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Biomedical subjects

O Hardiman

Publications and source records attributed to O Hardiman.

At least 37 records · Page 2Linked to original sources
PubMed2000

Amyotrophic lateral sclerosis mimic syndromes: a population-based study.

BACKGROUND: The Irish ALS Register is a population-based register of the epidemiological characteristics of amyotrophic lateral sclerosis (ALS) in the republic of Ireland. OBJECTIVE: To describe the clinical and demographic details of those patients included in the Irish ALS Register who were incorrectly diagnosed as having ALS (patients who were ultimately rediagnosed as having an "ALS mimic syndrome"). METHODS: The medical records of each patient referred to the register are routinely reviewed and, where possible, patients are examined by our group during their illness. RESULTS: Between January 1, 1993, and December 31, 1997, 32 patients (representing 7.3% of 437 referrals) were rediagnosed as having a condition other than ALS. The median age at onset for these 32 patients was 56.0 years (range, 19.5-85.8 years) for men and 53.5 years (range, 39.5-70.4 years) for women. Twenty-nine patients (91%) presented with symptoms referable to the limbs, and the remainder presented with symptoms involving the bulbar musculature. Multifocal motor neuropathy was the most common condition mistaken for ALS, accounting for 7 cases (22%), followed closely by Kennedy disease (4 cases [13%]). Factors leading to diagnostic revision included evolution of atypical symptoms, results of specific investigations, and failure of symptoms to progress. Twenty-seven (84%) of the patients with an ALS mimic syndrome fulfilled the El Escorial criteria for either "suspected" or "possible" ALS, 4 (13%) met the criteria for probable ALS, and 1 (3%) had definite ALS. CONCLUSIONS: The application of the El Escorial diagnostic criteria may facilitate early recognition of non-ALS cases. Misdiagnosis of ALS remains a common clinical problem despite the increased availability of investigations and a greater awareness among neurologists of potential diagnostic pitfalls.

Adult↗
PubMed2000

Symptomatic treatment of respiratory and nutritional failure in amyotrophic lateral sclerosis.

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterised by death of upper and lower motor neurones. Nutritional and respiratory failure occurs in most patients with ALS. Nutritional failure occurs primarily as a result of dysphagia, although malnutrition may also develop in the absence of clinically apparent dysphagia. The optimal management of nutrition in early ALS has not been established. In later stages of the disease, parenteral nutritional support using percutaneous endoscopic gastrostomy confers a significant survival benefit in selected patients. Respiratory failure occurs as a result of bulbar, cervical and thoracic loss of motor neurones. Inspiratory muscles are preferentially affected. Management of respiratory failure includes the use of strategies that limit aspiration pneumonia, the reduction in secretions, and positioning of the patient to a maximal mechanical advantage. Use of non-invasive positive pressure ventilation in appropriate patients significantly enhances survival. The decision to undertake invasive mechanical ventilation should be made prior to the development of symptoms that might warrant this intervention. The progressive nature of the condition should be taken into account when such a decision is discussed with the patient and carer. Further studies are required to determine the optimal nutritional requirements of patients with ALS, and to elucidate the physiological changes involved in the decline in respiratory function.

Amyotrophic Lateral Sclerosis↗
PubMed2000

Binding of 125I-insulin-like growth factor-II to cells cultured in fetal bovine serum: a complication.

Insulin-like growth factor II is an important fetal mitogen in mice and humans and its biological activity is regulated in a complex manner. The peptide interacts with three membrane-bound receptors, with a superfamily of insulin-like growth factor binding proteins and with the proteoglycan, glypican-3. Recently, the blood protein, vitronectin, has been identified as a novel insulin-like growth factor II-binding protein. Many studies have used cell lines maintained in fetal bovine serum to identify cell surface insulin-like growth factor II binding sites. We now describe a complication associated with the interpretation of such in vitro studies. Fetal bovine serum-derived vitronectin adheres very tightly to tissue culture dishes. When cells that have been maintained in fetal bovine serum are incubated with 125I-insulin-like growth factor II, a substantial fraction of the 125I-insulin-like growth factor II apparently associated with the cell surfaces may represent radioliogand bound by the fetal bovine serum-derived vitronectin. This may result in over-estimation of cell surface insulin-like growth factor II binding sites.

Animals↗
PubMed2000

Pitfalls in the diagnosis of motor neurone disease.

Motor neurone disease is characterized by progressive degeneration of upper and lower motor neurones with preservation of cognition. Recognition of classical motor neurone disease is not difficult, but during the early stages both false positive and false negative diagnoses are common. Careful examination, frequent follow-up and ancillary tests are necessary to avoid erroneous diagnoses.

Diagnosis, Differential↗
PubMed1999

Incidence and prevalence of ALS in Ireland, 1995-1997: a population-based study.

BACKGROUND: We conducted a prospective, population-based study of ALS in the Republic of Ireland for the 3-year period 1995 to 1997. METHODS: To ensure complete case ascertainment, multiple sources of information were used, including consultant neurologists, neurophysiologists, primary care physicians, and the Irish Motor Neuron Disease Association. The El Escorial diagnostic criteria for ALS were applied to all cases enrolled on the register and each patient was regularly followed up during his or her illness. RESULTS: Between January 1, 1995, and December 31, 1997, 231 patients were diagnosed with possible, probable, or definite ALS, including 133 men (57.6%) and 98 women (42.4%). The average annual incidence rate was 2.1 per 100,000 person-years (95% CI, 1.8 to 2.4), and 2.8 per 100,000 person-years for the population older than 15 years (95% CI, 2.4 to 3.1). The incidence rate was higher for men, being 2.5 per 100,000 person-years (95% CI, 2.0 to 2.9), than for women, at 1.8 per 100,000 person-years (95% CI, 1.5 to 2.2), and increased with age for both sexes. The median age at onset was 64.2 years for men and 67.8 years for women. On December 31, 1996, the crude prevalence was 4.7 per 100,000 of the total population (95% CI, 4.0 to 5.5), and 6.2 per 100,000 for the population older than 15 years (95% CI, 5.3 to 7.1). Adjusting to the 1996 Irish population as standard, the incidence of ALS in Ireland during the 3-year study period is the third highest reported to date. CONCLUSIONS: There was a trend toward a higher incidence of ALS in the northwestern region of Ireland, although the numbers of cases involved were small and further study is required.

Age Distribution↗
PubMed1998

Status epilepticus.

Explore the source record for details and available documents.

Diagnosis, Differential↗
PubMed1998

Service provision for patients with ALS/MND: a cost-effective multidisciplinary approach.

Optimal management of patients with ALS/MND requires a team approach, with early referral to paramedical services for clinical assessment and prompt intervention. As the condition progresses, a flexible approach to management must be adopted by the medical team, with an ability to intervene at very short notice. We have developed an efficient multi-disciplinary clinic that services the ALS/MND population of Ireland by combining the existing infrastructure of community services with a hospital-based specialist clinic. The clinic operates on a weekly basis, and is staffed by a core team including a neurologist, a liaison nurse, and the director of the ALS/MND Association. On-site and same-day physiotherapy, occupational therapy and speech therapy is available, as is pulmonary evaluation. All patients utilising the clinical services are automatically included on the Irish Register of Motor Neurone Disease, and are tracked by the liaison nurse. The core members of the clinic interact regularly with paramedical staff within the community, ensuring that necessary community services are made available within 1-2 weeks of the clinic visit. Equipment necessary for the patient's well being is made available free of charge by the Irish Motor Neurone Disease Association, following an appropriate request from the regional para-medical staff. We have thus demonstrated that an effective multi- disciplinary care service for ALS/MND can be developed at modest cost by close personal liaison between the existing health care structures and core members of a multidisciplinary team.

Amyotrophic Lateral Sclerosis↗
PubMed1997

Paramyotonia congenita and hyperkalemic periodic paralysis associated with a Met 1592 Val substitution in the skeletal muscle sodium channel alpha subunit--a large kindred with a novel phenotype.

Paramyotonia congenita (PC) and Hyperkalemic periodic paralysis (HyperPP) are caused by amino acid substitutions in the alpha subunit of the human skeletal muscle sodium channel. One such substitution, methionine for valine at position 1592, has been associated with HyperPP with myotonia and cold sensitivity. We report clinical, electromyographic (EMG), genetic and pathological features of a large kindred with the Met1592Val substitution. Affected members were phenotypically heterogenous and had episodic potassium-sensitive paralysis, and stiffness and weakness induced by exercise and cold, which was confirmed by EMG studies. These features indicate a combined PC-HyperPP phenotype not previously described with this mutation.

Adult↗
PubMed1997

Inflammatory myopathy in thyrotoxicosis.

A 45-year-old man with a 3-month history of episodic muscle weakness, MRC grade 4/5 symmetric hip flexor weakness, elevated CK, and an inflammatory myopathy was found to have elevated free thyroxine and T3. Treatment with carbimazole resulted in complete resolution of symptoms and return of muscle power to normal. A repeat biopsy revealed resolution of the inflammatory endomysial infiltrate and an absence of necrosis. Complete clinical and pathologic resolution of a thyrotoxicosis-associated inflammatory myopathy without steroid therapy has not been previously described. The favorable outcome experienced by this patient indicates that steroids may not be necessary in thyrotoxicosis-associated inflammatory myopathy.

Antithyroid Agents↗
PubMed1996

Adenylyl cyclase activity in clonally derived human myoblast cultures: evidence for myoblast heterogeneity.

In vitro myogenesis recapitulates the programme of myogenesis in vivo. During the process of muscle differentiation, cAMP plays an important role in the control of gene expression and in the integration of metabolic functions. cAMP generation may be affected by drugs or hormones that interact with the membrane-bound enzyme adenylyl cyclase, including adrenergic agents and glucocorticoids. In this study, adenylyl cyclase activity was evaluated in membranes prepared from human clonally derived muscle cultures. In control cultures, there was considerable inter-clonal variation in basal, sodium-fluoride and forskolin-stimulated adenylyl cyclase activity. Cultures differed in their response to steroids: adenylyl cyclase activity was markedly enhanced in some clones, and was significantly inhibited in other clones. Pre-treatment of cultures with pertussis toxin indicated that the effects of steroids are mediated in part by modulation of G-protein activity. These findings indicate a substantial heterogeneity among myoblast clones with respect to the modulating effect of steroids on adenylyl cyclase activity. This observation may account for the conflicting reports of steroid effects on muscle in vitro, and may be of relevance to the understanding of possible transmembrane signalling alterations in muscle disease.

Adenylate Cyclase Toxin↗
PubMed1994

Dystrophin deficiency, altered cell signalling and fibre hypertrophy.

Dystrophin is a subsarcolemmal protein which is defective in Duchenne and Becker muscular dystrophy (DMD/BMD), and in three animal models. Clinical manifestations of dystrophin deficiency in humans range from a mild calf muscle hypertrophy with cramps to the classical progressive degenerative hypertrophic myopathy of Duchenne. A common feature in the clinical presentation of dystrophin deficiency in humans and in the three documented animal models is the presence of muscle fibre hypertrophy. This paper explores the hypothesis that membrane-bound signalling processes are disrupted in the absence of dystrophin, and suggests that these abnormalities may contribute to both the hypertrophic and degenerative changes of dystrophin deficiency.

Animals↗
PubMed1993

Neuropathic findings in oculopharyngeal muscular dystrophy. A report of seven cases and a review of the literature.

We describe seven patients with clinical evidence of oculopharyngeal muscular dystrophy. Four of these patients were members of the same Italian-American family. The age at onset was after the fourth decade in all patients. All seven patients had extraocular muscle involvement, and six of the seven patients had clinical, electrophysiological, and/or pathological evidence of neuropathy in addition to features that were suggestive of myopathy. An autopsy was performed on one patient. We discuss the significance of the concurrence of neuropathic features with oculopharyngeal muscular dystrophy in relation to these patients and previously reported cases.

Aged↗
PubMed1993

Methylprednisolone selectively affects dystrophin expression in human muscle cultures.

Glucocorticoid therapy slows the progression of Duchenne muscular dystrophy. In muscle cultures, the addition of the glucocorticoid methylprednisolone increases myogenesis in most normal mixed and clonal cultures. Conversely, in some normal clonal and most dystrophic cultures, methylprednisolone inhibits fusion. However, in fusion-arrested normal and Becker muscular dystrophy cultures, dystrophin is expressed independently of fusion and of myosin heavy chain expression, and in some cases, expression is apparently enhanced by methylprednisolone. We suggest that dystrophin is a muscle-specific protein that does not require fusion for expression, and the methylprednisolone-induced enhancement of dystrophin expression may account for some of the clinical benefits of glucocorticoids in vivo.

Blotting, Western↗
PubMed1993

Expression of major histocompatibility complex antigens in cultures of clonally derived human myoblasts.

We examined class I and class II HLA antigen expression by flow cytometry in clonal cultures derived from normal human skeletal muscle biopsies. Both HLA class I and class II antigens were constitutively expressed in all clones studied. By altering the constituents of the culture medium, we could modulate the expression of HLA class II but not HLA class I antigens. We noted heterogeneity in the expression of HLA class II antigens among different clones; an increased expression was associated with an increased propensity of myoblasts to fuse. These findings indicate that normal aneurally cultured myoblasts may express both HLA class I and class II antigens, that this expression may be modulated by in vitro agents, and that the presence of these antigens may relate to the process of in vitro myoblast fusion.

Cell Adhesion Molecules, Neuronal↗
PubMed1993

Direct effects of cyclosporin A and cyclophosphamide on differentiation of normal human myoblasts in culture.

We examined the direct effects of the commonly used immunosuppressive agents cyclosporin A and cyclophosphamide on cultures of clonally derived aneural human myoblasts. When applied to cultures in doses reflecting the therapeutic dose in vivo, both cyclosporin A and cyclophosphamide had dose-related reproducible effects on myoblast fusion: fusion was enhanced by cyclophosphamide and inhibited by cyclosporin A. These findings indicate that immunosuppressive agents may have effects on muscle that are independent of their ability to regulate the immune system.

Cell Differentiation↗
PubMed1992

Differential glucocorticoid effects on the fusion of Duchenne/Becker and control muscle cultures: pharmacologic detection of accelerated aging in dystrophic muscle.

We report that the glucocorticoid methylprednisolone (Mepd) enhanced myogenesis in normal primary human muscle cultures, but inhibited myogenesis of most Duchenne/Becker muscle cultures. A decline in the magnitude of myogenic stimulation of Mepd correlated with age in a random group of control patients, including some with neurologic diseases other than Duchenne/Becker dystrophy. A case of Duchenne muscular dystrophy from an exceptionally young patient yielded a muscle culture that was myogenically stimulated by Mepd. These results suggest that continuous cycles of degeneration and regeneration of dystrophic muscle in vivo may result in a change of the glucocorticoid response of the muscle progenitor cells. The glucocorticoid effects suggest caution in the long-term clinical use of these agents for muscle disease such as Duchenne muscular dystrophy.

Adolescent↗
PubMed1988

Microdysgenesis in resected temporal neocortex: incidence and clinical significance in focal epilepsy.

Fifty patients underwent superficial temporal lobectomy for intractable temporal lobe epilepsy. Total cure rate was 52%, and significant improvement was achieved in 88%. Cytoarchitectural changes in gray and white tissue were analyzed under light microscopy. Neuronal dysgenesis was correlated with the duration of seizure disorder, age of onset, and other etiologic factors, and with clinical outcome. Temporal lobes from 33 neurologically normal autopsy brains which were age- and sex-matched with patients were examined as controls. Severe neuronal ectopia (greater than 8 neurons/2 mm2 white matter) was present in 42% of patients with epilepsy and in none of controls. There was neuronal clustering in 28% of those with epilepsy, and Chaslin's (subpial) gliosis in 38%. Controls did not have these changes. The presence of severe neuronal ectopia and clustering was predictive of a favorable clinical outcome following surgery (p less than 0.05). No correlation was found between microdysgenesis and other factors. These findings suggest that the presence of neuronal dysgenesis may be of significance in the clinical outcome following surgery, and that the abnormal tissue may be important as a morphologic substrate for seizures in some patients.

Adolescent↗