The inflammatory cytokine tumor necrosis factor-alpha regulates chemokine receptor expression on ovarian cancer cells

Epithelial ovarian cancer cells express the chemokine receptor, CXCR4, which may be associated with increased survival and metastatic potential, but the regulation of this receptor is not understood. The inflammatory cytokine tumor necrosis factor-alpha (TNF-alpha) is found in ovarian cancer biopsies and is associated with increased tumor grade. In this report, we show that CXCR4 expression on human epithelial ovarian cancer cells is associated with, and can be modulated by, TNF-alpha. Ovarian cancer cells with high endogenous expression of TNF-alpha expressed higher levels of CXCR4 mRNA and protein than cells with low TNF-alpha expression. Stimulation of ovarian cancer cell lines and primary epithelial cancer cells with TNF-alpha resulted in increased CXCR4 mRNA and protein. The TNF-alpha-stimulated increase in CXCR4 mRNA was due partly to de novo synthesis, and up-regulation of CXCR4 cell surface protein increased migration to the CXCR4 ligand CXCL12. CXCR4 mRNA and protein was down-regulated by anti-TNF-alpha antibody or by targeting TNF-alpha mRNA using RNAi. TNF-alpha stimulation activated components of the nuclear factor kappaB pathway, and overexpression of the inhibitor of kappaB also reduced CXCR4 expression. Coculture of macrophages with ovarian cancer cells also resulted in cancer cell up-regulation of CXCR4 mRNA in a TNF-alpha-dependent manner. Finally, there was a correlation between the levels of TNF-alpha and CXCR4 mRNA in clinical biopsies of ovarian cancer, and TNF-alpha protein was expressed in CXCR4-positive tumor cells. TNF-alpha is a critical mediator of tumor promotion in a number of experimental cancers. Our data suggest that one mechanism may be through nuclear factor kappaB-dependent induction of CXCR4.     

Provision of health care in rural Afghanistan: needs and challenges

Afghanistan's health system is severely limited in terms of preventive and curative services, referral systems, and human resources. Most of the country's citizens reside in rural areas, a majority of which are served by "basic health units" (small and simple facilities that provide primary care), and these rural residents face additional challenges regarding timely access to quality health care. The analysis described in this article, which focuses on data derived from 2 rural health units during a 1-year period, revealed that infectious diseases, mainly acute respiratory infections, were a primary concern and that there is a clear need for increasing access to health services. In addition, our results showed that women are underrepresented as patients and appear to be at higher risk than men of tuberculosis.     

Long-term follow-up after the mini-maze procedure

BACKGROUND: Atrial fibrillation (AF) is associated with significant morbidity and mortality. The standard to treat AF surgically is the Cox maze III procedure but owing to its complexity it is not performed on a regular basis. Meanwhile several maze variants have been developed but their long-term results are still not well known. METHODS: From November 1995 until May 2002 a mini-maze procedure was performed upon 77 patients aged 64 +/- 8.7 years with chronic symptomatic AF. Electrophysiological evaluation, magnetic resonance imaging, echocardiography and electrocardiographic evaluations were performed after 3 and 12 months. After a mean follow-up of 50 +/- 2.6 months a standard questionnaire was sent to all patients. RESULTS: Early and late mortality was 1.2% and 9.3% respectively. Actuarial survival was 91%, 90%, and 87% after 1, 3, and 5 years respectively. Left bundle branch block was an independent risk factor for late death (p = 0.02). Patients who were in sinus rhythm at follow-up had significantly better survival rate as compared with the patients still in AF. Seventy-one percent of patients were in sinus rhythm or paced by an atrial pacemaker. Predictors for restoration of sinus rhythm were absence of preoperative mitral insufficiency (p = 0.03) and larger left atrium (p = 0.04). The presence of preoperative tricuspid insufficiency (p = 0.03) and larger right atrium (p = 0.017) were predictors for postoperative pacemaker implantation. CONCLUSIONS: The mini-maze procedure can be carried out with satisfactory early and long-term results regarding mortality and restoration of sinus rhythm. Prophylactic implantation of biventricular pacemakers in patients with left bundle branch block may decrease late mortality. Every effort should be done to cure AF as it affects long-term survival.     

Proteomic patterns established with capillary electrophoresis and mass spectrometry for diagnostic purposes

BACKGROUND: Proteomics applied in large scale may provide a useful diagnostic tool. METHODS: We developed an online combination of capillary electrophoresis with mass spectrometry, allowing fast and sensitive evaluation of polypeptides found in body fluids. Utilizing this technology, polypeptide patterns from urine are established within 45 minutes. About 900 to 2500 polypeptides as well as their concentrations are detected in individual urine samples without the need for specific reagents such as antibodies. To test this method for clinical application, we examined spot urine samples from 57 healthy individuals, 16 patients with minimal change disease (MCD), 18 patients with membranous glomerulonephritis (MGN), and 10 patients with focal segmental glomerulosclerosis (FSGS). RESULTS: One-hundred seventy-three polypeptides were present in more than 90% of the urine samples obtained from healthy individuals, while 690 polypeptides were present with more than 50% probability. These data permitted the establishment of a "normal" polypeptide pattern in healthy individuals. Polypeptides found in the urine of patients differed significantly from the normal controls. These differences allowed the distinction of specific protein spectra in patients with different primary renal diseases. Abnormal pattern of proteins were found even in urine from patients in clinical remission. CONCLUSION: The data indicate that capillary electrophoresis with mass spectrometry coupling provides a promising tool that permits fast and accurate identification and differentiation of protein patterns in body fluids of healthy and diseased individuals, thus enabling diagnosis based on these patterns.     

Recovery of the posterior tibial muscle after late reconstruction following tendon rupture

The purpose of this study was to determine the recovery potential of the posterior tibial muscle after late reconstruction following tendon rupture in stage II of posterior tibial tendon dysfunction. Fourteen patients (18 women, 6 men; mean age 59.8 years) were investigated 47 months (range, 24-76 months) after surgical reconstruction of a completely ruptured posterior tibial tendon (end-to-end anastomosis, side-to-side augmentation with the flexor digitorum longus tendon) in combination with a distal calcaneal osteotomy with a tricortical iliac crest bone graft for lengthening of the lateral column. At follow-up, clinical and radiological investigations were performed, including strength measurement and qualitative and quantitative MRI investigation. The overall clinical results were graded excellent in 12 patients, good in one, fair in one, and poor in none. The average ankle-hindfoot score (American Orthopaedic Foot and Ankle Society) improved from preoperatively 49.1 (range, 32-60) to 93.1 (range, 76-100) at follow-up. The functional result correlated with patient's satisfaction and sports activities (p <.05). All patients showed a significant strength of the posterior tibial muscle on the affected side, but it was smaller than on non-affected side (p <.05). The mean posterior tibial muscle strength was 75.1 N on affected and 104.9 N on nonaffected side, corresponding to a ratio of 0.73 between the two legs. The mean area of the posterior tibial muscle was 1.89 cm(2) on affected side, and 3.48 cm(2) on nonaffected side, corresponding to a ratio of 0.55 between the two legs. While fatty degeneration for the posterior tibial muscle was found in all patients, it was found to decrease with increasing strength of the posterior tibial muscle (p <.05) and muscular size (p <.05). On postoperative MRI, the posterior tibial tendon could be found to be intact in all patients. The recovery potential of the posterior tibial muscle was shown to be significant even after delayed repair of its ruptured tendon. A ruptured and/or diseased posterior tibial tendon should not be transected as it excludes any recovery possibilities of the posterior tibial muscle.     

Permanent 125I-seed brachytherapy or radical prostatectomy: a prospective comparison considering oncological and quality of life results

OBJECTIVE: To assess the quality of life in patients with prostate cancer after permanent brachytherapy (BT) or radical perineal prostatectomy (RP). PATIENTS AND METHODS: The American Brachytherapy Society recommends the permanent implantation of radioactive seeds as a monotherapy for patients with T1-T2aN0M0 prostate cancer and a prostate-specific antigen (PSA) level of < or = 10 ng/mL, a Gleason score of <7 and a prostate volume of <60 mL. Using these criteria, 132 patients with low-risk prostate cancer were selected; 52 had BT with 125I-seed implantation, 38 had RP with unilateral nerve-sparing (RP + NS) and 42 extended RP (RP group). Only patients with unilateral tumour on biopsy were considered. Before therapy and 6, 12 and 24 months afterward, patients completed questionnaires to assess perceived health and function. PSA relapse was diagnosed with a PSA of >0.1 ng/mL for patients in the RP groups, and three consecutive PSA increases for those after BT. RESULTS: Extraprostatic tumours were found in 18% of specimens taken during RP, and bilateral tumours in 63% of patients. After a mean follow-up of 27 months, there was PSA relapse in two of the 80 patients in the RP and RP + NS groups, and six of the 52 patients in the BT group; a significant difference, with a hazard ratio of 5.2. The acute morbidity was low in all groups. At 1 year, more than two incontinence pads were used by 5% of patients after RP and by 4% after BT. Similarly, at 1 year 15% of patients after RP and 13% after BT were bothered by urinary incontinence. Newly-developed fecal soiling was reported by 4%, 5% and 11% of the RP, RP + NS and BT groups respectively; none of the patients after RP and 4% after BT were bothered by this symptom. The duration and stiffness of erection was assessed after 1 year and reported to be equal or slightly decreased by a third after RP + NS and 38% after BT. Taking a 5-10 point difference as clinically relevant, role, emotional and social functioning were improved considerably after RP + NS than after BT, but sexual activity was impaired significantly after RP + NS than after BT. CONCLUSIONS: Both therapies showed typical acute and late morbidity; the most bothersome late symptoms were urinary incontinence for patients after RP and fecal soiling after BT. Sexual function was impaired significantly in patients who were potent before RP + NS, whereas after BT men reported only a minor change in sexual performance at 1 year. Tumour control after a median follow-up of 27 months was better after RP but biochemical recurrence may still occur after > or = 5 years; therefore the present results are not mature enough and there were too few patients to provide a more definitive statement. As approximately 18% of patients considered to be appropriate candidates for BT had tumours extending beyond the prostate capsule or invading the seminal vesicles, nomograms are needed for more accurate information before therapy.     

Application of NMR spectroscopy to monitoring MELAS treatment: a case report

1H magnetic resonance spectroscopy (MRS) of the brain and (31)P MRS and saturation transfer of resting skeletal muscle were used to investigate intracellular metabolites and fluxes through the creatine kinase (CK) reaction in a patient with the syndrome of mitochondrial myopathy, encephalopathy, lactic acidosis, and strokelike episodes (MELAS). Acute cortical lesions were characterized by severely elevated lactate levels and reduced concentrations of N-acetylaspartyl compounds, glutamate, and myo-inositol. Similar but less extreme alterations were also observed in gray matter regions that appeared normal on magnetic resonance images. Investigation of the gastrocnemius muscle at rest demonstrated a reduced phosphocreatine level, elevated concentrations of inorganic phosphate and free adenosine 5'-diphosphate, and an abnormally low phosphorylation potential. Besides a moderately increased muscular phosphocreatine concentration, none of the metabolic disturbances detected on MRS improved with oral creatine supplementation. Forward and reverse fluxes through the CK reaction did not significantly change upon creatine treatment. Follow-up MRS investigations may thus provide objective markers of treatment response in vivo without the hazards or inconvenience of biopsy.     

Hydrodynamics of the new Medos aortic cannula

BACKGROUND: Postoperative neurologic complications in cardiac surgery patients are considered to be associated with the design of an aortic cannula and its hydrodynamic profile. To gain knowledge about the hydrodynamics of a new cannula type, based on the integration of a helical stator in its tip, was the aim of the present study. METHODS: Pressure gradients and back pressures of the new Medos aortic cannula were measured and compared with a commonly used single-stream cannula at varying flow rates in a mock circulation. Additionally, flow visualization was performed by ink injection. RESULTS: Pressure gradients across the Medos cannula were 25.5-31.8% lower at all flow rates measured when compared to the reference cannula. Back pressures of the Medos cannula were 64.1-67.9% lower than reference back pressures. CONCLUSIONS: The Medos cannula provides improved hydrodynamic characteristics, probably reducing the risk of atherosclerotic embolism and cerebral malperfusion by avoidance of high back pressures and sandblasting effect.