Prostaglandin E1 and misoprostol increase epidermal growth factor production in 3D-cultured human annulus cells

Background contextEpidermal growth factor (EGF) is a peptide known to modulate a number of cellular responses including embryogenesis, cell proliferation, and cell survival. Little is known about EGF and its regulation in human annulus cells. Previous work has identified EGF and its receptor in control outer annulus disc tissue, but not in herniated tissue.PurposeTo determine if human annulus cells express EGF in vitro, to determine if the epidermal growth factor-receptor (EGF-r) was expressed in vivo and in vitro in disc cells, to test the effect of EGF on annulus cell proliferation and proteoglycan production in vitro, and to test the effect of prostaglandin E1 (PGE1) and misoprostol on disc cell production of EGF in vitro.Study design/settingStudies were approved by the authors' Human Subjects Institutional review Board. Human disc tissue was used for immunocytochemistry, and human annulus cells were tested in vitro.Patient sampleThirty-four disc specimens were used for studies of proteoglycan production, cell proliferation, and EGF production in vitro. An additional nine discs were used for EGF-r immunolocalization.MethodsDisc tissue was used for immunocytochemical studies for the localization of EGF-r and as a source for cultured annulus cells. Monolayer culture was used to test proliferation responses to 0, 25, 50, or 75 ng/mL EGF over a 2-day culture period. Three-dimensional (3D) culture in a collagen sponge was used to test 100,000 cells cultured in a paired experimental design over 14 days for production of EGF and proteoglycans. Cells were exposed to control conditions, or to either misoprostol at 8 ng/mL or PGE1 at 10^?7 M. Conditioned media was harvested and assayed using an enzyme-linked immunosorbent assay (ELISA) assay with the Human Protein Cytokine Antibody Array I kit. Replicate EGF relative intensity values were averaged and normalized to controls assayed on the same membrane. 3D-cultured cells were also used to confirm EGF gene expression using microarray analysis. Standard statistical methods were used to analyze results.ResultsMicroarray analysis of mRNA from annulus cells in 3D culture confirmed expression of EGF, and immunocytochemistry verified the presence of EGF-r in vitro and in vivo. PGE1, at a dose of 10^?7 M, and misoprostol (a synthetic PGE1 analog) at a dose of 8 ng/mL, both significantly increased EGF levels in annulus cells cultured in 3D compared with control levels (p=.031 and .034, respectively). No significant difference, however, was seen in cell proliferation or in total sulfated proteoglycan production in EGF-exposed annulus cells.ConclusionsData showed that EGF is expressed and produced by annulus cells in vivo and in 3D culture, with significantly greater in vitro EGF produced in the presence of PGE1 or the PGE1 analog misoprostol. Misoprostol, developed for prevention/treatment of nonsteroidal anti-inflammatory-induced gastropathy, has now been reported to have some interesting anabolic effects stimulating osteoblasts during fracture healing and during ovariectomy in animal models. Exogenous EGF did not increase cell proliferation in monolayer, or total production of proteoglycans in 3D culture. Additional work is needed to further delineate the role of EGF in the human disc.     

Prognostic factors in recurrent glioblastoma multiforme and anaplastic astrocytoma treated with selective intra-arterial chemotherapy

BACKGROUND AND PURPOSE: Factors predictive of primary brain tumor outcome have been studied extensively, although the prognostic value of radiologic data, such as MR imaging and angiographic characteristics, has not been studied in depth. The purpose of this study was to determine whether radiologic data were prognostic factors among patients with recurrent glioblastoma multiforme and anaplastic astrocytoma treated with selective intra-arterial chemotherapy. METHODS: Forty-six patients were enrolled in a Phase II study of intra-arterial chemotherapy with carboplatin and Cereport (Alkermes Inc.; Cambridge, MA), a bradykinin analog that selectively increases permeability of the blood-tumor barrier. MR imaging volumes of enhancing tumor, resection cavity, and T2 signal abnormality were measured with T1-weighted and T2-weighted sequences. Volumes were analyzed individually and in various combinations. Tumor vascularity was graded on angiograms. Outcome was measured by time to tumor progression and survival. RESULTS: Of 46 patients included in this study, 41 underwent evaluation. Thirty were male and 11 were female; mean age was 48.5 years. Karnofsky scores ranged from 70 to 100. Thirty-two patients had glioblastoma multiforme, whereas nine had anaplastic astrocytoma. Twenty-eight patients had tumor progression and 13 had stable disease. Twenty-three patients died after an average of 205 days; 18 were surviving at an average of 324 days from the start of intra-arterial chemotherapy. In multivariate analysis, time from diagnosis to intra-arterial chemotherapy was predictive both of time to tumor progression and survival. Net tumor volume and vascularity also were significant for survival. Age, Karnofsky performance status, histologic findings, gender, MR imaging area, resection cavity volume, T2 signal abnormality volume, and various combined volumes were not significant. CONCLUSION: If confirmed by further studies, radiologic factors such as tumor volume and angiographic vascularity should be considered in design and stratification of future chemotherapy trials.     

Anatomic variations of the hook of hamate and the relationship to carpal tunnel syndrome

PURPOSE: To determine the incidence of anatomic variations of the hook of hamate and to evaluate its association with the development of carpal tunnel syndrome (CTS). METHODS: Radiographs of 3,218 hands (2,070 patients) were evaluated. This group included 2,866 hands diagnosed with CTS and 352 hands without the diagnosis of CTS. Using the carpal tunnel view variations of the hook of hamate were identified. Variants were classified based on appearance and measurements. Patients having variant hooks of hamate who were diagnosed with CTS then were compared with patients with variant hooks of hamate who had no evidence of CTS. Endoscopic carpal tunnel release using the Chow technique was performed on all patients with CTS who had a known variation of the hook of hamate without difficulty or complication. RESULTS: Variations of the hook of hamate were found in 96 hands: 42, bipartite hook; 50, hypoplastic hook; and 4, aplastic hook. Ninety-three hands with variant hooks of hamate were diagnosed with CTS. The remaining 3 hands identified with variants had no evidence of CTS. After comparing the 2 groups, we found that the incidence of a variant hook of hamate in the group with CTS was significantly greater than the incidence of variations in the group without CTS. CONCLUSIONS: Three variations of the hook of hamate were identified with radiographic evaluation using the carpal tunnel view. Variations are more prevalent than once thought. There was a significant increase in the incidence of variation in the hook of hamate in the group with CTS compared with the group without CTS.     

A Long-Term Cross-Sectional Study on Gastric Bypass Surgery: Impact of Self-Reported Past Sexual Abuse

Background  This study examined differences in gastric bypass surgical outcomes by comparing two groups of female patients: those with a history of sexual abuse (SA) and those without a history of sexual abuse (NSA). Methods  Participants who agreed to participate in the study were assessed at either 6–18 months or 19–40 months postsurgery. Outcome measures included body mass index (BMI), level of depression as measured through the Beck Depression Inventory, level of self-esteem as measured through the Rosenberg Self-esteem Scale, and BISS as measured through the Body Image State Scale. Two-by-two analyses of variance (ANOVAs) were conducted for each of the four outcome variables. Results  ANOVA results revealed that BMI was the only variable to be found statistically significant among the four dependent measures. At 6–18 months postsurgery, the SA group had significantly higher BMI than the NSA group. Compared BMI during the two postsurgery time periods, the SA group had a significantly lower BMI at 19–40 months than the SA group at 6–18 months postsurgery. Conclusion  The results suggest that females with a history of sexual abuse did not differ from their counterparts with regard to depression, self-esteem, and body dissatisfaction at baseline, as well as years after surgery. Given the improvement in BMI from the sexual abuse group at 6–18 months postsurgery to 19–40 month postsurgery, patients may not be as concerned with maintaining excess weight as a defense against potential future abuse as originally proposed.     

Preoperative FLAC/Granulocyte-Colony-Stimulating Factor Chemotherapy for Stage II Breast Cancer: A Prospective Randomized Trial

Background: Preoperative chemotherapy for stage II breast cancer may reduce locoregional tumors and provides initial treatment for systemic micrometastases. We conducted a prospective, randomized trial to evaluate the ability of intensive preoperative chemotherapy to enhance the outcome of this approach.Methods: Patients with clinical stage II breast cancer (T2N0, T1N1, and T2N1) were prospectively randomized to receive either preoperative or postoperative chemotherapy with five 21-day cycles of fluorouracil, leucovorin calcium, doxorubicin, and cyclophosphamide (FLAC)/granulocyte-colony-stimulating factor. Local therapy consisted of modified radical mastectomy or segmentectomy/axillary dissection/breast radiotherapy, according to patient preference.Results: Fifty-three women were randomized (26 preoperative chemotherapy and 27 postoperative chemotherapy). The objective clinical response rate of the primary tumor to preoperative chemotherapy was 80%, and the pathologic complete response rate was 20%. Preoperative chemotherapy reduced the overall incidence and number of axillary lymph node metastases. There was no difference in the use of breast-conserving local therapy between the two treatment arms. There were 20 local/regional or distant recurrences (9 preoperative and 11 postoperative). There was no difference in the overall or disease-free survival between the preoperative and postoperative chemotherapy arms.Conclusions: Preoperative FLAC/granulocyte-colony-stimulating factor chemotherapy was effective against local/regional tumors in stage II breast cancer but was otherwise comparable to postoperative chemotherapy.     

Diagnostic and therapeutic evaluation of 111In-vinorelbine-liposomes in a human colorectal carcinoma HT-29/luc-bearing animal model

Colorectal carcinoma is a highly prevalent and common cause of cancer in Taiwan. There is still no available cure for this malignant disease. To address this issue, we applied the multimodality of molecular imaging to explore the efficacy of diagnostic and therapeutic nanoradiopharmaceuticals in an animal model of human colorectal adenocarcinoma [colorectal cancer (CRC)] that stably expresses luciferase (luc) as a reporter. In this study, an in vivo therapeutic efficacy evaluation of dual-nanoliposome (100 nm in diameter) encaged vinorelbine (VNB) and (111)In-oxine on HT-29/luc mouse xenografts was carried out. HT-29/luc tumor cells were transplanted subcutaneously into male SCID mice. Multimodality of molecular imaging approaches including bioluminescence imaging (BLI), gamma scintigraphy, whole-body autoradiography (WBAR) and in vivo tumor growth tracing, histopathology and biochemistry/hematology analyses were applied on xenografted SCID mice to study the treatments with 6% polyethylene glycol (PEG) of (111)In-NanoX/VNB-liposomes. In vivo tumor growth tracing and BLI showed that tumor volume could be completely inhibited by the combination therapy with (111)In-VNB-liposomes and by chemotherapy with NanoX/VNB-liposomes (i.e., without Indium-111) (P<.01). The nuclear medicine images of gamma scintigraphy and WBAR also revealed the conspicuous inhibition of tumor growth by the combination therapy with (111)In-VNB-liposomes. Animal body weights, histopathology and biochemistry/hematology analyses were used to confirm the safety and feasibility of radiopharmaceuticals. A synergistic therapeutic effect on CRC xenografted SCID mice was proven by combining an Auger electron-emitting radioisotope (Indium-111) with an anticancer drug (VNB). This study further demonstrates the beneficial potential applications of multimodality molecular imaging as part of the diagnostic and therapeutic approaches available for the evaluation of new drugs and other strategic approaches to disease treatment.     

Functional angiotensin II type 2 receptors inhibit growth factor signaling in LNCaP and PC3 prostate cancer cell lines

BACKGROUND: There is clear evidence of a tissue-based renin-angiotensin system in the prostate and studies to date suggest that AT(1)-receptor blocking drugs inhibit the growth of some prostate cancer cell lines and delay the development of prostate cancer. The present studies examine the action of Ang II in two prostate cancer cell lines and report the presence of functional AT(2)-receptors that regulate the actions of growth factors. METHODS: Immunohistochemistry was used to identify the presence of Ang II and QPCR techniques to examine AT(1)- and AT(2)-receptor mRNA expression in androgen-dependent (LNCaP) and independent (PC3) cell lines. The effects of AT(1)- and AT(2)-receptor activation upon EGF-induced DNA synthesis and ERK2 phosphorylation in these cells were also examined. RESULTS: Functional AT(2)-receptors together with Ang II were identified in both cell lines and stimulation of these receptors inhibited EGF-induced DNA synthesis and ERK2 phosphorylation. AT(1)-receptors, although present in both cell lines, were only functional in LNCaP cells where activation stimulated DNA synthesis. CONCLUSIONS: Functional AT(2)-receptors are present and have the capacity to inhibit EGF-induced prostate cancer cell growth in LNCaP and fast growing androgen-independent PC3 cell lines, whereas functional AT(1)-receptors are found only in LNCaP cells where their activation stimulates DNA synthesis.     

Wound complication of minimally invasive plate osteosynthesis in distal tibia fractures

Nowadays, the use of minimally invasive plate osteosynthesis (MIPO) in the management of fracture of the distal tibia is common. The various advantages of the MIPO technique, namely, preserving blood supply and better bone healing, have been described extensively in the literature. However, this technique is not without complication. Among all the complications, infection is one of the commonest. In the last 3 years, we have performed 48 cases of MIPO in treating distal tibia fractures. Our study was to evaluate the clinical outcome of these cases, with special attention to the infection rate and our experience in managing these infection cases. Our results showed that the average time until the patient started to bear full weight was 9.4 weeks. The average time for bony union was 18.7 weeks. There were 7 cases of late infection among these 48 cases. The rate was 15%. The presence of late infection had no obvious effect on the time to bony union. Twenty-five patients (52%) had the implants removed and the most common reason was skin impingement by the implant. The clinical presentation and management of these late infections are discussed. In conclusion, MIPO fixation of distal tibia fractures using a metaphyseal locking plate is safe and efficient. However, complications such as late wound infection and impingement are relatively common. The overall clinical outcome is still good despite the presence of these complications.     

Selective parathyroid auto‐transplantation during thyroidectomy

Aim: Permanent hypoparathyroidism is a debilitating morbidity following thyroidectomy and parathyroid auto‐transplantation has been shown to be effective in preventing permanent hypoparathyroidism. Controversy exists regarding the benefit of routine versus selective auto‐transplantation. We evaluate the outcome of selective parathyroid auto‐transplantation in our hospital. Methods: A retrospective study was conducted to assess the incidence of postoperative hypocalcaemia. Indication for parathyroid auto‐transplant was doubtful viability of parathyroid gland during thyroidectomy. From 1 July 2000 to 30 June 2005, all patients who underwent total, subtotal and completion thyroidectomy were included. Other outcome measures including recurrent laryngeal nerve injury and operative time were also analyzed. Results: A total of 170 bilateral or completion thyroidectomies were performed within this period. Total, subtotal, and completion total thyroidectomies were performed in 103 (60.6%), 62 (36.5%), and five (2.9%) patients, respectively. Median age was 45 years (range 19–82). One hundred and twenty‐four patients (73%) had benign thyroid disease, and 46 patients (27%) had thyroid carcinoma. Parathyroid auto‐transplant was performed in 35 patients (20.6%). Mean operation time was 204 min (range 95–510 min). There was no difference in the operation time between the patients with parathyroid auto‐transplant and those without auto‐transplant (217 vs 200 min, P = 0.229). Transient hypocalcaemia occurred in 31 patients (18.2%) whereas two patients had permanent hypocalcaemia (1.2%). Permanent recurrent laryngeal nerve injury occurred in one patient (0.6%). Conclusions: The adoption of selective parathyroid auto‐transplant during thyroidectomy achieves an extremely low incidence of permanent hypoparathyroidism without excessive transient hypoparathyroidism.