Correlation of her-2/neu gene amplification with other prognostic and predictive factors in female breast carcinoma

The purpose of this study was to determine if any relationship exists between Her-2/neu gene amplification and estrogen receptor (ER), progesterone receptor (PR), MIB-1, grade, size and age in female breast cancer. Five hundred and eighteen female patients with invasive breast carcinoma, 390 ductal and 128 lobular, in which assessment of Her-2/neu amplification by fluorescence in-situ hybridization (FISH) has been performed, were reviewed retrospectively. Each patient was further assessed for ER, PR, MIB-1, grade, size and age at diagnosis. Chi-square analysis was then used to correlate the above observations. Overall gene amplification was seen in 76 (15%) of the cases, 68 (17%) were ductal and 8 (6%) were lobular. Her-2/neu gene was amplified in 37 (10%) out of 379 ER positive cases and in 39 (28%) out of 139 ER negative cases. Her-2/neu was amplified in 22 (7%) out of 301 PR positive cases and in 54 (25%) out of 217 PR negative cases. Amplification occurred in 18 (8%) out of 222 negative MIB-1 cases and amplified in 58 (20%) out of 296 positive cases. Amplification was seen in 5 (10%) out of 49 grade I tumors, 17 (12%) out of 143 grade II tumors and 54 (27%) out of 198 grade III tumors. Lobular carcinomas were not graded. Amplification was present in 52 (15%) out of 346 T1 lesions, in 17 (13%) out of 130 T2 lesions, in 5 (17%) out of 30 T3 lesions and in 2 (17%) out of 12 T4 lesions. Her-2/neu was amplified in 67 (14%) out of 467 woman 41 years and older, and in 9 (18%) out of 51 women 40 years and younger. Comparison of these frequencies using chi-square test revealed statistically significant correlation between Her-2/neu amplification and ductal versus lobular carcinoma (p<0.0003), ER (p=0.0001) and PR (p<0.0001) negative tumors, over-expression of MIB-1 (p<0.0005) and high tumor grade (p=0.0009), while size of the tumor (p=0.08) and age of the patients (p=0.67) were not statistically significant. Correlation was found between Her-2/neu amplification and tumor type, high histological grade, ER and PR negative tumors, and high proliferative MIB-1 index. No correlation was found between size of the tumor and age of the patient with Her-2/neu amplification.     

Maternal deaths and their causes in Ankara, Turkey, 1982-2001

This study was carried out to determine the incidence and causes of maternal deaths about a 20-year period at the Zekai Tahir Burak Women's Health Education and Research Hospital (ZTBWHERH), Ankara, Turkey. All maternal deaths from January 1982 to July 2001 were reviewed and classified retrospectively. Using a computer-generated list, 348 patients admitted to the Labour Department of ZTBWHERH during 1982-2001 were selected as controls. Medical records were reviewed for demographic data, history of antenatal care, route of delivery, referral history, and perinatal mortality. Cases and controls were compared, and standard tests were used for calculating odds ratio (OR) and 95% confidence interval (CI) for the association of demographic and delivery characteristics. During this period, there were 174 maternal deaths and 430,559 livebirths, giving a maternal mortality ratio of 40.4/100,000 livebirths. The mortality rate declined from 85.1/100,000 in 1982 to 11.6/100,000 in 2001. One hundred thirty (74.7%) deaths were due to direct obstetric causes and 24 (13.7%) were abortion-related, while 20 (11.4%) were due to indirect obstetric causes. The most common cause of direct obstetric deaths was pre-eclampsia/eclampsia, followed by obstetric haemorrhage and embolism. Abortion-related sepsis and haemorrhage, anesthesia-related deaths, obstetric sepsis, acute fatty liver of pregnancy, and ectopic pregnancy accounted for other causes of deaths. Cardiovascular disease was the leading indirect cause of death. Referral, lack of antenatal care, and foetal death at admittance were associated with 8-, 3-, and 6-fold increased risk of maternal mortality respectively (OR 8.89, 95% CI 5.7-13.8; OR 3.74, 95% CI 2.5-5.5; OR 6.38, 95% CI 3.1-13.1). Although maternal mortality ratios have declined at the hospital, especially in the past five years, the rate is still high, and further improvements are needed. The problem of maternal mortality remains multifactorial. Short-term objectives should be focused on improving both medical and administrative practices. Improving the status of women will necessarily remain a long-term objective.     

Efficacy of oral cochleate-amphotericin B in a mouse model of systemic candidiasis

Amphotericin B (AMB) remains the principal therapeutic choice for deep mycoses. However, its application is limited by toxicity and a route of administration requiring slow intravenous injection. An oral formulation of this drug is desirable to treat acute infections and provide prophylactic therapy for high-risk patients. Cochleates are a novel lipid-based delivery system that have the potential for oral administration of hydrophobic drugs. They are stable phospholipid-cation crystalline structures consisting of a spiral lipid bilayer sheet with no internal aqueous space. Cochleates containing AMB (CAMB) inhibit the growth of Candida albicans, and the in vivo therapeutic efficacy of CAMB administered orally was evaluated in a mouse model of systemic candidiasis. The results indicate that 100% of the mice treated at all CAMB doses, including a low dosage of 0.5 mg/kg of body weight/day, survived the experimental period (16 days). In contrast, 100% mortality was observed with untreated mice by day 12. The fungal tissue burden in kidneys and lungs was assessed in parallel, and a dose-dependent reduction in C. albicans from the kidneys was observed, with a maximum 3.5-log reduction in total cell counts at 2.5 mg/kg/day. However, complete clearance of the organism from the lungs, resulting in more than a 4-log reduction, was observed at the same dose. These results were comparable to a deoxycholate AMB formulation administered intraperitoneally at 2 mg/kg/day (P < 0.05). Overall, these data demonstrate that cochleates are an effective oral delivery system for AMB in a model of systemic candidiasis.     

The effect of dietary intake changes on nutritional status in acute leukaemia patients after first induction chemotherapy

This study aimed to evaluate how changes in dietary intake among acute lymphoblastic and acute myeloid leukaemia (ALL and AML) patients affect nutritional status after the first induction chemotherapy. Dietary intake was assessed using 24‐h recall and a 136‐item food frequency questionnaire. Nutritional status was assessed by Patients Subjective Global Assessment questionnaire before starting induction therapy and again after 1 month. All newly diagnosed acute leukaemia patients aged 15 years old and older who attended three referral hospitals for initiation of their induction chemotherapy were included in the sample selection provided that they gave informed consent. A total of 30 AML and 33 ALL patients participated in the study. Dietary intake and nutritional status worsened after the chemotherapy treatment. Dietary intake in terms of macronutrients, micronutrients, food variety and diet diversity score changed significantly after the induction chemotherapy. No significant relationship was found between the changes in dietary indices and nutritional status. Chemotherapy‐related side effects as an additional factor to cancer itself could affect dietary intake of leukaemia patients. The effectiveness of an early assessment of nutritional status and dietary intake should be further investigated in order to deter further deterioration.     

Biodistribution of Mixed Fluorocarbon–Hydrocarbon Dowel Molecules Used as Stabilizers of Fluorocarbon Emulsions: A Quantitative Study by Fluorine Nuclear Magnetic Resonance (NMR)

¹⁹F NMR spectroscopy was used to determine quantitatively the organ distribution and organ retention time in rats of the mixed fluorocarbon–hydrocarbon dowel molecule C₆F₁₃CH = CHC₁₀H₂₁ (F6H10E), which stabilizes highly concentrated injectable fluorocarbon emulsions destined for in vivo oxygen transport and delivery. The only fluorine resonances detected in the ¹⁹F NMR spectra of the organs analyzed were those of the F6H10E dowel itself, indicating that metabolites, if present, have very low concentrations (<10^–4 M, limit of our assay). The F6H10E content in the liver peaked 1 day after administration (7 days for the spleen). At a dose of 3.6 g/kg body weight, the half-life of F6H10E in the liver was 25 ± 5 days.