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Biomedical subjects

J Miller

Publications and source records attributed to J Miller.

At least 811 records · Page 45Linked to original sources

In vivo and in vitro induction of class II molecules on canine renal cells and their effect on the mixed lymphocyte kidney cell culture.

Canine renal cortical cells were obtained by collagenase extraction from allogeneic haploidentical, donor-recipient beagle littermate pairs and from unrelated mongrels. Peripheral blood lymphocytes (PBL) of the mongrels, as well as of one member of the beagle pair that exhibited high mixed lymphocyte culture (MLC) reactivity against the other were also stimulated by renal cortical cells derived from both normal and rejected transplanted kidneys in mixed lymphocyte kidney cell culture (MLKC). A moderate autologous MLKC reactivity occurred in response to normal renal cortical cells. However, rejected kidney cortical cells were markedly more stimulatory than normal renal cortical cells in both allogeneic and autologous MLKC reactions. Lymphocytes from donor animals responded more strongly to autologous cortical cells isolated during rejection of the transplant than to cortical cells from normal allogeneic kidneys. Recipient infiltrating lymphocytes and propagated T cell lines extracted from the rejected kidney also responded more strongly than PBL to cortical cells from this kidney. Gradient purification of the stimulating cortical cells resulted in one virtually pure preparation of distal tubular epithelial cells, as demonstrated by immunohistochemical stains and electron microscopy, which caused enhanced stimulation in MLKC. Class II marker analysis of the canine renal cells from rejected kidneys revealed the presence of these molecules on tubular cells that were absent on normal kidney cells. A 16-hr coculture of normal renal cortical cells not exhibiting class II surface markers in the presence of allogeneic or autologous lymphocytes induced the expression of these molecules, associated with an increased stimulatory capacity. This also occurred to a lesser extent with MLC (and MLKC) cell culture media supernatants. However, the low level of class II expression by all the various gradient-purified fractions in the absence of rejection or coculture, and the increased but equivalent expression on all fractions after coculture did not correlate with the preferential stimulatory capacity of the purified distal tubular cell layer. We conclude that two signals are necessary for the MLKC reaction, one involving tissue (kidney)-associated epitopes (the nominal antigen demonstrated in this study to be present in normal distal tubular cells), the other involving class II molecules as costimulatory (amplification) moieties.

Animals↗

Renal transplantation in systemic lupus erythematosus: one center's experience.

A retrospective analysis of 15 renal transplant patients with end-stage renal disease (ESRD) secondary to systemic lupus erythematosus (SLE) was performed. Overall actuarial patient and graft survival at 6 years was 93 and 84%, respectively. Recipients of HLA-identical kidneys did not appear to be at increased risk of allograft failure due to rejection or recurrent disease. Two biopsy-proven cases of recurrent lupus involving the allograft were observed and are discussed. Those patients currently experiencing excellent graft function (creatinine less than 2 mg/dl) had a significantly longer pretransplantation dialytic interval than the group whose most recent serum creatinine exceeds 2 mg/dl (or returned to dialysis). Posttransplantation monitoring of antinuclear antibody, antidouble-stranded DNA, C3, C4, and circulating immune complexes was not predictive of renal or extrarenal disease activity. Renal transplantation should be considered an excellent therapeutic modality for the lupus patient with ESRD, although an interim period on dialysis of at least 1 year seems warranted.

Follow-Up Studies↗

Echocardiographic left ventricular mass and function in the hypertensive baboon.

Nonhuman primates with chronic systemic hypertension provide an ideal model for studying structural and functional alterations associated with compensatory cardiac hypertrophy. Since noninvasive techniques are useful for the longitudinal evaluation of these animals, we sought to critically asses the M-mode echocardiographic estimation of left ventricular mass in the baboon and to characterize estimates of left ventricular size and function in baboons with chronic renal hypertension. In 23 baboons (12 normotensive, 11 chronic hypertensive), M-mode echocardiography-determined left ventricular mass was 73 +/- 13 (SE) g as compared with the necropsy weight of 69 +/- 11 g (p = NS), and the correlation was excellent (r = 0.94). When 30 chronically hypertensive baboons being observed longitudinally were compared with 10 normotensive control animals studied under identical conditions, several differences were noted in measures derived from echocardiography and high fidelity pressure measurements. Left ventricular systolic pressure was considerably higher in the hypertensive baboons (113 +/- 23 vs 90 +/- 11 mm Hg; p less than 0.001), as was left ventricular mass (148 +/- 60 vs 103 +/- 38 g; p less than 0.03). However, since the ratio of posterior wall thickness to cavity dimension was larger in the hypertensive baboons (0.52 +/- 0.17 vs 0.43 +/- 0.07; p less than 0.05), this concentric hypertrophy maintained values for left ventricular meridional stress at the same level as in the control animals. Despite matched heart rate and left ventricular stress, the rates of change in left ventricular dimensions and wall thickness in systole and diastole were all approximately 25% less in the hypertrophied baboons.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Long-term cardiopulmonary sequelae in patients with sleep apnea and chronic lung disease.

Both obstructive sleep apnea and chronic lung disease can be associated with intermittent or chronic hypoxemia leading to pulmonary hypertension and cor pulmonale. When these problems coexist, it is possible that the cardiopulmonary effects are additive. We hypothesized that hemodynamic disturbances in patients with apnea and lung disease would be more severe than in those with apnea alone, and that hemodynamic improvement should follow apnea cure, but perhaps at a slower rate than in those with apnea alone. To test these hypotheses, we prospectively followed 24 patients with sleep apnea syndrome. They were divided into 3 nonrandomized groups. Nineteen patients had both apnea and lung disease. Nine of these agreed to curative tracheostomy (Group 1). The other 10 subjects (Group 2) refused tracheostomy but accepted noncurative therapies, including nocturnal oxygen (n = 9), uvulopalatopharyngoplasty (n = 2), and protriptyline (n = 4). Five subjects with apnea but without clinically obvious lung disease received tracheostomies (Group 3). Subjects were followed at yearly intervals (mean follow-up, 27.2 months) with radionuclide motion studies and, in 15 of 24 who consented, right heart catheterization. The 3 groups did not vary with respect to age, percent ideal weight, or severity of apnea symptoms. The severity of right-sided hemodynamic dysfunction in the group with apnea but no obvious lung disease was less than that in the 2 groups with lung disease. A substantial decrease in pulmonary artery pressure (p = 0.056) and significant improvement in right ventricular ejection fraction occurred in the tracheostomized group with both apnea and lung disease. Pulmonary vascular resistance decreased in both groups receiving tracheostomy.(ABSTRACT TRUNCATED AT 250 WORDS)

Chronic Disease↗

Nocturnal oxyhemoglobin desaturation in COPD patients with arterial oxygen tensions above 60 mm Hg.

We studied 152 COPD patients with a daytime PaO2 greater than or equal to 60 mm Hg using formal polysomnography (EEG, airflow, respiratory muscle movement, ear oximeter) to detect the presence of nocturnal, nonapneic, oxyhemoglobin desaturation. Nine subjects were disqualified by the unexpected discovery of sleep apnea, as were another eight because they could not sleep in the laboratory setting. Of the remaining 135 subjects, 37 (27 percent) desaturated below a baseline sleep saturation of 90 percent for five minutes or more, reaching a nadir saturation of at least 85 percent. Anthropomorphic, pulmonary function, and historic factors comparing desaturators and nondesaturators failed to separate the groups. Awake PaO2 at rest in the desaturators was significantly lower than in the nondesaturators. The PaCO2 was higher in the desaturators. Reversibility of the desaturation phenomenon was demonstrated in three patients during subsequent polysomnographic studies following periods of clinical improvement. Continuous oxyhemoglobin monitoring during sleep remains the only reliable tool for detecting nocturnal desaturation.

Aged↗

Evidence of preliminary response preparation from a divided attention task.

In a divided attention situation, preliminary response activations produced by stimuli on one channel were revealed through their effects on responses to stimuli on a secondary probe channel. Subjects performed concurrent but independent four-choice reaction-time tasks using the same four response fingers (middle and index fingers on both hands). In the main task, targets were large and small Ss and Ts, and medium-sized Ss and Ts sometimes appeared as distractors. Targets in the probe task were squares differing in location. A response to a probe square was faster if a distractor letter presented just before it had the same name as the target letter corresponding to that square (i.e., assigned to the same response key) than if the distractor letter had a different name--a result indicating that distractor letters cause partial response preparation. The timecourse of the effect demonstrated that preparation was based on preliminary information about distractor name that was available before distractor size had been determined. The results support models in which response preparation can sometimes begin before stimulus recognition has finished.

Attention↗

Effects of fentanyl and sufentanil on peripheral mammalian nerves.

The effects of fentanyl and sufentanil on peripheral nerves were evaluated in isolated sheathed and desheathed rabbit vagus nerves. The action potential amplitudes of A and C fibers were recorded before and after a 30-min exposure to 50 and 100 micrograms/ml of fentanyl and sufentanil. A reversible decrease in the action potential amplitude of A fibers in desheathed nerves was observed after exposure to 100 micrograms/ml of each drug. The action potential amplitude of C fibers was also decreased but not to the same degree as was the A fiber action potential. Pretreatment with naloxone failed to block the reduction in action potential amplitude produced by the two opiates. No evidence of irreversible conduction blockade indicative of local neural toxicity was seen in these studies. The results suggest that high concentrations of fentanyl and sufentanil may exert a weak local anesthetic-type action on peripheral nerves.

Action Potentials↗

SKF 104353, a high affinity antagonist for human and guinea pig lung leukotriene D4 receptor, blocked phosphatidylinositol metabolism and thromboxane synthesis induced by leukotriene D4.

SKF 104353 (2(S)-hydroxyl-3(R)-carboxyethylthio)-3-[2-(8-phenyloctyl) phenyl] propanoic acid) is a synthetic structural analog of leukotrienes D4 and E4 (LTD4, LTE4). This compound binds to guinea pig and human lung LTD4 receptors with affinities (Ki) of 5 +/- 2 and 10 +/- 3 nM, respectively. The Ki values of a reference compound, FPL 55712, were 2200 and 4500 nM, respectively, approximately 400- and 500-fold less effective than SKF 104353. LTD4- and LTE4-induced biosynthesis of thromboxane B2 has been shown to be mediated by LTD4 receptors in guinea pig lung in vitro. SKF 104353 did not induce synthesis of TxB2 in this system at concentrations of 1-20 microM. When SKF 104353 and increasing concentrations of LTD4 were incubated with guinea pig lung, the dose response curve of LTD4-induced TxB2 biosynthesis was shifted to the right with a -log[KB] = 8.4 +/- 0.2. LTD4-induced phosphatidylinositol (PI) hydrolysis in guinea pig lung has been shown to be the major signal transduction mechanism. In this system, SKF 104353 (1-20 microM) did not promote PI hydrolysis. Pretreatment of the [3H]myo-inositol-labeled guinea pig lung with SKF 104353 shifted the LTD4-induced PI hydrolysis dose response curve to the right, indicating that SKF 104353 inhibited LTD4 receptor-mediated intracellular second messenger formation. These results demonstrate that SKF 104353 is a high affinity, specific LTD4 receptor antagonist. It inhibited LTD4-induced PI hydrolysis and TxB2 biosynthesis in guinea pig lung. SKF 104353 may prove to be an important research tool for research on the activities of leukotrienes and of value therapeutically in the treatment of leukotriene-mediated diseases.

Animals↗

The impact of nursing diagnoses in a long-term care setting.

Nursing diagnosis as a critical component of the nursing process provides a common taxonomy to describe problems that nurses can treat and is a convenient, logical way to reference nursing standards. Theory is translated into practice with the use of population-specific prototype care guides and a written orders system. Nurses in leadership are responsible for providing the necessary resources to promote professional growth and facilitate desired change. Recommendations to assist with the implementation of nursing diagnosis are identified in Table 1. The system is dependent on staff nurses' professional commitment to learning and willingness to actively participate in change. Involvement of staff nurses continues to be a critical factor in the improvement of nursing practice.

Hospital Bed Capacity, 500 and over↗