Cervical cancer metastatic to the breast: A rare presentation of tumor dissemination

Metastatic disease presenting in the mammary gland from gynecologic malignancies is a rare occurrence. A case of metastatic adenosquamous carcinoma of the cervix presenting as an inflammatory breast lesion is reported. Metastases within the breast have distinct clinical, radiographic, and histologic features and should be suspected in a patient with a breast mass and a known extramammary primary. As with other distant metastases of cervical cancer, mammary gland involvement portends a poor prognosis.     

Benzo[b]fluoranthene: tumorigenicity in strain A/J mouse lungs, DNA adducts and mutations in the Ki-ras oncogene

The polycyclic aromatic hydrocarbon benzo[b]fluoranthene (B[b]F)is a pervasive constituent of environmental combustion products.We sought to examine the lung tumorigenic activity of B[b]Fin strain A/J mice, to study the relationship between formationand decay of B[b]F-DNA adducts and to examine mutations in theKi-ras proto-oncogene in DNA from B[b]F-induced tumors. Micewere given i.p. injections of 0, 10, 50, 100 or 200 mg/kg bodywt and lung adenomas were scored after 8 months. B[b]F inducedsignificant numbers of mouse lung adenomas in a dose-relatedfashion, with the highest dose (200 mg/kg) yielding 6.95 adenomas/mouse, with 100% of the mice exhibiting an adenoma. In micegiven tricaprylin, the vehicle control, there were 0.60 adenomas/mouse,with 55% of the mice exhibiting an adenoma. Based on dose, B[b]Fwas less active than benzo[     

Integrity of crystalline lysozyme exceeds that of a spray-dried form

The development of proteins as therapeutic agents is challenging partly due to their inherent instabilities. Consequently, crystallisation and spray drying techniques were assessed to determine their effects on protein integrity using lysozyme as a model protein. Unprocessed, crystallised and spray-dried lysozyme were characterised by: thermal analysis using hot stage microscopy (HSM), differential scanning calorimetry (DSC), high sensitivity differential scanning calorimetry (HSDSC) and thermogravimetry (TGA); and spectroscopic analysis employing Fourier transform Raman (FT-Raman). Moisture contents were determined by TGA and Karl Fisher titration (KFT). Enzymatic assay measured biological activity. HSM showed no changes in crystals until complete melting. TGA and KFT indicated that spray-dried lysozyme contained a lower moisture content than crystals, hence the higher apparent thermal stability was shown by DSC. HSDSC revealed that crystallisation and spray drying did not affect the denaturation temperature of lysozyme in solution when compared with unprocessed material. However, in the solid state, FT-Raman spectra showed perturbation of the conformational structure of spray-dried sample, whereas crystal conformation remained intact. Enzymatic assay revealed increased activity retention of crystals compared with spray-dried powder. Hence, crystals maintained the conformational integrity and activity of lysozyme in solution.     

Angiogenic factors for the prediction of pre-eclampsia in women with abnormal midtrimester uterine artery Doppler velocimetry

OBJECTIVE: To determine whether assessing uterine perfusion and angiogenic factors concurrently in the second trimester improves the prediction of pre-eclampsia and intrauterine growth restriction (IUGR). METHOD: Plasma levels of soluble fms-like tyrosine kinase 1 (sFlt-1) and placental growth factor (PlGF) were measured for 108 women with abnormal uterine perfusion on Doppler velocimetry in the 23rd week. Later, 33 cases of pre-eclampsia and 9 of IUGR developed. RESULTS: Compared with the plasma levels of the women whose pregnancies remained normal, sFlt-1 levels were significantly higher and PlGF levels significantly lower in the women whose pregnancies became complicated by pre-eclampsia and/or IUGR (P<0.001). The alterations were more pronounced in cases of early-onset pre-eclampsia and in cases of IUGR that necessitated delivery before 34 weeks. Using the sFlt-1/PlGF ratio, these complications could be predicted with 98% sensitivity, 95% specificity, and 93% positive predictive value. CONCLUSION: Measuring uterine perfusion and angiogenic factors concurrently in the second trimester improved the prediction of pre-eclampsia and IUGR.     

Transfected beta3- but not beta2-adrenergic receptors regulate cystic fibrosis transmembrane conductance regulator activity via a new pathway involving the mitogen-activated protein kinases extracellular signal-regulated kinases

We have shown previously that in a heterologous mammalian expression system A549 cells, beta3-adrenoceptor (beta3-AR) stimulation regulates the activity of cystic fibrosis transmembrane conductance regulator (CFTR) chloride channel. The present investigation was carried out to determine the signaling pathway involved in this regulation. A549 cells were intranuclearly injected with plasmids encoding human CFTR and beta3-AR. CFTR activity was functionally assessed by microcytofluorimetry. The application of 1 microM 4-[3-t-butylamino-2-hydroxypropoxy]benzimidazol-2-1 hydrochloride (CGP-12177), a beta3-AR agonist, produced a CFTR activation that was not abolished by protein kinase A inhibitors. In pertussis toxin-pretreated cells, the CFTR activation induced by CGP-12177 was abolished. The overexpression of beta-adrenoceptor receptor kinase, an inhibitor of betagamma subunits, abolished the CGP-12177-induced CFTR activation, suggesting the involvement of betagamma subunits of Gi/o proteins. The pretreatment of A549 cells with selective inhibitors of either phosphoinositide 3-kinase (PI3K), wortmannin, and 2-(4-morpholinyl)-8-phenyl-1(4H)-benzopyran-4-one hydrochloride (LY294002), or extracellular signal-regulated kinases 1 and 2 (ERK1/2) mitogen-activated protein kinase (MAPK), 2'-amino-3'-methoxyflavone (PD98059), and 1,4-diamino-2,3-dicyano-1,4-bis(2-aminophynyltio)butadiene (U0126), abolished the effects of CGP-12177 on the CFTR activity. Immunohistochemical assays showed that only the cells expressing beta3-AR exhibited MAPK activation in response to CGP-12177. Furthermore, CFTR activity increased in cells pretreated with 10% fetal bovine serum both in A549 cells injected only with CFTR and in T84 cells, which endogenously express CFTR, indicating that CFTR activity can be regulated by the MAPK independently of the beta3-AR stimulation. In conclusion, we have demonstrated that CFTR is regulated through a Gi/o/PI3K/ERK1/2 MAPK signaling cascade dependently or not on an activation of beta3-ARs. This pathway represents a new regulation for CFTR.     

Profound hypothermia protects neurons and astrocytes, and preserves cognitive functions in a Swine model of lethal hemorrhage

BACKGROUND: Lethal injuries can be repaired under asanguineous hypothermic arrest (suspended animation) with excellent survival. This experiment was designed to test the impact of this strategy on neuronal and astroglial damage in a swine model of lethal hemorrhage. Furthermore, our goal was to correlate the histological changes in the brain with neurological outcome, and the levels of circulating brain specific markers. MATERIALS AND METHODS: Uncontrolled hemorrhage was induced in 32 female swine (80-120 lbs) by creating an iliac artery and vein injury, followed 30 min later by laceration of the thoracic aorta. Through a thoracotomy approach, organ preservation fluid was infused into the aorta using a roller pump. Experimental groups included normothermic controls (no cooling, NC), and groups where hypothermia was induced at three different rates: 0.5 degrees C/min (slow, SC), 1 degrees C/min (medium, MC), or 2 degrees C/min (fast, FC). Profound hypothermia (core temperature of 10 degrees C) was maintained for 60 min for repair of vascular injuries, after which the animals were re-warmed (0.5 degrees C/min) and resuscitated on cardiopulmonary bypass (CPB). Circulating levels of neuron specific enolase (NSE) and S-100beta were serially measured as markers of damage to neurons and astrocytes, respectively. Light microscopy and quantitative immunohistochemical techniques were used to evaluate hippocampal CA1 area and caudate putamen for neuronal injury and astrogliosis (astrocyte hyperplasia/hypertrophy). Surviving animals were observed for 6 weeks and neurological status was documented on an objective scale, and cognitive functions were evaluated using a technique based upon the concept of operant conditioning. RESULTS: Normothermic arrest resulted in clinical brain death in all of the animals. None of the surviving hypothermic animals displayed any neurological deficits or cognitive impairment. On histological examination, normothermic animals were found to have ischemic changes in the neurons and astrocytes (hypertrophy). In contrast, all of the hypothermic animals had histologically normal brains. The circulating levels of brain specific proteins did not correlate with the degree of brain damage. The changes in NSE levels were not statistically significant, whereas S-100beta increased in the circulation after CPB, largely independent of the temperature modulation. CONCLUSIONS: Profound hypothermia can preserve viability of neurons and astrocytes during prolonged periods of cerebral hypoxia. This approach is associated with excellent cognitive and neurological outcome following severe shock. Circulating markers of central nervous system injury did not correlate with the actual degree of brain damage in this model.     

Meta-analysis of survival models of lung cancer

Lung cancer is a common disease that is difficult to treat successfully. Despite the continuous improvement and development of diagnostic method, the disease is still diagnosed in advanced stages. The present study aimed to calculate the 5-years survival rate of patients with lung cancer, to construct different models of survival rates according to different factors and to perform a meta-analysis involving systematic statistical pooling of eligible studies concerning survival of lung cancer. A longitudinal retrospective study was conducted in the treatment centers of Faculty of Medicine and Gamal Abd-El Nasser Hospital. All available records of patients diagnosed and confirmed pathologically as lung cancer during the years 1992 to 2001,were reviewed, the total number amounted to 1099 patients, these patients were followed up for one year till the end of 2002. Life table revealed that the cumulative probability of survival was 18.7% and 16.7%, respectively at 36 -< 42 month and 42 -< 48 month. No one survived up to 5 years. The median survival time was 7.97 months .Kaplan-Meier survival curves yielded that the lowest probability of survival throughout the studied period was noticed among those aged 70 years or more, with stage IV and patients who were treated with radiotherapy alone. Cox regression delineated three significant predictors for survival within 5 years, which were age of patients, stage of tumor and grade of differentiation. Results of meta-analysis demonstrated that pooling the results of different studies yielded a trend toward a reduced relative risk of death by 22% among patients with stage I compared to stage II, and reduced relative risk of 33% for patients with stage I compared to stage III. It is essential to improve the strategies for prevention of smoking and health education program for cessation of smoking early for smokers. Diagnosis, staging and development of a management plan should be completed as quickly as possible. Focuses on the treatment of patients with lung cancer with chemotherapy and radiotherapy.     

Chronic renal failure in Kuwaiti children: an eight-year experience

Over an 8-year period (January 1996 to December 2003), a total of 171 patients below the age of 15 years were diagnosed with chronic renal failure. The mean incidence rate of CRF in Kuwaiti children was found to be 38.2 per million children per year, with a peak incidence of 55 per million children per year. While the mean age at diagnosis was 33±12 months (range: 1 month to 15 years), the male:female ratio was 2.7:1. Etiological factors for chronic renal failure included congenital urological malformation (61.9%), chronic glomerulopathies (5.2%), hereditary nephropathies (21%), multi-system disease (0.5%), chronic pyelonephritis (without VUR) (4.6%), tumors (0.6%), ischemic renal disease (1.1%) and unknown etiology (1.7%). Thirty percent of patients reached end-stage renal disease within a mean of 18 months following diagnosis. The overall mortality before reaching ESRD was reported to be 4%. Kuwait has one of the highest incidence and prevalence rates of CRF in children. It is likely that genetic and hereditary factors are the cause of these high rates.     

Impedance Cardiography: Noninvasive Assessment of Hemodynamics and Thoracic Fluid Content During Bariatric Surgery

Background: The effects of pneumoperitoneum (ppm) on hemodynamic parameters during bariatric surgery were investigated using the impedance cardiography monitor. Methods: 11 patients with BMI 46.5±10 kg/m² (range 38.9-60.8 kg/m²) underwent laparoscopic adjustable gastric banding under general anesthesia. Besides routine monitoring, the impedance cardiography (ICG) monitor was used to monitor cardiac output (CO), cardiac index (CI), systemic vascular resistance (SVR), and thoracic fluid content (TFC). Data were recorded at three stages: A) before ppm, B) during ppm, and C) after gas deflation. One-way analysis of variance (ANOVA) was used to analyze differences of the data before, during and after ppm, and post-hoc (Bonferoni test) for multiple comparisons of the data obtained. For all comparisons, P<0.05 was considered significant. Results: There were significant low mean values of heart rate (HR), CO and CI at stage B compared to stage A (P<0.05). The mean values of TFC at stages A, B, and C were 30.48 ± 4.69, 29.74 ± 2.86 and 31.72 ± 4.93 k/Ohm respectively, with a non-significant relationship (P>0.05). The mean values of SVR during the same stages A, B and C were 1299.18 ± 374.40, 1873.64 ± 276.26 and 1669.36 ± 537.92 dynes sec cm^-5 respectively, with significant high mean values at stages B and C compared to mean value at stage A (P<0.05). Conclusions: Morbid obesity and pneumoperitoneum have significant effects on hemodynamics. However, it appears that these changes were of marginal clinical significance.