Immunopathology of glomerulonephritis associated with chronic woodchuck hepatitis virus infection in woodchucks (Marmota monax).

Retrospective analysis of necropsy findings of 705 woodchucks was performed to determine the prevalence and morphology of immune-mediated glomerulonephritis, its relationship to woodchuck hepatitis virus (WHV) infection, and the presence of major WHV antigens. Twenty-six woodchucks had glomerular lesions. Renal tissue of the 26 animals was evaluated histologically and immunohistochemically for immune-mediated glomerulonephritis. Of these 26 animals, immune-mediated glomerulonephritis was diagnosed in six, all of which were chronic WHV carriers. Membranous glomerulonephritis was identified in three animals, two of which also had mesangial proliferation. Host immunoglobulin was present within the mesangium and along capillary loops in all three. Woodchuck hepatitis virus core antigen (WHcAg) was present along capillary loops of two of these animals, one membranous and one mixed, and in the mesangium of all three. Woodchuck hepatitis virus surface antigen (WHsAg) deposition was similar to WHcAg deposition but was only present along capillaries in those animals with mixed nephritis. The remaining three animals had mesangial proliferation. WHsAg and host immunoglobulin deposition were predominately mesangial; WHcAg was not detected. Transmission electron microscopy showed thickening of the capillary loop basement membranes and subepithelial electron-dense deposits in animal one, and deposits in the mesangium in animal six.     

Passive smoking and sudden infant death syndrome: review of the epidemiological evidence

BACKGROUND: This paper provides a systematic, quantitative review of the epidemiological evidence relating parental smoking and sudden infant death. METHODS: Thirty two relevant publications were identified after consideration of 692 articles selected by electronic search of the Embase and Medline databases using keywords and Mesh headings relevant to passive smoking in children. Eleven further articles were identified from reviews and by talking to authors. The search was completed in April 1997 and identified 39 studies. RESULTS: The unadjusted pooled odds ratio for prenatal maternal smoking was 2.77 (95% CI 2.45 to 3.13). After adjustment for a variety of confounders the pooled odds ratio was reduced to 2.08 (95% CI 1.83 to 2.38) and was similar in cohort and case-control studies. Four studies reported on maternal postnatal smoking after controlling for prenatal maternal smoking (pooled odds ratio 1.94 (95% CI 1.55 to 2.43)). Of three studies reporting on the risk of paternal smoking where the mother was a non-smoker, two found significant effects while one found no effect. Dose-response relationships with both prenatal and postnatal maternal smoking were present in most studies which provided data. CONCLUSIONS: Maternal smoking doubles the risk of sudden infant death syndrome. The relationship is almost certainly causal. There is good evidence that postnatal exposure to environmental tobacco smoke from both mother and father are important. Because prenatal smoking is almost invariably associated with postnatal smoking, the role of prenatal smoking per se will be difficult to resolve using epidemiological studies.


     

Revision of ankle arthrodesis with external fixation for non-union.

We evaluated the cases of twenty-six patients (twenty-six ankles) who had had revision of an ankle arthrodesis with external fixation for a nonunion, to determine the reasons for the failure of the previous arthrodesis. Eighteen patients had had supplemental bone-grafting in addition to the external fixation. The failure of the previous arthrodesis was related to inadequate fixation technique in seven patients and to technical problems in two patients; in the other seventeen patients at least one risk factor was identified. We also determined the functional results of the revision operation with external fixation for all patients. The average duration of follow-up was five years (range, two to ten years) in the twenty-two patients who did not have a reoperation for a persistent nonunion. The results were excellent in eleven patients, good in five, fair in four, and poor in six. The over-all rate of union was twenty (77 per cent) of twenty-six, comparable with that after primary arthrodesis; however, supplemental bone-grafting is usually necessary. In the current series, rigid fixation, precise apposition of bone and alignment of the foot, and early treatment of perioperative infection gave satisfactory results.     

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.