Gray matter textural heterogeneity as a potential in-vivo biomarker of fine structural abnormalities in Asperger syndrome.

Brain imaging studies contribute to the neurobiological understanding of Autism Spectrum Conditions (ASC). Herein, we tested the prediction that distributed neurodevelopmental abnormalities in brain development impact on the homogeneity of brain tissue measured using texture analysis (TA; a morphological method for surface pattern characterization). TA was applied to structural magnetic resonance brain scans of 54 adult participants (24 with Asperger syndrome (AS) and 30 controls). Measures of mean gray-level intensity, entropy and uniformity were extracted from gray matter images at fine, medium and coarse textures. Comparisons between AS and controls identified higher entropy and lower uniformity across textures in the AS group. Data reduction of texture parameters revealed three orthogonal principal components. These were used as regressors-of-interest in a voxel-based morphometry analysis that explored the relationship between surface texture variations and regional gray matter volume. Across the AS but not control group, measures of entropy and uniformity were related to the volume of the caudate nuclei, whereas mean gray-level was related to the size of the cerebellar vermis. Similar to neuropathological studies, our study provides evidence for distributed abnormalities in the structural integrity of gray matter in adults with ASC, in particular within corticostriatal and corticocerebellar networks. Additionally, this in-vivo technique may be more sensitive to fine microstructural organization than other more traditional magnetic resonance approaches and serves as a future testable biomarker in AS and other neurodevelopmental disorders.

Hepatic entropy and uniformity: additional parameters that can potentially increase the effectiveness of contrast enhancement during abdominal CT.

AIM: To determine how hepatic entropy and uniformity of computed tomography (CT) images of the liver change after the administration of contrast material and to assess whether these additional parameters are more sensitive to tumour-related changes in the liver than measurements of hepatic attenuation or perfusion. MATERIALS AND METHODS: Hepatic attenuation, entropy, uniformity, and perfusion were measured using multi-phase CT following resection of colorectal cancer. Based on conventional CT and fluorodeoxyglucose positron emission tomography, 12 patients were classified as having no evidence of malignancy, eight with extra-hepatic tumours only, and eight with metastatic liver disease. RESULTS: Hepatic attenuation and entropy increased after CM administration whereas uniformity decreased. Unlike hepatic attenuation, entropy and uniformity changed maximally in the arterial phase. No significant differences in hepatic perfusion or attenuation were found between patient groups, whereas arterial-phase entropy was lower (p=0.034) and arterial-phase uniformity was higher (p=0.034) in apparently disease-free areas of liver in patients with hepatic metastases compared with those with no metastases. CONCLUSION: Temporal changes in hepatic entropy and uniformity differ from those for hepatic attenuation. By reflecting the distribution of hepatic enhancement, these additional parameters are more sensitive to tumour-related changes in the liver than measurements of hepatic attenuation or perfusion.

Proceedings of a GOG workshop on intraperitoneal therapy for ovarian cancer.

Ovarian cancer is the leading cause of gynecologic cancer deaths in the U.S. The concept of intraperitoneal drug delivery for therapy of intraperitoneal cancers, such as ovarian cancer, arose in the 1960s. The field of intraperitoneal cisplatin therapy for ovarian cancer was initiated in the late 1970s and early 1980s. The markedly improved survival data resulting from a phase III trial of intraperitoneal cisplatin for ovarian cancer in early 2006 led to an NCI Clinical Announcement and a Gynecologic Oncology Group-sponsored workshop on intraperitoneal therapy in January, 2006, in San Diego, California. The proceedings of this workshop summarize both research trial results and practical implementation issues associated with intraperitoneal therapy discussed at this workshop.

Cognitive impairment in bipolar disorder in old age: literature review and findings in manic patients.

BACKGROUND: Descriptions of aged patients with bipolar (BP) disorder have commented on cognitive impairments. However, the literature regarding cognitive test performance in this population has apparently been scant. METHOD: 1. We reviewed studies reporting cognitive performance in aged BP patients. 2. We compared the performance of elderly BP manic patients and aged community comparison subjects on the Mini-Mental State Examination (MMSE) and the Mattis Dementia Rating Scale (DRS). RESULTS: 1. Seven published studies of cognitive measures in aged BP patients were identified. They utilized different assessment methods and addressed different illness states, but they indicate impairments in these patients. 2. In our sample, the manic patients (n=70) had lower MMSE scores and DRS scores than did the comparison subjects (n=37). In these patients, cognitive scores were not significantly associated with Mania Rating Scale scores. LIMITATIONS: The patients in our study were assessed cross-sectionally, and they were treated naturalistically. CONCLUSIONS: Manic or depressed BP elders have impaired cognitive function; in some patients these impairments may persist. Research characterizing these impairments and their clinical implications is warranted.

Paediatric upper limb contracture release following burn injury.

PURPOSE: The aim of this study was to assess the functional outcome in children who had undergone release of upper limb burn contractures at the axilla, elbow and wrist. METHODS: We studied a series of 10 patients reconstructed with local flaps (n = 5), Integra artificial skin (n = 10) and micro-vascular free tissue transfer (n = 5) to release contracted axillae (n = 8), elbows (n = 5) and wrists (n = 7). Follow-up ranged from 6 months to 6 years and outcome was assessed by functional improvement. RESULTS: Full functional release was achieved in all cases at the time of the surgery. Local flaps resulted in good or excellent outcomes in all five cases. Six patients reconstructed with Integra were assessed as having an excellent outcome whereas four had a poor outcome. Free tissue transfer with excellent result was achieved in five children. CONCLUSIONS: This series assessed the three treatment options that we have used for the release of upper limb post-burn contractures. We have shown that local flaps fashioned from burnt skin survive, Integra requires extended post-operative care to prevent recontraction and free tissue transfer is safe in young children. Each method when used appropriately has produced excellent results which have been maintained over the follow-up period.

The exploding worldwide cancer burden: the impact of cancer on women.

Although age-adjusted cancer death rates have started to decline in the United States and other developed nations - thanks in large part to widespread screening programs that detect cancers at early, treatable stages - cancer in developing countries is on the rise. Ironically, rising life expectancy in those nations along with the adoption of 'Western' lifestyles will leave many more people vulnerable to cancer. Unfortunately, the early detection tools and treatment technology that have helped control cancer in wealthier lands are often not readily available in many other countries. Much of this increased cancer burden will take the form of cancers that affect women - not only breast, cervical, and other gynecologic cancers but colorectal cancer, lung cancer, and other malignancies related to tobacco. Physicians specializing in cancer care for women need to be alert to every opportunity to improve cancer screening and prevention among the growing, aging populations of less-developed countries. Less precise but less costly and more widely available screening techniques may save thousands more lives than the most sophisticated technology because low-cost programs can be applied widely instead of being reserved for a fortunate few. In addition, education and prevention efforts directed toward tobacco use need to be put in place to help stem an epidemic of tobacco-related cancers that has largely peaked in developed countries but looms ominously in the future of developing nations.

A composite poly-hydroxybutyrate-glial growth factor conduit for long nerve gap repairs.

There is considerable evidence that peripheral nerves have the potential to regenerate in an appropriate microenvironment. We have developed a novel artificial nerve guide composed of poly 3-hydroxybutyrate (PHB) filled with glial growth factor (GGF) suspended in alginate hydrogel. Gaps of 2-4 cm in rabbit common peroneal nerve were bridged using a PHB conduit containing either GGF in alginate hydrogel (GGF) or alginate alone (Alginate), or with an empty PHB conduit (Empty). Tissues were harvested 21, 42 and 63 days post-operatively. Schwann cell and axonal regeneration were assessed using quantitative immunohistochemistry. At 21 days, addition of GGF increased significantly the distance of axonal and Schwann cells regeneration in comparison with that observed in Alginate and Empty conduits for both gap lengths. The axons bridged the 2-cm GGF conduits gap by 63 days, with a comparable rate of regeneration seen in 4-cm conduits. Schwann cells and axonal regeneration quantity was similar for both gap lengths in each group. However, at all time points the quantity of axonal and Schwann cells regeneration in GGF grafts was significantly greater than in both Alginate and Empty conduits, the latter showing better regeneration than Alginate conduits. The results indicate an inhibitory effect of alginate on regeneration, which is partially reversed by the addition of GGF to the conduits. In conclusion, GGF stimulates a progressive and sustainable regeneration increase in long nerve gap conduits.

Antidepressant-associated mania in late life.

BACKGROUND: Elderly patients can present with mania for the first time late in life, and some elders treated with antidepressants can present with mania. Clinical characteristics of antidepressant-associated mania (AAM) in late life have not been examined. OBJECTIVES: The aims of the study were to identify elders with AAM and to compare selected clinical characteristics to those of manic elders who had not been treated with an antidepressant. We hypothesized that AAM patients would have later age at presentation of bipolar disorder. METHODS: We retrospectively reviewed inpatients with manic disorder who were aged >or=60 years. The sample was selected from admissions prior to 1990. RESULTS: AAM patients (n = 11) were more often experiencing first manic episode, and they had later age at onset of first manic episode, compared to non-AAM patients (n = 46). Most of the AAM patients had been treated with tricyclic agents. CONCLUSIONS: These preliminary findings invite further investigation. Related studies may contribute to risk-benefit analyses for the use of particular antidepressants in the elderly. Also, first episode mania in late life may prove to be a useful model of vulnerability to AAM.

Chemical assaults in Hong Kong: a 10-year review.

The aim of this study was to assess the patients admitted to Prince of Wales Hospital Burns Unit, Hong Kong between September 1991 and August 2001 following chemical assault. A total of 2319 burns were admitted during the study period of which 19 had been subjected to chemical assault. All victims sustained a burn injury to the head and neck area and 47% of victims' eyes were burnt. A total of 84% required surgical intervention. Where a reason for the attack was admitted most were due to relationship difficulties. This study has defined the victims of chemical assault in Hong Kong. At a time when the overall number of assaults in Hong Kong is at its lowest level for 5 years it is of concern that there appears to have been a recent increase in the number of chemical assaults in Hong Kong.

Poly-3-hydroxybutyrate (PHB): a resorbable conduit for long-gap repair in peripheral nerves.

The repair of peripheral nerve injuries with an autologous nerve graft is still the treatment of choice, although it is widely recognised that the method is associated with donor-site morbidity and a suboptimal functional outcome. An alternative approach is to use a nerve conduit to provide a guidance channel for the regenerating nerve. This study investigates the potential of poly-3-hydroxybutyrate (PHB) nerve conduits to bridge long nerve gaps (up to 4 cm) in a rabbit common-peroneal-nerve injury model. Regeneration was assessed up to 63 days postoperatively, and compared with that achieved using nerve autografts. By 42 days, regenerating axons had bridged nerve gaps of all lengths in groups with nerve autografts and in those with PHB conduits. The regeneration distance increased with time but did not vary with gap length (P

Human papilloma virus (HPV)-E6/E7 and epidermal growth factor receptor (EGF-R) protein levels in cervical cancer and cervical intraepithelial neoplasia (CIN).

BACKGROUND: About 90% of cervical cancers and advanced cervical intraepithelial neoplasia (CIN II/III) are squamous epithelial cells with mRNA for human papillomavirus (HPV)16 and 18 and up-regulated epidermal growth factor receptor (EGF-R). Since presence of proteins rather than mRNA may be truly indicative of active infection or disease progression, establishing reliable methods for quantifying these proteins in cervical biopsies is important. METHOD: We have established an objective semi-quantitative immunofluorescent antibody assay to reliably assess the levels of HPV-E6/E7 and EGF-R proteins in the cervical biopsies from 12 normal women, five women with CIN I, 15 with CIN II/III and ten with cervical cancer. RESULTS: HPV-E6/E7 and EGF-R, when present, were specific to para-basal, basal and squamous epithelial cells (negative in stromal cells). Nine of ten women with cervical cancer and 15 (14 CIN II/III; 1 CIN I) of 20 women with CIN were positive for HPV-E6/E7. All 12 controls were HPV-negative. The controls and six women with CIN (four with CIN I) negative for HPV had low levels of EGF-R. The only exception was one woman with cervical cancer negative for HPV, with high levels of EGF-R. Levels of HPV-E6/E7 and EGF-R were significantly higher (P < 0.001 vs. controls) in women with advanced CIN II and III (P< 0.05 vs. controls in CIN I) and cervical cancer. The HPV-E6/E7 and EGF-R levels correlated significantly (r = 18.98; P < 0.001, by linear regression analysis). CONCLUSION: We have established a highly specific and sensitive semi-quantitative immunofluorescent antibody assay for measuring levels of HPV-E6/E7 proteins and EGF-R in archival cervical biopsies. Our data suggest an association between HPV-E6/E7 and EGF-R.

Nifedipine block of capacitative calcium entry in cultured human uterine smooth-muscle cells.

OBJECTIVE: To determine whether nifedipine inhibits capacitative calcium entry at clinically relevant concentrations using cultured human myocytes as a model for human myometrium. METHODS: Myocyte cultures were initiated from the myometrium of term pregnant women who underwent cesarean delivery. Paired cells were chosen for study. The cell of interest was stimulated by an intercellular calcium wave from the adjacent cell. In this fashion, release of sarcoplasmic reticulum (SR) calcium was accomplished with minimal disturbance of the plasma membrane and the subplasmalemmal space (SPS) of the cell studied. Depletion of the SR calcium stores by the calcium wave activated the capacitative calcium current, elevated calcium in the SPS, and activated calcium-activated potassium channels. A cell-attached patch clamp was used to monitor the outward current resulting from the calcium activation of these potassium channels. Calcium green-1 fluorescence was used to simultaneously monitor changes of the deep cytosolic calcium concentrations. Experiments were performed at varying concentrations of nifedipine (0-10 micromol/L). RESULTS: Nifedipine reduced outward potassium currents in a dose-dependent manner. Nifedipine at 100 nmol/L resulted in greater than a 50% reduction of outward current, indicating a significant inhibition of capacitative calcium entry at that concentration. Higher concentrations of nifedipine abolished outward current. Experiments designed to detect indirect effects of nifedipine on capacitative calcium entry were negative. CONCLUSIONS: Nifedipine block of capacitative calcium entry occurred at concentrations similar to those required to block L-type voltage-activated calcium channels. These data suggest that block of capacitative calcium entry may be an important mechanism of action when nifedipine is clinically used for tocolysis of preterm labor.

Differing mechanisms of inhibition of calcium increases in human uterine myocytes by indomethacin and nimesulide.

OBJECTIVE: Indomethacin, an inhibitor of cyclooxygenase types 1 and 2, and nimesulide, a cyclooxygenase 2 selective inhibitor, are both well-known inhibitors of prostaglandin production. It has been assumed that the tocolytic mechanism of nimesulide and indomethacin is only through decreased prostaglandin production. The purpose of this study was to test the hypothesis that either nimesulide or indomethacin, or both, has a mechanism of action on human myocytes other than inhibition of prostaglandin production. STUDY DESIGN: Human uterine myometrium was obtained from consenting patients during cesarean deliveries. Myocytes were cultured, plated, and loaded with a calcium-dependent fluorescent dye, calcium green 1. The relative concentrations of intracellular free calcium were determined by measurement of time-dependent fluorescence changes by means of a video fluorimeter. In all experiments, cells were stimulated with prostaglandin F2alpha, 30 micromol/L. Experiments were performed without pretreatment (control) or with pretreatment consisting of indomethacin, 10 micromol/L, or nimesulide, 30 micromol/L. The percentages of cells demonstrating calcium increases were counted and compared by means of the Fisher exact test. A P value =.05 was considered significant. RESULTS: After prostaglandin F2alpha exposure, 33% of cells showed an increase in intracellular free calcium under control conditions. When pretreated with nimesulide, 39% of cells responded to prostaglandin F2alpha (P =.59). When pretreated with indomethacin, only 16% of cells responded to prostaglandin F2alpha (P =.019). CONCLUSIONS: Pretreatment with nimesulide failed to reduce the fraction of cells that responded to prostaglandin F2alpha. In contrast, pretreatment with indomethacin significantly reduced the fraction of responding cells. These data suggest that, in vitro, indomethacin exhibits a mechanism of tocolysis other than inhibition of prostaglandin synthesis.

The mechanism of propagation of intracellular calcium waves in cultured human uterine myocytes.

OBJECTIVE: The primary goal of this work was to determine the relative importance of sarcoplasmic reticulum inositol 1,4,5-triphosphate receptors and ryanodine receptors in the mechanism of intracellular calcium wave propagation in human uterine myocytes. A secondary goal was to identify the rate-determining step of calcium wave propagation. STUDY DESIGN: Pregnant human myometrium was obtained at the time of cesarean delivery, enzymatically dispersed, and cultured through several passages. Intracellular calcium wave velocities were measured with video fluorescence microscopy and the calcium-dependent fluorescent dye calcium green 1. Experimental conditions were modified by exposure of the cells to ruthenium red (blocked ryanodine receptor), ryanodine (locked open ryanodine receptor), oxytocin (increased inositol-1,4,5-triphosphate), sodium butyrate (intracellular acidification), ammonium chloride (intracellular alkalinization), and elevation of temperature (from 19 degrees C to 30 degrees C). RESULTS: Wave velocities were found to be the same for spontaneously occurring (9.6 +/- 2.6 microm/s) and oxytocin-stimulated (10.3 +/- 3.4 microm/s) waves. Advance treatment of the cells with ryanodine or ruthenium red failed to change oxytocin-stimulated wave velocities from control values. The temperature dependence of calcium wave velocities was studied across the range 19 degrees C to 30 degrees C. Plots of wave velocities versus the inverse of the temperature yielded apparent activation energies that were the same for spontaneous (13.2 +/- 0.3 kcal/mol) and oxytocin-induced (14.3 +/- 1.6 kcal/mol) waves. After intracellular acidification by treatment with butyrate (20 mmol/L) wave velocities increased by 44%. Wave velocities decreased by 35% after treatment with ammonium chloride (20 mmol/L). CONCLUSION: Propagation of intracellular calcium waves in cultured human uterine myocytes exhibited mechanisms of sarcoplasmic reticulum calcium release that could use either inositol 1,4,5-triphosphate receptors alone or ryanodine receptors alone, or both together. The rate-determining step for calcium wave propagation was diffusion of calcium though a highly buffered cytoplasm.

Standards for assessment of lung function and respiratory health in minority populations: some challenges linger into the new millennium.

Results of pulmonary function tests (as an indicator of respiratory health) are from 11 to 13 percent lower in African Americans and other racial ethnic populations than in Caucasians when controlled for gender, age, and height. Environmental factors influencing these indices are circadian variation, altitude, air pollutants, technology, state of nutrition, smoking history, and other indicators of lifestyle. A combination of subtle, genetically determined anthropometric variants may also be operative, the extent of which is controversial. Population-based, population-specific standards are required to avoid erroneous diagnosis of cardiorespiratory disease, erroneous assessment of operative risk, unfair hiring practices when lung function tests are used for preemployment evaluation in dusty occupations, and unfair labeling when workers apply for disability compensation. Tailoring of statistical prediction standards from simple linear to more complex polynomial regression models will increase the accuracy of population prediction standards for pulmonary function variables into the 21st century.