Dorsolateral prefrontal and superior temporal volume deficits in first–episode psychoses that evolve into schizophrenia

Regions with a likely involvement in schizophrenia may differ between patients with firstepisodes of psychosis respectively with and without evolution into schizophrenia following the initial episode. We have used magnetic resonance imaging (MRI) to assess the volumes of dorsolateral prefrontal (DLPF) and superior temporal gyrus (STG) in a group of 37 first–episode psychotic patients. After an initial MRI study performed by the time of the first episode, the subjects were followed for two years. After this period 22 cases were diagnosed with schizophrenia, while the other 15 did not show clinical evidence for this illness. A Talairach–based tool was used for segmentation and volumetry of the MRI scans. A group of 44 healthy controls was used for comparison and, using lineal regression, to control for the normal effects of age and intracranial volume on the regional parameters of the patients. By the time of their first episode, patients with schizophrenia had significantly less grey matter in the right DLPF and STG regions as compared to both controls and FE without schizophrenia. Nevertheless, these parameters could not predict final diagnosis in a discriminant analysis model. Our findings indicate that subtle structural defects are already found by the time of the first psychotic break in schizophrenia, although clinical implications for these differences seem unclear.     

Midbrain dopamine D2/3 receptor binding in schizophrenia

Several studies suggest that dysregulation of dopaminergic transmission in the midbrain and thalamus may contribute to the symptomatology of schizophrenia. The objective of this study was to examine the putative alteration of dopamine D_2/3 receptor densities in the thalamus and midbrain of drug-naïve schizophrenic patients. We used the high-affinity single-photon emission tomography ligand [¹²³I]epidepride for imaging D_2/3 receptor binding sites in six neuroleptic-naïve schizophrenic patients, and seven healthy controls. Schizophrenic symptoms were evaluated by the Positive and Negative Syndrome Scale. Significantly lower D_2/3 values were observed in the midbrain of patients with schizophrenia compared to controls (P = 0.02). No statistically significant difference was observed in the thalamus between two groups. Negative correlations were found between thalamic D_2/3 receptor binding and general psychopathological schizophrenic symptoms (r from ?0.78 to ?0.92). These observations implicate altered dopaminergic activity in the midbrain of schizophrenic patients.     

Effect of Prior Salter or Chiari Osteotomy on THA with Developmental Hip Dysplasia

Background  

Controversy exists regarding the outcome of THA after prior pelvic osteotomy.     

Akt‐mediated mechanotransduction in murine fibroblasts during hypertrophic scar formation

Although numerous factors are implicated in skin fibrosis, the exact pathophysiology of hypertrophic scarring remains unknown. We recently demonstrated that mechanical force initiates hypertrophic scar formation in a murine model, potentially enhancing cellular survival through Akt. Here, we specifically examined Akt‐mediated mechanotransduction in fibroblasts using both strain culture systems and our murine scar model. In vitro, static strain increased fibroblast motility, an effect blocked by wortmannin (a phosphoinositide‐3‐kinase/Akt inhibitor). We also demonstrated that high‐frequency cyclic strain was more effective at inducing Akt phosphorylation than low frequency or static strain. In vivo, Akt phosphorylation was induced by mechanical loading of dermal fibroblasts in both unwounded and wounded murine skin. Mechanically loaded scars also exhibited strong expression of α‐smooth muscle actin, a putative marker of pathologic scar formation. In vivo inhibition of Akt increased apoptosis but did not significantly abrogate hypertrophic scar development. These data suggest that although Akt signaling is activated in fibroblasts during mechanical loading of skin, this is not the critical pathway in hypertrophic scar formation. Future studies are needed to fully elucidate the critical mechanotransduction components and pathways which activate skin fibrosis.     

Vasculogenic stem cell mobilization and wound recruitment in diabetic patients: Increased cell number and intracellular regulatory protein content associated with hyperbaric oxygen therapy

Diabetic patients undergoing hyperbaric oxygen therapies (HBO₂T) for refractory lower extremity neuropathic ulcers exhibit more than a twofold elevation (p=0.004) in circulating stem cells after treatments and the post‐HBO₂T CD34⁺ cell population contains two‐ to threefold higher levels of hypoxia inducible factors‐1, ‐2, and ‐3, as well as thioredoxin‐1 (p<0.003), than cells present in blood before HBO₂T. Skin margins obtained from 2‐day‐old abdominal wounds exhibit higher expression of CD133, CD34, hypoxia inducible factor‐1, and Trx‐1 vs. margins from refractory lower extremity wounds and expression of these proteins in all wounds is increased due to HBO₂T (p<0.003). HBO₂T is known to mobilize bone marrow stem cells by stimulating nitric oxide synthase. We found that nitric oxide synthase activity is acutely increased in patients' platelets following HBO₂T and remains elevated for at least 20 hours. We conclude that HBO₂T stimulates vasculogenic stem cell mobilization from bone marrow of diabetics and more cells are recruited to skin wounds.     

Update on DCIS Outcomes from the American Society of Breast Surgeons Accelerated Partial Breast Irradiation Registry Trial

Background

Since the initial reports on use of MammoSite accelerated partial breast irradiation (APBI) for treatment of ductal carcinoma in situ (DCIS), additional follow-up data were collected. We hypothesized that APBI delivered via MammoSite would continue to be well tolerated, associated with a good cosmetic outcome, and carry a low risk for recurrence in patients with DCIS.

Materials and Methods

From 2002–2004, 194 patients with DCIS were enrolled in a registry trial to assess the MammoSite. Follow-up data were available for all 194 patients. Median follow-up was 54.4 months; 63 patients had at least 5 years of follow-up. Data obtained included patient-, tumor-, and treatment-related factors, and recurrence incidence.

Results

Of the 194 patients, 87 (45%) had the MammoSite placed at lumpectomy; 107 patients (55%) had the device placed postlumpectomy. In the first year of follow-up, 16 patients developed a breast infection, though the method of device placement was not associated with infection risk. Also, 46 patients developed a seroma that was associated with applicator placement at the time of lumpectomy (P = 0.001). For patients with at least 5 years of follow-up, 92% had favorable cosmetic results. There were 6 patients (3.1%) who had an ipsilateral breast recurrence, with 1 (0.5%) experiencing recurrence in the breast and axilla, for a 5-year actuarial local recurrence rate of 3.39%.

Conclusions

During an extended follow-up period, APBI delivered via MammoSite continued to be well tolerated for patients with DCIS. Use of this device may make lumpectomy possible for patients who would otherwise choose mastectomy because of barriers associated with standard radiation therapy.     

Guideline Recommended Gastric Cancer Care in the Elderly: Insights into the Applicability of Cancer Trials to Real World

Background

Given the underrepresentation of older persons in cancer trials, the association between increasing age and receipt of recommended gastric cancer care in the United States was examined.

Materials and Methods

Using the 1998–2006 SEER database, 8637 Medicare-eligible patients, aged ≥65 years who underwent gastrectomy for nonmetastatic gastric adenocarcinoma were identified. Multivariate analyses was used to assess the effect of increasing age on receipt of recommended gastric cancer care (adequate lymph node evaluation [≥15 lymph nodes] and adjuvant radiation therapy for AJCC Ib–IVM0) and cancer-specific mortality controlling for covariates.

Results

While 61% of gastric cancer operations were performed in patients ≥65 years, less than 30% received adequate lymphadenectomy or adjuvant radiation therapy. Older patients were less likely to receive adequate nodal evaluation and adjuvant radiotherapy (P < 0.0001). These findings persisted on multivariate analyses. Older age was also associated with worse cancer-specific mortality. Because an age-tumor location interaction for cancer mortality (P = 0.047) was observed, stratified analyses were performed which showed that the adverse effect of older age on cancer-specific mortality was augmented in proximal gastric cancers.

Conclusions

This population-based study showed significant age-based variations in gastric cancer care. These results should encourage assessment of generalizability of gastric cancer trials to this expanding population of elderly in the era of comparative effectiveness research.     

Hepatic Intra-Arterial Injection of Drug-Eluting Bead, Irinotecan (DEBIRI) in Unresectable Colorectal Liver Metastases Refractory to Systemic Chemotherapy: Results of Multi-Institutional Study

Introduction

Response rates and overall outcome for patients who have failed first-line and in some cases second-line chemotherapy are as low as 12% and 7 months, respectively. The aim of this study is to evaluate the efficacy of hepatic arterial sulfonate hydrogel microsphere (drug-eluting beads), irinotecan preloaded therapy (DEBIRI) in metastatic colorectal cancer refractory to systemic chemotherapy.

Methods

This was a multicenter multinational single-arm study of metastatic colorectal cancer patients who received DEBIRI after failing systemic chemotherapy from 10/2006 to 8/2008. Primary endpoints were safety, tolerance, tumor response rates, and overall survival.

Results

Fifty-five patients who had received prior systemic chemotherapy and who underwent a total of 99 DEBIRI treatments were reviewed. The median number of DEBIRI treatments was 2 (range 1–5), median treatment dose was 100 mg (range 100–200 mg), with total hepatic treatment of 200 mg (range 200–650 mg), with 86% of treatments performed as lobar infusion and 30% of patients treated with concurrent simultaneous chemotherapy. Adverse events occurred in 28% of patients with median grade of 2 (range 1–3) with no deaths at 30 days post procedure. Response rates were 66% at 6 months and 75% at 12 months. Overall survival in these patients was 19 months, with progression-free survival of 11 months.

Conclusions

Hepatic arterial drug-eluting bead, irinotecan (DEBIRI) was safe and effective in treatment of metastatic colorectal cancer (MCC) refractory to multiple lines of systemic chemotherapy. DEBIRI is an acceptable therapy for treatment of metastatic colorectal cancer to the liver.