Showing papers by "Royal Adelaide Hospital published in 2002"

Bone formation by human postnatal bone marrow stromal stem cells is enhanced by telomerase expression.

Abstract: Human postnatal bone marrow stromal stem cells (BMSSCs) have a limited life-span and progressively lose their stem cell properties during ex vivo expansion. Here we report that ectopic expression of human telomerase reverse transcriptase (hTERT) in BMSSCs extended their life-span and maintained their osteogenic potential. In xenogenic transplants, hTERT-expressing BMSSCs (BMSSC-Ts) generated more bone tissue, with a mineralized lamellar bone structure and associated marrow, than did control BMSSCs. The enhanced bone-forming ability of BMSSC-Ts was correlated with a higher and sustained expression of the early pre-osteogenic stem cell marker STRO-1, indicating that telomerase expression helped to maintain the osteogenic stem cell pool during ex vivo expansion. These results show that telomerase expression can overcome critical technical barriers to the ex vivo expansion of BMSSCs, and suggest that telomerase therapy may be a useful strategy for bone regeneration and repair.

Rhabdomyolysis: a review.

Abstract: Rhabdomyolysis, a syndrome of skeletal muscle breakdown with leakage of muscle contents, is frequently accompanied by myoglobinuria, and if sufficiently severe, acute renal failure with potentially life-threatening metabolic derangements may ensue. A diverse spectrum of inherited and acquired disorders affecting muscle membranes, membrane ion channels, and muscle energy supply causes rhabdomyolysis. Common final pathophysiological mechanisms among these causes of rhabdomyolysis include an uncontrolled rise in free intracellular calcium and activation of calcium-dependent proteases, which lead to destruction of myofibrils and lysosomal digestion of muscle fiber contents. Recent advances in molecular genetics and muscle enzyme histochemistry may enable a specific metabolic diagnosis in many patients with idiopathic recurrent rhabdomyolysis.

Control of transient lower oesophageal sphincter relaxations and reflux by the GABA(B) agonist baclofen in patients with gastro-oesophageal reflux disease.

Abstract: Background and aims: Transient lower oesophageal sphincter relaxations (TLOSRs) are the major cause of gastro-oesophageal reflux in normal subjects and in most patients with reflux disease. The gamma aminobutyric acid (GABA) receptor type B agonist, baclofen, is a potent inhibitor of TLOSRs in normal subjects. The aim of this study was to investigate the effect of baclofen on TLOSRs and postprandial gastro-oesophageal reflux in patients with reflux disease. Methods: In 20 patients with reflux disease, oesophageal motility and pH were measured, with patients in the sitting position, for three hours after a 3000 kJ mixed nutrient meal. On separate days at least one week apart, 40 mg oral baclofen or placebo was given 90 minutes before the meal. Results: Baclofen reduced the rate of TLOSRs by 40% from 15 (13.8–18.3) to 9 (5.8–13.3) per three hours (p<0.0002) and increased basal lower oesophageal sphincter pressure. Baclofen also significantly reduced the rate of reflux episodes by 43% from 7.0 (4.0–12.0) to 4.0 (1.5–9) per three hours (median (interquartile range); p<0.02). However, baclofen had no effect on oesophageal acid exposure (baclofen 4.9% (1.7–12.4) v placebo 5.0% (2.7–15.5)). Conclusions: In patients with reflux disease, the GABAB agonist baclofen significantly inhibits gastro-oesophageal reflux episodes by inhibition of TLOSRs. These findings suggest that GABAB agonists may be useful as therapeutic agents for the management of reflux disease.

Stiff man syndrome and related conditions.

Abstract: The stiff man syndrome (SMS) and its variants, focal SMS, stiff limb (or leg) syndrome (SLS), jerking SMS, and progressive encephalomyelitis with rigidity and myoclonus (PERM), appear to occur more frequently than hitherto thought. A characteristic ensemble of symptoms and signs allows a tentative clinical diagnosis. Supportive ancillary findings include (1) the demonstration of continuous muscle activity in trunk and proximal limb muscles despite attempted relaxation, (2) enhanced exteroceptive reflexes, and (3) antibodies to glutamic acid decarboxylase (GAD) in both serum and spinal fluid. Antibodies to GAD are not diagnostic or specific for SMS and the role of these autoantibodies in the pathogenesis of SMS/SLS/PERM is the subject of debate and difficult to reconcile on the basis of our present knowledge. Nevertheless, evidence is emerging to suggest that SMS/SLS/PERM are manifestations of an immune-mediated chronic encephalomyelitis and immunomodulation is an effective therapeutic approach. © 2002 Movement Disorder Society

Vagal Mechanoreceptors and Chemoreceptors in Mouse Stomach and Esophagus

Abstract: We used a novel in vitro mouse vagus-gastro-esophageal preparation to study the properties of peripheral vagal afferent endings. We found two types of mechanoreceptive fiber, mucosal receptors and ...

Allium sativum (garlic) suppresses leukocyte inflammatory cytokine production in vitro : potential therapeutic use in the treatment of inflammatory bowel disease

Abstract: Background Cytokines involved in inflammatory bowel disease (IBD) direct a predominantly cell-mediated T- helper-1 (Th1) immune response. The nonspecific anti-inflammatory treatment being used in the management of patients with IBD has not changed much since the 1970s and new therapeutic agents are keenly sought. Several compounds isolated from Allium sativum (garlic) modulate leukocyte cell proliferation and cytokine production. Methods To investigate the possible therapeutic effects of garlic in the treatment of patients with IBD, whole blood and peripheral blood mononuclear cells (PBMCs) were stimulated in the presence of various concentrations of garlic extract and the effect on leukocyte cytokine production was determined in vitro using multiparameter flow cytometry. Results Monocyte interleukin (IL)-12 production was inhibited significantly in the presence of low concentrations of garlic extract (≥0.1 μg/ml total protein). Monocyte IL-10 production increased significantly and monocyte tumor necrosis factor-alpha (TNF-α), IL-1α, IL-6, IL-8, T-cell interferon-gamma (IFN-γ), IL-2, and TNF-α decreased significantly in the presence of ≥10 μg/ml garlic extract. Twenty to fifty percent of the immunomodulatory activity of garlic extract on cytokine production was acid labile. The inhibitory activity of methylprednisolone, a commonly used anti-inflammatory in IBD, with garlic on leukocyte cytokine production was additive. Conclusions By inhibiting Th1 and inflammatory cytokines while upregulating IL-10 production, treatment with garlic extract may help to resolve inflammation associated with IBD. An in vivo animal model study needs to be undertaken to determine the significance of these in vitro findings. Cytometry 48:209–215, 2002. © 2002 Wiley-Liss, Inc.

Effect of laparoscopy on immune function.

Abstract: Background: Laparoscopic surgery is believed to lessen surgical trauma and so cause less disturbance of immune function. This may contribute to the rapid recovery noted after many laparoscopic operations. Preservation of both systemic and intraperitoneal immunity is particularly important in surgery for sepsis or cancer and so an understanding of the impact of laparoscopy on immune function is relevant. Methods: Literature on immunological changes following laparoscopy and open surgery was identified from Medline, along with cross-referencing from the reference lists of major articles on the subject. Results and discussion: Despite a few contradictory reports, systemic immunity appears to be better preserved after laparoscopic surgery than after open surgery. However, the local intraperitoneal immune system behaves in a particular way when exposed to carbon dioxide pneumoperitoneum; suppression of intraperitoneal cell-mediated immunity has been demonstrated in a number of studies. This feature may be clinically important and should be acknowledged when considering laparoscopic surgery in patients with malignancy or sepsis. © 2001 British Journal of Surgery Society Ltd

Acitretin for chemoprevention of non‐melanoma skin cancers in renal transplant recipients

Abstract: A prospective, open randomized crossover trial was conducted to evaluate the efficacy of acitretin for chemoprevention of squamous cell carcinomas and basal cell carcinomas in renal allograft recipients. Analysis was performed according to the intention-to treat principle. Twenty-three patients with previous history of non-melanoma skin cancer enrolled into the study and were randomly allocated into two groups. They crossed over at the end of 1 year. Eleven (47.8%) patients completed the 2-year trial. Twelve (52.2%) patients withdrew from the trial. Nine of these withdrew because of side-effects of acitretin. The majority of the patients who continued with the acitretin could tolerate 25 mg of acitretin daily or on alternate days. The number of squamous cell carcinomas (SCC) observed in patients while on acitretin was significantly lower than that in the drug-free period (P = 0.002). A similar trend was observed in patients with basal cell carcinomas, but this was not significant and the numbers were small. Side-effects were a major limiting factor. A severe rebound increase in SCC occurred in one patient after the acitretin was ceased.

The Discursive Properties of “Hope”: A Qualitative Analysis of Cancer Patients’ Speech

Abstract: The authors of this article question the usefulness of the empirico-realist search for a definitive definition of hope. Semistructured interviews on "do-not-resuscitate" issues with 23 oncology clinic outpatients were tape-recorded, transcribed, and analyzed following grounded-theory methodology and discursive analytical methodology. Twelve patients spontaneously spoke about hope as objective or subjective, a burden or a resource. Hope represented an evaluation of empirical states of affairs or the wish for desired outcomes and was a warrant for action or an excuse for inaction. It was attributed to both patient and caregiver, to individuals or situations. Hope was present or future oriented, both vulnerable and enduring. The variety of versions of hope has implications for interactions between health care workers and patients. Recognizing a taxonomy of hope might prove more useful than searching for definitions.

Why certain dyes are useful for localizing the sentinel lymph node.

Abstract: Location of the sentinel lymph node in malignant melanoma and early breast cancer patients requires separate injections of radiocolloid and blue dye. These agents are administered at alternative times because of their different rates of transit. This study has elucidated why particular dyes are absorbed by the lymphatic system from an investigation of dye molecular structure as a function of protein binding ability. Methods: A dye-protein binding assay was developed using size-exclusion chromatography and ultraviolet spectrophotometry and applied to a series of 20 sulfonic acid group-containing dyes. Radiochemical analyses were also used with 3 99mTc-labeled dyes to rationalize which functional groups are involved in the protein binding reaction. Results: Methylene blue resulted in no protein affinity at 37°C, whereas disulfonate dyes separated by 1 atom such as Patent blue or Indigo carmine gave

Lessons from the Australian Patient Safety Foundation: setting up a national patient safety surveillance system—is this the right model?

Abstract: The evolution of the concepts and processes underpinning the Australian Patient Safety Foundation's systems over the last 15 years are traced. An ideal system should have the following attributes: an independent organisation to coordinate patient safety surveillance; agreed frameworks for patient safety and surveillance systems; common, agreed standards and terminology; a single, clinically useful classification for things that go wrong in health care; a national repository for information covering all of health care from all available sources; mechanisms for setting priorities at local, national and international levels; a just system which caters for the rights of patients, society, and healthcare practitioners and facilities; separate processes for accountability and "systems learnings"; the right to anonymity and legal privilege for reporters; systems for rapid feedback and evidence of action; mechanisms for involving and informing all stakeholders. There are powerful reasons for establishing national systems, for aligning terminology, tools and classification systems internationally, and for rapid dissemination of successful strategies.

Chemotherapeutic agents sensitize osteogenic sarcoma cells, but not normal human bone cells, to Apo2L/TRAIL-induced apoptosis.

Abstract: Apo2L/TRAIL is a member of the tumor necrosis factor (TNF) family of cytokines that induces death of cancer cells but not normal cells. Its potent apoptotic activity is mediated through its cell surface death domain-containing receptors, DR4 and DR5. Apo2L/TRAIL interacts also with 3 “decoy” receptors that do not induce apoptosis, DcR1, DcR2, which lack functional death domains, and osteoprotegerin (OPG). The aim of our study was to investigate the cytotoxic activity of Apo2L/TRAIL on established osteogenic sarcoma cell lines (BTK-143, HOS, MG-63, SJSA-1, G-292 and SAOS2) and in primary cultures of normal human bone (NHB) cells. When used alone, Apo2L/TRAIL at 100 ng/ml for 24 hr induced greater than 80% cell death in only 1 (BTK-143) of the 6 osteogenic sarcoma cell lines. In contrast, Apo2L/TRAIL-resistant cells were susceptible to Apo2L/TRAIL-mediated apoptosis in the presence of the anticancer drugs, Doxorubicin (DOX), Cisplatin (CDDP) and Etoposide (ETP) but not Methotrexate (MTX) or Cyclophosphamide (CPM). Importantly, neither Apo2L/TRAIL alone nor in combination with any of these drugs affected primary normal human bone cells under equivalent conditions. Apo2L/TRAIL-induced apoptosis, and its augmentation by chemotherapy in the resistant cell lines was mediated through caspase-8 and caspase-3 activation. Furthermore, Apo2L/TRAIL-induced apoptosis and its augmentation by chemotherapy was effectively inhibited by caspase-8 zIETD-fmk and caspase-3 zDEVD-fmk protease inhibitors and by the pan-caspase inhibitor zVAD-fmk. The pattern of basal Apo2L/TRAIL receptor mRNA expression, or expression of the intracellular caspase inhibitor FLICE-inhibitory protein, FLIP, could not be readily correlated with resistance or sensitivity to Apo2L/TRAIL-induced apoptosis. However, the augmentation of Apo2L/TRAIL effects by chemotherapy was associated with drug-induced up-regulation of death receptors DR4 and DR5 mRNA and protein. No obvious correlation was seen between the expression of OPG mRNA or protein and susceptibility of cells to Apo2L/TRAIL-induced apoptosis. Stable over-expression of a dominant negative form of the Fas-associated death domain protein (FADD) in the Apo2L/TRAIL-sensitive BTK-143 cells completely inhibited Apo2L/TRAIL-induced cell death. Our results indicate that chemotherapy and Apo2L/TRAIL act synergistically to kill cancer cells but not normal bone-derived osteoblast-like cells, which has implications for future therapy of osteosarcoma. © 2002 Wiley-Liss, Inc.

A review of physical restraint minimization in the acute and residential care settings.

Abstract: Objectives. The objective of this review was to investigate physical restraint minimization in acute and residential care settings. The first aim was to determine the effectiveness of attempts to minimize the use of physical restraint, and the second was to generate a description of the characteristics of restraint minimization programmes. Method. A comprehensive search was undertaken involving all major databases and the reference lists of all relevant papers. To be included in the review studies had to be an evaluation of restraint minimization in an acute or residential care setting. As only a single randomized controlled trial (RCT) was identified, it was not possible statistically to pool the findings of different studies on the effectiveness of restraint minimization. To generate a description of the characteristics of restraint minimization programmes, the reported components of these programmes were identified and categorized. Results. A total of 16 studies evaluating restraint minimization were identified: three in acute care and 13 in residential care. Of these, only one was an RCT, with the most common approach being the before and after study design. Based on the findings of the single RCT, education supported by expert consultation effectively reduced the use of restraint in residential care. There has been little evaluation of restraint minimization in acute care settings. The common approach to restraint minimization has involved a programme of multiple activities, with restraint education being the characteristic common to most programmes. Discussion. Evidence suggests that physical restraint can be safely reduced in residential care settings through a combination of education and expert clinical consultation. There is little information on restraint minimization in acute care settings. The major finding of this review is the need for further investigation into all aspects of restraint minimization.

Division of short gastric vessels at laparoscopic nissen fundoplication: a prospective double-blind randomized trial with 5-year follow-up.

Abstract: Objective To determine whether division of the short gastric vessels at laparoscopic fundoplication confers long-term clinical benefit to patients.

Excitation of rat colonic afferent fibres by 5-HT3 receptors

Abstract: The gastrointestinal tract contains most of the body's 5-hydroxytryptamine (5-HT) and releases large amounts after meals or exposure to toxins. Increased 5-HT release occurs in patients with irritable bowel syndrome (IBS) and their peak plasma 5-HT levels correlate with pain episodes. 5-HT3 receptor antagonists reduce symptoms of IBS clinically, but their site of action is unclear and the potential for other therapeutic targets is unexplored. Here we investigated effects of 5-HT on sensory afferents from the colon and the expression of 5-HT3 receptors on their cell bodies in the dorsal root ganglia (DRG). Distal colon, inferior mesenteric ganglion and the lumbar splanchnic nerve bundle (LSN) were placed in a specialized organ bath. Eighty-six single fibres were recorded from the LSN. Three classes of primary afferents were found: 70 high-threshold serosal afferents, four low-threshold muscular afferents and 12 mucosal afferents. Afferent cell bodies were retrogradely labelled from the distal colon to the lumbar DRG, where they were processed for 5-HT3 receptor-like immunoreactivity. Fifty-six percent of colonic afferents responded to 5-HT (between 10−6 and 10−3 M) and 30 % responded to the selective 5-HT3 agonist, 2-methyl-5-HT (between 10−6 and 10−2 M). Responses to 2-methyl-5-HT were blocked by the 5-HT3 receptor antagonist alosetron (2 × 10−7 M), whereas responses to 5-HT were only partly inhibited. Twenty-six percent of L1 DRG cell bodies retrogradely labelled from the colon displayed 5-HT3 receptor-like immunoreactivity. We conclude that colonic sensory neurones expressing 5-HT3 receptors also functionally express the receptors at their peripheral endings. Our data reveal actions of 5-HT on colonic afferent endings via both 5-HT3 and non-5-HT3 receptors.

Diagnosis and prognosis of breast cancer by magnetic resonance spectroscopy of fine-needle aspirates analysed using a statistical classification strategy.

Abstract: Background: The aim was to develop robust classifiers to analyse magnetic resonance spectroscopy (MRS) data of fine-needle aspirates taken from breast tumours. The resulting data could provide computerized, classification-based diagnosis and prognostic indicators. Methods: Fine-needle aspirate biopsies obtained at the time of surgery for both benign and malignant breast diseases were analysed by one-dimensional proton MRS at 8·5 Tesla. Diagnostic correlation was performed between the spectra and standard pathology reports, including the presence of vascular invasion by the primary cancer and involvement of the excised axillary lymph nodes. Results: Malignant tissue was distinguished from benign lesions with an overall accuracy of 93 per cent. From the same spectra, lymph node involvement was predicted with an overall accuracy of 95 per cent, and tumour vascular invasion with an overall accuracy of 94 per cent. Conclusion: The pathology, nodal involvement and tumour vascular invasion were predicted by computerized statistical classification of the proton MRS spectrum from a fine-needle aspirate biopsy taken from the primary breast lesion. © 2001 British Journal of Surgery Society Ltd

Relationships between intestinal calcium absorption, serum vitamin D metabolites and smoking in postmenopausal women.

Abstract: Smoking has been associated with low bone density, fractures and poor intestinal calcium absorption. Calcium absorption is a critical factor in calcium balance in postmenopausal women but the mechanisms causing decreased absorption efficiency in postmenopausal smokers are controversial and poorly defined. We performed a cross-sectional study of 405 postmenopausal women attending a clinic for the management of osteoporosis to compare intestinal calcium absorption efficiency, serum vitamin D metabolites and parathyroid hormone levels in postmenopausal women who had never smoked, who were smokers previously or who were current smokers, to examine the relationships between these variables in smokers. Two hundred and fifty-two of the women had never smoked, 79 had smoked previously and 74 were current smokers. The hourly fractional rate of calcium absorption was similar in non-smokers and those who had previously smoked. Radiocalcium absorption was less in the 74 smokers compared with the 331 non-smokers [0.60 (0.29 SD) vs 0.71 (0.27); p = 0.004], as were serum calcitriol (p<0.001) and parathyroid hormone (PTH) (p<0.01). There was no difference in the relationship between calcium absorption and serum calcitriol between smokers (r = 0.38) and non-smokers (r = 0.28); hence the impaired calcium absorption in the smokers was almost entirely attributable to suppression of the PTH-calcitriol endocrine axis. In postmenopausal women smoking is associated with a reduction in calcium absorption efficiency due to suppression of the PTH-calcitriol axis. This impairment of calcium absorption could lead to accelerated bone loss and limit the usefulness of dietary calcium supplementation.

Propofol: relation between brain concentrations, electroencephalogram, middle cerebral artery blood flow velocity, and cerebral oxygen extraction during induction of anesthesia.

Abstract: BackgroundThe potential benefit of propofol dose regimens that use physiologic pharmacokinetic modeling to target the brain has been demonstrated in animals, but no data are available on the rate of propofol distribution to the brain in humans. This study measured the brain uptake of propofol in hum

Four-year review of open eye injuries at the Royal Adelaide Hospital.

Abstract: Purpose: To review the epidemiology of penetrating eye injuries and ruptured globes presenting to the Royal Adelaide Hospital, South Australia. Methods: A retrospective case review over a 4-year period. Results: There were 109 penetrated or ruptured globes in 105 patients. The average age was 41 years and 80.2% were men. Over half were from rural areas. The commonest cause of injury was hammering metal followed by motor vehicle accidents. Falls in the elderly were the commenest cause of globe ruptures. A final visual acuity of 6/12 or better was found in 40% of eyes and no perception of light in 27%. Conclusions: At the Royal Adelaide Hospital, the predominant referral centre for serious ocular injury in South Australia, approximately 25 open globe injuries are encountered a year. Although the epidemiology of these injuries was found to be similar to those previously reported in Victoria and rural New South Wales, differences were thought to reflect to the ageing population of South Australia. Rupture of an old, healed large-incision cataract extraction wound was the commonest cause of ruptured globe. An effective preventive strategy to reduce the incidence of severe ocular trauma has yet to be implemented. The concept of a national population-based severe ocular trauma database is considered.

National study of adverse reactions after vaccination with bacille Calmette-Guérin.

Abstract: Few large prospective studies of adverse reactions after bacille Calmette-Guerin (BCG) vaccination are available. In a prospective national study of such adverse reactions among 918 subjects (aged 1 day to 54 years) over a 14-month period, 45 vaccinees (5%) reported 53 adverse reactions (23 injection-site abscesses, 14 severe local reactions, 10 cases of lymphadenitis, and 6 other reactions). Only 1% of vaccinees required medical attention. Reactions, particularly lymphadenitis, were significantly less common in infants or =6 months) vaccinated by trained (vs. untrained) providers (relative risk [RR], 0.24; 95% confidence interval [CI], 0.09-0.68). Injection-site abscesses (RR, 2.96; 95% CI, 1.11-7.90) and severe local reactions (RR, 4.93; 95% CI, 1.11-21.90) were significantly more common in older vaccinees. Local reactions were more frequently reported by adult females than by adult males (RR, 7.18; 95% CI, 1.59-32.45). Adverse reactions were not significantly associated with any currently available vaccine batch, previous receipt of BCG vaccine, or concomitant administration of other vaccines.

Preferences for female and male nurses: the role of age, gender and previous experience --year 2000 compared with 1984

Abstract: Preferences for female and male nurses: the role of age, gender and previous experience – year 2000 compared with 1984 Background. The situations in which patients prefer a male or female nurse are not clear, as the literature reports differing relationships between gender and preference. Furthermore, most research has focused on female preferences. Methods. This questionnaire study investigated the preferences of both males and females for a male or female nurse, depending on four clinical situations. The role of age and previous experience with a male nurse was also taken into account. Gender, age and experience were further examined in relation to attitudes towards professional nursing practice. To determine whether preferences and attitudes have changed over time, the study was replicated in 2000, having been first conducted in 1984. Data were collected from the same general practice waiting room on each occasion. Results. Consistent with previous research, the degree of intimacy in a clinical situation was found to be predictive of same-gender preferences. Younger females may prefer female nurses more than older females. Experience with male nurses was limited in both samples, but was not predictive of preferences or attitudes. Conclusions. Generally speaking, results from 1984 and 2000 were not significantly different. As a quantitative study, this research contributes to an understanding of patient preferences. However, in-depth, qualitative research is recommended to understand better the reasons for preferences and attitudes, for both male and female patients.

Factors influencing the decision to abandon manual wheelchairs for three individuals with a spinal cord injury.

Abstract: Purpose : This study was conducted to identify factors which influence individuals with a spinal cord injury to abandon their first wheelchair before five years of use It aims to provide prescribing therapists and manufacturers with insights which may assist in facilitating better outcomes for wheelchair users, thereby reducing abandonment rates and containing replacement costs Method : A descriptive, qualitative design was used to gather the perceptions of three individuals with a spinal cord injury Results : Thematic analysis yielded five themes: 'Participants' experience of the first prescription'; 'The physical issues with the wheelchair have functional implications'; 'Gaining experience is so important'; 'Participants' experience of the second prescription'; and 'Participants' suggestions' Conclusions : Factors influencing manual wheelchair abandonment for these participants were consistent with findings from the literature concerning dissatisfaction and abandonment of assistive technology For t

Induction of persistent changes in the organisation of the human motor cortex.

Abstract: Motor learning must involve changes in the organisation of the brain, and it seems axiomatic that afferent signals generated during repeated motor practice contribute to this. In this study, motor-point stimulation of the first dorsal interosseous (FDI) muscle was paired with transcranial magnetic stimulation of the human motor cortex on three successive days to determine whether repeated stimulation sessions result in enduring reorganisation of the motor cortex. This repeated “dual” stimulation induced significant changes in the excitability of the motor cortex together with expansion of the area of scalp from which these responses were elicited. The expansion in muscle representation was accompanied by large movements in the centre of gravity (CoG), suggesting a true reorganisation of the underlying cortical representational zone. The changes persisted for at least 2 days following the last stimulation session. It is concluded that repeated dual stimulation is capable of inducing long-lasting reorganisation within the motor cortex. These changes may be similar in nature to those seen in the motor cortex during motor learning. Moreover, these observations suggest that it may be possible to induce the motor cortex of patients who have suffered strokes to reorganise in a way that improves the voluntary control of the weakened muscles.

Comparison of the mechanisms of nongenomic actions of thyroid hormone and steroid hormones.

Abstract: Steroids and thyroid hormone are thought primarily to act via binding to hormonespecific nuclear receptor superfamily members. The nuclear ligand-receptor complexes then initiate transcriptional activity. Actions of steroids and iodothyronines that are nongenomic or extranuclear in mechanism have been recognized recently and new insights into such mechanisms are available. Despite their distinct structures and biologic effects, the two families of hormones have similarities in the mechanisms of their nongenomic actions. That is, both steroids and thyroid hormone appear to interact with specific cell surface G protein-coupled receptors and to activate signal transducing kinases such as those involved in the mitogen-activated protein kinase (MAPK) pathway. Much is known about the ability of certain steroids such as estrogen and mineralocorticoids to increase [Ca2+]i acutely and stimulation of the MAPK cascade by L-T4 appears to depend upon a hormone-induced increase in [Ca2+]i via phosphoinositide pathway activation. At least in the case of iodothyronines, hormone activation of the MAPK pathway modulates the cellular activities of certain cytokines and growth factors. One of the two cell surface estrogen receptors (ERs) may be an expression of the same transcript as that for nuclear ER, whereas the mineralocorticoid and progesteronebinding proteins in the plasma membrane appear to be products of genes different from those of nuclear receptors. Iodothyronine structure-activity relationships at the plasma membrane binding site for thyroid hormone suggest that the cell surface receptor for T4 that also binds 3,5,3′-triiodo-L-T3 is different from the nuclear T3 receptor (TR). There are interfaces of nongenomic and genomic mechanisms for both steroids and thyroid hormone. For example, by nongenomic mechanisms, estrogen and thyroid hormone can promote serine phosphorylation, respectively, of nuclear ER and TR. Transcriptional activity of the nuclear receptor proteins can be altered by such phosphorylation.