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Biomedical subjects

J M Davidson

Publications and source records attributed to J M Davidson.

At least 37 records · Page 2Linked to original sources
PubMed1999

Adhesion formation is reduced after laparoscopic surgery.

BACKGROUND: Adhesion formation after abdominal operations causes significant morbidity. METHODS: Adhesion formation in pigs was compared after placement of prosthetic mesh during celiotomy (group 1), laparoscopy with large incision (group 2), and laparoscopy (group 3). After peritoneum was excised, polypropylene mesh was fixed to the abdominal wall, then to the opposite abdominal wall in the preperitoneal space followed by peritoneal closure. Adhesion area, grade, and vascularity were measured. RESULTS: More adhesions (p < 0.02) covered intraperitoneal mesh (7.57 +/- 1.89 cm2) than covered reperitonealized mesh (2.16 +/- 1.13 cm2), and adhesion grade was significantly greater (p < 0.02). Adhesion areas were significantly greater in groups 1 and 2 than in group 3 (p = 0.001 and 0.03, respectively). Adhesion grade was significantly greater in groups 1 and 2 than in group 3 (p = 0.02 and p = 0.04, respectively). Groups 1 and 2 had more vascular adhesions than group 3 (p < 0.01 and p = 0.02, respectively) CONCLUSIONS: A foreign body within the peritoneum stimulates more numerous and denser adhesions. Tissue trauma distant from the site of adhesions increases their formation. A major advantage of laparoscopic surgery is decreased adhesion formation.

Abdomen↗
PubMed1999

Effect of sucrose on the perceived flavor intensity of chewing gum.

The release of sucrose and menthone from chewing gum was measured in-mouth and in-nose, respectively, during eating. Swabs of saliva were taken from the tongue and analyzed using a rapid, direct liquid-mass spectrometry procedure. Menthone concentration in-nose was monitored on a breath-by-breath basis using direct gas phase atmospheric pressure chemical ionization-mass spectrometry. Simultaneously with the volatile release, trained panelists followed the change in mint flavor by time-intensity (TI) analysis. Two types of commercial chewing gum were analyzed. Both showed that the panelists perception of mint flavor followed sucrose release rather than menthone release. The temporal analysis of the chemical stimuli, with simultaneous TI analysis, provided unequivocal evidence of the perceptual interaction between nonvolatile and volatile flavor compounds from chewing gum.

Breath Tests↗
PubMed1999

Career choices at the end of the pre-registration year of doctors who qualified in the united kingdom in 1996.

OBJECTIVE: To report the career intentions one year after qualification of doctors who qualified in the United Kingdom (UK) in 1996, and to compare their intentions with those of 1993 qualifiers at the same stage. DESIGN: Postal questionnaires. SETTING: United Kingdom. SUBJECTS: All doctors who qualified in the UK in 1996. MAIN OUTCOME MEASURES: Choices of eventual career expressed one year after qualifying. RESULTS: We report on detailed choices of long-term careers for all specialties. Only 20% of 1996 respondents chose general practice compared with 25.8% of 1993 respondents. The percentage choosing general practice fell more sharply among women, from 34.0% to 25.2%, than among men, from 17.5% to 14.1%. Choices for surgical specialties rose from 16.9% of 1993 respondents to 21. 4% of 1996 respondents. The percentage choosing the surgical specialties rose among women, from 7.8% to 11.6%, compared with a rise among men from 26.1% to 32.2%. The percentage of respondents who definitely or probably intended to pursue a long-term career in the UK was 77.7% compared with 75.7% of 1993 respondents. Most of the home-based respondents who had doubts about practising in the United Kingdom were considering practising abroad. Only 1% made an explicit first choice for a non-medical career. However, in all, 9. 4% said that there was a possibility that they might leave medicine. CONCLUSION: The substantial decline in intentions to enter general practice among newly qualified doctors, seen in the 1993 qualifiers, is continued in the 1996 qualifiers. A shortfall in recruitment of UK-trained doctors to general practice is the likely outcome. The rise in choices for the surgical specialties, particularly among women, may herald a renewed interest in hospital specialist training following the Calman changes. It is worrying that almost a quarter of respondents indicated some doubts about pursuing a medical career in the UK.

Attitude of Health Personnel↗
PubMed1999

Particle-mediated gene transfer of PDGF isoforms promotes wound repair.

Several techniques for cutaneous gene transfer have been investigated for either in vitro or in vivo applications. In the present study, we investigated whether the direct delivery of platelet-derived growth factor cDNA into skin results in improvement in tissue repair. Cutaneous transfections were carried out in rats using a particle-bombardment device (Accell). As revealed by reverse transcriptase-polymerase chain reaction, transgene expression in vivo was transient, with low level expression by day 5. When compared with wounds transfected with a control cytomegalovirus-luciferase plasmid, wounds transfected with platelet-derived growth factor A or B in the MFG vector showed a significant increase in wound tensile strength 7 and 14 d after transfection. At both time points platelet-derived growth factor A transfected wounds exhibited the highest increase in tensile strength over controls, resulting in a 3.5-fold increase at day 7 and a 1.5-fold increase at day 14. The degree of stimulation was not remarkably different between wounds transfected with platelet-derived growth factor B, which is predominantly cell associated, or a truncation mutant, platelet-derived growth factor B211, which is predominantly secreted. These findings demonstrate that in vivo gene transfer by particle bombardment can be used to improve the tissue repair response. This approach provides a robust tool to assess the biologic activity of various proteins and will aid in the development of therapeutic cutaneous gene delivery.

Animals↗
PubMed1999

Sustained microgravity reduces intrinsic wound healing and growth factor responses in the rat.

Spaceflight is known to diminish bone mass and reduce immune function, suggesting that repair of connective tissue might be impaired in a microgravity environment. Fisher 344 rats were used to test wound healing responses in the orbiting Space Shuttle Endeavour by preflight implantation of polyvinyl acetal sponge disks in which pellets were placed to release either platelet-derived growth factor (PDGF-BB), basic fibroblast growth factor (bFGF), or placebo. Control groups on the ground included a matched environment group in similar housing modules and temperature control groups in cages at 22 degreesC and 28 degreesC. After 12 days of implantation and 10 days in orbit, the removed sponges were analyzed for histological and biochemical responses. Growth factor responses were histologically evident after release of PDGF-BB and bFGF in ground controls, whereas only immediate-release bFGF and delayed-release PDGF-BB showed significant responses in microgravity. Biochemical data confirmed that cellularity was increased by both factors in ground sponges; however, this response was significantly blunted in flight sponges (P<0.005, ANOVA), irrespective timing of factor release. Collagen content was 62% lower in sponges from animals with 10 days of microgravity exposure (P<0.01, ANOVA) and further reduced by bFGF. These data suggest that orbital exposure retards the capacity of wounds to heal and respond to exogenous stimuli.

Animals↗
PubMed1999

The effect of caloric restriction on the aortic tissue of aging rats.

Connective tissue shows peculiar and complex age-related modifications, which can be, at least in part, responsible for altered functions and increased susceptibility to diseases. Food restriction has long been known to prolong life in rodents, having antiaging effects on a variety of physiologic and pathologic processes. Therefore, the aorta has been investigated in rats fed normal or hypocaloric diet, from weaning to senescence. Compared with controls, caloric-restricted animals showed less pronounced age-dependent alterations such as elastic fiber degradation, collagen accumulation and cellular modifications. Immunocytochemical analyses revealed that elastic fibers were positively labelled for biglycan, decorin, ApoB100 (LDL), ApoA1 (HDL) and elastase and that the intensity of the reactions was time- and diet-dependent. With age, the major changes affecting aortic elastic fibers were increased positivity for decorin, LDL and elastase. Compared with age-matched normal fed rats, caloric restricted animals revealed lower content of LDL, decorin and elastase and higher positivity for HDL. These data suggest that a caloric restricted diet might influence the aging process of the arterial wall in rats, delaying the appearance of age-related degenerative features, such as structural alterations of cells and matrix and modified interactions of elastin with cells and with other extracellular matrix molecules.

Aging↗
PubMed1999

Elastin gene expression is upregulated during pulmonary fibrosis.

Elastin is a chief component of lung interstitium, and it is central to lung morphology and function. Efforts to understand the pathogenesis of pulmonary fibrosis have focused primarily upon collagen turnover in the lung; few studies have focused on elastin. In this study, we examined steady-state elastin mRNA levels after lung injury in the mouse induced by (1) butylated hydroxytoluene (BHT) which causes acute lung injury with recovery, (2) BHT + 70% O2 (fibrosis), or (3) 70% O2. Total lung elastin mRNA increased 70-80-fold on d10-14 after BHT/O2, but was unchanged after BHT or O2 alone. In situ hybridization studies localized elastin mRNA to cells in the muscularis of conducting airways and to scattered interstitial cells in fibrotic foci. Elastic fiber morphology was markedly distorted after BHT/O2. Thus, marked upregulation of elastin gene expression is correlated with the histopathology of fibrotic lung disease.

Animals↗
PubMed1998

Career pathways and destinations 18 years on among doctors who qualified in the United Kingdom in 1977: postal questionnaire survey.

OBJECTIVE: To determine the career destinations, by 1995, of doctors who qualified in the United Kingdom in 1977; the relation between their destinations and early career choice; and their intentions regarding retirement age. DESIGN: Postal questionnaire. SETTING: United Kingdom. SUBJECTS: All (n=3135) medical qualifiers of 1977. MAIN OUTCOME MEASURES: Current employment; year by year trends in the percentage of doctors who worked in the NHS, in other medical posts in the United Kingdom, abroad, in non-medical posts, outside medicine, and in part time work; intentions regarding retirement age. RESULTS: After about 12 years the distribution of respondents by type of employment, and, for women, the percentage of doctors in part time rather than full time medical work, had stabilised. Of all 2997 qualifiers from medical schools in Great Britain, 2399 (80.0% (95% confidence interval 79.5% to 80.6%)) were working in medicine in the NHS in Great Britain 18 years after qualifying. Almost half the women (318/656) worked in the NHS part time. Of 1714 doctors in the NHS, 1125 intended to work in the NHS until normal retirement age, 392 did not, and 197 were undecided. Of the 1548 doctors for whom we had sufficient information, career destinations at 18 years matched the choices made at 1, 3, and 5 years in 58.9% (912), 78.2% (1211), and 86.6% (1341) of cases respectively. CONCLUSIONS: Planning for the medical workforce needs to be supported by information about doctors' career plans, destinations, and whole time equivalent years of work. Postgraduate training needs to take account of doctors' eventual choice of specialty (and the timing of this choice).

Adult↗
PubMed1998

Altered wound healing in mice lacking a functional osteopontin gene (spp1).

Osteopontin (OPN) is an arginine-glycine-aspartate (RGD)- containing glycoprotein encoded by the gene secreted phosphoprotein 1 (spp1). spp1 is expressed during embryogenesis, wound healing, and tumorigenesis; however, its in vivo functions are not well understood. Therefore, OPN null mutant mice were generated by targeted mutagenesis in embryonic stem cells. In OPN mutant mice, embryogenesis occurred normally, and mice were fertile. Since OPN shares receptors with vitronectin (VN), we tested for compensation by creating mice lacking both OPN and VN. The double mutants were also viable, suggesting that other RGD-containing ligands replace the embryonic loss of both proteins. We tested the healing of OPN mutants after skin incisions, where spp1 was upregulated as early as 6 h after wounding. Although the tensile properties of the wounds were unchanged, ultrastructural analysis showed a significantly decreased level of debridement, greater disorganization of matrix, and an alteration of collagen fibrillogenesis leading to small diameter collagen fibrils in the OPN mutant mice. These data indicate a role for OPN in tissue remodeling in vivo, and suggest physiological functions during matrix reorganization after injury.

Animals↗
PubMed1998

Animal models for wound repair.

Progress in wound pharmacology is dependent on the availability of suitable animal wound models. All animal models try to reflect human wound healing problems. In acute models it is easier to achieve approximations to the clinical situation than in models for the chronic wound.

Acute Disease↗
PubMed1998

Histologic study of oral mucosa wound healing: a comparison of a 6.0- to 6.8-micrometer pulsed laser and a carbon dioxide laser.

Incisional wound healing in the canine oral mucosa was histologically monitored at 3, 7, and 14 days after incision. Healing was compared from a scalpel, a carbon dioxide (CO2) laser at 10.6 microm, and the Vanderbilt free-electron laser tuned to 6.0, 6.45, and 6.8 microm. A significant delay in wound healing was observed when incisions were made with the CO2 laser, probably attributable to the excess thermal damage caused by the continuous-wave laser beam. When using the short pulsed, free-electron laser, a much smaller delay comparable to the scalpel wound healing was observed. This smaller delay tended to decrease with increasing tissue absorption. The results emphasize the greater importance of laser pulse duration rather than wavelength in relation to the subsequent wound healing.

Absorption↗
PubMed1997

Ascorbate differentially regulates elastin and collagen biosynthesis in vascular smooth muscle cells and skin fibroblasts by pretranslational mechanisms.

Ascorbate contributes to several metabolic processes including efficient hydroxylation of hydroxyproline in elastin, collagen, and proteins with collagenous domains, yet hydroxyproline in elastin has no known function. Prolyl hydroxylation is essential for efficient collagen production; in contrast, ascorbate has been shown to decrease elastin accumulation in vitro and to alter morphology of elastic tissues in vivo. Ascorbate doses that maximally stimulated collagen production (10-200 microM) antagonized elastin biosynthesis in vascular smooth muscle cells and skin fibroblasts, depending on a combination of dose and exposure time. Diminished elastin production paralleled reduced elastin mRNA levels, while collagen I and III mRNAs levels increased. We compared the stability of mRNAs for elastin and collagen I with a constitutive gene after ascorbate supplementation or withdrawal. Ascorbate decreased elastin mRNA stability, while collagen I mRNA was stabilized to a much greater extent. Ascorbate withdrawal decreased collagen I mRNA stability markedly (4.9-fold), while elastin mRNA became more stable. Transcription of elastin was reduced 72% by ascorbate exposure. Differential effects of ascorbic acid on collagen I and elastin mRNA abundance result from the combined, marked stabilization of collagen mRNA, the lesser stability of elastin mRNA, and the significant repression of elastin gene transcription.

Animals↗
PubMed1997

Bupropion and sexual function: a placebo-controlled prospective study on diabetic men with erectile dysfunction.

Many antidepressant agents interfere with sexual function. The purpose of this single-blind, prospective study was to determine sexual side effects, both positive and negative, of the amino-ketone antidepressant bupropion in a group of nondepressed diabetic men with somatic erectile dysfunction. Fourteen men participated in a 10-week protocol consisting sequentially of 2 weeks of baseline testing, 2 weeks of placebo, and 6 weeks of bupropion. Participants also completed daily and weekly questionnaires concerning sexual functioning, and a team of investigators rated various dimensions of sexual function every 2 weeks. In addition, a variety of physiologic measures, relevant either to erectile function or to neural/vascular systems that underlie sexual response, were assessed during baseline and bupropion treatment. Results indicated that neither subjective nor objective measures of erectile and overall sexual functioning worsened during bupropion. In fact, several measures suggested a trend toward improved sexual functioning. Furthermore, diabetic control was unaffected by bupropion administration. Given the lack of adverse effects on sexual function, along with the potential for improved erectile response, bupropion may provide an attractive choice for the treatment of depression in diabetic men or others for whom sexual dysfunction is a concern.

Adult↗
PubMed1996

Particle-mediated gene transfer with transforming growth factor-beta1 cDNAs enhances wound repair in rat skin.

Based on preliminary but variable results with direct DNA transfer into wounds, we evaluated in vivo gene transfer by particle-mediated DNA delivery to rat skin to determine whether overexpression of TGF-beta1 at the site of skin incisions would result in a significant improvement in repair. Optimization of the method with viral promoter-luciferase reporter constructs indicated that expression of luciferase activity persisted up to 5 d and was promoter, pressure, and site dependent (ventral > dorsal). Using cytomegalovirus (CMV)-driven human alpha1-antitrypsin, transgene expression was immunolocalized within keratinocytes of the stratum granulosum at 24 h. We measured tensile strength of skin incisions at 11-21 d in both normal and diabetic rats transfected with TGF-beta1 expression vectors at surgery. Native murine TGF-beta1 under an SV40 promoter produced positive effects, while wound strengthening was more pronounced in diabetic animals using a CMV-driven construct. Transfection of rat skin with constitutively active, mutant porcine TGF-beta1 under the control of the CMV and Moloney murine leukemia virus promoters significantly increased tensile strength up to 80% for 14-21 d after surgery. Transfection 24 h before surgery was more effective. Particle-mediated gene delivery can be used to deliver viral promoter-cytokine expression constructs into rat skin in a safe, efficient, and reproducible fashion. The extent of wound repair, as evidenced by enhanced tensile strength, can be markedly improved in tissues transfected with TGF-beta1 expression constructs.

Animals↗
PubMed1996

Patellar tendon and anterior cruciate ligament have different mitogenic responses to platelet-derived growth factor and transforming growth factor beta.

The healing responses of the anterior cruciate ligament and the patellar tendon differ markedly. The anterior cruciate ligament fails to heal, whereas the patellar tendon heals slowly. The basis of these differences is unknown. Since cellular proliferation is a critical element of healing, we investigated the response to explants of anterior cruciate ligament and patellar tendon from sheep knees to platelet-derived growth factor-AB and transforming growth factor beta 1 as a function of time and dose. Explants cultured for 48, 72, and 96 hours with transforming growth factor beta 1 (0-100 ng/ml) or platelet-derived growth factor-AB (0-200 ng/ml) were radiolabeled for the final 24 hours with [3H]thymidine, and DNA synthesis was quantified as trichloroacetic acid-precipitable radioactivity normalized to dry tissue weight. Statistical analyses (analysis of variance) showed that transforming growth factor beta 1 induced a significant proliferative response in the anterior cruciate ligament at 96 hours with equivalent responses at 10, 50, and 100 ng/ml, whereas the patellar tendon only responded to one condition, 10 ng/ml at 96 hours. Conversely, the patellar tendon had a significant dose-dependent response to platelet-derived growth factor-AB at 72 and 96 hours, whereas the anterior cruciate ligament showed no proliferative response to platelet-derived growth factor-AB. The minimal response of anterior cruciate ligament to platelet-derived growth factor-AB could explain, at least in part, the poor repair capacity of this tissue. The response of the anterior cruciate ligament to transforming growth factor beta suggests that exogenous transforming growth factor beta may promote initial healing. Although growth factors have the potential to modulate soft-tissue repair, tissue responses in tendons and ligaments may vary at different anatomic sites.

Animals↗
PubMed1996

Expression of collagen and matrix metalloproteinases in ruptured human anterior cruciate ligament: an in situ hybridization study.

The biological basis for failure of the human anterior cruciate ligament to heal after rupture is unknown. Since this failure could be influenced by abnormalities in matrix protein production or degradation, or both, several diverse matrix protein markers were utilized to survey the state of these extracellular proteins in intrinsic anterior cruciate ligament fibroblasts. Matrix gene expression was visualized by in situ hybridization 9 to 365 days after rupture using probes for type-I collagen, collagenase, 72kDa-gelatinase, and tissue inhibitor of metalloproteinase. Remnants of anterior cruciate ligament were biopsied arthroscopically from 20 patients at reconstruction, fixed in 4% paraformaldehyde, and processed with cDNA probes for the aforementioned mRNAs. mRNA expression of type-I collagen was detected in all specimens, was equally distributed throughout the remnants, and remained evident even at 1 year after injury. Neither of the matrix-degrading enzymes nor their inhibitor (tissue inhibitor of metalloproteinase) was expressed at substantial levels at any time point. Collagen expression within the anterior cruciate ligament confirmed the viability of the ligament remnants for as long as 1 year after rupture. The lack of significant expression of the two matrix-degrading metalloproteinases by the fibroblasts is not consistent with an autodegradation of the remaining ruptured ligament tissue, and whether the lack of matrix remodelling may account, at least in part, for the poor healing response of the anterior cruciate ligament remains to be determined. This initial investigation by in situ hybridization techniques provides a descriptive profile of matrix gene expression in the damaged human anterior cruciate ligament.

Adolescent↗
PubMed1996

Central propranolol and pindolol, but not atenolol nor metoprolol, inhibit sexual behavior in male rats.

Are the anti-sexual effects of propranolol and pindolol due to actions within the brain? To answer this, these agents were administered directly into the brain ventricular system (ICV). Additionally, atenolol and metoprolol were evaluated to see whether differential delivery to the brain contributed to the observed lack of effect of systemically administered beta 1-adrenoceptor antagonists. ICV administration of pindolol (45 or 90 micrograms) was followed by a suppression of copulation. At 45 micrograms, inhibition was limited to performance aspects of copulation, whereas at 90 micrograms, decrements in motivational and performance aspects of copulation were evident. ICV administration of propranolol also suppressed copulatory behavior. At 45 micrograms, no significant effects were observed, whereas at 90 micrograms decrements in motivational and performance aspects of copulation were evident. In contrast, ICV administration of the beta 1-adrenoceptor antagonists, atenolol and metoprolol, was not associated with any major modifications in copulatory behavior. We suggest that the inhibitory effects of propranolol and pindolol may involve interactions with 5-HT1A receptors in the CNS. Alternatively, it may be that the adverse effects of pindolol and propranolol are due to the simultaneous blockade of both beta 1- and beta 2-adrenoceptors.

Adrenergic beta-Antagonists↗