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Study Objective: To determine the incidence of and the risk factors associated with hyperkalemia, induced by ACEI-drug interactions among cardiac patients., Setting: Five medical and cardiology wards of a tertiary care center in Malaysia., Subjects: Five hundred cardiac inpatients, who received ACEIs concomitantly with other interacting drugs., Method: This was a prospective cohort study of 500 patients with cardiovascular diseases admitted to Penang Hospital between January to August 2006, who received ACEIs concomitantly with other interacting drugs. ACEI-drug interactions of clinical significance were identified using available drug information resources. Drug Interaction Probability Scale (DIPS) was used to assess the causality of association between ACEI-drug interactions and the adverse outcome (hyperkalemia)., Main Outcome Measure: Hyperkalemia as an adverse clinical outcome of the interaction was identified from laboratory investigations., Results: Of the 489 patients included in the analysis, 48 (9.8%) had hyperkalemia thought to be associated with ACEI-drug interactions. Univariate analysis using binary logistic regression revealed that advanced age (60 years or more), and taking more than 15 medications were independent risk factors significantly associated with hyperkalemia. However, current and previous smoking history appeared to be a protective factor. Risk factors identified as predictors of hyperkalemia secondary to ACEI-drug interactions by multi-logistic regression were: advanced age (adjusted OR 2.3, CI 1.07-5.01); renal disease (adjusted OR 4.7, CI 2.37-9.39); hepatic disease (adjusted OR 5.2, CI 1.08-25.03); taking 15-20 medications (adjusted OR 4.4, CI 2.08-9.19); and taking 21-26 medications (adjusted OR 9.0, CI 1.64-49.74)., Conclusion: Cardiac patients receiving ACEIs concomitantly with potentially interacting drugs are at high risk of experiencing hyperkalemia. Old age, renal disease, hepatic disease, and receiving large number of medications are factors that may significantly increase their vulnerability towards this adverse outcome; thus, frequent monitoring is advocated.

Paragangliomas of the mediastinum are rare neoplasms, representing less than 0.3% of mediastinal tumours and less than 2% of all paragangliomas. To date, no definitive morphologic criteria exist that correlate with the clinical outcome of these tumours. This report describes three patients with peculiar primary paragangliomas of the posterior mediastinum: gangliocytic, dumbbell and functional paraganglioma. The clinicopathological characteristics of these patients are presented and the literature reviewed.

Introduction: Studies on bronchoalveolar lavage (BAL) fluid samples profile characteristics in sarcoidosis patients hitherto reported in literature give rise to conflicting data. The typical finding is lymphocytic alveolitis with a high CD4/CD8 ratio, although a broad range of values has been found. THE AIM of the study was to evaluate different parameters of BAL fluid in patients with sarcoidosis before and after corticosteroid treatment and to determine the reliability of BAL in evaluating prognosis of sarcoidosis., Methods: The study involved 40 patients with clinical and histological evidence of sarcoidosis., Results: Before treatment, BAL fluid showed an increase in total cell count and a T lymphocytosis with an increase in the CD4/CD8 ratio. After treatment, we have noted a significantly increase in macrophage proportion, a significantly decrease in lymphocyte proportion and in CD4/CD8 ratio. A significant higher CD4/CD8 ratio was noted in patients with multiple extrathoracic lesions compared with patients with only intrathoracic involvement and in patients with unfavourable evolution compared with patients with improved evolution., Conclusion: When typical clinical and radiological findings definitely suggest sarcoidosis, BAL results may add a biological support. Our data suggests that a high CD4/CD8 ratio seems to be predictive of poor prognosis with a multiple extrathoracic organ involvement and an unfavourable outcome.

Pulmonary blastomycosis is an uncommon pathologic condition that is quite rare in Africa compared to endemic regions of Canada and the upper Midwest of the U.S. We describe a 45-year-old patient who complained of productive cough, hemoptysis, and dorsal rachiodynia. Chest imaging revealed a necrotic tissue-density pulmonary mass involving both the upper and lower right lobes. Chest MRI showed signal abnormality of the third thoracic vertebral body and the greater trochanter, consistent with metastatic lesions. Clinical and radiological findings were strongly suggestive of lung cancer. Diagnosis of pulmonary blastomycosis was made by visualization of yeast in bronchial biopsies and further confirmed by culture of bronchoalveolar lavage specimens. The patient was treated with itraconazole and his clinical condition improved markedly. Pulmonary blastomycosis is unusual in Africa and that fact caused a considerable delay in diagnosis. We suggest that this disease may be more common in Africa than has been previously suspected.

Introduction: Mature teratomas of the mediastinum are rare. However, they represent the most common mediastinal germ cell tumours. The aim of this study is to describe their clinical and pathological characteristics., Patients and Methods: Fourteen cases of mediastinal mature teratoma, diagnosed between January 1992 and December 2006, were reviewed retrospectively, noting the clinical, radiological, surgical, and pathological findings., Results: The patient population consisted of 10 females and 4 males with mean age of 29 years (5-56 years). Chest pain was the main symptom. Imaging features comprised a heterogeneous anterior mediastinal mass containing soft-tissue, fluid, fat, or calcium attenuation, or any combination of the four. Macroscopically all the tumours were cystic, or predominantly cystic, containing mostly grumous material. The mean size was 9 cm (5-12 cm). Histological examination constantly revealed skin with or without appendages. Other components identified were bronchial mucosa (12 cases), fat (12 cases), muscle (10 cases), cartilage (8 cases), bone (7 cases), gastrointestinal mucosa (7 cases), pancreas (5 cases), urothelial epithelium (3 cases), nervous and prostatic tissues (one case each). All the teratomas were mature, and 7 of them were intrathymic., Conclusion: Every form of teratoma occurs in the mediastinum (mature, immature and with malignant transformation) but, in our study, they were exclusively mature. The histology is essentially similar to that of teratomas of gonads. However, pancreatic tissue occurs frequently in mediastinum (54% in literature, 25% in our study) but not in the gonads. On the other hand, thyroid follicles have not yet been seen in mediastinal teratomas.

Friedreich ataxia (FRDA) is caused by a homozygous GAA repeat expansion mutation within intron 1 of the FXN gene, leading to reduced expression of frataxin protein. Evidence suggests that the mutation may induce epigenetic changes and heterochromatin formation, thereby impeding gene transcription. In particular, studies using FRDA patient blood and lymphoblastoid cell lines have detected increased DNA methylation of specific CpG sites upstream of the GAA repeat and histone modifications in regions flanking the GAA repeat. In this report we show that such epigenetic changes are also present in FRDA patient brain, cerebellum and heart tissues, the primary affected systems of the disorder. Bisulfite sequence analysis of the FXN flanking GAA regions reveals a shift in the FRDA DNA methylation profile, with upstream CpG sites becoming consistently hypermethylated and downstream CpG sites becoming consistently hypomethylated. We also identify differential DNA methylation at three specific CpG sites within the FXN promoter and one CpG site within exon 1. Furthermore, we show by chromatin immunoprecipitation analysis that there is overall decreased histone H3K9 acetylation together with increased H3K9 methylation of FRDA brain tissue. Further studies of brain, cerebellum and heart tissues from our GAA repeat expansion-containing FRDA YAC transgenic mice reveal comparable epigenetic changes to those detected in FRDA patient tissue. We have thus developed a mouse model that will be a valuable resource for future therapeutic studies targeting epigenetic modifications of the FXN gene to increase frataxin expression.

Objectives: To highlight therapeutic controversies, and present a critical review of the most recent evidence on the management of heparin-induced thrombocytopenia (HIT)., Data Sources: A MEDLINE search from October 1996 until October 2006 was carried out. Pertinent literature was identified and other references identified from the bibliographic citations of the articles identified on MEDLINE., Study Selection: Articles related to the treatment of HIT including meta-analyses, systematic reviews, critical reviews, randomized and non-randomized trials, as well as case-reports, were reviewed., Results and Conclusion: The diagnostic and therapeutic dilemmas associated with HIT can be overwhelming and call for an evidence-based approach in the management of this frequently fatal event. HIT is associated with significant morbidity and mortality. The evidence suggests when heparin is stopped, alternative anticoagulant therapy with one of the newer agents such as lepirudin and argatroban is of benefit in avoiding deaths and morbidity.

Introduction: A bioequivalence study of two oral formulations of 500 mg tablets of ciprofloxacin (RAZA Pharmaniaga, Malaysia) as test and Ciprobay (Bayer AG, Germany) as reference, was carried out in 24 healthy human volunteers. Each volunteer received a single dose of ciprofloxacin., Methods: The study method used was a double-blind, two-period, two-treatment, two-sequence, and crossover randomised design. Blood samples were taken before, and within 24 hours after drug administration. Plasma concentrations of ciprofloxacin were determined by a high-performance liquid chromatographic method with ultraviolet detection. The pharmacokinetic parameters, C(max) and T(max), were obtained directly from plasma data, k(e) was estimated by log-linear regression, and the area under the curve (AUC) was calculated by the linear trapezoidal rule. The parameters, AUC(0-infinity) and C(max), were tested for bioequivalence after log-transformation of data, while the differences of T(max) were evaluated nonparametrically., Results: When AUC(0-infinity) and C(max) were analysed using analysis of variance, no statistically significant difference was observed between the two different formulations. The 90 percent confidence intervals of the mean values for the test/reference ratios were 0.95-1.07 for AUC(0-infinity) and 0.90-1.07 for C(max), respectively. Both of these values were within the bioequivalence acceptance range of 0.80-1.25., Conclusion: We found that both formulations are bioequivalent and, therefore, interchangeable.

Background: Hydatidosis is an endemic affection in Tunisia. Bone echinococcosis is a relatively rare entity accounting for only 0.5-2% of all hydatid cysts in humans and chest wall is an uncommon site for the disease., Aim: Report of a new case, Case: We report about this talk 5 cases concerning 2 men and 3 women (mean of age 35.4 years) explored for parietal mass (4 cases), or chest pain (1 case). Diagnosis was suspected on radiologic findings in all cases. All patients underwent surgery. Medical treatment was associated in 2 cases. Histopathology of resected specimen confirmed diagnosis of echinococcosis. No recurrence was observed during follow-up period.

Chondromyxoid fibroma is a rare benign bone tumor observed in less than 1% of all bone tumors. Pathological diagnosis remains difficult. All bone sites may be involved with a predominance of the metaphysis of long tubular bones, particularly the proximal tibia. The tumor has been rarely reported in ribs. We present of case of chondromyxoid fibroma observed in this unusual location in a 31-year-old woman. Routine chest x-ray and computed tomography revealed an expansive destructive mass with a lobulated contour which arose in the fourth left rib. Local resection was performed and the histological examination showed benign chondromyxoid fibroma. The clinical outcome was favorable without recurrence after 15 months follow-up.

Background: Primary mediastinal seminomas (PMS) are rare tumors that are morphologically similar to their testicular counterparts but may have different biologic behavior due to their particular anatomical location., Aim: New cases report of PMS CASES: Three new cases of primary mediastinal seminoma are presented. The patients were men aged of 16, 33 and 47 years. Their clinical symptoms included cough, dyspnea, chest pain and superior vena cava syndrome. None of the patients had a previous history of testicular neoplasm or tumor elsewhere. Mediastinoscopic biopsy was performed and histological examination results revealed a seminoma. Immunohistochemical showed membranous staining with placental alkaline phosphatase in the three cases. Chemotherapy has largely replaced surgical resection and radiotherapy as the initial treatment in patients with mediastinal seminoma.

Clear-cell tumor of the lung is a rare entity of unknown etiology and histogenesis. This neoplasm typically presents as an asymptomatic, peripheral, sharply rounded mass in the lung, and histologically composed of large cells with a clear cytoplasm rich in glycogen, blended with an abundant network of sinusoid-type vessels. Immunohistochemical and ultrastructural procedures lead to diagnosis. We describe a primary pulmonary clear cell "sugar" tumor observed in a 28-year-old woman, and give a review of the literature. Clinical aspects, differential diagnosis, therapy and histogenetic aspects are discussed.

Tracheobronchopathia osteochondrodysplasias is a benign and rare chronic disease, whose etiology remains obscure. It is characterized by the presence of subepithelial osteocartilaginous focal lesions without any relation to tracheal rings, essentially localized in the lower two thirds of the trachea and the major bronchi. We report a new case of tracheobronchopathia osteochondrodysplasias in a 47-year-old man, localized at the lower half of the trachea, revealed by haemoptysis. The lesion was suspected by bronchoscopy and the diagnosis was made histologically, showing heterotopic bone formation. The evolution of this affection was marked by a good clinical tolerance with only a symptomatic treatment.

Inflammatory pseudotumors are uncommon benign lesions of the lung of unknown origin, that may show aggressive behavior. Although pseudotumors constitute less than 1% of all lung tumors, they are reported to be the most common cause of solitary lung masses in children. Complete resection, when possible, is safe and leads to excellent survival. The case presented here highlights difficulties in clinical and histologic diagnosis.

Mucormycosis is a rare, devastating, opportunistic fungal infection, which occurs principally in some particular conditions, specially in non-controlled diabetic patients, notably during keratoacidosis. We report two cases in 62 and 72 year-old diabetic women. In both cases, histologic examination of endobronchial biopsies showed tissue invasion by hyphae with characteristic morphology leading to the diagnosis of pulmonary zygomycosis. This difficult diagnosis must be evoked in diabetic patients with non-responsive lung infections in order to apply early aggressive therapy.

Unlabelled: Pulmonary sclerosing hemangioma is a rare, slow-growing, benign tumor. Its potential for progression and its histiogenesis remains controversial., Case Report: A routine chest X-ray revealed a right abdominal mass in 41-year-old woman. Search for a cause was negative. The patient underwent posterolateral thoracotomy for tumorectomy. Intraoperative pathology analysis revealed the benign nature of the tumor. No complication was observed postoperatively. The final pathological conclusion was sclerosing hemangioma of the lung. Pulmonary sclerosing hemangioma is a parenchymal tumor of the lung. The latest immunohistochemical studies of this lesion suggest a pneumocyte origin. Prognosis is good, but extension to lymph nodes may occur. Surgery is always required for cure, and must be associated with lymph node dissection for large tumors.

Desmoplastic fibroma is a very rare primary tumor of bone, closely related to aggressive fibromatosis of soft tissue. Although considered a benign lesion, it can be very aggressive locally and has a high rate of local recurrence after incomplete surgical excision. Radiologically, the lesion shows no distinctive features, often simulating osteosarcoma, fibrous dysplasia, or fibrosarcoma. Rib involvement by desmoplastic fibroma is extremely rare. We present two cases of desmoplastic fibroma involving this unusual location with lytic costal lesion and chest wall extension. Histological examination after surgical resection revealed that the tumor consisted of spindle cells with small, elongated nuclei in a background of numerous collagen fibers and infiltrating lamellar bone. There was no evidence of nuclear atypia, mitotic activity, or necrosis. We also discuss histological differential diagnosis as well as clinical features and the radiological and pathologic findings of this rare disease. Recognition of this entity is important to ensure proper surgical treatment.

This study was conducted to determine the tolerability and efficacy of valsartan (DIOVAN) compared to perindopril (COVERSYL) in Malaysian patients with mild to moderate hypertension. Two hundred and fifty adult Malaysian patients with a mean sitting diastolic blood pressure of more than 95 mmHg and less than 115 mmHg after a 14 day washout period were randomized to receive either valsartan 80 mg once daily (n=125) or perindopril 4 mg daily (n=125) for eight weeks. The primary end point for efficacy was the change in mean sitting systolic and diastolic blood pressure (SiSBP and SiDBP). The primary criteria for evaluation of tolerability was the incidence of adverse events. There were no significant differences between the two groups with respect to sex, age, weight, baseline sitting and standing systolic and diastolic blood pressure. At 0, 4 and 8 weeks the mean SiDBP in the valsartan group were 101.4, 92.8 and 91.0 mmHg respectively. The corresponding BP for the perindopril treated group was 102.6, 93.8 and 93.2 mmHg. (95% CI -1.39 to +3.27). There were no significant differences in the mean BP measurements between the valsartan and perindopril group at 0, 4 and 8 weeks. In each group there were significant differences between the BP at 4 and 8 weeks compared to baseline. A similar pattern was seen with SiSBP. At 4 weeks 28.7% of the valsartan and 25% of the perindopril group had their BP normalized (SiDBP <90 mmHg) The percentages of patients who responded (SiDBP reduction >10 mmHg but SiDBP >90 mmHg) were 21.3 in the valsartan group and 20.8 in the perindopril group. At 8 weeks, 31.1% of the valsartan group and 30.8% of the perindopril group had their BP normalized. The response rate was 27% and 22.5% for valsartan and perindopril respectively. The major adverse event was cough which occurred in 18 patients (14.4%) in the perindopril and 1 (0.8%) in the valsartan group at 4 weeks. At 8 weeks the figures were 24 (19.2%) and 2 (1.6%) respectively. The results indicate that Valsartan is safe and efficacious in the treatment of mild to moderate hypertension. It is equally efficacious to Perindopril and not associated with any major adverse event. It has a better tolerability profile with respect to dry cough.

Splenic marginal zone lymphoma is very rare B lymphoma, characterized by an indolent clinical course. We report the case of a 68-year-old woman with morphologic and immuno-phenotyping findings consistent with splenic marginal zone lymphoma. The patient had a splenomegaly and pancytopenia. The diagnosis was pathological based on a specimen provided by splenectomy. Two year after surgery, the patient had a normal blood count in the absence of any further treatment.

Phenytoin has been reported to have major interactions with warfarin. Phenytoin induces warfarin's metabolism. However, there are many case reports which provide conflicting conclusions. Here, we report a case of a 65-year-old man with mechanical heart valve on chronic warfarin therapy who experienced persistent fluctuations of INR and bleeding secondary to probable warfarin-phenytoin interactions. The patient's anticoagulation clinic visits prior to hospitalization were thoroughly evaluated and we continued to follow-up the case for 3 months post-hospitalization. The reported interaction could be reasonably explained from the chronology of events and the pattern of INR fluctuations whenever phenytoin was either added or discontinued from his drug regimen.

Background: Direct stenting (DS) has been shown to be associated with reduced radiation exposure and procedural costs but has a restenosis rate and clinical outcomes similar to conventional stenting (CS) with balloon predilatation. Whether DS confers benefit in diabetic patients, who have been shown to have high restenosis risk after stent implantation, remains unknown., Methods: In a multicenter randomized trial, diabetic patients undergoing elective coronary stent implantation for a de novo lesion in a native coronary artery between April 2001 and October 2002 were randomized into DS or CS treatment groups. All patients received NirElite stents (SciMed, Boston Scientific, Maple Grove, Minn). They were scheduled to undergo a 6-month angiographic follow-up with quantitative coronary analysis evaluation. The primary end point was a 6-month binary restenosis rate and the secondary end point involved 6-month all-cause mortality, nonfatal acute myocardial infarction, or target vessel revascularization rates., Results: A total of 128 diabetic patients were randomized into DS or CS treatment groups (n = 64, both groups). The 2 groups were well matched in baseline and lesion characteristics. The procedural success rate was similar (DC vs CS; 98.4% vs 96.9%). Nineteen patients (29.7%) crossed over from DS to CS. Six-month angiographic follow-up showed similar restenosis rates, minimum luminal diameter and late lumen loss. The binary restenosis rate was 43% in DS and 52% in CS groups (P = NS). The 6-month all-cause mortality, nonfatal acute myocardial infarction, or target vessel revascularization rates were also similar in both groups., Conclusions: Among diabetic patients undergoing elective coronary stent implantation, DS is safe and feasible. However, it is not associated with reduction in restenosis rate or improvement in clinical outcomes when compared with CS.

Benign myoepithelioma of the lung is a benign tumor caused by proliferating myoepithelial cells with no ductal component. These tumors are exceptional: only three cases have been reported in the literature. We report a fourth case in a 37-year-old woman at 8 months gestation. Pathological proof of diagnosis was obtained.

Dirofilariasis is a rare anthroponotic disease encountered only in the old world with most cases having been reported from Italy. The dog is the reservoir of this parasite. Man is accidentally infected by mosquitoes. We report the case involving a 27-year-old man living in a rural region of northern Tunisia who presented with a subcutaneous abscess-like scrotal nodule. Microscopic examination of the surgical specimen unexpectedly revealed parasitic involvement. Morphologic examination led to diagnosis of subcutaneous dirofilariasis due to Dirofilaria repens. This case of subcutaneous dirofilariasis brings the total number of cases reported in Tunisia to 6 and is a reminder that this parasitic disease is present in our country and that its incidence is probably underestimated. The scrotum is a rare location that poses the problem of differential diagnosis with malignant tumor or can simulate a surgical emergency. Excision allows diagnosis and treatment.

In order to study the long-term effects of balloon mitral valvoplasty (BMV) on childhood development, we followed up closely 20 mothers with severe mitral stenosis who were treated with BMV during pregnancy. Their offspring aged 63 +/- 39 (range 6-98) months were also regularly assessed using standard developmental charts and relevant laboratory tests. They were all found to have maintained normal growth, development, and speech for their appropriate ages. Developmental milestones were normal for their ages and comparable with those of their siblings. The laboratory tests revealed no abnormalities. Two losses occurred during the early course of follow-up, at the ages of 4 and 37 weeks, respectively. One of the pregnant patients suffered a stillbirth., (Copyright 2002 S. Karger AG, Basel)

The authors report a new case of mesenchymal chondrosarcoma (MCS), occurring in the upper jaw bone of a 19 year-old woman. Radiographic picture in the bone shows an aggressive osteolytic tumor suspect of malignancy. An incisional biopsy was practiced and the histologic examination has confirmed the diagnosis of MCS. Treatment have consisted of a large resection of maxilla with additional irradiation therapy. The postoperative course was marked by recurrence of the lesion one year later.

Background: The benefit of adding theophylline to beta 2 agonists in acute asthmatic attacks has been debated frequently., Methods: In an open randomised study 25 patients with severe acute asthma who presented to the emergency department were treated with either a combined nebulised salbutamol (5 mg/dose) and aminophylline infusion (0.6-0.9 mg/kg/hour), or nebulised salbutamol alone., Results: The responses to treatment as measured by peak expiratory flow (PEF) and the time taken to achieve maximum PEF were similar in both groups. Side effects were observed more commonly in patients receiving the combined treatment., Conclusions: Nebulised salbutamol is equally efficacious in acute asthma when given alone or in combination with aminophylline.

A 49 year old Malay women presented with pericardial tamponade 18 months following left segmentectomy and local irradiation for carcinoma of the breast. Subsequently she developed complete heart block terminating in cardiac arrest.

A 44-year-old Indian housewife presented with prolonged cough, intermittent fever, loss of weight and shortness of breath on exertion. Physical examination revealed a thin lady with fine crackles on both lungs. Marked eosinophilia and elevated erythrocyte sedimentation rate were noted on peripheral blood. Chest radiograph showed characteristic bilateral infiltrates affecting the periphery of both lungs. Treatment with corticosteroid resulted in dramatic improvement in symptoms, signs and radiographic changes within a few days.

Chloroquine resistance is a well established entity in South East Asia, and presents a problem of increasing importance. Strains of P. falciparum resistant to chloroquine have also been found to be resistant to amodiaquine and a combination of pyrimethamine and sulphadoxine. Knowledge of the drug sensitivity of the strains of malaria parasite in a given locality is important so that the right choice of drugs can be made in treatment of the disease. The treatment of chloroquine resistant malaria in West Malaysia is a subject of another paper but suffice it to say that increased doses of chloroquine have still been found to be effective in treating many cases of falciparum malaria from areas of chloroquine resistance.

The objective of the study was to determine whether discriminant analysis of characteristics of dyspepsia can differentiate peptic ulcer from non-ulcer dyspepsia in a Malaysian population. Two hundred and twenty six patients with dyspepsia were interviewed using a standard history questionnaire before undergoing upper gastrointestinal endoscopy. Forty seven patients had peptic ulcer while 149 others were classified as having non-ulcer dyspepsia. Stepwise logistic regression analysis was done on 25 variables. The study showed that only five of these variables could differentiate peptic ulcer from non-ulcer dyspepsia, namely, nocturnal pain, pain before meals or when hungry, absence of nausea, age and sex. A scoring system was devised based on these discriminant symptoms. At a sensitivity of 51%, the specificity for peptic ulcer was 83%, but only prospective studies will determine if this scoring system is of actual clinical value.