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Biomedical subjects

R Kelly

Publications and source records attributed to R Kelly.

At least 19 recordsLinked to original sources

Noninvasive determination of aortic input impedance and external left ventricular power output: a validation and repeatability study of a new technique.

OBJECTIVE: The study was designed to test whether aortic input impedance and left ventricular power output can be accurately assessed noninvasively. BACKGROUND: Aortic input impedance describes both the pulsatile and nonpulsatile artery load encountered by the left ventricle. Until now, this measure of afterload has only been determined by invasive techniques. METHODS: The aortic pressure wave was estimated by recording the calibrated carotid artery pressure wave noninvasively with use of a micromanometer-tipped probe by the technique of applanation tonometry. Flow was determined with pulsed wave Doppler measurement of ascending aortic velocity profile and aortic diameter. In 18 subjects undergoing cardiac catheterization, invasive measurements were taken to assess the accuracy of noninvasive data. In 17 other subjects noninvasive measurements were taken on different days to assess the reproducibility of results. RESULTS: Noninvasive pressure measurements correlated well with invasive data: systolic pressure (mm Hg), noninvasive 126 +/- 28 versus invasive 127 +/- 28, r = 0.96, p less than 0.001; diastolic pressure (mm Hg), noninvasive 71 +/- 10 versus invasive 66 +/- 7, r = 0.60, p less than 0.02; augmentation index (%), noninvasive 23.9 +/- 9.3 versus invasive 30.7 +/- 11.9, r = 0.87, p less than 0.001. Doppler-measured cardiac output was closely correlated with invasively measured flow (liters/min): Doppler, 5.3 +/- 1.2 versus invasive, 5.5 +/- 1.3, r = 0.98, p less than 0.001. Impedance and left ventricular power variables calculated from noninvasive and invasive techniques were also closely related: systemic vascular resistance (dynes.s.cm-5), noninvasive 1,479 +/- 488 versus invasive 1,502 +/- 498, r = 0.91, p less than 0.001; characteristic impedance (dynes.s.cm-5), noninvasive 137 +/- 52 versus invasive 136 +/- 79, r = 0.92, p less than 0.001; pulsatile power (mW), noninvasive 249 +/- 94 versus invasive 291 +/- 103, r = 0.91, p less than 0.001; mean power (mW), noninvasive 1,107 +/- 319 versus invasive 1,144 +/- 266, r = 0.93, p less than 0.001. Repeated measures of impedance variables and power output showed coefficients of variation of less than 9%. CONCLUSIONS: Measurement of noninvasive impedance by this technique provides an accurate and repeatable assessment of mean and pulsatile cardiac load.

Aorta

Clinical results of decompressive dermotomy-fasciotomy.

Seventy-three dermotomy-fasciotomies (DFs) were performed in 68 patients from 1986 to 1991. A database record was compiled on each patient. Variables included age, mode of injury, method of initial wound closure, and associated injuries. A multivariate stepwise logistic regression analysis was performed to determine which variables were associated with wound complications. Thirty-eight percent of patients who underwent DF developed wound complications. One hundred percent of those patients with postoperative arterial or graft thrombosis developed wound complications (p less than 0.01) as did 78% of those with thromboembolic disease (p less than 0.05). Conversely, only 5% of those who underwent closure of their DF wounds utilizing skin grafts developed wound complications (p less than 0.01) as compared with 51% of those who underwent secondary or primary closure only. Subsequent analysis of the remaining patients, excluding those with severe soft tissue injury, showed an association between location of DF (upper versus lower extremity) and the development of wound complications that approached statistical significance (p less than 0.06). DF is frequently necessary in the treatment of patients with compartment syndrome but is associated with significant morbidity. This study suggests that closure of DF wounds utilizing skin graft allows for continued osteofascial decompression while concomitantly minimizing invasive sepsis.

Adolescent

Selections from current literature: treatment of hypertension.

The three papers reviewed for this issue deal with unrelated aspects of hypertension, illustrating the broad range of questions that still exist about optimal diagnosis and management. Physicians have for years been unsure about the efficacy, safety, and impact on morbidity of treating ISH. The result of these concerns has been that many, if not most patients with ISH never received treatment. The SHEP data are a powerful argument for routine treatment of ISH, which would represent a new standard of care for this condition. Only clinical experience and future trials will indicate whether treatment of ISH in the general population will be accompanied by the low incidence of side effects and morbidity observed in the more highly selected population of the SHEP trial. The study of Zeller et al. adds to the evidence that less is more, or at least the same, when it comes to treatment of hypertensive urgencies. The practice of oral 'loading' doses was not shown to improve therapeutic results. It is still not completely clear what criteria physicians should use in making a decision about inpatient parenteral therapy versus outpatient oral therapy. In patients with evidence of acute onset and end-organ injury, it is probably prudent to admit. In the absence of these risk factors, institution of an outpatient oral antihypertensive regimen can probably be accomplished with safety and at dramatically lower cost. The study of Koren et al. demonstrated a marked additional risk when LVH was present in hypertensive patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged

Laboratory and field evaluation of five repellents against the black flies Prosimulium mixtum and P. fuscum (Diptera: Simuliidae).

Deet (N,N-diethyl-3-methyl-benzamide), the lactone CIC-4 ([2-hydroxy-methyl-cyclohexyl] acetic acid lactone), the USDA Proprietary Chemicals AI3-37220 (1- [3-cyclohexen-1-ylcarbonyl]-2-methylpiperidine) and ++[3-35765 (1-[3-cyclohexen-1-ylcarbonyl] piperidine), and the U.S. military extended duration repellent formulation (EDRF) of deet were evaluated for repellency in the laboratory and field against the black flies Prosimulium mixtum and P. fuscum. CIC-4, AI3-37220, and AI3-35765 were as effective as deet at repelling P. mixtum and P. fuscum in laboratory and field experiments. Only the EDRF provided significantly longer protection than the deet standard against these black flies in the field.

Animals

Multiple transmission of Plasmodium gallinaceum (Eucoccida: Plasmodiidae) during serial probing by Aedes aegypti (Diptera: Culicidae) on several hosts.

Mosquitoes salivate before ingesting blood, and sporozoites are transmitted during this phase of feeding. In the laboratory, malaria-infected Aedes aegypti were allowed to probe on a series of three chicks during a 5-min period. Probing on each host was interrupted after 10 s. Our results demonstrate that up to three hosts can be serially infected with avian malaria during a 5-min period.

Aedes

A zinc finger protein from Candida albicans is involved in sucrose utilization.

A sucrose-inducible alpha-glucosidase activity that hydrolyzes sucrose in Candida albicans has been demonstrated previously. The enzyme is assayable in whole cells and was inhibited by both sucrose and maltose. A C. albicans gene (CASUC1) that affects sucrose utilization and alpha-glucosidase activity was cloned by expression in a Saccharomyces cerevisiae suc2 mutant (2102) devoid of invertase genes. CASUC1 enabled the S. cerevisiae mutant to utilize both sucrose and maltose. DNA sequence analysis revealed that CASUC1 encodes a putative zinc finger-containing protein with 28% identity to a maltose-regulatory gene (MAL63) of S. cerevisiae. The gene products of CASUC1 and MAL63 are approximately the same size (501 and 470 amino acids, respectively), and each contains a single zinc finger located at the N terminus. The zinc fingers of CASUC1 and MAL63 comprise six conserved cysteines (C6 zinc finger) and are of the general form Cys-Xaa2-Cys-Xaa6-Cys-Xaavariable-Cys-Xaa2-Cys-+ ++Xaa6-Cys (where Xaan indicates a stretch of the indicated number of any amino acids). Both contain five amino acids in the variable region. CASUC1 also complemented the maltose utilization defect of an S. cerevisiae mutant (TCY-137) containing a defined mutation in a maltose-regulatory gene. The sucrose utilization defect of type II Candida stellatoidea, a sucrase-negative mutant of C. albicans, was corrected by CASUC1. Determinations of alpha-glucosidase activity in whole cells revealed that activity was restored in transformants cultivated on either sucrose or maltose. To our knowledge, this is the first zinc finger-encoding gene, as well as the first putative regulatory gene, to be identified in C. albicans.

Amino Acid Sequence

Nonclonal lymphocytic proliferation in cutaneous lymphoid hyperplasia: a flow-cytometric and morphological analysis.

Cutaneous lymphoid hyperplasia, follicular B cell pseudolymphoma or lymphadenosis benigna cutis and lymphocytic infiltration of Jessner-Kanof are a group of benign lymphoid hyperplastic disorders which usually involve the skin of the face or head and neck. These lesions may be difficult to differentiate from malignant lymphocytic lymphomas both morphologically and clinically. To evaluate whether quantitative flow-cytometric analysis and DNA ploidy determination of the lymphoid cells in the lesions would provide additional and more precise diagnostic parameters, we have correlatively analyzed a case by morphological, flow-cytometric and immunohistochemical methods. The two latter methods both revealed that the lesions harbored nonclonal heterogeneous subpopulations of lymphoid cells, but 62% of the cells analyzed were of B cell lineage progenies. No pre-B cells, immature B or T determinants were detected. Ploidy analysis of the isolated lymphocytes disclosed predominantly diploid (2 N) cells with about 1% 4 N and a few (less than 5%) hyperdiploid (2.2 N) cells. Cell cycle analysis showed that 97.2% of the cells were in G0-G1 phase. Phenotyping and DNA ploidy study of the lymphocytes of the lesion may provide quantitative diagnostic parameters to distinguish this benign lesion from true lymphocytic lymphoma involvement of skin. The eventual biological behavior of the minor hyperdiploid subpopulation of lymphoid cells found in this lesion is currently uncertain, however.

Antibodies, Monoclonal

Mosquito size and multiple transmission of avian malaria in the laboratory.

Probing mosquitoes salivate before ingesting blood, and malaria sporozoites are transmitted during this phase of feeding. Large and small Aedes aegypti infected with Plasmodium gallinaceum were allowed to probe briefly on a series of 3 naive chicks. Large mosquitoes were more infective overall, but there was no difference in the ability of either size class to infect the first host. Large mosquitoes were more likely than small mosquitoes to infect more than one host during serial feeding.

Aedes

Physician agreement with US Preventive Services Task Force recommendations.

BACKGROUND: No large-scale work has yet assessed the reactions of physicians to the report of the US Preventive Services Task Force (USPSTF), despite its potential for fostering a consensus among practitioners. This study undertook a survey of family physicians to assess their agreement with the recommendations of the Task Force. METHODS: A survey containing the verbatim summary recommendations of the USPSTF was mailed to all 1784 active members of the Ohio Academy of Family Physicians. RESULTS: No evidence of selection bias was found among the 898 responding physicians. The average physician agreed with 88% of the recommendations. For a number of recommendations, however, particularly those in which the Task Force differed with the American Cancer Society, there was a high level of disagreement. Physician disagreement with the recommendations was associated with older age, not having completed a residency, male sex, less prior exposure to the USPSTF guidelines, and greater perception of the impracticality of applying them. CONCLUSIONS: The high level of agreement with most USPSTF recommendations implies that they represent an emerging consensus about which preventive services should be delivered. Attempts at USPSTF guideline dissemination should focus on recommendations with high agreement. Additional research is needed to assess the reasons for disagreement.

Age Factors

Spontaneous mutation at the hypervariable mouse minisatellite locus Ms6-hm: flanking DNA sequence and analysis of germline and early somatic mutation events.

Hypervariability at minisatellite loci is maintained by spontaneous mutation to new-length alleles. At the most variable loci, mutation rate is directly measurable by pedigree analysis. The mouse minisatellite locus Ms6-hm has a germline mutation rate of 2.5% per gamete and is therefore one of the most unstable loci yet identified in the mouse genome. Mutation events at this locus also occur during early mouse development, resulting in mice mosaic for cells carrying a common non-parental allele in different somatic tissues and the germline. The DNA sequence flanking Ms6-hm is rich in dispersed repetitive elements; the minisatellite array has expanded from within a member of the Mouse Transcript family which is flanked by two additional Mouse Transcript elements, and a B2 element lies further 3' to the minisatellite. To define the characteristics of mutation events at Ms6-hm we have analysed 19 germline and 13 somatic length-change events. Germline mutation events at Ms6-hm are not accompanied by the exchange of flanking markers in three informative mutant alleles analysed.

Alleles

Liquorice.

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11-beta-Hydroxysteroid Dehydrogenases

Self-differentiation of human fetal lung organ culture: the role of prostaglandins PGE2 and PGF2 alpha.

Addition of PGE2, but not PGF2 alpha, to fetal lung organ cultures accelerates the process of self-differentiation with increased dilatation of terminal airsacs and differentiation of the epithelial lining. Indomethacin reduces the endogenous production by organ cultures of PGE2, PGF2 alpha, 13,14-dihydro-15-keto-PGE2, and 13,14-dihydro-15-keto-PGF2 alpha and retards the process of self-differentiation. Prolonged exposure of cultures to indomethacin results in cell necrosis. Indomethacin inhibition of self-differentiation can be reversed and accelerated by the addition of PGE2. Addition of PGF2 alpha in the presence of indomethacin prevents indomethacin-associated cell necrosis but does not accelerate dilatation or differentiation beyond that of cultures in sera-free media without additions. We propose that the endogenous production of PGE2 is a key process in the mechanism of self-differentiation of human fetal lung in organ culture.

Cell Differentiation

Block of current through single calcium channels by Fe, Co, and Ni. Location of the transition metal binding site in the pore.

The blocking actions of Fe2+, Co2+, and Ni2+ on unitary currents carried by Ba2+ through single dihydropyridine-sensitive Ca2+ channels were recorded from cell-attached patches on myotubes from the mouse C2 cell line. Adding millimolar concentrations of blocker to patch electrodes containing 110 mM BaCl2 produced discrete excursions to the closed channel level. The kinetics of blocking and unblocking were well described with a simple model of open channel block. Hyperpolarization speeded the exit of all of the blockers from the channel, as expected if the blocking site resides within the pore. The block by Ni2+ differs from that produced by Fe2+ and Co2+ because Ni2+ enters the channel approximately 20 times more slowly and exits approximately 50 times more slowly. Ni2+ also differs from the other transition metals because at millimolar concentrations it reduces the amplitude of the unitary current in a concentration-dependent manner. The results are consistent with the idea that the rate-limiting step for ion entry into the channel is water loss at its inner coordination sphere; unblocking, on the other hand, cannot be explained in terms of simple coulombic interactions arising from differences in ion size.

Animals

The adequacy of physician reimbursement for pediatric care under Medicaid.

This article examines 1989 Medicaid physician reimbursement for pediatric care in 47 states and the District of Columbia. To assess the adequacy of payment, several state reimbursement policies were analyzed, including physician payment methods, frequency of payment updates, and fee data for five common evaluation and management codes and two Early and Periodic Screening, Diagnosis, and Treatment visit categories. Physician payment rates were evaluated to determine overall state and regional patterns of Medicaid reimbursement. They were also compared with regional private market fee data and average national Medicare fees to assess their adequacy. The majority of state Medicaid programs used fixed fee schedules as their physician reimbursement method. Nearly one fourth of states that update their fees overall by physician specialty have not adjusted their rates since 1985 or before. Medicaid reimbursement rates for five commonly used evaluation and management Physicians' Current Procedural Terminology (4th ed) office visit codes and Early and Periodic Screening, Diagnosis, and Treatment screening and follow-up examinations varied substantially across states and among regions. States in the West paid the highest rates for most office visits, while Northeastern states generally paid the least. A comparison of Medicaid payment rates with private market fee data revealed that Medicaid payments for established patients averaged less than two thirds of market rates for pediatricians, family physicians, and general practitioners. New patient care is reimbursed somewhat better. Regional variations are substantial. In addition, a comparison of Medicaid payment rates with 1988 Medicare fee data showed that average Medicaid reimbursement rates were less than four fifths of average allowed Medicare charges. Policy implications include the need to increase Medicaid rates so that they are much closer to private insurance and Medicare rates, particularly in the Northeast and in selected states, in order to increase participation by pediatric providers in Medicaid. In addition, efforts to re-evaluate reimbursement relative to level of service, as used in Medicare's resource-based relative value scales, deserve further research. Finally, comparable access to comprehensive pediatric care especially in underserved urban areas will require not only improvements in physician reimbursement but also more deliberate efforts to affect the maldistribution of mainstream medical care. Approaches to measure the impact of enhanced reimbursement on access to care by Medicaid-eligible children are discussed.

Delivery of Health Care

Cloning and characterization of the 2,3-oxidosqualene cyclase-coding gene of Candida albicans.

2,3-Oxidosqualene (OS) cyclase (OSC) catalyzes the conversion of OS to lanosterol, an essential step in the biosynthesis of sterols. The Candida albicans gene (ERG7) encoding OSC was cloned by complementation of a Saccharomyces cerevisiae OSC mutant (erg7). Two different Erg+ clones were isolated that contain a common overlapping region. The minimum region required for complementation was determined to be approx. 3.2 kb and a single 2.7-kb ERG7 transcript was detected. The cloned Candida ERG7 DNA complemented an additional nonconditional erg7 allele and a temperature-sensitive erg7 mutation. OSC activity was restored in the mutants as determined by [14C]acetate incorporation in vivo as well as incorporation in vitro in cell-free extracts using either [14C]isopentenyl pyrophosphate or [3H]OS as substrate. The level of OSC produced from expression of a single copy of the Candida ERG7 sequence was sufficient to allow growth of the S. cerevisiae erg7 mutants in the absence of exogenous ergosterol. These data support the contention that the Candida ERG7 sequence is the structural gene for OSC.

Alleles

The efficacy of social-influence prevention programs versus "standard care": are new initiatives needed?

This study evaluates the effects of a school-based smoking prevention program after 1 year, using school (22 middle/elementary schools, 15 high schools) as both the unit of randomization and the unit of analysis. The multigrade level (grades 6 through 9) intervention was designed to address comprehensively the social influence factors that encourage smoking. Teacher survey data indicated that treatment schools had a median of 10 classroom sessions devoted to tobacco/drug use education, 5 of which were the sessions designed for this evaluation, and control schools had also dedicated a median of 10 classroom sessions to tobacco/drug education. Thus, the study evaluated the incremental effects of the social influence intervention compared to "standard-care" curricula. Among those who reported smoking one or more cigarettes in the month prior to the intervention, there was a significant treatment effect on rate of smoking at one year, but no grade level, gender, or interaction effects. The 1-year covariate-adjusted smoking rate among pretest smokers in the treatment schools was 76.6 cigarettes per month, compared to 111.6 cigarettes per month in control schools, a 31.4% difference. These effects were not accounted for by differential subject attrition. The analyses for nonsmokers, however, showed no significant effects, and the program did not affect self-reported alcohol or marijuana use. Taken together with the results of other prevention studies, these results point to the need for the development and evaluation of new initiatives to prevent substance use.

Adolescent