Delivery of drugs into brain tumors using multicomponent silica nanoparticles.

Glioblastomas are highly lethal cancers defined by resistance to conventional therapies and rapid recurrence. While new brain tumor cell-specific drugs are continuously becoming available, efficient drug delivery to brain tumors remains a limiting factor. We developed a multicomponent nanoparticle, consisting of an iron oxide core and a mesoporous silica shell that can effectively deliver drugs across the blood-brain barrier into glioma cells. When exposed to alternating low-power radiofrequency (RF) fields, the nanoparticle's mechanical tumbling releases the entrapped drug molecules from the pores of the silica shell. After directing the nanoparticle to target the near-perivascular regions and altered endothelium of the brain tumor via fibronectin-targeting ligands, rapid drug release from the nanoparticles is triggered by RF facilitating wide distribution of drug delivery across the blood-brain tumor interface.

Quantitative analysis of technetium-99m-methylene diphosphonate uptake in unilateral hydroxyapatite-coated total hip prostheses: first year of follow-up.

UNLABELLED: A prospective study was performed on 80 patients who had undergone a unilateral hydroxyapatite (HA)-coated total hip arthroplasty to establish the normal periprosthetic uptake of methylenediphosphonate (MDP) as a function of implant age. METHODS: Patients were imaged periodically while they were asymptomatic at 1, 3, 6 and 12 mo postoperatively. Quantitative measurements were performed with a region of interest (ROI) technique. The HA-coated and uncoated areas were marked in comparison with the normal contralateral femur. The uptake ratios of the MDP were determined postoperatively in the following 12 mo. RESULTS: It was found that a decrease of the uptake ratios occurred in all ROIs. However, for the HA-coated areas, the uptake ratios still remained raised as a result of bony ingrowth. CONCLUSION: The results of the first year of follow-up were considered to be a normal database that will be used as a reference when the same group of patients are followed up to 5 yr postoperatively to detect any potential modes of failure of the implant.

Multiparameter flow cytometry as a tool for the detection of micrometastatic tumour cells in the sentinel lymph node procedure of patients with breast cancer.

AIM: To investigate whether multiparameter flow cytometry (MP-FCM) can be used for the detection of micrometastasis in sentinel lymph nodes (SLNs) in breast cancer. METHODS: Formalin fixed, paraffin wax embedded sentinel lymph nodes (n = 238) from 98 patients were analysed. For each lymph node, sections for haematoxylin and eosin (H&E) staining and immunohistochemistry (IHC) for cytokeratin (MNF116) were cut at three levels with a distance of 500 microm. The intervening material was used for MP-FCM. Cells were immunostained with MNF116, followed by an incubation with fluorescein isothiocyanate (FITC) labelled goat antimouse immunoglobulin. DNA was stained using propidium iodide. From each lymph node 100,000 cells were analysed on the flow cytometer. RESULTS: Thirty eight of the 98 patients with breast carcinoma showed evidence of metastatic disease in the SLN by one ore more of the three methods. In 37 of 38 cases where metastatic cells were seen in the routine H&E and/or IHC, more than 1% cytokeratin positive cells were detected by MP-FCM. In 24 patients, metastatic foci were more than 2 mm (macrometastasis) and in 14 these foci were smaller than 2 mm (micrometastasis). In three of these 14 cases, MP-FCM revealed positive SLNs, although this was not seen at first glance in the H&E or IHC sections. After revision of the slides, one of these three remained negative. However, MP-FCM analysis of the cytokeratin positive cells showed an aneuploid DNA peak, which was almost identical to that of the primary breast tumour. Duplicate measurements, done in 41 cases, showed a 99% reproducibility. In five of 14 patients with micrometastasis, one or two metastatic foci were found in the non-SLN. However, in 15 of 24 macrometastases multiple non-SLNs were found to have metastatic tumour. All micrometastases except for the remaining negative one mentioned above showed only diploid tumour cells, despite the fact that their primary tumours contained both diploid and aneuploid tumour cells. In primary tumours with more than 60% aneuploid cells, predominantly aneuploid macrometastasis were found, whereas diploid primary tumours only showed diploid micrometastases or macrometastases in their SLN. Aneuploid SLN macrometastases were associated with non-SLN metastases in five of seven patients, whereas diploid cases showed additional non-SLN metastases in only seven of 16 patients. CONCLUSION: In all cases, MP-FCM was sufficient to detect micrometastatic tumour cells in a large volume of lymph node tissue from SLNs. In some cases it was superior to H&E and IHC staining. Approximately 30% of SLN micrometastases are accompanied by additional non-SLN metastases. The size of the aneuploid fraction (> 60%) in the primary tumour may influence the risk of having both SLN and non-SLN metastases.

Intracavitary brachytherapy of cystic craniopharyngiomas.

Visual function, endocrinological status, and radiological outcome are reported in 31 patients harboring a cystic craniopharyngioma, who underwent 35 intracavitary brachytherapy procedures with yttrium-90. In 26 of these patients intracavitary brachytherapy was the primary treatment. The follow-up period ranged from 2 to 80 months (41 +/- 22 months, mean +/- standard deviation). Five patients died from tumor-related causes. Endocrine recovery was modest. Prior to brachytherapy, visual acuity was diminished in 38 eyes and field defects were present in 46. Funduscopy before treatment revealed optic atrophy in 47% of the eyes. Visual acuity improved in 29% of the eyes studied, remained stable in 13%, and deteriorated in 58%. Visual field defects improved in 28% of the eyes studied, remained stable in 20%, and deteriorated in 52%. The possible causes for deterioration in visual function are discussed. Complete resolution of 10 cysts was noted. In 12 patients the size of the cyst decreased; however, in three of these patients new cyst formation took place. The cyst size stabilized in six cases and increased in three. Although there is still a substantial degree of visual function deterioration following intracavitary brachytherapy, morbidity is otherwise low, making this treatment modality a reasonable alternative to craniotomy.

Hydroxyapatite-coated acetabular components. Histological and histomorphometric analysis of six cups retrieved at autopsy between three and seven years after successful implantation.

BACKGROUND: Important questions remain regarding the use of hydroxyapatite-coated acetabular components in total hip arthroplasty. What is the relation of resorption of the hydroxyapatite coating to enduring fixation? Will unresorbed or dislodged hydroxyapatite particles cause adverse tissue reactions? Retrieval studies of clinically well-functioning acetabular components should help to answer these questions. METHODS: We examined six clinically successful hydroxyapatite-coated cementless acetabular components that were retrieved at autopsy between 3.3 and 6.6 years after implantation. All components were of the same design. The prostheses and the surrounding bone were prepared for qualitative histological and quantitative histomorphometric analysis. The percentage of bone growth onto the implant, the relative bone area around the implant, the extent of residual hydroxyapatite coating, and the coating thickness were measured. RESULTS: All of the cups showed bone ongrowth, with a mean bone-implant contact (and standard deviation) of 36.5% +/- 13.5%. The contact area was the same in all three zones delineated by DeLee and Charnley. The extent and thickness of the hydroxyapatite layer were much reduced in the specimens from older patients and in those associated with a longer duration of implantation. Degradation of the hydroxyapatite coating by osteoclasts was observed. We did not observe loose hydroxyapatite granules far from the coating, nor did we note any adverse tissue reaction to these granules. In contrast, polyethylene debris was noted in approximately half of the empty screw-holes. CONCLUSIONS: Cell-mediated hydroxyapatite resorption seems to be the main reason for loss of hydroxyapatite coating. The area of bone ongrowth was within a certain range (20% to 50%) of the measured surfaces, and it was independent of the amount of hydroxyapatite residue. The hydroxyapatite coating showed a slow rate of resorption with time, without any adverse tissue reactions.

Postmenopausal endometrial patterns and serum estradiol concentrations.

Eighty postmenopausal women were subjected to endometrial biopsy. Inadequate biopsy was recorded in 30 cases. In the remaining cases (n = 50) the correlation between endometrial patterns and serum estradiol (E2) was performed. These cases were presenting with uterine bleeding (n = 38) or minor gynecological symptoms (n = 12). Proliferative endometrium was the predominant endometrial pattern whereas endometrial malignancy was only present in 15.8% of the bleeding cases. Serum E2 was significantly elevated in cases having malignant endometrium or adenomatous hyperplasia compared to cases having other endometrial patterns. Serum E2 measurement is recommended as a simple screening test for the detection of postmenopausal endometrial hyperplasia and/or malignancy.

The influence of implant design on periprosthetic bone remodelling of two types of uncemented HA-coated hip stems. A two-year follow-up study using DEXA.

UNLABELLED: Proximal bone resorption and an increased fracture rate in the ABG-I stem has been shown. For these reasons the ABG-I stem design was changed to the ABG-II. In this study periprosthetic bone loss around the ABG-I vs ABG-II is compared to verify if the design changes resulted in improved proximal bone preservation. METHODS: 51 patients were randomised to either the ABG-I or ABG-II hip prosthesis. Periprosthetic BMD change at various time points was measured using DEXA. Between the two groups (age, gender, weight etc.) no statistical difference was encountered. Compared to the baseline at two years the ABG-II preserved bone better proximally (e.g. zone 7: ABG-II: -3.7%, ABG-I: -11.9%, p=0.05) than the ABG-I. Distally, the trend was opposite and less bone loss was measured for the ABG-I than the ABG-II in zones 3, 4 and 5 (n.s.). CONCLUSION: this study confirms the philosophy behind the design changes from the ABG-I to ABG-II stem where increased elasticity, more proximal HA-coating, a shorter and distally polished stem, were meant to reduce proximal bone resorption. In future this may lead to fewer periprosthetic fractures and to less complicated revision surgery.

The hydroxyapatite-ABG hip system: 5- to 7-year results from an international multicentre study. The International ABG Study Group.

A proximally hydroxyapatite (HA)-coated hip prosthesis designed for proximal stem bonding and stress transfer was studied in a consecutive series of 398 patients in an ongoing, prospective multicenter study. Follow-up was 5 to 7 years. The clinical results were excellent with a mean preoperative Merle d'Aubigné score of 8.5 and 17.3 at 5 years. Only mild thigh pain not necessitating analgesics or a walking stick was reported in 3.6% at 5 years. Three cups and 3 stems had to be revised, all before the 2-year assessment and mainly for technical reasons. No components needed revision after 2 years. The 5-year HA-coated component survival was 99.2%. Serial radiographs showed excellent osseointegration, which was independent of pre-existing bone stock. The rate of radiographic bone remodeling was highest during the first 3 years, and positive bone remodeling (bone formation) preceded negative bone remodeling (bone resorption). The concept of transitional load transfer from proximal to distal could be acknowledged, with proximal load transfer highest in 77%. The combination of anatomic stem design with distal overreaming and proximal HA coating was thought to be the reason for these excellent results. Proximal circumferential osseointegration seems to be real because no linear or distal osteolysis was observed.

Hydroxyapatite coated hip prosthesis followed up for 5 years.

We prospectively studied 250 patients with a proximal hydroxyapatite coated hip prosthesis. The follow-up period was 5 years. All components showed osseointegration except for one deep infection. The morphology of bone remodeling with either endosteal bone formation or periosteal bone formation was dependent on the way the stem filled the medullary canal. No linear or distal osteolysis around the stems was observed.

Periprosthetic bone remodelling of two types of uncemented femoral implant with proximal hydroxyapatite coating: a 3-year follow-up study addressing the influence of prosthesis design and preoperative bone density on periprosthetic bone loss.

Periprosthetic bone loss is a major cause of concern in patients undergoing total hip arthroplasty (THA). Further studies are required to identify the factors determining the pattern of bone remodelling following THA and obtain improvements in the design and durability of prostheses. In this study, we monitored periprosthetic bone loss around two different types of hydroxyapatite coated femoral implant over a 3-year period to evaluate their design and investigate the relationship with the preoperative bone mineral density (BMD) at the spine, hip and forearm. Sixty patients (35 F, 25 M, mean age 63 years, range 46-75 years) undergoing THA were randomised to either the Anatomic Benoist Girard (ABG) or Mallory-Head (MH) femoral stem. Preoperative dual-energy X-ray absorptiometry (DXA) scans were acquired of the posteroanterior (PA) and lateral lumbar spine, the contralateral hip and the non-dominant forearm. Postoperative DXA scans were performed to measure periprosthetic BMD at 10 days (treated as baseline), 6 weeks, and 3, 6, 12, 24 and 36 months after THA using a standard Gruen zone analysis. Results were expressed as the percentage change from baseline and the data examined for the differences in bone loss between the different Gruen zones, between the ABG and MH stems, and the relationship with preoperative BMD. A total of 50 patients (24 ABG, 26 MH) completed the study. Three months after THA there was a statistically significant BMD decrease in every Gruen zone that varied between 5.6% and 13.8% for the ABG prosthesis and between 3.8% and 8.7% for the MH prosthesis. Subsequently, in most zones BMD reached a plateau or showed a small recovery. However, BMD continued to fall in Gruen zones 1 and 7 in ABG patients and Gruen zone 1 in MH patients. Bone loss was less in every Gruen zone in MH patients compared with ABG with the largest difference (10%, P=0.018) in Gruen zone 7. Highly significant relationships were found between periprosthetic bone loss and preoperative BMD measured at the PA spine ( P<0.001), total hip ( P=0.004) and total distal radius ( P<0.001). This study showed differences between two different designs of hydroxyapatite-coated implant that confirmed that prosthesis design influences periprosthetic bone loss. The study also showed that patients' bone density measured at the spine, hip or forearm at the time of operation was a major factor influencing bone loss around the femoral stem.

Pneumocystis carinii: recognition of the infection in albino rats using different stains.

Pneumocystis carinii is a commensal protozoan which may cause pneumonia in hosts with compromised immune status and may end fatally. Since effective management of pneumocystic pneumonia depends on rapid and accurate recognition of the disease, so, the present study aims to throw lights on the best staining method for cytodiagnosis of this organism with the sequential pathological changes in the infected lungs. An immunosuppression state was induced in albino rats for 6-8 weeks then rats were sacrificed weekly & lungs were examined for infection using different stains. In stained smears, intracystic bodies have been identified using Giemsa, Papanicolaou & Toluidine blue stains. On the other hand, cysts were inspected in paraffin sections using Gomori methenamine silver nitrate (GMS) & weight gram stains. Histopathologically, in sections stained with H & E, features of Pneumocystis carinii pneumonia were obvious, foamy exudation, inflammatory infiltration formed mainly of histiocytes, plasma cells, lymphocytes, thickening of alveolar septa and lastly formation of hyaline membrane in some alveoli.

Oral contraceptive pills in experimental schistosomiasis mansoni: parasitological, biochemical, histopathological and ultrastructural studies.

This study examines the effect of intake of oral contraceptive steroid in S. mansoni infected mice as regards parasitological, biochemical, histopathological and ultrastructural changes. Three groups were studied group I: S. mansoni infected mice received contraceptive pills six weeks post-infection (p.i.), group II: S. mansoni infected control and group III: non-infected control. Administration of oral contraceptive pills to S. mansoni infected mice results in significant reduction in tissue egg count with a high percentage of dead eggs as observed in the oogram study. There was statistically significant increase in all parameters of the hepatic functions except the prothrombin activity which showed significant decrease. Histopathological examination revealed less cellular granulomas with marked fibrosis, foci of hyperplastic changes in the liver cells and accentuation of cellular degenerative changes. On the subcellular level, there were marked proliferation and dilatation of rER and SER, evident increase of ribosomes, alteration in mitochondrial cristae with intra luminal inclusions and increase glycogen content of hepatocytes.

Radiological and scintigraphic findings in patients with a clinical history of chronic inflammatory back pain.

The prevalence of radiological abnormalities of the sacroiliac joints, the manubriosternal joint, and the lumbar spine were assessed, and quantitative sacroiliac scintigraphy was performed in 151 patients with a history of chronic inflammatory back pain and in 31 controls with non-inflammatory back pain. Sacroiliitis was found in 124 patients (82%), manubriosternal lesions in 84 patients (56%), and lesions of the lumbar spine in 58 patients (38%). In 19 patients (13%), manubriosternal lesions provided the sole radiological abnormality and in five patients (3%) no radiological abnormality could be demonstrated at any of these sites. Quantitative sacroiliac scintigraphy showed increased values in 69 of 137 patients examined (50%), but also in 10 out of 12 control patients with disc degeneration (83%) and is, therefore, nonspecific for inflammatory lesions. Radiological examination of the manubriosternal joint is recommended in patients with inflammatory back pain without radiographic evidence of sacroiliitis.