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Home > Prostate Specific Antigen As a Risk Factor for Skeletal Metastases in Black African Men With Prostate Cancer

Prostate Specific Antigen As a Risk Factor for Skeletal Metastases in Black African Men With Prostate Cancer

Thesis Info

Author

Qureshi, Ayman Mahmood

Department

Imaging and Diagnostic Radiology (East Africa)

Program

MMed

Institute

Aga Khan University

Institute Type

Private

City

Karachi

Province

Sindh

Country

Pakistan

Thesis Completing Year

2013

Thesis Completion Status

Completed

Subject

Medicine

Language

English

Added

2021-02-17 19:49:13

Modified

2024-03-24 20:25:49

ARI ID

1676728064660

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Background: Prostate cancer is one of the commonest cancers in men worldwide. Several recognised risk factors are associated with this disease, amongst them, race. Despite this, there is a paucity of data in the native African setting. The skeletal system is a common site of metastasis, its incidence increasing with increase in prostate specific antigen (PSA) levels. Bone scans are used to detect skeletal metastases. Its use in prostate cancer patients with abnormal but low PSA has been subject of debate. Objectives: To test the association of PSA levels with skeletal metastasis in men with histologically proven prostate cancer. Methodology: Case control study. Using Radiology and Pathology records, a registry of prostate cancer patients recorded as being of Black African ethnicity previously investigated in the institution was assembled. Following anonymisation and coding, archive images were presented to a nuclear physician blinded to the PSA level, to determine presence and sites of skeletal metastases. The risk factor for the outcome of interest (skeletal metastases) was PSA level above 20ng/ml. The reliability of image reporting for bone scans was also analysed. Results: Of 122 patients, 50 (41%) had skeletal metastases, while 72 (59%) had no skeletal metastases. The prevalence of metastases among the high PSA group was 55.9% (44.1% to 67.7%) and 22.2% (11.1% to 33.3%) among the normal/low PSA group. The Odds Ratio (OR) for skeletal metastases in the exposed group was 4.4 (95% CI, 2.01 – 9.78.) There was an intra-observer agreement of 88.5% with a Kappa statistic of 0.76. Inter observer agreement was 85.3% (Kappa statistic of 0.70.) Conclusion: Significantly higher prevalence of skeletal metastasis is seen in regional Black African males with prostate cancer, at both low and high PSA levels. Bone scanning in this population should therefore be considered even at PSA levels below 20ng/ml.
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آسانی و سکون ، فراوانی ٹال کر

آسانی و سکون ، فراوانی ٹال کر
رہتا ہوں خوش میں خود کو مشقت میں ڈال کر

آنسو جو میرے آپ کے دامن پہ گر پڑے
ان موتیوں کو رکھنا مری جاں سنبھال کر

غم یہ کہ ہم کو دنیا نے تقسیم کر دیا
تو دل کے ٹوٹنے کا نہ اتنا ملال کر

میں نے پھر اُن کو مانگ لیا تھا جواب میں
جب مہربان ہو کے وہ بولے سوال کر

آ جائوں گا میں بزم میں تیری مگر ہے شرط
میری نشست پہلو میں اپنے بحال کر

سچ ہے اگر یہ بات تو پھر حوصلے سے سن
چہرے کو سُرخ اور نہ آنکھوں کو لال کر

تائبؔ فراق و ہجر کی تلخی کو جھیل جا
اے باکمال ایسا بھی کوئی کمال کر

From the Chief Editor's Desk

Medical journals are a credible source of disseminating research and innovations, and Launching a medical journal is a challenging task. Many medical science journals are establishing a platform to publish quality research but still the task is tough and requires perseverance and hard work. Shalamar Medical and Dental College (SMDC) Lahore, strives to promote a culture of research. As part of this initiative, SMDC had launched ‘Medical Journal of Sakina Begum Institute’, but publication of the second volume was delayed due to the pandemic. Moreover, the name of the journal had to be changed due to some administrative issues. However, the committed editorial team was successful in bringing efforts for the latest issue to fruition.

Pharmacological Investigations on Some Indigenous Plants of Cholistan Desert

Aims of study The present study was undertaken to validate traditional medicinal claims and to further explore pharmacological actions of four indigenous plants of Cholistan desert (Asphodelus tenuifolius, Corchorus depressus, Gisekia pharnaceoides and Salsola imbricata) in relation to gastrointestinal, respiratory and cardiovascular systems. Material and methods The dried and powdered plants materials were extracted by maceration using aqueous-ethanol as solvent to obtain crude extracts. The crude extracts, their ethyl acetate and aqueous fractions were tested for gastrointestinal, bronchodilator and cardiovascular activities; in vitro experiments were performed upon isolated tissue preparations of rabbit using standard tissue organ bath techniques and in vivo experiments were performed in mice and rats. Results The crude extract of Asphodelus tenuifolius (Cr.At) relaxed spontaneous, potassium (25 mM) and potassium (80 mM) mediated contractions in isolated jejunum preparations, while being equipotent in relaxing potassium (25 mM) and potassium (80 mM) mediated contractions, in manner similar to verapamil. Pretreatment of jejunum preparations with Cr.At or verapamil shifted calcium concentration response curves (CRCs) rightward with suppression of maximum effect. Aqueous fraction of Cr.At exhibited contractile effect upon spontaneous contractions in jejunum preparations. Oral administration of Cr.At to mice caused significant increase of charcoal meal intestinal transit at dose of 100 mg per kg; enhanced wet and total feces counts at doses of 50 and 100 mg per kg; but it significantly decreased charcoal meal intestinal transit at 500 mg per kg dose. Cr.At (300, 500 and 700 mg per kg; orally) reduced castor oil induced diarrhea in mice. In rabbit isolated tracheal preparations, Cr.At was more potent against potassium (80 mM) than carbachol (1 µM) mediated contractions and shifted carbachol CRCs rightward in non-parallel fashion. In rabbit isolated aortic preparations (endothelium denuded), Cr.At was more potent against potassium (80 mM) than phenylephrine (1 µM) mediated contractions. In isolated rabbit paired atria, Cr.At caused overall negative inotopic and chronotropic effects. Intravenous administration of Cr.At (3-30 mg per kg) to anesthetized normotensive rats produced hypotensive effect, which remained unchanged on pre-treating the animals with atropine. Spasmolytic constituents were found partitioned in ethyl acetate fraction of Cr.At, whereas aqueous fraction was found to contain spasmogenic activity. The crude extract of Corchorus depressus (Cr.Cd) relaxed spontaneous, potassium (25 mM), potassium (80 mM) and carbachol (1 µM) mediated contractions in rabbit isolated jejunum preparations; being most potent in relaxing carbachol (1 µM) mediated contractions, and equally potent in relaxing potassium (25 mM) and potassium (80 mM) mediated contractions, similar to that of dicyclomine. It shifted calcium CRCs upon jejunum preparations rightward in non-parallel manner, similar to that of dicyclomine. Aqueous fraction of Cr.Cd exhibited atropine sensitive contractile effect on spontaneous contractions of rabbit jejunum preparations. Oral administration of Cr.Cd to mice (50 and 100 mg per kg) caused significant increase in charcoal meal intestinal travel, enhanced formation of wet and total stool; but at 300 and 500 mg per kg doses, it significantly decreased charcoal meal intestinal travel. It also reduced castor oil induced diarrhea in mice at oral doses of 500 and 700 mg per kg. In isolated tracheal preparations, Cr.Cd was more potent in relaxing carbachol (1 µM) than potassium (80 mM) mediated contractions and shifted carbachol CRCs rightward, similar to that of dicyclomine. In isolated rabbit aorta, Cr.Cd relaxed potassium (80 mM) mediated contractions. In isolated rabbit paired atria, Cr.Cd was found to possess atropine sensitive cardio-depressant activity. Intravenous administration of Cr.Cd (1-30 mg per kg) to anesthetized normotensive rats produced hypotensive effect, which was reversed upon pre-treating animals with atropine. Gisekia pharnaceoides extract (Cr.Gp) and its ethyl acetate fraction caused preferential inhibition of potassium (25 mM) than potassium (80 mM) mediated contractions in rabbit isolated jejunum, tracheal and aortic preparations; which was attenuated in presence of glibenclamide (3 µM), in a manner similar to that of cromakalim. The aqueous fraction of Cr.Gp produced contractions on baseline of rabbit jejunum, tracheal and aortic preparations; which were attenuated subsequent to pre-incubation of tissues with caffeine (10 mM). Cr.Gp was found to possess glibenclamide sensitive cardio-depressant effects upon spontaneously beating rabbit paired atria. Oral administration of Cr.Gp to mice (50 and 100 mg per kg) resulted significant inhibition of castor oil induced diarrhea as well as significant decrease in charcoal meal intestinal travel; but at higher doses (300 and 500 mg per kg), it significantly increased charcoal meal intestinal travel and increased formation of diarrheal feces in normal mice. Intravenous administration of Cr.Gp (1-30 mg per kg) to anesthetized normotensive rats produced hypotensive effect. The crude extract of Salsola imbricata (Cr.Si) relaxed spontaneous, potassium (25 mM), potassium (80 mM) and carbachol (1 µM) mediated contractions in smooth muscle preparations of rabbit isolated jejunum. Pretreatment of tissue preparations with Cr.Si shifted calcium CRCs toward right with suppression of maximum effect, in a manner similar to verapamil. Pretreatment of tissue with propranolol (1 µM) partially antagonized the relaxant activity of the extract upon carbachol mediated contractions, similar to that of isoprenaline. Oral administration of Cr.Si (100, 300 and 500 mg per kg) in mice caused inhibition of charcoal meal intestinal travel and prevented castor oil induced diarrhea. In smooth muscle preparations of rabbit isolated trachea, Cr.Si relaxed potassium (80 mM) and carbachol (1 µM) mediated sustained contractions equipotently; shifted carbachol CRCs rightward in non-parallel fashion; and propranolol (1 µM) decreased its relaxant effect upon carbachol (1 µM) mediated contractions. In isolated aortic preparations, the Cr.Si caused doxazosin sensitive contractions upon baseline tension and relaxed potassium (80 mM) mediated contractions. Cr.Si demonstrated cardiotonic activity upon spontaneously beating paired atria, which was reversed in presence of propranolol (1 µM). Intravenous administration of Cr.Si (1-30 mg per kg) to normotensive anesthetized rats produced dose dependent hypertensive effect, which was blocked in co-presence of propranolol and doxazosin. Calcium channel blocking constituents were found to be concentrated in ethyl acetate fraction, whereas aqueous fraction of Cr.Si was found responsible for aortic contractions. The crude extracts, when administered orally to rats, increased urine and urinary electrolytes (Na+, K+ and Cl-) excretion to different extent. Conclusion The study concludes that Cr.At, Cr.Cd and Cr.Gp possess gut modulatory, bronchorelaxant, hypotensive and diuretic activities; whereas Cr.Si was found to exhibit gut relaxant, bronchorelaxant, hypertensive and diuretic activities. Possible mechanisms responsible for the observed pharmacological activities of the extracts include, but not limited to, calcium channel blocking mechanism in Asphodelus tenuifolius; calcium channel blocking, muscarinic and antimuscarinic mechanisms in Corchorus depressus; ATP dependent potassium channel opening and calcium channel blocking mechanisms in Gisekia pharnaceoides; and calcium channel blocking and adrenergic receptors agonistic mechanisms in Salsola imbricata. The study validated some of the ethnic medicinal claims of the plants along with mechanistic background.