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Biomedical subjects

B Rich

Publications and source records attributed to B Rich.

At least 19 recordsLinked to original sources

Effect of MPC-11 myeloma and MPC-11 + IL-1 receptor antagonist treatment on mouse bone properties.

This study examines the effects of an IL-6-producing murine multiple myeloma cell line on trabecular and cortical mouse bone, and evaluates the efficacy of interleukin-1 receptor antagonist (IL-1ra) in mitigating bone destruction. Six-week-old BALB/c mice were assigned to two groups: normal controls and myeloma animals (5 x 10(7) MPC-11 cells on day 0). Myeloma animals were further assigned to three unique groups: MPC-11 only; MPC-11 treated with hyaluronic acid (HA); and MPC-11 + IL-1ra/HA (100 mg/kg). Disease development was assessed at 14 and 21 days via spleen, liver, and proximal tibia histology; histomorphometry at the femoral middiaphysis; and long bone composition and mechanical testing. Histologic analysis revealed marked myeloma infiltration into organs and bone marrow and gross bone resorption of the proximal tibia. IL-1ra tended to decrease bone resorption at the proximal tibia; however, it had no effect on quantitatively measured bone parameters. Whole femur and tibia, and tibial epiphysis, percent mineralization was decreased (3.0%, 2.9%, and 6.3%, respectively) in all MPC-11 groups. The presence of myeloma did not affect long bone stiffness, strength, or length over the 3 week study. The percent of the femoral endosteal perimeter showing excessive resorption ( approximately 60%) in the MPC-11 groups increased significantly after 21 days. MPC-11 cell presence caused no change in bone formation or morphology. Normal growth mechanisms were not impacted, as the bones lengthened and increased in size and mass despite the presence of myeloma. IL-1 does not appear to be a primary factor in in vivo bone destruction caused by the MPC-11 cell line. These findings reveal the stochastic nature of bone lesions in multiple myeloma and suggest that IL-1 is not a cytokine critical to this disease pathology.

Animals↗

A comparative study of genetic and neurobiological findings in disintegrative psychosis and infantile autism.

Although disintegrative psychosis (DP) was first described in 1908, the validity of the syndrome has not yet been fully documented. To investigate the validity of DP as defined in ICD-9, 13 cases of DP were compared with 39 cases of infantile autism with reference to lifetime parental psychopathology, neuroradiological findings and genetic abnormalities. The groups were matched for gender, age, intellectual level and social class. Apart from a significantly higher rate of electroencephalogram abnormalities in the disintegrative group there was very little in the neurobiological background to support a clear distinction between DP and infantile autism.

Autistic Disorder↗

The natural history of somatic morbidity in disintegrative psychosis and infantile autism: a validation study.

In order to study the validity of disintegrative psychosis (DP) as defined in ICD-9, we compared the natural history of somatic morbidity of 13 patients given this diagnosis in childhood with a control group of 39 patients with infantile autism (IA) matched for gender, age, IQ and social class. Average follow-up time was 22 and 23 (11-33) years, respectively. Significantly more DP patients (85 versus 41%) had been admitted to a non-psychiatric hospital during the follow-up period. They also had significantly more admissions (3.6 versus 1.0) and stayed longer in hospital (78 versus 4 days) than patients with IA. Three of the DP individuals had an associated medical disorder and made extensive use of somatic services during the follow-up period. Altogether the DP group had utilised the medical health care system more than patients with IA suggesting that they had more medical symptoms than the IA group. On the whole our findings suggest that individuals with DP and IA should be conceptualised as essentially distinct and should be studied separately as regards aetiology, pathophysiology, course and treatment.

Adult↗

Epilepsy in disintegrative psychosis and infantile autism: a long-term validation study.

This study aimed to investigate the validity of disintegrative psychosis (DP) as defined in the ICD-9. The history of epilepsy in 13 subjects with DP was compared with that of 39 subjects with infantile autism (IA) who were matched for sex, age, IQ, and socioeconomic status (SES). The average follow-up time was 22 and 23 years (range 11 to 33 years). A significant difference was found between the DP and IA groups in terms of incidence of epilepsy, 77% versus 33% respectively. The peak period of onset of epilepsy occurred before puberty in both groups. Different types of epilepsy were seen, but the psychomotor variant accounted for 50% in the DP group, while 46% of the IA group had the psychomotor and 62% had the grand mal variant. The types are not mutually exclusive. Individuals without epilepsy had significantly higher IQ scores than those with epilepsy, but only within the IA group. The increased risk of developing epilepsy in the DP group is most likely a reflection of an underlying early brain pathology probably present in most individuals with DP. On the whole our findings can be seen as a contribution to the validation of DP as separate from IA, as these two conditions could be distinguished in terms of the way they develop with reference to epilepsy.

Adolescent↗

Effect of filgrastim treatment on inflammatory cytokines and lymphocyte functions.

Twenty-four healthy male volunteers received either placebo or 75, 150, or 300 microg filgrastim (recombinant methionyl human granulocyte colony-stimulating factor) for 12 days to study effects on monocytes and lymphocytes. In all filgrastim-treated groups, tumor necrosis factor alpha (TNF-alpha), interleukin-12 (IL-12), and interferon gamma (IFN-gamma) release by whole blood in response to endotoxin (lipopolysaccharide) was reduced. IL-12 added in vitro to lipopolysaccharide-stimulated blood of filgrastim-treated donors restored IFN-gamma and TNF-alpha release, suggesting that the anti-inflammatory effect of granulocyte colony-stimulating factor is exercised through IL-12 suppression. Phytohemagglutinin- or anti-CD3 antibody-induced lymphocyte proliferation ex vivo was reduced by 60% from day 5 to day 15, after a 50% increase at day 2 with concomitant doubled IL-2 release. In vivo, filgrastim induced doubling of all T-cell populations by day 8. Filgrastim decreased proinflammatory cytokine production and lymphocyte proliferation ex vivo throughout prolonged treatment at all doses. This indicates that endogenous granulocyte colony-stimulating factor may counterregulate the inflammatory cytokine cascade and implies a potential indication for filgrastim in chronic inflammatory conditions.

Adult↗

ACR and EULAR improvement criteria have comparable validity in rheumatoid arthritis trials. American College of Rheumatology European League of Associations for Rheumatology.

We compared the validity of the American College of Rheumatology (ACR) and the European League of Associations for Rheumatology (EULAR) definitions of response in rheumatoid arthritis (RA) clinical trials. US: ACR and EULAR improvement criteria were calculated in 7 large randomized RA clinical trials. The discriminant validity of the response criteria between treatment groups was studied using the Mantel-Haenszel chi-squared value. To compare both sets of criteria the chi-squared ratio was determined for each trial. Europe: In 2 large randomized RA clinical trials, ACR and EULAR criteria were calculated, once with extensive and once with 28 joint counts. The classification of patients with these 4 criteria were compared with each other using cross tables. We further studied the difference in response between treatment groups per trial, the association of response with patient and investigator assessment of improvement, and the association of response with radiological progression. US: The chi-squared ratio for most trials was close to 1. There was no clear pattern suggesting that the discriminant validity of the ACR criteria was stronger than the discriminant validity of the EULAR definition of response or vice versa. Europe: Conflicting results between ACR and EULAR were present in only 3% of patients in both trials. The discriminant validity of all 4 criteria (ACR and EULAR with reduced and extensive joint counts) was comparable. All criteria were related with the overall assessment of improvement by both investigator and patient. The association with radiographic progression was comparable for EULAR and ACR improvement criteria. There is a high level of agreement between ACR and EULAR improvement classification, and their validity is equivalent. The discriminating potential of the criteria between treatment groups is comparable, as is the association with patient's and investigator's overall assessment and with radiographic progression.

Antirheumatic Agents↗

Effects of interleukin 1 receptor antagonist alone and in combination with methotrexate in adjuvant arthritic rats.

OBJECTIVE: To determine the benefit of combination treatment with the interleukin 1 receptor antagonist (IL-1ra) and methotrexate (MTX) in adjuvant arthritic rats. METHODS: Rats with adjuvant arthritis were treated by continuous sc infusion with IL-1ra (5 mg/kg/h). Effects of IL-1ra treatment alone were compared to treatment with daily oral MTX (0.048, 0.06, or 0.075 mg/kg) or MTX in combination with IL-1ra. Efficacy was monitored by sequential caliper measurement of ankle joints, final paw weights, and histologic evaluation with particular emphasis on bone lesions. RESULTS: Treatment with IL-1ra alone resulted in 6% inhibition of paw swelling assessed by final paw weight. Treatment with MTX (0.075 mg/kg PO) gave 47% inhibition and the combination resulted in an 84% decrease in swelling. Histologic evaluation of ankle joints revealed 53% inhibition of bone resorption with IL-1ra alone, 58% inhibition with MTX alone, and 97% inhibition in combination treated rats. Lower doses of MTX in combination with IL-1ra also provided additive benefit on arthritis variables. CONCLUSION: Combination therapy with IL-1ra and MTX results in additive or synergistic benefit, with excellent inhibition of all arthritis variables. These data support clinical investigation of the use of combination therapy of IL-1ra and MTX in patients with rheumatoid arthritis.

Animals↗

Bone mineral density assessment in children with inflammatory bowel disease.

BACKGROUND & AIMS: Children with inflammatory bowel disease (IBD) are at risk for osteoporosis because of undernutrition, delayed puberty, and prolonged corticosteroid use. The aim of this study was to compare bone mineral density (BMD) in children with IBD with that in normal children and to assess the effects of nutritional and hormonal factors and corticosteroid dosages on BMD. METHODS: One hundred sixty-two subjects (99 with IBD and 63 healthy sibling controls) were enrolled. Patients underwent anthropometric assessment, pubertal staging, bone age radiography, and BMD assessment by dual energy x-ray absorptiometry of the lumbar spine, femoral neck, and radius. Laboratory evaluations included serum calcium, phosphate, alkaline phosphatase, 25-hydroxyvitamin D, 1,25-dihydroxyvitamin D, parathyroid hormone, osteocalcin, urinary N-telopeptides, albumin, insulin-like growth factor I, and testosterone or estradiol. Cumulative corticosteroid doses were calculated. RESULTS: BMD Z scores at the lumbar spine and femoral neck were lower in patients with IBD, and lower in those with Crohn's disease compared with those with ulcerative colitis. Low BMD persisted after correction for bone age in girls with Crohn's disease (lumbar spine, P = 0.004; femoral neck, P = 0.002). Cumulative corticosteroid dose was a significant predictor of reduced BMD. BMD did not correlate with measures of calcium homeostasis, except elevated serum phosphate and urine calcium levels in girls. CONCLUSIONS: Low BMD occurs in children with IBD (more in Crohn's disease than in ulcerative colitis), especially pubertal and postpubertal girls. Cumulative corticosteroid dose is a predictor of low BMD, but other factors in Crohn's disease remain undetermined.

Adolescent↗

The new removable denture patient: treatment procedures.

Dentists are beginning to see a new type of patient who requires removable prosthodontic rehabilitation. These patients are the result of both increases in longevity and dental treatment that has retained teeth, despite the onslaught of caries and periodontal disease. The current procedures for transitioning patients into removable prostheses can be modified for this new group of patients. This article presents a transition procedure for patients who are receiving removable prostheses, which dissociates the surgical phase of treatment from the prosthetic stage. The patient's existing teeth are incorporated into a removable prosthesis in a way that ensures the exact replication of the tooth position in the oral cavity. This method addresses many of the inadequacies of current procedures while at the same time requiring a minimum of chair time. Even with this procedure, this transition is still difficult for the patient.

Dental Abutments↗

Validity of childhood disintegrative psychosis. General findings of a long-term follow-up study.

BACKGROUND: Empirical evidence for the validity of the diagnostic label disintegrative psychosis is sparse. The issue of whether it is a separate form of infantile autism is unresolved. METHOD: To investigate the validity of disintegrative psychosis as defined in ICD-9, the natural history of 13 cases were compared with 39 matched cases of infantile autism on various outcome variables. Average follow-up time was 22 (11-33) years. RESULTS: Statistically significant differences were found between the two groups in terms of number of admissions to non-psychiatric departments, occurrence of comorbid epilepsy, social style, and score on the Global Assessment of Functioning scale. In most other areas assessed there was a tendency, although statistically insignificant, towards a better outcome in the infantile autism comparison group. CONCLUSIONS: Our findings provide some support for maintaining a diagnostic category of disintegrative psychosis as distinct from infantile autism.

Activities of Daily Living↗

Response to challenge with gonadotropin-releasing hormone agonist in a mother and her two sons with a constitutively activating mutation of the luteinizing hormone receptor--a clinical research center study.

The pituitary-gonadal axis was evaluated in a mother after two of her sons with familial male-limited pseudoprecocious puberty were found to have a constitutively activating mutation of the LH receptor (LHR). Genotyping demonstrated that all showed a mutation in one of the two alleles, a substitution of Gly for Asp578 in the sixth transmembrane segment of the LHR. Ovarian function was normal in the 36-yr-old mother as assessed by LH dynamics and FSH and androgen levels throughout the menstrual cycle. Hormonal responses to acute GnRH agonist (nafarelin) challenge, chronic GnRH agonist administration, and dexamethasone were also normal. Studies of the boys upon presentation at 2.4 and 3.5 yr of age revealed that acute LH responses to nafarelin were in the hypogonadotropic range, and the FSH responses were prepubertal despite the presence of late pubertal testosterone blood levels. Upon the inception of true puberty at 11 yr of age in the older brother, gonadotropin responses normalized for the state of development. The data show that this activating LHR mutation does not cause functional ovarian hyperandrogenism and causes only incomplete pubertal activation of Leydig cells. The results are compatible with relatively low constitutive activity associated with this structural abnormality of LHR.

Adult↗

Season of birth in infantile autism and other types of childhood psychoses.

Season of birth in 328 children with infantile autism and other types of childhood psychoses born between 1945 and 1980 was compared with that of a control population born in the same period. For some parts of the period (the years 1951-56, 1963-68 and 1975-80 combined) an excess of March born boys with infantile autism was found. For boys with autistic-like disorders, born in the same period a maximum occurred in November, while no seasonality was observed for a borderline sample.

Adolescent↗

Neurofibromatosis in infantile autism and other types of childhood psychoses.

Recent findings have suggested that the simultaneous occurrence of neurofibromatosis and childhood psychosis might be more than a coincidence. In this study of 341 children with infantile autism and other types of childhood psychosis seen as inpatients in two university clinics of child psychiatry in a 25-year period, only one case (0.3%) of concomitant occurrence of the disorders was found, which is a frequency no higher than expected by chance.

Autistic Disorder↗

Effects of prostaglandins E1, E2, and F2 alpha on mucin secretion from human bronchi in vitro.

The effects of three prostaglandins on the output of 35S labelled mucus glycoproteins (mucins), from explants of human bronchial tissue suspended in Ussing chambers, have been investigated. Prostaglandin F2 alpha, added to the Krebs-Henseleit solution bathing both luminal and submucosal sides of the tissue, significantly increased mucin output at concentrations of 0.1 and 1.0 micrograms/ml (0.28 and 2.8 microM), 11 preparations being used for each dose. Since prostaglandin F2 alpha has been shown to be released from human airways challenged by antigen, it may be important in the regulation of mucus secretion in these circumstances. Prostaglandins E1 and E2 had no significant effects on mucin output even at the highest concentration (1.0 micrograms/ml), though in half the tissues tested PGE2 stimulated secretion consistently. These results contrast with the findings in a previous study, which showed an inhibition of mucin output by PGE2.

Alprostadil↗