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Biomedical subjects

J Hasan

Publications and source records attributed to J Hasan.

At least 19 recordsLinked to original sources
PubMed2006

The interval from surgery to chemotherapy in the treatment of advanced epithelial ovarian carcinoma.

BACKGROUND: To study the effect of the interval between surgery and the start of chemotherapy in the treatment of patients with advanced ovarian cancer. METHODS: We stratified patients according to the start of platinum-based chemotherapy in group 1 (within 4 weeks from surgery), group 2 (between 4 and 8 weeks) and group 3 (between 8 and 12 weeks). RESULTS: Three hundred and ninty-four stage III ovarian cancer patients were analysed. In the multivariate analysis there were no differences in survival according to the interval between surgery and chemotherapy among the three groups. The independent prognostic variables were type of procedure (p = 0.014), performance status (p = 0.040) and post-chemotherapy CA-125 (p < 0.0001). CONCLUSIONS: The interval between surgery and chemotherapy does not affect outcome.

Adult↗
PubMed2006

Cyclosporine profiling with C2 and C0 monitoring improves outcomes after heart transplantation.

BACKGROUND: Cyclosporine (CsA) level at 2 hours post-dose (C2) is a more sensitive marker for rejection risk than trough (C0) level. A combination of C2 and C0 monitoring may prove optimal. METHODS: We compared efficacy and safety outcomes among 28 de novo heart transplant patients in whom both C2 and C0 monitoring were undertaken (Group 1), with a single CsA profile at Weeks 2 to 6, versus 28 historic controls monitored by only C0 (Group 2). Patients received anti-thymocyte globulin (ATG) induction with CsA, steroids and azathioprine maintenance therapy. RESULTS: The CsA microemulsion dose was significantly higher in Group 1 than Group 2 up to 3 months post-transplant. Mean C2 values in Group 1 at 3 and 12 months were 1,248 +/- 328 ng/ml and 1,039 +/- 362 ng/ml, respectively. One patient in Group 1 and 7 in Group 2 (25%) discontinued CsA, either due to CsA-related neurotoxicity or two or more episodes of early rejection. At 12 months, graft and patient survival were 100% in both groups. Six patients in Group 1 (21%) and 11 in Group 2 (39%) had at least one episode of biopsy-proven acute rejection (not significant). Over the first 12 months post-transplant, the proportion of biopsies showing Grade 3 rejection was 5% in Group 1 and 11% in Group 2 (p < 0.002). Gloerular filtration rate (GFR) was significantly lower in Group 1 than Group 2 at both 3 and 12 months. CONCLUSIONS: Combined use of C2 and C0 monitoring results in improved efficacy versus C0 monitoring alone. Regular measurement of C2 levels should be undertaken in de novo heart transplant recipients.

Adult↗
PubMed2005

Phase II trial of tamoxifen and goserelin in recurrent epithelial ovarian cancer.

Endocrine therapy is a recognised option in the treatment of chemo-resistant ovarian cancer. We conducted a nonrandomised phase II evaluation of combination endocrine therapy with tamoxifen and goserelin in patients with advanced ovarian cancer that had recurred following chemotherapy. In total, 26 patients entered the study, of which 17 had platinum-resistant disease. The median age was 63 years and enrolled patients had received a median of three chemotherapy regimens prior to trial entry. Patients were given oral tamoxifen 20 mg twice daily on a continuous basis and subcutaneous goserelin 3.6 mg once a month until disease progression. Using the definition of endocrine response that included patients with stable disease (SD) of 6 months or greater, the overall response rate (clinical benefit rate) was 50%. This included one complete response (CR) (3.8%), two partial responses (PR) (7.7%) and 10 patients with SD (38.5%). The median progression-free interval (PFI) was 4 months (95% CI 2.4-9.6) while the median overall survival (OS) was 13.6 months (95% CI 5.5-30.6). Four patients received treatment for more than 2 years (range 1-31) and one of them is still on treatment. In none of the four patients was there any evidence of recurrent or cumulative treatment related toxicity. Treatment-limiting toxicity was not seen in any of the study population. Endocrine data demonstrated a marked suppression of luteinising hormone (LH) and follicle-stimulating hormone (FSH) to less than 4% of baseline values. No consistent correlation could be established between LH/FSH suppression and tumour response. Likewise no relationship was observed between Inhibin A/B and pro-alpha C levels and tumour response. Inhibin is unlikely to be a useful surrogate marker for response in locally advanced or metastatic ovarian cancer. Combination endocrine therapy with tamoxifen and goserelin is an active regimen in platinum-resistant ovarian cancer patients. Hormonal therapy is advantageous in its relative lack of toxicity, ease of administration and tolerability, thus making it suitable for patients with heavily pretreated disease, compromised bone marrow function and other comorbid conditions that contraindicate cytotoxic therapy as well as in patients with indolent disease.

Aged↗
PubMed2003

Oral melphalan as a treatment for platinum-resistant ovarian cancer.

A large number of drugs have been used to treat recurrent ovarian cancer, yet there are few data that guide the physician's choice. Typically, the decision to re-treat with platinum-based therapy depends on the progression-free interval. However, the optimum agent for the treatment of platinum-resistant or refractory disease is not defined. In this study, we investigated the efficacy of oral melphalan in patients who have platinum refractory or resistant disease. A retrospective analysis was performed on 22 patients with ovarian carcinomas who had relapsed within 6 months of their platinum-based chemotherapy and were treated with oral melphalan. No objective responses were seen and the median overall survival was 3 months from commencement of therapy. Although the treatment was generally well tolerated, only two of the 22 patients managed to complete the planned six cycles of treatment. At the time of analysis, only two patients were alive. Other nonplatinum compounds have demonstrated response rates in the region of 20% in similar patient populations and it is unlikely that any positive responses could have been missed by chance (95% CI 0-15.4). The results of this study serve to eliminate oral melphalan as a treatment option in patients with platinum-resistant or refractory ovarian carcinoma.

Administration, Oral↗
PubMed2003

Automatic analysis of electro-encephalogram sleep spindle frequency throughout the night.

A fully automatic method to analyse electro-encephalogram (EEG) sleep spindle frequency evolution during the night was developed and tested. Twenty all-night recordings were studied from ten healthy control subjects and ten sleep apnoea patients. A total of 22,868 spindles were detected. The overall mean spindle frequency was significantly higher in the control subjects than in the apnoea patients (12.5 Hz against 11.7 Hz, respectively; p<0.004). The proposed method further identified the sleep depth cycles, and the mean spindle frequency was automatically determined inside each sleep depth cycle. In control subjects, the mean spindle frequency increased from 12.0 Hz in the first sleep depth cycle to 12.6 Hz in the fifth cycle. No such increase was observed in the sleep apnoea patients. This difference in the spindle frequency evolution was statistically significant (p<0.004). The advantage of the method is that no EEG amplitude thresholds are needed.

Adult↗
PubMed2002

Intra-tumoural microvessel density in human solid tumours.

Over the last decade assessment of angiogenesis has emerged as a potentially useful biological prognostic and predictive factor in human solid tumours. With the development of highly specific endothelial markers that can be assessed in histological archival specimens, several quantitative studies have been performed in various solid tumours. The majority of published studies have shown a positive correlation between intra-tumoural microvessel density, a measure of tumour angiogenesis, and prognosis in solid tumours. A minority of studies have not demonstrated an association and this may be attributed to significant differences in the methodologies employed for sample selection, immunostaining techniques, vessel counting and statistical analysis, although a number of biological differences may account for the discrepancy. In this review we evaluate the quantification of angiogenesis by immunohistochemistry, the relationship between tumour vascularity and metastasis, and the clinicopathological studies correlating intra-tumoral microvessel density with prognosis and response to anti-cancer therapy. In view of the extensive nature of this retrospective body of data, comparative studies are needed to identify the optimum technique and endothelial antigens (activated or pan-endothelial antigens) but subsequently prospective studies that allocate treatment on the basis of microvessel density are required.

Antibodies, Monoclonal↗
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↗