Biomedical subjects

Aisha Khan

Publications and source records attributed to Aisha Khan.

7 recordsLinked to original sources

PubMed2005

Rescue purification maximizes the use of human islet preparations for transplantation.

The relative inefficiency of the islet purification process may hamper obtaining enough islets for transplantation even with adequate pre-purification counts. In this study, we determined the effect of an additional purification step on total islet yields and pancreas utilization at our center. Twenty-five pancreata were processed using the automated method followed by continuous gradient purification (CGP), and the less pure islet fractions were subjected to additional rescue gradient purification (RGP). CGP and RGP islets were combined and transplanted into patients with type 1 diabetes. CGP and RGP islets showed no significant differences in cell viability, insulin secretion in vitro and function when transplanted into chemically diabetic mice. Mean RGP contribution to the final preparation was 27.9 +/- 19.9%. In 12 of 25 preparations, CGP yielded <5000 IEQ/kg of recipient body weight, and inclusion of RGP islets to the final preparation allowed to obtain the minimal islet number required for transplantation. Transplanted islets resulted in sustained C-peptide production, HbA1(C) normalization and insulin-independence or reduced insulin requirements. Taken together, our data suggest that RGP islets are comparable in terms of viability and potency to CGP islets. RGP may be of assistance in maximizing the number of islet preparations successfully used in transplant protocols.

Animals↗

PubMed2005

Islet transplantation in type 1 diabetes mellitus using cultured islets and steroid-free immunosuppression: Miami experience.

Following the success obtained with transplantation of fresh human islets under steroid-free immunosuppression, this trial evaluated the transplantation of islets that had undergone a period of in vitro culture and the potential of tumor necrosis factor (TNF-alpha) blockade to improve islet engraftment. Subjects included 16 patients with type 1 diabetes mellitus (T1DM); half were randomly assigned to receive Infliximab immediately preceding initial infusion. Immunosuppression consisted of daclizumab induction and sirolimus/tacrolimus maintenance. Out of 16 subjects 14 achieved insulin independence with one or two islet infusions; adverse events precluded completion in two. Without supplemental infusions, 11/14 (79%) subjects were insulin independent at 1 year, 6/14 (43%) at 18 months; these same subjects remain insulin independent at 33+/-6 months. While on immunosuppression, all patients maintained graft function. Out of 14 patients, 8 suffered chronic partial graft loss, likely immunological in nature, 5 of these received supplemental infusions. Currently, 11 subjects remain on immunosuppression, 8 (73%) are insulin independent, two with supplemental infusions. Insulin independent subjects demonstrated normalization of HbA1c, fructosamine and Mean Amplitude of Glycemic Excursions (MAGE) values. No clinical benefit of infliximab was identified. These results demonstrate that transplantation of cultured human islet allografts results in reproducible insulin independence in all subjects under this immunosuppressive regimen, comparable to that of freshly transplanted islets (Edmonton protocol).

Adult↗

PubMed2005

Association of angiotensin converting enzyme gene polymorphisms with left ventricular hypertrophy.

The angiotensin converting enzyme gene (ACE) is of much interest as a candidate gene conferring an individual's genetic susceptibility to left ventricular hypertrophy (LVH). LVH has long been thought to be an end point of essential hypertension (EH), rather than a separate entity, though it is influenced by a unique set of hormonal, vascular and genetic factors. In this study, we attempted to determine whether two representative polymorphisms of the ACE gene, ACE I/D and 2350 G>A, known to be associated with EH and to have a highly significant influence on plasma ACE levels, could implicate ACE as a quantitative trait locus (QTL) for LVH. We carried out a retrospective, case-control study of the two ACE polymorphisms amongst 180 nationals (50 LVH patients and 130 controls) from the United Arab Emirates (Emirati)--an ethnic group characterized by an absence of alcohol intake and cigarette smoking--for putative correlations with LVH. Clinical diagnoses of LVH were based on echocardiographic and ECG criteria. ACE I/D and 2350 G>A genotypes were determined by polymerase chain reaction (PCR) and restriction digestion. Univariate and multivariate logistic regression analyses revealed an association between ACE polymorphisms and LVH. Haplotype analysis further supported this finding. The ACE I/D and ACE 2350 G>A polymorphisms were in strong linkage disequilibrium and were independently associated with LVH, suggesting that ACE is likely to be a QTL for LVH. In conclusion, This is the first association study of the ACE 2350 G>A polymorphism with LVH; the results showed that this polymorphism, along with ACE I/D, is associated with LVH.

Adult↗

PubMed2005

Association of ACE polymorphisms with left ventricular hypertrophy.

The angiotensin converting enzyme gene (ACE) is a candidate gene for an individual's genetic susceptibility to left ventricular hypertrophy (LVH). LVH has long been thought to be an end point of essential hypertension (EH), rather than a separate entity, though it is influenced by a unique set of hormonal, vascular and genetic factors. In this study, we attempted to determine whether two representative polymorphisms of the ACE gene, ACE I/D and 2350 G>A, known to be associated with EH and to influence plasma ACE levels most significantly, could implicate ACE as a quantitative trait locus (QTL) for LVH. We carried out a retrospective, case-control study of the two ACE polymorphisms amongst 180 nationals (50 LVH patients and 130 controls) from the United Arab Emirates--an ethnic group characterized by no alcohol intake and no cigarette smoking--for correlations with LVH. Clinical diagnosis of LVH was based on echocardiographic and ECG criteria. ACE I/D and 2350 G>A genotypes were determined by PCR and restriction digestion. Univariate and multivariate logistic regression analyses revealed an association between ACE polymorphisms and LVH. Haplotype analysis further supported this finding. ACE I/D and ACE 2350 G>A polymorphisms are in strong linkage disequilibrium and are associated with LVH, suggesting that ACE is likely to be a QTL for LVH.

Adult↗

PubMed2004

The use of multiparametric monitoring during islet cell isolation and culture: a potential tool for in-process corrections of critical physiological factors.

Variables such as pH, pCO2, and PO2 have been established in the literature as critical factors that could affect the outcome of the islet cell processing and, therefore, the quality of the cells that could be transplanted. This report describes a highly accurate continuous multiparametric monitoring system and its evaluation for continuous monitoring of physiological variables during critical steps of the islet isolation procedure as well as during in vitro culture of the insulin-producing cells. Close monitoring of these variables could be of assistance to improve the outcome of islet cell processing, allowing to identify as soon as possible problems that could be corrected during the procedure, as well as during in vitro preservation, or shipment to remote sites.

Calibration↗

PubMed2003

Improved human islet isolation outcome from marginal donors following addition of oxygenated perfluorocarbon to the cold-storage solution.

Last year, from the approximately 6,000 organ donors, only approximately 1,500 pancreata were used for clinical transplantation. Factors that contribute to this poor pancreas use include strict donor selection criteria and the requirement for short cold-ischemia time (CIT). Numerous pancreata have not been used because of long ischemia times postprocurement. Given the oxygen-rich environment of the islets in the native pancreas, it is conceivable that islets are highly susceptible to irreversible damage following prolonged ischemia. The use of continuously oxygenated perfluorohydrocarbons (PFCs), known for their high oxygen-solubility coefficients, in a two-layer culture with standard University of Wisconsin preservation media, has extended the acceptable range CIT, and, furthermore, there has been no evidence of adverse effects from PFCs on the outcome of transplanted cells, whereas they often enhance islet cell function. The purpose of this study was to use the two-layer culture method to improve donor-organ use from marginal donors. Fifteen organs were procured using the two-layer method, and 18 without using it, from donors greater than 50 years of age. Despite nonsignificant differences in age, weight of the donors, weight of the organ and CIT, the PFC group yielded an average of twofold more islet equivalents than those harvested from the control group. As a result, from the control group, only 2 of 18 organs were used for clinical islet transplantation, whereas 8 of 15 were used from the PFC group. To this end, the two-layer method may help clinicians overcome the problem of organ underuse.

Adenosine↗

PubMed2003

The bag method for islet cell infusion.

As islet cell transplantation gains increasing interest following results published by the Edmonton group, results that have been successfully reproduced by several centers nationwide and abroad, the need of guidelines to standardize the procedure becomes highly important. We detail the key steps of the infusion procedure utilizing a closed gravity fed bag system utilized at our institution since 1990, which consists of a 600-ml transfer bag and a 150-ml rinse bag connected via sterile tubing. The use of gravity allows for a control rate of infusion as well as providing a safety mechanism through natural reduction of flow that parallels any increase in portal pressure, therefore allowing the operator to prevent precipitous pressure rises. Reports on significant rise in portal pressures during islet cell infusion as well as portal vein thrombosis have been published. Infusion at these centers was carried out using a syringe method. Using our technique, portal vein thrombosis (partial or complete) was not detected in any of the infusions performed at our institution. This method may be of assistance to minimize some of the observed complications associated with islet transplant procedures and has now been adapted by most centers performing clinical islet transplantation.

Infusions, Intravenous↗