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Biomedical subjects

T Ahsan

Publications and source records attributed to T Ahsan.

13 recordsLinked to original sources

Kinetics of collagen crosslinking in adult bovine articular cartilage.

OBJECTIVE: Determine the kinetics of collagen crosslinking in adult bovine articular cartilage explants using radiolabel pulse-chase studies. METHODS: Explant cultures of adult bovine articular cartilage were radiolabeled with [14C]lysine in medium including fetal bovine serum and ascorbate, and then maintained for chase periods up to 28 days. In some samples, beta-aminopropionitrile (BAPN) was included during chase to inhibit lysyl oxidase-mediated collagen crosslinking. Tissue was hydrolyzed and analyzed for [14C]metabolites in the forms of lysine, hydroxylysine, dehydrodihydroxylysinonorleucine (DeltaDHLNL), and hydroxylysyl pyridinoline (HP). RESULTS: Explant cultures of adult bovine articular cartilage metabolized lysine into hydroxylysine and the collagen crosslinks, DeltaDHLNL and HP. During chase, [14C]hydroxylysine maintained steady-state levels, [14C]DHLNL rose to a plateau, and [14C]HP increased gradually. Addition of BAPN inhibited formation of [14C]DHLNL. Analysis of raw data and that normalized to [14C]hydroxylysine gave characteristic time constants for formation of DeltaDHLNL and HP crosslinks of 1-2 and 7-30 days, respectively. The distribution of [14C]lysine metabolites in collagen crosslinks was described by peak values in [14C]DHLNL/[14C]hydroxylysine of 0.047-0.064 and in [14C]HP/[14C]hydroxylysine of 0.03. CONCLUSION: Collagen crosslinks form in cartilage explants in vitro according to the classical lysyl oxidase-mediated pathway.

Amino Acids↗

Bioengineered tissues: the science, the technology, and the industry.

OBJECTIVE: The bioengineering of tissues and organs, sometimes called tissue engineering and at other times regenerative medicine, is emerging as a science, as a technology, and as an industry. The goal is the repair, replacement, and/or the regeneration of tissues and organs. The objective of this paper is to identify and discuss the major issues that have become apparent. RESULTS: One of the critical issues is that of cell source, i.e. what will be the source of the cells to be employed? Another critical issue is the development of approaches for the fabrication of substitute tissues/organs and/or vehicles for the delivery of biological active molecules for use in the repair/regeneration of tissues. A third critical issue, one very much related to cell source, is that of immune acceptance. In addition, there are technological hurdles; there are additional issues such as the scale-up of manufacturing processes and the preservation of living-cell products for off-the-shelf availability. Although the initial products have been superficially applied skin substitutes, as this fledgling industry continues to evolve, it is beginning to focus on a wider range of more invasive and complicated products. From a public health perspective, the real opportunity may be in addressing chronic diseases, as well as the transplantation crisis (i.e. the tremendous disparity between patient need for vital organs and donor availability) and, equally important is the challenge of neural repair. CONCLUSION: These are the grand challenges, and the scientific community, business/private sector, and federal government must mobilize itself together in this emerging area to translate the benchtop science to the patient bedside.

Biocompatible Materials↗

Role of dexamethasone in acute bacterial meningitis in adults.

OBJECTIVE: To evaluate the role of dexamethasone as adjunctive therapy in adult acute bacterial meningitis (ABM) in two groups of patients treated with antibiotics alone or a combination of antibiotics and dexamethasone. DESIGN: Systematic sampling interventional open cohort study. SETTING: Department of Medicine (Medical Unit II), Jinnah Postgraduate Medical Centre, Karachi. PATIENTS: Sixty eight patients aged 12-85 years admitted in Medical Unit II and diagnosed to have ABM. Patients were divided into two groups. Group A received anti-microbial therapy for 14 days (a combination of benzyl penicillin 6 million units I/V 6 hourly and chloramphenicol 1 gm I/V 6 hourly) and group B received the same antimicrobial therapy with dexamethasone 0.6 mg/kg/day in 3 divided doses for 4 days. MAIN OUTCOME MEASURES: Differences in mortality and morbidity in the two groups and differences in the CSF inflammatory parameters between the two groups of patients. RESULTS: There was early resolution of fever, headache and altered consciousness in group B as compared to group A. Cranial nerves involvement was lower in group B. There was no difference in the occurrence of other focal neurological deficits between the two groups. CSF inflammatory parameters (glucose, protein and WBC count) were significantly better in group B by day 5. No complications attributable to dexamethasone were seen in group B. CONCLUSION: There was early resolution of symptoms and CSF inflammatory parameters in the group that received dexamethasone as adjuvant therapy. Mortality was lower in the group treated with dexamethasone but the difference was not statistically significant. Dexamethasone should be administered to all adults patients with ABM.

Adolescent↗

Diabetes mellitus is equally frequent in chronic HCV and HBV infection.

OBJECTIVE: To see the association of type 2 diabetes mellitus (Type 2 DM) in patients suffering from chronic HBV or HCV related liver disease. SETTING: Patients were selected from the gastroenterology OPD of the medical research centre, diabetic controls from private diabetes clinic and healthy controls from the blood bank of the hospital. METHODS: Patients with chronic liver disease had HBV, HCV tested using ELISA and blood sugar using a glucometer mostly as a 2 hour post prandial sample. Healthy controls had their sugar and ALT checked while donating blood and HBV, HCV were checked routinely. In diabetic controls, blood sample was taken as sera stored for HBV,HCV and ALT and later tested in batches. A random sugar of > or = 200 mg/dl was taken as diabetes. RESULTS: Of 400 patient with chronic liver disease 302 had HCV and 98 HBV infection. Diabetes was found in 24.5% HCV and 19.4% HBV related cases (not significant). Out of 410 healthy controls 18 were HCV and 17 HBV positive. Diabetes was found in only 1 (5.6%) HCV positive control and none of the HBV positive controls. Of 196 diabetics 10 (5.1%) were HCV positive and none HBV positive. Diabetes was more frequent in patients having liver cirrhosis than in those having chronic hepatitis (P < 0.01). CONCLUSION: Diabetes is equally frequent in both HBV and HCV related disease but is significantly more in those with chronic liver disease than in controls. The pancreatic damage secondary to extrahepatic viral replication appears to be the major cause but genetic factors also need to be explored.

Adult↗

Amoebic versus pyogenic liver abscess.

OBJECTIVES: To study the differences between the clinical presentation and complications of amoebic and pyogenic liver abscess. To correlate the diagnostic significance of Entamoeba Indirect Haemagglutination test (E.IHA) in establishing the diagnosis of amoebic liver abscess. DESIGN: Open cohort observational study. SETTING: Department of Medicine (Medical Unit II) Jinnah Postgraduate Medical Centre, Karachi. PARTICIPANTS: Fifty two patients aged 13-70 years admitted in Medical Unit II and diagnosed to have liver abscess. INTERVENTIONS: Group A comprised of patients clinically diagnosed to have amoebic liver abscess and received Metronidazole 500mg iv x 8 hourly for atleast 10 days or more if patient developed complications. Group B comprised of patients diagnosed to have pyogenic abscess and received Cefotaxime 1g iv x 8 hourly for the same duration or more if complicated (antibiotic reviewed in accordance with culture and sensitivity report). MAIN OUTCOME MEASURES: Differences in the clinical presentation, complications and diagnostic parameters between the two groups of patients. RESULTS: It was not possible to differentiate between amoebic and pyogenic liver abscess on clinical grounds, routine investigations and imaging techniques. Aspiration of pus, especially if the abscess was multiple, was most helpful in differentiating the two types of abscesses. Serological test of E.IHA was highly specific and sensitive for amoebic liver abscess. CONCLUSION: Majority of liver abscesses in Karachi are due to Entamoeba Histolytica. Pyogenic abscess though less frequent, must be excluded by pus aspiration and culture and sensitivity. E.IHA is a good rapid method of discriminating between the two types of abscesses.

Adolescent↗

Integrative cartilage repair: inhibition by beta-aminopropionitrile.

The effects of beta-aminopropionitrile, a known inhibitor of lysyl oxidase, on the extractability of newly synthesized collagen and integrative cartilage repair were determined in explant cultures of adult bovine articular cartilage. Dose-escalation studies indicated that treatment of cartilage explants for 6 days with beta-aminopropionitrile caused a dose-dependent inhibition of proteoglycan synthesis ([35S]sulfate incorporation) with a 50% inhibition at 2.2 mM. However, 0.25 mM beta-aminopropionitrile had no detectable effect on proteoglycan synthesis and was thus used for subsequent experiments. Treatment of cartilage with beta-aminopropionitrile for 14 days increased the extractability of newly synthesized collagen with 4 M guanidine-HCl while having little effect on proteoglycan synthesis, proteoglycan deposition, collagen synthesis (formation of [3H]hydroxyproline after labeling with [3H]proline), collagen deposition, or cartilage cellularity (DNA content). In untreated cultures, the percentage of radiolabeled collagen ([3H]hydroxyproline) that was extractable after 1 day of radiolabeling, 6 days of radiolabeling, or 6 days of label and 6 days of chase decreased from 81 to 25 and 9%, respectively. In beta-aminopropionitrile-treated cultures, the extractability was relatively higher (96, 62, and 47%, respectively). Treatment with beta-aminopropionitrile after radiolabeling with [14C]lysine also significantly inhibited the formation of the reducible crosslink [14C]dihydroxylysinonorleucine without affecting the overall deposition in cartilage of [14C]lysine and [14C]hydroxylysine. In functional repair studies, treatment with beta-aminopropionitrile caused an almost complete inhibition of integration between pairs of cartilage explants maintained in apposition for 2 weeks. These results indicate that beta-aminopropionitrile blocks the formation of collagen crosslinks in cartilage explants and suggest that such crosslinks are critical to integrative cartilage repair.

Aminopropionitrile↗

Biomechanics of integrative cartilage repair.

Cartilage repair is required in a number of orthopaedic conditions and rheumatic diseases. From a macroscopic viewpoint, the complete repair of an articular cartilage defect requires integration of opposing cartilage surfaces or the integration of repair tissue with the surrounding host cartilage. However, integrative cartilage repair does not occur readily or predictably in vivo. Consideration of the 'integrative cartilage repair process', at least in the relatively early stages, as the formation of a adhesive suggests several biomechanical approaches for characterizing the properties of the repair tissue. Both strength of materials and fracture mechanics approaches for characterizing adhesives have recently been applied to the study of integrative cartilage repair. Experimental configurations, such as the single-lap adhesive test, have been adapted to determine the strength of the biological repair that occurs between sections of bovine cartilage during explant culture, as well as the strength of adhesive materials that are applied to opposing cartilage surfaces. A variety of fracture mechanics test procedures, such as the (modified) single edge notch, 'T' peel, dynamic shear, and trouser tear tests, have been used to assess Mode I, II, and III fracture toughness values of normal articular cartilage and, in some cases, cartilaginous tissue undergoing integrative repair. The relationships between adhesive biomechanical properties and underlying cellular and molecular processes during integrative cartilage repair remain to be elucidated. The determination of such relationships may allow the design of tissue engineering procedures to stimulate integrative cartilage repair.

Animals↗

Falciparum malaria or fulminant hepatic failure?

Six cases of severe jaundice and encephalopathy due to falciparum hepatitis initially diagnosed as fulminant hepatic failure are reported. This rare presentation of falciparum malaria should be suspected in patients with persistent fever, jaundice, encephalopathy and hepatomegaly. The diagnosis should be further suspected when the liver function tests show a predominantly conjugated hyperbilirubinemia with only modest elevation of liver enzymes and alkaline phosphatase. Liver biopsy is valuable in establishing the diagnosis at all stages of the disease.

Adult↗

Enoxacin in the treatment of typhoid fever.

Enoxacin 400 mg twice daily was given orally to 40 patients who had Salmonella typhi- or Salmonella paratyphi-positive blood or bone marrow cultures. One patient was switched to parenteral therapy within 48 hours of study enrollment, but the remaining 39 patients were given enoxacin for 10 to 14 days. All 39 patients were cured by enoxacin, even though 23 (58.9%) strains were resistant to cotrimoxazole and 16 (41%) strains were multiply resistant to ampicillin, chloramphenicol, and cotrimoxazole. No adverse events necessitated the interruption of therapy. In this study, enoxacin was well tolerated and efficacious in the treatment of typhoid fever.

Adolescent↗