de Saúde , Fatores de Risco , Apoio Social , Fatores Socioeconômicos , Inquéritos e Questionários , Falha de Tratamento , Tuberculose/complicações , Tuberculose/epidemiologia , Tuberculose/psicologia
11.
(East. Mediterr. health j).
em Inglês | WHO IRIS | ID: who-119322

RESUMO

Treatment failure is a serious problem facing some national tuberculosis [TB] control programmes. Irregularity of treatment is a factor that can lead to treatment failure. A case-control study was carried out in TB centres in Egypt during April 2001-December 2002 aimed at investigating the predictors of treatment failure. We interviewed 119 people with treatment failure and an equal number of cured cases [controls] and their families regarding sociodemographic characteristics, information about TB, information about drugs, treatment compliance, family support and patient-family interaction. Significant risk factors for treatment failure were non-compliance to treatment, deficient health education to the patient, poor patient knowledge regarding the disease and diabetes mellitus as co-morbid condition


Assuntos
Estudos de Casos e Controles , Comorbidade , Complicações do Diabetes , Terapia Diretamente Observada , Escolaridade , Família , Conhecimentos, Atitudes e Prática em Saúde , Modelos Logísticos , Cooperação do Paciente , Valor Preditivo dos Testes , Apoio Social , Falha de Tratamento , Tuberculose , Antituberculosos
12.
Int J Tuberc Lung Dis ; 6(12): 1083-90, 2002 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-12546116

RESUMO

SETTING: The National Tuberculosis Programmes in Egypt and Syria. OBJECTIVES: To calculate the costs and effectiveness of alternative ways of implementing TB control in Egypt and Syria, in order to illustrate the factors influencing the cost-effectiveness of TB treatment in middle-income countries. DESIGN: We compared the costs and cure rates in Egypt and Syria of the World Health Organization recommended directly observed treatment, short-course (DOTS) strategy and alternative strategies. The study included costs both to the health services and to the patient. RESULTS: In Egypt and Syria, the cost-effectiveness of DOTS implemented through the primary health care (PHC) system was respectively $258 and $243 per patient cured. This compares to a cost per patient cured of $297 (Egypt) and $693 (Syria) for alternative strategies implemented through specialist clinics. In Egypt, when DOTS is implemented through specialist chest clinics it costs $585 per patient cured. Hospitalisation costs either $1490, $1621 or $1699 per patient cured, depending on treatment delivery in the continuation phase. CONCLUSION: This study demonstrates that the move towards DOTS integrated at the PHC level has substantially improved the effectiveness of TB treatment in Egypt and Syria, without substantially increasing costs. An analysis of the different costs and effectiveness of the variety of TB treatment strategies has enabled both National Tuberculosis Programmes to expand DOTS and implement it in a way that takes into account limited resources and local health systems.


Assuntos
Antituberculosos/economia , Antituberculosos/uso terapêutico , Terapia Diretamente Observada/economia , Custos de Cuidados de Saúde/estatística & dados numéricos , Tuberculose/tratamento farmacológico , Tuberculose/economia , Antituberculosos/administração & dosagem , Análise Custo-Benefício/economia , Análise Custo-Benefício/estatística & dados numéricos , Terapia Diretamente Observada/estatística & dados numéricos , Egito , Gastos em Saúde/estatística & dados numéricos , Humanos , Avaliação de Resultados em Cuidados de Saúde/economia , Avaliação de Resultados em Cuidados de Saúde/estatística & dados numéricos , Sensibilidade e Especificidade , Fatores Socioeconômicos , Síria
13.
Photodermatol Photoimmunol Photomed ; 17(4): 159-63, 2001 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-11499536

RESUMO

BACKGROUND/AIMS: The combination of psoralens with different types of ultraviolet (UVL) sources in the treatment of vitiligo has led to different reports of success. The purpose of this trial is to compare in a random right-left comparison study the efficacy and side effects of oral 8-MOP plus UVA (PUVA) and oral 8-MOP plus UVB (broadband, 290-320 nm P-UVB) in the treatment of vitiligo. METHODS: The study included 24 cases of extensive vitiligo involving more than 30% of the body surface area in a bilateral symmetrical distribution. Each patient received 0.7 mg/kg 8-MOP orally 2 h before the light session. The right side of the body was exposed to UVA (320-400 nm), while the left half was exposed to UVB (290-320 nm). The patients received 3 sessions/week for a total of 30 sessions. RESULTS: Both PUVA and PUVB produced moderate (50-60%) improvement, with similar incidences of phototoxic reaction and skin thickening. However, the study revealed a significant difference in the number of sessions needed to improve produce erythema and perifollicular pigmentation as well as a moderate response, the response on the UVA side always being earlier. Furthermore, the amount of joules needed to achieve the same response was 10 times greater on the UVA side than on the UVB side. CONCLUSION: The use of psoralen plus broadband UVB is as effective as PUVA in the treatment of vitiligo. However, the long-term side effects of psoralen plus UVB are unknown.


Assuntos
Ficusina/uso terapêutico , Fármacos Fotossensibilizantes/uso terapêutico , Terapia Ultravioleta/métodos , Vitiligo/tratamento farmacológico , Vitiligo/radioterapia , Administração Oral , Adolescente , Adulto , Criança , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
14.
J Morphol ; 249(3): 252-66, 2001 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-11517468

RESUMO

The skull of Acrochordus has been characterized by the absence of a crista circumfenestralis (a synapomorphy shared by all snakes), and by the absence of a recessus scalae tympani that in other squamates forms by subdivision of the embryonic metotic fissure. These traits have variably been identified as either plesiomorphic or paedomorphic. The study of the development of the osteocranium in a series of cleared and stained embryos of Acrochordus shows a close correspondence to the development of the skull in other snakes. The exception is the formation of the postorbital from two ossification centers. The significance of this observation, which might suggest the embryonic fusion of a postfrontal with a postorbital, remains enigmatic, as it is based on one side only of the skull of a single specimen. By contrast, a rudimentary and modified crista circumfenestralis can be identified in the skull of Acrochordus. Furthermore, absence of a recessus scalae tympani is not due to an undivided fissura metotica, but results from the obliteration of the anterior part of the metotic fissure instead. With respect to this character, Acrochordus is neither plesiomorphic, nor paedomorphic, but autapomorphic. This interpretation of the skull of Acrochordus is compatible with the sister-group relationships this genus shares with colubroid snakes.


Assuntos
Encéfalo/anatomia & histologia , Encéfalo/embriologia , Crânio/anatomia & histologia , Crânio/embriologia , Serpentes/anatomia & histologia , Serpentes/embriologia , Animais , Modelos Anatômicos , Modelos Biológicos
15.
Photodermatol Photoimmunol Photomed ; 16(2): 43-9, 2000 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-10823310

RESUMO

Until recently, various therapies for localized scleroderma have been used with limited success. Recently, phototherapy, with or without psoralen, was proposed as a successful treatment modality. The aim of this study was to evaluate the effect of broad-band low-dose ultraviolet A (UVA) phototherapy in patients with localized scleroderma, using a new method for evaluation. Twelve patients complaining of morphea were exposed to UVA irradiation at a dose of 20 J/cm2 3 times per week for 20 sessions. Selected covered plaques served as internal controls. The efficacy of therapy was judged clinically by sequential inspection and palpation. In biopsy specimens from exposed and covered plaques stained with hematoxylin and eosin (H & E) and Masson trichrome stains, the concentration of collagen per dermal surface area was measured with the use of a computerized image analyzer. All patients reported remarkable softening of skin lesions, confirmed by sequential palpatory assessment. A significant reduction in the mean concentration of collagen per surface area was detected in the plaques exposed to UVA (the P value being 0.007, P<0.01), whereas in the covered plaques the difference was not statistically significant (the P value being 0.10, P>0.05). The conclusion is that low-dose broad-band UVA phototherapy is a very effective and safe treatment modality for localized scleroderma.


Assuntos
Esclerodermia Localizada/radioterapia , Terapia Ultravioleta/métodos , Adolescente , Adulto , Idoso , Compostos Azo , Biópsia , Criança , Colágeno/análise , Colágeno/efeitos da radiação , Corantes , Derme/patologia , Derme/efeitos da radiação , Fracionamento da Dose de Radiação , Amarelo de Eosina-(YS) , Estudos de Avaliação como Assunto , Feminino , Corantes Fluorescentes , Hematoxilina , Humanos , Processamento de Imagem Assistida por Computador , Masculino , Verde de Metila , Pessoa de Meia-Idade , Palpação , Dosagem Radioterapêutica , Segurança , Esclerodermia Localizada/patologia , Resultado do Tratamento , Raios Ultravioleta/classificação
16.
Science ; 287(5460): 2010-2, 2000 Mar 17.
Artigo em Inglês | MEDLINE | ID: mdl-10720326

RESUMO

A 95-million-year-old fossil snake from the Middle East documents the most extreme hindlimb development of any known member of that group, as it preserves the tibia, fibula, tarsals, metatarsals, and phalanges. It is more complete than Pachyrhachis, a second fossil snake with hindlimbs that was recently portrayed to be basal to all other snakes. Phylogenetic analysis of the relationships of the new taxon, as well as reanalysis of Pachyrhachis, shows both to be related to macrostomatans, a group that includes relatively advanced snakes such as pythons, boas, and colubroids to the exclusion of more primitive snakes such as blindsnakes and pipesnakes.


Assuntos
Fósseis , Membro Posterior/anatomia & histologia , Filogenia , Serpentes/anatomia & histologia , Serpentes/classificação , Animais , Osso e Ossos/anatomia & histologia , Israel , Lagartos/anatomia & histologia , Crânio/anatomia & histologia
17.
Pharmacogenetics ; 10(8): 695-704, 2000 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-11186132

RESUMO

CYP1A2 activity has been demonstrated to be bimodally or trimodally distributed in several populations, consistent with a codominant or recessive functional genetic polymorphism. However, studies aimed at identifying polymorphisms in CYPIA2 have not yet adequately accounted for this distribution pattern. To search for functional polymorphisms, we performed genome-walking, polymerase chain reaction (PCR) sequencing, and cloning, and identified three novel polymorphisms in the 5' flanking region of CYP1A2: a T-3591G substitution, a G-3595T substitution, and a T-3605 insertion. The frequency of the T-3591G substitution was determined by a PCR-restriction fragment length polymorphism assay, and found to be significantly higher (P < 0.0001) in Taiwanese (allele frequency 0.128, n = 125) compared to Caucasians (0.017, n = 87) or African Americans (0.024, n = 104). The functional consequence of the T-3591G and the G-3595T substitutions was determined by site-directed mutagenesis followed by transient transfection experiments. The T-3591G mutation was shown to be nonfunctional, while although the G-3595T mutation appeared to result in an increase in promoter activity, this was only to a small degree and therefore unlikely to be important in vivo. In addition, we report 532 bases of 5' flanking sequence further upstream than that reported to date, and four sequence discrepancies compared to the original published sequence (G-3649C, deltaT-3650, deltaA-4072, and C-4093 ins).


Assuntos
Citocromo P-450 CYP1A2/genética , DNA Intergênico , Polimorfismo de Fragmento de Restrição , Grupos Raciais/genética , Negro ou Afro-Americano , Povo Asiático/genética , Sequência de Bases , População Negra/genética , Passeio de Cromossomo , Variação Genética , Humanos , Dados de Sequência Molecular , Mutação , Reação em Cadeia da Polimerase , Análise de Sequência de DNA , População Branca/genética
18.
J Psychopharmacol ; 14(4): 353-9, 2000.
Artigo em Inglês | MEDLINE | ID: mdl-11198052

RESUMO

The aim of this study was to use the CYP1A2-null mouse to investigate the in-vivo contribution of CYP1A2 to clozapine pharmacokinetics and pharmacodynamics. An intraperitoneal injection of 10 mg/kg clozapine was administered to four male CYP1A2 -/- mice and four male wild-type mice. Clozapine, desmethylclozapine, and clozapine N-oxide concentrations in sequential tail blood samples were measured by HPLC with UV detection. Behavioural parameters were recorded at each time point. The area under the curve (AUC) of clozapine was 2.6 times greater, the clearance of clozapine was 2.6 times slower, and the half-life was 1.2 times longer in the CYP1A2 -/- mice (p = 0.0143) as compared to the wild-type mice. Sixty-one percent of the clozapine clearance in wild-type mice was calculated to be mediated by CYP1A2. The AUC of desmethylclozapine was 1.6 times lower in the CYP1A2 -/- mice compared to the wild-type mice (p = 0.0286), while there was a trend for the AUC of clozapine N-oxide to be greater in the CYP1A2 -/- mice (p = 0.0571). The CYP1A2 -/- mice were significantly more drowsy and showed more motor impairment (p = 0.0145) and myoclonus than the wild-type mice. Our results indicate that, in vivo, CYP1A2 is the major determinant of clozapine clearance, contributes significantly to the demethylation of clozapine, and has a negligible contribution to the N-oxidation. Our data also indicate that CYP1A2 poor metabolizers might be more susceptible than extensive metabolizers to dose-related adverse effects of clozapine, such as sedation, myoclonus and seizures.


Assuntos
Antipsicóticos/farmacologia , Antipsicóticos/farmacocinética , Comportamento Animal/efeitos dos fármacos , Comportamento Animal/fisiologia , Clozapina/farmacologia , Clozapina/farmacocinética , Citocromo P-450 CYP1A2/genética , Animais , Área Sob a Curva , Biotransformação , Peso Corporal/genética , Cromatografia Líquida de Alta Pressão , Discinesia Induzida por Medicamentos/psicologia , Meia-Vida , Camundongos , Camundongos Knockout , Espectrofotometria Ultravioleta
19.
Int J Tuberc Lung Dis ; 3(4): 294-9, 1999 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-10206499

RESUMO

OBJECTIVE: To determine the trend in the risk of tuberculous infection in non-BCG vaccinated children in Egypt in the period 1950-1996. METHODS: In 1949-1952, a tuberculin survey was carried out in Egypt by the World Health Organization (WHO) covering 103 districts. In 1995-1997 a tuberculin survey was carried in 73 620 primary school children in grade one in the same districts, using international guidelines. The trend in tuberculous infection was determined by comparing the prevalence of Mantoux reactions of > or =6 mm in the two surveys in subjects without apparent BCG scar aged 6-7 years. For an estimate of current risk of infection the 17 mm cut-off point (number with 17 mm plus twice the number with greater than 17 mm) was used. RESULTS: In 1995-1997, 76% of children had a BCG scar. Infection prevalence estimates in 14 766 non-BCG-vaccinated children with a mean age of 6.7 years were 11.9%, 4.1%, and 2.1% for the cut-off points 6 mm, 10 mm, and 17 mm, respectively. Decline in the risk of infection was estimated to be in the order of 50% over 45 years, or 1.5% per year. The geometric mean annual risk of infection in the 6.7 years before the survey was estimated at 0.32% (95% confidence interval 0.27-0.40%). For Egypt, the incidence of smear-positive tuberculosis was estimated at 16 per 100000 population, giving a case detection rate of 85% (range 56-100%). CONCLUSION: This survey has shown that the size of the tuberculosis problem in Egypt is considerably smaller now than it was 45 years ago.


Assuntos
Tuberculose/epidemiologia , Vacina BCG , Distribuição de Qui-Quadrado , Criança , Pré-Escolar , Intervalos de Confiança , Egito/epidemiologia , Feminino , Humanos , Masculino , Vigilância da População , Prevalência , Fatores de Risco , Teste Tuberculínico , Tuberculose/prevenção & controle
20.
Toxicol Appl Pharmacol ; 152(1): 193-9, 1998 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-9772215

RESUMO

Acetaminophen (APAP) hepatotoxicity is due to its biotransformation to a reactive metabolite, N-acetyl-p-benzoquinone imine (NAPQI), that is capable of binding to cellular macromolecules. At least two forms of cytochrome P450, CYP2E1 and CYP1A2, have been implicated in this reaction in mice. To test the combined roles of CYP1A2 and CYP2E1 in an intact animal model, a double-null mouse line lacking functional expression of CYP1A2 and CYP2E1 was produced by cross-breeding Cyp1a2-/- mice with Cyp2e1-/- mice. Animals deficient in the expression of both P450s developed normally and exhibited no obvious phenotypic abnormalities. Comparison of the dose-response to APAP (200-1200 mg/kg) indicated that double-null animals were highly resistant to APAP-induced toxicity whereas the wild-type animals were sensitive. Administration of 600 to 800 mg/kg of this drug to male wild-type animals resulted in increased plasma concentrations of liver enzymes (alanine aminotransferase, sorbitol dehydrogenase), lipidosis, hepatic necrosis, and renal tubular necrosis. In contrast, when APAP of equivalent or higher dose was administered to the double-null mice, plasma levels of liver enzymes and liver histopathology were normal. However, administration of 1200 mg of APAP/kg to the double-null mice resulted in infrequent liver lipidosis and mild kidney lesions. Consistent with the protection from hepatotoxicity, the expected depletion of hepatic glutathione (GSH) content was significantly retarded and APAP covalent binding to hepatic cytosolic proteins was not detectable in the double-null mice. Likewise, in vitro activation of APAP by liver microsomes from the double-null mice was approximately one tenth of that in microsomes from wild-type mice. Thus, the protection against APAP toxicity afforded by deletion of both CYP2E1 and CYP1A2 likely reflects greatly diminished production of the toxic electrophile, NAPQI.


Assuntos
Acetaminofen/toxicidade , Analgésicos não Narcóticos/toxicidade , Citocromo P-450 CYP1A2/fisiologia , Citocromo P-450 CYP2E1/fisiologia , Túbulos Renais/efeitos dos fármacos , Fígado/efeitos dos fármacos , Microssomos Hepáticos/efeitos dos fármacos , Alanina Transaminase/metabolismo , Animais , Citocromo P-450 CYP1A2/genética , Citocromo P-450 CYP2E1/genética , DNA/análise , Relação Dose-Resposta a Droga , Deleção de Genes , Genótipo , Glutationa/metabolismo , Túbulos Renais/patologia , L-Iditol 2-Desidrogenase/metabolismo , Lipidoses/metabolismo , Fígado/enzimologia , Fígado/patologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Microssomos Hepáticos/enzimologia , Necrose , Compostos de Sulfidrila/metabolismo , Taxa de Sobrevida
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