The transforming mutation E17K/AKT1 is not a major event in B-cell-derived lymphoid leukaemias.

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.

Infections in adults with cancer in a developing country: a three year prospective study.

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.

Congenital hemorrhagic disorders in Jordan.

The results of a three year prospective study of inherited bleeding syndromes in Jordan is presented. There were 112 patients from 64 families. Of these there were 42 patients with hemophilia A, 23 with Glanzmann's thrombasthenia, 22 with von Willebrand's disease, 11 with Christmas disease, 6 with hypofibrinogenemia, 3 with afibrinogenemia, 2 with factor XIII deficiency, 2 with storage pool disease and 1 with factor XI deficiency. The pattern of inherited bleeding syndromes in Jordan is different from that seen in Europe and U.S.A. in that Glanzmann's thrombasthenia is very common. High proportion of hemophiliacs were severe. Arthropathy was common. A significant number of bleeders had fatal hemorrhage. In a high proportion of patients, no family history of bleeding was found.

Therapeutic effect of vincristine, adriamycin and prednisolone (VAP) in angioimmunoblastic lymphadenopathy (AIL).

Five patients, three males and two females, with angioimmunoblastic lymphadenopathy (AIL) are described. The two who received steroids had no response and died 2 and 6 months later. The three patients who received vincristine, adriamycin and prednisolone (VAP) went into remission early and are still in remission with a follow-up of 22-35 months. It is concluded that VAP is effective therapy in AIL.

Homozygous protein C deficiency with delayed onset of symptoms at 7 to 10 months.

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.

Massive bleeding in neurofibromatosis associated with congenital hypofibrinogenaemia: a case report.

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.

Spontaneous intracranial bleeding in hemorrhagic diathesis.

Eight patients with spontaneous intracranial bleeding secondary to hemophilia A, afibrinogenemia, and thrombocytopenia are described. The clinical picture was that of increased intracranial pressure of gradual onset with variable signs and symptoms. Both the hemostatic defect and the intracranial bleeding were proved by laboratory investigations and CT scanning. Mortality was 75% (six of eight patients). The two remaining patients recovered completely following combined medical and surgical treatment, and are alive and well.

Spontaneous intracranial hemorrhage secondary to von Willebrand's disease.

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.

Comparative study of white cell count and differential leukocyte count in school children at Dead Sea level and at Amman.

White cell and differential counts were studied in school children living at Amman (group A), Dead Sea natives (group B), and residents of the Dead Sea area who originated from different areas (group C). A total of 159 subjects from group A, 146 from group B, and 38 from group C, were studied. Significant leukopenia was observed in group B, as compared with groups A and C (p less than 0.005). This was due to selective neutropenia in group B (p less than 0.005). Careful analysis revealed that this difference was genetic and not environmental. Living at 390 m below sea level does not affect the white cell or the differential count.

Patterns of cigarette smoking in Jordan: A study of greater Amman area.

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.

Rare inherited bleeding disorders secondary to coagulation factors in Jordan: a nine-year study.

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.

Delivery of infants with Glanzmann thrombasthenia and subsequent blood transfusion requirements: a follow-up of 39 patients.

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.

A study of von Willebrand's disease in Jordan.

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.

Increased incidence of Glanzmann's thrombasthenia in Jordan as compared with Scandinavia.

12 Jordanian patients from 9 families with Glanzmann's thrombasthenia are described. All of them are products of consanguinous marriages. All cases are children with varying severity of mucosal bleeding. The clinical and laboratory findings are described. The importance of consanguinity is discussed and emphasized. Glanzmann's thrombasthenia is the second most common inherited haemorrhagic disorder in Jordan.

Two new glucose-6 phosphate dehydrogenase (G6PD) variants associated with hemolytic anemia: G6PD Amman-1 and G6PD Amman-2.

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.

Factor VIII R:Ag as a prognostic parameter in intracranial haemorrhage.

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.

Thrombotic thrombocytopenic purpura associated with pregnancy in two sisters.

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.

Comparative determination of phenytoin in plasma by fluorescence polarization immunoassay and high performance liquid chromatography.

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.

HLA antigens, blood groups and immunoglobulin levels in idiopathic thrombocytopenic purpura.

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.

Study of colorectal cancer in Qatar.

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.