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Biomedical subjects

E C Keystone

Publications and source records attributed to E C Keystone.

At least 55 records · Page 3Linked to original sources

Nifedipine in the treatment of idiopathic Raynaud's syndrome.

Thirty-nine patients with idiopathic Raynaud's syndrome were randomized into a double-blind controlled trial comparing nifedipine 10 mg TID to placebo during the winter months between November, 1981 and March, 1983. The pills were doubled at 5 weeks in the absence of subjective improvement. Frequency and severity of vasospastic attacks were recorded in a diary. Over the 10-week treatment period, there was a 48.2% reduction in frequency of attacks in the nifedipine group compared to a 24.6% reduction in the placebo group (p less than 0.05). Treatment reduced the frequency of attacks by at least 30% in 10 of 15 patients. The severity of attacks was also significantly improved. Further, analysis suggests a trend towards diminished effectiveness over time. Side effects occurred in all patients taking nifedipine but were usually mild and well tolerated. Nifedipine is effective in reducing the frequency and severity of vasospastic attacks in idiopathic Raynaud's syndrome over a 10-week period.

Adult

Digital blood flow and nailfold capillary microscopy in Raynaud's phenomenon.

Digital blood flow was assessed by photoplethysmography, ultrasonic arterial flow tracing and measurement of systolic blood pressure, and compared to nailfold capillary microscopy in 20 normal controls, 16 patients with primary Raynaud's phenomenon, 40 with undifferentiated connective tissue disease and 30 with systemic sclerosis. All 4 measurements showed significant differences between controls, Raynaud's phenomenon and systemic sclerosis but only capillaroscopy (mean number of enlarged capillary loops and avascular score) was able to differentiate between primary Raynauds and undifferentiated connective tissue disease. Capillaroscopy (mean numbers of enlarged capillary loops) was the most sensitive (100%) and specific (81%) test with a positive predictive value of 90% for systemic sclerosis.

Adult

Impaired release of a T-cell specific suppressor factor in rheumatoid arthritis.

Peripheral blood T cells from patients with rheumatoid arthritis (RA) and scleroderma (PSS) were assessed for their ability to release T-cell-specific suppressor activity (TRSA) upon incubation with a suppressor activating factor (SAF) derived from a human lymphoblastoid cell line (CEM). T cells from 11/20 (55%) RA patients exhibited impaired TRSA release in contrast to 1/12 (8%) of PSS patients. RA patients demonstrating impaired TRSA release exhibited more active arthritis than patients demonstrating normal TRSA release.

Adult

Invasive aspergillosis in a "healthy" patient.

A case of invasive aspergillosis complicated by the formation of an aspergilloma is described. The patient, a 48-year-old man, was apparently healthy except for mild alcoholic steatosis of the liver. A review of the literature revealed that 5 of the 14 previously reported cases of invasive aspergillosis in seemingly immunocompetent hosts were associated with liver disease. Immunologic investigation in this case revealed transient cutaneous anergy during the acute illness and normal lymphocyte function. Assessment of polymorphonuclear leukocyte function, however, showed abnormalities of phagocytosis as well as impairment of intracellular bactericidal activity. These abnormalities may have contributed to a relative immunodeficiency. Impairment of immune function may play a role in the pathogenesis of invasive aspergillosis in some apparently healthy patients.

Acquired Immunodeficiency Syndrome

Interleukin abnormalities in recently active rheumatoid arthritis.

Peripheral blood lymphocytes (PBL) from 14 patients with rheumatoid arthritis (RA) produced increased amounts of interleukin (IL) (p less than 0.05) as measured in a mouse thymocyte assay and showed enhanced proliferation in response to an IL containing supernatant (p less than 0.05) when compared with 9 age matched controls. Both enhanced IL production (p greater than 0.01) and responsiveness (p less than 0.002) were seen exclusively in a subgroup of 7 patients with a recent onset or exacerbation of their disease. PBL from RA patients with equally active disease which had been unchanged for more than 6 months produced and responded to IL normally. There was a direct correlation between IL production and responsiveness (r = 0.69, p less than 0.005). These 2 distinct IL abnormalities appear to reflect disease initiating or exacerbating factors in RA.

Arthritis, Rheumatoid

Aberrations in T-cell subpopulations in patients with psoriasis and psoriatic arthritis.

Peripheral blood T-cell subpopulations and B-cell numbers from 25 patients with uncomplicated psoriasis and 22 patients with psoriatic arthritis were compared with those of 24 age- and sex-matched healthy volunteers and 11 patients with radiologically defined erosive osteoarthritis. The numbers of early and late rosettes were found to be reduced in patients with psoriasis, with and without arthritis, while the total T-cell population (measured by aminoethylthiouronium bromide-rosettes) was found to be normal. There was no difference in the number of B cells between psoriatic patients and controls. Dose-response studies of mitogen stimulation with phytohemagglutinin and concanavalin A revealed generally higher proliferative responses in the psoriatic patients only at supraoptimal concentrations. The pokeweed mitogen response, however, was reduced in patients with cutaneous psoriasis and increased in patients with psoriatic arthritis. These studies further support the concept of an immunologic imbalance in lymphocyte populations from patients with psoriasis and psoriatic arthritis.

Adult

Evidence for activated peripheral blood T-cells in rheumatoid arthritis.

We have previously demonstrated defective antigen specific T-suppressor (Ts) cell function in the peripheral blood lymphocytes (PBL) from patients with rheumatoid arthritis (RA). Our study was designed to delineate whether diminished Ts activity is due to impaired interleukin (IL) dependent clonal expansion of Ts cells or to prior in vivo activation. Patients with recent onset of RA, or a disease flare, exhibited enhanced IL generation (IL-1 and /or IL-2). Increased proportions of active E-rosettes, elevated spontaneous production of IgM, and total immunoglobulin in mitogen free cultures were consistent with the concept of prior lymphocyte activation in vivo. Our results do not support defective clonal expansion of Ts cells as the basis of deficient IL generation, but do support the concept of in vivo activation of PBM cells in some patients with RA.

Adult

Spinal entheseal new bone formation: the early changes of spinal diffuse idiopathic skeletal hyperostosis.

Diffuse idiopathic skeletal hyperostosis is characterized by new bone growth at the point of insertion of ligaments and tendons to bone. We examined retrospectively the anatomical morphologic changes discernible at the insertion of spinal longitudinal ligamentous fibrous tissue to vertebral bodies. The earliest evidence of bone formation was in the "waist" of the vertebral body away from the intervertebral disc area. New bone arose along the insertion of the fibrous tissue to the anterior cortical surface of the vertebral body and progressed along the fibres at an angle to the cortical surface distinct from it until the advanced stages. With disc degeneration the 2 processes were distinct and separate. Degenerative disc disease occurred at the margin of the endplate of the vertebral body with associated changes in the disc itself. Entheseal ossification occurred remote from the margin of the intervertebral disc and remained distinct from the subjacent vertebral body as it followed the ligamentous tissue; fusion with the cortical surface of the subjacent vertebral body was only seen in the most advanced cases of disseminated idiopathic systemic hyperostosis.

Adult

Lymphomatoid granulomatosis involving the gastrointestinal tract. Two case reports and a review of the literature.

Two cases of lymphomatoid granulomatosis affecting the gastrointestinal tract in the form of gastric ulceration and intestinal perforation are described. This rare presentation of lymphomatoid granulomatosis is discussed in the context of previous reviews of the disease, and it is suggested that clinically overt gastrointestinal involvement represents a very poor prognostic indicator in this condition.

Adult

Lymphocytotoxic and phagocytotoxic activity in progressive systemic sclerosis.

Sera of 66 patients with progressive systemic sclerosis (PSS) were tested for cold and warm reacting lymphocytotoxins (LCT). Cold LCT were found in 30 (45%) patients, 18 of whom also had warm LCT. Warm LCT alone were found in 14 patients. Twenty-nine sera with cold LCT were tested and reacted with both peripheral B and T lymphocytes. There was predominant killing of B cells in 52% and of T cells in 14%. Ten cold LCT were absorbed to and eluted from peripheral blood lymphocytes. All eluates were cytotoxic to B and T cells; 1 killed predominantly T cells and 2 killed predominantly B cells. Clinical-laboratory and HLA correlations with cold LCT showed no significant differences between the LCT-positive group and the LCT-negative group. Granulocytotoxins were rare in PSS, but warm reacting monocytotoxins were found in 33 cases (57%). Crossreactivity of cytotoxins was tested using eluates from various cells. The majority of eluates from lymphocytes were cytotoxic against polymorphonuclears (PMN) and monocytes. Some eluates from PMN and from monocytes had lymphocytotoxic activity. This suggests existence of common antigenic determinants on various cells against which cytotoxins are directed.

Antibodies

Steady-state plasma levels of salicylate in patients with rheumatoid arthritis: effects of dosing interval and tablet strength.

Forty patients who were admitted to hospital with rheumatoid arthritis received a total of 3.9 g/d of enteric-coated acetylsalicylic acid (ASA) (Entrophen) according to one of four dosing schedules: group 1 (n = 13), three 325-mg tablets four times daily; group 2 (n = 11), two 650-mg tablets three times daily; group 3 (n = 10), three 650-mg tablets twice daily; and group 4 (n = 6), two 975-mg tablets twice daily. Five to seven days after the start of therapy, when steady-state plasma salicylate levels had been achieved, 10 blood samples, 1 per hour, were collected. Three healthy volunteers who received plain ASA formed a control group. There was little fluctuation in the salicylate levels over the sampling period, regardless of the dosing interval, and no significant difference in the fluctuations between the five groups. Likewise, there was no significant difference in the mean salicylate levels at each sampling time, regardless of the dosing interval or tablet strength. These results suggest that different tablet strengths of enteric-coated ASA and different dosing intervals produce comparable plasma salicylate levels. Less frequent dosing may improve patient acceptance of salicylate therapy in the treatment of arthritis.

Adult

The articular manifestations of progressive systemic sclerosis (scleroderma).

The articular manifestations of progressive systemic sclerosis (PSS) were studied in 38 patients. Of these, 66% experienced joint pain and 61% had signs of joint inflammation. Limitation of joint movement was seen in 45%. Radiological abnormalities included periarticular osteoporosis (42%), joint space narrowing (34%), and erosions (40%). Erosive disease did not correlate with disease duration, presence of rheumatoid factor, antinuclear antibodies, distal tuft resorption, or the extent of the scleroderma skin changes. Calcinosis was seen more frequently in those patients with articular erosions (67%). Erosive osteoarthritis of the distal interphalangeal joints (7 patients) was associated with impaired finger flexion. Joint involvement in PSS occurs frequently and may resemble rheumatoid arthritis in the early stages but is less destructive. The occurrence of unrelated arthropathy, such as primary osteoarthritis, is not uncommon, and its differentiation from true PSS joint disease can be difficult.

Adolescent

Immunoregulatory T cell subpopulations in patients with scleroderma using monoclonal antibodies.

Twenty-eight patients with scleroderma were compared with 22 healthy age-matched subjects. Monoclonal antibodies were used to detect the whole T cell population (OKT3), T helper cells (OKT4), and T suppressor/cytotoxic cells (OKT8) by indirect immunofluorescence on isolated peripheral blood mononuclear cells. A subset of scleroderma patients (i.e. 30% or eight of 28 patients) exhibited an elevated ratio of OKT4/OKT8 cells which could be accounted for, mainly by a reduction in OKT8 cells compared with controls. The scleroderma patients with an elevated OKT4/OKT8 ratio tended to be younger, have a shorter disease duration and more extensive skin involvement than patients with a normal OKT4/OKT8 ratio. There was no correlation with the presence of autoantibodies, drug therapy, or HLA-DR type. In order to further determine whether this imbalance in immunoregulatory cell subpopulations was specific for scleroderma, we further studied 16 patients with psoriatic arthritis but without manifest autoimmunity and delineated a similar subset of patients with an elevated OKT4/OKT8 cell ratio (i.e. 38% or six of 16 patients). The results demonstrate similar immunoregulatory T cell imbalances in patients with scleroderma and psoriatic arthritis. These findings suggest that numerical imbalances in lymphocyte subpopulations may not be specific for autoimmune disorders.

Adolescent

Role of antibody in the protection of mice from arthritis induced by Mycoplasma pulmonis.

C3H and C57Bl10 mice exhibit a differential susceptibility to arthritis induced by Mycoplasma pulmonis. Resistant C57Bl10 mice consistently demonstrated higher complement-fixing antibody titres than susceptible C3H mice throughout the development of the acute arthritis. A strong correlation was demonstrated between the levels of anti-mycoplasma antibody and resistance to acute arthritis in six strains of mice. To test the hypothesis that the difference of arthritis resistance of C3H and C57Bl10 mice was caused by a different susceptibility of their lymphocytes to mitogenic stimulation by M. pulmonis, we investigated the generation of non-specific immunoglobulin in vivo and in vitro. M. pulmonis acted as a polyclonal mitogen, but stimulated approximately equal responses in lymphocytes of both strains.

Animals

Intra-arterial alprostadil for nonatherosclerotic vasculopathy.

A 33-year-old man with a nonatherosclerotic vasculopathy of undetermined origin had progressive occlusive disease of the lower limb vessels. The resultant severe rest pain and ischemic ulceration of his foot were inoperable and unresponsive to conventional drug therapy. Treatment was begun with intra-arterially administered alprostadil (prostaglandin E1), a vasodilator and inhibitor of platelet aggregation. Although immediate benefit was equivocal, his rest pain had disappeared six weeks after infusion, and the ischemic ulcer almost healed completely. Blood flow studies showed increased flow to the feet, consistent with the subjective improvement. The beneficial effect of alprostadil suggests that further studies with this agent are warranted for patients with nonatherosclerotic vasculopathy.

Adult