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Biomedical subjects

J C Martin

Publications and source records attributed to J C Martin.

At least 73 records · Page 4Linked to original sources

Activation of factor VII during alimentary lipemia occurs in healthy adults and patients with congenital factor XII or factor XI deficiency, but not in patients with factor IX deficiency.

Factor VII activity (FVIIc), a risk marker for coronary heart disease, is increased during postprandial lipemia. Factor VII activation accompanies lipolysis of triglyceride-rich lipoproteins, but the nature of this association and whether it is causal remain uncertain. To explore this issue, four patients with homozygous factor XII deficiency, four with complete factor XI deficiency, six with factor IX deficiency, and their respective age- and sex-matched controls were given two isocaloric dietary regimens, one providing on average 136 g fat and the other 19 g fat. Blood was taken before breakfast, immediately before lunch at 195 minutes, and at completion of the study at 390 minutes. All samples for each subject and matched control were assayed as one batch for FVIIc, activated factor VII, and factor VII antigen (FVIIag). Activation of factor VII was observed with the high-fat regimen but not with the low-fat regimen in all controls, factor XII-deficient patients, and factor XI-deficient patients. No factor VII activation was observed during either regimen in factor IX-deficient patients, but a normal postprandial responsiveness of factor VII to dietary fat was restored in one patient who replicated the study after factor IX therapy. Plasma FVIIag was not altered postprandially in either regimen in any group of patients or controls. Factor IX apparently plays an obligatory role in the postprandial activation of factor VII, although the mechanism remains to be determined.

Adult↗

Chronic recurrent multifocal osteomyelitis: spinal involvement and radiological appearances.

We report a case of chronic recurrent multifocal osteomyelitis which presented as back pain in a 14-yr-old male. The full distribution of the spinal lesions was determined by MRI, which proved to be more sensitive than other imaging modalities. After 1 yr, in spite of a good symptomatic response to corticosteroid therapy, new MRI abnormalities had developed.

Adolescent↗

Monoclonal gammopathy associated with crescentic glomerulonephritis and antimyeloperoxidase antibodies.

A 68-year-old male patient suffering from dizziness, gait instability, deafness, and visual loss showed proteinuria, hematuria, reduced creatinine clearance, and a monoclonal IgA lambda component. Renal biopsy revealed crescentic glomerulonephritis. Serum antibodies against myeloperoxidase were identified. These antibodies were IgG, not related to the IgA monoclonal component. This clinical description adds new information to the spectrum of diseases associated with glomerulonephritis and antimyeloperoxidase antibodies and illustrates that a monoclonal component cannot be directly implicated in the pathogenesis of a vasculitic process associated with antineutrophil cytoplasm antibodies.

Aged↗

Appendicular measurements in screening women for low axial bone mineral density.

Assessment of bone density at hip, spine, radius and calcaneus can predict fracture risk. This paper examines whether women with low bone mineral density (BMD) at the hip and spine can be identified by radial or calcaneal BMD assessment, thus enabling pre-selection of such women for further investigation. BMD in the lumbar spine (LS), femoral neck (FN), trochanter (FT) and Ward's area (FW) was measured by dual energy X-ray absorptiometry (DEXA). These measurements were compared with total (Qtot), trabecular (Qtrab), subcortical (Qscort) and cortical (Qcort) BMD of the ultradistal radius measured by peripheral quantitative computed tomography (pQCT), and ultrasound attenuation (BUA) and velocity (VOS) at the os calcis. Measurements were performed on 216 perimenopausal women aged between 45 and 55 years who attended a randomized osteoporosis screening programme. Correlations for pQCT and ultrasound with DEXA measurements were, at best, moderate (r = 0.05-0.53), being poorest for Qcort and VOS. Similar correlations were found between ultrasound and pQCT measurements (r = 0.05-0.31). None of the pQCT or ultrasound measurements predicted low DEXA measurements. 50-56% of women in the lowest quartile (QU4) of Qtot, Qtrab, Qscort and BUA were also in QU4 of LS; 45-57% were in QU4 of FT and FW, but only 22-33% were in QU4 of FN. To detect all women with osteopenia at FN or LS using pQCT or ultrasound, almost the entire population would have to be screened. In conclusion, pQCT and os calcis ultrasound measurements cannot successfully predict hip and spine osteopenia and could not be used to pre-select women for DEXA hip and spine assessment.

Absorptiometry, Photon↗

Interleukin-1 beta, prostaglandin E2, and immunoglobulin G subclasses in gingival crevicular fluid in patients undergoing periodontal therapy.

Determination of the presence of inflammatory products found in gingival crevicular fluid (GCF) may be of value in evaluating both periodontal disease status and the outcome of therapy. Immunoglobulin G subclasses 1 through 4 (IgGs), interleukin 1-beta (IL-1 beta), and prostaglandin E2 (PGE2) have all been shown to be present in GCF. This study monitored IgGs, IL-1 beta, and PGE2 in GCF of 18 adult patients as they progressed through periodontal treatment toward maintenance therapy. Sites were selected from the most severely affected sextant as determined by probeable crevice depth (PD) at initial examination (IE). GCF was collected on four occasions: initial examination; 4 weeks after completion of initial therapy (oral hygiene counseling, and scaling and root planing); 3 months after completion of surgery; and 7 to 9 months later at a maintenance visit. All variables were reduced to binary form (positive or negative), and break points chosen to separate the approximately symmetrical bell-shaped areas (negatives) from the skewed tails (positives). Repeated measures analyses of variance were performed to detect significant changes in all variables across time. Significant improvements were observed for all the clinical variables measured: PD, attachment level, and bleeding on probing. However, significant reductions for the GCF components only occurred in the concentrations of IL-1 beta and PGE2, but were not evident until the maintenance sampling. Surprisingly, GCF:serum ratios of IgG subclasses did not change significantly over the course of the investigation. The robustness of the levels of these components may be due to inflammation associated with the healing process, or to a further plaque induced response.

Adult↗

Health-related practices and priorities: the health behaviors and beliefs of community-living Black older women.

Black older women were found to have a high mean level of adherence to recommended health-protecting behaviors. Participants perceived that adherence to health-protecting behaviors played a highly important role in helping them to live a long and health life. Nurses must direct increased attention and intervention to the importance of practicing primary prevention behaviors as an assertion of control over the future health, well-being, and quality of life of Black older women.

Black or African American↗

[Post-radiotherapy cutaneous neuro-endocrine carcinoma].

INTRODUCTION: Merkel cell carcinoma or cutaneous neuroendocrine carcinoma is an uncommon severe disease. The carcinogenic effect of ionizing radiations has been suspected in exceptional observations. We report the sixth case of Merkel cell neuroendocrine carcinoma in a patient with prior radiotherapy. CASE REPORT: An 86-year-old man underwent radiotherapy for a basal cell carcinoma of the tip of the nose and developed a highly aggressive Merkel cell carcinoma at the same location 6 years later. DISCUSSION: The development of Merkel cell carcinoma on irradiated tissue accounts for 2.6 p. 100 of the 227 publications where dermatological history was reported. This percentage may be underestimated. The similar localizations of the irradiated zone and the site of cancer development 5 years later suggest that the Merkell cell carcinoma may be a radio-induced tumor. The delay may vary from 5 to 47 years. The similarity of the carcinogenic factors involved in Merkel cell carcinoma and squamous cell or basal cell carcinomas (ultraviolet, ionizing irradiation) and the frequent association of different types favor an epidermal origin for Merkel cell carcinoma. In clinical practice, past history of radiotherapy in an area where Merkell cell carcinoma develops indicates that therapeutic management must exclude post-operative radiotherapy.

Aged↗

Simultaneous dual-frequency phase-sensitive flow cytometric measurements for rapid identification of heterogeneous fluorescence decays in fluorochrome-labeled cells and particles.

In frequency-domain lifetime spectroscopy, the apparent fluorescence lifetimes obtained from phase-shift measurements are independent of modulation frequency only in the special case of a single exponential fluorescence decay. For heterogeneous fluorescence decay, the apparent fluorescence lifetimes measured by the phase-shift methods are functions of the modulation frequency. This modulation-frequency dependent property of apparent fluorescence lifetimes may be used to identify heterogeneous fluorescence decays by measuring lifetimes at multiple frequencies. In this article we explore the requirements and experimental design considerations for making such measurements in flow. We report a phase-sensitive flow cytometric method that allows one to probe the excited state-lifetimes of labeled cells by using multiple simultaneous modulation frequencies. Application of this method is demonstrated by measuring fluorescence lifetimes of labeled cells at two frequencies simultaneously, using a continuous-wave, dual-frequency modulated excitation in flow. The dual-frequency method presented herein can be used to rapidly identify heterogeneity in the fluorescence decay on a cell-by-cell basis in real time. Information on the nature of the fluorescence decay is important in biological measurements because it can provide insight into intermolecular interactions at the subcellular level.

Animals↗

A rapid mix flow cytometer with subsecond kinetic resolution.

Kinetic approaches are valuable tools for mechanistic studies of cell function. Flow cytometry is well suited to make sensitive kinetic measurements, but the time required to deliver mixed samples to the point of measurement (10-20 s in a conventional cytometer) limits analysis of rapidly occurring events. To address this limitation, we adapted a syringe-based stopped-flow rapid mixing device to a modified commercial flow cytometer to achieve mixing and measurement of sample in under 1 s. Because such screw-driven mixers are designed to deliver fluid at rates of microliters per millisecond and cytometers accept samples at microliters per second, the syringe mixer was modified with a screw to allow sample delivery at rates as low as 1.8 microliters/s. A custom-made nozzle holder featuring a fast-acting three-way sample delivery valve and a 1.5- microliters dead volume was designed for a Becton Dickinson FACS stream-in-air flow nozzle. Syringe motors and valves are computer controlled, as is the start signal for an adjustable time ramp. A stable sample stream can be established within the sheath stream in less than 1 s, enabling fluorescence measurements of microspheres with coefficients of variation of approximately 5%. Light scatter gating to select particles in the center of the laser beam enables fluorescence measurements at times of under 300 ms. Efficient mixing of reagents is demonstrated by the iodide quenching of microspheres surface labeled with fluorescein isothiocyanate (FITC). The instrument is capable of quantitatively proportioning cells and reagent, thereby allowing precise control of reagent concentration and dilution. Rapid kinetic measurements of intact cells are demonstrated by FITC-formyl peptide binding to cell surface receptors.

Flow Cytometry↗

Spatial dependence of the optical collection efficiency in flow cytometry.

The sensitive flow cytometric detection of fluorescent species in liquid sample streams requires efficient collection of light from small [approximately 1 picoliter (pl)] sample volumes. This is often accomplished with high numerical aperture (NA) imaging collection optics used in combination with a spatial filter. A method to measure the spatial variation of the optical collection efficiency within the sample volume, using a submicrometer light source, is described. Measurements of the relative optical collection efficiency are presented for two optical collection systems used in our laboratory for single molecule detection. The measurement are in qualitative agreement with relative optical collection efficiency calculations using a simple geometrical optics model. Absolute measurements of the peak collection efficiencies for the two collection systems are also presented. These absolute collection efficiency measurements are in good quantitative agreement with ideal collection efficiencies calculated using measured transmissions and rated NAs of the collection optics. The utility of this information for the characterization and optimization of sensitive fluorescence detection apparatus is discussed.

Equipment Design↗

Activation of factors XII and VII induced in citrated plasma in the presence of contact surface.

Activated factor XII (XIIa), activated factor VII (VIIa) and factor VII coagulant activity (VIIc) were determined in non-treated and in treated (cold-incubated) citrated plasmas from women in late pregnancy and from norma volunteers. All three activities were higher in the non-treated plasmas from women in late pregnancy than from normal subjects. The incubation of citrated plasmas from women in late pregnancy, on ice for 24 hours, resulted in a many-fold increase of factor XIIa activity, factor VIIa levels and VIIc. The dilution of these plasmas resulted in a sharp decrease of all three activities in the post-incubation mixture, so that in the plasmas diluted 2:1 with buffer all three activities were similar to those in fresh plasmas. Similar incubations of diluted plasmas (1:1) from normal volunteers resulted in no increase of factor XIIa activity, factor VIIa levels and VIIc. However, the presence in the incubation mixture of micellar stearate resulted in a stearate concentration-dependent increase of all three activities in treated plasmas. Levels of factor XIIa activity and factor VIIa in the treated plasmas from both groups of subjects were highly correlated (r = 0.987; p < 0.001). There was also a highly significant correlation between VIIc and factor VIIa levels (0.989; p < 0.001). These results demonstrate that the in vitro increase in factor VIIa levels is due to the activation of the contact system of coagulation and is dependent on the potency of the contact surface. Moreover, VIIc over a wide range of values, observed in the present experiments, can provide an accurate measure of factor VIIa concentration.

Adult↗

(S)-1-[3-hydroxy-2-(phosphonylmethoxy)propyl]cytosine (cidofovir): results of a phase I/II study of a novel antiviral nucleotide analogue.

Cidofovir, (S)-1-[3-hydroxy-2-(phosphonylmethoxy)propyl]cytosine, is a novel antiviral nucleotide analogue with potent in vitro and in vivo activity against cytomegalovirus (CMV) and other herpesviruses. Thirty-one human immunodeficiency virus-seropositive patients with asymptomatic CMV excretion were evaluated in a phase I/II study with 2 regimens of cidofovir: cidofovir alone at doses of 0.5, 1.0, 3.0, or 10.0 mg/kg/week (20 patients) and cidofovir at 3.0, 5.0, or 7.5 mg/kg with concomitant oral probenecid, saline prehydration, extended dosing intervals, and drug interruption for proteinuria (19 patients). Prolonged and dose-dependent anti-CMV effect was observed with all cidofovir regimens > or = 3.0 mg/kg. The dose-limiting toxicity of cidofovir was dose- and schedule-dependent nephrotoxicity. Four of 20 patients had serum creatinine levels > or = 2.0 mg/dL after a mean cumulative exposure of 14.8 mg/kg cidofovir alone; however, none of 19 patients receiving the modified regimen had elevated creatinine (mean cidofovir exposure, 32.2 mg/kg). The clinical efficacy of cidofovir and its potential for cumulative nephrotoxicity needs further study in patients with end-organ CMV disease.

AIDS-Related Opportunistic Infections↗

Minocycline-associated lupus erythematosus.

We report a patient who developed symptoms of lupus erythematosus which was apparently related to minocycline therapy for acne vulgaris. To our knowledge, this is only the second reported case of minocycline-associated lupus erythematosus.

Acne Vulgaris↗

Decreased axial and peripheral bone density in patients taking long-term warfarin.

Impaired vitamin K metabolism is associated with under-carboxylation of the non-collagenous bone-matrix protein osteocalcin, which is required in its fully carboxylated state for normal bone formation. Post-menopausal women have under-carboxylation of osteocalcin which increases with age and is marked in the elderly. A similarly marked degree of impaired carboxylation occurs during coumarin therapy, and a key question is whether this may lead to accelerated loss of bone mass which is clinically important. We measured axial and peripheral bone mineral density (BMD) in 40 male patients on warfarin and 40 controls individually matched for age, disease and other drug therapy. A consistent trend for reduced BMD at all sites was observed in the warfarin-treated patients. This was particularly marked in the cancellous bone at the distal radius (9% reduction, p = 0.023) and at the cancellous rich lumbar spine site (10.4% reduction, p < 0.004). No significant relationship was observed between warfarin dose, International Normalized Ratio (INR) or duration of therapy and bone density. Because of the biochemical similarity, this study provides a new lead on post-menopausal osteoporosis, and supports the hypothesis that impaired carboxylation of osteocalcin plays a role in the pathogenesis of bone loss in the elderly through deficiency in vitamin K metabolism.

Absorptiometry, Photon↗

Synthesis, oral bioavailability determination, and in vitro evaluation of prodrugs of the antiviral agent 9-[2-(phosphonomethoxy)ethyl]adenine (PMEA).

A series of phosphonate prodrugs were evaluated in an attempt to increase the oral bioavailability of the anti-HIV agent 9-[2-(phosphonomethoxy)ethyl]adenine (PMEA; 1). The majority of the bis(alkyl ester) and bis(alkyl amide) prodrugs were prepared by alcohol or amine displacement of dichlorophosphonate 2. Basic hydrolysis of the bis(esters) or bis(amides) provided the corresponding monoesters or monoamides. Synthesis of bis[(acyloxy)alkyl] phosphonates 10a-c was accomplished by alkylation of PMEA with the appropriate chloromethyl ether in the presence of N,N'-dicyclohexylmorpholinecarboxamidine. The systemic levels of PMEA following oral administration of a PMEA prodrug to rats were determined by measuring the concentration of PMEA in the urine for 48 h after administration of the prodrug. The oral bioavailability of PMEA employing this method was determined to be 7.8%. Oral dosing with bis(alkyl) phosphonates 3a,b resulted in apparent absorption of the prodrugs (> or = 40%), although neither of the esters were completely cleaved to liberate the parent phosphonate PMEA. The mono(alkyl esters) 7a-e and 8a,b exhibited poor oral bioavailability (< or = 5%). Phosphonamides 5, 6, and 9 were unstable under acidic conditions and provided levels of PMEA comparable to the parent compound after oral administration. Bis[(acyloxy)alkyl] phosphonates 10a-c demonstrated significantly improved oral bioavailabilities of 17.6%, 14.6%, and 15.4%, respectively. When evaluated in vitro against HSV-2, (acyloxy)alkyl phosphonates 10a-c were greater than 200-fold more active than PMEA.

Adenine↗

Prodrugs of 2',3'-didehydro-3'-deoxythymidine (D4T): synthesis, antiviral activity, and rapid pharmacokinetic evaluation.

A series of 5'-derivatives and modified pyrimidine analogues of 2',3'-didehydro-3'-deoxythymidine (d4T, stavudine, 1) were synthesized to determine their potential as oral prodrugs of d4T. Utilizing a screen developed for the rapid evaluation of a variety of prodrugs in mice, it was determined that 5'-acetate 2 provided comparable plasma levels of d4T after oral administration of the prodrug to that when d4T was administered alone. The relative oral bioavailability of methoxy acetate 3 and cyclohexyl carbonate 5 was 79 and 41%, respectively. Dihydropyridine ester 6 did not provide detectable levels of d4T up to 1 h after oral administration of 6. Thiopyrimidines 8 and 9, as well as aminopyrimidine 10 also failed to provide measurable levels of d4T after oral administration. 5'-Derivatives 3, 5, and 6 showed similar activity to that of d4T against HIV and MuLV, as did 5'-benzoyl-4-thio derivative 8. However, the corresponding 4-thio 5'-alcohol 9 was inactive.

Animals↗