Development of a new dynamic method for quantitative evaluation of in vitro hemocompatibility of biomedical materials.

In this study a new dynamic method is introduced allowing the estimation of blood cell adhesion on flat test surfaces by measuring the cell loss in the bulk phase of surface contacting test blood under defined rheological conditions. This was achieved by constructing a novel test chamber permitting the contact of small amounts of blood with a large geometrical test surface. The construction consists of a spiral-shaped flow channel of 0.3 cm width, 0.02 cm height and 78 cm length covered with the biomaterials to be tested from both sides. Laminarity of blood flow in the conduit was confirmed theoretically by the calculation of an equivalent to the Reynolds number for curved systems the so-called Dean number. Furthermore, flow laminarity was proved experimentally finding that the flow rate of blood with different hematocrit values was proportional to the hydrostatic pressure applied. The applicability of the novel 'spiral method' for the estimation of hemocompatibility was demonstrated by evaluation of platelet adhesion onto different polymers in comparison to siliconized and fibrinogen coated glass as reference surfaces. Additionally, it was possible under distinct conditions to determine the adhesion of leucocytes and the detachment of platelet aggregates. Therefore, it was concluded that the spiral method can be used for the assessment of the hemocompatibility of flat biomedical polymers. As main advantages of the new method can be considered the high time efficiency and accuracy without labelling or optical detection of adherent cells.     

Bromine-76 and carbon-11 labelled NNC 13-8199, metabolically stable benzodiazepine receptor agonists as radioligands for positron emission tomography (PET)

NNC 13-8241 has recently been labelled with iodine-123 and developed as a metabolically stable benzodiazepine receptor ligand for single-photon emission computed tomography (SPECT) in monkeys and man. NNC 13-8199 is a bromo-analogue of NNC 13-8241. This partial agonist binds selectively and with subnanomolar affinity to the benzodiazepine receptors. We prepared ⁷⁶Br labelled NNC 13-8199 from the trimethyltin precursor by the chloramine-T method. Carbon-11 labelled NNC 13-8199 was synthesised by N-alkylation of the nitrogen of the amide group with [¹¹C]methyl iodide. Positron emission tomography (PET) examination with the two radioligands in monkeys demonstrated a high uptake of radioactivity in the occipital, temporal and frontal cortex. In the study with [⁷⁶Br]NNC 13-8199, the monkey brain uptake continued to increase until the time of displacement with flumazenil at 215 min after injection. For both radioligands the radioactivity in the cortical brain regions was markedly reduced after displacement with flumazenil. More than 98% of the radioactivity in monkey plasma represented unchanged radioligand 40 min after injection. The low degree of metabolism indicates that NNC 13-8199 is metabolically much more stable than hitherto developed PET radioligands for imaging of benzodiazepine receptors in the primate brain. [⁷⁶Br]NNC 13-8199 has potential as a radioligand in human PET studies using models where a slow metabolism is an advantage. Received 19 April and in revised form 10 June 1997     

Severe Neurological Complications after Central Neuraxial Blockades in Sweden 1990-1999

Background: Central neuraxial blockades find widespread applications. Severe complications are believed to be extremely rare, but the incidence is probably underestimated.

Methods: A retrospective study of severe neurologic complications after central neuraxial blockades in Sweden 1990-1999 was performed. Information was obtained from a postal survey and administrative files in the health care system. During the study period approximately 1,260,000 spinal blockades and 450,000 epidural blockades were administered, including 200,000 epidural blockades for pain relief in labor.

Results: The 127 complications found included spinal hematoma (33), cauda equina syndrome (32), meningitis (29), epidural abscess (13), and miscellaneous (20). Permanent neurologic damage was observed in 85 patients. Incidence of complications after spinal blockade was within 1:20-30,000 in all patient groups. Incidence after obstetric epidural blockade was 1:25,000; in the remaining patients it was 1:3600 (P < 0.0001). Spinal hematoma after obstetric epidural blockade carried the incidence 1:200,000, significantly lower than the incidence 1:3,600 females subject to knee arthroplasty (P < 0.0001).     

k-t2 BLAST: exploiting spatiotemporal structure in simultaneously cardiac and respiratory time-resolved volumetric imaging.

Multidimensional imaging resolving both the cardiac and respiratory cycles simultaneously has the potential to describe important physiological interdependences between the heart and pulmonary processes. A fully five-dimensional acquisition with three spatial and two temporal dimensions is hampered, however, by the long acquisition time and low spatial resolution. A technique is proposed to reduce the scan time substantially by extending the k-t BLAST framework to two temporal dimensions. By sampling the k-t space sparsely in a lattice grid, the signal in the transform domain, x-f space, can be densely packed, exploiting the fact that large regions in the field of view have low temporal bandwidth. A volumetric online prospective triggering approach with full cardiac and respiratory cycle coverage was implemented. Retrospective temporal interpolation was used to refine the timing estimates for the center of k-space, which is sampled for all cardiac and respiratory time frames. This resulted in reduced reconstruction error compared with conventional k-t BLAST reconstruction. The k-t(2) BLAST technique was evaluated by decimating a fully sampled five-dimensional data set, and feasibility was further demonstrated by performing sparsely sampled acquisitions. Compared to the fully sampled data, a fourfold improvement in spatial resolution was accomplished in approximately half the scan time.     

Hematogenous infection after knee arthroplasty

Twenty-five hematogenously infected knee arthroplasties in 20 patients (17 with rheumatoid arthritis and 3 with arthrosis) were followed for 3 years. Staphylococcus aureus was the major infecting organism. Three patients with four arthroplasties died of sepsis. Two patients had removal of the arthroplasty, one of which resulted in an above-the-knee amputation. Four out of five arthrodeses fused. Two knees healed after early debridement and two healed without surgery. Ten knees had successful revision arthroplasty.

Rheumatoid arthritis and constrained prostheses increase the risk of hematogenous infection. Any infection and especially cutaneous lesions in a patient with a knee arthroplasty should be treated vigorously.     

Different molecular forms of cholecystokinin and CCKB receptor binding in the rat brain after chronic antidepressant treatment

Cholecystokinin (CCK) is a neuropeptide recently implicated in affective disorders. This study aimed at measuring the levels of different molecular forms of CCK and the binding characteristics of CCK_B receptors in the rat brain after three weeks of treatment with four different antidepressants, imipramine, amitriptyline, desipramine, and citalopram (all at the dose of 10 mg/kg once per day i.p.). Chronic treatment with imipramine and desipramine had a significant immobility-reducing effect in the Porsolt‘s swim test. The effect of amitriptyline, albeit in the same direction, was not significant, and citalopram had no effect in this test. In the elevated plus-maze test of anxiety, all drugs tended to increase the number of open arm entries and the ratio open/total arm entries, but only the effects of imipramine were statistically significant. None of the treatments affected the total levels of CCK or the levels of CCK-8-sulphated, CCK-8-nonsulphated, CCK-5, or CCK-4 in the frontal cortex. There was no effect of the treatments on CCK_B receptor binding in the frontal cortex, hippocampus, or striatum. Imipramine and amitriptyline, however, increased the affinity of CCK_B receptor binding in the hypothalamus. Thus, no consistent effect of chronic antidepressant treatment on the CCK-ergic neurotransmission in the rats was found. Received: 4 June 1996 / Accepted: 26 August 1996     

Altered neuropeptide Y Y1 responses in mesenteric arteries in rats with congestive heart failure

The aim of the present study was to elucidate if the potentiating effect of neuropeptide Y on various vasoactive agents in vitro is (1) altered in mesenteric arteries from rats with congestive heart failure and (2) mediated by the neuropeptide Y Y₁ receptor. The direct vascular effects of neuropeptide Y and its modulating effects on the contractions induced by endothelin-1-, noradrenaline-, 5-hydroxytryptamine (5-HT)-, U46619-(9, 11-dideoxy-11, 9-epoxymethano-prostaglandin F₂) and ATP, and acetylcholine-induced dilatations were studied in the presence and absence of the neuropeptide Y Y₁ antagonist, BIBP3226 (BIBP3226{(R)-N2-(diphenylacetyl)-N-[(4-hydroxyphenyl)methyl]- -arginine-amide}). Neuropeptide Y, per se, had no vasoactive effect in the arteries. The potency of endothelin-1 was significantly decreased in congestive heart failure rats. Neuropeptide Y and neuropeptide Y-(13–36) potentiated the endothelin-1-induced contraction in congestive heart failure mesenteric arteries. In 20% of the congestive heart failure rats, sarafotoxin 6c induced a contraction of 31±4%. Neuropeptide Y also potentiated U46619- and noradrenaline-induced contractions but not 5-HT-induced contractions in congestive heart failure arteries. In sham-operated animals neuropeptide Y potentiated noradrenaline- and 5-HT-induced contractions. These potentiations were inhibited by BIBP3226. Acetylcholine induced an equipotent relaxation in both groups which was unaffected by neuropeptide Y. In conclusion, neuropeptide Y responses are altered in congestive heart failure rats. The potentiating effect differs between vasoactive substances. Neuropeptide Y Y₁ and non-neuropeptide Y₁ receptors are involved.     

PET examination of [11C]NNC 687 and [11C]NNC 756 as new radioligands for the D1-dopamine receptor

The benzazepines NNC 687 and NNC 756 have in animal studies been described as selective D₁-dopamine receptor antagonists. Both compounds have been labeled with¹¹C for examination by positron emission tomography (PET). In the present study central receptor binding was studied in monkeys and healthy men. After IV injection of both radioligands in Cynomolgus monkeys radioactivity accumulated markedly in the striatum, a region with a high density of D₁-dopamine receptors. This striatal uptake was displaced by high doses of the selective D₁-antagonist SCH 23390 (2 mg/kg) but not by the 5HT₂-antagonist ketanserin (1.5 mg/kg) or the selective D₂-antagonist raclopride (3 mg/kg). The cortical uptake after injection of [¹¹C]NNC 687 was not reduced in displacement experiments with ketanserin. The cortical uptake of [¹¹C]NNC 756 was reduced in displacement and protection experiments with ketanserin by 24–28% (1.5 mg/kg), whereas no reduction could be demonstrated on striatal uptake. In healthy males both compounds accumulated markedly in the striatum. For [¹¹C]NNC 687 the ratio of radioactivity in the putamen to cerebellum was about 1.5. For [¹¹C]NNC 756 the ratio was about 5. This ratio of 5 for [¹¹C]NNC 756 is the highest obtained so far for PET radioligands for the D₁-dopamine receptor.