PubMed Health⌕ Search

Biomedical subjects

S Shore

Publications and source records attributed to S Shore.

At least 19 recordsLinked to original sources
PubMed2005

Predicting progressive hepatic fibrosis stage on subsequent liver biopsy in chronic hepatitis C virus infection.

Retrospective cross-sectional studies indicate that 20% with chronic hepatitis C virus (HCV) infection become cirrhotic within 20 years. Known risk factors for advanced hepatic fibrosis include age at time of infection, male sex, excess alcohol consumption and cytokine polymorphisms. Prospective study to assess and identify factors predictive of change in hepatic fibrosis stage in chronic HCV infection by interval protocol liver biopsy was performed. One hundred and five patients with paired liver biopsy specimens separated by a mean 41 months were recruited from a cohort of 823 HCV carriers. Five per cent developed worsening hepatic fibrosis by more than two stages. In 43% there was no change in fibrosis stage. Excessive alcohol intake currently (P = 0.037) or previously (P = 0.07) predicted progression. In contrast, always having a normal alanine transaminase (P = 0.038) and always being negative in serum for HCV RNA (P =0.067) predicted no progression. Three models were developed to predict outcome. Progressive fibrosis was predicted by baseline fibrosis (P = 0.018), steatosis (P = 0.02) and age (P = 0.017). The rate of progressive fibrosis was predicted by baseline fibrosis (P = 0.0002), steatosis (P =0.039) and lobular inflammation (P = 0.09). Fibrosis stage on the second biopsy was predicted by baseline fibrosis alone (P = 0.01). The rate of progression varies widely. Alcohol misuse is an important co-factor. Progressive fibrosis can be predicted at first liver biopsy, where baseline fibrosis is most critical, allowing targeted therapy for those with early disease and a significant risk of progression.

Adult↗
PubMed2003

Review article: chemotherapy for pancreatic cancer.

Pancreatic cancer is a common, highly lethal disease that is rising in incidence. Chemotherapy based on 5-fluorouracil (5-FU) has been shown to prolong survival in advanced pancreatic cancer. Gemcitabine improves major symptoms and survival outcomes compared with bolus 5-FU. Many novel small molecules are being widely and actively researched. These compounds are based on classical mechanisms of action as well as biological therapies targeting novel cellular survival pathways, and include fluoropyrimidines, nucleoside cytidine analogues, platinum analogues, topoisomerase-inhibitors, antimicrotubule agents, proteasome inhibitors, vitamin D analogues, arachidonic acid pathway inhibitors, histone deacytylator inhibitors, farnesyltransferase inhibitors and epidermal growth factor receptor therapies. Adjuvant chemotherapy has also demonstrated the best survival outcomes following resection compared to other adjuvant or neo-adjuvant strategies such as radiation-based treatments. These benefits are superimposed on the dramatic increase in resectability rates and reduction in post-operative mortality achieved by centralisation of treatment in high-volume speciality centres. Newer 'small-molecule' drugs as well as the latest 'large-molecule' biological agents hold considerable promise for the future. Real advances are anticipated over the next five years but are dependent on large randomised controlled trials for success.

Antimetabolites, Antineoplastic↗
PubMed2002

Stress in UK intensive care unit doctors.

BACKGROUND: Doctors have long been considered at risk of occupational stress. METHODS: A postal survey of all members of the Intensive Care Society using validated instruments. RESULTS: Eight-five per cent of members returned questionnaires and 70% were eligible for the study. Twenty-nine per cent were suffering General Health Questionnaire-12 (GHQ-12) identified distress and 12% Symptom Checklist-Depression (SCL-D) defined depression. There were no significant age or sex differences between staff suffering distress or depression and those who did not. Dissatisfaction with career correlated highly with both distress and depression (P<0.01). Twenty doctors (3%) were bothered by suicidal thoughts. The most stressful aspects of work were bed allocation, being over-stretched, effect of hours of work and stress on personal/family life, and compromising standards when resources are short. Logistic regression revealed mental health problems were predicted by five stressors: 'lack of recognition of one's own contribution by others'; 'too much responsibility at times'; 'effect of stress on personal/family life'; 'keeping up to date with knowledge'; and 'making the right decision alone'. CONCLUSIONS: Nearly one in three ICU doctors appeared distressed (GHQ), and one in 10 depressed (SCL-D); this is no greater than that reported in other specialities. Perceived stressors reveal some key areas of concern for the employer and the specialty.

Adult↗
PubMed2001

Neonatal bone mass: influence of parental birthweight, maternal smoking, body composition, and activity during pregnancy.

Evidence is accumulating that intrauterine growth and development may influence an individual's risk of osteoporosis in later adult life. To examine maternal and paternal influences on intrauterine skeletal growth, we used dual-energy X-ray absorptiometry to measure the neonatal bone mineral content (BMC) and bone mineral density (BMD) of 145 infants born at term. Independently of the infant's duration of gestation at birth, the birthweights of both parents and the height of the father were positively correlated with neonatal whole body BMC. Women who smoked during pregnancy had infants with a lower whole body BMC and BMD; overall, there was a 7.1-g (11%) average difference between whole body BMC of infants whose mothers did and did not smoke during pregnancy (p = 0.005). Women with thinner triceps skinfold thicknesses (reflecting lower fat stores) and those who reported a faster walking pace and more frequent vigorous activity in late pregnancy also tended to have infants with a lower BMC and BMD (p values for BMC; 0.02, 0.03, and 0.05, respectively). Maternal thinness and faster walking pace but not maternal smoking or parental birthweight also were associated with lower bone mineral apparent density (BMAD). The influences on skeletal growth and mineralization were independent of placental weight, a marker of the placental capacity to deliver nutrients to the fetus. These observations point to a combination of genetic and intrauterine environmental influences on prenatal skeletal development and suggest that environmental modulation, even at this early stage of life, may reduce the risk of osteoporosis in adulthood.

Absorptiometry, Photon↗
PubMed1999

Further evidence for an association between non-insulin-dependent diabetes mellitus and chronic hepatitis C virus infection.

Non-insulin-dependent diabetes mellitus (NIDDM) may be associated with chronic hepatitis C virus (HCV) infection. This was studied further in two parts. First, 1,151 patients with HCV-related cirrhosis and 181 patients with hepatitis B virus (HBV)-related cirrhosis, well matched for age, sex, and severity of cirrhosis, were reviewed retrospectively. The prevalence of diabetes mellitus was higher in HCV-related cirrhosis (23.6%) than in HBV-related cirrhosis (9.4%; odds ratio [OR], 2.78; 95% confidence interval [CI], 1.6-4.79; P =.0002). The prevalence of diabetes mellitus was associated closely with the Child-Pugh score (OR, 3.83; 95% CI, 2. 38-6.17; P <.0001) and increasing age (OR, 1.02; 95% CI, 1.00-1.03; P =.0117). Second, 235 patients with biopsy confirmed chronic HBV or HCV underwent an oral glucose tolerance test. Only 1 of 70 patients with chronic viral hepatitis without cirrhosis was diabetic. However, 31 of 127 patients with HCV-related cirrhosis (24.4%) were diabetic compared with 3 of 38 patients with HBV-related cirrhosis (7.9%, P =.0477). The major variables associated with NIDDM were cirrhosis (OR, 14.39; 95% CI, 1.91-108; P =.0096) and male sex (OR, 4.64; 95% CI, 1. 32-16.18; P =.0161). Fasting insulin levels in 30 patients with HCV-related cirrhosis and diabetes mellitus were elevated significantly, which was consistent with insulin resistance. However, acute insulin responsiveness was reduced in all patients with HCV infection and diabetes suggesting concomitant B-cell dysfunction. This study confirms an association between HCV and NIDDM.

Adult↗
PubMed1999

Immune responses to training: how critical is training volume?

BACKGROUND: If the volume of training undertaken is sufficient to induce a negative energy balance, the anticipated benefit of an enhanced immune response may be reduced or lost. METHODS: 33 sedentary but healthy male volunteers aged 19-29 years, recruited from the university community. A peak oxygen intake measurement (cycle ergometer) and a 60-min exercise challenge at 60% of aerobic power were performed before and after 12 wk of treatment. Total leukocytes, subsets, CD3+, CD4+, CD8+, CD16+, CD19+, and CD25+ counts (FACScan), cytolytic activity (51Cr release) and cell proliferation (PHA and PWM) were measured, with subjects assigned arbitrarily to one of three groups: light training (18 subjects, aerobic exercise at 70-85% HRmax 3 times/wk), moderate training (9 subjects, similar programme 4-5 times/wk) and control (6 subjects). RESULTS: Groups were initially well-matched in physical and physiological terms. Training increased aerobic power (8%, light, 21% moderate training), with a loss of body mass and fat in the moderate training group. Controls showed no changes. Resting CD16+ counts increased by 27% (light training) and CD16+ CD56+ counts by 21% (moderate training), with less post-exercise suppression of counts than at recruitment. Light training also decreased CD3+ and CD4+ counts without changing the CD4+/CD8+ ratio. Moderate training decreased resting CD19+ count. CONCLUSIONS: From the viewpoint of immune function, the optimal training regimen is of low volume. Moderate training sufficient to induce a negative energy balance yields a smaller increase in numbers of non-MHC-restricted cytotoxic cells, and carries the negative consequence of diminished B cell counts.

Adult↗
PubMed1999

Immune responses to exercise in children treated for cancer.

BACKGROUND: Children treated for cancer commonly benefit physiologically from moderate aerobic training, but it is less clear if impairment of the immune system secondary to chemotherapy reduces the immunological tolerance of exercise relative to normal children. METHODS EXPERIMENTAL DESIGN: a case series. SETTING: hospital laboratory. PARTICIPANTS: six children aged 13-14 yr, successfully treated for acute lymphoblastic leukaemia and other types of neoplasms, were compared with 11 normal volunteer children. INTERVENTIONS: three of the sample underwent 12 weeks training at 70-85% of maximal heart rate; the remaining three provided initial and final test data only. MEASURES: mood state (Piers-Harris test), anthropometric data, maximal oxygen intake, response to 30 min exercise challenges at anaerobic threshold, and standard immune measures (differential count, cytolytic activity, and mitogen-induced lymphocyte proliferation) at rest, during and following submaximal exercise. RESULTS: A low maximal oxygen intake, excess of body fat, and high anxiety scores all improved with training. Children who were still receiving chemotherapy showed low resting CD3+, CD4+, CD8+, CD19+ and CD25+ counts and reduced PHA-induced proliferation. Acute exercise and training caused further impairment of immune responses, although changes remained insufficient to cause concern for health. CONCLUSIONS: Exercise therapy is beneficial following treatment of cancer, but should be prescribed individually, with a careful monitoring of immune responses.

Adolescent↗
PubMed1996

Arrest of endotoxin-induced hypotension by transforming growth factor beta1.

Septic shock is a cytokine-mediated process typically caused by a severe underlying infection. Toxins generated by the infecting organism trigger a cascade of events leading to hypotension, to multiple organ system failure, and frequently to death. Beyond supportive care, no effective therapy is available for the treatment of septic shock. Nitric oxide (NO) is a potent vasodilator generated late in the sepsis pathway leading to hypotension; therefore, NO represents a potential target for therapy. We have previously demonstrated that transforming growth factor (TGF) beta1 inhibits inducible NO synthase (iNOS) mRNA and NO production in vascular smooth muscle cells after its induction by cytokines critical in the sepsis cascade. Thus, we hypothesized that TGF-beta1 may inhibit iNOS gene expression in vivo and be beneficial in the treatment of septic shock. In a conscious rat model of septic shock produced by Salmonella typhosa lipopolysaccharide (LPS), TGF-beta1 markedly reduced iNOS mRNA and protein levels in several organs. In contrast, TGF-beta1 did not decrease endothelium-derived constitutive NOS mRNA in organs of rats receiving LPS. We also performed studies in anesthetized rats to evaluate the effect of TGF-beta1 on the hemodynamic compromise of septic shock; after an initial 25% decrease in mean arterial pressure, TGF-beta1 arrested LPS-induced hypotension and decreased mortality. A decrease in iNOS mRNA and protein levels in vascular smooth muscle cells was demonstrated by in situ hybridization and NADPH diaphorase staining in rats treated with TGF-beta1. Thus these studies suggest that TGF-beta1 inhibits iNOS in vivo and that TGF-beta1 may be of future benefit in the therapy of septic shock.

Animals↗
PubMed1996

The school health fair: an elementary choice.

School is a place where children work, play and learn. It is also a place where they can first develop an awareness of quality of life and its health components. With the current emphasis on health as a resource for living, emphasizing social and personal resources as well as physical capacity, the school community offers an important opportunity for the development of life skills to help children make informed health decisions.

Child↗
PubMed1995

The hypothalamic-pituitary-adrenal axis in obesity.

The hypothalamic-pituitary-adrenal (HPA) axis normally maintains the concentration of cortisol within a narrow range with a diurnal variation characterized by higher cortisol concentrations in the morning and reduced levels in the evening. Excessive or deficient secretion of cortisol is associated with pathologic changes. Obesity has been linked with age, sex and racial alterations in the functioning of the HPA axis which are reviewed. The possible relationship of altered HPA axis activity with the long-term complications of obesity are considered.

Adrenocorticotropic Hormone↗
PubMed1995

Increased airway responsiveness to inhaled methacholine in a rat model of chronic bronchitis.

Chronic exposure of rats to high concentrations of SO2 gas causes pathologic changes in airway similar to those seen in human chronic bronchitis. The purpose of this study was to examine the pulmonary mechanical correlates of these changes and to quantify the extent of mucous hypersecretion by measuring changes in mucous glycoproteins. Female Sprague-Dawley rats were exposed to 250 ppm SO2 gas, 5 h/d, 5 d/wk, for a period of 4 wk. Control rats were exposed to air only. On the day after the last SO2 exposure, rats were anesthetized, instrumented for the measurement of pulmonary resistance (RL) and dynamic compliance (Cdyn), and ventilated. Chronic SO2 exposure caused a small but significant increase in RL and decrease in Cdyn. Airway responsiveness to inhaled aerosolized methacholine was increased in SO2-exposed rats, as indicated by approximately 6.6- and 4.6-fold decreases respectively, in the doses of inhaled methacholine required to double RL or decrease Cdyn to 50% of baseline. SO2 exposure had no effect on the contractile response of the trachea measured in vitro. Tracheae and lungs from SO2-exposed animals exhibited 140 and 535% increases in measured neutral mucous glycoproteins, respectively, and 33 and 37% increases in acid glycoproteins. Our results indicate that this animal model of chronic bronchitis mimics the mucous hypersecretion, airway obstruction, and increased airway responsiveness observed in human bronchitis and may allow us to begin to probe their mechanistic basis.

Animals↗
PubMed1992

An unusual genotype in an Ashkenazi Jewish patient with Tay-Sachs disease.

The Ashkenazi Jewish population is enriched for carriers of a fatal form of Tay-Sachs disease, a recessive inherited disorder caused by mutations in the alpha-chain of the lysosomal enzyme beta-hexosaminidase A. Approximately 20% of the Ashkenazi carriers harbor a splice junction defect while about 78% bear a 4 base pair (bp) insertion. However, the Ashkenazi Jewish patient used in the original description of the 4 bp insertion carried this lesion in only 1 allele and was negative for the splice junction mutation. We cloned the insertion negative allele and by sequence analysis of the exons found a point mutation in exon 11 that results in substitution of Trp392 with a premature termination codon. Nine Ashkenazi Jewish carriers that tested negative for the major and minor mutations as well as for a lesion causing an adult form of Tay-Sachs disease did not carry the base change defect, suggesting that it may be a recent and/or rare mutation. This finding also indicates that screening the Ashkenazi population solely by recombinant DNA methods for the splice junction, 4 bp insertion, and adult mutations may result in occasional false negatives.

Alleles↗
PubMed1992

Acute exercise and immune function. Relationship between lymphocyte activity and changes in subset counts.

Twenty-one young male subjects exercised on a cycle ergometer for 60 min at 60% of VO2max. Blood samples collected every 30 min throughout exercise and continuing to 120 min recovery served for the immunological tests. Exercise induced biphasic changes in the various leucocyte subsets. There was a granulocytosis, lymphocytosis and monocytosis during exercise, and a further granulocytosis and a slight monocytosis, but a lymphocytopenia during recovery. All lymphocyte subsets (CD3+, CD19+, CD4+, CD8+, and CD16+ cells) increased in number during exercise, were decreased 30 min after exercise, and had not returned to baseline levels by 120 min of recovery. The apparent lymphocyte responsiveness to the mitogens phytohaemagglutinin (PHA) and pokeweed mitogen (PWM) declined significantly during exercise, returning to normal by 120 min of recovery. The natural killer (NK) activity rose markedly during exercise, but decreased to almost half the pre-exercise level at 30 and 60 min of recovery, returning to baseline levels after 120 min of recovery. Functional capability correlated well with the percentage of each major responder subset in the assay, suggesting that the in vitro lymphocyte PHA- and PWM-responsiveness and the NK activity did not change significantly on a per cell basis. The analysis of lymphocyte marker antigen density revealed that the CD3+, CD4+, CD8+ and CD19+ lymphocytes mobilized into the circulation during exercise did not express the respective CD3, CD4, CD8 and CD19 molecules as strongly as did the subsets circulating at rest, whereas the expression of the CD16 antigen on CD16+ lymphocytes remained unchanged.

Adult↗
PubMed1991

Airway luminal liquid. Sources and role as an amplifier of bronchoconstriction.

The release of mediators from inflammatory cells into the airway lumen can initiate a series of events leading to airway obstruction, particularly smooth muscle contraction and alteration of endothelial and epithelial permeability leading to mucosal edema and subsequent influx of liquid into the airway lumen. In this report we briefly review the effects of several inflammatory mediators, including eicosanoids, platelet-activating factor, and histamine, as well as the effects of plasma proteins and tachykinins that may be secondarily released because of the presence of inflammatory mediators on endothelial and epithelial permeability. We then consider physical mechanisms whereby the resulting airway luminal liquid could amplify the response of an airway previously constricted because of smooth muscle contraction. Specifically, liquid in the interstices between epithelial projections that are formed during muscular contraction could amplify the degree of luminal compromise by (1) further decreasing luminal cross-sectional area by occupying space, and (2) providing an additional source of inward recoil because of the surface tension of the air-liquid interface.

Animals↗
PubMed1990

A gel electrophoretic assay for detecting the insertion defect in Ashkenazi Jewish carriers of Tay-Sachs disease.

A simple, rapid, nonradioactive assay for detecting the 4-bp insertion defect found in the beta-hexosaminidase alpha-chain gene of 70% of the Ashkenazi Jewish carriers of Tay-Sachs disease is described. In this assay, DNA derived from such carriers serves as a template for the polymerase chain reaction. Following amplification of a 159-bp fragment of exon 11 inclusive of the insertion, a portion of the product is subjected to electrophoresis in a 4% NuSieve agarose minigel. Visualization of the DNA with ethidium bromide demonstrates that heterozygote carriers for the defect display two distinct bands. In contrast, DNA from carriers of the splice junction defect, a mutation found in 30% of the Ashkenazi Jewish carriers of Tay-Sachs disease, displays only one band.

Base Sequence↗
PubMed1987

Effect of endogenous prostaglandins on acetylcholine release from dog trachealis muscle.

We used a radioenzymatic technique to measure effects of the prostaglandin synthesis inhibitor indomethacin and of exogenous prostaglandin E2 (PGE2) and prostaglandin I2 (PGI2) on acetylcholine (ACh) efflux from canine tracheal smooth muscle (TSM) during sustained electrical field stimulation (EFS; 2 Hz, 2 ms pulse duration, 50 V for 15 min). ACh efflux from indomethacin (INDO, 10(-6) M)-pretreated and control TSM increased with consecutive stimulations. However, efflux of ACh was greater in INDO-treated than control muscles. INDO increased the tension produced by TSM in response to EFS. Neither PGE2 (10(-8) M) nor PGI2 (10(-6) M) had any effect on ACh efflux from INDO-pretreated TSM during the first of three periods of EFS. However, PGI2 and PGE2 prevented the progressive increase in ACh efflux observed on subsequent stimulations. PGE2 but not PGI2 decreased contractions of TSM caused by EFS. Our results demonstrate that endogenous prostaglandins, probably PGE2, do inhibit EFS-evoked ACh release from canine TSM in vitro, but suggest that these prostaglandins modulate EFS-evoked contractions predominantly by postsynaptic mechanisms.

Acetylcholine↗