High-performance liquid chromatographic determination of the binding of ceftriaxone to human serum albumin solution and albumin from diluted human serum.

The binding of ceftriaxone to human serum albumin has been studied by high-performance liquid chromatography. The gel permeation method of Hummel and Dreyer was used. Ceftriaxone was tested with two sources of albumin (aqueous solution and diluted serum). After internal calibration the binding parameters were determined for each albumin, and results compared. These data are in agreement with those from classical methods for the determination of protein binding of ceftriaxone.

Measurement and clinical and pharmacokinetic implications of diffusion coefficients of antibiotics in tissues.

A method for determining diffusion coefficients of four antibiotics in extracellular tissue space according to Fick's law is described. This new method was applied to rat brain tissue and to agar. After diffusion of the antibiotic in one axis, the gradient concentration was determined with microvoltammetric electrodes. These microelectrodes (1 micron at the extreme tip) measured the free diffusible form of electroactive antibiotics in the extracellular brain space. Metronidazole, chloramphenicol succinate, cefsulodin, and piperacillin gave diffusion coefficients ranging from 0.1 x 10(-6) to 0.2 x 10(-6) cm2 . s-1 in tissue; chloramphenicol base, which is positively charged, gave a coefficient of 0.04 x 10(-6) cm2 . s-1. The coefficient ranged from 0.6 x 10(-6) to 1.2 x 10(-6) cm2 . s-1 in agar. These coefficients were used to simulate antibiotic concentrations in infectious sites and between capillaries by using a simple model of plane diffusion.

Temporary ovarian failure in thyroid cancer patients after thyroid remnant ablation with radioactive iodine.

We studied ovarian function retrospectively in 66 women who had regular menstrual cycles before undergoing complete thyroidectomy for differentiated thyroid cancer and subsequent thyroid remnant ablation with 131I. Eighteen women developed temporary amenorrhea accompanied by increased serum gonadotropin concentrations during the first year after 131I therapy. No correlation was found between the radioactive iodine dose absorbed, thyroid uptake before treatment, oral contraceptive use, or thyroid autoimmunity. Only age was a determining factor, with the older women being the most affected. We conclude that radioiodine ablation therapy is followed by transient ovarian failure, especially in older women.

[Preoperative localization of parathyroid adenoma with technetium and thallium double-labeling scintigraphy. Difficulties related to associated thyroid lesions]. / Localisation préopératoire des adénomes parathyroïdiens par la scintigraphie en double marquage, technétium et thallium. Difficulties liées aux lésions thyroïdiennes associées.

Technetium and thallium double-labeling scintigraphy with image subtraction was carried out on 63 patients suspected of having primary hyperparathyroidism, with or without thyroid involvement. Forty-four patients had a normal thyroid image with technetium. The positive foci located by double-labeling in patients who were to undergo surgery always coincided with parathyroid adenoma. In the 16 cases where the initial diagnosis of hyperparathyroidism was not substantiated, the double-labeling test was normal. Thus for these 44 patients, scintigraphy sensitivity was 75% and specificity was 100%. Nineteen patients had an abnormal thyroid image with technetium. In 7 cases, image subtraction following double-labeling yielded uninterpretable data. In 12 other patients, the positive foci located outside the thyroid by double-labeling coincided with a parathyroid adenoma, whereas this was true for only one patient whose positive foci were located inside the thyroid; a parathyroid adenoma was not detected preoperatively in 4 patients. This double-labeling test is thus useful in locating parathyroid adenomas when technetium scintigraphy of the thyroid is normal; when it is abnormal, double-labeling is advantageous only in cases of extra-thyroid foci.

Solitary increased tibial uptake of 99mTc-diphosphonate unmasking pancreatic tumor-related medullary fat necrosis.

Pancreatic inflammation and tumors can induce various systemic lesions of steatonecrosis. We report here the case of a 73-year-old woman presenting a painful left leg. Roentgenograms and tomograms of the left tibia were normal. Radionuclide bone scan showed diffuse increased uptake in the whole tibia and a CT scan of the same region demonstrated an unusual pattern of bone tumor. Tibial biopsy revealed intra medullary steatonecrosis and led to the discovery of a pancreatic carcinoma.

Pharmacokinetics of cefsulodin in rat cerebrospinal fluid during experimental Pseudomonas aeruginosa meningitis.

Experimental meningitis was induced in rats with Pseudomonas aeruginosa. Bacteria were inoculated in the second ventricle. Twenty hours later cefsulodin penetration was studied in CSF by on-line cannula system which permitted sampling of CSF in the third ventricle. Comparison with healthy animals indicated breakdown of the blood-CSF barrier and high concentrations of cefsulodin were found in CSF.

Delayed gastric emptying in anorexia nervosa is improved by completion of a renutrition program.

The effects of renutrition on gastric emptying and upper gastrointestinal symptoms were evaluated in 14 anorexia nervosa patients before and after weight gain. A double-isotope technique was used to measure gastric emptying of both the solid and the liquid phases of the meal. Upper gastrointestinal symptoms were frequent before renutrition, occurring in 78% of the patients. Among these symptoms, nausea, vomiting and gastric fullness were correlated well with slowing in gastric emptying of both solid and liquid phases of the meal, which was demonstrated, respectively, in 10 (71%) and nine (64%) of the 14 patients. For the 11 patients who subsequently gained body weight, we observed, without any pharmacological treatment, an improvement of gastric emptying of both solid and liquid phases of the meal in eight (73%) and seven (64%) patients, respectively. Gastric emptying was unchanged in the three other patients who gained very little weight during the time of the study. As gastric emptying improved, so did nausea, vomiting, and gastric fullness. In three patients who had initially gained weight, nausea and gastric fullness recurred, associated again in all cases with a delay in gastric emptying. In conclusion, in anorexia nervosa, delayed gastric emptying, which is a frequent feature and which is well correlated with some of the upper digestive complaints, can return to normal without any pharmacological treatment. In this improvement, psychological assistance may play a role, together with the correction of the malnutrition.

Assessment by dipyridamole-thallium-201 myocardial scintigraphy of coronary risk before peripheral vascular surgery.

From October 1983 to January 1985, 46 patients (38 men and 8 women; average age, 60 years; range, 37 to 83 years) underwent peripheral vascular surgery of either the internal carotid artery or the arteries of the lower limbs. Each patient had a thorough clinical examination, an ECG, and a dipyridamole-thallium-201 myocardial scan before operation. On the basis of results, they were divided into two groups: 20 patients with and 26 patients without chronic ischemic heart disease. Three major cardiac events were noted during or after a period of 1 month after surgery: There were two deaths due to cardiac ischemic events and one patient had postoperative unstable angina pectoris. These three patients were classified in the coronary group (NS). When the patients were classified on the basis of whether or not there was thallium redistribution on serial images after infusion of dipyridamole, 14 with redistribution and 32 without redistribution were noted. The three patients who had major cardiac events were in the former group (p less than 0.04). Our data suggest that patients in whom redistribution occurs have a high incidence of postoperative ischemic events. These patients should be considered for particular preoperative coronary care to avoid major postoperative cardiac events and to increase chances of survival.

Asymptomatic diabetic cardiomyopathy: a noninvasive study.

Forty-nine diabetic patients (26 type I and 23 type II), free of cardiovascular disease symptoms, were compared with 32 controls in a noninvasive study of left ventricular (LV) function. Absence of ischemic cardiopathy was confirmed by routine investigations and an exercise electrocardiogram using 12 leads with a thallium-201 myocardial scintigraphy. Diabetic patients had (1) a significantly prolonged mean isovolumetric relaxation time (IVRT) assessed by M-mode echocardiography and phonomechanography; (2) a significantly reduced E-F slope; (3) an increased mean Weissler index (pre-ejection period/LV ejection time). The IVRT and E-F slope abnormalities reflect increased myocardial stiffness and impaired LV compliance. The increased Weissler index reflects impaired myocardial contractility. These abnormalities were not related to sex, age, duration of diabetes or to the presence or extent of complications. No significant difference was found between diabetic patients and controls for mean diastolic and systolic LV diameters, thickness of the posterior wall or of the interventricular septum, assessed by echocardiography, or for the ejection fraction, determined by radionuclide angiocardiography. Finally, more than half of the patients with a frankly abnormal IVRT, Weissler index and E-F slope had had diabetes for less than 5 years, some even less than 2 years, without complications. These data show: (1) evidence of LV dysfunction specific to diabetes and unrelated to ischemic cardiopathy and hypertension; (2) the possible involvement of a metabolic factor in this early asymptomatic LV abnormality rather than microangiopathy.

Determination of antibiotic lipophilicity with a micromethod: application to brain permeability in man and rats.

Lipophilicity of the injectable form of some antibiotics was measured with a micromethod. The antibiotic was dissolved in a small volume (1 ml) of phosphate buffer at a physiological pH (pH = 7.4) and was extracted by a small volume of octanol (1 ml). HPLC determinations of the antibiotic were performed in the two phases. log P ranged from +1.3 for chloramphenicol to -4.3 for ceftriaxone. A linear relationship was established for a few antibiotics between the log P values found in our experiments and the log permeability calculated from data in the literature for human and rat brain. This linear relationship enabled the brain concentrations of antibiotics to be predicted in man and rats.

[Evaluation by myocardial thallium-201 scintigraphy using dipyridamole of the coronary risk in peripheral vascular surgery]. / Evaluation par la scintigraphie myocardique au thallium 201 avec dipyridamole du risque coronarien de la chirurgie vasculaire périphérique.

From October 1983 to January 1985, 46 patients (38 men and 8 women; mean age 60 years, range 37-83) underwent peripheral vascular surgery either of the internal carotid artery or of arteries of the lower limbs. All patients had thorough clinical examination, ECG and thallium dipyridamole myocardial scanning before operation, as a result of which they were divided into 20 with, and 26 without chronic ischemic heart disease. Three major cardiac events were noted during or following a period of one month after surgery: two deaths due to a cardiac ischemic event and one post-operative unstable angina pectoris. The three patients with these complications were classified in the coronary group (NS). When the patients were reclassified according to the presence or absence of thallium redistribution on serial images after dipyridamole, 14 had redistribution and 32 had no redistribution. The three major cardiac events were found to have occurred in the group with redistribution (P less than 0.04). Our study suggests that patients with redistribution have a high incidence of postoperative ischemic events. They should be considered for a particular pre-operative coronary management to avoid post-operative major cardiac events and to improve survival.

Continuous sampling for determination of pharmacokinetics in rat cerebrospinal fluid.

A method for determining drug concentration relationships between plasma and cerebrospinal fluid (CSF) in rats is described. Continuous CSF samples were collected directly from the third anterior ventricle with an indwelling cannula inserted through the bregma point, and drug concentrations were determined by high-pressure liquid chromatography and radioimmunoassay micromethods. Three antibiotics with different abilities to cross the blood-CSF barrier (chloramphenicol, piperacillin, and gentamicin) were tested. This method was found to be reproducible for each drug even if the antibiotic levels were low and the sample volumes very small. Peak CSF concentrations occurred between 0.75 and 1.25 h after injection for all three antibiotics. Percent penetration values at 1 h were 50, 1.2, and 5.4% for chloramphenicol, piperacillin, and gentamicin, respectively.

Permeability of nitroimidazoles in rat cortex.

The right cerebral hemisphere of the rat was perfused in situ by retrograde bolus infusion of some nitroimidazole drugs into the external carotid artery. The right jugular vein served to collect blood samples. Drugs were continuously measured in the right cortex by microvoltametric electrodes and in blood samples by high-performance liquid chromatography during a few minutes. Cerebrovascular permeability coefficients of six nitroimidazoles ranged from 0.8 X 10(-4) to 3 X 10(-6) cm X s-1 and were directly proportional to the octanol-water partition coefficient of the solute. Thus, microvoltametry is a new method to study cerebrovascular transfer in the rat of electroactive antibiotics.

Cefsulodin penetration into rat brain: extracellular versus total concentration.

Disposition of cefsulodin (125 mg X kg-1) was studied in rat frontal cortex after intravenous injection of a bolus by two methods. In vivo voltametry and high performance liquid chromatography of cefsulodin in brain extracts gave different concentration values. The ratio of concentrations determined by the two methods was similar to the ratio of the extravascular volume to total volume. Thus, these findings evidenced the distribution of cefsulodin in the extravascular fluid of the rat frontal cortex.

Blood, liver and lung kinetics of technetium-99m-labelled granulocytes in the rat. Study by external monitoring with a gamma camera.

The external counting method was used to simultaneously measure the kinetics of intravenously injected polymorphonuclear cells labelled with Technetium 99m, in the lungs, liver and blood of rats. When radiolabelled polymorphonuclear leukocytes (PMN) are injected into animals, a large part is taken up by the various organs. This uptake may result from intravascular aggregation, capillary blocking (in which case the transit of the PMN is slowed down), vascular margination or, finally, from tissue infiltration. A rapid increase in PMN was observed initially in the lungs (first seconds), followed by a progressive decrease (t1/2 = 50 min). At the same time, PMN in the liver increased and that in the blood slowly decreased. The kinetics of distribution in the lungs, liver and blood were not modified when the PMN were injected through the aorta, via a carotid catheter, instead of intravenously. Since there was no shunt, vascular resistance was not the cause of the slow transit of PMN through the organs, and we favour the hypothesis that vascular margination of PMN is responsible for their kinetics. When heat damaged PMN were injected, the kinetics of their distribution in the lung, liver and in the blood were clearly altered.

[Exercise test coupled with thallium-201 myocardial scintigraphy after a primary posterior wall infarct. Apropos of 123 patients subjected to coronarography]. / Apport de l'épreuve d'effort couplée à la scintigraphie myocardique au thallium 201 dans les suites d'un primo-infarctus postérieur. A propos de 123 malades coronarographiés.

The following investigations were performed in 123 patients (118 men and 5 women) with an average age of 51 +/- 6 years, between the 3rd and 6 week after primary posterior infarction, a standard exercise stress test on a bicycle ergometer coupled with Thallium 201 myocardial scintigraphy, followed by coronary angiography in the following 15 days. The object of these investigations was to detect severe stenosis (greater than 70%) of the left anterior descending artery and 50% stenosis of the left main stem. Thirteen investigations could not be interpreted because of a submaximal exercise stress test which did not attain 85% of the theoretical maximal heart rate. The sensitivity of exercise stress testing was 73% and that of myocardial scintigraphy 71%. On the other hand, the specificity of scintigraphy was 94% compared to 68% for exercise stress testing. The predictive value of a positive scintigraphy was 88% compared to 47% for stress testing. However, the predictive value of a negative test was similar with both techniques (87% for exercise stress testing, 90% for scintigraphy). When all the positive results were considered, the sensitivity was 93% but the specificity only 66%. The simplest and most rational way of exploiting the information provided by these investigations is to combine the results: when they are concordant they indicate the true diagnosis in 90% of cases. Discordant results pose a more difficult problem with myocardial scintigraphy being the more reliable: its positive predictive value was 71% when exercise stress testing was negative; its negative predictive value was 87% when exercise stress testing was positive.(ABSTRACT TRUNCATED AT 250 WORDS)

Paradoxical technetium-thallium subtraction scan in a case of parathyroid adenoma.

A technetium-thallium (99mTcO4-201Tl) subtraction scan was performed in a patient with clinical and biological evidence of hyperparathyroidism. The 201Tl image indicated a normal thyroid gland. The 99mTcO4 image revealed a left inferior thyroidal extension with an intense and transient focus corresponding to an ultrasonographic nodule. The transient character of the focus was not explicable in terms of vascular kinetics. A supplementary scintigram using 123I confirmed the presence of an inferior extension of the thyroid, but no increased uptake was found. A nodule weighing 250 mg containing a parathyroid adenoma surrounded by normal thyroidal tissue was excised at the focus site. Biological serum levels returned to normal after the operation. It is concluded that the analysis of 99mTcO4 dynamic data could improve the accuracy of parathyroid subtraction scintigraphy.

[Existence of asymptomatic changes in left ventricular function in the diabetic. Noninvasive study]. / Existence d'altérations asymptomatiques de la fonction ventriculaire gauche chez le diabétique. Etude non invasive.

49 diabetics (D) (26 IDD and 23 NIDD) were compared to 32 controls (C). Absence of ischemic cardiopathy (IC) was confirmed by routine investigations and noninvasive cardiovascular techniques, including an exercise ECG using 12 leads and a thallium 201 scintigraphy. Our results show: a) a prolonged mean isovolumetric relaxation time (IVRT) as studied by the M mode echocardiography and phonomechanography: D = 0,10 sec +/- 0,04; C = 0,05 sec +/- 0,02; p less than 0,0001; b) a reduced mean EF slope: D = 97,48 +/- 37,08 mm / sec; C = 125,68 +/- 34,35; p less than 0,005; c) a high mean Weissler index (ratio of PEP to LVET): D = 40 +/- 0,08; C = 33 +/- 0,05; p less than 0,01. IVRT and EF slope abnormalities are related to increased myocardial stiffness and impaired LV compliance. In the absence of changes in preload and afterload, the high Weissler index reflects impaired contractility of the myocardium. These abnormalities are related neither to the duration of diabetes nor to the presence or severity of the complications. With the M mode echocardiography, mean diastolic and systolic thickness of the septum is greater in D with retinopathy than in C (p less than 0,005 and p less than 0,03 respectively); mean diastolic and systolic thickness of the posterior wall is greater in NIDD than in C (p less than 0,001 and p less than 0,025). We conclude that there is evidence of left ventricular functional abnormalities specific to diabetes and unrelated to IC and hypertension. Our findings support the hypothesis that they may be due to metabolic disorders and/or myocardial microangiopathy.