Pneumatically driven finger movement: a novel passive functional MR imaging technique for presurgical motor and sensory mapping.

Two of the most common reasons for failure to obtain adequate preoperative functional data are inadequate task performance and excessive head motion. With an MR imaging-compatible pneumatically driven manipulandum, passive motor tasks elicited reproducible contralateral activation in the M1 and S1 in 10 healthy controls and 6 patients. The SMA was localized in all healthy controls and in 5 of 6 patients. Head motion was reduced in passive tasks compared with active tasks.

Evaluation of clinical guidelines for the management of Staphylococcus aureus bacteraemia.

BACKGROUND: While treatment guidelines have been developed to guide the management of Staphylococcus aureus bacteraemia, there is a need to validate these guidelines in different clinical settings and to relate the effect of compliance to clinical outcome. AIMS: To assess the impact of adherence to treatment guidelines on clinical outcome and to explore the role of transoesophageal echocardiography (TOE) in risk stratification. METHODS: We undertook a 2-year mixed retrospective and prospective study of all cases of S. aureus bacteraemia at Fremantle Hospital, documenting the clinical and microbiological features of each case, the results of echocardiography, adherence with published clinical guidelines and clinical outcome. RESULTS: Failure to comply with guidelines was observed in 41% (38 of 93) of cases, the majority receiving abbreviated treatment. An increased rate of relapse was observed among patients who received inadequate therapy (5/38 vs 1/55; P= 0.04). Ten of 28 eligible patients underwent TOE and the test led to significant changes in management in two of those cases. CONCLUSIONS: While non-adherence with clinical guidelines was associated with an increased risk of relapse, the role of TOE in risk stratification was limited by factors including cost, limited acceptance of the test and the need for prolonged therapy for other indications.

Diastasis with low distal fibula fractures: an anatomic rationale.

Tibiofibular diastasis occurs infrequently in displaced ankle fractures that include a low fibula fracture. This is because the interosseous ligament, the major ligament resisting diastasis, lies above the level of the fracture. The anatomic study of the syndesmotic complex of the ankle reported here showed that the interosseous ligament has a variable attachment on the fibula, differing between specimens in its distance above the synovial reflection or joint line. Although most specimens had attachments approximately 1 cm or greater above the joint line, one of 18 specimens attached just above the synovial reflection. In such a case, a low fibula fracture would disrupt the interosseous ligament, which explains the anatomic basis for the infrequent diastasis in these ankle fractures.

Asleep-Awake-Asleep general anesthesia for open cervical rhizotomy: case report and description of the technique.

The authors describe the technique of Asleep-Awake-Asleep anesthesia for open dorsal rhizotomy in a 78-year-old female patient, admitted to the hospital with intractable pain in the distribution of C2 dermatome following a road traffic accident. The patient was anesthetised and the rhizotomy performed using the intradural approach. Anesthesia was conducted by Total Intravenous Anesthesia using a Target Controlled Infusion system. The patient was awakened twice intraoperatively to verify success of the rhizotomy. Complete pain relief was obtained and maintained at 1 year follow-up.

Secondary structure peptide mimetics: design, synthesis, and evaluation of beta-strand mimetic thrombin inhibitors.

Constrained dipeptide mimetic templates were designed to mimic the secondary structure of peptides in a beta-strand conformation. Two templates corresponding to the D-Phe-Pro portion of the thrombin inhibitor D-Phe-Pro-ArgCH2Cl were synthesized and converted into nine alpha-ketoamide and alpha-ketoheterocycle inhibitors of thrombin. Additionally, a template corresponding to L-Phe-Pro was synthesized and converted to a thrombin inhibitor. The in vitro inhibition of thrombin by these compounds was determined, and those corresponding to the D-Phe-Pro were found to be more potent inhibitors than the L-Phe-Pro mimetic. The alpha-ketoamides were found to be more potent than the alpha-ketoheterocycles but had much slower on rates. By comparison of a series of alpha-ketoamide analogues, it is apparent that the there is a preference for binding of bulky hydrophobic substituents in the P' portion of the thrombin active site. Three of the inhibitors (MOL098, MOL144, and MOL174) were screened against a series of coagulation and anticoagulation enzymes and found to be selective for inhibition of the coagulation enzymes. Two of the inhibitors were tested in in vitro models of intestinal absorption and found to have low absorption potential. The compounds were then tested in vivo in both rats and primates, and one of them (MOL144) was approximately 25% absorbed in both species. This study has delineated the synthesis of constrained dipeptide beta-strand mimetics and validated the potential for compounds of this type as potent thrombin inhibitors and possible drug leads.

Pharmacokinetics and distribution of a 33P-labeled anti-human immunodeficiency virus oligonucleotide (AR177) after single- and multiple-dose intravenous administration to rats.

AR177 is a 17-mer oligonucleotide that has anti-human immunodeficiency virus activity in vitro. The disposition of internally labeled 33P-AR177 was studied after the tail vein injection of single and multiple doses (0.7 mg/kg) to rats. After a single dose, the terminal half-life of AR177 in the blood and plasma was 367 and 271 hr, respectively, significantly longer than values reported for other oligonucleotides. Analysis of the AR177 tissue distribution showed that the majority of the dose was distributed to the liver (40%), bone marrow (17%) and renal cortex (15%) at 8 hr after single dosing. Analysis of the AR177 concentrations in tissues showed that the highest concentrations were achieved in the renal cortex (15.0 microg-eq/g), liver (7.4 microg-eq/g), bone marrow (3.9 microg-eq/g), mesenteric lymph node (3.0 microg-eq/g) and spleen (2.4 microg-eq/g) at 8 hr after single dosing. The half-life in these tissues was 9.6, 7.7, 36.8, 10.0 and 30.8 days, respectively. Forty-eight hours after the last of seven i.v. doses given every other day, the concentrations in tissues were as follows: renal cortex, 39.9 microg-eq/g; liver, 33.9 microg-eq/g; bone marrow, 12.7 microg-eq/g; spleen, 9.3 microg-eq/g; mesenteric lymph node, 5.1 microg-eq/g. Twenty-one days after administration of the last dose, tissue concentrations were still high, as follows: renal cortex, 18.6 microg-eq/g; liver, 6.2 microg-eq/g; bone marrow, 12.5 microg-eq/g; mesenteric lymph node, 3.9 microg-eq/g; spleen, 8.1 microg-eq/g. There was low urinary and fecal excretion (urinary excretion of 12.8% and fecal excretion of 6.0% of the total dose over 21 days) after a single dose. Gel filtration and anion-exchange high-performance liquid chromatography and electrophoretic analysis of the radioactivity in tissues indicated that >90% of the radioactivity represented intact AR177 for at least 7 days after drug dosing. These results demonstrate that AR177 has an extended plasma, blood and tissue half-life, is widely distributed and achieves high concentrations in lymphoid and nonlymphoid tissues in rats.

Pharmacokinetics of a 14C-labeled phosphorothioate oligonucleotide, ISIS 2105, after intradermal administration to rats.

After intradermal administration of 3.7 mg/kg of 14C-labeled 5'-TTGCTTCCATCTTCCTCGTC-3' (14C-labeled ISIS 2105) to rats, a phosphorothioate oligodeoxynucleotide, absorption was rapid. Approximately 65% of the administered dose was absorbed within 1 hr after the dose and peak blood levels were achieved within 30 min. After the initial rapid phase of absorption, a slower absorption phase ensued that resulted in more than 95% of the dose being cleared from the injection site. Slow metabolism of 14C-labeled ISIS 2105 occurred at the injection site. The rate and characteristics of metabolism in the skin were similar to those observed in other tissues. Once absorbed, the pharmacokinetics, distribution and metabolism of 14C-labeled ISIS 2105 after intradermal administration were comparable to those after an i.v. dose. The distribution and terminal half-lives were 0.5 and 53 hr, respectively. Levels of 14C-labeled ISIS 2105 in the blood were found in the plasma and the drug distributed broadly to all peripheral tissues; the liver, renal cortex and bone marrow accumulated the highest levels of drug. The 14C-labeled ISIS 2105 was eliminated principally by metabolism. Approximately 50% of the dose was found in expired air and 15% and 5% were found in urine and feces, respectively. No intact oligonucleotide was found in urine or feces at any time.

Disposition of the 14C-labeled phosphorothioate oligonucleotide ISIS 2105 after intravenous administration to rats.

5'-TTGCTTCCATCTTCCTCGTC-3' (ISIS 2105) is a phosphorothioate oligodeoxynucleotide currently being evaluated as an intralesional antiviral drug for the treatment of genital warts that are caused by the human papillomavirus. ISIS 2105, labeled with 14C (at the carbon-2 position of thymine) was administered as a single i.v. injection (3.6 mg/kg) to female Sprague-Dawley rats to assess the disposition of the drug. After i.v. administration of [14C]2105, blood radioactivity disappeared in a multiexponential manner with the half-lives of the phases equal to 0.4, 1.9, 7.1 and 5.1 hr. The initial volume of distribution was 22 ml and the postdistribution volume of distribution was 1076 ml, which indicated an extensive distribution of radioactivity. The apparent blood clearance was 14.7 ml/hr. The radioactivity in the expired air accounted for 51% of the administered dose over the 10-day period. Urinary and fecal radioactivity accounted for 15% and 5% of the administered dose, respectively. The major sites of radioactivity uptake were the liver (up to 22.6% of the dose), kidneys (renal cortex, up to 14% of the dose), bone marrow (up to 14% of the dose), skin (up to 13% of the dose) and skeletal muscle (up to 9% of the dose). Other tissues contained approximately 1% or less of the dose. The overall recovery of radioactivity 10 days postdosing was 95.1 +/- 7.5% (mean +/- S.D.) of the administered single dose. The radioactivity in the blood was almost completely in the plasma during the course of the study. In the plasma, the radioactivity was extensively bound to proteins, as assessed by size-exclusion high-performance liquid chromatography (HPLC), in samples up to 8 hr postdosing. Retention data on size-exclusion HPLC and in vitro incubations using purified proteins suggested that the plasma proteins that bound [14C]2105 were albumin and alpha 2-macroglobulin. The complex formed between the plasma proteins and [14C]2105-derived radioactivity was dissociated on anion-exchange HPLC to indicate that the great majority of plasma radioactivity coeluted with intact [14C]2105 in samples that contained sufficient radioactivity for analysis. There was a time-dependent decrease in the proportion of hepatic and renal radioactivity that coeluted with the intact [14C]2105 during the course of the study. The urine did not contain radioactivity that eluted with intact [14C]2105 on anion-exchange HPLC.

Myocardial hibernation identified by hyperbaric oxygen treatment and echocardiography in postinfarction patients: comparison with exercise thallium scintigraphy.

To evaluate the potential for hyperbaric oxygen (HBO) to produce transient improvement in function in areas of myocardium ischemic at rest (hibernating myocardium), 24 patients were studied within 1 week of acute myocardial infarction. Results were compared with single-photon emission computed tomography (SPECT) thallium-201 exercise scintigraphy. Echocardiography demonstrated improved contraction following HBO in 20 of 62 damaged left ventricular segments in 12 of 24 patients. Thirteen of the 28 segments and 9 of the 14 patients showing reversible ischemia on SPECT imaging showed improvement with HBO. There were eight segments with apparently normal resting contraction that showed a reversible thallium defect. Of 42 segments with fixed contraction abnormalities following HBO, eight had reversible thallium defects, four had normal thallium kinetics, and 30 had fixed thallium defects. Thus hyperbaric oxygen can demonstrate improvement in function in some segments of left ventricle after infarction. There is some overlap with viability as determined by thallium studies, but the two techniques may be complementary in describing myocardial ischemia.

Left atrial V waves following mitral valve replacement are not specific for significant mitral regurgitation.

Left atrial or pulmonary capillary wedge pressure V waves are used immediately after mitral valve replacement to evaluate valve competence. However, their correlation with hemodynamically significant regurgitation has not been established. Transesophageal echocardiography (TEE) was used to prospectively examine whether left atrial V waves represented significant mitral regurgitation in 11 patients undergoing mitral valve replacement. Left atrial pressure V waves were measured in the immediate postcardiopulmonary bypass period by direct cannulation of the right superior pulmonary vein and recorded on a paper chart recorder. In each patient, three evaluations of mitral regurgitation by Doppler TEE were made at 15-minute intervals. In 22 of 33 evaluations, left atrial V waves with peak V wave height more than 5 mm Hg above the mean left atrial pressure were present. However, only in 3 of these periods did transesophageal echocardiography show evidence of more than trace mitral regurgitation by pulsed Doppler and color flow mapping. As indicators of mild-to-severe mitral regurgitation diagnosed by TEE, left atrial V waves had a specificity for the three evaluation periods of 40%, 30%, and 40%. Left atrial V waves with peak height greater than 5 mm Hg above mean left atrial pressure frequently appear following mitral valve replacement, but these V waves are nonspecific signs of mitral regurgitation.

Unusual sequelae after percutaneous mitral valvuloplasty: a Doppler echocardiographic study.

Percutaneous mitral valvuloplasty is a promising new technique for the treatment of mitral stenosis, with a relatively low complication rate reported to date. To assess the sequelae of this procedure, Doppler echocardiographic studies were prospectively performed before and after percutaneous mitral valvuloplasty in a series of 172 patients (mean age 53 +/- 17 years). After balloon dilation, mitral valve area increased from 0.9 +/- 0.3 to 2 +/- 0.8 cm2 (p less than 0.0001), mean gradient decreased from 16 +/- 6 to 6 +/- 3 mm Hg (p less than 0.0001) and mean left atrial pressure decreased from 24 +/- 7 to 14 +/- 6 mm Hg (p less than 0.0001). Although most patients were symptomatically improved, six (4%) were identified who had unusual sequelae evident on Doppler echocardiographic examination immediately after percutaneous mitral valvuloplasty. These included rupture of a posterior mitral valve leaflet, producing a flail distal leaflet portion with severe mitral regurgitation detected on Doppler color flow mapping (n = 1); asymptomatic rupture of the chordae tendineae attached to the anterior mitral valve leaflet with systolic anterior motion of the ruptured chordae into the left ventricular outflow tract (n = 1); a double-orifice mitral valve (n = 1); and evidence of a tear in the anterior mitral valve leaflet (n = 3), producing on both pulsed Doppler ultrasound and color flow mapping a second discrete jet of mitral regurgitation in addition to regurgitation through the main mitral valve orifice. All six patients made a satisfactory recovery and none has required mitral valve replacement.(ABSTRACT TRUNCATED AT 250 WORDS)

Patterns of normal transvalvular regurgitation in mechanical valve prostheses.

The magnitude and spatial distribution of normal leakage through mechanical prosthetic valves were studied in an in vitro model of mitral regurgitation. The effective regurgitant orifice was calculated from regurgitant rate at different transvalvular pressure differences and flow velocities. This effective orifice area was 0.6 to 2 mm2 for three tilting disc prostheses (Medtronic-Hall sizes 21, 25 and 29) and 0.2 to 1.1 mm2 for three bileaflet valves (St. Jude Medical sizes 21, 25 and 33). In the single disc valves, Doppler color flow examination disclosed a prominent central regurgitant jet around the central hole for the strut, accompanied by minor leakage along the rim of the disc (central to peripheral jet area ratio 3.3 +/- 1.2). The bileaflet prostheses showed a peculiar complex pattern: in planes parallel to the two disc axes, convergent peripherally arising jets were visualized, whereas in orthogonal planes several diverging jets were seen. Mounting the disc and bileaflet valves on a water-filled tube allowed reproduction and interpretation of this pattern: for the bileaflet valve, the jets originated predominantly from valve ring protrusions that contained the axis hinge points and created a converging V pattern in planes parallel to the leaflets and a diverging V pattern in orthogonal planes. Similar patterns were observed during transesophageal echocardiography in 20 patients with a normally functioning St. Jude prosthesis. In 10 patients with a Medtronic-Hall valve, a dominant central jet was observed with one or more smaller peripheral jets. The median central to peripheral jet area ratio was 5 to 1.(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of prolonged transesophageal echocardiographic imaging and probe manipulation on the esophagus--an echocardiographic-pathologic study.

Transesophageal echocardiography is being increasingly utilized in the operating room and intensive care and ambulatory settings. However, to date no data are available concerning possible trauma of the transesophageal echocardiographic technique to the esophagus due to probe insertion, manipulation or direct ultrasound energy transmission. To test the hypothesis that transesophageal manipulations caused no traumatic or thermal injury to the esophageal mucosa, 12 animals were studied with continuous transesophageal echocardiography for a period of variable duration (mean 4.6 h +/- 51 min). The study group consisted of four monkeys (mean weight 5.7 +/- 0.6 kg and eight mongrel dogs (mean weight 29.8 +/- 1.4 kg). The eight dogs were studied during right heart bypass with full heparinization for 6.6 +/- 0.2 h, whereas the four monkeys were studied for 60 to 90 min in the absence of cardiopulmonary bypass and anticoagulation. Immediately after completion of transesophageal echocardiography in each case, the esophagus was entirely excised. Detailed macroscopic and microscopic examination of the esophagus revealed no significant mucosal or thermal injury. This preliminary animal study suggests that transesophageal echocardiography is safe for the esophageal mucosa in animals as small as 5 kg in weight, despite prolonged use and in the presence of systemic anticoagulation.

Impact of orifice geometry on the shape of jets: an in vitro Doppler color flow study.

To investigate the influence of orifice geometry on the three-dimensional shape of jets, an in vitro Doppler color flow study was performed. Jets were formed by discharging blood through round orifices and through orifices with major/minor axis ratios of 2:1, 3:1 and 5:1. These were repeated with orifice areas of 0.1, 0.3 and 0.5 cm2. For turbulent and laminar jets formed by these orifices, Doppler color flow images were obtained from two orthogonal scanning planes aligned with the major and minor orifice axes. Jet width was measured at 1 cm intervals from 0 to 5 cm from the orifice and used to calculate jet eccentricity (ratio of major to minor axis widths) and the rate of divergence of the jet walls. Jets were observed to diverge more rapidly along walls aligned with the orifice minor axis rather than along the major axis. This differential spreading led to the development of circular symmetry at a short distance from the orifice. Jet divergence (theta) occurred more rapidly for turbulent jets and for jets formed by larger orifices: theta (zero) = 0.80 + 6.3.A + 7.0.T + 0.47.E-OR (r = 95, p less than 0.0001, n = 48), where A is orifice area (cm2); T is 0 for laminar jets, 1 for turbulent jets and E-OR combines orifice eccentricity and scanning orientation, ranging from -5 for 5:1 orifices imaged along the major axis, 0 for circular orifices to 5 for 5:1 orifices imaged along the minor axis. Within the jet, eccentricity decayed approximately exponentially with distance from the orifice, more rapidly for turbulent jets, more slowly for the larger and more eccentric orifices.(ABSTRACT TRUNCATED AT 250 WORDS)

Prediction of successful outcome in 130 patients undergoing percutaneous balloon mitral valvotomy.

We studied 130 patients undergoing percutaneous balloon mitral valvotomy. The relation between valvular morphology according to a previously described echocardiographic scoring system and hemodynamic outcome expressed as qualitative ("good" and suboptimal) and as absolute change in valve area was analyzed. The relative importance of the individual components of this echocardiographic score (valvular thickening, mobility, calcification, and subvalvular disease) to the change in valve area after valvotomy was also examined. Mean transmitral pressure gradient decreased from 16 +/- 6 to 6 +/- 3 mm Hg (p less than 0.0001), and mitral valve area increased from 0.9 +/- 0.3 to 1.8 +/- 0.7 cm2 (p less than 0.0001). Results in individual patients were variable. Eighty-four percent (61 of 73) of patients with an echocardiographic score of 8 or less had a "good" outcome (final valve area greater than or equal to 1.5 cm2 and an increase in valve area of greater than or equal to 25%), whereas 58% (33 of 57) of patients with an echocardiographic score of 8 or more had a suboptimal result (p less than 0.001). The sensitivity of an echocardiographic score of 8 or less for predicting a "good" outcome was 72%, and the specificity was 73%. The echocardiographic score correlated negatively (r = -0.40, p less than 0.0001) with the absolute increase in mitral valve area after valvotomy, but there was substantial scatter in the data. Of the four components of the total echocardiographic score, valvular thickening correlated best with the absolute change in value area (r = -0.47, p less than 0.0001).(ABSTRACT TRUNCATED AT 250 WORDS)

Atrial septal defect after percutaneous mitral balloon valvuloplasty: immediate results and follow-up.

Percutaneous mitral balloon valvuloplasty was performed in 150 patients. There were 124 women and 26 men (mean age 53 +/- 1 years). A left to right shunt through the created atrial communication was present in 28 patients (19%) after valvuloplasty. The pulmonary to systemic flow ratio was greater than or equal to 2:1 in 4 patients and less than 2:1 in 24. Univariate predictors of left to right shunting after valvuloplasty included older age (p less than 0.01), lower cardiac output before mitral valvuloplasty (p less than 0.01), higher New York Heart Association functional class before valvuloplasty (p less than 0.05), presence of mitral valve calcification under fluoroscopy (p less than 0.01) and higher echocardiographic score (p less than 0.05). Multiple stepwise logistic regression analysis identified the presence of mitral valve calcification (p less than 0.02) and lower cardiac output (p less than 0.02) as the independent predictors of a left to right shunt through the atrial communication after balloon valvuloplasty. Follow-up (10 +/- 1 months) of patients with an atrial septal defect after valvuloplasty showed that 1) 6 patients died (3 in the hospital and 3 at 2, 16 and 18 months, respectively, after valvuloplasty); 2) an atrial septal defect was demonstrated in 3 of 6 patients who underwent mitral valve replacement (6 +/- 0.8 months after valvuloplasty); and 3) 13 patients were in functional class I, 2 patients were in class II and 1 patient was in class III at 13 +/- 1 months after valvuloplasty.(ABSTRACT TRUNCATED AT 250 WORDS)

Quantification of jet flow by momentum analysis. An in vitro color Doppler flow study.

Previous investigations have shown that the size of a regurgitant jet as assessed by color Doppler flow mapping is independently affected by the flow rate and velocity (or driving pressure) of the jet. Fluid dynamics theory predicts that jet momentum (given by the orifice flow rate multiplied by velocity) should best predict the appearance of the jet in the receiving chamber and also that this momentum should remain constant throughout the jet. To test this hypothesis, we measured jet area versus driving pressure, flow rate, velocity, orifice area, and momentum and showed that momentum is the optimal jet parameter: jet area = 1.25 (momentum).28, r = 0.989, p less than 0.0001. However, the very curvilinear nature of this function indicated that chamber constraint strongly affected jet area, which limited the ability to predict jet momentum from observed jet area. To circumvent this limitation, we analyzed the velocities per se within the Doppler flow map. For jets formed by 1-81-mm Hg driving pressure through 0.005-0.5-cm2 orifices, the velocity distribution confirmed the fluid dynamic prediction: Gaussian (bell-shaped) profiles across the jet at each level with the centerline velocity decaying inversely with distance from the orifice. Furthermore, momentum was calculated directly from the flow maps, which was relatively constant within the jet and in good agreement with the known jet momentum at the orifice (r = 0.99). Finally, the measured momentum was divided by orifice velocity to yield an accurate estimate of the orifice flow rate (r = 0.99). Momentum was also divided by the square of velocity to yield effective orifice area (r = 0.84). We conclude that momentum is the single jet parameter that best predicts the color area displayed by Doppler flow mapping. Momentum can be measured directly from the velocities within the flow map, and when combined with orifice velocity, momentum provides an accurate estimate of flow rate and orifice area.