Search PubMed⌕ Search

Biomedical subjects

R A Lew

Publications and source records attributed to R A Lew.

At least 55 records · Page 3Linked to original sources
PubMed1997

Evaluation of the Ultraviolet Index: media reactions and public response.

BACKGROUND: In response to the increasing rate of skin cancer, particularly melanoma in the United States, the Environmental Protection Agency, the National Weather Service, the Centers for Disease Control and Prevention, National Association of Physicians for the Environment, and the American Academy of Dermatology, developed the Ultraviolet Index (UVI) to inform the public of the strength of the sun's rays and advise on methods for sun protection. OBJECTIVE: Our purpose was to evaluate the extent to which television stations and newspapers reported the UVI and assess the public's response to it. METHODS: To evaluate the effect of this effort, we surveyed television weather forecasters at 185 stations and examined weather pages in 54 newspapers in 58 cities that received the UVI reports. We also conducted a population probability telephone survey of 700 white adults (18 years of age and older) in these 58 cities. RESULTS: Seventy-one percent of the 169 stations that provided survey data for both 1994 and 1995 broadcast the UVI; 61% of newspapers reported the UVI. Nearly 64% of the 700 respondents (n = 445) had heard of the UVI. Of these respondents, 38% (n = 170) stated that they or their family changed their sun protection practices as a result of the UVI. CONCLUSION: The majority of television weather forecasters and newspapers reported the UVI. Most of the public was aware of the UVI, causing some to change sun protection practices. Further evaluation is required to maximize the effect of the UVI on sun protection practices.

Adult↗
PubMed1997

Localization of bradykinin B2 binding sites in rat kidney following chronic ACE inhibitor treatment.

Bradykinin exerts important influences on renal hemodynamics and tubular function by acting on renal bradykinin B2 receptors. However, the precise sites and mechanisms of its actions on the kidney are not known. To help elucidate the mechanisms of renal actions of bradykinin in vivo, we have employed high resolution electron microscopic autoradiography to localize bradykinin B2 binding sites in the rat kidney following intravenous administration of a radiolabeled ligand, 125I-HPP-Hoe140 (3-4-Hydroxyphenyl-propionyl-DArg0-[Hyp3-Thi5-D-Tic 7-Oic8]-bradykinin), a derivative of the highly selective bradykinin B2 receptor antagonist, Hoe140. In non-treated rats, bradykinin B2 binding sites were localized to the cell bodies and the luminal brush border of the proximal convoluted tubules in the cortex. In the medulla (except for the outer stripe of the outer medulla), binding occurred in the distal tubules, thin limbs of the loop of Henle, collecting ducts, peritubular capillary endothelium and renomedullary interstitial cells. To exclude the possibility that the radioligand may bind to angiotensin converting enzyme, rats were pretreated with the angiotensin converting enzyme inhibitor, perindopril. In these rats, binding to the cell bodies and the luminal brush border of the proximal convoluted tubules in the cortex was completely abolished, while binding remained unaltered in the medulla. Further studies using high performance liquid chromatography revealed that while the radioligand was degraded following systemic administration in nontreated rats, the degradation was significantly reduced in the rats pretreated chronically with perindopril. These results indicate that binding detected in the proximal tubules in the normal rats is due primarily to the tubular uptake of the degraded radioligand, and that bradykinin B2 binding sites occur predominantly in the renal tubules, vascular endothelium, and renomedullary interstitial cells of the renal medulla.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1997

Peptidases that degrade gonadotropin-releasing hormone: influence on LH secretion in the ewe.

Several peptidases have been postulated to degrade the hypothalamic peptide gonadotropin-releasing hormone (GnRH), but it is not known if such enzymes contribute significantly to the delivery of GnRH to the pituitary in vivo. Furthermore, the activity of GnRH-inactivating peptidases may vary in different reproductive states, such as across the estrous cycle. In the present study, specific fluorescent substrates were used to measure the activity of the two major GnRH-degrading enzymes, prolyl endopeptidase (PEP) and endopeptidase 3.4.24.15 (EP 24.15), in soluble extracts of the median eminentes (ME) of ewes during different phases of the estrous cycle. Levels of EP 24.15 and PEP activity in the ME did not vary significantly across the cycle, although PEP activity was lowest at the time of the preovulatory luteinizing hormone (LH) surge. However, a statistically significant decline in PEP activity (18%, P = 0.02) was observed in the ME of OVX ewes in which a surge was induced by estrogen when compared to oil-treated OVX controls, suggesting a possible negative regulation of PEP activity by this steroid. The effect of intracerebroventricular (i.c.v.) infusion of several peptidase inhibitors on the pulsatile release of LH in the conscious OVX ewe was also examined. No consistent changes in the pattern of LH release were observed with i.c.v. infusion of the EP 24.15 inhibitor N-[1(R,S)-carboxy-3-phenylpropyl]-Ala-Ala-Tyr-p-aminobenzoate (cFP-AAY-pAB) or the angiotensin-converting enzyme (ACE) inhibitor captopril. Similarly, administration of the prolyl endopeptidase inhibitor bacitracin, or a more specific inhibitor of this enzyme, Z-Proprolinal (ZPP), did not alter LH release patterns. The results did not demonstrate a major role for changes in the activity of EP 24.15, PEP, or ACE in altering the pattern of GnRH secretion, but a minor reduction in PEP levels may occur at the time of the estrogen-induced LH surge.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1997

The globin fragment LVV-hemorphin-7 is an endogenous ligand for the AT4 receptor in the brain.

Angiotensin IV (Val-Tyr-Ile-His-Pro-Phe) has been reported to interact with specific high-affinity receptors to increase memory retrieval, enhance dopamine-induced stereotypy behavior, and induce c-fos expression in several brain nuclei. We have isolated a decapeptide (Leu-Val-Val-Tyr-Pro-Trp-Thr-Gln-Arg-Phe) from sheep brain that binds with high affinity to the angiotensin IV receptor. The peptide was isolated using 125I-angiotensin IV binding to bovine adrenal membranes to assay receptor binding activity. This peptide is identical to the amino acid sequence 30-39 of sheep betaA- and betaB-globins and has previously been named LVV-hemorphin-7. Pharmacological studies demonstrated that LVV-hemorphin-7 and angiotensin IV were equipotent in competing for 125I-angiotensin IV binding to sheep cerebellar membranes and displayed full cross-displacement. Using in vitro receptor autoradiography, 125I-LVV-hemorphin-7 binding to sheep brain sections was identical to 125I-angiotensin IV binding in its pattern of distribution and binding specificity. This study reveals the presence of a globin fragment in the sheep brain that exhibits a high affinity for, and displays an identical receptor distribution with, the angiotensin IV receptor. This globin fragment, LVV-hemorphin-7, may therefore represent an endogenous ligand for the angiotensin IV receptor in the CNS.

Adrenal Glands↗
PubMed1997

Sunbathing habits and sunscreen use among white adults: results of a national survey.

OBJECTIVES: This study assessed current levels of sunbathing and sunscreen use in the United States. METHODS: From a general-population telephone survey of aquatic activities among adults in 3042 US households, we examined responses by the 2459 Whites. RESULTS: Most adults (59%) reported sunbathing during the past year, and 25% reported frequent sunbathing. Of the subsample who reported sunbathing during the month before the interview, 47% routinely used sunscreen. Of these individuals, almost half did not use sunscreens with a solar protection factor of 15 or higher. CONCLUSIONS: About a quarter of US White adults report frequent sunbathing, and only about a quarter of sunbathers use sunscreens at recommended levels. These results should help focus future sun protection educational efforts.

Adolescent↗
PubMed1997

Prognostic value of a hand symptom diagram in surgery for carpal tunnel syndrome.

OBJECTIVE: To evaluate symptom patterns on a hand diagram as predictors of surgical outcome in carpal tunnel syndrome (CTS). METHODS: 202 patients with CTS enrolled in a prospective, community based cohort study in Maine completed a hand symptom diagram before surgery and at 6 month followup. They were asked to mark on the hand diagram the location of 3 symptoms: pain, numbness/tingling (NT), and "other" symptoms. The diagram was first divided into 6 regions following a standardized procedure. For the 6 regions, symptom patterns were identified separately for each of the 3 symptoms. Outcomes 6 months after surgery were expressed as the percentage of change on the Symptom Severity Scale and Function Status Scale of the Carpal Tunnel Syndrome Assessment Questionnaire, and the satisfaction with the results of the surgery. RESULTS: Several distinct symptom patterns were associated with the 3 principal outcomes in univariate and multivariate analysis. In linear regression models controlling for the baseline severity of symptoms and function, as well as other predictors, the hand symptom pattern variables accounted for 30, 14, and 24%, respectively, of the total explained variance in satisfaction, symptom severity, and functional status. Patients receiving Workers' Compensation (37% of the cohort) had more wrist pain and NT of the arm, and less pain involving the arm and upper palm. This group also had worse outcomes and were less satisfied with surgery. Drawing expansion was associated with a low score on the SF-36 mental health subscale. However, psychological impairment was not associated with a worse outcome. CONCLUSION: Symptom patterns identified preoperatively with a hand symptom diagram help to predict the outcome of carpal tunnel release.

Adult↗
PubMed1996

Differential activation of endopeptidase EC 3.4.24.15 toward natural and synthetic substrates by metal ions.

The activity of endopeptidase EC 3.4.24.15 (thimet oligopeptidase, EP 24.15), as measured by cleavage of a quenched fluorescent substrate, 7-methoxycoumarin-4-acetyl-Pro-Leu-Gly-Pro-D-Lys (2,4-dinitrophenyl), was increased 2-3 fold by the addition of 1 mM Mn2+ or of 10 mM Ca2+. The inhibitory capability of a specific EP. 24.15 inhibitor, N-[1-(R,S)-carboxy-3-phenylpropyl]-Ala-Ala-Tyr-p-aminobenzoate, was also increased at similar concentrations of these metal ions. However, the hydrolysis of naturally-occurring peptides, thought to be the physiological substrates for EP 24.15, was not affected by either Mn2+ or Ca2+. These results suggest that the binding of synthetic analogs to the enzyme may differ significantly from the binding, and thus hydrolysis, of natural peptide substrates and caution against drawing conclusions about substrate interactions with the active site from data obtained with modified peptide ligands.

Animals↗
PubMed1996

Classics in Spine. Surgery literature revisited.

STUDY DESIGN: This article reviews the criteria for evaluating the quality of clinical trials. OBJECTIVES: To outline the current methodologic standards by which the validity of controlled trials need to be evaluated. SUMMARY OF BACKGROUND DATA: Weber's study, published in 1983 in Spine, is the only randomized trial comparing surgery and conservative management of sciatica in herniated lumbar discs. METHODS: Weber's article is revisited to illustrate basic principles in the design of clinical trials. RESULTS: Weber's study is a classic in spine surgery and has changed thinking regarding the benefit of surgery in sciatica related to herniated lumbar discs. However, the authors found potentially critical flaws in this study: a large number of crossovers, inadequate sample size, and insensitive outcome measurements. CONCLUSIONS: A randomized, controlled trial is the most rigorous way to evaluate health intervention. Despite the difficulties of performing such studies, investigators should use the most appropriate scientific methodology.

Clinical Trials as Topic↗
PubMed1996

Utility of anti-Sm, anti-RNP, anti-Ro/SS-A, and anti-La/SS-B (extractable nuclear antigens) detected by enzyme-linked immunosorbent assay for the diagnosis of systemic lupus erythematosus.

OBJECTIVE: To determine the utility of anti-extractable nuclear antigen (anti-ENA) antibodies detected by enzyme-linked immunosorbent assay as a predictor for the diagnosis of systemic lupus erythematosus (SLE). METHODS: Among 2,185 serum samples sent for testing for antinuclear antibodies (ANA) by indirect immunofluorescence, 259 consecutive patients with positive ANA were identified. Medical charts of these patients were reviewed to assess the clinical diagnosis, with the reviewer having no knowledge of the anti-ENA result. Clinical data were abstracted for all patients, and diagnoses established using American College of Rheumatology criteria. The utility of ENA antibodies in the diagnosis of SLE was determined by univariate and multivariate analysis among all patients who were positive for ANA, patients who were positive for ANA and for anti-double-stranded DNA (anti-dsDNA), and patients who were positive for ANA and negative for anti-dsDNA. Clinical differences between SLE patients with and those without anti-ENA antibodies were assessed. RESULTS: Anti-ENA antibodies, especially anti-Ro/SS-A, showed strong predictive diagnostic value among ANA+/anti-dsDNA- patients, but were of no utility among ANA+/anti-dsDNA+ patients. The only clinical manifestations that were more common among anti-ENA+ SLE patients were pleuritis and the use of hydroxychloroquine. CONCLUSION: The presence of anti-ENA antibodies, especially anti-Ro/SS-A, is a useful predictor for the diagnosis of SLE, primarily among patients attending a referral rheumatology center who are positive for ANA and negative for anti-dsDNA. No major clinical differences were noted among ANA+ SLE patients with versus those without ENA.

Antibodies, Antinuclear↗
PubMed1996

Melanoma awareness and self-examination practices: results of a United States survey.

BACKGROUND: Skin cancers are common and there has been a dramatic increase in their incidence, particularly melanoma. However, little is known about awareness of melanoma and early detection practices in the general U.S. population. OBJECTIVE: In 1995, the American Academy of Dermatology increased their efforts to promote awareness of melanoma. This study was conducted to document current knowledge of melanoma and self-examination practices. METHODS: In February 1995, a telephone survey was conducted in a nationally representative sample of 1001 persons at least 18 years of age (3% margin of error) that included questions on knowledge, attitudes, and practices regarding early detection of melanoma. RESULTS: Almost 42% of those surveyed were unaware of melanoma, and only 26% of those who were aware could identify its specific signs. Most recognized at least one common risk factor for melanoma (e.g., sun exposure, fair skin). However, many did not distinguish melanoma from other skin cancers in terms of risk factors, signs of early disease, and body site distribution. The lowest measures of melanoma knowledge and attitudes were found among those who are male, nonwhite, and parents, and those with the lowest level of education and income. More than half (54%) did not conduct a self-examination. This practice was most frequently reported by women, white persons, and the elderly, as well as those with a greater knowledge of melanoma. CONCLUSION: Our research documents deficiencies in knowledge and practices related to early detection of melanoma in the general U.S. population and supports the need for public education about melanoma.

Adult↗
PubMed1996

Evaluation of the American Academy of Dermatology's National Skin Cancer Early Detection and Screening Program.

BACKGROUND: Increasing incidence and mortality rates from cutaneous melanoma are a major public health concern. As part of a national effort to enhance early detection of melanoma/skin cancer, the American Academy of Dermatology (AAD) has sponsored an annual education and early detection program that couples provision of skin cancer information to the general public with almost 750,000 free skin cancer examinations (1985-1994). OBJECTIVE: To begin to evaluate the impact of this effort, we determined the final pathology diagnosis of persons attending the 1992-1994 programs who had a suspected melanoma at the time of examination. METHODS: We directly contacted all such persons by telephone or mail and received pathology reports from those who had a subsequent biopsy. RESULTS: We contacted 96% of the 4458 persons with such lesions among the 282,555 screenings in the 1992-1994 programs. We obtained a final diagnosis for 72%, and the positive predictive value for melanoma was 17%. Three hundred seventy-one melanomas were found in 364 persons. More than 98% had localized disease. More than 90% of the confirmed melanomas with known histology were in situ or "thin" lesions (< or = 1.50 mm thick). The median thickness of all melanomas was 0.30 mm. The 8.3% of AAD cases with advanced melanoma (metastatic disease, regional disease, or lesions > or = 1.51 mm) is a lower proportion than that reported by the 1990 Surveillance, Epidemiology and End Result Registry. The rate of thickest lesions (> or = 4 mm) and late-stage melanomas among all participants was 2.83 per 100,000 population. Of persons with a confirmed melanoma, 39% indicated (before their examination) that without the free program, they would not have considered having a physician examine their skin. CONCLUSION: The 1992-1994 free AAD programs disseminated broad skin cancer educational messages, enabled thousands to obtain a free expert skin cancer examination, and found mostly thin, localized stage 1 melanomas (usually associated with a high projected 5-year survival rate). Because biases impose possible limitations, future studies with long-term follow-up and formal control groups should determine the impact of early detection programs on melanoma mortality.

Adult↗
PubMed1996

Synthetic inhibitors of endopeptidase EC 3.4.24.15: potency and stability in vitro and in vivo.

1. The role of the metalloendopeptidase EC 3.4.24.15 (EP 24.15) in peptide metabolism in vivo is unknown, in part reflecting the lack of a stable enzyme inhibitor. The most commonly used inhibitor, N-[1-(R,S)-carboxy-3-phenylpropyl]-Ala-Ala-Tyr-p-aminobenzoate (cFP-AAY-pAB, Ki = 16 nM), although selective in vitro, is rapidly degraded in the circulation to cFP-Ala-Ala, an angiotensin converting enzyme (ACE) inhibitor. This metabolite is thought to be generated by neutral endopeptidase (NEP; EC 3.4.24.11), as the Ala-Tyr bond of cFP-AAY-pAB is cleaved by NEP in vitro. In the present study, we have examined the role of NEP in the metabolism of cFP-AAY-pAB in vivo, and have tested a series of inhibitor analogues, substituted at the second alanine, for both potency and stability relative to the parent compound. 2. Analogues were screened for inhibition of fluorescent substrate cleavage by recombinant rat testes EP 24.15. D-Ala or Asp substitution abolished inhibitory activity, while Val-, Ser- and Leu-substituted analogues retained activity, albeit at a reduced potency. A relative potency order of Ala (1) > Val (0.3) > Ser (0.16) > Leu (0.06) was observed. Resistance to cleavage by NEP was assessed by incubation of the analogues with rabbit kidney membranes. The parent compound was readily degraded, but the analogues were twice (Ser) and greater than 10 fold (Leu and Val) more resistant to cleavage. 3. Metabolism of cFP-AAY-pAB and the Val-substituted analogue was also examined in conscious rabbits. A bolus injection of cFP-AAY-pAB (5 mg kg-1, i.v.) significantly reduced the blood pressure response to angiotensin I, indicating ACE inhibition. Pretreatment with NEP inhibitors, SCH 39370 or phosphoramidon, slowed the loss of cFP-AAY-pAB from the plasma, but did not prevent inhibition of ACE. Injection of 1 mg kg-1 inhibitor resulted in plasma concentrations at 10 s of 23.5 microM (cFP-AAY-pAB) and 18.0 microM (cFP-AVY-pAB), which fell 100 fold over 5 min. Co-injection of 125I-labelled inhibitor revealed that 80-85% of the radioactivity had disappeared from the circulation within 5 min, and h.p.l.c. analysis demonstrated that only 25-30% of the radiolabel remained as intact inhibitor at this time. Both analogues were cleared from the circulation at the same rate, and both inhibitors blunted the pressor response to angiotensin I, indicative of ACE inhibition. 4. These results suggest that both NEP and other clearance/degradation mechanisms severely limit the usefulness of peptide-based inhibitors such as cFP-AAY-pAB. To examine further EP 24.15 function in vivo, more stable inhibitors, preferably non-peptide, must be developed, for which these peptide-based inhibitors may serve as useful molecular templates.

Analysis of Variance↗
PubMed1996

Role of bradykinin receptors in the renal effects of inhibition of angiotensin converting enzyme and endopeptidases 24.11 and 24.15 in conscious rabbits.

1. We tested the effects on systemic haemodynamics and renal function, of inhibition of endopeptidase (EP) 24.15 (E.C. 3.4.24.15), in conscious uninephrectomized rabbits in which the activities of angiotensin converting enzyme (ACE, E.C. 3.4.15.1) and neutral endopeptidase (EP 24.11, E.C. 3.4.24.11) were already inhibited. To test the role of bradykinin B2-receptors in mediating the effects following inhibition of these enzymes, the antagonist Hoe 140 was used. 2. Hoe 140 (0.1 mg kg-1, i.v.) did not affect resting mean arterial pressure or heart rate, but antagonized the depressor effect of right atrial administration of bradykinin. The dose-response curve for bradykinin was shifted more than 1000 fold to the right for more than 4 h. Hoe 140 approximately doubled resting urine flow and increased fractional Na+ excretion from 4.2 to 6.0%; consistent with the hypothesis that it exerts a partial agonist effect on the kidney. 3. Combined inhibition of ACE (captopril; 0.25 mg kg-1 plus 0.2 mg kg-1h-1) and EP 24.11 (SCH 39370; 3 mg kg-1 plus 3 mg kg-1h-1) was followed by a sustained reduction in arterial pressure (-6 +/- 2 mmHg) and increase in heart rate (35 +/- 7 beats min-1). There was a small increase in renal blood flow (by 6.5 +/- 3.2% relative to vehicle-treatment) without a change in glomerular filtration rate, and about a 150% increase in Na+ excretion. Hoe 140 (0.1 mg kg-1, i.v.) pretreatment did not influence the renal effects of captopril and SCH 39370, although it did appear to blunt their hypotensive and tachycardic effects. 4. When EP 24.15 was inhibited with N-[1-(R,S)-carboxy-3-phenylpropyl]-Ala-Ala-Tyr-p-aminobenzoate (cFP-AAY-pAB; 5 mg kg-1 plus 3 mg kg-1h-1, i.v.) in rabbits pretreated with captopril and SCH 39370, no changes in systemic haemodynamics or renal function were observed. 5. We concluded that in conscious uninephrectomized rabbits, EP 24.15 does not play a major role in modulating renal function, at least under conditions where ACE and EP 24.11 are already inhibited. In contrast, ACE and/or EP 24.11 do modulate renal function in this model, but their influences are mediated chiefly through metabolism of peptides other than bradykinin.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1996

Cutaneous melanoma mortality among the socioeconomically disadvantaged in Massachusetts.

OBJECTIVES: To identify groups for melanoma prevention and early detection programs, this study explored the hypothesis that survival with cutaneous melanoma is disproportionately lower for persons of lower socioeconomic status. METHODS: Massachusetts Cancer Registry and Registry of Vital Records and Statistics data (1982 through 1987) on 3288 incident cases and 1023 deaths from cutaneous melanoma were analyzed. Mortality/incidence ratios were calculated and compared, predictors of late stage disease were examined with logistic regression analysis, and a proportional hazards regression analysis that used death registration as the outcome measure for incident cases was performed. RESULTS: Lower socioeconomic status was associated with a higher mortality/incidence ratio after adjustment for age and sex. For education, the mortality/incidence ratio was 0.37 in the lower group vs 0.25 in the higher group (rate ratio = 1.48, 95% confidence interval [CI] = 1.08, 2.03). Late stage disease was independently associated with lower income (rate ratio for lowest vs highest tertile = 1.64, 95% CI = 1.20, 2.25), and melanoma mortality among case patients was associated with lower education (rate ratio = 1.52, 95% CI = 1.09, 213). CONCLUSIONS: Melanoma patients of lower socioeconomic status may be more likely to die from their melanoma than patients of higher socioeconomic status. Low- SES communities may be appropriate intervention targets.

Adult↗
PubMed1996

Morbidity and mortality in children associated with the use of tobacco products by other people.

OBJECTIVE: To evaluate the impact of adult tobacco use on the health of children. DESIGN: A literature review identified relevant research reports. Meta-analysis was used to compute a pooled risk ratio for each condition studied. The risk ratios were combined with data on exposure rates to produce estimates of the population-attributable risk. RESULTS: Each year, among American children, tobacco is associated with an estimated 284 to 360 deaths from lower respiratory tract illnesses and fires initiated by smoking materials, more than 300 fire-related injuries, 354,000 to 2.2 million episodes of otitis media, 5200 to 165,000 tympanostomies, 14,000 to 21,000 tonsillectomies and/or adenoidectomies, 529,000 physician visits for asthma, 1.3 to 2 million visits for coughs, and in children younger than 5 years of age, 260,000 to 436,000 episodes of bronchitis and 115,000 to 190,000 episodes of pneumonia. CONCLUSIONS: The use of tobacco products by adults has an enormous adverse impact on the health of children. Although more research is needed in several areas, action to reduce the morbidity and mortality among children should not be delayed. New laws and policies are needed to grant children protection from bodily injury and death attributable to use of tobacco products by others.

Adenoidectomy↗