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Biomedical subjects

P Harwood

Publications and source records attributed to P Harwood.

14 recordsLinked to original sources

Accelerated bone healing and excessive callus formation in patients with femoral fracture and head injury.

The effect of head injury on systemic physiology, including bone healing is still a topic of vivid discussion. Whether the observed changes genuinely represent accelerated fracture healing or are a form of local heterotopic ossification remains unclear. We aimed to investigate whether in patients with long bone fractures the presence of head injury is associated with accelerated bone healing and excessive callus formation. In total 67 patients were studied 17 with head injury and 50 without head injury (25 treated with reamed and the other 25 with the unreamed nailing technique). Both groups were comparable in terms of age, sex, ISS. All underwent stabilisation of their femoral fracture with intramedullary nailing. The quantification of fracture healing response was estimated by taking the radiological ratio of the largest diameter of callus formed into two planes and the adjacent normal diameter of femoral canal. The minimum follow up of the patients was 12 months. In patients with head injury, the mean time to fracture union was significantly shorter than either the reamed or unreamed group (10.5 weeks compared with 20.5 and 26.9 weeks, p<0.001). The difference between the mean callus to diaphyseal ratio was statistically significant for both the AP and Lateral projections (AP: mean difference 0.462, 95% CI 0.312 to 0.602, p<0.0001, LAT: mean difference 0.289, 95% CI 0.142 to 0.436, p<0.001) with the head injured patients having more florid callus compared to the control group.

Adolescent↗

Open pelvic fractures: epidemiology, current concepts of management and outcome.

Open pelvic fractures constitute one of the most devastating injuries in musculo-skeletal trauma and must be treated aggressively, incorporating a multidisciplinary approach. Early treatment, focusing on prevention of haemorrhage and sepsis, is essential. The management of associated soft tissue injuries must also be aggressive, including early administration of broad-spectrum antibiotics and repeated, meticulous wound debridement and irrigation. Selective faecal diversion, based on wound location, is compulsory and safe, minimising the risk of sepsis and reducing mortality rates.

Algorithms↗

Radial nerve palsy associated with fractures of the shaft of the humerus: a systematic review.

The management of radial nerve palsy associated with fractures of the shaft of the humerus has been disputed for several decades. This study has systematically reviewed the published evidence and developed an algorithm to guide management. We searched web-based databases for studies published in the past 40 years and identified further pages through manual searches of the bibliography in papers identified electronically. Of 391 papers identified initially, encompassing a total of 1045 patients with radial nerve palsy, 35 papers met all our criteria for eligibility. Meticulous extraction of the data was carried out according to a preset protocol. The overall prevalence of radial nerve palsy after fracture of the shaft of the humerus in 21 papers was 11.8% (532 palsies in 4517 fractures). Fractures of the middle and middle-distal parts of the shaft had a significantly higher association with radial nerve palsy than those in other parts. Transverse and spiral fractures were more likely to be associated with radial nerve palsy than oblique and comminuted patterns of fracture (p < 0.001). The overall rate of recovery was 88.1% (921 of 1045), with spontaneous recovery reaching 70.7% (411 of 581) in patients treated conservatively. There was no significant difference in the final results when comparing groups which were initially managed expectantly with those explored early, suggesting that the initial expectant treatment did not affect the extent of nerve recovery adversely and would avoid many unnecessary operations. A treatment algorithm for the management of radial nerve palsy associated with fracture of the shaft of the humerus is recommended by the authors.

Algorithms↗

Are alterations of lymphocyte subpopulations in polymicrobial sepsis and DHEA treatment mediated by the tumour necrosis factor (TNF)-alpha receptor (TNF-RI)? A study in TNF-RI (TNF-RI(-/-)) knock-out rodents.

Sepsis is associated with depression of T cell-dependent immune reactivity with proinflammatory cytokines, such as tumour necrosis factor (TNF)-alpha, playing an important role. Recent investigations describe an association between these immunological alterations and disturbances of the endocrine system, related most frequently to sex steroid hormones. Dehydroepiandrosterone (DHEA), one of the most abundant adrenal sex steroid precursors, seems to have a protective immunological effect towards septic insults. In this study, both the role of TNF-receptor I (RI) and possible interactions in the protective role of DHEA were investigated in a murine model of polymicrobial sepsis. Polymicrobial sepsis was induced by caecal ligation and puncture (CLP) in a murine model. The effects of DHEA on survival, clinical parameters and cellular immunity (T lymphocytes and natural killer (NK) cells) were investigated. CLP was performed in genetically modified TNF-RI knock-out (TNF-RI(-/-)) and genetically unmodified (wild-type, WT) mice. DHEA application was associated with a decrease in the mortality rate in WT animals. A mortality rate of 91.7% was observed in TNF-RI(-/-) mice after CLP. This mortality rate was reduced to 37.5% by the application of DHEA. In sham-operated TNF-RI(-/-) animals, a significantly higher proportion of NK cells within the lymphocyte population was measured compared with the corresponding WT group. After CLP, a significant increase in the percentage cell count of NK cells was recorded in WT mice. Overall, following DHEA application in WT mice, an alteration in the cellular immune response was characterized by a reduction in the percentage counts of CD4(+), CD8(+) and NK cells. In the group of TNF-RI(-/-) mice treated with DHEA, no increase in the percentage cell count of NK cells was observed after CLP. No data for cell analysis were available from the CLP-TNF-RI(-/-) mice treated with saline, due to the high mortality rate in these animals. DHEA reduces the complications of sepsis in a TNF-RI-independent manner. Our study suggests that NK cells are involved in the protective mechanism of DHEA in WT mice. It would therefore seem that DHEA represents a feasible alternative therapy for the dysregulated immune system in sepsis.

Animals↗

Factors affecting rates of infection and nonunion in intramedullary nailing.

We report a retrospective study over five years to determine the incidence of infection and nonunion after intramedullary nailing in fractures of 214 long bones; 122 femoral, 75 tibial and 17 humeral. The indications for nailing were trauma (n = 161), pathological fracture (n = 30) and nonunion (n = 23). There were 30 open fractures. The overall rates of deep infection and nonunion were 3.8% and 14.2%, respectively. Using multiple logistic regression analysis, we determined the relationships between deep infection and nonunion and the pre- and peri-operative factors of age, ASA score, indication for nailing, the use of reaming, the use of antibiotics, whether the fracture was open and the operating time. Open fractures were found to be significantly associated with deep infection. The length of the operation may also affect the outcome. Opening of the fracture at the time of surgery and the ASA score were found to be significantly associated with the development of nonunion after intramedullary nailing. We have compared our findings with previously published data from large teaching hospital units.

Adolescent↗

HIV and dentistry: public perceptions from two towns in Kent.

A survey of general public attitudes towards dentists who are HIV-positive or who have AIDS was carried out on two occasions three months apart, in the Kentish towns of Dartford and Tunbridge Wells. The BBC television programme, Panorama discussing this issue was screened between the two survey times. The results show that in general the public in these areas perceive the risk of acquiring HIV infection through dental treatment to be very low: despite this they do not have a great knowledge of cross-infection control procedures in the dental setting.

Acquired Immunodeficiency Syndrome↗

Use of breath hydrogen and methane as markers of colonic fermentation in epidemiological studies: variability in excretion.

Breath hydrogen and methane are specific end products of colonic fermentation, a process which may play a protective role against colon cancer. To assess the possibility of using these markers in epidemiological studies, we characterized the intra- and intersubject variability of breath hydrogen and methane excretion over 15 consecutive days among 32 men and women of various ethnic backgrounds (16 Asians, 8 Caucasians, 8 Hawaiians). Participants were asked to collect four end-expiratory samples each day, which we had shown previously would optimally characterize daily hydrogen excretion. There was substantial within-subject variation in breath hydrogen over the study, although breath methane levels were more constant over time. We found that about 4 days of measurement of breath hydrogen and 1 day of measurement for breath methane are required to correctly characterize individuals according to their long-term excretion of these gases. This was true for Asians and non-Asians. Although breath methane appears to be more practical to measure, it is a less sensitive marker of colonic fermentation than breath hydrogen. Whereas all subjects excreted hydrogen, only 28% of the subjects excreted methane, and methane excretor status of a few participants varied during the study. Because the breath test is noninvasive and reliable, we tested the multiple day collection protocol among colon cancer patients and controls and found it to be well accepted. We conclude that it is practical to measure breath hydrogen and methane in large epidemiological studies conducted at the individual level. The potential use for these markers is discussed.

Aged↗

Breath hydrogen and methane in populations at different risk for colon cancer.

Results from laboratory and clinical studies have suggested that fermentation in the large bowel may play a protective role against colon cancer. Hydrogen and methane are end-products of colonic fermentation that are absorbed into the bloodstream and excreted via expired air in the breath. Thus, breath levels of hydrogen and methane have been used as markers for this process. Breath levels of these gases were compared among 10 ethnic and sex groups that exhibit marked differences for colon cancer risk in Hawaii. Four end-expiratory breath samples were used to characterize daily excretion of hydrogen and methane in a population-based sample of 244 men and women. There was no significant difference in breath hydrogen or methane by sex or age. Hawaiians produced significantly more hydrogen than Filipinos, and Hawaiians and Caucasians more methane than the 3 Asian groups. These differences did not correlate with risk of colon cancer among these ethnic populations.

Adult↗

Oligonucleotide fingerprinting of isolates of Candida species other than C. albicans and of atypical Candida species from human immunodeficiency virus-positive and AIDS patients.

Oligonucleotide fingerprinting of genomic DNA from oral isolates of four different Candida species other than C. albicans and atypical chlamydospore-positive isolates from human immunodeficiency virus (HIV)-positive individuals and AIDS patients was investigated as a means for differentiating between isolates within individual species. Oligonucleotides composed of simple repetitive sequence motifs, including (GACA)4, (GATA)4, (GGAT)4, (GTG)5, and (GT)8, all yielded fingerprints suitable for strain segregation of 8 C. tropicalis isolates, 12 Torulopsis (Candida) glabrata isolates, 8 atypical Candida isolates, and, except for (GATA)4, 2 C. krusei probe in turn and so generate several distinct DNA fingerprints of the same DNA sample. However, none of the probes yielded fingerprints suitable for strain segregation with three C. parapsilosis isolates. The (GATA)4 probe was also used to detect restriction fragment length polymorphisms among a genetically closely related group of atypical Candida isolates on primary isolation from an additional HIV-infected patient. These chlamydospore-positive atypical Candida isolates were sucrose positive, were of C. albicans serotype A, hybridized weakly with the C. albicans-specific mid-repeat sequence probe 27A, and yielded fingerprint profiles by random polymorphic DNA analysis that were distinct from those derived from C. albicans isolates. The C. stellatoidea ex-type strain NCPF 3108 was indistinguishable from the atypical Candida isolates in all these tests and also yielded an identical carbohydrate and nitrogen source assimilation profile by using the ID 32C yeast identification system.

AIDS-Related Opportunistic Infections↗

Use of breath hydrogen and methane as markers of colonic fermentation in epidemiologic studies: circadian patterns of excretion.

Fermentation in the large bowel has been postulated to play a protective role against colon cancer. Hydrogen and methane are end products of this fermentation process and are absorbed into the bloodstream and excreted via expired air in the breath. Breath levels of hydrogen and, to a lesser extent, methane correlate strongly with colonic fermentation and may serve as useful biomarkers for this process. In a preliminary study to assess the usefulness of these two markers in epidemiologic studies, we followed the hourly excretion of the two gases in expired alveolar air for 48 hr in 20 healthy subjects, using a Quintron gas chromatograph equipped with a solid-state detector specific for reducing gases. All subjects excreted hydrogen, but 71% did not excrete methane. Possible atmospheric contamination of the samples was corrected for on the basis of breath carbon dioxide levels. A clear circadian pattern of excretion was observed for breath hydrogen, with a decrease during the early morning followed by a progressive increase during the rest of the day. Methane excretion was constant throughout the day. This study shows that four samples collected at convenient times (0600, 1300, 1800, and 2200 hr) are optimal to characterize individuals by their breath excretions of hydrogen and methane during a 24-hr period.

Biomarkers↗

Erotomania in relation to childbirth.

A case of erotomania in relation to childbirth is reported. There was a good response to treatment and no evidence of relapse at 18-month follow-up.

Adult↗

Elimination of clonogenic malignant human T cells using monoclonal antibodies in combination with 2'-deoxycoformycin.

2'Deoxycoformycin (dCF) specifically inhibits adenosine deaminase (ADA) and causes selective cytotoxicity of normal and malignant T cells. In clinical trials, dCF caused rapid lysis of malignant T lymphoblasts. Although dCF has been associated with dose-limiting nonhematopoietic toxicities, myelosuppression has not been observed. Since dCF is relatively nontoxic to hematopoietic stem cells, we tested dCF for utility in the ex vivo purging of malignant T lymphoblasts from remission leukemic bone marrow for autologous bone marrow transplantation. We found that T lymphoblast cell lines were sensitive to dCF (plus deoxyadenosine [dAdo]) under conditions that did not ablate human hematopoietic colony-forming cells. Moreover, combined pharmacologic (dCF plus dAdo) and immunologic (anti-T cell monoclonal antibodies [McAb] plus complement) purging resulted in additive reduction in clonogenic T lymphoblasts. These results provide the basis for a clinical trial of bone marrow transplantation using combined pharmacologic/immunologic purging of T lymphoblasts from patients' harvested autologous marrow.

Antibodies, Monoclonal↗