Effects of pyridostigmine on spontaneous and growth hormone-releasing hormone stimulated growth hormone secretion in children on daily glucocorticoid therapy after liver transplantation

OBJECTIVES: We aimed to investigate both nocturnal spontaneous and morning growth hormone (GH)-releasing hormone (GHRH)-induced GH secretion in children on daily glucocorticoid treatment after liver transplantation and to evaluate the effect of pyridostigmine (an acetylcholinesterase inhibitor thought to reduce hypothalamic somatostatin tone) on GH secretion in these patients. DESIGN: We performed a randomized, single-blind, cross-over study. PATIENTS: We studied three male and three female juvenile patients, within a year of orthotopic liver transplantation and under immunosuppressive glucocorticoid therapy (mean dose +/- SEM, 5.92 +/- 0.63 mg/day) and five normal children (four males, one female). MEASUREMENTS: Both nocturnal spontaneous and morning GHRH-induced GH secretion were evaluated after administration of placebo, 1 tablet p.o., or pyridostigmine, 2 mg/kg p.o. RESULTS: Spontaneous GH. Placebo: in liver transplanted children nocturnal GH secretion (mean GH level 10.8 +/- 2.0 mU/l) was not significantly different with respect to normal children (mean GH level 12.8 +/- 1.2 mU/l); pyridostigmine: nocturnal GH secretion was significantly increased as compared to placebo in subjects with liver transplantation but not in normal children. GHRH test. Placebo: liver transplanted patients showed a blunted GH response to GHRH with respect to normal children; pyridostigmine: the GH responses to GHRH (P less than 0.05) increased as compared to placebo and did not differ significantly in the two groups. CONCLUSIONS: Our data suggest a steroid-mediated increase in hypothalamic somatostatin tone in liver transplanted children.     

Variation in the diagnosis of vesicoureteric reflux using micturating cystourethrography

  Variability in the interpretation of micturating cystourethrography by paediatric radiologists for the diagnosis of vesicoureteric reflux in children was evaluated. All 265 micturating cystourethrograms (MCUs) that were available from 304 consecutive children aged 0.5 – 61 months  –  who were investigated after their first urine infection between 1993 and 1995 as part of a prospective cohort study  –  were selected for interpretation. Three experienced paediatric radiologists from the same department independently interpreted the MCUs according to the grading system of the International Reflux Study in Children, from grades 0 to V, with the presence of intrarenal reflux also noted. Apart from being informed that urine infection was the indication for the MCU, no other clinical information was given to the radiologists. The indices of variability used were the percentage of agreement and the kappa statistic, expressed as a percentage. Both measures were weighted with integers representing the number of categories from perfect agreement. Disagreement was analysed for children and kidneys. For the diagnosis of vesicoureteric reflux in individual patients, including grade, the percentage of agreement was 96% – 97% (kappa 90% – 91%) and the weighted percentage of agreement was 96% – 98% (weighted kappa 93% – 94%). The same high level of agreement was present for individual kidneys, with a percentage of agreement of 97% – 98% (kappa 89% – 92%) and a weighted percentage of agreement of 98% – 99% (kappa 94% – 95%). There was near perfect agreement in the interpretation of radiological micturating cystourethrography among three experienced paediatric radiologists for the diagnosis and grade of vesicoureteric reflux. Any variations in the medical care of children suspected of having vesicoureteric reflux are not explained by differences in the reporting of this diagnostic test. Received June 19, 1996; received in revised form November 1, 1996; accepted December 6, 1996     

Synthesis and post-translational modification of the androgen receptor in LNCaP cells

Androgen receptor synthesis and modification were studied in the human LNCaP cell line. Immunoblotting with a specific polyclonal antibody showed that the androgen receptor migrated as a closely spaced 110–112 kDa doublet on sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) gels. Most of the receptor protein is present in the higher molecular mass form. Pulse labelling experiments with [³⁵S]methionine showed that the androgen receptor is synthesized as a single 110 kDa protein which is rapidly converted to a 112 kDa protein. Alkaline phosphatase treatment of cytosols from [³⁵S]methionine pulse labelled cells caused a gradual elimination of the 112 kDa isoform with a concomitant increase of the 110 kDa isoform. This indicates that the observed 110 to 112 kDa upshift of the newly synthesized androgen receptor reflects receptor phosphorylation. Both isoforms can bind hormone and can undergo a hormone dependent transformation to a tight nuclear binding form, indicating that the 110 to 112 kDa conversion is not an obligatory step for hormone binding or receptor transformation.     

Hemophilia A: genetic prediction and linkage studies in all available families in Finland

RFLP studies were done in 82 (75%) of all known hemophilia A families in the Finnish population (approximately 5 million). Two intragenic RFLPs (Bc1I/F8A, XbaI/p482.6) and two extragenic markers (TaqI/St14, Bg1II/DX13) were used. Among 263 females at risk, carriership could be evaluated with an intragenic marker in 47% and with an extragenic marker in 26%. In 27% of the females, carriership could be neither excluded nor confirmed; 68% of these females were relatives of an isolated patient. Eight recombinations between the factor VIII gene (F8C) and DXS52 (lod 25.02 at theta max 0.06), eight recombinations between F8C and DXS15 (lod 21.91 at theta max 0.05), and two recombinations between DXS52 and DXS15 (lod 33.56 at theta max 0.01) were found. Using multipoint linkage analysis, the most likely order of loci supported by the data was: F8C-DXS15-DXS52-DXS134. RFLP segregation analysis provides a highly useful method of carrier detection and prenatal diagnosis of hemophilia A, but its limitations must be carefully taken into account.     

Nitrate administration to enhance the detection of myocardial viability by technetium-99m tetrofosmin single-photon emission tomography

A comparison was performed between technetium-99m tetrofosmin myocardial perfusion tomography at baseline and after nitrate administration, using a 2-day protocol, and rest-reinjection thallium-201 single-photon emission tomography (SPET) studies in order to assess whether nitrates enhance the detection of viable myocardium with^99mTc-tetrofosmin. Fifteen patients with coronary artery disease, previous myocardial infarction and a left ventricular ejection fraction <40% underwent²⁰¹T1 rest-injection and^99mTc-tetrofosmin. baseline-postnitroglycerin (0.4 mg sublingually) SPET studies, within 48 h. Tomograms based on the three spatial planes were divided into 15 segments and regional tracer uptake was quantitatively analysed. Viability was defined as presence of tracer uptake >50% of peak activity on baseline studies or after reversibility. The percentage of peak activity of^99mTc-tetrofosmin at baseline correlated with that of 201T1 (r=0.82,P <0.001). On baseline^99mTc-tetrofosmin studies, 73 of the 225 segments that were analysed had <50% of peal. activity. Fifteen percent of these segments showed reversibility after nitrate administration, with an increase in^99mTc-tetrofosmin uptake from 40%±9% to 57%±9% of peak activity (P=0.003). All reversible segments after nitrate administration had viability criteria on²⁰¹Tl studies, but 20 segments that were non-viable on^99mTc-tetrofosmin. studies were viable on²⁰¹Tl studies. Using a threshold value of >40% of peak activity, only seven segments remained non-viable on^99mTc-tetrofosmin studies. Overall agreement between^99mTc-tetrofosmin with nitrates and²⁰¹Tl-reinjection regarding the presence of myocardial viability was 90%. Detection of myocardial viability with^99mTc-tetrofosmin. was enhanced after nitrate administration, correlating with viability criteria observed on thallium studies.     

Quantification of dopamine transporter binding using [18F]FP-beta-CIT and positron emission tomography.

The purpose of this study was to compare different kinetic and semi-quantitative methods for analysing human [18F]FP-beta-CIT studies: plasma input models, simplified (SRTM) and full (FRTM) reference tissue models, standard uptake values (SUV) and SUV ratios (SUVr). Both simulations and clinical evaluations were performed to determine the effects of noise, scan duration and blood volume on Akaike model selection, and on precision and accuracy of estimated parameters. For typical noise levels (COV approximately 2.5%) and scan durations (<90 mins), simulations provided poor fits (Akaike criterion) in case of reversible plasma input models showing a relatively high number of outliers compared with the two-tissue irreversible model. Reference tissue models provided more reliable fits, which were nearly independent of noise and scan duration. For clinical data, two tissue irreversible and reversible plasma input models fitted striatum curves equally well (Akaike criterion). BP with plasma input models were less precise and contained more outliers than BP obtained with SRTM or FRTM. Among all methods tested, SRTM showed the highest contrast between patients and controls. When differentiating between patients and controls, SUVr performed almost equally well as SRTM, although contrast between striatum and background was lower. In conclusion, SRTM provided BP estimates with the highest precision and accuracy. Moreover, SRTM provided good contrast between patients and controls, and between striatum and background. SRTM is therefore the method of choice for quantitative [18F]FP-beta-CIT studies. SUVr might be an alternative for larger clinical trials.     

Sevelamer hydrochloride with or without alphacalcidol or higher dialysate calcium vs calcium carbonate in dialysis patients: an open-label, randomized study.

BACKGROUND: Sevelamer hydrochloride was recently proposed as a phosphate binder to prevent hypercalcaemia in place of calcium alkaline salts in dialysis patients. So far, it has been evaluated only in patients receiving calcitriol, without comparison with CaCO(3) alone, although the latter was found to be as effective as the combination of calcitriol and Al(OH)(3) in suppressing parathyroid hormone (PTH) without inducing hypercalcaemia and to have a better lowering effect on serum phosphate. Moreover, this bile salt binder may decrease serum 25-OH vitamin D. Therefore, we compared for 5 months two strategies for controlling moderate hyperparathyroidism: CaCO(3) alone vs sevelamer in conjunction with measures to increase calcium balance. METHODS: Forty-two patients were randomized: 21 continued their treatment with 4.8 g/day CaCO(3) and 21 were switched to sevelamer (initial dose: 2.4 g/day, increased to 4.4 g/day). Each month, when serum-corrected calcium decreased below 2.30 mmol/l, dialysate calcium was increased or alphacalcidol was given at each dialysis session, according to serum PO(4) levels. The following parameters were monitored: serum Ca, PO(4), bicarbonate and protein, weekly; and serum PTH, 25-OH vitamin D and total, LDL and HDL cholesterol monthly. RESULTS: Except for higher serum phosphate at month 1, lower serum bicarbonate at month 2 and lower LDL cholesterol at month 5 in the sevelamer group, no difference was found between the two groups. Compared with baseline levels, PTH increased and 25-OH vitamin D decreased significantly in both groups, these two parameters being inversely correlated. CONCLUSIONS: Given comparable control of plasma calcium, phosphate and 25-OH vitamin D, PTH control is comparable in both strategies. Sevelamer does not induce greater vitamin D depletion than CaCO(3). The transient decrease of serum bicarbonate after discontinuation of CaCO(3) in the sevelamer group suggests a less optimal prevention of acidosis. The sevelamer-induced decrease in LDL cholesterol gives this drug a potential advantage in cardiovascular prevention.     

Does the health status of chronically ill patients predict their judgements of the quality of general practice care?

Patients' health status as well as patients' judgements of care are used for assessing patients' perspectives, but the relation between those two concepts is unclear. In this study we explored whether health status predicts patients' judgements of the quality of general practice care. Hand-distributed and mailed surveys were performed by 28 general practitioners in The Netherlands. Chronically ill patients were approached when visiting the general practice or drawn from the practice registers. Health status was measured by WONCA/COOP charts, and patients' judgements by the CEP, a previously validated questionnaire. The response rate was 63% (n=762). When controlled for other patient characteristics, a poor overall health predicted less positive judgements of medical care, information, counselling, relation and communication, continuity of care and the organization of appointments (p[lessthan]0.01). Poor mental well-being predicted less positive judgements of the cooperation between care providers and a stronger need for more care (p[lessthan]0.001). The four other aspects of health status did not predict the patients' judgements. Judgements about the premises and the availability for emergencies were not predicted by health status. It can be concluded that a multidimensional approach should be used for interpreting the relations between patients' health status and their judgements of general practice care.     

Acquired dyschromatopsia in combined exposure to solvents and alcohol

Hypothesis: Does occupational exposure to solvents in combination with alcohol intake give rise to acquired color vision defects? Method: A total of 138 individuals exposed to solvents (toluene, xylene, trichloroethylene, tetrachloroethylene) were examined using Lanthony’s D-15 test and compared with 100 nonexposed controls. The extent of color vision loss was quantitatively assessed based on Bowman’s color confusion index (CCI). A cumulative exposure index was calculated from the hours of exposure per day and the years of exposure. In 30 persons who were exposed to trichloroethylene and tetrachloroethylene, urinary trichloroacetic acid was assessed as a parameter of exposure. Alcohol intake was calculated as based on interviews of patients in grams of ethyl alcohol per week. Results: Individuals who consumed more than 250 g alcohol/week and were simultaneously exposed to solvents showed a significantly elevated CCI (P = 0.0044). No significant correlation emerged between trichloroacetid acid excretion in the urine or the cumulative exposure index and the CCI. Conclusion: The combination of alcohol intake and occupational exposure to solvents discloses the risk of acquired subclinical color vision defects.