Magnetic resonance imaging for detecting lesions of multiple sclerosis: comparison with computed tomography and clinical assessment.

Eighty-two patients with known or suspected multiple sclerosis (MS) were examined by means of magnetic resonance imaging (MRI) with a 0.15-T resistive scanner. The diagnosis could be made by MRI in 34 (97%) of the 35 patients with chronic, well-documented, stable MS and by high-volume delayed x-ray computed tomography (HVD CT) in only 6 (54%) of 11 patients in this group. The stage of the disease as judged from the MRI scans correlated poorly with the clinical status of the patient and with the known duration of the disease. MRI identified 28 (88%) of the 32 patients in whom MS was subsequently diagnosed by a neurologist, whereas regular contrast or HVD CT identified only 11 (52%) of 21 such patients. MRI is the most sensitive imaging modality for MS but is of little value in assessing the severity of the disease: many of the lesions seen on MRI scans are clinically "silent", and MRI does not usually detect small lesions in the brainstem, cerebellum or spinal cord that may be clinically significant.     

A specific enhanced recovery protocol decreases opioid use after thyroid and parathyroid surgery

BackgroundEnhanced recovery protocols have not been investigated previously for cervical endocrine surgery. The study aim was to determine whether systematic implementation of an enhanced recovery protocol specific for thyroid/parathyroid surgery can improve postoperative outcomes.MethodsA customized enhanced recovery protocol for thyroid/parathyroid surgery was designed and utilized systematically for all patients who underwent parathyroidectomy, thyroid lobectomy, or total thyroidectomy. Outcomes were assessed 12 months before enhanced recovery protocol implementation (n = 464 patients) and after enhanced recovery protocol implementation (n = 654 patients).ResultsEnhanced recovery protocol implementation was associated with a 72% decrease in mean oral morphine equivalents utilized in-house (before 82 ± 64 versus after 23 ± 28; P < .0001) and many enhanced recovery protocol patients were entirely opioid-free (0.2% vs 21%, P < .0001). When used, the enhanced recovery protocol was associated with a lesser mean amount of ondansetron to treat postoperative nausea and vomiting (5.5 mg ± 3 vs 4.5 ± 2: P < .0001). Duration of stay was short before implementation of the enhanced recovery protocol and did not change substantially after implementation (1.1 days ± 0.7 vs 1.1 ± 0.7; P = .26).ConclusionThe systematic use of a simple, cervical, endocrine surgery-specific enhanced recovery protocol decreased perioperative opioid use by ~70%, with significantly less postoperative nausea and vomiting. Implementation of a multidisciplinary enhanced recovery protocol may be an important initial step toward limiting opioid overuse during common operative procedures.     

Needle biopsy of renal allografts: comparison of two techniques

Two techniques for renal allograft biopsy were retrospectively evaluated to compare relative safety and efficacy. After ultrasound (US) localization of the kidney and biopsy with a hand-held 14-gauge cutting needle, an adequate specimen was obtained in 74 of 77 cases (96%). Major complications occurred in six of these 77 cases (8%). One hundred four biopsies were performed by using a smaller 18-gauge cutting needle with a spring-loaded biopsy "gun" and real-time US guidance. With this newer technique, specimens adequate for diagnosis were obtained in 99 biopsies (95%). There was a single major complication with this technique (1%). The 18-gauge needle with real-time US guidance yields comparably adequate specimens with a lower frequency of complications.     

Failure of Delta(9)-tetrahydrocannabinol and CP 55,940 to maintain intravenous self-administration under a fixed-interval schedule in rhesus monkeys

The lack of procedures which can unequivocally demonstrate cannabinoid self-administration in animals has been an obstacle to the study of the neural basis for the reinforcing effects of this drug class. Because delta(9)-tetrahydrocannabinol (delta(9)-THC) produce a relatively slow-onset, long-lasting behavioral effect, a self-administration procedure with widely spaced drug deliveries was evaluated as an alternative to fixed-ratio schedules which typically require frequent, closely spaced injections to demonstrate reinforcing effects. Three adult male rhesus monkeys were surgically implanted with intravenous catheters and trained to self-administer phencyclidine (PCP) under a 10min fixed-interval schedule of reinforcement. Three injections were available each day, separated by 2h periods during which responding had no programmed consequences. In an attempt to link the effect of the drug with the response which produced it, each 20s injection was paired with a red light which remained illuminated for 10min. PCP (100μg/kg/injection) maintained steady rates of responding during each availability period, ranging from approximately 0.2 to 0.7 responses/s. During 7 day substitution periods, Delta(9)-THC (17-100μg/kg/injection) maintained low rates of responding which occasionally surpassed those during vehicle substitutions, but fell far below rates maintained by PCP. Substitution tests with the potent Delta(9)-THC analog CP 55,940 also resulted in low rates of responding. These results demonstrate that Delta(9)-THC is a poor reinforcer in animals, even under conditions where some of its unfavourable biodispositional properties are taken into consideration.     

Proteolysis and invasiveness of brain tumors: Role of urokinase-type plasminogen activator receptor

Summary The cellular receptor for urokinase-type plasminogen activator (uPAR) in glioblastoma cell lines has been identified and found to be similar to the uPAR expressed by other tumor cell lines. Increased levels of uPAR have been found in primary malignant brain tumor tissues, especially highly malignant glioblastoma, and, to a lesser degree, in malignant astrocytomas, suggesting that this receptor might be involved in efficient activation of pro-uPA and confinement of uPA activity on the cell surface of invading brain tumors. The cell surface uPARs in gliomas could constitute an optimum environment for the generation and activity of plasmin, which is known to play a crucial role in the dissolution of the extracellular matrix during tumor cell invasion.In situ hybridization studies have shown that uPAR mRNA is expressed abundantly in tumor cells and is consistently present at the invasive edges of malignant gliomas. These results imply that uPAR is involved in plasmincatalyzed proteolysis during glioma invasion and that interference with the uPAuPAR interactions could constitute a novel approach for developing therapeutic strategies to counteract invasion of brain tumors.     

Interleukin-1β-converting enzyme and related proteases as potential targets in inflammation and apoptosis

Summary Interleukin-1-converting enzyme (ICE, EC 3.4.22.36) is the cysteine protease responsible for the production of interleukin-1 in monocytes. Since its discovery in 1989, this enzyme has been the subject of enthusiastic investigation because of the suspected role of this cytokine in the pathogenesis of inflammatory diseases such as rheumatoid arthritis. These studies have culminated in the purification and cloning of the enzyme, development of potent inhibitors, determination of its structure by X-ray crystallography and the development of knockout mice, which have confirmed an important role for this protease in inflammation. Late in 1993, the protease became the subject of further interest because of its homology to CED-3, the product of a gene required for programmed cell death in the nematodeC. elegans. It is now clear that ICE is the first identified member of a new cysteine protease family that includes CED-3 and at least four other human homologues. Although the extent to which ICE itself plays a role in mammalian apoptosis remains controversial, it is clear that at least one of these homologues, CPP32, is an important player. The recognition that members of this family play key biological roles in both inflammation and apoptosis, two extremely attractive targets for therapeutic intervention, has led to intense interest in these proteases.