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Biomedical subjects

S Hunt

Publications and source records attributed to S Hunt.

At least 37 records · Page 2Linked to original sources

Salary equity among male and female internists in Pennsylvania.

BACKGROUND: Women constitute an increasing proportion of physicians in the United States. Historically, inequities have existed between male and female physicians in professional advancement, but evidence has suggested that disparities in salary are resolving. OBJECTIVE: To examine the current state of salary equity among male and female internists. DESIGN: Population-based survey mailed to all Board-certified female internists and a matched group of male internists who had graduated from medical school 10 to 30 years ago and were currently practicing. SETTING: Pennsylvania. PARTICIPANTS: 232 male and 213 female internists for whom data were complete. MEASUREMENTS: Respondents answered questions about demographic characteristics, training, practice type and setting, status within the practice, family life, and salary. RESULTS: Women were more likely to be involved in the least lucrative practice arrangements. They were more likely to be in low-paying specialties, to not be a partner in the practice, and to be salaried employees; they also spent fewer hours per week seeing patients. Even after adjustment for these differences, hourly earnings were significantly higher (14%) among men than among their female colleagues. Men's earnings significantly exceeded women's earnings among physicians with no academic affiliation, those in high-earning specialties, and those in general internal medicine. CONCLUSIONS: Significant salary differentials exist between male and female internists overall and in various medical practice settings.

Adult↗

Pharmacological blockade or genetic deletion of substance P (NK(1)) receptors attenuates neonatal vocalisation in guinea-pigs and mice.

The regulation of stress-induced vocalisations by central NK(1) receptors was investigated using pharmacological antagonists in guinea-pigs, a species with human-like NK(1) receptors, and transgenic NK1R-/- mice. In guinea-pigs, i.c.v. infusion of the selective substance P agonist GR73632 (0.1 nmol) elicited a pronounced vocalisation response that was blocked enantioselectively by the NK(1) receptor antagonists CP-99,994 and L-733,060 (0.1-10 mg/kg). GR73632-induced vocalisations were also markedly attenuated by the antidepressant drugs imipramine and fluoxetine (30 mg/kg), but not by the benzodiazepine anxiolytic diazepam (3 mg/kg) or the 5-HT(1A) agonist buspirone (10 mg/kg). Similarly, vocalisations in guinea-pig pups separated from their mothers were blocked enantioselectively by the highly brain-penetrant NK(1) receptor antagonists L-733,060 and GR205171 (ID(50) 3 mg/kg), but not by the poorly brain-penetrant compounds LY303870 and CGP49823 (30 mg/kg). Separation-induced vocalisations were also blocked by the anxiolytic drugs diazepam, chlordiazepoxide and buspirone (ID(50) 0.5-1 mg/kg), and by the antidepressant drugs phenelzine, imipramine, fluoxetine and venlafaxine (ID(50) 3-8 mg/kg). In normal mouse pups, GR205171 attenuated neonatal vocalisations when administered at a high dose (30 mg/kg) only, consistent with its lower affinity for the rat than the guinea-pig NK(1) receptor. Ultrasound calls in NK1R-/- mouse pups were markedly reduced compared with those in WT pups, confirming the specific involvement of NK(1) receptors in the regulation of vocalisation. These observations suggest that centrally-acting NK(1) receptor antagonists may have clinical utility in the treatment of a range of anxiety and mood disorders.

Animals↗

Determinants of coronary remodeling in transplant coronary disease: a simultaneous intravascular ultrasound and Doppler flow study.

BACKGROUND: Coronary remodeling plays a significant role in lumen loss in transplant allograft vasculopathy (TxCAD), but the determinants of remodeling are unknown. We assessed the relationship between remodeling and plaque topography, coronary compliance, and blood flow in TxCAD. METHODS AND RESULTS: One artery in each of 27 transplant patients was investigated with simultaneous intravascular ultrasound and coronary flow measurements (basal and hyperemic by Doppler flow wire). At 4 to 8 different cross sections (mean 5.1+/-1. 2), plaque topography (concentric or eccentric) was determined, and total vessel area, lumen area, and intimal/medial area (IMA) were measured. Mean remodeling ratio (vessel area/IMA) in eccentric lesions (E, n=28) was significantly larger than that in concentric lesions (C, n=70) (E 5.87+/-0.93 versus C 3.58+/-0.62; P<0.001), despite similar IMA (E 3.89+/-0.68 versus C 3.90+/-0.41; P=NS) and distribution of imaged segments. Remodeling ratio was consistently larger in eccentric lesions in all 3 vessel segments when analyzed separately, and mean remodeling ratio for each artery was larger in vessels with predominantly eccentric lesions. Coronary compliance ([Delta lumen area/diastolic lumen area]/Delta mean arterial pressure x 10(3)) was also significantly greater in eccentric lesions versus concentric lesions (proximal 1.00+/-0.39 versus 0.22+/-0.04; mid 0.71+/-0.17 versus 0.21+/-0.10; distal 0.43+/-0.13 versus 0. 01+/-0.08; all P<0.01). Coronary flow reserve was also significantly higher in coronary arteries with primarily eccentric lesions (E 2. 49+/-0.64 versus C 1.87+/-0.28; P<0.01). CONCLUSIONS: Vessel remodeling in transplant vasculopathy is significantly greater in eccentric lesions than in concentric lesions, possibly due to greater coronary compliance and resistive vessel function.

Compliance↗

A painful cutaneous nodule as the presentation of metastatic transitional cell carcinoma of the renal pelvis.

We report a 43-year-old man with HIV who presented with a painful, vascular-appearing nodule as the initial manifestation of metastasis of a prior transitional cell carcinoma of the renal pelvis. The transitional cell carcinoma had been treated by nephroureterectomy 4 years before the appearance of the nodule. Histopathologic comparison of the nodule with the prior transitional cell carcinoma and immunoperoxidase staining with monoclonal antibodies confirmed that the nodule was a metastasis of the original transitional cell carcinoma. In general, metastasis of transitional cell carcinoma to the skin is quite uncommon. This case is the first reported episode of transitional cell carcinoma of the renal pelvis metastasizing to the skin in the form of a vascular-appearing nodule. The significance of this unusual metastasis occurring in a person with HIV is unknown.

Adult↗

Enhanced bioavailability of azathioprine compared to 6-mercaptopurine therapy in inflammatory bowel disease: correlation with treatment efficacy.

BACKGROUND: Azathioprine and 6-mercaptopurine have proven efficacy in the treatment of Crohn's disease. Immunosuppression is mediated by their intracellular metabolism into active 6-thioguanine metabolites, and clinical responsiveness to therapy in patients with inflammatory bowel disease has been correlated with the measure of erythrocyte 6-thioguanine levels. AIMS AND METHODS: To perform a dosing equivalency analysis and comparison of clinical efficacy in 82 patients with inflammatory bowel disease on long-term (> 2 months) therapy with either branded azathioprine (Imuran) (n=26), generic azathioprine (n=38), or 6-mercaptopurine (n=18), based on the measurement of erythrocyte 6-thioguanine metabolite levels. RESULTS: Disease remission was achieved in 51% (42 out of 82) of patients treated with either azathioprine or 6-mercaptopurine therapy, and correlated well with high erythrocyte 6-thioguanine levels (> 250 pmoles/8 x 108 RBCs). Patients treated with either branded azathioprine or 6-mercaptopurine achieved significantly higher erythrocyte 6-thioguanine levels than patients treated with generic azathioprine, thereby suggesting that branded azathioprine has improved oral bioavailability compared to generic azathioprine. These data are consistent with the putative immunosuppressive role of 6-thioguanine metabolites in the treatment of inflammatory bowel disease, and provides a basis for developing a therapeutic index of clinical efficacy based on the measurement of erythrocyte 6-thioguanine metabolite levels. CONCLUSIONS: Our results suggest that differences in bioavailability may have clinical relevance when considering the need to optimize erythrocyte 6-thioguanine metabolite levels in patients deemed unresponsive to treatment on conventional drug dosages.

Administration, Oral↗

Sjögren's syndrome, cavitating lung disease and high sustained levels of antibodies to serine proteinase 3.

A case is described involving Sjögren's syndrome, high sustained levels of antibodies to serine proteinase 3, and cavitating lung disease. Possible diagnoses accounting for this unusual combination include a novel association of Sjögren's syndrome and Wegener's granulomatosis (suggested by the high and sustained levels of antibodies to serine proteinase 3) or a rare presentation of bronchiolitis obliterans organising pneumonia. Identification of the true nature of the patients illness facilitated more active management and a swift resolution of the clinical problem.

Aged↗

Primary bronchogenic carcinoma after heart or lung transplantation: radiologic and clinical findings.

Chronic immunosuppression in organ transplant recipients predisposes to the development of malignant disease. The authors describe their 29-year institutional experience of bronchogenic carcinoma developing after heart and lung transplantation. Seven cases of bronchogenic carcinoma were diagnosed in 1,119 heart and lung transplant recipients. Computed tomography scans and radiographs at time of diagnosis, as well as prior radiographs available in six patients were retrospectively analyzed by two radiologists in consensus. The seven cases involved six heart and one lung transplant recipients. Six patients were smokers with a mean smoking history of 66 pack-years. Mean time interval from transplantation to cancer detection was 25 months. Radiologic findings consisted of a solitary pulmonary nodule (n = 3), mass with satellite nodules (n = 1), and obstructive pneumonitis (n = 1). In the sixth patient, the cancer was not radiographically visible because of obscuration by adjacent fibrosis. On review, radiographic abnormalities were present a mean of 12 months prior to diagnosis in 66% of patients. In the heart or lung transplant population, bronchogenic carcinoma develops in recipients with extensive smoking histories. It presents radiographically as a nodule, mass, or obstructive pneumonitis, and is usually visible on radiographs before the time of diagnosis.

Adult↗

Oxygen regulation of a nodule-located carbonic anhydrase in alfalfa.

Control of the permeability to oxygen is critical for the function of symbiotic nitrogen fixation in legume nodules. The inner cortex (IC) seems to be a primary site for this regulation. In alfalfa (Medicago sativa) nodules, expression of the Msca1 gene encoding a carbonic anhydrase (CA) was previously found to be restricted to the IC. We have now raised antibodies against recombinant Msca1 protein and used them, together with antibodies raised against potato leaf CA, to demonstrate the presence of two forms of CA in mature nodules. Each antibody recognizes a different CA isoform in nodule tissues. Immunolocalization revealed that leaf-related CAs were localized primarily in the nitrogen-fixing zone, whereas the Msca1 protein was restricted exclusively to the IC region, in indeterminate and determinate nodules. In alfalfa nodules grown at various O(2) concentrations, an inverse correlation was observed between the external oxygen pressure and Msca1 protein content in the IC, the site of the putative diffusion barrier. Thus Msca1 is a molecular target of physiological processes occurring in the IC cells involved in gas exchange in the nodule.

Blotting, Western↗

Peptide mapping and disulfide bond analysis of myeloid progenitor inhibitory chemokine and keratinocyte growth factor by matrix-assisted laser desorption ionization mass spectrometry.

Peptide mapping and matrix-assisted laser desorption ionization mass spectrometry (MALDI-MS) were conducted to characterize the human genome-based recombinant proteins. Accurate mass values for the deleted forms of the myeloid progenitor inhibitory factor chemokine (MPIF-1d23), and the keratinocyte growth factor (KGF-2d33) were measured as 8848.55 +/- 0.25 and 16,175.87 +/- 0.89 Da, respectively. The mass accuracy of delayed ion extraction MALDI-MS measurements was within 20 ppm of the cDNA predicted value. Reduction and alkylation of the chemokine showed the presence of six cysteine residues and three disulfide bonds. Additional confirmation of disulfide bonding among the cysteine residues of the chemokine was demonstrated by identifying the RP-HPLC separated tryptic and endoprotease Glu-C peptides. Three methionine residues of the chemokine were identified by MALDI-MS of its cyanogen bromide (CNBr) cleavage products. The KGF-2d33 growth factor, however, lacked the disulfide bonding between the two-cysteine residues and contained two free sulfhydryl groups. Direct analysis of the growth factor CNBr digest showed 7542.99, 4993.4, and 3107.7 Da peptides, which identified the methionine residues. Peptide mapping mass spectrometry indicated that host-specific posttranslational modifications had not influenced the gene expression work.

Amino Acid Sequence↗

Preferences for ultraviolet partners in the blue tit.

The preference of female blue tits, Parus caeruleus, is correlated with the brightness of the ultraviolet (UV) crest; there is also assortative mating with respect to the crest's UV/violet chroma. However, manipulation of plumage reflectance is necessary to infer a direct causal link between UV plumage and mate choice. We gave both male and female blue tits a choice between a UV-reflecting ('UV+') partner and a partner whose UV plumage reflectance had been removed ('UV-'). Male blue tits significantly preferred UV+ females. Similarly, female blue tits tended to prefer UV-reflecting males, but their UV+ preferences were nonsignificant. Neither sex showed a preference when conspecifics were replaced by a heterospecific. This study suggests mutual mate choice but male choice may be more strongly influenced by the visual appearance of potential mates. This is one of a few studies to show male mate preferences and the first demonstration of a direct relationship between UV reflectance and male mate choice. Copyright 1999 The Association for the Study of Animal Behaviour.

Journal Article↗

Safety and immunogenicity of Vi conjugate vaccines for typhoid fever in adults, teenagers, and 2- to 4-year-old children in Vietnam.

The capsular polysaccharide of Salmonella typhi, Vi, is an essential virulence factor and a protective vaccine for people older than 5 years. The safety and immunogenicity of two investigational Vi conjugate vaccines were evaluated in adults, 5- to 14-year-old children, and 2- to 4-year-old children in Vietnam. The conjugates were prepared with Pseudomonas aeruginosa recombinant exoprotein A (rEPA) as the carrier, using either N-succinimidyl-3-(2-pyridyldithio)-propionate (SPDP; Vi-rEPA(1)) or adipic acid dihydrazide (ADH; Vi-rEPA(2)) as linkers. None of the recipients experienced a temperature of >38.5 degrees C or significant local reactions. One injection of Vi-rEPA(2) into adults elicited a geometric mean (GM) increase in anti-Vi immunoglobulin G (IgG) from 9.62 enzyme-linked immunosorbent assay units/ml (EU) to 465 EU at 6 weeks; this level fell to 119 EU after 26 weeks. In the 5- to 14-year-old children, anti-Vi IgG levels at 6 weeks elicited by Vi-rEPA(2), Vi-rEPA(1), and Vi were 169, 22.8, and 18.9 EU, respectively (P = 0.0001 for Vi-rEPA(1) and Vi with respect to Vi-rEPA(2)). At 26 weeks, the anti-Vi IgG levels for recipients of Vi-rEPA(2), Vi-rEPA(1), and Vi were 30.0, 10.8, and 13.4 EU, respectively (P < 0.001 for Vi-rEPA(1) and Vi with respect to Vi-rEPA(2)); all were higher than the preinjection levels (P = 0. 0001). Vi-rEPA(2) also elicited the highest anti-Vi IgM and IgA levels of the three vaccines. In the 2- to 4-year-old children at 6 weeks following the first injection, Vi-rEPA(2) elicited an anti-Vi IgG level of 69.9 EU compared to 28.9 EU for Vi-rEPA(1) (P = 0.0001). Reinjection increased Vi antibody levels from 69.9 to 95.4 EU for Vi-rEPA(2) and from 28.9 to 83.0 EU for Vi-rEPA(1). At 26 weeks, anti-Vi IgG levels remained higher than those at preinjection (30.6 versus 0.18 for Vi-rEPA(2) and 12.8 versus 0.33 for Vi-rEPA(1); P = 0.0001 for both). Vi vaccine is recommended for individuals of 5 years of age or older. In the present study, the GM level of anti-Vi IgG elicited by two injections of Vi-rEPA(2) in the 2- to 4-year-old children was higher than that elicited by Vi in the 5- to 14-year-old children (30.6 versus 13.4; P = 0.0001). The safety and immunogenicity of the Vi-rEPA(2) conjugate warrant further investigation.

ADP Ribose Transferases↗

Dairy-product intake and hip fracture among older women: issues for health behavior.

The purpose of this study was to examine the association between dairy-product intake and hip fracture among a national sample of women aged 50 years and older. Univariate analyses using SAS procedures showed dairy-product intake was significantly associated with hip fracture. Women who had suffered hip fracture reported higher dairy use than women who had not experienced these fractures, a finding that is dramatically inconsistent with the literature. This finding may reflect positive behavioral changes resulting from the hip fracture event. Further research must focus on changes in health behavior after fracture, which may assist in understanding the roles of specific theories of health behavior. Application of principles of health behavior could improve the effectiveness of preventive treatment programs for osteoporosis.

Aged↗

Cervical metastases of head and neck squamous cell carcinoma correlate with loss of heterozygosity on chromosome 16q.

To assess the potential involvement of putative tumor suppressors or metastasis suppressors on chromosome 16q in head and neck squamous cell carcinoma (HNSCC), we have examined 42 primary HNSCCs for loss of heterozygosity (LOH) at 16q and correlated these findings with the occurrence of cervical nodal metastases and other clinical parameters. Seven of the 42 (17%) HNSCCs examined displayed LOH at chromosome 16q24. Three of the seven HNSCCs showed LOH at all of the informative loci analyzed along the chromosome arm, whereas the other four showed only loss of a subset of markers. When LOH at 16q was correlated with clinical parameters, there was no significant correlation with age, sex, clinical stage, T stage, N stage or survival. However, there was a correlation between LOH at chromosome 16q24 and involvement of cervical lymph nodes. Of the seven HNSCCs that had lost heterozygosity at 16q24, six had local metastases to lymph nodes indicating that LOH at 16q24 may have predictive value for the metastatic potential of HNSCCs.

Adult↗

Evidence for a third genetic locus causing familial hypercholesterolemia. A non-LDLR, non-APOB kindred.

Monogenically inherited hypercholesterolemia is most commonly caused by mutations at the low density lipoprotein receptor (LDLR) locus causing familial hypercholesterolemia (FH) or at the apolipoprotein B (APOB) locus causing the disorder familial defective apoB (FDB). Probands from 47 kindreds with a strict clinical diagnosis of FH were selected from the Cardiovascular Genetics Research Lipid Clinic, Utah, for molecular genetic analysis. Using a combination of single-strand conformation polymorphism (SSCP) and direct sequencing, 12 different LDLR gene mutations were found in 16 of the probands. Three of the probands were carriers of the APOB R3500Q mutation. In five of the remaining 28 pedigrees where no mutation had been detected, samples from enough relatives were available to examine co-segregation with the LDLR region using the microsatellite marker D19S221, which is within 1 Mb centromeric of the LDLR locus, and D19S394, sited within 150 kb telomeric of the LDLR locus. In four of the families there was strong evidence for co-segregation between the LDLR locus and the phenotype of hypercholesterolemia, but in one large family with 18 living affected members and clear-cut bimodal hypercholesterolemia, there were numerous exclusions of co-segregation. Using length polymorphic markers within and outside the APOB gene, linkage of phenotype in this family to the APOB region was similarly excluded. In this large family, the degree of hypercholesterolemia, prevalence of tendon xanthomata, and occurrence of early coronary disease were indistinguishable from the other families studied. In summary, the data provide unequivocal evidence that a third locus can be etiological for monogenic familial hypercholesterolemia and should be reinvigorating to research in this field.

Adolescent↗

A physical map of 30,000 human genes.

A map of 30,181 human gene-based markers was assembled and integrated with the current genetic map by radiation hybrid mapping. The new gene map contains nearly twice as many genes as the previous release, includes most genes that encode proteins of known function, and is twofold to threefold more accurate than the previous version. A redesigned, more informative and functional World Wide Web site (www.ncbi.nlm.nih.gov/genemap) provides the mapping information and associated data and annotations. This resource constitutes an important infrastructure and tool for the study of complex genetic traits, the positional cloning of disease genes, the cross-referencing of mammalian genomes, and validated human transcribed sequences for large-scale studies of gene expression.

Animals↗

Effects of oxygen on nodule physiology and expression of nodulins in alfalfa

Early nodulin 2 (ENOD2) transcripts and protein are specifically found in the inner cortex of legume nodules, a location that coincides with the site of a barrier to O2 diffusion. The extracellular glycoprotein that binds the monoclonal antibody MAC236 has also been localized to this site. Thus, it has been proposed that these proteins function in the regulation of nodule permeability to O2 diffusion. It would then be expected that the levels of ENOD2 mRNA/protein and MAC236 antigen would differ in nodules with different permeabilities to O2. We examined the expression of ENOD2 and other nodule-expressed genes in Rhizobium meliloti-induced alfalfa nodules grown under 8, 20, or 50% O2. Although there was a change in the amount of MAC236 glycoprotein, the levels of ENOD2 mRNA and protein did not differ significantly among nodules grown at the different [O2], suggesting that neither ENOD2 transcription nor synthesis is involved in the long-term regulation of nodule permeability. Moreover, although nodules from all treatments reduced their permeability to O2 as the partial pressure of O2 (pO2) was increased to 100%, the levels of extractable ENOD2 and MAC236 proteins did not differ from those measured at the growth pO2, further suggesting that if these proteins are involved in a short-term regulation of the diffusion barrier, they must be involved in a way that does not require increased transcription or protein synthesis.

Journal Article↗

Predictors for osteoporosis diagnosis among postmenopausal women: results from a national survey.

Osteoporosis is a serious health problem in the U.S. today resulting in premature mortality, deformity, pain, loss of function, and disability. Diagnosis of osteoporosis is key to obtaining treatment. The purpose of this study was to examine risk factors that are correlated with osteoporosis diagnosis among a national sample of postmenopausal women. Factors associated with osteoporosis diagnosis included age, race, and family history. Health care providers, including physicians, dietitians, nurses, physical therapists and social workers, can play a key role in improving diagnoses among at-risk women. They can work together to increase awareness and improve knowledge regarding the risk factors for osteoporosis including body mass index, physical activity, smoking and nutritional status.

Aged↗