Biomedical subjects

Charles Rohde

Publications and source records attributed to Charles Rohde.

13 recordsLinked to original sources

PubMed2006

A new method to estimate quantitatively seminal vesicle and prostate gland contributions to ejaculate.

AIMS: We sought to optimize a quantitative noninvasive method to determine the concentration in their glands of origin of biochemical markers of compartments of the male genital tract as the first step towards validation of a novel method for estimation of drug concentrations in these male genital tract compartments. METHODS: Sixty-eight men participated. We compared four collection devices to split ejaculate into fractions. Fractions were assayed for fructose and prostate specific antigen (PSA) as unique markers of the seminal vesicle and prostate, respectively. Seminal vesicle fructose and prostatic PSA were estimated using a linear regression method, based on fructose-PSA axis intercepts, and compared with an older method which solves a simultaneous series of equations. RESULTS: A five-compartment collection device performed best with mean (95% confidence interval) PSA vs. fructose r(2) of 0.84 (0.71, 0.98, P < 0.001). Using resampling simulations, glandular PSA and fructose estimates were highly variable and often implausible when using only two fractions. Using our method, the prostate contributed 37-44% to the whole ejaculate and the seminal vesicle contributed 55-61%. The novel regression method was highly correlated (r(2) > or = 0.98) with older methods. CONCLUSIONS: We developed a noninvasive quantitative method of male genital tract biochemical marker estimation using a five-compartment tray to collect three to five ejaculate fractions. Our novel regression method is quantitative and more fully developed than older methods. This noninvasive method for determining glandular marker concentrations should be useful to provide quantitative estimates of drug concentrations in these glands.

Andrology↗

PubMed2006

Increased occupancy of dopamine receptors in human striatum during cue-elicited cocaine craving.

In all, 19 research subjects, with current histories of frequent cocaine use, were exposed to cocaine-related cues to elicit drug craving. We measured the change of occupancy of dopamine at D2-like receptors with positron emission tomography (PET) and inferred a change of intrasynaptic dopamine (endogenous dopamine release), based on the displacement of radiotracer [(11)C]raclopride. Receptor occupancy by dopamine increased significantly in putamen of participants who reported cue-elicited craving compared to those who did not. Further, the intensity of craving was positively correlated with the increase in dopamine receptor occupancy in the putamen. These results provide direct evidence that occupancy of dopamine receptors in human dorsal striatum increased in proportion to subjective craving, presumably because of increased release of intrasynaptic dopamine.

Adult↗

PubMed2006

Enhanced surface-plasmon resonance absorption in metal-dielectric-metal layered microspheres.

We present a theoretical study of the dispersion relation of surface-plasmon resonances of mesoscopic metal-dielectric-metal microspheres. By analyzing the solutions to Maxwell's equations, we obtain a simple geometric condition for which the system exhibits a band of surface-plasmon modes whose resonant frequencies are weakly dependent on the multipole number. Using a modified Mie calculation, we find that a large number of modes belonging to this flat-dispersion band can be excited simultaneously by a plane wave, thus enhancing the absorption cross section. We demonstrate that the enhanced absorption peak of the sphere is geometrically tunable over the entire visible range.

Journal Article↗

PubMed2006

Quantitative assessment of seminal vesicle and prostate drug concentrations by use of a noninvasive method.

BACKGROUND: The male genital tract is a complex collection of anatomically and biochemically distinct compartments that contribute to the ejaculate. Understanding the pharmacokinetics in these compartments should inform rational therapeutics involving these glands. METHODS: Nineteen men were administered a single dose of 600 mg chloroquine (base) and 975 mg aspirin before providing a semen sample by masturbation with fractionation into a 5-compartment collection device. Fractions were assayed for fructose (unique seminal vesicle marker), prostate-specific antigen (unique prostate marker), salicylate, and chloroquine. Seminal vesicle and prostate concentrations of salicylate and chloroquine were estimated via a novel analytic method involving a multilevel latent-variable model implemented by use of Bayesian methods. RESULTS: The geometric mean chloroquine semen/blood ratio was 4.02 (95% confidence interval [CI], 2.36-6.86); for salicylate, the primary metabolite of aspirin, the semen/blood ratio was 0.10 (95% CI, 0.08-0.14). The estimated mean prostate/seminal vesicle ratio for salicylate, 0.38 (95% CI by Bayesian methods, 0.12-0.73), was consistent with our hypothesis that salicylate would achieve higher concentrations in the seminal vesicle than in the prostate. Chloroquine, however, did not demonstrate a statistically significant seminal vesicle/prostate difference (4.41; 95% CI by Bayesian methods, 0.14-30.52). CONCLUSIONS: We successfully demonstrated the quantitative, noninvasive estimation of drug concentrations in the prostate gland fluid distinct from the seminal vesicle fluid using our optimized method of split-ejaculate collection and a novel mixed-effects model with Bayesian estimation. Our methods can be applied to gland-specific quantitation of drugs and other substances of interest, thus enabling pharmacokinetic, pharmacodynamic, and pathophysiologic studies to inform rational therapeutics within different glands of the male genital tract.

Adult↗

PubMed2005

Peripheral pathways regulate motoneuron collateral dynamics.

Motor axons regenerating after repair of mixed nerve reinnervate pathways leading to muscle more often than those leading to skin [preferential motor reinnervation (PMR)]. Motoneurons that initially project collaterals to both muscle and skin prune incorrect projections to generate specificity. The number of motor axon collaterals maintained entirely within cutaneous or muscle pathways, however, is unknown. To overcome this shortcoming, dorsal root ganglion excision has been used to allow only motor axons to regenerate after a peripheral lesion. Motor axon number in reinnervated cutaneous and muscle pathways can then be correlated with the number of parent motoneurons determined by retrograde labeling. The number of collaterals per neuron can be calculated for each environment and the relative roles of pathway and end organ assessed by blocking the distal pathways to prevent target reinnervation. Without sensory competition, PMR develops in two stages: a limited response to muscle nerve and then a robust response to muscle that may involve retrograde signaling to the proximal pathway. Motoneurons maintain more collaterals in cutaneous nerve than in muscle nerve, even without muscle contact. This difference could result either from increased collateral formation in cutaneous nerve or from increased collateral pruning in muscle nerve. In either instance, these findings confirm that muscle and cutaneous pathways have functionally significant identities that can be recognized by motor axons and can regulate their arborization. Decreased arborization in muscle pathways could promote regeneration by focusing neuronal resources on high-yield projections; increased arborization in cutaneous pathways, conversely, would enhance pathfinding abilities.

Animals↗

PubMed2005

Pathway sampling by regenerating peripheral axons.

A century ago, Ramon y Cajal described the generalized response of regenerating peripheral axons to their environment. By using mice that express fluorescent proteins in their axons, we are now able to quantify the response of individual axons to nerve transection and repair. Sciatic nerves from nonexpressing mice were grafted into those expressing a yellow variant of green fluorescent protein, then examined at 5, 7, or 10 days after repair. Regeneration was found to be a staggered process, with only 25% of axons crossing the repair in the first week. In the setting of Wallerian degeneration, this stagger will expose growth cones to an evolving menu of molecular cues upon which to base pathway decisions. Many axons arborize, allowing them to interact simultaneously with several pathways. Arborization could serve as the anatomical substrate for specificity generation through collateral pruning. Axons often travel laterally across the face of the distal stump before choosing a pathway. As a result, the average unbranched axon has access to over 100 distal Schwann cell tubes. This extensive access, however, does not ensure correct matching of axon and end organ, suggesting that pathway choice is made on the basis of factors other than end organ identity. These observations explain the failure of refined surgical techniques to restore normal function after nerve injury. The apparent wandering of axons across the repair defies surgical control and mandates a biological approach to reuniting severed axons with appropriate distal pathways.

Animals↗

PubMed2005

Biosolids compost amendment for reducing soil lead hazards: a pilot study of Orgro amendment and grass seeding in urban yards.

In situ inactivation of soil Pb is an alternative to soil removal and replacement that has been demonstrated in recent years at industrial sites with hazardous soil Pb concentrations. Most children exposed to elevated soil Pb, however, reside in urban areas, and no government programs exist to remediate such soils unless an industrial source caused the contamination. Modern regulated biosolids composts have low Pb concentrations and low bioaccessible Pb fractions and can improve grass growth on urban soils. High Fe and P biosolids composts can reduce the bioavailability and bioaccessibility of soil Pb and can aid in establishing vegetation that would reduce soil transfer into homes. For these reasons, we conducted a field test of their use to reduce Pb bioaccessibility in urban soils in Baltimore, MD USA. We chose biosolids compost for its expected reduction in the bioaccessible Pb fraction of urban soils, ease of use by urban residents, and ability to beautify urban areas. Nine urban yards with mean soil Pb concentrations >800 mg Pb kg(-1) were selected and sampled at several distances from the house foundation before soil treatment. The soils were rototilled to 20 cm depth to prepare the sites, and resampled. The yards were then amended with 6-8 cm depth of Orgro biosolids compost (110-180 dry t/ha) rich in Fe and P, mixed well by rototilling, and resampled. Kentucky bluegrass (Poa pratensis) was seeded and became well established. Soils were resampled 1 year later. At each sampling time, total soil Pb was measured using a modified U.S. EPA nitric acid hotplate digestion method (SW 846 Method 3050) and bioaccessible Pb fraction was measured using the Solubility/Bioaccesibility Research Consortium standard operating procedure with modifications, including the use of glycine-buffered HCl at pH 2.2. Samples of untreated soils were collected from each yard and mixed well to serve as controls for the Pb bioaccessibility of field treated soils over time independent of positional variance within yards. At 1-year post-treatment, grass cover was healthy and reductions in bioaccessible Pb concentrations compared to pre-tillage were 64% (from 1655 to 595 mg kg(-1)) and 67% (from 1381 to 453 mg kg(-1)) at the sampling lines closest to the houses. Little or no reduction in bioaccessible Pb concentration was observed at sampling lines more remote from the house that also had the lowest bioaccessible Pb concentrations at pre-tillage (620 and 436 mg kg(-1), respectively). For the control soils, changes over time in total Pb and bioaccessible Pb concentrations and the bioaccessible Pb fraction were insignificant. This study confirms the viability of in situ remediation of soils in urban areas where children are at risk of high Pb exposure from lead in paint, dust and soil.

Biological Availability↗

PubMed2005

Electrical stimulation restores the specificity of sensory axon regeneration.

Electrical stimulation at the time of nerve repair promotes motoneurons to reinnervate appropriate pathways leading to muscle and stimulates sensory neurons to regenerate. The present experiments examine the effects of electrical stimulation on the specificity of sensory axon regeneration. The unoperated rat femoral cutaneous branch is served by 2-3 times more DRG neurons than is the muscle branch. After transection and repair of the femoral trunk, equal numbers of DRG neurons project to both branches. However, 1 h of electrical stimulation restores the normal proportion of DRG neurons reinnervating skin and muscle. To ask if the redistribution of stimulated neurons results from enhanced specificity of target reinnervation, we developed a new technique of sequential double labeling. DRG neurons projecting to the femoral muscle branch were prelabeled with Fluoro Gold 2 weeks before the nerve was transected proximally and repaired with or without 1 h of 20-Hz electrical stimulation. Three weeks after repair, the muscle nerve was labeled a second time with Fluororuby. The percentage of regenerating neurons that both originally served muscle and returned to muscle after nerve repair increased from 40% without stimulation to 75% with stimulation. Electrical stimulation thus dramatically alters the distribution of regenerating sensory axons, replacing normally random behavior with selective reinnervation of tissue-specific targets. If the enhanced regeneration specificity resulting from electrical stimulation is found to improve function in a large animal model, this convenient and safe technique may be a useful adjunct to clinical nerve repair.

Animals↗

PubMed2004

A study of urban housing demolition as a source of lead in ambient dust on sidewalks, streets, and alleys.

We examined changes in ambient dust lead (Pb) levels associated with the demolition of older row houses containing lead paint in Baltimore, MD, USA. Our previous paper describes the three study sites, the demolition processes, and increases in the Pb dustfall rate during demolition (>40-fold) and debris removal (>6-fold) within 10 m of sites where wetting was of limited effectiveness. This paper presents the analysis of settled dust collected using a cyclone device from streets, sidewalks, and alleys within 100 m of study sites before, immediately after, and 1 month after demolition. We found acute increases in Pb loadings and dust loadings after demolition and debris removal that are of public health concern. Streets and alleys had the greatest increases in Pb loadings and the highest levels overall. At one site, geometric mean (GM) Pb loadings immediately after demolition increased 200% for streets to 8080 microg/ft(2), 138% for alleys to 6020 microg/ft(2), and 26% for sidewalks to 2170 microg/ft(2). One month after demolition, the GM Pb loadings for streets, alleys, and sidewalks were reduced on average by 41-67% from post-demolition levels and were below baseline levels for alleys and sidewalks. The other main site had smaller increases in GM Pb loadings immediately after demolition-18% for alleys to 1740 microg/ft(2) and 18% for sidewalks to 2050 microg/ft(2)-and a decrease of 29% for streets to 2730 microg/ft(2). Exterior dust is a public health concern because it is a pathway of ambient Pb exposure and a potential source of residential exposure via tracking and re-aerosolization and re-deposition. Our findings highlight the need to control demolition-related Pb deposition and to educate planners, contractors, and health and housing agencies. This is particularly important given the large numbers of aging US dwellings that will be razed as part of future urban redevelopment efforts.

Air Pollutants↗

PubMed2003

Managed health plan effects on the specialty referral process: results from the Ambulatory Sentinel Practice Network referral study.

OBJECTIVES: The specialty referral process is one of the chief targets of managed care constraints on ambulatory medical decision-making. This study examines the influence of gatekeeping arrangements and capitated primary care physician (PCP) payment on the specialty referral process in primary care settings. RESEARCH DESIGN: Primary care practice-based study of referred and nonreferred office visits. SUBJECTS: The study comprised 14,709 visits made by privately insured, nonelderly patients who were seen by 139 primary care physicians in 80 practices located in 31 states. MEASURES: Visits were grouped by health plan type: gatekeeping with capitated PCP payment; gatekeeping with fee-for-service PCP payment; no gatekeeping. Dependent measures included the proportion of visits referred, characteristics of referrals, and physician coordination activities. RESULTS: The percentages of office visits resulting in a referral were similar between the two gatekeeping groups and higher than the no gatekeeping group. Patients in plans with capitated PCP payment were more likely to be referred for discretionary indications than those in nongatekeeping plans (15.5% v 9.9%, P < 0.05). The frequency of referring physician coordination activities did not vary by health plan type. The proportion of patients in gatekeeping health plans within a practice was directly related to employing staff as referral coordinators, allowing nurses to refer without physician consultation, and permitting patients to request referrals by leaving recorded telephone messages. CONCLUSION: The specialty referral process for privately insured nonelderly patients enrolled in managed health plans is generally similar, regardless of the presence of gatekeeping arrangements and capitated PCP payment. An increase in the number of discretionary referrals among patients in plans with capitated PCP payment provides support for exploring strategies that encourage PCPs to manage in their entirety conditions that straddle the boundaries between primary and specialty care. In response to increasing numbers of patients enrolled in managed health plans with gatekeeping arrangements, physicians appear to modify the structure of their practices to facilitate access to and coordination of referrals.

Capitation Fee↗

PubMed2003

Clinical variability in Rett syndrome.

The clinical variability of Rett syndrome, associated with mutations in the MECP2 gene, varies from classically symptomatic female patients to asymptomatic female patients, and male patients who have none of the diagnostic features considered pathognomonic of this disease. Multiple factors contribute to this variability. In our studies, mutations closer to the amino-terminus, prior to amino acid 255, led to severe clinical manifestations, such as inability to walk, severe dysphagia, and urinary organic acid abnormalities, compared with mutations toward the carboxyl-terminus. However, we found no correlation between severity and mutation type (missense versus nonsense). Despite the importance of mutation location to clinical severity, the widely varying severity within the same mutation suggests that in females, X-chromosome inactivation or other epigenetic phenomena also have roles in determining severity. We propose that stages 1 and 2 of the disease are a consequence of failed, time-linked, postnatal expression of MeCP2 in cerebellar neurons. This, in association with glutamate N-methyl-D-aspartate receptor-mediated neuroexcitotoxic injury to the differentiating neurons, results in the transient age-specific autistic-like behavior, motor, and cognitive dysfunction associated with these stages.

Animals↗

PubMed2003

A study of urban housing demolitions as sources of lead in ambient dust: demolition practices and exterior dust fall.

Demolition of older housing for urban redevelopment purposes benefits communities by removing housing with lead paint and dust hazards and by creating spaces for lead paint-free housing and other community resources. This study was conducted to assess changes, if any, in ambient dust lead levels associated with demolition of blocks of older lead-containing row houses in Baltimore, Maryland (USA). In this article we present results based on dust-fall samples collected from fixed locations within 10 m of three demolition sites. In subsequent reports we will describe dust lead changes on streets, sidewalks, and residential floors within 100 m of the demolition sites. Geometric mean (GM) lead dust-fall rate increased by > 40-fold during demolition to 410 micro g Pb/m2/hr (2,700 micro g Pb/m2 per typical work day) and by > 6-fold during debris removal to 61 micro g Pb/m2/hr (440 micro g Pb/m2 per typical work day). Lead concentrations in dust fall also increased during demolition (GM, 2,600 mg/kg) and debris removal (GM, 1,500 mg/kg) compared with baseline (GM, 950 mg/kg). In the absence of dust-fall standards, the results were compared with the U.S. Environmental Protection Agency's (U.S. EPA's) dust-lead surface loading standard for interior residential floors (40 micro g/ft2, equivalent to 431 micro g/m2); daily lead dust fall during demolition exceeded the U.S. EPA floor standard by 6-fold on average and as much as 81-fold on an individual sample basis. Dust fall is of public health concern because it settles on surfaces and becomes a pathway of ambient lead exposure and a potential pathway of residential exposure via tracking and blowing of exterior dust. The findings highlight the need to minimize demolition lead deposition and to educate urban planners, contractors, health agencies, and the public about lead and other community concerns so that society can maximize the benefits of future demolition activities nationwide.

Baltimore↗

PubMedDate not supplied

Primary care physician specialty referral decision making: patient, physician, and health care system determinants.

PURPOSE: To examine the effects of patient, physician, and health care system characteristics on primary care physicians' (PCPs') specialty referral decision making. METHODS: Physicians (n=142) and their practices (n=83) located in 30 states completed background questionnaires and collected survey data for all patient visits (n=34,069) made during 15 consecutive workdays. The authors modeled the occurrence of any specialty referral, which occurred during 5.2% of visits, as a function of patient, physician, and health care system structural characteristics. A subanalysis was done to examine determinants of referrals made for discretionary indications (17% of referrals), operationalized as problems commonly managed by PCPs, high level of diagnostic and therapeutic certainty, low urgency for specialist involvement, and cognitive assistance only requested from the specialist. RESULTS: Patient characteristics had the largest effects in the any-referral model. Other variables associated with an increased risk of referral included PCPs with less tolerance of uncertainty, larger practice size, health plans with gate-keeping arrangements, and practices with high levels of managed care. The risk of a referral being made for discretionary reasons was increased by capitated primary care payment, internal medicine specialty of the PCP, high concentration of specialists in the community, and higher levels of managed care in the practice. CONCLUSIONS: PCPs' referral decisions are influenced by a complex mix of patient, physician, and health care system structural characteristics. Factors associated with more discretionary referrals may lower PCPs' thresholds for referring problems that could have been managed in their entirety within primary care settings.

Adult↗