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Biomedical subjects

D Flanagan

Publications and source records attributed to D Flanagan.

At least 19 recordsLinked to original sources
PubMed1998

An expert system for EEG monitoring in the pediatric intensive care unit.

OBJECTIVES: was to design a warning system for the pediatric intensive care unit (PICU). The system should be able to make statements at regular intervals about the level of abnormality of the EEG. The warnings are aimed at alerting an expert that the EEG may be abnormal and needs to be examined. METHODS: A total of 188 EEG sections lasting 6 h each were obtained from 74 patients in the PICU. Features were extracted from these EEGs, and with the use of fuzzy logic and neural networks, we designed an expert system capable of imitating a trained EEGer in providing an overall judgment of abnormality about the EEG. The 188 sections were used in training and testing the system using the rotation method, thus separating training and testing data. RESULTS: The EEGer and the expert system classified the EEGs in 7 levels of abnormality. There was concordance between the two in 45% of cases. The expert system was within one abnormality level of the EEGer in 91% of cases and within two levels in 97%. CONCLUSIONS: We were therefore able to design a system capable of providing reliably an assessment of the level of abnormality of a 6 h section of EEG. This system was validated with a large data set, and could prove useful as a warning device during long-term ICU monitoring to alert a neurophysiologist that an EEG requires attention.

Algorithms↗
PubMed1998

Automatic EEG analysis during long-term monitoring in the ICU.

To assist in the reviewing of prolonged EEGs, we have developed an automatic EEG analysis method that can be used to compress the prolonged EEG into two pages. The proposed approach of Automatic Analysis of Segmented-EEG (AAS-EEG) consists of 4 basic steps: (1) segmentation; (2) feature extraction; (3) classification; and (4) presentation. The idea is to break down the EEG into stationary segments and extract features that can be used to classify the segments into groups of like patterns. The final step involves the presentation of the processed data in a compressed form. This is done by providing the EEGer with a representative sample from each group of EEG patterns and a compressed time profile of the complete EEG. To verify the above approach, 41 6 h EEG records were assessed for normality via the AAS-EEG and conventional EEG approaches. The difference between the overall assessment via compressed and conventional EEG was within one abnormality level 100% of the time, and within one-half level for 73.6% of the records. We demonstrated the feasibility and reliability of automatically segmenting and clustering the EEG, thus allowing the reduction of a 6 h tracing to a few representative segments and their time sequence. This should facilitate review of long recordings during monitoring in the ICU.

Child↗
PubMed1998

Gin and tonic and reactive hypoglycemia: what is important-the gin, the tonic, or both?

The objectives of this study were to test the hypothesis that alcohol can cause reactive hypoglycemia by attenuating the release of counterregulatory hormones. The subjects were eight healthy volunteers (five men and three women, aged 20-40 yr). Each subject drank, using a randomized, double blind design 1) three large gin with regular tonics (0.5 g/kg alcohol and 60 g carbohydrate, mainly sucrose (G+T); 2) the same amount of alcohol with Slim-line tonic (0.5 g carbohydrate; G alone); and 3) regular tonic without alcohol (T alone). Glucose, insulin, and counterregulatory hormone levels and middle cerebral artery velocity (MCAV), an index of cerebral blood flow, were measured. Alcohol levels averaged 60-70 mg/dL. Peak insulin levels were similar in both studies in which regular tonic was consumed (95% confidence interval for difference, -6 to 22 microU/mL). After the ingestion of G+T, the blood glucose nadir was lower compared to that with T alone (3.35 vs. 3.87 mmol/L; P < 0.02) or G alone (3.35 vs. 3.95 mmol/L; P < 0.01). After drinking gin, subjects reported typical hypoglycemic warning symptoms unrelated to the prevailing glucose level. In both alcohol studies, there was marked blunting of GH release (P < 0.01). Despite a blood glucose nadir of 3.35 mmol/L, plasma epinephrine levels rose only slightly from 267 to 455 pmol/L (P = NS) after G+T. Ingestion of alcohol also caused a transient rise in right MCAV (P < 0.05) followed by a late drop in velocity in both cerebral hemispheres in the G+T study (P < 0.05). In otherwise healthy individuals a combination of gin and regular tonic can induce reactive hypoglycemia. Acute ingestion of alcohol impairs the epinephrine response and markedly suppresses the release of GH in response to a fall in blood glucose levels.

Adult↗
PubMed1997

Automatic seizure detection in the newborn: methods and initial evaluation.

Seizures are most common in the newborn period, but at that age seizures can be very difficult to identify by clinical observation. Therefore the EEG plays an even greater role in newborns than in older children and adults. The electrographic features of seizures and EEG background in the newborn are, however, very different to those found in adults. We present a set of methods for the automatic detection of seizures in the newborn. The methods are aimed at detecting a wide range of patterns, including rhythmic paroxysmal discharges at a wide range of frequencies, as well as repetitive spike patterns, even when they are not very rhythmic. The methods were developed using EEGs obtained from 55 newborns, recorded at 3 hospitals that used differing monitoring protocols. A total of 281 h of recordings containing 679 seizures were analyzed. An initial evaluation indicated that 71% of the seizures and 78% of seizure clusters (group of seizures separated by less than 90 s) were detected, with a false detection rate of 1.7/h. The methods were developed so that they can be implemented to operate in real time.

Electroencephalography↗
PubMed1997

Evaluation of an automatic seizure detection method for the newborn EEG.

In another publication, we described a set of methods for automatic detection of EEG seizures in the newborn. We describe here the evaluation of these methods using a completely new set of data, which were not used in developing the method. This testing data set consisted of recording from 54 patients, lasting an average of 4.4 h. Recordings had 8-16 channels and were obtained, in approximately equal numbers, from 3 institutions in Canada, the USA and Australia. Recording conditions varied from short recordings fully attended by a technologist to overnight recordings largely unattended. The average seizure detection rate was 69% (77%, 53%, 84% in the 3 institutions). False detections occurred at the average rate of 2.3/h (4.1, 1.0, 2.7 in the 3 institutions), with fluctuations that reflected largely the technical quality and level of supervision of the recordings. The results are similar to those obtained in the commonly used method of epilepsy monitoring in adults and allow us to envisage clinical application.

Electroencephalography↗
PubMed1997

Outcome of neonates with electrographically identified seizures, or at risk of seizures.

A prospective study was conducted to investigate survival at 1 month and survival and developmental outcome at 1 year in a cohort of 53 neonates either suspected of or at risk of having seizures. For all patients, presence of seizures, diagnoses, and structural abnormalities were identified. If seizures were present, seizure variables were quantified. Correlations between neonatal parameters and subsequent outcome were investigated. Forty-three patients survived the first month of life. Background EEG was the only significant predictor of survival at 1 month. Three patients died after 1 month, and 2 of the three had extremely depressed interictal EEGs. Development outcome at 1 year was determined for all available surviving patients. Abnormal findings from brain imaging studies and number of independent electrographic seizure foci were correlated with some aspects of outcome at 1 year. No other correlations were identified between neonatal parameters and outcome.

Child Development↗
PubMed1996

Caval umbrella causing obstructive uropathy.

A 49-year-old woman had a vena caval filters inserted having suffered multiple pulmonary emboli and a large upper gastrointestinal bleed. She re-presented five years later with loin pain and obstructive uropathy. She was found to have a right pelvi-ureteric obstruction due to inferior vena caval wall perforation from the vena caval filter.

Female↗
PubMed1995

Anti-peptide sera against cell-CAM 105 determine high molecular-mass variants of the long isoform in rat hepatocytes.

The glycoprotein cell-CAM 105 is a member of the carcinoembryonic-antigen-(CEA)-gene family, involved in cell-cell adhesion of rat hepatocytes and expressed on the cell surface as a long (L) and a short (S) isoform with slightly differing molecular masses and isoelectric points. The cDNA of the L-isoform has been isolated and sequenced, as confirmed by the preparation of specific anti-peptide sera [Lin, S.-H., Culic, O., Flanagan, D. & Hixson, D. C. (1991) Biochem. J. 278, 155-161]. Recently, two additional cDNAs have been sequenced, which possess identical deduced primary structures, including short intracellular domains 10 amino acids in length, which differ from the cytoplasmic domain of the L-isoform specifically in the last four C-terminal amino acids. Here, we report on the production of the polyclonal antiserum [anti-(peptide 2)] by immunization with a synthetic hexapeptide (GGSGSF) corresponding to the unique intracellular C-terminal domain of these short cell-CAM 105 cDNA isoforms. This antiserum was specific in ELISA, immunoblot and immunoprecipitation assays for a protein with the same biochemical properties as the S-isoform of cell-CAM 105 expressed in rat liver. In addition, CNBr peptide maps of the S-isoform and the protein immunoprecipitated with anti-(peptide 2) serum were identical. Together, these results provide strong evidence that anti-(peptide 2) serum is specific for the S-isoform of rat liver cell-CAM 105. In immunoblot analysis on liver plasma membrane extracts prepared without collagenase perfusion, at least seven high molecular-mass proteins were observed which showed strong reactivity with mAbs against extracellular epitopes and L-isoform-specific antibodies but no reactivity with anti-(peptide 2) serum. Like the L-isoform, these proteins are expressed on the cell surface and might represent structural variants of cell-CAM 105.

Adenosine Triphosphatases↗
PubMed1995

Clinical features of neonatal seizures.

OBJECTIVE: Identification of seizures in neonates is difficult. This study analyses the clinical features of seizures in a cohort of neonates. METHODOLOGY: The clinical events of 41 neonates referred for investigation of suspected seizures were studied with prolonged video/electroencephalographic (EEG) telemetry. RESULTS: Sixteen neonates had no seizures recorded; 25 had confirmed seizures, 13 with clinical correlates. Each neonate with electroclinical seizures had paroxysms of abnormal movements in stereotyped patterns. These patterns were consistently found to have electrical correlates. Focal clonic movements were seen most frequently. Multiple clinical features characterized the seizure repertoire in six neonates. In five neonates the clinical features became less evident during monitoring and these seizures were difficult to recognize. This change was associated with anticonvulsant administration in three cases. CONCLUSIONS: Electroclinical seizures are characterized by abnormal paroxysmal stereotyped behaviour, often with multiple clinical features. Recommendations for the management of abnormal neonatal events are proposed.

Cohort Studies↗
PubMed1995

Electroencephalograms, clinical observations and the monitoring of neonatal seizures.

OBJECTIVE: To identify neonatal seizures and evaluate the efficiency of clinical observations and short duration electroencephalograms (EEG). METHODOLOGY: Sixty-three neonates were investigated using prolonged video/EEG monitoring. Patients with confirmed seizures were treated with sequential doses of phenobarbitone and, if seizures persisted, phenytoin. The likelihood of correct management if short duration EEG and clinical observations had been employed was determined. RESULTS: Thirty-two patients had confirmed seizures. After administration of anticonvulsants, clinical observations identified seizures in a mean of 66% (s.d. 7.3%) of the cohort. A 60 min EEG after each stage of phenobarbitone therapy would guarantee electrographic seizure capture in a mean of 76% (s.d. 10%) of the cohort. A 60 min EEG after addition of phenytoin would guarantee capture in 50%. CONCLUSIONS: An EEG would avoid misdiagnoses in most patients with ambiguous clinical signs. After anticonvulsant infusions, EEG add substantial information to that gained by clinical observations.

Anticonvulsants↗
PubMed1995

Spatial and temporal characteristics of neonatal seizures.

Thirty-two neonates (26 term and 6 premature) having seizures were prospectively recruited and studied. Using prolonged video/EEG monitoring, we quantified seizure variables (electrographic and clinical seizure durations, interictal periods and electrographic seizure spread) for all 1,420 seizures recorded. The effects of time and antiepileptic drug (AED) therapy were analyzed statistically. Seizures were generally frequent, with limited electrographic spread. However, some neonates had consistently longer interictal periods and 13% had mean interictal periods > 60 min. Seizure variables were relatively stable over time, but they changed with AED therapy. There was a trend to decreased seizure duration, increased length of interictal periods, and decreased electrographic spread. Furthermore, there was evidence of reduced clinical features after sequential AED infusions. Seizures ceased during the monitoring period in 22 neonates. Eighty-five percent of all seizures had no clinical manifestations. Among neonates with clear clinical correlates, clinical observations underestimated electrographic seizures in individual neonates by a mean of 54% (range 0-95%). Seizures generally had limited electrographic spread. Use of only four recording electrodes, characteristic of some portable EEG systems, underestimated seizures in 19 neonates, and missed all seizures in 2.

Anticonvulsants↗
PubMed1992

Molecular cloning and expression of a new rat liver cell-CAM105 isoform. Differential phosphorylation of isoforms.

An hepatocyte cell-adhesion molecule (cell-CAM105) was recently shown to be identical with the liver plasma-membrane ecto-ATPase. This protein has structural features of the immunoglobulin superfamily and is homologous with carcinoembryonic antigen proteins. We have cloned a cDNA encoding a new form of the cell-CAM105 which is a variant of the previously isolated clone. In addition to having a shorter cytoplasmic domain, the new isoform also has substitutions clustered in the first 130 amino acids of the extracellular domain. Both of these isoforms are expressed on the surface of hepatocytes with the shorter variant being the predominant form. The previously isolated cell-CAM105 (long form) has more potential phosphorylation sites than does the new isoform (short form). Both isoforms are found to be phosphorylated after incubation with [32P]phosphate in vitro, with the long form being phosphorylated to a significantly higher extent. This observed differential phosphorylation could be one of the mechanisms for the regulation of isoform functions. Using antipeptide antibodies specific for the long form and antibodies that are reactive with both isoforms, we have shown that both isoforms are localized in the canalicular domain of hepatocytes. The sequence differences between these two isoforms suggest that they are probably derived from different genes rather than from alternative splicing.

Adenosine Triphosphatases↗
PubMed1991

Immunochemical characterization of two isoforms of rat liver ecto-ATPase that show an immunological and structural identity with a glycoprotein cell-adhesion molecule with Mr 105,000.

One of the cell-adhesion molecules (CAMs) responsible for rat hepatocyte aggregation has been described as a glycoprotein having an Mr of 105,000 (cell-CAM105). The Mr and localization of cell-CAM105 in liver membranes are very similar to those of liver ecto-ATPase, an ATPase with its nucleotide-hydrolysing site localized on the outside of the cell membrane. The protein sequence of the ecto-ATPase has been deduced from cDNA cloning. Structural analysis of the sequence indicates that the ecto-ATPase has immunoglobulin-like domains and is a member of the immunoglobulin superfamily. Since a group of proteins in the immunoglobulin superfamily has been shown to have functions related to cell adhesion, the structural characteristics of the ecto-ATPase further led to the possibility that the ecto-ATPase may have functions related to cell adhesion. In this paper, using the cDNA for the ecto-ATPase, the anti-peptide antibodies produced against peptides derived from the ecto-ATPase cDNA sequence and monoclonal antibodies against the cell-CAM105, we present evidence of identity between cell-CAM105 and ecto-ATPase. First, in Western immunoblots, two anti-cell-CAM105 monoclonal antibodies cross-reacted with the purified ecto-ATPase. Secondly, in immunodepletion experiments, antibodies against the ecto-ATPase depleted the same protein recognized by the anti-cell-CAM105 antibodies. Thirdly, in two-dimensional gel-electrophoretic analysis, anti-peptide antibodies generated against an extracellular N-terminal peptide and the intracellular C-terminal peptides of the ecto-ATPase immunoprecipitated proteins of similar isoelectric points and Mr values to those of the cell-CAM105. Fourthly, proteins immunoprecipitated by anti-ecto-ATPase antibodies and anti-cell-CAM105 antibodies have similar V8-proteinase-digest peptide maps. Finally, monoclonal antibodies against the cell-CAM105 specifically recognized the protein expressed in COS cells transfected with the ecto-ATPase cDNA. These results indicate that the ecto-ATPase cDNA codes for a protein that is identical with the cell-CAM105. Since the ecto-ATPase has structural features of immunoglobulin domains, the identity of cell-CAM105 with ecto-ATPase leads to the conclusion that this liver CAM, similarly to neuronal CAM, is also a member of the immunoglobulin supergene family. Furthermore, immunological studies indicate that the cell-CAM105/ecto-ATPase is composed of two isoforms of different C-terminal sequences. The association of ATPase activity with cell-CAM105 raises the possibility that extracellular nucleotides may play important roles in regulating cell adhesion.

Adenosine Triphosphatases↗
PubMed1991

A Fischer rat substrain deficient in dipeptidyl peptidase IV activity makes normal steady-state RNA levels and an altered protein. Use as a liver-cell transplantation model.

Dipeptidyl peptidase IV (DPPIV) is a serine exoproteinase expressed at high levels in epithelial cells of kidney, liver and small intestine. Recently Watanabe, Kohima & Fujimoto [(1987) Experientia 43, 400-401] and Gossrau et al. [(1990) Histochem. J. 22, 172-173] reported that Fischer 344 rats are deficient in this enzyme. We have examined DPPIV expression in Fischer 344 rats available from U.S. and German suppliers and find that livers of the U.S. Fischer rats, in contrast with their German counterparts, express active DPPIV (D+). Northern analysis of liver RNA showed comparable levels of 3.4 kb and 5.6 kb DPPIV transcripts in both D+ rats from the U.S. and German (D-) rats. Monoclonal antibody (MAb) 236.3 to DPPIV immunoprecipitated at 150 kDa enzymically active (105 kDa, denatured) protein from surface-labelled D+ hepatocytes and reacted with canalicular and sinusoidal membranes (as shown by immunofluorescence microscopy). MAb 236.3 failed to immunoprecipitate a labelled peptide from D- cell extract or to stain D- liver sections. Polyclonal antibody (PAb) specific for DPPIV immunoprecipitated an enzymically active peptide from D+ hepatocyte extracts and a smaller, inactive peptide from D- hepatocyte extracts. Peptide maps of DPPIV immunoprecipitated from D+ extracts with MAb 236.3 and PAb were identical, but differed from that of the D- hepatocyte component recognized by PAb. The molecular basis of the DPPIV deficiency in the D- rats thus appears to be the translation of an enzymically inactive protein missing the epitope recognized by MAb 236.3. We have exploited these D- rats as hosts for syngeneic transplantation of liver cells from D+ Fischer rats. DPPIV expression is stable in the transplanted cells and allows them to be readily distinguished from the surrounding D- tissue.

Animals↗
PubMed1990

Macular detachment following laser treatment for proliferative diabetic retinopathy.

Case records of patients who had macular detachment following argon laser photocoagulation for proliferative diabetic retinopathy were reviewed. Thirteen eyes of 11 patients out of a total of 480 patients treated had this complication, and in 12 eyes of 10 patients the short latency suggested a true precipitating effect. This represents 2.1% of patients receiving panretinal photocoagulation. Patients with detachment were younger and developed diabetes earlier than the controls (P less than 0.025), and the detached eyes had received more numerous laser burns on average per session than the controls (P less than 0.001). In 5 eyes the last photocoagulation dose exceeded 1000 burns delivered in the presence of traction membranes in an attempt to arrest continuing neovascular proliferation not responding to earlier more moderate treatment. Only 1 eye had received early, extensive and repeated photocoagulation. Vigorous treatment at an early stage of the proliferation may prevent this complication, although the advantages or disadvantages of fractionation of photocoagulation will only be shown by a prospective trial.

Adult↗