2001: An artificial heart odyssey.

The quest to replace the natural heart with an artificial one as a permanent system is among the remaining holy grails in medicine and surgery. Beginning in 1969, when the first total artificial heart (TAH) was implanted into a human, to the present, several types have been developed-the AbioCor was among them. On November 5th, 2001, our team at Hahnemann University Hospital in Philadelphia, Pennsylvania placed the world's fifth AbioCor. Excerpts of that moment in time were recorded and serve as a memorial to the past and a testimony to the present and future quest of this elusive holy grail.

Investigation of parameters that determine Nano-DC vaccine transport.

Effective migration of dendritic cells into the lymphatic system organs is the prerequisite for a functional dendritic cell vaccine. We have previously developed a porous silicon microparticle (PSM)-based therapeutic dendritic cell vaccine (Nano-DC vaccine) where PSM serves both as the vehicle for antigen peptides and an adjuvant. Here, we analyzed parameters that determined dendritic cell uptake of PSM particles and Nano-DC vaccine accumulation in lymphatic tissues in a murine model of HER2-positive breast cancer. Our study revealed a positive correlation between sphericity of the PSM particles and their cellular uptake by circulating dendritic cells. In addition, the intravenously administered vaccines accumulated more in the spleens and inguinal lymph nodes, while the intradermally inoculated vaccines got enriched in the popliteal lymph nodes. Furthermore, mice with large tumors received more vaccines in the lymph nodes than those with small to medium size tumors. Information from this study will provide guidance on design and optimization of future therapeutic cancer vaccines.

The plasma glutamate concentration as a complementary tool to differentiate benign PET-positive lung lesions from lung cancer.

BACKGROUND: Pulmonary imaging often identifies suspicious abnormalities resulting in supplementary diagnostic procedures. This study aims to investigate whether the metabolic fingerprint of plasma allows to discriminate between patients with lung inflammation and patients with lung cancer. METHODS: Metabolic profiles of plasma from 347 controls, 269 cancer patients and 108 patients with inflammation were obtained by 1H-NMR spectroscopy. Models to discriminate between groups were trained by PLS-LDA. A test set was used for independent validation. A ROC curve was built to evaluate the diagnostic performance of potential biomarkers. RESULTS: Sensitivity, specificity, PPV and NPV of PET-CT to diagnose cancer are 96, 23, 76 and 71%. Metabolic profiles differentiate between cancer and inflammation with a sensitivity of 89%, a specificity of 87% and a MCE of 12%. Removal of the glutamate metabolite results in an increase of MCE (38%) and a decrease of both sensitivity and specificity (62%), demonstrating the importance of glutamate for discrimination. At the cut-off point 0.31 on the ROC curve, the relative glutamate concentration discriminates between cancer and inflammation with a sensitivity of 85%, a specificity of 81%, and an AUC of 0.88. PPV and NPV are 92 and 69%. In PET-positive patients with a relative glutamate level ≤ 0.31 the sensitivity to diagnose cancer reaches 100% with a PPV of 94%. In PET-negative patients, a relative glutamate level > 0.31 increases the specificity of PET from 23% to 58% and results in a high NPV of 100%. In case of discrepancy between SUVmax and the glutamate concentration, lung cancer is missed in 19% of the cases. CONCLUSION: This study indicates that the 1H-NMR-derived relative plasma concentration of glutamate allows discrimination between lung cancer and lung inflammation. A glutamate level ≤ 0.31 in PET-positive patients corresponds to the diagnosis of lung cancer with a higher specificity and PPV than PET-CT. Glutamate levels > 0.31 in patients with PET negative lung lesions is likely to correspond with inflammation. Caution is needed for patients with conflicting SUVmax values and glutamate concentrations. Confirmation is needed in a prospective study with external validation and by another analytical technique such as HPLC-MS.

Replacing dietary soybean meal with canola meal improves production and efficiency of lactating dairy cows.

Previous research suggested that crude protein (CP) from canola meal (CM) was used more efficiently than CP from solvent soybean meal (SBM) by lactating dairy cows. We tested whether dietary CP content influenced relative effectiveness of equal supplemental CP from either CM or SBM. Fifty lactating Holstein cows were blocked by parity and days in milk into 10 squares (2 squares with ruminal cannulas) in a replicated 5×5 Latin square trial. Five squares were fed: (1) low (14.5-14.8%) CP with SBM, (2) low CP with CM, (3) low CP with SBM plus CM, (4) high (16.4-16.7%) CP with SBM, and (5) high CP with CM; the other 5 squares were fed the same diets except with rumen-protected Met plus Lys (RPML) added as Mepron (Degussa Corp., Kennesaw, GA) and AminoShure-L (Balchem Corp., New Hampton, NY), which were assumed to provide 8g/d of absorbed dl-Met and 12g/d of absorbed l-Lys. Diets contained [dry matter (DM) basis] 40% corn silage, 26% alfalfa silage, 14 to 23% corn grain, 2.4% mineral-vitamin premixes, and 29 to 33% neutral detergent fiber. Periods were 3wk (total 15wk), and data from the last week of each period were analyzed using the Mixed procedures of SAS (SAS Institute Inc., Cary, NC). The only effects of RPML were increased DM intake and milk urea N (MUN) and urinary N excretion and trends for decreased milk lactose and solids-not-fat concentrations and milk-N:N intake; no significant RPML × protein source interactions were detected. Higher dietary CP increased milk fat yield and tended to increase milk yield but also elevated MUN, urine volume, urinary N excretion, ruminal concentrations of ammonia and branched-chain volatile fatty acids (VFA), lowered milk lactose concentration and milk-N:N intake, and had no effect on milk true protein yield. Feeding CM instead of SBM increased feed intake, yields of milk, energy-corrected milk, and true protein, and milk-N:N intake, tended to increase fat and lactose yields, and reduced MUN, urine volume, and urinary N excretion. At low CP, MUN was lower and intake tended to be greater on SBM plus CM versus SBM alone, but MUN and N excretion were not reduced to the same degree as on CM alone. Interactions of parity × protein source and parity × CP concentration indicated that primiparous cows were more responsive than multiparous cows to improved supply of metabolizable protein. Replacing SBM with CM reduced ruminal ammonia and branched-chain VFA concentrations, indicating lower ruminal degradation of CM protein. Replacing SBM with CM improved milk and protein yield and N-utilization in lactating cows fed both low- and high-CP diets.

Serum calprotectin as a biomarker for Crohn's disease.

BACKGROUND AND AIMS: In Crohn's disease, correlation between clinical assessment and disease activity at tissue level is weak. Our aim was to evaluate the value of serum calprotectin as a biomarker for Crohn's disease. METHODS: The STORI trial patients (n=115) were studied at baseline, in clinical remission before infliximab withdrawal, or at the time of relapse after infliximab withdrawal. Forty healthy controls were also studied. Serum calprotectin level was measured by ELISA. Data were analyzed through correlation analyses, Kaplan Meier curves and Cox model, using available Crohn's Disease Activity Index (CDAI), Crohn's Disease Endoscopic Index of Severity (CDEIS), fecal calprotectin and C-reactive protein levels (hsCRP). RESULTS: Median serum calprotectin was 8892 ng/mL (range: 410-125,000 ng/mL) in Crohn disease patients as compared with 1318 ng/mL (range: 215.8-3770 ng/mL) in controls (P<0.0001). Serum calprotectin was significantly higher for active disease (median=19,584 ng/mL) than for inactive disease (median=8353 ng/mL) (P<0.0001). Serum calprotectin correlated with hsCRP (r=0.4092, P<0.0001) and CDAI (r=0.4442, P<0.0001), but not with CDEIS, on the contrary to fecal calprotectin (r=0.6458, 0.5515, 0.2577 with P<0.0001, P<0.0001, P=0.019 respectively). In multivariate analysis, serum calprotectin used as a discrete variable (threshold: 5675 ng/ml), appeared complementary to hsCRP (>5 mg/l) and fecal calprotectin (>250 µg/g) to predict relapse after infliximab withdrawal (P=0.0173, 0.0024 and 0.0002; HR: 3.191, 3.561 and 4.120). CONCLUSIONS: As a CD biomarker, serum calprotectin has a similar profile as hsCRP. It is also complementary to fecal calprotectin and hsCRP for prediction of relapse after infliximab withdrawal.

Effects of hyperbaric oxygen on motor function in children with cerebral palsy.

OBJECTIVE: We conducted a randomized, double-blind, controlled clinical trial to determine whether hyperbaric oxygen (HBO) improves gross motor function in children with cerebral palsy. METHODS: Forty-nine children aged 3 to 8 years with spastic cerebral palsy were randomized to 40 treatments of HBO (100% oxygen at 1.5atm) or hyperbaric air (HBA, 14% oxygen at 1.5atm) over an 8-week period. The primary outcome was the Gross Motor Function Measure (GMFM) global score. Other outcomes included the Pediatric Evaluation of Disability Inventory (PEDI). Assessments were made before and immediately, 3 months, and 6 months after the treatment period. Within-group changes were analyzed with paired t tests or repeated measures analysis of variance. Analysis of covariance was used for between-group comparisons. RESULTS: Forty-six children (24 HBO, 22 HBA) were analyzed at the second interim analysis, which was scheduled to take place when at least half of the required number of patients in each group had completed pre- and post-treatment testing. No changes occurred in the GMFM from pre- to post-treatment in either group or between groups. Statistically significant increases occurred in both groups on the PEDI, with no difference between groups. The study was stopped because the calculated conditional probability of obtaining a difference between groups if the study continued to the end was only between 0.5% and 1.6%. INTERPRETATION: HBO was not effective in improving GMFM scores, and was no more effective than HBA in improving PEDI scores. These results do not support use of HBO as a therapy for cerebral palsy in young children who did not have neonatal hypoxic-ischemic encephalopathy.

[Lynch syndrome and microsatellite instability: a review]. / Le syndrome de Lynch et l'instabilité des microsatellites: revue de littérature.

Microsatellite instability (MSI) phenotype occurs in approximately 15 to 24% of colorectal cancer (CRC) patients and may be sporadic or hereditary. It reflects a mutator phenotype in the tumor due to a lack of mismatch repair system. MSI is indeed one of the characteristics of CRCs occurring in Lynch syndrome and some sporadic cases. CRCs with MSI have a better prognosis than CRCs with microsatellite stability (MSS). This is explained partly by a more important anti-tumor immune response and by apoptosis of tumor cells in which mutations accumulate. However, in some retrospective studies, microsatellite instability in stage II CRCs was associated with no benefit to or even a deleterious effect of 5-FU alone based adjuvant therapy. Nevertheless, results obtained in stage III CRCs with FOLFOX type adjuvant chemotherapy remain favorable in retrospective studies.

The medicinal use of chocolate in early North America.

The medicinal use of chocolate has a long history in North America dating back to the 16th century. From Mesoamerican Codices and European Treatises scholars have determined that for hundreds of years the beverage called chocolate was administered to the sick and prescribed homeopathically to prevent illness. Yet, little scholarship exists that focuses on medicinal chocolate usage in early North America (18th-19th century). This paper examines medical practices during this era and associated medicinal norms with special attention given to chocolate/cocoa usage. Given the current scientific attention on the relationship between dark chocolate consumption and heart disease attenuation it is timely to investigate and chronicle America's medical forebears' understanding of, and practices related to, the medicinal use of chocolate. Indeed, there is a significant amount of literature to suggest that chocolate was used for wellness and to treat illness.

Practice parameter: therapies for essential tremor: report of the Quality Standards Subcommittee of the American Academy of Neurology.

BACKGROUND: Essential tremor (ET) is one of the most common tremor disorders in adults and is characterized by kinetic and postural tremor. To develop this practice parameter, the authors reviewed available evidence regarding initiation of pharmacologic and surgical therapies, duration of their effect, their relative benefits and risks, and the strength of evidence supporting their use. METHODS: A literature review using MEDLINE, EMBASE, Science Citation Index, and CINAHL was performed to identify clinical trials in patients with ET published between 1966 and August 2004. Articles were classified according to a four-tiered level of evidence scheme and recommendations were based on the level of evidence. RESULTS AND CONCLUSIONS: Propranolol and primidone reduce limb tremor (Level A). Alprazolam, atenolol, gabapentin (monotherapy), sotalol, and topiramate are probably effective in reducing limb tremor (Level B). Limited studies suggest that propranolol reduces head tremor (Level B). Clonazepam, clozapine, nadolol, and nimodipine possibly reduce limb tremor (Level C). Botulinum toxin A may reduce hand tremor but is associated with dose-dependent hand weakness (Level C). Botulinum toxin A may reduce head tremor (Level C) and voice tremor (Level C), but breathiness, hoarseness, and swallowing difficulties may occur in the treatment of voice tremor. Chronic deep brain stimulation (DBS) (Level C) and thalamotomy (Level C) are highly efficacious in reducing tremor. Each procedure carries a small risk of major complications. Some adverse events from DBS may resolve with time or with adjustment of stimulator settings. There is insufficient evidence regarding the surgical treatment of head and voice tremor and the use of gamma knife thalamotomy (Level U). Additional prospective, double-blind, placebo-controlled trials are needed to better determine the efficacy and side effects of pharmacologic and surgical treatments of ET.

Mineral content of culinary and medicinal plants cultivated by Hmong refugees living in Sacramento, California.

Since the end of the American-Vietnamese War in 1975, more than 1.5 million refugees from Southeast Asia have resettled in the United States. Included among these displaced persons were the Hmong from Laos, a subsistence-based, shifting-cultivation, agricultural society. Hmong who resettled in urban areas have viewed vacant lots adjacent to urban dwellings as potential garden sites for production of familiar herbs and vegetables. In the present study exotic culinary and medicinal herbs grown by Hmong refugees in Sacramento, California were identified and analyzed for mineral composition. The herbs grown in these urban gardens were significant ingredients of Hmong recipes, and herb leaves, or infusions of steamed herb leaves were widely consumed as a component of pregnancy and post-partum diets. Six common species, Acorus gramineus, aff. Angelica, Dendranthema indicum, Eupatorium lindleyana, Sedum aff. sarmentosum, and Sedum aff. spectabile, were used in combination to season chicken. Polygonum odoratum, also widely cultivated, was used to season fish. Exotic culinary-medicinal species with highest mineral profiles included: Basella alba (Ca, Mg, Mn, Zn); Houttuynia cordata (Fe, Mg, Mn); Justica gendarussa (Ca, Mg, Zn); and Polygonum odoratum (Ca, Mg, Mn). While vacant lots sometimes are heavy metal contamination sites, we found no detectable levels of arsenic, cadmium, chromium, or lead in the samples analyzed.

Low-level laser effect on neural regeneration in Gore-Tex tubes.

PURPOSE: The purpose of this investigation was to determine the effects of low-level laser (LLL) irradiation on neural regeneration in surgically created defects in the rabbit inferior alveolar nerve. STUDY DESIGN: Five adult female New Zealand White rabbits underwent bilateral exposure of the inferior alveolar nerve. A 6-mm segment of nerve was resected, and the nerve gap was repaired via entubulation by using a Gore-Tex conduit. The experimental side received 10 postoperative LLL treatments with a 70-mW gallium-aluminum-arsenide diode at 4 sites per treatment. At 15 weeks after surgery, the nerve segments were harvested bilaterally and prepared for light microscopy. Basic fuchsin and toluidine blue were used to highlight myelinated axons. The segments were examined histomorphometrically by using computer analysis to determine mean axonal diameter, total fascicular surface area, and axonal density along the repair sites. RESULTS: Gross examination of all nerves showed intact neural bundles with variable degrees of osseous remodeling. Light microscopic evaluation revealed organized regenerated neural tissue in both groups with more intrafascicular perineural tissue in the control group. Histomorphometric evaluation revealed increased axonal density in the laser treated group as compared with the control. CONCLUSIONS: LLL irradiation may be a useful noninvasive adjunct to promote neuronal wound healing in surgically created defects repaired with expanded polytetrafluoroethylene entubulation.

Gathering practices of Karen women: questionable contribution to beta-carotene intake.

Gathering edible wild plants is widely recognized throughout rural southeast Asia for contributions to micronutrient intakes. Elderly Karen women in two northern Thailand communities (n = 32) were surveyed to determine household gathering practices and use of edible wild plants in the family diet. While all household members gathered most efforts were by women, who collected on average 1.3-3.5 times/week depending on the season. All respondents reported that local availability of wild species with culinary and medicinal value had declined in recent decades. Column chromatography and spectrophotometry were used to determine the beta-carotene content of 22 of the most commonly consumed species. Mean values ranged from 10,290 to 31 microg/100 g sample (858 to 3 microg RE/100 g); 14 species measured at least 2400 microg/100 g (300 microg RE/100 g). Most plants identified with reasonable to high quantities of beta-carotene were eaten raw, steamed for more than 20 min, or were cooked and consumed without the fat source needed to facilitate absorption. The contribution of beta-carotene from these species to Karen diet, therefore, is problematical.

[Neurostimulation in the treatment of chronic pain]. / Les techniques de neurostimulation dans le traitement de la douleur chronique.

Different types of neurostimulation are proposed essentially in cases of chronic neuropathic pain, non controlled by anticonvulsivants and antidepressants. The aim is usually to activate a failing inhibitory system, involved in the transmission and the modulation of the nociceptive stimulus. The site of stimulation (transcutaneous, spinal cord, thalamic) is choosen according to the severity of pain and especially the degree of lemniscal dysfunction evaluated by clinical and electrophysiological data. Transcutaneous electrical stimulation and spinal cord stimulation are efficient for neurogenic pain secondary to partial deafferentation. When dysfunction or lesion extend to the pre-ganglionic portion, it's preferable to propose stereotactic thalamic stimulation or central gyrus stimulation. The analgesic effect concerns permanent burning pain in the context of sensitive deafferentation: after distal nervous lesions, radicular, plexular or spinal lesions or after stroke with ischemic lesions along the nociceptive pathways. These different methods must only be proposed if there is a frequent clinical and technical monitoring.

Erb's explanation for the tendon reflexes. Links between science and the clinic.

OBJECTIVE: To determine whether 19th-century experimental neurophysiological concepts directly influenced Erb's initial explanation for the deep tendon reflexes (DTRs). BACKGROUND: There is extensive literature on the discovery of the clinical utility of the DTRs on the one hand and on the development of 19th-century experimental neurophysiological concepts and early scientific concepts of reflexology on the other. While it seems logical to assume that Erb's 1875 discovery of the clinical utility of the DTRs and his initial interpretation of the physiological meaning of heightened DTRs were grounded in some of these scientific concepts, the important link between the clinical and scientific realm has not, to our knowledge, been the subject of previous analysis. METHODS: Review of the 19th-century neurophysiological literature and translation of seminal manuscripts written by Erb in the years 1875 and 1876. RESULTS: The concepts of spinal inhibition and reflex action arose from 19th-century neurophysiological experimentation. Erb first described the term Patel-larsehnenreflex (patellar tendon reflex) in 1875, and his publications reveal clear insight into several fundamental scientific concepts, including spinal inhibition, the reflex arc, distinct motor and sensory neurons, and an excitomotor system in the spinal gray matter. CONCLUSION: While Erb's initial description and interpretation of the DTRs may be regarded as a fortuitous discovery by a keen clinical observer, on another level his observations were not made in isolation, but were based on his knowledge of the physiological work of the preceding decades.

Experimental models of chronic focal epilepsy: a critical review of four models.

A number of experimental (i.e., animal) models have been developed to induce chronic focal epilepsy. Three of the most commonly employed are the alumina cream, kainic acid, and the electrical kindling techniques. A fourth approach involving the application of minute quantities of tetanus toxin to discrete brain sites, although relatively under-utilized, may be favorably compared to the aforementioned models.