A comparison of 99Tcm-MDP and 99Tcm-MIBI in the detection of breast cancer

In this study, we made an intra-individual comparison of the uptake of 99Tcm-MDP and 99Tcm-MIBI in breast cancer. Twenty women with large breast masses (one dimension > or = 3 cm on mammography) underwent SPET in the supine position with both agents. All transverse sections demonstrating tumour activity were added together and the net (total) tumour uptake in a region of interest was compared to that of surrounding tissue activity (background). We also evaluated maximum tumour uptake versus background activity. Tumour uptake was observed in all examinations. In contrast to MIBI, eight MDP examinations showed increased uptake in normal breast parenchyma in addition to tumour uptake. There was no significant difference in net tumour uptake between the two tracers and non-parenchymal (indifferent) background activity, but the maximum tumour activity of MIBI was significantly higher than that of MDP. In the eight MDP examinations with parenchymal activity, mammograms were required to identify tumour uptake correctly. In conclusion, MDP may provide similar images to MIBI in postmenopausal women not receiving hormone replacement therapy. For other patients, MIBI gives better tumour depiction.     

The insulin-like growth factor-I receptor inhibitor picropodophyllin causes tumor regression and attenuates mechanisms involved in invasion of uveal melanoma cells.

PURPOSE: Uveal melanoma has a high mortality rate due to a high incidence of metastasis (up to 50%), which preferentially occurs in the liver. Conventional chemotherapy, being the only therapeutic option today against metastatic uveal melanoma, has not proved to be effective. Therefore, new molecular targets important for malignant phenotype of uveal melanoma have to be found to design efficient pharmacologic agents. EXPERIMENTAL DESIGN: We previously reported data indicating that the insulin-like growth factor-1 receptor (IGF-IR) is a metastasis predictor as well as a therapeutic target for uveal melanoma. In the present study, we made use of the cyclolignan picropodophyllin (PPP), which is an inhibitor of the IGF-IR. RESULTS: We showed that PPP efficiently blocks growth and viability of uveal melanoma cells in cultures and causes tumor regression in xenografted mice. In addition, treatment with PPP inhibited several mechanisms involved in metastasis, including tumor cell adhesion to extracellular matrix proteins, activity and expression of matrix metalloproteinase 2, and cell migration as well as invasion through basement membranes and endothelial cell layers. Furthermore, PPP significantly delayed establishment of uveal melanoma tumors and drastically reduced the incidence of liver metastasis in mice. CONCLUSIONS: Our data suggest that IGF-IR is crucial for growth and survival as well as invasion and metastasis of uveal melanoma cells. Targeting this receptor may therefore comprise a strategy to treat ongoing disease (today incurable) as well as a strategy to prevent development of metastases in patients with primary disease.     

Intrastriatal ventral mesencephalic xenografts of porcine tissue in rats: immune responses and functional effects

Transplantation of neural tissue from other species has the potential to improve function in patients with neurodegenerative disorders. We investigated the functional effects of embryonic porcine dopaminergic neurons transplanted in a rat model of Parkinson's disease and the immune responses to the grafts in immunosuppressed and nonimmunosuppressed hosts. Twenty-three rats with unilateral 6-hydroxydopamine lesions received dissociated, 27-day-old embryonic porcine ventral mesencephalic tissue in the right striatum. Eighteen rats received cyclosporine (10 mg/kg, IP, daily) during the whole period of 14 weeks, in combination with prednisolone (20 mg/kg, IP, daily) the first 4 days. Five rats served as nonimmunosuppressed controls. All rats were tested for amphetamine-induced rotational behavior at 3-week intervals. Two immunosuppressed rats were excluded due to severe side effects of the treatment. Functional recovery was seen in 9 of 16 immunosuppressed rats at 12 weeks. Six animals remained functionally recovered at 14 weeks and contained an average of 5750+/-1450 (SEM) dopaminergic neurons. Between 9 and 14 weeks, three immunosuppressed rats rejected their grafts, based on rotation scores and immunohistochemical demonstration of cell infiltrates. One additional immunosuppressed rat showed evidence of ongoing rejection at 14 weeks. The striata in animals with ongoing or recent rejection contained large numbers of CD4- and CD8-positive lymphocytes, NK cells, macrophages, and microglia cells, whereas scar tissue was found in rats with grafts rejected at earlier time points (n = 11). Embryonic porcine ventral mesencephalic tissue matures in the adult rat striatum, reinnervates the host brain, and restores behavioral defects. Immunosuppressive treatment was necessary for long-term graft survival and functional recovery, but did not sufficiently protect from rejection mechanisms. Porcine neural tissue is an interesting alternative to embryonic human tissue for intracerebral transplantation in neurodegenerative diseases. However, to achieve stable graft survival in discordant xenogeneic combinations, an appropriate immunosuppressive treatment or donor tissue modifications are needed.     

Gene transfer of endothelial nitric oxide synthase to pulmonary allografts: impact on acute rejection

Experiments were designed to study whether overexpression of nitric oxide (NO) from endothelial nitric oxide synthase (eNOS) affects acute rejection. Allogenic, orthotopic single-lung transplantation was performed after transbronchial adenoviral-mediated gene transfer (3 × 10⁸ pfu) of either of eNOS or β-galactosidase to donor lungs of rats (n = 6 each). No immunosuppression was used. After 4 days, transplanted lungs were prepared for enzyme activity, cGMP and histology. Calcium-dependent NOS activity, reflecting eNOS, was greater in eNOS-transduced lungs (587 ± 97 vs 2.1 ± 1.4 pmol/mg protein per h, P <0.001). In contrast, calcium-independent NOS activity, reflecting iNOS, was comparable. Concentrations of cGMP were higher in eNOS-transduced lungs (13.2 ± 2.3 vs 4.9 ± 0.5 pmol/mg protein). Positive immunostaining for eNOS was present in pneumocytes only in eNOS-transduced lungs. No difference in histological grade of rejection was observed. eNOS gene transfer to pulmonary allografts results in a functionally active transgene product and increased NO production. Increasing NO from eNOS does not affect histogically identified acute rejection.     

Increased levels of S-100 protein after cardiac surgery with cardiopulmonary bypass and general surgery in children

The aim of this study was to evaluate changes in concentrations of the neurospecific protein S-100 in relation to cardiac surgery with cardiopulmonary bypass (CPB) and noncardiac general surgery in children below 3 years of age. Seventeen children underwent surgery for congenital heart disease and all survived without clinical signs of neurological complications. Samples for plasma concentrations of S-100 in these patients were taken on three occasions in connection with surgery: before the start of surgery, after CPB and finally 16-20 h after CPB. In the noncardiac group of 31 children, S-100 concentrations were measured on two occasions: before surgery and during surgery. In both groups, a significant increase in S-100 concentrations was observed during surgery, although the increase in the CPB group was significantly higher than in the noncardiac group. The CPB group included four children with Down's syndrome who had higher mean S-100 concentrations on all sampling occasions compared to the remaining patients. The peak S-100 concentrations after cardiac surgery were related to the duration of CPB, the time from the termination of CPB to the first post-CPB sample, as well as mean arterial pressure and cerebral arteriovenous lactate difference during rewarming. All the children studied (Down's patients excluded) had age-dependent plasma concentrations of S-100 measured before surgery. It can be concluded that CPB initiates a marked but transient release of S-100 into the systemic circulation during open heart surgery in children who are not developing clinical signs of neurological sequelae.     

Ropivacaine pharmacokinetics after caudal block in 1-8 year old children

We studied the pharmacokinetics after caudal block of ropivacaine(2 mg ml^–1, 1 ml kg^–1) performed in 20 childrenaged 1–8 yr undergoing subumbilical surgery, in this open,non- comparative, multicentre study. Venous blood samples werecollected up to 12–36 h. The mean (SD) peak plasma concentration,0.47 (0.16) mg litre^–1, was achieved after 12–249min. The free fraction was 5% and the highest individual peakplasma concentration of free ropivacaine was 0.04 mg litre^–1.Clearance was 7.4 (1.9) ml min^–1 kg^–1 and the terminalhalf-life 3.2 (0.8) h. Thus, the free plasma concentrationsof ropivacaine were well below those associated with toxic symptomsin adults and the capacity to eliminate ropivacaine seems tobe well developed in this age group. In this open study of 20patients, ropivacaine was well tolerated and provided satisfactorypostoperative pain relief without observable motor block. Br J Anaesth 2000; 85: 506–11 ^* Corresponding author: Paediatric Anaesthesia and Intensive Care,KS/Astrid Lindgren’s Children’s Hospital, SE-17176 Stockholm, Sweden     

Cerebral hemodynamic changes measured by gradient-echo or spin-echo bolus tracking and its correlation to changes in ICA blood flow measured by phase-mapping MRI

Changes in cerebral blood flow (CBF) induced by Acetazolamide (ACZ) were measured using dynamic susceptibility contrast MRI (DSC-MRI) with both spin echo (SE) EPI and gradient echo (GE) EPI, and related to changes in internal carotid artery (ICA) flow measured by phase-mapping. Also examined was the effect of repeated bolus injections. CBF, cerebral blood volume (CBV), and mean transit time (MTT) were calculated by singular value decomposition (SVD) and by deconvolution using an exponential function as kernel. The results showed no dependency on calculation method. GE-EPI measured a significant increase in CBF and CBV in response to ACZ, while SE-EPI measured a significant increase in CBV and MTT. CBV and MTT change measured by SE-EPI was sensitive to previous bolus injections. There was a significant linear relation between change in CBF measured by GE-EPI and change in ICA flow. In conclusion, GE-EPI under the present condition was superior to SE-EPI in monitoring cerebral vascular changes.     

Extramedullary fixation of 569 unstable intertrochanteric fractures: a randomized multicenter trial of the Medoff sliding plate versus three other screw-plate systems

We compared the efficacy of the Medoff sliding plate (MSP) with 3 other screw-plate systems for fixation of unstable intertrochanteric fractures in a randomized multicenter trial of 569 elderly patients. The MSP has biaxial dynamic capacity along both the neck and the shaft of the femur unlike the other systems, which lack dynamic capacity along the shaft. 268 fractures were operated on with the MSP, and 301 with the dynamic hip screw (DHS), with or without a trochanteric stabilizing plate (DHS/TSP) or with the dynamic condylar screw (DCS). The MSP had recently been shown to the surgeons.The patients in the groups were similar as regards age, domestic situation, preinjury walking ability and type of fracture. We followed the patients clinically and radiographically for at least 1 year. There was no significant difference in walking ability at follow-up or rate of return to home. Fixation failure occurred in 18/268 fractures operated on with the MSP, in 8/238 with the DHS, in 3/49 with the DHS/TSP and in 1/14 with the DCS. The difference in the rate of fixation failure was not statistically significant when the MSP group was compared to the 3 other groups. In 14 of the 18 fixation failures in the MSP group, the biaxial dynamic capacity of the MSP had not been used due to technical errors by surgeons, unfamiliar with the new method. No selection bias was found regarding fracture types in the 2 subgroups of patients with correct or inadequate biaxial dynamization. Extramedullary fixation of unstable intertrochanteric fractures with these implants showed a low failure rate. When using the MSP, biaxial dynamization must be correctly performed.     

Rapid appearance and onset of action of insulin aspart in paediatric subjects with type 1 diabetes

The pharmacokinetics of the novel, rapid-acting insulin aspart were compared with those of soluble human insulin following subcutaneous administration in nine children (aged 6–12 years) and nine adolescents (aged 13–17 years) with stable type 1 diabetes. The study had a randomised, double-blind, two-period crossover design. Each patient received a single subcutaneous dose of insulin aspart or human insulin (0.15 IU/kg body weight) 5 min before breakfast and the plasma insulin and glucose concentrations were measured at intervals during the following 5 h. The pharmacokinetic profile of insulin aspart differed significantly from that of human insulin with a higher mean maximum serum insulin (C_{max ins}), 881 ± 321 (SD) pmol/l versus 422 ± 193 pmol/l for human insulin (P < 0.001); and with a shorter median serum insulin t _{max ins}, 40.0 min (interquartile range: 40–50 min) versus 75.0 min (interquartile range: 60–120 min) for human insulin, (P < 0.001). An age-related effect on C_{max ins} and area under the curve (AUC_{0–5h ins}) was observed with higher values in adolescents than in children for both insulin aspart and human insulin. Postprandial glycaemic control was improved with insulin aspart; the baseline-adjusted ΔC_{max glu} being lower for insulin aspart compared with human insulin (increase of 7.6 ± 5.1 versus 9.4 ± 4.4 mmol/l respectively, P < 0.05). The incidence of adverse events was similar for the two insulin types. Conclusion The more rapid onset of action of insulin aspart versus human insulin, previously observed in adults, is confirmed in a paediatric population with type 1 diabetes. Received: 30 June 1999 and in revised form: 20 September 1999 and 23 November 1999 /Accepted: 9 December 1999