The development of a magnetic resonance imaging index for fistulising Crohn's disease.

BACKGROUND: Magnetic resonance imaging (MRI) is the gold standard for assessment of perianal fistulising Crohn's disease (CD). The Van Assche index is the most commonly used MRI fistula index. AIMS: To assess the reliability of the Van Assche index, and to modify the instrument to improve reliability and create a novel index for fistulising CD. METHODS: A consensus process developed scoring conventions for existing Van Assche index component items and new items. Four experienced radiologists evaluated 50 MRI images in random order on three occasions. Reliability was assessed by estimates of intraclass correlation coefficients (ICCs). Common sources of disagreement were identified and recommendations made to minimise disagreement. A mixed effects model used a 100 mm visual anologue scale (VAS) for global severity as outcome and component items as predictors to create a modified Van Assche index. RESULTS: Intraclass correlation coefficients (95% confidence intervals) for intra-rater reliability of the original and modified Van Assche indices and the VAS were 0.86 (0.81-0.90), 0.90 (0.86-0.93) and 0.86 (0.82-0.89). Corresponding ICCs for inter-rater reliability were 0.66 (0.52-0.76), 0.67 (0.55-0.75) and 0.58 (0.47-0.66). Sources of disagreement included number, location, and extension of fistula tracts, and rectal wall involvement. A modified Van Assche index (range 0-24) was created that included seven component items. CONCLUSIONS: Although "almost perfect" intra-rater reliability was observed for the assessment of MRI images for fistulising CD using the Van Assche index, inter-rater reliability was considerably lower. Our modification of this index should result in a more optimal instrument.

Magnetic resonance enterography is feasible and reliable in multicenter clinical trials in patients with Crohn's disease, and may help select subjects with active inflammation.

BACKGROUND: Reliable tools for patient selection are critical for clinical drug trials. AIM: To evaluate a consensus-based, standardised magnetic resonance enterography (MRE) protocol for selecting patients for inclusion in Crohn's disease (CD) multicenter clinical trials. METHODS: This study recruited 20 patients [Crohn's Disease Activity Index (CDAI) scores: <150 (n = 8); 150-220 (n = 4); 220-450 (n = 8)], to undergo ileocolonoscopy and two MREs (with and without colonic contrast) within a 14-day period. Procedures were scored centrally using, Magnetic Resonance Index of Activity (MaRIA), and both Crohn's Disease Endoscopic Index of Severity (CDEIS) and Simplified Endoscopic Score (SES-CD). RESULTS: 37 MREs were acquired. Both MREs were evaluable in 16 patients for calculation of test-retest and inter-reader reliability scores. The MaRIA scores for the terminal ileum had excellent test-retest and inter-reader reliability, with correlations >0.9. The proximal ileum showed strong within-reader agreement (0.90-0.96), and fair between-reader agreement (0.59-0.72). MRE procedures were tolerable. MaRIA scores correlated with CDEIS and SES-CD (0.63 and 0.71), but not with CDAI (0.34). MRE identified 3 patients with intra-abdominal complications, who would otherwise have been included in clinical trials. Furthermore, both MRE and ileocolonoscopy identified active bowel wall inflammation in 2 patients with CDAI <150, and none in 1 patient with CDAI > 220. Data quality was good/excellent in 85% of scans, and fair or better in 96%. CONCLUSIONS: Magnetic resonance enterography of high-quality and reproducibility was feasible in a global multi- centre setting, with evidence for improved selectivity over CDAI and ileocolonoscopy in identifying appropriate CD patients for inclusion in therapeutic intervention trials.

Intravascular lipoma of the renal vein.

Lipomas are benign neoplasms composed of adipocytes encased in a fibrous capsule. Intravascular lipomas are rare and almost always incidental findings. In the published literature, the majority are described within the inferior vena cava (IVC) and less frequently reported in the superior vena cava, brachiocephalic vein, subclavian vein, internal jugular vein, external iliac vein and common femoral vein. We present the case of a 59-year-old male who presented with a symptomatic ureteral calculus and was found to have an intravascular lipoma of the right renal vein with extension into the IVC. To our knowledge, this is the first ever report of an intravascular lipoma in the renal vein. We discuss the imaging characteristics of intravascular lipomas and the differential diagnosis that should be considered.

MDCT diagnosis of gastroduodenal ulcers: key imaging features with endoscopic correlation.

Although the overall prevalence of peptic ulcer disease (PUD) and related hospitalizations are decreasing, the initial presentation of complicated PUD on CT remains common. It, therefore, remains critical for radiologists to recognize the findings of PUD at CT for initial diagnosis. While the CT findings of complicated PUD have been previously described in the literature, the CT findings of uncomplicated PUD have not been well documented. Furthermore, although CT is certainly not the diagnostic evaluation of choice for patients with suspected uncomplicated PUD, many patients with PUD will nonetheless present to the emergency department with unexplained abdominal pain and undergo MDCT evaluation as the initial diagnostic test. Therefore, recognizing the MDCT findings of uncomplicated PUD can help appropriately direct patient management, and help prevent the development of complications. To facilitate improved recognition of PUD on abdominal CT, we present an overview of the CT findings of both uncomplicated and complicated PUD, as well as several diagnostic pitfalls which can result in misdiagnosis from peptic ulcer mimics.

In vitro biocompatibility and antimicrobial activity of poly(ε-caprolactone)/montmorillonite nanocomposites.

A triblock copolymer based on poly(ε-caprolactone) (PCL) and 2-(N,N-diethylamino)ethyl methacrylate (DEAEMA)/2-(methyl-7-nitrobenzofurazan)amino ethyl acrylate (NBD-NAcri), was synthesized via atom transfer radical polymerization (ATRP). The corresponding chlorohydrated copolymer, named as PCL-b-DEAEMA, was prepared and anchored via cationic exchange on montmorillonite (MMT) surface. (PCL)/layered silicate nanocomposites were prepared through melt intercalation, and XRD and TEM analysis showed an exfoliated/intercalated morphology for organomodified clay. The surface characterization of the nanocomposites was undertaken by using contact angle and AFM. An increase in the contact angle was observed in the PCL/MMT(PCL-b-DEAEMA) nanocomposites with respect to PCL. The AFM analysis showed that the surface of the nanocomposites became rougher with respect to the PCL when MMTk10 or MMT(PCL-b-DEAEMA) was incorporated, and the value increased with the clay content. The antimicrobial activity of the nanocomposites against B. subtilis and P. putida was tested. It is remarkable that the biodegradation of PCL/MMT(PCL-b-DEAEMA) nanocomposites, monitored by the production of carbon dioxide and by chemiluminescence emission, was inhibited or retarded with respect to the PCL and PCL/1-MMTk10. It would indicate that nature of organomodifier in the clay play an important role in B. subtilis and P. putida adhesion processes. Biocompatibility studies demonstrate that both PCL and PCL/MMT materials allow the culture of murine L929 fibroblasts on its surface with high viability, very low apoptosis, and without plasma membrane damage, making these materials very adequate for tissue engineering.

Cell uptake survey of pegylated nanographene oxide.

Graphene and more specifically, nanographene oxide (GO) has been proposed as a highly efficient antitumoral therapy agent. Nevertheless, its cell uptake kinetics, its influence in different types of cells and the possibility of controlling cellular internalization timing, is still a field that remains unexplored. Herein, different cell types have been cultured in vitro for several incubation periods in the presence of 0.075 mg ml(-1) pegylated GO solutions. GO uptake kinetics revealed differences in the agent's uptake amount and speed as a function of the type of cell involved. Osteoblast-like cells GO uptake is higher and faster without resulting in greater cell membrane damage. Moreover, the dependence on the commonly used PEG nature (number of branches) also influences the viability and cell uptake speed. These facts play an important role in the future definition of timing parameters and selective cell uptake control in order to achieve an effective therapy.

Blind-ending branch of a bifid ureter: multidetector CT imaging findings.

A bifid ureter with a blind-ending branch is a rare congenital anomaly. Although typically found incidentally, this anomaly can be symptomatic and radiologists should be aware of this important variant. To our knowledge, there has been no previous report of this anomaly as seen on multidetector CT urography. We present a patient with haematuria and review the clinical significance, radiological findings and embryological aetiology of this anomaly.

Capsular retraction: an uncommon imaging finding in hepatic inflammatory pseudotumour.

Capsular retraction is an infrequent but characteristic feature of malignant liver lesions such as hepatic metastases and intrahepatic cholangiocarcinoma. Rarely, this finding may be observed in association with benign lesions, such as atypical haemangiomas. Capsular retraction has not previously been reported in association with hepatic inflammatory pseudotumour (IPT). Hepatic IPT is an uncommon benign hepatic lesion with a good clinical prognosis. In this report, we discuss the case of a 48-year-old woman with capsular retraction secondary to multifocal hepatic inflammatory IPTs.

High MMP-9 activity characterises pleural tuberculosis correlating with granuloma formation.

Tuberculosis (TB) pleural disease is complicated by extensive tissue destruction. Matrix metalloproteinase (MMP)-1 and -9 are implicated in immunopathology of pulmonary and central nervous system TB. There are few data on MMP activity in TB pleurisy. The present study investigated MMP-1, -2 and -9 and their specific inhibitors (tissue inhibitor of metalloproteinase (TIMP)-1 and -2) in tuberculous effusions, and correlated these with clinical and histopathological features. Clinical data, routine blood tests, and pleural fluid/biopsy material were obtained from 89 patients presenting with pleural effusions in a TB-endemic area. MMP-1, -2 and -9 were measured by zymography or western blot, and TIMP-1 and -2 by ELISA. Pleural biopsies were examined microscopically, cultured for acid-alcohol fast bacilli and immunostained for MMP-9. Tuberculous pleural effusions contained the highest concentrations of MMP-9 compared with malignant effusions or heart failure transudates. MMP-9 concentrations were highest in effusions from patients with granulomatous biopsies: median (interquartile range) 108 (61-218) pg x mL(-1) versus 43 (12-83) pg x mL(-1) in those with nongranulomatous pleural biopsies. MMP-1 and -2 were not upregulated in tuberculous pleural fluid. The ratio of MMP-9:TIMP-1 was significantly higher in TB effusions. Tuberculous pleurisy is characterised by a specific pattern of matrix metalloproteinase-9 upregulation, correlating with the presence of granulomas and suggesting a specific role for matrix metalloproteinase-9 in inflammatory responses in tuberculous pleural disease.

Tuberculosis skin testing, anergy and protein malnutrition in Peru.

SETTING: Malnutrition and intestinal parasites cause immunosuppression. This may cause false-negative tuberculin skin tests (TST) and failure to identify tuberculosis (TB) infection. OBJECTIVE: To assess factors associated with TST positivity and anergy in disadvantaged communities in Peru. DESIGN: A study of 212 randomly selected adults: 102 in a rural Amazonian village and 110 shanty town residents in urban Lima. RESULTS: Respectively 52% and 53% of urban and rural jungle populations were TST-positive. Using simultaneous tetanus and candida skin tests, 99% had at least one positive skin test. Generalised anergy was therefore rare, despite frequent intestinal parasitic infection, including 34% helminth infection prevalence in the jungle. TST positivity was associated with age (P = 0.001), known TB contact (P = 0.02) and poor household ventilation (P = 0.007). TST positivity was not significantly associated with crowding, reported past TB, single/multiple BCG vaccination, income, intestinal parasites, dietary factors, body mass index or body fat. Individuals with lower anthropometric body protein, as measured by corrected arm muscle area, were less likely to be TST-positive (P = 0.02), implying that protein malnutrition caused tuberculin-specific anergy. CONCLUSION: These results identify the importance of household ventilation for community TB transmission and add to the evidence that protein malnutrition suppresses TB immunity, causing false-negative TST results.

Worker functions and traits associated with occupations and the development of AD.

OBJECTIVE: To investigate the association between Alzheimer disease (AD) and worker functions and traits associated with occupations. BACKGROUND: Studies have reported that occupational attainment is related to AD. However, most have not identified specific worker functions and traits (i.e., occupational demands) of occupations that may explain the association, nor have they accounted for changing occupational demands over time. METHODS: Within- and between-group differences in mental, motor, physical, and social occupational demands of 122 AD cases and 235 control subjects were compared across four decades of life (20s, 30s, 40s, and 50s) using repeated-measures analyses of covariance adjusted for race, gender, year of birth, and education. RESULTS: Overall, mental occupational demands were significantly lower and physical occupational demands were significantly higher for cases than for control subjects. Case/control differences in mental demand scores were not found in their 20s but only in later decades. Differences in physical demands were found in all decades but their 30s. Social and motor demands did not differ between cases and control subjects. Among cases only, there were no significant occupational demand score differences across decades. In contrast, mental and social demand scores of control subjects increased in later decades, and motor demand scores declined. Like cases, physical demand scores of control subjects remained stable across the decades. CONCLUSIONS: The authors' results may indicate a relatively early influence of Alzheimer disease neuropathology on capacity to pursue mentally demanding occupations. However, results also are consistent with the notion that mentally demanding occupations have a direct influence on Alzheimer disease neuropathology.

Brachial plexopathy in diabetic ketoacidosis.

We report the clinical and electrodiagnostic findings of a 39-year-old patient who presented with severe, bilateral and asymmetrical, axon-loss brachial plexopathies occurring in the midst of diabetic ketoacidosis. This patient's unusual presentation is not consistent with the rare diabetic polyradiculopathy of the upper extremities usually occurring in association with diabetic amyotrophy.

Autoantibody Testing in Neuromuscular Disorders, Part II: Neuromuscular Junction, Hyperexcitability, and Muscle Disorders.

In myasthenia gravis and Lambert-Eaton myasthenic syndrome, antibodies against ion channels are clearly related to pathogenesis; however, in the inflammatory myopathies, a link to disease causation is not as evident, except as a marker of autoimmunity. Autoantibody testing in patients with neuromuscular junction and skeletal muscle disorders is useful in diagnosis and, in some diseases, prognosis. This review briefly summarizes methods of autoantibody testing and then proceeds to a clinician-friendly guide to autoantibody testing of neuromuscular junction disorders, hyperexcitability syndromes, and inflammatory muscle diseases.

Guamanian neurodegenerative disease: electrophysiologic findings.

Amyotrophic lateral sclerosis (ALS), parkinsonism and/or dementia are highly prevalent among the Chamorro population of Guam. The incidence of Guamanian ALS has markedly declined in recent years, but these incidence figures may reflect underascertainment of subclinical disease. Guamanian Chamorro patients have not been systematically studied using modern clinical neurophysiological techniques. Electromyography (EMG: needle exam and nerve conduction studies) was used to study 29 patients with the major subtypes of Guamanian neurodegenerative disease, as well as 11 neurologically normal Guamanian Chamorro subjects. Central conduction was assessed by somatosensory evoked potentials (SEP's) in 16 patients. EMG evidence of peripheral neuropathy, (often subclinical) was found in 45% of Guamanian patients but no Chamorro control subjects. Diabetes mellitus, which is highly prevalent in this population, was present in some, but not all of these cases. Clinically unsuspected motor neuron disease was identified by EMG in only one of the 23 Guamanian patients with parkinsonism and/or dementia and in none of the 11 Chamorro control subjects. Two of seven patients with the clinical phenotype of Guamanian ALS had a more benign EMG pattern on the needle electrode exam with absence of fibrillation and fasciculation potentials. Three of 16 patients (all with parkinsonism and dementia) had mildly abnormal tibial SEP's. No patient had EMG evidence of myopathy or a defect of neuromuscular transmission. We conclude: (1) peripheral neuropathy may be a manifestation of Guamanian neurodegenerative disease; (2) the declining prevalence of ALS on Guam is not associated with the development of a subclinical form of motor neuron disease; (3) the substantial overlap of Guamanian ALS with parkinsonism-dementia reported in prior decades is no longer apparent; (4) abnormal central conduction, as assessed by tibial SEP's, is present in some patients with Guamanian parkinsonism-dementia.

Olfactory dysfunction in Guamanian ALS, parkinsonism, and dementia.

OBJECTIVES: To assess whether olfactory deficits are present in the general Guamanian Chamorro population and to evaluate olfaction in each of the four neurodegenerative disease syndromes of Guam: ALS, pure parkinsonism, pure dementia, and the combined parkinsonism-dementia complex (PDC). BACKGROUND: Olfactory dysfunction was previously reported in patients with PDC of Guam. METHODS: We developed a culturally adjusted olfactory test battery, derived from the original University of Pennsylvania Smell Identification Test (UPSIT), and administered this to Chamorro residents with ALS (n=9), pure parkinsonism (n=9), pure dementia (n=11), PDC (n=31), and 53 neurologically normal Chamorro and 25 North American control subjects. RESULTS: Similar, marked olfactory dysfunction was found in all four syndromes of Guamanian neurodegenerative disease. This correlated poorly with measures of parkinsonism and cognition. In the neurologically normal Chamorro control group, six subjects (11%) had very low olfactory scores; these were less than the lowest North American score, raising a question of subclinical neurodegenerative disease. CONCLUSIONS: Marked olfactory deficits are common to all four Guamanian neurodegenerative syndromes, and suggest the possibility of similar central neuropathologic substrates. The deficit in the Guamanian ALS group contrasts with idiopathic ALS, in which olfactory function has been reported to be only slightly compromised.

Synthesis, characterization, and antitumor activity of new platinum(IV) trans-carboxylate complexes: crystal structure of [Pt(cis-1,4-DACH)trans-(acetate)2Cl2].

A series of novel platinum(IV) cisplatin analogues of the type [Pt(cis-1,4-DACH)trans-(L)2Cl2] (where cis-1,4-DACH = cis-1,4-diaminocyclohexane and L = acetate, propionate, butyrate, valerate, hexanoate, heptanoate, octanoate, nonanoate, or decanoate) was synthesized and characterized by elemental analysis, IR, 13C-NMR, and 195Pt-NMR spectroscopy. The structure of [Pt(cis-1,4-DACH)trans-(acetate)2Cl2] (1) was determined by X-ray crystallography. The crystals were monoclinic, space group P2(1)/n (no. 14) with a = 10.193(2), b = 10.687(2), c = 14.265(3) A, beta = 99.67(3) degrees, Z = 4. The total reflections collected were 2556. The structure refinement converged to R1 = 0.0539 and wR2 = 0.1531. In this complex, platinum has distorted octahedral geometry, and cis-1,4-DACH is in a unique twist-boat configuration. cis-1,4-DACH forms a seven-member chelating ring with platinum, leading to considerable strain in bidentate DACH binding. The strain is evidenced by a large 126.5(9) degrees C-N-Pt angle. The N-Pt-N angle is expanded to 97.4(5) degrees owing to geometric constraints of the cis-1,4-DACH geometry. Three lower homologs of the cis-1,4-DACH-Pt(IV) series were tested in the murine L1210/0 leukemia model for antitumor activity. The results indicate that activity decreases in ascending the homologous series, and that the activity of two of the complexes is substantially better than that of cisplatin with respect to increase in life span and cures.

Clock drawing test in very mild Alzheimer's disease.

OBJECTIVES: The primary objective of this study was to determine the efficacy of the clock drawing test to predict the presence of very mild Alzheimer's disease (AD). A secondary objective was to identify elements of clock drawing that were most useful in differentiating cognitively intact older adults from those with mild Alzheimer's disease. DESIGN: Cohort based comparison of retrospective data. SETTING: Academic research center. PARTICIPANTS: Clock drawings from 41 outpatient cases of mild AD with Mini-Mental State Exam scores of 24 or higher and 39 age- and education-matched older adults were scored. MEASUREMENTS: Clock drawings were blindly and independently scored by two raters using the Clock Drawing Interpretation Scale and the scoring system reported by Rouleau et al. Predictive values for positive and negative tests were calculated using cut-off scores for total score and component subscores from each of these two systems. RESULTS: Two or more errors in the depiction of the clock hands on the Clock Drawing Interpretation Scale had a positive predictive value for AD of 100% and a negative predictive value of 51%. A score of 2 or less on the 4-point hand-placement component of the Rouleau et al. scoring system provided a positive predictive value for AD of 94% and was associated with a negative predictive value of 62%. CONCLUSION: An individual who commits two errors or more in drawing the clock hands deserves further investigation for a possible dementia. Normal hand placement on the clock drawing test does not exclude AD. However, when prevalence rates of dementia in community-dwelling older adults are considered, these results argue that normal clock hand placement indicates that dementia is unlikely.

Autonomic failure in Guamanian neurodegenerative disease.

Autonomic impairment is minor in idiopathic amyotrophic lateral sclerosis (ALS) and Alzheimer's-type dementia (D) and is usually not marked in Parkinson's disease. The autonomic status of Guamanian parkinsonism (P), ALS, and parkinsonism-dementia complex (PDC) is essentially unknown. We therefore evaluated the autonomic nervous system in Guamanian D, ALS, P, and PDC. Cardiovagal, adrenergic, and postganglionic sudomotor functions were quantitated in 16 patients and 14 paired household controls. Patients comprised PDC (N = 11), D (N = 2), P (N = 2), and ALS (N = 1). Autonomic deficit was expressed on a composite autonomic scoring scale (CASS) and its subsets that corrects for the effects of age and gender. CASS severity was rated from 0 to 10 and the maximal subset scores were 3, 3, and 4 for postganglionic sudomotor, cardiovagal, and adrenergic deficits, respectively. CASS scores for mild, moderate, and severe autonomic failure are 1 to 3, 4 to 6, and 7 to 10, respectively. Symptoms were scored by an Autonomic Symptom Profile (ASP). The affected patients were older than and had a sex distribution different from paired controls (64.2 +/- 8.0 versus 53.1 +/- 13.5; p < 0.01; male/female = 9/7 versus 2/12; p = 0.045). CASS scores were markedly increased over paired controls (6.2 +/- 2.3 versus 1.9 +/- 1.3; p < 0.001), and involvement was generalized by system. There were deficits in sudomotor, cardiovagal, and adrenergic function. Orthostatic hypotension occurred in 6 of 16 patients and 2 of 14 paired controls. Guamanian patients had more autonomic dysfunction than non-Guamanian Parkinson's disease. ASP scores were higher in patients than controls and regressed with CASS. These differences persisted when corrected for the confounding effects of age, gender, and diabetes. We conclude that Guamanian patients have autonomic failure to a greater extent than non-Guamanian Parkinson's disease or ALS. This autonomic failure suggests multisystem autonomic involvement similar to but less severe than in multiple system atrophy.

Guamanian neurodegenerative disease: are diabetes mellitus and altered humoral immunity clues to pathogenesis?

On the western Pacific island of Guam, parkinsonism, dementia, and amyotrophic lateral sclerosis are highly prevalent but the cause is not known. To assess the possibility that the pathologic process extends beyond the nervous system, we studied patients with Guamanian neurodegenerative disease (N = 16) and Guamanian Chamorro control subjects (N = 16) in the Clinical Research Center of the Mayo Clinic, Rochester, MN. The principal abnormalities found in those with neurodegenerative disease included diabetes mellitus in 44%, elevated levels of serum immunoglobulin A (IgA) in 50%, and elevated IgG in 44%. The mean serum IgM level in the patient group was significantly lower than in the control group. Diabetes mellitus and elevated IgA and IgG levels were also present in 31% of neurologically normal Guamanian subjects. Some of these control subjects, however, probably have preclinical neurodegenerative disease, as found in previously published postmortem studies. Extensive serologic testing did not reveal any consistent profile of autoimmunity. Other blood and urine studies failed to identify hematologic, nutritional, renal, hepatic, or metabolic abnormalities that distinguished patients. Whether diabetes mellitus or abnormalities of immune regulation share common etiopathology with Guamanian neurodegenerative disease deserves further study.

Guamanian neurodegenerative disease: investigation of the calcium metabolism/heavy metal hypothesis.

OBJECTIVE: There is a high prevalence of neurodegenerative disease (parkinsonism, dementia, and motor neuron disease) on the western Pacific island of Guam. We sought evidence in support of the hypothesis that these conditions are triggered by nutritional deficiencies of calcium and magnesium leading to secondary hyperparathyroidism that then facilitates the entry of calcium and toxic heavy metals into the brain. METHODS: We analyzed indices of calcium metabolism plus blood-serum, urine, nail, and hair heavy metal concentrations in 12 patients with Guamanian neurodegenerative disease and 12 Chamorro control subjects. RESULTS: All 12 patients with Guamanian neurodegenerative disease had normal values for serum total and ionized calcium, 25-hydroxyvitamin D, and 24-hour urine collections for calcium. Eleven of 12 patients had normal serum parathyroid hormone values and alkaline phosphatase levels. No patient had reduced serum phosphorus or magnesium values although a minority of patients and controls had low urinary magnesium concentrations. Median blood-serum and 24-hour urine collections for heavy metals (aluminum, arsenic, cadmium, copper, iron, lead, manganese, mercury, and zinc) were statistically similar in the patient and control groups except for a slight elevation of blood, but not urine, lead in the patient group. Concentrations of heavy metals in hair and nails were similar in the two groups. CONCLUSIONS: We could find no evidence in support of abnormalities of calcium metabolism or heavy metal absorption as a major causative factor in the development of neurodegenerative disease on the island of Guam.