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Biomedical subjects

M B Smith

Publications and source records attributed to M B Smith.

At least 37 records · Page 2Linked to original sources

Sigmund Koch as critical humanist.

Just as Sigmund Koch was a good scientist without succumbing to scientism, he was a good humanist without succumbing to the popular distortions trading on the name of humanism. When humanistic psychology was seduced by the touchy-feely encounter group movement, Koch derided its technology of authenticity as shamelessly meretricious. Later, when postmodern humanists of deconstruction and textual analysis began to be heard in psychology, Koch wryly expressed his preference for the old-fashioned kind of humanism. Koch's interests and his conception of the domain of psychology thus transcended scientific and humanistic labels and boundaries. To be good science, human psychological studies have to start with and be guided by openness to all aspects of being human. No less in the present and future than during his lifetime, the implications of Koch's vision of psychological inquiry warrant discerning and disciplined attention.

History, 20th Century↗

Monte Carlo calculations on HIV-1 reverse transcriptase complexed with the non-nucleoside inhibitor 8-Cl TIBO: contribution of the L100I and Y181C variants to protein stability and biological activity.

A computational model of the non-nucleoside inhibitor 8-Cl TIBO complexed with HIV-1 reverse transcriptase (RT) was constructed in order to determine the binding free energies. Using Monte Carlo simulations, both free energy perturbation and linear response calculations were carried out for the transformation of wild-type RT to two key mutants, Y181C and L100I. The newer linear response method estimates binding free energies based on changes in electrostatic and van der Waals energies and solvent-accessible surface areas. In addition, the change in stability of the protein between the folded and unfolded states was estimated for each of these mutations, which are known to emerge upon treatment with the inhibitor. Results from the calculations revealed that there is a large hydrophobic contribution to protein stability in the native, folded state. The calculated absolute free energies of binding from both the linear response, and also the more rigorous free energy perturbation method, gave excellent agreement with the experimental differences in activity. The success of the relatively rapid linear response method in predicting experimental activities holds promise for estimating the activity of the inhibitors not only against the wild-type RT, but also against key protein variants whose emergence undermines the efficacy of the drugs.

Amino Acid Substitution↗

Human articular cartilage: influence of aging and early symptomatic degeneration on the spatial variation of T2--preliminary findings at 3 T.

PURPOSE: To determine if age and early symptomatic degeneration alter the spatial dependency of cartilage T2. MATERIALS AND METHODS: In 25 asymptomatic volunteers and six volunteers with symptoms of patellar chondromalacia, quantitative T2 maps of patellar cartilage were obtained with a multiecho, spin-echo magnetic resonance imaging sequence at 3.0 T. Spatial variation in T2 was evaluated as a function of participant age and symptoms. RESULTS: All asymptomatic volunteers demonstrated a continuous increase in T2 from the radial zone to the articular surface. In the population aged 46-60 years compared with younger volunteers, there was a statistically significant (P < .05) increase in T2 of the transitional zone. In symptomatic volunteers, the increase in T2 was larger in magnitude and focal in distribution. In five of the six symptomatic volunteers, the increase in T2 was greater than the 95% prediction interval determined from data in the corresponding age-matched asymptomatic population. CONCLUSION: Aging is associated with an asymptomatic increase in T2 of the transitional zone of articular cartilage. Preliminary results indicate this diffuse increase in T2 in senescent cartilage is different in appearance than the focally increased T2 observed in damaged articular cartilage.

Adult↗

Effects of forearm bier block with bretylium on the hemodynamic and metabolic responses to handgrip.

We tested the hypothesis that a reduction in sympathetic tone to exercising forearm muscle would increase blood flow, reduce muscle acidosis, and attenuate reflex responses. Subjects performed a progressive, four-stage rhythmic handgrip protocol before and after forearm bier block with bretylium as forearm blood flow (Doppler) and metabolic (venous effluent metabolite concentration and (31)P-NMR indexes) and autonomic reflex responses (heart rate, blood pressure, and sympathetic nerve traffic) were measured. Bretylium inhibits the release of norepinephrine at the neurovascular junction. Bier block increased blood flow as well as oxygen consumption in the exercising forearm (P < 0.03 and P < 0.02, respectively). However, despite this increase in flow, venous K(+) release and H(+) release were both increased during exercise (P < 0.002 for both indexes). Additionally, minimal muscle pH measured during the first minute of recovery with NMR was lower after bier block (6.41 +/- 0.08 vs. 6.20 +/- 0.06; P < 0.036, simple effects). Meanwhile, reflex effects were unaffected by the bretylium bier block. The results support the conclusion that sympathetic stimulation to muscle during exercise not only limits muscle blood flow but also appears to limit anaerobiosis and H(+) release, presumably through a preferential recruitment of oxidative fibers.

Adult↗

Ischemic exercise and the muscle metaboreflex.

In exercising muscle, interstitial metabolites accumulate and stimulate muscle afferents. This evokes the muscle metaboreflex and raises arterial blood pressure (BP). In this report, we examined the effects of tension generation on muscle metabolites and BP during ischemic forearm exercise in humans. Heart rate (HR), BP, P(i), H(2)PO(4)(-), and pH ((31)P-NMR spectroscopy) data were collected in 10 normal healthy men (age 23 +/- 1 yr) during rhythmic handgrip exercise. After baseline measurements, the subjects performed rhythmic handgrip for 2 min. At 2 min, a 250-mmHg occlusion cuff was inflated, and ischemic handgrip exercise was continued until near fatigue (Borg 19). Measurements were continued for an additional 30 s of ischemia. This protocol was performed at 15, 30, 45, and 60% of the subjects' maximum voluntary contraction (MVC) in random order. As tension increased, the time to fatigue decreased. In addition, mean arterial pressure and HR were higher at 60% MVC than at any of the other lower tensions. The NMR data showed significantly greater increases in H(2)PO(4)(-), P(i), and H(+) at 60% than at 15 and 30% MVC. Therefore, despite the subjects working to the same perceived effort level, a greater reflex response (represented by BP and HR data) was elicited at 60% MVC than at any of the other ischemic tensions. These data are consistent with the hypothesis that, as tension increases, factors aside from insufficient blood flow contribute to the work effect on muscle metabolites and the magnitude of the reflex response.

Adult↗

Increased plasma beta-hydroxybutyrate, preserved cerebral energy metabolism, and amelioration of brain damage during neonatal hypoxia ischemia with dexamethasone pretreatment.

Dexamethasone (DEX) pretreatment has been shown to be neuroprotective in a neonatal rat model of hypoxia ischemia (HI). The exact mechanism of this neuroprotection is still unknown. This study used 31P nuclear magnetic resonance spectroscopy to monitor energy metabolism during a 3-h episode of HI in 7-d-old rat pups in one of two groups. The first group was pretreated with 0.1 mL saline (i.p.) and the second group was treated with 0.1 mL of 0.1mg/kg DEX (i.p.) 22 h before HI. Animals pretreated with DEX had elevated nucleoside triphosphate and phosphocreatine levels during HI when compared with controls. Saline-treated animals had significant decreases in nucleoside triphosphate and phosphocreatine and increases in inorganic phosphate over this same period. 31P nuclear magnetic resonance data unequivocally demonstrate preservation of energy metabolism during HI in neonatal rats pretreated with DEX. Animals pretreated with DEX had little or no brain damage following 3 h of HI when compared with matched controls, which experienced severe neuronal loss and cortical infarction. These same pretreated animals had an increase in blood beta-hydroxybutyrate levels before ischemia, suggesting an increase in ketone bodies, which is the neonate's primary energy source. Elevation of ketone bodies appears to be one of the mechanisms by which DEX pretreatment provides neuroprotection during HI in the neonatal rat.

3-Hydroxybutyric Acid↗

Spatial partitioning of host habitat by chewing lice of the genera Geomydoecus and Thomomydoecus (Phthiraptera: Trichodectidae).

Chewing lice, Geomydoecus and Thomomydoecus, coexist on pocket gophers, Thomomys spp. We investigated the spatial distribution of the 2 genera on their hosts and explored possible mechanisms of resource partitioning by chewing lice. Chewing lice appear to partition available host resources spatially, with Geomydoecus occurring primarily on the lateral and dorsal regions of the host, and Thomomydoecus occurring primarily on the lateral and ventral regions. Although spatial partitioning of the host habitat is evident, it does not appear to be explained by hair diameter. Spatial partitioning of the host's body could be the result of some other factor, possibly temperature or humidity gradients of the host's body.

Animals↗

Generalized tuberculosis in the acquired immune deficiency syndrome.

OBJECTIVE: Generalized, or hematogenously disseminated, tuberculosis (TB) in patients with the acquired immune deficiency syndrome (AIDS) has been associated with a high incidence of cases remaining undiagnosed until postmortem. To better characterize generalized TB in the setting of AIDS, this report describes the clinical, laboratory, radiologic, and pathologic features of 20 fatal cases. DESIGN: The medical records, autopsy protocols, and histologic material from patients with AIDS and concomitant TB were reviewed. All patients were autopsied at a tertiary care medical center during the years 1985-1997. RESULTS: In 50% of our 20 cases, diagnosis was not made until postmortem. Signs and symptoms were few, including the absence of fever (temperature > or = 38 degrees C) in 55% of patients. Consistent laboratory abnormalities of a nonspecific nature were limited to hyponatremia (sodium <135 mmol/L) in 60%. Both peripheral and deep (thoracic and abdominal) lymphadenopathy, unusual in adults with TB, occurred in 45% and 95% of cases, respectively. In contrast to previous reports, all of the 6 cases of tuberculous meningitis presented as acute meningitis with a predominance of neutrophils in cerebrospinal fluid. Necrotizing encephalitis with extension of the acute inflammation into the superficial cortex was seen in all cases and tuberculous brain abscesses occurred in 50% of cases, a higher frequency than previously reported. Despite lung involvement in 90% of the cases, 33% of chest radiographs were interpreted as normal and disseminated mycobacterial disease was not suggested in the radiograph report in any of the other cases. Soft tissue abscesses in uncharacteristic locations such as the neck, mediastinum, and perirectal area occurred in these patients. Histologically, 95% of organs sampled showed inflammatory foci characterized by extensive necrosis with numerous neutrophils and/or karyorrhectic debris, numerous acid-fast bacilli, few or no epithelioid histiocytes, and no Langhans giant cells. CONCLUSION: Clinically and pathologically, generalized TB in the setting of AIDS is characterized by either unusual features or a lack of the typical features described for generalized TB in patients who do not have AIDS. This absence of classic features contributes to the high incidence of cases that remain undiagnosed until postmortem examination.

Acquired Immunodeficiency Syndrome↗

Rat model of perinatal hypoxic-ischemic brain damage.

To gain insights into the pathogenesis and management of perinatal hypoxic-ischemic brain damage, the authors have used an immature rat model which they developed many years ago. The model entails ligation of one common carotid artery followed thereafter by systemic hypoxia. The insult produces permanent hypoxic-ischemic brain damage limited to the cerebral hemisphere ipsilateral to the carotid artery occlusion. The mini-review describes recently accomplished research pertaining to the use of the immature rat model, specifically, investigations involving energy metabolism, glucose transporter proteins, free radical injury, and seizures superimposed upon cerebral hypoxia-ischemia. Future research will focus on molecular mechanisms of neuronal injury with a continuing focus on therapeutic strategies to prevent or minimize hypoxic-ischemic brain damage.

Animals↗

Multiple echo frequency-domain image contrast: improved signal-to-noise ratio and T2 (T2*) weighting.

Conventional T2- and T2*-weighted image contrasts are produced by waiting a TE period for the transverse magnetic resonance (MR) signals to decay to differentiate tissue types with distinct relaxation rates. Significant image signal-to-noise ratio (SNR) is compromised by this contrast-producing process. In this report, a multiple echo frequency-domain image contrast (MEFIC) method is presented. During the conventional TE period, a multiple echo train modulated by T2 or T2* decay is acquired. A third Fourier transform along the echo direction produces an image set with pixel signal intensity modulated by the spectrum of the decay curve. This method simultaneously enhances image contrast with a large increase in SNR. Experimental studies of cerebral vasogenic edema in immature rats and functional MR imaging studies of the human motor cortex have demonstrated that the MEFIC method produces superior image quality over conventional methods for generating T2- and T2* weighted images.

Animals↗

Microimaging at 14 tesla using GESEPI for removal of magnetic susceptibility artifacts in T(2)(*)-weighted image contrast.

In magnetic resonance imaging (MRI), T(2)(*)-weighted contrast is significantly enhanced by extremely high magnetic field strength, offering broad potential applications. However, the T(2)(*)-weighted image contrast distortion and signal loss artifact arising from discontinuities of magnetic susceptibility within and around the sample are also increased, limiting utilization of high field systems for T(2)(*)-weighted contrast applications. Due to the B(0) dependence of the contrast distortions and signal losses, and the heterogeneity of magnetic susceptibility in biological samples, magnetic susceptibility artifacts worsen dramatically for in vivo microimaging at higher fields. Practical applications of T(2)(*)-sensitive techniques enhanced by higher magnetic fields are therefore challenged. This report shows that magnetic susceptibility artifacts dominate T(2)(*)-weighted image contrast at 14 T, and demonstrates that the GESEPI (gradient echo slice excitation profile imaging) technique effectively reduces or eliminates these artifacts at long TE in the highest field (14 T) currently available for (1)H imaging.

Algorithms↗

Primary care: choices and opportunities for racial/ethnic minority populations in the USA and UK--a comparative analysis.

This paper examines and compares the choices made and the opportunities provided by the United States and the United Kingdom in delivering primary care services to their racial/ethnic minority populations. While both nations agree that the most effective strategy for health service delivery to a diverse population lies in primary care, their approaches to obtaining this goal have been quite different. Sociological theories of functionalism and conflict perspective provide the analytical and organizing framework of the paper. Within this theoretical context, the health systems in place in each country are examined as an outgrowth of the larger socio-political, economic and cultural structures of the US and UK. Analysis of the advance of managed care in the US and the recent NHS reforms are also discussed in terms of lessons learned and the difficulties that lay ahead in order to ensure that these new developments contribute significantly to eliminating the disproportionately worse health status of racial ethnic minorities. Towards that goal the paper identifies opportunities for collaboration and specific recommendations for future action by both countries.

Ethnicity↗

Comparative performance of the RapID Yeast Plus System and the API 20C AUX Clinical Yeast System.

The performance of the RapID Yeast Plus System (Innovative Diagnostic Systems, Norcross, Ga.), a 4-h micropanel using single-substrate enzymatic test reactions, was compared with that of the API 20C AUX Clinical Yeast System (bioMerieux Vitek, Hazelwood, Mo.), a 48- to 72-h carbohydrate assimilation panel. Two hundred twenty-five yeasts, yeast-like fungi, and algae, comprising 28 species and including 30 isolates of Cryptococcus neoformans, an important pathogen not tested in appreciable numbers in other comparisons, were tested by both methods. On initial testing, 196 (87.1%) and 215 (95.6%) isolates were correctly identified by the RapID and API systems, respectively. Upon repeat testing, the number of correctly identified isolates increased to 220 (97.8%) for the RapID system and 223 (99.1%) for the API system. Reducing the turbidity of the test inoculum to that of a no. 3 McFarland turbidity standard, which is below that recommended by the manufacturer, resulted in the correct identification of most of the isolates initially misidentified by the RapID system, including 10 of 30 C. neoformans isolates. Concordance between the RapID and API results after repeat testing was 97.3%.

Fungi↗

Zygomycosis due to Apophysomyces elegans: report of 2 cases and review of the literature.

OBJECTIVE: The zygomycete Apophysomyces elegans is an unusual human pathogen that is being reported with increasing frequency as a cause of infection in previously healthy patients following trauma or after invasive procedures. We report 2 cases of infection caused by this emerging fungal pathogen. METHODS: Histologic sections of tissue removed from the infected patients and the isolates in culture were examined. Other infections caused by A. elegans that have been reported in the literature were reviewed. RESULTS: Both patients developed infection due to A. elegans after sustaining trauma that required tissue debridement because of tissue necrosis. Histologic examination showed broad, sparsely septate, thin-walled hyphae and angioinvasion with thrombosis. Extensive coagulation necrosis of surrounding tissue was seen. A rapidly growing mold with sporangiophores having funnel-shaped apophyses and pyriform sporangia, characteristic of A. elegans, was isolated from each case. CONCLUSION: Apophysomyces elegans is an opportunistic pathogen that can cause infection in previously healthy patients who suffer an injury to the cutaneous barrier, such as trauma or burns. Infection with this zygomycete should be considered when there is progressive necrosis of a wound in a previously healthy patient. Successful treatment requires tissue debridement and amphotericin B. Histologic examination for early diagnosis and frozen section evaluation of surgical margins are required for optimal therapy.

Child↗

Evaluation of the enhanced amplified Mycobacterium tuberculosis direct test for direct detection of Mycobacterium tuberculosis complex in respiratory specimens.

OBJECTIVE: To evaluate the performance of the enhanced Mycobacterium Tuberculosis Direct Test (E-MTD), for the direct detection of M tuberculosis complex (MTBC) in respiratory specimens. DESIGN: Two hundred seventy-four respiratory specimens from 151 patients in respiratory isolation were tested with the E-MTD, and the results were compared with the results of mycobacterial smear, culture, and the earlier form of the test, MTD-1. RESULTS: Forty-one specimens were culture positive for mycobacteria (20 MTBC and 21 nontuberculous mycobacteria), 23 of which were smear positive (16 MTBC, 7 nontuberculous mycobacteria). Twenty-four specimens were positive by E-MTD, and 21 were positive by MTD-1. Of the 20 MTBC culture-positive specimens, 19 were positive by the E-MTD and 19 were positive by the MTD-1. The remaining specimens were MTBC negative by all methods. After resolution of discrepancies, the sensitivity, specificity, and positive and negative predictive values were 95.2%, 100%, 100%, 99.6% for the MTD-1 and 95.2%, 98.8%, 87.0%, and 99.6%, for the E-MTD. For the E-MTD smear-positive and smear-negative specimens, these same values were 93.8%, 100%, 100%, and 87.5% and 100%, 98.8%, 62.5%, and 100%, respectively. CONCLUSION: The results suggest that the E-MTD is a reliable method for the direct detection of MTBC in smear-positive respiratory specimens.

Bacteriological Techniques↗

Removal of local field gradient artifacts in T2*-weighted images at high fields by gradient-echo slice excitation profile imaging.

Development of high magnetic field MRI techniques is hampered by the significant artifacts produced by B0 field inhomogeneities in the excited slices. A technique, gradient-echo slice excitation profile imaging (GESEPI), is presented for recovering the signal lost caused by intravoxel phase dispersion in T2*-weighted images. This technique superimposes an incremental gradient offset on the slice refocusing gradient to sample k-space over the full range of spatial frequencies of the excitation profile. A third Fourier transform of the initial two-dimensional image set generates an image set in which the artifacts produced by the low-order B0 inhomogeneity field gradients in the sample are separated and removed from the high-order microscopic field gradients responsible for T2* contrast. Application to high field brain imaging, at 3.0 T for human and at 9.4 T for immature rat imaging demonstrates the significant improvement in quality of the T2*-weighted contrast images.

Algorithms↗

SAR and B1 field distributions in a heterogeneous human head model within a birdcage coil. Specific energy absorption rate.

Calculations of radiofrequency magnetic (B1) field and specific energy absorption rate (SAR) distributions in a sphere of tissue and a multi-tissue human head model in a 12-element birdcage coil are presented. The coil model is driven in linear and quadrature modes at 63, 175, 200, and 300 MHz. Plots of B1 field magnitude and SAR distributions, average SAR, maximum local SAR, and measures of B1 field homogeneity and signal-to-noise ratio are given. SAR levels for arbitrary pulse sequences can be estimated from the calculated data. Maximum local SAR levels are lower at lower frequencies, in quadrature rather than in linear coils, and in linear fields oriented posterior-to-anterior rather than left-to-right in the head. It should be possible to perform many experiments in the head at frequencies up to 300 MHz without exceeding standard limits for local or average SAR levels.

Color↗