Canalicular stenosis secondary to weekly versus every-3-weeks docetaxel in patients with metastatic breast cancer

PURPOSE: To compare the frequency of canalicular stenosis as a side effect of weekly versus every-3-weeks docetaxel in patients with metastatic breast cancer. DESIGN: Retrospective nonrandomized comparative trial. PATIENTS AND METHODS: Eighteen patients enrolled in a phase II study of weekly docetaxel plus trastuzumab and 18 patients enrolled in a phase II study of every-3-weeks docetaxel plus doxorubicin were evaluated. Each patient underwent a comprehensive ophthalmologic examination, probing and irrigation of the nasolacrimal duct, and, in some instances, a nuclear lacrimal scan. MAIN OUTCOME MEASURES: If epiphora (excessive tearing) was reported by the patient, its time of onset was documented. In patients with epiphora, presence or absence of canalicular stenosis was evaluated on the basis of the findings on probing and irrigation. The duration of treatment with docetaxel, the dose frequency, and the cumulative dose of docetaxel were recorded in each case. RESULTS: Fourteen patients (77%) receiving weekly docetaxel plus trastuzumab had epiphora. Nine of these patients had significant anatomic narrowing of the canaliculi. Bicanalicular silicone intubation or dacryocystorhinostomy was recommended in all nine patients. Eight patients underwent surgery and experienced complete or near complete resolution of epiphora. Although two patients (11%) receiving every-3-weeks docetaxel plus doxorubicin reported transient symptoms of epiphora, neither patient was found to have narrowing of the canaliculi, and the epiphora was not severe enough to justify surgical intervention. The mean duration of docetaxel therapy for the patients in this study was 19 weeks. The mean cumulative dose of docetaxel was higher in patients with canalicular stenosis than in patients without this side effect. CONCLUSIONS: Canalicular stenosis was more common in patients receiving weekly docetaxel than in those receiving every-3-weeks docetaxel for metastatic breast cancer. Bicanalicular silicone intubation early in the course of weekly docetaxel therapy should be considered, because this intervention can prevent complete closure of the canaliculi. Once complete or near complete stenosis of the canaliculi occurs, placement of a permanent Pyrex glass tube may become necessary to overcome the blockage of tear outflow.     

Marginal keratitis associated with administration of filgrastim and sargramostim in a healthy peripheral blood progenitor cell donor

PURPOSE: To describe a 61-year-old healthy peripheral blood progenitor cell (PBPC) donor who developed marginal keratitis and mild uveitis on the third day after receiving daily recombinant human granulocyte colony-stimulating factor (rhG-CSF; filgrastim) and recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF; sargramostim) to mobilize PBPCs for allogeneic transplantation. METHODS: Interventional case report. RESULTS: The keratitis was treated with topical administration of 1% prednisolone acetate solution and resolved within 24 hours. The topical steroid dose was tapered and ultimately discontinued without recurrence of keratitis. CONCLUSION: Healthy PBPC donors receiving rhG-CSF or rhGM-CSF should be monitored for ocular complications, particularly marginal keratitis and uveitis.     

Buprenorphine maintenance treatment of heroin dependence: the first experience from Iran

The aim of this study was to assess the efficacy of 1-, 2-, and 4-mg-per-day sublingual doses of buprenorphine in the maintenance treatment of heroin-dependent patients over a 17-week treatment period. Subjects were randomized to three dosage groups. Participants consisted of 105 heroin addicts (102 men and 3 women) who met the DSM-IV criteria for opioid dependence and were seeking treatment. Subjects received buprenorphine at a dose of 1, 2, or 4 mg per day and were treated in an urban outpatient clinic, including a weekly 1-hour individual counseling session. Days retained in treatment were measured. Overall, 49 patients (46.7%) completed the 17-week study. Completion rates by dosage group were 34.3% for the 1 mg dose group, 42.9% for the 2 mg dose group, and 62.9% for the 4 mg dose group. Retention in the 4 mg dose group was significantly better than in the 1 mg dose group (P = .017). None of the other comparisons was significant. The results support the efficacy and safety of buprenorphine for outpatient treatment of heroin dependence and seem to indicate that the highest dose (4 mg) of buprenorphine was the best of the three doses for Iranian heroin addicts to increase their retention in treatment.     

Hemostatic markers with bolus versus prolonged heparin after carotid artery stenting

BACKGROUND: The evolving technique of carotid stenting (CS) requires optimal antithrombotic strategies to reduce periinterventional thromboembolic risk. In animal models of balloon injury, tissue factor (TF) was shown to be the major procoagulant of the atherosclerotic plaque mediating prolonged procoagulant activity. METHODS: We analyzed TF and TF-dependent hemostatic markers before and 2, 6 and 24 h after CS with two antithrombotic drug regimens. Group A (n=20) received prolonged unfractionated heparin (UFH) for 18-20 h starting at intervention next to aspirin and thienopyridine. In group B (n=16), single bolus UFH was administered next to combined antiplatelet therapy. Natural anticoagulants were determined at baseline. RESULTS: Patients with symptomatic and asymptomatic cerebrovascular disease did not differ in plasma TF levels. Furthermore, no statistically significant difference for TF, TFPI/Xa-complex and prothrombin fragment F1.2 was observed between bolus and prolonged heparin treatment. No significant change was found in time course for these parameters. Two patients (5.5%; one in each treatment group) suffered periinterventional minor stroke associated with increased levels of F1.2 and TFPI/Xa-complex. Both were resistant to activated protein C (APC ratio<1.9) due to heterozygous factor V Leiden mutation. CONCLUSIONS: No significant activation of the TF pathway was seen with both antithrombotic regimens suggesting that single bolus UFH combined with antiplatelet therapy is generally sufficient to control TF-dependent procoagulant activity after CS. However, patients with resistance to activated protein C may be at increased periinterventional stroke risk.     

Experimental monitoring of hepatic glucose,lactate, and glutamate metabolism by microdialysis during surgical preparation of the liver hilus

Mechanical liver manipulation can lead to hepatic microcirculation (MC) impairment. The pathobiochemical relevance of this phenomenon is not fully understood. Microdialysis (MD) allows a quantification of metabolic products in interstitial fluid, thus enabling analysis of the hepatic metabolic state during changes of liver perfusion. The aim of the study was to quantify the functional effects of standardized surgical liver preparation both on liver metabolism and microperfusion. Two groups of animals (pigs, n = 25) were formed: In the trial group (TG; n = 13) the liver was mobilized, followed by hilar preparation. In the control group (CG; n = 12) mobilization of the liver without hilar dissection was performed. Surgical manipulation was followed by an observation in both groups. Hepatic interstitial glucose, lactate, and glutamate concentrations were detected by MD and liver MC by thermodiffusion. During liver mobilization MC decreased significantly in both groups (TG; 86.7 +/- 2.0 to 73.4 +/- 2.3 ml/100 g min; and CG; 88.3 +/- 3.1 to 71.9 +/- 2.2 ml/100 g/min). In the trial group levels decreased further during hilar preparation reaching minimal values of 65.6 +/- 2.8. After preparation MC recovered to baseline. Glucose, lactate, and glutamate concentrations increased significantly during liver mobilization in the trial (glucose; 0.52 +/- 0.13 to 0.88 +/- 0.19 mmol/L; lactate; 0.34 +/- 0.07 to 0.54 +/- 0.07 mmol/L; glutamate; 34.5 +/- 3.6 to 52.6 +/- 8.0 micromol/L) and control group (glucose; 0.58 +/- 0.06 to 0.95 +/- 0.13 mmol/L; lactate; 0.30 +/- 0.06 to 0.49 +/- 0.07 mmol/L; glutamate; 32.9 +/- 2.36 to 56.1 +/- 5.12 micromol/L). Throughout hilus preparation maximum values could be measured in TG (glucose; 1.69 +/- 0.34; lactate; 0.90 +/- 0.18; glutamate; 63.5 +/- 7.2). After termination of mobilization or preparation baseline concentrations were reached again. MD allows monitoring of metabolic changes in hepatic parenchyma. Surgical liver preparation leads to changes of intrahepatic glucose, lactate, and glutamate levels (without alterations of parameters in systemic plasma) along with hepatic MC impairment. Reconstitution of hepatic MC was accompanied by rapid normalization of metabolic parameters. By measuring specific parameters, MD could prove to be of use for functional assessment of metabolic effects due to MC disturbances.     

Fibrinogen predicts restenosis after endovascular treatment of the iliac arteries

OBJECTIVE: Fibrinogen is an acute phase protein as well as a component of the coagulation cascade. Vascular inflammation and disturbed coagulation are suggested to cause restenosis after percutaneous transluminal angioplasty (PTA). We investigated the prognostic impact of fibrinogen on restenosis after endovascular treatment of iliac artery occlusive disease. METHODS: In a prospective cohort study 137 consecutive patients after iliac artery PTA (n = 74) and PTA plus selective stent implantation (n = 63) were included, 109 patients after lower limb angiography served as a control group. Patients were followed for 6 months with oscillography, ankle brachial index and duplex sonography for occurrence of restenosis. Fibrinogen and serum amyloid A (SAA), as a control parameter of inflammation, were obtained at baseline, 8, 24 and 48 h postintervention. RESULTS: PTA (adjusted OR 3.1, p = 0.05) and stenting (adjusted OR 13.3, p = 0.001) were independently associated with a higher postintervention increase of fibrinogen compared to angiography. Restenosis was found in 29 patients (21%). Patients with pre-intervention fibrinogen values in the third quartile (411-463 mg/dl) had a 6.2-fold increased adjusted risk for restenosis (p = 0.03), patients in the fourth quartile (> 463 mg/dl) had a 8.9-fold increased adjusted risk (p = 0.007). Pre-intervention SAA values were also significantly associated with restenosis (p < 0.0001). Postintervention fibrinogen and SAA levels showed no association with outcome. CONCLUSION: Balloon angioplasty and stenting of the iliac arteries cause an elevation of postintervention fibrinogen levels independently of angiographic factors. A higher pre-procedure fibrinogen level, presumably a marker of inflammatory activity, indicates a higher risk for restenosis.     

Interaction between smoking and glutathione S-transferase polymorphisms in solvent-induced chronic toxic encephalopathy

Exposure to organic solvents is still common in industrial and other work environments, and increases the risk of chronic toxic encephalopathy (CTE). Genetic variation in metabolic enzymes for solvents and other xenobiotics may modify the risk of developing toxic effects. Therefore, we investigated the presence of null genotypes for glutathione S-transferases M1 and T1 (GSTM1, GSTT1) and two genetic polymorphisms of microsomal epoxide hydrolase (mEPHX) in relation to the risk for chronic toxic encephalopathy (CTE) when exposed to solvents and smoking. We genotyped 115 patients who were classified into three categories: CTE (n = 56), incipient CTE (n = 27) and non-CTE (n = 32) patients. DNA was isolated from leucocytes and the GSTM1 and GSTT1 null genotypes were determined by multiplex-polymerase chain reaction. The two polymorphisms of mEPHX were analysed by PCR-RFLP (restriction fragment length polymorphism) based assays. All analyses were performed blindly with regard to both exposure and disease status. An increased binomial regression risk ratio = 2.5, 95% confidence interval (CI) 1.5-4.2, of the GSTM1 null genotype for CTE was found in smokers and for the GSTT1 null genotype (binomial regression risk ratio 1.5, 95% CI 1.0-2.0). In nonsmokers, the GSTM1 null genotype did not confer any risk for CTE. None of the studied mEPHX polymorphisms were associated with an increased risk for CTE. We suggest that the GSTM1 null genotype in smokers is a possible risk for solvent-induced CTE.     

Treatment of subclavian-axillary vein thrombosis: long-term outcome of anticoagulation versus systemic thrombolysis

Objective: To investigate long-term clinical and morphological outcome of patients with subclavian–axillary vein thrombosis treated with systemic thrombolysis compared to anticoagulation in a retrospective, nonrandomised study. Methods: We studied 95 consecutive inpatients with subclavian–axillary vein thrombosis treated either with systemic urokinase thrombolysis and subsequent oral anticoagulation (n=33) or with anticoagulation only (n=62). Anticoagulation was performed with heparin and phenprocoumon. Patients were followed for median 40 months (IQR 14 to 94) for symptomatic upper extremity post-thrombotic syndrome and for venous recanalisation by duplex ultrasound. Results: Primary technical success rate of the systemic thrombolysis was 88% (n=29) with seven peri-intervention bleeding complications (21%). No complication was observed in patients with anticoagulation only (p<0.0001). At the time of follow-up, duplex sonography showed a thrombotic subclavian vein in 40 of 83 patients (48%), but only 9 of 95 patients (10%) had a symptomatic upper extremity post-thrombotic syndrome. Patients with systemic thrombolysis exhibited a 60% adjusted reduced risk for a thrombotic subclavian vein at the time of follow-up compared to patients with anticoagulation only (95% CI: 0.2 to 0.9, p=0.03). However, the frequency of symptomatic post-thrombotic syndrome after thrombolysis and anticoagulation was similar (adjusted p=0.6). Conclusion: Systemic thrombolysis of subclavian–axillary vein thrombosis has an acceptable primary technical success rate and improves venous recanalisation rates compared to anticoagulation. However, the high rate of complications during thrombolysis and the lack of clinical benefit suggest that conservative treatment may be favoured.