Alendronate for the treatment of pediatric osteogenesis imperfecta: a randomized placebo-controlled study.

CONTEXT: Information on the use of oral bisphosphonate agents to treat pediatric osteogenesis imperfecta (OI) is limited. OBJECTIVE: The objective of the investigation was to study the efficacy and safety of daily oral alendronate (ALN) in children with OI. DESIGN AND PARTICIPANTS: We conducted a multicenter, double-blind, randomized, placebo-controlled study. One hundred thirty-nine children (aged 4-19 yr) with type I, III, or IV OI were randomized to either placebo (n = 30) or ALN (n = 109) for 2 yr. ALN doses were 5 mg/d in children less than 40 kg and 10 mg/d for those 40 kg and greater. MAIN OUTCOME MEASURES: Spine areal bone mineral density (BMD) z-score, urinary N-telopeptide of collagen type I, extremity fracture incidence, vertebral area, iliac cortical width, bone pain, physical activity, and safety parameters were measured. RESULTS: ALN increased spine areal BMD by 51% vs. a 12% increase with placebo (P < 0.001); the mean spine areal BMD z-score increased significantly from -4.6 to -3.3 (P < 0.001) with ALN, whereas the change in the placebo group (from -4.6 to -4.5) was insignificant. Urinary N-telopeptide of collagen type I decreased by 62% in the ALN-treated group, compared with 32% with placebo (P < 0.001). Long-bone fracture incidence, average midline vertebral height, iliac cortical width, bone pain, and physical activity were similar between groups. The incidences of clinical and laboratory adverse experiences were also similar between the treatment and placebo groups. CONCLUSIONS: Oral ALN for 2 yr in pediatric patients with OI significantly decreased bone turnover and increased spine areal BMD but was not associated with improved fracture outcomes.

Soluble HLA-II expression in African-Americans.

OBJECTIVE: In this study we evaluated the contribution of major histocompatibility complex (MHC) genes to soluble histocompatibility antigen class II (sHLA-II) secretion in African American patients with rheumatoid arthritis (RA). METHODS: A sensitive enzyme-linked immunoassay was used to quantitate sHLA-II in the serum of 7 patients with RA, as well as 28 of their kinships and 49 HLA typed normal African American individuals. RESULTS: Mean sHLA-II values were higher in patients with RA than those in healthy African American individuals (p < 0.05). There were variations in concentrations in individual patients but these were unrelated to any apparent clinical event. The proportion of unaffected family members with detectable levels of sHLA-II was not significantly different than those in normal controls. Neither specific HLA-haplotype, or HLA-allele(s) correlated with high or low sHLA-II secretion. CONCLUSIONS: Our data suggest that sHLA-II molecules are not regulated by MHC linked genes but may be regulated by non-MHC linked genes and racial background may reflect genetic heterogeneity of the expression of this soluble HLA material. These observations contrast with previous observations concerning soluble HLA class I (sHLA-I) molecules in a described population sample which were almost the precise reverse.

A family retreat as a comprehensive intervention for children with arthritis and their families.

OBJECTIVE: Family resources and coping skills are important to adaptation to pediatric chronic illness. Psychological and educational interventions have been found to enhance the coping skills of children with juvenile rheumatic disease (JRD) and their families. We examined the efficacy of a 3-day family retreat as a multidisciplinary, comprehensive treatment. METHODS: Children with JRD and their caregivers completed questionnaires assessing the children's behavioral and emotional functioning, pain, strain on caregivers' work and leisure activities, and caregivers' psychological distress before and 6 months after the family retreat. Principal caregivers were both parents for 16 children, mothers only for 10 children, and an aunt for 1 child. RESULTS: Improvements were found in children's emotional functioning, strain on caregivers' work, and strain on caregivers' leisure activities. Reductions in reported pain were not consistently revealed. CONCLUSIONS: Family retreats are an efficacious, multidisciplinary approach to helping families of children with JRD cope with the disease and its manifestations. Importantly, retreats offer a comprehensive intervention package that might not be available to families on an individual basis.

Facilitating adaptation to juvenile rheumatic disease with family retreats.

Children with juvenile rheumatic disease (JRD) and their families face numerous challenges associated with disease symptomatology and treatment. Although many families cope well with these challenges, many are at risk for poor outcome. Children with JRD may have emotional, behavioral, and academic difficulties. Their parents also may have emotional distress, as well as marital conflict and reduced social activity. Identified risk factors for poor outcome include compromised family coping, poor adherence to treatment, and unmet academic needs. These risk factors are reviewed and an initial assessment of the effect of a family retreat on family coping is described. Twenty-seven families completed a coping questionnaire first at a family retreat and again 3 months later. Improvements were observed in reported ability to communicate about JRD, knowledge of arthritis, certainty of disease course, and ability to overcome difficulties related to JRD. Family retreats hold the potential to significantly enhance children's and caregivers' adaptation to JRD.

Soluble class I HLA antigens in patients with rheumatoid arthritis and their families.

OBJECTIVE: To study Class I soluble HLA in black patients with rheumatoid arthritis (RA) and their families, and to compare the findings to a group of healthy families of the same racial background. METHODS: ELISA was developed measure soluble HLA Class I (sHLAI) in the serum of 25 patients with RA. Family studies were performed in seven patients with RA and their 28 first degree relatives. These family studies were compared to similar measurements for 66 members of 13 healthy families. RESULTS: Mean sHLAI values were higher in patients with RA than those observed in healthy black individuals. Patients with RA were characterized by elevated serum HLAI, while no change was observed between patients with RA positive or negative for rheumatoid factor. The relatives of patients with RA had high concentrations of sHLAI, compared to families without RA. Highest serum concentrations of sHLAI were found in individuals who were HLA-A23 or HLA-Aw33 positive. CONCLUSION: sHLAI may play a role in the pathophysiology of RA, and there is an association between either augmented release or production of sHLAI and specific HLA allotypes.

The use of nonsteroidal anti-inflammatory medications: a therapeutic dilemma.

Nonsteroidal anti-inflammatory drugs are the mainstay of therapy for musculoskeletal disorders. Despite being effective for many people they may have serious side effects and their use should be carefully considered in some groups of patients. This article reviews basic information about nonsteroidals including usage, side effects, groups at high risk, and suggestions for decreasing toxicities.

Short- and long-term hemodynamic effects of captopril in patients with pulmonary hypertension and selected connective tissue disease.

To assess the pulmonary and systemic hemodynamic effects of oral captopril in patients with connective tissue disease and pulmonary hypertension, we performed right heart catheterization in eight patients with diffuse systemic sclerosis, the CREST syndrome, or mixed connective tissue diseases prior to and immediately following administration of captopril (dose range 12.5 to 50.0 mg, short-term study). Four of these patients underwent repeat right heart catheterization after three to six months of oral captopril therapy (long-term study). In the short-term study, oral captopril produced a significant decrease in mean pulmonary vascular resistance from 6.2 +/- 3.6 to 4.6 +/- 3.8 units (p < 0.01). This was accompanied by a significant decrease in mean pulmonary artery pressure, mean blood pressure, mean systemic vascular resistance and a significant increase in cardiac output. Similar changes in pulmonary hemodynamics were noted in the long-term study. Thus, oral captopril is capable of producing an acute and sustained reduction in pulmonary vascular resistance in patients with pulmonary hypertension associated with the aforementioned connective tissue diseases.

Acute and long-term effects of nifedipine on pulmonary and systemic hemodynamics in patients with pulmonary hypertension associated with diffuse systemic sclerosis, the CREST syndrome and mixed connective tissue disease.

Ten patients with pulmonary hypertension associated with diffuse systemic sclerosis (1 patient), the CREST syndrome (calcinosis cutis, Reynaud's phenomenon, esophageal dysmotility, sclerodactyl, telangiectasia) (6 patients) and mixed connective tissue disease (3 patients) were studied to assess the effect of oral nifedipine on pulmonary and systemic hemodynamics. Each patient underwent right-sided cardiac catheterization just before nifedipine administration. Thereafter, oral nifedipine was administered in 10 mg increments every 90 minutes until pulmonary vascular resistance normalized or a total dose of 30 mg was achieved. Hemodynamic measurements were obtained at 30-minute intervals for 3 hours, then hourly for 9 hours (acute study). Hemodynamic studies were repeated 3 to 6 months after the initial catheterization with the minimum dose of oral nifedipine (administered every 8 hours) required to achieve maximal reduction of pulmonary vascular resistance in the acute study (long-term study). In the acute study, oral nifedipine produced a significant decrease in mean pulmonary vascular resistance from 6.3 +/- 3.8 to 4.3 +/- 3.6 U (p less than 0.001). Similar changes in pulmonary vascular resistance were noted in the long-term study (n = 6). The results indicate that oral nifedipine is capable of producing an acute and sustained reduction in pulmonary vascular resistance in patients with pulmonary hypertension associated with diffuse systemic sclerosis, the CREST syndrome and mixed connective tissue disease.

Eosinophilic fasciitis with porphyria cutanea tarda and progressive destructive arthritis.

The course of arthritis with eosinophilic fasciitis is poorly documented. We report a patient in whom polyarthritis preceded the clinical appearance of eosinophilic fasciitis and progressed over a 14-year period to a destructive process with inflammatory and degenerative characteristics. Porphyria cutanea tarda and transient extramedullary pancytopenia complicated this patient's disease.

Value and limitations of calcium channel blockade in the treatment of pulmonary hypertension associated with CREST--case reports.

Reversible vasospasm has been hypothesized to underlie the development of pulmonary hypertension in patients with CREST. Drugs that prevent arterial spasm have been used to treat pulmonary hypertension with variable results. The disparate pulmonary hemodynamic responses to calcium channel blockade reported herein suggest that CREST patients with mild pulmonary hypertension may have a component of reversible vasospasm responsive to vasodilator therapy, whereas patients with moderate to severe pulmonary hypertension may have fixed vessel lesions precluding a satisfactory response to calcium channel blockade.

Metacarpophalangeal arthropathy associated with manual labor (Missouri metacarpal syndrome). Clinical radiographic, and pathologic characteristics of an unusual degeneration process.

We describe 7 manual laborers with painful, palpably enlarged metacarpophalangeal joints. Characteristic radiographic changes were joint space loss, prominent osteophytes, and cystic metacarpal heads most prominent in the second and third metacarpophalangeal joints. In 3 of 4 patients, joint biopsy specimens showed subsynovial fibrosis and villous hyperplasia. All 7 patients had similar backgrounds of heavy work demanding sustained gripping motions of both hands, for periods that exceeded 30 years. We designated their condition metacarpophalangeal arthropathy associated with manual labor.

Ocular complications of Tangier disease.

Tangier disease, or familial high-density lipoprotein deficiency, is an inherited disorder resulting in tissue deposition of excessive cholesterol esters. Although associated corneal clouding has been reported to produce little visual impairment, this patient with Tangier disease had corneal clouding, decreased corneal sensation, and cicatricial ectropion and experienced slowly progressive marked visual impairment. All ocular cases of Tangier disease are reviewed. Ectropion and incomplete eyelid closure may precede corneal clouding and should be recognized as signs associated with Tangier disease. The combination of exposure keratopathy and corneal infiltration can cause significant visual impairment.

Cytomegalovirus retinitis in rheumatic disease: a case report.

We describe a 67-year-old white man with Wegener's granulomatosis who was treated with cyclophosphamide, then with azathioprine, and who subsequently developed cytomegalovirus retinitis. The patient initially improved on a course of adenine arabinosine, but his retinitis has progressed, despite discontinuation of immunosuppressive therapy. We show that cytomegalovirus retinitis does occur in patients with rheumatic diseases who receive immunosuppressive therapy.