3D Parylene sheath neural probe for chronic recordings.

OBJECTIVE: Reliable chronic recordings from implanted neural probes remain a significant challenge; current silicon-based and microwire technologies experience a wide range of biotic and abiotic failure modes contributing to loss of signal quality. APPROACH: A multi-prong alternative strategy with potential to overcome these hurdles is introduced that combines a novel three dimensional (3D), polymer-based probe structure with coatings. Specifically, the Parylene C sheath-based neural probe is coated with neurotrophic and anti-inflammatory factors loaded onto a Matrigel carrier to encourage the ingrowth of neuronal processes for improved recording quality, reduce the immune response, and promote improved probe integration into brain tissue for reliable, long-term implementation compared to its rigid counterparts. MAIN RESULTS: The 3D sheath structure of the probe was formed by thermal molding of a surface micromachined Parylene C microchannel, with electrode sites lining the interior and exterior regions of the lumen. Electrochemical characterization of the probes via cyclic voltammetry and electrochemical impedance spectroscopy was performed and indicated suitable electrode properties for neural recordings (1 kHz electrical impedance of ∼200 kΩ in vitro). A novel introducer tool for the insertion of the compliant polymer probe into neural tissue was developed and validated both in vitro using agarose gel and in vivo in the rat cerebral cortex. In vivo electrical functionality of the Parylene C-based 3D probes and their suitability for recording the neuronal activity over a 28-day period was demonstrated by maintaining the 1 kHz electrical impedance within a functional range (<400 kΩ) and achieving a reasonably high signal-to-noise ratio for detection of resolvable multi-unit neuronal activity on most recording sites in the probe. Immunohistochemical analysis of the implant site indicated strong correlations between the quality of recorded activity and the neuronal/astrocytic density around the probe. SIGNIFICANCE: The provided electrophysiological and immunohistochemical data provide strong support to the viability of the developed probe technology. Furthermore, the obtained data provide insights into further optimization of the probe design, including tip geometry, use of neurotrophic and anti-inflammatory drugs in the Matrigel coating, and placement of the recording sites.

[Evaluation of different fibroscopic sampling techniques for the diagnosis of isolated peripheral pulmonary nodules. A prospective study of 74 cases in Vietnam]. / Evaluation des différentes techniques de prélèvement par fibroscopie pour le diagnostic des nodules pulmonaires isolés périphériques. Etude prospective de 74 cas, réalisée au Viêt-nam.

Isolated pulmonary nodules raise serious diagnostic problems. Combined imaging and endoscopic methods can often avoid exploratory thoracotomy. The situation is different however in developing countries where health facilities and technical availability are quite variable. Bronchial fibroscopy without image guidance can provide the diagnosis is an acceptable number of cases. We conducted a prospective study in 74 patients. After chest x-ray and CT scan of the lesion of interest, bronchial lavage was performed in each patient with brushings samples in 71 and transbronchial biopsy in 68. Riu staining was performed immediately in the endoscopy suite, providing an almost immediate diagnostic approach. The combination of lavage, brushing and biopsy provided a diagnostic yield as good as the brushings and biopsy combination. These endoscopic techniques gave the diagnosis of the specific lesion in 52 cases (70%). Most involved cancer but there were 15 cases of tuberculosis diagnosis, which remains frequent in developing countries.

In vivo magnetic resonance spectroscopy of human fetal neural transplants.

To better define the survival and cellular composition of human fetal neurotransplants in vivo, we performed quantitative 1H MRS to determine the concentration of the neuronal amino acid [N-acetylaspartate] within MRI-visible grafts. In all, 71 grafts in 38 patients [24 Parkinson's disease (PD), 14 Huntington's disease (HD)] were examined, as well as 24 untreated PD and HD patients and 13 age-matched normal controls. MRI appearances of edema were present in three out of 71 grafts, the remainder being consistent with histologically identified viable neural transplant tissue. N-acetylaspartate (NAA), creatine, choline, myoinositol and glutamine plus glutamate (Glx) were identified in all post-transplant putamens, with abnormal metabolites, lactate and/or lipid detectable in only three patients. Of 71 grafts, 19 occupied more than 60% of the MRS-examined volume (VOI) (mean 84.2 +/- 3%; range 61-100%). In those, [NAA] was 8.50 +/- 0.99 mM in eight PD spectra and 6.59 +/- 0.81 mM in 11 HD spectra, and was not significantly different from controls. In contrast, transplanted fetal neurones contain less than 0.4 mM of the neuronal amino acid NAA. This suggests that established fetal neurotransplants in the human putamen of both PD and HD patients are populated by adult neurones, axons and dendrites.

Quantitative proton-decoupled 31P MRS and 1H MRS in the evaluation of Huntington's and Parkinson's diseases.

OBJECTIVE: To determine cerebral energy status in patients with Huntington's disease (HD) and Parkinson's disease (PD). METHODS: The study included 15 patients with DNA-proven, symptomatic HD and five patients with medically treated, idiopathic PD, all of whom were candidates for neurotransplant treatment, as well as 20 age-related normal subjects. Quantitative noninvasive, MRI-guided proton MRS was performed of single volumes in putamen of basal ganglia (BG), occipital gray matter, and posterior parietal white matter; in addition, quantitative phosphorus and proton-decoupled phosphorus MRS of superior biparietal white and gray matter was done. Outcome measures were quantitative metabolite ratios and millimolar concentrations of neuronal and glial markers, creatine (Cr) and adenosine triphosphate (ATP), and intracellular pH. RESULTS: In volume-corrected control BG (10.46 +/- 0.37 mM), [Cr] was 29% (p < 0.05) higher than in control gray matter (8.10 +/- 1.04 mM). In HD and PD, energy metabolism was not abnormal in the four cerebral locations measured by MRS. No increase in cerebral lactate or decrease in phosphocreatine and ATP was detected. Small, systematic abnormalities in N-acetylaspartate (NAA, decreased), Cr (decreased), choline-containing compounds (Cho, increased), and myoinositol (mI, increased) were demonstrable in all patient's individually and in summed spectra but were insufficient to make diagnosis possible in the individual patient. CONCLUSION: Previously described failure of global energy metabolism in HD was not confirmed. However, quantitative 1-hydrogen MRS and decoupled 31-phosphorus MRS are sensitive to +/-10% alterations in key cerebral metabolites, and may be of value in noninvasive monitoring of appropriate therapies.

Agent orange and the risk of gestational trophoblastic disease in Vietnam.

There have been claims of an increased risk for gestational trophoblastic disease (i.e., hydatidiform mole and choriocarcinoma) in Vietnam since the period of Agent Orange sprayings. In 1990, we conducted a case-control study in Ho Chi Minh City to investigate risk factors for gestational trophoblastic disease in Vietnam. Eighty-seven married women, all of whom had a recent pathologic diagnosis of gestational trophoblastic disease, identified in the Obstetrical and Gynecological Hospital, were included in the study. Eighty-seven married women who were admitted mainly in the surgery departments of the same hospital were the controls, and they were matched to cases for age and area of residence. Odds ratios (ORs), adjusted for matching variables and other potential confounders, were estimated with unconditional logistic regression. A statistically significant trend in risk was observed with previous live births (p = .01). Cases were found to eat less meat per wk (OR = 0.4, 95% confidence interval [95% CI] = 0.2-0.9 for > or = five meat dishes) and to own fewer consumer goods than controls. An increase in risk was associated with the breeding of pigs (OR = 5.7, 95% CI = 1.2-27.6 for raising three or more pigs). A cumulative Agent Orange exposure index was constructed, using the patient's complete residence history. No significant difference was found between cases and controls for this index (OR = 0.7, 95% CI = 0.2-1.8 for high-exposure category), nor was such a difference noted for the agricultural use of pesticides.

Chlorinated and brominated dioxins and dibenzofurans in human tissue following exposure.

With substantial improvements in analytic techniques over the past decade, it has become possible to measure polychlorinated dioxins (PCDDs) and dibenzofurans (PCDFs) in human tissue in a congener-specific fashion down to the low parts per trillion level. This paper reviews findings using these new techniques from a number of recent medical and environmental case studies. These studies include those of workers exposed to a polychlorinated biphenyl (PCB) transformer fire in the United States, German chemical workers exposed to 2,3,7,8-tetrachlorodibenzodioxin (2,3,7,8-TCDD) while cleaning up after an explosion, workers at a municipal incinerator in New York City, a chemist exposed to brominated and chlorinated dioxins, U.S. veterans and also Vietnamese civilians exposed to Agent Orange contaminated with TCDD in Vietnam, and victims of the polychlorinated dibenzofuran and PCB contaminated rice oil (Yusho) incident in Japan.

Chlorinated dioxins and dibenzofurans in human tissue from general populations: a selective review.

During the past decade a considerable amount of data has been generated concerning polychlorinated dibenzodioxin (PCDD) and polychlorinated dibenzofuran (PCDF) levels in humans from many geographical locations. To organize these data in a useful fashion for environmental purposes and for consideration of human toxicity, selected portions of our data are presented in a somewhat atypical fashion, by percentage contribution of individual congeners to total PCDD/Fs in human tissue, and to the total dioxin equivalents (TEq). This is done to better characterize congener contributions from environmental contamination in various geographical regions at this time and health-related levels. To present the findings in a global perspective, data from widely different locations are presented including the United States, Germany, Vietnam, the former Soviet Union, Thailand, Cambodia, China, South Africa, and Guam.

[An original experience through the creation of a new functional rehabilitation center for Vietnamese lepers]. / Une expérience originale à travers la création d'un nouveau centre de réhabilitation fonctionnelle pour les lépreux vietnamiens.

Since 1990, the creation of a Rehabilitation Center for Vietnamese leprosy patients under the aegis of "Oeuvres Hospitalières Françaises de l'Ordre de Malte" is the result of emphasized collaboration between governmental and non-governmental organizations, and between medical and paramedical specialists. This humanitarian action is not "a present home delivery". The end of this action is to set progressively a realist enterprise that depends on preliminary epidemiologic investigations on the spot to analyse means and necessities. Frequency of disabilities (49.6%) and predominance of grades 1 and 2 (83.5%) require aids. The realisation of technology transfer at all medical care levels is necessary. But at the same time, it is essential to build surroundings adapted infrastructure, to equip with effective material giving comfort and security for patients, and even to supply with pharmaceutic drugs in order to continue rehabilitation's activities. In short range, patient's selection and regular control give first objective results.

Viral infections and chemical exposures as risk factors for hepatocellular carcinoma in Vietnam.

A case-control study investigating risk factors for hepatocellular carcinoma (HCC) was conducted in Hanoi, in the north of Vietnam, between 1989 and 1992. Male cases of HCC (152) diagnosed in 2 hospitals were included. Hospital controls (241) admitted mainly to abdominal surgery departments were frequency-matched to cases for sex, age, hospital and place of residence (Hanoi, province). Odds ratios adjusted for matching variables and other potential confounders were estimated using unconditional logistic regression, or exact non-parametric statistical inference when numbers were small. Positivity for hepatitis B surface antigen (HBsAg) was the main risk factor for HCC in this sample. Five subjects (3 cases, 2 controls) had been infected by hepatitis C virus (HCV), and none of them were carriers of HBsAg, giving an OR of 38 associated with HCV infection among HBsAG-negative subjects. Alcohol drinking was associated with HCC and interacted with HBsAg positivity. Agricultural use of organophosphorous pesticides (30 liters/year or more) and military service in the south of Vietnam for 10 years or more were also associated with an increased risk of HCC. This study confirms the major role played by HBV infection and its association with HCC in south-east Asia. It also suggests how other factors such as alcohol consumption or exposure to chemicals may interact with HBV infection.