Bacillus cereus endocarditis in native aortic valve.

Bacillus cereus endocarditis is rare. It has been implicated in immunocompromised individuals, especially in intravenous drug users as well as in those with a cardiac prosthesis. The patient was a 31-year-old ex-intravenous drug addict with a past history of staphylococcal pulmonary valve endocarditis, who presented with symptoms of decompensated cardiac failure. Echocardiography showed severe aortic regurgitation with an oscillating vegetation seen on the right coronary cusp of the aortic valve. The blood cultures grew Bacillus cereus. We report this as a rare case of Bacillus cereus endocarditis affecting a native aortic valve.

Clinical relevance of VKORC1 (G-1639A and C1173T) and CYP2C9*3 among patients on warfarin.

WHAT IS KNOWN AND OBJECTIVES: Testing for cytochrome P450-2C9 (CYP2C9) and vitamin K epoxide reductase complex subunit 1 (VKORC1) variant alleles is recommended by the FDA for dosing of warfarin. However, dose prediction models derived from data obtained in one population may not be applicable to another. We therefore studied the impact of genetic polymorphisms of CYP2C9 and VKORC1 on warfarin dose requirement in Malaysia. METHODS: Patients who were attending clinics at our hospital and prescribed warfarin with stabilized INR levels of 2-4 were selected. DNA was extracted from blood samples and subsequently genotyped for CYP2C9*1, *2, *3, VKORC1 (G-1639A) and VKORC1 C1173T. Linear regression modelling using age, CYP2C9 and VKORC1 genotypes, sex, weight and height was undertaken to define a warfarin dosing algorithm. An initial model was developed using data from one cohort of patients and validated using data from a second cohort. RESULTS AND DISCUSSION: A model which included age and variants of CYP2C9 and VKORC1 account for about 37% of the variability in warfarin dose required to achieve INR of 2-4. Among the parameters evaluated, only VKORC1 (G-1639A) and (C1173T) alleles, and age correlated with warfarin dose at 6 month. The mean dose predicted using the algorithm derived from cohort 1 was lower than the actual dose for cohort 2 (3·30mg, SD 0·84 vs. 3·45mg, SD 1·42). There was no relationship between INR values and the dose taken by the patients. Race, sex, weight and height did not correlate with dose. WHAT IS NEW AND CONCLUSION: This study identifies factors which affect warfarin dosing in the Malaysia population. However, our best model does not account sufficiently for the variability in dose requirements for it to be used in dose prediction for the individual patient. Other important influential factors affecting warfarin dose requirement remain to be identified.

The risk of recurrence in breast cancer patients treated with tamoxifen: polymorphisms of CYP2D6 and ABCB1.

CYP2D6 plays a major role in the metabolism of tamoxifen, and polymorphism of P-glycoprotein has been associated with resistance of many drug therapies. This study investigates the clinical impact of genetic variants of CYP2D6 and ABCB1 in breast cancer patients treated with tamoxifen. Blood samples from 95 breast cancer patients treated with tamoxifen were collected and genotyped for CYP2D6 and ABCB1 variants using allele-specific PCR method. Recurrence risks were calculated using Kaplan-Meier analysis and compared using the log-rank test. Patients carrying CYP2D6*10/*10 and heterozygous null allele (IM) showed higher risks of developing recurrence and metastasis (OR 13.14; 95% CI 1.57-109.94; P = 0.004) than patients with CYP2D6*1/*1 and *1/*10 genotypes. Patients with homozygous CC genotypes of ABCB1 C3435T showed a shorter time to recurrence. Patients who were CYP2D6 IM and homozygous CC genotype of C3435T have statistically significant higher risks of recurrence (P = 0.002). Similarly, median time to recurrence in these patients was only 12 months (95% CI = 0.79-23.2) compared to those without this combination which was 48 months (95% CI = 14.7-81.2). Patients with CYP2D6 IM and homozygous CC genotype of ABCB1 C3435T have shorter times to recurrence. The results confirmed the findings of previous studies and support FDA recommendation to perform pre-genotyping in patients before the choice of therapy is determined in breast cancer patients.

CYP2C9 polymorphism: prevalence in healthy and warfarin-treated Malay and Chinese in Malaysia.

INTRODUCTION: Genetic polymorphisms of CYP2C9 among different populations in different geographical regions could be different. CYP2C9 has been reported to be the enzyme responsible for the metabolism of many drugs, including warfarin and other drugs with a narrow therapeutic index. Realising the importance of inter-individual differences in the genetic profile in determining the outcome of a drug therapy, this study was conducted to explore the types and frequencies of CYP2C9 alleles in healthy and warfarin-treated Malays and Chinese, the two major ethnic groups in Malaysia. We aimed to evaluate the prevalence of the types and frequencies of common CYP2C9 alleles (*1, *2, *3 and *4) among the healthy unrelated individuals and diseased patients prescribed with warfarin. METHODS: A total of 565 Malay and Chinese subjects, including 191 patients prescribed warfarin, were recruited into the study. The healthy unrelated volunteers were also blood donors and they were confirmed to be physically fit before participating in the study. For the patients group, their medical records were reviewed for the relevant clinical data. 5 ml of blood was taken from each subject, and DNA was isolated and used for identification of the CYP2C9 allele *1, *2, *3 and *4 using nested-allele-specific-multiplex-polymerase chain reaction. RESULTS: CYP2C9*1,*2 and *3 were detected among the healthy unrelated individuals but only CYP2C9*1 and *3 were found in the diseased patients. Among the healthy Malays, 92.8 percent had CYP2C9*1/*1, 2.6 percent had CYP2C9*1/*2 and 4.6 percent had CYP2C9*1/*3 genotypes. Among the Chinese, 92.3 percent had CYP2C9*1/*1 and 7.7 percent had CYP2C9*1/*3, but CYP2C9*2 and *4 were not found in the Chinese. Among the warfarin-treated group, only CYP2C9*1 and *3 were detected. Even though some alleles were not detected among the patients, suggesting the possible role of CYP2C9 in certain disorders, the sample size of the current study is too small to be able to arrive at any conclusive results. CONCLUSION: Based on the above-observed genotypes, the prevalence of CYP2C9*2 and *3 was low in healthy and warfarin-treated Malays and Chinese in Malaysia. Further studies are required to support the clinical effectiveness of pharmacogenomics testing.

Recurrent Bell's palsy in a young woman.

Bell's palsy is a benign lower motor neuron facial nerve disorder. It is almost always unilateral. We report a 20-year-old nulliparous woman with five episodes of recurrent Bell's palsy. A review of recent medical literature revealed a paucity of case reports involving an individual with five episodes of recurrent Bell's palsy, with none found in Asian neurology medical literature. Despite the multiple episodes of Bell's palsy recurrences, the patient did not suffer much neurological sequelae from the disease.

Angioinvasive cerebral aspergillosis presenting as acute ischaemic stroke in a patient with diabetes mellitus.

Cerebral angioinvasive aspergillosis is a rare manifestation of disseminated aspergillosis which may result in stroke in immunocompromised individuals. Reports of such disease in patients with diabetes mellitus are rare. We describe a 45-year-old man with diabetes mellitus who presented with a three-day history of right-sided limb weakness and aphasia. Cerebral computed tomography showed features of an acute infarct involving the left anterior and middle cerebral arteries. He was initially treated for an acute ischaemic stroke. Further history revealed that he was investigated for a growth in the sphenoid sinus two months earlier. Culture of the biopsied material from the sphenoid sinus grew Aspergillus fumigatus. Magnetic resonance imaging showed an extension of the growth to the brain, causing the acute ischaemic stroke. He was subsequently diagnosed with angioinvasive cerebral aspergillosis and was commenced on intravenous amphotericin B. Unfortunately, he succumbed to his illness despite treatment.