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Biomedical subjects

J Petersen

Publications and source records attributed to J Petersen.

At least 109 records · Page 6Linked to original sources

The dialysis prescription: reuse.

Despite the widespread long practice of reuse there is continued criticism of the technique both in the media, journals and more recently at specially convened meetings. In the United States there are three principal sterilant/germicides used in reprocessing hemodialyzers: peracetic acid, formaldehyde and glutaraldehyde. The use of peracetic acid now exceeds that of formaldehyde while the more recent development of heat sterilization is only practiced in a few units. The major advantages of reprocessing include reduced cost, reduced first use syndrome and intradialytic symptoms which may be a result of increased biocompatibility with reuse. There is little data with regard to hospitalization and the recent reports of mortality rates are discussed. The major disadvantages associated with reprocessing include risks of infection, chronic exposure and accidental exposure to patients and staff to the sterilant germicide. We conclude that the reuse of dialyzers continues to be appropriate provided units follow the manufacturer's guidelines, the AAMI Recommended Practices and have a method in place to ensure the prescribed dialysis prescription is delivered.

Biocompatible Materials↗

Arginine vasopressin and oxytocin increase intracellular calcium and cAMP in human glomerular epithelial cells in culture.

The signal transduction linkages of arginine vasopressin (AVP) and oxytocin receptors were investigated in human glomerular epithelial cells (GEC) in culture. AVP (ED50, 10(-7) mol/l) and oxytocin (ED50, 3 x 10(-8) mol/l) induced a rapid, transient and dose-dependent increase in [Ca2+]i as detected by fura-2 microfluorimetry. The baseline of [Ca2+]i in human GEC was 109 +/- 2.8 nmol/l (n = 60). The V1a receptor antagonist [d(CH2)5(1), Tyr(Me)2, Arg8]-vasopressin inhibited the AVP-(IC50, 5 x 10(-9) mol/l) and oxytocin-induced (IC50, 3 x 10(-8) mol/l) increase in [Ca2+]i in a dose-dependent manner. Both, AVP and oxytocin caused accumulation of cAMP. The AVP-stimulated cAMP increase was blocked by pretreatment of human GEC with the V1a receptor antagonist (10(-7) mol/l), whereas the oxytocin-induced cAMP accumulation remained uninfluenced. In conclusion the present results indicate that: (1) V1a receptor activation, AVP and oxytocin induce a transient elevation in [Ca2+]i in human GEC; (2) AVP and oxytocin cause cAMP accumulation; (3) the AVP-induced cAMP accumulation is inhibited by a V1a receptor antagonist, whereas (4) the oxytocin response showed no effect. In addition, a different receptor might be possible, at least in oxytocin-induced-cAMP accumulation.

Antidiuretic Hormone Receptor Antagonists↗

[Calculated birth date as critical temporal marker for cryocoagulation of retinopathy of prematurity].

UNLABELLED: The time course of retinopathy of prematurity (ROP) is investigated for all preterm babies who underwent initial ocular therapy (cryocoagulation, encircling band or vitrectomy; 1983-1992; 156 eyes, 82 children; mean gestational age 28.1 weeks; mean birth weight: 864 g). Group I (ROP3+ in 5 adjacent or 8 accumulated clock hours): 63 eyes, 34 babies. The conceptional age at the time of cryo was 37.4 +/- 2.1 weeks. The disease progressed to cryo threshold before the presumed date of birth in 81% of cases. Group 2 (ROP4 and 5): 51 eyes, 27 babies. The gestational age at the time of first observation of ROP4 was 41.7 +/- 3.5 weeks. At least 39% of the detached cases arrived at stage 4 before the presumed date of birth. Group 3 (ROP3+ in less than 5 clock hours): Cryo-application in this grade of ROP is not generally accepted. We treated 42 eyes of 21 babies. Conceptional age at cryo therapy was 39.2 +/- 3.4 weeks. CONCLUSIONS: The time window for efficient ablative cryotherapy of ROP is clearly before the presumed date of birth. Eyes requiring therapy are at high risk for retinal detachment (ROP4) to be already present at 40 weeks conceptional age and later. Exceptions are ROP3+ cases of minor lateral extension.

Cryosurgery↗

[DIN-compatible vision assessment of increased reproducibility using staircase measurement and maximum likelihood analysis].

PROBLEM: Visual acuity determination according to DIN 58,220 does not make full use of the information received about the patient, in contrast to the staircase method. Thus, testing the same number of optotypes, the staircase method should yield more reproducible acuity results. On the other hand, the staircase method gives systematically higher acuity values because it converges on the 48% point of the psychometric function (for Landolt rings in eight positions) and not on the 65% probability, as DIN 58,220 with criterion 3/5 does. This bias can be avoided by means of a modified evaluation. Using the staircase data we performed a maximum likelihood estimate of the psychometric function as a whole and computed the acuity value for 65% probability of correct answers. METHOD: We determined monocular visual acuity in 102 persons with widely differing visual performance. Each subject underwent four tests in random order, two according to DIN 58,220 and two using the modified staircase method (Landolt rings in eight positions scaled by a factor 1.26; PC monitor with 1024 x 768 pixels; distance 4.5 m). Each test was performed with 25 optotypes. RESULTS: The two procedures provide the same mean visual acuity values (difference less than 0.02 acuity steps). The test-retest results match in 30.4% of DIN repetitions but in 50% of the staircases. The standard deviation of the test-retest difference is 1.41 (DIN) and 1.06 (modified staircase) acuity steps. Thus the standard deviation of the single test is 1.0 (DIN) and 0.75 (modified staircase) acuity steps. SUMMARY: The new method provides visual acuity values identical to DIN 58,220 but is superior with respect to reproducibility.

Computer Graphics↗

Selection of the living liver donor.

Living related liver transplantation offers several advantages in comparison to transplantation of cadaver organs. To achieve maximal donor safety evaluation, selection criteria and complications of the donor operation were retrospectively analyzed in living donors of segmental liver transplants. Seventy-three liver donor candidates were evaluated between October 1991 and June 1994. The median age of 42 mothers and 31 fathers was 31 years (range, 19-50 years). The median volume of the left lateral liver lobe comprised 230 ml (100-350 ml). Twenty-four of 73 (33%) donor candidates were not accepted for living donation. Rejection was due to unsuitability of the donor's liver as a graft (n = 13) or due to an increased risk for living donation (n = 11). Of 35 living donations performed so far, one was a full left hemihepatectomy and 34 were left lateral segmentectomies. The length of the donor operation was, on average, 4.3 hr. No heterologous blood was needed. Postoperative complications included death due to pulmonary embolism (n = 1), seizure due to a previously undiagnosed ependymoma (n = 1), bile duct injury (n = 1), incisional hernia necessitating late revision (n = 2), and duodenal ulcer (n = 2). Long-term follow-up revealed no persistent complications. Using our standardized protocol, 33% of young, presumably healthy donor candidates were rejected for living donation.

Adult↗

Urinary secretory immunoglobulin A and free secretory component in pyelonephritis.

The immune defense mechanisms of mucosal surfaces involve secretory immunoglobulin A (sIgA) antibodies and, to a lesser degree, other specific and nonspecific immune factors. These antibodies are dependent on a secretory component (SC) for their transmission through the epithelium. This SC is also secreted without Ig as free SC (FSC). The kidney does produce these proteins; however, the ability of the lower urinary tract to secrete them has not been shown. Thus, an upper urinary tract infection should produce more urinary sIg and possibly more FSC than a lower tract infection. To demonstrate this, urine was obtained from normal controls (N = 33), cystitis patients (N = 22), and pyelonephritis patients (N = 27). Monoclonal antibodies binding to specific conformational epitopes were used in an enzyme-linked immunosorbent assay to detect the levels of sIgA and FSC in these groups. Previous sIgA measurements have been hampered by lack of specificity of the capture antibody. Urine creatinine was obtained to correct for the effect of diuresis. A one-tailed Student's t-test for nonparametric populations was performed to assess differences. The sIgA levels in the normal and cystitis groups were equivalent (1.4 micrograms/mg/mL and 1.3 micrograms/mg/mL, respectively; P = 0.32). When these two groups were compared with the pyelonephritis group (24.1 micrograms/mg/mL), a statistically significant difference was seen (P = 0.012 and P = 0.011, respectively), with no overlap. There was a statistical difference in the levels of FSC in these same groups, but a large degree of overlap.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

The incidence of renal failure in one hundred consecutive heart-lung transplant recipients.

Between March 1981 and November 1992, 100 heart-lung transplantations were performed at our institution. We report on the renal function in the 67 patients who survived a minimum of 6 months posttransplantation, and who were aged more than 10 years at the time of transplant. Renal function was determined by serial measurement of serum creatinine. Mean serum creatinine increased from 0.96 +/- 0.03 mg/dL at baseline to 1.55 +/- 0.07 mg/dL at 6 months posttransplantation, to 1.88 +/- 0.11 mg/dL at the end of follow-up (mean follow-up, 50.0 months; range, 6 to 140 months). The decline in renal function was biphasic, with a rapid decrease in the first 6 months, followed by a much slower decline. Three patients developed end-stage renal failure. This compares with 14 of 416 cardiac transplant recipients at Stanford who developed end-stage renal failure over the same period. We conclude that in our large series at a single center the incidence of renal impairment and end-stage renal failure is low and similar between heart-lung and heart transplant patients.

Adolescent↗

Screening for anti-neutrophil cytoplasmic antibodies (ANCA): is indirect immunofluorescence the method of choice?

Detection of ANCA has become an important tool for the diagnosis and monitoring of disease activity in Wegener's granulomatosis (WG). Unfortunately, a group of sera positive by the standard method for ANCA detection, indirect immunofluorescence (IIF), are negative when more specific tests with purified proteins are used. In order to examine this discrepancy we examined groups of sera selected for being (i) C-ANCA-positive by IIF; (ii) positive in proteinase 3 (PR3)-ANCA ELISA; and (iii) from 24 patients with WG. The following assays were used: IIF, PR3-ANCA ELISA and capture PR3-ANCA ELISA using MoAbs against PR3. Furthermore, since granule enzymes are released during coagulation, we also measured ANCA in complex with PR3. To test if granule enzyme release had any influence on ANCA detection, both serum and EDTA-plasma were collected from a patient with active WG. No difference, however, was found. In the IIF-positive group (n = 60) 68% of the sera were positive in PR3-ANCA ELISA, 86% in capture PR3-ANCA ELISA and 80% were positive for the PR3/IgG-ANCA complex. In the PR3-ANCA ELISA group (n = 105) 88% of the sera were positive by IIF, 98% in capture PR3-ANCA ELISA and 53% in the PR3/IgG-ANCA assay. To evaluate the tests clinically sera from 24 patients with WG were examined. In the remission group (n = 10) two patients were positive by IIF, four in the PR3-ANCA ELISA, and five in the capture PR3-ANCA ELISA. Fourteen had active disease, and in this group 11/14 were positive by IIF, 10/14 in PR3-ANCA ELISA and 12/14 by capture-ELISA. The correlation between IIF and capture PR3-ANCA ELISA titre (r = 0.72, P = 0.0095) was better than between PR3-ANCA ELISA and IIF (r = 0.56, P = 0.043). It is concluded that the capture PR3-ANCA ELISA is more sensitive than PR3-ANCA ELISA, and that the capture ELISA can be used for screening of PR3-ANCA.

Antibodies, Antineutrophil Cytoplasmic↗

Characterization of fus1 of Schizosaccharomyces pombe: a developmentally controlled function needed for conjugation.

In Schizosaccharomyces pombe, the fus1 mutation blocks conjugation at a point after cell contact and agglutination. The cell walls separating the mating partners are not degraded, which prevents cytoplasmic fusion. In order to investigate the molecular mechanism of conjugation, we cloned the fus1 gene and found that it is capable of encoding a 1,372-amino-acid protein with no significant similarities to other known proteins. Expression of the fus1 gene is regulated by the developmental state of the cells. Transcription is induced by nitrogen starvation and requires a pheromone signal in both P and M cell types. Consequently, mutants defective in the pheromone response pathway fail to induce fus1 expression. The ste11 gene, which encodes a transcription factor controlling expression of many genes involved in sexual differentiation, is also required for transcription of fus1. Furthermore, deletion of two potential Ste11 recognition sites in the fus1 promoter region abolished transcription, and expression could be restored when we inserted a different Ste11 site from the mat1-P promoter. Since this element was inverted relative to the fus1 element, we conclude that activation of transcription by Ste11 is independent of orientation. Although the fus1 mutant has a phenotype very similar to that of Saccharomyces cerevisiae fus1 mutants, the two proteins appear to have different roles in the process of cell fusion. Budding yeast Fus1 is a typical membrane protein and contains an SH3 domain. Fission yeast Fus1 has no features of a membrane protein, yet it appears to localize to the projection tip. A characteristic proline-rich potential SH3 binding site may mediate interaction with other proteins.

Amino Acid Sequence↗

IgG for intravenous use, autologous serum and plasma induce comparable interleukin-1 receptor antagonist liberation from human mononuclear cells: an in vitro phenomenon depending upon plastic adherence.

Immunoglobulin G (IgG) for intravenous use (IVIg) selectively stimulates production of interleukin-1 receptor antagonist protein (IL-1ra) by mononuclear cells in vitro and has been proposed to stimulate IL-1ra production in vivo as part of the therapeutic effect. We tested if IVIg differed from human IgG-containing media (i.e., autologous serum (HS) and plasma (HP)) in stimulating IL-1ra release by MNC in vitro and whether IVIg induced a delayed increase in serum levels of IL-1ra. IVIg, 0.01-0.5 mg/ml, increased the IL-1ra liberation from MNC 10-15 times over that of untreated controls. HP and HS (5% v/v) had comparable effects. However, the stimulated IL-1ra liberation was reduced to less than twice the background liberation when fetal calf serum (FCS)-precoated tubes were used. Three days of high-dose IgG infusion had no significant effect on the serum levels of IL-1ra. It is concluded that therapeutic effects of IVIg cannot be ascribed to significant stimulation of IL-1ra production in vivo, as previously suggested, and that the observed stimulation of IL-1ra production in vitro is an epiphenomenon strictly dependent upon adherence of human serum and plasma constituents.

Adult↗

Regulation of phosphoinositide hydrolysis and cytosolic free calcium induced by endothelin in human glomerular epithelial cells.

The regulation of the inositide signalling pathway and [Ca2+]i by endothelin (ET) peptides was investigated in human glomerular epithelial cells in culture. Endothelin-1 and -2 induced an accumulation of inositol phosphates in a time- and dose-dependent manner. The baseline of [Ca2+]i in glomerular epithelial cells was 109 +/- 2.8 nmol/l, n = 60. Endothelin-1 (ED50: approx. 3 x 10(-9) mol/l) caused a rapid and transient rise in [Ca2+]i as detected by fura-2 microfluorimetry studies. The endothelin-1-induced inositol phosphate accumulation was inhibited by the selective ETA receptor antagonist BQ123. Endothelin-3 and BQ3020, a selective ETB receptor agonist, showed no effect. The results suggest an ETA-mediated pathway. This study demonstrates an ETA-mediated transmembrane signalling via phospholipase C with consecutive elevation of inositol phosphates and intracellular calcium. Since endothelin peptides contribute to both normal renal function and renal dysfunction, this study adds further knowledge on glomerular cell regulation.

Calcium↗

Measurements of proteinase 3 and its complexes with alpha 1-proteinase inhibitor and anti-neutrophil cytoplasm antibodies (ANCA) in plasma.

Wegener's granulomatosis (WG) is a systemic vasculitis which is diagnosed on clinicopathological findings. The diagnosis may be aided by the presence of anti-neutrophil cytoplasm antibodies (ANCA). In WG, ANCA are primarily directed to proteinase 3 (PR3), a serine protease of the azurophilic granules of the neutrophilic granulocyte. The main plasma inhibitor of PR3 is alpha 1-proteinase inhibitor (PI). To study if free PR3 or complexes between the enzyme and PI or PR3 and ANCA could be found in the plasma from patients with WG we have developed three ELISA systems for the detection of these complexes and free PR3. In all three assays monoclonal antibodies against PR3 were used as capture antibodies. After incubation with plasma, free PR3 was detected by affinity purified rabbit anti-PR3 followed by alkaline phosphatase-labelled swine anti-rabbit IgG. Serial dilutions of purified PR3 was used as standard. The detection limit was 3 ng/ml. PR3 complexed with PI was measured by rabbit anti-PI antibodies and alkaline phosphatase-labelled swine anti-rabbit IgG. Pre-formed in vitro complexes of PR3/PI in serial dilutions were used as standard. The detection limit of this assay was 1 ng/ml. PR3/IgG-ANCA complexes were detected by alkaline phosphatase labelled goat anti-human IgG. A positive plasma sample in serial dilutions was used as standard. Plasma samples from nine patients with WG, eight patients with fever of infectious origin without evidence of vasculitis and ten healthy donors were examined by these methods. Free PR3 could not be found in any of the plasma samples. PR3/PI complexes were detected in healthy donors at levels between 41-85 ng/ml. All WG patients, both active and inactive, had PR3/PI concentrations above this level, and so had all patients with fever. PR3/IgG-ANCA was found in three of the patients with WG, two being ANCA negative with inactive disease and one was ANCA positive with active disease. Thus, the developed methods can be useful for future studies of the clinical relevance of these complexes in patients with WG and possibly other vasculitides.

Antibodies, Antineutrophil Cytoplasmic↗

[Disseminated histoplasmosis in AIDS].

A 41-year-old man infected with HIV-1 developed fever up to 39.8 degrees C together with nonproductive cough and dyspnoea. Lactate dehydrogenase concentration rose from a level of 998 U/l to 6307 U/l. As pneumocystis carinii pneumonia was at first suspected he was treated with co-trimoxazole (1600 mg sulfamethoxazole and 320 mg trimethoprim, four times daily). But the symptoms did not abate. Bone-marrow puncture revealed numerous macrophages containing ovoid inclusions typical of Histoplasma capsulatum varietas capsulatum. The diagnosis of disseminated histoplasmosis was confirmed by culture and serologically by an increase in Histoplasma polysaccharide antigen. On treatment with amphotericin B (at first 10 mg, then 50 mg daily for 4 weeks) the symptoms regressed within a few days. After the concentrations of lactate dehydrogenase and Histoplasma antigen had become normal again, maintenance treatment was changed to itraconazole (200 mg twice daily), after a total amphotericin B dose of 1150 mg. The patient has remained free of recurrence.

AIDS-Related Opportunistic Infections↗