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Biomedical subjects

J Petersen

Publications and source records attributed to J Petersen.

At least 19 recordsLinked to original sources

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

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

Management of thyroid papillary carcinoma with radioiodine in a patient with end stage renal disease on hemodialysis.

Metastatic papillary carcinoma was diagnosed in a 42-year-old woman. The cancer had invaded out of the gland and was present in many lymph nodes. After her surgical procedure, she was advised to have radioiodine. However, the patient had total renal failure and was on dialysis. Studies were carried out using a tracer dose of 2 mCi of radioiodine, demonstrating that approximately 60% of the radioactivity in the body was removed with each dialysis. Calculations indicated that a meaningful dose of radiation could be delivered to residual thyroid and metastases with 100 mCi of radioiodine and the total body radiation would be < 100 rad delivered over several days. Based on these analyses, she received 100 mCi of I-131 on two separate occasions and on follow-up scan, clinical evaluation and thyroglobulin measurement is free of disease.

Adult

Myoglobinuric acute renal failure in a cardiac transplant patient taking lovastatin and cyclosporine.

Acute renal failure can occur in cardiac transplant patients for a variety of reasons. A case of a patient who developed acute renal failure secondarily to drug-induced rhabdomyolysis is reported. The literature regarding acute renal failure and lovastatin and other 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors is reviewed. The potential mechanisms of myoglobinuria and nephrotoxicity and the therapeutic implications are discussed.

Acute Kidney Injury

Capillary electrophoretic determination of the protease Savinase in cultivation broth.

The highly basic washing enzyme Savinase and various analogues were analysed by micellar electrokinetic chromatography (MEKC) and electrophoresis. Broth samples were withdrawn during the cultivation of Savinase by recombinant microorganisms. Savinase peak areas obtained by MEKC-electrophoretic analysis were normalized with respect to migration time and compared with traditional enzyme activity measurements. The electropherograms indicated thermal degradation of the Savinase molecule at high field strengths. Baseline separation of Savinase and two analogues was achieved.

Bacillus

[Pregnant women's knowledge about HIV and AIDS].

This investigation is based upon information from 820 pregnant women who replied to a questionnaire about AIDS during the period 17.4.1989-14.7.1989. The questions included sources of information, knowledge about routes of infection and risk groups and the extent of spread of infection and disease in the population. 95% agreed to participate. Knowledge had been obtained primarily via the electronic media, while the health services had limited significance. The employment of sources of information depended on age and occupation. Apart from knowledge about the risk involved in breast feeding, the women were, in general, well informed about routes of infection. Knowledge about risk groups and the current extent of spread of infection was, on the the other hand, deficient. Defective knowledge was concentrated in groups which may be characterized by age (less than 24 years) and occupation (trained and untrained workers and the group of "other occupations"). Information obtained from health staff was connected with better knowledge about the extent of spread of infection. The majority of women desired routine information about AIDS in connection with antenatal control. Prophylactic measures should be based, among other things, on knowledge about development in the knowledge in the population and its employment of sources of information, so that specific information may be directed to certain groups of the population by using the most frequently employed and most effective routes of information. The knowledge of population groups, the attitudes and behaviour should be followed continuously.

Acquired Immunodeficiency Syndrome

Glutamic acid decarboxylase (GAD) autoantibodies are additional predictive markers of type 1 (insulin-dependent) diabetes mellitus in high risk individuals.

The prevalence of glutamic acid decarboxylase autoantibodies was determined with an immunotrapping enzyme activity assay in newly-diagnosed Type 1 (insulin-dependent) diabetic patients as well as in first-degree relatives using rat brain homogenate as a source of glutamate decarboxylase. Twenty-six out of 86 islet-cell cytoplasmic auto-antibody positive and one out of 24 islet cell autoantibody negative patients of recent onset, had autoantibodies to glutamate decarboxylase above the upper 99% confidence limit obtained from 89 control sera. Among 27 islet cell autoantibody positive relatives including 19 siblings and 8 parents, antibodies to glutamate decarboxylase were found in 8 of 9 (89%) relatives and 7 of 8 (87.5%) siblings with islet cell auto-antibody titres above 20 JDF units, in 1 of 19 (5.2%) relatives with islet cell autoantibody titres between 2 and 5 JDF units, in 2 of 263 (0.7%) siblings and 1 of 139 parents without islet cell autoantibodies. In first-degree relatives, high titre islet cell autoantibodies and autoantibodies to glutamate decarboxylase were tightly associated (X2 = 182, p = 0.0001). None of the relatives with low genetic risk (n = 64), i.e. HLA-different to the diabetic proband, was found to be antibody positive. Antibodies to glutamate decarboxylase were present only in those relatives sharing at least one haplotype with the diabetic proband, including two islet cell autoantibody negative but HLA-identical siblings. Autoantibodies to glutamate decarboxylase were present in 7 of 9 (77%) relatives who developed the disease, including one islet cell autoantibody negative sibling.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent

Direct and correlated responses to bidirectional selection for dustbathing activity in Japanese quail (Coturnix coturnix japonica).

Bidirectional selection was conducted for dustbathing activity in male Japanese quail over 17 generations. The response to selection was slightly asymmetrical, due mainly to scale effects and a threshold imposing discontinuity on the visible expression of dustbathing in the low line. Correlated responses to selection were found for latency to dustbathe, duration, intensity, and incidence of nonbathers. In general, changes followed linear patterns over time in both lines with the exception of quadratic change in nonbathers in the high line. Under artificial environment, only minor natural selection pressure is assumed to act on the expression of dustbathing behavior.

Animals

Variability among methods to assess patients' well-being and consequent effect on a cost-effectiveness analysis.

Cost-effectiveness analysis is emerging as an approach for determining the relative value of health care programs, technologic innovations, and clinical decisions. Increasingly, patients' stated values for quality of life are applied as adjustment in these analyses; the results may vary depending on how individuals assess their well-being. We interviewed 58 patients with chronic renal failure to determine the level of agreement among six methods for assessing well-being, and to determine the effects of variation in assessed well-being on the results of a cost-effectiveness analysis of in-center hemodialysis. Patients reported well-being using the Sickness Impact Profile, Campbell Index of Well-being, Kaplan-Bush Index of Well-being, categorical scaling, standard gamble, and time trade-off. We found that patient well-being was substantially higher as evaluated by the Sickness Impact Profile compared to the other five methods. The Sickness Impact Profile and the Kaplan-Bush Index of Well-being provided much narrower distributions of assessed values relative to other measures. Correlations among assessment methods were poor (Spearman rank-correlation coefficients range: 0.094-0.519). Discrepancies among indices were particularly vivid when we evaluated data at the individual level; many patients reported a high level of well-being according to one index and a low level of well-being according to a different index. The cost effectiveness of in-center hemodialysis varied from $34,893 to $45,254 per quality-adjusted life-year saved according to the Sickness Impact Profile and standard-gamble technique respectively. The substantial variability in patients' stated quality of life may preclude the use of a single method to analyze the cost effectiveness of a health program.

Cost-Benefit Analysis

An in vivo analysis of reverse ultrafiltration during high-flux and high-efficiency dialysis.

We have developed an in vivo pressure monitoring system to study the phenomenon of reverse ultrafiltration of dialysate during high-flux and high-efficiency dialysis. Under the usual operating conditions of either type of dialysis, driving pressures existed for reverse ultrafiltration of dialysate into the venous end of the blood compartment. Whether or not reverse ultrafiltration could be abolished at higher ultrafiltration rates was dialyzer-dependent, being least with high-efficiency dialysis. In addition, the degree of reverse ultrafiltration was affected by patients hematocrit, dialyzer inlet and outlet oncotic pressures, and the rate and direction of dialysate flow.

Equipment Design

A model of the volumetrically-controlled hemodialysis circuit.

We developed a model that predicts the hemodynamics of the volumetrically-controlled circuit used to administer high flux hemodialysis. The equations simulate the entire blood side of the circuit so that blood and dialysate pressures can be predicted from a knowledge of circuit component and patient characteristics. An alternative method of computation has also been devised which permits measured circuit pressures to be used to predict patient blood access pressure, dialyzer resistance to flow and membrane hydraulic conductivity. Success of the model was evaluated by measuring both circuit pressure and component characteristics. The model successfully predicted circuit pressures when measured component characteristics were employed as model inputs. Conversely, the model accurately predicted circuit component characteristics when measured pressures were employed as inputs (8 patients, 30 dialyses). Specific predictions of the model include the following. Elevations of patient blood access pressure will cause blood and dialysate pressures to rise equivalently without affecting the rate of back-filtration or location of pressure equilibrium along the dialyzer axis. Elevated hematocrit is predicted to increase circuit pressures to a degree that is similar to a poorly functioning blood access, however, high hematocrit markedly augments back-filtration and moves the point of pressure equilibrium toward the dialyzer entrance. We conclude that the model provides a predictive tool that can be used to optimize circuit design. Alternatively, the model can be used to separate the influence of a poorly functioning patient access from other factors which can elevate circuit pressures.

Blood Flow Velocity