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Biomedical subjects

M Hayes

Publications and source records attributed to M Hayes.

At least 37 records · Page 2Linked to original sources
PubMed2001

Response to HBV vaccine in relation to vaccine dose and anti-HCV positivity: a New South Wales correctional facilities' study.

Currently, about two-thirds of inmates in NSW correctional facilities have a history of injection drug use, and about half have serological evidence of exposure to hepatitis C virus. The introduction of an accelerated hepatitis B vaccination program (0-1-2 months) in 1998, using a 20 microg/dose vaccine was necessitated by the need to vaccinate eligible inmates in this high-risk environment characterised by rapid client mobility. Since 1999, both 10 and 20 microg doses of vaccine were introduced. We found that sero-response rates were not significantly influenced by HCV antibody status, but were significantly lower in cohorts of inmates vaccinated with the 10 microg dose of vaccine.

Dose-Response Relationship, Immunologic↗
PubMed2001

Nitric oxide-mediated expression of Bcl-2 and Bcl-xl and protection from tumor necrosis factor-alpha-mediated apoptosis in porcine endothelial cells after exposure to low concentrations of xenoreactive natural antibody.

BACKGROUND: Cardiac and renal allo- and xenografts can acquire a natural resistance to vascular rejection. This "accommodation" involves endothelial cell (EC) expression of "survival genes" such as Bcl family members and hemoxygenase 1. Understanding what initiates this protective process would have profound implications; our hypothesis is that low concentrations of antigraft antibodies may mediate these changes. METHODS: In vitro cultured primary and immortalized porcine EC were incubated with polyclonal human IgG for 6 days and then examined for phenotype changes. RESULTS: The cells acquired resistance to tumor necrosis factor-alpha-mediated apoptosis (50-100% reduction at 6 hr) and up-regulated expression of Bcl-2 and Bcl-xl; sustained expression was accompanied by inducible nitric oxide (NO) synthase expression and by enhanced production of NO by EC. Two observations suggested that NO was actively involved in the process of Bcl-2 and Bcl-xl induction. First, (z)-1-2-[2-aminoethyl)-N- (2-ammonioethyl)amino]diazen-1-ium-1,2-diolate, an NO donor, was able to induce similar changes in porcine EC to those induced by anti-pig antibodies. Second, an NO synthase inhibitor NG-monomethyl-L-arginine.monoacetate was able to specifically inhibit the anti-pig antibody-mediated expression of Bcl-2 or Bcl-xl. CONCLUSIONS: These data strongly support the hypothesis that Bcl-2 and Bcl-xl expression and protection from apoptosis in EC may result from antibody-mediated NO production through the neoexpression of inducible NO synthase.

Animals↗
PubMed2001

Comparative performance of herpes simplex virus type 2-specific serologic assays from Meridian Diagnostics and MRL diagnostics.

MRL Diagnostics and Meridian Diagnostics have recently designed herpes simplex virus type 2 (HSV-2)-specific enzyme immunoassays for HSV-2 antibody detection. Blood donor sera were assayed for HSV-2 antibodies by both methods. The sensitivity, specificity, and efficiency were 97.9, 95.4, and 95.9% for the MRL assay and 83.2, 98.2, and 95.5% for the Meridian assay, respectively.

Antibodies, Viral↗
PubMed2001

Histopathological analysis of Leri-Weill dyschondrosteosis: disordered growth plate.

Leri-Weill syndrome (LWS) is a dominant (pseudoautosomal) skeletal dysplasia with mesomelic short stature and bilateral Madelung deformity, due to dyschondrosteosis of the distal radius. It results from the loss of one copy of the Short Stature Homeobox Gene (SHOX) from the tip of the short arm of the X or Y chromosome. SHOX molecular testing enabled us to evaluate the histopathology of the radial physis in LWS patients with a documented SHOX abnormality. A widespread disorganisation of physeal anatomy was revealed with disruption of the normal parallel columnar arrangement of chondrocytes. Tandem stacking of maturing chondrocytes within columns was replaced by a side-by-side arrangement. The presence of hypertrophic osteoid with micro-enchondromata in the radial metaphysis suggests abnormal endochondral ossification. The Vickers' ligament was confirmed to blend with the triangular fibrocartilage complex (TFCC). This histopathological study demonstrates that the zone of dyschondrosteosis in LWS is characterised by marked disruption of normal physeal chondrocyte processes and that a generalised physeal abnormality is present.

Adolescent↗
PubMed2000

Domain rotations between open, closed and bullet-shaped forms of the thermosome, an archaeal chaperonin.

Three conformations of the thermosome, an archaeal group II chaperonin, have been determined by cryo-electron microscopy (EM). We describe an open form of the double-ring oligomer, a closed form and a bullet-shaped form with one ring open and the other closed. Domain movements have been deduced by docking atomic coordinates into the EM maps. The subunit apical domains, bearing the putative substrate binding sites, rotate about 30 degrees upwards and twist in the plane of the ring from the closed to the open conformation. The closed rings have their nucleotide binding pockets closed by the intermediate domains, but in the open rings, the pocket is accessible.

Archaea↗
PubMed2000

High-throughput analysis of everolimus (RAD001) and cyclosporin A (CsA) in whole blood by liquid chromatography/mass spectrometry using a semi-automated 96-well solid-phase extraction system.

A semi-automated solid-phase extraction (SPE) liquid chromatography/mass spectrometry (LC/MS) procedure was validated for the simultaneous determination of everolimus (RAD001) and cyclosporin A (CsA) in human blood. Whole blood samples (350microL) were pretreated with acetonitrile/zinc sulfate mixture to precipitate the sample proteins. The samples were centrifuged and the resulting supernatants were manually transferred to a 96-well plate format. All subsequent sample transfer and solid phase extraction was automated using a Tomtec Quadra 96 workstation. Samples were analyzed by LC/MS using an atmospheric pressure chemical ionization (APcI) interface. In order to enhance sensitivity, the MS method used negative ion mode for RAD001 ([M]-) and its internal standard and positive ion mode for CsA ([M + H]+) and its internal standard. The lower limit of quantitation was 0.375 ng.ml(-1) for RAD001 and 6.95 ng.ml(-1) for CsA. The reproducibility of the method was evaluated by analyzing six replicates at five or more quality control (QC) levels over the nominal concentration range 0.375 to 253 ng.ml(-1) for RAD001 and 6.95 to 1,530 ng.ml(-1) for CsA. The inter- and intra-day accuracy was found to range from 89.7 to 114% with precision (% CV) of less than 12% for both compounds. The sensitivity, small sample volume needed and high sample throughput of this method make it an attractive option for pharmacokinetic studies in pediatric patients.

Automation↗
PubMed2000

Reducing unintended pregnancy by increasing access to emergency contraceptive pills.

OBJECTIVES: National and state data on the health, social, and economic consequences of unintended pregnancy prompted Washington policy makers to identify strategies to reduce such pregnancies. Though not well known, emergency contraceptive pills (ECPs) are a safe and effective contraceptive method that can prevent pregnancy if taken within 72 hr after unprotected intercourse. A coalition conceived the idea of enabling pharmacists to prescribe ECPs directly to women through collaborative drug therapy agreements (CDTAs) with physicians. METHODS: Following a feasibility study, five agencies initiated a novel pilot project in western Washington. Key components included informing pharmacists about ECPs and CDTAs; developing tools, providing training, and developing systems to establish pharmacist/ prescriber collaborative agreements; conducting a public awareness campaign; evaluating the impact of the project; and disseminating the results. RESULTS: More than 1000 pharmacists received training in all aspects of providing ECPs and 140 pharmacies participated in the project, with more than 145 CDTA on file. In the 16 months of pharmacy service provision, 11,969 ECP prescriptions were provided, possibly preventing 700 or more unintended pregnancies. The media launch led to 200 broadcast stories and increased calls to the ECP Hotline from 116 to an average of 1160 per month. CONCLUSION: Enabling pharmacists to provide ECPs directly to women is a convenient delivery system for a time-limited therapy. It increases the chances that women will use the therapy effectively and connects women without a provider to a source of care. By increasing access to an effective contraceptive, this projects supports the Washington State goal of reducing unintended pregnancy.

Contraceptives, Postcoital↗
PubMed2000

Early experience of intra-ureteric capsaicin infusion in loin pain haematuria syndrome.

OBJECTIVES: To evaluate early results of the intra-ureteric instillation of capsaicin for the treatment of loin pain haematuria syndrome (LPHS). PATIENTS AND METHODS: Ten patients with LPHS were treated using intra-ureteric capsaicin instillation. A solution of capsaicin was infused into the affected ureter through an embolectomy catheter, under anaesthesia. The success of the treatment was assessed using patient questionnaires and the quantitative reduction in the patients' analgesic requirements measured. RESULTS: During a mean follow-up of 6 months, six of the 10 patients had short- to medium-term symptomatic relief after one or more treatments; four had no relief from their symptoms. One patient had a mucosal ulceration in the bladder after extravasation of the capsaicin solution. Two patients subsequently underwent simple nephrectomy for symptomatic nonfunctioning kidneys. CONCLUSION: These results are consistent with other preliminary reports of the efficacy of capsaicin treatment in LPHS and such treatment therefore has a definite therapeutic role in this difficult condition. We are uncertain if the treatment contributed to the deterioration of the excised kidneys. This early experience suggests a need for careful consideration when contemplating this treatment, with attention directed to both the initial diagnosis and possibly the technique of capsaicin/instillation. We include a protocol to follow when preparing patients for capsaicin treatment.

Administration, Topical↗
PubMed2000

Urine screening for gonococcal and chlamydial infections at community-based organizations in a high-morbidity area.

BACKGROUND: Increasing availability of urine testing for Neisseria gonorrhoeae (GC) and Chlamydia trachomatis (CT) offers expanded opportunities to collaborate with community-based organizations (CBOs) to screen high-risk populations for sexually transmitted diseases (STDs). GOAL: To determine the prevalence and correlates of genital tract gonococcal and chlamydial infection among CBO clients, and to assess the feasibility of implementing widespread community-based STD screening programs. DESIGN: Free, voluntary, confidential first-catch urine screening was conducted at 20 CBOs serving disadvantaged populations in St. Louis, MO. Brief demographic, behavioral, and sexual contact data were obtained from all participants. Urine samples were tested by ligase chain reaction (LCR). Persons testing positive were promptly notified and directed to seek treatment. RESULTS: A GC and/or CT infection was identified in 24 of 277 persons (8.7%) screened; 2 persons were infected with GC only, 17 with CT only, and 5 with GC and CT. Treatment was documented for 22 persons (91.7%) testing positive. The highest rates of infection were found at shelters (12.3%) and residence facilities (11.1%). Costs of screening were $38 per sample collected and $453 per case identified. CONCLUSION: Community-based urine testing successfully identified GC and CT infections, and was well accepted by community members and CBOs. Community-based screening can significantly impact STD epidemiology by facilitating early detection, treatment, and interruption of transmission.

Adolescent↗
PubMed2000

Ten years of breast screening in the Screening Mammography Program of British Columbia, 1988-97.

OBJECTIVES: To evaluate 10 years outcomes of the Screening Mammography Program of British Columbia (SMPBC) and determine if breast screening targets were being achieved among women aged 40-80+ years. SETTING: Organised breast screening programme in British Columbia, Canada. METHODS: Rates of participation, abnormal referral, cancer detection, and interval cancer were calculated for asymptomatic women receiving an SMPBC mammography from 1988-97. RESULTS: 895,849 screening mammographies were provided to 335,433 women. 51.3% of women were age 50-69 years. Abnormalities were identified on 57,454 screens (6.4%) from which 3304 cancers were detected. Abnormal call rates were higher on first (9.8%), compared with subsequent screens (4.4%) and declined with age: 7.7% at age < 40 to 5.4% for age 70-79 years. Cancer detection rates were higher on first (5.0 per 1000) compared with subsequent screens (2.8 per 1000) and increased smoothly with age from 1.4 to 8.2 per 1000 from age < 40 to age 80 years and older. Twenty per cent of cancers were non-invasive. The median size of invasive cancers was 14 mm and 81% had no axillary lymph node metastases. The 12 month interval cancer rate was 0.6 per 1000 and did not vary significantly with age or screening history. The prevalence to expected incidence ratio was 3.1 for women age 50-79 years. CONCLUSION: Across a broad range of ages, surrogate indices of screening mammography success have been achieved in a population based, North American, organised breast cancer screening programme.

Adult↗
PubMed2000

Cholesteatoma: an unusual presentation.

A case is described of an extensive cholesteatoma presenting as a lump on the side of a patient's head overlying the squamous temporal bone, with erosion of the underlying bone and intracranial extension. The patient was otherwise asymptomatic. This case highlights the bone-eroding capacity of cholesteatoma and the vigilance required in assessing lumps on the head.

Aged↗
PubMed2000

The labeled dissimilarity scale: a metric of perceptual dissimilarity.

Fundamental to the concept of psychological distance is the idea that confusability allows discovery of the perceptual relationships between objects, which provides understanding of the underlying principles that govern the functioning of a system. Thus, judgments of dissimilarity (conceptually proportional to the inverse of confusability) may provide insight into the elusive underlying quality-coding mechanisms in that sensory system. In the present experiments, a labeled dissimilarity scale (LDS) that reflects the magnitude of odorant dissimilarity was developed in a fashion similar to that reported by Green (Green, Shaffer, & Gilmore, 1993). This scale was produced by rating the perceptual intensity implied by adverbs describing different levels of dissimilarity, and then attaching those descriptors to appropriate locations on a numerical scale. The usefulness of the scale was demonstrated by its ability to produce visual color space with ratings of dissimilarity of Munsell color chips. The stability and reliability of the LDS was evaluated by comparing it with the traditional scaling technique of magnitude estimation (ME). It was found that the scales produced similar ratings of odorant dissimilarity and showed a similar susceptibility to the effects of contrast convergence. However, the coefficients of variation of dissimilarities rated with ME were much higher than those produced with the LDS. The subjects also dealt with the LDS without the anxiety that usually accompanies first-time users of ME. The LDS provided stable ratings of odorant dissimilarity and preserved the inferred ratio scale properties of ME.

Adult↗
PubMed1999

Divergence of binding, signaling, and biological responses to recombinant human hybrid IFN.

Three human IFN-alpha hybrids, HY-1 [IFN-alpha21a(1-75)/alpha2c(76-165)], HY-2 [IFN-alpha21a(1-95)/alpha2c(96-165)], and HY-3 [IFN-alpha2c(1-95)/alpha21a(96-166)], were constructed, cloned, and expressed. The hybrids had comparable specific antiviral activities on Madin-Darby bovine kidney (MDBK) cells but exhibited very different antiproliferative and binding properties on human Daudi and WISH cells and primary human lymphocytes. Our data suggest that a portion of the N-terminal region of the molecule is important for interaction with components involved in binding of IFN-alpha2b while the C-terminal portion of IFN is critical for antiproliferative activity. A domain affecting the antiproliferative activity was found within the C-terminal region from amino acid residues 75-166. The signal transduction properties of HY-2 and HY-3 were evaluated by EMSA and RNase protection assays. Both HY-2 and HY-3 induced activation of STAT1 and 2. However, HY-2 exhibited essentially no antiproliferative effects at concentrations that activated STAT1 and 2. Additionally, at concentrations where no antiproliferative activity was seen, HY-2 induced a variety of IFN-responsive genes to the same degree as HY-3. RNase protection assays also indicate that, at concentrations where no antiproliferative activity was seen for HY-2, this construct retained the ability to induce a variety of IFN-inducible genes. These data suggest that the antiproliferative response may not be solely directed by the activation of the STAT1 and STAT2 pathway in the cells tested.

Amino Acid Sequence↗
PubMed1999

Liquid chromatography/atmospheric pressure chemical ionization tandem mass spectrometry enantiomeric separation of dl-threo-methylphenidate, (Ritalin) using a macrocyclic antibiotic as the chiral selector.

Vancomycin, a macrocyclic antibiotic, is an amphoteric glycopeptide produced by Streptomyces orientalis which has proven to be a viable chiral selector for high performance liquid chromatograph (HPLC) (D. W. Armstrong, Y. Tang, S. Chen, Y. Zhou, C. Bagwill and J-R. Chen, Anal. Chem. (1994; 66: 1473). While it is related to other glycopeptide antibiotics, vancomycin has a number of unique structural features, including 18 stereogenic centers, five aromatic rings, and two side chains one of which is a carbohydrate dimer. Therefore, a vancomycin-based stationary phase appears to be multimodal in that it can be utilized in both normal-phase and reversed-phase liquid chromatography. Consequently, the enantiomeric separation may be operative via several mechanisms, including pi-pi complexation, dipole stacking, inclusion, hydrogen bonding, or combinations of these interactions. LC/MS/MS is a powerful tool for quantitative analysis when evaluated on the basis of speed, specificity, reliability and sensitivity. For these reasons, the present paper explored the feasibility of bonded macrocyclic glycopeptide phases for chiral LC/MS/MS quantitative analysis. Methylphenidate was used as a model compound. A rapid chiral bioanalytical method (<7.5 min) for the determination of the enantiomers of methylphenidate was developed. A lower limit of quantification (LLOQ) of 87 pg/mL was attained for the human plasma assay. This is to our knowledge the first example of enantioselective reversed-phase LC/MS/MS for methylphenidate. The chiral column was relatively cost effective and exhibited excellent performance with no separation deterioration observed after approximately 2500 injections.

Atmospheric Pressure↗
PubMed1999

Intrauterine growth restriction is associated with persistent juxtamedullary expression of renin in the fetal kidney.

BACKGROUND: Intrauterine growth restriction (IUGR) has been linked to impaired renal function and hypertension, suggesting that an adverse prenatal environment could alter kidney development and renin production. METHODS: Immunohistochemistry and in situ hybridization were employed to localize renin-containing cells (RCCs) in the deep, middle, and superficial zones of autopsy kidney sections, in parallel with histologic maturation, from unexplained stillborn fetuses of normal weight (N = 26) and stillborn fetuses with IUGR (N = 17). RESULTS: In the control group, the number of RCC per 100 glomeruli in the deep zone decreased with advancing gestation from 40 at 20 weeks gestation to five at term (P < 0.001), whereas the opposite change was found in the superficial zone (increase from 5 per 100 to 55 per 100; P < 0.001). In the IUGR group, the density of RCCs in both the superficial and deep zones was similar to the control group at 20 weeks, and no shift in renin gene expression was observed as gestation advanced. Histologic maturation was unaltered. CONCLUSIONS: Renin gene expression persists and predominates in the deep renal cortex of the stillborn IUGR fetus, and could contribute to the pathogenesis of neonatal oliguria and/or hypertension during postnatal life.

Embryonic and Fetal Development↗
PubMed1999

The efficacy of bupivacaine with adrenaline in reducing pain and bleeding associated with breast reduction: a prospective trial.

In a randomised, double-blind, placebo-controlled trial, the effect of preoperative local anaesthesia vasoconstrictor infiltration on peri- and postoperative bleeding and postoperative pain was evaluated in 24 consecutive patients undergoing breast reduction. After the induction of general anaesthesia, one breast was infiltrated with a solution of bupivacaine with adrenaline and the other with the same amount of normal saline solution simultaneously. The perioperative blood loss was calculated by weighing swabs, and postoperative drainage was measured at 3, 24 and 48 h by using suction drains. Postoperative pain was assessed using visual analogue scales and verbal response scores at 3, 6, 10 and 24 h post-infiltration. There was a reduction in perioperative blood loss in the breast infiltrated with bupivacaine and adrenaline (P < 0.01). The mean blood loss in the drains from the infiltrated breasts was also less than that from the control sides at 3 and 24 h post-infiltration (P < 0.05). Pain was significantly less (P < 0.01) at 3 h on the local anaesthetic side. At 6, 10 and 24 h, pain tended to be less on the local anaesthetic side, but this did not reach statistical significance. No major complications were seen. Our results confirm a beneficial effect of bupivacaine with adrenaline on peri- and postoperative bleeding as well as in the early postoperative phase of pain.

Adult↗
PubMed1999

A 12-year follow-up of a methadone medical maintenance program.

Methadone Medical Maintenance (MDM) is an alternative for treatment of stable methadone maintained individuals. It involves a monthly physician's visit, at which methadone take-home doses are dispensed to last until the next appointment. The safety and efficacy of this treatment modality is currently under investigation. The purpose of this study was to evaluate the long-term safety and efficacy of MDM in a methadone program in Baltimore. A sample of 21 patients was enrolled in the study and followed for 12 years. They were evaluated once a month by a primary care physician affiliated with a methadone clinic who collected urine toxicology samples and dispensed the monthly methadone dose. The results showed that only 6 (28.6%) patients dropped out during the 12 years of the study. Twelve (0.5%) of 2,290 urine samples collected were positive for drugs. No methadone overdose or diversion was observed. Participants reported significant improvement in their quality of life. The results of this study support the safety and efficacy of medical maintenance of stable methadone maintained individuals.

Adult↗