[REGULATION OF CALCIUM METABOLISM AND PRIMARY HYPERPARATHYROIDISM].
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After reviewing the literature on the vitamin D3-like activity of certain plants [Solanum malacoxylon, Cestrum diurnum and Trisetum flavescens], the authors present results of experiments in which dried Trisetum flavescens was administered perorally to rats. The addition of 2.5% dried Trisetum flavescens to the standard laboratory diet caused a drop in blood phosphate levels and a simultaneous marked increase in the calcium and phosphorus content of bones of the experimental animals. The mechanism of the action of Trisetum flavescens on phosphocalcium metabolism is discussed.
Magnesium plays an essential role in the processes of myocardial contraction and conduction. In cardiovascular surgery, extracorporeal circulation (ECC) in haemodilution results in various electrolyte distrubances, with invariably hypomagnesaemia. A group of 13 children undergoing open heart surgery was compared with a group of 17 children operated upon under the same conditions but with the addition of magnesium to the filling solution for the extracorporeal circulation. Changes in blood and urinary electrolytes during and after ECC were studied. Hypomagnesaemia was seen in both groups after surgery but the provision of magnesium supplements shortened the duration. In addition, blood phosphate levels remained significantly higher in the group receiving magnesium. The significance of these various findings is discussed and a technique for the provision of magnesium supplements is proposed.
Parenteral realimentation in the patient with severely impaired nutrition is sometimes associated with the development of a metabolic encephalopathy with coma. The onset of this complication is sudden. The coma is deep, accompanied by signs of neuromuscular hyperexcitability and very marked hyperventilation. It generally regresses rapidly, without sequellae. The onset of such a realimentation coma should be feared in the presence of a certain combination of conditions : severely impaired nutrition, parenteral alimentation with a high level of nitrogen and calories, transfer to the anabolic phase (perfect carbohydrate utilisation, fall in blood phosphate levels with hypophosphaturia, sometimes very marked positivisation of nitrogen balance) and, sometimes, mild premonitory clinical signs. The relationship between this type of complication and hypophosphoraemia is quite definite, but the fall in serum phosphates would not appear to be directly responsible for the coma. The exact mechanism is not known. In order to avoid such complications, great caution should be observed in both the quality as well as the quantity of the intake, as well as in the clinical and laboratory surveillance of the malnourished patient undergoing realimentation.
Twenty patients with rhabdomyolysis with and without acute renal failure (ARF) were studied. The patients consisted of 9 males and 11 females with a mean age of 64.5 +/- 3.2 years. Infection, compression and metabolic derangement were implicated as the most common etiologic factors. While 7 patients developed ARF during hospitalization, renal functions were normal in the remaining 13. While the mean ages, serum ARF, significant increases in potassium, phosphate, blood urea nitrogen, creatinine and uric acid were observed. While the mean blood pressure was similar, significant increases in hematocrit and total protein were observed in the patients with ARF. The detailed results indicated that infection, compression and metabolic derangement were the most common etiology factors of rhabdomyolysis, and plasma volume contraction might be responsible for the development of ARF.
The overproduction of parathyroid hormone as caused by a simple hyperplasia or an adenoma leads to pathological changes in various organs which are termed primary hyperparathyroidism. The blood phosphates increase in case of long-standing disturbances of the metabolism, e.g. chronic renal insufficiency. In this way and due to other causes, the production of parathyroid hormone is increased. The resultant clinical picture is termed secondary hyperparathyroidism. Both forms are associated with osseous changes also in the maxillofacial skeleton. Tertiary hyperparathyroidism may develop from secondary hyperparathyroidism if the metabolic disorder in the renal form cannot be eliminated by kidney transplantation and if the process in the parathyroid becomes independent (autonomous hyperparathyroidism). Besides these three forms, there are two others, quaternary hyperparathyroidism and quinary hyperparathyroidism, which are described.
We report the case of a 43 year old man with multiple endocrine neoplasia (Zollinger-Ellison syndrome-hyperparathyroidism) diagnosed during investigations for a severe ulcer with diarrhoea. The history suggested Zollinger-Ellison syndrome, especially as basal acid production and blood gastrin levels were high. Hypercalcaemia and low blood phosphate levels suggested hyperparathyroidism, which was confirmed by ultra-sound of the neck, showing two parathyroid adenomas. The aim of treatment was two-fold: suppress the hyperparathyroidism and treat the Zollinger-Ellison syndrome. The approach is surgical in most cases, but the tumour is often impossible to remove and total gastrectomy has become rare with the progress in anti-secretory therapy. When the tumour behind a case of Zollinger-Ellison syndrome cannot be found, complementary chemotherapy is indicated. Other endocrine lesions must always be sought and the family investigated to exclude Wermer syndrome.
Whole body hyperthermia therapy (WBHT) is the elevation of the core body temperature to 42 degrees C. In vitro studies have confirmed that 42 degrees C is cytocidal for virally infected lymphocytes, and even more effective when heating is repeated 4 days later. The safety and efficacy of two successive sessions of WBHT (4 days apart) was evaluated in 30 patients with AIDS (not on protease inhibitors), randomized to: 1) untreated controls, 2) low temperature WBHT for 1 hour at 40 degrees C and repeated 96 hours later, and 3) high temperature WBHT for 1 hour at 42 degrees C and repeated 96 hours later. The sorbent suspension in the ThermoChem System (HemoCleanse, West Lafayette, IN) system automatically controlled blood phosphate, calcium, and other electrolyte concentrations during WBHT. In 1 year of follow-up after WBHT, there were positive effects of the therapy on frequency of AIDS defining events, Karnofsky score, and weight maintenance. However, effects on plasma HIV RNA and CD4 counts were transient. Two successive WBHT treatments were performed in four patients who were on protease inhibitor/triple drug therapy, but had suboptimal response. In follow-up for 6 months, plasma HIV RNA and CD4 improved after WBHT, and the patients remained clinically well. This WBHT may have specific advantages in patients with suboptimal response to protease inhibitor therapy.
The pool of chemical energy in an organism represented by high-energy compounds can be assessed by means of adenosine triphosphate (ATP) determination in whole blood and tissues. The elegant manner for the determination of adenosine phosphates (ATP, ADP, AMP) in a single assay is offered by the technique of capillary zone electrophoresis. For this purpose, the BioFocus 3000 Capillary Electrophoresis System (BIO-RAD Laboratories, Inc., Hercules, CA, USA) was used. For the construction of calibration curves, pure preparations of ATP, ADP and AMP were analyzed. The method was used for adenosine phosphates determination in the umbilical blood samples from physiological and immature newborns. Capillary zone electrophoresis enables a specific and simultaneous determination of adenosine phosphates and, thus, monitoring of unusual metabolic situations.
1. Total inositol phosphate formation was measured in labelled femoral and iliac arteries and veins of 14 week-old spontaneously hypertensive rats (SHR) and age-matched Wistar Kyoto (WKY) controls, either unstimulated or in the presence of noradrenaline. 2. Basal levels of [3H]-inositol phosphates and [3H]-phosphatidylinositol were significantly enhanced in SHR femoral artery, but not in the other 3 vessels, compared with WKY. 3. Noradrenaline stimulated phosphoinositide hydrolysis in all four vessels of SHR and WKY. Pretreatment with prazosin (10(-7)-10(-6) M) but not with yohimbine (10(-7) M), inhibited the noradrenaline-induced inositol phosphate formation indicating an alpha 1-adrenoceptor-mediated response. 4. In the femoral artery of SHR compared to WKY, [3H]-inositol phosphate accumulation induced by noradrenaline (10(-7)-10(-5) M) was significantly reduced when expressed relative to basal values although the response to higher concentrations (10(-4)-10(-3) M) was not altered. In contrast, a significant reduction of inositol phosphates was seen only with 10(-7) M noradrenaline when absolute values were compared. In the other three vessels, no difference in noradrenaline-induced [3H]-inositol phosphate formation was observed between strains. 5. These data suggest that phosphoinositide hydrolysis-mediated by alpha 1-adrenoceptors may be reduced in some but not all blood vessels of adult SHR.
Clindamycin phosphate (CLDM) was administered to 33 surgical cases in orthopedics to treat or prevent infection (600 mg in 15 cases and 1,200 mg in 18 cases by intravenous drip infusion over 60 minutes) and the concentrations of CLDM in the bone marrow blood and tissue of the operative field as well as in venous blood were determined with the cup plate method of bioassay by collecting specimens immediately after completion of infusion or 30 or 60 minutes later. The concentration of CLDM in bone marrow blood averaged 104.3 approximately 105.5% of the corresponding concentration in venous blood in the cases receiving 600 mg and 101.3% in those receiving 1,200 mg. The concentration of CLDM in bone marrow tissue averaged 154.0 approximately 163.7% of the corresponding concentration in venous blood in the group receiving 600 mg but 78.8 approximately 86.2% in the group receiving 1,200 mg. This difference between the 2 groups was considered to reflect largely the difference in specimens collected. Thus, the concentration of CLDM in bone marrow tissue was interpreted as the amount of drug penetrating and remaining in bone marrow tissue and its adjacent area. The MIC75 of CLDM for clinical isolates were 0.20 micrograms/ml for S. aureus, 0.78 micrograms/ml for B. fragilis and 0.20 micrograms/ml for Peptostreptococcus spp. The concentrations of CLDM attained in bone marrow blood and tissue and its adjacent area after administration of 600 mg or 1,200 mg were thus sufficient to eliminate these organisms. The above results indicate that CLDM is a useful antibiotic for treatment and prevention of infection in orthopedics.
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Phosphate depletion (PD) adversely affects myocardial function but its influence on blood pressure is not well elucidated. In this study we evaluated whether PD influences blood pressure and/or affects its hormonal regulation or the peripheral vascular response to pressor agonists. Mean arterial pressure (MAP) in PD rats was lower than in normal animals, whereas heart rate was not significantly different between the two groups. Cardiac index (CI) in PD rats was lower and systemic vascular resistance (SVR) was higher than in controls. Plasma norepinephrine (NE) in the resting state and during the stress of immobilization was significantly greater in PD rats than in controls. Base-line plasma renin activity was also significantly higher in PD rats and increased similarly in the two groups of rats after administration of isoproterenol. Bolus injections of NE or angiotensin II produced a smaller rise in MAP in PD rats than in controls. Reduced responsiveness to NE was also demonstrated in isolated hind-limb preparation from PD rats. When NE was infused to achieve a rise in MAP of 30 mmHg, the dose required in PD was higher than in controls. Treatment with indomethacin did not affect the response in MAP to NE. The content and affinity of both alpha- and beta-receptors in PD hearts were not different from those of control hearts. The contents of PiATP, and AMP in the mesenteric vessels of PD rats were significantly lower than in control animals. These data show that PD leads to reductions in MAP, arteriolar response to pressor agents, and CI with appropriate compensatory rise in NE but with inadequate compensatory increase in SVR.(ABSTRACT TRUNCATED AT 250 WORDS)
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We demonstrate a liquid-chromatographic method involving post-column derivatization for determining the concentration of thiamin and its phosphate esters in human blood. Blood, erythrocytes, or plasma is deproteinized and centrifuged. Aliquots of the samples are applied to a mu Bondapak C18 column attached to a "high-performance" liquid chromatograph. Addition of potassium ferricyanide/sodium hydroxide solution to the column effluent with a proportioning pump converts thiamin phosphates into fluorophores, the intensities of which are measured with a spectrofluorophotometer. Thiamin, thiamin monophosphate, thiamin pyrophosphate, and thiamin triphosphate eluted as single peaks; no coeluting substances were detected. Thiamin pyrophosphate was the ester present in greatest concentration, followed by thiamin triphosphate; thiamin monophosphate and thiamin were present in slight amounts. This method allows easy determination of thiamin and its phosphate esters in 0.1 mL of blood.
This study was focused on the changes of high energy phosphates and tissue blood flow (TBF) in ischemia and reperfusion, of jaundiced rat liver. We ligated and cut the bile duct of male Wistar rats to induce jaundice. The rats were divided into two groups, BDL-4W which had ligation four weeks before examination and control which had no ligation. Two studies were performed; In study A, ischemia was induced by clamping portal vein and hepatic artery for 60 minutes. In study B, 15 minutes of ischemia was repeated four times with intervals of 10 minutes of reperfusion. A: 1) In BDL-4W, ATP was significantly lower than that in control at pre-ischemia and reperfusion. Recovery ratios (RR) of ATP in BDL-4W were significantly lower than those in control. 2) RR or TBF in BDL-4W were significantly lower than those in control. 3) In BDL-4W, xanthine was significantly higher than that in control at reperfusion. B: 4) There were no significant differences in the RR of ATP after reperfusion between two groups. 5) There were no significant differences in the RR of TBF between two groups. 6) There were no significant differences in xanthine after reperfusion between two groups. We concluded that intermittent brief ischemia was useful when 60 minutes of ischemia was required for the operation of jaundiced liver.
A colorimetric microassay for the simultaneous quantitative determination of galactose (Gal) and galactose-1-phosphate (Gal-1-P) in dried blood spots is described. An enzymatic reaction involving alkaline phosphatase (EC 3.1.3.1) and galactose dehydrogenase (EC 1.1.1.48) produces NADH, which is coupled with diaphorase (EC 1.8.1.4) and iodonitrotetrazolium violet (INT). The colourless INT is converted to a formazan of red colour the intensity of which is quantitated either photometrically by a microplate reader or determined visually with sufficient sensitivity for screening purposes. We evaluated the assay on 200,000 blood samples in a newborn screening program, and were able to distinguish between classical and milder forms of galactosemia with ease.
A liquid chromatographic method involving precolumn derivatization for determining thiamine and its phosphate esters in human blood has been optimized. Blood sample stored at - 20 degrees C were haemolysed and deproteinized by perchloric acid. The supernatants of the samples were oxidized by addition of potassium ferricyanide-sodium hydroxide, and phosphoric acid was added to obtain a neutral pH in order to extend the column life. The samples were stable after derivatization for at least 24 h, if protected from light and kept at room temperature. Gradient separation with 140 mmol phosphate buffer (pH 7.0), and methanol, tert-butylammonium hydroxide and dimethylformamide as modifiers, on a 3-microns Chromsphere octadecylsilica column gave an analysis time of 15 min. The method was found to be very suitable for the determination of thiamine components in whole blood. The minimal detectable amount is 0.5 nmol/l and the method is linear to at least 1000 nmol/l. The recovery (98 +/- 3%) and precision are very good.