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Biomedical subjects

J Davidson

Publications and source records attributed to J Davidson.

At least 55 records · Page 3Linked to original sources

Research remembered.

Another good question to ask yourself and indeed others, is on Jeannette's lips. Of course nursing is not exactly well-endowed with research findings--perioperative practice even less so--but it's the 'change in practice' that must be the key phase for evaluation. So, read on and then reach for the proposal form to the Education and Research Fellowship Fund (ERFF) at NATN, or similar funding body, to join the search for evidence of effective practice. Become one of the 'remembered' in due course.

Diffusion of Innovation↗

Efficacy of surgical salvage for advanced neck metastases after radiotherapy failure.

OBJECTIVE: To analyze the efficacy of surgical salvage in patients with metastatic squamous cell carcinoma to the neck of stage N2 or N3 initially treated with radiotherapy. DESIGN: Retrospective review. SETTING: Tertiary care institution. METHODS: Four hundred and twenty-five patients received neck dissection at Sunnybrook Health Sciences Centre between 1990 and 1996. Sixty-one patients had neck dissection for salvage after radical radiotherapy for advanced neck disease of stage N2 or N3. These patients were selected from the Sunnybrook Head and Neck Database and reviewed. OUTCOME MEASURES: Survival and recurrence. RESULTS: Sixty-one patients underwent neck dissection for salvage after radiotherapy. Five-year overall survival was 30%. The majority (72%) failed locoregionally after surgical salvage. CONCLUSIONS: Surgical salvage after radiotherapy for advanced neck disease has a 30% 5-year survival rate. Surgical salvage after radiotherapy for advanced neck disease is effective in a minority of patients.

Combined Modality Therapy↗

Influence of psychological response on survival in breast cancer: a population-based cohort study.

BACKGROUND: The psychological response to breast cancer, such as a fighting spirit or an attitude of helplessness and hopelessness toward the disease, has been suggested as a prognostic factor with an influence on survival. We have investigated the effect of psychological response on disease outcome in a large cohort of women with early-stage breast cancer. METHODS: 578 women with early-stage breast cancer were enrolled in a prospective survival study. Psychological response was measured by the mental adjustment to cancer (MAC) scale, the Courtauld emotional control (CEC) scale, and the hospital anxiety and depression (HAD) scale 4-12 weeks and 12 months after diagnosis. The women were followed up for at least 5 years. Cox's proportional-hazards regression was used to obtain the hazard ratios for the measures of psychological response, with adjustment for known clinical factors associated with survival. FINDINGS: At 5 years, 395 women were alive and without relapse, 50 were alive with relapse, and 133 had died. There was a significantly increased risk of death from all causes by 5 years in women with a high score on the HAD scale category of depression (hazard ratio 3.59 [95% CI 1.39-9.24]). There was a significantly increased risk of relapse or death at 5 years in women with high scores on the helplessness and hopelessness category of the MAC scale compared with those with a low score in this category (1.55 [1.07-2.25]). There were no significant results found for the category of "fighting spirit". INTERPRETATION: For 5-year event-free survival a high helplessness/hopelessness score has a moderate but detrimental effect. A high score for depression is linked to a significantly reduced chance of survival; however, this result is based on a small number of patients and should be interpreted with caution.

Aged↗

Four polymorphic variations in the PEDF gene identified during the mutation screening of patients with Leber congenital amaurosis.

PURPOSE: Leber congenital amaurosis (LCA) has been mapped to chromosome 17p13.1. From the candidate genes mapped to this region, thus far, only Retinal Guanylate Cyclase (RetGC), has been found to have pathogenic LCA mutations, in families from North African origin. However, early reports, demonstrated eight LCA families linked to 17p13.1, but only four of them showed mutations in RetGC. Mapped in proximity to this locus is the candidate gene Pigment Epithelium Derived actor (PEDF), a factor implicated in photoreceptor differentiation and neuronal survival. Our purpose in this study was to identify mutations and polymorphisms in the PEDF gene in LCA patients of diverse ethnic origin. METHODS: Automated genotyping with four 17p13.1 markers flanking the PEDF gene was performed to assess homozygosity and PCR-SSCP combined with direct sequencing was used to detect mutations in the PEDF gene in 17 LCA patients. RESULTS: Homozygosity of markers D17S796 and D17S804 was found and four new intragenic basepair alterations were discovered: a Met72Thr polymorphism in exon 3 (T331C), a Thr130Thr polymorphism in exon 4 (T506C), a G to A transition in intron 5 (nine base pairs upstream from splice acceptor site), and a Tyr321Tyr polymorphism in exon 7 (C1079T) were detected. CONCLUSIONS: We report the discovery of four new polymorphic alterations in the PEDF gene in LCA patients and exclude by RFLP analysis the PEDF gene as a common cause of Leber congenital amaurosis. These single nucleotide polymorphisms will aid in future linkage analysis of complex multifactorial diseases involving retinal and RPE dysfunctions.

Amino Acid Substitution↗

Analysis of prothrombotic and vascular risk factors in patients with nonarteritic anterior ischemic optic neuropathy.

OBJECTIVE: To determine whether genetic or acquired thrombophilias and other risk factors are associated with nonarteritic anterior ischemic optic neuropathy (NAION). DESIGN: Retrospective case-control study. PARTICIPANTS: Sixty-one patients with NAION diagnosed between 1984 and 1997. Ninety consecutive patients who visited the Eye Institute made up the control group. INTERVENTION: Protein C, protein S, antithrombin III, lupus anticoagulant, and three recently described prothrombotic polymorphisms (i.e., factor V G1691A, factor II G20210A, and methylenetetrahydrofolate reductase [MTHFR] C677T) were analyzed. In addition, risk factors for arteriosclerotic vascular disease were assessed. MAIN OUTCOME MEASURES: Parameters of thrombophilia. RESULTS: None of the thrombophilic markers (genetic and acquired) constituted a significant risk factor for NAION. Ischemic heart disease, hypercholesterolemia, and diabetes mellitus were discerned as risk factors for NAION with odds ratios of 2.9 (95% confidence interval [CI], 1.3-6.4), 2.6 (95% CI, 1.2-5.5), and 2.3 (95% CI, 1.1-4.8), respectively. Multiple logistic regression analysis indicated that ischemic heart disease and hypercholesterolemia exerted an additive risk for NAION with a combined odds ratio of 4.5 (95% CI, 1.4-14.5). However, none of these risk factors statistically predicted second eye involvement. CONCLUSION: NAION was not found to be associated with thrombophilic risk factors, yet it was related to ischemic heart disease, hypercholesterolemia, and diabetes mellitus.

Adult↗

The impact of genetic counselling on risk perception and mental health in women with a family history of breast cancer.

The present study investigated: (1) perception of genetic risk and, (2) the psychological effects of genetic counselling in women with a family history of breast cancer. Using a prospective design, with assessment pre- and post-genetic counselling at clinics and by postal follow-up at 1, 6 and 12 months, attenders at four South London genetic clinics were assessed. Participants included 282 women with a family history of breast cancer. Outcome was measured in terms of mental health, cancer-specific distress and risk perception. High levels of cancer-specific distress were found pre-genetic counselling, with 28% of participants reporting that they worried about breast cancer 'frequently or constantly' and 18% that worry about breast cancer was 'a severe or definite problem'. Following genetic counselling, levels of cancer-specific distress were unchanged. General mental health remained unchanged over time (33% psychiatric cases detected pre-genetic counselling, 27% at 12 months after genetic counselling). Prior to their genetics consultation, participants showed poor knowledge of their lifetime risk of breast cancer since there was no association between their perceived lifetime risk (when they were asked to express this as a 1 in x odds ratio) and their actual risk, when the latter was calculated by the geneticist at the clinic using the CASH model. In contrast, women were more accurate about their risk of breast cancer pre-genetic counselling when this was assessed in broad categorical terms (i.e. very much lower/very much higher than the average woman) with a significant association between this rating and the subsequently calculated CASH risk figure (P = 0.001). Genetic counselling produced a modest shift in the accuracy of perceived lifetime risk, expressed as an odds ratio, which was maintained at 12 months' follow-up. A significant minority failed to benefit from genetic counselling; 77 women continued to over-estimate their risk and maintain high levels of cancer-related worry. Most clinic attenders were inaccurate in their estimates of the population risk of breast cancer with only 24% able to give the correct figure prior to genetic counselling and 36% over-estimating this risk. There was some improvement following genetic counselling with 62% able to give the correct figure, but this information was poorly retained and this figure had dropped to 34% by the 1-year follow-up. The study showed that women attending for genetic counselling are worried about breast cancer, with 34% indicating that they had initiated the referral to the genetic clinic themselves. This anxiety is not alleviated by genetic counselling, although women reported that it was less of a problem at follow-up. Women who continue to over-estimate their risk and worry about breast cancer are likely to go on seeking unnecessary screening if they are not reassured.

Adult↗

Successful human umbilical cord blood stem cell transplantation without conditioning in severe combined immune deficiency.

A 2-month-old girl with severe combined immunodeficiency (SCID), presented with mild staphylococcal skin infection, lymphopenia, low T cell number, absence of B cells, high number of NK cells, and a negligible response to mitogens. Since her older brother died as a result of SCID 2 years earlier, cord blood was harvested from a sister born 2 1/2 years earlier, who was normal and fully matched both by serology and molecular typing. In view of her clinical condition and in spite of a high number of NK cells with normal activity, HUCBT without preparative conditioning was performed. No G-CSF was administered. Engraftment with mixed chimerism was evident 3 weeks post transplantation. There were no peritransplantation complications. Eighteen months post transplantation, the girl is in excellent condition, blood counts are normal, T cell engraftment is complete, B cell engraftment is proceeding gradually, and the mitogen stimulation tests are normal. Due to the unique nature of HUCB hematopoietic cells, engraftment without conditioning may be possible in patients with SCID with fully matched donors. This is the first HUCBT performed without conditioning.

Female↗

Nefazodone in post-traumatic stress disorder: results from six open-label trials.

Nefazodone, an antidepressant which blocks serotonin (5-HT)2 receptors and 5-HT reuptake, was evaluated in the treatment of post-traumatic stress disorder (PTSD) in six open-label studies involving both civilians and combat veterans. Our objective was to report this available pooled data to characterize the response of this drug in PTSD. Specifically, we looked at response rates using three different criteria, the effect of nefazodone on each PTSD cluster and individual symptoms and, lastly, variables that might predict response. One hundred and five outpatients with chronic PTSD were treated with nefazodone titrated up to 600 mg/day, 92 of whom were entered in an intent to treat analysis. We used the percentage drop in score between baseline and endpoint on main scale as a common measure to evaluate outcome. The response criterion of a drop in score of at least 30%, 40% and 50% revealed response rates of 46, 36 and 26%, respectively. Nefazodone showed a broad spectrum of action on PTSD symptoms. This profile might make nefazodone a useful drug to treat PTSD. Predictors of response include age, sex and trauma type. Double-blind, placebo-controlled clinical trials in PTSD are in progress to assess the utility of nefazodone as a treatment in this disorder.

Adult↗

Extracranial drainage of cerebrospinal fluid: a study of beta-transferrins in nasal and lymphatic tissues.

OBJECTIVE: To determine whether an alternative route of cerebrospinal fluid (CSF) drainage exists through the nasal mucosa and the cervical lymphatic system. STUDY DESIGN: A prospective study was carried out on 18 patients at a university teaching hospital. METHODS: Ten patients undergoing routine endoscopic sinus surgeries and eight patients undergoing neck dissections were recruited for this study. Tissues were sampled from the middle turbinate, nasopharynx, and upper septum in the first group; jugulodigastric lymph nodes and nasopharyngeal tissues were obtained from the second group. Specimens were subjected to immunofixation electrophoresis in an attempt to identify the presence of beta-1 and beta-2 transferrins. Serum samples were obtained from each subject to serve as controls. RESULTS: All tissue specimens contained beta-1 transferrin; none showed evidence of beta-2 transferrin. CONCLUSION: Using this technique, an alternate route of CSF drainage through the nose and the cervical lymphatic system could not be confirmed. Nevertheless, a new technique of performing immunofixation in solid tissues for the purpose of beta-transferrin identification is described.

Cerebrospinal Fluid Rhinorrhea↗

Endoscopic orbital decompression with preservation of an inferomedial bony strut: minimization of postoperative diplopia.

With the increasing sophistication and safety of endoscopic orbital decompression, the technique is seen by many as an attractive and less morbid alternative to traditional open techniques. This rationale also makes the procedure more acceptable for individuals considering decompression for cosmetic reasons. As a result, complications such as postoperative diplopia assume greater significance. Preservation of an inferomedial bony strut has been postulated to reduce the incidence of postoperative diplopia in transconjunctival, but not endoscopic, orbital decompression for dysthyroid ophthalmopathy. We present a consecutive series of 11 subjects (21 eyes) who underwent transnasal endoscopic medial and inferior decompression of the orbits bilaterally. All patient charts were reviewed in a retrospective fashion and ophthalmologic, surgical, and cosmetic data were recorded, with callback of patients with incomplete data sets. All cases were performed under general anaesthesia. Preservation of the strut was possible in 15 of 21 eyes. Visual acuity was preserved or improved in all 21 eyes. Average ocular recession based on Hertel measurements was 3.6 mm and there were no surgical complications. New-onset or worsening diplopia was noted postoperatively in 2 of 11 subjects. However, in patients where both struts were preserved, there was zero incidence of postoperative diplopia (0/6). These results indicate that preservation of an inferomedial bony strut is not only technically feasible but also does not compromise the adequacy of decompression. The results also suggest that preservation of the inferomedial bony strut during endoscopic orbital decompression can reduce the incidence of postoperative diplopia.

Chi-Square Distribution↗

Development of the Royal Marsden Hospital paediatric oncology quality of life questionnaire.

Our objective was to develop a health-related quality of life measure for use in pediatric oncology. The development process followed the EORTC Quality of Life Study Group (QLSG) guidelines but utilized a parental proxy rating methodology developed within the framework of the EORTC QLSG. Data are reported on the preliminary stages of development, which include interviews in the target population, specialist review of questionnaire content and initial results on the psychometric structure of the measure. The questionnaire has been translated from English to Swedish and Dutch and is available for international field testing. Suggestions for further development of the new measure are described, including the need for parallel forms for use with children and adolescents as well as the parental proxy rating form described here.

Child↗

Evaluation of adjuvant psychological therapy in patients with testicular cancer: randomised controlled trial.

OBJECTIVE: To determine the efficacy of adjuvant psychological therapy in patients with testicular cancer and to compare the characteristics and psychosocial outcomes of men who agreed to participate with those who declined to participate in a randomised trial of psychological intervention. DESIGN: Newly diagnosed patients were asked to participate in a randomised trial of psychological support compared with standard medical care. Participants and non-participants completed self assessment questionnaires at baseline and at 2, 4 and 12 months. SETTING: Testicular Tumour Unit of the Royal Marsden Hospital. SUBJECTS: 73 of 184 (40%) eligible patients agreed to enter the randomised trial (participants) and 81 (44%) declined to participate but agreed to complete further assessments (non-participants). 30 patients wanted no further contact with the researchers. OUTCOME MEASURES: Hospital anxiety and depression scale, psychosocial adjustment to illness scale, Rotterdam symptom checklist, mental adjustment to cancer scale. Only scores on the hospital anxiety and depression scale are reported for evaluating treatment efficacy. RESULTS: 111 of 184 (60%) eligible men declined to participate in the trial. Patients with stage I disease were most likely to refuse to participate. A patient was less likely to participate if he had low volume disease and was receiving no further treatment. Likelihood of participation was associated with stage of disease and with type of primary treatment (P < 0.001 for heterogeneity). Patients with early stage disease (P < 0.001) and fewer physical symptoms (P < 0.001) were less likely to participate. Psychosocial factors associated with participation included anxious preoccupation regarding disease (P = 0.01). There were no differences in outcome between participants and non-participants during follow up. Patients seemed to gain little benefit from adjuvant psychological therapy. At 2 months change from baseline favoured the treated group in the anxiety subscale (mean difference between groups -1.41 (95% confidence interval -2.86 to 0.03)). This was not sustained when adjusted for factors related to the disease. By 12 months change from baseline seemed to favour the control group (mean difference between groups 1.66 (-0.18 to 3.50)). CONCLUSIONS: Patients with testicular cancer seem to have considerable coping abilities. Those who declined to participate in the trial differed from those who participated. Those who agreed to participate may comprise the clinical group who perceive a need for psychological support. No evidence was found to indicate a need for routinely offering adjuvant psychological therapy.

Adolescent↗

The effectiveness of the routine clinic visit in the follow-up of breast cancer patients: analysis of a defined patient cohort.

The study aimed to identify the proportion of patients with relapse or a contralateral breast tumour who are diagnosed as a consequence of regular follow-up in a specialist breast clinic after breast conserving surgery and radiotherapy for early breast cancer. A retrospective review was undertaken of 490 consecutive patients entered into a randomized clinical trial of radiotherapy fractionation at a single institution. As part of the trial, patients were reviewed in a multidisciplinary breast clinic 3-monthly for the first 3 years, 6-monthly between 3 and 5 years and annually thereafter, with biennial mammography. For this study, information was retrieved from hospital records to ascertain: (a) whether patients were symptomatic at the time of relapse or contralateral breast tumour; and (b) whether they presented at a scheduled appointment or brought their appointment dates forward. The subsequent management of patients with relapse was reviewed to determine whether or not this may have been influenced favourably by a policy of regular follow-up. Twenty-one (44%) of the 48 patients with locoregional relapse were asymptomatic. Of these, 17 were detected by clinical examination (that is, directly as a result of a routine clinic attendance), while four were detected by routine mammography. Ten of the 17 patients diagnosed by clinical examination had successful surgery for locoregional relapse and all have remained disease free. Five of 17 developed distant metastases within 6 months and two others had skin nodules on the breast excised. Only three of the 67 patients with distant relapses were asymptomatic. Two of the 11 patients with contralateral breast tumours were asymptomatic and were diagnosed on routine mammography. The benefits and cost-effectiveness of less rigid approaches to follow-up of breast cancer patients needs to be evaluated in large prospective randomized trials.

Adult↗

Prostaglandin and fatty acid modulation of Escherichia coli O157 phagocytosis by human monocytic cells.

Phagocytosis by human monocytes is an important primary survival mechanism particularly during bacterial infection. However, the processes that control the events and mediators involved in the activation of monocytes and their impact on the phagocytosis of bacteria are poorly understood. The effect of bacterial endotoxin, interleukin-1 beta (IL-1 beta), fatty acids and prostaglandin E2 (PGE2) on the phagocytosis of fluoroscein isothiocyanate (FITC)-labelled Escherichia coli (O157) by human blood monocytes and U937 cells was studied by flow cytometry. Endotoxin increased the phagocytosis of labelled bacteria by both monocytes and U937 cells. IL-1 beta and the polyunsaturated fatty acids; dihomo-gamma-linolenic and arachidonic acids also increased the phagocytic activity of both monocytes and U937 cells. In contrast, PGE2 suppressed phagocytosis in a concentration-dependent manner. The cyclo-oxygenase inhibitor, ketoprofen, further enhanced the increased phagocytic activity in the presence of endotoxin and interleukin-1 (IL-1) indicating suppression by endogenous prostaglandins. This was confirmed by the data which showed that lipopolysaccharide (LPS) and IL-1 increased PGE2 release and ketoprofen inhibited release. Endotoxin and fatty acids increased IL-1 beta release also, whereas PGE2 inhibited release. The data suggest that phagocytic activity may be linked to changes in IL-1 levels. The data presented in this study also suggest that monocyte phagocytosis in the course of bacterial infection would be altered during pathophysiological events which result in elevation of extracellular fatty acids.

Cell Culture Techniques↗

Microsurgical replantation of the lip: a multi-institutional experience.

Traumatic amputation of the lip is a rare yet devastating event affecting both form and function. Considering the available methods for reconstruction, replantation may offer a reasonable solution. We sought to characterize the variables associated with lip replantation and to assess the outcome in a retrospective review of 13 lip replantations performed in 12 institutions utilizing a form database and clinical and photographic analysis. Lip replantation was successful in all 13 patients; partial flap loss occurred in one patient owing to iatrogenic injury. Follow-up averaged 3.1 years. Average patient age at the time of injury was 21.1 years. There were six male and seven female patients. Injuries in two patients were the result of a human bite, the remaining injuries resulted from dog bites. One patient had significant associated injuries. Average length of hospital stay was 11.9 days. Ten patients suffered amputations of the upper lip, and three suffered amputations of the lower lip. Average defect size was 10.6 cm2. Operative time averaged 5.7 hours (range 2.5 to 12 hours). Warm ischemia time averaged 2.9 hours, and cold ischemia time averaged 2.7 hours. Donor and recipient veins were often scarce; all patients had at least one arterial anastomosis, whereas no vein was available in 7 of 13 patients; vein grafts were required in one patient. Leech therapy was employed in 11 of 13 patients. Anticoagulant therapy was administered in the majority of patients. Systemic heparin was utilized in 10 of 13 patients, low molecular weight dextran was used in 7 of 13 patients, and aspirin was given to 7 of 13 patients. One bleeding complication was incurred. An average of 6.2 units of packed red blood cells was administered to 12 of 13 patients (adjusted to 250 cc/unit). Antispasmodic therapy was employed in six of eight patients intraoperatively and in two of eight patients postoperatively. Intraoperative complications included difficulty identifying veins in 7 of 13 patients, arterial spasm in 1 of 13 patients, and vessel diameter < 0.5 mm in 4 patients. Postoperatively, one patient suffered vein thrombosis requiring anastomotic revision. Broad spectrum antibiotics were administered to all patients, and there were no infections. Nearly one-third (4 of 13) patients suffered prolonged edema lasting > 4 months. Color match of the replanted lip segment was rated excellent in all cases. Hypertrophic scarring occurred in 6 of 13 patients. A total of 12 revision procedures was performed in six patients. Interestingly, leech therapy resulted in permanent visible scarring as a result of the leech bite in 6 of 11 patients treated. Ten patients demonstrated active orbicularis muscle contraction in the replanted lip segment. Stomal continence was present in all lips. Sensibility return in the replanted lip segment was quite good with 12 of 13 patients demonstrating at least protective moving two-point sensibility (> or = 10 mm). Partial replant necrosis in one patient resulted in significant scar and contraction that compromised the aesthetic appearance. Overall, however, all patients were uniformly pleased with their final results. This clinical study is one of the largest of its kind on lip replantation. Although this represents a multi-institutional experience, the data are remarkably consistent. Re-establishment of venous outflow seems to be the most problematic technical challenge. By incorporating the adjuncts of anticoagulation, leech therapy, and antispasmodics, a successful outcome can be expected despite the paucity of vessels and small vessel size. The risks of blood transfusion, lengthy operative time, and hospital stay must be weighed against the functional benefits.

Adolescent↗

Blindness as a complication of Le Fort osteotomies: role of atypical fracture patterns and distortion of the optic canal.

Blindness in patients suffering maxillofacial trauma is usually caused by optic nerve or optic canal injuries. It is, however, an uncommon complication of facial trauma, with a reported incidence of only 3 to 5 percent. This incidence drops dramatically when fractures are performed in the controlled situation of orthognathic surgery. Given the rarity of ophthalmic complications after traumatic Le Fort I injuries, it is not surprising that few cases have been reported after orthognathic surgery. In this article, three cases of visual loss or skull base injury after elective Le Fort I osteotomy are described. All of these cases were presumably straightforward surgically and were performed by experienced surgeons. The literature is reviewed and the pathomechanics of each injury are experimentally explored in a cadaver model. To determine the presence of increased pressure on the optic nerve, optic canal deformation, or fractures extending to the skull base, two separate experiments were devised. In the first experiment, a pressure transduction system was used to document any significant forces that may be directly transmitted to the contents of the optic canal during pterygomaxillary separation. Then tested was the hypothesis that a stepped or tapered osteotomy will allow for a more predictable pterygomaxillary fracture. One of five cadaver specimens in group 1 demonstrated a transient increase in the right optic canal pressure during down-fracture of the maxilla. This change was less than 10 mmHg, and its duration was less than 5 seconds. The canal pressure returned to baseline with the completion of the fracture. In group 2, there was no documented pressure change with either osteotomy technique. Of note, in group 2, all specimens undergoing standard Le Fort osteotomy demonstrated uncontrolled propagation of the fracture lines superiorly in the pterygoid bones. The uncontrolled and unpredictable nature of pterygomaxillary disjunction may result in the extension of fractures to the skull base or the generation of deforming forces to the optic canal may compress or injure the optic nerve and its circulation. It is proposed that a stepped or tapered osteotomy will generate a more controlled pterygomaxillary separation during orthognathic surgery and may reduce the risk of devastating ophthalmologic complications.

Adolescent↗