Hepatic arterial therapy with oxaliplatin and systemic capecitabine for patients with liver metastases from breast cancer.

OBJECTIVES: Hepatic arterial treatment (HAT) for liver metastases in patients with metastatic breast cancer (MBC) has only been investigated in few studies. MATERIALS AND METHODS: Two phase II trials were initiated simultaneously to evaluate capecitabine in combination with oxaliplatin in patients with MBC and liver metastases. These two trials are reported together. Continuous capecitabine (1300 mg/m2) was combined with oxaliplatin (85 mg/m2) alternating between systemic treatment and HAT followed by degradable starch microspheres with EmboCept® S every second week. Four patients participated in a pharmacokinetic analysis of oxaliplatin. Each patient had samples taken when receiving oxaliplatin systemically and as HAT with and without EmboCept® S. RESULTS: Totally, 52 patients received HAT: 14 with liver metastases only and 38 patients with additional limited metastatic disease. The patients had previously received a median of 2 (range 0-6) chemotherapeutic regimens for MBC. The response rate was 42.3% (95% confidence interval (CI) 28.7-56.8%) with 7.7% complete and 34.6% partial responses. Median progression free survival was 10.8 months (95% CI 6.9-14.7 months) and median overall survival 27.6 months (95% CI 20.4-34.8 months). The toxicity was moderate with hand-foot syndrome (15.4%), neuropathy (9.6%), fatigue (9.6%), and abdominal pain (9.6%) being the most common grade 3 adverse events. There was no clear difference between systemic blood concentrations of oxaliplatin when given systemic or as HAT. CONCLUSION: HAT oxaliplatin in combination with capecitabine is safe and efficient in patients with MBC. The results are promising with high response rates and a long median progression free and overall survival.

Influence of nitrogen sources on the enzymatic activity and grown by Lentinula edodes in biomass Eucalyptus benthamii.

Lignocellulose is the most abundant environmental component and a renewable organic resource in soil. There are some filamentous fungi which developed the ability to break down and use cellulose, hemicellulose and lignin as an energy source. The objective of this research was to analyze the effect of three nitrogen resources (ammonium sulfate, saltpetre, soybean) in the holocellulolitic activity of Lentinula edodes EF 50 using as substrate sawdust E. benthamii. An experimental design mixture was applied with repetition in the central point consisting of seven treatments (T) of equal concentrations of nitrogen in ammonium sulfate, potassium nitrate and soybean. The enzymatic activity of avicelase, carboxymetilcellulase, ß-glucosidase, xylanases and manganese peroxidase was determined. The humidity, pH, water activity (aw) and qualitative analysis of mycelial growth in 8 times of cultivation were evaluated. The results showed negative effect on enzyme production in treatments with maximum concentration of ammonium sulfate and potassium nitrate. The treatments with cooked soybean flour expressed higher enzymatic activities in times of 3, 6 and 9 days of culture, except in the activity of manganese peroxidase. The highest production was observed in the treatment with ammonium sulfate, and soybean (83.86 UI.L-1) at 20 days of cultivation.

Influence of nitrogen sources on the enzymatic activity and grown by Lentinula edodes in biomass Eucalyptus benthamii / Influência das fontes de nitrogênio na atividade enzimática e crescimento de Lentinula edodes na biomassa Eucalyptus benthamii

Abstract Lignocellulose is the most abundant environmental component and a renewable organic resource in soil. There are some filamentous fungi which developed the ability to break down and use cellulose, hemicellulose and lignin as an energy source. The objective of this research was to analyze the effect of three nitrogen resources (ammonium sulfate, saltpetre, soybean) in the holocellulolitic activity of Lentinula edodes EF 50 using as substrate sawdust E. benthamii. An experimental design mixture was applied with repetition in the central point consisting of seven treatments (T) of equal concentrations of nitrogen in ammonium sulfate, potassium nitrate and soybean. The enzymatic activity of avicelase, carboxymetilcellulase, β-glucosidase, xylanases and manganese peroxidase was determined. The humidity, pH, water activity (aw) and qualitative analysis of mycelial growth in 8 times of cultivation were evaluated. The results showed negative effect on enzyme production in treatments with maximum concentration of ammonium sulfate and potassium nitrate. The treatments with cooked soybean flour expressed higher enzymatic activities in times of 3, 6 and 9 days of culture, except in the activity of manganese peroxidase. The highest production was observed in the treatment with ammonium sulfate, and soybean (83.86 UI.L–1) at 20 days of cultivation.

Resumo Lignocelulose é o componente mais abundante do meio ambiente e recurso orgânico renovável no solo. Alguns fungos filamentosos têm desenvolvido a habilidade de degradar e utilizar celulose, hemicelulose e lignina como fonte de energia. O objetivo deste trabalho foi analisar o efeito de três fontes de nitrogênio (sulfato de amônio, nitrato de potássio e farelo de soja) na atividade enzimática de Lentinula edodes EF 50 utilizando como substrato serragem de E. benthamii. Foi aplicado um planejamento experimental de mistura com três repetições no ponto central constituído de sete tratamentos (T) de iguais concentrações em nitrogênio de sulfato de amônia, nitrato de potássio e farinha de soja cozida. Foram determinadas a atividade enzimática da avicelase, carboximetilcelulase, β-glicosidase, xilanases e manganês peroxidase. Foram avaliados o teor de umidade, pH, atividade de água (aw) e análise qualitativa do crescimento micelial em 8 tempos de cultivo. Os resultados mostraram efeito negativo na produção das enzimas nos tratamentos com máxima concentração de sulfato de amônia e nitrato de potássio. Os tratamentos com farinha de soja cozida expressaram maiores atividades enzimáticas, nos tempos de 3, 6 e 9 dias de cultivo exceto na atividade do manganês peroxidase. A maior produção foi observada no tratamento com sulfato de amônia e farinha de soja cozida (83.86 UI.L–1) em 20 dias de cultivo.

The importance of adequate stem anteversion for rotational stability in cemented total hip replacement: a radiostereometric study with ten-year follow-up.

Progressive retroversion of a cemented stem is predictive of early loosening and failure. We assessed the relationship between direct post-operative stem anteversion, measured with CT, and the resulting rotational stability, measured with repeated radiostereometric analysis over ten years. The study comprised 60 cemented total hip replacements using one of two types of matt collared stem with a rounded cross-section. The patients were divided into three groups depending on their measured post-operative anteversion (< 10°, 10° to 25°, > 25°). There was a strong correlation between direct post-operative anteversion and later posterior rotation. At one year the < 10° group showed significantly more progressive retroversion together with distal migration, and this persisted to the ten-year follow-up. In the < 10° group four of ten stems (40%) had been revised at ten years, and an additional two stems (20%) were radiologically loose. In the 'normal' (10° to 25°) anteversion group there was one revised (3%) and one loose stem (3%) of a total of 30 stems, and in the > 25° group one stem (5%) was revised and another loose (5%) out of 20 stems. This poor outcome is partly dependent on the design of this prosthesis, but the results strongly suggest that the initial rotational position of cemented stems during surgery affects the subsequent progressive retroversion, subsidence and eventual loosening. The degree of retroversion may be sensitive to prosthetic design and stem size, but < 10° of anteversion appears deleterious to the long-term outcome for cemented hip prosthetic stems.

Intrahepatic and systemic therapy with oxaliplatin combined with capecitabine in patients with hepatic metastases from breast cancer.

BACKGROUND: The aim was to evaluate activity and toxicity of hepatic arterial infusion of oxaliplatin in combination with capecitabine in patients with metastatic breast cancer with liver metastases and limited extrahepatic disease. PATIENTS AND METHODS: Sixteen consecutive patients received capecitabine 13 00mg/m(2) daily combined with oxaliplatin 85 mg/m(2) every two weeks. Seven patients alternated between intrahepatic and systemic oxaliplatin, and in 9 oxaliplatin was primarily given intrahepatic. Five patients had liver-only metastases and 11 had additionally bone metastases. The patients had received median two previous chemotherapeutic regimens for metastatic disease. RESULTS: The response rate was 50% and the stable disease (≥6 months) rate 44%. Median progression free and overall survival was 7.9 and 19.2 months, respectively. The toxicity was moderate with abdominal pain, neuropathy, and hand foot syndrome as the most common adverse events. CONCLUSION: The combination of capecitabine and intrahepatic/systemic therapy with oxaliplatin was active in pretreated patients with liver metastasis from breast cancer.

Maximal exercise capacity is related to cardiovascular structure in patients with longstanding hypertension. A LIFE substudy. Losartan Intervention For Endpoint-Reduction in Hypertension.

BACKGROUND: Cardiovascular hypertrophy and remodeling in patients with never-treated hypertension has been associated with impaired exercise capacity, but whether this relationship remains in patients with longstanding hypertension and target organ damage is less elucidated. METHODS: In 43 unmedicated patients with essential hypertension and electrocardiographic left ventricular (LV) hypertrophy, we measured maximal workload and oxygen reserve by bicycle test, 24-h ambulatory blood pressure (BP), LV mass index by magnetic resonance imaging (LVMI(MRI), n = 31), LVMI(echo) and systemic vascular compliance by echocardiography, minimal forearm vascular resistance (MFVR) by plethysmography, and intima media thickness and distensibility in the common carotid arteries by ultrasound. RESULTS: The patients did not achieve the maximal workload as predicted by age, gender and body composition (146[129-163] v 162[146-179] Watt, P = .01). This impaired exercise capacity, calculated as the ratio between achieved and predicted maximal workload, was in simple regression analyses related to lower distensibility of the common carotid artery (r = 0.38, P = .01) and lower oxygen reserve (r = 0.68, P < .001). In multiple regression analyses, lower oxygen reserve was related to higher LVMI(MRI) (beta = -0.44), lower systemic vascular compliance (beta = -0.36), and higher MFVR (beta = -0.52) (adjusted R2 = 0.53, P < .001). CONCLUSIONS: Patients with longstanding hypertension and target organ damage cannot achieve the predicted maximal workload. This impaired exercise capacity was associated with lower common carotid distensibility and lower oxygen reserve. The latter was independently related to LV hypertrophy, low systemic vascular compliance and peripheral vascular remodeling, suggesting that cardiovascular hypertrophy and remodeling may reduce exercise capacity by itself.

Measuring anteversion in the femoral neck from routine radiographs.

PURPOSE: To describe a new method for measuring femoral neck anteversion (FNA) that requires only one lateral radiograph of the knee in addition to routine radiographs of the hip for evaluation of total hip replacement; and to compare the proposed method with FNA measurement by means of 3D CT. MATERIAL AND METHODS: In 18 femoral specimens, radiographic examinations of the hip and knee, in three different rotational positions, and one CT examination were made, and the measurements of FNA were compared. Similarly, in 38 patients with 40 total hip replacements, measurements from routine radiographic examinations of the hip and knee and from CT examinations were compared. The accuracy and reproducibility of the FNA measurements produced by this proposed method were calculated. RESULTS: Accuracy and reproducibility were 2 degree and 2 degree for the proposed method in the femoral specimen study, and accuracy was 4 degree in the hip patient study. The proposed method had a minor flaw that was caused almost solely by differences in knee size at inward rotation of the femur. CONCLUSION: FNA measurement can be made from a routine radiographic examination of the hip and a lateral view of the knee. This method achieves an acceptable level of accuracy and reproducibility.

CT measurement of anteversion in the femoral neck. The influence of femur positioning.

PURPOSE: To evaluate CT methods of measuring anteversion in the femoral neck with respect to measurement accuracy and with respect to the influence exerted by different femoral shaft positions; and to describe a new CT measurement concept that introduces a mathematical adjustment for different femoral shaft positions. The new technique facilitates the taking of measurements in patients who cannot be correctly positioned in traditional methods. MATERIAL AND METHODS: CT examinations of previously measured anteversions in the femoral neck were reviewed in retrospect in 30 patients with fractures of the femoral neck. The position of the femoral shaft was assessed. A reference angle was compared with direct traditional measurements and with measurements adjusted for the actual position of the femoral shaft by means of a 3D mathematical reconstruction. Reproducibility and inter- and intraobserver variability were assessed in 10 cases. RESULTS: All femurs varied in position within the gantry. The mean difference between the direct CT measurement and the adjusted CT measurement compared to the reference angle were -8.8 degrees (range -35.0-16.3 degrees) and -0.1 degrees (range -1.4-1.4 degrees), respectively. For the adjusted CT method, reproducibility and inter- and intraobserver variability were 1.4 degrees, 1.6 degrees and 1.4 degrees (SD of difference), respectively. CONCLUSION: CT measurement of femoral anteversion in clinical practice can only be accurate when corrected for variation in the position of the femoral shaft.

Urinary excretion of inactive renin during blockade of the renal tubular protein reabsorption with lysine.

The purpose was to study whether the kidneys eliminate inactive renin from the circulation of mice. The urinary concentration, excretion rate and clearance of inactive renin were very low during basal conditions. After blockade of the reabsorption of proteins in the renal tubules with the basic amino acid lysine, the urinary concentration, excretion rate and clearance of inactive renin increased very markedly. This finding indicates that inactive plasma renin is subjected to glomerular ultrafiltration followed by reabsorption in the renal tubules by mechanisms which are most likely the same as for active renin and other filtered proteins. The urinary clearance of inactive renin after blockade of the renal tubular protein reabsorption was 13% of that of active renin. Our findings demonstrate that glomerular ultrafiltration is a route of elimination from the circulation for inactive renin.

Ultrafiltration of renin in the mouse kidney studied by inhibition of tubular protein reabsorption with lysine.

1. In order to study the role of the kidney in the elimination of endogenous plasma renin, renin was measured in the plasma and urine of female mice. 2. The renin concentration was two orders of magnitude lower in urine than in plasma, but it increased after intraperitoneal injection of submandibular mouse renin. No correlation between the plasma renin concentration and the urinary renin concentration and renin excretion rate could be demonstrated. 3. Blockade of the tubular reabsorption of proteins by intraperitoneal injection of the basic amino acid lysine increased the urinary renin concentration, renin excretion rate and renin clearance two to three orders of magnitude, without affecting the plasma renin concentration. 4. This finding demonstrates that ultrafiltered renin is reabsorbed almost completely in the renal tubules and that the mechanism most likely is the same as for other filtered proteins. 5. The large renal renin clearance obtained after intraperitoneal lysine is in accordance with a major role of the kidneys in the elimination of renin from the circulation, by a glomerular ultrafiltration and tubular reabsorption and metabolization of renin.

Evidence for a predominant renal secretion and clearance of inactive plasma renin, studied by in vivo inhibition of protein synthesis, and inhibition of renal tubular protein reabsorption.

Inactive plasma renin is mainly secreted and eliminated by the kidneys in the mouse. The half-life of inactive plasma renin is 6 hours or less. The kidneys remove inactive renin from the circulation by glomerular ultrafiltration.