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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.

Background: This study compared adhesion reformation after open and laparoscopic adhesiolysis in a rat model., Methods: Adhesions were induced by surgically creating ischaemic buttons on the peritoneal side wall. After 7 days the animals underwent laparoscopy with carbon dioxide insufflation or laparotomy to score and lyse adhesions. Peritoneal tissue and fluid were collected after 24 h in a subset of animals, and adhesion reformation was scored 7 days after lysis in the remainder. Tissue plasminogen activator (tPA), plasminogen activator inhibitor (PAI) 1, transforming growth factor (TGF) beta1 and tumour necrosis factor (TNF) alpha mRNA, and total fibrinolytic activity were assessed. The abdomen of non-operated animals was insufflated for 7, 15 or 30 min with carbon dioxide, after which tPA and PAI-1 mRNA and total fibrinolytic activity were measured., Results: Animals that underwent open adhesiolysis had 60 per cent fewer reformed adhesions than the laparoscopic adhesiolysis group (P < 0.001). There were no differences in tPA activity or tPA, PAI-1 and TNF-alpha mRNA between groups, but TGF-beta1 mRNA levels were significantly increased in the open group. Carbon dioxide insufflation did not affect peritoneal tPA activity., Conclusion: Open adhesiolysis may be more beneficial in minimizing adhesion reformation in the management of adhesion-related complications., ((c) 2010 British Journal of Surgery Society Ltd. Published by John Wiley & Sons, Ltd.)

The development of accurate in vitro screening assays to assess lung hazard potential of nanomaterials is a highly desirable goal. However, some studies have noted little correlation between in vitro and in vivo results. Moreover, a recent National Academy of Sciences report predicts that future hazard testing will be conducted primarily using cell culture assays. The three major objectives of this study were to compare lung toxicity impacts of nanoscale (NZnO) vs fine zinc oxide (FZnO) particulates, assess predictability of in vitro cell culture systems, and compare effects of instillation vs inhalation exposures in rats. Physicochemical aspects of ZnO particle types were rigorously characterized and did not agree with specifications provided by the supplier; i.e., the ZnO particle types were closer in size than advertised. Rats were exposed in vivo either by intratracheal instillation to 1 or 5 mg/kg of nanoscale or fine size zinc oxide particle types or by inhalation to aerosols of 25 or 50 mg/m3 for 1 or 3 h. Lung inflammation, cytotoxicity, and histopathological endpoints were assessed at several time points postexposure. Three different in vitro culture conditions were utilized. Cultures of (1) rat lung epithelial cells, (2) primary alveolar macrophages, and (3) alveolar macrophages-L2 lung epithelial cell cocultures were incubated with fine or nano ZnO particles and evaluated for cytotoxicity biomarkers (LDH) and proinflammatory cytokines (MIP-2 and TNF-alpha). In vivo exposures to instilled or inhaled fine or nanoscale ZnO produced "metal fume fever" responses, characterized by transient short-term lung inflammatory or cytotoxic responses. Alternatively, in vitro exposures to fine or nanoscale ZnO particles produced minor cytotoxic responses at 4 and 24 h, only in cocultures and at the highest (particle overload) dose with little detectable proinflammatory cytokine generation (MIP-2, and TNF-alpha). To summarize, the comparisons of in vivo and in vitro toxicity measurements following nano or fine ZnO particle exposures demonstrated little convergence and few differences in potency.

Background: Up to 94% of patients experience fibrous adhesions after abdominal surgery, and a significant number of these patients require a second operation for open or laparoscopic lysis of adhesions (LOA). The authors have previously shown that inhibition of the binding of tachykinin ligands to the neurokinin 1 receptor (NK-1R) using the neurokinin 1 receptor antagonist (NK-1RA) CJ-12,255 decreases primary adhesion formation and upregulates the peritoneal fibrinolytic system in a rat model. Whereas most studies have focused on the prevention of primary adhesions, few have addressed adhesion reformation after LOA. This study aimed to determine the effects of NK-1RA administration on adhesion reformation and peritoneal fibrinolytic activity after laparoscopic LOA., Methods: Adhesions were induced in 31 rats using our previously described ischemic button model. The rats underwent laparoscopy 7 days later, during which adhesions were scored and lysed followed by administration of the NK-1RA or saline. Then 7 days after LOA, 23 rats were killed and adhesions were scored. Eight rats also were killed 24 h after the LOA to obtain peritoneal tissue and fluid, which were analyzed for tissue plasminogen activator (tPA) mRNA expression and peritoneal fibrinolytic activity by reverse transcriptase-polymerase chain reaction (RT-PCR) and bioassay, respectively., Results: At laparoscopy, 79% +/- 3% of the buttons formed adhesions. In the saline-administered control animals, 42% +/- 3.2% of the buttons reformed adhesions after LOA (p < 0.05), whereas in the animals that received the NK-1RA, 18.2% +/- 3.5% of the buttons reformed adhesions (p < 0.05). As compared with control animals, NK-1RA administration increased tPA mRNA levels by 38% and fibrinolytic activity sixfold (p < 0.05; 7.0 +/- 2.1 U/ml vs 1.2 +/- 0.54 U/ml)., Conclusions: When administered during laparoscopic LOA, an NK-1RA significantly upregulates peritoneal fibrinolytic activity and decreases adhesion reformation.

The aim of this study was to evaluate the acute lung toxicity in rats of intratracheally instilled TiO2 particles that have been substantially encapsulated with pyrogenically deposited, amorphous silica. Groups of rats were intratracheally instilled either with doses of 1 or 5 mg/kg of hydrophilic Pigment A TiO2 particles or doses of 1 or 5 mg/kg of the following control or particle-types: 1) R-100 TiO2 particles (hydrophilic in nature); 2) quartz particles, 3) carbonyl iron particles. Phosphate-buffered saline (PBS) instilled rats served as additional controls. Following exposures, the lungs of PBS and particle-exposed rats were evaluated for bronchoalveolar lavage (BAL) fluid inflammatory markers, cell proliferation, and by histopathology at post-instillation time points of 24 hrs, 1 week, 1 month and 3 months. The bronchoalveolar lavage results demonstrated that lung exposures to quartz particles, at both concentrations but particularly at the higher dose, produced significant increases vs. controls in pulmonary inflammation and cytotoxicity indices. Exposures to Pigment A or R-100 TiO2 particles produced transient inflammatory and cell injury effects at 24 hours postexposure (pe), but these effects were not sustained when compared to quartz-related effects. Exposures to carbonyl iron particles or PBS resulted only in minor, short-term and reversible lung inflammation, likely related to the effects of the instillation procedure. Histopathological analyses of lung tissues revealed that pulmonary exposures to Pigment A TiO2 particles produced minor inflammation at 24 hours postexposure and these effects were not significantly different from exposures to R-100 or carbonyl iron particles. Pigment A-exposed lung tissue sections appeared normal at 1 and 3 months postexposure. In contrast, pulmonary exposures to quartz particles in rats produced a dose-dependent lung inflammatory response characterized by neutrophils and foamy (lipid-containing) alveolar macrophage accumulation as well as evidence of early lung tissue thickening consistent with the development of pulmonary fibrosis. Based on our results, we conclude the following: 1) Pulmonary instillation exposures to Pigment A TiO2 particles at 5 mg/kg produced a transient lung inflammatory response which was not different from the lung response to R-100 TiO2 particles or carbonyl iron particles; 2) the response to Pigment A was substantially less active in terms of inflammation, cytotoxicity, and fibrogenic effects than the positive control particle-type, quartz particles. Thus, based on the findings of this study, we would expect that inhaled Pigment A TiO2 particles would have a low risk potential for producing adverse pulmonary health effects.

Using both in vivo (inhalation) and in vitro (cell culture) studies, we previously reported that p-aramid respirable fibers (RFP--defined as respirable-sized fiber-shaped particulates) are biodegraded in lungs and lung cells of rats following exposures. The current studies were undertaken to determine whether shortening mechanisms of p-aramid RFP biodegradability are also operative in human lung cells. Cultures of human A549 lung epithelial cells (A549), primary alveolar macrophages (HBAL) (collected via bronchoalveolar lavage [BAL]) from volunteers), and co-cultures (Co) of the A549 and HBAL were incubated with p-aramid RFP for either 1 h, 1 day, or 1 week to assess RFP shortening. Lengths of RFP were measured using scanning electron microscopy (SEM) following fixation, digestion of culture tissue components, and processing. Similar to findings using rat lung cells, only slight RFP shortening was measured in A549 cultures at 1-day and 1-week post-incubation. More importantly, in HBAL and Co groups, greater transverse cleavage of p-aramid RFP was measured at 1-day and 1-week postexposure compared to 1-h HBAL or Co groups, or in any A549 groups. In contrast, cellulose RFP, a biopersistent reference control fiber, were not measurably shortened under similar circumstances. Second, p-aramid RFP were incubated either with phosphate-buffered saline (PBS), or acellular BAL fluids from human volunteers or rats and processed for SEM analysis of RFP lengths. Mean lengths of p-aramid RFP incubated with human or rat BAL fluids were substantially decreased compared to PBS. Similar to our findings with rat lung cells, components of human lung fluids coat the p-aramid RFP as a prerequisite for subsequent enzymatic cleavage by human phagocytic lung cells and this finding reinforces the concept that inhaled p-aramid RFP are likely to be biodegradable in the lungs of humans.

Most pigment-grade titanium dioxide (TiO(2)) samples that have been tested in pulmonary toxicity tests have been of a generic variety-i.e., generally either uncoated particles or TiO(2) particles containing slightly hydrophilic surface treatments/coatings (i.e., base TiO(2)). The objectives of these studies were to assess in rats, the pulmonary toxicity of inhaled or intratracheally instilled TiO(2) particle formulations with various surface treatments, ranging from 0-6% alumina (Al(2)O(3)) or alumina and 0-11% amorphous silica (SiO(2)). The pulmonary effects induced by TiO(2) particles with different surface treatments were compared to reference base TiO(2) particles and controls. In the first study, groups of rats were exposed to high exposure (dose) concentrations of TiO(2) particle formulations for 4 weeks at aerosol concentrations ranging from 1130-1300 mg/m(3) and lung tissues were evaluated by histopathology immediately after exposure, as well as at 2 weeks and 3, 6, and 12 months postexposure. In the second study, groups of rats were intratracheally instilled with nearly identical TiO(2) particle formulations (when compared to the inhalation study) at doses of 2 and 10 mg/kg. Subsequently, the lungs of saline-instilled and TiO(2)-exposed rats were assessed using both bronchoalveolar (BAL) biomarkers and by histopathology/cell proliferation assessment of lung tissues at 24 h, 1 week, 1 and 3 months postexposure. The results from these studies demonstrated that for both inhalation and instillation, only the TiO(2) particle formulations with the largest components of both alumina and amorphous silica surface treatments produced mildly adverse pulmonary effects when compared to the base reference control particles. In summary, two major conclusions can be drawn from these studies: (1) surface treatments can influence the toxicity of TiO(2) particles in the lung; and (2) the intratracheal instillation-derived, pulmonary bioassay studies represent an effective preliminary screening tool for inhalation studies with the identical particle-types used in this study.

The aim of this study was to evaluate the acute lung toxicity of intratracheally instilled single-wall carbon nanotubes (SWCNT) in rats. The lungs of rats were instilled either with 1 or 5 mg/kg of the following control or particle types: (1) SWCNT, (2) quartz particles (positive control), (3) carbonyl iron particles (negative control), (4) phosphate-buffered saline (PBS) + 1% Tween 80, or (5) graphite particles (lung tissue studies only). Following exposures, the lungs of PBS and particle-exposed rats were assessed using bronchoalveolar lavage (BAL) fluid biomarkers and cell proliferation methods, and by histopathological evaluation of lung tissue at 24 h, 1 week, 1 month, and 3 months postinstillation. Exposures to high-dose (5 mg/kg) SWCNT produced mortality in ~15% of the SWCNT-instilled rats within 24 h postinstillation. This mortality resulted from mechanical blockage of the upper airways by the instillate and was not due to inherent pulmonary toxicity of the instilled SWCNT particulate. Exposures to quartz particles produced significant increases versus controls in pulmonary inflammation, cytotoxicity, and lung cell parenchymal cell proliferation indices. Exposures to SWCNT produced transient inflammatory and cell injury effects. Results from the lung histopathology component of the study indicated that pulmonary exposures to quartz particles (5 mg/kg) produced dose-dependent inflammatory responses, concomitant with foamy alveolar macrophage accumulation and lung tissue thickening at the sites of normal particle deposition. Pulmonary exposures to carbonyl iron or graphite particles produced no significant adverse effects. Pulmonary exposures to SWCNT in rats produced a non-dose-dependent series of multifocal granulomas, which were evidence of a foreign tissue body reaction and were nonuniform in distribution and not progressive beyond 1 month postexposure (pe). The observation of SWCNT-induced multifocal granulomas is inconsistent with the following: (1) lack of lung toxicity by assessing lavage parameters, (2) lack of lung toxicity by measuring cell proliferation parameters, (3) an apparent lack of a dose response relationship, (4) nonuniform distribution of lesions, (5) the paradigm of dust-related lung toxicity effects, (6) possible regression of effects over time. In addition, the results of two recent exposure assessment studies indicate very low aerosol SWCNT exposures at the workplace. Thus, the physiological relevance of these findings should ultimately be determined by conducting an inhalation toxicity study.

The aim of this study was to assess and compare the acute lung toxicities of intratracheally instilled hydrophobic relative to hydrophilic surface-coated titanium dioxide (TiO(2)) particles using a pulmonary bridging methodology. In addition, the results of these instillation studies were bridged with data previously generated from inhalation studies with hydrophilic, pigment-grade (base) TiO(2) particles, using the base, pigment-grade TiO(2) particles as the inhalation/instillation bridge material. To conduct toxicity comparisons, the surface coatings of base pigment-grade TiO(2) particles were made hydrophobic by application of triethoxyoctylsilane (OTES), a commercial product used in plastics applications. For the bioassay experimental design, rats were intratracheally instilled with 2 or 10 mg/kg of the following TiO(2) particle-types: (1) base (hydrophilic) TiO(2) particles; (2) TiO(2) with OTES surface coating; (3) base TiO(2) with Tween 80; or (4) OTES TiO(2) with Tween 80. Saline instilled rats served as controls. Following exposures, the lungs of sham- and TiO(2)-exposed rats were assessed both using bronchoalveolar lavage (BAL) biomarkers and by histopathology of lung tissue at 24 hours, 1 week, 1 month, and 3 months post exposure. The results demonstrated that only the base, high-dose (10 mg/kg) pigment-grade TiO(2) particles and those with particle-types containing Tween 80 produced a transient pulmonary inflammatory response, and this was reversible within 1 week postexposure. The authors conclude that the OTES hydrophobic coating on the pigment-grade TiO(2) particle does not cause significant pulmonary toxicity.

These studies elucidated mechanisms of inhaled p-aramid respirable fiber-shaped particulates (RFP) biodegradation in the lungs of exposed rats and hamsters. We postulate that lung fluids coat/activate inhaled p-aramid RFP which deposits in the lung and promote enzymatic attack and consequent shortening. 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 techniques. In vivo, the enzyme but not the KOH solution produced shortening of p-aramid but not cellulose RFP recovered from the lungs. For in vitro studies, the two RFP-types were incubated with BAL fluids and underwent simulated digestions; also rat lung epithelial cells, macrophages or co-cultures were incubated with p-aramid and digested at 1, 24, or 168 h postexposure. The results of in vitro acellular studies demonstrated that only p-aramid RFP incubated in BAL fluids and digested by the enzyme method were shortened. In vitro cellular studies demonstrated a shortening of p-aramid RFP in macrophages and co-cultures but not in lung epithelial cells at 24 h and 1 week postexposure. These results demonstrate that lung fluids coat and catalyze the p-aramid RFP as a prelude for shortening and describe a likely mechanism for the biodegradability of inhaled p-aramid RFP in the lungs of exposed animals.

Biopersistence represents an important health-related issue in fiber toxicology. These studies were undertaken to elucidate the mechanism(s) through which inhaled p-aramid respirable-sized fiber-shaped particulates (RFP) are biodegraded in the lungs of exposed rats and hamsters. Previously, we and others have reported that, following deposition in the lung, long p-aramid RFPs are cleaved into shorter fibrous fragments. To investigate the mechanisms of RFP biodegradation, we have postulated that lung fluids coat/activate p-aramid RFP following deposition in the alveolar regions of the lung, thus predisposing the RFP to enzymatic attack and consequent shortening. This process enhances the rate of clearance of the inhaled RFP. To test this hypothesis, we have conducted both in vivo and in vitro cellular and noncellular investigations. First, p-aramid or cellulose RFP were instilled into the lungs of rats and the lungs were digested 24 h postexposure using two different digestion techniques: (1) a conventional ethanolic KOH method and (2) an enzymatic method that simulates the action of lung enzymes. Cellulose RFP were utilized as a control organic fiber-type that is known to be biopersistent. The results demonstrated that the enzymatic but not the KOH method resulted in transverse cleavage of the p-aramid RFP; the lengths of cellulose RFP recovered from rat lungs were not reduced by either method. Next, standardized preparations of p-aramid RFP or cellulose RFP were incubated with saline or lung fluids and then processed by one of two tissue digestion techniques. Mean lengths of p-aramid RFP incubated with saline and processed with KOH or the enzyme method were not found to be altered. Indeed, only the preparation of p-aramid RFP that had been incubated with bronchoalveolar lavage (BAL) fluids and processed with the enzyme solution resulted in cleavage of p-aramid RFP. Moreover, when the BAL fluids were autoclaved to denature proteins, the length dimensions of p-aramid RFP were intermediate between saline controls and RFP incubated with normal BAL fluids and processed via the enzymatic technique. In contrast to the in vitro noncellular 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 to that fiber-type. In a final set of in vitro cellular studies, cultures of rat lung epithelial cells, alveolar macrophages, or co-cultures of epithelial cells and macrophages were treated with p-aramid RFP for 1 h, 1 day, or 1 week to determine whether RFP shortening occurs directly in the phagocytic cells. The lengths of fibrils were measured using scanning electron microscopy techniques. The results demonstrated that (1) no shortening occurred in the epithelial cell cultures at any time point; however, (2) in the macrophage and cocultures, cleavage of p-aramid RFP was observed at 1 day and 1 week postexposure. Our data suggest that components of lung fluids coat and catalyze the p-aramid RFP as a prerequisite for enzymatic cleavage. This process could play a significant role in facilitating the transverse cleavage or shortening of inhaled p-aramid RFP in the lungs of exposed rats and hamsters., (Copyright 2001 Academic Press.)

In an effort to assess potential ecological hazards to amphibian species in selected regions within New Hampshire, the traditional Frog Embryo Teratogenesis Assay-Xenopus (FETAX), a 14-/21 day tail resorption thyroid disruption assay and >30 day limb development tests were conducted with representative surface water and sediment samples. Two separate sets of samples collected from five sites were evaluated. The primary objectives of the study were to determine if samples were capable of inducing early embryo-larval maldevelopment, to determine if maldevelopment included limb defects, to determine if thyroxine co-administration altered the rates of limb malformation and to evaluate the impact of the samples on growth rates, developmental progress and metamorphic climax. Results from these studies suggested that pond water and sediment extract samples, but not whole sediment samples, from B2, FW, LP and W ponds were capable of inducing abnormal early embryo-larval development. In addition, water samples from B2 and W ponds induced significant abnormal hindlimb development. Some abnormal forelimb development was noted in the tail resorption studies, but not to the same extent as the hindlimbs. Each of the water samples induced appreciable developmental delay, including the paired reference site B1, which could be reversed by the addition of exogenous thyroxine., (Copyright 2001 John Wiley & Sons, Ltd.)

Man-made organic fibers (MMOFs) have been manufactured for over 50 years. Until recently, there have been few concerns raised regarding the safety of organic fiber dusts. This is due, in large part, to the perception that the dimensions of most, if not all, of these products were too large to be inhaled into the distal lungs of workers, i.e., were considered to be nonrespirable. A brief review of some of the issues related to organic fiber toxicology is presented herein. Some of the organic fiber-types used in commerce are identified and some fundamental tenets of fiber toxicology are discussed. In addition, the European Union, in their recent consideration for banning chrysotile asbestos fibers, evaluated some organic fiber substitutes and compared them to the hazards of asbestos. A brief review of their conclusions is described below. Finally, the results of some recent studies assessing the mechanisms of biodegradability of para-aramid respirable-sized, fiber-shaped particulates (RFP) are presented. Para-aramid (p-aramid) RFP are the most extensively-studied respirable organic fiber-type and RFP is the new term which describes respirable-sized organic fibers (ECETOC, 1996) (1). The results of these studies provide clues regarding the mechanism(s) of p-aramid RFP shortening in the lungs of exposed animals, and may be relevant for humans.

The emu (Dromaius novaehollandiae) shows potential as a unique animal model for replicating the femoral head collapse process seen in end-stage human osteonecrosis. Since the collapse phenomenon (and interventions to prevent it) involve mechanical processes, it is important to elucidate the similarities and differences of emus versus humans in terms of hip joint biomechanics. A first step for comparison is the intrinsic mechanical properties of the respective bone tissues, as reflected in cortical bone flexural stiffness and strength. In four-point bending, emu cortical bone was found to have an elastic modulus of 13.1 GPa. Its yield stress was determined to be 113 MPa and the ultimate strength was 146 MPa. Emu cortical bone's elastic modulus was similar to that of other avian species, and falls approximately 25% below that of the human (17.3 GPa).

Declines in amphibian populations, and amphibians with gross malformations, have prompted concern regarding the biological status of many anuran species. A survey of bullfrogs, Rana catesbeiana, and green frogs, Rana clamitans, conducted in central and southern New Hampshire showed malformed frogs at 81% of the sites sampled (13 of 16 sites). Brain gonadotropin-releasing hormone (GnRH) and the synthesis of androgens and estradiol, hormones essential to reproductive processes, were measured from limb-malformed and normal (no limb malformation) frogs. Normal frogs had significantly higher concentrations (nearly 3-fold) of in vitro produced androgens and of brain GnRH than malformed frogs. Because most malformations are thought to occur during development, we propose that environmental factors or endocrine-disrupting chemicals that may cause developmental abnormalities also act during early development to ultimately cause abnormally reduced GnRH and androgen production in adult frogs. The consequences of reduced GnRH and androgens on anuran reproductive behavior and population dynamics are unknown but certainly may be profound and warrant further research.

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.

Allergic asthma is a pulmonary disease characterized by antigen-induced pulmonary eosinophilia, airway hyperresponsiveness, antigen-specific IgE antibody responses, and broncho-constriction. In attempting to elucidate mechanisms associated with the pathogenesis of this disease, a number of animal models have been developed. The current studies were undertaken to develop a model of allergic asthma model in Brown Norway rats. Unlike the neutrophilic inflammatory response to inhaled particles in most strains of rats, inhalation of antigens in sensitized Brown Norway rats results in a complex cellular response which is characterized by a variety of inflammatory cell types, and is dependent on the time course of inflammatory cell recruitment. In characterizing this ovalbumin-challenge model of allergic asthma, it was important to assess the time course of pulmonary inflammation, cell proliferation, and apoptosis. Male Brown Norway rats were sensitized and boosted with intraperitoneal injections of ovalbumin in aluminum hydroxide on experimental days 1 and 8. On days 15-17, rats were challenged by an inhalation exposure to 5% ovalbumin and were evaluated by bronchoalveolar lavage (BAL) at 24 or 48 h postexposure (PE). Control rats were similarly treated to ovalbumin aerosol exposures; however, these animals had been sensitized and boosted with aluminum hydroxide (minus the ovalbumin). Cell differential evaluations demonstrated that the rats exposed for 3 days/24 h postexposure and for 2 days/ 48 h postexposure produced the greatest numbers of BAL eosinophils and corresponding indicators of pulmonary toxicity. It was interesting to note that earlier exposure time periods (i.e., 1 day/24 h PE) generated a predominantly neutrophilic inflammatory response, while longer exposure/postexposure time periods (i.e., 3 days/48 h) produced a predominant mononuclear inflammatory response. Subsequent studies demonstrated that the 2-day/ 48-h protocol produced the optimum eosinophilic, cytotoxic, cell proliferative, and apoptotic response. Histopathological evaluations demonstrated a chronically active alveolitis and bronchiolitis, characterized by epithelial cell proliferation in the airways and inflammatory cell proliferation in the alveoli. Studies are ongoing to assess the cell types undergoing apoptosis in both the airway and parenchymal regions to fully characterize this model in order to assess its relevance and utility for studying asthma in humans.

The extraordinary growth of the Internet has created a revolutionary leap in the ability of health professionals to easily communicate and access information. These resources are readily available to the public as well, and an understanding of these sources is important in determining the validity of the content. A few Internet sites of interest to dentists interested in anesthesia and pain control are presented to demonstrate the depth and breadth of these resources via the Internet.

Clinical and experimental evidence suggest that periprosthetic bone loss following total hip arthroplasty is caused in part by stress-shielding. Changes in bone stress in the proximal femur following implantation can be estimated with use of composite beam theory. We hypothesized that the degree of stress-shielding predicted by beam theory correlates with the magnitude of bone loss following cemented total hip arthroplasty. We analyzed cross sections from the proximal femur of 13 patients who had undergone unilateral cemented total hip arthroplasty. A matching implant was inserted contralaterally, and the cross-sectional properties of the implant and bone and the bone density were determined. Bone loss was calculated on the basis of differences between contralateral (control) and ipsilateral (remodeled) sections and correlated to several beam-theory parameters calculated from the control sections: implant rigidity, bone rigidity, ratio of implant to bone rigidity, and predicted decrease in bone stress. All parameters except implant rigidity were significantly correlated with bone loss (p < 0.05). Parameters that included implant and bone properties were more strongly correlated with bone loss than were those based on bone properties alone. The predicted decrease in bone stress explained 50-60% of the variance in bone loss. The data also indicated that patients were not likely to lose substantial amounts of bone unless the reduction in bone stress exceeded a threshold value. Although limited by a small and heterogeneous sample, these results indicate that beam-theory predictions correlate with the degree of femoral resorption and should be investigated further as a means to identify patients at high risk for bone loss.

Occupational therapy, formally organized in the United States in 1917, is considered an allied health field. Mapping occupational therapy literature is part of a bibliometric project of the Medical Library Association's Nursing and Allied Health Resources Section's project for mapping the literature of allied health. Three core journals were selected from the years 1995 and 1996 and a determination was made of the extent to which the cited journal references were covered by standard indexing sources. Using Bradford's Law of Scattering three zones were created, each containing approximately one-third of the cited journal references. The results showed that three journals made up the first zone, 117 journals the second, and 657 the third. The most cited journal was the American Journal of Occupational Therapy. In the second zone, journals from twelve disciplines were identified. While MEDLINE provided the best overall indexing, the Cumulative Index to Nursing and Allied Health Literature (CINAHL) was the only database that indexed the three most cited journals plus nine of the currently active titles in occupational therapy. MEDLINE could improve its coverage of occupational therapy by indexing the journals of the British, Canadian, and Australian national associations.

Objective. To present a novel approach for treatment of intractable occipital neuralgia using percutaneous peripheral nerve electrostimulation techniques. Methods. Thirteen patients underwent 17 implant procedures for medically refractory occipital neuralgia. A subcutaneous electrode placed transversely at the level of C1 across the base of the occipital nerve trunk produced paresthesias and pain relief covering the regions of occipital nerve pain Results. With follow-up ranging from 1-½ to 6 years, 12 patients continue to report good to excellent response with greater than 50% pain control and requiring little or no additional medications. The 13th patient (first in the series) was subsequently explanted following symptom resolution. Conclusions. In patients with medically intractable occipital neuralgia, peripheral nerve electrostimulation subcutaneously at the level of C1 appears to be a reasonable alternative to more invasive surgical procedures following failure of more conservative therapies.

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.

The endogenous factors that underlie the transient induction of the gene encoding spermidine/spermine N1-acetyltransferase (SSAT), the rate-limiting enzyme in cellular polyamine catabolism, in pig uterine endometrium during periimplantation are not known. The present study examined a number of peptide growth factors and regulatory molecules that are present within the uterine environment at early pregnancy, coincident with maximal SSAT gene expression, for their ability to manifest endogenous SSAT gene-inducing activity. Basal SSAT expression in luminal epithelial cells was higher (p < 0. 01) than that for glandular epithelial (GE) or stromal (ST) cells. Recombinant human insulin-like growth factor-I (IGF-I; 50 ng/ml) had no effect on steady-state SSAT mRNA levels, but it increased mitogenesis in all three cell types. In contrast, IGF-I caused a marked induction (p < 0.01) of SSAT mRNA levels in the human endometrial carcinoma cell line Hec-1-A. Uterine explants incubated with interleukin-6, transforming growth factor alpha, epidermal growth factor (each at 1, 10, and 100 ng/ml), retinoic acid and retinol (each at 0.01, 0.1, and 1 microM), and estradiol-17beta (10 nM) had SSAT mRNA levels similar to controls. By contrast, leukemia inhibitory factor (LIF; at 10 and 100 ng/ml) caused a modest, but significant (p < 0.05), increase in SSAT mRNA levels over those of untreated explants. This effect of LIF, however, did not approach the level of induction observed in GE or ST cells after addition of medium conditioned by Day 12 or 17 porcine conceptuses and in endometrial explants supplemented with medium conditioned by Day 21 porcine conceptuses or a continuous cell line (Jag-1) derived from Day 14 porcine trophoblast. We suggest that transient induction of endometrial SSAT gene expression at implantation is mediated by the functional interactions of specific conceptus-derived regulatory factors, distinct from estrogen, with endometrial-derived factor(s) such as LIF. These complex interactions are probably requisite for the transient, yet dramatic, induction of SSAT gene expression and may be critical for successful implantation.

The S-1 peplomer gene sequences of 31 strains of avian coronavirus infectious bronchitis virus (IBV) from North America, Europe, and Australia were compared to identify common and unique regions for possible diagnostic applications. S-1 sequences that were conserved among serotypes and sequences that were variable between serotypes were identified. Based on conserved S-1 gene sequences, "general" degenerate oligonucleotide primers were designed that amplified IBV genomic RNA by the reverse transcriptase polymerase chain reaction (RT-PCR) procedure regardless of serotype. Primers specific for IBV serotypes Massachusetts, Connecticut, Arkansas, JMK, Delaware (DE/072/92), and California (CA/633/85) were designed from regions of the S-1 gene exhibiting extensive sequence hypervariability. The ability to identify these six serotypes of IBV by RT-PCR was demonstrated by testing the serotype-specific primers on a panel of unknown samples that included 30 reference strains and field isolates previously characterized by virus neutralization (VN). The use of serotype-specific primers in RT-PCR provides a rapid and accurate means of identifying IBV.

The contributions of the conceptus (embryo and associated membranes) and of the maternal endocrine milieu to control of endometrial secretory leukocyte protease inhibitor (SLPI, also designated antileukoproteinase) expression during the periimplantation stages of embryo development were examined in the present study. Uterine endometrium from distinct sites was collected from pigs at Days 16-25 of pregnancy and analyzed for steady-state SLPI mRNA levels. Endometrium situated directly beneath conceptuses (mesometrial) had greater (p < 0.05) SLPI mRNA levels than that obtained from antimesometrial and interimplantation sites and myometrium. This site-specific difference was most pronounced during late (Days 19-21) and post (Days 23-25)-implantation stages and was also observed, albeit to a lesser degree, for the mRNA encoding uteroferrin (Uf). Conditioned medium (CM; 50% v:v) from Day 21, but not Day 12, conceptuses increased (p < 0.05) SLPI mRNA levels, while neither CM affected mRNA levels for Uf and several other genes expressed in endometrial explants. One inducing factor in Day 21 CM was characterized as a low-molecular-mass (< 12 kDa), relatively heat-stable protein. Transforming growth factor (TGF alpha) increased (p < 0.05), epidermal growth factor (EGF) tended to increase (p = 0.10), and insulin-like growth factor (IGF)-I and IGF-II had no effect (p > 0.10) on, SLPI mRNA levels in Day 12 endometrial explants. Medium conditioned by the pig trophoblast cell line, Jag-1, but not by other mammalian cell lines, had SLPI inducer activity. The maternal endocrine contribution to SLPI gene expression was examined using freshly isolated and short-term-cultured Day 12 and Day 21 pregnant pig endometrium. Steady-state SLPI mRNA levels were increased (p < 0.05) in Day 12, but not Day 21, tissues upon short-term culture in serum-free medium. This increase was time dependent, was similarly demonstrated for Uf mRNA, was not observed in corresponding lung and liver, and was inhibited by inclusion of serum from pigs of diverse endocrine status. In summary, two potential modulators of endometrial SLPI gene expression were identified: 1) a conceptus-derived low-molecular-mass protein, possibly TGF alpha, that mediates in part the up-regulation of SLPI gene expression in endometrium closely associated with implantation sites, and 2) an inhibitory component(s) present in maternal serum. Results suggest opposing actions of maternal and embryonic factors at the maternal-embryo interface and highlight involvement of the periimplantation embryo in directing the spatiotemporal expression of endometrial genes implicated in its development.

Intrauterine growth restriction is associated with abnormalities in the fetal circulation. These abnormalities are currently best understood in the umbilical arterial and venous systems. Changes in intracardiac velocities are more variable as well as more difficult to detect. Doppler ultrasound, particularly of the umbilical circulation, has been useful in the fetus at risk for growth restriction, particularly in serial studies of a fetus identified as requiring increased surveillance. Doppler ultrasound also can add to the general understanding of the physiologic changes that occur in growth-restricted fetuses.

Objective: To identify the source of umbilical venous velocity pulsations, times of transmission from the atrial contraction pressure waveform to velocity waves in the inferior vena cava, ductus venosus, intra-abdominal umbilical vein, and intra-amniotic umbilical vein were examined., Methods: Five lamb fetuses at 125-135 days' gestation were instrumented with solid state pressure transducers in the inferior vena cava, fluid-filled catheters in the inferior vena cava and descending aorta, and epicardial pacemakers. Three to 5 days postoperatively, inferior vena cava, ductus venosus, and umbilical vein velocities were examined with Doppler ultrasound. Normal saline was administered and umbilical vein velocity pulsations developed (180 +/- 60 mL). In three fetuses, premature atrial contractions were induced under baseline conditions and after umbilical vein velocity pulsations developed., Results: Times of transmission from the atrial contraction pressure waveform until velocity decreases in the fetal venous system were significantly different in the inferior vena cava, ductus venosus, intra-abdominal umbilical vein, and intra-amniotic umbilical vein (P < .001). Times increased with the distance from the atrium. Inferior vena cava pressure increased with fluid administration from 3.7 +/- 4.7 mmHg to 9.3 +/- 2.3 mmHg (P < .01). Time from increased pressure waveforms with induced premature atrial contractions to the nadir of subsequent umbilical vein velocity waves decreased from 0.123 +/- 0.047 seconds before saline administration to 0.072 +/- 0.039 seconds after saline administration (P < .001)., Conclusion: Transmission time of atrial pressure into the venous circulation increases with distance from the atrium and decreases with volume loading. Umbilical venous velocity pulsations derive from atrial pressure changes transmitted in a retrograde fashion.

The aim of this study was to compare ketoprofen to acetaminophen with hydrocodone (A/H) in a postoperative periodontal pain model. A double-blind protocol was used. Thirty minutes prior to each procedure, subjects were given orally either 100 mg ketoprofen or a placebo tablet. Four hours later, the subjects took either 50 mg ketoprofen (ketoprofen group) or 1000 mg acetaminophen with 10 mg hydrocodone (placebo group). Subjects reported levels of overall discomfort and pain using visual analog scales at eight hourly intervals following the first dose of ketoprofen or placebo. Information about adverse side effects was requested from the patients in the form of a checklist. The results revealed only small differences between the two drug regimens with respect to levels of pain or overall discomfort. A/H provided significantly better pain relief at Hours 5 and 6, while overall discomfort levels were significantly higher with ketoprofen than with placebo at Hours 3 and 4. Pain levels were low for both groups. It is recommended that additional analgesics for mild to moderate pain should be tested.

The aim of this investigation was to establish a homologous culture system for study of the transcriptional mechanisms underlying endometrial expression of the pregnancy-associated genes encoding antileukoproteinase (ALP), an elastase/cathepsin G protease inhibitor, and uteroferrin (Uf), a transplacental iron transport protein. Glandular epithelial (GE), Luminal epithelial (LE), and stromal (ST) cells were isolated from pig endometrium at Day 12 of pregnancy by differential enzymatic digestion and sieve filtration. The three cell populations differed with respect to their morphology in culture and with respect to their expression of ALP and Uf. Expression of the ALP gene was much higher in GE than in LE cells and was undetectable in ST cells. Similarly, GE had the highest expression of the Uf gene, and expression in ST was lower but distinct. Western blot analysis of conditioned media (72 h) from GE, LE, and ST, using antiporcine Uf antiserum, detected significant levels of secreted Uf only in GE. The steroid hormone responsiveness of GE cells was monitored by changes in steady-state levels of ALP mRNA after 24-h exposure to estradiol 17 beta (E2; 10 nM) and/or progesterone (P; 10 nM). Glandular epithelial cells treated with E2, P, and E2 + P had increased (p < 0.05) ALP mRNA levels relative to those in control cultures. Glandular epithelial cells were transiently transfected with reporter constructs containing the 5'-flanking genomic regions of each gene. For ALP, the 1266-nucleotide (nt) region of the ALP 5'-flanking genomic DNA, and progressive 5' deletions within this region, were coupled to a luciferase reporter gene (LUCE). The most proximal 119-bp fragment (-119ALP LUCE), which contains the TATAA box (-21 to -26 nt) and a GC-rich sequence (-66 to -74 nt), was sufficient to confer transcriptional activity to the reporter vector. Progressively longer 5'-genomic fragments had promoter activities higher than or similar to those of the 119-nt fragment. Estrogen had no effect on the transcriptional activities of any of the ALP constructs. Uteroferrin 5'-flanking and promoter DNA constructs containing the chloramphenicol acetyl transferase (CAT) reporter gene also exhibited transcriptional activity in GE cells. The presence of multiple interacting cis-regulatory sequences within this region was demonstrated by increased promoter activity, relative to that of the smallest construct (-182 UFCAT-E; basal activity), with the inclusion of sequences between -182 and -484 nf, and drastic reduction to basal activity with the inclusion of sequences between -484 and -831 nt. In summary, primary cultures of GE from early-pregnant porcine endometrium express ALP and Uf, are steroid hormone-responsive, and support the transcriptional activity of endometrial-associated gene promoter and regulatory sequences. The use of primary GE cells thus provides a convenient in vitro system for further study of the endocrine, paracrine, and autocrine factors regulating endometrial gene expression during pregnancy.

Neuroscience and occupational therapy in physical rehabilitation have developed along parallel tracks. As physicians began to study the neural bases of motor control, they also began to reconsider the sequelae of "hopeless" diagnoses as conditions that they could influence. This change in some physicians' understanding of the neural mechanisms of motor control influenced other clinicians' ideas about patient care. Early work on treatment of patients with cerebral palsy and polio led to improvements in treatment approaches used to facilitate motor skill and functional motor ability in patients with upper motor neuron disorders. From the 1950s to the present, therapists have refined their treatment techniques as knowledge from neuroscience has become available. A few therapists, who are gradually increasing in number, have turned to the laboratory to study basic neuroscience problems that affect clinical treatment. This article describes the development of neuroscience research and neurorehabilitation theories and indicates common themes.

Objective: To examine effects of fluid administration on inferior vena cava pressure and umbilical venous Doppler velocities in the term fetal lamb., Methods: With the ewe given inhalation anesthetics, eight chronically instrumented intrauterine fetal lambs at 125-135 days' gestation were given normal saline fluid boluses. Inferior vena cava peak pressures and umbilical venous Doppler velocities were measured before, during, and after administration of normal saline. Pressures were obtained with fluid-filled and solid state pressure transducers., Results: Umbilical venous Doppler velocity pulsations developed in six fetuses after 120 mL and all eight fetuses after 240 mL of fluid were administered. Inferior vena cava peak pressure increased from 5.15 +/- 2.7 to 10.9 +/- 3.9 mmHg (P < .001). Heart rate did not change significantly, and umbilical arterial systolic-to-diastolic velocity ratios decreased (P < .03)., Conclusion: Umbilical venous Doppler velocity pulsations developed after fluid administration and were associated with increases in inferior vena cava peak pressure. These findings suggest that umbilical venous pulsations develop when fetal venous pressures are elevated.

Objective: To examine the incidence of very low birth weight (VLBW) neonates, defined as those weighing less than 1500 g, delivered by adolescents compared with the general obstetric population., Methods: A retrospective observational study of 16,857 women delivering live-born infants from January 1, 1989, to June 30, 1993, was conducted at the University of Arizona Health Sciences Center. Adolescents were defined as those having a maternal age of 18 years or less at the time of delivery. The rate of VLBW infants delivered to adolescent mothers was compared with the general obstetric population (women at least 19 years old) using chi 2 analysis, multiple analysis of variance, and multiple linear regression., Results: During the study period, 204 VLBW infants were delivered, yielding an overall VLBW delivery rate of 1.2%. Adolescents had a VLBW delivery rate that was considerably higher than the general obstetrical population: 35 of 1758 (2.0%) versus 169 of 15,099 (1.1%) (P = .002). Whereas adolescents accounted for 10.6% of the total deliveries during the study period, they delivered 17% of the VLBW neonates. The relative risk of an adolescent delivering a VLBW infant was 1.7 (95% confidence interval 1.2-2.2)., Conclusion: Preterm birth is one of the major unresolved problems in modern obstetrics. Although the association between adolescence and preterm birth has been reported previously, specific attention has not been focused on the VLBW neonate. We conclude that adolescents deliver a disproportionate number of VLBW infants.

When evaluated for promotion or tenure, faculty members are increasingly judged more on the quality than on the quantity of their scholarly publications. As a result, they want help from librarians in locating all citations to their published works for documentation in their curriculum vitae. Citation analysis using Science Citation Index and Social Science Citation Index provides a logical starting point in measuring quality, but the limitations of these sources leave a void in coverage of citations to an author's work. This article discusses alternative and additional methods of locating citations to published works.

Background: Adequate amniotic fluid (AF) volume is one of several factors felt to be essential for normal lung development. Renal agenesis and urinary tract obstruction usually result in oligohydramnios and pulmonary hypoplasia., Case: Two sets of monoamiotic twins with discordant urinary tract anomalies were seen. One twin in each set had anomalies that in a singleton or diamiotic pregnancy would likely have resulted in fetal pulmonary hypoplasia and subsequent death. However, neither of these infants had pulmonary hypoplasia. One infant is unique in being the first case reported of normal pulmonary function and survival despite the anomaly., Conclusion: Adequate AF provided by a monoamniotic twin environment may prevent pulmonary hypoplasia, which usually results from oligohydramnios due to certain fetal urinary tract anomalies.

Objective: To describe ethnic differences in tobacco use during pregnancy in a clinical population of Mexican-American and non-Hispanic white women., Methods: Subjects were randomly selected from all patients attending a university-based obstetrics clinic in Tucson, Arizona. Of 555 subjects selected, 367 were interviewed and had their urinary cotinine levels measured. The 37 subjects who refused an interview and the 136 who were selected but not interviewed did not differ from other subjects regarding ethnicity, education, obstetric history, or smoking status. The interviewer gathered standard demographic and obstetric information as well as data on smoking behavior. Subjects were interviewed in Spanish or English by a bilingual interviewer using a standardized questionnaire. Statistical techniques included chi 2 test, t test, and logistic regression., Results: The odds for Mexican-American women to have been smokers were 3.39 times lower than for non-Hispanic white women. The odds of quitting during pregnancy were 4.71 times higher for Mexican-Americans (95% confidence interval 1.66-13.38). Urinary cotinine values verified the latter rates. Mexican-American smokers reported smoking significantly fewer cigarettes than non-Hispanic white women (t = 2.34, P < .05)., Conclusions: In comparing Mexican-American and non-Hispanic white women, we found marked differences in smoking behavior during pregnancy. Mexican-Americans were nearly three times more likely to quit than non-Hispanic whites, and those who continued to smoke showed greater reductions in cigarettes per day. These results show behavioral changes in Mexican-Americans during pregnancy that meaningfully alter the risk profile for the fetus. Understanding the basis for this behavioral change may facilitate the development of preventive measures for other ethnic groups.

Objective: To compare umbilical arterial and venous Doppler velocity waveforms during labor in fetuses with normal heart rate tracings and fetuses with late decelerations., Methods: During labor, umbilical arterial and venous Doppler flow velocity waveforms were obtained between and during contractions in 20 fetuses (ten with normal heart rate tracings and ten with late decelerations). The umbilical arterial systolic-diastolic (S/D) velocity ratios were compared, and umbilical venous velocities were examined for the presence or absence of venous pulsations., Results: Fetuses with late decelerations had a significant increase in the umbilical arterial S/D ratio between contractions compared to normal fetuses (2.43 +/- 0.74 versus 1.56 +/- 0.27, P = .003). There was no significant difference in S/D ratios obtained between contractions compared with those obtained during contractions in either the normal or late deceleration group. Umbilical venous pulsations were significantly more common (90 versus 0%, P < .00001) during contractions in fetuses with late decelerations; umbilical venous pulsations were not seen in these fetuses between contractions and were not present at any time in fetuses with normal heart rate tracings., Conclusions: Increased umbilical arterial velocity ratios and the presence of umbilical venous pulsations during contractions in fetuses with late decelerations suggest that the cardiovascular pathophysiology of late decelerations involves changes in placental resistance as well as cardiac performance. The presence of umbilical venous pulsations during late decelerations is consistent with the hypoxic fetal cardiovascular changes (hypertension and myocardial depression) previously reported from animal studies.

We hypothesized that changes in intrathoracic pressure during fetal breathing episodes result in quantifiable variations in umbilical arterial and venous blood flow velocities, and that these variations are related to compliance properties of each system. We further hypothesized that these variations in velocities are different in fetuses with normal and abnormal umbilical arterial Doppler velocities. Umbilical arterial and venous Doppler velocities were measured simultaneously during breathing episodes in 15 normal fetuses and 14 fetuses with elevated systolic-to-diastolic (S/D) umbilical arterial Doppler velocity ratios. Umbilical arterial end-diastolic velocity changes were less than umbilical venous velocity changes in normal fetuses, but were significantly greater in four fetuses with elevated S/D ratios (p < 0.004). Furthermore, umbilical arterial diastolic velocity minima preceded umbilical venous velocity minima by a time lag that was greater in fetuses with elevated S/D ratios (p < 0.002). These results suggest that differences in umbilical arterial and venous velocity variation during fetal breathing episodes may be related in part to vascular compliance, which may be altered in fetuses with abnormal umbilical arterial Doppler velocity., (Copyright 1994 International Society of Ultrasound in Obstetrics and Gynecology)

The fetal heart is the organ system most commonly affected with congenital disease. Though risk factors exist for congenital heart disease (eg, family history, toxin exposure, maternal illness, abnormal karyotype, and other fetal anomalies), the fetal heart is most often examined as part of a routine evaluation of the fetal anatomy in the fetus with no identifiable risk factors. The importance of a systematic, complete assessment of the cardiac axis cannot be overemphasized. All aspects of sonography (ie, real time, M-mode, pulsed, and color Doppler) can provide unique and integral information in evaluating the fetal heart and thorax.

Objective: To assess the validity of Doppler flow sonography for the prediction of malignancy in adnexal masses and to compare the results with two-dimensional ultrasonographic examination and CA 125 levels., Methods: In a cross-sectional study, 55 patients with adnexal masses were examined using Doppler sonography to measure the resistance index of tumor-associated blood flow profiles. In addition, abdominal and transvaginal ultrasound examinations were performed and preoperative CA 125 serum levels were assessed., Results: Sixteen patients had malignant tumors and 39 had benign tumors. A resistance index cutoff of less than or equal to 0.8 showed the highest sensitivity (93.8%), with a specificity of 56.4%, a positive predictive value of 46.8%, and a negative predictive value of 95.7%. Compared with two-dimensional sonographic evaluation using either a scoring system or subjective assessment, and with CA 125 levels, the resistance index showed higher sensitivity and negative predictive value but lower specificity and positive predictive value. False-positive resistance index values were prevalent with endometriosis, leiomyomata, and mucinous cystadenoma. The combination of the resistance index with either the sonographic features or CA 125 increased the sensitivity and negative predictive value to 100%, with only a slight decrease in specificity and positive predictive value, but was not superior to the combination of two-dimensional sonography and CA 125., Conclusion: Doppler sonographic evaluation of resistance indexes in the vessels of adnexal masses increased the sensitivity of two-dimensional sonography and CA 125. However, 46% of positive Doppler results were false and 37.5% of the benign tumors had low resistance indexes, thus limiting the validity of this technique for screening programs.

This paper discusses federal legislation relating to persons with disabilities and it divides into 13 areas. Several areas of legislation, such as education and basic education, have a long history beginning with World War I. Laws related to other areas, such as federal support for developing technology, have been adopted only within the past 5 years. The Americans With Disabilities Act of 1990 (ADA) (Public Law 101-336), which guarantees civil rights to Americans with disabilities, has five titles, and each is summarized. Although the ADA provides for Americans with disabilities to be included in American society, it has some major limitations, including the lack of an affirmative action requirement and of provisions for the education and training of persons with disabilities so that they can qualify for employment. Several of the federal laws related to persons with disabilities have affected the field of occupational therapy either favorably or adversely. The conclusion is drawn that occupational therapists need to be alert to pending legislation to promote the role of occupational therapy in serving persons with disabilities.

We have isolated clones of an established cell line which express defects in intracellular cholesterol metabolism. Chinese hamster ovary cells were mutagenized, and clones unable to mobilize low density lipoprotein (LDL)-derived cholesterol to the plasma membrane were selected. Biochemical analysis of two mutant clones revealed a phenotype characteristic of the lysosomal storage disease, Niemann-Pick type C. The mutant cell lines were found to be defective in the regulatory responses elicited by LDL-derived cholesterol. LDL-mediated stimulation of cholesterol esterification was grossly defective, and LDL suppression of 3-hydroxy-3-methylglutaryl-CoA reductase was impaired. However, the mutants modulated these activities normally in response to 25-hydroxycholesterol or mevalonate. The LDL-specific defects were predicated by the inability of these mutants to mobilize LDL-derived cholesterol from lysosomes. Cell fractionation studies showed that LDL-derived, unesterified cholesterol accumulated in the lysosomes of mutant cells to significantly higher levels than normal, commensurate with defective movement of cholesterol to other cellular membranes. Characterization of cell lines defective in intracellular cholesterol transport will facilitate identification of the gene(s) required for intracellular cholesterol movement and regulation.