Effects of CYP2B6 genetic polymorphisms in patients receiving cyclophosphamide combination chemotherapy for breast cancer.

PURPOSE: The purpose of this study was to measure the frequency of three CYP2B6 [CYP2B6*4 (rs2279343), CYP2B6*5 (rs3211371) and CYP2B6*9 (rs3745274)] alleles in patients with breast cancer receiving cyclophosphamide (CP) therapy and test whether these variants are predictors of CP-associated toxicity and efficacy. METHODS: A total of 145 female breast cancer patients admitted to the American University of Beirut Medical Center for breast cancer-related therapy were included. Chart review was performed for collection of toxicity data. A time-to-event analysis was performed with a subset of 38 patients. RESULTS: The minor allele frequencies of CYP2B6*9, CYP2B6*4 and CYP2B6*5 were 0.27, 0.29 and 0.07, respectively. CYP2B6 *5/*6, *6/*9 or *6/*6 haplotypes were associated with a significantly shorter time to recurrence of the disease. There were no significant associations with myelo-toxicity. CONCLUSIONS: This is the first report on the pharmacogenetic profile of patients with breast cancer and the therapeutic and myelo-toxic behavior of CP in women from an Arab Middle Eastern country. Our results show that genotyping for these CYP2B6 alleles does not help in personalizing therapy from a toxicity perspective, and the association of shorter survival in these subjects with homozygous variants is interesting yet insufficient to justify routine genotyping prior to therapy, or to consider using a higher CP dose. Larger future studies or meta-analyses will be needed to further clarify the potential implication of these genetic polymorphisms.

KIR genotype distribution among patients with multiple myeloma: Higher prevalence of KIR 2DS4 and KIR 2DS5 genes.

INTRODUCTION: Natural killer (NK) cells possess an antitumor activity against multiple myeloma cells proven by the susceptibility of plasmocytes to NK lysis. In the early stage of MM, the killing of MM cells is mediated by natural cytotoxicity receptors (NRC) and NKG2D-dependent pathway, while in the late stage, NK cells lose their killing potential against MM cells due to the high expression of HLA class I molecules on MM cells. AIM: The aim of this paper is to study KIR expression of NK cells in MM patients and in healthy controls, to check for any association between KIR genotypes and MM. METHODS: KIR genotype was analyzed in 120 healthy Lebanese individuals and 34 MM patients using the KIR Genotyping SSP kit. RESULTS: KIR 2DS4*001/002 and KIR 2DS5 were found to be significantly more prevalent among MM patients as compared to controls. For MM patients, the AA, AB, and BB genotype frequencies were, respectively, 38.23%, 47.06% and 14.71% with an A:B ratio of 1.62:1. As for the healthy controls, the AA, AB, and BB genotype frequencies were, respectively, 39.17%, 50%, and 10.83% with an A:B ratio of 1.80:1. CONCLUSION: The interesting observation of the significant presence of KIR2DS4 and KIR2DS5 genes more among multiple myeloma patients than controls is worth further clinical, translational as well as survival research studies in these cases.

Abdominoplastia clásica con lipoaspiración de contorno versus lipoabdominoplastia: estudio aleatorio doble ciego / Classic abdominoplasty with liposuction contour versus lipoabdominoplasty: randomized double-blind

Con el advenimiento de la lipoaspiración en 1980, existió un gran progreso del abordaje de la pared abdominal, evolucionando a nuevos conceptos de remodelación del contorno corporal, como la lipoabominoplastia descrita por Saldanha en el año 2001. El objetivo del estudio es comparar los resultados de la abdominoplastia clásica con Lipoaspiración de contorno contra la lipoabdominoplastia. Analizando morbilidad postoperatoria y grado de satisfacción. Se estudiaron prospectivamente todos los pacientes intervenidos en la ciudad de Valdivia, excluyendo a los pacientes con IMC mayor de 35, hernias abdominales asociadas, cicatrices quirúrgicas extensas de la pared abdominal. Se designaron aleatoriamente mediante método de distribución de probabilidad uniforme. El paciente ni el encuestador supieron la técnica empleada. Los análisis estadísticos fueron realizados mediante estadística descriptiva y chi cuadrado. Hubo 30 pacientes por grupo. Ambos grupos fueron comparables según las variables demográficas. Hubo complicaciones en el 16,7 por ciento de las intervenciones. Siendo más frecuentes los seromas en el grupo de la abdominoplastia. El grado de satisfacción fue elevado en ambos grupos, sin embargo, los "retoques" solicitados por los pacientes fue mayor en el grupo de la abdominoplastia clásica. Nuestros resultados son comparables con otras series, creemos que el mayor porcentaje de seromas fue dado por el mayor tallaje del colgajo dermo graso. Sin duda que las técnicas de remodelación de la pared abdominal se deben analizar en forma particular, teniendo en consideración los distintos parámetros anatómicos de cada paciente.

With the advent of liposuction in 1980, there was a great progress in addressing the abdominal wall, evolving into new concepts of body contouring, as Lipoabdominoplasty described by Saldanha in 2001. The objective of the study is to compare the results of classical abdominoplasty contour liposuction against Lipoabdominoplasty. Analyzing postoperative, morbidity and satisfaction. All patients operated in the city of Valdivia, excluding patients with BMI greater than 35, associated abdominal hernias, extensive surgical scarring of the abdominal wall were prospectively studied. They were randomly designated using uniform probability distribution. Neither the patient nor the interviewer knew the technique. Statistical analyzes were performed using descriptive statistics and chi square. There were 30 patients per group. Both groups were comparable according to demographic variables. Complications occurred in 16.7 percent of the interventions. The most frequent was seroma in abdominoplasty group. The degree of satisfaction was high in both groups, however the "tweaks" requested by patients was higher in the classical abdominoplasty group. Our results are comparable with other series, we believe that the highest percentage of seromas was given by the largest sizing fatty dermal flap. Certainly the indication of technical remodeling of the abdominal wall should be analyzed on an individual basis taking into account the different anatomical parameters of each patient.

Nutritional status in a sample of the Afghan immigrant children within Iran.

Anthropometric studies in Afghan immigrants in Iran have not been yet performed; therefore the aim of the present study is to identify Body Mass Index (BMI) in a sample of Afghan immigrant children in Iran during the year 2005. In this cross-sectional study 606 Afghan children aged between 6-14 years have been randomly selected within Shahriar County of Tehran Province of Iran and their weight and height have been measured. Then, using BMI formula BMI = Weight (kg)/Height (m2) their BMI was calculated and based on CDC (Centers for Disease and Prevention Control) indices, children were categorized as: under weight, normal and obese. Results of this study showed that 97 cases (16%) had low weight whereas, 429 cases (81.2%) had normal weight and 17 cases (2.8%) had over weight. More percentage of girls had lower weight than the boys (15.2 versus 16.9%), Afghan children who were born in Iran had also lower weight (17.3%) than those who were born in Afghanistan (15.2%) and third and upper birth order children had lower weight compared to first and second birth order (17 versus 15.3%). However, none of these differences were statistically significant. The researchers suggest that due to high incidence of malnutrition in Afghan immigrant children in Iran interventional and educational programs are needed in order to improve their level of health and nutritional status.

Epidemiology of animal bites in Rafsanjan, southeast of Islamic Republic of Iran, 2003-05.

The incidence of animal bites in the Islamic Republic of Iran has been increasing in recent years. In a descriptive study of 1542 patients referred to a health centre in Rafsanjan city from 2003 to 2005, the incidence of animal bites in the area was estimated as 180, 195 and 241 per 100 000 in 2003, 2004 and 2005 respectively. Of the patients, 74% were bitten by dogs, 23% by cats and 3% by other animals (monkeys, rats, foxes, bats, donkeys, etc.). The mean time delay from injury to initial management was 15.1 (SD 29.8) hours. Rabies vaccine was given to 85% of cases, rabies vaccine plus rabies immunoglobulin to 15% and tetanus toxoid vaccine to 66%.

Epidemiology of animal bites in Rafsanjan, southeast of Islamic Republic of Iran, 2003-05

The incidence of animal bites in the Islamic Republic of Iran has been increasing in recent years. In a descriptive study of 1542 patients referred to a health centre in Rafsanjan city from 2003 to 2005, the incidence of animal bites in the area was estimated as 180, 195 and 241 per 100 000 in 2003, 2004 and 2005 respectively. Of the patients, 74% were bitten by dogs, 23% by cats and 3% by other animals [monkeys, rats, foxes, bats, donkeys, etc.]. The mean time delay from injury to initial management was 15.1 [SD 29.8] hours. Rabies vaccine was given to 85% of cases, rabies vaccine plus rabies immunoglobulin to 15% and tetanus toxoid vaccine to 66%

Hematopoietic stem cell transplantation in Lebanon: first comprehensive report.

Hematopoietic SCT (HSCT) has become a curative therapeutic strategy for several malignant and nonmalignant diseases. We report the comprehensive results of the first 10 years of experience in HSCT from the two major BMT units in Lebanon: Makassed University Hospital and the American University of Beirut Medical Center. The median and the 5-year overall survival (OS) were 97 months and 58%, respectively, for the 84 patients who received allogeneic HSCT, and 60 months and 50%, respectively, for the 228 patients who received autologous BMT. The results for myeloablative allogeneic transplantation were as follows: AML (n=28, 5-year OS 58%, 5-year disease-free survival (DFS) 48%), CML (n=9, 5-year OS 66%, 5-year DFS 52%), ALL (n=13, 2-year OS 10%, 2-year DFS 10%), thalassemia (n=10, 5-year transfusion-free survival 67%). The results for autologous HSCT were as follows: diffuse large B-cell lymphoma (DLBCL) in relapse (n=37, 5-year OS 68%, 5-year progression-free survival (PFS) 65%), Hodgkin's lymphoma (n=55, 5-year OS 55%, 5-year PFS 36%), and first-line multiple myeloma (n=71, 5-year OS 53%, 5-year PFS 24%). For allogeneic transplanted patients, the cumulative TRM was 23% and the incidence of acute GVHD was 23%. For autografted patients, TRM was 2.6%. These results indicate that despite the relatively low socioeconomic status of the Lebanese population, both allogeneic and autologous HSCT are feasible with outcomes similar to developed countries.

Reconstrucción labial: principios y técnicas / Labial reconstruction: principles and techniques

Los labios constituyen estructuras de gran importancia funcional y estética que puede ser alterada por diferentes mecanismos como trauma, quemaduras de diversas índole y tumores benignos o malignos. Su reconstrucción ha sido objeto de innumerables publicaciones, sin embargo no se encuentra fácilmente en la literatura una sistematización de técnicas que permita orientar al cirujano general y al especialista, sobre su enfrentamiento. El objetivo de este trabajo es dar una visión global del tema y hacer hincapié en los principios generales que debe respetar el cirujano, detallando gráficamente las técnicas existentes.

Hemiatrofia facial y lipoinyección: una alternativa terapéutica / Facial hemiatrophy and lipoinyection: a therapeutic alternative

Se presenta el caso clínico de una paciente de 27 años, portadora de una hemiatrofia facial izquierda, a la cual se le realizó plastia facial mediante lipoinyección de tejido adiposo, intervención quirúrgica que se llevó a cabo sin complicaciones. Presentó reabsorción parcial del tejido graso implantado, por lo cual se repitió el procedimiento en 2 oportunidades (12 y 60 meses después). El resultado estético final excelente, con la consiguiente mejoría de la calidad de vida de la paciente. Después de 72 meses de observación, a partir del primer procedimiento, la paciente mantiene el efecto estético logrado con el injerto adiposo, el cual se ha incrementado, asociado a un aumento del peso corporal con acumulación grasa en la pared abdominal. Esta situación corroboraría clínicamente la teoría de la mantención de los caracteres genéticos de un injerto en el área receptora. Consideramos que la lipoinyección constituye una alternativa terapéutica válida en la corrección de esta patología.

In vitro activity of telithromycin (HMR 3647) against Greek Streptococcus pyogenes and Streptococcus pneumoniae clinical isolates with different macrolide susceptibilities.

The susceptibilities to macrolides and telithromycin of 161 Streptococcus pyogenes and 145 Streptococcus pyogenes strains, consecutively isolated from five Greek hospitals, were determined by Etest. Moreover, mechanisms of resistance to macrolides were phenotypically and genetically determined by double disk induction test and PCR, respectively. Of the S. pneumoniae and S. pyogenes isolates, 42.8% and 30.8%, respectively, were found to be resistant to erythromycin. Of the erythromycin-resistant S. pneumoniae and S. pyogenes isolates, 57.5% and 59.5%, respectively, displayed the M phenotype and harbored the mefA/E gene. Telithromycin was found to be more active than both erythromycin and clarithromycin against both species, with considerably lower MIC50 and MIC90 values.

Hepatitis C virus infection in Lebanese patients with B-cell non-Hodgkin's lymphoma.

Several studies from many countries have reported a high prevalence (> 9%) of hepatitis C virus (HCV) infection in patients with B-cell non-Hodgkin lymphoma (B-NHL) suggesting a possible etiological role of HCV in the development of B-NHL. Data from the United Kingdom and Turkey, however, did not confirm these observations. To determine the prevalence of HCV infection in patients with B-cell lymphoma in Lebanon, a controlled study was conducted in which 318 Lebanese patients were investigated. These included 35 patients with B-NHL, 63 patients with various malignant conditions (control group 1) and 220 patients with non-malignant conditions (control group 2). Samples were tested in duplicates for antibodies to HCV (anti-HCV) by enzyme-linked immunosorbant assay (ELISA). None of the 318 patients investigated were anti-HCV positive. Based on our findings, it can be concluded, that, there is no sufficient evidence to indicate that HCV plays role in the development of B-NHL in Lebanese patients. Predisposing factors in lymphoproliferative disorders are numerous including both genetic and environmental factors that could vary from one geographic region to another.

Short duration neoadjuvant chemotherapy followed by radiotherapy for advanced carcinoma of the cervix: results and prognostic variables.

PURPOSE: The value of neoadjuvant chemotherapy in squamous cell carcinomas of the cervix has not been proven. It has been suggested that the potential benefit of this therapy on local and occult metastatic disease could be offset by delaying effective radiation therapy and selection of more aggressive tumor clones. This report examines the potential impact of short duration neoadjuvant chemotherapy on the response and outcome of advanced carcinoma of the cervix. MATERIALS AND METHODS: Between 1993 and 1997, 37 patients with advanced squamous cell carcinoma of the cervix (FIGO Stages IIB to IV) were enrolled in a prospective nonrandomized study using short duration neoadjuvant chemotherapy. Median age was 57 years (range: 34-70). Twenty-one patients (57%) had Stage IIB disease, one (3%) had Stage IIIA, 11 (30%) Stage IIIB, and four (11%) had Stage IV disease. The average tumor diameter at presentation assessed by physical examination and by CT scan measurements was 5.3 + 1.9 cm and 5.3 + 1.4 cm, respectively. Patients received three cycles of chemotherapy consisting of cisplatin 50 mg/m2 and vincristine 1 mg/m2 for 1 dose and bleomycin 25 mg/m2 daily for three days. Cycles were repeated every ten days. All patients started definitive radiotherapy within a week from the end of chemotherapy. Radiation therapy consisted of whole pelvis radiotherapy followed by 1-3 sessions of low dose rate brachytherapy. RESULTS: Response to neoadjuvant chemotherapy was as follows: seven patients (19%) had minor or no response, one patient had progressive disease, and 28 (76%) had more than 50% tumor reduction; 14 of them (38%) had no clinical evidence of residual tumor. Chemotherapy was discontinued in one patient after the second cycle because of significant changes in pulmonary function tests (PFT), and one patient developed a grade 4 urinary complication after radiotherapy. Median follow-up time for the whole group was 24 months (range: 1-67). Five-year actuarial rates of local control and disease-free survival were 47 and 42%, respectively. At three years, 20 patients (54%) were alive or had died without evidence of disease, and 17 (46%) had succumbed to their disease, with a median time to recurrence of 25 months. Stage and response to neoadjuvant chemotherapy had significant impact on survival, while age. tumor size, and menopausal status did not influence survival. CONCLUSIONS: Our data indicate that short duration chemotherapy followed by definitive radiotherapy is well tolerated and feasible. However, despite a high rate of objective response (76%), and improved survival for responders, there was no obvious long-term survival benefit for the entire group.

Quiste paratiroideo sintomático: a propósito de un caso / Symptomatic parathyroid cyst: report 1 case

Parathyroid cysts are unusual and do not have specific clinical manifestations or ultrasonographic findings. Therefore, they are usually confused with thyroid nodules. We report a 43 years old male, with normal thyroid function and normal calcium serum levels, that presented a nodule in the lower right third of the neck. Ultrasonography and CAT scan showed a well delimited 6 x 4.5 cm ovoid cyst that compressed and displaced the trachea and esophagus. A fine needle aspiration was done on three occasions, extracting 18, 40 and 60 ml of liquid. As the cyst recurred and symptoms intensified, the patient was operated removing the cyst and the right thyroid lobe. Pathological study disclosed a parathyroid cyst

Reconstrucción auricular / Auricular reconstruction

La reconstrucción auricular constituye un capítulo apasionante y representa todo un desafío para el médico de urgencia, el cirujano general e incluso para el más avezado de los cirujanos plásticos. Debido a su proyección y exposición, el pabellón auricular es susceptible a una infinidad de injurias traumáticas que van desde pequeñas heridas hasta la evolución completa; también es afectado por neoplasias cutáneas inducidas por daño actínico. Una amplia variedad de defectos congénitos, incluyendo microtia y orejas aladas, como las más frecuentes, afectan a esta estructura desafiando al cirujano a elejir entre variada y sofisticadas técnicas reconstructivas, presentes hoy en el arsenal quirúrgico. El objetivo de este artículo es dar a conocer en líneas generales el manejo en la reconstrucción del pabellón auricular.

Hypercalcemia in Langerhans' cell granulomatosis with elevated 1,25 dihydroxyvitamin D (calcitriol) level.

A 48-year-old woman presented with a history of premature menopause, polyuria, polydipsia, fever, and diffuse bony tenderness. Her evaluation revealed central diabetes insipidus, hypothalamic amenorrhea, an elevated free calcium on multiple occasions with an elevated 1,25 dihydroxyvitamin D level, and osteoporosis by densitometry. Skeletal series revealed multiple lytic lesions involving the long bones. The diagnosis of Langerhans' cell granulomatosis was made. She was treated with hormone replacement therapy, radiotherapy, and vinblastine, with a dramatic improvement in her pain and a near normalization of her free calcium. Whereas hypercalcemia has been described in several granulomatous disorders and is secondary to unregulated extrarenal production of 1,25 dihydroxyvitamin D, it is, however, extremely rare in Langerhans' cell granulomatosis. This is the first case report of Langerhans' cell granulomatosis with hypercalcemia and documented elevated increased 1,25 dihydroxyvitamin D level that responded to the treatment of her primary disease.

Tamoxifen and ovarian cysts: a prospective study.

PURPOSE: To prospectively follow a group of women with breast cancer on tamoxifen for the development of ovarian cysts. METHODS: 72 women were followed every 6 months with pelvic examination and vaginal ultrasound. Chi square and Student's t-test were used for statistical analysis. RESULTS: The duration of treatment was 31.5+/-20 months. The mean age was 51.2+/-9.8 years. 55.6% were post-menopausal. Out of 72 women, 18 (25%) developed ovarian cysts. The mean age of women who developed ovarian cysts was significantly lower than in those who did not (47.0+/-7.0 and 52.5+/-10.2 years, respectively, P=0.03), however, the mean duration of treatment was not significantly different (33.3+/-17.4 and 29.3+/-20 months, respectively, P=0.45). Out of 32, 14 (43.8%) pre-menopausal and out of 40, 4 (10%) post-menopausal women developed ovarian cysts (P=0.003). They developed the cysts after an average duration of 33.3+/-18 and 50.7+/-6.2 months, respectively (P=0.7). The average diameter of the cysts was 2.8+/-1.2 cm. All cysts were simple except for one pre-menopausal women. All the cysts in post-menopausal women resolved spontaneously. One pre-menopausal patient had a multi-loculated cyst, was operated and had a serious cystadenoma. In nine patients, the cysts resolved spontaneously and in three after discontinuation of tamoxifen, and one patient was lost to follow-up. All cysts were asymptomatic. CONCLUSION: Ovarian cysts frequently develop in women with breast cancer on tamoxifen. The majority of the cysts resolve spontaneously, therefore an expectant management with follow-up ultrasonography is recommended.