RESUMO
We report a consanguineous family of three girls and one boy affected with a novel syndrome involving the lens and the basal ganglia. The phenotype is strikingly similar between affected siblings with cognitive impairment, attention deficit hyperactivity disorder (ADHD), microcephaly, growth retardation, congenital cataract, and dystonia. The magnetic resonance imaging showed unusual pattern of swelling of the caudate heads and thinning of the putamina with severe degree of hypometabolism on the [18F] deoxyglucose positron emission tomography. Furthermore, the clinical assessment provides the evidence that the neurological phenotype is very slowly progressive. We utilized the 10K single-nucleotide polymorphism (SNP) microarray genotyping for linkage analysis. Genome-wide scan indicated a 45.9-Mb region with a 4.2353 logarithm of the odds score on chromosome 11. Affymetrix genome-wide human SNP array 6.0 assay did not show any gross chromosomal abnormality. Targeted sequencing of two candidate genes within the linkage interval (PAX6 and B3GALTL) as well as mtDNA genome sequencing did not reveal any putative mutations.
Assuntos
Catarata/congênito , Corpo Estriado/anormalidades , Anormalidades Múltiplas/diagnóstico , Anormalidades Múltiplas/genética , Adolescente , Adulto , Encéfalo/diagnóstico por imagem , Encéfalo/patologia , Criança , Cromossomos Humanos Par 11 , Consanguinidade , Variações do Número de Cópias de DNA , DNA Mitocondrial/genética , Feminino , Ligação Genética , Humanos , Masculino , Fenótipo , Polimorfismo de Nucleotídeo Único , Radiografia , Cintilografia , Síndrome , Adulto JovemRESUMO
Hereditary hyperekplexia (HH) is a disorder of the inhibitory glycinergic neurotransmitter system. Mutations in five genes have been reported to cause the disease. However, only single mutation in GLRB, the gene encoding beta-subunit of the glycine receptor, in a singleton patient with HH has been found to date. In this study, 13 patients with HH were identified through neurology and genetic clinics. Formal clinical examinations, linkage analysis, homozygosity mapping, in-mutation screening of GLRB and in silico functional analyses were carried out. A novel mutation in GLRB among nine patients was identified. This c.596 T>G perturbation results in the change of the highly conserved methionine at position 177 to arginine. Besides the classical HH phenotype, seven patients had esotropia and few of them had behavioral problems. This study presents a large family with HH as a result of homozygous mutation in GLRB and expands the clinical spectrum of HH to include eye misalignment disorder. Moreover, the report of these familial cases supports the previous evidence in a single patient of an autosomal recessive inheritance of HH because of defects in GLRB.
Assuntos
Rigidez Muscular/diagnóstico , Rigidez Muscular/genética , Mutação , Receptores de Glicina/genética , Adolescente , Adulto , Sequência de Aminoácidos , Sequência de Bases , Criança , Família , Feminino , Genótipo , Humanos , Escore Lod , Masculino , Modelos Moleculares , Dados de Sequência Molecular , Linhagem , Estrutura Secundária de Proteína , Receptores de Glicina/química , Adulto JovemRESUMO
BACKGROUND: Posttransplant lymphoproliferative disease (PTLD) is a serious complication associated with the use of chronic immunosuppression for solid organ transplantation. This study represents a retrospective analysis of UCLA's experience with PTLD in all pediatric liver transplant recipients between 1984-1997. We assessed the clinical presentation, risk factors, incidence density, immunological characteristics, management, and outcome of patients who developed PTLD when receiving either primary cyclosporin A (CsA) or tacrolimus. METHODS: A total of 251 children received primary CsA therapy of which 70 required OKT3 for steroid resistant rejection and 29 required tacrolimus rescue for OKT3 resistance and/or chronic rejection. One hundred forty one children received tacrolimus as primary therapy. Sixty patients who survived for less than 6 months after transplantation were excluded from the study. RESULTS: The total incidence density (ID) rate of PTLD was 1.8+/-0.4 per 100 patient-years (30/392). The overall ID rate of PTLD in the CsA group was 0.93+/-0.2 per 100 patient-years (15/251). Within this group of primary CsA-treated patients, the ID rate of PTLD was 0.49+/-0.1 without OKT3 or tacrolimus, 0.67+/-0.2 with OKT3, and 6.42+/-1.1 with tacrolimus rescue. The overall PTLD ID rate in the primary tacrolimus-treated patients was 4.86+/-1.2 per 100 person-years (15/141). There was a 5-fold increase in the ID rate of PTLD in the primary tacrolimus group when compared to the comparable, primary CsA group (P<0.001). The mean time to PTLD was 5-fold longer (49.7+/-20.7 months) in the CsA group when compared to the CsA/tacrolimus rescue group (9.8+/-3 months, P<0.05) or the tacrolimus primary group (12.6+/-5.1 months, P<0.05). Five patients had monoclonal disease in the CsA group, but only one in the tacrolimus group (P<0.05). Clinical presentations with enlarged lymph nodes, fevers, malaise, anorexia, weight loss, hypoalbuminemia, and gastrointestinal blood loss were common. Mortality was 20%, three patients died in each group. CONCLUSION: The use of primary tacrolimus therapy was associated with a significant 5-fold higher rate of PTLD when compared to those treated with primary cyclosporine. Early diagnosis, decrease and/or discontinuation of potent immunosuppressive agents may contribute to decrease morbidity and mortality of this entity.
Assuntos
Imunossupressores/efeitos adversos , Transplante de Fígado/efeitos adversos , Transtornos Linfoproliferativos/etiologia , Adolescente , Fatores Etários , Criança , Pré-Escolar , Ciclosporina/efeitos adversos , Herpesvirus Humano 4/isolamento & purificação , Humanos , Incidência , Lactente , Transtornos Linfoproliferativos/epidemiologia , Transtornos Linfoproliferativos/terapia , Muromonab-CD3/efeitos adversos , Estudos Retrospectivos , Fatores de Risco , Tacrolimo/efeitos adversosRESUMO
BACKGROUND: Posttransplant lymphoproliferative disease (PTLD) is a serious complication associated with the use of immunosuppression after transplantation. In a retrospective study the clinical features of PTLD located primarily in the gastrointestinal tract were analyzed. METHODS: Three hundred ninety-two consecutive pediatric patients who underwent orthotopic liver transplantation (OLT) during a 13-year period with a survival of more than 6 months were reviewed. Two immunosuppression protocols were used: cyclosporin A, or tacrolimus-based primary therapy. Twenty-nine randomly selected liver transplant recipients without PTLD were used for comparison of signs and symptoms of gastrointestinal PTLD. RESULTS: Among the 30 patients identified with PTLD, 9 had gastrointestinal PTLD. The overall incidence density of PTLD was 1.8 per 100 patient-years (30/392). Nine patients (30%) had involvement of the gastrointestinal tract, whereas 7 (23%) had the gastrointestinal tract as the only involved site. When compared with a cohort of liver transplant recipients without PTLD, only gastrointestinal bleeding, weight loss, hypoalbuminemia, and protein-losing enteropathy were signs most likely associated with gastrointestinal PTLD. Hypoalbuminemia was the most sensitive sign of gastrointestinal PTLD. The lower tract (ileum and colon) was the most common site of involvement. CONCLUSIONS: gastrointestinal involvement is common and occurs in 30% of all patients with PTLD. It may be the only affected organ in a subgroup of patients. Hypoalbuminemia, gastrointestinal bleeding, and weight loss are features that are characteristic of gastrointestinal PTLD. Patients with aggressive gastrointestinal signs and symptoms should undergo upper and lower gastrointestinal tract endoscopy with biopsy, to establish the diagnosis.
Assuntos
Gastroenteropatias/etiologia , Transplante de Fígado/efeitos adversos , Transtornos Linfoproliferativos/etiologia , Adolescente , Criança , Pré-Escolar , Infecções por Vírus Epstein-Barr , Feminino , Gastroenteropatias/diagnóstico , Gastroenteropatias/patologia , Hemorragia Gastrointestinal , Humanos , Terapia de Imunossupressão/efeitos adversos , Lactente , Transtornos Linfoproliferativos/diagnóstico , Transtornos Linfoproliferativos/virologia , Masculino , Estudos Retrospectivos , Albumina Sérica/deficiência , Redução de PesoRESUMO
Preliminary results of a mixed technique of cervical bladder suspension by retroperitoneal laparoscopy and vaginal route. 35 patients, average age 55 years with stress incontinence. Every patients had positive Bonney test. Associated lesions were prolapse (72%). In this retrospective study, we give technique in details. Average operative time: 65 minutes. Average hospital stay: 5.4 days. Success rate: 89%. Retzius hematoma were treated by laparoscopy. Average lapse of time: 10.5 months. Interesting technique in associated prolapse.
Assuntos
Laparoscopia/métodos , Bexiga Urinária/cirurgia , Incontinência Urinária por Estresse/cirurgia , Adulto , Idoso , Feminino , Humanos , Tempo de Internação , Pessoa de Meia-Idade , Espaço Retroperitoneal , Estudos Retrospectivos , Fatores de Tempo , Resultado do Tratamento , VaginaRESUMO
A light microscopy study was carried out on 48 placentae. Seventeen placentae were obtained from non-diabetic mothers while the other 31 placentae were from both women with controlled diabetes and women who had an abnormality of the glucose tolerance test. All the women delivered at 38-40 weeks of gestation. Placentae from diabetic patients showed immaturity of the villi, hypertrophy of the capillaries and thickening of the basement membrane of the trophoblastic villi (3.2 +/- 0.35 microns) and the amniotic membrane (1.8 +/- 0.3 microns). Focal fibrinoid necrosis, an increase in the number of Hofbauer cells and dilatation of villi capillaries were also commonly observed in placentae from diabetic mothers, and the normal cuboidal cells lining the amniotic membrane tended to become tall columnar (17.6 +/- 6.3 microns) with distally located nuclei. Similar findings were observed in patients who had a potentially abnormal glucose tolerance test, which suggests the possibility of primary lesion in origin. Therefore, control of hyperglycemia may only partially prevent the development of placental abnormalities.
Assuntos
Vilosidades Coriônicas/patologia , Diabetes Gestacional/patologia , Doenças Placentárias/patologia , Adulto , Âmnio/patologia , Membrana Basal/patologia , Feminino , Humanos , Hipertrofia , Tamanho do Órgão , Gravidez , Terceiro Trimestre da GravidezRESUMO
OBJECTIVE: To identify trends and factors related to maternal death, and areas that need improvement. METHODS: A prospective national survey, a multistage sample of the hospitals of Saudi Arabia. The setting was a maternal mortality survey committee in Riyadh with field/area coordinators in different areas of the Kingdom. The subjects were women who died or who were dead on arrival in hospital during pregnancy or within 6 weeks of the end of pregnancy. All the data were coded and analyzed. EPINFO software was used to calculate the maternal mortality ratio (MMR) and the relative risk for the necessary variables. RESULTS: The MMR was 18 per 100,000 births (155/880 248). Mortality was higher in older multiparous women of low income and no education. Hemorrhage, both antepartum and postpartum, was the leading cause of maternal death, together with rupture of the uterus and abortive bleeding, constituting 43% of direct and 29% of total maternal deaths. Substandard care was identified in 73% of direct maternal deaths. CONCLUSIONS: The MMR in Saudi Arabia compares favorably with that of developed countries and the oil-producing Gulf states. Improving the number of booked patients, especially older grand multiparas, increasing the availability of banked blood and adopting a positive approach towards life-saving surgery are likely to reduce maternal deaths.
Assuntos
Mortalidade Materna/tendências , Complicações na Gravidez/mortalidade , Adulto , Fatores Etários , Cesárea/mortalidade , Feminino , Humanos , Incidência , Paridade , Gravidez , Complicações na Gravidez/etiologia , Cuidado Pré-Natal , Estudos Prospectivos , Embolia Pulmonar/mortalidade , Arábia Saudita/epidemiologia , Hemorragia Uterina/mortalidadeRESUMO
The treatment of recurrent vulvovaginal fungal infections is difficult. Pathogenic mechanisms are discussed. Available pharmacologic treatments and their mechanisms of action are reviewed. Patients clearly prefer oral treatment. Ketoconazole is toxic. Only topical or nonabsorbed oral agents can be used during pregnancy. Agents absorbed via the digestive tract can be used in women who use effective contraceptive methods. Published data demonstrate that trifluconazole (which has not yet been granted a license in France) is potent and less toxic than ketoconazole, and that recurrences at discontinuation of this drug are less common. A few hypotheses for future research are presented.
Assuntos
Antifúngicos/uso terapêutico , Candidíase Vulvovaginal/tratamento farmacológico , Administração Intravaginal , Administração Oral , Candidíase Vulvovaginal/diagnóstico , Candidíase Vulvovaginal/etiologia , Feminino , Humanos , Satisfação do Paciente , Gravidez , Recidiva , Fatores de Risco , Resultado do TratamentoRESUMO
A three year maternal mortality survey in Saudi Arabia has identified the various epidemiologic risk factors for maternal deaths. Unbooked, uneducated and economically underprivileged females were at increased risk of maternal death, especially >para 7 females, who were found to be at increased risk of maternal death, particularly deaths due to hemorrhage, pulmonary embolism and uterine rupture. In Saudi Arabia, there are contradictory risk factors for maternal death; e.g. low female literacy rate, early marriage and unregulated high fertility, and affluence which has brought about improvements in all walks of life including health services. Increasing the number of booked patients, especially among the elderly grand multipara, improving the quality of emergency obstetric services and achieving a higher female education rate are likely to bring the present maternal mortality ratio (MMR) of 18 per 100,000 births down to a minimum. The MMR obtained in this study compared favorably with those of the oil-producing Gulf countries and the developing and developed countries of the world.
RESUMO
Lead poisoning has proven to be one of the most difficult environmental health problems. Part of this difficulty is based on the lack of distinctive manifestations at an early phase in the process. Breast milk feeding with high lead concentration is one of the first sources of lead exposure in neonates. This study reported that lead in breast milk samples from 81% of nursing mothers varied from a low concentration of 0.318 microg/dL to a high of 2.5 microg/dL with an average of 0.768 +/- 0.42 microg/dL. The high lead concentration of 2.5 microg/dL recorded in this study is similar to the average lead concentration reported by others. Lead concentration was found to be low in young mothers and higher in mothers age 36 years or more with an average of 0.515 +/- 0.14 and 1.344 +/- 0.65 microg/dL respectively. There were no significant differences between lead concentration in samples obtained from right or left breasts and similarly, there were no significant differences in lead concentrations in milk samples in relation to the length of period of lactation (P>/=0.1). Breast milk samples obtained from mothers residing near industrial areas or highways, using copper casserole coated with white (rich in lead) inner coat and eating food material preserved for long periods in metal containers showed higher lead concentration than from those living in remote areas with reduced exposure. The diagnosis of lead poisoning required a constant awareness of its prevalence.
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The filtered backprojection images obtained from classical SPECT studies are not adequate for evaluation of volumes or parameters of clinical interest. Noise, scattering, boundary accuracy and attenuation are the main problems of SPECT quantification. It is the aim of the following study to overcome these difficulties. The first step of all correction algorithm is the contour detection of the attenuation medium. A new procedure, previously described by the authors, accurately and automatically found the boundaries of the surrounding body. The Compton scattering elimination is carried out by a modified version of Jaszczak's method. This alteration is essential to implement the iterative attenuation correction algorithm derived from Chang's method. Results obtained using computer simulation and real phantoms or clinical studies demonstrate the high improvement of contrast and count levels in the corrected slices. The process is fully automatic and the efficiency of the procedures allow fast processing of the daily SPECT examination.