Odontogenic myxofibroma synchronous with primary angiosarcoma of the spleen.

Odontogenic myxofibroma of the temporomandibular joint (TMJ) is a rare tumour; moreover, primary splenic angiosarcoma (PAS) in paediatric patients is extremely rare. We report on a 15-year-old boy who presented with right TMJ swelling and subsequently developed epigastric and right upper quadrant pain. The TMJ swelling proved to be odontogenic myxofibroma and the abdominal pain was a result of primary splenic angiosarcoma with hepatic metastasis. We report for the first time the synchronous presentation of PAS and odontogenic myxofibroma in a paediatric patient, and we describe the radiological features along with the histological diagnosis and clinical outcome. Uptake in (18)F-2-fluoro-2-deoxy-D-glucose positron emission tomography is also described for the first time for both these tumours.

Study of mutations in Jordanian patients with haemophilia A: identification of five novel mutations.

Haemophilia A (HA) is an X-linked recessive bleeding disorder caused by mutations in the factor VIII gene (F8), which encodes factor VIII (FVIII) protein, a plasma glycoprotein, that plays an important role in the blood coagulation cascade. In the present study, our aim was to identify F8 gene mutations in HA patients from Jordan. One hundred and seventy-five HA patients from 42 unrelated families were included in this study. Among these patients, 117 (67%) had severe HA, 13 (7%) had moderate HA and 45 (26%) had mild HA. Severe patients were first tested for intron-22 inversion using long range polymerase chain reaction (PCR), then negative patients were tested for intron-1 inversion using PCR. Sequencing for the entire F8 gene was performed for all severe HA patients who were found negative for intron-22 and -1 inversions and it was also performed for moderate and mild HA patients. HA causative mutations were identified in all patients. Intron-22 and -1 inversions were detected in 52% and 2% of families respectively. Beside these two mutations, 19 different mutations were identified, which include 15 missense and four frameshift mutations. Five novel mutations were identified including one frameshift and four missense mutations. No large deletions or nonsense mutations were detected in patients who participated in this study. Only 17 patients with severe HA were found positive for FVIII inhibitors. The data presented will play an important role for genetic counselling and health care of HA patients in Jordan.

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.

A 13-bp deletion in alpha(IIb) gene is a founder mutation that predominates in Palestinian-Arab patients with Glanzmann thrombasthenia.

Glanzmann thrombasthenia (GT) is a rare autosomal recessive bleeding disorder caused by lack or dysfunction of alpha(IIb)beta3 in platelets. GT is relatively frequent in highly inbred populations. We previously identified a 13-bp deletion in the alpha(IIb) gene that causes in-frame deletion of six amino acids in three Palestinian GT patients. In this study, we determined the molecular basis of GT in all known Palestinian patients, examined whether Jordanian patients harbor the same mutations, analyzed whether there is a founder effect for the 13-bp deletion, and determined the mechanism by which the 13-bp deletion abolishes alpha(IIb)beta3 surface expression. Of 11 unrelated Palestinian patients, eight were homozygous for the 13-bp deletion that displayed common ancestry by haplotype analysis, and was estimated to have occurred 300-600 years ago. Expression studies in baby hamster kidney cells showed that substitution of Cys107 or Trp110 located within the deletion caused defective alpha(IIb)beta3 maturation. Substitution of Trp110, but not of Cys107, prevented fibrinogen binding. The other Palestinian patients harbored three novel mutations: G2374 deletion in alpha(IIb) gene, TT1616-7 deletion in beta3 gene, and IVS14: -3C --> G in beta3 gene. The latter mutation caused cryptic splicing predicting an extended cytoplasmic tail of beta3 and was expressed as dysfunctional alpha(IIb)beta(3). None of 15 unrelated Jordanian patients carried any of the described mutations.

Normal outcome of pregnancy in chronic myeloid leukemia treated with interferon-alpha in 1st trimester: report of 3 cases and review of the literature.

Three patients with chronic myeloid leukemia (CML) in chronic phase received interferon-alpha during pregnancy, starting from the 1st trimester. No maternal complications were reported. The 3 patients delivered normal looking babies apart from one baby who was found to have transient mild thrombocytopenia. Subsequently these children were followed for 30, 12, and 4 months and all had normal growth and development.

Double-blind, placebo-controlled cross-over study of oral pilocarpine for the prevention of chemotherapy-induced oral mucositis in adult patients with cancer.

This study aimed to investigate the effect of oral pilocarpine (OP) in reducing the incidence of chemotherapy-induced oral mucositis. 32 adult cancer patients completed a total of 82 courses of chemotherapy in which either OP or placebo was given prophylactically in a double-blind cross-over design to prevent mucositis. Mucositis was documented in 20 out of 41 courses in which patients were given placebo, whereas mucositis was documented in only six out of 41 courses when patients were given OP (P<0.005). OP treatment was found to significantly reduce the mucositis score when assessed by the method of Donnelly and colleagues (Donnelly JP, Muus P, Schattenberg A, De Witte T, Horrevorts A, De Pauw BE. Bone Marrow Transplant 1992, 9, 409-413). Using this score, all patients scored a total of 52 when they were given the placebo versus eleven when they were treated with OP (P<0.001). A similar reduction in mucositis score was noticed using the World Health Organization (WHO) mucositis score; the total patient score was 25 for the placebo-treated group versus 6 for the OP group (P<0.001). We therefore conclude that oral pilocarpine is highly effective in the prevention of oral mucositis when given prophylactically to adult patients receiving a variety of cancer chemotherapy regimens.

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.

Bleeding tendency in Wolfram syndrome: a newly identified feature with phenotype genotype correlation.

Wolfram syndrome (WS) is a recessively inherited disorder associated with recognised clinical features. Bleeding tendency was noticed in some of our patients, although this has not been reported before. We therefore studied this problem in all our WS patients and tried to postulate a possible pathogenesis. At the same time, a genetic linkage study provided evidence of locus heterogeneity of this syndrome and showed that the majority of our patients belong to the second WS locus identified in that study. Our study group consisted of 13 WS patients, belonging to WSF2 locus (group I). Controls consisted of 4 healthy siblings of WS patients (group II) and 7 diabetics who do not have WS (group III). Relevant clinical data were obtained, and a coagulation screen was carried out for all groups. All individuals in the three study groups have normal platelet count, thrombin time (TT), prothrombin time (PT), activated partial thromboplastin time (aPTT), clot retraction, Factor VIII activity (FVIIIc) and von Willebrand factor antigen (vWAg). Eleven of the WS patients have prolonged template bleeding time (BT) compared with both control groups. Patients with WS have a longer BT (mean 9.6 min, 95% CL 8.61-10.53 min) than the siblings group (mean 6.75 min, 95% CL 5.52-7.98 min) and the diabetic group (mean 5.49 min, 95% CL 4.56-6.42 min). The differences between the study group and controls are statistically significant, p = 0.02 and 0.0002, respectively. In the three groups, platelet aggregation studies were normal using adenosine diphosphate (ADP), ristocetin and epinephrine. Aggregation with collagen was either absent or impaired, with failure of secondary wave being noticed in 11 of the WS patients (85%) and normal in the control groups. The pathogenesis of this problem is not known, but could be due to an inhibitory effect of vWAgII, deficiency of thrombospondin or a defect in the platelet membrane GPIa/IIa. Bleeding diathesis is a new additional feature to the clinical spectrum of WS, which is probably a feature of the disorder WFS2 and not WFS1, as bleeding has never been reported in the latter. This provides further evidence for the phenotypic and genotypic heterogeneity of this complex disorder and may provide clues to the search for the second gene responsible for this phenotype.

High prevalence of factor V Leiden in healthy Jordanian Arabs.

The prevalence of APC resistance in healthy Jordanian Arabs was studied. Between October 1996 through September 1997 a total of 400 healthy subjects were studied. There were 212 males and 188 females. APC resistance was studied by functional and DNA methods. There were a total of 52 subjects (13%) who were APC resistant by the functional test. There were 49 subjects (12.25%) who had FV Q506 by DNA test. Of these there were 42 heterozygous and 7 homozygous (allele frequency 0.07). None of the subjects had clinical thrombosis. It is concluded that the prevalence of APC resistance due to FV Q506 is high in Jordanian Arabs.

Hereditary thrombophilia among 217 consecutive patients with thromboembolic disease in Jordan.

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.

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.

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.

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.

Arginine-vasopressin and endothelium-associated proteins in thyroid disease.

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)

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.

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.

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.

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.