Temperature-controlled power modulation compensates for heterogeneous nanoparticle distributions: a computational optimization analysis for magnetic hyperthermia

Purpose: To study, with computational models, the utility of power modulation to reduce tissue temperature heterogeneity for variable nanoparticle distributions in magnetic nanoparticle hyperthermia.

Methods: Tumour and surrounding tissue were modeled by elliptical two- and three-dimensional computational phantoms having six different nanoparticle distributions. Nanoparticles were modeled as point heat sources having amplitude-dependent loss power. The total number of nanoparticles was fixed, and their spatial distribution and heat output were varied. Heat transfer was computed by solving the Pennes’ bioheat equation using finite element methods (FEM) with temperature-dependent blood perfusion. Local temperature was regulated using a proportional-integral-derivative (PID) controller. Tissue temperature, thermal dose and tissue damage were calculated. The required minimum thermal dose delivered to the tumor was kept constant, and heating power was adjusted for comparison of both the heating methods.

Results: Modulated power heating produced lower and more homogeneous temperature distributions than did constant power heating for all studied nanoparticle distributions. For a concentrated nanoparticle distribution, located off-center within the tumor, the maximum temperatures inside the tumor were 16% lower for modulated power heating when compared to constant power heating. This resulted in less damage to surrounding normal tissue. Modulated power heating reached target thermal doses up to nine-fold more rapidly when compared to constant power heating.

Conclusions: Controlling the temperature at the tumor-healthy tissue boundary by modulating the heating power of magnetic nanoparticles demonstrably compensates for a variable nanoparticle distribution to deliver effective treatment.     

Alterations of paraoxonase and platelet-activating factor acetylhydrolase activities in patients on peritoneal dialysis.

OBJECTIVE: The more atherogenic lipid profile seen in peritoneal dialysis (PD) patients cannot fully explain the increased incidence of atherosclerosis in this population. Oxidative modification of low-density lipoproteins (LDL) is considered to play a central role in the atherogenic process, whereas high-density lipoprotein (HDL) protects LDL from oxidation. On the other hand, it has been suggested that the LDL and HDL of PD patients are more resistant to oxidation than those of control subjects, while PD-HDL equally protects LDL from oxidation compared to control-HDL. Two HDL-associated enzymes have been shown to protect both LDL and HDL from oxidation: paraoxonase (PON1) and HDL-associated platelet-activating factor acetylhydrolase (HDL-PAF-AH). Furthermore, low PON1 activity and high total plasma PAF-AH concentration, which represents mainly the LDL-associated enzyme, have been shown to be independent risk factors for coronary artery events in the general population. However, there are limited data regarding possible alterations of these enzymes in PD patients. The aim of our study was to examine the possible alterations of PON1 and PAF-AH activities in patients undergoing PD. DESIGN: A cross-sectional study. SETTING: A university medical center. PARTICIPANTS: 56 PD patients of Caucasian origin and 86 matched controls were studied. MEASUREMENTS: In all subjects, serum PON1 activity toward paraoxon (paraoxonase) and phenylacetate (arylesterase), as well as total serum and HDL-PAF-AH activities were measured; PON1 genetic polymorphisms known to influence PON1 activity (Q192R and M55L) were determined. RESULTS: The PD patients exhibited significantly increased serum PON1 (paraoxonase) and PON1 (arylesterase) activities compared to controls, regardless of the PON1 polymorphisms or the levels of HDL cholesterol. Additionally, PD patients had significantly elevated activities of total serum PAF-AH and HDL-PAF-AH, independently of the levels of LDL or HDL cholesterol. The ratio of HDL-PAF-AH/ total PAF-AH, which has recently been suggested to be a potential marker of atherogenicity, was decreased in these patients compared to controls. Moreover, no difference in the prevalence of PON1 polymorphisms between PD patients and controls was found. CONCLUSION: The elevated activities of PON1 and HDL-PAF-AH could explain the increased resistance of PD-HDL to oxidation; the higher activity of total PAF-AH and the decreased HDL-PAF-AH/ total PAF-AH ratio could contribute to the increased incidence of atherosclerosis in these patients.     

Aggregation of childhood leukemia in geographic areas of Greece)

A total of 872 children aged up to 14 years, who were diagnosed withleukemia in Greece during the decade 1980-89, were allocated by place ofresidence to the 601 administrative districts of the country. Evaluation ofspatial clustering was done using the Potthoff-Whittinghill method, whichvalidly assesses heterogeneity of leukemia risk among districts with variableexpected numbers of cases. There was highly significant evidence for spatialclustering occurring particularly among children living in urban and, to alesser extent, semi-urban areas. The evidence was stronger for childrenyounger than 10 years old, applied also to children in different five-yearage groups, and persisted when cases of acute lymphoblastic leukemia wereanalyzed separately. These findings provide support to the hypothesis thatlocalized environmental exposures could contribute to the etiology ofchildhood leukemia, but they cannot distinguish between exposures of physicalor chemical nature, nor can they exclude socially conditioned patterns ofexposure to infectious agents.     

Primary ilio-psoas abscess extending to the thigh in a neonate: US, CT and MR findings

Psoas abscess in children, and especially in neonates, is an uncommon condition which is difficult to diagnose clinically. The US, CT and MR findings of a psoas abscess in a neonate, which extended to the thigh, are reported. Imaging was helpful in revealing the abnormality, in demonstrating its extension and in determining its nature. The child was treated conservatively and the abscess resolved, leaving atrophy of the psoas muscle. Received: 24 June 1997 Accepted: 9 January 1998     

Antipsychotics increase vesicular glutamate transporter 2 (VGLUT2) expression in thalamolimbic pathways

Recently the two vesicular-glutamate-transporters VGLUT1 and VGLUT2 have been cloned and characterized. VGLUT1 and VGLUT2 together label all glutamatergic neurons, but because of their distinct expression patterns in the brain they facilitate our ability to define between a VGLUT1-positive cortical and a VGLUT2-positive subcortical glutamatergic systems. We have previously demonstrated an increased cortical VGLUT1 expression as marker of antidepressant activity. Here, we assessed the effects of different psychotropic drugs on brain VGLUT2 mRNA and protein expression. The typical antipsychotic haloperidol, and the atypicals clozapine and risperidone increased VGLUT2 mRNA selectively in the central medial/medial parafascicular, paraventricular and intermediodorsal thalamic nuclei; VGLUT2 protein was accordingly amplified in paraventricular and ventral striatum and in prefrontal cortex. The antidepressants fluoxetine and desipramine and the sedative anxiolytic diazepam had no effect. These results highlight the implication of thalamo-limbic glutamatergic pathways in the action of antipsychotics. Increased VGLUT2 expression in these neurons might constitute a marker for antipsychotic activity and subcortical glutamate neurotransmission might be a possible novel target for future generation antipsychotics.     

Laparoscopic transabdominal preperitoneal repair of inguinal hernia under spinal anesthesia: a pilot study

Background

The laparoscopic transabdominal preperitoneal (TAPP) inguinal hernia repair is an evolving technique associated with the well-known advantages of a minimally invasive approach. However, general anesthesia is routinely required for the procedure. Based on our previous experience in regional anesthesia for laparoscopic procedures, we designed a pilot study to assess the feasibility and safety of performing laparoscopic TAPP repair under spinal anesthesia.

Methods

Forty-five American Society of Anesthesiologists I or II patients with a total of 50 inguinal hernias underwent TAPP repair under spinal anesthesia, using a low-pressure CO₂ pneumoperitoneum. Five patients had bilateral hernias, and 4 patients had recurrent hernias. Thirty hernias were indirect and the remaining direct. Intraoperative incidents, postoperative pain complications, and recovery in general as well as patient satisfaction at the follow-up examination were prospectively recorded.

Results

There was 1 conversion from spinal to general anesthesia and 2 conversions from laparoscopic to the open procedure at a median operative time of 50 minutes (range 30-130). Ten patients complained of shoulder pain during the procedure, and 6 patients suffered hypotension intraoperatively. The median pain score (visual analog scale) was 1 (0-5) at 4 hours after the completion of the procedure, 1.5 (0-6) at 8 hours, and 1.5 (0-5) at 24 hours, and the median hospital stay was 1 day (range 1-2). Sixteen patients had urinary retention requiring instant catheterization. At a median follow-up of 20 months (range 10 months-28 months), no recurrence was detected.

Conclusions

TAPP repair is feasible and safe under spinal anesthesia. However, it seems to be associated with a high incidence of urinary retention. Further studies are required to validate this technique.     

Endoscopic and laparoscopic treatment of ureteropelvic junction obstruction

PURPOSE: Although open pyeloplasty remains the gold standard for treating ureteropelvic junction obstruction, endourology and laparoscopy have revolutionized the management of upper tract stenosis. We present our diagnostic and minimally invasive therapeutic algorithm for the treatment of ureteropelvic junction obstruction. MATERIALS AND METHODS: A total of 13 females and 9 males with a mean age of 34.2 years suffering from ureteropelvic junction obstruction were treated with percutaneous endopyelotomy or laparoscopic dismembered pyeloplasty and followed for 47 to 61 months (mean 53.8) and 47 to 62 months (mean 52.5), respectively. Diagnosis was based on findings of ultrasound, excretory urography, furosemide washout renogram and retrograde ureteropyelography. In cases of ureteral kinking color duplex sonography and spiral computerized tomography were performed. In 14 patients with intrinsic stenosis percutaneous endopyelotomy was performed, while the remaining 8 patients (5 with crossing vessels, 2 with an extremely distended pelvis and 1 with a 2.5 cm. stricture) were treated with a laparoscopic dismembered Anderson-Hynes pyeloplasty. RESULTS: In the endopyelotomy group (success rate 92.8%), mean operation time was 1.2 hours, estimated blood loss was 152 ml., unit doses of analgesics were 5.4 tablets, days of hospitalization were 4.2 and time to return to normal activities was 15.7 days. In the laparoscopic group (success rate of 100%) the aforementioned variables were 3.5 hours (p <0.05), 150 ml., 6.3 tablets, 5 and 17.8 days, respectively. Long-term followup excretory urography and/or diuretic renal scan demonstrated improvement in all patients. CONCLUSIONS: Percutaneous endopyelotomy should be the treatment of choice for intrinsic ureteropelvic junction obstruction. Laparoscopic dismembered pyeloplasty, although technically challenging, provides excellent results for extrinsic or complicated ureteropelvic junction stenosis.