Estimation of average flow in ungated 3D phase contrast angiograms

Three dimensional (3D) phase contrast angiograms contain velocity data, which is discarded after the reconstruction of the projections. In extension to earlier work on velocity quantification with ungated 2D phase data, this paper shows that a useful estimate of the average velocity and flow rate can be extracted from ungated 3D phase contrast angiograms. Simulations and experiments in a phantom and in vivo were performed. For pulsatile flow and strong spin saturation, an over-estimation of the flow rate at the net in-flow end of the imaging volume and underestimation at the net out-flow end was observed. Imaging at lower RF tip angles yielded flow rates close to the correct value within the entire imaging volume. In contrast to ungated 2D experiments, the flow rates determined by repeated 3D experiments showed no variation.     

Radiotherapy in the treatment of low-grade astrocytomas

Between 1954 and 1986 inclusive, 160 children in the North West Region of England were registered with histologically proven lowgrade astrocytomas (grade 1 or 2). Ten died before receiving any treatment, and a further seven died within 28 days of surgery, leaving 143 children whose survival in relation to treatment modality is the subject of this paper. Low-grade astrocytomas are responsive to radiation therapy. This treatment has no clear benefit to offer children with superficial tumours that can be resected completely or nearly so, but significantly improves survival rates when tumours are deep-seated and not amenable to excision.     

Uninformed Decisionmaking The Case of Surrogate Research Consent

A New York court recently struck down state Office of Mental Health regulations governing research involving subjects with impaired decisionmaking capacity. The court held that neither incapacitated adults nor minors could participate in any research protocol that contained a nontherapeutic element, irrespective of possible benefits to the subject or the importance of the knowledge to be gained. Although the decision rested on a technical point of law and dealt only with psychiatric research, the court's holding has significantly broader implications.     

Imaging of thoracic and lumbar spinal extradural arachnoid cysts: report of two cases

Extradural arachnoid cysts are uncommon expanding lesions in the spinal canal which may communicate with the subarachnoid space. Usually in the lower thoracic spine, they may cause symptoms by compressing the spinal cord or nerve roots. We report cases of thoracic and lumbar arachnoid cysts studied by cystography, myelography, CT and MRI. These techniques showed extradural cystic lesions containing cerebrospinal fluid, with variable communication with the subarachnoid space, causing anterior displacement and flattening of the spinal cord. Received: 3 November 1995 Accepted: 16 April 1996     

Digital movement analysis,a new objective method of measuring tardive dyskinesia and drug-induced parkinsonian tremor: acceptability,reliability and validity

Digital movment analysis (DMA) is a new instrumental approach to assessing oral tardive dyskinesia (TD) by means of digital image processing of a video signal, tracking five paper dots placed around the patient's mouth. A total of 40 schizophrenic patients, 30 with and 10 without TD, were examined twice (with a 3-month interval) with this new device. The patients were further examined with two TD rating scales: the St. Hans Rating Scale for extrapyramidal syndromes (SHRS) and the Abnormal Involuntary Movement Scale (AIMS).The schizophrenic patients accepted the instrumental assessment without any anxiety or resistance. The internal relibility of the apparatus was high, with correlation coefficients of 0.80–0.99. The DMA TD values correlated with the SHRS and AIMS scores with correlation coefficients of 0.48–0.73 indicating an acceptable, although not strong, concurrent validity. Fluctuations occurred from the first to the second examination independent of medication. For these fluctuations no correlation was found between DMA values and rating scores. Finally, the DMA device was able to detect perioral tremor as a sign of parkinsonism.It has been concluded that DMA is a useful supplement to classical TD rating, although further validity evaluation is warranted.     

Normal intracortical excitability in developmental stuttering.

Persistent developmental stuttering (PDS) shares clinical features with task-specific dystonias. In these dystonias, intracortical inhibition is abnormally weak. We therefore sought to determine intracortical inhibition and intracortical facilitation in PDS. In 18 subjects with PDS since childhood (mean age, 39.4 [SD 13.0] years) and 18 speech-fluent controls (43.6 [14.3] years), we investigated resting and active motor thresholds as well as intracortical inhibition and facilitation of the optimal representation of the abductor digiti minimi of the dominant hand using transcranial magnetic stimulation. In PDS, the resting and active motor thresholds were increased, whereas intracortical inhibition and facilitation were normal. Normal intracortical excitability makes a pathophysiological analogy between focal dystonia and PDS less likely. The enhanced motor threshold suggests reduced motor cortical neuronal membrane excitability in PDS.     

The synthetic prostaglandin E1 analogue rioprostil reduces the nephrotoxic potential of cyclosporine A

Acute CyA nephrotoxicity involves alteration in the proximal tubule and leads to glomerular lesions. Administration of a vasodilatator agent such as the prostaglandin E1 analogue Rioprostil (Bayer AG, BAY 06893) might prevent preglomerular vasoconstriction and hence reduce cyclosporin nephrotoxicity. As an increased excretion of urinary enzymes as a consequence of CyA-nephrotoxicity is well known we investigated in 40 male Wistar rats the excretion of three urinary enzymes: the brush border enzyme gamma-glutamyltransferase (GGT), the leucine aminopeptidase (LAP), and the lysosomal enzyme N-acetyl-beta-glucosaminidase (NAG). Additionally we determined s-creatinine and CyA plasma level. The kidneys were studied histologically at the end of the study. Wistar rats receiving 20 or 50 mg CyA/kg/d showed a marked deterioration in renal function and an increase of all urinary enzymes determined. In the rats receiving 20 mg CyA/kg/d and Rioprostil (150 micrograms/d) renal function and the enzymes determined remained in the normal range. There was no change in the enzyme excretion and only a minor improvement of renal function in rats receiving 50 mg CyA/kg/d and Rioprostil. Histological findings showed prevention of CyA nephrotoxicity in the 20 mg/kg/d group and diminished renal damage in the 50 mg/kg/d group.     

Single- vs Multiple-Dose Pharmacokinetics of Clozapine in Psychiatric Patients

Clozapine plasma levels were monitored in 16 patients during a series of three consecutive treatments (single dose-multiple dose-single dose). Each patient received a single 75-mg dose (3 x 25 mg) with clozapine tablets, and serial plasma samples were collected over 48 hr after the dose. At 48 hr, a multiple-dose regimen was started, consisting of an initial dose escalation period followed by dosing at a constant regimen for at least 6 days. After the last dose, serial plasma samples were again obtained over 72 hr. Drug was then withheld for at least 7 days, a final single 75-mg dose was given, and plasma sampling was repeated. A subset of the patient population (N = 7) was used to test for a food effect during the single-dose treatments. The pharmacokinetic parameters between the initial and the final single dose periods were not significantly different. Similarly, there were no differences within patients when given the dose after fasting (fed 1 hr after dose) or with a meal. In contrast, the terminal elimination rate differed between the single-dose and the multiple-dose treatments (t1/2 m3 = 7.9 hr single dose and 14.2 hr multiple dose) (P less than 0.05) and the dose-normalized area under the plasma concentration/time curves increased 27% with multiple dosing. Since a previous study in patients (Choc et al., Pharm. Res. 4:402-405, 1987) showed dose proportionality of clozapine plasma concentrations during multiple-dose regimens, the present results cannot be described by Michaelis-Menten kinetics.     

Tissue distribution, disposition, and metabolism of cyclosporine in rats

Tissue distribution, disposition, and metabolism of 3H-cyclosporine were studied in rats after single and repeated oral doses of 10 and 30 mg/kg and after an iv dose of 3 mg/kg. The oral doses of 10 and 30 mg/kg were dissolved in polyethylene glycol 200/ethanol or in olive oil/Labrafil/ethanol. Absorption from both formulations was slow and incomplete, with peak 3H blood levels at 3-4 hr. Approximately 30% of the radioactive dose was absorbed, which is consistent with oral bioavailability data for cyclosporine. More than 70% of the radioactivity was excreted in feces and up to 15% in urine. Elimination via the bile accounted for 10 and 60% of the oral and iv doses, respectively. Since unchanged cyclosporine predominated in both blood and tissues at early time points, the half-lives of the distribution phases (t 1/2 alpha) of parent drug and of total radioactivity were similar. In blood, kidney, liver, and lymph nodes, t 1/2 alpha of cyclosporine ranged from 6-10 hr. Elimination of radioactivity from the systemic circulation was multiphasic, with a terminal half-life of 20-30 hr. 3H-Cyclosporine was extensively distributed throughout the body, with highest concentrations in liver, kidney, endocrine glands, and adipose tissue. The concentrations of both total radioactivity and parent drug were greater in tissues than in blood, which is consistent with the high lipid solubility of cyclosporine and some of its metabolites. Skin and adipose tissue were the main storage sites for unchanged cyclosporine. Elimination half-lives were slower for most tissues than for blood and increased with multiple dosing. The amount of unchanged drug was negligible in urine and bile.(ABSTRACT TRUNCATED AT 250 WORDS)     

Einsatz von Bone-morphogenetic Protein-7 (BMP-7) in der Behandlung von Pseudarthrosen der oberen und unteren Extremität

Bone morphogenetic proteins (BMPs) are bone growth factors, which regulate bone formation during fetal development and bone repair after injury in postfetal life. Since 1992 BMP-7 has been produced by recombinant technique (rhBMP-7). Numerous animal models and clinical trials have shown that rhBMP-7 can induce de novo bone formation in segmental defects of bones and in cases of nonunion. Since 2001 rhBMP-7 has been approved for treatment of tibial nonunion in Europe. The effect of rhBMP-7 is comparable to the clinical and radiological results achieved with bone autografts. The problem of donor site morbidity (which occurs in up to 20% of all cases) is eliminated by the use of BMP-7. Long-term results and experience in clinical practice are not yet available.