A multicenter clinical trial of gadolite oral suspension as a contrast agent for MRI

The purpose of this study was to assess the effectiveness and safety of Gadolite Oral Suspension as a gastrointestinal (GI) contrast agent for MRI in a phase II and two phase III multicenter clinical trials. Gadolite was administered to 306 patients with known or suspected abdominal and/or pelvic disease. MRI with T1- and T2-weighted sequences was performed before and after ingestion. Efficacy was evaluated by having two masked readers rate the certainty of their MR diagnosis (0 = uncertain, 1 = probable, 2 = definite) on randomly presented pre- and post-Gadolite Oral Suspension enhanced images. Principal investigators also evaluated the images and established the final diagnosis. Vital signs, clinical chemistries, and adverse events were documented. Blood and urine samples were analyzed for gadolinium content to determine whether Gadolite Oral Suspension was absorbed systemically. Certainty in MR diagnosis increased significantly (P < .001) for both blinded readers between pre- and post-Gadolite images (.49–1.18 for reader 1; .46–1.53 for reader 2). Sensitivity, specificity, and accuracy also increased for both masked readers. No gadolinium was detected in blood or urine samples. There were no serious adverse events and no apparent drug-related trends in mean vital signs or laboratory values. Gadolite is a highly effective, safe, and well tolerated contrast agent for clinical use with MRI.     

Amphetamine affects the extinction of self-stimulation differently in prefrontal cortex and posterior hypothalamus of rats

The effects of amphetamine on the extinction of intracranial self-stimulation (ICSS) and on postextinction ICSS performance were examined in rats implanted with electrodes either in medial prefrontal cortex (mPFC) or in the posterior hypothalamus-ventral tegmental area (PH-VTA). Lever-pressing for ICSS was allowed to stabilize in daily 15-minute sessions before each animal was exposed to 5 minutes of extinction (responding without reward). Animals were administered either 0.25 mg/kg d-amphetamine or saline before baseline, extinction and postextinction sessions. After amphetamine treatment, the number of lever presses during extinction was higher in mPFC animals and lower in PH-VTA animals compared with saline-treated controls. Rates did not change immediately after extinction but, one day later, rates had increased in all saline-treated animals (both PH-VTA and mPFC animals) and had decreased in all amphetamine-treated animals. These findings demonstrated that the effects of amphetamine on the extinction of ICSS were different in cortical and hypothalamic sites, possibly because of regional differences in stimulus-evoked reinforcement and inhibitory processes.     

Carpal tunnel syndrome and gynaecomastia during growth hormone treatment of elderly men with low circulating IGF-I concentrations

OBJECTIVE We studied the relationship between plasma level of insulin-like growth hormone I (IGF-I), changes in lean body mass and in adipose mass, and adverse side-effects during human growth hormone (hGH) treatment of elderly men who had low IGF-I levels. DESIGN The first six months was a period of baseline observation. The subjects were then randomized into two groups so that during months 7–18, men in group I received hGH, and men in group II served as untreated controls. SUBJECTS Eighty-three overtly healthy elderly men, who were selected because their plasma IGF-I level was less than 0.35 units/ml. The men were randomly assigned in a ratio of three to one into group I (n= 62) or into group II (n= 21). MEASUREMENTS Plasma IGF-I level was measured monthly. Lean body mass and adipose mass were measured every six months. RESULTS Fifteen men left the study during the baseline period because of personal reasons or intercurrent medical events. In those who received drug (group I), there were a number of adverse reactions which could have been related to the hGH therapy: carpal tunnel syndrome 10, gynaecomastia 4, and hyperglycaemia 3. In total there were 27 dropouts from group I and two dropouts from group II after the six-month point, for a variety of medical and non-medical reasons, the majority probably not related to hGH therapy. During the hGH treatment of group I, plasma IGF-I increased from the range 0.10–0.35 units/ml into the range 0.5–2.2 units/ml. Among the 18 men who completed 12 months of hGH treatment without experiencing one of the three above-noted presumed hGH side-effects, mean and peak plasma IGF-I during treatment were significantly lower than among the 13 men who experienced carpal tunnel syndrome or gynaecomastia (one subject had both) while on hGH. With one exception, neither carpal tunnel syndrome nor gynaecomastia occurred in any individual with a mean IGF-I level less than 10 units/ml during hGH treatment. Twelve months of hGH treatment (group I) caused an increase in lean body mass to 106% of the initial baseline (month one of the protocol), and a reduction in adipose mass to 84% of the baseline. Meanwhile, the lean body mass of the untreated men in group II declined to 97% of the initial baseline. The body composition responses after 12 months of treatment in group I were larger in the men whose mean intra-treatment IGF-I level was 0.5–1.0 units/ ml, than in the men whose mean intra-treatment IGF-I level was 1.0–1.5 units/ml. CONCLUSIONS These observations show that when elderly men with low circulating IGF-I concentrations are treated continuously with hGH, elevation of plasma IGF-I above 10 units/ml is associated with a substantial frequency of carpal tunnel syndrome or gynaecomastia. It may be that the effects of the hormone in expanding lean body mass and reducing adipose mass can be achieved, and the side-effects avoided, by maintaining the mean IGF-I level in the range 0.5–1.0 units/ml.     

Behavioral effects of vehicles: DMSO, ethanol, Tween-20, Tween-80, and emulphor-620

Experimental drugs and compounds that do not easily dissolve in water or saline are frequently combined with vehicles like solvents, detergents, or vegetable oils. Yet very little has been reported on the behavioral effects of vehicles. In this study, we assessed the effects of a vegetable oil (emulphor-620), two detergents (Tween-20 and Tween-80), and two solvents [dimethyl sulphoxide (DMSO) and ethanol] on the locomotor activity in CD2F1 male mice. Locomotor activity was monitored for 12 h after vehicle administration (IP). The concentrations for each vehicle were expressed as percent of vehicle in saline (v/v). Emulphor-620 did not affect locomotor activity at any concentration tested (2%, 4%, 8%, 16%, and 32%). Tween-20 significantly decreased locomotor activity at a concentration of 16% and Tween-80 at 32%. DMSO significantly decreased locomotor activity at concentrations of 32% and 64%. In contrast, ethanol produced a biphasic behavioral response: increased activity at a concentration of 16% and decreased activity at a concentration of 32%. These results will facilitate the selection and concentration of vehicles to be used in combination with experimental drugs or test agents.     

Conus medullaris injury following both tetracaine and lidocaine spinal anesthesia

Multiple reports of cauda equina syndrome and transient radicular nerve root irritation have suggested that lidocaine spinal anesthesia may be responsible. In this case report, a patient with a preexisting diabetic neuropathy received a partial block following a tetracaine spinal, which was followed by a lidocaine spinal. Following block resolution, a new conus medullaris syndrome was diagnosed. Because of the close proximity of the cauda equina and the conus medullaris, differentiation between these syndromes can be difficult. The preexisting diabetic neuropathy may have predisposed this patient to neurologic injury. The choice of a different local anesthetic drug with less neurotoxic potential such as bupivacaine may have prevented this injury.     

Isolation of a peptide that inhibits the posttranslational arginylation of proteins in rat brain

All eukaryotic cells contain enzymes that are able to catalyze the transfer of Arg from tRNA to the N-terminus of naturally short lived or damaged cytosolic proteins. For certain test proteins, it has been shown that the addition of Arg to the N-terminus leads to their degradation via the ubiquitin proteolytic pathway. The mechanisms used by cells for identifying proteins for arginylation and regulating arginylation are not known. The present study reports the isolation of a peptide from rat brain that is able to inhibit the arginylation of proteins in brain extracts. We suggest that this peptide is the physiological regulator of arginylation in rat brain.     

RELATIONSHIP OF COMBINATIONS OF AIDS COUNSELLING AND TESTING TO SAFER SEX AND CONDOM USE IN HOMOSEXUAL MEN

In a cross-sectional survey of 172 homosexual men in a city of one million inhabitants, questions were asked on testing for AIDS and counselling history, sexual practices, prophylactic behaviours, condom use and associations with the gay subculture along with other background variables. Respondents were divided into four groups: those who had had both HIV testing and safer sex counselling, those who had only had testing, those who had only had counselling, and those who had had neither. All but 4 per cent of respondents had heard of safer sex. Results showed that increase in comdom use for both oral and anal sex, and stopping prior to ejaculation were associated with the combined testing and counselling group, and occurred significantly more often than the counselling only and no intervention groups. The testing only group fell midway between the counselling plus testing and the counselling only, and no intervention groups. A scale constructed by summing the four measures of safer sex showed that testing only, and counselling and testing combined were significantly superior in terms of safer sex practices than the counselling and no intervention groups. Correlates of being given a condom at point of testing included increased insertive anal intercourse and stopping before ejaculation as well as increased condom use during anal intercourse. These findings suggest that provision of free condoms in a context of professional and peer support may enhance condom usage during behaviours known to transmit HIV. While these data may be interpreted with caution with regard to causality, they do imply (in the absence of evidence that such behaviours characterise individuals who present for HIV-related interventions) that some interventions or combinations of interventions are significantly more effective than others.