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A novel approach to the treatment of chronic migraine headaches based on neurostimulation of both occipital and supraorbital nerves was developed and reduced to clinical practice in a series of patients with headaches unresponsive to currently available therapies. Following positive trials, seven patients with chronic migraine and refractory chronic migraine headaches had permanent combined occipital nerve–supraorbital nerve neurostimulation systems implanted. The relative responses to two stimulation programs were evaluated: one that stimulated only the occipital leads and one that stimulated both the occipital and supraorbital leads together. With follow-up ranging from 1 to 35 months all patients reported a full therapeutic response but only to combined supraorbital–occipital neurostimulation. Occipital nerve stimulation alone provided a markedly inferior and inadequate response. Combined occipital nerve–supraorbital nerve neurostimulation systems may provide effective treatment for patients with chronic migraine and refractory chronic migraine headaches. For patients with chronic migraine headaches the response to combined systems appears to be substantially better than occipital nerve stimulation alone. [ABSTRACT FROM PUBLISHER]

The article discusses a study to evaluate the acute lung toxicity in rats of intratracheally instilled TiO2 particles that were substantially encapsulated with pyrogenically deposited, amorphous silica. It aims to determine if Pigment A TiO2 particles impart significant toxicity in the lungs of rats and how its activity compares with other reference particulate materials. It suggests that the inhalation of Pigment A TiO2 particles have a low risk potential for producing detrimental pulmonary health effects.

Objective: The purpose of this study was to determine the direction of transmission of umbilical venous Doppler flow velocity changes in human fetuses.Study Design: Strip chart recordings of simultaneously measured umbilical arterial and venous velocities were examined at two sites in the umbilical cord, one near the fetus (proximal) and one near the placenta (distal). Fetuses with venous pulsations or breathing episodes were included. At both locations time from venous pulsation to arterial systole was measured in fetuses with venous pulsations and duration of phase delay between arterial diastolic velocity minimum and venous velocity minimum was measured in fetuses with breathing episodes.Results: In 21 fetuses with venous pulsations the pulsations occurred earlier in the cardiac cycle at proximal sites (0.12 +/- 0.04 second before systole) and later at distal sites (0.02 +/- 0.04 second before systole;P <.001). Phase delays in venous velocities in the 5 fetuses with breathing episodes were also longer at distal sites than at proximal sites (P <.011).Conclusion: Changes in umbilical venous velocities occurred earlier at sites that were closer to the fetus. These findings suggest that changes in umbilical venous velocities originate in the fetal venous system and are transmitted to, rather than from, the placenta. [ABSTRACT FROM AUTHOR]

Varicella zoster virus (VZV) infection is a frequent complication following bone marrow transplantation (BMT). Involvement of the ophthalmic division of the trigeminal nerve, herpes zoster ophthalmicus (HZO), can result in significant and potentially vision-threatening ocular complications. We report the frequency and characteristics of HZO following BMT, including the timing of infection, treatment, ocular complications, and visual outcome. Between 1983 and 1997, 572 patients underwent BMT and seven children developed HZO at a median of 150 days following transplantation. All but one of the children had undergone allogeneic BMT. All of the children were treated with acyclovir after onset of the rash but none had received prophylactic therapy. All seven children developed ocular complications within the first 4 weeks following the onset of the dermatomal rash but none reported any symptoms during this period. Complications included keratitis in six, anterior uveitis in three and scleritis in one. Keratitis was an early complication developing within the first 4 weeks, while anterior uveitis and scleritis occurred later in the course of the disease. The high frequency of ocular complications and lack of symptoms in children with HZO following BMT suggests that early ophthalmologic evaluation is warranted in this group of patients. Prompt diagnosis and treatment of ocular complications is essential in the prevention of acute and long-term ocular sequelae in these children. [ABSTRACT FROM AUTHOR]

The aim of these studies is to develop a respiratory allergy model in Brown Norway (BN) rats using ovalbumin (Ova) as the antigenic stimulus. Specifically, we are interested in studying the mechanisms underlying the development of pulmonary T helper type 2 (Th2) responses following Ova sensitization and inhalation challenge. We have previously reported on the development of an active pulmonary inflammatory response characterized by the presence of eosinophils and measurement of serum immunoglobulin E levels in Ova-sensitized but not in alum-treated, Ova-challenged or sham control rats. In the current study, we have used cDNA microarray technology to assess the gene expression in tracheobronchial, mesenteric and submaxillary lymph nodes, as well as in pulmonary cells and tissues of Ova-sensitized, alum-sensitized or sham control BN rats. Preliminary cDNA microarray results of lung tissue from BN rats exposed to ova-ova (Ova-sensitized, Ova-challenged) 4 or 24 h after ova challenge did not show up-regulation (relative to sham controls) of mRNA for interleukin-4 (IL-4) or IL-5 but did show up-regulation of eotaxin (4 h), intercellular adhesion molecules (ICAM) and vascular cell adhesion molecules (VCAMs), which are likely to be prerequisites for eosinophilic pulmonary inflammatory responses measured at 24 and 48 h post Ova inhalation exposure. In addition, reverse transcriptase-polymerase chain reaction analysis of lung tissue from BN rats exposed to ova-ova 4 and 24 h after challenge demonstrated up-regulation of mRNA for IL-10 (Th2 response). Studies are ongoing to identify the time course and anatomic location of Th2 responses related to the development of Ova-induced respiratory allergy responses in BN rats. [ABSTRACT FROM AUTHOR]

The aims of this study were to assess in rats, using a well-developed, short-term pulmonary bioassay, the acute pulmonary toxicity of intratracheally instilled triethoxyoctylsilane (OTES)-coated (i.e. hydrophobic) pigment-grade TiO2 particles relative to uncoated, hydrophilic TiO2 particle control samples and to bridge the results of these instillation studies with data previously generated from inhalation studies with uncoated, pigment-grade TiO2 particles, using these uncoated pigment-grade TiO2 particles as the inhalation/instillation bridge material. Rats were intratracheally instilled with 2 or 10 mg/kg of the following TiO2 particle types: TiO2 with OTES, TiO2 with Tween 80, or TiO2 with OTES and Tween 80. Saline-instilled rats served as controls. The lungs of sham and exposed rats were evaluated by bronchoalveolar lavage and histopathology at 24 h, 1 week, 1 month and 3 months post-exposure. The results demonstrated that only the high dose (10 mg/kg) pigment-grade TiO2 particles and those with Tween 80 produced a transient pulmonary inflammatory response, and this reached control levels within 1 month post-exposure. We conclude that the OTES coating on the pigment-grade TiO2 particle does not cause significant pulmonary toxicity. [ABSTRACT FROM AUTHOR]

Four groups of 48 male rats each were exposed, nose-only, 6 h/day, 5 days/week, for a total of 4 weeks (i.e. 20 exposures) to aerosols of Nylon respirable-sized, fiber-shaped particulates (RFPs) at concentrations of 0, 4, 15 and 57 f/cm³ (ratio of RFPs:particles = 1:10-20). The samples containing Nylon RFPs were prepared using flock rotary cutters followed by vigorous opening procedures. Following 4 week exposures, the lungs of sham and Nylon-exposed rats were evaluated at 1 day, 1 week, as well as 1, 3, 6 and 12 months after exposure. At each of the post-exposure time points, the lungs of rats were either lavaged (for 3 months after exposure) or infusion fixed for cell proliferation, histopathology and fiber clearance/retention studies. This report contains data obtained during a 6 month post-exposure period. Preliminary results show that the retained mean lung burdens at 1 day after exposure were 1.75 × 107 (high level), 3.4 × 106 (mid level) and 4.8 × 105 (low level) RFPs/lung. Mean lengths and diameters of the Nylon aerosol were 9.8 and 1.6 µm, respectively. There were no significant increases in lung weights or indications of pulmonary inflammation in Nylon-exposed animals versus controls--based on cell differentials, bronchoalveolar lavage (BAL) fluid analyses and chemotaxis activity. More than 90% of the alveolar macrophages recovered by BAL (high level) contained Nylon RFPs or particles within their cytoplasm. Interim histopathological analyses have thus far revealed no adverse lower pulmonary or upper respiratory effects. [ABSTRACT FROM AUTHOR]

These studies were designed to investigate mechanisms through which inhaled p-aramid respirable- sized fiber-shaped particulates (RFP) are biodegraded in the lungs of exposed rats and hamsters. We have postulated that lung fluids coat/activate inhaled p-aramid RFP which deposit in the lung and promote enzymatic attack and consequent shortening. Aliquots of p-aramid or cellulose (biopersistent control) RFP were instilled into the lungs of rats and the lungs digested 24 h later using two different (KOH or enzymatic) digestion methods. For in vitro studies the two RFP types were incubated with lavage fluid and processed via simulated digestion; in addition, rat lung epithelial cells, macrophages or co-cultures were incubated with p-aramid and digested 1, 24 or 168 h post-exposure. In vivo the enzyme but not the KOH digestion method resulted in shortening of p-aramid but not cellulose RFP recovered from rat lungs. The results of in vitro studies showed that mean lengths of p-aramid RFP incubated with saline and processed by either digestion method were not found to be altered. Indeed, only the preparation of p-aramid RFP that had been incubated with BAL fluid and processed with the enzyme solution resulted in cleavage of p-aramid RFP. In contrast to the in vitro acellular studies with p-aramid RFP, the combination of BAL fluid incubation and enzyme digestion method had no measurable effect on shortening of cellulose RFP, indicating that the results with p-aramid were specific. In vitro cellular studies demonstrated a shortening of p-aramid RFP in exposed macrophages and co-cultures but not in lung epithelial cells 24 h and 1 week post-exposure. These findings demonstrate that lung fluids coat and activate the p-aramid RFP as a prerequisite for cleavage and describe a likely mechanism for the biodegradability of inhaled p-aramid RFP in the lungs of exposed animals. [ABSTRACT FROM AUTHOR]

The aims of this study were to assess in rats, using a well-developed, short-term pulmonary bioassay, the acute pulmonary toxicity of intratracheally instilled triethoxyoctylsilane (OTES)-coated (i.e. hydrophobic) pigment-grade TiO2 particles relative to uncoated, hydrophilic TiO2 particle control samples and to bridge the results of these instillation studies with data previously generated from inhalation studies with uncoated, pigment-grade TiO2 particles, using these uncoated pigment-grade TiO2 particles as the inhalation/instillation bridge material. Rats were intratracheally instilled with 2 or 10 mg/kg of the following TiO2 particle types: TiO2 with OTES, TiO2 with Tween 80, or TiO2 with OTES and Tween 80. Saline-instilled rats served as controls. The lungs of sham and exposed rats were evaluated by bronchoalveolar lavage and histopathology at 24 h, 1 week, 1 month and 3 months post-exposure. The results demonstrated that only the high dose (10 mg/kg) pigment-grade TiO2 particles and those with Tween 80 produced a transient pulmonary inflammatory response, and this reached control levels within 1 month post-exposure. We conclude that the OTES coating on the pigment-grade TiO2 particle does not cause significant pulmonary toxicity. [ABSTRACT FROM AUTHOR]