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Biomedical subjects

G Defer

Publications and source records attributed to G Defer.

At least 37 records · Page 2Linked to original sources

Comparison of brain SPECT using 99mTc-bicisate (L,L-ECD) and [123I]IMP in cortical and subcortical strokes.

Single photon emission computed tomography (SPECT) using 99mTc-bicisate and N-isopropyl-p-[123I]iodoamphetamine ([123I]IMP) was compared in 25 patients suffering cerebral ischemia during the subacute phase (7-14 days) of stroke. Patients were classified as cortical strokes (15) and subcortical strokes (10) according to clinical and CT data. Images were analyzed by five independent blinded observers. Then, using a cross-matching method between normal and abnormal brain areas, we evaluated the sensitivity and specificity for 99mTc-bicisate and [123I]IMP and inter- and intraobserver reproducibility. A semiquantitative analysis was performed to compare abnormal hypoactive areas versus the corresponding contralateral areas for 99mTc-bicisate and [123I]IMP in the two patient groups. There was no significant difference for sensitivity and specificity between 99mTc-bicisate and [123I]IMP. Matching was approximately 90% in the two groups. The kappa-concordance index was satisfactory and slightly better for 99mTc-bicisate (0.485) than for [123I]IMP (0.435). Level of hypoactivity in the abnormal areas was significantly higher for 99mTc-bicisate (p < 0.03, n = 25) than for [123I]IMP, especially for cortical strokes. This comparative study demonstrates that 99mTc-bicisate is a very useful tracer for the detection of focal cerebral ischemia by SPECT during the subacute phase of stroke.

Adult

Lyme disease presenting as a stroke in the vertebrobasilar territory: MRI.

A 28-year-old female farmer, without vascular risk factors, developed a limited infarct of the pons, associated with a lymphocytic cerebrospinal fluid (CSF) pleocytosis. Titres of specific antibodies against Borrelia burgdorferi were high in serum and CSF. MRI confirmed an infarct in the territory of the medial pontine arteries, but angiography showed no evidence of cerebral angiopathy. Antibiotic therapy rapidly led to a return to normal of CSF cytology and serology. We suggest that Lyme disease is a possible cause of cerebral ischaemia.

Adult

Fate of isopropyl-iodoamphetamine (IMP) in rat liver microsomes.

Para-iodoamphetamines are currently used in nuclear medicine to detect brain perfusion abnormalities with tomoscintigraphy. Little is known about their metabolism pathways in rat and humans. N-isopropyl-125I-iodoamphetamine (IMP) interactions were studied with rat liver microsomes. The first dealkylated metabolite (IAMP) at low concentration gave a type I binding complex then, with a high concentration, a very stable type II complex with oxidized cytochrome P-450 FeIII. In contrast, IMP only gave a type I binding complex in the absence of NADPH. In the presence of NADPH, IAMP and IMP produced 455 nm absorbing complexes, which were enhanced when phenobarbital-treated rat liver microsomes were used. During in vitro metabolic activation, covalent binding of IMP and IAMP on rat liver microsomal proteins was observed. This process was mixed function oxidase (MFO) dependent. The covalent binding level was higher with IAMP and was not affected by flavine oxidase inhibitors. These results confirm the interaction of IMP and IAMP with microsome proteins and cytochrome P-450 and suggest that an N-oxidation of IMP occurs after N-dealkylation. As cytochrome P-450 and dealkylated IMP (IAMP) were found in brain, cerebral metabolism in brain and evolution of activity biodistribution with the course of time can be suggested.

Amphetamines

Visual toxicity following intra-arterial chemotherapy with hydroxyethyl-CNU in patients with malignant gliomas. A prospective study with statistical analysis.

We studied the effects of intra-arterial chemotherapy (IAC) with a new nitrosourea (hydroxyethyl-chloroethyl nitrosourea: HeCNU) on the visual system of 68 patients with malignant gliomas. The intra-arterial chemotherapy was given as a complementary treatment of glioma after surgery (19 patients), after tumor recurrence (28 patients) and as the preliminary treatment before radiotherapy (21 patients). Eleven patients (16%) suffered a visual complication after two or more courses of chemotherapy. The main visual symptoms included mild to major decrease of visual acuity and in some cases ocular pain, palpebral edema and conjunctival injection. The delay in onset of ocular symptoms from the last course of IAC varied from 1 week to 9 months. From ophthalmoscopic findings, visual field testing and fluorescein angiography, the visual symptoms presented by our patients could be related to ischemic optic neuropathy or retinal vasculopathy. None of the patients had hypertension, diabetes, cardiopathy or hematological disease. Statistical analysis failed to demonstrate a relationship between the occurrence of visual toxicity and patient age, number of courses of HeCNU, the vascular axis treated, total systemic dose or dose by carotid artery, suggesting a possible specific sensitivity of some patients to chemotherapy. The pathophysiology and the therapeutic implications of this visual toxicity are discussed.

Adult

Increased growth of myoblasts from hypertrophic muscles in syringomyelia.

Proliferation and differentiation of myoblasts from hypertrophic muscles were studied "in vitro" in two cases of syringomyelia with muscle hypertrophy (MH). Their myoblast growth was compared with that of muscle cells sampled on the contralateral side in the same patients and in control subjects. The effect of a circulating factor was tested using patient sera in place of fetal calf and horse sera. The results showed that MH cells were morphologically abnormal (giant and granular). MH myoblasts proliferated more rapidly than contralateral and normal myoblasts, their fusion was accelerated and the resulting myotubes synthesized higher levels of protein. MH sera increased these effects. Serum factors are therefore likely to be involved in "in vivo" muscle hypertrophy. These findings suggest that the pathogenesis of muscle hypertrophy in syringomyelia involves acquired abnormalities due to molecules released in response to neural lesions.

Adult

"Luxury perfusion" with 99mTc-HMPAO and 123I-IMP SPECT imaging during the subacute phase of stroke.

To compare the merits of 123I-isopropyl-iodoamphetamine (123I-IMP) and 99mTc-HMPAO in showing abnormal brain uptake distribution during cerebral ischemia, we studied ten patients during the subacute phase of their stroke, a period where metabolism and blood flow are frequently uncoupled. SPECT imaging was performed using both radiopharmaceuticals in the 10 patients from 48 h to 4 weeks after onset of symptoms. Two patients out of the 10 had similar defects with 123I-IMP and 99mTc-HMPAO SPECT, the location of the defects corresponding to the area of infarction observed on CT. Six patients had normal 99mTc-HMPAO SPECT and abnormal 123I-IMP SPECT with defects in the area of infarction shown by CT. The remaining 2 patients had hyperactive abnormalities on 99mTc-HMPAO in areas corresponding to defects on the 123I-IMP images. Two of the patients with SPECT mismatches were studied again more than 1 month after onset. On reexamination, 99mTc-HMPAO SPECT which was previously normal or hyperactive became hypoactive with a focal area of decreased activity corresponding to the defect on 123I-IMP. Crossed cerebellar diaschisis was found in 7 patients with 99mTc-HMPAO and was absent for both 123I-IMP and 99mTc-HMPAO in 3. We suggest that SPECT with 99mTc-HMPAO could show transient hyperemia not demonstrated by 123I-IMP whereas in some cases cerebral infarction would be more difficult to demonstrate with 99mTc-HMPAO than with 123I-IMP. SPECT with both tracers is recommended to follow the evolution of strokes in terms of regional cerebral blood flow and tissue metabolism.

Adult

Peripheral neuropathy, coagulopathy and nodular regenerative hyperplasia of the liver in a patient with multiple serologic auto-antibody activities and IgM B-cell lymphoma.

A patient with IgM-secreting B-cell lymphoma developed demyelinating peripheral neuropathy, nodular regenerative hyperplasia of the liver, coagulopathy, and terminal miliary lymphomatous spreading. Serologic auto-antibody activities directed against myelin associated glycoprotein, prothrombinase complex (i.e. lupus anticoagulant) and smooth muscle cells were detected. It is suggested that there is a link between the IgM gammopathy, the immunological abnormalities and the various clinico-pathological conditions.

Autoantibodies

Hormonal and metabolic response to physical exercise, fasting and cold exposure in the rat. Effects on ketogenesis in isolated hepatocytes.

Four groups of rats were subjected to the following conditions: (1) 48 h fasting, (2) 48 h of 4 degrees C cold exposure, (3) 5 h treadmill running, (4) 48 h fasting with 4 degrees C cold exposure. The groups were compared to fed control rats in order to study hormonal and metabolic responses in blood and tissue samples. Isolated hepatocytes were used to evaluate the rate of ketogenesis. Decreases in liver glycogen and increases in blood free fatty acids (FFA) confirmed that glycogenolysis and lipolysis occur in these situations of metabolic stress. Increases in the glucagon/insulin plasma ratio were also noted. Plasma catecholamine levels were only enhanced after running and after cold exposure. Production of blood ketone bodies was stimulated more by running and by fasting than by cold exposure. The low ketone body production observed after cold exposure seems to be linked to increases liver glycogen levels and decreased FFA availability. Liver cells isolated after cold exposure exhibited higher ketogenesis than these isolated after running. This difference in ketogenic capacity could result both from the longer hormonal stimulation by high glucagon/insulin plasma ratios and from the metabolic state of the liver.

3-Hydroxybutyric Acid

Dissociated response of aldosterone from plasma renin activity during prolonged exercise under hypoxia.

6 healthy male subjects on a fixed salt-diet performed 1 hour ergocycle exercise at 65% of VO2 max in normoxic (N) and hypoxic (H) conditions. Blood samples were taken at intervals for estimations of plasma aldosterone (PAC), angiotensin converting enzyme (ACE), adrenocorticotrophic hormone (ACTH) and catecholamine concentrations. Plasma volume reductions with exercise were similar in N (4.3 +/- 1%) and H (4.0 +/- 1%). PRA response to exercise was increased by hypoxia while PAC and plasma catecholamine rose to a similar extent in both conditions. Increases in ACTH concentration occurred at the end of exercise but no difference was found between high and low altitudes. Plasma ACE remained unchanged throughout exercise in either condition. These results indicate that hypoxemia interferes with PRA-mediated aldosterone secretion. The variations in plasma ACTH levels during exercise in hypoxia do not appear responsible for this interference.

Adult

Metabolic and blood catecholamine responses to exercise during alkalosis.

The effects of metabolic alkalosis on muscle lactate accumulation and plasma catecholamine concentrations were studied in six highly trained subjects during short-term ergocycle exercises to exhaustion (375 W). The studies were performed after oral administration of NaHCO3 (alkalosis) and CaCO3 (placebo). There was a significant increase in resting blood pH after NaHCO3 ingestion (7.35 +/- 0.02) compared to placebo (7.27 +/- 0.02). A longer endurance time was achieved during alkalosis (75.3 +/- 8 s) than during control (61.5 +/- 2 s), but similar blood pH and HCO3- levels were found at exhaustion in both treatments. Metabolic alkalosis resulted in higher elevation in muscle lactate concentration (31.7 +/- 4.6 mmol.kg-1 wet weight) compared to control (17 +/- 4 mmol.kg-1 wet weight). Despite longer exercise duration in alkalosis, plasma norepinephrine and epinephrine concentrations at exhaustion were reduced by 30 and 34%, respectively. These results indicate that alkalosis increased muscle lactate accumulation during exhaustive exercise. These changes were associated with a reduced blood catecholamine response to exercise.

Adult

Early and delayed SPECT using N-isopropyl p-iodoamphetamine iodine 123 in cerebral ischemia. A prognostic index for clinical recovery.

Sixteen patients with stroke, five patients with permanent regressive ischemic neurologic deficit, and three patients with transient ischemic attacks were studied by single photon emission computed tomography performed within the first hour (early scan) and four hours (delayed scan) after injection of N-isopropyl-p-iodoamphetamine-iodine-123 (IMP). These patients were classified into three groups according to their clinical improvement three months later, and results of single photon emission computed tomography were compared with computed tomographic scan results and correlated to the clinical outcome. Regional brain hypoactivity of IMP differed in some cases between early and delayed IMP scans, showing in those cases a "redistribution" activity. The amplitude of this redistribution was significantly correlated with the clinical outcome of patients with stroke, whereas the value of hypoactivity on early IMP scan did not show such a correlation. The higher the redistribution amplitude was, the better was the clinical outcome. Comparative regional brain hypoactivity of IMP on early and delayed scans could represent a prognostic index of clinical recovery inasmuch as it gives information concerning viability of ischemic brain tissue.

Adult

Oxygen consumption, lactate accumulation, and sympathetic response during prolonged exercise under hypoxia.

Six men (33 +/- 3 years old) performed 1 h ergocycle exercise (60% VO2 max) at sea level and at a simulated altitude of 3000 m. A similar relative exercise intensity corresponded to a lower absolute work load (139 +/- 4 W) in hypoxic than normoxic (163 +/- 4 W) conditions. Lower oxygen uptake (VO2) with no change in ventilation (VE), respiratory exchange ratio (R), and heart rate (Hr) were observed during exercise under hypoxia compared to normoxia. A slow rise in VO2, after the initial 5 min exercise, was observed in normoxic (+ 230 ml/min) as well as in hypoxic (250 ml/min) conditions that might be, in part, related to oxidative removal of blood lactate. Peak blood lactate concentration reached at 30 min of exercise was similar in normoxia (4.5 +/- 0.4) and in hypoxia (4.7 +/- 0.5). However, while the lactate level decreased during exercise at sea level, it remained elevated throughout exercise in altitude. Blood lactate concentration measured at the end of exercise was significantly (P less than 0.05) higher in hypoxic (4.4 +/- 0.3) than in normoxic (3.2 +/- 0.4) conditions. Catecholamine response to exercise was similar in both conditions. We conclude that during prolonged exercise at a given relative work load, hypoxia does not affect cardiorespiratory and sympathetic responses but tends to increase blood lactate accumulation. Higher blood lactate concentrations during hypoxic exercise seems to reflect alterations in the removal of blood lactate rather than changes in glycolytic flux.

Adult

Effects of ketanserin on cardiovascular, sympatho-adrenal and endocrine systems during physical exercise in man.

Blood pressure, heart rate, oxygen consumption, plasma concentrations of catecholamines, renin, aldosterone and lactate were measured in 6 normotensive volunteers during a randomized cross-over study of oral ketanserin (20 mg X 7) and placebo; measurements were made at rest and during maximal dynamic exercise on a bicycle ergometer. At rest ketanserin reduced blood pressure without modifying heart rate or plasma noradrenaline and adrenaline. Duration of exercise and blood lactate levels did not differ between the ketanserin and the control group. During exercise only systolic blood pressure was significantly decreased on ketanserin at maximal work rate whereas heart rate did not change. Plasma noradrenaline was significantly increased and plasma aldosterone significantly decreased during exercise in ketanserin-treated subjects whereas plasma renin activity and plasma adrenaline remained unchanged. Finally, under ketanserin oxygen consumption during exercise was reduced. The results suggest that ketanserin might interfere with the sympathetic nervous system and aldosterone secretion in man.

Adrenal Glands

Metabolic and hormonal responses to lipid and carbohydrate diets during exercise in man.

Nine healthy subjects were studied to determine their performance and the metabolic and hormonal responses to prolonged exercise after ingestion of a carbohydrate or a lipid diet. Subjects exercised on a bicycle ergometer (60% VO2max) until exhaustion four times at weekly intervals. The exercise test was performed 1 h after ingestion of three different isocaloric meals (400 Kcal) containing either glucose, medium-chain triglycerides (MCTs) or long-chain triglycerides (LCTs). The fourth test was performed after a night fast. The metabolism of these nutriments was followed using [U-13C]glucose, [1-13C]octanoate, and [1-13C]palmitate added as tracers. The average work time was comparable whatever nutriment used (116 +/- 11 min). Oxidation of the ingested nutriment over this period was 80% for glucose, 45% for MCTs, and 9% for LCTs. Glucose ingestion produced an early insulin peak associated at the end of the exercise with a lower glycemia compared to the fat diets. After MCT ingestion, an increase in ketone bodies was observed. Catecholamine response to physical exercise was decreased by all the meals when compared to fasting. Thus, we conclude that a different lipid meal, MCTs, or LCTs, compared to glucose feeding, do not modify exhaustion time in spite of differences in hormonal and metabolic responses.

Adult