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Biomedical subjects

I M Hassan

Publications and source records attributed to I M Hassan.

At least 19 recordsLinked to original sources

Ultrastructural changes in rat livers perfused in vitro and in vivo with a high dose of methotrexate.

Methotrexate is an antifolate that is widely used in the treatment of malignant tumours and other diseases. The present study was undertaken to examine the short-term effects of high doses of methotrexate (HD-MTX) on the ultrastructure and metabolic activity of isolated rat livers. The authenticity of the drug-induced changes was substantiated by the concomitant use of in vivo experiments. Isolated rat livers were infused with HD-MTX via the portal vein for 3 hours (total dose for each liver 2000 mg). For in vivo experiments, each rat received a single intravenous injection of a maximum tolerated dose of MTX (100 mg/kg body weight) that allowed the animals to survive for 3 days. At the end of each experimental period, MTX-treated and control livers were processed for light microscopy (LM), scanning (SEM) and transmission electron (TEM) microscopy. Oxygen consumption and thyroxine metabolism were measured in treated and control isolated livers. With the exception of a few minor differences, the structural changes in the hepatocytes after MTX treatment in vitro and vivo were similar. There were focal changes consisting of disruption of normal hepatic plates and swelling and vacuolation of the hepatocytes, with no clear evidence of restriction to a specific hepatic zone. SEM revealed striking changes in the plasma membrane, the microvillar system, intercellular junctions and the sinusoidal endothelium. TEM revealed disorganized endoplasmic reticulum, dispersion of the polyribosomes, a variety of mitochondrial changes, and glycogen redistribution. In MTX-treated isolated rat livers, the uptake of tetraiodothyronine (T4) was not affected, but triiodothyronine (T3) release was impaired. Oxygen consumption was increased in livers treated with MTX. Employing an organotypic liver perfusion model in conjunction with the in vivo experiment and the use of SEM, TEM and hepatic thyroxine measurements, this investigation revealed that infusion of HD-MTX induced early ultrastructual changes in cell membrane, intercellular junctions and cell organelles and disturbance in the functional integrity of the hepatocytes in isolated rat liver.

Animals↗

Assessment of women's satisfaction with medical termination of pregnancy.

This was a prospective study involving 205 women seeking medical abortion with gestational age<or=63 days. Questionnaires regarding expectations, experience and satisfaction with medical abortion were self-completed at the end of the procedure. Women's satisfaction was assessed using the visual analogue scale from 0 to 10. Satisfaction and acceptability parameters were correlated with socio-demographic and obstetric data. The mean degree of overall satisfaction was 8.3 (range 1-10). Around 90% of women would select the method again and would recommend it to a friend or relative. The degree of satisfaction showed a positive correlation with women's age (P<0.001) and number of children (P<0.05) and a significant negative correlation with gestational age (P<0.005). Marital status, type of financial support and acceptable pain and bleeding experience also showed a correlation with the satisfaction score. On the other hand, acceptability was correlated with husband/partner agreement and support during the procedure and adequate counselling regarding pain and bleeding.

Abortion, Induced↗

Bisphosphonate space measurement and dosage requirement for intravenous clodronate treatment of Paget's disease.

It has been claimed that the bisphosphonate space, a scintigraphic technique which simultaneously estimates bone uptake and renal clearance of bisphosphonate, can be used to predict the dose of bisphosphonate required to induce biochemical remission in Paget's disease. In a prospective study of 15 newly diagnosed patients with Paget's disease, bisphosphonate space measurements were made prior to treatment with intravenous clodronate. Treatment with clodronate 0.6 g was given four times weekly until the alkaline phosphatase (ALP) suppressed below the upper level of the reference range (120 u/l) or reached a plateau, and the cumulative dose required (1.8-7.8 g) was calculated. Overall, the bisphosphonate space correlated poorly with the total dose requirement (r = 0.441, P = 0.100), but the relationship was weakened by an outlier, who had the poorest renal function. Excluding this subject improved the correlation coefficient (r = 0.852, P <0.0001). The relationship between dose requirement and log10 initial ALP was not as strong (r = 0.672, P <0.01). However, for both ALP and the bisphosphonate space the 95% prediction intervals were wide. We conclude that the bisphosphonate space does relate to dose requirements for intravenous bisphosphonates, but that it is unreliable when renal function is poor, and may not offer much gain over the pretreatment ALP levels. Both ALP and the bisphosphonate space have wide prediction intervals, and are therefore poor guides to dose requirement.

Aged↗

"FUR"--one size suits all.

This work used amalgamated data from previous projects in order to test the concept that when organ function is expressed in terms of tracer kinetics, the results are independent of patient size or gender. Dynamic gamma camera studies were analysed by measuring the rate of movement of tracers from the blood into various organs. These rates were expressed as a "fractional uptake rate" (FUR), which is the fraction of tracer in the blood taken up by the organ per unit time. As these values were small, it was convenient to express the FUR per million seconds. The FUR was calculated using the expression FUR = SLOPE (of Rutland-Patlak plot), multiplied by B(0) (the blood curve value back-extrapolated to time zero), and divided by the TOTAL amount of tracer injected. Data were used from adult patients between the ages of 20 and 49 years who had normal organ function. Organ/tracer groups studied were the skeletal uptake of 99mTc-MDP, the renal uptake of 99mTc-MAG3, the renal uptake of 99mTc-MDP, the renal uptake of 99mTc-DTPA, the hepatic uptake of 99mTc-colloid, the splenic uptake of 99mTc-colloid, and the hepatic uptake of 99mTc-DISIDA. Each organ/tracer group was divided into three subgroups according to patient size (smallest, middle and largest), and also into subgroups according to gender. Comparison of these subgroups did not show any significant size- or gender-related differences in FUR values. It is concluded that for patients with normally functioning organs the FUR is independent of patient size or gender. Thus, the FUR is a valuable way of expressing organ function, particularly in patients with unusual or rapidly changing body size, such as children.

Adult↗

Left ventricular ejection fraction and volumes calculated from dual gated SPECT myocardial imaging with 99Tcm-MIBI.

Dual gated (DG) cardiac single photon emission computed tomographic (SPECT) studies at end-diastole (ED) and end-systole (ES) were acquired in 27 ischaemic heart disease (IHD) patients after intravenous injection of 555-740 MBq 99Tcm-MIBI. Acquisition parameters were: 180 degrees from LPO to RAO, 32 projections, 64 x 64 matrix, 75 cardiac beats per projection, 80 ms at ED and 80 ms at ES for each cardiac cycle. A computer program was developed to calculate the ED and ES left ventricular (LV) volumes and LV ejection fraction (EF). The computational approach is interactive, semi-automatic and iterative with built-in visual quality control. Short axis slices are used with corresponding ED and ES slices processed as pairs from apex to base. Left ventricular cavity pixels are identified and summed on a slice-by-slice basis. Myocardial pixels are similarly identified. The computed LVEF and ED and ES volumes have been correlated with those from contrast ventriculography (CV). The mean calculated EF for 27 patients was 53.6 +/- 10.7% from DG SPECT versus 55.3 +/- 12.1% from CV (NS). The EF linear correlation coefficient was r = 0.97.

Gated Blood-Pool Imaging↗

Iatrogenic obstructive jaundice caused by the balloon of a Foley catheter. Case report.

A rare kind of obstructive jaundice caused by compression on the common bile duct due to an inflated Foley catheter balloon placed in the duodenum after Suguira surgery for bleeding esophageal vesicles secondary to portal hypertension is presented. After deflating the balloon, the obstruction was relieved. Tc-99m HIDA studies were helpful in the diagnosis of obstruction of the common bile duct and the response following the deflation.

Catheterization↗

Segmental analysis of SPECT 99mTc-methoxy isobutyl isonitrile and 201Tl myocardial imaging in ischaemic heart disease.

To study the potential usefulness of 99mTc-methoxy isobutyl isonitrile (99mTc-MIBI) as a substitute for 201Tl in assessing patients with ischaemic heart disease, 24 patients underwent 1 day rest and exercise 99mTc-MIBI single photon emission computerised tomography (SPECT) 1 week after SPECT exercise 201Tl. All patients were catheterized within 1 month after myocardial imaging. In 17 patients, resting first pass radionuclide angiography (FPRNA) was performed with 99mTc-MIBI. The heart to lung ratio for 99mTc-MIBI and 201Tl was calculated both at rest and exercise. The segmental analysis for myocardial perfusion reveals that 87/96 segments (91%) were correctly classified by SPECT 201Tl and 84/96 segments (88%) were correctly classified by 99mTc-MIBI. A significant correlation was present between LVEF measured by 99mTc-MIBI FPRNA and contrast ventriculography (r = 0.85, P less than 0.0001). The heart to lung ratio both at rest and exercise for 99mTc-MIBI is significantly higher than 201Tl (P less than 0.01 and less than 0.001 respectively). We conclude that 99mTc-MIBI is a promising agent for simultaneous evaluation of myocardial perfusion and cardiac function.

Contrast Media↗

Factors affecting the Gates' measurement of glomerular filtration rate.

The following technical factors affect the Gates' measurement of glomerular filtration rate (GFR): 1) net injected activity, 2) kidney depth, 3) corrected kidney counts. In the syringe measurement prior to injection, self-attenuation causes 16% data loss for a volume of 0.5 ml if the syringe is positioned perpendicular to the collimator face. A +/- 1 cm error in true kidney depth may cause a 16% difference in GFR in an adult. The choice of the background region of interest (ROI), for background subtraction significantly affects the calculation. To minimize errors in the Gates' estimate of GFR we recommend 1) that syringe counting be done with the syringe parallel to the collimator face; 2) that the i.v. set be included in the postsyringe measurement; in cases of extravasation, the injection site should also be counted; 3) that kidney depth, especially for ectopic and transplanted kidneys be estimated by ultrasound or using lateral views; and 4) that a background ROI for each kidney be used.

Glomerular Filtration Rate↗

Plasma chloroquine measurement in the evaluation of Plasmodium falciparum sensitivity.

In-vivo assessment of the sensitivity of Plasmodium falciparum to chloroquine was carried out in 63 patients in eastern Sudan. Standard triple-dose therapy with chloroquine (25 mg base kg-1 body wt) failed in curing 30 patients. All grades of resistance were demonstrated in the study, confirming that the phenomenon of chloroquine resistance is well established in this area. Factors which may have accelerated the spread of resistant strains include: a drop in the immunity of the local people caused by previous drought, introduction of non-immune refugees, increased transmission following heavy rains, and massive drug pressure. Plasma levels of chloroquine attained in our patients exceeded the therapeutic level and thus ruled out ineffective levels as a possible cause of treatment failure. Moreover, there was no significant difference between chloroquine levels in patients infected with sensitive or resistant strains. As some patients were cured with an additional dose of chloroquine, it is proposed that chloroquine measurement be carried out in patients treated for falciparum malaria with a view to defining new effective levels for semi-immune populations.

Animals↗

Problems of duodenogastric reflux in Tc-99m Hexa MIBI planar, tomographic and bull's eye display.

Tc-99m Hexa MIBI (RP-30) is excreted through hepatobiliary pathways. Myocardial imaging with RP-30 is recommended 45-60 minutes after injection. During this waiting period duodenogastric reflux (DGR) is occasionally seen. Fundal activity due to duodenogastrix reflux presents problems in planar, tomographic, and Bull's eye display. The authors recommend in those cases to give the patient a light meal and wait 15-30 minutes more for the gastric activity to empty in the small intestine before starting myocardial imaging.

Coronary Disease↗

Uptake and kinetics of Tc-99m hexakis 2-methoxy isobutyl isonitrile in benign and malignant lesions in the lungs.

Kinetics of Tc-99m MIBI uptake was studied in 19 patients with lung lesions (6 benign, 13 malignant). Two dynamic studies were acquired after the I.V. injection of 10-15mCi (370-550 MBq); the first was every second for 60 seconds, followed by a second one every minute for 30 minutes. Delayed images were acquired at two and three hours. By assigning regions of interest (ROI) over the lung lesions (TR), contralateral normal lung (NL) and the heart (Ht), time activity curves (TAC) were generated and time to peak activity was calculated as well as the ratios of TR/NL, Ht/TR and Ht/NL. The Ht/NL ratio was also assessed in five patients referred with diagnosis of ischaemic heart disease (IHD) for myocardial imaging. There was a localized increase of Tc-99m MIBI uptake in ten patients with untreated malignant tumours of the lung. No localized uptake was found in one patient with untreated poorly differentiated squamous cell carcinoma, two treated lung cancer and four patients with non-malignant lesions of the lungs. Two patients with fibrosing alveolitis showed diffuse increase lung uptake. In all positive studies peak tumour was reached within the first minute. There was no statistical difference in the ratio of Ht/NL between all groups except in patients with fibrosing alveolitis. There was no significant difference between the ratios TR/NL, Ht/TR and Ht/NL at 5-10 minutes and 25-30 minutes. The ratio of TR/NL at 25-30 minutes was 1.58 +/- 0.36 in the positive cases versus 1 +/- 0.22 in the negative ones.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Ventricular systolic and diastolic rate indices in patients with either normal or low resting left ventricular ejection fraction.

To investigate the potential uses of right and left ventricular systolic and diastolic rate indices in identifying patients with ischaemic heart disease (IHD), gated blood-pool imaging was performed for 19 normal subjects (group 1) and 56 patients, of whom 31 had resting LVEF greater than or equal to 50% (group 2) and 25 had resting LVEF less than or equal to 50 (group 3). The peak ejection rate (PER) and peak filling rate (PFR), their timing and the mean filling rate (MFR) were derived from the time-activity curves analysis. Group 2 patients had significantly reduced LV PER and PFR (3.00 +/- 0.58 EDV/s, p less than 0.005, 2.29 +/- 0.54 EDV/s, p less than 0.0009) as compared to normal (3.90 +/- 0.70 EDV/s and 3.35 +/- 0.80 EDV/s respectively). Patients with profoundly depressed LVEF had significantly low PER and PFR (1.96 +/- 0.50 EDV/s, 1.46 +/- 0.27 EDV/s respectively). However, there was considerable overlap in values between groups. Therefore, we conclude that there is no single parameter more sensitive than LVEF in identifying IHD patients with normal LVEF at rest.

Adult↗

Ultrastructural and hormonal metabolic studies of rat liver maintained in vitro by perfusion at 30 degrees C and 37 degrees C: a time course study by TEM, SEM and RIA.

Isolated rat liver perfusion system has been extensively used for metabolic and functional studies. Results derived from the application of this system may reflect true biochemical changes but they may also be associated with some structural changes. This study was undertaken to correlate the cytological changes and functional integrity of isolated rat liver perfused in vitro at normal physiological temperature (37 degrees C) and 30 degrees C, using a non-recirculating system. The livers were perfused for 3 hours with modified Ham's F10 culture medium supplemented with thyroxine hormone (T4). The hepatocyte structural integrity was studied by light microscopy, transmission and scanning electron microscopy. The triiodothyronine (T3) and T4 hormones in the perfusion medium and the effluent fractions were assessed by radioimmunoassay. The livers perfused at 30 degrees C remained morphologically intact at the ultrastructural level for 3 hours whilst at 37 degrees C, hepatocytes in the centrilobular zone exhibited marked structural alterations. The percentage of T4 uptake was significantly higher (P less than 0.01) in livers perfused at 30 degrees C (50.8 +/- 7.7% vs 38 +/- 7.7%, 37 degrees C), but the net T3 output (3.16 +/- 1.04 micrograms) and the conversion of T4 to T3 (4 +/- 0.62%) were significantly higher (P less than 0.001) in livers perfused at 37 degrees C in comparison to livers perfused at 30 degrees C (1.61 +/- 0.84 micrograms and 1.68 +/- 0.76%, respectively). In conclusion, at 30 degrees C the hepatic T4 uptake is not inhibited, but the rate of T4 to T3 conversion has decreased, additionally the livers remain morphologically well preserved throughout the experimental period.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Experience with thallium-201 imaging in head and neck cancer.

TI-201 chloride was used for tumor imaging in patients with head and neck cancer. It is of value in detecting the extent of tumor involvement, the presence of residual tumor after radical courses of treatment, and the presence of local recurrence and distant metastases.

Adolescent↗

Response of left and right ventricle rate indices to exercise in normal volunteers.

Changes in left ventricular (LV) performance between rest (Re) and exercise (Ex) in normal hearts has been analysed in great detail using various parameters (P) of radionuclide MUGA studies. Little attention was given in this regard to right ventricular (RV) performance. We developed a program on the Informatik Sims V Computer applying the first derivative technique to analyse the time activity curve of both R and LV to study the changes in the following (P) between Re and Ex. 1. Ejection fraction (EF) 2. Peak ejection rate (PER) 3. Time to peak ejection rate (TPER) 4. Normalized TPER to the ejection period (EP) 5. Peak filling rate (PFR) 6. Time to peak filling rate (TPFR) 7. Normalized TPFR to the filling period (FP) 8. The time from peak filling rate to peak ejection rate (TPFR-TPER). Nineteen volunteers performed gated blood pool studies at Re and Ex in the semi-supine bicycle position. The results show that there were significant differences (P less than 0.0001) between all the parameters of the right and left ventricles at rest in comparison with those during exercise except for the normalized TPER in both right and left ventricles. In this study not only do we confirm the changes in LV performance between Re and Ex in healthy volunteers that has been previously reported, but we also report for the first time the changes in RV (P) in the same group of volunteers.

Adult↗

Morphological changes in the isolated rat liver perfused in a non-recirculating system: scanning and transmission electron microscopy.

Isolated perfused rat livers have been used for various studies, but detailed investigation into the structural integrity of hepatocytes of this system is lacking. In this study, isolated rat livers were perfused in vitro with oxygenated Krebs-Ringer bicarbonate buffer solution, for 2 minutes and 1, 2, 3, and 4 hour(s) at 37 degrees C, using a non-recirculating perfusion system. The perfused livers were processed for semithin section light microscopy, transmission electron microscopy, and scanning electron microscopy. Sectional areas of cell deaths were measured by a camera-tracing assembly from 1.5 microns thick Araldite sections stained with toluidine blue. Progressive nuclear and cytoplasmic changes, leading to cell death, occurred in the hepatocytes of the centrilobular zone, during the 2nd, 3rd, and 4th hour of the perfusion at a rate of 9.03% +/- 1.5%, 38.7% +/- 2.7%, and 55.1% +/- 5.9% (mean +/- standard deviation) of the total sectional areas respectively. Midzonal hepatocytes showed normal basophilic staining but exhibited loss of glycogen granules, loss of microvilli, development of aqueous vacuoles and formation of blebs. The fine structures of cell organelles, glycogen granules, microvilli and plasma membrane of the cells in the periportal zone were well preserved throughout the experimental period. For further quantitative, metabolic and functional studies using isolated rat liver perfused with Krebs-Ringer solution, it is evident from the present investigation that the periportal zone represents the functional region of the hepatic lobule. Whilst progressive changes, leading to cell death, occurred in the centrilobular zone.

Animals↗

A comparison of two radionuclide ejection-fraction techniques with contrast angiography in ischemic heart disease and valvular heart disease.

First-pass radionuclide angiography (FPRA) in the 30 degree right anterior oblique and equilibrium gated radionuclide angiography (EGNA) in the 45 degree left anterior oblique were used for quantitative measurements of left ventricular ejection fraction (LVEF). Equipment used was a 400T gamma-camera interfaced with a Simis III Informatek computer. The results were compared with contrast angiography (CA). The aim of this study was to determine the sensitivity of both radionuclide techniques. The present data are based on 65 patients in whom CA and EGNA were performed. In 47 patients both FPRA and EGNA were performed. Results suggested that in ischemic heart disease (IHD) and valvular heart disease (VHD) the EGNA technique is well correlated with CA (r = 0.9 and 0.73, respectively). FPRA correlated well only with CA in IHD (r = 0.86), but not in VHD (r = 0.18). This study indicates that both FPRA and EGNA are sensitive, noninvasive techniques for measuring ejection fraction in IHD, while in VHD, EGNA is more sensitive technique than FPRA.

Adolescent↗