Haloperidol impairs classically conditioned nictitating membrane responses and conditioning-related cerebellar interpositus nucleus activity in rabbits

Rabbits, chronically implanted with recording electrodes in the cerebellar interpositus nucleus and following acquisition of a classically conditioned eyelid response, were injected with haloperidol (HAL, 250 micrograms/kg). HAL significantly reduced the number of conditioned responses when a 75 and 85 dB tone conditioned stimulus (CS) was presented but not when a 95 dB tone CS was used. There was a corresponding decrease in interpositus activity at the 75 and 85 dB CS intensities but not at the 95 dB intensity. HAL appeared to disrupt CRs and interpositus activity by increasing the intensity threshold of the tone CS for eliciting conditioned responses. Possible mechanisms for the effect of HAL on neural circuitry involved in classical eyelid conditioning are discussed.     

The use of the polymerase chain reaction to map CD4+ T cell epitopes.

CD4+ T cells recognize processed exogenous antigen in the form of peptides bound to syngeneic major histocompatibility complex class II molecules on antigen-presenting cells. We have developed a novel and convenient method to synthesize and map CD4+ T cell epitopes of cloned antigens using polymerase chain reaction (PCR)-directed construction of genes expressing recombinant protein fragments. Unique restriction sites incorporated into the PCR primers were employed for the unidirectional cloning of gene fragments into a bacterial expression vector that can be induced to high-level expression. The bacterial lysate could be used directly in T cell proliferation assays. Overlapping recombinant fragments spanning the entire protein were generated and tested. The length of the sequence containing the epitope was further reduced by utilizing PCR to generate 3' truncations. Finally, a small number of overlapping peptides spanning a sequence of 39 amino acids were synthesized to identify a thirteen-amino acid peptide epitope within chicken transferrin that stimulates the T helper cell clone D10.G4.1. PCR-directed construction of fragments of antigen allows for optimal design of strategies for the mapping and analysis of CD4+ T cell epitopes.     

Effects of the long acting beta agonist formoterol on asthma control in asthmatic patients using inhaled corticosteroids. The Netherlands and Canadian Formoterol Study Investigators

BACKGROUND: The long acting beta 2 agonist formoterol has proved to be an effective bronchodilator with a prolonged action of 12-14 hours. However, the precise role of formoterol in the maintenance treatment of asthma is still under debate. A study was performed to investigate the efficacy and safety of treatment with formoterol for six months in subjects with asthma. METHODS: In a multicentre double blind, placebo controlled, parallel group study 239 subjects with mild to moderate asthma were randomly assigned to treatment with either inhaled formoterol 24 micrograms twice daily (n = 125) or placebo (n = 114) during eight months. The study consisted of a four week run in period, a 24 week treatment period, and a four week washout period. All subjects were using regular inhaled corticosteroids (100-3200 micrograms daily) but were still needing at least five inhalations of short acting beta 2 agonist per week for symptom relief. The study was performed in 10 outpatient clinics in Canada, and five outpatient clinics and one coordinating centre for 44 Dutch general practitioners in The Netherlands. Twice daily self-reported peak expiratory flow (PEF) measurements, symptom scores, and rescue beta 2 agonist use during the last 28 treatment days compared with baseline values were used as main outcome measures. Spirometric values were measured at entry, at the start of treatment, after four, 12 and 24 weeks of treatment, and after four weeks washout. RESULTS: One hundred and twenty five subjects received formoterol 24 micrograms twice daily via Turbohaler and 114 received placebo. Baseline FEV1 was 67.1% predicted and mean bronchodilator reversibility was 26%. The mean total asthma symptom score was 3.6 (maximum possible 21). A significant decrease in symptoms in favour of formoterol (difference from placebo -0.64, 95% CI -0.04 to -1.23, p = 0.04) was observed. Compared with placebo, morning PEF increased (difference from placebo 28 l/min, 95% CI 18.3 to 37.7, p = 0.0001) and the use of short acting beta 1 agonists decreased (daytime difference from placebo -1.1 inhalation, 95% CI -1.4 to -0.7, p = 0.0001) in the formoterol group. PEF returned to baseline following discontinuation of formoterol, as did asthma symptom scores. Thirty three patients treated with formoterol and 32 treated with placebo required treatment with prednisolone during the study (58 and 55 courses, respectively). CONCLUSIONS: Adding formoterol 24 micrograms twice daily by Turbohaler to inhaled corticosteroids was effective in improving symptom scores and morning PEF, and decreasing the use of rescue beta 2 agonists. There was no apparent loss of asthma control during 24 weeks of treatment with formoterol.


     

Axial diffusion of retinol in isolated frog rod outer segments following substantial bleaches of visual pigment

Partial bleaches of rhodopsin were made in either the proximal or distal halves of isolated Rana pipiens rod outer segments. The fluorescence of all-trans retinol was recorded 15, 60 and 120 min following 17% and 63% bleaches. Some of the retinol that formed remained immobilized in the bleached halves of the outer segments, while another portion was slowly mobilized and diffused along the cell axis.     

THE PITUITARY-LEYDIG CELL AXIS IN MEN WITH SEVERE DAMAGE TO THE GERMINAL EPITHELIUM

Eighteen men (mean age 27, range 18-30 years) treated for Hodgkin's disease with 6-8 courses of MVPP (Mustine, Vinblastine, Procarbazine and Prednisolone) have had Leydig cell function assessed by their steroidogenic responses to stimulation by a single bolus dose of HCG (1000 units intramuscularly). Normal age-matched men (n = 16) acted as controls. Baseline immunoreactive FSH was markedly raised in the patients (mean 18.1 +/- SD 6.9 vs 2.0 +/- 1.5 IU/l, P less than 0.0001) reflecting damage to the germinal epithelium. Immunoreactive LH was also greater in patients (10.3 +/- 3.9 IU/l) than in controls (3.9 +/- 1.9 IU/l, P less than 0.0001). There were no differences between the baseline testosterone, androstenedione, oestradiol, oestrone and sex hormone binding globulin (SHBG) concentrations. The testosterone/SHBG ratios were similar in the two groups and there was no correlation between baseline LH and testosterone concentrations or testosterone/SHBG ratios. Testosterone, androstenedione, oestradiol and oestrone secretion in response to HCG stimulation were similar at 24 h and 96 h in both groups. In order to explain the paradox of elevated immunoreactive LH in the face of normal testicular steroidogenesis in such patients, LH biological activity (B) as well as LH immunoreactivity (I) and FSH and testosterone were estimated in a second similar group of patients (n = 17, mean age 27, range 17-43 years) and in a further age-matched control group (n = 17). Bioactive and immunoreactive LH levels were significantly increased (P less than 0.005 and P less than 0.001, respectively) in the patient group.(ABSTRACT TRUNCATED AT 250 WORDS)     

Membrane flow within the myelin sheath in IDPN neuropathy

This report describes some aspects of beta,beta'-iminodipropionitrile (IDPN) neuropathy in rats as observed by ultrastructural methods and X-ray diffraction. Light microscopy shows gross swelling of the axons in proximal lumbar spinal roots 8 days after intraperitoneal injection of IDPN. Mean axon cross-sectional area and mean axon perimeter increased to 280% and 160% of their control values, respectively. At the same time, myelin membrane packing was not visibly disturbed. In addition, X-ray diffraction patterns, recorded under physiological conditions, demonstrate that the myelin lipid bilayer thickness and widths of the aqueous spaces between bilayers did not change. Related observations are made on posterior tibial nerve (PNS myelin) and ventral spinal cord (CNS myelin). The various observations together are interpreted in terms of a fluid myelin membrane. It is proposed that the myelin membrane flows during axon swelling even though normal membrane-membrane contacts are maintained within the sheath. Membrane flow and slippage between membranes are explained in terms of a molecular model of the myelin multilayer.     

Closed suction wound drainage and lower-segment caesarean section

Summary. In a randomized controlled study of wound suction drainage after transverse suprapubic incision for lower-segment caesarean section no significant advantages could be demonstrated for routine drainage in terms of wound infection, haematoma formation, duration of hospital stay or analgesic requirements.     

Posterior lumbar interbody fusion for degenerative spondylolisthesis: restoration of sagittal balance using insert-and-rotate interbody spacers.

BACKGROUND CONTEXT: Although satisfactory clinical outcomes have been reported for degenerative spondylolisthesis using a variety of surgical techniques, its optimal management remains controversial. Laboratory and clinical evidence is emerging that if fusion surgery is undertaken, improved short- and longer-term outcomes may be achieved by correcting any sagittal deformity present. The insert-and-rotate posterior lumbar interbody fusion (PLIF) technique, first described by Jaslow in 1946, may enable surgeons to safely and effectively correct sagittal balance through a single posterior approach. PURPOSE: To examine the clinical outcomes and determine whether the focal sagittal imbalance associated with a degenerative lumbar spondylolisthesis can be safely and effectively corrected using a posterior distraction/reduction technique and insert-and-rotate interbody fusion spacers. STUDY DESIGN/SETTING: A prospective, single-cohort, observational study of the clinical outcomes and retrospective radiological review, in a series of 34 patients with degenerative spondylolisthesis, who underwent surgery between September 2000 and October 2002. PATIENT SAMPLE: Mean age of 65.1 years (range, 35 to 82 years). Thirty-two of the 34 patients underwent surgery principally for the relief of radicular leg pain. The principal indication for the fusion was the prevention of anticipated postdecompression instability in 68% of the patients. Mean preoperative slip was 20.0% (range, 12% to 33%). Mean preoperative focal lordosis was 13.2 degrees. OUTCOME MEASURES: Patients were administered pre- and postoperative clinical outcome surveys recording Visual Analogue Pain Score (VAS), Low Back Outcome Score (LBOS), Short Form (SF)-12 and patient satisfaction questionnaires. Pre- and postoperative measurements of the percentage slip and lumbar lordosis of the involved segments were available on 17 patients. Statistical analysis was done using a two tailed, paired t test. SURGICAL METHODS: Decompressive laminectomy was followed by reduction of the spondylolisthesis using intervertebral disc space distraction and pedicle screw instrumentation. The vertebral bodies were supported with bilateral intervertebral lordotic spacers, inserted on their sides and rotated 90 degrees before placing bone graft to either side of them, within the disc space. RESULTS: Mean follow-up time was 21.2 months (range, 12-32 months). No patients were lost to follow-up. Mean preoperative measures of VAS and LBOS of 5.3+/-2.2 and 24.8+/-15.6, respectively, improved to 2.2+/-2.1 (p<.001) and 44.8+/-18.0 (p<.001) at last follow-up. Thirty-one of 34 patients (91%) considered their outcome to be good or excellent. Mean preoperative slip reduced from 20.2% to 1.7% (92% correction, p<.001). Mean focal lordosis increased from 13.1 to 16.1 degrees (26.0% increase, p=.01). There were no device-related procedural complications. Postoperatively, three patients developed an ileus and one a possible deep wound infection, which settled on antibiotics. One patient required extension of his fusion at 12 months for adjacent segment stenosis. CONCLUSIONS: This series suggests that PLIF for degenerative spondylolisthesis using an insert-and-rotate technique can yield high levels of patient satisfaction with low levels of complications and substantial deformity correction using a posterior only approach. Longer-term outcome studies are required regarding the relevance of the restoration of spinal balance.