Plasma, urinary and biliary residues in cattle following intramuscular injection of nortestosterone laurate

The synthetic androgen 19-nortestosterone (beta-NT) has been used illegally as a growth promoter in cattle production in the European Union. Elimination of beta-NT and its metabolites in plasma, urine and bile was studied in three cattle with cannulated gallbladders following intramuscular injection at a single site of 500 mg of the laurate ester (NTL) containing 300.5 mg beta-NT. Using enzyme immunoassay quantification, plasma Cmax of free beta-NT was 0.5 +/- 0.15 microgram/L (mean +/- SEM). Concentrations of free beta-NT in plasma were consistently greater than the assay limit of quantification (0.12 microgram/L) for 32.7 +/- 13.42 days. Mean residence time for the beta-NT in plasma was 68.5 +/- 20.75 days. Following sample preparation by immunoaffinity chromatography, high-resolution GC-MS was used to quantify beta-NT and alpha-NT in urine and bile. beta-NT was detected irregularly in urine from two of the three animals post injection. The principal metabolite present in the urine, alpha-NT, was detected for 160.3 +/- 22.67 days post injection. Cmax for alpha-NT in urine was 13.7 +/- 5.14 micrograms/L. Mean urinary AUC0-183 days for alpha-NT was 845.7 +/- 400.90 (microgram h)/L. In bile, alpha-NT was the only metabolite detected for 174.3 +/- 8.67 days post treatment. Cmax for alpha-NT in bile was 40.8 +/- 12.70 micrograms/L and mean biliary AUC0-183 days for alpha-NT was 1982.6 +/- 373.81 (microgram h)/L. Concentrations of alpha-NT in bile samples were greater than those in urine samples taken at the same time. The mean ratio of biliary:urinary AUC0-183 days was 3.0 +/- 0.72. It is concluded that bile is a superior fluid for detection of alpha-NT following injection of NTL, owing to the longer period during which residues may be detected after administration.     

Hyaluronan in human cerebrospinal fluid

We studied the concentration of hyaluronan in cerebrospinal fluid (CSF) in various diseases and attempted to define its reference interval. A radioassay utilizing cartilage proteins with affinity for hyaluronan was used in determining the concentration of 200 lumbar and 27 ventricular CSF specimens and 11 brain cyst fluids. Molecular weight distributions were determined by gel chromatography and localization in brain tissue by histochemistry. The hyaluronan level of lumbar CSF showed an increase with age; comparatively healthy children had (mean +/- SD) 50 +/- 41 micrograms/L (n = 40) and adults 166 +/- 77 micrograms/L (n = 9); i.e. significantly different values. The highest level was recorded in a patient with meningitis (> 8000 micrograms/L). More than 4000 micrograms/ L was noted in a patient with tumour metastasis in the cerebellum. Significantly elevated levels were especially found with spinal stenosis, head injury and cerebral infarction, but also in inflammatory medical disorders, hydrocephalus and encephalitis. We found no significant increase in multiple sclerosis and some other neurological diseases. Ventricular CSF of adults contained significantly less hyaluronan (53 +/- 73 micrograms/L; n = 16) than lumbar CSF. Hyaluronan in cyst fluids varied from 31 to 25,000 micrograms/L. Weight average molecular weight of hyaluronan in CSF was 2.9-3.0 x 10(5) and in brain tumour cyst fluid 2.4 x 10(6). In search for the origin of hyaluronan in CSF it was found that its concentration in the choroid plexus and leptomeninges was low, but that hyaluronan was accumulated in the superficial layer of the cerebral cortex. Continued screening for hyaluronan in CSF may be valuable in cases of inflammatory diseases, tumours and obstruction to CSF flow.     

The relationship between concentration of growth hormone in serum and microangiopathy in patients with diabetes mellitus

OBJECTIVE: To study the relationship between growth hormone (GH) and microangiopathy in patients with diabetes mellitus in order to elucidate pathogenesis on microangiopathy in diabetics. METHODS: GH and insulin (INS) were detected by rdioimmunoassay, and blood sugar (BS) was detected by oxydase method. RESULTS: 138 NIDDM diabetics were examined. The concentration of serum GH in diabetics without microangiopathy (2.3 +/- 1.2 micrograms/L) was higher than in normal people (1.0 +/- 1.2 micrograms/L) and GH in diabetics with microangiopathy (5.74 +/- 1.94 micrograms/L) was higher than in diabetics without microangiopathy. The differences were significant (P < 0.01). As the history of diabetes went on, the level of GH in serum increased, and the incidence of microangiopathy increased too. The correlation of GH in serum with BS was parallel. The correlation of GH in serum with INS was not apparent. 27 ID-DM diabetics were examined, their level of GH in serum (6.8 +/- 3.4 micrograms/L) was higher than that of NIDDM diabetics (4.6 +/- 1.8 micrograms/L). They were all patients with microangiopathy. CONCLUSION: The rise of GH in serum may be an important pathogeny that causes microangiopathy in diabetics.     

Effect of ultrafiltration during cardiopulmonary bypass for pediatric cardiac surgery

The effect of ultrafiltration during cardiopulmonary bypass (CPB) was evaluated for correcting ventricular septal defects with associated pulmonary hypertension in patients less than 18 months old. Interleukin (IL)-6 and IL-8 concentrations in the blood, ultrafiltrate, and urine were measured. The blood IL-6 concentration increased to 128.4+/-20.2 pg/ml by the end of surgery, which is lower than the concentration seen in adult patients (273.1+/-48.2 pg/ml, p < 0.02). The blood IL-8 concentration was not significantly different than that of adults. The total amounts of excreted IL-6 in the ultrafiltrate and urine during CPB were 11.5+/-0.32 pg/kg and 0.32+/-0.07 pg/kg, respectively (p < 0.05). The total amounts of excreted IL-8 in the ultrafiltrate and urine were 4.64+/-0.69 pg/kg and 1.92+/-0.56 pg/kg, respectively (p < 0.05). No differences were seen in these values for excretion between children and adults. We conclude that ultrafiltration during CPB in pediatric patients is more effective in removing proinflammatory cytokines than in adults and more effective than renal filtration alone.     

Gingival fluid tetracycline release from bioerodible gels

Intracrevicular antimicrobial therapy is consistent with the site-specific nature of periodontitis. Considerable research has focused on the use of nonresorbable fibers. However, a bioerodible system is desirable. The purpose of this study was to assess tetracycline release and safety following a single application of a syringable 35% tetracycline hydrochloride in a lactic-glycolic acid gel. 31 generally healthy adult volunteers (mean age = 59 years) were enrolled in and completed this randomized, double-blind eight day study. 2, 6-10 mm non-adjacent interproximal pockets that bled on pocket probing were chosen as experimental sites in each subject. I experimental site and the surrounding gingival crevice received small particle size tetracycline in gel while the other site received larger particle size tetracycline in gel. Gingival crevicular fluid (GCF) was collected prior to treatment and 15 min, 1, 2, 3, 4 and 8 days post-treatment. GCF tetracyline concentrations were determined by agar diffusion bioassay and GCF volume measurements. 61% and 71% of sites had > or = 100 micrograms/ml tetracycline 3 days following application of large (mean concentration = 430 +/- 92 micrograms/ml) and small particle gels (mean concentration = 418 +/- 70 micrograms/ml), respectively. 37% and 55% of sites had measurable tetracycline 8 days after placement of large (mean concentration = 86 +/- 31 micrograms/ml) and small particle gels (mean concentration = 293 +/- 79 micrograms/ml), respectively. The most common adverse event was "bitter taste" (10% of subjects). Based upon the reduction in probing depths and % of sites bleeding on probing at 8 days relative to pretreatment, and the absence of any serious adverse events, it is concluded that these bioerodible gels are safe, and since the bacteriostatic range for most putative periodontopathogens is in the 2-10 micrograms/ml range, the tetracycline levels observed at days 3 and 8 likely represent significant antimicrobial efficacy.     

Standards of hourly excretion of B group vitamins with urine for children aged 9 to 13 years

Values of hour excretion of vitamins B1, B2, B6 and PP with urine in children of 9-13 years, studied under conditions of normal consumption of these vitamins, were estimated considering the correlation between the vitamins B concentration in blood and excretion of their metabolites with urine as well as using these parameters dependence on content of the vitamins in daily ration; for this purpose 35 adult persons and 31 children of both sexes were examined. Normal rate of riboflavin excretion with urine constituted 10-11 micrograms/h in children of this age, while of thiamine-11-12 micrograms/h. Under conditions of normal thiamine consumption, activity of erythrocyte transketolase, measured after preinactivation of transaldolase, exceeded 35 mumol/h/I ml of erythrocytes. Rates of excretion with urine of 4-pyridoxic acid and I-methyl nicotinamide were similar both in children and in adult persons and were equal to more than 40 micrograms/h and 400-600 micrograms/h, respectively.     

Fenoldopam improves renal hemodynamics impaired by positive end-expiratory pressure

BACKGROUND: Mechanical ventilation with positive end-expiratory pressure (PEEP) can impair renal hemodynamics. Fenoldopam, a dopamine receptor agonist, has been shown, in animal experiments, to improve renal perfusion. The purpose of the current study was to examine the effects of this agent on altered renal hemodynamics secondary to positive pressure ventilation. METHODS: Twelve patients requiring mechanical ventilation of their lungs and PEEP for the treatment of hypoxemia after multiple trauma or visceral surgery were studied. Hemodynamic variables, renal vascular resistance, urine flow, creatinine, inulin and PAH clearance, and excretion of sodium and potassium (NaE and KE) were measured before and after introduction of a level of PEEP high enough to decrease urine flow rate by 25% or more, and after administration of intravenous fenoldopam. RESULTS: No hemodynamic effect resulted from 0.1 microgram.kg-1.min-1, but 0.2 micrograms.kg-1.min-1 fenoldopam decreased both diastolic and mean arterial blood pressure from 66 +/- 37 (mean +/- SEM) to 57 +/- 21 mmHg, and from 83 +/- 3 to 74 +/- 4 mmHg, respectively. Renal vascular resistance was reduced from 54 +/- 12 to 19 +/- 5 dynes.s.cm-5 at 0.2 micrograms.kg-1.min-1. Fenoldopam produced a dose-related increase in renal blood flow and PAH clearance. With 0.2 micrograms.kg-1.min-1 fenoldopam, urine flow increased from 81 +/- 25 to 116 +/- 29 ml/h, NaE from 28 +/- 7 to 85 +/- 70 microM/min, and KE from 65 +/- 12 to 109 +/- 16 microM/min. CONCLUSIONS: The results of the current study indicate that intravenous fenoldopam at a dose of 0.2 micrograms.kg-1.min-1 improves renal hemodynamics and increases Na and K excretion in patients requiring mechanical ventilation of their lungs and PEEP. These effects are probably caused by an increased kidney perfusion secondary to renal artery vasodilation.     

Changes in vitamin E concentration after surgery and anesthesia

The aim of this randomized study was to examine changes in vitamin E concentration in female subjects (age 30-60, ASA I) after cholecystectomy and halothane (N = 16) or isoflurane (N = 16) anaesthesia. Vitamin E concentration was measured two days before, and then one, five and twenty-four hours and four days after surgery. High-pressure liquid chromatography was used for its determination. Simultaneously activities of alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma glutamyltransferase (GGT) were determined. Statistical analysis: ANOVA, Tukay HSD test. The research has been accepted by the Drugs Committee of the Karlovac County Hospital. Preoperative vitamin E concentrations in the halothane group were 8.69 +/- 2.35 micrograms/L, median 8.67 micrograms/L and in the isoflurane group 9.43 +/- 2.4 micrograms/L, median 9.08 micrograms/L. Statistically lower vitamin E concentrations compared with preoperative values were noted one hour (P < 0.05), 5 hours (P < 0.01), 24 hours (P < 0.01), as well as 4 days (P < 0.01) after the operation. The lowest vitamin E concentrations were noted 24 hours after the operation with statistically insignificantly higher values in the isoflurane group (halothane group 5.98 +/- 2.08 micrograms/L, isoflurane group 6.58 +/- 1.51 micrograms/L). Analyzing enzyme (ALT, AST and GGT) pre- and postoperative values, no statistically significant differences between the investigated groups and during the time were observed. Statistically significant differences were found between individual measurement times, with no statistical significance of the differences between the halothane and isoflurane groups. It seems that neither the difference in halothane and isoflurane biotransformation nor their distinct effect on perfusion of some organs are the determining factors in post-operative changes in vitamin E concentration.     

Exposure to lead among the population of Barcelona: chronologic trends from 1984 to 1995

BACKGROUND: This study was designed to determine current lead exposure in the Barcelona population and to evaluate the changes occurred during the last 10 years. Blood lead concentration was investigated in a random sample of 694 healthy subjects (age range: 0-65 years). PATIENTS AND METHODS: Adults were random selected from a group of blood donors. Samples of children analysed were selected from subjects with a preoperatory analyses without any disease that could modify blood lead levels. Lead levels were determined by atomic absorption spectrometry. RESULTS: Blood lead concentration was 4.06 +/- 1.4 micrograms/dl in umbilical cord, 8.9 +/- 2.9 micrograms/dl in the paediatric population and 7.8 +/- 4.2 micrograms/dl in the total of adults analyzed. There was statistical differences between the younger subjects and the older population. In 1984 the results found were 18.6 +/- 6.6 micrograms/dl. CONCLUSIONS: The results obtained show that in the last 10 years a reduction on the blood lead levels was occurred. This reduction is parallel with a diminish in the lead petrol concentration in the ambient air.     

The trans-syn-I thymine dimer bends DNA by approximately 22 degrees and unwinds DNA by approximately 15 degrees

Chromium metabolism of lactating women was evaluated by measuring diet, breast milk, urine, and serum chromium in 17 subjects 60 d postpartum. Breast milk chromium concentration was similar for the 3 d of collection with a mean +/- SE concentration of 3.54 +/- 0.40 nmol/L (0.18 ng/mL). Dietary intake and urinary chromium values were also similar for each of the 3 collection days. Total chromium intake of lactating mothers (0.79 +/- 0.08 mumol/d) was greater than that of reference female subjects (0.48 +/- 0.02). There was a significant correlation (r = 0.84) between serum chromium and urinary chromium excretion. If a breast milk volume of 715 mL is assumed, chromium intake of exclusively breast-fed infants is < 2% of the estimated safe and adequate daily intake of 10 micrograms. In summary, breast milk chromium content is independent of dietary chromium intake and serum or urinary chromium values. Chromium intake also did not correlate with serum or urine chromium but there was a significant relationship between serum and urinary chromium concentrations.     

Serum iron concentrations and symptoms of acute iron poisoning in children

STUDY OBJECTIVE: To determine whether serum iron concentrations correlate with the development of symptoms of iron poisoning in children. DESIGN: A retrospective study of medical records from January 1976 through June 1992. SETTING: A tertiary care children's medical center. PATIENTS: Criteria for patient selection included an acute ingestion of iron-containing drugs, measurement of serum iron prior to deferoxamine administration, and a serum iron concentration (obtained within 2-9 hours of exposure) that was greater than 150 micrograms/dl (27 mumol/L). Of the 128 children who were hospitalized for acute iron poisoning, 92 patients (mean age 2.3 +/- 2.2 years) met the selection criteria. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The mean (+/-SD) serum iron concentrations (microgram/dl) of patients who exhibited cardiovascular instability (725 +/- 555, n = 6; p < 0.001) differed from those categorized with central nervous system changes (373 +/- 77, n = 30), gastrointestinal symptoms (334 +/- 83, n = 44), and no symptoms (368 +/- 102, n = 12). Serum iron concentrations in patients with cardiovascular instability ranged from 205-500 micrograms/dl (37-269 mumol/L), whereas those with no symptoms ranged from 170-513 micrograms/dl (30 to 92 mumol/L) demonstrating considerable overlap of ranges. CONCLUSIONS: Serum iron concentrations do not necessarily relate to acute toxicity, and further study is needed to demonstrate the value of serum iron concentrations and to identify alternative strategies in the emergency assessment of the acutely poisoned child.     

Effect of antacid on bioavailability of a sustained-release theophylline preparation

The effect of coadministration of an antacid on bioavailability of a sustained-release theophylline tablet preparation (Theo-Dur) was studied by crossover comparison in five young, healthy, nonsmoking volunteers. Water 90 ml, or "high potency" aluminum-magnesium hydroxide antacid (Mylanta II) 10 ml and water 80 ml were administered concurrently with sustained-release theophylline 600 mg. Eleven blood samples were collected over the next 24 hours. Serum was analyzed with high pressure liquid chromatography technique to determine theophylline concentration. Peak serum concentration (Cmax) and time to peak concentration (tmax) were determined, and area under the 24-hour serum concentration-time curve (AUC) was calculated by the trapezoidal rule for each subject at each study interval. The Student's paired t-test was used to compare Cmax, tmax, and AUC for both treatments. A uniform difference was found between groups in Cmax. Cmax was higher in subjects when treated with the antacid (10.45 +/- 3.03 vs. 8.30 +/- 2.90 micrograms/ml, p less than 0.05) than when given theophylline alone. The mean tmax for the two treatments did not differ (10.4 +/- 1.67 h-combination vs. 10.8 +/- 1.1 h-theophylline, p greater than 0.05). Likewise, mean AUC was unchanged by the coadministration of antacid (140.65 +/- 41.6 micrograms/ml.h--combination vs. 155.13 +/- 46.6 micrograms/h--theophylline, p greater than 0.05). The use of a high-potency antacid product did not decrease the extent of theophylline absorption from this sustained-release product, but did increase Cmax and, presumably, rate of absorption. High-potency aluminum-magnesium antacids can probably be used in combination with this sustained-release theophylline tablet without detriment to therapy.     

Internal hazardous substance burden of persons from various regions of origin--studies of lead, mercury, arsenic and cadmium exposure

AIM OF THE STUDY: The aim of this study was to investigate the concentration of metals of environmental-medical relevance in biological materials in persons seeking asylum with regard to their country of origin. COLLECTIVE AND METHOD: During medical examination after entry into Germany of persons seeking asylum, samples were taken for determination of the following biological monitoring parameters: lead in blood, and arsenic, cadmium and mercury in urine. A total of 103 males were investigated (13 from former Yugoslavia, 29 from the former USSR, 33 Africans and 28 Asians) ranging from 16 to 53 years of age (median 27 years). 34 male Germans without occupational exposure to these substances and a similar age structure (age 25-36 years; median 26 years) served as a control group. RESULTS: The countries of origin had a significant influence on all the biological monitoring parameters investigated. The mean blood lead concentration in the Asians of 75.4 micrograms/L was the highest level found, while the lowest concentration of 38.0 micrograms/L was measured in the German controls. Also the level of arsenic excreted in the urine was on average much higher in the persons seeking asylum than in the German controls. In the Africans a mean level of 9.7 micrograms/g creatinine was reached. The Germans had the lowest arsenic concentrations in urine of 5.3 micrograms/g creatinine. There were, however, considerable interindividual fluctuations, which are probably due to oral uptake of arsenic compounds as a result of eating seafoods. The highest mean concentration of mercury excreted in urine was found in the German controls. Values of 0.9 microgram/g creatinine were determined. The men seeking asylum from former Yugoslavia had significantly higher values than other groups for cadmium excreted in urine. The median of 0.6 microgram/g creatinine was nearly three times as high as found in the Germans. CONCLUSIONS: For all parameters investigated, with the exception of mercury, higher internal exposure was found in the persons seeking asylum than in the German controls. This may be due to individual life style, dietary habits or environmental conditions in the country of origin. For clinical environmental medicine, the 95th percentile, as the upper limit of the reference range, can only be regarded as an orientation aid for classifying the exposure to hazardous substances of an individual compared to other persons from the same environment.     

Renal hemodynamics during norepinephrine and low-dose dopamine infusions in man

OBJECTIVE: To characterize the effects of pressor doses of norepinephrine and low-dose dopamine (3 micrograms/kg/min) on renal hemodynamics in man, as well as to determine the clinical relevance of combining dopamine with norepinephrine. DESIGN: Prospective, single-blind, randomized study. SETTING: Clinical research unit of a tertiary care hospital. SUBJECTS. Six healthy male volunteers ranging in age between 20 and 28 yrs. INTERVENTIONS: The subjects were assigned randomly to four treatments (1 wk apart) in which renal hemodynamics and electrolyte excretion were assessed. Treatments consisted of 180-min infusions of the following: a) 0.9% sodium chloride (control); b) pressor doses of norepinephrine; c) dopamine at 3 micrograms/kg/min; and d) pressor doses of norepinephrine and dopamine at 3 micrograms/kg/min. Pressor doses of norepinephrine was defined as doses required to increase mean arterial pressure (MAP) by 20 mm Hg. MEASUREMENTS AND MAIN RESULTS: Glomerular filtration rate and renal blood flow were derived from inulin and para-aminohippurate clearances, respectively. Urine output and urine solute excretion were also determined. The mean norepinephrine dose required to increase MAP by 22 +/- 2 mm Hg was 118 +/- 30 ng/kg/min (range 76 to 164). After the addition of dopamine, similar doses of norepinephrine resulted in an MAP increase of 15 +/- 4 mm Hg. Glomerular filtration rate and urine output were comparable under all conditions. The infusion of norepinephrine decreased renal blood flow from 1241 +/- 208 to 922 +/- 143 mL/min/1.73 m2 (p = .03). The addition of dopamine returned renal blood flow to baseline values. The clearance of urine sodium increased significantly with the infusion of dopamine alone (p = .03). All subjects completed the four treatment periods. Adverse events, manifested mostly as palpitations and flushing, were rare and self-limiting. CONCLUSIONS: The addition of dopamine (3 micrograms/kg/min) to pressor doses of norepinephrine normalized renal blood flow in healthy volunteers. These hemodynamic changes were not reflected in urine output and glomerular filtration rate; hence, these monitoring parameters may be unreliable indicators of renal function in the setting of vasopressor therapy. In addition, systemic effects were observed with dopamine (3 micrograms/kg/min), as indicated by a decrease in MAP.     

Lack of interaction between glipizide and co-trimoxazole

To identify the effects of co-trimoxazole on the elimination and disposition kinetics of glipizide, eight healthy male volunteers were studied in an unblinded, randomized, cross-over trial with two phases (no treatment or co-trimoxazole 160/800 mg twice a day). During each phase, subjects were treated at home for 7 days with one of the treatment regimens, followed by a 24-hour hospitalization for a single-dose challenge with 10-mg oral glipizide and detailed blood studies. A 7-day washout period was interspersed between the phases. Pharmacokinetic and pharmacodynamic parameters were determined and compared using the Student's t-test for paired observations. Glipizide area under the curve (AUC), clearance, and half life for treatment and control phases were 5758 +/- 1874 versus 5176 +/- 1505 micrograms/L/hour (P = .21), 0.41 +/- 0.15 versus 0.45 +/- 0.14 mL/min/kg (P = .27), and 5.13 +/- 2.10 versus 3.95 +/- 1.37 hours (P = .04), respectively. Twenty-four-hour glucose AUCs for treatment and control phases were 112.24 +/- 8.76 versus 114.86 +/- 11.98 mmol/L/hour (P = .55), respectively. The only parameter reaching statistical significance was glipizide half life, but the difference is of doubtful clinical significance because of difficulty in identifying a clear elimination phase in several subjects. It is concluded that co-trimoxazole administration did not significantly alter glipizide disposition and elimination kinetics in this study population.     

Stimulation of statural growth by recombinant insulin-like growth factor I in a child with growth hormone insensitivity syndrome (Laron type)

We studied the effects of 9 months of treatment with twice-daily subcutaneous injections of insulin-like growth factor I (IGF-I), 120 micrograms/kg per dose, in a 9.7-year-old child with growth hormone insensitivity syndrome, in whom short-term studies had suggested that IGF-I might promote linear growth. Height velocity increased from 6.5 cm/yr (+1.7 SD score) to 11.4 cm/yr (+8.8 SD score). Serum concentrations of IGF-I increased from pretreatment values of 9 +/- 2 micrograms/L to a peak of 347 +/- 26 micrograms/L after 2 hours. Serum concentrations of IGF-II were unchanged. Basal but not stimulated growth hormone concentrations were decreased. During the first 12 days of treatment, serum concentrations and the 24-hour urinary excretion of urea nitrogen were decreased by 28% and 10%, respectively (p < 0.05), there was a 2.4-fold increase in urinary excretion of calcium (p < 0.001), and creatinine clearance and urine volume increased by 22% and 55%, respectively (p < 0.02). The changes in serum levels of urea nitrogen and in urinary calcium and creatinine clearance were still evident at 10 weeks. Fasting and postprandial serum glucose concentrations remained normal. We conclude that IGF-I given as twice-daily subcutaneous injections is effective in stimulating statural growth without producing the hypoglycemia and hyperglycemia observed when IGF-I is infused continuously.     

Bacillus thermoamyloliquefaciens KP1071 alpha-glucosidase II is a thermostable M(r) 540,000 homohexameric alpha-glucosidase with both exo-alpha-1,4-glucosidase and oligo-1,6-glucosidase activities

The lethality of acute renal failure exceeds 50% due to multiorgan dysfunction. In such critically ill patients a reduction of thyroid hormone concentrations without clinical symptoms or laboratory evidence of hypothyroidism frequently occurs. Selenium has recently been shown to play a major role in thyroid hormone metabolism. The aim of this study was to investigate the possible influence of selenium on thyroid hormone metabolism in acute renal failure. Changes in thyroid metabolism were related to the severity of multiorgan failure and to the clinical course. Thyroxine (T4), tri-iodothyronine (T3), free-T4, free-T3, thyrotropin (TSH), serum creatinine, and plasma selenium concentrations in 28 patients (mean age 60 +/- 13) with acute renal failure and multiple-organ dysfunction syndrome were determined initially, and every 3 days after hospital admission. The plasma selenium concentration was found to be reduced compared to normal controls (32 +/- 14 vs. 70-120 micrograms/L). T4 (56 +/- 15 nmol/L, normal range 64-148), T3 (1.31 +/- 0.38 nmol/L, normal range 1.42-2.46), free-T3 (3.1 +/- 1.0 pmol/L, normal range 4.7-9.0), and free-T4 (10.8 +/- 4.0 pmol/L, normal range 10.3-25.8) values were low in 50-70% of the patients at the time of presentation. Plasma TSH concentrations were within the normal range (0.59 +/- 0.79 mU/L, normal range 0.25-3.1), and no clinical symptoms of hypothyroidism were observed. T4 concentration was higher in patients who survived acute renal failure compared to nonsurvivors (62 +/- 22 vs. 51 +/- 16 nmol/L, p < 0.05). Plasma selenium concentration was lower in patients with a severe organ dysfunction syndrome (36 +/- 10 vs. 29 +/- 19 micrograms/L) and correlated with the number of organ failures in these patients (r = -0.247, p < 0.05). T4 and free-T4 values paralleled decreasing selenium concentrations (r = 0.35, p < 0.05). Thyroid hormone levels were reduced in patients with acute renal failure without an increase in TSH. An increase in T4 concentrations became apparent during treatment and may be related to a favorable outcome in acute renal failure. Thyroid hormone concentrations paralleled plasma selenium levels, indicating a possible influence of selenium on thyroid function in acute renal failure.     

Serum concentrations of type I and III procollagen propeptides in healthy children and girls with central precocious puberty during treatment with gonadotropin-releasing hormone analog and cyproterone acetate

Serum levels of type I and III procollagen propeptides (s-PICP and s-PIIINP) were measured in 466 healthy school children and in 23 girls with central precocious puberty (CPP) during GnRH analog and cyproterone acetate therapy, using two commercially available RIAs. In normal children, s-PICP and s-PIIINP changed significantly with age and pubertal development stages. For s-PIIINP, a peak was seen at 12 yr for girls and 13 yr for boys; no peak could be discerned for s-PICP. The prepubertal (Tanner stage 1) s-PICP value (mean +/- SD) for girls was 374 +/- 132 micrograms/L, the midpubertal value (stage 3) was 442 +/- 135 micrograms/L, and the postpubertal value (stage 5) was 203 +/- 103 micrograms/L. The mean s-PIIINP levels for girls were 9.1 +/- 2.4, 15.0 +/- 4.3, and 6.8 +/- 3.1 micrograms/L, respectively. For boys, levels were 362 +/- 119, 544 +/- 138, and 359 +/- 256 micrograms/L for s-PICP and 8.5 +/- 2.2, 14.5 +/- 5.0, and 8.6 +/- 3.8 micrograms/L for s-PIIINP (P < 0.001 for both propeptides in both boys and girls). There was, however, a large variation in normal values for both propeptides within the age groups and pubertal stages. There was a significant correlation of s-PICP and s-PIIINP levels to height velocity in girls (r = 0.35; P < 0.001 and r = 0.33; P < 0.001, respectively), while in boys, only s-PIIINP showed significant correlation to height velocity (r = 0.40; P < 0.001). In untreated girls with CPP, serum levels of s-PIIINP were elevated [PIIINP SD score (SDS), 2.13]. Levels of s-PICP were normal (PICP SDS, 0.39). Levels of both propeptides decreased within 2 months after initiation of therapy and remained below initial values (P < 0.01). The decrease in s-PIIINP after 2 months of therapy showed a significant correlation with the fall in height velocity SDS for chronological age after 6 months of therapy (r = 0.64; P < 0.01). We conclude that s-PIIINP and, to a lesser degree, s-PICP reflect growth in normal children, but due to the large variation, both propeptides seem unsuitable as markers for screening of growth disorders in children.     

Eradication of urinary tract infection following spinal cord injury

A prospective study to evaluate the microbiological efficacy of antimicrobial treatment for urinary tract infection (UTI) was performed in 64 catheter-free spinal cord injured (SCI) patients who were visited monthly by a public health nurse who collected urine for culture and urinalysis. Patients also mailed urine dip slides for weekly bacterial counts. UTI was defined as a culture yielding > or = 100,000 colonies/ml. Treatment was given to asymptomatic patients only if pyuria (> or = 10 urinary leukocytes/high powered microscopic field) was present. Initial treatment was for 7-14 days (group 1). When it became apparent during the study that eradication was difficult and relapse or reinfection frequently occurred within a short time after cessation of antibiotic, a second treatment course of > or = 28 days (group 2) was given. By the end of the study, in which all patients were followed for a minimum of 30 days post treatment, 39/42 (93%) cases in group 1 and 11/13 (85%) in group 2 who had initial eradication, had relapsed or become reinfected. The median number of days and standard error for group 1 to relapse or become reinfected was 16 +/- 2.5, and for group 2 it was 27 +/- 6. Development of drug resistance was documented when bacteria isolated prior to any treatment were compared with strains isolated after > or = 28 days of antibiotics. In this study, urine sterility was achieved in a minority of treated UTIs and was relatively short lived.(ABSTRACT TRUNCATED AT 250 WORDS)     

Cardiovascular and metabolic responses to adrenaline infusion in patients with short-term hypothyroidism

OBJECTIVE: The relation between the clinical manifestations of thyroid disease (both hypo and hyper-thyroidism) and tissue sensitivity to catecholamines remains uncertain. It has been suggested that tissue adrenergic responsiveness is decreased in hypothyroidism, but the reports have been conflicting and have invariably focused on a single physiological response. Therefore the aim of the present study was to determine in patients with moderate, short-term, symptomatic hypothyroidism the responses of heart rate, systolic and diastolic blood pressure, forearm blood flow and metabolic rate to adrenaline infused at a rate known to achieve plasma concentrations in the middle of the physiological range. PATIENTS: Ten subjects (5M, age 43 +/- 3 years, mean +/- SEM) were studied. All were on thyroxine replacement for hypothyroidism following either thyroidectomy or radioactive iodine and had been biochemically euthyroid for at least 6 months. DESIGN: Studies were performed in random order. One study was undertaken on full replacement therapy and the other after 50 micrograms thyroxine daily for 2 weeks. After basal, supine measurements adrenaline was infused at 25 ng/kg/min for 30 minutes. MEASUREMENTS: Heart rate, blood pressure, blood glucose, metabolic rate and forearm blood flow were measured at rest and at 10-minute intervals throughout the adrenaline infusion. RESULTS: Free T4 (10.6 +/- 1.3 vs 17.6 +/- 2.0 pmol/l, P < 0.001) and free T3 (3.6 +/- 0.2 vs 4.6 +/- 0.3 pmol/l, P < 0.01) concentrations were significantly lower on 50 micrograms thyroxine than full replacement therapy. Fasting blood glucose concentrations (4.7 +/- 0.2 vs 4.7 +/- 0.1 mmol/l) were similar. The resting adrenaline concentrations were comparable, 0.29 +/- 0.18 and 0.24 +/- 0.14 nmol/l on 50 micrograms thyroxine and full replacement therapy respectively, and increased to a similar level (2.36 +/- 0.39 and 2.36 +/- 0.35 nmol/l) throughout the adrenaline infusion. The resting heart rate and metabolic rate were significantly lower on 50 micrograms thyroxine than full replacement therapy (68 +/- 2 vs 72 +/- 3 beats/min, P < 0.01; and 4.48 +/- 0.35 vs 4.88 +/- 0.39 kJ/min, P < 0.01) respectively, but the increase in heart rate (7 +/- 2 vs 8 +/- 2 beats/min) and metabolic rate (0.43 +/- 0.09 vs 0.43 +/- 0.06 kJ/min) did not differ on the two study days. Resting systolic blood pressure, diastolic blood pressure and forearm blood flow were comparable on 50 micrograms thyroxine and full replacement therapy as were the changes in systolic blood pressure (1 +/- 1 vs 1 +/- 1 mmHg), diastolic blood pressure (-7 +/- 2 vs -7 +/- 1 mmHg), forearm blood flow (1.4 +/- 0.1 vs 1.7 +/- 0.2 ml/min/100ml forearm) and blood glucose concentration (0.7 +/- 0.1 vs 0.7 +/- 0.1 mmol/l). CONCLUSIONS: Patients with short-term hypothyroidism appear to have a normal response to adrenaline infusion despite reduced baseline heart rate and metabolic rate. Thus, under physiological and mild pathophysiological conditions there appears to be no evidence of any synergy between thyroid status and sensitivity to catecholamines.