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C Lutz

Publications and source records attributed to C Lutz.

34 records · Page 2Linked to original sources
PubMed1995

Longitudinal and radial differences in the subsurface cisternal system in the gerbil cochlea.

Many features of cochlear anatomy vary systematically radially and longitudinally within the organ of Corti. There is limited evidence that along the longitudinal axis of the cochlea the thickness of the subsurface cisternal system in the outer hair cells (OHCs) changes. Similarly a radial gradient may exist. The thickness of the subsurface cisternal system in OHCs was measured in gerbils to determine if there are differences between the three rows of OHCs and in OHCs in different locations along the length of the organ of Corti. The results suggest that there is a longitudinal as well as a radial gradient of subsurface cisternal system thickness. These gradients are the inverse to those for efferent innervation of OHCs. It is possible that these differences may contribute to the increased susceptibility to trauma and ototoxic compounds characteristic of the innermost and basalmost OHCs.

Analysis of Variance↗
PubMed1995

Analysis of T cell receptor-gamma gene rearrangements by denaturing gradient gel electrophoresis of GC-clamped polymerase chain reaction products. Correlation with tumor-specific sequences.

We describe a modified denaturing gradient gel electrophoresis (DGGE) procedure with a 40-nucleotide GC clamp in the polymerase chain reaction to improve resolution in amplifying T cell receptor-gamma (TCR-gamma) rearrangements. DNA from 46 cases of lymphoblastic leukemia/lymphoma, 5T cell lines, 2 B cell lines, 7 normal lymphocytes, and 3 cases of Hodgkin's disease was amplified by polymerase chain reaction. In addition, 20 cases of paraffin-embedded T cell lymphomas and 5 cases of reactive hyperplasia were also studied. Clonal TCR-gamma rearrangements were identified on DGGE by the presence of a predominant band. Results obtained from 5 T cell lines and 12 lymphoblastic leukemia/lymphomas containing known TCR-gamma gene rearrangements revealed 100% concordance in detecting clonal rearrangements between DGGE and traditional Southern blot analysis. Of the remaining 34 lymphoblastic leukemia/lymphoma cases studied by DGGE alone, 30 were positive. DGGE analysis of 10 lymphoblastic leukemia/lymphoma cases with known group IV gamma to J gamma 1 or J gamma 2 rearrangement sequences confirmed that the electrophoretic migration was dependent on the tumor-specific rearranged TCR-gamma sequence. In addition, 17 of 20 cases of paraffin-embedded T cell lymphomas were positive by DGGE, 6 of which had the clonal population also identified in fresh tissue DNA. DGGE analysis of GC-clamped polymerase chain reaction products can provide a way to more accurately detect TCR-gamma clonality of lymphoid tumors and can be applied to archival tissues.

Base Sequence↗
PubMed1994

Selection and characterization of 5-fluoroorotate-resistant Plasmodium falciparum.

Previous studies have shown that 100 nM 5-fluoroorotate (5-FO) is sufficient to block the in vitro proliferation of Plasmodium falciparum without causing toxicity to mammalian cells. In anticipation of potential drug resistance, a study was undertaken to identify P. falciparum cells that would proliferate in the presence of 5-FO. About 3 x 10(6) UV-irradiated as well as nonirradiated parasites were subjected to a one-step selection with 100 nM 5-FO both in the absence and in the presence of preformed pyrimidines (uracil, uridine, thymine, and thymidine). The P. falciparum cells that emerged after 3 weeks were cloned, and the 90% inhibitory concentration of 5-FO for the cloned cells was found to be 100- to 400-fold greater than that for the parent cell line. Two clones that were further characterized retained resistance to 5-FO even after prolonged propagation in culture without drug pressure. Since the mutants were not cross-resistant to 5-fluorouracil or to dihydrofolate reductase inhibitors, it was unlikely that alteration of thymidylate synthase or overproduction of the bifunctional dihydrofolate reductase-thymidylate synthase was responsible for 5-FO resistance. Similarly, resistance was not due to the expression of a pyrimidine salvage pathway since the cells were not pyrimidine auxotrophs, they did not show increased utilization of pyrimidine nucleosides, and they did not show increased susceptibility to 5-fluoropyrimidine nucleosides. When the selection experiments were repeated, without mutagenesis, in the presence of 10(-7) M 5-FO with fewer than 10(6) parasites or in the presence of more than 10(-7) M 5-FO with more than 10(8) parasites, viable mutants could not be recovered from the cultures. The implications of these findings for the in vivo use of 5-FO for malaria chemotherapy are discussed.

Animals↗
PubMed1992

Analysis of VH251 gene mutation in chronic lymphocytic leukemia (CLL) and normal B-cell subsets.

B-cell chronic lymphocytic leukemia (CLL) is the malignant, monoclonal equivalent of a human CD5+ B cell. Previous studies have shown that the VH and VL genes rearranged and/or expressed in CLL have low and random mutations. In this study, however, we have found that the rearranged VH251 gene, one of the three-membered VH5 family, has extensive and selective mutations in B-CLL cells. Somatic mutation at the nucleotide level is 6.03%, and there is a high ratio of replacement to silent mutation in CDRs relative to FWRs. CDR1 mutation is particularly prevalent, and interchanges often lead to acquisition of charge. In VH251 rearranged in CD5+ and CD5- cord-blood B cells, adult peripheral-blood B cells and EBV-transformed CD5+ B-cell lines, the somatic mutation levels are much lower (0.45%, 0.93%, and 1.92%, respectively) with concomitantly lower replacement to silent ratios in CDRs relative to FWRs. The extensive and highly selective somatic mutation of VH251 used in CD5+ CLL cells strongly suggests that part of CLL is generated under the influence of antigen selection and stimulation.

B-Lymphocyte Subsets↗
PubMed1992

Evaluation of the Multi-Test device for immediate hypersensitivity skin testing.

Test-to-test reproducibility, user variability, and the effect of positive reactions on adjacent negative sites were evaluated for the Multi-Test skin testing device. Twenty-five subjects had skin tests with 24 histamine (1 mg/ml), four glycerosaline controls, and four "dry" controls on two testings 7 days apart. To assess reproducibility from large and smaller histamine reactions and/or their effect on adjacent negative controls, 10 of the 25 subjects were retested once with the same testing format, but histamine at 10 mg/ml was substituted. To determine whether large allergen reactions affect adjacent negative controls differently than histamine reactions, 24 additional patients were retested on arms and back with negative controls adjacent to allergens to which they had prior 3+ to 4+ skin test reactions. Conclusions from 2688 skin tests on 49 patients are as follows: large (mean > 10 mm) histamine reactions reproduced better than smaller (mean < 7 mm) responses--coefficients of variation were 12.3 and 21.4 respectively. A 14% user variability occurred when comparing mean wheal sizes from histamine produced by each nurse and 1.2% when comparing their coefficients of variation. Neither small histamine reactions nor large reactions from histamine and allergens affected adjacent negative controls. We conclude that Multi-Test is a highly reliable skin testing technique that provides good reproducibility of results and low user variability.

Adolescent↗
PubMed1992

Effect of increasing dosage of an inhaled beta-2 specific agonist on pulmonary function, tremor, and cardiovascular indices.

In this investigation we evaluated the effect of increasing dosage, using an inhaled beta-2 specific agonist, pirbuterol, administered by a metered dose inhaler on pulmonary function, tremor, and cardiovascular parameters in nonacute adult asthmatic patients. This study was conducted with a randomized crossover study design in which each individual was administered a single dose of pirbuterol (0.4, 0.8 and 1.2 mg) [corrected] on separate days. Measurements of pulmonary function, tremor (by accelerometer readings), electrocardiogram, blood pressure and pulse were obtained at 0, 15, 30, 60, 90, 120, and 180 minutes following test drug administration where appropriate. These measurements were performed until there had been no change from baseline in tremor by 60 minutes or return of tremor measurements to within 15% of baseline for up to six hours. The data demonstrated that the onset of bronchodilator effectiveness had occurred by 15 minutes after test drug administration (the first testing time). The peak percent change from baseline for the FEV1 occurred at 60 minutes after administration for all three test doses. The duration of activity was never truly established as there was no significant difference between any of the potential side effects for any of the three test drugs at any testing time period. This study demonstrated that with the beta-2 specific agent pirbuterol, administered as a metered dose inhaler, there is little risk of development of skeletal muscle or cardiovascular toxicity when as much as three times the recommended dose is used in a single usage, and that there is no direct correlation between the onset, peak, and/or duration of tremor with the onset and peak of bronchodilator efficacy with this agent.

Adolescent↗
PubMed1991

Analysis of breath sounds in normal and asthmatic children and adults using computer digitized airway phonopneumography (CDAP).

Analysis of breath sounds using the stethoscope is a major part of physicians evaluation of their patients. However, the use of a stethoscope is often inadequate to give quantitative measurements of the clinical state of the individual. In this study a modification of a previously described computer analysis of breath sounds was used to measure sound intensity levels in both normal and asthmatic children who, in most cases, were unable to perform pulmonary function. The intensity levels were derived using a microcomputer-based program that digitizes audio signals and calculates energy values at 25-ms intervals throughout each signal. There were statistical differences between mean intensity levels for normal breath sounds in children between 2 and 6 years and the mean intensity levels for wheezing sounds in the same age group, as well as wheezing sounds in asthmatic patients over the age of 8 years (P less than 0.002). Also, the mean intensity levels for normal breath sounds could be clearly differentiated from intensity levels for other sounds from the chest, including heart sounds and voice sounds. Thus, computer digitized airway phonopneumography (CDAP) proved to be a reproducible, quantifiable method for demonstrating airway obstruction in those children and patients unable to perform pulmonary function testing.

Adolescent↗
PubMed1991

Utilizing lung sounds analysis for the evaluation of acute asthma in small children.

One of the most difficult aspects of management of acute asthma in the small child is the clinician's inability to quantitate the response or lack of response to bronchodilator agents because of the inability of a child this age to perform objective lung measurements in the acute state. The present study was designed to evaluate bronchodilator responsiveness in children between 2 and 6 years of age with wheezing by means of a computerized lung sound analysis, computer digitized airway phonopneumonography. Children between ages 2 and 6 who were experiencing acute exacerbations of asthma were included in this study population. The 43 children were evaluated by physical examination, pulmonary function testing, if possible, by use of (spirometry or peak flow meter) and transmission of lung sounds to a computer using an electronic stethoscope to obtain a phonopneumograph with sound intensity level determinations during tidal breathing. A control group of 20 known asthmatic patients between the ages of 8 and 52 years who also presented to the office with acute asthma were evaluated similarly. In each of these individuals, a physical examination was followed by complete spirometry as well as computer digitized airway phonopneumonography recordings. Following initial measurements, all patients were treated with nebulized albuterol (0.25 mL in 2 mL of saline). Five minutes after completion of the nebulization all patients were reexamined and repeat pulmonary function tests were performed followed by CDAP recordings. In the study group of children, the mean pretreatment sound intensity level was 1,694 (range 557 to 4,950 SD +/- 745).(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Disease↗
PubMed1991

Methacholine challenges in the management of young children.

Methacholine bronchial challenges (MBCs) have been used as an important diagnostic and management tool for physicians who treat children with chronic asthma. Despite this, children less than 5 years of age present significant diagnostic and management questions that can not easily be answered because of their inability to perform standard spirometry, and thus methacholine bronchial challenges. The present study was designed to evaluate with methacholine bronchial challenge small children (between 2 and 6 years of age) with the diagnosis of or a suspected diagnosis of asthma, utilizing a new method of evaluating airflow in small children through sound analysis, Computer Digitized Airway Phonopneumography (CDAP). There were 23 children in the study between the ages of 2 and 6 years with suspected asthma who could not perform pulmonary function tests. A control group consisting of 12 subjects between the ages of 8 and 38 years of age with a history of chronic cough and/or wheezing who could perform pulmonary function tests was also studied. Of the 12 patients over the age of 8 who had MBC, 11 of them had positive challenges with a fall in FEV1 of 19% or greater. The percent change in sound intensity levels from baseline range from 232% to 396% of baseline. There was greater than 200% change in mean intensity levels with a concentration of methacholine that produced a 19% fall in FEV1 in all of the eleven patients. For one individual who had a negative MBC there was only a 16% change in pulmonary function at 25 mg of methacholine with essentially no change in sound intensity level from baseline.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1990

Evaluation of tremor and efficacy of oral procaterol in adult patients with asthma.

Tremor, the most common side effect of ordinary doses of beta 2-agonists, was evaluated in a quantitative manner and compared to improvement in pulmonary function in respect to time of onset, duration, peak effect, and tachyphylaxis with procaterol in adults. Forty-five adult patients with reversible obstructive airway disease were studied during administration of three different dosages of procaterol, 25 micrograms escalating to 100 micrograms, and 100 micrograms twice daily. Tremor was quantitatively evaluated with a Grass model accelerometer. The patients were evaluated during 8 hours approximately every 2 weeks for 8 weeks. Daily diaries of symptoms and side effects were also maintained. The study demonstrated no direct relationship between tremor and pulmonary function as far as time of onset, peak effect, or duration. Although tachyphylaxis was demonstrated, much of the tolerance developed to the tremor was explained by an increase in baseline tremor. Procaterol was demonstrated to be an effective bronchodilator, and tolerance to tremor was demonstrated to develop with time but is highly variable. There was not a direct relationship between tremor and pulmonary function, indicating possible differences between lung and peripheral muscle beta 2-receptors. It appeared that the best way to minimize the problem of tremor is to begin with a lower dose and increase the dose gradually during a period of weeks.

Administration, Oral↗
PubMed1989

Three-dimensional computer reconstruction of a temporal bone.

The complexities of the temporal bone and the critical inter-relationships among its key structures can be simplified with three-dimensional computer-assisted reconstruction. Knowledge of the topography of these structures and their mutual relationships in essential in any surgical approach to the temporal bone. Sixty sagittal histologic sections of a normal left temporal bone were examined. Each section, 30 microns in thickness, was optically enlarged. Segments representing the facial nerve, internal carotid artery, and inner ear structures from individual slides were traced and data were entered into a computer. A personal computer was used for data processing and analysis. Graphic software developed in our laboratory generated images with x-y-z coordinates that could be rotated in any plane. The high resolution of the computer graphics system, combined with the precision of histologic sections, permitted study of the critical three-dimensional anatomic relationships among essential intratemporal bone structures. The capability of reproducing individual and joint images of the intratemporal bone structures and viewing them from all surgical angles gives skull base and otologic surgeons important topographic guidance. Accurate spatial measurements of temporal bone anatomy are now possible with the application of computer graphic technology.

Carotid Artery, Internal↗
PubMed1975

[Studies on the skin surface dosage of dermatopharmaceutical preparations].

In human volunteers presenting with normal skin an investigation has been carried out to determine the specific skin surface dose, the actual application volume, and the theoretical surface film thickness resulting from thin and thick layer inunction of 4 common corticosteroid topicals. The findings obtained indicate that the skin surface dose provides the most suitable criterion for the terrain saturation behaviour exhibited by different formulation types of semi-solid topical preparations (inunguenda). Various aspects of the surface dosage concept are discussed with regard to the active agents and forms of application of external skin remedies. Predicative clinical determinations of the skin surface doses of topicals relating to special therapeutic and assessment procedures are believed to be a valuable complement to experimental (predictive) determinations of this parameter; some problems involved are pointed out by reference to a clinical trial example. Data on the application dosage of topicals--either by skin surface dose or by volume or layer thickness quantification--have been extracted from the dermatological literature and are reviewed with the aim of furnishing a basis for comparative estimation of our experimental results.

Adult↗
PubMedDate not supplied

Feedback regulation of bile acid synthesis in the rat by dietary vs. intravenous cholate or taurocholate.

The regulation of bile acid synthesis was studied (i) in intact or colectomized rats receiving cholate or taurocholate as a dietary supplement and (ii) in experiments using chow-fed animals with a graded intravenous or intraduodenal taurocholate infusion. After the 2-week diet period a bile fistula was established and rates of taurocholate, tauromuricholate and taurochenodeoxycholate secretion were quantitated by high-performance liquid chromatography. During the infusion experiments taurocholate production was calculated from the difference in specific activity of [14C]taurocholate between infusate and bile, whereas tauromuricholate and taurochenodeoxycholate synthesis was derived directly from their secretion rates after pool depletion. Both the 0.5% cholate and taurocholate diet suppressed tauromuricholate and taurochenodeoxycholate secretion nearly totally, but only cholate led to a prolonged inhibition taurocholate synthesis. The diets stimulated total bile acid secretion and expanded the total bile acid pool size 2- to 3-fold, but they also prompted a dramatic increase in the biliary secretion of taurodeoxycholate. In contrast, colectomized animals did not secrete taurodeoxycholate following the cholate diet and, despite a comparable increase in bile acid pool size, tauromuricholate and taurochenodeoxycholate secretion was inhibited to a lesser extent. In addition, the rate of bile acid secretion and synthesis was significantly enhanced when compared to that of intact rats. To determine whether taurocholate affected bile acid synthesis directly, the bile acid was infused intravenously or intraduodenally at varying rates up to 300 mumoles per kg per hr for 54 hr, i.e. a rate exceeding normal total bile acid secretion in these acute bile fistula animals nearly 3-fold.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMedDate not supplied

Long-term results of high tibial osteotomy for medial osteoarthritis of the knee.

We reviewed retrospectively the results in patients who had undergone one hundred and four high tibial lateral osteotomies. The operations were all performed between 1985 and 1993. Each one of fifty men and forty nine women demonstrated a varus deformity of the knee with a coexistent medial osteoarthritis. Results were reviewed in 49 patients (62 knees) with an average follow-up of 10.2 years (range 6-14 years). Of the remaining 42 patients, 8 were lost to follow-up, 10 had died, and 24 were subsequently treated with total knee arthroplasty at an average 4.7 years after having had a high tibial osteotomy. Clinical results were evaluated using the Hospital for Special Surgery Score (HSS) and the Knee Society Score. Radiographs were systematically analysed to evaluate osteoarthritis and leg axis. Forty four (90 per cent) of the forty nine patients stated the results met their expectations and given the same circumstances, they would have the operation once again. In these patients the knee score results were excellent. The same patients had excellent HSS and Knee Society Scores. Five patients (10 per cent) had a poor result and twenty four patients were treated later by total knee arthroplasty because of pain. The following factors set these patients apart from those with more favorable results: previous arthroscopic debridement, obesity, lateral knee osteoarthritis, insufficient valgus correction, and an age of more than 55 years. High tibial valgus osteotomy provides good pain relief and improved function in carefully selected patients. Our results support this conclusion.

Adult↗
PubMedDate not supplied

Mometasone furoate nasal spray is rapidly effective in the treatment of seasonal allergic rhinitis in an outdoor (park), acute exposure setting.

The objective of this study was to determine the time to onset of symptom relief following a single dose of mometasone furoate nasal spray (MFNS) in symptomatic patients with seasonal allergic rhinitis (SAR). This was a single-center, placebo-controlled, double-blind, randomized, parallel-group study with a 7-day run-in period followed by a single-dose administration of medication or placebo in an outdoor park setting. The park site provided an acute exposure to seasonal (tree and grass) pollens. Patients remained in the park of approximately 12 hours after dosing, during which time hourly assessments of SAR symptoms were recorded on a diary card. Two hundred thirty-nine patients with symptoms of SAR entered the study. Patients receiving any concurrent medication for treatment of their symptoms were excluded. Patients were randomized in a 1:1 ratio to receive treatment with either a single dose of MFNS (200 micrograms/or matching placebo nasal spray. Outcome measures included an assessment of overall therapeutic response and change from baseline in total nasal plus non-nasal sign/symptom severity score, total nasal sign/symptom severity score, and total non-nasal sign/symptom severity score. Improvement in total nasal symptom scores, total non-nasal symptom scores, and total nasal plus non-nasal symptom scores were greater and more sustained in patients receiving MFNS than in patients receiving placebo. The mean decrease from baseline in total nasal plus non-nasal symptom scores was significantly greater in MFNS-dosed patients than in placebo-dosed patients at 5 hours after dosing (p < 0.01). The mean decrease from baseline in total nasal symptom scores was significantly greater in MFNS-dosed patients than in placebo-dosed patients at 7 hours after dosing (p < 0.01). The between-treatment differences in total nasal plus non-nasal symptom scores and total nasal symptom scores remained significant for all subsequent hourly assessments through 12 hours post-dose. Patient assessments of overall response to therapy at end point were significantly different between treatment groups (p < 0.01) with 60.5% of MFNS-treated patients reporting complete, marked, or moderate relief compared with 46.5% of placebo-treated patients. Mometasone furoate nasal spray produces a statistically significant improvement in nasal symptom scores in patients with SAR by 7 hours after administration of a single 200 micrograms dose (100 micrograms in each nostril).

Administration, Topical↗