Acoustic characterization of a miniature matrix transducer for pediatric 3D transesophageal echocardiography

This paper presents the design, fabrication and characterization of a miniature PZT-on-CMOS matrix transducer for real-time pediatric 3-dimensional (3D) transesophageal echocardiography (TEE). This 3D TEE probe consists of a 32?×?32 array of PZT elements integrated on top of an Application Specific Integrated Circuit (ASIC). We propose a partitioned transmit/receive array architecture wherein the 8?×?8 transmitter elements, located at the centre of the array, are directly wired out and the remaining receive elements are grouped into 96 sub-arrays of 3?×?3 elements. The echoes received by these sub-groups are locally processed by micro-beamformer circuits in the ASIC that allow pre-steering up to ±37°. The PZT-on-CMOS matrix transducer has been characterized acoustically and has a centre frequency of 5.8 MHz, -6 dB bandwidth of 67%, a transmit efficiency of 6 kPa/V at 30 mm, and a receive dynamic range of 85 dB with minimum and maximum detectable pressures of 5 Pa and 84 kPa respectively. The properties are very suitable for a miniature pediatric real-time 3D TEE probe.     

Identification of the human P450 enzymes involved in the in vitro metabolism of the synthetic steroidal hormones Org 4060 and Org 30659

1. The type of human P450 enzymes involved in the in vitro metabolism of Org 4060 and Org 30659, two synthetic steroidal hormones currently under clinical development by NV Organon for use in oral contraceptive and hormone replacement therapy, was investigated. 2. Both steroids were mainly hydroxylated at the 6 β -position in incubations with human liver microsomes. 3. The results from experiments with supersomes, correlation studies as well as inhibition studies with ketoconazole, a selective inhibitor of CYP3A, strongly suggest that the CYP3A family plays a significant role in the 6 β -hydroxylation of both steroids. 4. Measurements of kinetic parameters of P450 enzymes that could metabolize both steroids, combined with the fact that CYP3A4 is known to be the most abundant P450 enzyme in the human liver, indicate that CYP3A4 will be of major importance for the in vivo human metabolism of Org 4060 and Org 30659.     

Cognitive impairment in survivors of out-of-hospital cardiac arrest

Background

The huge importance of rapid provision of care, especially early defibrillation, for survival of out-of-hospital cardiac arrest (OHCA) is well known. This prospective cohort study investigated cognitive functioning of OHCA survivors in relation to the time-related elements of the resuscitation.

Methods

Fifty-seven consecutive survivors, from a cohort of 308 witnessed OHCA patients with ventricular fibrillation as the initial rhythm, underwent extensive neuropsychologic examination, including tests of memory, attention, and executive functioning, 6 months after the resuscitation. Time-related aspects of the resuscitation were collected on scene. Cognitive functioning was studied in relation to the administration of cardiopulmonary resuscitation (CPR) prior to ambulance arrival, and time from collapse to start of CPR, defibrillation, and return of spontaneous circulation (ROSC).

Results

Depending of the test, between 11% and 28% of survivors were cognitively impaired, while 58% scored unimpaired for all tests. Daily life activities were limited in 19% of the patients. Patients who received CPR prior to arrival of the ambulance showed a trend towards overall better cognitive functioning and significant better immediate memory and visuomotor tracking (P = .03 and P < .01). We found a weak correlation between the time to CPR, time to defibrillation, or time to ROSC and cognitive functioning.

Conclusions

The majority of survivors of OHCA with ventricular fibrillation as the initial rhythm are cognitively unimpaired. Long delays to ROSC are compatible with good cognitive outcome. Initiation and cessation of resuscitation efforts should not be based on the duration of circulatory arrest.     

Budesonide in collagenous colitis: a double-blind placebo-controlled trial with histologic follow-up.

BACKGROUND & AIMS: Collagenous colitis (CC) is a well-described entity causing chronic diarrhea and characteristic histologic findings. Several treatment options have been suggested, but no controlled data are available. We conducted a placebo-controlled trial to show the clinical and histologic effects of budesonide in CC. METHODS: Twenty-eight patients were randomly assigned to receive placebo (n = 14) or budesonide 9 mg daily (n = 14) for 8 weeks. Patients were evaluated clinically, and blinded biopsy specimens were analyzed from fixed locations at weeks 0 and 8. Clinical response was defined as a decrease of at least 50% in the disease activity score (number of bowel movements in the last 7 days). At week 8, nonresponders received open-label budesonide for the next 8-week period; responders discontinued treatment and were followed up. RESULTS: Three patients discontinued the study prematurely. Intention-to-treat analysis showed clinical response in 8 of 14 patients in the budesonide group compared with 3 of 14 responders for placebo (P = 0.05) after 8 weeks of blinded therapy, together with improved stool consistency. Histologically, there was no change in the mean thickness of the collagen band but a significant decrease of the lamina propria infiltrate in the budesonide group (P < 0.001). CONCLUSIONS: Budesonide is efficacious in inducing short-term clinical response in CC with significant reduction of the histologic infiltrate in the lamina propria.     

Epinephrine induces a late thromboxane-dependent platelet shape change and enhances synergistically the shape change induced by other platelet agonists

Epinephrine is the only physiological platelet activator which induces platelet aggregation without a preceding change in platelet shape. The reason why epinephrine cannot induce this shape change is not known. Electron microscopically, we could show that during the first phase of epinephrine-induced platelet aggregation, the platelet aggregate is composed of discoid platelets, lying in rather loose contact with neighbouring platelets. During the second wave of epinephrine-induced aggregation (this is when thromboxane (TX)A(2) production has taken place), platelets have completely lost their discoid shape and are very tightly bound. In EDTA-platelet rich plasma (PRP), we could demonstrate a clear synergistic action of epinephrine 10-20 μM on the first phase of shape change (disc-to-sphere transformation), induced by low concentrations of arachidonic acid (AA), collagen, adenosine diphosphate (ADP) and platelet activating factor (PAF). In combination with moderate concentrations of AA or collagen, epinephrine induced a clear aggregation-independent secretion of platelet granules, which in the absence of epinephrine, only takes place with higher inducer concentrations. All these synergistic actions could be demonstrated in the aggregometer and electron microscopically. To explain these findings, we hypothesize that the inability of epinephrine to induce a shape change that precedes aggregation is due to slow generation of TXA(2) which is only formed as a positive feedback mechanism of aggregation. This TXA(2) will bind to its own receptor and produce a shape change coinciding with the second wave of epinephrine-induced aggregation. Collagen, in contrast, induces very rapid TXA(2) generation, causing Ca(2+) mobilization and myosin light chain-phosphorylation, leading to shape change, clearly before aggregation starts.