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Biomedical subjects

P Abraham

Publications and source records attributed to P Abraham.

At least 145 records · Page 8Linked to original sources

Heart rate-corrected ankle-to-arm index in the diagnosis of moderate lower extremity arterial disease.

UNLABELLED: Although the ratio of ankle-to-arm systolic pressures (AAI) at rest is widely used in the clinical diagnosis of peripheral arterial disease, the heart rate (HR) at which the measurements are performed is rarely reported. The relation of ankle-to-arm index (AAI) to HR was studied in a normal population (n = 65) and in a population of patients (n = 101) suspected of moderate lower extremity arterial disease (LEAD). In the normal population, a significant inverse correlation was found between AAI and HR at rest: AAI = -0.277 x HR/100 + 1.303; r = -0.52, P < 0.001. In the second population suspected of LEAD, the authors recorded AAI and HR at rest on both legs; 80 normal legs, 110 diseased legs. Thereafter, with normal limits as superior to 0.8, 0.9, and 0.95, sensitivity was respectively 16, 39, and 46%, and specificity was 100, 100, and 98%. In defining normal limit as superior to -2 standard deviations of the AAI-HR relation found in the normal population, sensitivity and specificity were 57 and 100%, respectively. IN CONCLUSION: In screening for LEAD in the general population with the use of AAI at rest, the authors suggest that the heart rate at which arterial pressure measurements are performed should be reported.

Adult↗

Ankle systolic blood pressure following sub-maximal and maximal exercises in healthy young men.

Although recent studies have compared the effect of progressive exercise tests to constant moderate work load tests on ankle systolic blood pressure (ASBP) and ankle to arm index (AAI) in claudicants, little is known about the relation of ASBP and AAI to work load in healthy young men. Fifteen normal volunteers were asked to cycle 40, 60, 80, 100% of VO2max. Ankle and humeral pressures were recorded simultaneously, at rest and 1 minute after the end of each test. Thereafter, AAI was calculated as the ratio of ankle to humeral systolic pressure. Compared to resting values: 134.8 +/- 13.9 mmHg, ASBP increased significantly following sub maximal tests up to 157.8 +/- 28.1 mmHg (p < 0.005), but was not increased following maximal exercise: 141.5 +/- 28.2 mmHg (NS). On the other hand, AAI showed a progressive decrease from 1.14 +/- 0.06 at rest to 1.06 +/- 0.08 (p < 0.005), but 0.98 +/- 0.07 (p < 0.005), to 0.84 +/- 0.06 (p < 0.005) and to 0.75 +/- 0.09 (p < 0.005) following 40, 60, 80 and 100% of VO2max respectively. In summary, AAI following exercise is inversely related to workload whereas ASBP is not. We suggest that when studying ankle systolic blood pressure response to heavy load exercises, results should always be compared to humeral pressure, and expressed as ankle to arms indexes.

Adult↗

Selective labeling of the dopamine transporter by the high affinity ligand 3 beta-(4-[125I]iodophenyl)tropane-2 beta-carboxylic acid isopropyl ester.

The iodine-125 analog of the dopaminergically selective cocaine analog 3 beta-(4-iodophenyl)tropane-2 beta-carboxylic acid isopropyl ester (RT1-121) was evaluated as a probe for the dopamine transporter in rat striatum. Saturation and kinetic studies indicated that [125I]RTI-121 binds to both high and low affinity components. The Kd of the high affinity component was 0.14 +/- 0.01 nM (mean +/- standard error), whereas the low affinity component demonstrated an affinity of 1.59 +/- 0.09 nM. The corresponding numbers of striatal binding sites labeled by [125I]RTI-121 were 295 +/- 6 and 472 +/- 59 pmol/g of tissue (original wet weight), respectively. Intrastriatal injections of 6-hydroxydopamine eliminated > 90% of specific [125I]RTI-121 binding in the striatum. The pharmacological profile of specific [125I]RTI-121 binding in the rat striatum was consistent with that of the dopamine transporter. There was a strong (r = 0.98, p < 0.0001) correlation between the potencies of drugs that displaced specific [125I]RTI-121 binding and the potencies of these drugs to inhibit the uptake of [3H]dopamine. In contrast, no correlation was found for the potencies of drugs to inhibit the uptake of either [3H]norepinephrine or [3H]serotonin. Autoradiographs produced using [125I]RTI-121 demonstrated a distribution of label consistent with the distribution of dopaminergic neurons in rat brain. Because of its high affinity and high selectivity for the dopamine transporter, [125I]RTI-121 may be an extremely useful ligand for the dopamine transporter.

Animals↗

Correlation of manometric and radiographic diagnosis in esophageal motility disorders.

BACKGROUND: Radiography and manometry are complementary investigations in the diagnosis of esophageal motility disorders. In most centers, however, manometry is not available and diagnosis is based on radiography alone. AIMS: To correlate the findings on radiography in patients with esophageal motility disorders in whom a manometric diagnosis was available. METHODS: Retrospective analysis of esophageal manometry and barium contrast studies of 138 patients, done for suspected motility disorders, over a period of two years. RESULTS: Manometry was abnormal in 111 (80.4%) cases [achalasia 87, scleroderma 6, non specific esophageal motility disorders (NEMD) 13, diffuse esophageal spasm (DES) 5]. Radiology was abnormal in 106 cases; the overall radiographic sensitivity was 73.9% (achalasia 87.4%, scleroderma 83.3%, NEMD 38.5%) and the positive predictive value was 75.5% (achalasia 95%, scleroderma 100%, NEMD 29.4%). CONCLUSION: Radiography has a high sensitivity and positive predictive value in esophageal motility disorders like achalasia and scleroderma but in DES and NEMD the two investigative modalities (radiography and manometry) do not correlate well.

Adult↗

Total and segmental colonic transit time in non ulcer dyspepsia.

BACKGROUND: Patients with non ulcer dyspepsia (NUD) often have associated lower alimentary tract symptoms which are labelled as due to the irritable bowel syndrome. AIMS: To asymptomatic colonic dysmotility is present in patients with NUD. METHODS: We studied total and segmental colonic transit times in 25 patients with NUD (14 men age range 20-70 yr), and 25 matched normal controls (13 men; 18-50 yr), using the multiple-marker, single-film technique. Twenty markers each were administered at 0, 9 and 18 h and an abdominal film taken at 27 h. RESULTS: Total colonic transit time was shorter (median 9 h) in patients with NUD as compared to controls (median 15.8 h) p = 0.0018, with similar segmental motility pattern as in controls. There was no significant difference between the symptom subgroups of NUD. CONCLUSIONS: Patients with NUD often have altered colonic transit even in the absence of symptoms. NUD may therefore be only a subset of diffuse gastrointestinal dysmotility with predominant proximal alimentary tract symptoms, whereas the term irritable bowel syndrome is used when lower tract symptoms predominate.

Adult↗

Gastric bacterial overgrowth accompanies profound acid suppression.

BACKGROUND: Suppression of gastric acid may lead to gastric colonization by aerobic and anaerobic bacteria, and consequent clinical manifestations. The risk is likely to be higher with poor environmental hygiene. AIMS: To study the effect of short-term acid suppression with omeprazole on gastric bacterial flora. METHODS: Twenty-five ambulatory patients with acid-peptic diseases underwent clinical assessment and gastric juice collection (for pH and culture) prior to start of therapy with 20 mg omeprazole daily, on days 7 and 14 of therapy, and 7 days after omission of therapy (day 21). RESULTS: Eighteen patients completed the study. The median gastric pH was 1.8, 7.5, 7.5 and 3.4 on days 0, 7, 14 and 21 respectively. Positive gastric cultures were obtained in 13 of 25, 17 of 21, 18 of 18 and 14 of 18 patients on respective study days, with median colony counts of 1.5 x 10(4), 7.5 x 10(5), 8.7 x 10(7) and 7.3 x 10(4) cfu/mL respectively. Three patients developed self-limiting diarrhea during therapy and two more immediately after discontinuing therapy. CONCLUSIONS: Gastric colonization is common with short-term profound acid-suppression, and may cause diarrhea. Acid suppressive therapy should be used with caution especially in patients with poor environmental hygiene.

Adult↗

Synthesis, ligand binding, and QSAR (CoMFA and classical) study of 3 beta-(3'-substituted phenyl)-, 3 beta-(4'-substituted phenyl)-, and 3 beta-(3',4'-disubstituted phenyl)tropane-2 beta-carboxylic acid methyl esters.

Several new 3 beta-(4'-substituted phenyl)-, 3-beta-(3'-substituted phenyl)-, and 3 beta-(3',4'-disubstituted phenyl)tropane-2 beta-carboxylic acid methyl esters were prepared and assayed for inhibition of [3H]WIN 35,428 binding to the dopamine transporter. The 3 beta-(3',4'-dichloro) and 3 beta-(4'-chloro-3'-methyl) analogues (2w and 2y; RTI-111 and RTI-112, respectively) with IC50 values of 0.79 and 0.81 nM showed the highest affinity. The contributions of quantitative structure-activity relationship (QSAR) models derived from the classical and comparative molecular field analysis (CoMFA) approaches to rational drug design were examined. CoMFA models were derived using steric and electrostatic potentials with SYBYL default values while the classical models were derived from pi and MR parameters. Using a 12-compound training set, both models were used for predicting the binding affinity of compounds both inside and outside the training set. The CoMFA study provided new insight into the steric and electrostatic factors influencing binding to the DA transporter and provided additional support for our original finding that CoMFA is useful in predicting and designing new compounds for study. The classical QSAR models, which were easier to obtain, suggest that the distribution property (pi) of the compounds is an important factor. Overall, the SAR, CoMFA, and conventional QSAR studies elaborated some features of the cocaine binding site pharmacophore and provided useful predictive information.

Animals↗

Secondary amine analogues of 3 beta-(4'-substituted phenyl)tropane-2 beta-carboxylic acid esters and N-norcocaine exhibit enhanced affinity for serotonin and norepinephrine transporters.

N-Norcocaine (2) and six N-nor-3 beta-(4'-substituted phenyl)tropane-2 beta-carboxylic acid esters (4a-f) were synthesized by N-demethylation of cocaine (1) and the appropriate 3 beta-(substituted phenyl)-tropane analogues (3a-f) with alpha-chloroethyl chloroformate. Radioligand binding affinities of 2 and 4a-f at the DA, 5-HT, and NE transporter were measured and compared to those of 1 and 3a-f. N-Demethylation produced relatively small effects at the DA transporter. In contrast, 4-19-fold and 2-44-fold enhanced affinity at the serotonin and norepinephrine transporter resulted from demethylation. N-Nor-3 beta-(4'-iodophenyl)tropane-2 beta-carboxylic acid methyl ester (4d) with an IC50 = 0.36 nM showed the greatest affinity for the serotonin transporter. However, N-nor-3 beta-(4'-ethylphenyl)tropane-2 beta-carboxylic acid methyl ester (4e) showed the greatest selectivity for the serotonin transporter.

Animals↗

Diameter and blood velocity changes in the saphenous vein during thermal stress.

Although volume, pressure or flow in superficial veins have been studied extensively, little is known about venous blood velocity during thermal stress. Most authors have suggested that the velocity is decreased in the dilated superficial veins during heat stress to facilitate heat loss, and is increased during cooling as the vein is constricted. Duplex ultrasound has been used to study saphenous cross sectional area (CSA) and mean maximal venous blood velocity (BV) in ten healthy volunteers (age 22-31 years). Compared with unstressed mean values, 4.8 (SD 2.6) mm2, CSA increased to 9.3 (SD 2.1) mm2 (P < 0.005) during heat stress and decreased to 2.1 (SD 1.9) mm2 (P < 0.005) during cold stress. These results are consistent with previous studies, but the absolute CSA of the saphenous vein has never been estimated during thermal stress. The BV increased from 0.07 (SD 0.02) m.s-1 to 0.29 (SD 0.11) m.s-1 (P < 0.005) during warming. During cooling, BV tended to decrease: 0.05 (SD 0.03) m.s-1 (N.S). We would suggest that heat loss during thermal stress can be facilitated by the rapid turnover of warm blood, and not (as usually suggested) by the prolonged cooling of each blood sample in the dilated superficial veins.

Adult↗

Diameter and velocity changes in the femoral vein during thermal stress in humans.

Unlike most studies on deep veins performed with simultaneous suppression of cutaneous blood flow, a sonographic study of femoral diameter and blood flow velocity changes in response to thermal stress was performed while cutaneous flow was preserved. In 11 normal subjects, mean peak blood flow velocity and diameter of the femoral vein were measured at rest and during indirect whole body heating and cooling. Mean peak venous blood flow velocity was 0.12 +/- 0.06 m s-1 at rest, 0.35 +/- 0.23 m s-1 (P < 0.001) during heat stress, and 0.13 +/- 0.07 m s-1 during cold stress (NS). Femoral venous diameter was 5.3 +/- 0.9 mm at rest, 5.1 +/- 1.0 mm (P < 0.05) during warming, and 5.4 +/- 81.0 mm (NS) during cooling. This study showed a decrease in diameter during thermal stress. However, as mean femoral venous blood-flow velocity was doubled during heat stress, femoral venous blood flow was increased. Thus, it is suggested that during heat stress part of the increase in cutaneous flow is returned through deep veins.

Adult↗

Venous return in lower limb during heat stress.

We used ultrasound to study venous return during heat stress. We measured venous cross-sectional area (CSA) and blood flow velocity (BFV) of nine femoral veins and nine saphenous veins. During heat stress, saphenous CSA increased from 4.7 +/- 2.6 mm2 (mean +/- SD) to 9.1 +/- 2.3 mm2 (P < 0.01), whereas femoral CSA was 22.7 +/- 9.5 mm2 at rest and 22.0 +/- 9.6 mm2 during heat stress (NS). Meanwhile, BFV increased from 0.06 +/- 0.02 to 0.30 +/- 0.10 m/s (P < 0.01) in the saphenous vein and from 0.14 +/- 0.08 to 0.38 +/- 0.23 m/s (P < 0.005) in the femoral vein. Maximal venous outflow (MVO) was the product of CSA and BFV. During heat stress, MVO showed an eightfold increase in the saphenous veins (from 22.7 +/- 18.2 to 180.7 +/- 86.7 ml/min) and a 2.5-fold increase in the femoral veins (from 143.4 +/- 52.9 to 354.0 +/- 126.9 ml/min). The results showed that one-half of the cutaneous blood flow increase during heat stress returned through the deep collecting veins in the lower limb. Thereafter, although there was no venodilation of deep veins compared with superficial veins, the deep veins remain the main pathway for the venous return during heat stress.

Adult↗

Comparison of the indirect immunofluorescence assay with western blot for the detection of HIV antibody.

With the increase in the prevalence of human immunodeficiency virus (HIV) infection in India, there is an urgent need to explore cost-containing methods of HIV antibody detection. We compared the indirect immunofluorescence assay (IFA) with the widely used but expensive confirmatory test, the Western blot (WBT). A panel of sera comprising 42 WB positive, 46 antibody negative (27 ELISA negative and 19 ELISA reactive but WB negative) and 58 sera with indeterminate WB profiles were tested by a commercial IFA kit. The sensitivity of IFA was found to be 97.6 per cent and specificity 97.8 per cent. Of the indeterminate sera, 18 (31%) were positive in IFA while 26 (45%) were negative and 14 (24%) were equivocal. In general, the IFA positivity was associated with the presence of the gag and env antibodies of HIV while negativity associated with the presence of lone antibodies. The cost of testing by IFA is less than 20 per cent of that of WB testing. Thus IFA appears to be a cost-containing alternative to WB in centres in India where immunofluorescent microscopy is routinely done.

Blotting, Western↗

3-Aryl-2-(3'-substituted-1',2',4'-oxadiazol-5'-yl)tropane analogues of cocaine: affinities at the cocaine binding site at the dopamine, serotonin, and norepinephrine transporters.

Previous studies have shown that 3 beta-(substituted phenyl)tropan-2 beta-carboxylic acid esters possess high affinity for the cocaine binding site on the dopamine transporter both in vitro and in vivo and inhibit dopamine uptake in vitro. Since 1,2,4-oxadiazoles are excellent bioisosteres of ester groups, we have prepared several 3 beta-(substituted phenyl)-2 beta-(3-substituted 1',2',4'-oxadiazol-5'-yl)tropanes (5b-h) and all four stereoisomers of (1R,5S)-3 phenyl-2-(3-methyl-1',2',4'-oxadiazol-5'-yl)tropane (5a and 6-8). The 3 alpha-phenyl-2-alpha-(3'-methyl-1',2',4'-oxadiazole) isomer 7 was prepared from a stereoselective addition of phenyllithium to (1R,5S)-2-(3'-methyl-1',2',4'-oxadiazol-5-yl)-8-methyl-8- azabicyclo[3.2.1]oct-2-ene (11). The binding affinities for 5a-h and 6-8 at the dopamine, serotonin, and norepinephrine transporters were obtained. In general these bioisosteres showed potencies for the dopamine transporter similar to those of their parent esters. 3 beta-(4'-Chlorophenyl)-2 beta-(3'-phenyl-1',2',4'-oxadiazol-5'-yl)tropane (5d) was the most potent analogue with an IC50 of 1.62nM. However, 3 beta-(4'-chlorophenyl)-2 beta-(3'-methoxyphenyl-1',2'4'- oxadiazol-5'-yl)tropane (5e) with an IC50 of 1.81 nM was the most selective analogue for the dopamine transporter showing NE/DA and 5-HT/DA ratios of 461 and 186, respectively. The cis- and trans-3 alpha-phenyl-2-(3'-methyl-1',2',4'-oxadiazol-5'-yl)tropanes (7 and 8), which exist in a boat conformation, have IC50 values only slightly greater than that of the 3 beta,2 beta-isomer (5a) which possesses the cocaine stereochemistry.

Animals↗

Congestive jejunopathy in portal hypertension.

Twenty six patients with portal hypertension of different aetiologies were studied for endoscopic evidence of congestive gastroduodenopathy and histological evidence of congestive gastropathy and jejunopathy. Per oral biopsies of jejunum were taken by Watson's capsule. Normal biopsy tissues obtained from the antrum (26), fundus (10), and jejunum (26) were used as controls. Endoscopy showed congestive changes in the fundus (17 cases), antrum (17), and duodenum (4). Duodenopathy correlated with changes in the antrum but not in the fundus. Histology showed an increase in the size and number of vessels in the jejunal villi ('congestive jejunopathy') in 22 patients. These correlated with histological evidence of gastropathy in the fundus but not in the antrum. The incidence of congestive jejunopathy did not correlate with the Child-Pugh score in patients with cirrhosis or with the number of sclerotherapy sessions received. Congestive jejunopathy is part of the spectrum of congestive gastroenteropathy and occurs at least as frequently as changes in the stomach and duodenum. The clinical import of these jejunal changes remains to be explained.

Adult↗

Detection of rectal and pararectal varices in patients with portal hypertension: efficacy of transvaginal sonography.

OBJECTIVE: The appearance and frequency of pararectal varices in patients with portal hypertension have not been studied. Accordingly, we used transvaginal sonography to detect pararectal varices and to compare their appearance and frequency with those of rectal varices in patients with portal hypertension. SUBJECTS AND METHODS: Transvaginal sonography was performed in 21 women with portal hypertension of different causes. The frequency and appearance of pararectal varices were determined and compared with those of rectal varices detected either in the same sonographic study or by sigmoidoscopy. RESULTS: Pararectal varices were detected in 17 (81%) of 21 patients. The varices varied in diameter from 2.1 to 5.5 mm (median, 3.5 mm). Seven of the patients with pararectal varices did not have rectal varices. Rectal varices were detected in 10 of 21 patients by transvaginal sonography and in nine patients by sigmoidoscopy; the two methods together showed rectal varices in 13 patients. CONCLUSION: Transvaginal sonography is useful for detecting pararectal and rectal varices in patients with portal hypertension. Pararectal varices are more common than rectal varices in these patients.

Adult↗

Intrapulmonary vascular dilatations with hypoxemia in extrahepatic portal vein obstruction.

Several mechanisms have been suggested for the development of hypoxemia in cirrhosis. A few patients of portal hypertension due to non cirrhotic liver disease with cyanosis have also been reported earlier. We report probably the first documented case of portal hypertension with portal cavernoma and a normal liver, who had intrapulmonary vascular dilatations leading to hypoxemia and cyanosis. Our case suggests that changes leading to hypoxemia can occur due to portal hypertension alone, in the presence of a normal liver.

Dilatation, Pathologic↗