Inhibition and reversal of platelet-rich arterial thrombus in vivo: direct vs. indirect factor Xa inhibition

BACKGROUND/OBJECTIVE: The efficacy of a direct factor (F)Xa inhibitor, ZK-807834, was compared with indirect inhibition by enoxaparin for inhibition and deaggregation of acute platelet-rich thrombi in a well-characterized porcine carotid injury model. METHODS: A crush injury was performed on a randomly chosen carotid artery and the thrombus allowed to propagate for 30 min. Pigs then received intravenous drug for 35 min: ZK-807834-Dose 1 (40 microg kg(-1) bolus + 1.5 microg kg(-1) min(-1) infusion, n=6); ZK-807834-Dose 2 (20 microg kg(-1) bolus + 0.75 microg kg(-1) min(-1) infusion; n=6); enoxaparin (1 mg kg(-1) bolus; n=6); or saline (n=6). Five minutes after drug initiation, the contralateral artery was injured. Thrombus size was monitored by scintillation detection of autologous 111In-platelets. RESULTS: The prothrombin time ratio was 2.2 +/- 0.1; 1.4 +/- 0.3; 1.2 +/- 0.9 and 1.1 +/- 0.2, respectively. ZK-807834-Dose 1 significantly inhibited carotid platelet deposition (525 +/- 226 x 10(6) cm(-2); P = 0.008), whereas ZK-807834-Dose 2 (2325 +/- 768) and enoxaparin (1236 +/- 383) were not different from saline (2776 +/- 642). Thrombus deaggregation was greatest for animals receiving ZK-807834-Dose 1 (473 +/- 185). Neither ZK-807834-Dose 2 (1588 +/- 480) nor enoxaparin (1618 +/- 686) was different from saline control (2222 +/- 598). CONCLUSIONS: Direct FXa inhibition with ZK-807834, at a prothrombin time ratio of 2.2, effectively inhibits thrombosis and promptly deaggregates thrombi induced by arterial injury. In contrast, indirect FXa inhibition with enoxaparin was ineffective.     

Policy Perspective on Housing and HIV/AIDS

For persons battling HIV/AIDS a stable place to live may decide the length and quality of life itself. It is nearly impossible for a person on the streets to engage in a needed continuous AIDS treatment regimen when the very basic question of where that person will rest his or her head when darkness comes in just a few hours is unresolved. When danger lurks on the streets, when cold numbs the limbs, when tiredness overwhelms the mind, when fear breaks the spirit, a place to call home would make all the difference.     

Nekrosen der Kieferknochen unter Bisphosphonattherapie

Bisphosphonates are widely used in the treatment of cancer patients with hypercalcemia and bone metastases or in osteoporosis therapy. Current reports have focused on therapy-resistant osteonecrosis of the jaws as a possible side effect of bisphosphonates. Official German drug committees have recently warned about the possibility of these side effects. So far we have experience with 12 patients showing therapy-resistant osteonecrosis of the mandible under bisphosphonate medication, three of whom received oral bisphosphonates for osteoporosis treatment. Presentation of these three cases provides more information on this clinically important side effect of oral bisphosphonate medication, also in osteoporosis therapy.     

Relevance of 10-min delayed recall in dementia screening

Within the context of early diagnosis of Alzheimer's disease (AD), there is a growing interest in neuropsychological screening tests. Amongst these tests, we focused on the largely used Memory Impairment Screen (MIS). The objective of the present work was to show that adding a 10-min delayed recall to the MIS, improves the test psychometric characteristics in order to detect dementia in the earliest stages. A prospective study was carried out on a cohort of 270 consecutive elderly ambulatory subjects attending the Broca Hospital Memory Clinic: normal controls ( n  = 67), mild cognitive impairment subjects ( n  = 98) and mildly demented patients [ n  = 105, Mini Mental State Examination (MMSE) = 23 ± 4]. This study consisted in testing the advantage of the 10-min delayed recall entitled MIS-D compared with the MIS. At a cut-off score of 6, the MIS-D revealed satisfying psychometric characteristics with a sensitivity of 81% and a specificity of 91%, whilst the MIS alone indicated a sensitivity of 60% and a specificity of 88% in detecting dementia. In demented patients with MMSE score ≥26, MIS-D properties still remained satisfying (sensitivity: 75%, specificity: 92%). MIS-D is a more relevant screening test than MIS alone at very early stages of dementia.     

Pelvic Ring Fractures: Utility of Clinical Examination in Patients with Impaired Consciousness or Tracheal Intubation

Abstract Objective: To define the diagnostic accuracy of clinical examination in patients with impaired consciousness or endotracheal intubation to detect pelvic ring fractures and to identify those with severe bleeding. Methods: Included in this prospective data collection with retrolective data analysis were a consecutive series of blunt trauma victims with either a Glasgow Coma Scale ≤ 13 or tracheal intubation. Clinical examination comprised testing for stability of the iliac wings. Results: From 784 subjects (injury severity score 23.3 ± 17.4) 93 patients (11.9%) were found to have a pelvic ring fracture. Clinical instability of the pelvic ring was found in 42 patients. There was only one false positive. Fifty-two fractures could not be identified by clinical examination, including nine fractures (17%) that required surgical fracture stabilization (sensitivity of clinical examination 44.1%). Seventeen fractures (18.3%) were associated with a blood loss larger than 20% of circulating blood volume. Sixteen of those were identified by clinical instability of the pelvic ring (sensitivity 94.1%, specificity 97.0%, positive predictive value 38.1%, negative predictive value 99.9%). Conclusions: Clinical examination for stability of the pelvis in this selected group of patients missed a significant number of pelvic ring fractures including fractures that require surgical stabilization. The finding of a clinically unstable identifies most of the patients with the pelvic ring fracture being a major source of bleeding. A stable pelvis makes pelvic ring fracture as being the source of bleeding quite unlikely.     

The antinociceptive effects of anterior pretectal stimulation in tests using thermal, mechanical and chemical noxious stimuli

Four behavioural tests have been used to study the antinociceptive effects of electrical stimulation of the anterior pretectal nucleus (APtN) in the rat. The antinociceptive effects of stimulating this nucleus, which lies dorsally in the posterior diencephalon, have recently been studied extensively but always using briefly applied heat stimuli. It is reported here that APtN stimulation effectively inhibited responses to briefly applied noxious pressure and longer-lasting noxious chemical (formalin) stimuli. Although the tail-flick reflex to noxious heat was very potently depressed by APtN stimulation, responses to noxious heat in the hot-plate test were not. Three doses of morphine were also studied with each test and it was concluded that 15 sec of 35 microA r.m.s. current into the APtN was as effective as 3-5 mg/kg morphine s.c. in the rat.     

The clinical features and prognosis of pseudoseizures diagnosed using video-EEG telemetry

A total of 110 patients underwent diagnostic evaluation for attacks of uncertain origin by means of video-EEG telemetry and had a diagnosis of pseudoseizures confirmed. Eighty-six patients (78%) were female, mean age of onset 25 years, and mean duration of attacks was 3 years. Many of the patients had erroneously been thought to be suffering from epilepsy. The attacks could be divided into two broad categories: attacks of collapse (one-third) and attacks with prominent motor activity (two-thirds). In some patients, the attacks were associated with incontinence and injury. The differential diagnosis and clinical features of the attacks are described. Additional psychiatric features were present in 52 (47%) patients. Follow-up (for a median 5 years; range, 1 to 14 years) showed that 40% of these patients stopped having pseudoseizures. This favorable outcome was associated with being female, leading an independent life, a formal psychological approach to therapy and counseling, and the absence of coexisting epilepsy, but not with the duration of pseudoepilepsy, prior episodes of pseudostatus, the coexistence of overt psychiatric disease, or the clinical features of the attacks.     

Control of detrusor hyperreflexia by the intravesical instillation of oxybutynine hydrochloride

This report deals with the control of detrusor hyperreflexia by the intravesical instillation of oxybutynin hydrochloride (OH) in 10 male and 3 female patients with complete suprasacral spinal cord lesions having clean intermittent catheterisation (CIC) because of unbalanced voiding. The indication for intravesical OH application was persisting urinary incontinence despite CIC in 11 patients and in 2 patients detrusor hypercontractility. One 5 mg tablet of OH was dissolved in distilled water and the solution was instilled into the bladder through the catheter, which has been used for urodynamics and which was then removed. Six hours later cystometry was repeated and the clinical effects were studied especially with regard to continence/incontinence and side-effects. The differences in the cystometric bladder capacity and maximum detrusor pressure before and after instillation of OH are statistically highly significant. Clinically, from those 10 patients who were incontinent between CIC before, 9 remained dry during the 6-hour period. None of the patients reported any side-effect after intravesical application of OH. However, with subsequent oral medication 8 out of 12 patients complained of typical anticholinergic side-effects. These results indicate that treatment with topical OH is an effective alternative to treating detrusor hyperreflexia, especially in patients already on CIC because of unbalanced voiding, but with persisting urinary incontinence due to detrusor hyperreflexia. OH is well absorbed from the bladder, however absorption seems to be protracted compared to oral intake.