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J Schaeffer

Publications and source records attributed to J Schaeffer.

At least 37 records · Page 2Linked to original sources
PubMed1996

Long-term performance of hemofilters in continuous hemofiltration.

We measured the filter performance of six polyamide hemofilters with a running time exceeding 72 h applied for continuous hemofiltration in intensive care patients. The sieving coefficients for urea and creatinine were close to unity and remained constant. The sieving coefficient of polyfructosan (mean molecular weight 3 kD) was around 0.75 and did not change with running time. The hydraulic permeability remained also unchanged. The relationships between blood pressure and blood flow and between blood flow and filtration rate remained linear, and the gradient did not change with time. We conclude that a daily routine change of polyamide hemofilters applied in continuous arteriovenous hemofiltration and presumably in continuous venovenous hemofiltration is not necessary within the first 72 h of treatment, unless a major decrease in the filtration rate occurs.

Acute Kidney Injury↗
PubMed1995

Pathogenetic and diagnostic aspects of dialysis-related amyloidosis.

Dialysis-related amyloidosis (DRA) is a major cause of morbidity in end-stage renal disease patients. While retention of the precursor protein beta 2-microglobulin (beta 2-m) forms the essential basis for DRA, pathogenetic concepts include: qualitative and quantitative alterations in beta 2-m metabolism; local and systemic inflammatory changes, partly related to different treatment modes; general predisposing factors such as age at the onset of dialysis treatment. Clinical and radiological signs, as well as synovial thickening on sonography, suggest the presence of DRA, but histomorphological demonstration of beta 2m-amyloid is required for definitive proof. Scintigraphic imaging of DRA represents an additional, sensitive non-invasive diagnostic tool. Successful kidney transplantation stops the progression of DRA.

Amyloidosis↗
PubMed1995

Beta 2-microglobulin amyloidosis: why and how to look for it.

Thirty years after the introduction of chronic dialysis into clinical practice, amyloidosis based on the precursor molecule beta 2-microglobulin (beta 2m-A) has emerged as an important complication of end-stage renal disease in patients on renal replacement therapies other than transplantation. For the individual patient, diagnosis of beta 2m-A is important to exclude other treatable causes of the symptoms, initiate symptomatic treatment, prevent possible life-threatening complications, and assign a high priority for transplantation. For the ESRD population as a whole, early specific diagnosis should help to assess the influence of various therapeutic modes on the development and course of beta 2m-A and to guide further the optimization of renal replacement therapy. Besides, sophisticated diagnostic techniques may yield valuable information on underlying pathogenetic mechanisms of beta 2m-A. Morphology, including immunohistochemistry, as the most definitive and specific diagnostic proof must rely on invasive procedures to obtain the appropriate material from clinically affected sites. Clinical assessment and imaging techniques such as x-ray and joint sonography suffer from non-specificity. Scintigraphic imaging of beta 2m-A after injection of radiolabelled beta 2-microglobulin is a non-invasive, specific, and highly sensitive way of diagnosis. Further refinement and more widespread use of this method can be expected to enhance the understanding of beta 2m-A pathogenesis and promote therapeutic and preventive efforts against this complication.

Amyloidosis↗
PubMed1994

Comparative analysis of mutations in the p53 and K-ras genes in pancreatic cancer.

Mutations in codon 12 of K-ras occur in a high proportion of pancreatic cancer cases. Although there is evidence that p53 mutations also occur in this tumor, few studies have been reported to date and no comparison has been made of K-ras and p53 mutations in the same tissues. Single-strand conformation polymorphism and sequencing of the PCR products were used to determine mutations in p53 gene; to detect mutations in K-ras genes, the artificial restriction fragment length polymorphism (RFLP) approach was used. Eight out of 30 tissues from primary pancreas cancer and 3 of 4 samples from metastases showed p53 mutations. Fifteen out of 17 pancreatic cancer cell lines had p53 mutations. In 2 cases, the same p53 mutation was identified in the original tumor and in a tumor-derived cell line. The majority of p53 mutations were present in exons 5-9 of the gene. Mutations at codon 12 of the K-ras gene were identified in 23/32 pancreas cancer tissues and in 14/17 cell lines. There was no relationship between the types of mutation observed in the 2 genes. In conclusion, mutations in K-ras and p53 genes are common in pancreatic cancer. p53 mutations may occur more frequently in metastatic lesions than in primary tumors, although further work is necessary to investigate this point.

Base Sequence↗
PubMed1993

Genetic heterogeneity of the c-K-ras locus in colorectal adenomas but not in adenocarcinomas.

BACKGROUND: Previous molecular genetics studies of colorectal cancer have identified multiple mutations in the c-K-ras gene (also known as KRAS2) in all phases of its development. Because of technical difficulty, prior studies rarely focused attention on the detailed distribution of c-K-ras mutations in multiple regions of the same primary tumor specimen. However, with recent development of the selective UV radiation fractionation method, characterization of c-K-ras mutations in multiple regions of the same primary tumor specimen can be performed. PURPOSE: Our purpose was to describe how c-K-ras mutations were distributed among cells obtained from multiple regions of the same primary tumor in an attempt to describe differences between early and late colorectal carcinogenesis. METHODS: Formalin-fixed, paraffin-embedded tissue blocks were obtained. Seven adenocarcinomas and seven adenomas were selected for the presence of mutant c-K-ras genes and histologic transitions between normal and neoplastic tissue. Tissue sections were prepared for analysis by the selective UV radiation fractionation method by placing thin, fixed tissue sections on a plastic slide with no coverslip. Under the microscope, small ink dots from a felt-tip pen were manually placed directly on relatively pure cell subpopulations. The slides were placed with the tissue side exposed to a UV transilluminator for 2-4 hours to inactivate the DNA present in the unprotected ("undotted") cells. Individual dots were cut out of the plastic slide into 2 x 2-mm squares and placed into microfuge tubes. The DNA was extracted and supernatant used for polymerase chain reaction (PCR) analysis. Mutations at c-K-ras codons 12 and 13 were detected. RESULTS: The selective UV radiation fractionation method and PCR analysis revealed that c-K-ras mutations never extended into normal mucosa and were present in all neoplastic cells regardless of phenotypes in all seven adenocarcinomas and three of the seven adenomas. Further examination of two carcinomas for p53 (also known as TP53) mutations or loss of heterozygosity demonstrated that these additional mutations were also present in all tumor cells, suggesting that a single transformed clone was responsible for the majority of growth. However, in four other adenomas, tumor heterogeneity was demonstrated, since c-K-ras mutations were detected only in discrete portions. CONCLUSIONS: Adenoma formation may include a stage in which multiple and genetically distinct neoplastic clones are present, while most carcinomas appear to have a homogeneous composition that may result from the successful progression of one of these clones.

Adenocarcinoma↗
PubMed1992

Colour Doppler ultrasound assessment of arteriovenous haemodialysis fistulas.

Satisfactory function of the arteriovenous fistula (AVF) is essential for adequate haemodialysis in patients with chronic renal failure. Existing methods to assess AVF function are imprecise (eg, clinical examination) or invasive (eg, angiography). We assessed the value of colour flow-doppler ultrasound (CFDU) in the investigation of clinically suspected AVF dysfunction. 51 patients with suspected impairment of AVF function were studied by CFDU, and 28 also underwent angiography. The findings were compared with the reference standard of the findings at reoperation. CFDU showed AVF stenoses in 18 patients, which were all confirmed at reoperation; the results of angiography in 13 of these 18 patients showed complete agreement with the findings of CFDU and surgery. CFDU showed partial or complete AVF thrombosis in 33 patients, confirmed in all patients at reoperation; 15 patients also underwent angiography, and thrombi were not found in 6 (in 4 because of technical failure). 7 patients had aneurysms on CFDU that were confirmed by surgery in all patients and by angiography in 2 of the 3 patients studied. CFDU enables reliable non-invasive assessment of AVF morphology and function and may become the procedure of choice for AVF assessment in patients with suspected AVF abnormalities.

Adult↗
PubMed1992

Inpatient group processes parallel unit dynamics.

The authors conducted a quantitative examination of parallels between milieu and therapy group dynamics on a short-term inpatient unit. The Ward Atmosphere Scale was used to assess the milieu, and the Group Climate Questionnaire-S to measure processes in key groups. Assessments were made by patients and staff once each week for 10 months. The authors found clear parallels between ward and therapy group processes. The parallels reflected the impact of patterns utilization of the unit, its treatment philosophy, and the emotional dynamics of its constituents. Examination of these associations also revealed limitations of the treatment setting, clarified the potential impact of particular staff interventions, and demonstrated biases in the rating methods. Study of parallel process on the psychiatric unit is a rich source of information on the nature of inpatient treatment.

Adolescent↗
PubMed1990

Hypocalcemia and hypercalcitoninemia in critically ill children.

To study Ca metabolism in critically ill children, we measured ionized Ca (Ca2+), parathyroid hormone (PTH), calcitonin, 25 hydroxycholecalciferol (25[OH] D3), 1-25 dihydroxycholecalciferol (1-25[OH]2D3, and gastrin levels in critically ill children and in healthy controls. Patients were considered hypocalcemic if Ca2+ was less than 1.1 mmol/L. Six (14%) of 45 patients were hypocalcemic. Five hypocalcemic patients were studied and were found to have higher calcitonin levels than normocalcemic patients and healthy controls and higher PTH levels than healthy controls. 25(OH)D3 and 1-25(OH)2D3 were not significantly different in the three groups of patients. Gastrin levels were low in critically ill patients, whether or not they were hypocalcemic. We conclude that hypocalcemia occurs frequently in critically ill children. It is associated with raised levels of calcitonin and PTH. The mechanism for the increase in calcitonin is unknown.

Acute Disease↗
PubMed1989

The influence of the transmembrane sodium gradient on the responses of pulmonary arteries to decreases in oxygen tension.

A Na/Ca exchange system has been demonstrated in systemic vascular smooth muscle and has been suggested as a mechanism for the entry and extrusion of Ca2+. Using isolated rings of bovine intrapulmonary arteries, we sought to determine whether a Na/Ca exchange mechanism is present in pulmonary vascular smooth muscle, and if so, whether it contributes to the modulation of vascular tone during hypoxia. Under both normoxic (PO2 greater than or equal to 120 mm Hg) and hypoxic (PO2 less than or equal to 40 mm Hg) conditions, the amplitude of the 40 mM K+ contraction was significantly (p less than 0.005) enhanced when most of the external Na+ was replaced with N-methylglucamine (NMG) (Na+ = 1.2 mM). The rate of contraction was also increased by replacing Na+ with NMG during normoxia (1.02 +/- 0.24 to 2.52 +/- 0.57 mg/mg weight/s, p less than 0.005) and hypoxia (1.72 +/- 0.74 to 4.08 +/- 1.63 mg/mg weight/s, p less than 0.05). Although the relaxation rate was slowed in the low Na+ media during normoxia (3.48 +/- 1.07 with Na+ versus 2.58 +/- 0.81 mg/mg weight/s with NMG, p less than 0.02), it was unaltered during hypoxia (3.15 +/- 0.90 with Na+ versus 2.95 +/- 0.83 mg/mg weight/s with NMG, p = 0.3). The ratio of relaxation rates in the normal and low Na+ media correlated with the perfusate PO2 (r = 0.76, p less than 0.001). During normoxia and hypoxia, inhibition of the Na+,K+ pump by strophanthidin, which increases intracellular [Na+], reversibly enhanced the amplitude of the K+ contraction, even when the voltage-gated channels were blocked with verapamil.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1988

Relationship of dialysis modality and other factors to cognitive function in chronic dialysis patients.

To determine if dialysis modality may be an independent factor in the level of cognitive function in chronic dialysis patients, cognitive function was studied in 17 pairs of continuous ambulatory peritoneal dialysis (CAPD) and center hemodialysis (CHD) subjects matched for sex, age, diabetic status, and interval since dialysis onset. Data on current metabolic, medical, psychological, and vocational function status were obtained. Neuropsychological (NP) measures included the Number Cancellation Protocol (NCP), Trailmaking test forms A and B (TMT A, TMT B), Symbol Digit Modalities (SDM), and the Rey Auditory Verbal Learning Test (RAVLT). The CAPD subject group had consistently more efficient cognitive function than the CHD subject group. Regardless of modality, the groups of subjects under age 51 and those who were vocationally active had significantly better NP performance. No cognitive function differences were found in groups categorized by sex or duration of dialysis. Creatinine levels were more highly correlated with NP scores than were BUN levels, with higher creatinine levels associated with better cognitive function. Serum calcium, CO2, total protein, albumin, and SGOT levels also were correlated with NP scores. CAPD may be more effective than HD in reversing uremic encephalopathy by mechanisms mostly unrelated to serum creatinine and BUN levels. Longitudinal studies will be needed to determine if dialysis modality is an independent factor in the degree of reversal of uremic encephalopathy.

Adult↗
PubMed1988

Role of sarcoplasmic reticulum in arterial contraction: comparison of ryanodines's effect in a conduit and a muscular artery.

Ryanodine interferes with sarcoplasmic reticulum function in various types of muscle; in vascular smooth muscle, it can inhibit contractions that depend on sarcoplasmic reticulum calcium release, probably by depleting the sarcoplasmic reticulum calcium store. We tested ryanodine and calcium channel blockers (verapamil, diltiazem, and nitrendipine) on small rings of rat thoracic aorta (RA) and bovine tail artery (BTA) to determine the relative contributions of sarcoplasmic reticulum calcium release and gated calcium entry to contractions induced by norepinephrine, caffeine, and 100 mM K depolarization. Ryanodine blocked caffeine contractions in both tissues and attenuated norepinephrine responses (by 52% in RA, 14% in BTA) but minimally altered potassium contractions. Calcium channel blockers almost completely abolished potassium contractions and reduced norepinephrine contractions (by 45% in RA, 82% in BTA) but hardly affected caffeine responses. The blocking effects of ryanodine and calcium channel antagonists on the norepinephrine responses were additive. Ryanodine had no effect on baseline tension in the standard media; however, when calcium extrusion via Na-Ca exchange was inhibited by low external sodium (0-calcium, low-sodium solution), tension increased progressively after introduction of ryanodine. This indicates that the sarcoplasmic reticulum calcium released by ryanodine then accumulated in the cytosol and activated contraction; restoration of external sodium caused prompt relaxation. The smaller effects of caffeine and ryanodine in BTA indicate that sarcoplasmic reticulum plays a less important role in calcium control in this tissue, with gated calcium entry dominating. These functional findings are correlated with electron-microscopic evidence that BTA has about 60% less sarcoplasmic reticulum than does RA. Ryanodine appears to be a useful tool for determining the functional relevance of sarcoplasmic reticulum for contraction in different arterial smooth muscles.

Alkaloids↗
PubMed1987

Differences in matrix vesicle concentration among growth plate zones.

We studied the proximal tibial growth plates of 15-day-old mice to determine if matrix vesicle concentration varies among growth plate zones or between the pericellular and territorial matrix compartment and the interterritorial matrix compartment. Growth plates were examined by electron microscopy and divided into five zones: reserve zone (RZ), upper proliferative zone (UPZ), lower proliferative zone (LPZ), upper hypertrophic zone (UHZ), and lower hypertrophic zone (LHZ) which included the calcifying zone. We measured the diameter and volume fraction of matrix vesicles and calculated their numerical density and volume per cell and number per cell in the pericellular and territorial matrix and in the interterritorial matrix of each zone. In the pericellular and territorial matrix compartment, the matrix vesicle concentration progressively decreased from the RZ to the LHZ. Changes in matrix vesicle concentration in the interterritorial matrix followed a different pattern. Between the RZ and the UPZ, matrix vesicle numerical density declined slightly and then increased to peak values in the LPZ and UHZ, followed by a decline between the UHZ and the LHZ. These changes in matrix vesicle concentration paralleled previously reported changes in intramitochondrial calcium content, suggesting that matrix vesicle production in growth plate may be related to intracellular calcium concentration. The existence of the maximum concentration of matrix vesicles in the LPZ and UHZ longitudinal septa which do not mineralize followed by a decline in matrix vesicle concentration in the LHZ longitudinal septa which mineralize suggests that a high concentration of matrix vesicles may be needed to prepare the matrix for mineralization or to initiate mineralization and that matrix vesicles are depleted during mineralization.

Animals↗
PubMed1986

Morphometric analysis of chondrocyte hypertrophy.

In the hypertrophic zone of the cartilaginous growth plate, chondrocytes enlarge, assume a more spherical shape, and form a population of cells called the hypertrophic chondrocytes. The mechanisms that are involved in the formation of hypertrophic chondrocytes are poorly understood. Cell hypertrophy usually refers to an increase in cell size and volume associated with an increase in organelles. In this study, we sought to determine whether the formation of hypertrophic chondrocytes represents true cell hypertrophy associated with an increase in organelles or whether it is due to swelling and fluid accumulation. Morphometric analyses of electron micrographs were carried out to determine changes in cell number, cell volume, cell organelle volumes, and matrix volumes in the reserve zone, upper proliferative zone, lower proliferative zone, upper hypertrophic zone, and lower hypertrophic zone. Between the upper proliferative zone and the lower hypertrophic zone, the cells increased their mean volume more than 500 per cent. As they enlarged, their matrices altered; territorial matrix volume increased as its collagen content decreased, and interterritorial matrix volume decreased as its collagen content increased between the lower proliferative zone and the lower hypertrophic zone. Between the upper proliferative zone and the lower hypertrophic zone, the absolute volume per cell of endoplasmic reticulum, Golgi membranes, and mitochondria increased 126 per cent, while the volume of cytoplasm and nucleoplasm increased 779 per cent, apparently by accumulation of water. Cell organelles of the lower hypertrophic zone did not show the changes that are associated with cell injury or death. Thus, the synthesis of organelles contributed to chondrocyte enlargement, but the primary mechanism of cell enlargement was cytoplasmic and nuclear swelling.

Animals↗
PubMed1984

Investigations on the Na+, K+-pump in erythrocytes of patients with renal hypertension.

The ouabain-sensitive 42K+ flux from an artificial medium into erythrocytes was measured in 29 control subjects, 66 patients with chronic parenchymatous renal disease and in 32 subjects with primary hypertension. The ouabain-sensitive 42K+ influx was reduced in subjects with chronic renal disease by about 20%, even when they were normotensive. The reduction in these patients was greater than that in patients with essential hypertension. The changes in 42K+ influx and Na+ content with a decrease in the 42K+ influx/Na+ content ratio suggest an inhibition of the Na+ pump in the patients with chronic renal disease. The inhibition of the Na+ pump may be secondary to the hypervolaemia which we suggest is the initial event leading to renal hypertension.

Adult↗
PubMed1984

Coping with transient intellectual dysfunction after coronary bypass surgery.

In summary, we believe that the impact of our findings on the patient and clinician includes recognition and acknowledgment that transient cognitive dysfunction frequently follows coronary bypass surgery. With this recognition comes the reassurance to the patient and his family that it is a temporary phenomenon that should resolve in time. To help the patient comply with his postoperative instructions during this difficult time period, there should be individual, slow-paced presentation of material with intentional repetition of information to help him remember the specific details of his postoperative instruction; the individual most involved with assisting in the patient's postoperative recovery should be included in all teaching sessions; and instructive audiovisual material should be used in postoperative home care.

Adaptation, Psychological↗
PubMed1983

Laboratory diagnosis of lupus inhibitors: a comparison of the tissue thromboplastin inhibition procedure with a new platelet neutralization procedure.

The introduction of the activated partial thromboplastin time (APTT) as a screening test has resulted in increased recognition of circulating anticoagulants. The most frequently encountered inhibitor is the lupus-type anticoagulant. However, criteria for differentiation of this inhibitor are not well-established. We evaluated the ability of two procedures, tissue thromboplastin inhibition (TTI) and a new platelet neutralization procedure (PNP), to differentiate between various types of coagulation inhibitors. The TTI, widely used for the diagnosis of lupus anticoagulants, proved to be nonspecific. The PNP specifically separated lupus-type inhibitors from Factor VIII, X, and V inhibitors. The PNP may be a useful test for the diagnosis of lupus anticoagulants.

Blood Coagulation↗