Biomedical subjects
Publications and source records attributed to J M Boots.
An update is given about some factors leading to loss of renal allograft, especially in relation to the use of tacrolimus and cyclosporine. We discuss both immunological, such as suboptimal immunosuppression, acute rejection, and noncompliance, as well as nonimmunological factor's such as hypertension, hyperlipidemia, chronic toxic effects of immunosuppressants, older donors, and delayed graft function.
Tacrolimus has proven to be superior to cyclosporine-Sandimmune with regard to the prevention of acute rejections, but data comparing tacrolimus with Neoral are scarce. A total of 128 consecutive renal transplant recipients was studied. The patients were treated with Neoral-based (n = 74) or tacrolimus-based (n = 54) immunosuppressive regimens. Survival analyses (Cox regression analysis) were performed on an intention-to-treat basis. Renal function and cardiovascular risk profile were analyzed by means of a repeated-measures analysis of variance (ANOVA) up to 12 months after transplantation. Immunological features were less favorable in the tacrolimus group. Two-year patient and graft survival were comparable. Acute-rejection-free survival was 82 % in the tacrolimus group versus 40 % in the Neoral group (P < 0.0001). The severity of the rejections (1997 Banff classification) was comparable (P = 0.43). Immunological graft loss (3.7 % vs. 12.2 %, P = 0.02) and conversion because of rejection (0 % vs. 28.4 %, P < 0.001) were less in the tacrolimus group. A higher proportion (68.5 % vs. 14.9 %, P < 0.001) was successfully put on monotherapy. Creatinine clearance, proteinuria, and fractional uric acid clearance were similar. In the tacrolimus group mean blood pressure was comparable, but patients needed less anti-hypertensive drugs (P < 0.001) and, even with fewer patients on lipid-lowering drugs, total cholesterol was lower (5.2 vs. 6.0 mmol/l, P = 0.003). Treatment for post-transplant diabetes mellitus was 18.5 % versus 10.8 % (P = 0.22). In both groups, antidiabetic medication could be withdrawn for most patients. This study indicates that tacrolimus is superior to cyclosporine-Neoral in preventing acute rejection with comparable patient and graft survival rates. Because of a lower need for treatment of hypertension and hypercholesterolemia, the cardiovascular risk profile is more favorable. A considerable proportion of patients can be successfully weaned off co-medication and treated with tacrolimus monotherapy.
Hypertension is an important risk factor for chronic transplant nephropathy. Therapy is usually based on casual office blood pressure (BP) measurements. However, it is not well known how casual BP predicts 24-hour BP in this population. The main focus of this study is to compare casual office BP with 24-hour ambulatory BP monitoring in renal transplant recipients with signs of chronic transplant nephropathy. Moreover, in this group, the day-night BP profile was assessed. In 36 renal transplant recipients with incipient or progressive proteinuria or an increase in serum creatinine level greater than 20%, 24-hour ambulatory BP was performed. Patients were defined as a nondipper if the mean BP decreased by less than 10% during the nighttime period. The correlation between single office and 24-hour ambulatory BPs was 0.61 for systolic BP and 0.55 for diastolic BP (P < 0.001). The mean difference between 24-hour ambulatory and single office BPs was -4.2 +/- 18.6 mm Hg (range, -44 to 36 mm Hg) for systolic BP and -1.1 +/- 10.7 mm Hg (range, -34 to 27 mm Hg) for diastolic BP; 94.5% of patients were classified as nondippers. There was a significant relation between the nightly decline in mean arterial pressure and calculated creatinine clearance (r = 0.34; P < 0.05). In conclusion, in renal transplant recipients with chronic transplant nephropathy, a large difference between office and ambulatory BPs is present, with both overestimation and underestimation of 24-hour BP by office BP measurements. Moreover, a severely disturbed day-night BP rhythm was observed. In transplant recipients with compromised graft function, office BP may not reflect 24-hour BP adequately, and ambulatory BP measurements should be considered.
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This report describes a forty-seven-year-old female patient with a complex medical history. She was suffering from an unspecified interstitial lung disease, papillary thyroid carcinoma which had been treated, hypoparathyroidism after thyroidectomy for which she was receiving dihydrotachysterol and calcium, and atrial fibrillation and congestive heart failure as a result of mitral stenosis. Shortly after mitral valve replacement she developed a severe hypercalcemia (serum calcium 5.95 mmol/l) during a febrile illness. At that time anti-tuberculous agents were also being administered for presumed tuberculosis. The possible mechanisms for this severe elevation of the calcium level are discussed. Immobilization, while Paget's bone disease was present, and perhaps enhanced activation of dihydrotachysterol by rifampicin, could have led to increased calcium-release into the circulation. Continuous supplecation of calcium and vitamin D, provoked dehydration and the mechanism of the milk-alkali syndrome also contributed to this extremely high calcium level. It is concluded that hypoparathyroid patients being treated with vitamin D and calcium should be carefully monitored in the case of an intercurrent illness or a change in medication.
1. The major drawback of the cardiovascular reflex tests used to study autonomic failure is the time involved in calculating the results. To overcome this disadvantage, we have developed an automated computerized program using a FINger Arterial PRESsure instrument for the measurement of beat-to-beat heart rate and blood pressure on a finger. 2. This program calculates heart rate variability during three standardized tests, forced breathing, standing up and the Valsalva manoeuvre, and records blood pressure values in response to standing up and sustained handgrip. The time taken to perform the test and to calculate the results is usually 25 min. 3. The reproducibility of the tests in 21 normal subjects was comparable with the reproducibility obtained with conventional test methods using an ECG and a sphygmomanometer. 4. In addition, we determined the age-dependent normal values of the seven test parameters in 124 subjects aged 20-90 years. 5. Using this program in 10 patients with longstanding (14-50 years) complicated diabetes, in each of them four or more abnormal test results were found.
The cumulative intake curves of 50 obese and 86 normal weight women during test meals were related to body mass index, age and the three factors of Stunkard & Messick's questionnaire (Journal of Psychosomatic Research, 29, 71-83), cognitive restraint, disinhibition and perceived hunger. Eating behaviour was monitored by a concealed camera and rate of intake via an electronic balance built into the table under the plate. The eating behaviour of each subject was very consistent over a series of three or six lunches of the same solid food consumed solitarily in a constant environment, with marked differences between subjects. Differences in body mass index over the whole sample were not related to the shape of the cumulative intake curve during test meals. In multiple regression analysis, the normal-weight subjects who scored high on disinhibition of restraint in response to emotions and external influences showed a more nearly constant rate of intake. In a separate multiple regression, the overweight subjects with the same characteristic showed a decelerating rate of intake. Susceptibility to hunger had no discernible relationship to the shape of the cumulative intake curve in either normal or overweight subjects. We conclude that the shape of the cumulative intake curve can be attributed more to cognitive than to biological factors.