Long-term trends in carpal tunnel syndrome.

OBJECTIVE: To assess temporal trends in carpal tunnel syndrome (CTS) incidence, surgical treatment, and work-related lost time. METHODS: Incident CTS and first-time carpal tunnel release among Olmsted County, Minnesota, residents were identified using the medical records linkage system of the Rochester Epidemiology Project; 80% of a sample were confirmed by medical record review. Work-related CTS was identified from the Minnesota Department of Labor and Industry. RESULTS: Altogether, 10,069 Olmsted County residents were initially diagnosed with CTS in 1981-2005. Overall incidence (adjusted to the 2000 US population) was 491 and 258 per 100,000 person-years for women vs men (p < 0.0001) and 376 per 100,000 for both sexes combined. Adjusted annual rates increased from 258 per 100,000 in 1981-1985 to 424 in 2000-2005 (p < 0.0001). The average annual incidence of carpal tunnel release surgery was 109 per 100,000, while that for work-related CTS was 11 per 100,000. An increase in young, working-age individuals seeking medical attention for symptoms of less severe CTS in the early to mid-1980s was followed in the 1990s by an increasing incidence in elderly people. CONCLUSIONS: The incidence of medically diagnosed carpal tunnel syndrome (CTS) accelerated in the 1980s. The cause of the increase is unclear, but it corresponds to an epidemic of CTS cases resulting in lost work days that began in the mid-1980s and lasted through the mid-1990s. The elderly present with more severe disease and are more likely to have carpal tunnel surgery, which may have significant health policy implications given the aging population.

Syncope associated with pain as the presenting feature of neck malignancy: failure of cardiac pacemaker to prevent attacks in two cases.

Two patients are described in whom syncope was the presenting clinical feature of an undiagnosed neck malignancy. Both patients also had attacks associated with paroxysms of severe neck pain. Neither patient responded to cardiac pacing.

Optic chiasm enhancement associated with giant aneurysm and yttrium treated pituitary adenoma.

A patient with a history of pituitary tumour treated with yttrium 29 years before presented with an asymmetrical chiasmal neuropathy. Magnetic resonance imaging showed a partially thrombosed giant aneurysm of the right internal carotid artery, with enhancement of the chiasm and right optic tract adjacent to the aneurysm. It was thought that, in addition to the effects of compression, a peri-aneurysmal inflammatory reaction had developed, causing breakdown of the blood-brain barrier and consequent inflammatory changes in the optic chiasm. High dose steroid treatment led to significant improvement in vision within two weeks. Steroids may have a role in the acute preservation of vision in similar cases, as well as in cases of deterioration following coiling or embolisation of aneurysms where thrombosis within the aneurysm has been induced.

Practice parameter: early detection of dementia: mild cognitive impairment (an evidence-based review). Report of the Quality Standards Subcommittee of the American Academy of Neurology.

OBJECTIVE: The goal of this project was to determine whether screening different groups of elderly individuals in a general or specialty practice would be beneficial in detecting dementia. BACKGROUND: Epidemiologic studies of aging and dementia have demonstrated that the use of research criteria for the classification of dementia has yielded three groups of subjects: those who are demented, those who are not demented, and a third group of individuals who cannot be classified as normal or demented but who are cognitively (usually memory) impaired. METHODS: The authors conducted computerized literature searches and generated a set of abstracts based on text and index words selected to reflect the key issues to be addressed. Articles were abstracted to determine whether there were sufficient data to recommend the screening of asymptomatic individuals. Other research studies were evaluated to determine whether there was value in identifying individuals who were memory-impaired beyond what one would expect for age but who were not demented. Finally, screening instruments and evaluation techniques for the identification of cognitive impairment were reviewed. RESULTS: There were insufficient data to make any recommendations regarding cognitive screening of asymptomatic individuals. Persons with memory impairment who were not demented were characterized in the literature as having mild cognitive impairment. These subjects were at increased risk for developing dementia or AD when compared with similarly aged individuals in the general population. RECOMMENDATIONS: There were sufficient data to recommend the evaluation and clinical monitoring of persons with mild cognitive impairment due to their increased risk for developing dementia (Guideline). Screening instruments, e.g., Mini-Mental State Examination, were found to be useful to the clinician for assessing the degree of cognitive impairment (Guideline), as were neuropsychologic batteries (Guideline), brief focused cognitive instruments (Option), and certain structured informant interviews (Option). Increasing attention is being paid to persons with mild cognitive impairment for whom treatment options are being evaluated that may alter the rate of progression to dementia.

Use of transient evoked otoacoustic emissions to detect and monitor cochlear damage caused by platinum-containing drugs.

Transient evoked otoacoustic emissions (TEOAE) have been evaluated as a means of monitoring cochlear function in patients receiving the chemotherapeutic agents cisplatin and carboplatin (-cis-diammine, 1,1-cyclobutane dicarboxylate (2) -0,0-platinum). Patients receiving these drugs were monitored prospectively with pure tone audiometry (PTA), tympanometry and TEOAE. Data was collected on 22 subjects receiving cisplatin and nine subjects receiving carboplatin. Significant deterioration in both PTA thresholds and TEOAE energy levels (with no change in tympanometry) were detected in the cisplatin group. No significant deterioration in audiological parameters occurred in the carboplatin group. It is indicated that cisplatin has a significant ototoxic effect in the majority of patients, whereas any ototoxic effect of carboplatin was undetectable. Our findings were different from previous studies in that the measurable changes in TEOAE occurred later than changes in the pure tone audiogram for the cisplatin group.

The costs of early hearing screening in England and Wales.

A survey was carried out in 10 centres in England and Wales to determine the costs of hearing screening in the first year of life. The screens that were studied were targeted neonatal, universal neonatal, and the health visitor distraction test (HVDT) or alternative surveillance. Valid data were available from five centres for targeted neonatal screening (TNS), three for universal neonatal screening (UNS), and nine for the HVDT, although only five of the HVDT screens had valid data for follow up costs. The neonatal costs were consistent across the centres surveyed, whereas those for the HVDT screen varied considerably. The mean service costs for TNS, UNS, and the HVDT at 1994 prices were 5052 Pounds, 13,881 Pounds, and 24,519 Pounds for a standardised district of 1000 live births. Three conclusions seem justified. Firstly, UNS need not be prohibitively expensive as it costs considerably less than HVDT screening. Secondly, TNS appears to be a relatively inexpensive way of improving the age of identification of a proportion of the congenitally hearing impaired. Thirdly, given the published yields for UNS and the HVDT, the results indicate that UNS offers the most cost effective overall approach with alternative systems in place to identify late onset permanent hearing losses.

Pancreatic enzyme supplementation in cystic fibrosis patients before and after fibrosing colonopathy.

BACKGROUND: In 1994 we cared for nine cystic fibrosis patients with fibrosing colonopathy. To evaluate the relationship between fibrosing colonopathy and supplemental pancreatic enzymes we reviewed our dosing of enzymes prior to fibrosing colonopathy development and then evaluated the subsequent effect of drastically reducing pancreatic enzyme dose. METHODS: We retrospectively reviewed pancreatic enzyme dosing for 267 cystic fibrosis patients with pancreatic insufficiency. The supplemental enzyme history of nine patients with fibrosing colonopathy was contrasted with the history of 258 nonaffected patients. The pancreatic enzyme doses of 75 patients taking at least 6,000 U lipase/kg/meal were systematically reduced to approximately 2,000 lipase units/kg/meal. We evaluated the effect of this dose reduction on change in height and weight z scores one year after achievement of stable enzyme dose. RESULTS: In the year prior to diagnosis patients with fibrosing colonopathy took a significantly larger pancreatic enzyme dose, whether assessed by highest dose or cumulative dose, than did nonaffected patients. Similar results were observed after controlling for sex and age. All 75 patients on at least 6,000 U lipase/kg/meal were able to tolerate a significant reduction in dose while achieving clinically acceptable nutrient absorption, with no change over one year in height and weight z scores. CONCLUSIONS: Our data demonstrate a strong relationship between very high doses of pancreatic enzyme supplementation and formation of fibrosing colonopathy. These very high doses do not appear to be needed for adequate nutrient absorption and growth.

Sequential ciprofloxacin therapy in pediatric cystic fibrosis: comparative study vs. ceftazidime/tobramycin in the treatment of acute pulmonary exacerbations. The Cystic Fibrosis Study Group.

BACKGROUND: Cystic fibrosis patients have chronic bacterial infections of the respiratory tract, most commonly Pseudomonas aeruginosa. Although controversial, administration of antibiotic therapy during acute pulmonary exacerbations is standard practice. Fluoroquinolones are currently not indicated for use in young children because of the observation of arthropathy and damage to growing cartilage in beagle puppies. Because of its activity against P. aeruginosa and excellent oral bioavailability, ciprofloxacin offers a unique therapeutic alternative for this patient population. OBJECTIVE: This prospective, randomized, double blind study compared the efficacy and safety of sequential intravenous/oral ciprofloxacin vs. ceftazidime/tobramycin in hospitalized pediatric cystic fibrosis patients with an acute pulmonary exacerbation associated with P. aeruginosa infection. METHODS: One hundred thirty patients (ages 5 to 17 years) were randomized to receive either i.v. ciprofloxacin 10 mg/kg every 8 h for 7 days followed by oral ciprofloxacin 20 mg/kg every 12 h for a minimum of 3 days or i.v. ceftazidime 50 mg/kg every 8 h plus i.v. tobramycin 3 mg/kg every 8 h for a minimum of 10 days. Clinical, bacteriologic and safety responses were assessed throughout the study. RESULTS: All 84 patients (median age, 11 years; range, 5 to 17 years) valid for efficacy in both treatment groups demonstrated clinical improvement. Five patients experienced clinical relapses (3 ciprofloxacin, 2 ceftazidime/tobramycin) by the 2- to 4-week follow-up. Intent-to-treat analysis demonstrated similar clinical findings between the two treatment groups at both the end of therapy and follow-up. Clinical improvement correlated with improvement in pulmonary function studies and the acute clinical scoring system but not with bacteriologic eradication of Pseudomonas. DNA profiles demonstrated that irrespective of colony morphology, usually one clonal strain was associated with each patient's pulmonary exacerbation. Treatment-associated musculoskeletal events occurred with equal frequency (22% vs. 21%) in both study drug groups (n = 129), and arthralgias were within the range of rates for cystic fibrosis arthropathy. None of these events required study drug discontinuation. CONCLUSION: Sequential i.v./oral ciprofloxacin monotherapy offers a safe and efficacious alternative to standard parenteral therapy for acute pulmonary exacerbations in pediatric cystic fibrosis patients.

Catalytic role of cytochrome P4502B6 in the N-demethylation of S-mephenytoin.

In vitro methods were used to identify the cytochrome P450 (CYP) enzyme(s) involved in S-mephenytoin N-demethylation. S-Mephenytoin (200 microM) was incubated with human liver microsomes, and nirvanol formation was quantitated by reversed-phase HPLC. S-Mephenytoin N-demethylase activity in a panel of human liver microsomes ranged 35-fold from 9 to 319 pmol/min/mg protein and correlated strongly with microsomal CYP2B6 activity (r = 0.91). Additional correlations were found with microsomal CYP2A6 and CYP3A4 activity (r = 0.88 and 0.74, respectively). Microsomes prepared from human beta-lymphoblastoid cells transformed with individual P450 cDNAs were assayed for S-mephenytoin N-demethylase activity. Of 11 P450 isoforms (P450s 1A1, 1A2, 2A6, 2B6, 2E1, 2D6, 2C8, 2C9, 2C19, 3A4, and 3A5) tested, only CYP2B6 catalyzed the N-demethylation of S-mephenytoin with an apparent K(m) of 564 microM. Experiments with P450 form-selective chemical inhibitors, competitive substrates, and anti-P450 antibodies were also performed. Troleandomycin, a mechanism-based CYP3A selective inhibitor, and coumarin, a substrate for CYP2A6 and therefore a potential competitive inhibitor, failed to inhibit human liver microsomal S-mephenytoin N-demethylation. In contrast, orphenadrine, an inhibitor of CYP2B forms, produced a 51 +/- 4% decrease in S-mephenytoin N-demethylase activity in human liver microsomes and a 45% decrease in recombinant microsomes expressing CYP2B6. Also, both CYP2B6-marker 7-ethoxytrifluoromethylcoumarin O-deethylase and S-mephenytoin N-demethylase activities were inhibited by approximately 65% by 5 mg anti-CYP2B1 IgG/mg microsomal protein. Finally, polyclonal antibody inhibitory to CYP3A1 failed to inhibit S-mephenytoin N-demethylase activity. Taken together, these studies indicate that the N-demethylation of S-mephenytoin by human liver microsomes is catalyzed primarily by CYP2B6.

Neuropathy and vasculopathy in colonic strictures from children with cystic fibrosis.

Colonic strictures are rare in patients who have cystic fibrosis, but recently have developed in those who have been treated with delayed-release high-dose pancreatic enzyme supplements. Colonic strictures from eight such pediatric patients showed neural abnormalities consisting of ganglion cell hyperplasia and ectopia, and intermyenteric plexus hyperplasia. Cholinergic and adrenergic stains of mucosal nerve fibers were more prominent in histological sections of the cystic fibrosis strictures than in sections from colons of children without cystic fibrosis. The mean grade of staining with acetylcholinesterase in the lamina propria of the strictured cystic fibrosis colons was 2.38 +/- 1.25, compared with .93 +/- .93 (P < .055) in bowels from children without cystic fibrosis. The mean grade for tyrosine hydroxylase staining in the lamina propria was 2 +/- .97 in the strictures and was .79 +/- .81 (P < .05) in the bowels of children who did not have cystic fibrosis. Vasoactive intestinal peptide staining in bowels from children with cystic fibrosis with and without stricture did not differ significantly from that of children without cystic fibrosis. Vasculopathy consisting of fibrointimal hyperplasia in submucosal veins and mesenteric arteries was found only in colonic strictures owing to cystic fibrosis. Colonic strictures in patients with cystic fibrosis who received high-dose pancreatic enzyme supplements contain ganglion cell abnormalities, and mucosal cholinergic and adrenergic activity may be increased in these strictures. The stricture vasculopathy may be drug-related and/or related to increased catecholamine activity.

Colonic strictures in children with cystic fibrosis.

PURPOSE: To determine the radiographic, clinical, surgical, and histologic findings in children with cystic fibrosis who develop strictures of the colon. MATERIALS AND METHODS: Ten children (five boys, five girls; age range, 2.5-9.0 years; mean age, 5.5 years), who were treated at the practices of the authors, were retrospectively identified and their medical records reviewed. RESULTS: Radiographic manifestations of the colonic disease included mucosal irregularity and spiculation with nodular thickening of the colonic wall and loss of normal colonic haustration. Luminal narrowing involved long segments of the colon. Longitudinal shortening of the colon was also a prominent feature. The decrease in caliber of the bowel ranged from mild narrowing to complete occlusion of the lumen. Histologic examination revealed severe submucosal fibrosis and fatty infiltration with transmural extension of the fibrosis to involve the serosa in some cases. Unlike in Crohn disease, however, acute inflammatory changes were minimal or absent. CONCLUSION: Colonic stricture in children with cystic fibrosis is due to irreversible and frequently progressive narrowing of the colonic lumen.

Successful treatment response of granuloma annulare and carpal tunnel syndrome to chlorambucil.

We describe a 62-year-old woman in whom skin biopsies verified the clinical diagnosis of granuloma annulare and neurologic and electromyographic studies confirmed the neurologic diagnosis of carpal tunnel syndrome. Short-term treatment with a low dose of chlorambucil taken orally was prescribed. Within weeks, the granuloma annulare had disappeared, and the clinical symptoms of carpal tunnel syndrome had resolved. Electromyography showed variable improvement at the end of treatment and resolution at 9-month follow-up. Our case confirms that short-term treatment of granuloma annulare and associated carpal tunnel syndrome with low-dose chlorambucil is successful.

Seronegativity for type 1 antineuronal nuclear antibodies ('anti-Hu') in subacute sensory neuronopathy patients without cancer.

We followed 21 patients with sensory neuronopathy without evidence of cancer for up to 23 years. All were seronegative for type 1 antineuronal nuclear antibodies (ANNA-1, also called "anti-Hu"). We additionally studied 67 seropositive patients with sensory neuropathy or a related neurologic syndrome. Ninety-one percent of the seropositive patients had a small-cell lung carcinoma. One, with a normal chest x-ray, had been followed for 7 years for sensory neuronopathy of indeterminate cause before serologic testing for ANNA-1 led to the discovery of the tumor by CT. We conclude that ANNA-1 seropositivity in a patient with sensory neuronopathy is strong evidence for an underlying small-cell lung cancer.

Variability of olfactory threshold and its role in assessment of aging.

Olfactory thresholds of elderly persons (over 65 years) average one to two orders of magnitude higher than those of young adults (under 30 years). Past studies reveal enormous spreads (typically about three orders of magnitude) of individual thresholds within each age group and extensive overlap between the two groups--enough to question how typically decline in sensitivity characterizes the individual aged person. The present study shows that much of the observed overlap is misleading, because the brief threshold tests usually administered tend to exaggerate individual differences. A more representative assessment of an individual's threshold (for 1-butanol) was achieved by averaging the thresholds from two to eight separate short tests, spread over 4 days. The spread of each group's thresholds (12 young and 12 elderly subjects) narrowed strikingly as the number of tests averaged increased from one to four; further tests accomplished no additional narrowing of spread. Based on a single test, thresholds of young and elderly overlapped in the usual way; but based on four or more tests, thresholds of young and elderly overlapped little or not at all. The outcome (1) argues that decline in smell sensitivity seems to be, after all, a common feature of aging, and (2) sheds light on the sources of variability of sensory thresholds.

Characteristics of Groningen tracheo-oesophageal speaking valves prior to insertion and after removal for failure.

The Groningen valve was first used in Sheffield in 1986 in a patient who underwent laryngectomy for malignant disease. Since then it has been the main tracheo-oesophageal prosthesis used on our Unit for speech rehabilitation post-laryngectomy. This biflanged device inserted primarily or as a secondary procedure remains in situ until failure occurs either because of leakage or because increased effort is required to produce satisfactory phonation. This in vitro study we examined the differences between new valves prior to insertion and those removed for failure. The mean forward opening pressures were shown to be similar in the two populations but the mean forward resistances were increased in those valves which were defective (P less than 0.001). In addition the mean reverse opening pressure was found to be significantly lower in the defective valves when compared with their new counterparts (P less than 0.05).

Mechanism-based inactivation of bovine adrenal cytochromes P450 C-21 and P450 17 alpha by 17 beta-substituted steroids.

A series of progesterone derivatives has been studied as potential inactivators of the bovine adrenocortical cytochromes P450, P450 17 alpha, and P450 C-21. Replacement of the 21-methyl group of progesterone with a difluoromethyl group resulted in a selective inactivator of P450 C-21 in a reconstituted system. The loss of 21-hydroxylase activity caused by this compound exhibits a number of characteristics of mechanism-based inactivation including NADPH dependence, pseudo-first-order kinetics, saturability, irreversibility, and protection by substrate. In addition to the difluoro compound, 21,21-dichloroprogesterone, the acetylenic compound pregn-4-en-20-yn-3-one, and the olefinic compound pregna-4,20-dien-3-one all inactivate P450 C-21. In contrast, the only compound to inactivate the rabbit adrenal progesterone 21-hydroxylase is 21,21-dichloroprogesterone. In binding studies, the 21,21-dihalo steroids produce a greater maximal type I spectral shift of P450 C-21 than the two 17 beta-unsaturated steroids. The dihalo compounds inactivate P450 C-21 by both heme destruction and protein modification as shown by significant decreases in residual 21-hydroxylase activity and spectrally detectable P450 after incubation with P450 C-21 in a reconstituted system. Liquid chromatographic and mass spectral analyses of the organic extracts from these incubations showed that 21-pregnenoic acid is a major metabolite of the dihalo compounds with a partition ratio of 5 nmol of acid produced/nmol of P450 C-21 inactivated. This supports the hypothesis that inactivation proceeds in part through an acyl halide intermediate. In contrast, the acetylenic compound pregn-4-en-20-yn-3-one inactivates P450 C-21 mainly by protein modification, producing an NADPH-dependent irreversible type I spectral shift. The stoichiometry of inactivation is approximately 1.5 nmol of compound bound/nmol of enzyme inactivated, indicating selective modification of the enzyme at or near the substrate binding site.

Auditory screening in high risk neonates: selection of a test protocol.

As part of a programme evaluating evoked oto-acoustic emissions (EOAE) as a screen for hearing impairment in graduates of a neonatal intensive care unit (NICU), a detailed study has been carried out on 250 infants to determine the best test protocol. EOAE and air conduction auditory brain-stem response (ABR) tests have been carried out on all infants and bone conduction ABR on air conduction ABR failures. Screen failure rates were not dependent on age when tested but were affected by gestational age if the infant was tested before discharge. Coverage was 98% for infants tested before discharge but was 81% for infants tested as out-patients at a mean age of 47 weeks (post-conception). Consideration of different test protocols and the shorter test time for the EOAE test led to the conclusion that, where large numbers are involved, the most cost-effective method is to screen initially by EOAE. Failures would then be re-tested before discharge by ABR. Where numbers are small then ABR alone would be used. Follow up would be by ABR rather than EOAE as this gave a lower failure rate and threshold can be measured. Bone conduction ABR was found to be a feasible test in routine use allowing differentiation between conductive and sensorineural losses.

The biochemical basis for the species difference in hepatic microsomal 4-vinylcyclohexene epoxidation between female mice and rats.

Mice but not rats are susceptible to 4-vinylcyclohexene (VCH)-induced ovarian toxicity and carcinogenicity. This is due in part to a 4- to 6-fold greater rate of hepatic microsomal bioactivation of VCH to the ovotoxicant VCH-1,2-epoxide. The biochemical basis for this difference was investigated in microsomes using enzyme induction, enzyme inhibition with chloramphenicol or specific inhibitory antibodies, and correlation with marker steroid hydroxylase activities to associate VCH epoxidation with particular cytochrome P450 forms. Testosterone 6 beta- and 15 alpha-hydroxylase activities and VCH epoxidation were decreased in microsomes from chloramphenicol-treated mice, initially suggesting the possible involvement of P450IIIA and P450IIA forms in VCH metabolism. Although both testosterone 6 beta-hydroxylase and VCH epoxidase activities were increased by dexamethasone treatment (P450IIIA inducer), anti-rat P450IIIA IgG inhibited testosterone 6 beta-hydroxylase (68%) but not VCH epoxidase activity. These latter results do not support the involvement of mouse P450IIIA forms in VCH epoxidation. However, results were obtained which indicated that mouse P450IIA forms are involved in VCH epoxidation. In microsomes from untreated female mice VCH epoxidase activity was inhibited 48% by antibodies to mouse P45015 alpha (P450IIA3) at a concentration that inhibited testosterone 15 alpha-hydroxylase activity by 86%. No protein immunochemically related to mouse P45015 alpha was detected in female rat hepatic microsomes. VCH epoxidation by hepatic microsomes was increased in female mice and rats by phenobarbital treatment and was inhibited by approximately one-third by anti-rat-P450IIB1 IgG in microsomes from untreated animals of both species. Furthermore, microsomal VCH epoxidase and testosterone 16 alpha-hydroxylase activities were lower (34%) in female 129/J mice (deficient in constitutive expression of P450IIB forms) than in B6C3F1 mice. These results suggested partial involvement of P450IIB forms in the microsomal epoxidation of VCH. Therefore, P450 forms IIA and IIB account for the majority of VCH bioactivation in female mouse liver, which explains in part the susceptibility of mice to VCH-induced ovarian toxicity and carcinogenicity.

Click evoked otoacoustic emissions compared with brain stem electric response.

The hearing of 346 babies taken largely from a neonatal intensive care unit has been tested by otoacoustic emissions and brain stem electric response audiometry. A total of 336 (97%) of the babies have been followed up by hearing tests from the age of 8 months. The otoacoustic emission test has been found to be practical with a mean test time of 12.1 minutes compared with 21.0 minutes for brain stem electric response. An otoacoustic emission was recorded bilaterally in 274 (79%) babies. Twenty of the 21 surviving infants who failed brain stem electric response in the neonatal period did not produce an emission. It is concluded that the otoacoustic emission test would make a good first screen to be followed by the brain stem electric response if no otoacoustic emission was present. There is poor agreement between the test results in the neonatal period and those of the follow up period, however, indicating the need for continuous monitoring of those babies failed by brain stem electric response.

Inclusion body myositis. Observations in 40 patients.

Inclusion body myositis (IBM) was suspected on light microscopic grounds in 48 of 170 consecutive patients with inflammatory myopathies. One or more vacuoles containing membranous material, groups of atrophic fibres, and an autoaggressive endomysial inflammatory exudate occurred in 100, 96 and 92% of the muscle specimens. All three of these features were present in 88% of the specimens. Electron microscopy confirmed the presence of filamentous inclusions in 40 of 43 patients. The inclusions are typically near vacuoles and a minimum of three vacuolated fibres must be scrutinized to detect them with confidence. There is no electromyographic pattern that can reliably distinguish IBM from other inflammatory myopathies. The typical clinical features in the patients diagnosed by histological criteria as IBM were: insidious onset after age 50 yrs with painless, proximal lower extremity weakness; slow but relentless progression with selectively severe involvement of quadriceps, iliopsoas, tibialis anterior, biceps and triceps muscles; relatively early depression of the knee reflexes; and a normal or mildly elevated serum creatine kinase level. The male: female ratio was 3:1. Distal weakness occurred in about 50%, but only in 35% was it as great or greater than proximal weakness. Significant associated illnesses include other autoimmune disorders (15%), diabetes mellitus (20%), and diffuse peripheral neuropathy (18%). Prednisone treatment at dose levels frequently effective in polymyositis failed to prevent disease progression in those patients observed for 2 or more years. Our findings support the notion that IBM is a distinct entity in which a set of pathological features is associated with a constellation of clinical findings.