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Biomedical subjects

J Hasan

Publications and source records attributed to J Hasan.

At least 19 recordsLinked to original sources
PubMed2001

VEGF antagonists.

The majority of cancer have an absolute requirement for angiogenesis, the process by which new blood vessels are formed. The most potent angiogenic cytokine is vascular endothelial growth factor (VEGF) and there has been substantial research into the development of VEGF/VEGF receptor (VEGFR) antagonists. To date these strategies have included gene therapy techniques that deliver antisense oligonucleotides, soluble VEGFRs that function in a dominant negative fashion and ribozymes. Additional strategies have included the development of receptor tyrosine kinase (RTK) inhibitors and monoclonal antibodies (mAbs) directed against VEGF or the signalling receptor. The most promising agents appear to be the monoclonal anti-VEGF antibodies and the RTK inhibitors as these have demonstrated broad spectrum antitumour activity in vivo and single agent activity in early phase clinical trials in patients with advanced pre-treated breast and colorectal carcinoma and Kaposi's sarcoma. The RTK inhibitors are of particular interest as they can be administered by mouth. Collation of the early clinical trial data suggests that VEGF antagonists are largely well-tolerated but may be associated with vascular toxicities such as haemorrhage and thromboembolic events. Combination studies of chemotherapy and VEGF antagonists are underway but the benefit of these regimens will need to be established in adequately powered Phase III studies. Potentially these agents may play a role in the treatment of both early (adjuvant) and advanced cancer. The efficacy of the drugs will be explored in a number of non-malignant conditions including rheumatoid arthritis (RA), psoriasis, diabetic retinopathy and possibly as non-steroidal contraceptives but the overall clinical development of these agents can only be optimised if appropriate biological end points are identified and incorporated into clinical trials.

Adult↗
PubMed2000

Vigilance stages and performance in OSAS patients in a monotonous reaction time task.

OBJECTIVES: To develop improved methods for objective assessment of daytime vigilance. This is important in the diagnosis and therapy control of sleep disorders associated with excessive daytime sleepiness (EDS). METHODS: Twenty-one patients with EDS due to obstructive sleep apnea were recorded during a daytime 90 min reaction time (RT) test in a monotonous situation. Two EEG, two EOG and a submental EMG channel were recorded simultaneously. The recordings were divided into short, stationary segments of variable length (0.5-2 s) and classified into 7 stages using our previously described system, which includes additional stages for drowsiness. RESULTS: The duration of RT was linearly correlated to the vigilance state (P<0.05). The appearance of slow eye movements (SEM) was more consistently related to performance impairment than EEG changes. CONCLUSIONS: Our system can provide a better tracking of vigilance changes than the standardized sleep stage scoring. A 1-2 h test is useful in the assessment of the performance of a subject suffering from EDS. We found that SEMs indicate more sensitive and consistent EDS-related performance impairment than changes in EEG activity.

Adult↗
PubMed2000

Autoassociative MLP in sleep spindle detection.

Spindles are one of the most important short-lasting waveforms in sleep EEG. They are the hallmarks of the so-called Stage 2 sleep. Visual spindle scoring is a tedious workload, since there are often a thousand spindles in one all-night recording of some 8 hr. Automated methods for spindle detection typically use some form of fixed spindle amplitude threshold, which is poor with respect to inter-subject variability. In this work a spindle detection system allowing spindle detection without an amplitude threshold was developed. This system can be used for automatic decision making of whether or not a sleep spindle is present in the EEG at a certain point of time. An Autoassociative Multilayer Perceptron (A-MLP) network was employed for the decision making. A novel training procedure was developed to remove inconsistencies from the training data, which was found to improve the system performance significantly.

Adult↗
PubMed2000

Optimization of sigma amplitude threshold in sleep spindle detection.

Sleep spindles are transient EEG waveforms of non-rapid eye movement sleep. There is considerable intersubject variability in spindle amplitudes. The problem in automatic spindle detection has been that, despite this fact, a fixed amplitude threshold has been used. Selection of the spindle detection threshold value is critical with respect to the sensitivity of spindle detection. In this study a method was developed to estimate the optimal recording-specific threshold value for each all-night recording without any visual scorings. The performance of the proposed method was validated using four test recordings each having a very different number of visually scored spindles. The optimal threshold values for the test recordings could be estimated well. The presented method seems very promising in providing information about sleep spindle amplitudes of individual all-night recordings.

Electroencephalography↗
PubMed1999

Vigilance transitions in reaction time test: a method of describing the state of alertness more objectively.

Electrophysiological recordings are considered a reliable method of assessing a person's alertness. The aim of this study was to show, firstly, that changes in alertness during a Reaction Time Test (RTT) can be determined with certain adaptive scoring stages but not with R&K scoring and secondly, that the different adaptive stages can explain findings in reaction time. In 17 male patients (50.8+/-9.7 years, Body-Mass Index (BMI) 31.9+/-5.1 kg/m2) diagnosed with Obstructive Sleep Apnea Syndrome (OSAS) (Respiratory Disturbance Index (RDI) 53.3+/-24.1 /h sleep) a 90 min daytime vigilance test was performed twice, after the diagnostic polysomnographic investigation and after two nights spent with nCPAP. After a computerised adaptive segmentation analysis, a visual rule-defined classification system categorised alertness into one of 12 adaptive scoring stages. 6 of the 12 stages are described by the alertness conditions comparable to WAKE and NREM1.4 stages are nearly classified as NREM2-4, Rapid Eye Movement (REM) and Movement Time (MT), and one stage reflects the increase of alertness from drowsiness. The typical stage of an alert subject increased significantly from a median of 65.9% before therapy to 80.8% in the second investigation. The percentages of clearly drowsy stages decreased significantly. In contrast, there were no significant changes in the percentages of sleep stages according to R&K criteria for both investigations. According to R&K criteria 178 of 398 failed reactions (Reaction time >10 s) occurred in stage WAKE. According to adaptive scoring, only 12 failed reactions appeared in the alert stage. During the other failed reactions the electrophysiological recordings showed decreases in alertness. Neither the visual assessment nor the descriptive statistical results of R&K scoring were helpful to interpret the patient's alertness condition. In contrast, the patients' increases in alertness with nCPAP could be described by the adaptive scoring stages. This method could be a very useful procedure, when an expert opinion is necessary. It also has an actual context to the discussion of the effectiveness of CPAP in the treatment of OSAS.

Adult↗
PubMed1999

Small intestinal Na+,K+-adenosine triphosphatase activity and gene expression in experimental diabetes mellitus.

The Na+,K+-ATPase plays a key role in the absorption of electrolytes, water, and nutrients from the small intestine. The effect of streptozotocin-induced diabetes mellitus (STZ-DM) on the activity and expression of Na+,K+-ATPase in the rat small intestine was examined in the present study. Diabetes mellitus was induced by a single intraperitoneal injection of STZ (75 mg/kg) and control and STZ-DM rats were killed at day 30 (chronic diabetic state). Levels of Na+,K+-ATPase activity and numbers of sodium pumps were increased two- to threefold in the jejunum and ileum. Sodium pump kinetics were unaltered in STZ-DM. The levels of Na+,K+-ATPase alpha1 and beta1 isoform protein, corresponding mRNAs, and levels of transcription were increased in the jejunal and ileal mucosa of the chronically diabetic rat. The increases in Na+,K+-ATPase functional activity, protein expression, and mRNA were most marked at the level of the ileal mucosa. While a proximal to distal gradient in Na+,K+-ATPase activity and subunit isoform protein levels were observed in both control and diabetic rats, levels of subunit isoform mRNA abundance were similar in both regions of the small intestine in both groups of rats. The alterations in small intestinal Na+,K+-ATPase expression in the chronic diabetic state appear to involve alterations in transcriptional and posttranscriptional events and may likely represent an adaptive response that leads to increased Na+-coupled monosaccharide absorption in the context of a perceived state of nutrient depletion.

Animals↗
PubMed1998

Small bowel review: Part I.

In the past year there have been many advances in the area of small bowel physiology and pathology. In preparation for this review, over 500 papers were assessed, and some have been selected and reviewed, with a particular focus on presenting clinically useful information for the practising gastroenterologist.

Celiac Disease↗
PubMed1997

The detection of drowsiness and sleep onset periods from ambulatory recorded polygraphic data.

A 30 min sample recording at the sleep onset of 7 healthy male subjects was used to further develop a computer-scoring algorithm applied earlier for the analysis of MSLT recordings. The performance of this algorithm was tested on 7 patients with obstructive sleep apnea by using 6 h daytime recordings including drowsiness and sleep episodes. The total epoch-by-epoch agreement between visual and computer scoring was over 90% and the accurate detection rate of non-REM sleep was 64%. The hypnograms produced by the computer scoring corresponded sufficiently to those obtained by visual scoring. Our automatic scoring system can give a good estimation of the daytime vigilance profile but for clinical diagnosis the results have to be verified visually. However, by using modern digital recording, analyzing and scoring techniques the speed of analysis and thus the costs can markedly been reduced as compared to traditional visual analysis.

Adult↗
PubMed1997

Circulating endothelin-1 in obstructive sleep apnea.

Endothelin (ET)-1 is a potent vasoconstrictive and mitogenic peptide produced by endothelial cells and degraded predominantly in pulmonary vasculature. We measured ET-1 in 9-normotensive and 14 hypertensive men with obstructive sleep apnea. The ET-1 levels were higher in both normotensive (mean +/- SD, 6.3 +/- 2.8 pg/ml) and hypertensive (7.8 +/- 3.0 pg/ml) groups than in 66 healthy controls (2.9 +/- 1.2 pg/ml). Ten patients were restudied after three months of nCPAP treatment. No decrease in ET-1 was observed.

Adult↗
PubMed1996

Nonlinear eye movement detection method for drowsiness studies.

Automatic long-term vigilance analysis systems require information about the occurrence and type of eye movements, in addition to information about other physiological signals. This paper presents a method to detect different types of eye movements in ambulatory recordings. The method is based on the application of a weighted FIR-median-hybrid filter in the preprocessing of the signal and on the novel use of linear correlation between two EOG signals which are obtained using a new, improved electrode montage. The evaluation of the method showed that it performed well in detecting isolated unambiguous eye movements, but differences were observed in comparison to visual scoring in borderline cases. The method was found to be suitable for use as part of a signal analysis system for drowsiness studies.

Electrooculography↗
PubMed1996

Effect of nasal CPAP treatment on plasma volume, aldosterone and 24-h blood pressure in obstructive sleep apnoea.

Polycythaemia, peripheral oedema formation and hypertension have classically been described in association with obstructive sleep apnoea (OSA). However, there is very limited information about blood volume in OSA and how it changes during long-term treatment with nasal continuous positive airway pressure (nCPAP). Plasma (PV) and red-cell volumes (RCV), 24-h ambulatory blood pressure (BP), 24-h natriuresis and morning plasma aldosterone, renin activity and atrial natriuretic peptide in 11 men with a mean age of 47 y (range 37-55), apnoea index (AI) of 55 (22-106), body mass index of 36 (30-43) and seated BP of > or = 140/90 mmHg without any medication were measured. BP-measurements were repeated after 3 weeks and all measurements after 3 mo of nCPAP treatment. Aldosterone and 24-h mean heart rates decreased during treatment. Twenty-four-h BP decreased after 3 weeks but that decrease did not persist after 3 mo of treatment. There was a relationship between changes in night-time mean BP and PV and aldosterone. The haematocrit declined in every patient. No significant changes were found in the mean PV or RCV. They were in all instances lower than has earlier been described for normal, non-obese subjects. These data also suggest that OSA causes divergent individual disturbances in blood volume homeostasis which can be corrected by nCPAP.

Adult↗
PubMed1996

Past and future of computer-assisted sleep analysis and drowsiness assessment.

The development of computerized sleep analysis has been very much technology-driven by both mathematical tools and available hardware but, additionally and unfortunately, by the almost-30-year-old standard used for manual sleep stage scoring of paper recordings. There are no technical restrictions in terms of computing power, storage space, and costs anymore. However, the standards of visual sleep stage scoring have proven insufficient and ambiguous, and their utilization evidently provides misleading and erroneous information. The low temporal resolution provided by the one-page epoch, the crude division of the sleep processes into a few discrete stages, and the total ignorance of spatial information are the major drawbacks. It is meaningless to try to improve the computerised systems if the algorithms are based on erroneous concepts. Instead, the focus should be changed to studies dealing with the identification and modelling of true biological sleep-related processes. This work cannot be performed without the successful application of computerized methods, some of which have been used in related fields but have not yet been applied to sleep studies. It is extremely important that basic findings are confirmed with a wide variety of methods in several laboratories. The use of predetermined, fixed criteria for methods, waveforms, and states too early is scientifically erroneous and hazardous. Instead standards should describe the minimum requirements for the recording and analysis of the signals in terms of sampling rate, dynamic range, linearity, and documentation of the methods used. With the development of better technology, these standards ought to be constantly reevaluated and modified. The development toward more open commercial digital systems, including standardized programming methods and data formats, would have great positive impact to the field. These trends have long been established in many other fields of industry.

Algorithms↗
PubMed1996

Role of weaning in the nutritional status of infant--a longitudinal study in the rural area of Aligarh.

Influences of weaning practices on nutritional status were studied in a cohort of 200 infants over a period of one year in the rural area of Aligarh. Weaning was late in most of the infants under study. The nutritional status of infants up to 6 months was significantly better than that of infants more than 6 months of age. Most of them used the family-type food as weaning food.

Developing Countries↗
PubMed1995

Multi-centre comparison of five eye movement detection algorithms.

Although various investigators have suggested algorithms for the automatic detection of eye movements during sleep, objective comparisons of the proposed methods have previously been difficult due to different recording arrangements of different investigators. In this study the results of five eye movement detection algorithms applied to the same data were compared to visually scored data. The percentages of true and false detections are given for various threshold levels in rapid and slow eye movement detections. The methods gave best results when they were used with the same electrode montage they were designed for but the performance decreased when other montages were used. Subtracting the cross-talk of EEG delta activity improved the correctness of eye movement detections.

Journal Article↗
PubMed1995

Quantitative topographic electroencephalographic mapping during drowsiness and sleep onset.

The topographic EEG features of drowsiness and sleep onset are much less well documented than are their temporal aspects. A commercial topographical mapping system was used to assess the main EEG features employing all 19 international 10/20 system electrode sites referenced to linked ears during wakefulness, stages 1A and 1B drowsiness, stage 2 sleep, and sleep onset REM periods in 19 patients. All patients had been referred for a diagnostic EEG or a Multiple Sleep Latency Test and had essentially normal EEGs. Anterior alpha of drowsiness seldom represented frontal spread of the occipital alpha rhythm but usually was a distinct activity of apparent separate origin. Theta activities of drowsiness were maximum at CZ and FZ. Vertex sharp waves and sawtooth waves of rapid eye movement (REM) sleep had similar fields maximum at the midline with a steep decrease laterally. Isolated anterior mainly negative waves were identified. Sleep spindles were usually maximal in fronto central, occasionally centro parietal, or even parietal areas.

Adolescent↗
PubMed1994

The relationship between EEG delta activity and autonomic activity as measured by SCSB during daytime sleep.

The aim of the present work was to study the applicability of the static-charge-sensitive bed (SCSB) method to sleep studies, by comparing autonomic nervous activity measured with the SCSB and EEG delta activity (0.5-2 Hz). Simultaneous polygraphic and SCSB measurements of the first sleep cycle (110 min) were recorded from seven subjects. The amount of delta activity filtered from the EEG was compared in 3 min epochs to an autonomic activity index (AAI) based on cardiac, respiratory and body movement activity. Individual Spearman rank order correlation coefficients between delta amplitude and the AAI varied from 0.17 to -0.60. Therefore, it is concluded that the relationship between the delta activity and the AAI is not systematic enough for defining 'depth' of sleep at any point in time by using the AAI. However, on average, the SCSB differentiates high and low delta values quite well. With some further improvement of the scoring system the SCSB is a useful tool in comparative sleep studies.

Journal Article↗