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Biomedical subjects

A Frost

Publications and source records attributed to A Frost.

At least 19 recordsLinked to original sources
PubMed2006

Successful liver transplantation following medical management of portopulmonary hypertension: a single-center series.

Severe portopulmonary hypertension (POPH) is an absolute contraindication to orthotopic liver transplantation (OLT). Vasodilators have been used, but the safety of subsequent transplantation and the reversibility of pulmonary hypertension after transplantation are uncertain. This study examined the feasibility and post-transplant effects of liver transplantation following medical control of POPH. Eight consecutive patients (three females and five males, ages 39-51) with POPH as their only contraindication to transplantation were treated with continuous intravenous epoprostenol. Liver transplantation was considered if the mean pulmonary artery pressure (PAM) was lowered to <35 mmHg. Epoprostenol 2-8 ng/kg/min successfully improved hemodynamics in seven of eight patients, usually within 6.5 months of initiating therapy. PAM declined from an average of 43-33 mmHg (p=0.03); mean pulmonary vascular resistance declined from 410 to 192 dyn s cm-5 (p=0.01) and cardiac output increased from 6.6 to 10 L/min (p=0.02). Six of the seven responders were actively listed for liver transplantation. Two died on the waiting list; the remaining four were transplanted and remain alive and well 9-18 months post-OLT-two without vasodilators, and two on oral medication. We conclude that pulmonary vasodilators permit safe liver transplantation in some cases, and that POPH may be reversible after transplantation.

Adult↗
PubMed2005

The anatomy of the dorsal cutaneous branch of the ulnar nerve - a safe zone for positioning of the 6R portal in wrist arthroscopy.

The dorsal branch of the ulnar nerve passes close to the 6 Radial portal used in wrist arthroscopy. We examined 20 cadaveric limbs to establish the course of this nerve. We found it consistently crossed a line between the ulnar styloid and the fourth web space at an average of 2.4 cm from the ulnar styloid (range 1.8-2.8 cm). This represented 23% (+/- 2.5 STD range 19-27%) of the distance from the styloid process to the fourth web space. Recommendations are made to help avoid iatrogenic injury to the nerve during arthroscopy. The literature on the anatomy of this nerve and its variations and the clinical relevance of this knowledge are discussed.

Arm↗
PubMed2004

Agricultural environmental management; case studies from theory to practice.

Six farms were examined, each from a different sector of Scottish agriculture. Surveys were carried out to identify both diffuse pollution risks and options for habitat conservation and enhancement. Financial data were also gathered to determine the current sources of farm income, both from sale of produce and from grants. Whole farm plans were produced aimed at bringing about reductions in diffuse pollution to water, soil and air and also habitat improvements. The assembled information was used to devise a possible agri-environment grant scheme to aid the implementation of the whole farm plans.

Agriculture↗
PubMed2003

Is visual outcome compromised when next day review is omitted after phacoemulsification surgery? A randomised control trial.

AIMS: To examine the safety implications of omitting first day clinical review following phacoemulsification cataract surgery. METHODS: 362 patients were randomly assigned to "same day discharge" (SDD) or "next day review" (NDR). All patients were reviewed approximately 2 weeks after surgery. RESULTS: Of the 174 patients randomised to NDR, 14 (8.0%) were treated for raised intraocular pressure (25-48 mm Hg) on the first postoperative day. Four received increased topical steroids for uveitis (two) and corneal oedema (two). One patient was treated for a significant wound leak. 12 (6.9%) required additional reviews before 2 week follow up for treatment of the following complications: drop toxicity (six), raised intraocular pressure (five), and corneal abrasion (one). Of the 188 randomised to SDD, six (3.2%) returned to the department before the planned review for reassurance of patients' concerns regarding eye symptoms (three), drop toxicity (one) and follow up of previously raised intraocular pressure (one). There were two cases of iris prolapse in the SDD group. In one case, the complication was anticipated and early review had been arranged. Postoperative acuities of 6/12 or better were achieved in 83% of both SDD and NDR patients (p = 0.96 by chi(2) test). Postoperative quality of life scores at 4 months indicating "no or hardly any concern about vision" (VCM1 questionnaire index <1.0) were achieved in 67% SDD and 72.5% NDR (p = 0.26). CONCLUSION: The intention to discharge patients on the day of surgery, with planned postoperative review at 2 weeks, was associated with a low frequency of serious ocular complications. Differences in the proportions achieving a good visual outcome between the two groups, based on 2 week visual acuity and 4 month quality of life, were not significant.

Adult↗
PubMed2003

Risk biomarker assessment for breast cancer progression: replication precision of nuclear morphometry.

Nuclear morphometry is a method for quantitative measurement of histopathologic changes in the appearance of stained cell nuclei. Numerous studies have indicated that these assessments may provide clinically relevant information related to the degree of progression and malignant potential of breast neoplasia. Nuclear features are derived from computerized analysis of digitized microscope images, and a quantitative Feulgen stain for DNA was used. Features analyzed included: (1) DNA content; (2) nuclear size and shape; and (3) texture features, describing spatial features of chromatin distribution. In this study replicated measurements are described on a series of 54 breast carcinoma specimens of differing pathologic grades. Duplicate measurements were performed using two serial sections, which were processed and analyzed separately. The value of a single feature measurement, the nuclear area profile, was shown to be the strongest indicator of progression. A quantitative nuclear grade was derived and shown to be strongly correlated with not only the pathologic nuclear grade, but also with tubule formation, mitotic grade, and with the overall histopathologic grade. Analysis of replication precision showed that the standard methods of the histopathology laboratory, if practiced in a uniform manner, are sufficient to ensure reproducibility of these assessments. We argue that nuclear morphometry provides a standardized and reproducible framework for quantitative pathologic assessments.

Algorithms↗
PubMed2001

Effects of the dual endothelin-receptor antagonist bosentan in patients with pulmonary hypertension: a randomised placebo-controlled study.

BACKGROUND: Endothelin 1, a powerful endogenous vasoconstrictor and mitogen, might be a cause of pulmonary hypertension. We describe the efficacy and safety of bosentan, a dual endothelin-receptor antagonist that can be taken orally, in patients with severe pulmonary hypertension. METHODS: In this double-blind, placebo-controlled study, 32 patients with pulmonary hypertension (primary or associated with scleroderma) were randomly assigned to bosentan (62.5mg taken twice daily for 4 weeks then 125 mg twice daily) or placebo for a minimum of 12 weeks. The primary endpoint was change in exercise capacity. Secondary endpoints included changes in cardiopulmonary haemodynamics, Borg dyspnoea index, WHO functional class, and withdrawal due to clinical worsening. Analysis was by intention to treat. FINDINGS: In patients given bosentan, the distance walked in 6 min improved by 70 m at 12 weeks compared with baseline, whereas it worsened by 6 m in those on placebo (difference 76 m [95% CI 12-139], p=0.021). The improvement was maintained for at least 20 weeks. The cardiac index was 1.0 L min(-1) m(-2) (95% CI 0.6-1.4, p<0.0001) greater in patients given bosentan than in those given placebo. Pulmonary vascular resistance decreased by 223 dyn s cm(-)(5) with bosentan, but increased by 191 dyn s cm(-5) with placebo (difference -415 [-608 to -221], p=0.0002). Patients given bosentan had a reduced Borg dyspnoea index and an improved WHO functional class. All three withdrawals from clinical worsening were in the placebo group (p=0.033). The number and nature of adverse events did not differ between the two groups. INTERPRETATION: Bosentan increases exercise capacity and improves haemodynamics in patients with pulmonary hypertension, suggesting that endothelin has an important role in pulmonary hypertension.

Antihypertensive Agents↗
PubMed2001

The role of best management practices in alleviating water quality problems associated with diffuse pollution.

This paper introduces the concept of best management practices for the control of diffuse pollution. It considers where they are appropriate, and how the concept of a best management practice approach differs from the conventional means of controlling pollution by regulating each point source, in relation to established environmental quality standards and available dilution.

Agriculture↗
PubMed2001

Interleukin (IL)-13 and IL-4 inhibit proliferation and stimulate IL-6 formation in human osteoblasts: evidence for involvement of receptor subunits IL-13R, IL-13Ralpha, and IL-4Ralpha.

Interleukin-13 (IL-13) inhibits cell proliferation and stimulates interleukin-6 (IL-6) formation in isolated human osteoblasts (hOBs). Because the related cytokine, interleukin-4 (IL-4), is known to exert effects similar to IL-13 in other tissues, and because IL-4 has been implicated as a regulator of bone metabolism, we compared the effects of IL-13 and IL-4 on cell proliferation, IL-6 synthesis, the expression of osteoblastic phenotypic markers in hOB cultures. Also, the receptor proteins mediating these effects in hOBs have been partly characterized. IL-4 and IL-13 dose-dependently inhibited [(3)H]-thymidine incorporation into the DNA of human osteoblasts and stimulated secretion of IL-6 into culture supernatants. IL-13 and IL-4 also increased the mRNA levels of IL-6, as measured by RNAse protection assay. Furthermore, IL-13 and IL-4 dose-dependently enhanced alkaline phosphatase (ALP) activity, but did not affect osteocalcin or collagen type I synthesis. IL-4 was tenfold more potent than IL-13 in inducing both ALP activity and IL-6 secretion, whereas the cytokines were equipotent as inhibitors of cell proliferation. The expression of mRNA for receptor subunits previously implicated in IL-4 and IL-13 signaling was investigated by reverse transcriptase-polymerase chain reaction. IL-13R, IL-13Ralpha, and IL-4Ralpha mRNA were repeatedly detected in hOBs, whereas mRNA for IL-2Rgamma(C) was not detected. Receptor-blocking antibodies to IL-4Ralpha inhibited the induction of IL-6 formation by both IL-4 and IL-13, indicating that both cytokines utilize this receptor subunit in signaling. However, the antibodies did not affect the IL-4/-13-induced inhibition of [(3)H]-thymidine incorporation or the stimulation of alkaline phosphatase (ALP), suggesting that IL-4Ralpha does not mediate these effects of IL-4/-13 in hOBs. We conclude that the cytokines IL-13 and IL-4, through sharing of receptor components, induce similar effects on hOBs, causing inhibition of cell proliferation, stimulation of IL-6, and enhanced ALP activity.

Antibodies, Monoclonal↗
PubMed2001

Vision-related quality of life impairment in an elderly UK population: associations with age, sex, social class and material deprivation.

PURPOSE: To describe the prevalence of vision-related quality of life (VR-QOL) impairment in an elderly UK population sample. METHOD: The survey, using the VCM1 questionnaire, was based on an age- and sex-stratified random population sample of 2783 individuals aged 55 years or over. RESULTS: One thousand eight hundred and forty-six (69.7%) of 2647 eligible subjects responded. One thousand six hundred and eighty-three individuals completed all 10 VCM1 items. Overall the prevalence of a VCM1 score >2.0 ('more than a little' concern about vision) was 4.6% (95% CI = 3.7% to 5.7%), leading to an estimate of more than 550,000 individuals in England with substantial VR-QOL impairment. The prevalence increased with age from 2.1% in the 55-64 year age group to 17.9% in the group aged 85 years and older. The prevalence also increased as social class became lower, from 0 in social class I to 10.2% in social class V, and increased with increasing material deprivation, from 1.2% in the most affluent quintile to 6.8% in the most deprived quintile. Multivariable logistic regression analysis showed that age (p = 0.0001), decreasing social class (p = 0.03) and increasing material deprivation (p = 0.008) were independently associated with VR-QOL impairment (VCM1 score >2.0), whilst gender and means of questionnaire administration were not associated with VR-QOL impairment at the 5% level. CONCLUSIONS: The findings suggest a substantial national prevalence of VR-QOL impairment, and are consistent with earlier studies linking ocular disease with social deprivation. Consideration should be given to directing resources more carefully towards groups at higher risk of VR-QOL impairment, in particular the very elderly and socially deprived.

Age Factors↗
PubMed2001

The population requirement for cataract extraction: a cross-sectional study.

PURPOSE: To examine the distribution in the population of indications for cataract extraction in order to relate demand for this procedure to the capacity for satisfying it. METHODS: An age-stratified random population sample of 2783 individuals aged 55 years and over was taken from inner-city, urban and rural areas of Avon and Somerset. The requirement for cataract extraction was estimated on the basis of measures of vision-related quality of life, refracted visual acuity, and application of the Oxford Clinical Cataract Classification and Grading System. Data were also collected concerning suitability for surgery, including relative contraindications to surgery and whether participants considered their eyesight bad enough to merit surgery. Three sets of composite indications were defined. RESULTS: Estimated prevalent requirements for cataract extraction for the three sets of composite criteria were: 29 per 1000 aged over 55 years (95% CI 20-41) for the most inclusive criterion; 17 per thousand (95% CI 10-27) for the intermediate criterion; and 7 per thousand (95% CI 3-14) for the most stringent criterion. These rates are equivalent to a national prevalent requirement for England of 384,000 for the most inclusive criterion. If the approximately 15% of individuals whose desire or fitness for surgery was questionable are removed from this estimate, the prevalent requirement, including the backlog from previous unsatisfied demand, becomes 325,000 individuals. CONCLUSIONS: The findings suggest only a modest imbalance between supply and demand for cataract surgery. In particular there was a very small prevalence of untreated severe cataract, less than the annual health service surgical capacity, suggesting that the current National Health Service surgical capacity is adequate for cases of severe cataract.

Age Distribution↗
PubMed2001

The effect of volatile fatty acids in acidified fermented piggery effluent on shiga-toxigenic and non-toxic resident strains of Escherichia coli.

AIMS: To examine the effects of acidified acidogenically fermented piggery effluent containing Volatile Fatty Acids (VFA) on shiga-toxigenic and resident strains of Escherichia coli (E. coli) as part of the development of a waste treatment process. METHODS AND RESULTS: Four shiga-toxigenic E. coli strains (O157:H7, 091.H-, 0111.H-, and 0123.H-) and four non-toxic resident enzootic strains were all killed by 3 h treatment with fermented piggery effluent liquor (153 mmol l(-1) total VFA) at pH 4.3. The shiga-toxigenic strains showed greater sensitivity after 1 h of treatment. The fermented liquor at pH 6.8 was not inhibitory. CONCLUSIONS: The shiga-toxigenic strains were no more resistant to the toxic effects of VFA than the non-toxic strains tested. SIGNIFICANCE AND IMPACT OF THE STUDY: Shiga-toxigenic strains and resident enzootic non-toxigenic strains are equally susceptible to inactivation by this waste treatment process and by acidified VFA in general.

Animals↗
PubMed2000

Continuous intravenous epoprostenol for pulmonary hypertension due to the scleroderma spectrum of disease. A randomized, controlled trial.

BACKGROUND: Pulmonary hypertension is a progressive and often fatal complication of the scleroderma spectrum of disease for which no treatment has been proven effective in a randomized trial. OBJECTIVE: To determine the effect of epoprostenol on pulmonary hypertension secondary to the scleroderma spectrum of disease. DESIGN: Randomized, open-label, controlled trial. SETTING: 17 pulmonary hypertension referral centers. PATIENTS: 111 patients with moderate to severe pulmonary hypertension. INTERVENTION: Epoprostenol plus conventional therapy or conventional therapy alone. MEASUREMENTS: The primary outcome measure was exercise capacity. Other measures were cardiopulmonary hemodynamics, signs and symptoms of pulmonary hypertension and scleroderma, and survival. RESULTS: Exercise capacity improved with epoprostenol (median distance walked in 6 minutes, 316 m at 12 weeks compared with 270 m at baseline) but decreased with conventional therapy (192 m at 12 weeks compared with 240 m at baseline). The difference between treatment groups in the median distance walked at week 12 was 108 m (95% CI, 55.2 m to 180.0 m) (P < 0.001). Hemodynamics improved at 12 weeks with epoprostenol. The changes in mean pulmonary artery pressure for the epoprostenol and conventional therapy groups were -5.0 and 0.9 mm Hg, respectively (difference, -6.0 mm Hg [CI, -9.0 to -3.0 mm Hg), and the mean changes in pulmonary vascular resistance were -4.6 and 0.9 mm Hg/L per minute, respectively (difference, -5.5 mm Hg/L per minute [CI, -7.3 to -3.7 mm Hg/L per minute). Twenty-one patients treated with epoprostenol and no patients receiving conventional therapy showed improved New York Heart Association functional class. Borg Dyspnea Scores and Dyspnea-Fatigue Ratings improved in the epoprostenol group. Trends toward greater improvement in severity of the Raynaud phenomenon and fewer new digital ulcers were seen in the epoprostenol group. Four patients in the epoprostenol group and five in the conventional therapy group died (P value not significant). Side effects of epoprostenol therapy included jaw pain, nausea, and anorexia. Adverse events related to the epoprostenol delivery system included sepsis, cellulitis, hemorrhage, and pneumothorax (4% incidence for each condition). CONCLUSIONS: Continuous epoprostenol therapy improves exercise capacity and cardiopulmonary hemodynamics in patients with pulmonary hypertension due to the scleroderma spectrum of disease.

Adult↗
PubMed2000

Phagocytic uptake and killing of virulent and avirulent strains of Pasteurella multocida of capsular serotype A by chicken macrophages.

The susceptibility of two highly virulent (VP161 and VP138) and two less virulent (VP17 and VP21) strains of Pasteurella multocida to phagocytic uptake and killing by chicken macrophages was compared using in vitro phagocytosis and bactericidal assays. When compared with VP17 and VP21, particularly after they were preopsonised with specific immune serum, VP161 and VP138 were more resistant to phagocytosis by chicken macrophages. The uptake of these bacteria increased following the removal of the bacterial capsules with hyaluronidase. All strains preopsonised with specific immune serum were killed to some extent by chicken macrophages. However, the percentages of killing for VP17 and VP21 were higher than those of VP161 and VP138. When the capsules of VP161 and VP138 were removed, the susceptibility of the bacteria to bactericidal activity of chicken macrophages increased. It can be concluded that the virulent strains of P. multocida were more resistant to phagocytosis and phagocytic killing by chicken macrophages compared with the less virulent strains. The hyaluronic acid capsule was considered to be important in the resistance, but might not be the only factor contributing to the resistance since the less virulent strains of P. multocida also possess capsules.

Animals↗
PubMed1999

Three isolation techniques for primary culture of human osteoblast-like cells: a comparison.

The culture of osteoblast-like cells of human origin has become an important experimental model in bone biology. We report here a comparison and evaluation of three of the most widely used systems available today: bone marrow stroma cell cultures (BMSC), human osteoblast explant cultures (hOB) and osteoblast explant cultures from collagenase-treated bone (hOBcol). Cultures from 16 bone specimens obtained from various donors were established and their expression of the osteoblast phenotype were then compared in secondary cultures by use of biochemical markers. BMSC had the highest basal and 1,25-dihydroxyvitaminD3 (1,25(OH)2D3)-induced alkaline phosphatase activities in all cell isolations, with levels approximately twice those in explant cultures. Basal osteocalcin secretion was low-to-undetectable in all cell cultures but was detected in 1,25(OH)2D3-stimulated cultures. BMSC produced half of the amount of osteocalcin synthesized in explant cultures. The BMSC cultures also synthesized the lowest amounts of type I collagen, whereas collagen type III synthesis did not differ significantly among the various cultures. When secondary cultures were treated with 100 nM dexamethasone in the presence of ascorbic acid (50 microg/mL) and beta-glycerophosphate (10 mM), cultures deposited calcium mineral into the cell layer within 2-4 weeks. PTH-induced cAMP formation was detected in only 5 of 15 isolations and no consistent isolation-dependent response pattern was seen. We conclude that BMSC cultures differ significantly from explant cultures obtained from the same bone specimen. However, all cultures represent cells which can differentiate further and induce mineralization of the extracellular matrix in response to osteoinductive drugs.

Adolescent↗
PubMed1999

Thrombin, but not bradykinin, stimulates proliferation in isolated human osteoblasts, via a mechanism not dependent on endogenous prostaglandin formation.

Osteolysis or osteosclerosis often occurs in bone tissue adjacent to chronic inflammatory processes. Numerous cytokines and inflammatory mediators have been implicated as osteoclast-activating agents, explaining inflammation-induced bone resorption. In many cases, the cause of the sclerosis seen in these lesions is less thoroughly investigated. We have studied the effects of thrombin and bradykinin, 2 inflammatory mediators, on the rate of proliferation in isolated human osteoblasts (hOBs). Thrombin, at and above 1 U/mL, stimulated the rate of thymidine incorporation into hOBs. The absolute cell number also increased, as measured by an assay based on the detection of cell metabolism. A synthetic peptide ligand for the thrombin receptor enhanced the rate of [3H]thymidine incorporation in hOBs, indicating that thrombin-induced proliferation is mediated via the tetheric thrombin receptor. The thrombin-induced proliferation was not affected by indomethacin, excluding prostanoids as mediators of this effect. Bradykinin did not affect either the rate of thymidine incorporation, or number of cells in long-term cultures of hOBs. In conclusion, the inflammatory mediator, thrombin, stimulates proliferation in isolated human osteoblasts probably via the recently described G-protein-coupled tetheric thrombin receptor. Thrombin may therefore be involved as a mediator of inflammation-induced sclerosis and bone formation.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed1998

Detection of genital human papillomavirus and associated cytological abnormalities among college women.

BACKGROUND AND OBJECTIVES: Human papillomavirus (HPV) is strongly implicated in the etiology of cervical neoplasia; however, the frequency, rate, and predictors of neoplastic progression are unknown. GOAL: To measure the type-specific prevalence of cervical HPV and the rate of development of cytological abnormalities among a cohort of college women and to elucidate factors associated with acquisition of HPV DNA and progression to cytological abnormalities. STUDY DESIGN: Women 18 to 40 years of age seeking routine gynecologic care at a university health center were enrolled in a cross-sectional study with prospective, longitudinal follow-up of a subset of women. Demographic and behavioral data were collected using a written questionnaire. HPV DNA was detected in cervical scrapes by polymerase chain reaction using L1 consensus primers and a generic and 25 type-specific probes, and cervical cytological abnormalities were identified by Papanicolaou's (Pap) smear. RESULTS: HPV DNA was detected in 35% of the 414 women in the cross-sectional study; 66% of infections were with intermediate or high cancer risk HPV types. Multiple lifetime sex partners was an independent predictor of prevalent infection. Longitudinal analysis of 205 women showed that detection was transient (HPV DNA absent at follow-up) in 38% of the 84 women who were HPV-positive at enrollment. Persistent detection of the same HPV type at > or = 2 visits occurred in 14% of women and was significantly more common when intermediate or high cancer risk types were present. After 16 months of observation, 9% of HPV-infected women developed low-grade squamous intraepithelial lesions (SIL) and 5% developed high-grade SIL; the risk of incident SIL was 7.8-fold higher among women who had persistent HPV detection with the same type. CONCLUSIONS: It was concluded that cervical HPV infection is highly prevalent among college women. Although most infections are caused by intermediate of high cancer risk types, few women (5%) developed high-grade SIL during 16 months of observation.

Adolescent↗