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Biomedical subjects

P Halberg

Publications and source records attributed to P Halberg.

At least 55 records · Page 3Linked to original sources

[Systemic lupus erythematosus. 1. Disease manifestations, infections, thrombotic episodes, causes of death and survival in a case load of 173 patients followed for 13.9 years].

One hundred and seventy-three patients had systemic lupus erythematosus according to the 1982-ARA-criteria. The mean disease duration at the time of the study was 16.4 years, and the patients were followed by three Copenhagen clinics for a mean of 13.9 years until 1987/88 or death. Half of the patients had nephropathy, 61 patients developed severe infections, and 39 patients had thrombotic episodes. Fifty-six patients died during the observation period, 24 due to active lupus (12 of kidney failure), 12 because of infections, and 11 because of atherosclerotic cardio-vascular disease. The patients had 10-, 15- and 20-year survival rates of 80, 65 and 48 per cent. The deaths were evenly distributed throughout the observation period.

Adult↗

[Systemic lupus erythematosus. 2. Factors of predictive significance for survival].

Sixty-one of 173 patients with systemic lupus erythematosus followed for a mean of 13.9 years had severe infections which influenced their survival more than could be accounted for by the mortality (20 per cent) caused by the infections. Patients with infections had more SLE manifestations than patients without infections, and they died of lupus manifestations more often than patients without infections. Patients who went into a permanent remission and patients who died of lupus differed most markedly by the rates of infection. The rate of infection was increased more than tenfold in patients treated with high dosages of glucocorticoid compared with patients who received low dosages. Treatment with cytostatics influenced the rate of infections to a moderate degree. Nephropathy also influenced survival but half of the patients with nephropathy maintained a normal plasma creatinine in spite of the long observation period. 16 per cent of the patients with nephropathy died of kidney failure or are receiving chronic hemodialysis.

Adult↗

Sjögren's syndrome in patients with multiple sclerosis.

Twenty female patients with clinically multiple sclerosis were evaluated with regard to a possible underlying Sjögren syndrome. Two patients (10%) demonstrated a clinical Sjögren syndrome which does not differ significantly from the prevalence in an unselected population. Dry eye-symptoms occurred among MS-patients and should be subjected to relevant diagnostic procedures.

Adult↗

Autoantibodies to lamins A and C in sera of patients showing peripheral fluorescent antinuclear antibody pattern on HEP-2 cells.

Lamins A, B, and C are the major proteins of a polymeric structure called nuclear lamina, which is intercalated between chromatin and the inner membrane of the nuclear envelope. Using immunofluorescence on HEp-2 cells, specific enzyme-linked immunosorbent assay, and Western blotting performed against nuclear lamina preparation from Ehrlich ascites tumor cells, we characterized three patients, whose sera contained antibodies to nuclear lamins. The reaction pattern observed in two of the patients may result from single or combined occurrence of anti-lamin A and C antibodies. The third patient had antibodies that probably recognized an epitope in the carboxy-terminal region of lamin C. The sera were donated by a heterogeneous group of patients, and no common clinical or laboratory signs seemed to link them together.

Adult↗

[Systemic lupus erythematosus and pregnancy].

The literature about pregnancies in patients with systemic lupus erythematosus (SLE) was reviewed. Information about 1,164 pregnancies was compiled. Fifty-four per cent of the pregnancies were normal, 15 per cent of the babies were premature, and 29 per cent of the pregnancies resulted in fetal wastage. In a background population of 50,000 women the corresponding figures were 80, 4 and 16 per cent, respectively. The neonatal mortality of babies borne by women with SLE was 2 per cent. About one third of the patients had an exacerbation of their disease, mostly post-partum or during the last trimester of the pregnancy. The risk of a exacerbation for patients with active disease at the time of conception was double that of patients with inactive disease. Therapeutic abortions were followed by improvement as well as deterioration of the disease. Two per cent of the patients died during pregnancy or post-partum. Cardiolipin-antibody may be a marker of fetal wastage and Ro-antibody may be a marker of fetal heart block in babies borne by women with SLE. Pregnancy was previously considered inadvisable in all patients with SLE. During recent years, the attitude to this problem has been less rigid. However the patients should be fully informed about the risk of exacerbation, fetal wastage, and premature delivery and patients with active disease should be advised to postpone pregnancy until a remission has been achieved.

Female↗

Scintimetric assessment of synovitis activity during treatment with disease modifying antirheumatic drugs.

In a double blind trial of 36 patients with rheumatoid arthritis a new scintimetric method was applied to three comparable patient groups before and after eight months' treatment with levamisole, penicillamine, or azathioprine. Technetium-99m pyrophosphate scintigraphy of both hands was performed on a gammacamera with a computer attached, immediately after the administration of the tracer. The uptake ratio of each proximal interphalangeal (PIP) joint and the mid-half of the adjacent proximal phalanx was calculated from the activity counted for one minute. A scintimetric index was expressed as the sum of eight uptake ratios. This index was higher for each of the three patient groups before start of treatment than that for 10 age matched controls. After eight months of treatment the index, the number of PIP joints with clinical signs of synovitis, and the total circumference of the PIP joints decreased in the penicillamine and azathioprine groups. The scintimetric method reliably reflected local synovitis activity and its changes but, like grip strength and PIP circumference, was not a representative measure of the overall activity of the disease.

Adult↗

Serum amino terminal type III procollagen peptide and serum hyaluronan in rheumatoid arthritis: relation to clinical and serological parameters of inflammation during 8 and 24 months' treatment with levamisole, penicillamine, or azathioprine.

Increased serum levels of the amino terminal type III procollagen peptide and serum hyaluronan were demonstrated in patients with rheumatoid arthritis. In patients with active disease a significant correlation was shown between serum levels of the propeptide and hyaluronan and the clinical signs of synovitis reflecting the extent of synovial inflammation. During recovery the serum propeptide and serum hyaluronan showed a delayed decline as compared with the clinical signs of synovitis and the acute phase protein response. This probably reflects the presence of persistent subclinical chronic inflammation. Normal serum propeptide levels in rheumatoid arthritis were associated with a good prognosis without progression of erosive joint lesions. Azathioprine reduced the number of patients with progression of erosive joint lesions and caused a more marked suppression of the serum propeptide than levamisole and penicillamine.

Adult↗

Systemic lupus erythematosus: follow-up study of 148 patients. I: Classification, clinical and laboratory findings, course and outcome.

The present paper is a description of 148 patients with circulating antinuclear antibodies and multisystemic disease filed during 18 years by one of the authors and followed up to date in 1981-83. Seventy-eight per cent of the patients satisfied the 1971 ARA criteria for the classification of systemic lupus erythematosus and 92 per cent fulfilled the 1982 ARA criteria. Eighty-five per cent were women, the mean age at onset of SLE was 32 years. Malar rash and arthritis were early manifestations in 80 per cent of the patients whereas the onset of nephropathy, CNS manifestations, serositis, and peripheral cytopenia was delayed in about half of the patients. Nephropathy and thrombocytopenia were observed particularly in the youngest patients. The mean duration of the observation period was 8 years. The 10-year-survival was 80 per cent. Half of the deaths were presumably unrelated to SLE. The mean ages at entry of patients who died of SLE and of unrelated causes were 30 and 52 years respectively. Eighteen per cent of the deaths were caused by uremia and 18 per cent by infections. The total and the SLE related mortalities were evenly distributed throughout the observation period. The morbidity (incidence of new ARA criteria and other findings indicating active disease) decreased during the first year of observation but rarely subsided completely during the following years. All patients observed for more than 10 years showed evidence of active disease during the rest of the observation period and most showed evidence of renal disease.

Adolescent↗

Systemic lupus erythematosus. Follow-up study of 148 patients. II: Predictive factors of importance for course and outcome.

The predictive value of a number of clinical and laboratory variables for the mortality of 148 patients with systemic lupus erythematosus (SLE) with a mean observation period of 8 years and a 10-year-survival of 80 per cent was calculated by means of differentiated survival rate analyses and stepwise regression analyses. The predictive power of several variables increased if the calculations were based on deaths caused by SLE rather than on the total mortality rate. The survival rate decreased after 1973 because a diagnosis of SLE was made in some patients with terminal disease who would have remained without a diagnosis before that time. The causes of death and the treatment were identical before and after 1973. The presence of a high number of diagnostic ARA criteria within the first year of observation was a predictor of decreased survival. Severe but non-fatal infections (meningitis, septicemia, pneumonia) significantly reduced the survival rate. Patients with proteinuria and azotemia, within the first 2 years of observation, had a 10-year-survival of 70 per cent. The survival of patients with CNS manifestations was not significantly reduced. The butterfly rash and the presence of lymphopenia were predictors of decreased survival, whereas the presence of DNA antibodies had no predictive value for survival.

Adolescent↗

Acute phase proteins and clinical synovitis activity in patients with rheumatoid arthritis.

A number of laboratory variables, including Hb., ESR and several phase proteins, fluctuated in concord with the clinical signs of synovitis activity in patients with rheumatoid arthritis during a controlled study of 3 disease-modifying anti-rheumatic drugs (DMARD). The correlation between laboratory variables and clinical synovitis was significant in a large patient population but the correlation coefficients were not of such magnitude that any of the laboratory variables reflected clinical synovitis activity in a reliable manner in the individual patients. In patients treated with azathioprine, the response of the Hb, (and consequently of the ESR), was reduced compared to patients given other DMARD. This phenomenon was caused by the bone marrow suppressing effect of azathioprine. However, the effect of azathioprine on the clinical synovitis activity did not differ from that of the 2 other drugs. Similar results were found by reviewing the literature about controlled trials of DMARD. In the present trial the clinical evaluation was performed under optimal conditions. In daily clinical practice the evaluations of the joints may be less than optimal since they may be performed by different rheumatologists with varying experience. Consequently, it may be difficult to do without the unreliable laboratory variables mentioned in the routine assessments of disease activity, unless the quality of routine evaluations of synovitis activity is improved considerably.

Acute-Phase Proteins↗

Clinical implications of ribonucleoprotein antibody.

Out of 97 patients with circulating ribonucleoprotein antibodies, 44 (45%) satisfied the criteria for systemic sclerosis, systemic lupus erythematosus, polymyositis/dermatomyositis, or rheumatoid arthritis. Forty-two (43%) of the 97 patients whose cases did not fulfill these criteria had at least two of the following three clinical manifestations: arthritis, Raynaud's phenomenon, and swollen or sclerotic fingers. A fifth of the latter group of patients had chronic, restrictive pulmonary disease or myopathy and two thirds had hypergammaglobulinemia, IgM rheumatoid factor, and sensitized epidermal nuclei. Few patients had hypocomplementemia. One patient had nephropathy. Most patients had an unchanged, benign disease course for, on the average, nine years. It is suggested that the term mixed connective tissue disease (MCTD) be reserved for such patients, and that the acronym MCTD be changed to SRA (swollen fingers, Raynaud's phenomenon, and arthritis). Treatment with glucocorticoids is necessary for only a minority of patients.

Antibodies, Antinuclear↗

Influence of previous gold treatment and other patient variables on outcome of treatment with disease modifying anti-rheumatic drugs (DMARD) in patients with rheumatoid arthritis.

Based on a 2-year controlled double-blind trial of levamisole, penicillamine, and azathioprine (L, P, and A), a computer aided search for predictive factors of outcome was instituted. Already at month 4 several indicators of synovitis activity were able to discriminate between patients staying in the trial for 24 months and patients whose treatment was discontinued before that time. Patients who had previously received gold therapy responded less favourably to L, P, and A than those who had not received gold. This reduction of response was more pronounced in gold resistant patients than in patients whose gold treatment had been discontinued for other reasons. The only phase protein (of several) with a predictive value was haptoglobin. If, after 4 months of treatment, haptoglobin did not normalize, this finding indicated a lack of response to treatment or a deterioration of synovitis activity during the following 4 months. The response to treatment was not influenced by HLA-types, sex, age, or clinical synovitis, disease duration, functional or anatomical aberrations at the start of treatment. The shape of the response curve as reflected by means of monthly measurements of serum-albumin and ESR was not related to disease duration, HLA-types, or previous gold treatment.

Arthritis, Rheumatoid↗