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Biomedical subjects

M Khan

Publications and source records attributed to M Khan.

At least 199 records · Page 11Linked to original sources
PubMed1994

Conservative management with symptomatic treatment and delayed hormonal manipulation is justified in men with locally advanced carcinoma of the prostate.

OBJECTIVE: To examine the clinical course following surveillance and symptomatic treatment, and compare the outcomes of immediate and delayed hormonal treatment in men with locally advanced prostatic cancer. PATIENTS AND METHODS: Of a consecutive series of 199 men (mean age 74 years) with T2-T4 Nx M0 prostatic cancer, 110 (55%) were followed until death and the rest had a mean follow-up of 4.2 years. Fifty-one men received immediate orchidectomy, 88 had this treatment delayed until metastatic progression, and 60 had the treatment in the intervening period. The actuarial survival was compared with the expected survival for an age-matched healthy population in Scotland. The adjusted effect of the timing for hormonal manipulation was assessed by including it with age, Gleason score and clinical stage in a multiple Cox regression. RESULTS: The actuarial survival for the whole group was 17% less at 5 years and 15% less at 10 years when compared with the expected survival for an age-matched population in Scotland. This was despite the fact that their nodal status was unknown and also those with occult metastasis (elevated serum prostatic acid phosphatase, M1a) at presentation were not excluded. In terms of metastatic progression, overall survival and cause-specific survival, there was no significant difference between immediate and delayed hormonal treatment. CONCLUSION: A conservative approach with surveillance and symptomatic treatment for locally advanced prostatic cancer is justified by the present evidence on disease progression and survival, which do not differ from alternative methods of treatment as reported in contemporary literature. This study has the limitations relative to the ideal of a prospective randomized trial on immediate versus delayed hormonal treatment, but the lack of significant differences in outcome even after adjustment for other established prognostic factors does suggest that there may be little to be gained from an immediate orchidectomy.

Actuarial Analysis↗
PubMed1994

Molecular and biological characteristics of echovirus 22, a representative of a new picornavirus group.

Recent sequence analysis revealed that the human pathogen echovirus 22 (EV22) is genetically distant from all the other picornaviruses studied to date (T. Hyypiä, C. Horsnell, M. Maaronen, M. Khan, N. Kalkkinen, P. Auvinen, L. Kinnunen, and G. Stanway, Proc. Natl. Acad. Sci. USA 89:8847-8851, 1992). We have further characterized the biological properties of the virus and show here that the virion has properties similar to those of other picornaviruses. However, the protein composition is unique, in that most copies of one of the three major capsid proteins, VP0, do not undergo the further processing to VP2 and VP4 observed during the maturation of the virus in previously studied picornaviruses. Alignment of the capsid protein sequences with those of other picornaviruses revealed, furthermore, that the VP3 polypeptide contains an apparent insertion of approximately 25 amino acids at its amino terminus. An arginine-glycine-aspartic acid (RGD) motif is found in VP1, and by using synthetic peptides, it was shown that this sequence plays a role in cell surface receptor recognition. Finally, EV23 was shown to share remarkable identity with EV22 in certain parts of the genome and also belongs to this previously unrecognized picornavirus group.

Amino Acid Sequence↗
PubMed1994

Effect of U-73,122, an inhibitor of phospholipase C, on actions of parathyroid hormone in opossum kidney cells.

The relative roles of the adenylate cyclase-protein kinase A system (AC-PKA), the phospholipase C-protein kinase C system (PLC-PKC), and increases in cytosolic calcium in mediating the final actions of parathyroid hormone (PTH) remain ill defined. Although an important role for the PLC-PKC system in the regulation of phosphate transport in response to PTH has been suggested, previous studies from our laboratory and others, in OK cells, have emphasized the major role of AC-PKA. The present studies were designed to dissociate the second messengers for PTH by using an inhibitor of PLC (U-73,122). Studies were performed in confluent cultures of OK cells with and without preincubation with U-73,122 (1 microM). This inhibitor did not alter adenosine 3',5'-cyclic monophosphate (cAMP) production or the activation of PKA in response to PTH. Preincubation with U-73,122, however, totally abolished PTH-stimulated increases in diglyceride mass, consistent with inhibition of PLC. Activation of particulate PKC was then examined in response to PTH in the absence and presence of U-73,122. Although PTH resulted in an increase in particulate PKC activity in control cultures, this effect was abolished in the presence of U-73,122 and actually decreased significantly. Therefore, having documented marked attenuation of PLC-PKC, we next examined the effects of PTH on phosphate transport. Basal phosphate uptake was not altered by 1 microM U-73,122. Dose-response curves of the inhibition of phosphate transport in response to PTH were identical in the presence or absence of U-73,122. Thus inhibition of PLC and PKC activities did not alter the effects of PTH on phosphate transport.(ABSTRACT TRUNCATED AT 250 WORDS)

1-Methyl-3-isobutylxanthine↗
PubMed1994

Role of DNA content determination by image analysis in confirmation of dysplasia in Barrett's esophagus.

Progression to cancer in Barrett's esophageal columnar metaplasia is classically heralded by the presence of epithelial dysplasia. Differentiation of reactive epithelial atypia and mild dysplasia from severe dysplasia, however, may often be difficult especially with limited biopsy material. We performed DNA content analysis of 11 cases of Barrett's esophagus showing variable reactive atypia, 24 cases of Barrett's with low- and high-grade dysplasia, and 30 cases of Barrett's with invasive adenocarcinoma (BCA) using Feulgen-stained paraffin sections and the CAS 200 image analyzer. The mean DNA index of the uniformly diploid BE was 1.06. The 1.26 mean DNA index for the low-grade Barrett's esophagus with dysplasia, 1.62 for high grade, and 1.88 DI for BCA were significantly greater than for variable reactive atypia (P < 0.004) but not different from each other. Six BCA cases (20%) were diploid; 24 cases (80%) were aneuploid. Mean survival of diploid BCA at 20.4 mo was nearly double the survival of 10.6 mo for aneuploid BCA. However, this difference was not statistically significant (P < 0.21) and survival at 3 yr was identical for all BCA cases. Tumor grade, stage, and lymph node status did not significantly correlate with ploidy pattern. Thus, although DNA analysis does not seem to predict ultimate outcome in BCA, aneuploidy and high DNA index are associated with Barrett's esophagus with dysplasia and BCA and may be of significant value in the differentiation from variable reactive atypia in small biopsies.

Adenocarcinoma↗
PubMed1994

Cervical pregnancy: case reports and a current literature review.

The increasing number of reports of successful conservative treatment of cervical pregnancy, such as using the folinic acid antagonist methotrexate, constitutes a breakthrough in the management of this unusual but potentially life-threatening complication of pregnancy. We are reporting two cases of cervical pregnancy, both diagnosed in the first trimester of pregnancy. The first one was successfully treated by transvaginal ultrasound-guided administration of 2 mEq KCI intraamniotically in order to stop the fetal heart activity, followed by administration of 84 mg of methotrexate intraaminiotically (1 mg/kg); whereas in the second case, we encountered a technical failure of the above method. Both patients expressed desire to maintain their reproductive capability. These two cases gave us the opportunity to review the recent literature on cervical pregnancy.

Adult↗
PubMed1993

Repeated use of ablation catheters: a prospective study.

OBJECTIVES: The objective of this study was to provide insight into the time course of electrical, physical and mechanical changes in ablation catheters after each use that may affect the safety and efficacy of the ablation procedure. BACKGROUND: An increasing number of institutions are reusing deflectable ablation catheters. At present, there are no data concerning the safety of reusing ablation catheters. METHODS: Over a period of 1 year, 69 Webster/Mansfield deflectable catheters used in 336 ablation procedures were prospectively studied. An additional 18 new catheters were tested after multiple sterilizations only. The catheters were evaluated for electrical and physical integrity and mechanical capabilities. These include deflection at room temperature and 37 degrees C, shaft compression and buckling during deflection, tip craters, torquing ability, glue separation and tip attachment using a stereoscope at x30 magnification and electrical resistance for each electrode. After each use, the catheters were gas-sterilized with ethylene oxide. RESULTS: The most common reasons for catheter rejection were tip electrode glue separation after 4.3 +/- 4.3 uses and loss of deflection after 5.0 +/- 3.3 uses. Electrical discontinuity between the catheter handle and electrodes was observed after 10.0 +/- 3.7 uses. There was no significant decrease in catheter torquing ability with repeated use. In this study the total estimated savings was $128,133, which includes the cost of catheter reprocessing. The reuse of Webster/Mansfield ablation catheters has not resulted in any major catheter failure or any major adverse clinical complications. CONCLUSIONS: On the basis of these observations, we believe that the Webster/Mansfield catheter can be reused an average of five times. It is strongly recommended that after each use catheters be carefully examined under appropriate magnification (x30) and that special attention be given to the ablation tip electrode. The catheters should also be tested for deflection and electrical integrity.

Catheter Ablation↗
PubMed1993

Quantitative analysis of molecules which distinguish functional compartments within germinal centers.

Five zones in the secondary follicles of human tonsils are described, which are distinguished by the phenotype of their constituent cells. Moving from the apex to the base of the follicle the zones are termed: follicular mantle, outer zone, apical light zone, basal light zone and dark zone. The dark zone contains proliferating, CD77high, centroblasts and thin, widely spaced processes of follicular dendritic cells (FDC). The apical and basal light zones on the other hand contain a dense network of FDC which express CD21 and CD54 strongly. The FDC of the apical light zone differ from those of the basal light zone by their high expression of CD23. Centroblasts of the dark zone give rise to non-proliferating centrocytes which move apically through the light zone (Eur. J. Immunol. 1991. 21:2951). The centrocytes of the basal light zone are more pyroninophilic, more closely-packed and larger than those in the apical light zone. Consequently, by conventional histology the basal light zone appears to be part of the dark zone. The nomenclature adopted, however, adheres to the convention that the dark zone is filled with proliferating centroblasts. Cells undergoing apoptosis were identified both in the dark and light zones, but more than half of these cells were located in the basal light zone. This is consistent with the concept that the progeny of cells which undergo somatic mutation in their immunoglobulin variable region genes in the dark zone migrate to the light zone where they are selected on the basis of their capacity to bind to antigen held on FDC. Cells receiving an antigen-dependent signal survive while those that do not kill themselves by apoptosis. The outer zone does not contain CD23high cells and in this way is distinguished from the adjacent follicular mantle and apical light zone. It contains small lymphoid cells, blasts and plasmacytoid cells. Many cells of the outer zone express CDw75 strongly. The outer zone also extends as a narrow band around the dark zone. Possible roles of FDC and T cells of the light zone and outer zone in inducing centrocytes to differentiate to memory cells or plasmablasts are discussed.

Antigens, CD↗
PubMed1993

Histologic and ultrastructural features of experimental duodenal ulcers in Sprague-Dawley rats.

The histologic and ultrastructural features of a time sequence study of the development, evolution, and healing of acetic acid-induced experimental duodenal ulcer are presented. Duodenal ulcers produced by serosal application of acetic acid featured microvascular injury with progressive disintegration of the tips of the mucosal villi and subtotal necrosis of the duodenal wall. At 3 days ulcers transformed into a chronic state with regenerating epithelium originating from the crypts of the intact bordering mucosa extending toward the center of the ulcers. By 21 days healed ulcers were covered by distorted duodenal surface mucosa. We conclude that this reproducible and standardized model of duodenal ulcer features vascular injury as the earliest microscopic event, that ischemic necrosis leads to ulceration, and that the chronic phase bears morphologic resemblance to human duodenal ulcer.

Animals↗
PubMed1993

Comparison of seroepidemiology of hepatitis C in blood donors between Bangladesh and Japan.

To compare the seroepidemiology of hepatitis C and hepatitis B between Bangladesh and Japan, we tested the second generation antibody to hepatitis C virus (anti-HCV-2) and hepatitis B surface antigen (HBsAg) in serum samples from 163 professional blood donors (161 males and 2 females, mean age 28.6 yr.) and 83 voluntary blood donors from Bangladesh, and 7479 Japanese voluntary blood donors (5036 males and 2443 females; mean age 37.1 yr.). In Bangladesh, anti-HCV-2 is detected in 2.4% of professional blood donors and 0% of voluntary blood donors, furthermore, HBsAg is detected in 29% and in 2.4% of professional and voluntary blood donors, respectively. In Japan, anti-HCV-2 is detected in 0.6% in voluntary blood donors, and HBsAg also in 0.6%. These results indicate that professional blood donors in Bangladesh are highly contaminated by hepatitis B virus and moderately by hepatitis C virus, while voluntary blood donors in both countries are not so highly contaminated by either hepatitis viruses.

Adult↗
PubMed1993

Physics and engineering of transcatheter cardiac tissue ablation.

Ablation of arrhythmogenic cardiac tissues has emerged as one of the most important advances in cardiac electrophysiology. With the introduction of transcatheter ablation, the treatment of ventricular tachycardia, Wolff-Parkinson-White syndrome and other cardiac arrhythmias has progressed from an expensive and painful surgical therapy accompanied by a long recovery period to the less expensive, less traumatic transcatheter approach. The feasibility of cardiac ablation, along with the increasing number of physicians using the technique, requires understanding of the anatomic and electrophysiologic bases of transcatheter ablation as well as the different technologies, their limitations and complications. This report provides an overview of the physical, scientific and technical aspects of cardiac ablation performed with the methods currently available and a summary of the limitations of each method and expected future technologic developments in this growing field. Emphasis is placed on radiofrequency and direct current energies, the primary methods now used. Methods such as cryoablation and laser, and microwave and chemical ablation are discussed with less detail because the method of delivering energy for these ablative procedures has not been fully developed.

Animals↗
PubMed1993

Congenital hypothyroidism: the Riyadh Military Hospital experience.

OBJECTIVE: We aimed to find out the incidence of primary congenital hypothyroidism (CH) among infants born within the Riyadh Al-Kharj Hospital Programme in addition to early detection and treatment of these infants. DESIGN: All babies born within the Riyadh Al-Kharj Hospital Programme were screened by cord blood TSH. Blood spot TSH were done in the majority of infants between 2 and 5 days after birth. All suspected cases were recalled for confirmatory tests. 123I thyroid scan and X-ray of the knee and maternal blood for thyroid antibodies were done for confirmed cases. MEASUREMENTS: A cut off TSH level of 30 mIU/l for cord blood and 25 mIU/l for spot blood were used. All samples were assayed by immunoassay methods. RESULTS: 44,778 (99.4% of the total births) infants were screened. Twenty-five cases were detected, four of which were excluded. The incidence of primary congenital hypothyroidism was 1/2096. Five cases were missed on the initial screen. Eight out of 17 children who had 123I thyroid scan were found to have dyshormonogenesis. Associated malformation and diseases were diagnosed in 42.85%. Two had chromosomal anomalies; ring chromosome 9 has not been previously reported in association with congenital hypothyroidism. CONCLUSION: The incidence of congenital hypothyroidism, dyshormonogenesis and the associated malformations and diseases are higher than those reported in the literature. Cord blood as a screening method is associated with a significant number of missed cases.

Congenital Hypothyroidism↗
PubMed1993

Patterns of bone metastasis and their prognostic significance in patients with carcinoma of the prostate.

The different patterns of bone metastasis, metastatic load and their prognostic significance were examined in a consecutive series of 169 men with prostatic cancer and bone metastasis at presentation. Patients with an isolated metastasis in the pelvis or dorsal vertebrae had a better prognosis than those whose metastases were either diffuse or involved more distal sites such as the skull or the sternum, although all of these patients were classified as having M1 disease. Bone metastasis involving an area equivalent to 1 vertebral body equalled a metastatic load of 2. Based on their total metastatic load, 3 prognostic groups were identified with significant differences in case-specific survival despite receiving the same hormonal treatment. When comparing the potential efficacy of various treatments one must stratify the metastatic load, which is a powerful prognostic indicator of the outcome in patients with metastatic carcinoma of the prostate.

Bone Neoplasms↗
PubMed1993

Effect of brain edema on infarct volume in a focal cerebral ischemia model in rats.

BACKGROUND AND PURPOSE: Infarct volume is one of the common indexes for assessing the extent of ischemic brain injury following focal cerebral ischemia. Accuracy in the measurement of infarct volume is compounded by postischemic brain edema that may increase brain volume in the infarcted region. We evaluated the effect of brain edema on infarct volume determined by triphenyltetrazolium chloride and hematoxylin and eosin stains in a focal cerebral ischemia model in rats. METHODS: In a middle cerebral artery occlusion model in rats, infarction is confined to the cerebral cortex. The infarct was delineated by triphenyltetrazolium chloride stain and, in selected samples, by hematoxylin and eosin stain. We determined infarct size at different times after the ischemic insult (6 hours to 7 days) in relation to the evolution of brain edema by the direct measurement of infarct volume. Indirect measurement to reduce the effect of edema on infarct volume was also conducted in the same brain samples. RESULTS: Direct measurement showed that infarct volume fluctuated with the evolution of brain edema (one-way analysis of variance, p < 0.0001). Infarct volume determined by indirect measurement was independent of the extent of brain edema and remained stable from 6 hours to 3 days after ischemia. There was a good correlation between triphenyltetrazolium chloride and hematoxylin and eosin stains in delineating infarct volume with both direct and indirect measurement. CONCLUSION: Traditional direct measurement of infarct volume is associated with an overestimation of infarct volume during the development of brain edema in the first 3 days after ischemia. This artifact can be reduced with indirect measurement, which is based on noninfarcted cortex volume.

Animals↗
PubMed1993

Nuclear DNA content and clinical follow-up in resected pancreatic adenocarcinoma.

Nuclear DNA content was determined by image analysis of paraffin-embedded tissue sections in 20 cases of resected pancreatic ductal adenocarcinoma. Seven cases (35%) showed a diploid pattern; 13 (65%) were aneuploid. Mean survival time of patients with diploid tumors was significantly greater (17 months) than for patients with aneuploid carcinomas, 7.5 months (P < .03, Kaplan-Meier and Cox univariate analysis). Patient age, grade of differentiation, primary tumor size and lymph node status did not correlate significantly with ploidy pattern and survival. In four cases atypical hyperplasia/adenocarcinoma in situ was present in the main duct epithelium at the pancreatectomy resection line. These intraductal foci were uniformly diploid. We conclude that despite the uniform fatality of pancreatic cancer, adenocarcinomas with aneuploid patterns pursue a significantly more rapid and aggressive clinical course than do diploid tumors and that the atypical intraductal epithelial foci that may accompany resected specimens from invasive adenocarcinoma are DNA diploid, may represent noninvasive precursor lesions and are of uncertain clinical significance.

Aged↗
PubMed1993

Integrins, adhesion molecules and surgical research.

Integrins and adhesion molecules are a group of closely related glycoproteins expressed by a wide variety of cells. In vitro experiments have shown these families of cell surface receptors to be essential to the interactions between the cytoskeleton and the extracellular matrix. Although the designations of families of integrins and adhesion molecules is complex, this review attempts to present an organization in which the result is to provide surgeons with an understanding of their structure and function. This is particularly important because integrins and adhesion molecules have a critical role in such diverse processes as embryogenesis, inflammation, wound healing, thrombosis, transplantation and oncogenic transformation. It is, therefore, highly probable that they will be critical to future advances in surgical research and ultimately in surgical practice. It should be remembered that this area of investigation is so dynamic that the interval involved in publication of this article will in itself be characterized by a plethora of publications in the basic science and surgical literature, which warrants careful attention.

Animals↗