CHEK2-positive breast cancers in young Polish women.

PURPOSE: To investigate the contribution of CHEK2 mutations to early-onset breast cancer in Poland and to establish the characteristic features of these cancers. EXPERIMENTAL DESIGN: We studied 3,228 women diagnosed with breast cancer under the age of 51 years and 5,496 population controls. CHEK2 mutations were detected by RFLP-PCR or allele-specific oligonucleotide-PCR assays. Clinical and pathologic features of CHEK2-positive cases and CHEK2-negative cases were compared. RESULTS: A truncating CHEK2 mutation (1100delC or IVS2+1G>A) was seen in 47 of 3,228 cases and in 34 of 5,496 controls (odds ratio, 2.4; P = 0.0001). The CHEK2 I157T missense mutation was present in 207 of 3,228 cases, compared with 264 of 5,496 controls (odds ratio, 1.4; P = 0.002). Breast cancers in women with a CHEK2 mutation were more commonly of lobular histology (21.5% versus 15.8%; P = 0.05), of size >2 cm (54.8% versus 43.5%; P = 0.01), or of multicentric origin (28.7% versus 19.5%; P = 0.01) than were cancers from women without a CHEK2 mutation. Bilateral cancers were equally common in both subgroups. CONCLUSION: Three founder alleles in CHEK2 contribute to early-onset breast cancer in Poland. Breast tumors which arise in carriers of CHEK2 mutations seem to be similar to those of breast cancers in the population at large.     

Common Carotid Artery Remodeling Studied by Sonomorphological Criteria

BACKGROUND AND PURPOSE: Only a few attempts have been made to establish the impact of critical intima-media thickness (IMT) on narrowing of the lumen of the common carotid artery (CCA). In the present study, sonomorphological criteria have been used to assess how intima-media thickening in the CCA may influence the artery geometry. METHODS: High-resolution ultrasonography was employed in 233 patients (466 arteries) to quantify the selected parameters of CCA biometry: IMT, arterial lumen diameter (LD), interadventitial diameter (IAD), and outer artery diameter (OAD). RESULTS: With an increase of CCA IMT up to the critical point of 1.2 mm, the LD showed parallel compensatory increases. Above the inflection point of 1.3 mm, the lumen became progressively narrower proportionally to the increasing IMT. CONCLUSION: There are limits to the compensatory enlargement of the CCA lumen. Above the inflection point of CCA IMT of 1.3 mm, the artery lumen becomes progressively narrower with increasing IMT.     

The lack of influence of normobaric oxygen on the generalized Shwartzman reaction in the rabbit

The influence of breathing oxygen on the generalized Shwartzman reaction in the rabbit was studied. We did not observe any effect of oxygen in the results of the ethanol gelation test, on the fibrinogen level in plasma nor on the fibrinolytic activity in euglobulins and in the renal cortex and outer medulla. The endotoxin-induced intraglomerular fibrin deposition was also unchanged in oxygen-breathing rabbits. It is concluded that the mechanism of the generalized Shwartzman reaction is unaffected by breathing normobaric oxygen.     

Recruitment maneuvers after a positive end-expiratory pressure trial do not induce sustained effects in early adult respiratory distress syndrome

BACKGROUND: Recruitment maneuvers performed in early adult respiratory distress syndrome remain a matter of dispute in patients ventilated with low tidal volumes and high levels of positive end-expiratory pressure (PEEP). In this prospective, randomized controlled study the authors evaluated the impact of recruitment maneuvers after a PEEP trial on oxygenation and venous admixture (Qs/Qt) in patients with early extrapulmonary adult respiratory distress syndrome. METHODS: After a PEEP trial 30 consecutive patients ventilated with low tidal volumes and high levels of PEEP were randomly assigned to either undergo a recruitment maneuver or not. Data were recorded at baseline, 3 min after the recruitment maneuver, and 30 min after baseline. Recruitment maneuvers were performed with a sustained inflation of 50 cm H2O maintained for 30 s. RESULTS: Compared with baseline the ratio of the arterial oxygen partial pressure to the fraction of inspired oxygen (Pao2/Fio2) and Qs/Qt improved significantly at 3 min after the recruitment maneuver (Pao2/Fio2, 139 +/- 46 mm Hg versus 246 +/- 111 mm Hg, P < 0.001; Qs/Qt, 30.8 +/- 5.8% versus 21.5 +/- 9.7%, P < 0.005), but baseline values were reached again within 30 min. No significant differences in Pao2/Fio2 and Qs/Qt were detected between the recruitment maneuver group and the control group at baseline and after 30 min (recruitment maneuver group [n = 15]: Pao2/Fio2, 139 +/- 46 mm Hg versus 138 +/- 39 mm Hg; Qs/Qt, 30.8 +/- 5.8% versus 29.2 +/- 7.4%; control group: [n = 15]: Pao2/Fio2, 145 +/- 33 mm Hg versus 155 +/- 52 mm Hg; Qs/Qt, 30.2 +/- 8.5% versus 28.1 +/- 5.4%). CONCLUSION: In patients with early extrapulmonary adult respiratory distress syndrome who underwent a PEEP trial, recruitment maneuvers failed to induce a sustained improvement of oxygenation and venous admixture.     

Simultaneous lung resection for cancer and myocardial revascularization without cardiopulmonary bypass (off-pump coronary artery bypass grafting)

Backround

Patients with resectable lung cancer and unstable coronary heart disease are at high risk of postoperative death or severe cardiovascular complications. The aim of this study was to present the early results of radical lung resection for cancer with simultaneous myocardial revascularization on the beating heart (off-pump coronary artery bypass [OPCAB]).

Methods

From 1999 to 2002, thirteen patients (9 men and 4 women, aged 54 to 71 years, mean age 64 yrs) with resectable lung cancer and unstable angina or a recent history of myocardial infarction, were operated on. All of them underwent coronary angiography and neither coronary angioplasty nor stenting were feasible. Eight lobectomies, three pneumonectomies, and two wedge resections were carried out together with aortocoronary graft implantation (mean number of grafts: 1.7 per patient). Myocardial revascularization without cardiopulmonary bypass (OPCAB) preceded the lung resections. The preferred approach to the heart and lung was by sternotomy.

Results

There were no postoperative deaths in this group of patients. The most frequent postoperative complication was prolonged air leakage and one patient required respiratory support for two days. In one patient, significant blood loss was observed with a need for rethoracotomy. Transient supraventricular cardiac arrhythmias occurred in three patients. None of the patients showed evidence of myocardial ischemia after surgery. Patients were followed up for 7 to 36 months. None had acute myocardial infarction. In one patient, who underwent lobectomy, local recurrence was found. In another patient, who underwent pneumonectomy, distant metastases occurred in the third year of observation.

Conclusions

Lung resection carried out simultaneously with OPCAB is a safe and effective method for the treatment of lung cancer and myocardial ischemia.     

Atypical phenylketonuria treatment effectiveness

Atypical phenylketonuria is the consequence of the deficiency of tetrahydrobiopterin (BH4) - cofactor of phenylalanine hydroxylation. The type of the disease depends on the metabolic defect of synthesis or regeneration of the cofactor. The secondary deficiency of neurotransmitters - dopamine and serotonin is the reason of very severe clinical course and brain damage. Ten cases of atypical phenylketonuria are presented: 8 of the defect of 6-pyrogronyl-tetrahydropterin synthase, 1 of dihydropteridine reductase, 1 of GTP cyclohydrolase. In 7 cases the diagnosis was confirmed by molecular studies. The age of the children at the time of diagnosis was from 3 weeks to 7 years. In 8 children pharmacological treatment was implemented without limitation of dietary intake of phenylalanine. Treatment period was from 9 months to 18.5 years. Treatment effectiveness is differentiated and independent of the age of diagnosis. Physical development in all but one patient is retarded and in all of them microcephaly is present. After treatment, mental development scores in 6 cases improved evidently (in 2 - up to normal values, in 4 - close to normal). No improvement was achieved in 2 cases (brothers). Detailed analysis of the clinical course in patients with similar age of diagnosis and start of treatment and with identical genotypes revealed significant differences in clinical course and treatment effectiveness. No explanation for this fact has been found.     

Multivariate relationships between international normalized ratio and vitamin K-dependent coagulation-derived parameters in normal healthy donors and oral anticoagulant therapy patients

Background and objectives  

International Normalized Ratio (INR) is a world-wide routinely used factor in the monitoring of oral anticoagulation treatment (OAT). However, it was reported that other factors, e. g. factor II, may even better reflect therapeutic efficacy of OAT and, therefore, may be potentialy useful for OAT monitoring. The primary purpose of this study was to characterize the associations of INR with other vitamin K-dependent plasma proteins in a heterogenous group of individuals, including healthy donors, patients on OAT and patients not receiving OAT. The study aimed also at establishing the influence of co-morbid conditions (incl. accompanying diseases) and co-medications (incl. different intensity of OAT) on INR.