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Biomedical subjects

K Miller

Publications and source records attributed to K Miller.

At least 397 records · Page 22Linked to original sources

[Itching following therapy with hydroxyethyl starch (HES) in otoneurological diseases].

It is generally assumed, that a disturbance of microcirculation is the common pathogenetic end factor in various cochleovestibular disorders of different etiology. Therefore improvement of microcirculation is an important therapeutic goal. Several studies demonstrated, that hydroxyethylstarch (HES) has better haemorheological effects than Dextran and less side effects. For this reason we have changed the therapy with Dextran since 1987 to hydroxyethylstarch in several oto-neurological disorders (as sudden hearing loss, neuronopathia vestibularis, idiopathic facial palsy). As after the therapy with HES--generally after dismissal from the ENT-department--some patients complained of general pruritus, so we performed a retrospective study with a standardized interview-protocol. Of 481 treated patients we investigated 237 (49%): of 149 patients treated with HES 200/0.5, 43 patients (28.8%) complained of pruritus; from 88 patients treated with Dextran 40, only 5 patients (5.7%) reported pruritus. The difference is significant (p less than 0.0001). In nearly half of the patients (more than 40%) the pruritus started in normal skin 1 to 3 weeks after the HES-therapy and lasted for 6 weeks to 6 months; the itching was very resistant to therapy (f.e. with antihistaminics). We want to draw the attention to this possible, in the literature until now quite neglected, for some patients extremely uncomfortable and socially embarrassing side effects after HES-therapy when given in relatively high doses. It is therefore suggested therapeutic recommendations should be developed to prevent this undesired side effect.

Cochlear Diseases↗

[Ileal neobladder].

Since April 1986, 227 patients received an ileal neobladder at our institution. Of these patients 206 underwent simultaneous radical cystectomy for bladder cancer, and 21 received a bladder augmentation. The mean postoperative follow-up ranges from 3-71 months. Perioperative mortality was 2.55 percent, 15 percent of the patients died later than 2 months postoperatively, 13.4 percent due to tumor progression, 1.5 percent because of pneumonia, severe metabolic acidosis, myocardial infarction and apoplexia. Day and night continence was preserved in 77 percent of the patients with a follow-up of more than 2 years; severe stress incontinence was found in 2 patients, and night time incontinence needing some external device in 4.6 percent. 11.5 percent with mild stress incontinence do not require further treatment. Our experience with this relatively simple procedure is excellent: the need for re-operation is low and the high reservoir capacity results in early continence in most cases. This concept offers a genuine alternative to any form of cutaneous urinary diversion with an incidence of complications not higher than after standard supravesical urinary diversion.

Adult↗

An immunohistochemical study of mesothelial cell seeding for knitted Dacron.

Six greyhounds underwent bilateral femoral artery replacement with knitted Dacron, one side seeded with omental digest at graft preclotting, the other acting as an unseeded control. Grafts were removed at 24 hours and two months. Tissue was examined using a monoclonal antibody (MNF116) directed against a broad range of human cytokeratins to differentiate mesothelial cells (MC) from microvascular endothelial cells (MEC), which stained only with a polyclonal antibody directed against von Willebrand Factor (anti-vWF). Cells released from omentum by collagenase stained with MNF116 and reacted poorly with anti-vWF. Identical cells were observed to be within the interstices of seeded but not control knitted Dacron. Few remained in seeded grafts (n = 2) removed at 24 hours and none at two months (n = 4).

Animals↗

[Kidney carcinoma in Bourneville-Pringle disease].

We report a case of renal cell carcinoma in a 28-year-old woman with Bourneville-Pringle's disease. A review of the literature revealed 16 cases of renal cell carcinoma associated with tuberous sclerosis. The incidence of angiomyolipoma among patients with Bourneville-Pringle's disease is cited in the literature as 40-80%, but this is based solely on two early publications, while other publications suggest a considerably higher incidence of renal cell carcinoma in Bourneville-Pringle's disease, as in other phacomatoses (Hippel-Lindau's disease). We therefore recommend screening for renal cell carcinoma in patients with Bourneville-Pringle's disease.

Adult↗

Transferrin receptors promote the formation of clathrin lattices.

Gold conjugates have been used to quantitate human transferrin receptors (hTfnRs) on transfected chick embryo fibroblasts. No relationship could be found between the number of hTfnRs and the number of clathrin-coated pits. However, hTfnRs are also associated with flat clathrin lattices that lie outside invaginated pits. With increasing levels of receptor expression, the density of hTfnRs within flat lattices increases, and at the highest levels of expression the total area of flat lattice increases up to 3-fold. These results show that increased receptor numbers can promote clathrin lattice growth and suggest that the recruitment of receptors like hTfnRs is an essential step in lattice construction. We conclude that the process of invagination, which gives rise to coated pits, is regulated separately.

Animals↗

Assembly of Octopus dofleini hemocyanin. A study of the kinetics by sedimentation, light scattering and electron microscopy.

The kinetics of association of Octopus dofleini hemocyanin subunits to form the native decameric molecule have been studied with a combination of sedimentation, light scattering and electron microscopy. The reaction, initiated by addition of magnesium, is relatively slow, requiring hours to reach completion, with monomer and decamer as predominant molecular species throughout. Analysis of the light-scattering data, including stopped-flow studies, reveals an initial lag period in the reaction, followed by a second-order process that is rate limiting. The lag period depends on both protein and magnesium ion concentration. Electron microscope studies reveal intermediates in the process, and support a model of assembly in which nucleation begins at the dimer level. Theoretical models for the process are compared.

Animals↗

Occurrence of Pneumocystis carinii organisms in a peritoneal effusion from a patient with the acquired immunodeficiency syndrome.

We describe a unique case of Pneumocystis carinii organisms within a peritoneal effusion of a patient with acquired immunodeficiency syndrome (AIDS). The patient, a 28-yr-old homosexual male with profound immunosuppression, presented with splenomegaly and ascites. A peritoneal tap was performed for diagnostic purposes. Cytologic examination of the cytospin specimen showed reactive mesothelial cells along with aggregates of debris reminiscent of the foamy exudates seen in the alveoli of lungs infected with the Pneumocystis carinii organism. A modified methanamine silver stain was performed and revealed the presence of scattered Pneumocystis carinii in the specimen. Extrapulmonary Pneumocystis carinii infection is occasionally seen in AIDS, but we could find no other reports of its detection in peritoneal fluid.

Acquired Immunodeficiency Syndrome↗

Photodynamic therapy of bladder cancer--uptake and phototoxicity of photosan in vitro.

The uptake of photosan and the intracellular sites of photoradiation-induced damage were investigated in vitro in bladder carcinoma cells and in normal bladder cells. Cells were examined by phase contrast, fluorescence and electron microscopy. The concentration of photosan, measured in microgram/10(6) cells, showed a good correlation to the incubation time. At all incubation times, control cells showed a lower uptake when compared with tumor cells. Following photodynamic therapy (PDT), phase-contrast microscopy revealed marked changes in tumor cells, whereas only minor effects could be detected at the cell membrane of the control cells. Following PDT, most of the investigated cells showed changes of the mitochondria and cytoplasma. These changes consisted of dissolution of the cristae, predominantly in the central part of the mitochondria. Twenty-four hours after PDT the shape of the mitochondria had changed markedly and the cristae were found to be completely destroyed. Moreover, the cystoplasma showed numerous vacuoles, and the number of mitochondria was decreased compared to non-treated cells.

Antineoplastic Agents↗

Does pancreas transplantation influence the course of diabetic retinopathy?

Between March 1983 and December 1989 a total of 57 pancreas transplants were performed in 54 patients, of whom 49 also received a kidney for end-stage diabetic nephropathy. Of the surviving 44 patients, 39 had regular pre-operative and post-operative ophthalmological examinations. Diabetic retinopathy was classified according to the original "Early treatment diabetic retinopathy study" (ETDRS) protocol. At the time of this analysis a total of 25 patients had a functioning pancreas transplant and 23 of them also a functioning renal allograft after a mean observation time of 43.2 months (Group 1). They were all free of exogenous insulin, HbA1c being 6.2% (5.1-6.9%; normal value 4.2-5.9%). Fourteen patients in Group 2 lost their pancreas transplant during the first four years. Six of them still have a functioning renal allograft, four patients regularly undergo hemodialysis. Mean HbA1c is 7.5% (5.7-9.2%). Before transplantation, grade of retinopathy according the ETDRS protocol was 6.7 (2-10) in group 1 patients and 7.9 (3-10) in group 2. In group 1 patients stabilisation of retinopathy was observed in 33 eyes (73.3%) and clear improvement achieved in 4 eyes (8.8%). Detoriation occurred in 8 eyes (17.7%) only. In group 2, 14 eyes (54%) remained stable, whereas progression of the disease continued in 12 eyes (46%). From these results it is concluded that the course of diabetic retinopathy is positively influenced by successful pancreas transplantation.

Adult↗

Sister-chromatid exchange in human B- and T-lymphocytes exposed to bleomycin, cyclophosphamide, and ethyl methanesulfonate.

Sister-chromatid exchange (SCE) frequencies were investigated in mitogen-stimulated cultures of highly purified human peripheral blood B- and T-lymphocytes exposed to bleomycin (BM), cyclophosphamide (CP), or ethyl methanesulfonate (EMS). In untreated controls, T-lymphocytes showed twice as many SCEs as B-lymphocytes. CP (with metabolic activation) and EMS significantly increased the SCE frequencies. EMS induced a similar, dose-dependent SCE increase in both cell populations, whereas CP induced more SCEs in T- than in B-lymphocytes. No clear SCE increase was found in B- and T-lymphocytes treated with BM.

B-Lymphocytes↗

Clastogenic effects of bleomycin, cyclophosphamide, and ethyl methanesulfonate on resting and proliferating human B- and T-lymphocytes.

The effects of bleomycin (BM), cyclophosphamide (CP), and ethyl methanesulfonate (EMS) on the frequencies of chromosomal aberrations were tested in mitogen-stimulated highly purified human B- and T-lymphocytes. In unstimulated G0/G1 B- and T-lymphocytes the clastogen induction of chromosome fragments was investigated in prematurely condensed chromosomes (PCC) induced by cell fusion with xenogenic mitotic cells. BM, CP (with metabolic activation), and EMS induced a significant increase in chromosome aberrations in proliferating human B- and T-lymphocytes. There were no significant differences in the BM-induced aberration rates between the cell populations. CP and EMS induced more aberrations in T- than in B-lymphocytes. In the PCC tests, BM-exposed G0/G1 lymphocytes showed dose-dependent high yields of chromosome fragments. No significant differences between B- and T-lymphocytes were observed. CP and EMS induced no clear increase in fragments in either cell population.

Adult↗

The murine local lymph node assay: results of an inter-laboratory trial.

The local lymph node assay is a novel predictive test for the identification of contact allergens. The collaborative study reported here was performed to evaluate the reliability of the method when performed in independent laboratories. Eight chemicals were examined in each of 4 participating laboratories and results compared with predictions of skin-sensitizing activity made from concurrent Magnusson and Kligman guinea-pig maximization tests performed in a single laboratory. The local lymph node assay has as its theoretical basis the fact that contact allergens induce T-lymphocyte proliferative responses. In practice, predictions of contact-sensitizing potential are made following measurement of proliferation in lymph nodes draining the site of exposure to chemical, and derivation of a stimulation index using control values as the comparator. Although in the present study there was some variation between laboratories with respect to the absolute stimulation indices recorded, it was found that with all chemicals each laboratory made the same predictions of sensitizing activity. Six chemicals (2,4-dinitrochlorobenzene, formalin, eugenol, isoeugenol, p-phenylenediamine and potassium dichromate) yielded positive responses, and two (methyl salicylate and benzocaine) were negative, in each laboratory. Furthermore, with 7 of the 8 chemicals tested there was no significant difference between laboratories in terms of the characteristics of the dose-response relationships recorded. With the exception of one chemical (benzocaine), predictions made with the local lymph node assay were in accord with those derived from guinea-pig maximization tests. These inter-laboratory comparisons demonstrate that the local lymph node assay is a robust and reliable method for the identification of at least moderate and strong contact allergens.

Allergens↗

A new algorithm for minimizing pacemaker polarization artifact: universally applicable in permanent pacing systems.

Polarization artifacts that result from pacing may interfere with analysis of paced evoked responses during, e.g., automatic threshold tracking. We have developed a method for reduction of such artifacts that relies on the introduction of pacing stimuli during the refractory period of unipolar or bipolar paced captured beats after previous identification of a refractory period "template" or baseline. The refractory pacing stimuli cannot capture the heart, and thus any deviation from the template is due to polarization artifact alone. The artifact amplitude is measured and the precharge duration of the triphasic stimulus waveform is changed each time until artifact is minimized, as detected by repeated reversals in the polarity of the polarization artifact. In a series of 11 patients with unipolar and bipolar permanent pacing leads, mean initial artifact before balancing was 1.44 +/- 0.84 mV, which was reduced to 0.44 +/- 0.30 mV after balancing (P = 0.001). Initial precharge duration was 3.2 msec by design; mean final precharge duration was 3.30 +/- 0.34 msec. This algorithm is universally applicable in permanent pacing systems, as it is valid in unipolar and bipolar pacing and it does not require an intrinsic cardiac rhythm.

Algorithms↗

Automatic reduction of stimulus polarization artifact for accurate evaluation of ventricular evoked responses.

The ventricular evoked response, the cardiac depolarization generated in response to a pacing stimulus, is potentially useful as a sensor for rate responsive pacing and automatic threshold tracking. It is necessary to minimize the polarization artifact that results from pacing in order to sense cardiac depolarizations from the same electrodes that pace the heart. To accomplish this, a triphasic stimulus waveform consisting of precharge, stimulus, and postcharge was used. An algorithm was developed that introduced pacing stimuli during the refractory period of sensed beats, when cardiac depolarization could not occur by definition and polarization artifact could be evaluated. Precharge duration was varied until the amplitude of the polarization artifact was small compared to the evoked response. In 18 patients with temporary electrode catheters, polarization artifact was reduced from 6.8 +/- 3.4 mV to 1.9 +/- 1.1 mV after balancing (P less than 0.005). Initial precharge duration was 3200 mu sec and the mean final precharge duration was 3551 +/- 516 mu sec. In 14 patients with permanent bipolar pacing leads, polarization artifact was reduced from 3.2 +/- 3.5 mV to 0.7 +/- 0.6 mV (P less than 0.025). Final precharge duration averaged 3440 +/- 310 mu sec. Under a wide variety of pacing conditions, this algorithm simply and quickly reduces polarization artifact to a minimum to allow accurate analysis of evoked responses.

Algorithms↗

Effects of fetal anemia on PO2 difference between uterine venous and umbilical venous blood.

In the fetus, the functional equivalent of the alveolar-arterial blood PO2 difference is the uterine venous-umbilical venous blood PO2 difference. Generally, factors that affect one of the venous blood PO2s produce equivalent effects on the other. We previously showed that fetal anemia produces increases in umbilical venous blood PO2. To determine whether this increase was associated either with equivalent increases in uterine venous blood PO2 or with reductions in the uterine venous-umbilical venous PO2 difference, we studied eight chronically catheterized pregnant sheep and fetal lambs. Measurements of O2 gas tensions and O2 saturations, uterine and umbilical blood flows, and uterine, fetal, and placental O2 consumptions were made in animals with normal fetal hematocrits and during reductions in fetal hematocrit of 35% (moderate fetal anemia) or 60% (severe fetal anemia). Fetal anemia produced reductions in the uterine venous-umbilical venous blood PO2 difference; in some cases the PO2 difference was less than 2 mmHg (compared with normal values of 20 mmHg). The development of both moderate and severe fetal anemia had no effect on uterine and umbilical blood flows or placental O2 consumption but did reduce total uterine and fetal O2 consumption. These data indicate that fetal anemia induces changes in placental gas transport. These changes may be due to improvements in gas diffusion, reductions in perfusion mismatching, or reductions in vascular shunting. Our data further indicate that placental O2 consumption rate, which is high in normal pregnant sheep, plays no role in the maintenance of the uterine venous-umbilical venous blood PO2 difference in pregnant sheep.

Anemia↗