Radioisotopic evaluation of renal function in cyclosporine-treated pediatric and adult renal transplant recipients and their living donors. A study of 152 donor-recipient pairs

Renal function was studied in 2 groups of renal transplant recipients and their donors by technetium-99m diethylenetriamine pentaacetic acid and a gamma camera. The pediatric group (group A) comprised 40 children and their adult kidney donors. The adult group (group B) consisted of 112 consecutive adult renal transplant recipients and their adult donors. All patients received kidneys from living donors and were given the same immunosuppression protocol (PRED plus CSA). Donor glomerular filtration rate (GFR) was determined before nephrectomy and at a mean period of 30 (range 10-50) months after nephrectomy. The graft GFR was measured at 1, 3, 6, and 12 months and at the most recent follow-up visit. Moreover, the functional reserve of the graft was assessed by infusion of dopamine and an amino acid. The postnephrectomy GFR of donors in groups A and B were 74 +/- 18 and 72 +/- 20 ml/min/1.73 m2, respectively. The GFR of pediatric recipients was significantly lower than that of adult recipients at corresponding time points along the course of follow-up. The mean values of graft GFR were 47.6 +/- 20 and 63.8 +/- 29.6 ml/min/1.73 m2 for pediatric and adult recipients, respectively (P < 0.001). Moreover, the graft functional reserve was significantly lower in pediatric recipients. These data demonstrate that adult kidneys transplanted into pediatric recipients have lower GFR than those transplanted into adults, despite corrections for body surface area. Although the reason for this phenomenon is unknown, the observation may have important implications for management of pediatric recipients.     

Estimating multiple tumor transition rates based on data from survival-sacrifice experiments

The development of two types of tumors in an animal survival-sacrifice experiment can be described by a Markov illness-and-death process with four unknown tumor transition rates and four unknown death rates. Due to the occult nature of tumors, these transition rates cannot be identified through the use of a completely nonparametric model. We propose a semiparametric model that assumes that the four tumor transition rates are proportional to each other and can be described by a known parametric function. We show that these tumor transition rates can be estimated using an ECM algorithm and that inferences about these parameters can be drawn using the likelihood ratio test. We illustrate this model and the algorithm with data from the ED01 study.     

Serum immunoglobulin G concentration in goat kids fed colostrum or a colostrum substitute

To determine the suitability of a new colostrum substitute derived from goat serum and to determine the amount of colostral IgG needed to achieve serum IgG concentration > 800 mg/dl, twin kids from 14 does were fed colostrum or a colostrum substitute. The volume of colostrum or colostrum substitute fed was calculated so that half the kids in each group received IgG at a low dosage (1.5 g/kg of body weight) and the other half received IgG at a high dosage (3 g/kg). Kids were bottle fed the colostrum or colostrum substitute and then fed pooled goat's milk until 18 hours old, at which time they were allowed to nurse their dams. Does were milked manually every 2 hours after parturition until specific gravity of mammary secretions was < 1.02, the specific gravity of goat's milk. Serum IgG concentration of each kid was determined by means of single radial immunodiffusion at birth and 12, 18, and 24 hours and 7, 21, and 42 days after birth. Kids were weighed at each blood collection and monitored for illness daily. None of the kids had measurable serum IgG concentrations at birth. Mean serum IgG concentration was significantly higher in kids fed colostrum than in kids fed colostrum substitute at all times, except days 7 and 42 (P < 0.05). By 24 hours after birth, serum IgG concentration was > 800 mg/dl in all kids fed colostrum, in 4 of 7 kids fed the substitute at the higher dosage, and in 2 of 7 kids fed the substitute at the lower dosage.(ABSTRACT TRUNCATED AT 250 WORDS)     

The relation of exercise habits to health beliefs and knowledge about osteoporosis

The relation of exercise habits of 113 female college students to their knowledge about osteoporosis and their health beliefs was investigated, using the health belief model to determine why some people participate in self-care preventive actions but others do not. Age was positively correlated with the level of osteoporosis knowledge, awareness of personal susceptibility, and motivation for general health behaviors. Older participants, however, perceived more barriers to exercise as an osteoporosis-prevention measure than did the younger respondents. The authors' conclusions support the importance of early osteoporosis education and lifetime physical activities to prevent osteoporosis.     

Advances and controversies in the diagnosis and management of medullary thyroid carcinoma

In tasks requiring sustained attention, human alertness varies on a minute time scale. This can have serious consequences in occupations ranging from air traffic control to monitoring of nuclear power plants. Changes in the electroencephalographic (EEG) power spectrum accompany these fluctuations in the level of alertness, as assessed by measuring simultaneous changes in EEG and performance on an auditory monitoring task. By combining power spectrum estimation, principal component analysis and artificial neural networks, we show that continuous, accurate, noninvasive, and near real-time estimation of an operator's global level of alertness is feasible using EEG measures recorded from as few as two central scalp sites. This demonstration could lead to a practical system for noninvasive monitoring of the cognitive state of human operators in attention-critical settings.     

5-fluorouracil/leucovorin-induced inhibition of thymidylate synthase in normal tissues of mouse and man

We evaluated the effects of 5-fluorouracil (5FU) and leucovorin (LV) on thymidylate synthase (TS) in normal rapidly dividing tissues, which may contribute to toxic side-effects of treatment with 5FU and LV. TS levels were determined in biopsies of human liver and colon mucosa and murine bone marrow, liver and intestinal mucosa at several time points after administration of therapeutic doses of 5FU or LV/5FU. In murine liver, after treatment with 100 mg/kg 5FU, TS inhibition was significantly higher than after LV/5FU administration (P < 0.001). A similar trend was observed in human liver tissue. Murine intestinal mucosa had TS levels below the limit of detection after 5FU or LV/5FU treatment. In human colon mucosa samples, administration of 500 mg/m2 5FU resulted in a large extent of TS inhibition but the small number of samples did not allow a time- or 5FU-LV/5FU-related evaluation. TS activity in murine bone marrow cells was strongly inhibited to 10% of the control value during 48 h. LV/5FU administration resulted in a slightly higher inhibition. No human bone marrow was available to measure TS levels. Both in mice and humans the most pronounced TS inhibition occurred in the tissue that was involved in dose-limiting toxicity. Therefore it is very likely that TS inhibition in normal tissues contributes to the toxic side-effects of 5FU treatment.     

Effect of permeabilizing agents on antibacterial activity against a simple Pseudomonas aeruginosa biofilm

In 1994, the Malm?-Klaipeda twinning programme was approved by the World Federation of Hemophilia. One of the first steps in the collaboration has been to set up a registry of the haemophilia patients in the Klaipeda area. In order to collect important clinical data the patients have been examined jointly by experts on haemophilia from the two centres. Seventeen out of 25 patients with severe haemophilia known at the Klaipeda centre were examined and compared to a matched cohort of patients from the Malm? centre. The main differences between the cohorts were that home treatment was not available to the Klaipeda patients, they received less treatment in general, had higher joint scores and more frequent bleeds. The pattern of transmission of blood-borne virus was very similar, with a high prevalence of hepatitis C antibodies. We conclude that the twinning programme between Malm? and Klaipeda has resulted in several achievements, including training of staff and a necessary inventory of the patients. This should not only form a suitable platform for the future development of haemophilia care in Lithuania, but could also serve as an example for liaisons between other haemophilia centres.     

The parathyroid hormone (PTH)/PTH-related peptide receptor mediates actions of both ligands in murine bone

PTH and PTH-related peptide (PTHrP) have been shown to bind to and activate the same PTH/PTHrP receptor. Recent studies have demonstrated, however, the presence of additional receptors specific for each ligand. We used the PTHrP and PTH/PTHrP receptor gene knock-out models to investigate whether this receptor mediates the actions of both ligands in bone. The similar phenotype of the PTHrP (-/-) and PTH/PTHrP receptor (-/-) animals in the growth plate of the tibia suggests that this receptor mediates the actions of PTHrP. Electron microscopic studies have confirmed the accelerated differentiation and disordered organization of chondrocytes, with the accumulation of large amounts of dispersed glycogen granules in the cytoplasm of proliferative and maturing cells of both genotypes. The contrasting growth plate mineralization patterns of the PTHrP (-/-) and PTH/PTHrP receptor (-/-) mice, however, suggest that the actions of PTHrP and the PTH/PTHrP receptor are not identical. Studies using calvariae from PTH/PTHrP receptor (-/-) embryos demonstrate that this receptor solely mediates the ability of PTH and PTHrP to stimulate adenylate cyclase in bone and to stimulate bone resorption. Furthermore, we show that osteoblasts of PTH/PTHrP receptor (-/-) animals, but not PTHrP (-/-) animals, have decreased levels of collagenase 3, osteopontin, and osteocalcin messenger RNAs. The PTH/PTHrP receptor, therefore, mediates distinct physiologic actions of both PTH and PTHrP.