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Biomedical subjects

B Kiberd

Publications and source records attributed to B Kiberd.

At least 19 recordsLinked to original sources

Diabetes mellitus in transplantation: 2002 consensus guidelines.

Diabetes mellitus is a serious complication following organ transplantation that is underdiagnosed, possibly due to the inadequate definitions used in published literature and the lack of standardized screening. Diabetes in transplantation amplifies the already increased risk of cardiovascular disease among transplant patients, and increases the risk of graft loss and death. Patients at risk of developing diabetes in transplantation should therefore be prospectively identified and given individualized immunosuppressive therapy to minimize the risk of developing this disease. These guidelines are intended to: (1) help identify patients at risk for diabetes after transplantation; (2) set down a standard definition of posttransplant diabetes mellitus (PTDM); (3) create a standard monitoring protocol for the diagnosis of PTDM; and (4) optimize the management of patients at risk of developing or who develop diabetes after transplantation. With improved diagnosis, individualization of therapy, and proper early management, the incidence of diabetes in transplantation, and the accompanying additional burden of illness the disease carries, may be diminished. In turn, this will help achieve the therapeutic goals of reducing the risk of graft complications, improving quality of life, and reducing postoperative morbidity and mortality in transplant patients.

Consensus↗

A pilot study of steroid-free immunosuppression in the prevention of acute rejection in renal allograft recipients.

BACKGROUND: Corticosteroids have been a mainstay of rejection prophylaxis for several decades, despite the multiple adverse effects of long-term use, including weight gain, hyperlipidemia, diabetes, hypertension, and bone disease. The detrimental effect of steroids on the metabolic profile begins in the early posttransplantation period, and the complete avoidance of steroids in transplantation would therefore be optimal. We hypothesized that the addition of mycophenolate mofetil (MMF) and a humanized monoclonal anti-CD25 antibody (daclizumab) to a cyclosporine (CsA microemulsion)-based immunosuppression protocol would permit transplantation without steroids. METHODS: Steroid-free renal transplantation was attempted in 57 patients treated with daclizumab, MMF, and CsA. Twenty-eight patients received kidneys from living donors; the remaining 29 received cadaveric grafts. RESULTS: At 1 year, patient and graft survival were 95% and 89%, respectively. Fourteen patients (25%) experienced rejections, of which 13 were readily reversed with steroids; 1 patient required OKT3. Mean serum creatinine at 12 months for patients not experiencing rejection was 149+/-58 micromol/L, compared with 158+/-102 micromol/L for those experiencing rejection. Five patients required hospitalization for infection; no patients developed lymphoproliferative disease. At baseline, 17 patients required 3 or more antihypertensive medications, compared with 2 patients at 1 year. Three of 43 nondiabetic patients developed diabetes during the study. There was no significant reduction in lumbar or femoral bone density. CONCLUSIONS: On the basis of these positive results, we believe steroid avoidance with this immunosuppressive regimen merits further study.

Acute Disease↗

International Child Care Practices Study: infant sleeping environment.

BACKGROUND: The International Child Care Practices Study (ICCPS) has collected descriptive data from 21 centres in 17 countries. In this report, data are presented on the infant sleeping environment with the main focus being sudden infant death syndrome (SIDS) risk factors (bedsharing and infant using a pillow) and protective factors (infant sharing a room with adult) that are not yet well established in the literature. METHODS: Using a standardised protocol, parents of infants were surveyed at birth by interview and at 3 months of age mainly by postal questionnaire. Centres were grouped according to geographic location. Also indicated was the level of SIDS awareness in the community, i.e. whether any campaigns or messages to "reduce the risks of SIDS" were available at the time of the survey. RESULTS: Birth interview data were available for 5488 individual families and 4656 (85%) returned questionnaires at 3 months. Rates of bedsharing varied considerably (2-88%) and it appeared to be more common in the samples with a lower awareness of SIDS, but not necessarily a high SIDS rate. Countries with higher rates of bedsharing appeared to have a greater proportion of infants bedsharing for a longer duration (>5 h). Rates of room sharing varied (58-100%) with some of the lowest rates noted in centres with a higher awareness of SIDS. Rates of pillow use ranged from 4% to 95%. CONCLUSIONS: It is likely that methods of bedsharing differ cross-culturally, and although further details were sought on different bedsharing practices, it was not possible to build up a composite picture of "typical" bedsharing practices in these different communities. These data highlight interesting patterns in child care in these diverse populations. Although these results should not be used to imply that any particular child care practice either increases or decreases the risk of SIDS, these findings should help to inject caution into the process of developing SIDS prevention campaigns for non-Western cultures.

Beds↗

Conversion to rapamycin immunosuppression in renal transplant recipients: report of an initial experience.

BACKGROUND: The aim of this study is to evaluate the effects of RAPA conversion in patients undergoing cyclosporine (CsA) or tacrolimus (Tac) toxicity. METHODS: Twenty renal transplant recipients were switched to fixed dose rapamycin (RAPA) (5 mg/day) 0 to 204 months posttransplant. Drug monitoring was not initially used to adjust doses. The indications for switch were chronic CsA or Tac nephrotoxicity (12), acute CsA or Tac toxicity (3), severe facial dysmorphism (2), posttransplant lymphoproliferative disorder (PTLD) in remission (2), and hepatotoxicity in 1. Follow-up is 7 to 24 months. RESULTS: In the 12 patients switched because of chronic nephrotoxicity there was a significant decrease in serum creatinine [233+/-34 to 210+/-56 micromol/liter (P<0.05) at 6 months]. Facial dysmorphism improved in two patients. No relapse of PTLD was observed. Five patients developed pneumonia (two Pneumocystis carinii pneumonia, one infectious mononucleosis with polyclonal PTLD lung infiltrate) and two had bronchiolitis obliterans. There were no deaths. RAPA was discontinued in four patients, because of pneumonia in two, PTLD in one, and oral aphtous ulcers in one. RAPA levels were high (>15 ng/ml) in 7 of 13 (54%) patients. CONCLUSIONS: RAPA conversion provides adequate immunosuppression to enable CsA withdrawal. However, when converting patients to RAPA drug levels should be monitored to avoid over-immunosuppression and adequate antiviral and Pneumocystis carinii pneumonia prophylaxis should be given.

Adult↗

Is routine ureteric stenting needed in kidney transplantation? A randomized trial.

BACKGROUND: Whether routine ureteric stenting in low-urological-risk patients reduces the risk of urological complications in kidney transplantation is not established. METHODS: Eligible patients were recipients of single-organ renal transplants with normal lower urinary tracts. Patients were randomized intraoperatively to receive either routine stenting or stenting only in the event of technical difficulties with the anastomosis. All patients underwent Lich-Gregoire ureteroneocystostomy. RESULTS: Between June 1994 and December 1997, 331 kidney transplants were performed at a single center, 305 patients were eligible, and 280 patients were enrolled and randomized. Donor and recipient age, sex, donor source, whether first or subsequent grafts, ureteric length, native renal disease, and immunosuppression were similar in each group. In the no-routine-stenting group 6 of 137 patients (4.4%) received stents after randomization for intraoperative events that in the surgeon's opinion required use of a stent. In an intention-to-treat analysis there was no difference between groups in the primary outcome cluster of obstruction or leak [routine stenting 5 of 143 (3.5%) vs. no routine stenting 9 of 137 (6.6%); P=0.23], or in either of these complications analyzed separately. All urological complications were successfully managed without major morbidity. Living donor organs and shorter ureteric length (after trimming) were univariate risk factors for leaks, although increasing donor age was associated with obstruction. CONCLUSIONS: Routine ureteric stenting is unnecessary in kidney transplantation in patients at low risk for urological complications. Careful surgical technique with selective stenting of problematic anastomoses yields similar results.

Adult↗

Intravenous mycophenolate mofetil: safety, tolerability, and pharmacokinetics.

An intravenous (i.v.) formulation of mycophenolate mofetil (MMF; CellCept, Roche Pharmaceuticals, Inc., Palo Alto, CA) that will enable its administration to patients unable to tolerate oral medication is available. Two separate studies, an open-labeled pharmacokinetic (PK) study and a double-blind safety study, were performed. Within 24 h after transplant, 153 (safety study) and 45 (PK study) first or second renal transplant recipients were started on i.v. MMF 1 g Q12h or placebo (used in the safety study only, 2:1 MMF:placebo), given over 2 h via a dedicated peripheral venous catheter. In the safety study, per os (p.o.) MMF (1g Q12h) or placebo was administered, starting within 72 h after transplant, whereas in the PK study, p.o. MMF was started on the evening of day 5. Sequential blood samples obtained on study days 5 (i.v. MMF) and 6 (p.o. MMF) before and up to 12 h after the AM dose were analyzed for mycophenolic acid (MPA) and MPA glucuronide (MPAG) concentrations by high-performance liquid chromatography. The area under the concentration curve (AUC) was calculated using the linear trapezoidal rule. The MPA AUC(0-12) was higher for i.v. MMF than p.o. MMF (40.8 +/- 11.4 microg x h/ mL vs. 32.9 +/- 15, p < 0.001). There were no other significant PK differences for plasma MPA or MPAG. In the safety study (n = 98 i.v. MMF vs. n = 55 placebo), 11 patients (11%, i.v. MMF) and 4 patients (7%, placebo) discontinued their use of the drug because of an adverse event (AE). Overall, AEs were similar between i.v. MMF and placebo. Injection site phlebitis (4%) and thrombosis (4%) were observed only with i.v. MMF. MMF i.v. 1 g twice daily (b.i.d.) should provide efficacy at least equivalent to p.o. MMF without increased toxicity, and it provides an acceptable alternative dose form in the immediate period after transplant.

Administration, Oral↗

Effect of recipient sensitization (peak PRA) on graft outcome in haploidentical living related kidney transplants.

OBJECTIVE: To evaluate the influence of pre-transplant recipient sensitization on the outcome of 1-haploidentical live related donor (LRD) kidney transplants. METHOD: We reviewed 141 consecutive cyclosporine-treated adult haploidentical first transplants for which panel reactive antibody (PRA) levels were available. Patients were divided into three groups according to their peak PRA levels: group I, PRA = 0 (n = 97); group II, PRA = 1-50% (n = 24); and group III, PRA = 51-100% (n = 20). RESULTS: Differences in PRA were associated with significant differences in short- and longer-term graft survival, unrelated to patient survival. Graft survival at 1, 3, and 5 yr was only 74, 40, and 27% in group III, compared to 92, 87, and 52% in group II, and 96, 91, and 85% in group I (p < 0.001). Increasing PRA was associated with shorter time-to-graft failure. In group III, 20% lost their transplant from acute rejection in the first 6 months, versus 4% in group II and 3% in group I (p < 0.01). Graft survival in group II diverged from that of group I only after 3 yr, due to an increase in loss from chronic rejection. Hospitalization was longer in group III, in association with a significantly higher incidence of acute rejection during the first 3 months after transplantation (p < 0.02). Serum creatinine was higher in sensitized than nonsensitized patients at all time points. CONCLUSIONS: Sensitization has a significant negative impact on the outcome of haploidentical LRD kidney transplants. Sensitized potential recipients and their potential donors should be aware of this in arriving at informed decision-making for transplantation. These patients may benefit from more sensitive cross-match testing, more intense or more novel immunosuppression, or immunomodulation to modify their immune responsiveness.

Adult↗

Concentrations of antimony in infants dying from SIDS and infants dying from other causes.

OBJECTIVES: Raised concentrations of antimony have been found in infants dying of sudden infant death syndrome (SIDS). The presumed source of this antimony is toxic gases generated from fire retardants that are present in cot mattresses. The aim of this study was to determine the role of antimony in SIDS. DESIGN: Samples of liver, brain, serum, and urine were collected from all patients dying from SIDS and a group of aged matched control infants who had died of other causes. SETTING: Nationwide study in Ireland. SUBJECTS: 52 infants dying from SIDS and 19 control infants aged > 7 days and < 1 year. RESULTS: The median concentration of antimony in the liver and brain of infants dying of SIDS was < 1 ng/g, with no difference detected between the infants dying from SIDS and the control infants. The range of antimony in the serum of infants dying of SIDS was 0.09-0.71 microg/litre (median, 0.26). Although no difference was found between infants dying from SIDS and control infants, SIDS infants were found to have higher concentrations when compared with healthy infants in the 1st year of life, probably as a result of release of antimony into serum after death. Urine antimony concentrations in infants dying from SIDS were < 3.91 ng/mg (corrected for creatinine) and similar to values found both in control infants and healthy infants. CONCLUSION: There is no evidence to support a causal role for antimony in SIDS.

Antimony↗

Is 3-hour cyclosporine blood level superior to trough level in early post-renal transplantation period?

PURPOSE: Cyclosporine dose is traditionally based on trough blood levels. Cyclosporine trough blood level correlates poorly with acute rejection and cyclosporine nephrotoxicity after renal transplantation. We determined whether cyclosporine blood level at any other time point is superior to cyclosporine trough blood level as a predictor of acute rejection and cyclosporine nephrotoxicity. MATERIALS AND METHODS: Cyclosporine blood level was measured before (trough), and 1, 2, 3 and 4 hours after the dose in 156 initial renal transplant cases 2 to 4 days after the initiation of cyclosporine micro-emulsion formula administration. The cylosporine micro-emulsion dose was based on cyclosporine trough blood level targeting 250 to 400 microg./l. RESULTS: Regression analysis revealed that only delayed graft function (p = 0.007) and cyclosporine blood level after 3 hours (p = 0.008) predicted acute rejection. Mean cyclosporine trough blood level plus or minus standard error was not significantly different in patients with and without acute rejection (293+/-21 versus 294+/-11 microg./l.). Mean cyclosporine blood level after 3 hours was significantly lower in patients with acute rejection (1,156+/-90 versus 1,421+/-50, p = 0.008). Cases were divided into tertiles at levels after 3 hours (1,100 and 1,500 microg./l.). The group in which the level after 3 hours was less than 1,100 microg./l. had the highest acute rejection rate (22 of 50 patients, 44%) and a cyclosporine nephrotoxicity rate of 13% (7 of 52 patients). The group in which the level after 3 hours was 1,100 to 1,500 microg./l. had the lowest acute rejection rate (5 of 46 patients, 11%) without increased cyclosporine nephrotoxicity (7 of 52 patients, 13%). A level after 3 hours of greater than 1,500 microg./l. was associated with a rejection rate of 15% (7 of 47 patients) but significantly higher cyclosporine nephrotoxicity (16 of 52 patients, 30%). CONCLUSIONS: Cyclosporine blood level after 3 hours in the early post-transplantation period is associated with acute rejection and cyclosporine nephrotoxicity. A cyclosporine blood level range after 3 hours of 1,100 to 1,500 microg./l. is associated with an optimal outcome. Our data suggest that cyclosporine blood level after 3 hours may represent a better method of monitoring cyclosporine micro-emulsion dose than cyclosporine trough blood level. This hypothesis must be further studied in randomized trials.

Cyclosporine↗

Feeding infants - an investment in the future.

Because nutrition during infancy not only determines growth but also impacts on future adult health, it is essential that healthy eating habits be promoted from a very young age. This study examines current feeding practices among Irish infants in the first year of life. Although 51% of Irish mothers commenced breast-feeding their infants at birth, the number of women who continued to breast-feed their infants at 3 months of age was among the lowest in Europe. Over two-thirds of infants (70%) received some formula by 4 weeks of age and the majority of infants changed formulas at least once or twice in the first year. The use of follow-up milk formulas was particularly prevalent in Ireland. Only 16% of infants were given unmodified cow's milk in their first year of life but none had been prescribed supplemental iron or vitamins. On average, Irish infants were weaned between 3 and 4 months of age but few families used home-prepared foods in the initial weaning period. Areas for future intervention include the encouragement of a longer duration of breast-feeding, appropriate vitamin and iron supplementation and the promotion of home-prepared foods.

Adult↗

The current epidemiology of SIDS in Ireland.

This paper examines some epidemiological factors associated with SIDS to give a general profile of SIDS cases occurring in Ireland between the years 1993 to 1997. There has been a dramatic decrease in the incidence of the Sudden Infant Death Syndrome (SIDS) in the Republic of Ireland in the last decade from an average rate of 2.2/1000 live-births in the 1980s to 0.8/1000 live-births in the years 1993-1997, a decrease of 100 deaths a year. The fall in the SIDS rate has been seen in many countries and is felt to be associated with Reduce The Risks (RTR) of SIDS campaigns and the avoidance of the prone sleeping position. The use of the prone sleep position averaged at 6% of children being put prone in the years 1993-1997 but the prone position has progressively decreased from 13% of children being put prone in 1994 to only 2% in 1997. The profile of the Irish SIDS cases is similar to that of SIDS cases in other countries following similar RTR campaigns with a male predominance, the characteristic clustering of deaths in the first six months of life and the majority of cases (75%) occuring in the night sleep period. The loss of the seasonal variation of the time of death is also shown and factors such as lower socio-economic status, unemployment and medical card eligibility were seen in higher proportions in SIDS families than in the general population. A high percentage of SIDS mothers smoked (73%). Higher smoking rates were seen among younger and single mothers and smoking rates were inversely related to educational level and socioeconomic grouping. An urgent question that needs to be addressed is how socioeconomic disadvantage increases the SIDS risk and what factors influence socioeconomically disadvantaged families to adopt life style and parenting practices such as smoking that influence their children's health.

Adult↗

The morbidity of prolonged wound drainage after kidney transplantation.

PURPOSE: The consequences of prolonged wound drainage, defined as extravasation of more than 50 ml. fluid daily for more than 1 week through a drain or wound after renal transplantation, have not been well described in the literature. We examine the association of prolonged wound drainage with other clinical events, and its impact on hospitalization, and patient and graft survival. MATERIALS AND METHODS: We prospectively documented prolonged wound drainage in 392 recipients of cadaver and live renal transplants from July 1993 to December 1997. Potential risk factors, associated outcomes within the first 6 months and effect on length of hospital stay due to prolonged wound drainage were determined. RESULTS: Prolonged wound drainage was significantly associated with pre-transplantation weight, weight gain by post-transplantation day 3, delayed graft function and continuous ambulatory peritoneal dialysis on univariate analysis but only with delayed graft function (odds ratio 2.8, 95% confidence intervals 1.4 to 5.6) on multivariate analysis. Post-transplantation lymphoceles (5.2, 9 to 14), wound infection (27, 5.7 to 130) and wound dehiscence (5.8, 1.7 to 20) were associated with prolonged wound drainage. Patients with prolonged wound drainage stayed 8.7 additional days during the first hospitalization and overall 11.3 additional days during the first 6 months after transplantation independent of other co-morbid events, such as delayed graft function, rejection or cytomegalovirus disease. CONCLUSIONS: Prolonged wound drainage is an important post-renal transplantation event that impacts patient outcomes and hospital resource use. Efforts to prevent this complication should be considered.

Adult↗

Reduce the risk of cot death guidelines. The effect of a revised intervention programme. National Sudden Infant Death Register, Dublin.

In March 1992 the 'Reduce the Risk of Cot Death' guidelines were launched in the Republic of Ireland. In response to epidemiological surveys conducted in 1993 and 1994 these guidelines were revised in November 1995 and a new leaflet was distributed. The study set out to compare parents interviewed in 1994 (n = 153) and 1996 (n = 132) to determine their source of information on the guidelines and the extent of parental change in infant care practice as recommended in these guidelines. In both time periods the media was the most frequent source of information with 63% (n = 97) of respondents having received advice from the media in 1994 compared to 55% (n = 72) in 1996. However a significant number of parents especially young (64%) and new (58%) mothers were uninterested or unable to access the relevant health care literature indicating a group needing a tailored educational package in the future. Medical sources especially Public Health Nurses ranked second in delivering information at 47% (n = 72) in 1994 vs 46% (n = 60) in 1996 while other sources such as family and friends were the least frequent sources of information. In 1996 more respondents (59%; n = 78) put their children to sleep on their back than in 1994 (35%; n = 54) but they used heat more frequently at night [73% (n = 96) in 1996 vs 57% (n = 87) in 1994]. There was no significant difference in the percentage of parents smoking [29% (n = 45) vs 33% (n = 43)], the uptake of breast feeding [40% (n = 61) vs 49% (n = 64)] and the way parents clothed their children [60% (n = 92) vs 58% (n = 77) used more than ten tog] between 1994 and 1996. Although in 1996 the message to reduce the risks of cot death was more specific and direct, it seems to have had less effect on further changing parents' practices. However, the overall effect of the two education programmes has been successful in yielding a low percentage (2%; n = 2) of babies sleeping prone in 1996). Smoking remains the major modifiable risk factor for SIDS in Ireland.

Humans↗

Antimony in blood and urine of infants.

AIM: To establish a reference range for antimony in the serum and urine of infants in the first year of life. METHODS: 100 infants were selected randomly from the population. Each infant had a single blood and urine sample taken. Antimony was assayed using inductively coupled plasma mass spectrometry. RESULTS: The reference range for antimony in the serum of infants in the first year of life was established as 0.09-0.25 microgram/l. The upper 95% centile for urinary antimony, corrected for creatinine, in the same population was 2.6 ng/mg creatinine. There was a very weak correlation between the serum and urine concentrations. CONCLUSIONS: This study confirms the presence of low concentrations of antimony in the serum and urine of healthy infants.

Age Factors↗

A profile of attenders at the A&E Department of the Children's Hospital, Temple Street, Dublin.

The Department of Health state that the prime function of the A&E department is to provide for the reception and initial management of every variety of medical emergency, provided that the condition could not be treated by the General Practitioner. The A&E department in the Children's Hospital, Temple Street, Dublin receives an average of 55,000 visits annually. The study profiled attenders according to their: socioeconomic status; reasons for attendance; appropriateness of attendance; and outcome of attendance. Attenders parents were more likely to be unemployed (22%), single (26%) and GMS card holders (52%) than national average figures. Families who attended out of hours (i.e. after 5pm) and/or who were self-referred did not differ socio-economically from other attenders. 74% of all attenders were self-referred and the self-referred group were more likely to attend after 5pm. 54% of attenders had attended the department more than once in the previous twelve months. 37% of all attendance were due to accidents. Casualty doctors assessed that 39% of all attendance did not require hospital services. However, the percentage of 'GP referred' and 'self-referred' groups deemed to require hospital services were comparable (47% v 38%). Furthermore, only 19% of GP referrals were admitted. These figures suggest that a large number of children who attend the A&E department should be attending a medical paediatric out patient unit, rather than an A&E department.

Accidents↗