In vivo evaluation of the third generation biodegradable stent: a novel approach to avoiding the forgotten stent syndrome.

PURPOSE: Ureteral stents are prone to irritation, encrustation and infection, and they require additional procedures for removal. Furthermore, indwelling polymer stents are often forgotten with devastating consequences to the patient. We describe the degradation time, and physiological and histological responses elicited by a novel biodegradable ureteral stent in a porcine model. MATERIALS AND METHODS: A total of 16 female Yorkshire pigs were used in the study. Ten biodegradable Uriprene™ stents and 6 biostable Polaris™ stents were cystoscopically inserted unilaterally in 2 groups of animals. Excretory urogram, and blood and urine tests were performed on different days until day 28. Biostable stents were removed on day 21. On day 28 all pigs underwent necropsy for microscopic and histological evaluation. RESULTS: Nine of the 10 biodegradable stents (90%) degraded completely by 4 weeks, while 1 pig had 3 fragments smaller than 1.5 cm in the bladder. Excretory urogram showed equivalent drainage and significantly less hydronephrosis in biodegradable stented kidneys. Blood and urine parameters were similar in the 2 groups. A transient increase in serum creatinine on day 7 in 40% of the pigs with a degradable stent resolved by day 10. There were significantly fewer abnormal histological findings in the degradable stent group. We evaluated drainage characteristics in an unobstructed ureter and results may not be representative of what develops in obstructed ureters. CONCLUSIONS: The third generation biodegradable stent is a safe, effective alternative to conventional polymer stents, resulting in equivalent drainage and less hydronephrosis.

Effect of mesh construction on the physicomechanical properties of bicomponent knit mesh using yarns derived from degradable copolyesters.

The use of mesh to repair abdominal wall defects has significantly increased over the past two decades owing to a perceived reduction in recurrence rates compared to primary repairs. However, the use of a mesh in vivo has introduced undesirable patient complications. As a result, there exists an unmet need for a mesh design which exhibits improved biocompatibility. In the present study, the in vitro conditioned modulation of biocompatibility-relevant physical and mechanical mesh properties using (1) absorbable yarns with different degradation profiles and (2) different mesh constructions employing the warp and weft knitting technologies was investigated. A novel warp-knit, bicomponent mesh (WK1) was developed that modulates physicomechanical properties and that (1) possesses short-term structural stiffness, (2) provides a gradual transition phase, and (3) possesses long-term compliance with force-extension properties similar to the abdominal wall. The use of two different degradable copolyester yarns facilitated the modulation of mesh physicomechanical properties, whereas the knit construction determined the resultant porosity, area weight, thickness, strength, and extension of the mesh. The lack of variation in the knit pattern for the weft knit (DM1) mesh made it one-dimensional, producing strength loss with time but showing no change in extensibility following the substantial degradation of the fast-degrading yarn.

Injectable in situ forming controlled release implant composed of a poly-ether-ester-carbonate and applications in the field of chemotherapy.

Polymeric controlled delivery systems hold great promise in the field of modern medicine. Such technology has already been converted into commercially viable products in a myriad of fields. Chemotherapy is an example of such an area where constant efficacious levels of drug can greatly enhance clinical outcomes. The key to designing such therapies is the preparation of the proper delivery system. To this end, a series of bioresorbable polyether-ester-carbonate copolymers have been developed, which when combined with a diluent, are capable injection into the body and consistently forming a drug delivery depot. The study delineated here aimed at producing a more effective treatment of a common drug, paclitaxel, using the polymeric carrier. The polymer carrier system exhibited controlled release of paclitaxel both in vitro and in vivo. Drug concentrations were analyzed by high performance liquid chromatography and apoptotic activity was confirmed through flow cytometry. Relevant success was exhibited by the regression of tumor size following a multiple injection treatment regimen in a murine xenograft model. This multiple injection treatment shows promising results when compared to the traditional paclitaxel paradigm of a single injection for a period of 3 weeks.

Development of novel biodegradable polymer scaffolds for vascular tissue engineering.

Functional connective tissues have been developed using tissue engineering approach by seeding cells on biodegradable scaffolds such as polyglycolic acid (PGA). However, a major drawback of tissue engineering approaches that utilize synthetic polymers is the persistence of polymer remnants in engineered tissues at the end of culture. Such polymer fragments may significantly degrade tissue mechanics and stimulate local inflammatory responses in vivo. In this study, several polymeric materials with a range of degradation profiles were developed and evaluated for their potential applications in construction of collagen matrix-rich tissues, particularly tissue-engineered blood vessels. The degradation characteristics of these polymers were compared as were their characteristics vis-à-vis cell adhesion and proliferation, collagen synthesis, and ability to support growth of engineered vessels. Under aqueous conditions at 37°C, Polymer I (comprising 84% glycolide and 16% trimethylene carbonate [TMC]) had a similar degradation profile to PGA, Polymer II (comprising 84% glycolide, 14% TMC, and 2% polyethylene succinate) degradedly more slowly, but Polymer III (comprising 87% glycolide, 7% TMC, and 6% polyethylene glycol) had a more extensive degradation as compared to PGA. All polymers supported cell proliferation, but Polymer III improved collagen production and engineered vessel mechanics as compared with PGA. In addition, more slowly degrading polymers were associated with poorer final vessel mechanics. These results suggest that polymers that degrade more quickly during tissue culture actually result in improved engineered tissue mechanics, by virtue of decreased disruption of collagenous extracellular matrix.

Next generation biodegradable ureteral stent in a yucatan pig model.

PURPOSE: Ureteral stents are commonly used to facilitate kidney drainage but they may produce significant stent symptoms and morbidity, and require a secondary procedure for removal. Previous biodegradable stents showed bio-incompatibility or inconsistent degradation, requiring extra procedures to remove undegraded stent fragments. We previously reported a first generation biodegradable stent composed of suture-like material that required placement through the lumen of a sheath and degraded by 10 weeks. We now report second and third generation biodegradable stents that degrade more rapidly and can be placed directly over a polytetrafluoroethylene guidewire. MATERIALS AND METHODS: Two groups of 16 Yucatan pigs each were unilaterally stented endoscopically with a control nondegradable (biostable) stent or a second generation degradable Uriprene stent. Blood studies, renal ultrasound and excretory urography were done throughout the study to determine renal function, hydronephrosis and stent degradation. Genitourinary organs were harvested at necropsy for pathological analysis. A third generation stent designed to improve degradation time was bilaterally implanted endoscopically into 4 Yorkshire Farm pigs (total of 8 stents), followed by excretory urography weekly to assess degradation and kidney function. Biomaterial parameters were tested. RESULTS: Second generation stents began degrading at 2 weeks and were completely degraded by 10 weeks. All third generation stents were degraded by 4 weeks. Hydronephrosis was considerably less in the Uriprene group than in control biostable stented kidneys. Biostable stented ureters showed an average higher degree of inflammation, uropathy and nephropathy. Physical characteristics indicate that Uriprene stents are significantly more resistant to stent compression and have markedly higher tensile strength and coil strength comparable to that of other commercially available plastic stents. CONCLUSIONS: Our study confirms that Uriprene stents are biocompatible and provide good renal drainage. They hold promise for decreasing the need for a secondary procedure and stent related morbidity, such as infection and irritative symptoms.

A pilot safety and tolerability study of a nonhormonal vaginal contraceptive ring.

OBJECTIVE: To conduct a pilot safety and tolerability study of the Ovaprene ring (Poly-Med Inc., Clemson University, Clemson, South Carolina) as a barrier contraceptive. STUDY DESIGN: Open-label, single-arm, observational study in a convenient sample of volunteers. Women meeting inclusion criteria and using another contraceptive method were instructed in proper insertion of the ring at the completion of their menses, with removal at their subsequent menses or 29 days. Baseline Pap smears, vaginal cultures and colposcopy were performed, with follow-up postcoital testing and acceptability questionnaires. RESULTS: Twenty women enrolled; all completed one cycle of use. Rings were inserted properly and retained in place (range, 5-29 days). Patient questionnaires revealed no pain or bleeding, and no colposcopic abnormalities were seen. Semiquantitative cultures yielded no significant changes in vaginal flora. Postcoital testing revealed nonviable sperm (motile/total, mean count/10 high power fields) 2/ > 20 in the vaginal pool and 0/0 in cervical mucus. There were no serious adverse effects. CONCLUSION: The Ovaprene device is well tolerated and acceptable to sexually active women and their partners.

Investigation of a novel degradable ureteral stent in a porcine model.

PURPOSE: Ureteral stents often result in patient morbidity and the potential for a forgotten stent. When the suture tether is detached, a secondary procedure is required for removal. Previous attempts at developing biodegradable ureteral stents have been unsuccessful since those stents were not biocompatible or they failed to degrade in timely fashion. We evaluated a new biodegradable Double-J stent in a porcine model. MATERIALS AND METHODS: A total of 36 Yorkshire pigs were stented unilaterally with a biodegradable Uriprene stent or a standard biostable control stent. Excretory urograms, and blood and urine tests were performed at weeks 2, 3, 4, 5, 7 and 10. Four animals per group were sacrificed after 2, 4, 7 and 10 weeks to determine stent degradation and obtain samples for pathological evaluation. RESULTS: Degradable ureteral stents began to degrade at 3 weeks. By weeks 7 and 10, 60% and 100% of the stents, respectively, were fully degraded. There was no significant difference in laboratory parameters or the amount of hydronephrosis between the 2 groups. However, ureteral dilatation was significantly more pronounced in the control group than in the Uriprene group. The novel stent was biocompatible on histological evaluation and it led to significantly less urinary tract infections than in controls. CONCLUSIONS: The novel Uriprene stents provided drainage similar to that of regular stents and they were completely degraded by 10 weeks. Moreover, these stents resulted in less ureteral dilatation and fewer positive urine cultures. Biocompatibility was good and human trials will be forthcoming.

Probe hybridization array typing: a binary typing method for Escherichia coli.

The ability to distinguish between Escherichia coli strains is critical for outbreak investigations. Binary typing, based on the presence or absence of genetic material, provides a high-throughput alternative to gel- and PCR-based typing techniques that generate complex banding patterns and lack uniform interpretation criteria. We developed, validated, and determined the discriminatory power of an E. coli binary typing method, probe hybridization array typing (PHAT). In PHAT, the absence or presence of genetic material is identified by using DNA hybridization to produce a reproducible and portable fingerprint for each genome. PHAT probes were generated from genome subtractive hybridization experiments. We PHAT typed the ECOR collection of strains from a variety of geographical locations, and 33 rectal E. coli strains selected from college-aged women with urinary tract infection. In the set of 33 human rectal strains, the discriminatory power of PHAT (98%) equaled that of multilocus sequence typing (MLST) and pulsed-field gel electrophoresis. However, for ECOR strains, which include nonhuman strains, the current set of PHAT probes was less discriminating than MLST, ribotyping, and enterobacterial repetitive intergenic consensus sequence PCR (80% versus 97, 92, and 97%, respectively). When we limited the analysis to ECOR strains of B2 and D lineage, which are associated with human infection, current PHAT probes were highly discriminatory (94%). PHAT can be applied in a high-throughput format (i.e., "library on a slide"), the discriminatory ability can be varied based on the probe set, and PHAT is readily adapted to other bacterial species with high variation in genetic content.

Direct correlation between adsorption-induced changes in protein structure and platelet adhesion.

It is widely recognized that adsorbed proteins on biomaterial surfaces tend to initiate thrombus formation, although the specific mechanisms involved are still not well understood. In attempts to decrease the conformational change of adsorbed proteins, surface treatments that reduce surface hydrophobicity have been considered, such as the sulfonation of low-density polyethylene and isotactic polypropylene. The objectives of this present research were to study how changes in surface chemistry influence the degree of conformational change of adsorbing proteins and to investigate the correlation between the change in adsorbed protein structure and platelet response. Adsorbed porcine serum albumin and porcine fibrinogen were used as the model proteins for determining the effects of sulfonation on protein conformational change. Circular dichroism spectroscopy studies showed that the proteins were less altered structurally on the sulfonated surfaces. Platelet adhesion studies were used to correlate the number of adhered platelets with the amount of conformational change in adsorbed proteins on the polymer surface. The results of these studies show a linear correlation between platelet adhesion and the degree of adsorption-induced protein conformational change. These findings suggest that the degree of protein conformational change after adsorption is a dominant mechanism governing platelet interactions with biomaterial surfaces.

Absorbable microparticulate cation exchanger for immunotherapeutic delivery.

An absorbable microparticulate cation exchanger was synthesized as a versatile carrier for biologically active proteins. In this work, acid-terminated polyglycolide (or polyglycolic acid) microparticulates (PG-MP) were surface modified for either sustained release of cytokines or as a platform for immunomodulation. The intended goal was to achieve in situ recruitment/maturation of dendritic cells and activation of T cells for tumor immunotherapy. PG-MP were prepared with a volume weighted mean diameter of 7.02 micro (range: 2.09-14.58 micro). Accessible carboxylic acid groups were determined to be 0.3 mmol/g with a corresponding zeta potential of -21.87 mV in phosphate-buffered saline. Under low magnification, scanning electron microscopy (SEM) revealed a highly textured surface due to processing from repetitive jet milling. However, a moderately porous architecture was noted at higher magnification. Electron spectroscopy for chemical analysis was used to characterize the PG-MP surface before and after adsorption of human granulocyte-macrophage colony stimulating factor (GM-CSF). Adsorption of GM-CSF on PG-MP (PG-GMCSF) resulted in a modest increase in the surface atomic concentration of nitrogen (0.97%). Pretreating the surface with poly-L-lysine (PG/Lys-GMCSF) prior to adding GM-CSF produced a nearly threefold increase in the surface nitrogen concentration (4.20% compared to 1.47%). This manipulation not only increased loading content, but also prolonged the release of GM-CSF released from 6 days to 26 days. ESCA on the post-release PG-MP samples (PG-GMCSF and PG/Lys-GMCSF) revealed a similar residual surface nitrogen concentration (2.26% vs. 2.35%). The observation was consistent with irreversibly adsorbed GM-CSF. It is postulated that irreversibly bound GM-CSF is released over time as a function of microparticulate degradation. Biological activity of released GM-CSF was confirmed by the proliferation of a GM-CSF-dependent cell line (TF-1) in the presence of microparticulates. PG-MP mediated activation of T cells was achieved through irreversible adsorption of either antimouse cd3 plus antimouse cd28 monoclonal antibodies (alpha-cd3/cd28-MP) or antihuman CD3 plus antihuman CD28 monoclonal antibodies (alpha-CD3/CD28-MP) on PG-MP. Irreversibly adsorbed antibodies were capable of activating both resting mouse and human T cells. Intracellular flow cytometry on mouse T cells revealed that nearly 50% of the activated cells produced interferon-gamma (IFN-gamma). This was consistent with a TH-1 or cell-mediated response. In vivo efficacy was evaluated in a mouse flank tumor model showing a significant antitumor effect both alone and in combination. Combination therapy was most effective at preventing tumor implantation (8/8 mice) and was able induce tumor regression (4/7 mice) and/or stable disease (3/7 mice) in a regression model. In these studies, immunohistochemistry was used to confirm local recruitment of dendritic cells. In conclusion, the PG-MP represents a novel absorbable cation exchanger that can be readily manipulated to deliver biologically active proteins for immunotherapy.

Development of novel substrates for tumor immunotherapy.

Acid-terminated polyglycolide microparticles (PG-MP) were prepared as a versatile substrate that could be surface-modified for either immobilization of anti-cd3 and anti-cd28 mAb to activate T cells or sustained release of granulocyte-macrophage colony stimulating factor (GM-CSF) for dendritic cell (DC) recruitment and maturation. PG-MP were prepared with a volume-weighted mean diameter of 56 or 57 microm. Accessible carboxylic acid group concentration was determined by potentiometric titration to be 0.3 mmole/g and corresponded to a zeta potential of -21.87 mV. PG-MP immobilized with either anti-human CD3/CD28 or anti-mouse cd3/cd28 induced significant proliferation of T cells. Intracellular flow cytometry in activated mouse T cells was significant for IFN-gamma, but not IL-4. Microparticles surface-modified for GM-CSF release were prepared from either PG-MP or PG pre-treated with poly-L-lysine (PG-Lys) to manipulate surface charge. GM-CSF released from PG-Lys-MP was observed for up to 26 days. The biologic activity of released GM-CSF was confirmed by using a h-GM-CSF-dependent cell line. The efficacy of the alpha-cd3/cd28-MP and GMCSF-MP was studied in a syngeneic mouse tumor prevention and regression model. Co-injection of Meth A fibrosarcoma cells with alpha-cd3/cd28-MP and GMCSF-MP completely prevented tumor implantation (0/24). The regression model showed complete tumor regression in four of seven animals and stable disease in three of seven. In the latter study, a dramatic level of DC infiltration was observed compared to controls.

In vitro evaluation of phosphonylated low-density polyethylene for vascular applications.

The use of catheters for vascular applications is often complicated by the development of friction between the catheter material and the vessel wall, which leads to endothelial cell removal and intimal lesions. Phosphonylation, a chemical surface treatment, has been proposed as a means of increasing the hydrophilicity of low-density polyethylene (LDPE), a commonly used catheter material, in efforts to impart lubricity to the material and reduce vascular tissue damage. In an in vitro tribological study, phosphonylated LDPE produced a lower coefficient of friction and allowed greater retention of endothelial cells on vessels as compared to untreated LDPE when the materials were reciprocated against normal porcine aorta. Chemical characterizations of the LDPE before and after friction testing involving Fourier transform infrared and energy-dispersive X-ray (EDX) confirmed the phosphorus content on phosphonylated LDPE. Election spectroscopy for chemical analysis (ESCA) and atomic force micrscope (AFM) analyses verified that proteins initially adsorb to both the phosphonylated and untreated LDPE surfaces and that the proteins interfere with water to lubricate the surfaces. However, with repeated friction, proteins are removed from the surface and hydrophilicity, as imparted by phosphonylation, becomes a principal factor in the lubrication process.

[Suitability of polyvinylpyrrolidone (PVP) as a substance for hydrogel intraocular lenses]. / Eignung von Polyvinylpyrrolidon als Material für Hydrogelintraokularlinsen.

UNLABELLED: Conventional PMMA intraocular lenses (IOLs) have been shown to restore vision successfully after cataract surgery, but have been associated with complications such as decentration, destruction of intraocular tissue, and posterior capsule opacification. Expansile IOLs based on cross-inked polyhydroxyethylmethacrylate (PHEMA) also undergo chemically induced hydrolysis, polymer leaching and gel fragmentation. The focus of this research is to prepare and characterize hydrogel IOLs prepared from PVP using gamma-irradiation. METHODS: Hydrogels were prepared from aqueous solutions of PVP by free radical polymerization as a function of gamma-irradiation dose (0.5 x 106 to 2.5 x 106 rad), PVP concentration (4% to 16% w/v), molecular weight (MW) (10 x 103 to 360 x 103 Da), and blending with low and high MW PVP. Viscometric analysis, swelling characterization studies, and polymer leaching studies were carried out to access network formation. In addition changes in lens geometry in an animal model were measured in response to cycloplegic eyedrops. RESULTS: Cross-linking efficiency was greatest with an initial MW of 360 x 103 Da and lowest with an initial MW of 10 x 103 Da. The time to reach equilibrium from the glassy state and the degree of swelling in saline decreased with increasing gamma-irradiation dose and increased with concentration of PVP and blending of low and high MW PVP. The equilibrium water content ranged from 90 to 98% (w/w). Eighty-five percent of the equilibrium dimensions could be achieved within 90 min. Gravimetric analysis and HPLC indicate that the amount of PVP that is not incorporated into the network ranges from 0.25% to 6% (w/w). This was inversely related to the gamma-irradiation dose. The MW of the leached samples was estimated to be greater than 10 x 103 Da in all cases. CONCLUSIONS: PVP hydrogel IOLs prepared by gamma-irradiation have advantages in terms of chemical stability, high water content, and ease of preparation. They may not need further purification or sterilization prior to implantation. In addition, they may allow for accommodation. No comments can be made regarding the biocompatibility, long-term stability, or optical quality at this time.

Development of oral vaccines to stimulate mucosal and systemic immunity: barriers and novel strategies.

Many questions regarding the induction of mucosal and humoral immunity through oral vaccination exist. Efficacy is dependent on the physicochemical properties of the antigen, the gastrointestinal environment, the presence of adjuvants, and the mode of delivery. Understanding how these factors interrelate will be critical to the development of new oral vaccines. A number of approaches are currently being studied to enhance the immune response. These include chemical conjugation, immunization with recombinant bacteria and viruses, and mucosal adjuvants. Vaccine delivery systems prepared from natural or synthetic polymers is a particularly promising area because many of the current methods to induce mucosal stimulation can be incorporated within these systems. Thus, the polymeric delivery system functions as a platform to facilitate uptake by M-cells and prolong antigen presentation and stimulation of the Peyer's patches. This Review examines some of the physiological and immunological barriers associated with oral vaccination and discusses novel strategies to overcome such barriers.

Evaluation of an orally administered vaccine, using hydrogels containing bacterial exotoxins of Pasteurella haemolytica, in cattle.

Poly(methacrylic acid) hydrogels were tested for oral delivery of a vaccine against Pasteurella haemolytica infection in cattle. Culture supernatants of P haemolytica, the most common bacterium associated with pneumonia in cattle, were used as the antigens in the vaccine. Hydrogels containing culture supernatants were administered orally to calves. Calves were then challenge-exposed with virulent P haemolytica. Calves were euthanatized 3 days after challenge exposure. The lungs of each calf were scored for severity and size of pneumonic lesions. Results indicated that vaccinated calves had smaller, less severe pneumonic lesions and lived longer than nonvaccinated calves. These results indicated that hydrogels can be used to deliver vaccines orally to calves to enhance resistance to pneumonia caused by P haemolytica.

Use of ultrasound imaging and fluoroscopic imaging to study gastric retention of enzyme-digestible hydrogels.

Ultrasound and fluoroscopic imaging techniques were used to monitor the gastric retention of enzyme-digestible hydrogels in the canine stomach. When water was present in the stomach, ultrasound imaging was very effective in monitoring the position of the hydrogel in the stomach, solvent penetration into the gel, and the gastric tissue-gel interactions during peristalsis. Rubbery or fully swollen hydrogels appeared as sonolucent objects with ultrasound imaging. Partially swollen hydrogels displayed a sonolucent outer layer due to solvent penetration and a centrally located bright echo resulting from the acoustic impedance mismatch at the glassy/rubbery interface. The degree of gastric tissue-gel interactions during peristalsis was inversely related to the extent of lumenal distention with water. The effectiveness of peristaltic contractions in driving the hydrogel toward the pyloric sphincter increased as the water was emptied from the stomach. In the absence of water, imaging of the gel with ultrasound became difficult. For this reason, gels were loaded with diatrizoate meglumine/sodium diatrizoate to visualize in real-time using fluoroscopic imaging. Fluoroscopic imaging allowed only indirect assessment of the hydrogel movement during peristalsis and the degree of hydrogel swelling. The gastric retention of the hydrogel under fasted conditions was influenced by the degree of gel deformation in response to peristaltic contractions. Hydrogels with a low degree of deformation during peristalsis showed long gastric retention times. The utilization of ultrasound imaging and fluoroscopic imaging for monitoring dynamic events in the stomach provided information on hydrogel properties which are important to gastric retention. The use of these imaging techniques in the development of long-term oral drug delivery systems is described.

Biochemical and mechanical characterization of enzyme-digestible hydrogels.

Albumin-cross-linked hydrogels were prepared by free radical polymerization using 1-vinyl-2-pyrrolidinone as a monomer and functionalized albumin as a crosslinking agent. The degree of chemical cross-linking was controlled by varying the degree of albumin functionality and the concentration of albumin. With emphasis placed on the potential use of these hydrogels for long-term oral drug delivery, gel characterization studies examined both the swelling and the mechanical properties in the absence and presence of pepsin. In the absence of pepsin, the equilibrium swelling ratio in simulated gastric fluid ranged from 17 to 55, depending on the degree of albumin functionality and the albumin concentration. Swelling was pH dependent at pH's greater than 7. The uptake of solvent into the dried hydrogels was determined to be Fickian. The integrity of swelling gels was dependent on the concentration of the functionalized albumin as well as on the degree of albumin functionality. In the presence of pepsin, a predominance of either surface or bulk degradation was observed, depending on the functionality of the albumin used as a cross-linker. Gel integrity during pepsin degradation also showed a marked dependence on the albumin functionality.

Potassium changes with age.

Measurements of total exchangeable potassium and total exchangeable sodium, total body water and extracellular fluid volumes were made in 69 patients aged 30-90+ years, using multiple isotope techniques. The patients were not suffering from any chronic disorder or having potassium or diuretic therapy and were considered to be having a normal hospital diet. The study showed a direct correlation between potassium and age, in that total exchangeable potassium decreased as age increased. The same relation was obtained when total exchangeable potassium was related to dry body weight and fat-free body water to age. Although total exchangeable sodium diminished with increasing age, the ratio of total exchangeable potassium was approximately 1 at 30 years of age rising to approximately 2 at 90+ years of age.