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Biomedical subjects

J Akhter

Publications and source records attributed to J Akhter.

At least 19 recordsLinked to original sources

A new source of hepatocytes for transplantation.

INTRODUCTION: The most effective treatment for acute or chronic liver failure is orthotopic liver transplantation. Worldwide there is a shortage of organs for transplantation. This shortage has called for research into new treatments for management of patients with liver failure. One such treatment is hepatocyte transplantation. During liver resections considerable amounts of normal liver are unavoidably resected. We aim to harvest these hepatocytes and to filter the tumor cells from them to provide a source for transplantation. MATERIALS AND METHODS: After liver resection, the largest vessel at the resected liver edge was identified and cannulated. Seglen's two-stage technique of perfusing the liver with EDTA and collagenase was performed to harvest the hepatocytes. Ep-CAM Ags are consistently present on the surface of epithelial cells and in particular in colorectal cancer cells. Therefore, MOC31 antibodies (selective Abs for Ep-CAM) attached to magnetic beads were used to target the tumor cells. These tumor cells are selectively removed using a magnet. CEA staining was then used to ensure the hepatocyte collection was tumor cell free. Five million hepatocytes were rosetted with one million HT29 CRC cells to assess the immunomagnetic filtration technique. RESULTS: The hepatocyte harvesting resulted in 864,000 viable hepatocytes to be harvested per gram of liver. Histochemical staining using CEA demonstrated 75% of the HT29 cells in the hepatocyte collection were removed after one use of magnetic beads. CONCLUSION: We have demonstrated the successful initial stages of harvesting tumor-free hepatocytes from liver resected for malignancy.

Aged↗

Clinical characteristics and outcomes of diabetic ketoacidosis in Pakistani adults with Type 2 diabetes mellitus.

AIMS: The aim of this study was to describe the clinical characteristics and outcomes of diabetic ketoacidosis (DKA) in Pakistani adult population with Type 2 diabetes mellitus. METHODS: We reviewed the medical records of all adult patients admitted with a diagnosis of DKA and Type 2 diabetes mellitus (DM) and followed their clinical course and outcome. Follow-up data were obtained by chart review or telephone contact where necessary. RESULTS: Fifty-seven patients fulfilled criteria for inclusion in the study. Their mean age was 48 +/- 7 years. The mean body mass index was 25.5 +/- 6.2 kg/m2. Forty-nine had a prior history of Type 2 DM but DKA was the initial presentation in 14%. Nine were on no treatment, 40 were using oral hypoglycaemic agents and eight were on insulin. A history of prior DKA was noted in eight patients. Infections were the most common precipitating factor (63%). There were 12 deaths. Follow-up after a period ranging between 12 and 43 months revealed that 30/45 patients remained on OHA without recurrence of DKA. CONCLUSION: This report highlights the need for the growing recognition of DKA occurring in adults with Type 2 DM in the South Asian population. Mortality rates are unacceptably high but the majority of survivors remain insulin independent.

Body Mass Index↗

In vitro and in vivo suppression of growth of hepatocellular carcinoma cells by albendazole.

Tubulin protein is a major target of drug molecules, and consequently, tubulin inhibitors have attracted great attention as antimitotic antitumor agents for chemotherapeutic use. It has been shown that, the benzimidazole carbamate group of antiparasitics including albendazole act by inhibiting tubulin polymerization. In this study, albendazole was tested in culture against a range of human, rat and mice hepatocellular carcinoma (HCC) cells and in vivo against human SKHEP-1 tumor growth in nude mice. Albendazole induced a dose-dependent inhibition of [(3)H]thymidine incorporation in all cell lines examined and a dramatic decline in cell numbers in SKHEP-1 cells. The inhibitory effect of albendazole was evident at the 100 nM concentration and at 1000 nM, proliferation in all cell lines examined was inhibited by more than 80%, while, proliferation of HepG2, Hep3B and SKHEP-1 were suppressed by more than 90%, compared to control. Cell cycle analysis revealed that, depending on the dose employed, albendazole can arrest SKHEP-1 cells at both G0-G1 (250 nM) and G2-M (1000 nM) phases of the cycle. Albendazole treatment (300 mg/kg per day oral for 20 days) of nude mice inoculated subcutaneously with SKHEP-1, led to profound suppression of tumor growth. Immunohistochemical analysis of these tumors revealed that compared to control, those treated with albendazole have lower growth fractions. These findings demonstrate that albendazole strongly suppresses both in vitro and in vivo proliferation of HCC cells.

Albendazole↗

1alpha,25-Dihydroxyvitamin D3 and its analogues, EB1089 and CB1093, profoundly inhibit the in vitro proliferation of the human hepatoblastoma cell line HepG2.

BACKGROUND: 1alpha,25-dihydroxyvitamin D3 (1,25[OH]2D3) has been shown to inhibit the proliferation of various cancer cells including colon, prostate, melanoma, osteosarcoma and breast cancer. METHODS: The human hepatoma cell line (HepG2) was cultured with 1,25(OH)2D3 or one of two analogues EB1089 or CB1093 for various durations. Cellular proliferation was measured by uptake of [3H]thymidine, and cell numbers were determined by trypan blue exclusion counting. RESULTS: 1,25(OH)2D3, EB1089 and CB1093 all inhibited proliferation of HepG2 by up to 90% after 5 days of treatment, compared to the untreated controls. Decreased proliferation was associated with an approximately 50% reduction in cell numbers at concentrations of up to 10(-10) mol/L after 5 days of treatment with 1,25(OH)2D3. Cell proliferation rapidly recovered in cultures treated with lower concentrations of 1,25(OH)2D3 (10(-10) and 10(-11) mol/L) when 1,25(OH)2D3 was removed from the cultures by placing cells in serum containing medium without 1,25(OH)2D3. When HepG2 cells were treated with 10(-8) mol/L 1,25(OH)2D3 for 5 weeks, there was still significant inhibition of proliferation, although at week 5 there was 66% inhibition compared to 93% at the end of week 1. CONCLUSIONS: 1,25(OH)2D3, EB1089 and CB1093 all significantly inhibit the proliferation of HepG2 hepatoblastoma cells, with EB1089 being the most potent at lower concentrations. Inhibition can be maintained for at least 4 weeks, but is reversed after removal of vitamin D3.

Antineoplastic Agents↗

Antimicrobial susceptibility testing and patterns of resistance at a tertiary care center.

Clinical microbiology laboratories are faced with the challenge of accurately detecting emerging antibiotic resistance in bacterial pathogens. In recent years, vancomycin resistant enterococci have emerged, as have penicillin resistant pneumococci and more recently, methicillin-resistant Staphylococcus aureus with reduced susceptibility to vancomycin. In order to detect these emerging resistant pathogens it is essential that antimicrobial susceptibility be carried out by laboratories as an integral part of therapeutic strategies. In this review, we discuss patterns of susceptibility of different antimicrobials as experienced at King Faisal Specialist Hospital and Research Centre, a tertiary care center in Riyadh.

Anti-Bacterial Agents↗

Use of nucleic acid testing for blood donor screening of human immunodeficiency virus and hepatitis C virus in the Saudi population.

OBJECTIVE: To determine the risk of transfusion associated infection for human immunodeficiency virus and Hepatitis C virus using nucleic acid testing. METHODS: During March 1998, 400 donor blood samples from the Saudi population that were negative by serology were further tested for human immunodeficiency virus 1 and 2 and Hepatitis C virus using nucleic acid testing. RESULTS: A total of 400 were tested by nucleic acid testing, 381 of these were negative, 4 were indeterminate but were found to be negative on repeat testing and one seronegative sample was found to be positive for Hepatitis C virus. CONCLUSION: Due to the low prevalence of human immuno-deficiency virus in the Kingdom of Saudi Arabia, nucleic acid testing of blood donors by serology is adequate for screening. But the higher prevalence of Hepatitis C virus and increased risk of transmission would indicate that nucleic acid testing may be warranted for Hepatitis C virus in the near future.

Blood Donors↗

In vitro and in vivo inhibition of liver cancer cells by 1,25-dihydroxyvitamin D3.

Inhibitory effects of 1,25-dihydroxyvitamin D3 (1,25-(OH)2D3) on the proliferation of a variety of cancer cell lines have been extensively reported. We have studied the effect of 1,25-(OH)2D3 (10(-11)-10(-6) M) on the proliferation of a number of human and rat liver cancer cell lines. Additionally, the effect of 1,25-(OH)2D3 (0.02-0.5 microg/kg per day) on the rate of growth of liver cancer cell line xenografts in nude mice was also investigated. In vitro, proliferation of Hep-3B, PLC/PRF/5, and SKHEP-1 cells was significantly inhibited by 1,25-(OH)2D3, while HTC and Novikoff cells were more resistant to the inhibitory effects of the drug. In vivo, treatment of SKHEP-1 tumor bearing nude mice with different doses of 1,25-(OH)2D3 significantly retarded tumor growth without the development of hypercalcemia.

Animals↗

Cutaneous myiasis due to Dermatobia hominis in Saudis.

Cutaneous myiasis infestations are normally found in South and Central America but increasing travel has resulted in their spread to non-indigenous countries with increasing frequency. We report two cases of cutaneous infestation by Dermatobia hominis in Taif, Saudi Arabia. There was no history of travel outside Saudi Arabia. The source of infection appears to be domestic cattle indicating that these infestations may be endemic in this region.

Adult↗

Lipids increase after solitary pancreas transplantation.

OBJECTIVE: The aims of this study were to determine 1) changes in lipids after solitary pancreas transplantation (SPTX) in patients with type 1 diabetes and 2) factors that influence those changes. RESEARCH DESIGN AND METHODS: Lipids were evaluated prospectively in 24 patients who underwent SPTX. Three were excluded because of early graft failure. The remaining patients (n = 21; 13 men, 8 women) were studied for changes in lipids over time (pre-SPTX, 0-2, 3-6, 7-12, and > 12 months). Glycohemoglobin, serum creatinine, BMI, and medications were also analyzed for their effects on lipid changes. RESULTS: Cholesterol, HDL, and LDL decreased in the immediate postoperative period (0-2 months), whereas triglycerides (TGs) increased (P < 0.05). At 3-6 months, cholesterol, HDL, and TG were higher than before the SPTX, whereas LDL returned to pre-SPTX levels. After 12 months, HDL and TG remained higher than their pre-SPTX levels (P < 0.05). During the study, systolic and diastolic blood pressure increased, renal function decreased, glyco-hemoglobin improved, and weight was unchanged. Changes in cholesterol/HDL ratio, HDL, and TG correlated with changes in prednisone dose (P < 0.05), and changes in TG correlated with changes in creatinine (P < 0.05). The same pattern of lipids occurred in patients prescribed or not prescribed hypolipidemic agents. CONCLUSIONS: Lipids do not improve within the 1st year after SPTX, despite improved glycemic control and blood pressure control, and renal function is worse. These results are in contrast to those reported for combined kidney-pancreas transplantation, where lipids, blood pressure, and renal function improved immediately after transplant. Further studies are needed to determine whether lipids continue to change with time after SPTX. The impact of these changes after SPTX on overall cardiovascular risk is unknown.

Blood Pressure↗

Respiratory viruses in children attending a major referral centre in Saudi Arabia.

Viral respiratory infections are common causes of illness in infants and children. Examination of clinical specimens submitted for diagnosis during a 3-year period (August 1993-July 1996) at King Faisal Specialist Hospital and Research Center (KFSH & RC) in Riyadh revealed a wide spectrum of diseases associated with the isolation of five respiratory viruses. Severity of disease ranged from mild upper respiratory illness to threatening lower respiratory illnesses including bronchiolitis and pneumonia. Of the 256 isolates, respiratory syncytial virus (RSV) accounted for 73 (28.5%), adenoviruses for 70 (27.3%), influenza viruses for 61 (23.8%), enteroviruses for 39 (15.2%) and para-influenza for 13 (2.3%). Viruses were found more frequently in children attending emergency or paediatric wards than in outpatients. RSV appears in November and the seasonal peak occurs during January and February. Influenza activity begins in September and peaks in November and December. Para-influenza type I emerges in winter and para-influenza type III follows the influenza epidemic and may be detected sporadically in summer. The other viruses (enteroviruses, adenoviruses) were isolated throughout the year.

Adenoviruses, Human↗

A comparative laboratory study of liquid nitrogen and argon gas cryosurgery systems.

Cryotherapy can now be applied using a variety of delivery systems and cryogens. We compared the Cryotech LCS 3000 liquid nitrogen system (Spembly, Andover, UK) with the CRYOcare argon gas-based system (Irvine, CA, U.S.A.) using three different 3-mm cryoprobes: an old liquid nitrogen probe (N-probe), a new N-probe featuring gas bypass and an argon gas probe. Each probe was tested in two models: (i) fresh sheep liver at 20 degrees C--the probe was inserted to a depth of 1.5 cm; the rate of ice ball formation was monitored by recording radial temperatures every 15 s at 5, 10, 15, and 20 mm from the cryoprobe, and the ice-ball diameter was measured every 2.5 min. After 10 min, the probe was warmed and the time taken until it could be extracted from the liver was recorded. (ii) Warm water bath--the probe was immersed in warm water (42 degrees C) for 15 min and the ice-ball diameter was measured at 5-min intervals. Radial temperatures in liver declined more rapidly (P < 0.001) and time to probe extraction was less (P < 0.01) when the argon gas system was used. The new N-probe performed better than its older counterpart, but was still slower than the argon gas system. In liver (20 degrees C), ice-ball diameters were similar after 10 min, but in warm water, they were larger when the new N-probe was used (P < 0.02). It would appear that the argon gas system is initially faster, but it does not achieve as large an ice ball in a warm environment as the liquid nitrogen system.

Animals↗

Vitamin D3 analog, EB1089, inhibits growth of subcutaneous xenografts of the human colon cancer cell line, LoVo, in a nude mouse model.

PURPOSE: In this study, we investigated the effect of the vitamin D3 analog, EB1089, on the growth of subcutaneous xenografts of the human colon cancer cell line, LoVo, in a nude mouse model. METHODS: BALB/c Nu/Nu nude mice were inoculated subcutaneously with 10(6) LoVo cells. EB1089 dissolved in isopropanol was administered intraperitoneally and orally on alternate days at doses of 0.1, 0.5, and 2.5 microg/kg/day. Control animals received isopropanol alone. Tumor volumes estimated using the formula 0.5 X length X (width)2. The tumor kinetic index was determined by immunohistochemical detection of proliferating cell nuclear antigen. RESULTS: Significant dose-dependent inhibition of tumor growth was seen. After 20 days of treatment with 0.1 microg/kg/day EB1089, mean tumor volume in treated mice was 41 to 49 percent less than that in control animals (P < 0.01). Significant inhibition of tumor growth was also seen with 0.5 microg/kg/day EB1089 after 22 days of treatment (51 percent of control P < 0.01). Treatment with 2.5 microg/kg/day resulted in weight loss that required termination of this group; these mice were subsequently found to be hypercalcemic. The tumor kinetic index was significantly lower in tumors treated with 0.1 microg/kg/day EB1089 compared with that for control tumors (8 vs. 30 percent in controls). CONCLUSION: These findings suggest that the vitamin D3 analog, EB1089, is a potent antiproliferative agent for some human colon cancers.

Animals↗

Histamine content in colorectal cancer. Are there sufficient levels of histamine to affect lymphocyte function?

Histamine has been found to stimulate growth of colorectal cancer in vitro and in vivo. Histamine has also been found to inhibit lymphocyte activity in vitro at concentrations greater than 10(-7) M. The aim of our study was to determine if the histamine concentrations in human colorectal cancer were sufficient to achieve these effects. We measured the histamine content in 31 colorectal cancer specimens using a radioenzymatic assay. Results were expressed as microgram histamine per gram of fresh tissue weight. Recovery and reproducibility studies were also carried out. The median histamine concentration in colorectal cancer tissue was 8.4 micrograms/g [7.6 x 10(-5)M], ranging from 0.3 microgram/g to 20.6 micrograms/g. The high concentration of histamine in colon cancer is enough to be locally immunosuppressive.

Adult↗

The in vitro effect of vitamin D3 analogue EB-1089 on a human prostate cancer cell line (PC-3).

OBJECTIVE: To determine the effect of vitamin D3 analogue (EB-1089) on the growth and proliferation of a prostate cancer cell line (PC-3). MATERIALS AND METHODS: PC-3 cells (10(4) cells per well) were plated into 24-well tissue culture plates. After 24 h, the culture medium was replaced with one containing the vitamin D3 analogue EB-1089; a control treatment using only replacement medium was conducted in parallel. Cell proliferation was measured by the incorporation of 3H-thymidine 7 and 12 days after the addition of the vitamin D3 analogue. Cells were precipitated with 5% trichloroacetic acid and the radioactivity determined using a scintillation counter. Each experiment was performed at least five times. RESULTS: There was a significant dose-dependent inhibition of cell growth after 7 and 12 days of treatment with EB-1089, varying from 40 to 70% of the 3H-thymidine incorporation by controls, respectively. The maximum inhibition occurred with 0.1 micromol/L EB-1089 on day 7 and day 12 (both P < 0.01). Longer incubation times appeared to have a greater effect when higher concentrations of EB-1089 were used. CONCLUSION: These in vitro studies have shown that the vitamin D3 analogue EB-1089 can significantly reduce the growth rate of the prostate cancer cell line PC-3. This would support the hypothesis that deficiency of vitamin D increases the risk of prostate cancer and further in vivo testing of vitamin D is warranted for its potential role in active therapy.

Antineoplastic Agents↗