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Biomedical subjects

A Palmer

Publications and source records attributed to A Palmer.

At least 19 recordsLinked to original sources
PubMed2006

Mycophenolic acid 12-h trough level monitoring in renal transplantation: association with acute rejection and toxicity.

Studies of renal transplantation utilizing trough plasma level monitoring of mycophenolic acid (MPA) have shown inconsistent associations with toxicity and rejection. In this study, 5600 12-h trough MPA samples from 121 renal transplant recipients immunosuppressed with mycophenolate mofetil (MMF) and tacrolimus in a steroid sparing protocol (steroids for 7 days only) were sequentially analyzed. Higher MPA levels were associated with lower hemoglobin concentrations and anemia (hemoglobin <10 g/dL). Similarly, higher MPA levels were associated with lower total white cell counts and an increased incidence of leucopenia (total white cell count <4.0 x 10(9)/L). Hypoalbuminemia and renal impairment were also associated with hemotoxicity. MMF-associated diarrhea and viral infection were associated with higher MPA levels. Conversely, biopsy-proven acute rejection within the first month post-transplantation was associated with lower MPA levels. Anti-CD25 antibody induction was also associated with reduced rejection rates. No association was seen between MPA levels and platelet count, thrombocytopenia or bacterial infection. An MPA level of 1.60 mg/L early post-transplantation best discriminated patients with and without rejection, and an MPA level of 2.75 mg/L best discriminated patients with and without toxicity later post-transplantation.

Adult↗
PubMed2006

A health economic model to determine the long-term costs and clinical outcomes of raising low HDL-cholesterol in the prevention of coronary heart disease.

OBJECTIVES: The aim of this study was to describe a health economic model developed to project lifetime clinical and cost outcomes of lipid-modifying interventions in patients not reaching target lipid levels and to assess the validity of the model. METHODS: The internet-based, computer simulation model is made up of two decision analytic sub-models, the first utilizing Monte Carlo simulation, and the second applying Markov modeling techniques. Monte Carlo simulation generates a baseline cohort for long-term simulation by assigning an individual lipid profile to each patient, and applying the treatment effects of interventions under investigation. The Markov model then estimates the long-term clinical (coronary heart disease events, life expectancy, and quality-adjusted life expectancy) and cost outcomes up to a lifetime horizon, based on risk equations from the Framingham study. Internal and external validation analyses were performed. RESULTS: The results of the model validation analyses, plotted against corresponding real-life values from Framingham, 4S, AFCAPS/TexCAPS, and a meta-analysis by Gordon et al., showed that the majority of values were close to the y = x line, which indicates a perfect fit. The R2 value was 0.9575 and the gradient of the regression line was 0.9329, both very close to the perfect fit (= 1). CONCLUSIONS: Validation analyses of the computer simulation model suggest the model is able to recreate the outcomes from published clinical studies and would be a valuable tool for the evaluation of new and existing therapy options for patients with persistent dyslipidemia.

Cholesterol, HDL↗
PubMed2005

Late steroid withdrawal for renal transplant recipients on tacrolimus and MMF is safe.

INTRODUCTION: We conducted a study to assess the safety of staged, late steroid withdrawal in kidney or kidney/pancreas transplant recipients on steroids, tacrolimus, and mycophenolate mofetil (MMF). MATERIALS AND METHODS: We studied 50 patients including 33 recipients of cadaveric kidneys, eight living donor kidneys, and nine kidney-pancreas transplants. The mean time posttransplantation was 5.1 years (range 2.1 to 7.9 years). All patients were induced on prednisolone, tacrolimus, and MMF; steroids were withdrawn over 5 to 6 months. The rate of steroid reduction was altered in the face of typical steroid withdrawal symptoms (limb-girdle arthralgia/myalgia). RESULTS: No rejection episodes occurred during steroid withdrawal. No patient required transplant biopsy for graft dysfunction. Six patients failed steroid withdrawal: five due to arthralgia/myalgia and one due to recurrent pulmonary sarcoidosis. The unexplained rise in serum creatinine following steroid withdrawal described in several other steroid withdrawal studies was not observed in this patient cohort. The mean serum creatinine was 137 micromol/L with deltacreatinine -6.8 micromol/y per year prior to steroid cessation versus 132 micromol/L with deltacreatinine -5.9 micromol/y in the year post-steroid cessation. There were 14 patients with posttransplant diabetes mellitus in this cohort: eight on gliclazide and six on insulin. We observed a reduction in their daily insulin/gliclazide requirements from 52 units to 41 units, and 73 mg to 65 mg, respectively. Two patients became gliclazide-independent at the time of steroid cessation. CONCLUSIONS: Careful steroid withdrawal from a platform of tacrolimus and MMF is safe and not associated with a significant risk of rejection or graft dysfunction.

Adult↗
PubMed2005

Steroid sparing in renal transplantation with tacrolimus and mycophenolate mofetil: three-year results.

Although renal transplantation with a 7-day steroid-sparing regimen, tacrolimus and mycophenolate, is associated with good short-term outcomes, late allograft dysfunction and failure remain concerns. In this study 101 consecutive patients underwent renal transplantation using this immunosuppressive regimen. In addition, anti-CD25 monoclonal antibody was used in 25 high-risk patients (regrafts, two-antigen human leukocyte antigen (HLA)-DR mismatch or sensitized with anti-HLA panel reactivity >30%). After a median follow-up of 39 months (range 29 to 49), overall patient survival is 98%, with two cardiac deaths. Three other graft losses occurred, one each to early venous thrombosis, polyoma viral nephropathy, and late rejection due to noncompliance. Therefore, overall graft survival is 95%. The acute rejection rate at 6 and 12 months was 19% (no rejection occurred between months 6 and 12). Late rejection was uncommon, with only two further episodes beyond 12 months. Mean creatinine at 12 months was 144 micromol/L and mean estimated glomerular filtration rate (GFR) of 55 mL/min. Graft function was stable at 3 years with a mean creatinine of 142 micromol/L and mean estimated GFR 56 mL/min. During the study, five patients developed posttransplant diabetes mellitus (two cases beyond 12 months). Tissue-invasive cytomegalovirus disease and BK viral nephropathy each occurred in three patients, with all episodes in the first 12 months. Mean weight gain is 3.3 kg and mean blood pressure is 135/81 on an average of 1.5 antihypertensive agents. This steroid-avoidance regimen is associated with excellent medium-term patient and graft outcomes and a low incidence of side effects.

Antibodies, Monoclonal↗
PubMed2005

Cytokine polymorphisms do not influence acute rejection in renal transplantation under tacrolimus-based immunosuppression.

INTRODUCTION: Acute rejection remains an important cause of graft loss after renal transplantation. It has been suggested that cytokine genotyping may play a predictive role in identifying individuals who are at higher risk of acute rejection with a view to individualizing their immunosuppression. The aim of this study was to investigate any possible associations between acute rejection and certain cytokine polymorphisms. METHODS: We genotyped 91 cadaveric renal transplant recipients on tacrolimus-based immunosuppression and 84 of their donors. The cytokine polymorphisms studied were the following: tumor necrosis factor (TNF)-alpha-1032 T/C, TNF-alpha-865 C/A, TNF-alpha-859 G/A, interleukin (IL)1-R1-970 C/T, IL-10 haplotype [-1082, -819, -592], and IL-6-174 C/G. RESULTS: We found no association between any polymorphism and the incidence of acute rejection. This was true for both the recipient and donor population. CONCLUSION: Cytokine polymorphisms did not influence acute rejection in our study. We conclude that in the modern era of immunosuppression cytokine genotyping is not a significant predictor of acute rejection in renal transplantation.

Adult↗
PubMed2005

Tacrolimus monitoring in renal transplantation: a comparison between high-performance liquid chromatography and immunoassay.

It is recommended that specific methods of tacrolimus monitoring rather than immunoassays, which overestimate tacrolimus levels, should be used in transplant recipients. Direct comparison of these techniques, however, has not been conducted in renal transplantation. In this study, 40 renal transplant recipients with tacrolimus monitoring by microparticle enzyme immunoassay (MEIA; target trough level 10 to 15 ng/mL) were compared with 40 patients monitored by high-performance liquid chromatography with tandem mass spectrometry (HPLC-MS; target trough level 8 to 13 ng/mL). All patients received anti CD25 antibody induction and mycophenolate mofetil in a steroid-sparing protocol. No differences were seen between MEIA and HPLC-MS groups in patient demographics. All patients were followed for 6 months. Patient survival was 100% in both groups; graft survival was 100% in the MEIA group and 97.5% in the HPLC-MS group. The groups did not differ in the number of dose changes required in the first 6 months or in the number of patients displaying tacrolimus levels within target range at 3 and 6 months. Delayed graft function occurred in 14 patients in the MEIA group and 12 patients in the HPLC-MS group (P = NS). Biopsy-proven acute rejection occurred in four patients in the MEIA group and one patient in the HPLC-MS group (P < .2). No differences were seen for the following parameters at 3 or 6 months: biopsy-proven tacrolimus nephrotoxicity, serum creatinine or estimated creatinine clearance, systolic or diastolic blood pressure, cholesterol, cytomegalovirus disease, posttransplant diabetes, or tremor. This study suggests that renal transplantation with HPLC-MS monitoring of tacrolimus is safe and effective.

Blood Pressure↗
PubMed2004

Echogenicity of breast cancer: is it of prognostic value?

Echogenicity of colorectal metastases to the liver has been shown to correlate with prognosis. While there have been many studies looking at the echogenicity of breast cancer, there has been no study relating the issue of echogenicity to prognosis of breast cancer. In this study, we found that hyperechoic and mixed echogenicity breast cancers are rare compared to hypoechoic breast cancers. There was, however, no difference in the groups with respect to histological size, grade, axillary metastases, hormone receptor status and lymphovascular invasion.

Adenocarcinoma↗
PubMed2004

Grey water characterisation and its impact on the selection and operation of technologies for urban reuse.

Characterisation of grey water reveals a source water that is similar in organic strength to a low-medium strength municipal sewage influent but with physical and biodegradability characteristics similar to a tertiary treated effluent. The characteristics of the water suggest biological processes are the most suitable unit processes for treating grey water. The highly variable nature of the source requires that selected technologies must be inherently robust in their operation. One potential area of concern is the high COD/BOD ratio and nutrient deficiency in terms of both macro and micro nutrients which grey water exhibits potentially retard the efficacy of biological processes.

Biodegradation, Environmental↗
PubMed2003

Five-year results of kidney transplantation under tacrolimus-based regimes: the persisting significance of vascular rejection.

BACKGROUND: Acute rejection has been the major risk factor for medium-term kidney graft loss because of chronic allograft nephropathy. We investigated whether the use of improved immunosuppression has altered the relationship between acute and chronic rejection by analyzing data from 245 renal transplant patients receiving Tacrolimus-based immunosuppression. RESULTS: Five-year graft survival (censored for death with functioning graft) was 88.8% with no significant difference between living and cadaveric kidney transplants. The only significant predictor of medium-term graft loss was acute vascular rejection. CONCLUSION: Under Tacrolimus-based immunosuppression, the occurrence of acute interstitial rejection, even when occurring late, repeatedly, or with failure of graft function to return to baseline, was not associated with chronic allograft nephropathy or medium-term graft loss. Vascular rejection remains the major immunological obstacle to long-term transplant success. Five-year overall survival rates with a functioning graft of 80% with 90% graft survival censored for death with function seem to be realistic and achievable goals.

Adult↗
PubMed2003

Vaccines for children: policies, politics and poverty.

The dawn of the 21st century ushered in spectacular advances in vaccine production technology. However, the benefits of these developments have been largely confined to the world's most affluent and least afflicted. Of the 14 million deaths that occur world-wide in children aged less than 5 years, over 95% of these occur in developing countries and at least 70% are caused by infections for which vaccines are already available in other countries. While impoverished countries do not have a right to be assisted with the provision of funds or vaccines by affluent developed countries, an initiative for the global eradication of a vaccine preventable disease, requires a global effort. Assisting developing countries to achieve such goals should be a high priority for wealthy nations, even if only to protect their own populations. With improved international travel, not only can newly emerging diseases spread across the globe, but pathogens eliminated from one population can be re-imported by travellers or immigrants. In contrast, the recent decline in acceptance of immunisation programmes in developed countries are secondary to strong anti-vaccine movements attributing unproven adverse reactions to vaccines, placing these life-saving vaccines into disrepute. A fertile ground for propagation of these ideologies is created by parents who in their lifetime may not have seen a child killed or maimed from bacterial meningitis or measles and therefore have little understanding of the risk-benefit of vaccination. The development and deployment of vaccines must be a global effort as are the treaties for global disarmament for weapons of mass destruction.

Child↗
PubMed2002

Reconsideration of the wavelength dependence of extinction: a gamma-ray case.

The wavelength dependence of extinction has been re-examined by means of new gamma-ray diffraction data collected from NiF(2) at 0.0205, 0.0265 and 0.0392 A. The standard model of extinction has been confirmed and substantiated by experimentally accessible parameters such as the intrinsic mosaic width. The predicted kinematic limit values are in accordance with the results from charge-density analyses. The model proposed by Mathieson & Stevenson [Acta Cryst. (2002), A58, 185-189] leads to a purely phenomenological polynomial fit function. The extrapolated values are shown to be inconsistent with structure analyses based on extended gamma-ray data sets and cannot be recommended for use.

Journal Article↗
PubMed2001

Pharmacogenetic interactions between beta-blocker therapy and the angiotensin-converting enzyme deletion polymorphism in patients with congestive heart failure.

BACKGROUND: Activation of the renin-angiotensin and sympathetic nervous systems adversely affect heart failure progression. The ACE deletion allele (ACE D) is associated with increased renin-angiotensin activation; however, its influence on patient outcomes remains uncertain, and the pharmacogenetic interactions with beta-blocker therapy have not been previously evaluated. METHODS AND RESULTS: We prospectively followed 328 patients (age, 56.1+/-11.9 years) with systolic dysfunction (left ventricular ejection fraction, 0.24+/-0.08) to assess the impact of the ACE D allele on transplant-free survival (median follow-up, 21 months). Transplant-free survival was compared by genotype for the whole cohort and separately in patients with (n=120) and those without beta-blocker therapy (n=208) at the time of entry. Transplant-free survival was significantly poorer for patients with the D: allele (1-year percent survival II/ID/DD=94/77/75; 2-year=78/65/60; ordered log-rank test, P:=0.044). In patients not treated with beta-blockers, the adverse impact of ACE D allele was dramatically increased (1-year percent survival II/ID/DD=95/75/67; 2-year=81/61/48; P:=0.005). In contrast, in patients receiving beta-blocker therapy, no influence of ACE genotype on transplant-free survival was evident (1-year percent survival II/ID/DD=91/80/86; 2-year=70/71/77; P:=0.73). CONCLUSIONS: In a cohort of patients with systolic dysfunction, the ACE D allele was associated with a significantly poorer transplant-free survival. This effect was primarily evident in patients not treated with beta-blockers and was not seen in patients receiving therapy. These findings suggest a potential pharmacogenetic interaction between the ACE D/I polymorphism and therapy with beta-blockers in the determination of heart failure survival.

Adrenergic beta-Antagonists↗
PubMed2001

European randomised trial of dual versus triple tacrolimus-based regimens for control of acute rejection in renal allograft recipients.

Two large multicentre studies have shown superiority of tacrolimus-based immunosuppressive regimens compared with standard cyclosporine-based therapy in renal transplantation. In these studies, tacrolimus was used in a triple drug regimen of tacrolimus, corticosteroids, and azathioprine. The present study aimed to determine whether a tacrolimus-based dual regimen achieves a similar efficacy and safety profile compared with conventional triple therapy. In this prospective, open, multicentre trial, 249 patients were randomised to receive either dual therapy (n = 125) of oral tacrolimus (initial daily dose of 0.2 mg/kg) and oral prednisone or additionally, as a triple therapy (n = 124), oral azathioprine. The primary endpoint was the incidence of acute rejection at month 3. In addition, all patients were included into a follow-up evaluation at 1 year after transplantation. Both treatment groups had similar baseline characteristics. At month 3, patient survival was 97.6 % (dual) and 96.7 % (triple); graft survival was 92.7 % (dual) and 91.7 % (triple). The incidence of treated acute rejection confirmed by biopsy was 27.4 % (dual) and 24.8 % (triple); difference 2.6 %, 95 % CI [-9.4 %-12.9 %], P = 0.755. The incidence of corticosteroid-resistant rejection (biopsy-confirmed) was 9.7 % (dual) and 10.7 % (triple). The overall adverse events profile was similar; leukopenia (1.6 % vs 11.6 %, P = 0.002) was more frequent with triple therapy. Between months 4 and 12, six (dual) and eight (triple) patients had a rejection. At month 12, patient survival was 95.6 % (dual) and 93.6 % (triple); graft survival was 91.8 % (dual) and 90.7 % (triple). Tacrolimus proved to be efficacious and safe with both dual and triple low-dose regimens. The addition of azathioprine to a tacrolimus/corticosteroid-based therapy did not result in an increased efficacy.

Acute Disease↗
PubMed2001

Why is there so much end-stage renal failure of undetermined cause in UK Indo-Asians?

There is a high incidence of end-stage renal failure (ESRF) of undetermined cause in the Indo-Asian population of the UK. We studied patients presenting from the district of Brent and Harrow, which has a large Indo-Asian community, and whose renal services are largely provided by our centre. The diagnosis and ethnicity of patients starting renal replacement therapy and/or undergoing renal biopsy were collated. The incidences of ESRF, rates of renal biopsy and underlying diagnoses were calculated for Indo-Asians and Caucasians. Requirement for renal replacement therapy in Indo-Asians presenting to our centre from Brent and Harrow was 221/10(6)/year; no underlying diagnosis was identified in 77/10(6)/year. Renal biopsy rate in these patients was 456/10(6)/year, and the diagnostic categories significantly over-represented compared to Caucasians were: hypertension and ischaemia, focal segmental glomerulosclerosis (FSGS), idiopathic interstitial nephritis (IIN), diabetic nephropathy, minor glomerular abnormality, lupus nephritis and non-specific advanced chronic renal disease (p<0.001). The first three of these had a combined incidence of 135/10(6)/year in Indo-Asians and 31/10(6)/year in Caucasians. ESRF of undetermined cause is common in UK Indo-Asians, as is requirement for renal biopsy. Hypertension with ischaemia, FSGS and IIN are over-represented in the Indo-Asian population, and should be targeted for early diagnosis and treatment in this group.

Adult↗
PubMed2000

Large-scale test of hypothesised associations between the angiotensin-converting-enzyme insertion/deletion polymorphism and myocardial infarction in about 5000 cases and 6000 controls. International Studies of Infarct Survival (ISIS) Collaborators.

BACKGROUND: The original report of a possible association between myocardial infarction and the insertion/deletion (I/D) polymorphism of the gene for the angiotensin-1-converting enzyme (ACE) indicated a risk ratio for myocardial infarction with the DD genotype of 1.34 (95% CI 1.05-1.70), and the association was claimed to be particularly strong in a retrospectively defined low-risk subgroup (3.2 [95% CI 1.7-5.9). Subsequent investigations reached varying conclusions, but all were small, and much larger studies were needed. METHODS: 4629 myocardial infarction cases and 5934 controls were compared. Cases were UK men aged 30-54 years and women aged 30-64 years recruited on presentation to hospital with confirmed myocardial infarction. Controls were aged 30-64 years with no history of cardiovascular disease, but were siblings or children of myocardial infarction survivors, or spouses of such relatives. All risk-ratio calculations allow for this relatedness of some of the controls. An updated meta-analysis of previous studies was also conducted. FINDINGS: The ACE DD genotype was found in 1359 (29.4%) of the myocardial infarction cases and in 1637 (27.6%) of the controls (risk ratio 1.10 [95% CI 1.00-1.21]). The association between myocardial infarction and the DD genotype did not seem to be stronger in the subgroup defined as low risk by previously used criteria (234 [28%] of 836 cases and 911 [28%] of 3253 controls: risk ratio 1.04 [95% CI 0.87-1.24]), or in any other subgroup. Nor was the ACE I/D genotype predictive of subsequent survival. INTERPRETATION: This study involved many more cases than any previously reported study of this question, but did not confirm the existence of any substantial association. In an updated meta-analysis of these results with those of previously published studies, the risk ratio for myocardial infarction with the DD genotype seems to lie in the range 1.0 to about 1.1. Although an increase in risk of up to about 10-15% cannot be ruled out, substantially more extreme risks can be. Moreover, there are not especially strong associations in the subgroups previously selected for emphasis. These findings illustrate the need for some studies of candidate genes to involve much larger populations than is customary, without undue emphasis on retrospectively defined subgroups.

Adult↗