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Biomedical subjects

W F Clark

Publications and source records attributed to W F Clark.

At least 55 records · Page 3Linked to original sources
PubMed1987

Calcium and the Fc receptor on human platelets.

We have described the calcium dependence of the IgG Fc receptor (Fc-R) on human platelets by analyzing the direct binding of radiolabelled Fc fragments, monomers and dimers of IgG. Specific binding to platelets was undetectable at 37 degrees C in a calcium-free preparation but readily detected when calcium was restored. Scatchard analysis of the binding data for the calcium-restored platelets permitted calculation of the available Fc-R and the Ka of binding for the different IgG ligands. The mean Ka of binding for 12 normal subjects varied from 10(7) to 10(8) L/M, with an equal receptor number measured by Fc fragments and dimers of IgG, but a lesser amount for monomeric IgG. There was no apparent difference in Fc-R number for platelets from 6 normal male versus 6 normal female subjects. At 4 degrees C binding was detectable for dimers and polymers of IgG in a calcium-free preparation and this was markedly increased with recalcification. Thus, our data are consistent with an Fc receptor population on human platelets whose avidity for binding is significantly enhanced in a calcium-restored medium.

Blood Platelets↗
PubMed1987

Multipurpose Senior Service Program Deinstitutionalization Screen.

The Multipurpose Senior Services Program Deinstitutionalization Screening Instrument has been designed to identify easily and quickly those patients in nursing homes who are likely to be returned to the community through case-management efforts. The six-item screen and tables allow the interviewer to determine the probability of a patient being successfully discharged from a nursing home.

Activities of Daily Living↗
PubMed1987

The effects of a thromboxane synthase inhibitor, a prostacyclin analog and PGE1 on the nephritis of the NZB/W F1 mouse.

One hundred NZB/W F1 female mice were studied to compare the effects of a thromboxane synthase inhibitor (TSI), a stable prostacyclin analog (iloprost) and prostaglandin E1 (PGE1) in the evolution of the nephritis. At 10 weeks of age mice were randomly assigned to cohorts of 20 to receive either no treatment, vehicle control, PGE1, iloprost or TSI. Proteinuria, mortality, systemic blood pressure, renal immune complex deposition, urinary TX B2 and 6 keto PGF1 alpha levels were measured. Mice receiving PGE1 and iloprost had a significant delay in the onset of proteinuria and reduction in mortality at 40 weeks. The TSI treatment had no apparent effect on proteinuria or mortality. The amelioration of the nephritis was not associated with an alteration in immune complex deposition in survivors at 40 weeks. Although PGE1 and iloprost lessened the age related increase in urinary TX B2, increased the urinary 6 keto PGF1 alpha levels and the ratio of 6 keto PGF1 alpha to TX B2; so did the TSI. The PGE1 treated mice did experience a marked and persistent reduction in blood pressure but this was not observed in the iloprost- or the TSI-treated mice. All drugs tested reduced the age-related increase in thromboxane B2 but only the PGE1 and iloprost had a significant effect on the evolution of the nephritis.

6-Ketoprostaglandin F1 alpha↗
PubMed1985

The comparative evaluation of California's multipurpose senior services project.

The Multipurpose Senior Services Project implemented a case management model of service coordination for aged Medicaid recipients at eight sites throughout California. The answers to the evaluation questions--"What works?", "For whom?", and "At what cost?" provide policy direction for long-term care programs. The research and demonstration Project ended in June 1983 and an on-going Program began in July 1983. Dynamic modeling of the outcomes of MSSP and of a comparison group served by the existing service system showed that MSSP increased longevity, decreased nursing home days, and decreased hospital days (in 1982); these results were most efficient for the frailest clients. This group had the greatest savings on public service dollars, with the Federal government the beneficiary through lower than expected Medicare expenditures. In-home supportive services proved to be the most productive non-medical service in both systems, but was more productive through MSSP. The evaluation methodology provides a multivariate frailty measure based on expected nursing home entry that can be used to identify those individuals for whom case management is most likely to have efficient outcomes.

Aged↗
PubMed1985

Gallium67 scintigraphy in the diagnosis of acute renal disease.

67Ga scintigraphy was performed in 44 patients with various biopsy proven forms of renal disease and in a further 64 patients, some with clinically diagnosed renal disease and some with non-renal disorders. Renal uptake of gallium at 48 hours was graded by two blinded observers and by tissue ratios determined by computer. All 11 patients with biopsy proven acute drug-induced interstitial nephritis demonstrated intense, diffuse, bilateral renal 67Ga uptake, a phenomenon observed in only five of the other 30 patients with biopsy proven renal disease and in four of the 64 patients with clinical diagnoses only. No patient with acute tubular necrosis demonstrated significant renal gallium uptake. It is suggested that 67Ga scintigraphy is an excellent screening test for the presence of acute interstitial nephritis and helps to identify which patients with unexplained acute renal failure require renal biopsy.

Acute Disease↗
PubMed1984

Plasma exchange in thrombotic thrombocytopenic purpura.

Three patients were recently treated for thrombotic thrombocytopenic purpura (TTP). One presented with toxic shock syndrome; TTP developed but promptly responded to a regimen of antiplatelet agents, steroids and plasma exchange. In another the manifestations of TTP developed after presentation with hypertension and abdominal pain. This patient responded to a similar regimen but required extended treatment before remission could be maintained with medications alone. In the third patient the full TTP syndrome appeared after several days of plasma exchange treatment for hemolyticuremic syndrome. He did not respond. It is suggested that TTP may present in many forms initially, that microangiopathic hemolysis may be a late manifestation and that the optimal therapy is not known.

Adult↗
PubMed1984

An ultrasensitive radioligand assay for IgG using the protein A on Staphylococcus aureus bacteria.

The purpose of this study was to develop a simple and sensitive assay to measure IgG. Human IgG was radiolabelled with 125Iodine and 7.5 ng was incubated with heat-killed Staphylococcus aureus bacteria (Cowan 1 strain). To replicate sets of tubes, increasing amounts of a standard IgG preparation were added. The samples were incubated at room temperature for two hours and separated by centrifugation. Using this assay it was found that the IgG concentration could readily be determined in one nanoliter or less of human serum. There was no significant cross-reactivity with IgA, IgE and IgM or the F(ab')2 fragment of IgG. Serial dilutions of normal human or SLE sera, rabbit or guinea pig sera, the Fc fragment of human IgG and a mouse monoclonal anti-human DNA antibody parallelled the dose response curve obtained with standard human IgG. The method correlated well (r=0.89) with a routinely used nephelometric method. The mean (+/- SD) IgG concentration in 20 normal subjects measured by this assay was 10 +/- 3.6 g/L.

Humans↗
PubMed1984

Successful treatment of dialysis osteomalacia and dementia, using desferrioxamine infusions and oral 1-alpha hydroxycholecalciferol.

A 54-year-old patient with fracturing dialysis osteomalacia and dementia demonstrated rapid deterioration following parathyroidectomy which was performed for sustained hypercalcemia. Reduction of the total body aluminum burden was attempted using desferrioxamine (DFO) as a chelating agent. After 6 months, DFO infusion resulted in sustained clinical remission of both neurological and skeletal symptoms, associated with an improvement in the EEG and improved mineralization of bone. A reduction in total body aluminum burden was reflected by reduced skeletal aluminum content, quantitated histochemically in iliac crest bone biopsies before and after DFO therapy. Dramatic increases in serum aluminum levels were documented in the initial weeks of DFO therapy leading to increased removal of aluminum during dialysis; in vitro studies indicated that the ultrafiltrable fraction of serum aluminum increased from 17 to more than 60% after initiating DFO treatment. However, after 6 months of therapy, serum aluminum levels remained unchanged after DFO infusion. These findings suggest that the serum aluminum response to DFO infusion might be a useful reflection of the total-body aluminum burden and also a reflection of the adequacy of a chelation program designed to reduce whole-body aluminum content.

Aluminum↗
PubMed1984

HLA antigens in systemic lupus erythematosus: relationship to disease severity, age at onset, and sex.

Sixty-two Caucasian patients with systemic lupus erythematosus (SLE) were studied to determine whether any significant clinical correlations existed with various HLA antigens. While HLA-B8 and DR3 were significantly increased among the SLE population in general, these or other HLA antigens did not correlate with the severity of renal disease. HLA-B8 was significantly higher only in SLE males compared to male controls. The age of onset of disease in females was clustered into 2 groups, one with early age of onset (mean = 21.6 years, range 12-32 years) and another with later age of onset (mean = 48 years; range 38-60 years). SLE females with later age of onset showed an increased frequency of HLA-DR3 compared to sex and age matched controls, while those with early onset SLE showed no significant increase in any HLA antigens. Therefore any risk conferred by the presence of genes associated with HLA-B8 or DR3 is significant only in SLE males and SLE females whose disease onset was over the age of 35. Despite the greater frequency of HLA-B8, DR3 in SLE females with later onset of disease, this group did not have a greater frequency of anti-Ro antibodies compared to females with early age onset of SLE.

Adolescent↗
PubMed1983

Chronic plasma exchange in systemic lupus erythematosus nephritis.

Thirty-nine patients with systemic lupus erythematosus (SLE) and diffuse proliferative glomerulonephritis have been enrolled in a multi-centre randomised controlled prospective study of chronic 4L plasma exchange therapy performed every three to four weeks. In the patients randomised to the pheresis (P) group and who received either albumin or plasma as replacement, there was a difference of 33 per cent better renal function at this time in the study. This difference did not achieve a significance with a p value of less than 0.05. However, the 30 patients randomised into the P group to receive albumin replacement did demonstrate a 50 per cent difference from the C group which was significant at a p value of less than 0.045. This also correlated with a statistically significant reduction in immune complex titres in the P versus the C groups. Chronic 4L plasma exchange with albumin replacement may be a useful therapeutic adjunct in patients with SLE and diffuse proliferative glomerulonephritis.

Adult↗
PubMed1983

The effect of alterations of uremic retention products upon platelet and peripheral nerve function.

Attempts at the identification of specific uremic toxins have, to date, been unrewarding and yet there is vogue for the measurement of, and the control by devices of hypothetical levels of, "middle molecular weight" toxins. In an attempt to elucidate whether small or middle molecular weight retention products are responsible for uremic platelet and peripheral nerve conduction defects, 14 patients with end-stage renal disease established on hemodialysis were studied using a conventional hemodialyzer and an experimental device which combined hemodialysis and hemoperfusion and which has enhanced in vitro vitamin B12 clearances. With the latter device reduced BUN and creatinine clearances were encountered and over a 2-month treatment period patient's serum BUN rose. In spite of this, there was improvement in the velocity of platelet aggregation to 10 microM adenosine diphosphate and to a standard collagen preparation associated with treatment by the experimental device. There was not, however, any demonstrable influence made on nerve conduction studies. The study suggests that different uremic retention products influence platelet and peripheral nerve function and that further efforts into studying the function of living cells or systems, in uremia might have better yield in the future guidance of the adequacy of dialysis than will the biochemical measurements of various waste products.

Humans↗
PubMed1982

Human platelet-immune complex interaction in plasma.

The plasmas of four patients with SLE were found to contain two anti-DNA antibody populations of widely varying affinity. The addition of double-stranded DNA to the anti-DNA plasmas resulted in formation of precipitating (insoluble) and soluble immune complexes. Human platelets suspended at physiologic concentrations in the anti-DNA plasmas during the immune complex formation underwent aggregation and release that correlated positively with precipitating (insoluble) immune complex formation but not with soluble complex formation. Preformed insoluble immune complexes induced platelet aggregation and release in a significant linear fashion, and release was inhibited by increasing concentrations of soluble immune complexes or Fc-fragments. The release reaction was completely inhibited by blocking the Fc-pieces of the preformed insoluble DNA-anti-DNA immune complexes. Soluble complexes of DNA-anti-DNA and A-anti-A at equimolar IgG concentrations produced similar degrees of inhibition, which were much greater than equimolar concentrations of Fc-fragments. The ability of increasing concentrations of soluble immune complex formed at fixed antibody concentration to cause greater inhibition of platelet release suggests that occupancy of the antigen binding sites of the antibody increases its ability to block the platelet Fc-receptor. The inhibition is similar for soluble complexes of varying antigen molecular size. This is compatible with the concept that a conformational change in the antibody occurs after antigen binding and results in an increase in binding strength at the platelet Fc-receptor site. We conclude that insoluble DNA-anti-DNA immune complexes induce aggregation and release of human platelets at physiologic concentrations in plasma via the platelet Fc-receptor.

Antibodies, Antinuclear↗
PubMed1981

Monthly plasmapheresis for systemic lupus erythematosus with diffuse proliferative glomerulonephritis: a pilot study.

Twelve patients with systemic lupus erythematosus and biopsy-proved diffuse proliferative glomerulonephritis were randomly allocated to a control group (to continue receiving conventional therapy only) or to a plasmapheresis group (to receive conventional therapy along with one 4-I plasma exchange a month). The six patients treated with plasmapheresis had better preservation of renal function, reduced disease activity, fewer admissions to hospital and less need for steroid and immunosuppressive therapy than the six control patients. The patients treated with plasmapheresis also showed evidence of reduced immunologic activity and had no side effects attributable to the plasma exchange. These results suggest that monthly plasma exchange should be assessed in a controlled randomized trial as a possible therapeutic adjunct in patients with systemic lupus erythematosus and diffuse proliferative glomerulonephritis.

Creatinine↗
PubMed1981

Chronic plasma exchange therapy in SLE nephritis.

Eight patients who met the clinical, immunological and renal morphologic criteria for systemic lupus erythematosus with diffuse proliferative nephritis were plasma exchanged on a monthly basis for a total of 119 months. Renal function, episodes of disease activity, hospitalizations, frequency of immunological abnormalities, and monthly quantity of steroid and azathioprine therapy were compared with their course up to one year prior to the onset of the plasma exchange program. The changes noted in these parameters indicate that chronic plasma exchange therapy is safe, may be beneficial and requires controlled prospective study to determine the role in the treatment of patients with systemic lupus erythematosus and diffuse proliferative glomerulonephritis.

Azathioprine↗