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Biomedical subjects

J Petersen

Publications and source records attributed to J Petersen.

At least 199 records · Page 11Linked to original sources

Spontaneous and induced immunoglobulin synthesis and anti-neutrophil cytoplasm antibodies in Wegener's granulomatosis: relation to leukocyte subpopulations in blood and active lesions.

Using a reverse plaque forming cell (PFC) assay the production of immunoglobulin (Ig) by peripheral blood mononuclear cells (MNCs) in vitro was studied in 12 patients with Wegener's granulomatosis (WG). Spontaneous IgG production was increased in two of six untreated patients. The IgG response of MNCs from eight untreated patients to pokeweed mitogen (PWM) and Epstein-Barr virus (EBV) stimulation was significantly depressed. The IgM and IgA production followed the individual pattern of IgG. Blood B-cell and T-cell subset concentrations were normal before therapy, whereas the monocyte concentration was increased in four of six patients. Titers of anti-neutrophil cytoplasm autoantibodies (ANCAs) did not correlate with spontaneous or induced Ig production nor with blood leukocyte subset concentrations. Biopsy specimens from upper respiratory tract lesions in seven untreated patients showed numerous macrophages, activated T lymphocytes, and plasma cells, suggesting a pathogenetic role of these cells in the development of lesions and local production of ANCAs.

Antibodies↗

Fast-phase instabilities in normally sighted relatives of congenital nystagmus patients--autosomal dominant and x-chromosome recessive modes of inheritance.

Verification of inheritance in congenital nystagmus (CN) is only possible through the identification of more than one affected member in a family since in a single case there are no accurate clinical differentiations between "spontaneous" and inherited CN. We performed electronystagmographic examinations (ENG) to search for abnormal involuntary eye movements as a sign of heredity in seemingly unaffected members of CN families. ENG registrations were performed under three test conditions: (1) with the subject fixating a target, (2) with the room lights off and (3) with closed eyes. Fifty normally sighted individuals (group (a] underwent the test procedure to provide a baseline of normality. Five CN families (three dominant, two sex-linked recessive) were tested as group (b). The eye movement recordings were analysed in terms of nystagmus intensity (amplitude x frequency of the involuntary saccade). In every one of the five families, abnormalities in seemingly non-affected members could be demonstrated: in four families, fast-phase instabilities, in the fifth family a true (CN) (slow-phase instability). All certain gene carriers were diagnosed correctly by the ENG. These findings indicate a method for detecting slightly affected members in dominant pedigrees and female gene carriers in sex-linked mode of transmission.

Adult↗

Continuous arteriovenous hemofiltration: an in vitro simulation and mathematical model.

In vitro and mathematical models of continuous arteriovenous hemofiltration (CAVH) have been developed. Human erythrocytes resuspended in normal saline containing 5% bovine albumin were used to perfuse the circuit from a gravity driven pressure source. Membrane hydraulic permeability was observed to decline from 31.2 x 10(-5) +/- 11.9 x 10(-5) cm/(min.mm Hg) before use to 12.3 x 10(-5) +/- 3.3 x 10(-5) (mean +/- SD) after use. This fall occurred during the first one to two hours whether perfused with blood or 5% albumin alone. Pressure-flow relationships of each circuit component, measured with 40% sucrose as a calibration medium, conformed to Poiseuille's equation. Use of high resistance blood access on the venous end of the circuit resulted in a low blood flow rate and high filtration fraction. The same access, when placed on the arterial end, produced both low blood flow rate and low filtration fraction. These results were a consequence of pressure distribution within the circuit as demonstrated by measurements of perfusion, prefilter, and postfilter pressures. The importance of negative pressure applied to the filter chamber in order to maintain favorable Starling forces, when the system was operated with a small bore arterial access, was demonstrated by similar methods. Enhancement of urea clearance by predilution was verified. Model simulations suggest that predilution will be of less benefit or even detrimental for other solutes which fail to distribute across the erythrocyte membrane. Comparison of results with predictions of a mathematical model demonstrated good agreement, but with some tendency to overestimate filtrate production. The latter was attributed to neglect of concentration polarization of plasma proteins in model development.

Hemofiltration↗

Incidence and prognostic importance of silent ischaemia after PTCA: a prospective study.

To evaluate the influence of PTCA on symptomatic and asymptomatic ischaemic episodes in 94 patients, 24-h ambulatory, electrocardiographic Holter recordings were obtained before and after successful PTCA. Sixty-four per cent of patients had one-vessel disease, 28% two-vessel disease and 8% had three-vessel disease. Ischaemic episodes were present in 36% of patients before PTCA, of which 71% were silent; after PTCA, 23% of patients had ischaemic episodes, of which 98% were silent; thus silent ischaemic episodes were improved by PTCA to a lesser degree than symptomatic ischaemic episodes. Successful PTCA lead to a significant reduction in total number and duration of ischaemic episodes but not to a complete abolition. Patients with silent ischaemic episodes after PTCA had also a higher incidence of silent ischaemic episodes before PTCA. Functional and haemodynamic improvement was comparable in patients with and without silent ischaemic episodes. No specific cause for the persistent or newly appearing silent ischaemic episodes after PTCA could be identified; they are not indicative of an inadequate dilatation and cannot be considered as a risk factor for early restenosis. A possible explanation could be a traumatically induced, increased vascular tone in susceptible patients.

Angioplasty, Balloon↗

Conservatively treated patients with cerebral arteriovenous malformation: mental and physical outcome.

Twenty five patients with conservatively treated cerebral arteriovenous malformation were followed up for a mean of 10.6 years after diagnosis. The follow up included neuropsychological examination. Bleeding did not occur after the time of diagnosis. Three patients had moderate to severe neurological deficits, five had moderate to severe intellectual impairment. Nineteen had an unaffected occupational status. It is concluded that the outcome in conservatively treated patients may be no worse than in surgically treated patients.

Adolescent↗

Effect of insulin therapy on established diabetic nephropathy in rats.

The effectiveness of insulin therapy on early diabetic nephropathy has not been established. In this study we examined the influence of continuous subcutaneous insulin on the progression of established nephropathy in streptozocin-induced diabetic rats. Normal controls and diabetic rats were studied for 11 mo. During the first 6 mo, all the diabetic rats received 2 U protamine zinc insulin s.c. twice weekly. During the last 5 mo of study, diabetic rats either continued on the occasional subcutaneous insulin regimen or received regular insulin by continuous subcutaneous infusion. Six months after the initiation of the study, the diabetic rats were severely hyperglycemic, and their relative mesangial areas had increased. Continued poor glycemic control in the rats receiving occasional insulin was associated with relative increased mesangial area (25.2 +/- 1.0% of glomerular area) and significant proteinuria (148 +/- 17 mg/24 h) compared with normal controls. In contrast, the use of continuous subcutaneous insulin therapy with improved glycemic control arrested mesangial changes (19.5 +/- 1.4% of glomerular area) and prevented the excessive proteinuria (71 +/- 13 mg/24 h). Indeed, these parameters did not differ from age-matched controls. We conclude that in the rat, continuous subcutaneous insulin therapy instituted after the development of early glomerular pathology is effective in arresting the disease process.

Animals↗

B lymphocyte function in patients with rheumatoid arthritis: impact of regulatory T lymphocytes and macrophages--modulation by antirheumatic drugs.

The present work analyses B lymphocyte functions in vitro in patients with rheumatoid arthritis (RA). The impact of gold salts and penicillamine on human B lymphocyte function in vitro is discussed. Synovial fluid monocytes/macrophages increased both the polyclonally induced and the antigen-induced blood lymphocyte proliferation and increased the numbers of immunoglobulin-secreting blood B lymphocytes generated by pokeweed mitogen (PWM), a T cell-dependent polyclonal activator. The lymphostimulatory factor(s) interleukin-1, which can be produced by monocytes/macrophages, was found in most cell-free synovial fluid specimens, but only in a few paired serum samples. Thus, in vivo activated synovial monocytes/macrophages may modulate lymphocyte functions. Compared to blood, synovial fluid T lymphocytes comprised fewer T4+ (helper/inducer) cells and more T8+ (suppressor/cytotoxic) cells. Synovial fluid lymphocytes proliferated poorly when stimulated polyclonally. However, the proliferative responses to microbial antigens as well as the lectin-induced lymphokine production equaled those of blood lymphocytes. In about half of RA patients, T4+ cells from synovial fluid increased the PWM-induced immunoglobulin secretion by autologous blood B lymphocytes to higher levels as compared to similar experiments with blood T4+ cells. Synovial fluid T8+ cells suppressed PWM-induced immunoglobulin production of autologous mononuclear cells to the same degree as seen with blood T8+ cells. A large proportion of synovial fluid T subsets expressed Ia antigens, probably due to in vivo activation. Thus, synovial T helper/inducer and T suppressor/cytotoxic cells may modulate the functional activities of synovial B lymphocytes. Among mononuclear cells isolated from synovial fluid and synovial tissue, considerable numbers of B lymphocytes spontaneously secreting IgG were found; fewer B cells secreted IgM and IgA. Rheumatoid factor activity was noted in about 7% of the IgG-producing cells. Synovial fluid mononuclear cells did not produce immunoglobulins in cultures stimulated with PWM, unless synovial T cells were removed and replaced with autologous blood T cells. Under these conditions synovial fluid B lymphocytes were induced by PWM to considerable IgG synthesis; fewer cells secreted IgM and IgA. About 8-9% of the induced IgM- and IgG-synthesizing cells displayed rheumatoid factor activity. Aurothiomalate markedly inhibited PWM-induced immunoglobulin production by normal lymphocytes cultured in vitro, probably by affecting monocyte/macrophage-lymphocyte interactions. The drug also had a direct inhibitory action on B lymphocytes, whereas T cells were resistant.(ABSTRACT TRUNCATED AT 400 WORDS)

Anti-Inflammatory Agents↗

The effect of dietary protein restriction on high dose gentamicin nephrotoxicity in rats.

Gentamicin (120 mg/kg/day) was administered for 10 days to Sprague-Dawley rats given either a low (5% w/w) or normal (18% w/w) protein diet. Serum protein concentrations remained normal in all rats during the study. Nephrotoxicity was slightly less severe in rats fed a low protein diet as shown by: (i) a mean creatinine clearance rate (14 +/- 4 ml/min) which was significantly greater than that (8 +/- 3 ml/min) recorded from the rats maintained on the normal diet (P less than 0.05); (ii) lower activities of urinary N-acetyl-beta-D glucosaminidase (NAG); and (iii) less marked histological changes. Mean tissue concentrations of gentamicin were considerably lower in both renal cortex and medulla from rats maintained on the low protein diet than from those animals on the normal diet (P less than 0.01 and P less than 0.05, respectively). These differences were, however, not reflected in the mean trough serum gentamicin concentrations which were not significantly different between the two groups. These results are discussed in relation to the proposed mechanisms involved in gentamicin-induced nephrotoxicity.

Acetylglucosaminidase↗