Phosphate kinetics during hemodialysis: Evidence for biphasic regulation

BACKGROUND: Hyperphosphatemia in the hemodialysis population is ubiquitous, but phosphate kinetics during hemodialysis is poorly understood. METHODS: Twenty-nine hemodialysis patients each received one long and one short dialysis, equivalent in terms of urea clearance. Phosphate concentrations were measured during each treatment and for one hour thereafter. A new model of phosphate kinetics was developed and implemented in VisSim. This model characterized additional processes involved in phosphate kinetics explaining the departure of the measured data from a standard two-pool model. RESULTS: Pre-dialysis phosphate concentrations were similar in long and short dialysis groups. Post-dialysis phosphate concentrations in long dialysis were higher than in short dialysis (P < 0.02) despite removal of a greater mass of phosphate (P < 0.001). In both long and short dialysis serum phosphate concentrations initially fell in accordance with two-pool kinetics, but thereafter plateaued or increased despite continuing phosphate removal. Implementation of an additional regulatory mechanism such that a third pool liberates phosphate to maintain an intrinsic target concentration (1.18 +/- 0.06 mmol/L; 95% confidence intervals, CI) explained the data in 24% of treatments. The further addition of a fourth pool hysteresis element triggered by critically low phosphate levels (0.80 +/- 0.07 mmol/L, CI) yielded an excellent correlation with the observed data in the remaining 76% of treatments (cumulative standard deviation 0.027 +/- 0.004 mmol/L, CI). The critically low concentration correlated with pre-dialysis phosphate levels (r=0.67, P < 0.0001). CONCLUSION: Modeling of phosphate kinetics during hemodialysis implies regulation involving up to four phosphate pools. The accuracy of this model suggests that the proposed mechanisms have physiological validity.     

Patterns of illness and injury encountered in amateur ocean yacht racing: an analysis of the British Telecom Round the World Yacht Race 1996-1997

OBJECTIVES: To quantify the incidence and type of medical problem arising during an amateur circumnavigation yacht race, the BT Global Challenge. METHODS: All cases from 14 participating yachts in a confidential medical log completed by an appointed medic were reported. RESULTS: A total of 685 cases were reported, of which 299 (43.6%) were injuries and 386 (56.4%) illnesses. The subtype of injury, illness, and three evacuations at sea are described. CONCLUSION: Injury and other forms of medical problem are relatively common in an amateur long distance ocean yacht race. Most can be adequately managed at sea, provided that optimal communication, training, and equipment are provided and maintained.     

Vitamin A supplementation in Tanzania: the impact of a change in programmatic delivery strategy on coverage

Background  

Efficient delivery strategies for health interventions are essential for high and sustainable coverage. We report impact of a change in programmatic delivery strategy from routine delivery through the Expanded Programme on Immunization (EPI+) approach to twice-yearly mass distribution campaigns on coverage of vitamin A supplementation in Tanzania     

Vagal and cardiac reactivity to psychological stressors in trained and untrained men

PURPOSE: The aim of this study was to determine whether higher aerobic fitness is associated with enhanced vagal influences on the myocardium, resulting in moderation of chronotropic cardiac activity during psychological stress and recovery. METHOD: Heart period (HP) and respiratory sinus arrhythmia (RSA) were obtained from 10 aerobically trained (AT) and 10 untrained (UT) college-aged men at rest and during three contiguous psychological challenges and 3 min of recovery. Ratings of perceived stress were obtained at the end of the rest period, at the midpoint of each stressor, and at 30 s into recovery. Time series methods were used to quantify RSA from the beat-to-beat HP series. Responsivity was assessed both in terms of absolute levels of activity and phasic changes in activity (task or recovery minus baseline). RESULTS: Both groups reported similar levels of subjective stress throughout the experiment. The AT exhibited longer HP at rest and during psychological stress and recovery than did the UT. However, the groups did not differ on RSA at rest or during psychological stress and recovery, nor did they differ on phasic changes in RSA or HP during stress or recovery. Additionally, aerobic capacity was not correlated with absolute levels or phasic changes in RSA during psychological challenge for either group and, except in Min 2 for the UT, similar results were obtained for recovery. CONCLUSIONS: The results supported the hypothesis that, among young men, higher aerobic fitness is associated with longer HP at rest and during psychological stress and recovery. However, the lower cardiac chronotropic activation observed among the AT relative to the UT was not paralleled by a group difference in the amplitude of RSA. These results suggest that the group difference in HP was not mediated directly by the vagal mechanisms manifested in the amplitude of RSA.     

Differential growth control of normal, preneoplastic and neoplastic Syrian hamster embryo cells in serum-free media

The objective of this work was to develop a serum-free mediumthat supported the growth of secondary Syrian hamster embryo(SHE) cells suitable for use in the morphological transformationassay (MTA). The current assay employs high levels of fetalbovine serum, each lot of which must be selected for its efficacyin the assay. To circumvent the problems associated with theuse of serum, two serum-free media (CGM–4 and CGM–9)were developed. The approach used was to replace serum withmore defined hormones and growth factors. DME/F12 with low NaHCO₃(pH 6.7) was chosen as a basal nutrient medium since this pHhas been reported to give enhanced transformation. Both serum-freemedia supported the clonal high density growth of normal secondarySHE cells. These media were also found to support the growthof several established SHE cell lines exhibiting successivestages of neoplastic progression. However, significant differentialresponses of the individual cell lines to CGM-4 and CGM-9 wereobserved, whereas, in serum-supplemented medium all three linesresponded similarly. These results raise the hope that CGM-4and CGM-9 will be useful for studies of altered autocrine functionduring transformation and progression as well as for use inthe transformation assay itself.     

A new amino acid mixture permits new approaches to the treatment of phenylketonuria

A new amino acid mixture for incorporation into medical foods for the treatment of hyperphenylalaninemia has been tested in a regular clinic. The mix is designed to be as unobtrusive as possible, consistent with good nutrition. After more than 1 year of trial as a beverage, we have shown that it is safe and well tolerated but that plasma phenylalanine is no better controlled than with some other products. The mix can be incorporated into a large number of different foods without affecting the taste. Occult monitoring of the quantity of medical foods purchased compared with the amounts reported to be consumed in diet histories provides an excellent way to monitor dietary compliance.     

Induction of hepatic cell proliferation and unscheduled DNA synthesis in mouse hepatocytes following in vivo treatment

We have modified the in vivo-in vitro hepatocyte DNA repairassay for measurement of unscheduled DNA synthesis (UDS) andhepatic cell proliferation in B6C3F1 mice. Dimethylnitros-amineand methylmethane sulfonate produced significant increases inUDS in both rats and mice. 2-Acetylaminofluorene induced a significantincrease in UDS in rats, but not in mice. The mouse hepatocarcinogens,carbon tetrachloride, trichloroethylene, polybrominated biphenylsand 2,6-dichloro-p-phenylenediamine all failed to induce UDSin male and female mice, but all induced significant elevationsin hepatic cell proliferation. Increased cell turnover in theliver may therefore be an important mechanism in hepatocarcinogenicityin the mouse.     

Supraacetabular insufficiency fractures

Insufficiency fractures in the supraacetabular region were identified in five women, aged 55-83 years. Factors contributing to the diminished resistance of their bones included postmenopausal osteoporosis, steroid therapy, radiation therapy, and rheumatoid arthritis. The supraacetabular fractures were seen on routine radiographs as hazy bands of sclerosis located immediately above and parallel to the acetabular roof. All five patients had additional fractures in the spine or pelvis. Supraacetabular insufficiency fractures may be an unsuspected cause of hip pain, especially in older women.