A double-blind randomised controlled trial of the effects of medroxyprogesterone acetate on bone density of women taking oestrogen replacement therapy

Objective To assess the effects of medroxyprogesterone acetate on bone density in women who have had a hysterectomy
Design Randomised, double-blind, placebo-controlled trial of medroxyprogesterone acetate 10 mg, 20 mg or placebo as an adjunct to oestrogen therapy.
Participants One hundred and twenty-three women, aged 18 to 45 years and currently receiving daily oestrogen, who presented at a university-based rheumatology practice.
Interventions The women were randomly assigned to receive either medroxyprogesterone acetate 10 mg, 20 mg or placebo daily beginning on day 15 of each month for one year. Forty-one women were randomised into each group.
Main outcome measure The primary outcome measurement was the percentage of change from baseline in bone mineral density of the lumbar spine (L2–L4). Secondary outcome measures included differences in femoral neck bone density, cholesterol and triglyceride levels between groups.
Results At one year, change in bone mineral density did not differ between either the treatment or placebo groups. Medroxyprogesterone acetate 20 mg and 10 mg led to statistically significant reductions in very low density lipoprotein cholesterol, total triglycerides, and very low density lipoprotein triglycerides when compared with placebo. Medroxyprogesterone acetate 20 mg also led to a statistically significant reduction in high density lipoprotein cholesterol, high density lipo-protein-2 cholesterol, and high density lipoprotein-2 triglycerides.
Conclusions Medroxyprogesterone acetate at either dose as an adjunct to oestrogen did not improve bone mineral density at one year when compared with placebo. Medroxyprogesterone acetate 10 mg may not adversely affect lipids. Medroxyprogesterone acetate 20 mg, however, did reduce high density lipoprotein cholestrol and therefore may increase cardiovascular risk.     

Genetic, environmental, and gender effects on individual differences in toddler expressive language.

In this article, the authors examined the genetic and environmental factors influencing expressive language development in a sample of 386 toddler twin pairs participating in the Wisconsin Twin Project. Expressive language was assessed using 2 measures from the MacArthur Communicative Development Inventories-Short Form: Total Vocabulary and Two-Word Combination Use (L. Fenson et al., 2000). A sex-limitation structural equation model estimated the contribution of genetics, shared environment, and nonshared environment to individual variation. For vocabulary, heritability was higher for boys than for girls (20% vs. 8%). For word combination use, heritability was higher for girls (28% vs. 10%). However, the majority of individual variation in both boys and girls could be attributed to shared environment (54%-78%).     

Analysis of pulmonary fat embolism in blunt force fatalities

OBJECTIVE: To investigate the incidence, severity, and origin of pulmonary fat embolism (PFE) in persons dying from blunt force trauma within 24 hours of injury. METHODS: The study population consisted of blunt force fatalities. Controls were subjects dying from natural causes or nonblunt force injury. Tissue was removed from lung lobes and prepared for histologic examination using osmium tetroxide to stain for fat. Lung sections were graded for PFE on a scale of 0 (no emboli) to 4 (five or more emboli in a majority of fields). RESULTS: The blunt force group consisted of 56 decedents. Mortality was 93% within 4 hours. Fractures were present in 54 (96%) of decedents, and soft tissue injury was universal. Thirty eight (68%) of decedents were positive for PFE vs. 3 of 20 (15%) in controls. Mean score for PFE was 2.94 +/- 1.15 and 1.01 +/- 0.94, respectively (p < 0.005). Bone marrow emboli were not observed in any of the sections. Severity of PFE was positively associated with survival time. Analysis of PFE against sex, age, height, weight, number of injuries, and number of fractures showed no significant correlations. CONCLUSIONS: A significant degree of PFE develops rapidly in a majority of persons dying of blunt force trauma. Although the source of fat for embolization has been suggested to be bone marrow, no evidence of myeloid tissue was found in any of the lung sections. Nor was there a correlation of PFE and number of fractures. Soft tissue injury is considered the primary cause of PFE.     

Abbreviated chemotherapy with fludarabine followed by tositumomab and iodine I 131 tositumomab for untreated follicular lymphoma.

PURPOSE: To evaluate the safety and efficacy of a sequential chemotherapy plus radioimmunotherapy (RIT) regimen in previously untreated follicular non-Hodgkin's lymphoma. PATIENTS AND METHODS: Thirty-five patients received an abbreviated course (three cycles) of fludarabine followed 6 to 8 weeks later by tositumomab and iodine I 131 tositumomab. RESULTS: After fludarabine, 31 (89%) of 35 patients responded, with three (9%) of 31 patients achieving a complete response (CR). After the full regimen of fludarabine and iodine I 131 tositumomab, all 35 patients responded; 30 (86%) of 35 patients achieved CR, and five (14%) of 35 achieved partial response. After a median follow-up of 58 months, the median progression-free survival (PFS) had not been reached (95% CI, 27 months to not reached), but it will be at least 48 months. The 5-year estimated PFS rate is 60%. Baseline Follicular Lymphoma International Prognostic Index (FLIPI) was significantly associated (P = .003) with PFS. Five of six patients with more than 25% bone marrow involvement at baseline achieved adequate bone marrow cytoreduction to receive standard-dose iodine I 131 tositumomab. Ten (77%) of 13 patients with baseline bone marrow Bcl-2 positivity demonstrated molecular remissions at month 12. Toxicities were manageable and principally hematologic. Two (6%) of 35 patients developed human antimurine antibodies (HAMA) after RIT. CONCLUSION: Use of abbreviated fludarabine before iodine I 131 tositumomab can reduce bone marrow involvement, when needed, to allow the use of RIT and can suppress HAMA responses. This sequential treatment regimen is highly effective as front-line therapy for follicular lymphoma, particularly for low- or intermediate-risk FLIPI patients.     

Childhood Lyme arthritis: experience in an endemic area

We report 25 children with oligoarticular arthritis associated with Lyme disease. There were 16 boys (male/female ratio 1.8:1); ages ranged from 2 to 15 years. Thirteen (52%) children had no history of erythema chronicum migrans or other rash. Thirteen had temperatures as high as 41 degrees C for up to 2 months before the onset of arthritis. Twelve recalled definite tick bites. Ten (40%) children, of whom seven had no history of rash, were hospitalized for presumed septic arthritis. Another four had diagnoses of pauciarticular juvenile rheumatoid arthritis for as long as 3 years. Seven patients had less acute, recurrent episodes of synovitis. Two children had seventh nerve palsies 2 months before onset of arthritis. All patients had antibodies to the Lyme spirochete. In 14 patients, synovial fluid white blood cell counts ranged from 180 to 97,700/mm3 (greater than or equal to 76% polymorphonuclear leukocytes). Antibiotic therapy was effective in all patients; in 13, orally administered therapy alone resulted in elimination of synovitis and recurrent attacks. Lyme arthritis may be confused with acute bacterial septic arthritis or recurrent "pauciarticular juvenile rheumatoid arthritis," particularly when there is no history of erythema chronicum migrans.