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Biomedical subjects

L Goldberg

Publications and source records attributed to L Goldberg.

At least 19 recordsLinked to original sources

Breath alcohol concentration determined with a new analyzer using free exhalation predicts almost precisely the arterial blood alcohol concentration.

A new breath alcohol (ethanol) analyzer has been developed, which allows free exhalation, standardizes measured exhaled alcohol concentration to fully saturated water vapor at a body temperature of 37 degrees C (43.95 mg/L) and includes a built-in self-calibration system. We evaluated the performance of this instrument by comparing standardized alcohol concentration in freely expired breath (BrAC) with arterial (ABAC) and venous (VBAC) blood alcohol concentrations in fifteen healthy volunteers who drank 0.6 g of alcohol per kg body weight. The precision (coefficient of variation, CV) of the analyzer based on in vivo duplicate measurements in all phases of the alcohol metabolism was 1.7%. The ABAC/BrAC ratio was 2251+/-46 (mean+/-S.D.) in the post-absorptive phase and the mean bias between ABAC and BrAC x 2251 was 0.0035 g/L with 95% limits of agreement of 0.033 and -0.026. The ABAC and BrAC x 2251 were highly correlated (r=0.998, p<0.001) and the regression relationship was ABAC = 0.00045 + 1.0069 x (BrAC x 2251) indicating excellent agreement and no fixed or proportional bias. In the absorption phase, ABAC exceeded BrAC x 2251 by at most 0.04+/-0.03 g/L when tests were made at 10 min post-dosing (p<0.05). The VBAC/BrAC ratio never stabilized and varied continuously between 1834 and 3259. There was a proportional bias between VBAC and BrAC x 2251 (ABAC) in the post-absorptive phase (p<0.001). The pharmacokinetic analysis of the elimination rates of alcohol and times to zero BAC confirmed that BrAC x 2251 and ABAC agreed very well with each other, but not with VBAC (p<0.001). We conclude that this new breath analyzer using free exhalation has a high precision for in vivo testing. The BrAC reflects very accurately ABAC in the post-absorption phase and substantially well in the absorption phase and thereby reflects the concentration of alcohol reaching the brain. Our findings highlight the magnitude of arterio-venous differences in alcohol concentration and support the use of breath alcohol analyzers as a stand-alone test for medical and legal purposes.

Adult↗

A terminological and ontological analysis of the NCI Thesaurus.

OBJECTIVE: The National Cancer Institute Thesaurus is described by its authors as "a biomedical vocabulary that provides consistent, unambiguous codes and definitions for concepts used in cancer research" and which "exhibits ontology-like properties in its construction and use". We performed a qualitative analysis of the Thesaurus in order to assess its conformity with principles of good practice in terminology and ontology design. MATERIALS AND METHODS: We used both the on-line browsable version of the Thesaurus and its OWL-representation (version 04.08b, released on August 2, 2004), measuring each in light of the requirements put forward in relevant ISO terminology standards and in light of ontological principles advanced in the recent literature. RESULTS: We found many mistakes and inconsistencies with respect to the term-formation principles used, the underlying knowledge representation system, and missing or inappropriately assigned verbal and formal definitions. CONCLUSION: Version 04.08b of the NCI Thesaurus suffers from the same broad range of problems that have been observed in other biomedical terminologies. For its further development, we recommend the use of a more principled approach that allows the Thesaurus to be tested not just for internal consistency but also for its degree of correspondence to that part of reality which it is designed to represent.

Computational Biology↗

Fetal muscle gene transfer is not enhanced by an RGD capsid modification to high-capacity adenoviral vectors.

High levels of alpha(v) integrin expression by fetal muscle suggested that vector re-targeting to integrins could enhance adenoviral vector-mediated transduction, thereby increasing safety and efficacy of muscle gene transfer in utero. High-capacity adenoviral (HC-Ad) vectors modified by an Arg-Gly-Asp (RGD) peptide motif in the HI loop of the adenoviral fiber (RGD-HC-Ad) have demonstrated efficient gene transfer through binding to alpha(v) integrins. To test integrin targeting of HC-Ad vectors for fetal muscle gene transfer, we compared unmodified and RGD-modified HC-Ad vectors. In vivo, unmodified HC-Ad vector transduced fetal mouse muscle with four-fold higher efficiency compared to RGD-HC-Ad vector. Confirming that the difference was due to muscle cell autonomous factors and not mechanical barriers, transduction of primary myogenic cells isolated from murine fetal muscle in vitro demonstrated a three-fold better transduction by HC-Ad vector than by RGD-HC-Ad vector. We hypothesized that the high expression level of coxsackievirus and adenovirus receptor (CAR), demonstrated in fetal muscle cells both in vitro and in vivo, was the crucial variable influencing the relative transduction efficiencies of HC-Ad and RGD-HC-Ad vectors. To explore this further, we studied transduction by HC-Ad and RGD-HC-Ad vectors in paired cell lines that expressed alpha(v) integrins and differed only by the presence or absence of CAR expression. The results increase our understanding of factors that will be important for retargeting HC-Ad vectors to enhance gene transfer to fetal muscle.

Adenoviridae↗

A possible role for CXCR4 and its ligand, the CXC chemokine stromal cell-derived factor-1, in the development of bone marrow metastases in neuroblastoma.

The homing of hemopoietic stem cells to the bone marrow is mediated by specific interactions occurring between CXCR4, which is expressed on hemopoietic stem cells, and its ligand, stromal cell-derived factor-1 (SDF-1), a CXC chemokine secreted by bone marrow stromal cells. In the present study we evaluated the possibility that neuroblastoma cells use a mechanism similar to that used by hemopoietic stem cells to home to the bone marrow and adhere to bone marrow stromal cells. Our study suggests that CXCR4 expression may be a general characteristic of neuroblastoma cells. SH-SY5Y neuroblastoma cells express not only CXCR4, but also its ligand, SDF-1. CXCR4 expression on SH-SY5Y neuroblastoma cells is tightly regulated by tumor cell-derived SDF-1, as demonstrated by the ability of neutralizing Abs against human SDF-1alpha to up-regulate CXCR4 expression on the tumor cells. The reduction in CXCR4 expression following short term exposure to recombinant human SDF-1alpha can be recovered as a result of de novo receptor synthesis. Recombinant human SDF-1alpha induces the migration of CXCR4-expressing SH-SY5Y neuroblastoma cells in CXCR4- and heterotrimeric G protein-dependent manners. Furthermore, SH-SY5Y cells interact at multiple levels with bone marrow components, as evidenced by the fact that bone marrow-derived constituents promote SH-SY5Y cell migration, adhesion to bone marrow stromal cells, and proliferation. These results suggest that SH-SY5Y neuroblastoma cells are equipped with adequate machinery to support their homing to the bone marrow. Therefore, the ability of neuroblastoma tumors to preferentially form metastases in the bone marrow may be influenced by a set of complex CXCR4-SDF-1 interactions.

Animals↗

Progressive decreases in nuclear retinoid receptors during skin squamous carcinogenesis.

Retinoids are essential for normal skin growth, differentiation, and apoptosis and are active pharmacologically in the prevention and treatment of skin cancers and other lesions. Retinoid effects are mediated mainly by retinoic acid receptors (RARs) and retinoid X receptors (RXRs), which act as transcription factors to alter gene expression. Using in situ hybridization, we analyzed the expression of RARs and RXRs in normal sun-exposed skin (n = 85), squamous cell carcinoma (SCC; n = 28), and actinic keratosis [AK (a precursor to SCC); n = 38]. The expressions of five receptors (RAR-alpha and -gamma and RXR-alpha, -beta, and -gamma) were moderate to very strong in normal skin, with higher expressions in spinous and granular layers than in the basal layer. RAR-beta expression was weak or absent in normal and lesion samples. All five receptors expressed in the skin were suppressed progressively from normal skin to premalignant skin (AK) to invasive skin SCC. Specific receptor decreases in lesions relative to normal skin ranged from 75% (RXR-beta) to 96% (RAR-alpha) in SCC and from 37% (RAR-gamma) to 68% (RXR-beta) in AK. The degree of suppression of RXR-alpha and RAR-gamma, the two predominant retinoid receptors in skin, was relatively less for RXR-alpha (58% versus 86%; P = 0.015) and relatively greater for RAR-gamma (37% versus 89%; P = 0.0001) between AK and SCC, suggesting that suppression of RXR-alpha may be an earlier event and expression of RAR-gamma may be a later event of multistep squamous skin carcinogenesis. Our results indicate that suppressed expression of retinoid receptors occurs early (in AK) and is associated with progression of squamous skin carcinogenesis to SCC.

Aged↗

Mediating mechanisms in a program to reduce intentions to use anabolic steroids and improve exercise self-efficacy and dietary behavior.

This study investigated the mediating mechanisms responsible for the effects of a program designed to reduce intentions to use anabolic steroids, improve nutrition, and increase strength training self-efficacy. Fifteen of 31 high school football teams (N = 1,506 players at baseline) in Oregon and Washington were assigned to receive the intervention. The multicomponent program addressed the social influences promoting ergogenic drug use and engaging students in healthy nutrition and strength training alternative behaviors. Although the results differed across the three dependent variables, the program appeared to work by changing team norms. Unlike prevention of other drugs, changes in knowledge and perceived severity were mediators of program effects in this study.

Adolescent↗

Initial treatment of peritoneal dialysis peritonitis without vancomycin with a once-daily cefazolin-based regimen.

To reduce the use of vancomycin, the current recommendations of the International Society of Peritoneal Dialysis (PD) for the initial treatment of peritonitis complicating PD are to administer intraperitoneal (IP) cefazolin or cephalothin in every PD fluid bag, together with once-daily gentamicin. In view of the inherent impracticalities of this regimen, we studied the efficacy of once-daily cefazolin (1.5 g) IP with gentamicin IP as initial treatment for primary (nonrecurrent) PD peritonitis. This regimen has been used in all episodes of peritonitis not associated with tunnel or exit-site infections or fluid leaks. Sixty-nine episodes in 61 patients were analyzed (44 patients, continuous ambulatory PD; 22 patients, automated PD; and 3 patients, hospital-based intermittent PD), of which 38 episodes (55%) were gram-positive infections, 6 episodes (9%) were gram-negative infections, and 18 episodes (26%) had negative culture results. Four patients died within 4 weeks of infection (none considered attributable to inadequate treatment of their peritonitis). Ten catheters (14.5%) required removal to clear the infection; 7 catheters were in patients with gram-negative infections. The relapse rate within 4 weeks of ceasing antibiotic therapy was 8.9%. Compared with the results of 40 episodes of peritonitis treated initially with our previous IP vancomycin and gentamicin regimen, successful treatment (no death, catheter removal, or recurrence) was achieved in 52 of 69 episodes in the cefazolin group (75.4%) versus 23 of 40 episodes in the vancomycin group (57.5%; P: = 0.058). In conclusion, once-daily IP cefazolin and gentamicin for the initial treatment of PD peritonitis is at least as effective as a vancomycin-based regimen and is well tolerated.

Adult↗

Psychophysiological insomnia: combined effects of pharmacotherapy and relaxation-based treatments.

Objective: To compare treatment outcomes associated with combined pharmacologic and non-pharmacologic treatments for psychophysiological insomnia.Background: Treatments for insomnia have included a variety of pharmacotherapy and cognitive-behavioral interventions, although few studies have investigated the combined efficacy of drug and non-drug therapy.Methods: Forty-one patients with primary insomnia were randomly assigned to one of three treatment groups: (i) estazolam + muscle relaxation, (ii) estazolam + guided imagery, and (iii) estazolam + sleep education. After 4 weeks of active treatment, subjects were withdrawn from medication and followed for an additional 6 months.Results: Significant improvements were observed in self-report measures of total sleep time, sleep efficiency, and wakefulness after sleep onset in the combined drug and relaxation groups, compared to a significant improvement in total sleep time only in the educational control group. At follow-up, all three groups showed significant improvements across the major sleep measures. Positive changes were also observed in quality of life measures, including mood state and self- ratings of daytime arousal.Conclusions: These findings provide support for the value of combined pharmacotherapy and relaxation training in the treatment of psychophysiological insomnia.

Journal Article↗

The adolescents training and learning to avoid steroids program: preventing drug use and promoting health behaviors.

BACKGROUND: Use of alcohol and other illicit drugs by adolescent male athletes is a significant problem. Participation in sports may encourage use of drugs that enhance athletic performance, especially anabolic steroids (AS). Because, to our knowledge, no other intervention has successfully altered substance abuse by athletes, we developed and assessed the efficacy of a team-centered, sex-specific education program designed to reduce adolescent athletes' intentions to use and use of AS and alcohol and other illicit drugs. METHODS: We studied 31 high school football teams that comprised 3207 athletes in 3 successive annual cohorts (1994-1996). The intervention included interactive classroom and exercise training sessions given by peer educators and facilitated by coaches and strength trainers. Program content included discussion of sports nutrition, exercise alternatives to AS and sport supplements, and the effects of substance abuse in sports, drug refusal role-playing, and the creation of health promotion messages. Questionnaires assessing AS, the use of sport supplements and alcohol and other illicit drugs, and potential risk and protective factors were administered before and after the intervention (before and after the football season) and up to 1 year after the program. RESULTS: At season's end, intentions to use (P<.05) and actual AS use (P<.04) were significantly lower among students who participated in the study. Although AS reduction did not achieve significance at 1 year (P<.08), intentions to use AS remained lower (P = .02). Illicit drug use (marijuana, amphetamines, and narcotics) was reduced at 1 year, whether alcohol was included (P = .04) or excluded (P = .02) from the index. Other long-term effects included fewer students reporting drinking and driving (P = .004), less sport supplement use (P = .009), and improved nutrition behaviors (P<.02). CONCLUSIONS: Use of alcohol and other illicit drugs and associated harmful activities can be prevented with a sex-specific, team-centered education. School athletic teams provide an optimal environment in which to provide drug prevention and health promotion education.

Adolescent↗

Screening to the converted: an educational intervention in African American churches.

BACKGROUND: African American women have higher incidences of breast and cervical cancers and African American men present with more advanced stages of colon and prostate cancers than do their non-African American counterparts. Since the church is central to the organization of the African American community, the authors set out to determine whether a church-directed educational project could influence parishioners to obtain cancer screening. METHODS: Three African American churches having memberships of 250, 500, and 1,500, respectively, were selected for their different socioeconomic strata: one congregation was composed mostly of working poor, the second was more affluent, and the third consisted primarily of retirees. During a five-week summer period, appropriate literature, health fairs, testimonials by cancer survivors, and visits by representatives of the medical community were used to increase awareness of cancer screening. Surveys regarding cancer-screening behaviors were distributed at the end of church services. Using the guidelines established by the American Cancer Society, individual recommendations for screening examinations were developed and sent to parishioners based on their survey responses. RESULTS: Of 437 parishioners surveyed (73% female, 27% male), 75% were 40 years old or older. Many reported up-to-date screening for breast (84%), cervical (78%), colon (62%), and prostate (89%) cancers. The results were remarkably similar in all three churches. Telephone follow-up seven months after the survey directed at the 120 parishioners identified as noncompliant for at least one cancer screening revealed that 49% had obtained the appropriate screenings. CONCLUSIONS: These African American churchgoers were well screened compared with estimated national averages, possibly due to previous efforts of the activist ministers in the churches selected. The message for cancer screening is heeded when delivered through the African American church.

Adult↗

High-power continuous-wave mid-infrared radiation generated by difference frequency mixing of diode-laser-seeded fiber amplifiers and its application to dual-beam spectroscopy.

We report the generation of up to 0.7 mW of narrow-linewidth (<60-MHz) radiation at 3.3 micrometers by difference frequency mixing of a Nd:YAG-seeded 1.6-W Yb fiber amplifier and a 1.5-micrometers diode-laser-seeded 0.6-W Er/Yb fiber amplifier in periodically poled LiNbO3. A conversion efficiency of 0.09%/W (0.47 mWW-2 cm-1) was achieved. A room-air CH4 spectrum acquired with a compact 80-m multipass cell and a dual-beam spectroscopic configuration indicates an absorption sensitivity of +/-2.8 x 10(-5) (+/-1 sigma), corresponding to a sub-parts-in-10(9) (ppb) CH4 sensitivity (0.8 ppb).

Air Pollution, Indoor↗

Effects of pranidipine, a calcium channel antagonist, in an avian model of heart failure.

We have previously demonstrated that turkey poults fed furazolidone (Fz) in high concentrations (700 ppm) develop dilated cardiomyopathy (DCM) which approximates the human condition [1-3]. We wanted to study the effects of a calcium channel blocker in an animal model with a documented decrease in beta-receptor density, increased levels of circulating catecholamines, and abnormal calcium metabolism. The effects of a third generation calcium channel blocker has not been studied in our model. We hypothesized that the model would be predictive of the human condition and provide additional insights into the potential use of Ca2+ channel blockers in the setting of DCM. In the present study, we examined the effect of pranidipine, a new dihydropyridine calcium antagonist, in the setting of DCM on the gross and microscopic morphology of the heart and the overall contractile performance of the myocardium. A state of symptomatic to mild cardiomyopathy was induced in Broad-Breasted White turkey poults by administration of Fz for three weeks. Blood pressure, heart rate, fractional shortening, and body weight were monitored and compared in DCM animals treated with pranidipine and those given a placebo. After four weeks of treatment or no treatment with pranidipine, animals were euthanized and heart weight, cardiac dimensions, and microscopic morphology were compared. Progressive left ventricular (LV) dilatation and wall thinning was prevented with pranidipine treatment. In addition, microscopic examination demonstrated myocyte hypertrophy regression in DCM animals treated with pranidipine. In DCM animals, treatment with pranidipine resulted in significantly smaller left ventricular dimensions. We conclude that the calcium channel blocker pranidipine was not detrimental to global cardiac function in animals with dilated cardiomyopathy.

Animals↗

Amelanotic lentigo maligna melanoma: a unique case presentation.

Amelanotic melanomas comprise only 2% of melanomas and are commonly a difficult clinical diagnosis, due to the lack of melanin pigment typically found in melanomas. Even rarer is the amelanotic lentigo maligna, which may have an unusual clinical presentation, such as erythema, pruritus, or edema. Biopsy is the key to diagnosis. Multiple therapies for amelanotic lentigo malignas have been tried, but excision, with margin control (Mohs micrographic surgery-frozen or paraffin sections), remains the treatment of choice.

Aged↗

Mid-infrared difference-frequency generation source pumped by 1.1-1.5 micrometer dual-wavelength fiber amplifier for trace-gas detection.

Continuous-wave mid-infrared radiation near 3.5 micrometers is generated by difference-frequency mixing of the output of a compact 1.1-1.5 micrometer dual-wavelength fiber amplifier in periodically poled LiNbO3. The diode side-pumped amplifier is constructed with double-cladding Yb-doped fiber followed by single-mode Er/Yb codoped fiber. Output powers of as much as 11 microW at 3.4 micrometers are obtained, and spectroscopic detection of CH4 and H2CO is demonstrated.

Environmental Monitoring↗