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Biomedical subjects

S Orloff

Publications and source records attributed to S Orloff.

At least 19 recordsLinked to original sources

Long-term sequelae of pelvis irradiation: histological and microradiographical study of a femoral head.

Despite the lack of radiological signs, a femoral head showed histological and microradiographical features of osteonecrosis, 54 years after massive irradiation of the right hip. Intertrabecular spaces were invaded by connectivo-vascular tissue with focal accumulation of mast cells, and several resorption foci were filled with mononucleated cells. Moreover, all the microradiographs showed peculiar hypercalcified lines, sometimes containing empty osteocytic lacunae, the origin of which is difficult to precise. This study suggests that massive irradiation of weight-bearing epiphyses may be responsible for particularly long-term hypovascularity, osteonecrosis and disturbed bone remodeling.

Female

Analysis of synergism/antagonism between HIV-1 antibody-positive human sera and soluble CD4 in blocking HIV-1 binding and infectivity.

We tested human immunodeficiency virus type 1 (HIV-1) antibody-positive human sera and sCD4, alone and in combination, for synergistic, additive, or antagonistic effects on blocking of HIV binding and infectivity. Data were analyzed by an application of the median effect principle derived from the law of mass action. This allows the assessment of synergism/antagonism at any desired level of effect. Using three assays (whole virus binding to CD4 cells, neutralization of HIV infectivity, and binding of purified gp120 to solid-phase sCD4), we generally observed additive effects or slight synergism between antibody and sCD4 in inhibiting gp120-CD4 interaction. We used a fourth assay to measure the irreversible inactivation of HIV infectivity by sCD4, a property that can also be mediated by antibody but with considerably less potency than sCD4. The reduction in HIV infectivity mediated by mixtures of sCD4 and antibody was always equal to or greater than the arithmetic sum of the reductions by either agent alone. The relevant antiviral effects of sCD4 and anti-HIV sera may include reversible blockage of receptor binding, irreversible inactivation of HIV infectivity, and in the case of antibody, additional reactions that are independent of receptor binding. Although predictions concerning the in vivo situation are speculative, we find no evidence in vitro for antagonism between sCD4 and antibody with respect to the net effect of the two in blocking HIV binding and infectivity.

Binding, Competitive

Bilateral non-traumatic aseptic osteonecrosis in the femoral head. An experimental study of incidence.

Thirty-five patients who were seen with non-traumatic aseptic osteonecrosis of the femoral head were included in a study of the contralateral hip to evaluate the incidence of bilateral disease. We used not only conventional radiography and scintigraphy but also measurement of intramedullary pressure and core biopsy. Pain was caused by 14.3 per cent of the contralateral hips, a lesion was demonstrated on plain radiographs in 51.4 per cent, and increased isotopic uptake was seen in 31.4 per cent. Histological study of specimens obtained by osteomedullary biopsy (after special procedure) showed bilateral necrosis in 88.5 per cent of the patients. After a mean follow-up of thirty-four months, only one of nine hips that were painless and had negative radiographic and isotopic findings, but had positive findings on biopsy, became painful and radiographically positive. The intramedullary pressure in the intertrochanteric area was recorded in each hip, and no correlation was found with the radiographic stage or with pain.

Adult

Relationship of cell growth to collagen synthesis in glucocorticoid treated A/J and C57BL6/J neonatal mouse dermal fibroblasts.

Primary cultures of neonatal dermal fibroblasts from two strains of mice (A/J and C57BL6/J) were utilized as an in vitro system to investigate the effects of glucocorticoids on cell growth and collagen synthesis. Protein and DNA synthesis were lower in untreated (control) A/J fibroblasts than in C57BL6/J fibroblasts. Treatment with glucocorticoids for 4 days resulted in dose-dependent inhibition of [3H]thymidine incorporation into DNA and a reduction in collagen synthesis. Collagen synthesis was differentially more susceptible to glucocorticoids than was total protein synthesis. Neonatal dermal fibroblasts obtained from A/J mice were more sensitive to glucocorticoids than were cells from C57BL6/J mice. Reduction in collagen production by anti-inflammatory steroids in this system may be related to adverse effects observed in vivo following treatment with these steroids.

Animals

Gonococcal arthritis-dermatitis syndrome. Study of serum and synovial fluid immune complex levels.

Immune complexes from serum and synovial fluid were detected by the C1q binding assay in 12 patients with disseminated gonococcal infection. Since immune complexes were regularly higher in synovial fluids than in paired sera and were not detected by the monoclonal rheumatoid factor radioimmunoassay, we suggest that IgM may be present in these complexes and that this represents a primary immune response. In contrast, only 2 of 10 patients with local gonococcal infection were slightly positive both with the C1q assay and the monoclonal rheumatoid factor assay. In patients with disseminated gonococcal infection, immune complexes closely paralleled the disease activity and negatively correlated with complement levels. Synovial fluid immune complexes seem to occur in the early and aseptic phase of polyarthritis and to aid the entrance of circulating gonococcal organisms. From the results of our study, it seems that immunologic processes initiate and/or sustain inflammation in disseminated gonococcal infections that appear, at least in part, as a form of reactive arthritis.

Adolescent

Synovial fluid beta 2 microglobulin and hydroxyproline fractions in rheumatoid arthritis and nonautoimmune arthropathies.

Fourteen patients with classical and definite seropositive rheumatoid arthritis (RA), 5 patients with microcrystalline arthritis, and 7 patients with osteoarthrosis were studied with respect to markers of newly synthesised collagen (synovial NDOH pro levels); markers of connective tissue resorption (synovial DOH pro and NBH levels); markers of lymphoid tissue activity (synovial and plasma beta 2m levels). Higher amounts of NDOH pro in RA synovial fluid are compatible with the hypothesis of a local connective tissue production as suggested by Uitto et al. on basis of a higher protocollagen proline hydroxylase activity in RA synovial tissue. DOH pro and NBH do not differ significantly in synovial fluid from RA or gouty patients, but the correlations between these forms of OH pro and, respectively, synovial lymphocytes and polymorphonuclear leucocytes are indicative of different processes of connective tissue remodelling in the 2 conditions. Synovial beta 2m levels are a direct function of total synovial lymphocyte counts independently of the type of arthropathy being explored. The ratio of synovial to plasma beta 2m is systematically above unity in RA patients only.

Arthritis, Rheumatoid

Pituitary resistance to thyroid hormone in cystinosis.

Eleven children with nephropathic cystinosis without clinical features of hyperthyroidism or hypothyroidism had elevated serum levels of immunoreactive TSH. The mean TSH level (+/- SE) was 37.4 +/- 12.3 microM/ml. Serial determinations of thyroid function during 1 yr were: mean (+/- SE) serum T4, 10.8 +/- 0.7 microgram/dl; free T4, 2.1 +/- 0.2 ng/dl; and T3, 239 +/- 6 ng/dl. After 500 microgram TRH iv, the peak TSH level exceeded 100 microU/ml in 6 of 10 patients, whereas T3 responses were variable. Studies of parameters influenced by thyroid hormone, including red cell sodium content, serum cholesterol, and 24-h urinary hydroxylysine excretion, were consistent with euthyroidism. On the other hand, the mean pulse wave arrival time was significantly reduced, consistent with hyperthyroidism. Three control patients, 2 with Lowe's syndrome and 1 with benign cystinosis, had normal thyroid studies. Eight of the patients were given either exogenous L-T4 or T3 in doses which were increased at weekly intervals. The serum TSH concentrations were suppressed to normal only after elevation of serum levels of thyroid hormones and with high exogenous thyroid replacement doses. The data suggest abnormal pituitary resistance to feedback by thyroid hormone in patients with cystinosis. We believe this to be the first description of the association of a heritable metabolic disease with such pituitary resistance.

Child

Ineffectiveness of ascorbic acid therapy in nephropathic cystinosis.

Because high concentrations of ascorbic acid (0.57 mM) lower the free (nonprotein) cystine content of cultured cystinotic skin fibroblasts by over 50 per cent, we did a double-blind clinical trial to establish whether this drug would benefit cystinotic children. Sixty-four patients were randomized into the study; 32 received ascorbic acid (200 mg per kilogram of body weight per day), and 32 placebo. The study was terminated after approximately two years because there was no indication that vitamin C was beneficial and accumulating evidence that it might be harmful. Of 11 patients who left the study because of death or the requirement for dialysis or renal transplantation, eight were receiving ascorbic acid. The estimated relative risk (treatment vs. control) of an adverse event was R = 2.7, with a 90 per cent confidence interval of (0.8, 11.5). The serum creatinine concentration increased 0.53 mg per deciliter per year in patients receiving vitamin C and 0.24 mg per deciliter per year in patients receiving placebo (P = 0.08).

Ascorbic Acid

Intrauterine growth retardation in renal insufficiency: an experimental model in the rat.

Experiments described here with partially nephrectomized pregnant rats with pair-fed controls and controls fed at will indicate that decreased maternal food intake is a major factor in the intrauterine growth retardation associated with moderate renal insufficiency during the last trimester of gestation. Although renal disease in human pregnancy is often associated with vascular insufficiency, the possibility that maternal undernutrition may also play a contributory role in the fetal growth failure associated with certain cases of human renal compromise merits further study.

Animals

A comparison of essential and general amino acid infusions in protein-depleted patients receiving parenteral alimentation.

Six malnourished patients were studied during intravenous nutrition therapy to compare the efficiency of essential and general amino acids when given as the sole nitrogen source during intravenous nitrogen therapy. A cross-over design was used so that each patient received both essential amino acids plus arginine and histidine and a general amino acid solution in random order. Glucose provided the remainder of the energy and both infusions contained 2 g of amino acid per 100 kcal. Each patient's daily urea nitrogen production was greater during infusion of the general amino acid solution. Consequently, nitrogen intake minus urea nitrogen production was significantly greater when the essential amino acid solution was infused. Plasma amino acid levels were determined on each patient during both essential and general amino acid infusion. Abnormalities tend to reflect the composition of the amino acid solutions as well as their administration directly into the systemic circulation bypassing the portal circulation.

Adult

Placental transfer of analogs of glucose and amino acids in experimental intrauterine growth retardation.

We have employed the model in which one uterine artery is ligated to study maternofetal transport and tissue uptake of glucose and amino acids in the intrauterine growth-retarded rat. On the 18th day of gestation, the artery supplying one uterine horn was ligated. Two days later the rats received [3H]2-deoxyglucose and [14C]alpha-aminoisobutyric acid iv. One hour later the growth-retarded and control fetuses were delivered by Cesarean section and appropriate blood samples were obtained. The growth-retarded fetuses had an average weight reduction of 27%, significantly increased placental to fetal weight ratio and brain to body ratio, and a significantly reduced liver to body body ratio. Total radioactivity derived from tritiated deoxyglucose in whole fetal tissues, placenta, liver, and brain were significantly decreased in the intrauterine growth-retarded (IUGR) fetuses; this was also true per gram of tissue except for liver. Liver to plasma, brain to plasma, and whole fetal tissue to plasma 3H ratios were significantly increased in the IUGR group. The radioactivity derived from [14C]alpha-aminoisobutyric acid was significantly reduced in whole fetal tissues, placenta, liver, and brain in the IUGR fetuses whether expressed per whole organ or per gram of tissue. Significant differences in liver to plasma, brain to plasma, and whole tissue to plasma 14C ratios were not observed.

Aminoisobutyric Acids

Synovial fluid and serum hydroxyproline fractions in rheumatoid arthritis.

In rheumatoid arthritis (RA) the synovial fluid lymphocyte count closely parallels the synovial fluid dialysable hydroxyproline, a marker of collagen resorption. This observation stresses the primordial role of lymphocytes in RA joint injury. The actual and eventually potential destruction of any single joint, as expressed by synovial fluid dialysable hydroxyproline levels, seems to reflect the general picture of disease activity as evaluated by the number of active joints (joint count), ESR and rheumatoid factor titres (latex fixation). Although urinary hydroxyproline levels are generally within the normal range in RA, they can be used as index of articular tissue destruction and as a parameter of overall disease activity when groups of patients are studied longitudinally in detail. The present study sheds no further light on the significance of synovial fluid and blood non-dialysable hydroxyproline levels.

Arthritis, Rheumatoid

Serum and synovial fluid hydroxyproline fractions in microcrystalline arthritis and osteoarthritis.

Synovial fluid and serum hydroxyproline fractions were investigated in patients with osteoarthritis and microcrystalline arthritis. Synovial fluid dialysable hydroxyproline levels are higher than serum levels in both conditions. Synovial fluid total and dialysable hydroxyproline are higher in microcrystalline arthritis than in osteoarthritis, while non-dialysable hydroxyproline values are similar in both conditions. In microcrystalline arthritis, synovial fluid dialysable hydroxyproline and polymorphonuclear leukocyte counts closely parallel each other. Irrespective of the type of arthropathy, synovial fluid dialysable hydroxyproline levels correlate with urinary hydroxyproline excretion. While the data suggest overproduction of dialysable hydroxyproline by joints in both conditions, the overproduction appears to be mediated by polymorphonuclear leukocytes in microcrystalline arthritis only. The ratio of serum to synovial total hydroxyproline are further suggestive of a possible differentiation between osteoarthritis and microcrystalline arthritis. In the conditions governing the present study, urinary hydroxyproline may be used as an index of joint tissue collagen resorption. Finally the significance of synovial fluid and serum non-dialysable hydroxyproline is discussed.

Chondrocalcinosis