Cooperative study on the radioimmunological thyrotropin determination (hTSH) in serum (author''s transl)

The increased incidence of drowsiness in hypoalbuminemic patients administered diazepam and more rapid clearance of tolbutamide in cirrhotics may be due to changes in plasma protein binding. The binding of diazepam and tolbutamide was studied by equilibrium dialysis at 37degreesC over a total drug concentration range of 1 to 10 mug/ml and 50 to 300 mug/ml, respectively, in plasma from 21 normal and 14 alcoholic subjects. At 1 mug/ml, diazepam plasma protein binding (+/- S.D.) was 98.5+/-0.4 per cent in normals and 97.8+/-1.2 per cent in alcoholics; at 100 mug/ml, tolbutamide binding was 97.8+/-0.3 per cent in normals and 95.1+/-4.2 per cent in alcoholics. For both agents at all concentrations, the binding to plasma from alcoholics was significantly decreased (P less than 0.01-less than 0.02). The extent of binding of both drugs was dependent on the albumin concentration. These findings suggest that important changes in pharmacologic effect, distribution, and clearance of diazepam and tolbutamide can be anticipated in alcoholics with hypoalbuminemia.     

Clindamycin enhances a nondepolarizing neuromuscular blockade

Neuromuscular blockades induced by clindamycin alone and with d-tubocurarine or pancuronium were examined in the in-vitro guinea pig lumbrical muscle-nerve preparation. Clindamycin, 80-240 mug/ml, initially increased twitch tension. With higher concentrations (180-240 mug/ml) twitch tension subsequently decreased. With 15 to 20 per cent depression of twitch tension by clindamycin, neostigmine (5-20 ng/ml) or calcium (81 mug/ml) slightly but not completely antagonized the blockade. Clindamycin, 40 mug/ml, a dose that did not depress twitch tension, potentiated d-tubocurarine- or pancuronium-induced neuromuscular bloackade. Plasma concentrations of clindamycin of 10-40 mug/ml were recommended for treating serious infections. The authors conclude that the administration of clindamycin may augment nondepolarizing blockade in man, and antagonism by neostigmine and calcium may be incomplete.     

Influence of serum, estrogen, and gonadotropins upon growth and progesterone secretion by cultures of granulosa cells from small porcine follicles

Granulosa cells from small (less than 2mm) antral porcine follicles were grown in culture to study the effects of various hormones on growth, morphology and progesterone secretion. Culture medium 199D + 4% serum was found to be most suitable since it maintained a fairly constant cell population. Estradiol (1mug/ml) and human FSH stimulated cell growth. LH and FSH stimulated progesterone secretion and induced morphological changes associated with luteinization. Estradiol (0.1 mug/ml) inhibited progesterone secretion by granulosa cells.     

Gas chromatographic assay for free and total plasma levels of thiopental

A rapid gas chromatographic assay for the determination of free and total plasma thiopental is described. Free thiopental was obtained by ultrafiltration through Amicon Centroflo membrane cones. Gas chromatographic assay utilized secobarbital as an internal standard and employed on-column methylation of the barbiturates to improve peak resolution. In 73 blood samples from 22 patients total thiopental concentrations ranged from 4.2 to 134 mug/ml plasma, with a mean of 28 mug/ml. Free thiopental values ranged from 8.6 to 22.7 per cent of total, with a mean of 13.7 per cent free thiopental and a standard deviation of 3.2 per cent. At a total thiopental level of 10 mug/ml, unbound thiopental averaged 10.7 per cent with ultrafiltration, compared with 11.5 per cent with equilibrium dialysis. Assays of thiopental by gas chromatography and 14C scintillation counting gave similar results. There were progressive increases in the percentages of thiopental that were unbound when thiopental was added to plasma, purified crystalline albumin (4.5 g/l), and normal serum albumin (5 g/l), and a solution of purified protein fractions (5 g/l). Differences in protein binding determined by this method and previously reported methods are discussed.     

Mechanism of steroid action in inflammation: inhibition of prostaglandin synthesis and release

Acute arthritis was induced by injection of cell-free extract of group A Streptococci into the knee joints of mature male rats. Slices of control and inflamed synovia were incubated for 30 to 240 minutes and the rate of prostaglandin E (PGE) released into the medium was measured by radioimmunoassay. PGE release from inflamed synovia was 5-8 fold higher than that in normal tissue. Incubation of inflamed synovia with corticosterone acetate, dexamethasone or prednisone (100 mug/ml) for one or four hours reduced PGE release by 33% and 55% respectively. Lower concentrations of corticosterone (10 - 30 mug/ml) were ineffective. Aldosterone and progesterone (100 mug/ml) had no effect on PGE release throughout the incubation period. Chloroquine (10 mug/ml) inhibited PGE release from inflamed synovia by 50%. Indomethacin (1 mug/ml) abolished PGE release by 90%. Corticosterone, dexamethasone and prednisone reduced PGE content of inflamed synovia by approximately 45% during a 4-h incubation period. Aldosterone and progesterone were ineffective, while indomethacin reduced PGE content by 70%. The suppressive action of corticosterone on PGE release was prevented by addition to the medium of arachidonic acid (2 mug/ml). By contrast, the inhibitory action of indomethacin was not affected by provision of exogenous substrate. We suggest that glucocorticosteroids reduce PGE release by limiting the availability of the substrate for prostaglandin biosynthesis, and this may well explain some of their anti-inflammatory properties.     

Uniform susceptibility of various strains of Coccidioides immitis to amphotericin B

The susceptibility of 12 strains of Coccidioides immitis to amphotericin B (amB) was studied in vitro and in vivo. The minimal inhibitory concentration (MIC) of the mycelial phase of these strains was 0.078 to 0.16 mug/ml after 3 days of incubation, but by 15 days all strains were inhibited by 2.5 mug/ml. Mice infected intraperitoneally with these strains were sucessfully treated with 0.5 mg of amB per kg per day. These strains included several studied by others and which reportedly varied widely in susceptibility (MIC from 0.24 to 24.01 mug/ml) to amB. Four of these strains representing this putative broad range of susceptibility were used to infect mice intranasally. Regardless of infecting strain, mice were sucessfully treated with 0.38, 0.75, and 1.5 mg/kg, but 0.19 mg/kg was only partially effective. Thus, in vivo as well as in vitro there was a uniform response of C. immitis strains to amB.     

Intraocular pressure in snorkling and diving (author''s transl)]

The in vitro susceptibility of 145 anaerobic clinical isolates and 96 gram-positive aerobic clinical isolates to josamycin, a new macrolide antibiotic, was studied using the agar dilution technique. Ninety-five of the aerobes were susceptible to 1.56 mug or less of josamycin per ml. The median minimal inhibitory concentration of these organisms was 相似文献   

Brain scanning with the Anger multiplane tomographic scanner as a second examination evaluation by the ROC method

The disposition kinetics and systemic availability of ketamine, a dissociative anaesthetic agent, was studied in normal domestic cats. A similar dose (25 mg/kg) of ketamine hydrochloride was administered by the i.v. and i.m. routes; drug concentrations in plasma were measured by a gas-liquid chromatographic procedure. A rapid distribution phase (t1/2 (alpha) = 3 min) was followed by a slower first-order elimination phase. The half-life of the drug (66.9 +/- 24.1 min) was independent of the route of parenteral administration. Absorption from i.m. site of administration was rapid, with peak plasma level at 10 min, and ca. 92 per cent of the dose was available systemically. Extent of plasma protein binding, measured in vitro at 5 and 20 mug/ml by equilibrium dialysis technique, was 53 per cent and independent of ketamine concentration. Simulated plasma and tissue level curves, which were generated by an analogue computer programmed with the individual rate constants of the two-compartment open model, showed that 10 and 15 per cent of the dose were present in the central and peripheral compartments, respectively, at 90 min after i.v. administration of the drug. Peak tissue level of 42 per cent of the dose was reached at 12 to 15 min. Parenteral administration of ketamine, at the dosage rate studied, quickly produced an immobilizing effect of variable duration (0.75 to 1.75 hr) in normal cats.     

A simple electrode for metallic replication

The effect of ritodrine upon uterine artery blood flow (UtBF) and umbilical vein blood flow (UmBF) was investigated in near-term chronic sheep preparations. During intravenous ritodrine infusions to the ewe in sequential dose rates from 100 to 800 mug per minute, UtBF fell progressively to 43 per cent below control levels and mean maternal arterial pressure (MMAP) declined 20 per cent. During constant infusions of 100, 400, or 800 mug per minute of ritodrine to the ewe for 120 minutes,, UtBF decreased 10, 37, and 31 per cent, respectively, and MMAP decreased 6, 20 and 25 per cent respectively. Dose-related maternal tachycardia and hyperglycemia occurred. There were no significant changes in UmBF, mean fetal arterial pressure, or fetal heart rate. During all infusions, maternal and fetal arterial pH, PCO2, and PO2 remained within normal physiologic limits. Simultaneous infusion of ritodrine (400 mug per minute) and propranolol (100 mug per minute) blocked the maternal tachycardia, but decreases in UtBF, MMAP, and UmBF were observed. Ritodrine infusions to the fetus (25 mug per minute) resulted in fetal tachycardia and a variable increase in UmBF.     

Reversal of somatostatin inhibition of insulin and glucagon secretion

These studies were designed to elucidate the mechanism of inhibitory action of somatostatin (SRIF) on glucagon (IRG) and insulin (IRI) secretion. Studies were carried out in the unrecirculated isolated rat pancreas perfusion with arginine 19.2 mM and glucose 5.5 mM as stimulus primarily for IRG but also IRI secretion. The effects of excess Ca++ (15.2 mEq./L.) and excess K+ (12.8 mEq./L.) on IRG, IRI, and the SRIF-inhibited pancreas were studied. Ca++ excess in five perfusions strikingly stimulated IRG secretion (+92 per cent) but only stabilized IRI secretion compared with control perfusions. K+ excess (in seven perfusions) markedly inhibited IRG secretion (-39 per cent) while stimulating IRI secretion (+16 per cent). Restoration of normal concentrations of K+ resulted in a rebound of IRG to levels 120 per cent that of controls. SRIF, at concentrations from 0.1-20 ng./ml., produced inhibition of both IRG and IRI. In 11 perfusions, with SRIF at 10 ng./ml., IRG decreased more than IRI (-75.2 per cent IRG and -46.9 per cent IRI). In five perfusions, addition of Ca++ (15.2 mEq./L.) 10 minutes after SRIF was started resulted in a reversal of IRG inhibition to 69.4 per cent and IRI to 73.2 per cent of the arginine controls. The reversal by Ca++ of SRIF effect on IRG was greater at higher concentrations of Ca++, suggesting some form of competition. In four perfusions, excess K+ reversed SRIF-induced IRI inhibition to 79.6 per cent that of controls but had no effect on IRG inhibition. Studies in vitro with isolated islets revealed that SRIF (2 mug./ml.) inhibited 45Ca uptake of islets as did epinephrine (10(-5) M). It was concluded that SRIF-induced inhibition of hormone release appears related to an action on Ca++ uptake.     

Investigations of the normal stability of Chopart''s joint (author''s transl)

A total of 132 strains of anaerobic bacteria were tested for susceptibility to josamycin, using a broth dilution technique. All strains of Peptococcus species, Peptostreptococcus species, and Bacteroides fragilis were inhibited by 2 mug or less per ml. Seventy percent of these susceptible strains were also killed by 2 mug or less of josamycin per ml. However, 2 of 12 Clostridium species and 6 of 10 Fusobacterium species had minimum inhibitory concentrations of 32 mug or more per ml.     

Occupational lead poisoning, animal deaths, and environmental contamination at a scrap smelter

Occupational lead poisoning and environmental contamination were evaluated at a lead scrap smelter. Thirty of 37 employees (81 per cent) has blood lead levels of greater than or equal to 80 mug/100 ml, indicating unacceptable absorption, and 35 had free erythrocyte protoporphyrin (FEP) levels greater than 60mug/100ml rbc, indicating toxicity of lead on heme metabolism in red blood cells; eight current and previous employees had been hospitalized with lead colic, and another with encephalopathy. Levels of lead in surface soil (1,800 ppm) and vegetation (20,000 ppm) at the smelter were high and decreased with distance. Animals on nearby pasture had died, and lead levels in the blood, milk, and hair of large and small animals were elevated. Adults living within 100 meters of the smelter had higher blood and hair lead levels than controls, who lived at greater distances, but there was no evidence in them of lead toxicity.     

Interaction between radiation and drug damage in mammalian cells. II. The effect of actinomycin-D on the repair of the sublethal radiation damage in plateau phase cells

The effect of actinomycin-D (AMD) on radiation damage repair was studied in plateau phase V79 Chinese hamster cells. Sublethal radiation damage repair, as demonstrated by survival fluctuations following two x-ray exposures separted by time, was observed in our plateau phase cells. Plateau phase cells exposed to 0.01-0.04 mug/ml AMD (a nontoxic regimen to 8 hours) between x-ray exposures were less able to repair sublethal damage. If plateau phase cells were plated at low dilutions into fresh medium (conditions for resuming exponential growth) immediately after the first x-ray dose, and exposed to 0.01--0.04 mug/ml AMD until the second dose, inhibition of sublethal damage repair and additional cell killing were observed particularly at 0.04 mug/ml AMD. It is suggested that radiation-drug damage interactions should be studied in plateau phase cells and in cells resuming exponential growth after plateau phase (possibly analogous to "recruitment"), as well as in exponential phase cultures.     

Simple, direct broth-disk method for antibiotic susceptibility testing of Ureaplasma urealyticum

A simple, direct broth-disk test, utilizing urine sediment as the inoculum and impregnated paper disks as the source of antibiotic, was developed and used to test the susceptibility of 54 isolates of Ureaplasma urealyticum (T-strain mycoplasmas) to minocycline, doxycycline, demeclocycline, tetracycline, and erythromycin. The concentration of each antibiotic was calculated to approximate the attainable blood level. Resistance or susceptibility to each antibiotic was determined by growth, indicated by a color change of the medium in each tube, comparable to that of a control culture without antibiotic. Of the 54 T-mycoplasmas tested, 46 (85.2%) were inhibited by 1 mug of minocycline per ml, 45 (83.3%) were inhibited by 1 mug of doxycycline per ml, 38 (72.2%) were inhibited by 1 mug of demeclocycline per ml, 18 (33.3%) were inhibited by 1 mug of tetracycline per ml, and only 2 (3.7%) were inhibited by 3 mug of erythromycin per ml. Seven (13%) of the 54 T-mycoplasmas tested were resistant to all five antibiotics. There was good correlation between results obtained by this direct broth-disk method and minimal inhibitory concentrations obtained by the direct broth dilution method.     

Daily measurements and in-vitro effects of human chorionic gonadotrophin in the early luteal phase

The purpose of the present study was to analyse daily measurements of human chorionic gonadotrophin (HCG) in in-vitro fertilization (IVF) cycles and to reproduce the effects of HCG in vitro using human granulosa-luteinized cells from the same patients. The study population consisted of nine women undergoing IVF because of tubal infertility in whom blood was drawn every 24 h from the day of the ovulatory dose of HCG (10,000 IU) until 6 days after ovum pick-up. Granulosa-luteal cells from the follicular aspirates were collected and cultured in vitro up to 6 days in the presence of increasing concentrations (0, 0.01, 0.1, 1.0 and 100.0 IU/ml) of HCG. Serum progesterone and HCG in vivo as well as progesterone accumulation in vitro on days 2, 4 and 6, were the main outcome measures. Maximum HCG concentrations (0.25 IU/ml) were reached the day before ovum pick-up, and continuously decreased until day 6 after ovum retrieval. HCG did not stimulate progesterone production in vitro at any dose tested until day 6 after ovum pick-up. Then, 0.01 IU/ml resulted significantly (P < 0.05) stimulatory compared to controls, while 1.0 IU/ml was inhibitory (P < 0.05). It is concluded that HCG supplementation in an IVF cycle is unnecessary until day 6 after ovum pick-up. On day 6, progesterone production is stimulated with very low concentrations of HCG.     

Plasma levels of carbamazepine and carbamazepine-10,11-epoxide during treatment of epilepsy

Carbamazepine and its epoxide in plasma were measured by liquid chromatography in 25 patients treated with a mean dose of carbamazepine of 12.5 +/- 3.3 mg/kg body weight. The mean concentrations of parent drug and metabolite were 5.4 +/- 2.5 mug/ml and 1.10 +/- 0.42 mug/ml, respectively. A singificant correlation was found between the plasma concentrations of the two compounds (r = 0.64; p less than 0.001), but marked interindividual variation existed in the ratio of carbamazepine to carbamazepine to epoxide. Based on simultaneous measurements in plasma and cerebrospinal fluid, the unbound fraction of carbamazepine in plasma was of the order of 20% as compared to 45% for the epoxide. Thirteen ambulant patients suffering from partial epilepsy with complex symptomatology, who were already being treated with phenytoin in optimal doses (plasma level 14-20 mug/ml) were also given carbamazepine. At plasma levels of the latter of about 5 mug/ml there was no further reduction in the frequency of partial or generalized epileptic seizures. In five patients the dose was increased to produce plasma concentrations of 7 - 8 mug/ml. There was still no improvement and side-effects were seen in three patients.     

The metabolic clearance rates and interconversion of cortisol and cortisone in pregnant and nonpregnant baboons

Pregnancy alters the pattern of maternal cortisol (F) metabolism and increases the maternal serum cortisol-binding capacity (CBC) of baboons. To determine whether these changes are associated with alterations in F clearance,the metabolic clearance rate (MCR) and interconversion (p) of F and cortisone (E) were measured by continuous infusion of (3H)F and (14C)E in 9 regularly menstruating and 7 pregnant baboons (Papio papio). In nonpregnant animals, the values (X +/- SE) for MCR-E (488 +/- 48 1/day) were greater (P less than 0.001) than those for MCR-F (214 +/- 22 1/day). The p value for the conversion of E leads to F (62.8 +/- 4.7%) was greater (P less than 0.001) than that for the reaction F leads to E (41.6 +/- 3.7%), indicating that F formation is favored. Consistent with MCR-E greater than MCR-F, the per cent of F bound to proteins other than albumin (75 +/- 2) was greater (P less than 0.001) than the per cent of E bound (52 +/-3). The production rate (MCR x peripheral concentration; mug/min) of F (55.1 +/- 7.9) was greater (P less than 0.001) than that of E (28.5 +/-3.9) with essentially all of the F being secreted directly (secretion rate 51.2 +/- 7.9 mug/min). Essentially all of the E produced was derived from circulating F, vitually none being secreted directly (secretion rate 4.6 +/- 3.9 mug/min). Pregnancy did not alter the MCR-F (190 +/- 23 1/day), MCR-E 525+/- 51 1/day), per cent of F (79 +/- 3), or per cent of E (49 +/-3) bound,or F (57.2 +/- 9.2 mug/min) or E (35.5 +/- 4.9 mug/min) production rates. CBC (mug F/100 ml) was significantly (P less than 0.01) elevated (25.3 +/- 2.3, nonpregnant vs 35.1 +/- u.6, pregnant). In addition, p E leads to F was increased (75.5 +/- 1.8%) as was p F leads to E (54.3 +/- 3.7%; P less than 0.01). We have concluded that the MCR-F during pregnancy is more dependent on alterations in maternal metabolism than on the increased serum CBC characteristic of gestation. We suggest that the latter factor may be important in regulating the physiologic levels of the other steroids which bind to it.     

Letter: Academic mischief

Concentrations of trimethoprim (TMP) and sulfamethoxazole (SMZ) in blood were determined in seven healthy volunteers after ingestion of 720 mg of TMP and 3,600 mg of SMZ (nine tablets of TMP-SMZ, 1:5 ratio) as a single oral dose. The mean levels of drug in blood achieved during the first 8 h after drug administration ranged from 6.12 to 8.32 mug/ml for TMP and 98 to 120 mug/ml for SMZ. These concentrations easily exceeded the previously reported minimal inhibitory concentrations for clinical isolates of Neisseria gonorrhoeae. The combination of TMP-SMZ given as a single, large oral dose may be a useful therapeutic regimen for patients with uncomplicated gonorrhea and susceptible microorganisms.     

Inhibitory action of the residues of some new disinfecting agents on the microflora of Bulgarian milk]

Studied were the amounts of residues of disinfection solutions such as antigerm 0.3 per cent, bradophen 0.2 per cent, abosanit 0.35 per cent, trosilin 0.5 per cent, and oxania 2 per cent which could produce inhibitory effects of the microflora of the Bulgarian sour milk. It was established that the presence of more than 25 ml/1 of a given disinfection solution in the milk of the above-mentioned ones at the concentrations cited (with the exception of trosilin) exert a strong inhibitory action on milk microflora and the enzyme processes. As a result no curdling sets in. The use of Bac. stearothermophilus as a test organism can detect but the presence of 150 mg/1 antigerm in the milk.