Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0000737 (abdominal pain)
 31,184 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Ten patients with multiple sclerosis (MS) were enrolled in a preliminary trial of the potassium channel blocker, 3,4-diaminopyridine, to evaluate drug toxicity and pharmacokinetics. The patients were treated with oral 3,4-diaminopyridine, first with increasing single doses up to 100 mg and then with divided dosage for up to 3 weeks. Paresthesias were reported by all patients and abdominal pain was dose limiting in 6 patients. 3,4-Diaminopyridine levels and half-life varied widely from patient to patient. Cerebrospinal fluid levels of 3,4-diaminopyridine were about 10% of those in serum. Neither seizures nor epileptiform changes on electroencephalographic examination occurred. Small reversible improvements in specific neurological deficits were seen on examination in all patients and reversible improvement in visual evoked response latencies were found in 2 patients. These results suggest that further study of 3,4-diaminopyridine in patients with MS is warranted.
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PMID:Preliminary trial of 3,4-diaminopyridine in patients with multiple sclerosis. 235 97

To determine the prevalence and nature of pain in multiple sclerosis, we evaluated by questionnaire, interview, and chart review 159 patients residing in Middlesex County and followed in the MS Clinic at University Hospital, London, Ontario, Canada. Eighty-eight patients (55%) had either an acute or chronic pain syndrome at some time during their disease. Fifteen patients (9%) with acute pain syndromes had episodes of paroxysmal tic-like pain diagnosed in seven as trigeminal neuralgia. Chronic pain syndromes, present for a mean duration of 4.9 years, occurred in 76 patients (48%) and included dysesthetic extremity pain (29%), back pain (14%), painful leg spasms (13%), and abdominal pain (2%). MS patients with pain were similar to the pain-free group in mean age of onset (34.0 versus 31.9 years), average duration of disease (13.3 versus 12.1 years), spinal cord involvement (97% for each group), and mean rating on Kurtzke Disability Status Scale (4.2 versus 3.5). They differed in sex ratio with a higher female-to-male ratio in the pain group (3:1 versus 1.4:1). Chronic pain is a common feature of well-established MS and is usually associated with a myelopathy. Therapy must be individualized for each specific pain syndrome.
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PMID:Pain syndromes in multiple sclerosis. 273 10

Because the symptomatic treatments for multiple sclerosis (MS) are limited, new approaches have been sought. Anatomical studies of MS lesions show a relative preservation of axons, and clinical studies suggest that some of the neurological impairment in patients with MS is physiological. Electrophysiological studies suggest that demyelination exposes axonal potassium channels that decrease action-potential duration and amplitude, hindering action-potential propagation. Potassium channel blockers, including aminopyridines, have been shown to improve nerve conduction in experimentally demyelinated nerves. Two potassium channel blockers, 4-aminopyridine (AP) and 3,4 diaminopyridine (DAP) have been tested in patients with MS. Preliminary studies of AP demonstrated benefit in many temperature-sensitive patients with MS, and improvement of function was found in a large randomized double-blind, placebo-controlled crossover trial of 3 months of oral treatment in 68 patients with MS. An open-label trial of DAP showed improvement in some deficits, and a double-blind placebo-controlled trial showed significant improvements in prospectively defined neurological deficits. A crossover comparison of the two agents suggested that AP produces more central nervous system side effects (dizziness and confusion), whereas DAP produces more peripheral side effects (paresthesias and abdominal pain). Both agents have rarely caused seizures. These studies suggest that aminopyridines may provide a new approach to the symptomatic treatment of MS.
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PMID:The current status of studies of aminopyridines in patients with multiple sclerosis. 801 70

1. Aminopyridines have been used as beneficial symptomatic treatments in a variety of neurological conditions including multiple sclerosis but have been associated with considerable toxicity in the form of abdominal pain, paraesthesias and (rarely) convulsions. 2. Extracellular and intracellular recording was used to characterize action potentials in rat sciatic nerves and dorsal roots and the effects of 4-aminopyridine (4-AP). 3. In sciatic nerve trunks, 1 mM 4-AP produced pronounced after potentials at room temperature secondary to regenerative firing in affected axons (5-10 spikes per stimulus). At physiological temperatures, after potentials (2-3 spikes) were greatly attenuated in peripheral axons. 4. 4-AP evoked more pronounced and prolonged after discharges in isolated dorsal roots at 37 degrees C (3-5.5 mV and 80-100 ms succeeded by a smaller inhibitory/depolarizing voltage shift) which were used to assess the effects of anticonvulsants. 5. Phenytoin, carbamazepine and lamotrigine dose-dependently reduced the area of 4-AP-induced after potentials at 100 and 320 microM but the amplitude of compound action potentials (evoked at 0.5 Hz) was depressed in parallel. 6. The tonic block of sensory action potentials by all three drugs (at 320 microM) was enhanced by high frequency stimulation (5-500 Hz). 7. The lack of selectivity of these frequency-dependent Na+ channel blockers for burst firing compared to low-frequency spikes, is discussed in contrast to their effects on 4-AP-induced seizures and paroxysmal activity in CNS tissue (which is associated with large and sustained depolarizing plateau potentials). 8. In conclusion, these in vitro results confirm the marked sensitivity of sensory axons to 4-AP (the presumptive basis for paraesthesias). Burst firing was not preferentially impaired at relatively high concentrations suggesting that anticonvulsants will not overcome the toxic peripheral actions of 4-AP in neurological patients.
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PMID:The effects of anticonvulsants on 4-aminopyridine-induced bursting: in vitro studies on rat peripheral nerve and dorsal roots. 882 51

To examine the efficacy and toxicity of oral 3,4 diaminopyridine (DAP) in dosages up to 100 mg/day, 36 patients with multiple sclerosis (MS) enrolled in a randomized, double-blind, placebo-controlled, crossover trial. The primary outcome measure was improvement of a prospectively defined neurologic deficit, which was leg weakness in 34 patients. Secondary outcome measures included the patient's subjective response, scored manual motor testing (MMT) of leg strength, scored leg strength from videotaped motor testing (VMT), quadriceps and hamstrings strength (QMT) measured by isometric dynamometry, neuropsychological testing (NPT), ambulation index (AI), and Expanded Disability Status Scale (EDSS) score. Paresthesias and abdominal pain were common and were dose limiting in eight patients. Three patients had episodes of confusion, and one patient had a seizure while on DAP. Eight patients withdrew from the study, leaving 28 evaluable patients for the efficacy analysis. The prospectively defined neurologic deficit improved in 24 patients-22 on DAP and 2 on placebo (p = 0.0005). All improvements were in leg weakness. Subjective response and measures of leg strength and function (MMT, VMT, QMT, and AI) improved on DAP compared with placebo. Neither NPT nor EDSS scores improved. DAP treatment can induce improvements in leg strength in MS patients, but toxicity is limiting in many patients.
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PMID:Treatment with oral 3,4 diaminopyridine improves leg strength in multiple sclerosis patients: results of a randomized, double-blind, placebo-controlled, crossover trial. 896 Jul 27

Pneumatosis intestinalis is defined as the presence of gas within the bowel wall. Small bowel pneumatosis is less commonly reported and more severe than colonic disease in adults. Pneumatosis coli is characterised by multiple collections of encysted gas occurring within the sub-mucosa and subserosa of the colon and rectum. It is an uncommon condition which typically presents in late middle age and has been associated with a number of gastrointestinal (e.g. pyloric stenosis, sigmoid volvulus and ischaemic bowel) and non-gastrointestinal (e.g. chronic obstructive pulmonary disease, depression and multiple sclerosis) diseases. Some cases, however, are idiopathic or primary. Symptoms can include diarrhoea, constipation, mucus per rectum, bleeding, flatus, abdominal pain and, rarely, faecal incontinence. We report on two patients, one of whom presented with faecal incontinence, the other who had troublesome lower gastrointestinal symptoms including faecal incontinence. Both responded well to continuous oxygen therapy.
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PMID:Pneumatosis coli: an uncommon but treatable cause of faecal incontinence. 1062 93

We report the coexistence of multiple sclerosis (MS) and an intradural extramedullary spinal cord tumour in a 46-year-old woman with a 2-year history of MS. The patient presented with right hemitrunk and lower extremity paraesthesias, urinary incontinence, and intermittent lower right back and abdominal pain, which did not respond to pulse steroid therapy. A spinal magnetic resonance imaging (MRI) study revealed an intradural extramedullary spinal cord tumour in the lower thoracic spine, later diagnosed as schwannoma. We call attention to this rare association of MS and a spinal cord tumour, and emphasize the need for scrutiny of new and uncommon symptoms during the follow-up of MS patients.
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PMID:Multiple sclerosis and coexisting intradural extramedullary spinal cord tumour: a case report. 1239 96

Tumour necrosis factor receptor-associated periodic syndrome (TRAPS), a rare autosomal dominant disorder, is characterised by recurrent attacks of fever, myalgias, and abdominal pain. However, manifestations in the central nervous system are hardly known. We describe a family in which one of three affected members developed central nervous system symptoms. First diagnosed as multiple sclerosis (MS), the demyelinisation seems to be a feature of TRAPS rather than MS. The syndrome is discussed as a rare differential diagnosis of MS.
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PMID:[Tumour necrosis factor receptor-associated periodic syndrome. A rare differential diagnosis of multiple sclerosis]. 1583 93

A 46-year-old man with multiple sclerosis had severe generalised pain for which treatment with paracetamol, ibuprofen, gabapentin and methyl-prednisolone had been unsuccessful. In addition normocytic anaemia without haemolysis and with a normal iron load was found. Due to bright red rectal blood loss and nausea, vomiting, weight loss, anorexia, abdominal pain and constipation a colonoscopy was planned. However, before this was performed, manual slide differentiation of a blood smear showed basophilic stippling and it turned out that the patient had been taking Ayurvedic medication up to one month before presentation. A moderately severe lead intoxication was diagnosed: 0.77 mg/l. The herbal medication had a very high lead content. The patient was successfully treated with the oral lead chelator 23-dimercaptosuccinic acid. Traditional and folk remedies often are important causes of lead poisoning.
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PMID:[Chronic lead intoxication associated with Ayurvedic medication]. 1640 16

Crohn's disease and ulcerative colitis (UC) are common, chronic inflammatory bowel diseases (IBDs) characterized by episodes of life-altering symptoms such as diarrhea, bleeding, fecal urgency and incontinence, abdominal pain and cramps, and fever lasting weeks to months at a time. Existing treatments are 5-aminosalicyclates or immunosuppressants, but long-term control of IBD is a major problem for a large number of patients. Phosphodiesterase 4 (PDE4) is a key enzyme in cell homeostasis and inflammation and its inhibition has been useful in diseases such as asthma and chronic obstructive pulmonary disease, rheumatoid arthritis and multiple sclerosis. This review focuses on the role of oxidative stress in IBD and the PDE4 inhibitor OPC-6535 (tetomilast), an investigational agent for the treatment of UC. The authors detail the clinical development of the compound and report and provide insight into some of the unpublished data from the recently completed multicenter Phase III trials in UC.
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PMID:Phosphodiesterase 4 inhibitors and inflammatory bowel disease: emerging therapies in inflammatory bowel disease. 1771 33


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