Biomedical subjects
Publications and source records attributed to C Conrad.
To assess the impact of training programs, including a visualization test for hand disinfection, we monitored the hand-alcohol consumption of medical staff. The consumption increased steadily from 5.7 L of hand alcohol per capita per year in 1990 to 9.1 L in 1998. There was no significant increase in skin problems.
OBJECTIVE: Gastrointestinal prokinetic agents, such as cisapride, are commonly used in pediatric practice to improve gastric emptying, to decrease emesis, to improve lower esophageal sphincter tone, and to improve irritability and feeding aversion associated with gastroesophageal reflux (GER). Although cisapride seems to be effective in infants from 2 months to 14 years old, data for younger and preterm infants are not available. Whether reflux is a significant cause of reflex apnea or feeding intolerance in the preterm infant is controversial. The objective of this 1-year prospective study, started in 1998, was to determine the efficacy of cisapride for treatment of reflux and reflux-associated apnea (RAAP) in preterm infants. Before this study, the diagnosis of reflux was often made clinically and the effect of therapy on reflux or the decision to increase the dose of cisapride was made empirically. The clinical bias was that persistent apnea, not responding to caffeine, was caused by GER. We reasoned that a systematic approach to the diagnosis and treatment of reflux would improve the care of preterm infants and reduce the risk of toxicity, especially if an increased dose of cisapride showed no improvement in reflux or apnea. STUDY DESIGN: Twenty-four preterm infants (24-36 weeks' gestational age) had clinical apnea/pH studies when they were referred by the attending neonatologist for suspected GER. These infants were born at 28.8 +/- 3.1 weeks with birth weight of 1169 +/- 387 g (range: 631-2263 g). Each infant was studied before and 8 days after starting cisapride treatment. Cisapride dose was 0.09 to 0.25 mg/kg every 6 hours enterally. Treatment decisions regarding dose of cisapride were the responsibility of the attending neonatologist. The pH was recorded continuously for 24 hours at 0.25 Hz and was analyzed using EsopHogram software. A single sensor pH catheter was inserted to ~2 cm above the esophageal gastric junction. GER was defined as a drop in esophageal pH below 4.0 for a least 5 seconds, or pathologic GER was defined as a reflux index (RI) >2 standard deviation (SD) from the mean based on published norms for term infants. The following parameters were calculated from the pH recording: number of reflux events per 24 hours, duration of the longest episode, number of episodes >5 minutes per 24 hours, and RI, ie, percentage of time with pH <4.0. Each study had a combined time-lapse video recording and multichannel digital recording. Recorded parameters were: continuous pulse oximetry, electrocardiogram, respiratory effort (piezo sensor), and airflow (temperature sensor at nostrils and mouth). The recording was scored for central apneas of 10 to 14 seconds and >/=15 seconds (prolonged) and >/=10 seconds for obstructive and mixed apneas. RAAP was scored when an apnea (irrespective of the type) occurred within 1 minute of a GER event. Baseline, after cisapride, and follow-up electrocardiograms were performed because of concern about prolonged QTc and cardiac arrhythmias. The infants were 35.6 +/- 4.5 weeks postconceptional age when first studied. Twelve infants (mean birth weight: 1821 +/- 749 g; gestational age: 32 +/- 2 weeks; postconceptional age: 35.6 +/- 2.6 weeks) were identified retrospectively as controls because their baseline GER parameters were within the normal range using Vandenplas' criteria. RESULTS: Overall, cisapride treatment significantly improved the RI from 16.6 +/- 15.2 to 9.1 +/- 8.4 SD. The number of reflux episodes >/=5 minutes was reduced from 7.1 +/- 5.8 to 4.3 +/- 4.4 SD. No significant effect was seen on the total number of refluxes (/24 hours). Eight infants (33%) had no decrease in the RI after a week of treatment. Three of these infants improved after cisapride dose was increased from 0.09 to 0.25 mg/kg/dose every 6 hours. Although 0.09 mg/kg/day is the minimum effective dose, 67% of our infants did respond to this low dose. Cisapride was discontinued in 3 infants because of prolonged QTc >/=0.450 seconds (0.473 in 1 and 0.470 in 2). More data about the effect of cisapride on QTc interval are reported in Pediatrics in a separate article. Only 1 infant showed no improvement with increased dose. Caffeine treatment had no effect on the baseline or follow-up GER values. Although apnea indexes for central and obstructive apnea were similar before and after cisapride, mixed apnea was less during treatment. There was a significant decrease (0.32 +/- 0.40 to 0.12 +/- 0.17/hour) in RAAP when the one infant who had increased reflux on increased dose of cisapride was excluded as an outlier. The statistical difference, before and after cisapride, for the group is significant with the outlier omitted. The clinical significance is unclear because ~50% of the infants had minimal changes in their apnea indexes. Furthermore, ~40% of infants did not have RAAP. (ABSTRACT TRUNCATED)
BACKGROUND AND AIM OF THE STUDY: The use of flexible structures within cardiovascular prostheses such as valves, stents and vascular grafts has been proposed as a means of more closely modeling native mechanics, and thereby reducing the biomechanical problems associated with rigid materials. However, the design of such materials has been hampered by the paucity of quantitative information on the in-vivo behavior of such structures. The aim of this study was to explore the use of 3D ultrasound imaging coupled with finite element analysis (FEA) as a tool to estimate deformation and forces imposed in vivo on a novel bioprosthetic valve design. METHODS: The method was first tested using in-vitro static loading conditions, where good agreement between displacements seen on video and those obtained from application of the identical force within the finite element program was seen. The method was then tested in a porcine model with valves implanted in the mitral position. Images of the deforming annular ring were obtained over the cardiac cycle using 3D intravascular ultrasound; these images were fed into the FEA program for calculation of reaction forces. RESULTS: Results in vitro showed that a force of 2.7-8.0 Newtons (N) was required to produce a deformation of between 1.0 and 3.0 mm in the radial direction. A time history of deformation and force around the ring of the valve stent could be obtained for the in-vivo conditions. These results revealed a maximum deformation of 0.5-1.7 mm along the short axis (anteroposterior) of the mitral valve. Coupled to this, a peak reaction force of 4.4-13.9 N was found at the points corresponding to maximal deflection. Both deformation and reaction force reached maximum during atrial contraction. CONCLUSION: This method provides an accurate means of estimating deformation and corresponding forces imposed in vivo on intracardiac prostheses. The results provide information on the dynamic behavior of the mitral valve annulus. Such information should be useful in the design of flexible cardiovascular prostheses.
Drug addiction is linked with increased prevalence of various illnesses. Of major importance are skin diseases which often have a powerful influence on the health. Analysis of the situation in Switzerland at the outset of the 1990s showed that not all drug addicts could be reached with the existing range of treatments. For this reason, heroin-supported treatment was examined as a new therapy option from 1994 on. The influence on the skin's health are examined in this study. The minimum age of those admitted was set at age 20. Heroin addiction had to date back at least two years, and several treatment efforts had to have failed. Data of 1,035 patients was based on tests at admission and after six, 12, and 18 months of treatment. Some 18% of drug consumers indicated abcesses at admission, and almost 30% showed phlegmones. The prevalence of all skin diseases examined show significant declines over the 18 months of treatment. The relative risk resulting from puncture points fell to 0.35 (SD: 0.26-0.47), from phlegmones to 0.24 (SD: 0.14-0.41), from absesses to 0.31 (SD: 0.15-0.60). This study shows that skin diseases are a frequent and important complication among intravenous drug addicts. Heroin-supported treatment led to favourable progress of the dermatological situation among patients.
Gene therapy is being studied for the treatment of a variety of acquired and inherited disorders. Retroviruses, adenoviruses, poxviruses, adeno-associated viruses, herpesviruses, and others are being engineered to transfer genes into humans. Treatment protocols using recombinant viruses are being introduced into clinical settings. Infection control professionals will be involved in reviewing the safety of these agents in their clinics and hospitals. To date, only a limited number of articles have been written on infection control in gene therapy, and no widely available recommendations exist from federal or private organizations to guide infection control professionals. The goals of the conference were to provide a forum where gene therapy experts could share their perspectives and experience with infection control in gene therapy and to provide an opportunity for newcomers to the field to learn about issues specific to infection control in gene therapy. Recommendations for infection control in gene therapy were proposed.
The use of antisense oligodeoxynucleotides (AS-ODN) remains a viable method to downregulate selected gene function. However, limitations to the antisense approach remain, such as (1) difficulties in delivery of the AS-ODN into target tissues, (2) instability of AS-ODN in vivo, (3) uncertanties about the precise mode of action, and (4) toxic effects in animal and human studies. To circumvent some of these difficulties, we designed a vector set that directs the in vivo production of single-stranded DNA (ssDNA) of a desired target sequence with limited extraneous vector nucleotide sequences. One plasmid was designed to express Moloney murine leukemia virus (MoMuLV) reverse transcriptase (RT). Another expression plasmid contains the MoMuLV primer binding site at the 3'-end of its RNA transcript so that an ssDNA would be synthesized by RT when both plasmids are cotransfected into cells. To test this expression system, we constructed a plasmid set, pssXA/pssXB that produces ssRNA-cleaving DNA 10-23 enzyme (Santoro, S.W., and Joyce, G.F. [1997]. Proc. Natl. Acad. Sci. USA 37, 13330-13342). The DNA enzyme sequence was placed between two oligonucleotide arms that are complementary and able to specifically target C-raf kinase mRNA. These plasmids were transfected into the A549 lung carcinoma cell line. Reduced C-raf mRNA levels by up to 34%-36%, as determined by Northern blot analysis, were observed in the transfected cells. Our results demonstrate the feasibility of using this novel ssDNA expression system to generate any sequence of interest in vivo for antisense, RNA-cleavage DNA enzyme, or triplex-forming strategies.
This study is concerned with physicians' consistency, aggressiveness, and perception of importance in screening children for Fetal Alcohol Syndrome (FAS). Although irreversible, early intervention can improve an affected infant's survival and success in developing to his/her best potential. This study surveyed obstetricians. Pediatricians, family and general practitioners in San Antonio, Texas in 1993 and asked them to express their perceptions of the factors most important in FAS births. They also responded to questions about the rank of importance of FAS compared to other congenital disorders and indicated that alcoholism was the most influential factor in FAS births and that FAS was the third most common congenital disorder among their pediatric patients. The study further explored the physicians' clinical method to screen for FAS and their estimates of how many of their colleagues evaluate their patients for the syndrome.
AIMS: Pre-operatively, to exclude multiple invasive tumours not discovered by mammography and sonography in patients referred for breast conservation surgery. METHODS: A supplementary MR-mammography was offered to all patients with mammographic and/or sonographic ascertained tumours less than 2 cm in diameter. RESULTS: Forty patients were offered this additional examination. In accordance with the MR diagnosis, 51% of the planned surgical procedures were changed. Nine patients had more than one invasive tumour, and in four patients the tumour was >2cm in diameter. One patient had no tumour at all, and in four patients the MR-mammography suggested benign fibroadenomas, which resulted in small excisions. One patient with a suspect MR-mammography presented sclerosing adenosis at surgery. Three patients had to be excluded due to MR problems. Ten patients preferred mastectomy, although the MR-mammography had shown only a single invasive tumour. CONCLUSION: MR-mammography is recommended as a pre-surgical diagnostic procedure in patients allocated to breast conservation surgery.
The standard methods of scoring sleep patterns do not ensure an accurate clinical impression of sleep quality. This is important especially in depressed insomniacs because persistent poor sleep increases the likelihood of recurrent depressive episodes. Changes in cyclic alternating patterns (CAP) in sleep have been shown to reflect corresponding changes in sleep quality. We evaluated the effects of nefazodone on CAP and standard sleep architecture in depressed insomniacs. The study was a single-center, single-blind, 6-week treatment of nefazodone hydrochloride followed by placebo withdrawal in 16 subjects meeting the DSM-IV criteria for depression who had a score of at least 18 on the 17-item Hamilton Depression Rating Scale, with insomnia-related items 4, 5, and 6 having a total score of 3 or greater. A mean daily dose of 339.1 +/- 141.7 mg at endpoint of nefazodone significantly reduced Hamilton Depression Scores from 21.7 +/- 3.0 on baseline to 5.8 +/- 5.3 (P <.05) by the end of the study. Polysomnography showed an improvement in sleep latency and sleep efficiency (P <.05), but no alterations in rapid-eye-movement or slow-wave sleep. Subjective estimates of sleep quality improved throughout the study, but CAP rates did not show a significant improvement. The disparity between CAP rates and sleep quality in depressed insomniacs is discussed.
A study was conducted at the Tri-State Sleep Disorders Center of Cincinnati, Ohio, to evaluate both quantitative and qualitative daily function and productivity outcomes of treating obstructive sleep apnea (OSA) with nasal continuous positive airway pressure (NCPAP). This was a prospective outcome study conducted in 316 patients with diagnosed and treated OSA. There were 234 men and 82 women, mean age, 48.79 +/- 0.67 years; weight averaged 250.39 +/- 3.55 pounds; mean pretreatment respiratory disturbance index was 42.9 +/- 1.7 episodes per hour and 2.8 +/- 0.2 episodes per hour with NCPAP treatment. Patients were surveyed by questionnaire, administered on polysomnographic confirmation of OSA and after 6 months of nightly treatment with NCPAP as to their perceptions of their level of daytime functioning and quality of life over the previous 6 months. Main outcome measures included number of incidents of excessive daytime sleepiness; number of headaches on awakening; number of automobile accidents and near-miss automobile accidents; number of days absent from work; number of physician visits; and a series of subjective scales, measuring job productivity, quality of life, general physical and mental condition, short-term memory, and changes in blood pressure. Significant decreases were found in the number of incidents of excessive daytime sleepiness, headaches on awakening, physician visits, days absent from work, and automobile accidents or near misses with NCPAP therapy. Patients also reported subjective increases in productivity, quality of life, physical and mental condition, and short-term memory and reduction in both diastolic and systolic blood pressure. Effective treatment of OSA results in improvement both in preexisting symptoms and in quality of life. Improvement in many of the major problems experienced by patients seeking treatment has important implications for preventive medicine as well as health care cost containment.
Anti-lymphocyte globulins (ALG) are immunosuppressive agents of animal origin currently used in clinical organ transplantation and for the treatment of severe aplastic anaemia. The potency of each batch is tested in vivo using primates as recipients for allogeneic skin grafts. The two in vitro methods commonly used are (i) a cytotoxic assay and (ii) the rosette inhibition assay, both of which are evaluated by microscopy. In addition to animal welfare aspects, these methods require considerable experience, are difficult to validate, and the information as to the biological potency of the sera is questionable. The aim of our study is a better characterization of the biological properties of ALG in order to subsequently define an in vitro alternative for the potency test in monkeys. Several antibody specificities directed against functional molecules on T-cells, B-cells, NK-cells, macrophages as well as non-lineage specificities can be identified in competition assays with monoclonal antibodies. The cytotoxic capacity of ALG in the presence or absence of complement as well as DNA-fragmentation characteristic for apoptosis can be analysed by flow cytometry using propidiumiodide- (PI) incorporation. Immunoprecipitation of cell lysate with ALG and subsequent incubation with radioactive ATP (kinase-assay) shows specific bands which seem to be identical between different batches of one product.
23S rRNA in Rhodobacter capsulatus shows endoribonuclease III (RNase III)-dependent fragmentation in vivo at a unique extra stem-loop extending from position 1271 to 1331. RNase III is a double strand (ds)-specific endoribonuclease. This substrate preference is mediated by a double-stranded RNA binding domain (dsRBD) within the protein. Although a certain degree of double strandedness is a prerequisite, the question arises what structural features exactly make this extra stem-loop an RNase III cleavage site, distinguishing it from the plethora of stem-loops in 23S rRNA? We used RNase III purified from R.capsulatus and Escherichia coli, respectively, together with well known substrates for E.coli RNase III and RNA substrates derived from the special cleavage site in R.capsulatus 23S rRNA to study the interaction between the Rhodobacter enzyme and the fragmentation site. Although both enzymes are very similar in their amino acid sequence, they exhibit significant differences in binding and cleavage of these in vitro substrates.
Previous studies of a tau polymorphism in Caucasian subjects with progressive supranuclear palsy (PSP) showed an over-representation of one genotype, A0/A0, versus normal control subjects. This result suggested that tau may be playing a genetic role in the progression of PSP. This study examines whether the over-representation of A0/A0 is Caucasian-specific or universal to PSP. Unfortunately, we found this dinucleotide repeat was relatively non-polymorphic in Japanese subjects. As a result, the genotypes were virtually the same, A0/A0, between Japanese PSP and control subjects. However, this outcome, albeit negative, does suggest two possible roles of the tau gene in PSP pathogenesis: (1) the role of this dinucleotide repeat in PSP may be different between Caucasian and Japanese populations or (2) this repeat may not be causal for PSP but represents a marker for other molecular genetic risk factors within or close to the tau gene on chromosome 17.
Tamoxifen (TAM), an anti-estrogen compound, is widely used for chemotherapy of breast cancer, although the molecular mechanisms underlying TAM cytotoxicity are obscure. Here, we show that TAM dramatically caused degradation of vimentin (VIM) in human skin fibroblasts, in a time and dose dependent manner. Addition of caspase-3 inhibitor, Z-DEVD-FMK, inhibited formation of some fragments of VIM, and caspase-3 was proteolytically activated by TAM treatment. Expression of functional estrogen receptors were negative in these cells, and neither transcription nor protein synthesis was required for TAM-induced degradation of VIM. Moreover, quinestrol, an ethinyl estradiol derivative, weakly degraded VIM, whereas neither estradiols nor estriol had any effects. Taken together, TAM may induce fragmentation of VIM associated with an activation of caspase-3, which may be attributed to non-genomic actions of TAM.
Cell migration may depend on integrin-mediated adhesion to and deadhesion from extracellular matrix ligands. This concept, however, has not yet been confirmed for T lymphocytes migrating in three-dimensional extracellular matrices. We investigated receptor involvement in T cell migration combining a three-dimensional collagen matrix model with time-lapse videomicroscopy, computer-assisted cell tracking and confocal microscopy. In collagen lattices, the migration of CD4+ T cells (1) involved interactions with collagen fibers at the leading edge and uropod likewise, (2) occurred independently of the co-clustering of beta1, beta2, or beta3 integrins with F-actin, focal adhesion kinase, and phosphotyrosine at interactions with collagen fibers, (3) was counteracted by high-affinity beta1 integrin binding induced by antibody TS2/16; however, (4) the migration could not be blocked by a combination of adhesion-perturbing anti-beta1, -beta2, -beta3, and alpha v integrin antibodies. Integrin blocking neither affected cell polarization, interaction with fibers, beta1 integrin distribution, migration velocity, path structure, nor the number of locomoting cells in spontaneously migrating or concanavalin A-activated cells. Hence, T lymphocytes migrating in three-dimensional collagen matrices may utilize highly transient interactions with collagen fibers of low adhesivity, thereby differing from focal adhesion-dependent migration strategies employed by other cells.
METHODS: In a 300-bed acute-care hospital we compared optical instruments employed, for orthopedic, urological and gynecological operations during their use in practice. The comparison between 33 ethylene oxide(EO)-sterilized optical instruments and 14 steam-sterilized optical instruments took into account the following criteria: frequency of use; availability; sterilization cycles; kind, cost and number of repairs. RESULTS: The 33 EO-sterilized optical instruments were handled 1043 times and were repaired 10 times (at a cost of up to 2000 SFR). The 14 steam-sterilized optical instruments were treated 1101 times and were repaired 8 times (2000 SFR). The total costs were 77,000 SFR for the 14 steam-sterilized instruments and 132,000 SFR for the 33 EO-sterilized instruments. INTERPRETATION: Steam-sterilization is a reasonable, safe and fast method of sterilizing optical instruments. We prefer this method, given its advantages (less toxicity, personal care and pollution control).
OBJECTIVE: To reduce the use of amoxicillin-clavulanate after high-resistance rates in Escherichia coli were detected. DESIGN: Intervention study; the interventions were introduced successively over a 4-year period while closely monitoring the resistance patterns. SETTING: A 260-bed acute-care hospital in Switzerland. INTERVENTIONS: Introduction of therapeutic guidelines for specific departments or indications, which proposed alternative antibiotics to amoxicillin-clavulanate. The perioperative prophylactic use of amoxicillin-clavulanate was eliminated completely. RESULTS: The absolute amount of amoxicillin-clavulanate consumed decreased by 23%, from 24.8 g per 100 patient days in 1992 to 18.5 g per 100 patient days in 1995. The number of courses, a parameter that takes the prophylactic use into account, decreased by 62% from 2.3 per 100 patient days in 1992 to 0.9 per 100 patient days in 1995. The percentage of sensitive strains increased from 54.9% (n=512) in 1992 and 54.0% (n=506) in 1993 to 72.1% (n=546) in 1994 and 83.1% (n=668) in 1995. No major changes were detected for other antimicrobials, such as cotrimoxazole, tetracycline, or cefuroxime, used in this 4-year period. CONCLUSIONS: A decrease in the use of amoxicillin-clavulanate was followed by an increase in susceptibility of E coli to it. It was not possible to prove a causative relationship. Only a temporal association was discovered. The reduction of the use of amoxicillin-clavulanate was achieved through the implementation of treatment guidelines, facilitated through a close collaboration among the clinical pharmacists, the infection control practitioner, the microbiology laboratory, and the physicians in charge of the respective departments.
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