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Biomedical subjects

E Barry

Publications and source records attributed to E Barry.

At least 19 recordsLinked to original sources

Local and regional air pollution in Ireland during an intensive aerosol measurement campaign.

An intensive two month measurement campaign has been performed during a two year study of major component composition of urban PM10 and PM2.5 in Ireland (J. Yin, A. G. Allen, R. M. Harrison, S. G. Jennings, E. Wright, M. Fitzpatrick, T. Healy, E. Barry, D. Ceburnis and D. McCusker, Atmos. Res., 2005, 78(3-4), 149-165). Measurements included size-segregated mass, soluble ions, elemental carbon (EC) distributions, fine and coarse fraction organic carbon (OC) and major gases along with standard meteorological measurements. The study revealed that urban emissions in Ireland had mainly a local character and therefore were confined within a limited area of 20-30 km radius, without significantly affecting regional air quality. Gaseous measurements have shown that urban emissions in Ireland had clear, but fairly limited influence on the regional air quality due to favorable mixing conditions at higher wind speeds, in particular from the western sector. Size-segregated mass and chemical measurements revealed a clear demarcation size between accumulation and coarse modes at about 0.8 microm which was constant at all sites. Carbonaceous compounds at the urban site accounted for up to 90% of the particle mass in a size range of 0.066-0.61 microm. Nss SO4(2-) concentrations in PM2.5 were only slightly higher at the urban site compared to the rural or coastal sites, while NO3- and NH4+ concentrations were similar at the urban and coastal sites, but were a factor of 2 to 3 higher than at the rural site. OC was highly variable between the sites and revealed clear seasonal differences. Natural or biogenic OC component accounted for <10% in winter and up to 30% in summer of the PM2.5 OC at urban sites. A contribution of biogenic OC component to PM2.5 OC mass at rural site was dominant.

Aerosols↗

Limestone-particle-stabilized macroemulsion of liquid and supercritical carbon dioxide in water for ocean sequestration.

When liquid or supercritical CO2 is mixed with an aqueous slurry of finely pulverized (1-20 microm) limestone (CaCO3) in a high-pressure reactor, a macroemulsion is formed consisting of droplets of CO2 coated with a sheath of CaCO3 particles dispersed in water. The coated droplets are called globules. Depending on the globule diameter and the CaCO3 sheath thickness, the globules sink to the bottom of the water column, are neutrally buoyant, or float on top of the water. The CaCO3 particles are lodged at the CO2/ H2O interface, preventing the coalescence of the CO2 droplets, and thus stabilizing the CO2-in-water emulsion. We describe the expected behavior of a CO2/H2O/CaCO3 emulsion plume released in the deep ocean for sequestration of CO2 in the ocean to ameliorate global warming. Depending on the amount of CO2 injected, the dense plume will descend a few hundred meters while entraining ambient seawater until it acquires neutral buoyancy in the stratified ocean. After equilibration, the globules will rain out from the plume toward the ocean bottom. This mode of CO2 release will prevent acidification of the seawater around the release point, which is a major environmental drawback of ocean sequestration of liquid, unemulsified CO2.

Calcium Carbonate↗

Preventing accidental falls among older people in long stay units.

A fall prevention programme for older long-stay patients in a 95 bedded District Hospital was undertaken. Data on falls and resulting injuries for the year prior to the intervention were compared with equivalent data after one year (Year 1) and after two years (Year 2) of the intervention. In the pre-intervention year 25% of patients had at least one fall compared with 20.9% and 17.4% in Year 1 and Year 2 respectively. This difference was not statistically significant. However, there were 21% fewer falls in Year 1 and 49.3% fewer in Year 2 than in the pre-intervention year. This difference was significant in Year 2. In both intervention years there was a significant reduction in the incidence of fracture from 20.5% of falls (pre-intervention) to 2.8% in Year 1 and no fractures occurred in Year 2. Significant reductions in soft tissue injuries occurred in Year 2 but not in Year 1, dropping from 38.5% (pre-intervention) to 36.1% and 15.4% respectively. The percentage of patients uninjured after a fall increased from 41% to 61.1% to 84.6%. This intervention reduced falls and their adverse consequences for older people living in the long stay unit. The effect of the intervention escalated in Year 2. The intervention cost IR4,800 pounds. Fall prevention should be part of the routine care of older people in all types of long stay care.

Accidental Falls↗

Cloning and expression profiling of Hpa2, a novel mammalian heparanase family member.

Heparan sulfate proteoglycans are important constituents of the extracellular matrix and basement membrane. Cleavage of heparan sulfate by heparanase, an endoglycosidase, is implicated in the extravasation of leukocytes and metastatic tumour cells, identifying this enzyme(s) as a target for anti-inflammatory and anti-metastatic therapies. The cloning of a cDNA encoding human heparanase (Hpa1) was reported recently, together with evidence indicating that the hpa1 gene is unique and unlikely to belong to a family of related genes. Here we report the cloning of a cDNA encoding a novel human protein, HPA2, with significant homology to Hpa1. Alternative splicing of the hpa2 transcript yields three different mRNAs, encoding putative proteins of 480, 534, and 592 amino acids. Sequence analyses predict that all three Hpa2 proteins are intracellular, membrane-bound enzymes. Hpa2 also shows a markedly different mRNA distribution to Hpa1 in both normal and cancer tissues. The difference in expression profiles and predicted cellular locations suggests that Hpa2 and Hpa1 proteins have distinct biological functions.

Alternative Splicing↗

Regulatory science: a special update from the United States Food and Drug Administration: Preclinical issues and status of investigation of botanical drug products in the United States.

A recent survey was conducted across the therapeutic divisions within the CDER, U.S. FDA regarding the number of submissions related to botanical drug products over the past ten years. The overall number of botanical submissions as expressed in the parenthesis are as follows: 1990 (1), 1991 (4), 1992 (4), 1993 (5), 1994 (6), 1995 (5), 1996 (13), 1997 (16), 1998 (10). In the total of 64 counted, 50 of them are submitted in original IND and the rest (14) in pre-IND format. The therapeutic categories are focused on dermatological and topical (19), anti AIDS/antiviral (12), oncologic (13), neuropharmacologic (8), endocrine and metabolic (3), urologic (2), tobacco (2), and cardio-renal products (1). The regulatory actions taken on these submissions showed that 68% of them are evaluated as safe to proceed for the human trials, while the rest (32%) of submissions required agency's regulatory guidance. Among the submissions that required further guidance, 81% were deficient in preclinical pharmacology/toxicology information and the rest (19%) lacks information in other areas (chemistry, clinical protocols). Following agency's guidance, 93% of the submissions that were put on hold were allowed to proceed. In summary, a total of 94% of all the botanical INDs submitted to the agency were allowed to proceed without additional animal toxicity studies conducted. In conclusion, this survey indicates that the growing public interest in botanical supplements has prompted more formal evaluation of the efficacy/safety claims of these products.

Databases, Factual↗

Constitutive expression of the Vi polysaccharide capsular antigen in attenuated Salmonella enterica serovar typhi oral vaccine strain CVD 909.

Live oral Ty21a and parenteral Vi polysaccharide vaccines provide significant protection against typhoid fever, albeit by distinct immune mechanisms. Vi stimulates serum immunoglobulin G Vi antibodies, whereas Ty21a, which does not express Vi, elicits humoral and cell-mediated immune responses other than Vi antibodies. Protection may be enhanced if serum Vi antibody as well as cell-mediated and humoral responses can be stimulated. Disappointingly, several new attenuated Salmonella enterica serovar Typhi oral vaccines (e.g., CVD 908-htrA and Ty800) that elicit serum O and H antibody and cell-mediated responses following a single dose do not stimulate serum Vi antibody. Vi expression is regulated in response to environmental signals such as osmolarity by controlling the transcription of tviA in the viaB locus. To investigate if Vi antibodies can be stimulated if Vi expression is rendered constitutive, we replaced P(tviA) in serovar Typhi vaccine CVD 908-htrA with the constitutive promoter P(tac), resulting in CVD 909. CVD 909 expresses Vi even under high-osmolarity conditions and is less invasive for Henle 407 cells. In mice immunized with a single intranasal dose, CVD 909 was more immunogenic than CVD 908-htrA in eliciting serum Vi antibodies (geometric mean titer of 160 versus 49, P = 0.0007), whereas O antibody responses were virtually identical (geometric mean titer of 87 versus 80). In mice challenged intraperitoneally with wild-type serovar Typhi 4 weeks after a single intranasal immunization, the mortality of those immunized with CVD 909 (3 of 8) was significantly lower than that of control mice (10 of 10, P = 0.043) or mice given CVD 908-htrA (9 of 10, P = 0.0065).

Administration, Oral↗

Nonepileptic posttraumatic seizures.

PURPOSE: Epileptic posttraumatic seizures (PTSs) are a well-recognized consequence of head injury (HI), but HI and nonepileptic seizures (NESs) have not been related. We describe a significant subset of patients with NESs who had their seizures attributed to HI. METHODS: We reviewed the records of all patients diagnosed with NES at the University of Maryland Medical Center over a 6-year period (1989-1995) and selected patients with seizures attributed to a head injury occurring < or =3 years before the onset of their seizures. RESULTS: Of 157 patients with video-EEG confirmed NES, 37 (24%) had the onset of their seizures attributed to an HI. Their average age was 34 years (range, 15-56 years); 68% were women. Nonepileptic PTS usually developed within the first year after HI (89%). Convulsive symptoms were present in 54%. Whereas epileptic PTSs characteristically follow severe HI, the majority (78%) of our patients with nonepileptic PTSs sustained only mild HI. Before their HI, 76% of our patients were employed, working in the home, or students, but only 11% could continue those activities after developing nonepileptic PTSs. CONCLUSIONS: Nonepileptic PTSs are frequently mistaken for epileptic PTSs and result in serious disability. The misdiagnosis of nonepileptic PTSs leads to ineffective and inappropriate treatment. Patients with intractable seizures after HIs, particularly mild HIs, should be carefully evaluated for NESs.

Adolescent↗

Attenuated Salmonella as live oral vaccines against typhoid fever and as live vectors.

Attenuated Salmonella typhi vaccine strain CVD 908, which harbors deletion mutations in aroC and aroD, has been shown to be well-tolerated and highly immunogenic, eliciting impressive serum antibody, mucosal IgA and cell-mediated immune responses. A further derivative prepared by introducing a deletion in htrA (which encodes a heat-shock protein that also has activity as a serine protease in CVD 908 (Chatfield et al., unpublished data) resulted in CVD 908-htrA. In phase 1 clinical trials, CVD 908-htrA appears very attractive as a live oral vaccine candidate. Both CVD 908 and CVD 908-htrA are useful as live vector vaccines to deliver foreign antigens to the immune system. Conditions that enhance the expression and immunogenicity of foreign antigens carried by CVD 908 and CVD 908-htrA are being investigated.

Administration, Oral↗

Analysis of clinical and environment Yersinia isolates in the Republic of Georgia.

The Center for Infectious Diseases Control, Georgian Ministry of Health, isolated 2,493 Yersinia enterocolitica and Y. enterocolitica-like strains, 22 Y. pestis strains, and 21 Y. pseudotuberculosis strains from 130,574 clinical and environmental samples. Analysis of 100 Y. enterocolitica and Y. enterocolitica-like strains showed none to be within traditional pathogenic biogroups or serogroups, and none carried genetic markers for virulence. However, some strains were enterotoxigenic in infant mice, while others were associated with prolonged carriage in adult mice.

Adult↗

Panic attacks as ictal manifestations of parietal lobe seizures.

Although most panic attacks appear to be primary psychiatric disturbances, some evidence suggests a biologic basis for panic disorder, possibly associated with temporal lobe dysfunction. Fear is a common affective change associated with some complex partial seizures (CPS) originating from the right temporal lobe. We describe a previously unreported association between panic attacks and seizures originating from the parietal lobe in 2 patients with right parietal lobe tumors. Intracranial monitoring documented correlations between the symptoms of fear and restricted regional parietal cortical discharges. Surgical resections of the lesions (one total, one subtotal) resulted in complete recovery or improvement.

Adult↗

Radiologic appearance of the dysembryoplastic neuroepithelial tumor.

PURPOSE: To evaluate the computed tomographic (CT) and magnetic resonance (MR) imaging features of dysembryoplastic neuroepithelial tumor (DNT). MATERIALS AND METHODS: Six CT studies (four with contrast material enhancement) and 10 MR imaging studies (seven with gadolinium enhancement) obtained in 10 patients with a history of seizures and pathologically proved DNT were retrospectively reviewed. RESULTS: All tumors were intracortical or subcortical. CT showed a low-attenuation mass in all cases except one of mixed isoattenuation and low attenuation. The DNT had decreased signal intensity on T1-weighted MR images and well-demarcated increased signal intensity on T2-weighted images without peritumoral edema. Prominent MR imaging features were a gyriform configuration on T1- or T2-weighted images in 10 patients (100%), well-demarcated lobular tumor margins on T2-weighted images in eight (80%), and a high rate of bone remodeling of the adjacent calvaria on MR (60% [n = 6]) and CT (67% [n = 4]) images. CONCLUSION: Diagnosis of DNT with imaging modalities alone may be difficult, but these radiologic features may aid in differentiating DNT from other gliomas.

Adolescent↗

Complex partial status epilepticus accompanied by serious morbidity and mortality.

Nonconvulsive status epilepticus (NCSE) accounts for approximately 20% of all status epilepticus (SE). Although convulsive SE is recognized as a medical emergency, prompt diagnosis and treatment of patients with NCSE is often not emphasized because its consequences are thought to be benign. We report 10 patients with persistent neurologic deficits or death after well-documented NCSE in the form of complex partial status epilepticus (CPSE). All patients had prolonged CPSE lasting 36 hours or longer, as documented by clinical and EEG findings. Causes for CPSE were preexisting epilepsy with partial and secondarily generalized seizures (3 patients), vascular disease (2 patients), encephalitis (2 patients), and metabolic disease (1 patient); causes were unknown for two patients. Poor outcomes identified included persistent (lasting at least 3 months) or permanent cognitive or memory loss (5 patients), cognitive or memory loss plus motor and sensory dysfunction (3 patients), and death (3 patients). NCSE in the form of CPSE is not a benign entity. Serious morbidity and mortality may occur due to the adverse effects of prolonged seizures and as a result of acute brain disorders that precipitate the seizures.

Adult↗

Pleocytosis after status epilepticus.

OBJECTIVE: To determine the incidence of pleocytosis in patients experiencing status epilepticus (SE), regardless of seizure type or cause. DESIGN: A retrospective medical chart review. SETTING: Columbia-Presbyterian Medical Center, New York, NY. PATIENTS: Of 217 patients seen by the Neurology Service for SE during a 3-year period, 138 had a cerebrospinal fluid (CSF) analysis performed and were included in the study. All seizure types and etiologies were included. MAIN OUTCOME MEASURES: Status epilepticus was defined as a seizure or a series of continuing seizures lasting longer than 30 minutes. An abnormal CSF specimen was defined as a white blood cell (WBC) count of 6 x 10(6)/L or greater or one or more polymorphonuclear leukocytes present. RESULTS: Overall, 22.5% of patients demonstrated abnormal WBC count or morphology. There were 21 patients (15%) with a WBC count of 6 x 10(6)/L or greater, and another 10 patients with a normal WBC count, who had polymorphonuclear leukocytes present. Among patients with illnesses usually associated with pleocytosis (such as meningitis or acute head trauma), a large proportion had abnormal CSF WBC counts. Among patients with conditions usually associated with normal CSF (including idiopathic epilepsy), a small proportion had abnormal CSF WBC counts, and the abnormalities were less severe. The highest CSF WBC count in patients with no acute insult was 28 x 10(6)/L. CONCLUSIONS: The most important influence on the CSF WBC count is the underlying cause of the SE. Although minor elevations in WBC count can occur after SE of any type, pleocytosis should not be attributed to SE alone unless all other causes have been eliminated.

Blood Cell Count↗

Cytokine-gene expression in measles-infected adult human glial cells.

The expression of interleukin (IL)-1 beta, IL-6 and tumor necrosis factor (TNF) alpha transcripts in cultured human glial cells was examined using reverse transcription followed by polymerase chain reaction (PCR) amplification and Southern blot quantitation. Microglial cultures derived from brain biopsy specimens from three different individuals expressed transcripts for the three cytokines under basal culture conditions. This expression was enhanced in response to measles virus (MV) infection (IL-1 beta, 2.2-8.8-fold; IL-6, 2.5-8.4-fold; TNF alpha, 2.2-3.2-fold). Neither IL-1 beta nor TNF alpha transcripts were detectable in undissociated brain tissue from two individuals, suggesting that the basal expression of these cytokines in culture may have been induced by tissue dissociation or by the culture conditions. Oligodendrocytes did not express cytokine transcripts under basal culture conditions, and IL-1 beta and IL-6 but not TNF alpha transcripts could be induced by MV. Similarly, meningeal fibroblasts expressed IL-1 beta and IL-6 but not TNF alpha in response to MV-infection, suggesting that the production of TNF alpha is more cell type-restricted than either IL-1 beta or IL-6. The results indicate that adult human microglia can participate in the inflammatory response to MV infection in the CNS by producing cytokines that contribute to inflammation and demyelination. In addition, besides their role in myelination, oligodendrocytes can potentially influence immunoreactivity in the CNS by producing IL-1 beta and IL-6.

Adolescent↗

Status epilepticus and antiepileptic medication levels.

To investigate the association between withdrawal from antiepileptic drugs (AEDs) and status epilepticus (SE), we evaluated AED levels at the time of, and prior to, an episode of SE in 65 patients with epilepsy. At least one AED was therapeutic in 65% of patients at the time of SE, and all prescribed AEDs were therapeutic in 48%. Ten patients had subtherapeutic AED levels before, and at the time of, SE. Sixteen patients with previously therapeutic levels (25%) had one or more subtherapeutic AED level at the time of SE. Many of the patients had other acute or remote factors that could be associated with SE, and 46 had had previous episodes of SE. Low AED levels or withdrawal can explain only some cases of SE. Citing AED irregularity as the major cause of SE in patients with epilepsy oversimplifies a complex, poorly understood situation.

Anticonvulsants↗

Status epilepticus: the interaction of epilepsy and acute brain disease.

We identified 217 patients with status epilepticus (SE), including all seizure types from all etiologies, over a 3-year period. There was a significant interaction between organic brain disease and a history of epilepsy in the development of SE. The majority of patients (59%) had no history of epilepsy. These patients were more likely to have acute precipitants associated with SE and less likely to have had prior brain disease. They were older, were more likely to have generalized convulsive seizures, and had a high proportionate mortality. Among the 88 patients with a history of epilepsy, a higher proportion had prior brain insults, but fewer had acute precipitants. These patients were younger and their mortality was low, but they often had recurrent SE before and after the identified episode. Significant acute or prior brain disease is an important factor in the development of SE, even in patients with a history of epilepsy.

Acute Disease↗