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Biomedical subjects

G Smith

Publications and source records attributed to G Smith.

At least 181 records · Page 10Linked to original sources
PubMed2000

PHLS works towards effective interaction with primary care.

The PHLS primary care initiative was set up to develop and maintain links with primary care professionals, including researchers, GP research networks, and primary care groups in order to prioritize research and laboratory service developments. Such collaboration has spawned the development of antibiotic guidance, which has been posted on the Internet, and participation of the PHLS in other infectious disease guidance (for example, Prodigy). The implementation of the NHS information strategy will further facilitate the development of and access to local and national primary care guidance, laboratory reporting, and participation in surveillance. Primary care professionals identified several main research priorities in an exercise that facilitated collaboration in the development of research projects and grant applications. These priorities are the natural history of infections presenting to GPs, antibiotic resistance, the role of clinical scores and the laboratory in the diagnosis of infection, the importance of patient and professional attitudes in modifying antimicrobial prescribing, and the role of health professionals in community infection control. Current rapid changes in primary care in the new NHS--such as NHS Direct and the establishment of walk-in centres--may affect the surveillance of communicable disease by offering opportunities for improved data collection but also by posing threats to current systems of surveillance.

Communicable Disease Control↗
PubMed2000

Perceived skills in palliative medicine of newly qualified doctors in the U.K.

AIM: To ascertain the perceived skills of students at U.K. medical schools in palliative medicine. DESIGN: A validated questionnaire survey. PARTICIPANTS: Newly qualified U.K. pre-registration house officers (PRHOs). MEASURES: A Likert scale from 0 to 5 for respondents to rate their perceived skills in four clinical scenarios, and their anxiety in caring for the dying. RESULTS: Mean confidence rating in breaking bad news was 2.9, in ability to empathize was 3.2, in discussing prognosis was 3.3, and in providing symptom control was 2.8. Mean anxiety rating in caring for a dying patient was 2.9. Of the comments, 24% wished for more "hands on" experience and 23% suggested further curriculum recommendations. CONCLUSION: Teaching of palliative medicine is still inadequate for the needs of recently qualified doctors. Although PRHOs have identified a need for further instruction there is also acknowledgment that it is a difficult subject to teach. Recommendations are made for coordination of current interdepartmental teaching programs.

Adult↗
PubMed1999

Molecular co-crystals of 2-aminothiazole derivatives.

A series of molecular adducts of 2-aminothiazole derivatives - 2-aminothiazole, 2-amino-2-thiazoline and 2-aminobenzothiazole with the carboxylic-acid-substituted heterocyclics indole-2-carboxylic acid, N-methylpyrrole-2-carboxylic acid and thiophene-2-carboxylic acid - have been prepared and characterized using X-ray powder diffraction and in five cases by single-crystal X-ray diffraction methods. These five compounds are the adducts of 2-amino-2-thiazolium with indole-2-carboxylate [(C(3)H(7)N(2)S)(+)(C(9)H(6)NO(2))(-)], and N-methylpyrrole-2-carboxylate [(C(3)H(7)N(2)S)(+)-(C(6)H(6)NO(2))(-)], 2-aminobenzothiazolium with indole-2-carboxylate [(C(7)H(7)N(2)S)(+)(C(9)H(6)NO(2))(-)], N-methylpyrrole-2-carboxylate [(C(7)H(7)N(2)S)(+)(C(6)H(6)NO(2))(-)] and thiophene-2-carboxylate [(C(7)H(7)N(2)S)(+)(C(5)H(3)O(2)S)(-)]. All complexes involve proton transfer, as indicated by IR spectroscopy, while the five crystal structures display similar hydrogen-bonding patterns with the dominant interaction being an R(2)(2)(8) graph set dimer association between carboxylate groups and the amine/heterocyclic nitrogen sites. Futhermore, in each case a subsiduary interaction between an amino proton and a carboxylate oxygen completes a linear hydrogen-bonded chain. In addition to this, the indole-2-carboxylate molecules in the adduct structure with 2-amino-2-thiazolium form associated dimers which add to the hydrogen-bonding network.

Journal Article↗
PubMed1999

Biodistribution of filamentous phage-Fab in nude mice.

In vivo panning of peptide libraries in mice has allowed the isolation of peptides which target the vasculature of specific organs. The application of this approach to phage displaying Fab fragments (phage-Fab) could lead to the isolation of antibodies which recognize novel tumor antigens. In this study, we have evaluated the biodistribution of phage-Fab in nude mice. Balb/c nude mice were injected intravenously with 10(9) TU of phage displaying the anti-colon cancer Fab c30.6. Blood samples were collected at nine time points over a period of 72 h and three groups of four mice were sacrificed at 4 min, 24 h and 72 h. Normal tissues (liver, colon, spleen, kidneys, lungs, skeletal muscle) and faeces were collected at these time points and the number of viable phage in each sample was determined. The distribution of phage in tissues was also examined by immunohistochemical analysis of paraffin-embedded tissues. Regression analysis of plasma kinetic data showed that the half-life and the volume of distribution of phage was 3.6 h and 1 ml, respectively. Phage uptake occurred predominantly in lungs, kidneys, spleen and liver. Relatively few phage were distributed to colon and muscle, and phage were eliminated from the circulation by 72 h. Immunohistochemical analysis showed phage to be mainly within the vasculature at 4 min, whereas notable phage extravasation was observed at 24 h and 72 h. In conclusion, this study provides information on the in vivo behavior of phage-Fab which will be useful in the design of in vivo panning strategies. By choosing appropriate time points for tissue collection, it may be possible to isolate novel Fabs against both intra- and extravascular targets.

Animals↗
PubMed1999

Baculovirus-derived hemagglutinin vaccines protect against lethal influenza infections by avian H5 and H7 subtypes.

Baculoviruses were engineered to express hemagglutinin (HA) genes of recent avian influenza (AI) isolates of the H5 and H7 subtypes. The proteins were expressed as either intact (H7) or slightly truncated versions (H5). In both cases purified HA proteins from insect cell cultures retained hemagglutination activity and formed rosettes in solution, indicating proper folding. Although immunogenic in this form, these proteins were more effective when administered subcutaneously in a water-in-oil emulsion. One or two-day-old specific pathogen free (SPF) White Rock chickens, free of maternal AI antibodies, responded with variable serum HI titers, but in some cases the titers were comparable to those achieved using whole virus preparations. Vaccination of three-week-old chickens with 1.0 microg of protein per bird generated a more consistent serum antibody response with an average geometric mean titer (GMT) of 121 (H5) and 293 (H7) at 21 days postvaccination. When challenged with highly pathogenic strains of the corresponding AI subtypes, the vaccinated birds were completely protected against lethal infection and in some cases exhibited reduced or no cloacal shedding at 3 days postinfection. Vaccine protocols employing these recombinant HA proteins will not elicit an immune response against internal AI proteins and thus will not interfere with epidemiological surveys of natural influenza infections in the field.

Amino Acid Sequence↗
PubMed1999

Optimisation of the P2 pharmacophore in a series of thrombin inhibitors: ion-dipole interactions with lysine 60G.

The optimisation of the P2 pharmacophore in a series of thrombin inhibitors is described. The interaction of a number of piperidine P2 functionalities with lysine 60G of thrombin is explored with reference to the crystal structure of inhibitor enzyme complexes. A primary ion-dipole interaction between the terminal P2 side chain group and lysine 60G is evoked to explain the SAR in this series.

Crystallography, X-Ray↗
PubMed1999

Effect of pre-emptive NMDA antagonist treatment on long-term Fos expression and hyperalgesia in a model of chronic neuropathic pain.

The unilateral sciatic nerve chronic constriction injury (CCI) model of Bennett and Xie [G.J. Bennett, Y.-K. Xie, A peripheral neuropathy in rat that produces disorders of pain sensation like those seen in man, Pain, 33 (1988) 87-108] shows features of a neuropathic pain state. We examined mechanical hyperalgesia and Fos protein staining in the lumbar spinal cord 1, 7, 14 and 28 days after unilateral CCI to the sciatic nerve or sham operation. In addition, we examined the effect of the NMDA antagonist MK-801 (0.3 mg/kg s.c. administered 30 min prior to and 6 h following operation) on Fos expression and hyperalgesia at 28 days. CCI animals were hyperalgesic compared to the sham operated animals at 14 and 28 days post injury. MK-801 reduced hyperalgesia by 68% in CCI animals on day 28 (p=0.0001). In the spinal cord, Fos positive cells were present bilaterally in deeper laminae in both sham and CCI animals at all time points examined. Relatively few Fos positive cells were present in laminae 1-2 at any time point examined. At days 1 and 7, there were increased numbers of Fos positive cells ipsilaterally in the deeper laminae of the spinal cord in CCI animals compared to sham animals, but by 14 and 28 days Fos counts were similar in sham and CCI despite the obvious behavioural differences between the two groups. Fos counts ipsilateral to the injury in laminae 3-10 correlated with hyperalgesia scores in the CCI but not sham animals. Analysis at the 28-day time point showed that MK-801 differentially affected Fos expression: MK-801 significantly reduced the Fos count bilaterally in laminae 3-10 in the CCI but not in the sham group animals. These results indicate that Fos expression is initiated by different peripheral and central mechanisms following nerve injury or sham operation.

Animals↗
PubMed1999

Effect of post-injury NMDA antagonist treatment on long-term Fos expression and hyperalgesia in a model of chronic neuropathic pain.

Chronic constriction injury (CCI) of the sciatic nerve results in persistent mechanical hyperalgesia together with Fos protein expression in the lumbar spinal cord. We have examined the relationship between mechanical hyperalgesia and Fos expression within the lumbar spinal cord on days 14, 35 and 55 after either CCI or sham operation. To determine the role of NMDA receptor mechanisms in the maintenance of hyperalgesia and Fos expression, the NMDA antagonist MK-801 (0.3 mg kg-1 s.c.) was administered daily on days 28 to 34 after operation. CCI animals developed unilateral hind limb hyperalgesia that persisted unchanged from days 14 to 55 of the study. MK-801 treatment reduced hyperalgesia by 57% (p=0.02) on day 35 in CCI animals but did influence hyperalgesia at day 55. In the spinal cord, Fos positive cells were present bilaterally throughout laminae 3-10 at all time points examined in both CCI and sham group animals. Fos counts ipsilateral to the side of injury in laminae 3-10 correlated significantly with hyperalgesia scores in the CCI but not sham animals. MK-801 treatment resulted in a suppression of Fos expression in ipsilateral laminae 3-4 (p=0.0017) and laminae 5-10 (p=0.0026) of CCI animals on day 35. Fos expression in sham group animals was not inhibited by MK-801 treatment at day 35. These results indicate that Fos expression is maintained by differing mechanisms following nerve injury or sham operation. The functional consequences of Fos expression following nerve injury and sham operation are discussed.

Animals↗
PubMed1999

Sperm chromatin damage associated with male smoking.

Cigarette smoke is a rich source of mutagens and carcinogens; thus, we have investigated the effects of male smoking on the DNA of human sperm. This was performed using the sperm chromatin structure assay (SCSA), which measures the sensitivity of sperm DNA to acid induced denaturation, and the terminal deoxynucleotidyl transferase assay (TdTA), which measures DNA strand breaks by addition of the biotinylated nucleotide dUTP to 3'-OH ends of DNA, sites of DNA breakage, using the enzyme terminal deoxynucleotidyl transferase. Sperm from subjects who smoked were significantly more sensitive to acid induced denaturation than non-smokers (P<0.02) and possessed higher levels of DNA strand breaks (P<0.05). We hypothesise that smoking damages the chromatin structure and produces endogenous DNA strand breaks in human sperm. These changes may result in sperm DNA mutations, that predispose offspring to greater risk of malformations, cancer and genetic diseases.

Chromatin↗
PubMed1999

Correlation of the osteoblastic phenotype with prostate-specific antigen expression in metastatic prostate cancer: implications for paracrine growth.

The characteristic sclerotic appearance of bone metastases from prostate cancer is unexplained but could involve excess peritumoural activity of osteoblast mitogens such as the insulin-like growth factors (IGFs). Since prostatic metastases are distinguished by androgen-dependent secretion of prostate-specific antigen (PSA), a serine protease which cleaves extracellular IGF-binding proteins and thereby enhances the bioavailability of IGFs, the relationship was examined between tumour PSA expression and the osteoblastic phenotype. To this end, a cohort of 27 prostate cancer patients was evaluated to determine the relationship between serum PSA and radiographic bone lesion density at first presentation with metastatic disease. No linear correlation between absolute PSA levels and metastatic osteosclerosis was apparent. However, non-parametric statistical analysis revealed a highly significant link between low-PSA (<20 ng/ml) metastatic prostate cancer and osteolytic bone lesions (p<0.0001, chi(2)=21.5). This finding raises the possibility that the osteoblastic phenotype of prostate cancer derives in part from PSA-dependent proteolysis of IGF-binding proteins within bone matrix.

Bone Neoplasms↗
PubMed1999

The plantar fasciotomy: MR imaging findings in asymptomatic volunteers.

OBJECTIVE: To determine the postoperative appearance of the plantar fascia on MR imaging after a fasciotomy has been performed, and to compare the postsurgical appearance of the fascia after an open and endoscopic procedure. DESIGN AND PATIENTS: Fifteen asymptomatic volunteers (12 women, 3 men; age range 22-49 years, mean age 33 years) with prior fasciotomies for treatment of longstanding plantar fasciitis were studied. Fourteen volunteers had a unilateral release and one volunteer had bilateral releases, allowing for assessment of 16 ankles. Eight fasciotomies were performed through an open incision and eight were performed endoscopically. The average time between surgery and imaging was 24 months (range 11-46 months). The site of surgery was established from the operative reports. Proton density (PD)-weighted and T2-weighted images in three orthogonal planes were obtained on a 1.5-T magnet. In eight studies, T1-weighted sagittal and STIR sagittal images were included. The fascia in each ankle was assessed for morphology and signal intensity. Perifascial soft tissues and bone marrow were assessed for edema. Preoperative MR studies were available in five volunteers. RESULTS: There was no apparent difference in the postoperative appearance of the ankle after an open or endoscopic procedure except for scar formation in the subcutaneous fat which was common after an open procedure (P<0.05). Three ankles had a gap in the fascia (one open, two endoscopic). The plantar fascia measured a mean of 7.0 mm (range 5-10 mm) at the fasciotomy, and 8.3 mm (range 6-12 mm) at the enthesis. At the fasciotomy, 11 of 13 ankles had an indistinct deep contour and 9 of 13 had an indistinct superficial contour. At the enthesis, 13 of 16 ankles had an indistinct deep contour and 6 of 16 had an indistinct superficial contour. Compared with preoperative MR studies there was an average reduction in the fascial thickness at the enthesis of 14% (range 9-20%), but the thickness at the fasciotomy nearly doubled. No edema was evident in the fascia, perifascial tissues, deep plantar muscles, or calcaneal bone marrow. CONCLUSIONS: The average thickness of the plantar fascia in asymptomatic volunteers after surgery is nearly 2-3 times that of normal. While there is increased thickness at the site of surgery, the changes in morphology and signal intensity were most prominent at the enthesis. The key observation was absence of edema in the fascia and perifascial soft tissues. This baseline information may be of value when assessing MR studies of symptomatic patients.

Adult↗