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Biomedical subjects

J Akhter

Publications and source records attributed to J Akhter.

60 records · Page 4Linked to original sources

Determination of insulin requirements: excessive insulin dosages common in type 1 diabetes mellitus.

OBJECTIVE: To report our experience of determining insulin requirements for initiating continuous subcutaneous insulin infusion (CSII) pump therapy, using an algorithm for intravenous administration of insulin, in patients with poorly controlled diabetes. METHODS: We describe assessment of insulin requirements and analyze data from 27 consecutive admissions. All patients had type 1 diabetes mellitus and were being converted to CSII pump therapy. Twenty-four-hour intravenous insulin requirements were used to initiate CSII pump therapy, and further dose adjustments were undertaken, to optimize glycemic control. Basal, bolus, and total daily insulin requirements were calculated before, during, and 3 months after conversion to CSII therapy. RESULTS: At entry, the mean glycohemoglobin was 11.2% (normal, 5.0 to 8.0%), and the mean daily insulin dose were 45.8 U (0.59 U/kg). Calculated daily insulin requirements using an algorithm for intravenously administered insulin were 37.3 U (0.50 U/kg). At 3 months, mean daily insulin requirements had increased to 39.2 U (0.52 U/kg), and glycohemoglobin improved to 9.4%. Most patients (78%) remained on insulin doses within 10% of the calculated requirements. All patients who were receiving more than 0.6 U/kg daily before assessment required a reduction in insulin dosage to improve glycemic control. CONCLUSION: Many patients with type 1 diabetes are receiving excessive insulin doses. An algorithm for intravenous administration of insulin may be useful for determining requirements and appropriate insulin doses for CSII pump therapy, especially in patients with poor glycemic control.

Journal Article↗

1,25-dihydroxyvitamin D3 dissolved in lipiodol produces a sustained antiproliferative effect in the human hepatoblastoma cell line HepG2.

The steroid hormone 1,25-dihydroxyvitamin D3 [1,25-(OH)2D3] has potential to be used as an anti-tumor agent, but its clinical application has been restricted by the strong systemic calcemic activity. Regional administration of the drug dissolved in lipiodol, might be a way of selectively delivering high concentrations of the drug to lipiodol avid tumor cells without causing systemic side effects. In acute (1 day treatment) and chronic (5 days treatment) experiments, efficacy of the drug dissolved in ethanol (control) or lipiodol and subsequently diluted in the culture medium was tested in vitro against the hepatoblastoma cell line HepG2. Using [3H]thymidine incorporation and cell count, antiproliferative effects of 1,25-(OH)2D3 dissolved in the two different solvents was compared. Microscopic examination of cells exposed to the lipiodol containing media revealed intra-cellular presence of the oil in abundance. Chronic treatment of cells with either formulation of 1,25-(OH)2D3 resulted in profound inhibition of cell proliferation. However, exposure of cells to 1,25-(OH)2D3 in lipiodol was followed by significantly greater and lasting inhibition of cell proliferation in both acute and chronic studies. These results indicate that, 1,25-(OH)2D3 dissolved in lipiodol probably acts as a sustained release drug depot formulation, in which case it could have some potential for the regional treatment of liver tumors.

Antineoplastic Agents↗

The use of lipiodol and medium chain triglyceride as delivery agents for hepatic arterial administration of 1, 25-dihydroxyvitamin D3--a potential new treatment for hepatocellular carcinoma.

It is well established that 1, 25 dihydroxyvitamin D3 is capable of inhibiting the proliferation of a number of human cancer cell lines, including hepatoma cell lines. However, clinical usage in the treatment of cancers has been limited by its hypercalaemic effects. We hypothesised that by delivering 1, 25 dihydroxyvitamin D3 dissolved in a lipid based carrier agent as a hepatic arterial infusion it would be possible to achieve high local concentrations within hepatomas for prolonged periods, whilst avoiding high systemic concentrations and hypercalcaemia. We examined this hypothesis by administering a hepatic arterial infusion of 1, 25 dihydroxyvitamin D3 in either Lipiodol, Medium Chain Triglyceride (MCT), or saline to hepatoma bearing rats. Assay of serum and tissue concentrations revealed that this approach using lipiodol or triglyceride results in selective distribution of 1, 25-dihydroxyvitamin D3 into, and retention within hepatoma tissue and low initial systemic serum levels. Lipiodol was more effective in these respects than MCT. This method of administration has potential in the treatment of hepatoma.

Animals↗

Hepatic intra-arterial injection of lipiodol-1,25-dihydroxyvitamin D3 for hepatocellular carcinoma in rats.

BACKGROUND: 1,25-(OH)2 D3 has an in vitro growth regulator effect on different cancers. Unfortunately, dose-limiting toxicity (hypercalcemia) limits its use in anticancer therapy. For primary liver tumors, loco-regional delivery of 1,25-(OH)2 D3 in lipiodol might avoid high systemic concentrations and development of hypercalcemia. MATERIALS AND METHODS: 1,25-(OH)2 D3 alone or mixed in lipiodol, was delivered at different concentrations into the hepatic artery of rats bearing a primary liver tumor. Calcium levels, tumor volume and proliferation index were assessed after treatment. RESULTS: Serum calcium values were significantly lower when the drug was mixed into lipiodol. Treatment with 10 micrograms of 1,25-(OH)2 D3 in ethanol resulted in a decrease in proliferation index within the tumor. CONCLUSIONS: The delivery of 1,25-(OH)2 D3 mixed in lipiodol reduces the subsequent elevation of serum calcium. Locoregional treatment with 1,25-(OH)2 D3 was shown for the first time to be effective on primary liver tumor growth in vivo.

Animals↗

In vitro antiproliferative activity of a medium-chain triglyceride solution of 1,25-dihydroxyvitamin D3 in HepG2 cells.

BACKGROUND: Successful targeted delivery of 1,25-dihydroxyvitamin D3 [1,25-D3] for the treatment of liver cancer would necessitate the use of an appropriate delivery agent. MATERIALS AND METHODS: Using liver cancer cell line HepG2 in culture, we examined, the possibility of using medium-chain triglyceride (MCT) as a solvent for targeted delivery of 1,25-D3. The drug was made up in either the medium or first dissolved in MCT and subsequently diluted in the medium. Cells were exposed for 1 (acute) or 5 days (chronic) to the 2 different formulations of the drug and cell proliferation was measured by [3H]thymidine and cell count methods. RESULTS: In chronic experiments, exposure of cells to the MCT containing formulation of 1,25-D3 led to significantly greater inhibition of cell proliferation. In the acute experiments where, 1 day 1,25-D3 treatment was followed by 4 days of incubation with normal medium (no drug, no MCT), inhibition of proliferation was more than 2 fold greater in cells exposed to the 1,25-D3/MCT preparation. CONCLUSION: These results indicate that, 1,25-D3 dissolved in MCT probably accumulates and then acts as a sustained release drug depot formulation, in which case it may have potential for the regional treatment of liver tumors.

Calcitriol↗

Current status and changing trends of antimicrobial resistance in Saudi Arabia.

Due to modern travel and ease of spread of infections, it is desirable to widen knowledge of susceptibility of common bacterial isolates from different parts of the world for optimal clinical management and control programs. Over the past decades, antimicrobial resistance has emerged in all kinds of micro-organisms worldwide including Saudi Arabia. This phenomenon is primarily due to increasing antibiotic use and misuse in humans, animals and agriculture. Additionally, the presence of a large expatriate population and a significant number of visitors to the Kingdom annually for pilgrimage and/or work from all over the world may have also facilitated the importation to Saudi Arabia of drug resistant micro-organisms from other countries. Saudi Arabia has witnessed an increase of drug resistant Mycobacterium tuberculosis, Streptococcus pneumoniae, Staphylococcus aureus and some Enterobacteriaceae in the last decade. We describe the status of antimicrobial resistance in Saudi Arabia which is an important focus of antimicrobial resistance for the Gulf Region.

Anti-Bacterial Agents↗