Phenotypic abnormalities in CD8+ T lymphocyte subsets in patients with rheumatoid arthritis.

We analyzed the cell surface phenotype of CD8+ cells in both peripheral blood and synovial fluid (SF) of patients with rheumatoid arthritis (RA) and osteoarthritis (OA). Utilizing the monoclonal antibodies anti-CD45RA, anti-CD29 and anti-S6F1-, one can define both suppressor effector (CD45RA+CD29-S6F1-) and killer effector (CD45RA-CD29+S6F1+) cells within the CD8 population. In patients with OA, normal proportions of CD8+CD45RA+, CD8+CD29+ and CD8+S6F1+ cells were found in both peripheral blood and SF. The peripheral blood of patients with RA, in contrast, showed a decreased percentage of CD8+CD45RA+ cells (13.4 +/- 2.6) (p less than 0.05), but a normal percentage of CD8+CD29+ and CD8+S6F1+ cells. In the SF of patients with RA, we observed a more dramatic decrease in CD8+CD45RA+ suppressor effector cells (6.4 +/- 5.0) (p less than 0.001), a significant increase in killer effector cells as measured by both CD8 + CD29+ (35.5 +/- 9.9) (p less than 0.001) and CD8 + S6F1+ cells (28.2 +/- 11.4) (p less than 0.01). These changes may contribute to the immunologic abnormalities previously noted in this disease and may provide some insight into the pathophysiologic mechanisms of RA.     

Immunogenicity of four Haemophilus influenzae type b conjugate vaccines in 17- to 19-month-old children

OBJECTIVE: To compare the immunogenicity of four Haemophilus influenzae type b (Hib) conjugate vaccines in different populations of 17- to 19-month-old children in the United States. DESIGN: Four immunogenicity trials with sera were assayed in one laboratory. Trials 1 and 2 each compared one vaccine in two regions, and trials 3 and 4 were randomized comparisons of multiple vaccines within a region. SUBJECTS: A convenience sample of 313 healthy children recruited from pediatric practices in Minneapolis, Minn., Dallas and Houston, Tex., and Sellersville, Pa. MEASUREMENTS AND RESULTS: Children with prevaccination antibody greater than 0.15 microgram/ml showed higher antibody responses to vaccination than children with less than or equal to 0.15 microgram/ml (p less than 0.001). Among the former, there were no significant differences in antibody response to vaccination with the different conjugates within any of the trials. Among children with less than or equal to 0.15 microgram/ml of antibody before vaccination, there were no significant differences in the geometric mean antibody responses of children in trial 1 vaccinated with polyribosylribitol phosphate-diphtheria toxoid (PRP-D) in Dallas or in Minneapolis, or of children in trial 3 in Dallas randomly assigned to receive Hib oligosaccharide-CRM197 (HbOC) or PRP-D. In contrast, in trial 2, children given PRP-tetanus toxoid (PRP-T) in Pennsylvania had a significantly higher geometric mean antibody response than children given PRP-T in Houston (13.5 vs 3.0 micrograms/ml; p = 0.005). In trial 4 in Minneapolis, the geometric mean antibody response was highest in children randomly assigned to receive PRP-outer membrane protein (OMP) (9.3 micrograms/ml), followed by PRP-D (5.0 micrograms/ml) and HbOC (2.3 micrograms/ml) (PRP-OMP vs HbOC; p = 0.005). In all four trials, IgG1 responses predominated compared with IgG2 responses. CONCLUSIONS: All four conjugate vaccines are immunogenic in children 17 to 19 months of age. However, the magnitude of the anticapsular antibody response varied by vaccine type, the level of antibody in prevaccination sera, and geographic location.     

Resolution of otitis media with effusion with the use of a stepped treatment regimen of trimethoprim-sulfamethoxazole and prednisone

This double blind, placebo-controlled trial was designed to determine whether intervention with a stepped regimen of trimethoprim-sulfamethoxazole (TMP-SMX) and prednisone would prevent high risk children from developing chronic otitis media with effusion (OME) and recurrent acute otitis media. Forty-two children were enrolled, assigned to treatment with active drug or placebo and then examined at 2-week intervals. They received TMP-SMX (or placebo) during the first 2 weeks, TMP-SMX and prednisone (or placebo) during Weeks 3 and 4 for persistent OME and TMP-SMX (or placebo) for Weeks 5 and 6 if OME was still unresolved. After treatment 48% of active drug and 14% of placebo subjects resolved OME bilaterally (P less than 0.05). Active drug subjects also had fewer acute otitis media episodes than placebo subjects while receiving study treatment (P less than 0.01). Although this treatment regimen produced short term OME resolution, long term benefits were not demonstrated.     

Sleeping position and rectal temperature.

The effects of sleeping position upon body temperature were assessed by continuous monitoring of rectal temperature in 137 babies sleeping at home under conditions chosen by their parents. There were three groups of subjects: (1) normal babies aged 12-22 weeks whose temperature rhythms were developed, (2) normal babies aged 6-12 weeks who were developing their night time temperature rhythms, and (3) babies the night after diphtheria, pertussis, and tetanus immunisation, whose temperature rhythms were disturbed. Sleeping in the prone position was not associated with higher rectal temperatures at any time of night in young babies, nor did it exaggerate the disturbance of rectal temperature rhythm after immunisation. In older normal babies the prone position did not disturb rectal temperature in the first part of the night, though prone sleepers warmed a little faster prior to walking, especially in warm conditions. Prone sleepers were, however, born earlier in gestation and tended to be of lower birth weight. Normal babies can therefore thermoregulate effectively whatever their sleeping posture, even in warm conditions, though the prone position may make it slightly more difficult to lose heat. It is difficult to see how the prone position, even interacting with warm conditions, could induce lethal hyperthermia in otherwise normal babies. Perhaps the prone position is associated with other risk factors for sudden infant death syndrome.     

Physiologic comparison and validation of Stairobic stepping with bench stepping.

To compare the oxygen cost of submaximal exercise on the Stairobic stepping (SS) machine with bench stepping (BS), 12 healthy men and women (mean age 23 years) underwent six different five minute exercise bouts that were randomly assigned. Tests were conducted using standard open circuit calorimetry. SS at 40 and 60 st/min was equal to BS at 20 st/min and SS at 80 st/min was equal to BS at 30 st/min for VE and RER. VO2 was equal at 20 st/min (BS) and 60 st/min (SS), and 30 st/min (BS) and 80 st/min (SS). Stairobic MET (SM) displayed values over-estimated actual MET (AM) values at the two lowest SS rates and under-estimated the AM value at the highest SS rate. Forty-eight observations of the MET response of SS were conducted and analyzed (BMDP2R) in a forward stepping solution. The multiple regression equation calculated for AM was: AM = -0.567 + -0.012 (WT) + 0.063 (rate) + 0.612 (SM) with an adjusted R2 of 0.82 and a SEE of 0.90. The physiologic cost of BS was approximately equal to SS at two to three times the BS rate of stepping.     

Novel therapeutic approaches for multiple myeloma

Summary: Multiple myeloma (MM) affects 15 000 new patients annually in the US, with 50 000 total patients, and remains incurable. Our preliminary in vitro and animal studies suggest a role for MM–host interactions in regulating MM cell growth, drug resistance, and migration in the bone marrow. Importantly, treatment strategies which target mechanisms whereby MM cells grow and survive in the bone marrow, including thalidomide and its potent immunomodulatory derivatives and proteasome inhibitor PS‐341, can overcome classical drug resistance in preclinical and early clinical studies.     

Clinical trial of a prevention and treatment protocol for skin breakdown in two nursing homes.

OBJECTIVE: Our objective was to assess the effectiveness of skin care protocols, including a body wash and skin protectant, on skin breakdown in 2 nursing homes. DESIGN: This was a quasi-experimental pretest/posttest design study.Setting and subjects Adult residents (n = 136) of 2 skilled nursing homes consented to participate in this study. Seventy percent were women; the sample average age of 82 years. INSTRUMENTS: A researcher-designed data recording form documented resident demographics, incidence and type of skin breakdown or pressure ulcer, presence of urinary or fecal incontinence, and assessment of the effectiveness of body wash and skin protectant. METHODS: Baseline data on prevalence of pressure ulcers and skin protocol were collected weekly for a 3-month period followed by a week-long educational program by the researchers about skin care and the body wash and skin protectant. During the 3-month trial with the body wash and skin protectant incorporated into routine care, research assistants recorded resident data weekly and researchers again assessed prevalence and incidence of pressure ulcers and skin breakdown weekly. RESULTS: Incorporation of a body wash and skin protectant into a skin care prevention and early intervention protocol in 2 nursing homes documented a decrease in skin breakdowns from 68 pre-intervention to 40 postintervention; the decrease in agency B was statistically significant. There was a statistically significant decrease in stage I and II pressure ulcer incidence overall (pre-intervention = 19.9%, postintervention = 8.1%). Nurses evaluated the body wash and skin protectant as effective for 98% of the time used. CONCLUSION: Implementation of a protocol for skin care along with staff education, including the prophylactic use of a body wash and skin protectant, reduced the incidence of skin breakdown, including pressure ulcers and perineal dermatitis, in 2 long-term care facilities.     

Proximal femoral focal deficiency: radiologic analysis of 49 cases

Proximal femoral focal deficiency, an uncommon congenital anomaly, necessitates early radiologic classification for surgical planning and treatment. Objective radiographic criteria, including femoral length index, acetabular depth index, acetabular angle index, and shape of the proximal femur were determined in 49 patients before cartilaginous ossification of the femoral capital epiphysis; final classification was based on follow-up radiographs or findings at arthrography or surgery. These parameters were analyzed to determine the accuracy and contributions of each in classification. Correct classification into one of three groups was possible in 86% of cases with use of three of the parameters: femoral length index, acetabular depth index, and shape of the proximal femur. The acetabular angle was found to contribute insignificantly to classification. Magnetic resonance imaging, used in only one case, depicted the nonossified cartilaginous femoral capital epiphysis, thus obviating the need for invasive diagnostic procedures and facilitating early classification.     

3-Hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors. 3. 7-(3,5-Disubstituted [1,1'-biphenyl]-2-yl)-3,5-dihydroxy-6-heptenoic acids and their lactone derivatives

The syntheses of a series of 7-(3,5-disubstituted [1,1'-bephenyl]-2-yl)-3,5-dihydroxy-6-heptenoic acids and their lactones are reported. Intrinsic 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitory activity is enhanced markedly when the biphenyl moiety is substituted by chloro or methyl groups at positions 3 and 5 and a fluoro group at position 4'. These substitutions, followed by resolution, provided compounds 100(+) and 110(+) with 2.8 times the intrinsic inhibitory activity of compactin. Compound 100(+) was shown to possess the same chirality in the lactone ring as compactin by single-crystal X-ray crystallography.