Significant Differences In Serum Concentrations Research Articles

Serum Lp(a) lipoprotein concentrations in insulin dependent diabetic patients with microalbuminuria.

To compare the serum concentrations of lipoproteins and apolipoproteins in insulin dependent diabetic patients with and without microalbuminuria. Cross sectional study. Paediatric and medical outpatient clinic at a university hospital. 76 insulin dependent diabetic patients: 41 with microalbuminuria (20 males, 21 females) and 35 controls without microalbuminuria (18 males, 17 females). The two groups were similar with respect to age, duration of disease, and haemoglobin A1c concentrations before the study. Serum concentrations of Lp(a) lipoprotein, total cholesterol, high density lipoprotein cholesterol, very low density lipoprotein cholesterol, low density lipoprotein cholesterol, triglycerides, and apolipoproteins A-I, A-II, and B. Median serum Lp(a) lipoprotein concentration was 10.0 mg/100 ml in the microalbuminuric group and 4.9 mg/100 ml in the control group (p = 0.007). 17 (41%) of the microalbuminuric patients and five (14%) of the control patients had Lp(a) lipoprotein values above the upper quartile of a normal population. Median serum triglycerides concentrations in the microalbuminuric and control groups were 1.15 mmol/l and 0.88 mmol/l respectively (p = 0.03). Median very low density lipoprotein cholesterol concentration was 0.52 mmol/l in the microalbuminuric group and 0.40 mmol/l in the control group (p = 0.03). No significant differences in serum concentrations of total cholesterol, high density lipoprotein cholesterol, low density lipoprotein cholesterol, or apolipoproteins A-I, A-II, and B were found between the groups. Serum concentrations of Lp(a) lipoprotein are twice as high in insulin dependent diabetic patients with microalbuminuria as in those without microalbuminuria. Increased concentrations of Lp(a) lipoprotein might partly explain the increased morbidity and mortality from cardiovascular disease observed among patients with diabetic nephropathy.

Delivery of ultraviolet-inactivated 35S-herpesvirus across an osmotically modified blood-brain barrier

The present studies were undertaken to determine if viral particles can be delivered across the rat blood-brain barrier (BBB). Osmotic BBB modification with intracarotid mannitol (25%) was immediately followed by bolus intracarotid administration of 0.5 ml purified, ultraviolet-inactivated, herpes simplex virus type 1 endogenously labeled with 35S-labeled methionine (2.0 x 10(6) cpm, approximately 5 x 10(8) plaque-forming units/ml). After 60 minutes, intravascular virus was cleared by saline perfusion and the animals were sacrificed. A marked increase (fourfold, p less than or equal to 0.02) in radioactivity was observed in the ipsilateral brain hemisphere when compared to control animals without barrier modification. Administration of intravenous virus immediately after BBB modification displayed no difference in delivery when compared to intracarotid saline-infused controls (without BBB modification) suggesting the importance of a first-pass phenomenon. There were no significant differences in serum concentrations among intracarotid or intravenous groups. These preliminary studies suggest the possibility of delivering viral particles across the BBB with osmotic disruption, which may permit delivery of genetic material in replication-defective viral vectors in the feline model of GM2-gangliosidosis.

Inadequacy of FDA dosing guidelines for theophylline use in neonates.

The efficacy of the FDA guidelines for theophylline dosing in newborns was evaluated retrospectively in 224 patients who had clearance data available. Mean projected post loading dose serum concentration was 4.1 +/- 1.0 mg/L in 160 patients. Mean projected steady-state concentration was 4.8 +/- 1.6 mg/L in 189 patients receiving intravenous aminophylline and 4.2 +/- 1.3 mg/L in 35 patients on oral therapy. Projected serum concentrations were subtherapeutic (less than 6.0 mg/L) in 181 of the 224 patients analyzed. There was a statistically significant difference in serum concentrations between asphyxiated and nonasphyxiated patients (p less than 0.001). There was no significant difference in mean projected serum concentrations between patients age 26-41 weeks (postconceptional age). This study suggests that the FDA dosing guidelines for theophylline in infants is inadequate and results in subtherapeutic (less than 6.0 mg/L) serum concentrations in the majority of newborns.

Contribution of the ovary versus hypothalamus-pituitary to termination of estrous cycles in aging rats using ovarian transplants.

Vaginal smear patterns were monitored for 80 days after orthotopic ovarian transplants (OvTr) between young and old rats to examine the importance of the ovary and the hypothalamuspituitary in the termination of estrous cyclic activity. At the end of this period, the rats were sacrificed at 2200 h, blood was collected for measurement of ovarian steroids and gonadotropins, and ovaries were prepared for histological study. A second experiment examined the effect of a reduction in ovarian tissue by unilateral ovariectomy of old rats on estrous cyclicity during the first 16 days following surgery. During the 80 days of observation, 25% of the old and 0% of the young sham-operated rats showed irregular estrous cycles. This decrease in cyclicity followed a decrease in the total number of oocytes in the ovaries. Rats with OvTr did not cycle as regularly as young or old intact rats; and 75% of both young and old recipients with OvTr were acydic by Day 80. Ovarian factors were implicated in the termination of cyclicity since: 1) old ovaries in either old or young recipients were found to have a limited ability to maintain cyclicity compared to young or prepuberal ovaries; 2) rats with OvTr which continued to cycle had more ovarian tissue and oocytes than rats which had become constantly estrous or anestrous, but fewer oocytes than intact rats; and 3) in Experiment 2, a greater number of old unilaterally ovariectomized rats demonstrated irregular cycles by 16 days after surgery compared to old intact rats. Within the group of acyclic rats with OvTr, more (P<0.05) old than young recipients became constantly estrous, while more young than old recipients became anestrous. Since numbers of follicles were not different between rats with constant estrus and anestrus, this suggested that there also were alterations at the hypothalamicpituitary axis with advancing age. As long as cyclicity was maintained, there were no significant differences in serum concentrations of the 6 measured steroids or prolactin at 2200 h on metestrus between intact rats and rats with OvTr. However, compared to intact rats, concentrations of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) were increased in the cycling rats with OvTr. A further increase in Lii and FSH occurred during constant estrus, with castration levels found in anestrous rats. The increase in gonadotropins and the decrease in estrous cyclic activity accompanied a decrease in the number of growing follicles. This increase in gonadotropins cannot be explained by changes in steroids alone, since a significant decline in ovarian steroids was not found at this particular sampling time, except in rats with OvTr which were anestrous. It is concluded that a reduced amount of ovarian tissue and number of follicles plays a major role in the decline in reproductive function, probably through a reduction in inhibin. However, some difference at the hypothalamic-pituitary axis is responsible for the increased incidence of constant estrus in older rats.

A prospective study of the differential changes in serum thyroglobulin and its autoantibodies during propylthiouracil or radioiodine therapy of patients with Graves' disease.

Measurement of serum thyroglobulin (Tg) and its autoantibody (TgAb) by radioimmunological methods was performed in 48 patients with Graves' disease during treatment with radioiodine (n = 16) or propylthiouracil (PTU) (n = 32). Twenty-five of the 48 patients were TgAb positive, their sera being inaccessible to measurement of serum Tg. TgAb showed only minor changes during PTU treatment, whereas TgAb fell rapidly after radioiodine, in 5 of 16 patients to unmeasurable levels, followed by a secondary rise to 4.5 times pre-treatment level after 20 weeks. Serum Tg showed a steady increase during the first weeks after radioiodine treatment, but fell to lower levels after one year. PTU caused only minor changes in the serum Tg concentration. There was no shift in molecular sizes of either Tg or TgAb during the course of the treatments. Five of 16 131I-treated patients developed myxoedema, 4 of whom were TgAb positive. Another 3 patients had high increases in TgAb without myxoedema. Six of 18 patients had relapse of thyrotoxicosis after withdrawal of PTU-treatment. There was no significant difference in serum concentrations of TgAb or Tg between those developing relapse and those remaining in remission, and it is concluded that serum Tg is a poor predictor of relapse in medically treated thyrotoxicosis.

SPECIFIC RADIOASSAY OF 24,25 DIHYDROXYVITAMIN D (24,25(OH)2D) IN SERA OF NEWBORNS, CHILDREN AND ADOLESCENTS

To further evaluate vitamin D metabolism in children, serum concentrations of 24,25(OH)2D, a metabolite produced by the renal 25OHD-24 hydroxylase system, were measured by a competitive radioassay utilizing normal rat serum as binding protein, 3H-25OHD as tracer and reference 24, 25(OH)2D3 as standard. Blosynthesized 3H-24, 25(OH)2D3 was used to monitor recoveries. The 24, 25(OH)2D and 25OHD from serum lipid extracts were isolated by chromatography on 24 × 0.5 cm columns of Sephadex LH20. Mean (±S.D.) serum 24, 25(OH)2D in children (age 2-17 yrs, N=20) was significantly (p < .01) higher (3.3±1.3 ng/ml) than in newborns (N=14, 1.87±0.6 ng/ml). Mean radioassayable serum 25OHD was also significantly (p < .01) higher (31.3±11 ng/ml) in children than in newborns (14.4±3.4 ng/ml). No significant difference in serum concentrations of 24, 25(OH)2D was found between term (N=7) and preterm (N=7) neonates (2.0±0.5 vs 1.7±0.7 ng/ml) nor between prepubertal (N=9) and pubertal (N=11) children (3.8±1.4 vs 2.9±1.1 ng/ml). A significant positive correlation (r=0.87, p<.01) was found between serum 25OHD and 24.25OHD concentrations in children. However, no such relationship was found among newborns. Conclusions: 1) Radioassay of 24, 25(OH)2D will provide further data concerning the specific metabolism of vitamin D in normal and abnormal subjects; 2) Synthesis of 24, 25(OH)2D in neonates is apparently independent of the levels of its precursor, 25OHD; 3) Utilization of column chromatography is essential for measurement of absolute levels of 24, 25(OH)2D and 25OHD.

Letter: Digitalis: digoxin availability, toxicity.

Comments and Corrections1 December 1973Digitalis: Digoxin Availability, ToxicityGORDON M. TRENHOLME, M.D.GORDON M. TRENHOLME, M.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-79-6-908_2 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptTo the editor: In his article, "Digitalis Glycosides" (Ann Intern Med79:229-238, 1973) Dr. Doherty recommends adjustment of digitalis dosage in patients with thyroid disorders. He attributes the alteration in digitalis requirements in these patients to an altered end-organ responsiveness to digoxin. The data he presents in Figure 8 of his article, however, show significant differences in serum concentrations of tritiated digoxin in hypothyroid, hyperthyroid, and euthyroid patients given the same dose of digoxin. The differences in serum digoxin concentrations adequately explain the increased requirement for digoxin in hyperthyroid patients and the decreased requirement for digoxin in hypothyroid patients, without...Reference1. FORDOWENSCURD RJG: Kidney function in various thyroid states. J Clin Endocrinol Metab 21:548-553, 1961 CrossrefMedlineGoogle Scholar1. DOHERTYPERKINS JW: Digoxin metabolism in hypo- and hyperthyroidism. Studies with tritiated digoxin in thyroid disease. Ann Intern Med 64:489-507, 1966 LinkGoogle Scholar1. WAGNERCHRISTENSENSAKMAR JME: Equivalence lack in digoxin plasma levels. JAMA 224:199-204, 1973 CrossrefMedlineGoogle Scholar2. LINDENBAUMMELLOWBLACKSTONE JMM: Variation in biologic availability of digoxin from four preparations. N Engl J Med 285:1344-1347, 1971 CrossrefMedlineGoogle Scholar3. WOTMANBIGGERMANDEL SJI: Salivary electrolytes in the detection of digitalis toxicity. N Engl J Med 285:871-876, 1971 CrossrefMedlineGoogle Scholar4. SWANSONCACACECHUN MLG: Saliva calcium and potassium concentrations in the detection of digitalis toxicity. Circulation 47:736-743, 1973 CrossrefMedlineGoogle Scholar1. DOHERTY J: Digitalis assay by salivary electrolytes (editorial). N Engl J Med 285:1540-1541, 1971 CrossrefGoogle Scholar2. GOULDRAMANA REDDYGOMPRECHT LCR: Evaluation of digitalis toxicity by salivary electrolytes (letter). N Engl J Med 286:47, 1972 CrossrefMedlineGoogle Scholar3. FOGELMANLA MONTFINKLESTEIN AJS: Fallibility of plasma-digoxin in differentiating toxic from non-toxic patients. Lancet 2:727-729, 1971 CrossrefMedlineGoogle Scholar4. JOHNSONGREERMCCRERIE BH: Rate of dissolution of digoxin tablets as a predictor of absorption. Lan cet 1:1473-1475, 1973 CrossrefMedlineGoogle Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAuthors: GORDON M. TRENHOLME, M.D.Affiliations: Walter Reed Army Institute of Research Duty Station: Laboratory for Tropical Diseases Joliet, Illinois PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 December 1973Volume 79, Issue 6Page: 908-910KeywordsAttentionGlycosidesThyroid diseasesToxicity ePublished: 1 December 2008 Issue Published: 1 December 1973 PDF downloadLoading ...

Studies of neurophysin release.

The serum concentration of neurophysin measured by radioimmunoassay in rats during a 24–hr period was 4.0 ± 1.0μg/ml. Electrical stimulation of the median eminence increased the serum concentration of neurophysin to 25.0 ± 4.5 μg/ml. Similar stimuli applied to the paraventricular or supraoptic nuclei resulted in an increase of serum neurophysin to 17.0 ± μg/ml and 9.0 ± 1.0 μg/ml, respectively. No effect was observed when electrical stimulation was applied to the cerebral cortex or the mid—brain reticular formation. Electrical stimulation of the supraoptic nuclei in rats which were dehydrated failed to cause a further increase in the serum concentration of neurophysin which was already elevated. Stimulation of the paraventricular nuclei of lactating rats, however, caused the expected increase in serum neurophysin. No significant difference in serum concentration of neurophysin was observed in lactating rats before, during or after suckling. In vitro studies on the release of neurophysin showed that the sa...

Physiological factors regulating secretion of neurophysin

A radioimmunoassay for serum neurophysin has been developed. In pigs serum neurophysin increased immediately following hemorrhage, and it increased threefold above basal concentration 4 minutes after removing 10 per cent of the total blood volume. It remained elevated for several hours, but after reinfusing the blood which had been with-drawn, serum neurophysin decreased gradually towards the basal concentration. No significant difference in serum concentration of neurophysin was observed in rats of different age, sex, or following ether anesthesia; but the concentration in hypophysectomized rats was one third normal. Serum neurophysin in the external jugular vein was fivefold greater than that in the inferior vena cava. Serum neurophysin increased progressively with the amount of blood removed by hemorrhage and increased more than tenfold upon removing 40 percent of the total blood volume. Prolonged dehydration, ingestion of hypertonic saline, and intravenous infusion of hypertonic solutions caused a significant increase in the concentration of serum neurophysin. An acute reduction in extracellular fluid volume also raised the concentration of serum neurophysin. Thirty minutes after suckling, no change in neurophysin was observed in rats. The rate of release of neurophysin in vitro increased by a factor of 10 when the potassium concentration in the incubation medium was raised from 5.6 mM K+ to 56 mM K+ solution.