Prolonged international normalized ratio during the first year of warfarin treatment.

OBJECTIVE: Oral anticoagulants (OAC) are effective in the prevention of thromboembolic events but are underused. The 1st year following the beginning of vitamin K antagonists is associated with higher bleeding rate, especially in patients with international normalized ratio (INR) of >4, leading to discontinuation of OAC. We hypothesized that the decision to discontinue OAC during the 1st year in patients with events of overanticoagulation is not fully justified. SETTING: A retrospective study of the association between warfarin overanticoagulation during the 1st year of treatment and the outcome and complications in patients admitted to an internal medicine department with INR>4. SUBJECTS: A cohort of 249 patients was divided according to OAC treatment duration: ≤12 months (group I, n=72; mean age, 79.1 years) and >12 months (group II, n=177; mean age, 78.3 years). RESULTS: International normalized ratio upon admission was higher in group I (INR, 6.88 versus 6.16; P=0.003). Patients in group I were overanticoagulated for a longer period (46.4% versus 18.5%; P<0.001) but had lower time in therapeutic range (39.0% versus 60.2%; P=0.001). The frequency of INR monitoring was higher in group I. The incidence of major and minor bleeding events and survival was similar. CONCLUSIONS: Patients who are admitted with INR>4 during the 1st year of OAC therapy are overanticoagulated for a longer period, have lower time in therapeutic range, but do not present with higher incidence of bleeding events, all compared with patients treated for longer than 12 months. Stricter INR monitoring and careful patient selection may prevent the discontinuation of OAC.

Do androgen deprivation drugs affect the immune cross-talk between mononuclear and prostate cancer cells?

The aim of the study was to examine the effect of androgen deprivation drugs, i.e. leuprolide and bicalutamide on the immune cross-talk between human peripheral blood mononuclear cells (PBMC) and cells from PC-3 and LNCaP human prostate cancer lines. PBMC, PC-3 and LNCaP were separately incubated without and with two androgen-deprivation drugs, i.e. leuprolide and bicalutamide, and the secretion of IL-1ß, IL-6, IL-1ra and IL-10 was examined. In addition, the effect of both drugs on the production of those cytokines was carried out after 24 hours incubation of PBMC with both types of cancer cells. Leuprolide or bicalutamide did not affect the production of the cytokines by PBMC or by the prostate cancer cells from the two lines. Incubation of PBMC with PC-3 or LNCaP cells caused increased production of IL-1ß, IL-6 and IL-10 as compared with PBMC incubated without malignant cells. While 10(-7) M and 10(-8) M of leuprolide caused a decreased secretion of IL-1ß by PBMC previously incubated with prostate cancer cells without the drug, bicalutamide did not affect this PBMC activity at any drug concentration. This observation suggests the existence of an additional mechanism explaining the effect of androgen deprivation therapy in prostate cancer patients.

A study of elderly adults taking warfarin admitted with prolonged international normalized ratio: a community hospital's experience.

OBJECTIVES: To assess bleeding complications and outcome of individuals receiving oral anticoagulants who were admitted to the hospital with an international normalized ratio (INR) greater than 4 by comparing them according to age (≤ 80, >80). DESIGN: Retrospective cohort study. SETTING: Community hospital. PARTICIPANTS: All individuals (N = 253) admitted to the Department of Internal Medicine over a period of 4 years with an INR greater than 4: Group I, aged 80 and younger (n = 127); Group II, older than 80 (n = 126). Data included bleeding complications, survival, and quality of INR control before admission and up to 48 months after admission. RESULTS: Atrial fibrillation was the most common indication for warfarin therapy. Its incidence was higher in the older group (88% vs 73%, P = .004). More elderly participants lived in nursing homes (23% vs 9.4%. P = .004) or received in-home assistance (38.9% vs 20.5%, P = .002). There was no difference in INR upon admission, duration of warfarin treatment, or frequency of INR tests before admission. The incidence of bleeding events was 18.1% in Group I and 12.7% in Group II (P = .30). Major bleeding events occurred in 1.6% of Group I and none of Group II (P = .50). During follow-up after the first admission, the incidence of INR greater than 4 was higher in Group II (87.3% vs 70%, P = .02), without a difference in the number of additional admissions or bleeding events. CONCLUSION: Primary care physicians can safely maintain warfarin treatment in elderly adults, even in those with a history of hospitalization for high INR, using frequent INR measurements.

An alternative facility for a stroke unit in a community hospital.

OBJECTIVE: The administration of tissue plasminogen activator (tPA) to patients with acute ischemic stroke (AIS) within three hours from onset of neurological symptoms is presently accepted as the standard treatment for suitable individuals, since it has been shown that it improves their outcome. The aim of this retrospective study was to report our experience with tPA administration in a subunit of a department of internal medicine adapted specifically for that goal. SETTING: The study was carried out in a subunit of a department of internal medicine. This subunit was equipped with all necessary items for monitoring vital signs. The patients received 0.9mg/kg of tPA intravenously and remained under around-the-clock supervision by highly trained nurses. SUBJECTS: Thirty one patients (11 women and 20 men), diagnosed with AIS between 2004 and 2008, and eligible for tPA treatment, were included in the study. RESULTS: The interval from the onset of stroke to tPA administration (onset to treat time OTT) was 145±2.2min, whereas the interval from door-to-needle was 100±4min. Two patients (6.4%) died during hospitalization because of severe intracerebral hemorrhage. Three patients with hemiparesis (9.6%) developed minor hemorrhages detected by brain CT. The mean length of stay was 8.8±0.6days. CONCLUSIONS: Our results are comparable with those obtained in stroke units in other countries. The suggested model offers a possibility for appropriate and rapid thrombolysis for AIS in a community hospital lacking special stroke unit. Moreover, the suggested alternative does not require extensive economic investment, since there is no need for additional staff, and permits the use of already existing hospital facilities.

Coenzyme Q10 decreases TNF-alpha and IL-2 secretion by human peripheral blood mononuclear cells.

The beneficial effect of coenzyme Q10 (CoQ10) on human health occurs through various mechanisms including the possibility of immunomodulation. Therefore, the purpose of study was to examine the in vitro effect of CoQ10 on cytokine production and superoxide anion generation by human peripheral blood mononuclear cells (PBMC). 2x10(6)/mL PBMC obtained from 19 volunteers were incubated for 24 h without or with 0.6, 1.25, 2.5 and 5.0 muM of CoQ10. The production of the following cytokines were examined: IL-1beta, IL-1ra, IL-6, IL-10, IL-2 and IFNgamma. Superoxide anion production was examined by incubation of 4x10(6)/mL cells with CoQ10 and 2x10(-3) mM phorbol merystate acetate (PMA) for 60 min. The production of the proinflammatory cytokines IL-1beta, IL-6 and IFNgamma and that of the anti-inflammatory cytokines IL-1ra and IL-10 by PBMC was not affected by CoQ10, whereas TNFalpha secretion was significantly decreased when the cells were incubated with 0.6 and 1.25 muM of CoQ10. On the other hand, increasing doses of CoQ10 caused mild, but statistically significant inhibition of IL-2 secretion. The generation of superoxide anion by PBMC did not differ significantly between cells incubated with or without CoQ10 at concentrations between 0.3 and 5.0 muM. The results suggest that CoQ10 exerts a certain effect on cytokine production by PBMC related to its capacity to modulate human immune function.

[Contained rupture of the aorta as a cause of prolonged abdominal pain].

Abdominal pain is a frequent complaint. In this report, a woman who presented with abdominal pain was found to have a contained rupture of the abdominal aorta that extended into the retroperitoneum. The diagnosis was difficult due to the multiple manifestations in the clinical presentation. Rupture of the aorta is more frequent in patients who suffer from an aortic aneurysm. The patient described, however, did not have an aneurysm, as illustrated by the abdominal CT scan and surgical findings. Therefore, abdominal or back pain may be caused by a rupture of the aorta, even in the absence of an aortic aneurysm.