Serum VEGF and bFGF adds prognostic information in patients with normal platelet counts when sampled before, during and after treatment for locally advanced non-small cell lung cancer

Vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) have both been implicated to have roles in tumour angiogenesis. In the present retrospective study, serum VEGF and bFGF from patients with locally advanced non-small cell lung cancer (NSCLC) were analysed before, during and after treatment. Seventy-three patients and a total of 460 serum samples were analysed for VEGF and 443 serum samples were analysed for bFGF. Pre-treatment bFGF levels in patients with normal platelet counts, were correlated to poorer survival, P-value = 0.047. During chemotherapy, each rise of one unit bFGF corresponded to a hazard ratio of 4.06 (P=0.022). In patients with normal platelet counts, VEGF levels after radiotherapy significantly correlated to good prognosis (P=0.023), during radiotherapy VEGF levels indicated the same correlation (P=0.085). We conclude that serum VEGF and especially bFGF are of clinical interest as prognostic factors, especially in patients presenting with normal platelet counts.     

Familial insensitivity to pain (HSAN V) and a mutation in the NGFB gene. A neurophysiological and pathological study

We have studied a large Swedish family with a mutation in the nerve growth factor beta (NGFB) gene causing insensitivity to deep pain without anhidrosis (hereditary sensory and autonomic neuropathy, type V; HSAN V). Painfree joint destruction and fractures were common. Peripheral nerve conduction was normal, but temperature thresholds were increased. Sural nerve biopsies showed a moderate loss of A delta fibers and a severe reduction of C fibers. The three most severely affected cases were all born to consanguineous parents, and were homozygotes for the causal genetic mutation. Treatment of these patients is discussed.     

An instrument for measuring health-related quality of life in patients with Deep Venous Thrombosis (DVT): development and validation of Deep Venous Thrombosis Quality of Life (DVTQOL) questionnaire

Background

Few studies have evaluated patient-reported outcomes in connection with a primary event of deep venous thrombosis, partly due to a lack of disease-specific measures. The aim here was to develop a disease-specific health-related quality of life (HRQL) measure, the deep venous thrombosis quality of life questionnaire (DVTQOL), for patients with recent exposition and treatment of proximal deep venous thrombosis.

Methods

A total of 121 consecutive outpatients (50 % males; mean age 61.2 ± 14 years) treated with warfarin (Waran^®) for symptomatic proximal deep venous thrombosis were included in the study. Patients completed the SF-36, EQ-5D and the pilot version of the DVTQOL.

Results

Items having: high ceiling and floor effect, items with lower factor loadings than 0.50 and items loading in several factors were removed from the pilot version of DVTQOL. In addition, overlapping and redundant items identified by the Rasch analysis were excluded. The final DVTQOL questionnaire consists of 29 items composing six dimensions depicting problems with: emotional distress; symptoms (e.g. pain, swollen ankles, cramp, bruising); limitation in physical activity; hassle with coagulation monitoring; sleep disturbance; and dietary problems. The internal consistency reliability was high (alpha value ranged from 0.79 to 0.93). The relevant domains of the SF-36 and EQ-5D significantly correlated with DVTQOL, thereby confirming its construct validity.

Conclusions

The DVTQOL is a short and user-friendly instrument with good reliability and validity. Its test-retest reliability and responsiveness to change in clinical trials, however, must be explored.

     

Anticoagulant treatment of patients with chronic atrial fibrillation in primary health care in Sweden--a retrospective study of incidence and quality in a registered population

BACKGROUND: The number of patients receiving anticoagulant treatment is increasing. Chronic atrial fibrillation is the most common treatment diagnosis. The literature indicates a variable level of treatment control. Estimates of time within the therapeutic range have been recommended as a measurement of quality. Electronic patient records are providing clinical data that are useful for audits concerning anticoagulant treatment in real-life practice. OBJECTIVE: Our aim was to assess warfarin treatment for chronic atrial fibrillation in primary health care with regard to prevalence, incidence and quality. METHODS: A 2 year retrospective study was carried out of electronic patient records up to April 2002 in primary health care in Stockholm, including 12 primary health care centres with a registered population of 203 407. Main outcome measures were the number of new patients on wafarin treatment for chronic atrial fibrillation, and time within the therapeutic prothrombin range in the first 90 days of treatment using a linear interpolation method. RESULTS: In total, 827 patients were on warfarin treatment for chronic atrial fibrillation, giving a prevalence of 0.41%. Of these, 144 patients (study group) started treatment with warfarin for chronic atrial fibrillation during the study period, giving a yearly incidence of 0.07%. Their mean age was 73.1 years and 61.1% were men. There were 1721 prothrombin monitoring episodes registered in the first 90 days of treatment, on average once a week per patient. The average proportion of time within the therapeutic range was 54.1% (95% confidence interval (CI) 50.1-58.1), and the proportion of therapeutic tests was 50.2% (95% CI 47.8-52.6). CONCLUSIONS: During the first, second and third months of warfarin treatment for chronic atrial fibrillation, patients were outside the therapeutic range time nearly half the time. There was a gender difference favouring men regarding initiation of treatment.     

Effects of zinc pyrithione and copper pyrithione on microbial community function and structure in sediments

The effects of the new antifouling biocides, zinc pyrithione (ZPT) and copper pyrithione (CPT), on microbial communities in estuarine sediments were studied in microcosms. As functional endpoints, fluxes of nutrients (NO3-, NH4+, HPO4(2-), Si(OH)4) and protein synthesis ([14C]leucine incorporation) were used, whereas molecular fingerprinting methods (polymerase chain reaction/denaturing gradient gel electrophoresis) were used to describe the bacterial community structure. The lowest-observed-effect concentration (LOEC) for ZPT was 0.001 nmol/g dry sediment for the phosphate flux and total DNA content, whereas the LOEC for CPT was 0.1 nmol/g dry sediment for the nitrate flux and total DNA content. Nitrate fluxes increased significantly following additions of both ZPT and CPT, whereas ammonium fluxes decreased significantly after ZPT addition, suggesting changes in the nitrification and denitrification processes. The total DNA content decreased significantly following addition of both ZPT and CPT, but at the highest addition of ZPT (10 nmol ZPT/g dry sediment), an increase in total DNA content was found. Increased protein synthesis and bacterial diversity were also observed at this concentration of ZPT, suggesting growth of tolerant opportunistic species.     

Serum semicarbazide-sensitive amine oxidase (SSAO) activity correlates with VEGF in non-small-cell lung cancer patients

Semicarbazide-sensitive amine oxidase (SSAO) is an enzyme associated with vascular systems in mammals. SSAO catalyzes the deamination of primary monoamines and has been suggested to be a risk factor in vascular disorders, e.g., diabetic vascular complications. The primary aim of the present study was to investigate if serum SSAO activity is associated with clinical parameters in non-small cell lung cancer (NSCLC) patients. Secondary aims were to investigate if there is a correlation between SSAO activity and the angiogenic factors vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF).Thirty-three patients donated 231 serum samples. Detectable levels of bFGF, VEGF, and SSAO were observed in all patients. Serum SSAO activity was not statistically associated with survival (p = 0.35). A highly significant statistical correlation was found between SSAO activity and VEGF (p < 0.0001). No significant correlation between SSAO and bFGF was observed.We conclude that SSAO was not associated with survival in patients with NSCLC. However, a strong correlation between serum SSAO activity and the angiogenic factor VEGF was found that might implicate new aspects of the mechanisms controlling angiogenesis.     

Arterial stiffness is not improved in long-term use of estrogen

OBJECTIVE: The purpose of this study was to compare arterial stiffness in long-term users of estrogen who were postmenopausal, age-matched women who did not use estrogen, and women of fertile age. STUDY DESIGN: In this clinical cross-sectional study, carotid, femoral, and aortic stiffness (estimated as elastic modulus and stiffness beta index) were assessed by ultrasonic phase-locked echo-tracking in 17 women who were postmenopausal and who were treated with 17 beta-estradiol implants (mean age, 68.8 years; mean duration of treatment, 20 years), 17 age-matched (+/-1 year) untreated women, and 20 women in the fertile age period. RESULTS: Compared with women of fertile age, both postmenopausal groups had significantly higher stiffness elastic modulus and stiffness beta index (carotid, P <.001; femoral, P <.05; aorta, P <.001). However, for all 3 arteries, both stiffness indices were similar in estrogen users and nonusers and did not differ significantly. These results remained after an adjustment for systolic blood pressure, body mass index, and low-density lipoprotein cholesterol levels. CONCLUSION: These data indicate that the arterial stiffening that is related to aging/menopause is not substantially affected by long-term estrogen therapy.     

Budesonide/formoterol (Symbicort) is well tolerated and effective in patients with moderate persistent asthma

The aim of this study was to compare the safety and efficacy of budesonide/formoterol 160/4.5 microg, two inhalations twice daily, with that of the mono-products administered at the same daily doses via separate inhalers. A total of 586 patients (mean age 45 years) was included in this six-month, open, randomised, multicentre study. Patients received either budesonide/formoterol (n=390) or budesonide plus formoterol (n=190). Safety was assessed by adverse events, vital signs and laboratory values. Efficacy was evaluated using spirometry tests, the Mini Asthma Quality of Life Questionnaire and the Asthma Control Questionnaire. Both treatments were well tolerated, with no differences in safety parameters between the groups. Mean FEV1 increased by 5-6% over baseline in both groups. There was no significant difference in the change from baseline between the groups using the disease-specific questionnaires. Asthma exacerbations occurred with low frequency in both groups. Withdrawal rates were also comparable between the groups (p=0.085). Budesonide/formoterol in a single inhaler was as effective and as well tolerated as budesonide plus formoterol via separate inhalers.     

Renal hemodynamics during carbon dioxide pneumoperitoneum

Background: Laparoscopic living donor nephrectomy is increasingly being performed, although the effects of carbon dioxide pneumoperitoneum (CO2 PP) on renal function and hemodynamics and the levels of vasopressin are not well studied. Methods: Renal blood flow, renal venous pressure, urine output, and vasopressin concentrations in renal venous blood were measured in pigs subjected to 12 mmHg of CO2 PP for 150 min. Results: Renal blood flow was decreased at induction of PP and increased during the first 30 min after exsufflation. Renal venous pressure was increased during PP. There was indirect evidence of a decrease in urine output during PP. No changes in renal venous vasopressin concentrations were seen. Conclusion: A CO2 PP of 12 mmHg causes changes in renal hemodynamics and urine output. No changes in vasopressin levels were seen in this pig model, suggesting that other explanations for the observed changes must be sought.