Accuracy evaluation of image registration and segmentation tools used in conformal treatment planning of prostate cancer.

Segmentation and registration tools are commonly used in radiotherapy for target and at risk organs localisation. In this work the performances of three different segmentation tools and of a surface matching registration technique, used on computed tomography (CT) and magnetic resonance (MR) images for the treatment planning of conformal prostate carcinoma, are studied. The accuracy of the segmentation and registration tools was evaluated by phantom experiment and on patient data, respectively. A preliminary estimate of MR image distortion was also performed.     

Hemoglobin adducts of benzo[a]pyrene diolepoxide in newspaper vendors: association with traffic exhaust

Benzo[a]pyrene diol epoxide adducts with hemoglobin (Hb) weremeasured to detect human exposure to environmental benzo[a]pyrenefrom traffic exhaust. Benzo[a]pyrene tetrahydrotetrols (BPTs)released from Hb after acid hydrolysis were quantitated by gaschromatography-mass spectrometry after immunoaffinity chromatography.Fifty three newspaper vendors were enrolled. The median adductconcentration was 0.3 fmol BPTs/mg Hb in high density traffic-exposedvendors and     

Homocysteine-Lowering Therapy and Early Progression of Transplant Vasculopathy: A Prospective, Randomized, IVUS-Based Study

Although observational studies suggest that hyperhomocysteinemia may be a risk factor for coronary allograft vasculopathy (CAV), prospective data on homocysteine-lowering interventions and CAV development are lacking. We, therefore, randomized 44 de novo heart transplant (HT) recipients to 15 mg/day of 5-methyl-tetrahydrofolate (n=22), or standard therapy (control group, n=22) to investigate the effect of homocysteine lowering on the change in coronary intimal hyperplasia during the first 12 months after transplant, as detected by intra-vascular ultrasound (IVUS). Although 12 months after HT, homocysteinemia was lower in folate-treated patients (p<0.001), coronary intimal area increased similarly in the two groups (p>0.4). Conversely, hypercholesterolemia and cytomegalovirus infection were both associated with increased intimal hyperplasia (p<0.04), independently from folate intake. Sub-group analysis revealed that folate therapy reduced intimal hyperplasia in patients with hyperhomocysteinemia before randomization (n=19; p=0.02), but increased intimal hyperplasia in patients with normal homocysteine plasma concentrations (p=0.02). This bimodal effect of folate therapy persisted significantly after adjusting for cytomegalovirus infection and hypercholesterolemia. Despite effective in prevent hyperhomocysteinemia after heart transplantation, folate therapy does not seem to affect early CAV onset. However, sub-group analysis suggests that folate therapy may delay CAV development only in patients with baseline hyperhomocysteinemia, while may favor CAV progression in recipients with normal baseline homocysteinemia.     

Inhibition of murine hepatitis virus infections by the immunomodulator 2,3,5,6,7,8-hexahydro-2-phenyl-8,8-dimethoxy-imidazo[1,2a]pyridine (PR-879-317A).

PR-879-317A (2,3,5,6,7,8-hexahydro-2-phenyl-8,8-dimethoxy-imidazo [1,2a]pyridine) has been found to be a T-cell-selective immunomodulating agent. In the current studies, a series of experiments was designed to determine the potential antiviral activity of this compound in mice infected with murine hepatitis virus. In a comparative antiviral experiment, the activity seen was superior to that of levamisole, a known immunorestorative agent. This activity was characterized by an increase in the 21-day survival frequency, a decrease in hepatic discoloration, a decrease in the amount of infectious virus recoverable from the liver, and normalization of serum glutamic oxalacetate and pyruvate transaminase levels. A comparison of treatment routes indicated the relative efficacies as intraperitoneal greater than per os greater than intramuscular greater than or equal to subcutaneous. Alteration of the treatment schedule markedly affected the antiviral effect; prophylactic or therapeutic treatments once or twice daily for 3 days were usually effective. Single treatments begun 4 h before or 24 h after virus inoculation were highly efficacious. Three treatments administered on alternate days, beginning 48 h before virus inoculation, proved moderately effective. Thrice-daily treatments were ineffective, as were treatments with durations of greater than 3 days. The optimal dosage varied according to the treatment route and dosage schedule. When assessed for direct antiviral activity in vitro, PR-879-317A failed to demonstrate any significant activity against murine hepatitis virus. The positive in vivo activity noted might therefore be the result of immune modulation rather than a direct antiviral effect.     

Safety and efficacy of topical norfloxacin versus tobramycin in the treatment of external ocular infections.

Bacterial conjunctivitis appears to resolve more rapidly when treated with appropriate topical antimicrobial agents. In this multicenter, randomized, double-blind study of efficacy and safety, patients with presumed bacterial external eye infections were assigned to topical therapy with 0.3% norfloxacin or 0.3% tobramycin. A total of 120 patients were enrolled. Of the total, 65 had documented bacterial infections and were evaluable; 59 of these patients had bacterial conjunctivitis. All of the patients with documented infections were cured or improved regardless of the drug treatment regimen or in vitro susceptibility testing results. The most common bacteria isolated were Haemophilus influenzae, Streptococcus pneumoniae, alpha-hemolytic streptococci, Staphylococcus aureus, and Staphylococcus sp. No patients had serious adverse reactions attributed to their therapy. Norfloxacin ophthalmic solution seems to be a safe, effective, and appropriate agent for the treatment of bacterial external eye infections.     

Effect of cyclosporin a on proteinuria in patients with Alport's syndrome

Eight patients with Alport's syndrome and massive proteinuria (129±60.57 mg/m² per hour) were treated with cyclosporin A (CyA) for 8 months. The average dose of CyA administered to all patients was 4.21±0.26 mg/kg per day and blood CyA levels of 63.4±4.1 ng/ml were attained. In five patients, proteinuria abated during the 3rd week of treatment. In the remaining three, all of whom had low creatinine clearance (82.0, 46.0 and 43.2 ml/min per 1.73 m² respectively), proteinuria persisted but at levels lower than before treatment: 32.5±15.9 mg/m² per hour versus 183.3±29.7 mg/m² per hour. No permanent decrease in creatinine clearance was observed in any of these patients throughout treatment. In those patients in whom proteinuria abated, it reappeared 2 weeks after discontinuation of CyA treatment. We observed no significant increases in angiotensin II plasma levels in our patients during CyA administration. Although we have shown that CyA will reduce massive proteinuria in patients with Alport's syndrome, we cannot yet recommend its use as a therapeutic measure.     

Epilepsy and family expressed emotion: results of a prospective study.

PURPOSE: To verify the emotional components expressed by the relatives of adult patients with a diagnosis of epilepsy, and whether they are related to adjustment to the illness and the course of the illness over time. METHODS: We studied a consecutive sample of 43 outpatients suffering from epilepsy and 43 key relatives using the Camberwell Family Interview (CFI), with the expressed emotion (EE) of the relatives being rated at baseline (T0). EE refers to a construct representing some key aspects of interpersonal relationships: the relatives were assigned to the high-EE group if they scored 3 or more on the emotional over involvement (EOI) scale, or showed hostility, or made 6 or more critical comments. The patients were clinically evaluated at baseline and for 1 year of appropriate treatment by an epileptologist who was blinded to the EE ratings. They also completed STAI XI, STAI X2 and Beck's Depression Inventory at baseline. RESULTS: Twenty-six relatives (60%) were rated as showing a high degree of EE. In the 12-month follow-up study, high EE and high EOI were found to be associated with a significantly higher seizure frequency than that recorded for the patients living in low-EE households (p<0.05). The patients from households assessed as reflecting a high degree of criticism showed poor drug compliance (p<0.01), whereas those with relatives assessed as having a high degree of warmth showed better clinical and pharmacological compliance (p<0.01). High family criticism scores also correlated with higher study entry levels of depression (p<0.05) and trait and state anxiety (p<0.05) among the patients. CONCLUSIONS: The study findings highlight the impact of particular components of the family emotional climate on the clinical course and psychological adjustment of patients with epilepsy.     

Functioning human insulinomas

Sixty-seven insulinomas were investigated by immunohistochemistry using site-directed antibodies against insulin, proinsulin, chromogranin A, HISL-19, and four proteins directly or indirectly involved in the proteolytic processing of proinsulin: the prohormone convertases PC2 and PC3, carboxypeptidase H (CPH) and 7B2. Results were expressed in a six-grade score according to the frequency of immunoreactive tumour cells. Insulin was expressed by all tumours, appearing in either a diffuse or a polarized pattern and being detected in more than 30% of tumour cells in all cases but three. Proinsulin was also expressed in all tumours, with more than 50% of tumour cells immunoreactive in all cases but 5. It was consistently localized in the Golgi apparatus. In about half the cases, moreover, it also showed diffuse cytoplasmic staining, usually with a very sparse distribution. Trabecular and solid insulinomas did not present specific, homogeneous patterns of insulin immunostaining. However, insulin immunoreactivity was much more abundant in trabecular than in solid neoplasms, being present in virtually all tumour cells (score 6) in 50% and 8% of cases, respectively. Virtually all insulinomas expressed PC2, PC3, CPH and 7B2, usually in 30–100% of tumour cells, with a frequency significantly related to that of insulin. However, detection of PC2 and 7B2 was slightly less frequent than that of PC3 and CPH. In consecutive sections these proteins were found to be mostly co-localized with insulin and chromogranin A but not with proinsulin. They were heavily expressed in all 10 tumours with more than 10% of cells showing cytoplasmic proinsulin immunoreactivity, indicating that the leakage of proinsulin from the Golgi compartment is not associated with faulty expression of converting enzymes and possibly reflects a saturated processing capacity. HISL-19 immunoreactivity was found in both Golgi apparatus and insulin stores, indicating that the relevant antigen is different from all other proteins investigated. These results do not support a defect in expression or localization of proinsulin-processing enzymes in most insulinomas.     

Effect of interferon-alpha therapy on epitope-specific cytotoxic T lymphocyte responses in hepatitis C virus-infected individuals.

The majority of hepatitis C virus (HCV)-infected individuals fail to resolve the infection and become chronically infected despite the presence of HCV-specific CTL responses directed to different HCV-derived peptide antigens. Only a minority of individuals is able to clear the virus by mounting efficient CTL responses early after acute infection, but at present it is not clear whether viral clearance is associated with CTL responses of defined specificity. To elucidate those responses associated with improvement of the disease, we analyzed CTL responses to 16 different HLA-A2-presented, HCV-derived epitopes in 12 chronically infected patients, 14 chronically infected patients treated with interferon-alpha, and in one patient with acute symptomatic disease. We show here that the majority of chronically infected individuals present CTL responses directed to an NS4-derived peptide antigen (amino acids 1789-1797). Treated patients presented stronger HCV-specific CTL responses and therapy-induced changes in CTL target choice. In particular, 13 out of 14 individuals responded to an NS3-derived epitope (amino acids 1073-1081). By longitudinal analysis we show that five individuals responding to IFN-alpha therapy with decreases in alanine aminotransferase levels presented a strong CTL activity directed to the NS3-derived epitope. One patient that spontaneously resolved the infection presented a generally strong CTL activity specific for HCV-derived epitopes with a dominant response to the NS3-derived peptide antigen. This suggests that CTL responses directed to this NS3-derived antigen may be beneficial for the control of HCV infection. Improvement of these responses may represent a therapeutic intervention in chronic HCV infection.