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Biomedical subjects

J A Schmidt

Publications and source records attributed to J A Schmidt.

At least 19 recordsLinked to original sources

Characterization of Aspergillus oryzae fermentation extract effects on the rumen fungus Neocallimastix frontalis, EB 188. Part 1. Zoospore development and physiology.

Experiments were performed to determine the effect of Aspergillus oryzae (AO) fermentation extract on zoospore development in the rumen fungus Neocallimastix frontalis EB 188. Powdered product, or liquid extract prepared from such powder, was added at the recommended value for supplementation in dairy cattle. Stationary and stirred cultures were periodically sampled and assayed for extracellular and intracellular protein and enzymes, gas production, zoospore production and maturation, and carbon source utilization. Soluble extract increased fungal physiology when grown in stirred vessels or stationary cultures. Treated cultures produced higher levels of enzymes (nearly double). Mobile zoospores matured into germination entities more rapidly in treated cultures, and when powdered product was used, nearly 3 times more motile zoospores were produced at 56 h of fungal growth. Levels of the intracellular enzyme malate dehydrogenase increased by 6-fold in the presence of powdered product. Product wheat bran carrier used as soluble extract or powder had very little effect on fungal cultures. Medium cellulose was completely hydrolyzed in all cultures but this occurred earlier in those containing AO treatment.

Amylases↗

Characterization of Aspergillus oryzae fermentation extract effects on the rumen fungus Neocallimastix frontalis, EB 188. Part 2. Carbon source utilization and effects on zoospore production.

The effect of a commercial Aspergillus oryzae fermentation extract on the utilization of carbon source and zoospore production by the rumen fungus Neocallimastix frontalis EB 188 was determined. In addition, the composition of a soluble extract prepared from the commercial product was analyzed. This extract was added to N. frontalis EB 188 cultures grown on a variety of substrates and periodically assayed for protein, enzymes, zoospore production, and carbon source utilization. The powdered product contained 93% dry matter, more than 3,000 A. oryzaespores per gram, and did not contain strong buffers or high concentrations of salt. Measurable concentrations of DNA, protein, carbohydrate and several enzymes including cellulase and amylase were also found. Soluble extract increased fungal physiology and treated cultures produced significantly higher levels of supernatant protein and enzymes including amylase, cellulase and beta-glucosidase. The fungal response depended on culture carbon source. However, culture zoospore production was increased regardless of substrate provided. Culture utilization of glucose was more rapid in treated cultures, yet high levels of the extract greatly inhibited glucose utilization.

Amylases↗

Older people with impaired mobility have specific loci of periventricular abnormality on MRI.

BACKGROUND: Recent investigations using MRI suggest that older persons with mobility impairment have a greater volume of abnormal cerebral white matter compared with persons with normal mobility, thus raising the possibility that those with impairment have lesions in areas critical for the control of mobility. OBJECTIVE: To utilize automated image analysis methods to localize the specific regions of abnormal white matter that distinguish subjects with lower mobility from subjects with higher mobility. METHODS: Tissue classification was performed on subjects' dual-echo long repetition time spin-echo MRI using computer algorithms operating on intensity criteria integrated with anatomic information. Statistical analysis of group differences was obtained after spatially normalizing each brain to a standard reference brain. RESULTS: Four discrete periventricular regions, including bilaterally symmetric frontal and bilateral occipitoparietal regions, were identified as being sensitive (frontal) or specific (occipitoparietal) in discriminating the subjects with lower mobility from subjects with higher mobility. The symmetry of these lesions in individual subjects suggested pathology other than arteriolar infarction. CONCLUSIONS: These results suggest that damage to discrete frontal and occipitoparietal periventricular white matter locations may be associated with a mobility disorder of aging.

Aged↗

The discovery of sulfonylated dipeptides as potent VLA-4 antagonists.

Directed screening of a carboxylic acid-containing combinatorial library led to the discovery of potent inhibitors of the integrin VLA-4. Subsequent optimization by solid-phase synthesis afforded a series of sulfonylated dipeptide inhibitors with structural components that when combined in a single hybrid molecule gave a sub-nanomolar inhibitor as a lead for medicinal chemistry. Preliminary metabolic studies led to the discovery of substituted biphenyl derivatives with low picomolar activities. SAR and pharmacokinetic characterization of this series are presented.

Animals↗

Measuring the elastic properties of fine wire.

The elastic moduli of fine wires made from MP35N and 304SS used in implantable biomedical devices are assumed to be the same as those published in the literature. However, the cold working required to manufacture the wire significantly alters the elastic moduli of the material. We describe three experiments performed on fine wire made from MP35N and 304SS. The experimentally determined Young's and shear modulus of both wire types were significantly less than the moduli reported in the literature. Young's modulus differed by as much as 26%, and the shear modulus differed by as much as 14% from reported values.

Alloys↗

Attrition in an exercise intervention: a comparison of early and later dropouts.

OBJECTIVE: To identify reasons for dropout and factors that may predict dropout from an exercise intervention aimed at improving physical function in frail older persons. DESIGN/SETTING: An 18-month randomized controlled intervention in a community setting. The intervention comprised 2 groups: class-based and self-paced exercise. PARTICIPANTS: 155 community-dwelling older persons, mean age 77.4, with mildly to moderately compromised mobility. MEASUREMENTS: The primary outcome measure was dropout. Dropouts were grouped as: D0, dropout between baseline and 3-month assessment, and D3, dropout after 3-month assessment. MEASUREMENTS: Measurements of demographics, health, and physical performance included self-rated health, SF-36, disease burden, adverse events, PPT-8, MacArthur battery, 6-minute walk, and gait velocity. RESULTS: There were 56 dropouts (36%), 31 in first 3 months. Compared with retained subjects (R), the D0 group had greater disease burden (P = .011), worse self-perceived physical health (P = .014), slower usual gait speed (P = .001), and walked a shorter distance over 6 minutes (P<.001). No differences were found between R and D3. Multinomial logistic regression showed 6-minute walk (P<.001) and usual gait velocity (P<.001) were the strongest independent predictors of dropout. Controlling for all other variables, adverse events after randomization and 6-minute walk distance were the strongest independent predictors of dropout, and self-paced exercise assignment increased the risk of dropout. CONCLUSIONS: We observed baseline differences between early dropouts and retained subjects in disease burden, physical function, and endurance, suggesting that these factors at baseline may predict dropout. Improved understanding of factors that lead to and predict dropout could allow researchers to identify subjects at risk of dropout before randomization. Assigning targeted retention techniques in accordance with these factors could result in decreased attrition in future studies. Therefore, the results of selective attrition of frailer subjects, such as decreased heterogeneity, restricted generalizability of study findings, and limited understanding of exercise effects in this population, would be avoided.

Activities of Daily Living↗

Fixed-dose, body weight-independent subcutaneous LMW heparin versus adjusted dose unfractionated intravenous heparin in the initial treatment of proximal venous thrombosis. EASTERN Investigators.

BACKGROUND: Body weight-adjusted subcutaneous low-molecular-weight heparin (LMWH) has been proven to be at least as effective and safe as dose-adjusted intravenous unfractionated heparin (UFH) for the treatment of patients with venous thromboembolism. However, body weight-adjusted dosage of low-molecular-weight heparin may be cumbersome and could lead possibly to incorrect dosing. Therefore a fixed LMWH dose, independent of body-weight, might rationalize initial treatment for venous thromboembolism. METHODS: Patients with proven proximal deep-vein thrombosis were randomly assigned to fixed dose subcutaneous LMWH Certoparin (8,000 anti-factor Xa U b.i.d.; 265 patients) or to adjusted dose i.v. UFH (273 patients) for 12 days. Vitamin K antagonists were started between day 3 and 7 and continued for up to 6 months. The primary outcome measure was a 30 percent or greater improvement in the Marder Score, as revealed by repeated venography on day 12 (end of the initial treatment). The secondary composite outcome measure included death, recurrent venous thromboembolism and major bleeding and was assessed at day 12 and after 6 months by a blinded adjunction committee. RESULTS: The Marder score improved by 30% or more in 30.3% and 25.0% of patients assigned to LMWH (198 paired venograms) and UFH (192 paired venograms), respectively (2p = 0.26). At the end of the initial treatment, the composite outcome was observed in 4 of the 265 patients (1.5%) randomized to LMWH, as compared with 14 of the 273 patients (5.1%) randomized to UFH (2p = 0.03). At 6 months these figures were 6.8% and 12.8%, respectively (risk reduction 0.53, confidence interval 0.31-0.90, 2p = 0.02). CONCLUSION: Fixed dose subcutaneous LMWH certoparin is at least as efficacious as UFH in resolving proximal vein thrombosis.

Acute Disease↗

Quantitative, low cycle, crack initiation fatigue testing of fine wires and CENELEC standard pacing coil.

Uniaxial fatigue testing was performed on different diameters of fine wires made from MP35N. The fatigue limits of the wires differed from each other based on the diameter of the wire. Multiaxial (shear) fatigue testing was also performed on a benchmark coil used to evaluate the fatigue life of all modern pacemaker leads (the CENELEC standard coil). A computer algorithm was used to quantify the maximum shear stress and strain on the coil. The bend radius, coil diameter, wire diameter, and pitch of the coil all affect the shear stress and strain and therefore the fatigue properties of conductor coils. Based on the analysis presented, it was determined that the portion of the CENELEC standard dealing with fatigue, when used in its present format, is not a valid fatigue test for pacemaker leads.

Biocompatible Materials↗

The role of ultrasound in patients with possible penetrating cardiac wounds: a prospective multicenter study.

BACKGROUND: Ultrasound is quickly becoming part of the trauma surgeon's practice, but its role in the patient with a penetrating truncal injury is not well defined. The purpose of this study was to evaluate the accuracy of emergency ultrasound as it was introduced into five Level I trauma centers for the diagnosis of acute hemopericardium. METHODS: Surgeons or cardiologists (four centers) and technicians (one center) performed pericardial ultrasound examinations on patients with penetrating truncal wounds. By protocol, patients with positive examinations underwent immediate operation. Vital signs, base deficit, time from examination to operation, operative findings, treatment, and outcome were recorded. RESULTS: Pericardial ultrasound examinations were performed in 261 patients. There were 225 (86.2%) true-negative, 29 (11.1%) true-positive, 0 false-negative, and 7 (2.7%) false-positive examinations, resulting in sensitivity of 100%, specificity of 96.9%, and accuracy of 97.3%. The mean time from ultrasound to operation was 12.1+/-5 minutes. CONCLUSION: Ultrasound should be the initial modality for the evaluation of patients with penetrating precordial wounds because it is accurate and rapid.

Acute Disease↗

Characterization and quantitation of NF-kappaB nuclear translocation induced by interleukin-1 and tumor necrosis factor-alpha. Development and use of a high capacity fluorescence cytometric system.

A new quantitative cytometric technique, termed the ArrayScanTM, is described and used to measure NF-kappaB nuclear translocation induced by interleukin (IL)-1 and tumor necrosis factor-alpha (TNFalpha). The amount of p65 staining is measured in both the nuclei defined by Hoechst 33342 labeling and in the surrounding cytoplasmic area within a preselected number of cells/well in 96-well plates. Using this technique in synchronously activated human chondrocytes or HeLa cells, NF-kappaB was found to move to the nucleus with a half-time of 7-8 min for HeLa and 12-13 min for chondrocytes, a rate in each case about 4-5 min slower than that of Ikappa Balpha degradation. IL-1 receptor antagonist and anti-TypeI IL-1 receptor antiserum on the one hand and anti-TNFalpha and monoclonal anti-TNF receptor 1 antibodies on the other hand could be shown to respectively inhibit IL-1 and TNFalpha stimulation in both cell types. In contrast, a polyclonal anti-TNF receptor 1 antiserum exhibited both a 50% agonism and a 50% antagonism to a TNFalpha stimulation in a dose-dependent fashion, indicating that subtle functional responses to complex agonist and antagonist stimuli could be measured. The effects of different proteasome inhibitors to prevent Ikappa Balpha degradation and subsequent NF-kappaB translocation could also be discriminated; Leu-Leu-Leu aldehyde was only a partial inhibitor with an IC50 of 2 microM, while clastolactacystin beta-lactone was a complete inhibitor with an IC50 of 10 microM. The nonselective kinase inhibitor K252a completely inhibited both IL-1 and TNFalpha stimulation in both cell types with an IC50 of 0.4 microM. This concentration, determined after a 20-min stimulation, was shown to be comparable with that obtained for inhibition of IL-6 production induced by a 100-fold lower IL-1 and TNFalpha concentration measured after 17 h of stimulation. These results suggest that the ArrayScanTM technology provides a rapid, sensitive, quantitative technique for measuring early events in the signal transduction of NF-kappaB.

Biological Transport↗

Validation of surgeon-performed emergency abdominal ultrasonography in pediatric trauma patients.

BACKGROUND/PURPOSE: The focused assessment for the sonographic evaluation of trauma patients (FAST) in adults is effective in detecting intraperitoneal and intrapericardial fluid and can be performed quickly by surgeons in the emergency department (ED). The authors sought to validate the accuracy of FAST performed by surgeons during ED resuscitation of pediatric trauma patients. METHODS: Patients were assigned to one of three groups based on standard clinical criteria: immediate surgery, abdominal computed tomography (CT), or observation alone. FAST was then performed in the ED by a surgery resident (postgraduate year 3 or higher) or an attending trauma surgeon. Four views were used to assess the possible presence of fluid in the pericardial, subphrenic, subhepatic, and pelvic spaces. Time needed to conduct FAST was noted. Presence of peritoneal or pericardial fluid by FAST was compared with that determined by CT or surgery. Sensitivity, specificity, and predictive values were calculated. For those who did not undergo CT or surgery, FAST findings were compared with the clinical course. RESULTS: Technically adequate studies could be performed on 192 of 196 eligible children. Their ages ranged from 3 months to 14 years (mean, 6.9 years); 119 were boys (62%), and 188 (98%) had sustained a blunt injury. FAST was performed in a mean time of 3.9 minutes (range, 1-17 minutes). All FAST examinations were reviewed by our senior surgeon-sonographer (GSR). Interrater agreement between the performing and reviewing surgeon-sonographer was 100%. Sixty (31%) patients underwent either abdominal CT (n = 56; mean Injury Severity Score (ISS), 9.6) or immediate operation (n = 4; mean ISS, 18.8). Of the 10 patients with verified presence of intraperitoneal fluid, eight had positive and two had false-negative FAST examination results. Of the 50 patients with verified absence of intraperitoneal fluid, none had a positive FAST (ie, no false-positives); sensitivity was 80%; specificity, 100%; predictive value positive, 100%; predictive value negative, 96%. None of the 132 patients followed up clinically without CT or surgery (mean ISS, 4.5) had fluid documented by FAST, and all did well. CONCLUSIONS: The focused assessment for the sonographic evaluation of pediatric blunt trauma patients performed by surgical residents and attendings in the ED rapidly and accurately predicted the presence or absence of intraperitoneal fluid. The FAST is a potentially valuable tool to rapidly prioritize the need for laparotomy in the child with multiple injuries and extraabdominal sources of bleeding.

Abdominal Injuries↗

Electron microscopy and capillaroscopically guided nailfold biopsy in connective tissue diseases: detection of ultrastructural changes of the microcirculatory vessels.

The aims of the study were to describe and compare the frequency and nature of histologically detectable microvascular lesions in patients with various connective tissue diseases (CTD). An electron microscopic examination of specimens obtained by the technique of capillaroscopically guided nailfold biopsy was performed in 52 patients with CTD [nine systemic lupus erythematosus (SLE), eight mixed CTD, 18 scleroderma, 17 undifferentiated CTD] and 27 controls. The microvascular changes most frequently observed by electron microscopy were multilayering of the basal lamina (approximately 70% of the CTD patients), an increased amount of perivascular connective tissue, perivascular oedema formation, and an increased number of perivascular fibroblasts and mast cells (each in 30-37% of the CTD patients). In contrast, no particular histopathological feature was found in > 25% of the controls, multilayering (22.6%) being the most frequently observed. Comparing the different conditions studied, there were distinct differences in the frequency and nature of the histologically observed microvascular changes. In particular, SLE seems to be based on a separable type of vasculopathy consisting of significantly less frequent microvascular abnormalities. In conclusion, ultrastructural abnormalities of the microvascular system are a frequent finding in CTD. Electron microscopic examination of specimens obtained by capillaroscopically guided nailfold biopsy is able to disclose histopathological differences between defined entities. Therefore, this approach may be a useful tool to gain further insights into potentially separable aetiopathological mechanisms of the various types of CTD.

Adult↗

Surgeon-performed ultrasound for the assessment of truncal injuries: lessons learned from 1540 patients.

OBJECTIVE: To determine the accuracy of the Focused Assessment for the Sonographic examination of the Trauma patient (FAST) when performed by trauma team members during a 3-year period, and to determine the clinical conditions in which the FAST is most accurate in the assessment of injured patients. SUMMARY BACKGROUND DATA: The FAST is a rapid test that sequentially surveys the pericardial region for hemopericardium and then the right and left upper quadrants and pelvis for hemoperitoneum in patients with potential truncal injuries. The clinical conditions in which the FAST is most accurate in the assessment of injured patients have yet to be determined. METHODS: FAST examinations were performed on patients with precordial or transthoracic wounds or blunt abdominal trauma. Patients with a positive ultrasound (US) examination for hemopericardium underwent immediate surgery, whereas those with a positive US for hemoperitoneum underwent a computed tomography scan (if they were hemodynamically stable) or immediate celiotomy (if they were hemodynamically unstable- blood pressure < or = 90 mmHg). RESULTS: FAST examinations were performed in 1540 patients (1227 with blunt injuries, 313 with penetrating injuries). There were 1440 true-negative results, 80 true-positive results, 16 false-negative results, and 4 false-positive results; the sensitivity was 83.3%, the specificity 99.7%. US was most sensitive and specific for the evaluation of patients with precordial or transthoracic wounds (sensitivity 100%, specificity 99.3%) and hypotensive patients with blunt abdominal trauma (sensitivity 100%, specificity 100%). CONCLUSIONS: US should be the initial diagnostic modality for the evaluation of patients with precordial wounds and blunt truncal injuries because it is rapid and accurate. Because of the high sensitivity and specificity of US in the evaluation of patients with precordial wounds and hypotensive patients with blunt torso trauma, immediate surgical intervention is justified when those patients have a positive US examination.

Abdominal Injuries↗

Early detection of hemoperitoneum by ultrasound examination of the right upper quadrant: a multicenter study.

BACKGROUND: The focused assessment for the sonographic examination of the trauma patient (FAST) is a rapid diagnostic test that sequentially surveys for hemopericardium and then the right upper quadrant (RUQ), left upper quadrant (LUQ), and pelvis for hemoperitoneum in patients with potential truncal injuries. The sequence of the abdominal part of the examination, however, has yet to be validated. The objectives of this multicenter study were as follows: (1) to determine where hemoperitoneum is most frequently identified on positive FAST examinations; and (2) to determine if a relationship exists between that areas and the organs injured. METHODS: Ultrasound registries from four Level I trauma centers identified patients who had true-positive FAST examinations. Demographic data, areas positive on the FAST, and organs injured were recorded; injuries were classified as multiple, single solid organ (liver or spleen), isolated hollow viscus, or retroperitoneal. Relationships between positive locations on the FAST examinations and the associations of organs injured to areas positive were assessed using McNamara's chi2 test; a p value < 0.05 was considered statistically significant. RESULTS: The RUQ was the most common site where hemoperitoneum was detected, and this was statistically significant compared with either the LUQ or the pelvis. Also, statistically significant correlations (p < 0.001) were observed between positive RUQ areas on the FAST and multiple injuries, single solid organ (liver or spleen) injury, and retroperitoneal injuries. CONCLUSION: Blood is most often found on the FAST in the RUQ area in patients with multiple intraperitoneal injuries or isolated injury to the liver, spleen, or retroperitoneum, but not when there is injury to a hollow viscus.

Abdominal Injuries↗

Infrared thermography in the diagnosis of Raynaud's phenomenon in vibration-induced white finger.

BACKGROUND: Frequent use of vibrating tools over several years may lead to a neurovascular disturbance of finger circulation with the development of typical Raynaud's phenomenon, attacks being triggered by vibration and/or cold exposure. The condition is recognized as an occupational disease and known as vibration-induced white finger (VWF). Aim of the present study was to evaluate the usefulness of infrared thermography (IRT) with a cold provocation test in the diagnosis of Raynaud's phenomenon in VWF. PATIENTS AND METHODS: 24 patients with the diagnosis of VWF, previously established by other methods, were compared with 12 matched control subjects. We carried out IRT-measurements simultaneously on both hands before, directly after and 5, 10, 15, 20, and 30 mins following a 3 min exposure of both hands to a waterbath of 12 degrees C. The results of temperature measurements of all fingers were analyzed and the time to complete rewarming of all fingers was recorded. RESULTS: The basal thermograms did not differ between both groups, whereas the mean finger temperatures after cold exposure were significantly lower in VWF-patients compared to controls, with a considerable individual overlap between both groups. Therefore, determination of absolute finger temperature reveals not to be a useful diagnostic tool in individual cases, but might be helpful for pharmacological studies (group-analysis). In contrast to absolute finger temperatures, the parameter of rewarming time after cold exposure revealed to be diagnostic on an individual basis: a complete rewarming after 15 min indicates a normal vascular reactivity and an incomplete rewarming 30 min following the cold provocation points to an impaired vascular reactivity due to VWF. CONCLUSIONS: IRT revealed to be a useful tool in the diagnosis of Raynaud's phenomenon in VWF, and provides a sufficient documentation suitable for further follow-up examination.

Adult↗