RESUMO
Despite the major role of the AKT/PKB family of proteins in the regulation of many growth and survival mechanisms in the cell, and the increasing evidence suggesting that AKT disruption could play a key role in many human malignancies, no major mutations of AKT genes had been reported, until very recently when Carpten et al reported a novel transforming mutation (E17K) in the pleckstrin homology domain of the AKT1 gene in solid tumours. Several laboratories are now screening for this mutation in different malignancies, and, recently, the mutation was described by Malanga et al in 1.9% of lung cancer patients. Considering the importance of the PI3K/AKT pathway in mediating survival and antiapoptotic signals in the B-cell types of chronic lymphocytic leukaemia (CLL) and acute lymphoblastic leukaemia (ALL), we sequenced the AKT1 exon 3 for the above mentioned mutation in 87 specimens, representing 45 CLLs, 38 ALLs and 4 prolymphocytic leukaemia (PLL) cases, which are all of B-cell origin. Our results show that the mutation E17K/AKT1 was not detected in the pleckstrin homology domain of AKT1 of the investigated cases. We conclude that this mutation is not a major event in B-cell-derived lymphoid leukaemias.
Assuntos
Linfoma de Burkitt/genética , Transformação Celular Neoplásica/genética , Leucemia Linfocítica Crônica de Células B/genética , Leucemia Promielocítica Aguda/genética , Mutação Puntual , Proteínas Proto-Oncogênicas c-akt/genética , Sequência de Bases , Linfoma de Burkitt/patologia , Primers do DNA , Éxons , Feminino , Humanos , Leucemia Linfocítica Crônica de Células B/patologia , Leucemia Promielocítica Aguda/patologia , MasculinoRESUMO
OBJECTIVE: To study the epidemiology of colorectal cancer in Qatar and compare it with other parts of the world. To collect demographic data on colorectal cancer in Qatar (age and sex distribution) and to collect anatomic pathology data on colorectal cancer in Qatar. METHODS: Retrospective analysis of data collected from hospital records was used to review the incidence and prevalence of colorectal cancer in Qatar. During the period 1994-1998, one hundred and twenty patients with colorectal cancer were seen at Hamad General Hospital. RESULTS: Mean annual incidence was 24 patients/year. Forty-five patients were Qataris and 75 were non Qataris. Of the Qatari patients 26 (58%) were males and 19 (42%) females, male/female ratio was 1.4:1. Nine (20%) patients were under the age of 40 years, the presenting symptoms, physical signs and the stage of the disease were similar to other studies. Descending and sigmoid colon was the most common anatomical site affected. The most common histopathological type was adenocarcinoma. CONCLUSION: The overall incidence of colorectal cancer in Qatar is lower than most of the industrial countries, this may be due to certain factors such as young population, high intake of fruits and vegetables and the life style of the people in Qatar. The incidence in the people below the age of 40 years is higher than industrial countries and, in males due to the demographic structure of the population in Qatar.
Assuntos
Neoplasias Colorretais/epidemiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias Colorretais/patologia , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Catar/epidemiologia , Estudos Retrospectivos , Fatores de RiscoRESUMO
This is a four-year prospective study on patients admitted or referred with thromboembolic disease to Jordan University Hospital or to the Thrombosis/Haemostasis Laboratory at the University of Jordan. The aim of the study was to find the relative prevalence of hereditary thrombophilia. For the purpose of this work, hereditary thrombophilia was diagnosed in the absence of an acquired cause of thrombophilia in addition to two of the following: 1) positive family history of thrombophilia, 2) confirmed same deficiency in a closely related family member, 3) the deficient protein is constantly below 2 SD of the normal mean on repeated testing. All ages were admitted to the study. Acquired systemic factors or local factors known to cause thrombosis or affect the levels of proteins opposing thrombosis were excluded. There were a total of 217 patients (102 males and 115 females) with confirmed thromboembolic disease. Their mean age was 34 years. A total of 49 patients (26 males and 23 females) fulfilled the criteria of hereditary thrombophilia. There were 17 cases of protein C deficiency (PC), 15 protein S deficiency (PS), 10 antithrombin III deficiency (ATIII), 3 dyfibrinogenemia, 2 heparin cofactor II deficiency, and 2 plasminogen defects. In this group most of the thrombosis was venous. A positive family history was obtained in 65.3% of patients with hereditary thrombophilia. Twenty-seven additional relatives with deficiency were identified upon family studies. The calculated prevalence of hereditary thrombophilia in Jordan is put at 1/25,000. Screening for PC, PS, and ATIII is advocated in young patients who have thromboembolic disease, especially when there is a positive family history of thrombosis.
Assuntos
Tromboembolia/complicações , Tromboembolia/epidemiologia , Trombose/complicações , Trombose/genética , Adolescente , Adulto , Idoso , Antitrombina III/análise , Deficiência de Antitrombina III , Criança , Pré-Escolar , Saúde da Família , Feminino , Humanos , Lactente , Jordânia/epidemiologia , Masculino , Pessoa de Meia-Idade , Plasminogênio/análise , Plasminogênio/deficiência , Prevalência , Estudos Prospectivos , Proteína C/análise , Deficiência de Proteína C , Proteína S/análise , Deficiência de Proteína S , Trombose/epidemiologiaRESUMO
Two sisters suffered from thrombotic thrombocytopenic purpura late in their first pregnancies. HLA typing of the patients and their immediate family members demonstrated no obvious relationship. Hereditary aspects, association with pregnancy, prognosis and management of pregnant women with TTP are discussed.
Assuntos
Complicações Cardiovasculares na Gravidez , Púrpura Trombocitopênica Idiopática/genética , Adulto , Saúde da Família , Feminino , Humanos , Linhagem , Gravidez , Resultado da GravidezRESUMO
This work reports on the results of a 9-year study of von Willebrand's disease and its subtypes in Jordan, a country with a predominantly Arab population. There were a total of 65 patients in 32 families. Detailed study of 61 patients including von Willebrand factor multimers was done for the purpose of subtyping them. Type I and variants were seen in 36 patients (59%). Type II A and variants with decreased ristocetin response accounted for seven patients (11.5%), while 11 (18%) were of type II B. The severe type (type III) accounted for seven patients (11.5%). Von Willebrand's disease was the second most commonly seen inherited bleeding disorder after hemophilia A. It is concluded that although the observed frequency of von Willebrand's disease in this study in Jordan is lower than that in Europe and the USA, the true prevalence cannot be ascertained since many of the mild cases presumably were missed because of referral patterns. Type I and its variants was the most common type found, but the observed frequency of types II B and III was more than that reported in Europeans and Americans.
Assuntos
Doenças de von Willebrand/epidemiologia , Humanos , Jordânia/epidemiologia , PrevalênciaRESUMO
Plasma concentrations of endothelium-derived proteins (fibronectin and von Willebrand factor), liver synthesized proteins (haptoglobin, transferrin, ceruloplasmin, alpha 1-antitrypsin, antithrombin III and factor VIII-coagulant) and plasma arginine-vasopressin (AVP) were measured in 12 hyperthyroid, 9 hypothyroid and 15 age- and sex-matched normal controls. In hyperthyroid patients the plasma concentrations of AVP and endothelium-associated proteins (EAP) were significantly higher than in the control group (p less than 0.05 and p less than 0.01 respectively). Rendering hyperthyroid patients into the euthyroid state significantly lowered AVP (p less than 0.01), fibronectin (p less than 0.05) and von Willebrand factor (p less than 0.01) compared with pretreatment levels. Hypothyroid patients were studied at diagnosis and after replacement therapy with levothyroxine. Compared with pretreatment values, significant increases were noted in plasma concentrations of von Willebrand factor, fibronectin and AVP (p less than 0.01). With the exception of factor VIII-coagulant, the concentrations of hepatic synthesized proteins did not deviate from normal values in hyperthyroid and hypothyroid patients. Significant correlations were found between serum-free thyroxine on the one hand and the plasma concentrations of fibronectin (p less than 0.005), von Willebrand factor (p less than 0.001) and AVP (p less than 0.0001). Similarly, there was significant correlation between the plasma concentrations of AVP on the one hand and fibronectin (p less than 0.002) and von Willebrand factor (p less than 0.01). The results demonstrate elevated plasma levels of AVP in hyperthyroid patients and an increase during levothyroxine treatment of hypothyroid patients.(ABSTRACT TRUNCATED AT 250 WORDS)
Assuntos
Arginina Vasopressina/sangue , Proteínas Sanguíneas/biossíntese , Endotélio Vascular/metabolismo , Doenças da Glândula Tireoide/sangue , Adulto , Proteínas Sanguíneas/análise , Feminino , Fibronectinas/sangue , Humanos , Masculino , Estudos Prospectivos , Doenças da Glândula Tireoide/terapia , Tiroxina/sangue , Fator de von Willebrand/análiseRESUMO
The delivery and transfusion requirements of 39 patients with Glanzmann thrombasthenia are described. Of these, type I thrombasthenia was found in 21 females and 12 males, and type II thrombasthenia was found in four females and two males. Eighteen of these patients were born in the hospital and 21 at home. All were delivered vaginally. Absence of excessive hemorrhagic symptoms was noted in neonates affected with thrombasthenia. The patients were followed for a total of 220 patient years and received a total of 276 units of blood during this period. In females, the dominant reason for transfusion was menorrhagia followed by gum bleeding and epistaxis, while in males epistaxis, gum bleeding, and circumcision accounted for most of the transfusions.
Assuntos
Doenças do Recém-Nascido/terapia , Trombastenia/terapia , Transfusão de Sangue , Seguimentos , Humanos , Recém-NascidoRESUMO
This work reports on rare inherited coagulation factors defects which were seen in a developing country over a 9-year period. There were a total of 30 cases which fulfilled this diagnosis. Fibrinogen abnormalities were the most frequently encountered. There were 10 patients with afibrinogenemia, 2 with hypofibrinogenemia and 1 case with dysfibrinogenemia. Factor XI deficiency was found in 7 patients, factor V and VII deficiencies accounted for 3 cases each. Factor X and XIII deficiencies were found in 2 patients each. All these rare deficiencies accounted for 10% of all inherited bleeding disorders in the population studied over 9 years.
Assuntos
Transtornos da Coagulação Sanguínea/epidemiologia , Fatores de Coagulação Sanguínea/análise , Transtornos da Coagulação Sanguínea/diagnóstico , Transtornos da Coagulação Sanguínea/genética , Testes de Coagulação Sanguínea , Humanos , Jordânia/epidemiologia , PrevalênciaRESUMO
The patterns of smoking in Jordan were determined in a sample of 3489 subjects representing various strata of society. The sample included 2103 students and 1386 nonstudents. In the nonstudent population, 58.5% of the male and 27.4% of the female subjects were smokers; overall, 96% smoked manufactures cigarettes. Males smoked an average of 25 cigarettes per day, and females an average of 16 cigarettes per day. Males had smoked for an average of 16 years and females an average of 13.4 years. Smoking was highest among skilled and non-skilled workers and illiterate persons. Among students, smoking was higher in males at the university (52.9%) and college (54.3%) level; 16.7% of high school males smoked. In female students at the university or college level, 20.3% and 9.1% smoked, respectively. In female of high school females smoked. Manufactured cigarettes were used by 99.3% of the students. Male students smoked a mean of 15.5 cigarettes per day for an average of 6.4 years. Female students smoked a mean of 9.6 cigarettes per day for an average of 6.2 years. Based on our findings, it is apparent that a rigorous antismoking campaign is needed.
RESUMO
319 episodes of infections in 174 cancer patients over a period of 3 years are reported in a developing country. 178 episodes were seen in leukaemias, 83 in lymphomas and 58 in other cancers. 146 episodes appeared in 89 neutropenic patients and 173 in non-neutropenic patients. In 163 (51%) episodes positive cultures were obtained with a total of 212 organisms. 192 (90.6%) of the isolates were bacteria; of these 107 (55.7%) were gram positive and 85 (44.3%) were gram negative. The findings are consistent with those reported in developed countries. Most commonly isolated bacteria were: staphylococcus, Escherichia coli, streptococcus, enterobacter, pseudomonas, diphtheroids and salmonella. 15 isolates (7%) were of candida. Most common sites of infection were respiratory tract, kidney and urinary tract and skin. There were a total of 64 deaths: 36 were directly related to infections. 11 of these patients died of hospital acquired infections; most commonly isolated organisms in these infections were staphylococcus, E. coli, pseudomonas and streptococcus.
Assuntos
Países em Desenvolvimento , Infecções/etiologia , Neoplasias/complicações , Adolescente , Adulto , Idoso , Antibacterianos/uso terapêutico , Infecções Bacterianas/etiologia , Infecção Hospitalar/epidemiologia , Feminino , Humanos , Infecções/epidemiologia , Infecções/mortalidade , Jordânia/epidemiologia , Masculino , Pessoa de Meia-Idade , Neutropenia/complicações , Estudos ProspectivosRESUMO
We report an inbred family with two cases of homozygous protein C deficiency and review 11 other such cases. Both patients presented in the second half of their first year of life with recurrent rapidly disappearing ecchymotic skin lesions, disseminated intravascular coagulation, and venous thrombosis. Successful treatment has been achieved by frequent infusions of plasma or prothrombin complex then maintained with Warfarin. Homozygous recessive protein C deficiency usually presents in the neonatal period with purpura fulminans. Two cases have been described elsewhere which presented in the second decade of life with milder symptoms. The present cases appear to be intermediate in time of presentation and severity of symptoms. We also review the distinction that is now evident between recessive and dominant protein C deficiency.
Assuntos
Deficiência de Proteína C , Consanguinidade , Feminino , Genes Recessivos , Homozigoto , Humanos , Lactente , Masculino , Linhagem , Proteína C/genéticaRESUMO
The effect of ofloxacin taken for 8 days (200 mg twice daily) on the pharmacokinetics of a single intravenous dose of theophylline (4.3 mg/kg over 15 min) was studied in a crossover procedure among seven healthy male volunteers. Theophylline concentrations were measured serially for 10 h by the immunofluorescence polarization technique. No significant effect of ofloxacin was found on theophylline clearance, half-life, or volume of distribution. It is therefore concluded that ofloxacin and theophylline can be safely administered together.
Assuntos
Anti-Infecciosos/farmacologia , Oxazinas/farmacologia , Teofilina/farmacocinética , Adulto , Interações Medicamentosas , Meia-Vida , Humanos , Injeções Intravenosas , Masculino , Ofloxacino , Teofilina/administração & dosagemRESUMO
The need for careful monitoring of plasma concentrations of phenytoin during use of the drug in the treatment of epilepsy is well recognized; there can be great intersubject variation in the absorption rate and clearance rate of the drug, and its therapeutic ratio is narrow. In this study, two methods for determining plasma phenytoin concentrations were compared. One, based on fluorescence polarisation immunoassay (FPIA), is utilised in a commercially-available kit. The other, our own modification of a published procedure, was based on high performance liquid chromatography (HPLC). The accuracy and precision of both methods were evaluated, and the coefficients of variation (C.V.) were calculated. The C.V.'s ranged from 0.71 to 1.86% for the FPIA method, and from 2.81 to 8.69% for the HPLC method. Corresponding bias values were 1.20 to 1.60%, and 2.81 to 8.69%, respectively. A good correlation coefficient (0.977) was obtained, but estimated phenytoin concentrations were significantly higher (95% confidence level) using the HPLC method. We conclude that both methods perform adequately for clinical purposes. The HPLC method is, however, less expensive than the FPIA method.
Assuntos
Fenitoína/sangue , Cromatografia Líquida de Alta Pressão/métodos , Epilepsia/tratamento farmacológico , Imunofluorescência , Humanos , Fenitoína/uso terapêutico , Kit de Reagentes para DiagnósticoRESUMO
Factor VIII R:Ag was measured serially in 42 patients who had intracranial haemorrhage. It was found that the factor decreased or remained static in the 24 patients who improved (p less than 0.025), while it increased in the 18 who died (p less than 0.0005). It is suggested that this factor can be used as a prognostic parameter to predict the outcome after intracranial haemorrhage.
Assuntos
Antígenos/análise , Hemorragia Cerebral/sangue , Fator VIII/imunologia , Adulto , Testes de Coagulação Sanguínea , Ritmo Circadiano , Fator VIII/análise , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Fator de von WillebrandRESUMO
Four cases of spontaneous intracranial hemorrhage secondary to von Willebrand's disease are presented. The hemostatic management of the disease is discussed. A policy for screening of patients afflicted with intracranial hemorrhage secondary to von Willebrand's disease is proposed.
Assuntos
Hemorragia Cerebral/etiologia , Doenças de von Willebrand/complicações , Adolescente , Adulto , Idoso , Tempo de Sangramento , Hemorragia Cerebral/sangue , Hemorragia Cerebral/diagnóstico por imagem , Feminino , Humanos , Masculino , Tomografia Computadorizada por Raios X , Fator de von Willebrand/antagonistas & inibidoresRESUMO
Two glucose-6-phosphate dehydrogenase (G6PD) variants were investigated. G6PD Amman-1 was partially purified from the red cells of a patient suffering from recurrent jaundice and spontaneous episodic attacks of severe hemolysis in the absence of oxidant drugs, infection, or fava beans. The enzymatic characteristics of G6PD Amman-1 were markedly reduced activity, fast eletrophoretic mobility, slightly increased km for NADP, normal km for G-6-P, normal heat stability, normal utilization of substrate analogues 2-deoxy G-6-P and deamino-NADP, and a monophasic pH curve with a peak at 8.5 to 9.3. The second variant, G6PD Amman-2, was partially purified from the red cells of a patient suffering from recurrent jaundice with episodic mild hemolysis caused by infection or unknown factors. G6PD Amman-2 characteristics were severely reduced activity, slow electrophoretic mobility, normal km for NADP, decreased km for G-6-P, decreased heat stability, increased utilization of substrate analogues, and a monophasic pH curve with a narrow peak at pH 9.5. The red cell level of reduced glutathione was markedly decreased with twofold increase in the activity of glutathione reductase in the patient with G6PD Amman-2.
Assuntos
Deficiência de Glucosefosfato Desidrogenase/enzimologia , Glucosefosfato Desidrogenase/sangue , Isoenzimas/sangue , Adulto , Anemia Hemolítica Congênita/enzimologia , Criança , Eritrócitos/enzimologia , Humanos , Cinética , Masculino , MutaçãoRESUMO
Thirty-three patients with idiopathic thrombocytopenic purpura (ITP) were tested for HLA-A, B and C antigens, platelet antibodies, immunoglobulin levels and ABO blood groups. With one exception, ITP proved not to be significantly associated with the HLA antigens studied; an increased frequency of HLA-A28 was found in chronic ITP patients (50 vs. 18.7% in the control population). An increased incidence of blood group A was found in ITP patients (64 vs. 37.98% in the control population), especially in those with acute ITP (84.7%). A significant reduction of IgG levels was noted in patients with chronic ITP, while below-normal levels of IgA were found in both chronic and acute ITP patients. There was no difference in levels of IgM. Circulating platelet isoantibodies were demonstrated in 67.6% of the ITP patients. No correlation was demonstrated between the presence of platelet antibodies, immunoglobulin levels of HLA antigens.
Assuntos
Antígenos HLA/genética , Púrpura Trombocitopênica/genética , Doença Aguda , Antígenos de Grupos Sanguíneos/genética , Plaquetas/imunologia , Doença Crônica , Complemento C3/análise , Complemento C4/análise , Frequência do Gene , Humanos , Imunoglobulinas/análise , Isoanticorpos/análise , Púrpura Trombocitopênica/sangue , Púrpura Trombocitopênica/imunologiaRESUMO
A 22 year old male who bled profusely at operation for excision of an extensive scalp and facial neurofibromata is reported. He was found to have congenital hypofibrinogenaemia. It is suggested that hypofibrinogenaemia should be considered as a cause of excessive bleeding in cases of Von Recklinghausen's neurofibromatosis.