Search PubMed⌕ Search

Biomedical subjects

J Fox

Publications and source records attributed to J Fox.

At least 217 records · Page 12Linked to original sources

Changes in renal function of the chicken associated with calcitonin and parathyroid hormone.

We have studied the effects of bovine parathyroid hormone (PTH) and salmon calcitonin (CT) on plasma calcium (Ca) and phosphate levels and on renal function in intact and parathyroidectomized (PTX) chickens, using a simple technique that separates urine from feces. In immature males and egg-laying females, the intravenous injection of PTH (10-20 IU/kg body wt) caused a transient fall in plasma Ca and phosphate levels, which was followed by an increase to a maximal level 20-30 min after the injection. By contrast, adult cockerels seldom showed any variation in plasma Ca or phosphate levels. In all birds, treatment with PTH increased glomerular filtration rate, urine flow rate, phosphate clearance, and Ca clearance, although this peaked later and remained elevated longer than did the phosphate clearance. The infusion of CT (1-20 U/kg over 30 min) caused a significant decrease in plasma Ca only in PTX or partially PTX chickens. All birds showed an increased GFR, urine volume, and urinary Ca excretion. In parathyroid-intact birds, the renal clearance of phosphate also increased, but peaked later and remained high longer than did Ca clearance, suggesting an increased endogenous PTH secretion. We conclude that plasma Ca and phosphate homeostasis in the chicken, as in the mammal, depends on a balanced release of PTH and CT. However, in the chicken, the response time is faster, thus minimizing the fluctuations in plasma Ca and phosphate levels resulting from exogenous hormone administration. This rapid homeostatic response is less effective when Ca demands by the body are high as in the growing or laying bird.

Age Factors↗

The financial impact of Medicare diagnosis-related groups. Effect upon hospitals receiving cardiac patients referred for tertiary care.

To evaluate the financial effects of diagnosis-related groups, we compared 128 Medicare and 183 non-Medicare cardiac patients aeromedically evacuated to a major referral center for critical care. A significant difference (p less than 0.05) was found between Medicare patients vs non-Medicare patients for age (71 +/- 7 vs 51 +/- 9 years) and mortality (13 percent vs 6 percent). No significant difference was found for admissions to the intensive care unit (95 percent vs 95 percent), mean length of stay in intensive care (4.7 +/- 5.3 vs 3.9 +/- 5.4 days), mean length of hospitalization (9.6 +/- 7.5 vs 7.9 +/- 7.0 days), mean number of International Classification Diagnoses (ICD-9) surgical operations (0.8 +/- 1.3 vs 0.6 +/- 1.2), and mean number of ICD procedures (3.0 +/- 2.3 vs 3.3 +/- 2.1). The average cost of care ($13,427 +/- $12,700 per patient) for Medicare patients was higher but not statistically different from non-Medicare patients ($10,474 +/- $10,114 per patient). Prior cost-based Medicare payments ($10,594 +/- $9,861 per patient) have been significantly (p less than 0.01) reduced by 24 percent under the Medicare diagnosis-related group (DRG) prospective payment system ($8,024 +/- $4,824). The DRG payments are significantly less than (p less than 0.001) and provide only 60 percent of the true hospital cost required to care for Medicare cardiac patients referred for tertiary care ($13,427 +/- $12,700 per patient). A Medicare DRG system adopted by third-party payers would reduce present hospital revenues from $9,524 +/- $8,422 per patient to $7,968 +/- $4,800 per patient and would provide only 68 percent of the cost required in the care of all cardiac patients referred for tertiary care ($11,690 +/- $11,344). The results of this study indicate that hospitals that receive large numbers of seriously ill cardiac patients, especially Medicare patients, referred for critical care are at a significant financial disadvantage under the Medicare DRG system. Future economic pressures may prohibit critical care treatment centers from accepting large numbers of cardiac patients referred for intensive care and reimbursed under the current Medicare DRG payment policy.

Aged↗

Direct effects of calcium channel blockers on duodenal calcium transport in vivo.

The direct effects of verapamil, diltiazem and nifedipine on duodenal calcium transport were assessed in rats by the in vivo ligated loop technique, using luminal calcium concentrations at which active and passive transport mechanisms predominate (2 and 50 mM Ca, respectively). At 2 mM Ca, addition of verapamil (0.3-10 mM) to the luminal solution caused a concentration-dependent decrease in calcium lumen-to-plasma uptake and an increase in calcium plasma-to-lumen translocation, such that at 10 mM verapamil there was a net secretion of calcium into the duodenal lumen. In contrast, nifedipine (0.3-3 mM) was without effect on calcium transport, and diltiazem reduced calcium lumen-to-plasma uptake and net calcium absorption only at 10 mM, without influencing plasma-to-lumen translocation. The verapamil-induced increase in calcium plasma-to-lumen translocation was abolished by bile duct ligation. Calcium transport was unaffected by any calcium channel blocker at 50 mM luminal calcium. Thus, verapamil can directly influence active calcium translocation in the intestine, in vivo, and may affect calcium homeostasis during chronic oral treatment with this drug.

Animals↗

Clinical application of DNA analysis in a family with OTC deficiency.

We describe the clinical application of DNA restriction fragment analysis to the genetic evaluation of a family with a child deficient in ornithine transcarbamylase (OTC). The results of protein loading studies and the interpretation of the DNA haplotype profiles for the human OTC gene are reported. DNA restriction fragment analysis may be a reliable technique for the prenatal diagnosis of OTC deficiency and identification of obligate carriers of this gene.

Amino Acid Metabolism, Inborn Errors↗

Maintaining social initiations of withdrawn handicapped and nonhandicapped preschoolers through a response-dependent fading tactic.

The effects of a teacher-implemented intervention and fading package on the social initiations of three withdrawn preschool children were investigated. Subjects' social initiations and any peer responses were recorded sequentially during free play. Intervention involved teacher prompting and contingent praise of specific social initiations (sharing, assisting, verbally organizing play) by each subject toward an available peer. Results indicated that teacher prompts and praise increased the frequency of subjects' target initiation, target initiations typically received a positive peer response, subjects' extended interactions with peers also increased, abrupt, complete removal of teacher prompting resulted in similarly abrupt reductions in subjects' social initiations, whereas response-dependent fading maintained subjects' initiations and interactions above baseline levels. Follow-up data 2 1/2 months later showed that the social initiations and interactions of two of the children remained above baseline levels.

Behavior Therapy↗

Ultrastructure of the gastric mucosa harboring Campylobacter-like organisms.

The association between Campylobacter-like organisms (CLOs) and lesions of the gastric mucosa was studied in 59 consecutive biopsies. Hematoxylin and eosin and Warthin-Starry silver stains, as well as high-resolution light microscopy (HRLM) and transmission electron microscopy (TEM), were used. The organisms were found in intimate contact with foveolar cells showing abundant phagolysosomes and alterations of the intercellular complexes. CLOs also were seen in close proximity of parietal cells in resting phase, some of which showed degenerative changes. The findings are discussed in light of recent reports linking CLOs to the cause of gastritis.

Campylobacter↗

2'-Fluoro-5-iodoarabinosylcytosine, a new potent antiviral agent: efficacy in immunosuppressed individuals with herpes zoster.

2'-Fluoro-5-iodoarabinosylcytosine (FIAC) has potent antiviral activity in vivo against herpes simplex virus types 1 and 2 and cytomegalovirus. For examination of the clinical efficacy of FIAC, a randomized, double-blind study of FIAC versus adenine arabinoside (ara-A) was conducted in 34 immunosuppressed individuals with varicella-zoster virus infections. The median time to the appearance of the last new lesion was shorter in patients who received FIAC relative to those who received ara-A (two versus five days, respectively; P less than .001) FIAC also reduced pain and accelerated initial crusting within 72 hr in a significantly greater proportion of patients when compared with ara-A (P = .004 and P = .0009, respectively). FIAC caused few toxic reactions (mild nausea and transient elevation in activity of serum aspartate aminotransferase). Thus FIAC is therapeutically superior to ara-A for the treatment of varicella-zoster virus infections in immunosuppressed subjects.

Adolescent↗

Dose independent pharmacokinetics of mexiletine in healthy volunteers.

In 12 healthy volunteers who received orally 100, 200, 300, 400 and 600 mg mexiletine at weekly intervals, the maximum plasma concentration of mexiletine and AUC increased linearly with the dose of mexiletine. Between doses there were no significant differences in the values for clearance and volume of distribution of mexiletine but there were for plasma elimination half-life. These results indicate that the kinetics of mexiletine are linear.

Administration, Oral↗

Respiratory volume perception through the nose and mouth determined noninvasively.

The relative importance of the nose vs. the mouth in the perception of respiratory volumes has never been assessed, nor have previous respiratory perception studies been performed noninvasively. Using respiratory inductive plethysmography, we monitored 12 normal subjects noninvasively when breathing either exclusively through the nose or mouth. The sensation of inspired volume mouth breathing was compared with that of nose breathing over a wide range of the inspiratory capacity. The psychophysical techniques of tidal volume duplication, tidal volume doubling, and magnitude estimation were utilized. A just noticeable difference was calculated from the constant error of the tidal volume duplication trials. The exponents for magnitude estimation were 1.06 and 1.07 for nose and mouth breathing, respectively. The other psychophysical techniques also revealed no differences in nose and mouth volume perception. These results suggest that tidal volume changes are perceived equally well through the nose and mouth. Furthermore, the location of the receptors, important in volume perception, is probably at a distal point common to the nose and mouth.

Adult↗

Experimental and theoretical studies on Tl+ interactions with the cation-selective channel of the sarcoplasmic reticulum.

This paper presents an experimental study and a theoretical interpretation of the effects of thallous ion on the electrical properties of the cation-selective channel of the sarcoplasmic reticulum (SR channel). The properties of this channel in solutions which do not contain thallous ion are consistent with the predictions of Läuger's theory for singly occupied pores (P. Lüger, 1973, Biochim. Biophys. Acta 311:423-441). However, this theory does not account for SR channel properties in mixtures containing thallous ion. SR channel conductance is less than predicted in mixed salt solutions of thallium with either potassium or ammonium (J. Fox, 1983, Biochim. Biophys. Acta 736:241-245), yet is greater than expected in mixtures of lithium and thallium. In a simple single-ion pore, the ratio of the products of the single-salt binding constants and maximum conductances is equal to the permeability ratio calculated from zero-current potential experiments under near equilibrium conditions. This is not found for the SR channel when thallous ion is present. SR channel properties in the presence of thallous ion can, however, be explained by a model which postulates the existence of two external modulatory sites on the channel, without implying double-occupancy in the permeation pathway. When thallous ion is bound to a modulatory site the maximum conductance of the channel to all permeating ions is altered (thallous included). Two other models (a three-barrier, two-internal-site pore which allows multiple occupancy, and a pore with fluctuating barriers) are discussed, but are found to be unable to fit our conductance data at different concentrations.

Animals↗

Vitamin D-dependent rickets type I in pigs.

We have bred a strain of pigs with an inherited condition of hypocalcaemic rickets, transmitted by an autosomal-recessive mechanism. Homozygous (affected) piglets grew at half the rate of their heterozygous (clinically normal) littermates, and developed profound hypocalcaemia with severe secondary hyperparathyroidism and hypophosphataemia by 8 weeks of age. In the hypocalcaemic piglets, plasma 1,25-dihydroxyvitamin D levels were low or undetectable, and 24,25-dihydroxyvitamin D3 levels were also reduced despite 25-hydroxyvitamin D3 levels being 2-fold higher. There was no detectable 25-hydroxyvitamin D3-1- or -24-hydroxylase enzyme activity in renal homogenates prepared from affected animals. Plasma and intestinal calcium-binding protein levels were reduced in the hypocalcaemic piglets. Sucrose density gradient analysis of intestinal cytosol, prepared in high-salt buffer, revealed the presence of a similar amount of a specific less than 4.2S 1,25-dihydroxyvitamin D3 binder in both groups of piglets. Administration of pharmacological doses of vitamin D3 to affected animals reversed the hypocalcaemia. We conclude that this strain of pigs has vitamin D-dependent rickets type I.

25-Hydroxyvitamin D3 1-alpha-Hydroxylase↗

Effect of 1,25-dihydroxyvitamin D deficiency on the metabolic clearance rate of 1,25-dihydroxyvitamin D3: studies using pigs with vitamin D-dependent rickets type 1.

We have used pigs with inherited vitamin D-dependent rickets type 1 to study the effect of 1,25-dihydroxyvitamin D deficiency on the metabolic clearance rate of 3H-1,25-dihydroxyvitamin D3 infused to steady-state levels in plasma. Plasma levels of 1,25-dihydroxyvitamin D were 24 +/- 1 (SEM) pmol/l in the hypocalcaemic, homozygous piglets and 196 +/- 27 pmol/l in their normocalcaemic, heterozygous siblings. The metabolic clearance rate of 1,25-dihydroxyvitamin D3 was the same in both normal heterozygous (0.90 +/- 0.02) and hypocalcaemic, homozygous piglets (0.90 +/- 0.01 ml-1 min-1 kg-1 metabolic body size). We conclude that a deficiency of circulating 1,25-dihydroxyvitamin D does not influence the clearance of 1,25-dihydroxyvitamin D3 from the circulation of pigs.

Animals↗

Effects of acute and chronic treatment with glucocorticoids on the intestinal absorption of calcium and phosphate and on plasma 1,25-dihydroxyvitamin D levels in pigs.

We have used young pigs, each prepared surgically with a Thiry-Vella loop of proximal small intestine, to study the time course of changes in the intestinal absorption of calcium, phosphate, sodium, glucose and water and on the plasma levels of 1,25-dihydroxyvitamin D after treatment of the animals with glucocorticoids. Perfusion of the intestinal loop for 6 h with a solution containing hydrocortisone or beta-methasone was without effect on the absorption of calcium or phosphate. The oral administration of betamethasone stimulated the absorption of calcium and phosphate by 15-20% for 2-3 days before the trend was reversed and absorption was progressively reduced. Chronic treatment with betamethasone inhibited only the active component of calcium and phosphate absorption. Treatment with betamethasone was associated with a sustained 25-50% increase, to a maximum by 2 days, in the absorption of sodium, glucose and water. Plasma levels of 1,25-dihydroxyvitamin D were reduced within 2 days of the start of treatment and reached a minimum (40-50% decrease) in 4-6 days. We conclude that the initial stimulation of calcium and phosphate absorption is caused by the increased absorption of water. The long-term decrease in absorption may not be caused solely by the decreased circulating levels of 1,25-dihydroxyvitamin D since absorption continued to fall for several weeks after 1,25-dihydroxyvitamin D levels had reached a minimum.

Animals↗