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Nail patella syndrome (NPS) is a rare autosomal dominant disorder resulting from a heterogeneous loss of function in the LMX1B gene. It is associated with multiple skeletal deformities, yet it is unknown whether this is associated with osteoporosis. To examine bone mass and the prevalence of fragility fractures, we assessed bone mineral density (BMD) of the spine and hip in 31 adults and 12 children with mutation-confirmed NPS and 60 healthy age- and gender-matched adult controls. For the adults with NPS, BMD was 11-20% lower at the hip sites (P < or = 0.001) and 8% lower at the spine (P < 0.05) than that of controls. Even when adjusted for body mass index, the BMD remained significantly lower in patients with NPS in all hip regions but not in the spine. Adults with NPS also had a significantly lower Z-score (sd values from normal) at all hip sites (all P < 0.05), compared with age- and gender-matched controls in the manufacturer's database. However, children had significantly lower Z-scores only at the femoral neck and trochanter. Participants with NPS also had a higher prevalence of fractures (odds ratio 30.9, 95% confidence interval 6.4-149.6, P < 0.001) and scoliosis (odds ratio 16.0, 95% confidence interval 3.3-78.2, P < 0.001). The majority of these fractures occurred in women before puberty and in long bones, especially the clavicle. We conclude that adults with NPS have a BMD that is 8-20% lower than controls, which is associated with an increase in the prevalence of fractures and scoliosis. Future studies are needed to determine whether bone quality, geometry, or turnover could account for these findings.

OBJECTIVE: To describe the types and severity of adverse drug-related events (ADEs) observed in patients receiving cyclooxygenase-2 (COX-2) inhibitors and to increase the awareness of risk factors that predispose patients to ADEs associated with COX-2 inhibitors. METHODS: A review of ADEs reported at the University of Pittsburgh Medical Center Presbyterian Hospital (UPMC-P) revealed significant events related to use of celecoxib or rofecoxib. A query of the internal ADE database was performed to identify ADEs involving COX-2 inhibitors from January 1999 to June 2002. A similar query was performed to identify ADEs involving nonselective nonsteroidal antiinflammatory drugs (NSAIDs) reported during this same time period. Utilization data were also collected. RESULTS: Forty-eight ADEs involving 24 patients receiving COX-2 inhibitors were reported and validated via the UPMC-P ADE review process compared with 38 events in 33 patients receiving nonselective NSAIDs. The types of ADEs reported as related to COX-2 inhibitors were similar to those reported in association with nonselective NSAIDs. Forty-two percent of ADEs (n = 20) involving COX-2 inhibitors and 45% of events (n = 17) involving nonselective NSAIDs were classified as severe. All patients receiving COX-2 inhibitors and 91% of patients receiving nonselective NSAIDs exhibited risk factors that increased their risk to experience an ADE; all but 1 of these patients were receiving outpatient COX-2 inhibitor therapy. CONCLUSIONS: The observed ADEs involving COX-2 inhibitors were similar to those associated with nonselective NSAIDs. Most events may have been preventable, highlighting the need for education regarding the appropriate use of COX-2 inhibitors.

Vitamin B 12 deficiency is common in elderly persons, yet its role in dementia and psychiatric illness is unclear. The authors examined the relationship between vitamin B 12 serum levels and cognitive and neuropsychiatric symptoms in dementia. Community-dwelling elderly subjects (N = 643) meeting NINCDS-ADRDA criteria for probable or possible Alzheimer disease (AD) underwent comprehensive neuropsychiatric evaluation and measurement of vitamin B 12 serum levels. Thirty-seven subjects (5.7%) had low B 12 serum levels (200 pcg/ml or less). Subjects with low B 12 levels were significantly older and had significantly lower scores on the Mini-Mental State Exam and higher scores on the Blessed Dementia Scale, but not a different pattern of cognitive or behavior disturbances compared with the normal-B 12 subjects. In AD, the prevalence of low vitamin B 12 serum levels is consistent with that found in community-dwelling elderly persons in general but is associated with greater overall cognitive impairment.

OBJECTIVE: To describe a case of fulminant hepatitis possibly related to concomitant donepezil and seratriline therapy. PATIENT AND SETTING: An 83-year-old woman treated in a dementia care facility and later in a tertiary medical center. INTERVENTION AND MANAGEMENT: Discontinuation of donepezil and sertraline therapy with subsequent improvement evidenced by liver biopsy and liver function tests. RESULTS: An older woman with Alzheimer's disease was admitted to a dementia care facility because of aggressive behavior. Treatment with sertraline was initiated in February 1998. Sertraline doses were increased gradually to 200 mg daily by May 1998, and some improvement in behavior was seen. Concomitant therapy with donepezil 5 mg qhs was initiated June 26, 1998. Ten days later, confusion and jaundice were noted. Total bilirubin was 5.6 mg/dL, GGTP was 1208 IU/L, and alkaline phosphatase was 369 IU/L. Computed tomography revealed cholelithiasis without ductal dilation. Liver, spleen, and pancreas seemed normal. Donepezil and sertraline were discontinued. The patient was admitted to our institution and treated for dehydration. A liver biopsy revealed scattered portal eosinophils and prominent cholestasis consistent with acute chemical hepatitis. The GGTP and total bilirubin of this patient peaked at 2235 IU/L and 22.6 mg/dL, respectively. The patient improved, and her liver function tests normalized over the next 2 months.

OBJECTIVE: To identify dietary, psychological, and physiological characteristics of older individuals with chronic constipation, compared with a control group of individuals without constipation, and identify correlates of colonic transit time. DESIGN: Cohort study. SETTING: University hospital and affiliated clinics. PARTICIPANTS: Eighteen constipated and 18 control subjects who were nondemented, ambulatory, community-dwelling outpatients over the age of 60 years. MEASURES: Measures included a 1-week food diary, diet questionnaire, bowel diary, the Hopkins Symptom Checklist (SCL-90R), colonic transit study, and medical history, including queries about activity, medications, medical illnesses, and bowel symptoms. MAIN RESULTS: Constipated subjects reported consuming fewer meals per day compared with control subjects (P < 0.01) and a tendency to consume fewer calories (P = 0.07). There were no differences between groups on fiber or fluid intake or any of the other dietary parameters. However, slow colonic transit was significantly related to low caloric intake (P < 0.0001), higher percent of protein in the diet (P < 0.05), low fluid intake (P < 0.05), and to psychological symptoms of somatization, obsessive-compulsiveness, depression, anxiety, and the global severity index (P < 0.05). Transit times were unrelated to crude or dietary fiber intake, activity level, or age. CONCLUSIONS: The data suggest that constipation in this older population is related to caloric intake rather than fiber consumption or other dietary qualities. Psychological distress is associated with slowed colonic transit and should be investigated further as a possible etiologic factor in constipation.

Hyponatremia sometimes occurs in elderly depressed patients treated wtih a serotonin reuptake inhibitor (SRI). The cause of the hyponatremia is not yet understood. The objective of this study was to determine the effects of paroxetine, an SRI, on osmoregulated release of vasopressin (also termed antidiuretic hormone) in elderly depressed patients with normal serum sodium. Four women and one man ages 61 to 74 years with a major depressive disorder were administered a water load after they had been treated with a therapeutic dose of paroxetine for 3 to 11 months. Three healthy elderly subjects not receiving paroxetine served as controls. Both the patients and the control subjects excreted > 90% of the ingested water and lowered urine osmolality to < 100 mosmol/kg. We conclude that long-term treatment with paroxetine alone does not appear to affect the ability to excrete a water load or appropriately dilute the urine during a water load (both indices of vasopressin function) in a small group of elderly patients without other risk factors for the development of hyponatremia. (J Geriatr Psychiatry Neurol 2000; 13:212-216).