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Biomedical subjects

M Stringer

Publications and source records attributed to M Stringer.

At least 19 recordsLinked to original sources

Investigation of the use of the pulsed dye laser in the treatment of Bowen's disease using 5-aminolaevulinic acid phototherapy.

BACKGROUND: The use of 5-aminolaevulinic acid photodynamic therapy (ALA-PDT) for the treatment of Bowen's disease is well established. However, treatment with a continuous light source has the disadvantage of prolonged treatment time during which patients often experience significant discomfort requiring the use of local anaesthetic. OBJECTIVES: The aim of this study was to assess the efficacy and safety of the pulsed dye laser (PDL) as the light source for photoactivation of the protoporphyrin IX to treat Bowen's disease by PDT. METHODS: Thirteen patients with a total of 17 patches of histologically proven Bowen's disease were treated with 20% 5-ALA in Unguentum M (Crookes Healthcare, Nottingham, U.K.) under occlusion for 4 h. The patches were then irradiated using a Candela SPLTL-1b (Candela Corporation, Wayland, MA, U.S.A.) PDL using a wavelength of 585 nm, with a 7-mm diameter spot at a fluence of 10 J cm(-2). The spots overlapped by 50% to cover the lesion and extend beyond the clinical margin of the patch of Bowen's disease by 0.5 cm. Patients were then followed up initially at 2 months, then at 3-monthly intervals for a period of 12 months to assess treatment success and recurrence rate. RESULTS: Subjects consisted of 10 females and three males, between 47 and 88 years. The mean area of the patches of Bowen's disease was 315.4 mm(2) (range 36-2464 mm(2)) requiring a median of 32 pulses (range 3-260). Lesions sites were hands (two), foot (one) and lower leg (14). All patients experienced varying degrees of discomfort during treatment but none required the use of local anaesthetic. At 2 months eight treatment sites could not be assessed due to loose overlying crusts and removal of these revealed superficial erosions in seven patients. Of the 17 lesions treated, on follow-up at 1 year, 14 patches (82%) demonstrated a complete clinical response, although one of these had required a second treatment. Two patients with three lesions that would have required further therapy refused a second treatment. Prolonged crusting lasting 8 weeks occurred in eight patches and prolonged discomfort lasting 6 weeks occurred in four patients. CONCLUSIONS: This study has shown that the PDL is an effective light source for ALA-PDT of Bowen's disease. Light source exposure times are shorter, although overall treatment time may not always be significantly reduced for larger lesions. The procedure was well tolerated. However, the post-treatment morbidity was relatively high compared with the more conventional treatment modalities. Further studies are needed to determine whether lower energy fluences can maintain similar efficacy while reducing post-treatment morbidity.

Aged↗

Guidelines for topical photodynamic therapy: report of a workshop of the British Photodermatology Group.

Topical photodynamic therapy (PDT) is effective in the treatment of certain non-melanoma skin cancers and is under evaluation in other dermatoses. Its development has been enhanced by a low rate of adverse events and good cosmesis. 5-Aminolaevulinic acid (ALA) is the main agent used, converted within cells into the photosensitizer protoporphyrin IX, with surface illumination then triggering the photodynamic reaction. Despite the relative simplicity of the technique, accurate dosimetry in PDT is complicated by multiple variables in drug formulation, delivery and duration of application, in addition to light-specific parameters. Several non-coherent and coherent light sources are effective in PDT. Optimal disease-specific irradiance, wavelength and total dose characteristics have yet to be established, and are compounded by difficulties comparing light sources. The carcinogenic risk of ALA-PDT appears to be low. Current evidence indicates topical PDT to be effective in actinic keratoses on the face and scalp, Bowen's disease and superficial basal cell carcinomas (BCCs). PDT may prove advantageous where size, site or number of lesions limits the efficacy and/or acceptability of conventional therapies. Topical ALA-PDT alone is a relatively poor option for both nodular BCCs and squamous cell carcinomas. Experience of the modality in other skin diseases remains limited; areas where there is potential benefit include viral warts, acne, psoriasis and cutaneous T-cell lymphoma. A recent British Photodermatology Group workshop considered published evidence on topical PDT in order to establish guidelines to promote the efficacy and safety of this increasingly practised treatment modality.

Aminolevulinic Acid↗

d-morphine, but not l-morphine, has low micromolar affinity for the non-competitive N-methyl-D-aspartate site in rat forebrain. Possible clinical implications for the management of neuropathic pain.

A diverse range of opioids and enantiomers were examined for their ability to displace binding at the [(3)H] MK-801-labelled site of the N-methyl-D-aspartate (NMDA) receptor in rat forebrain, displacement which is equitable with non-competitive NMDA receptor antagonist activity. Surprisingly, d-morphine, but not natural l-morphine, has low micromolar affinity for the site, suggesting clinical potential for racemic dl-morphine in the treatment of neuropathic pain with reduced development of tolerance. The opioid mu-receptor agonists: levorphanol, d- and dl-methadone, displayed similar properties. With the exception of the case of d-morphine, the structural requirements for affinity correspond closely with those previously found for the inhibitory effects of opioids on monoamine uptake.

Analgesics, Opioid↗

Psychosocial factors influencing personal control in pain relief.

A questionnaire was administered to 100 women (50 primigravidae, 50 multigravidae) to investigate the influence of psychosocial factors on personal control in pain relief. Personal control was measured using a 36-item scale based on the concept of 'Rule'. The women were asked to rate each rule on a 7-point Likert scale. Measures of psychosocial factors included assessment of the women's expectations of labour pain, maternal confidence, pain intensity, antenatal training and partner support. Demographic variables including parity were also recorded. The questionnaires were completed prior to and within 48 h following the women's delivery (whilst they were inpatients on the postnatal ward).Two variables, antenatal training and pain intensity, emerged as predictors of personal control in pain relief following stepwise multiple regression analysis. These findings have implications for clinical practice particularly in the area of antenatal care and planning care during labour.

Adult↗

The role of photodynamic therapy (PDT) in inoperable oesophageal cancer.

OBJECTIVE: To evaluate the role of PDT in palliation of patients with inoperable oesophageal cancer and to identify subgroups in which this role is of particular significance. METHODS: Sixty-five patients (37 male, 28 female) aged 42-89 (mean 65.6) with advanced and inoperable oesophageal cancer were the subjects of this study. Inoperability was due to advanced stage of the disease in 61 and because of general condition in 4. Fifty-eight (89%) had previous treatments, other than PDT. All patients had dysphagia of whom 20 could not swallow fluid. Pre-PDT clinical, radiological and endoscopic examinations were carried out. Performance status (PS) and clinical staging was assessed. PDT protocol consisted of: intravenous injection of 2 mg/kg; photofrin (or equivalent polyhaematoporphyrin) followed 24-72 h later by endoscopic illumination using 630 nm laser light. MAIN OUTCOME MEASUREMENTS: (1) Relief of dysphagia generally and specifically in those with cervical and post-cricoid carcinoma who were previously treated by external beam radiotherapy (EBR) (n=6) and those with previous intubation or stent (n=9); (2) Survival. RESULTS: There was no PDT related mortality. Three patients (4.6%) developed a mild skin photosensitivity reaction. Dysphagia was relieved in all patients. The mean and median survival of the 58 patients who have died was 7. 7 and 6 months respectively. Seven patients are alive from 2-30 months (mean 16). Survival was not significantly influenced by tumour histology, location in the oesophagus, severity of dysphagia on admission, or by previous therapy. Survival was significantly influenced by Performance Status prior to treatment (P=0.03 log rank, for PS < or =2 vs. PS=3), an most significantly by the stage of the disease (P=0.0001 log rank, for Stage III vs. Stage IV). CONCLUSIONS: (1) PDT is safe and effective for palliation of dysphagia in inoperable oesophageal cancer. This is particularly important in post-cricoid and cervical oesophageal cancer previously treated by other methods and for patients with recurrent malignant obstruction who previously had intubation or stent placement. (2) Survival is influenced by better PS (< or =2) and in those with disease Stage III rather than patients in Stage IV. This study has not been able to determine the influence of complete tumour staging on survival because, apart from four patients, all others were Stages III and IV cancer.

Aged↗

Personal control in pain relief during labour.

Personal control is a central feature of women's involvement in their childbirth experiences. To achieve this control tacit rules and guidelines are applied to define how women and the professionals who care for them should behave. This study investigated the extent to which women exercised control in pain relief during the first stage of labour by comparing (a) the rules which they held prior to childbirth (2-3 cm cervical dilatation) with those which they afterwards felt applied to their labour and (b) the rules held by the women before and after childbirth with those held by the midwives. In a quantitative study using a repeated measures design, a questionnaire was administered to 35 midwives and to 100 women prior to and within 24 hours following their delivery. Consistency of the women's scores before and after childbirth, indicated by few statistically significant differences, tended to confirm their rules on control of pain relief. Some of the rules were held even more strongly following childbirth. A surprising finding was the even stronger agreement by midwives with some of the rules. There was a definite trend for many of the rules held by the women prior to childbirth to increase following birth towards those of the midwives. This could be the result of the experience of childbirth per se but the possibility that it was contributed to by the influence of the midwives cannot be ruled out and warrants further research. An interesting hierarchy in the rules for compliance with professional care has been highlighted.

Adaptation, Psychological↗

Waiting for coronary artery bypass surgery: a qualitative analysis.

Waiting lists for coronary artery bypass surgery (CABS) are common in many developed countries. Yet, there is limited information available regarding patients' health care needs at this time. This paper reports on a prospective study which aimed to investigate the experience of waiting for CABS from a qualitative perspective. An inductive research approach was used to conduct interviews with 70 randomly selected patients at three intervals over the first year on the waiting list - referral for surgery, again after waiting 6 months (n=49), and finally after waiting for 1 year (n=28). Attrition was mainly caused by surgery having been performed (n=36), although death (n=4) and refusal to participate (n=2) also contributed. Domicilliary interviews were taped and transcribed verbatim. Thematic content analysis identified three central themes in this experience - uncertainty, chest pain and anxiety; with six secondary themes - powerless, dissatisfaction with treatment, anger/frustration, physical incapacity, reduced self-esteem, and altered family and social relationships. The nature and meaning inherent in each theme is described using interview quotations, and a model is proposed which summarizes this data and the relationship between themes. From this analysis, uncertainty, chest pain and anxiety emerge as important indicators of a negative outcome for these patients. This report strongly suggests that patients awaiting bypass surgery require more information regarding the waiting time for such a surgery. Nurses should also offer advice regarding pain management to help improve patients' skills and decrease the fear associated with angina. Nursing intervention and support should also be directed at reducing patients' anxiety levels. This is the first known qualitative study which specifically examines patients' perception of the waiting period prior to bypass surgery. It may therefore provide new evidence on which to base practice for nurses in both hospital and community, and may also stimulate further research in this area.

Activities of Daily Living↗

Hydrotherapy use during labor: an integrative review.

Hydrotherapy is an effective, alternative intervention that can be used by care providers to provide a nonpharmacological method to assist low risk, laboring women cope with labor. This article provides a synthesis of the state of the science on the effects of hydrotherapy with labor and delivery. The indications, physiologic mechanism, benefits, practice implications, and needed research are discussed. The data-based articles support numerous benefits such as increased relaxation, increased satisfaction, lower blood pressure, and increased diuresis with women who bathe during labor. These studies found that there was no difference in maternal and neonatal morbidity such as infections between bathers and nonbathers. Additionally, there was no difference in maternal and neonatal infection rates between women with intact or ruptured membranes. The use of hydrotherapy during established labor increases cervical dilation while bathing although there is no difference in the total length of labor between bathers and nonbathers. Researchers conclude that hydrotherapy is a safe, nonpharmacological alternative for women to use during labor and delivery.

Journal Article↗

The place of bronchoscopic photodynamic therapy in advanced unresectable lung cancer: experience of 100 cases.

OBJECTIVES: The objectives of the study were: (1) to evaluate effectiveness of photodynamic therapy (PDT) for symptom palliation in patients with inoperable lung cancer; (2) to determine survival benefit in a subset of patients. METHODS: One hundred patients, 68 male, 32 female, aged 44-81 years (mean 62.5) with advanced inoperable bronchogenic cancer and endobronchial luminal obstruction were prospectively studied. Eighty-two percent had previous chemo/radiotherapy. The pre-treatment protocol consisted of: clinical, radiological and bronchoscopic examination, pulmonary function testing, assessment of WHO performance status and clinical staging. Treatment protocol was: intravenous injection of 2 mg/kg body weight of photofrin/polyhaematoporphyrin and interstitial illumination using 630 nm laser light 24-72 h later. Follow-up was at 6-8 weeks for 1 year. Then every 3-6 months if applicable. Repeat PDT as necessary. RESULTS: All patients were stage IIIa-IV. The histology of the tumour was: non small cell in 90 and small cell in 10. There was no treatment related mortality. Mean endoluminal obstruction fell from 85.8% to 17.5%, mean forced vital capacity (FVC) and forced expiratory volume in 1s (FEVI) improvement was 430 ml and 280 ml, respectively. Ninety patients died from 6 weeks to 37 months, mean and median survival: 9 months and 5 months, respectively. Ten patients are alive from 13 to 72 months, mean 36 months, median 29 months. Overall 2-year survival was 19%. Multivariant analysis indicated that age, sex, histology and stage of disease did not influence survival significantly but performance status did. Patients with WHO < 2 had mean and median survival of 17.8 and 14 months versus WHO > 2, 6.9 mean and 4 months median survival (log-rank P < 0.0001). CONCLUSIONS: (1) PDT is effective in palliation of inoperable advanced lung cancer. (2) Subset of patients with a better performance status have added survival benefit.

Adult↗

Fetal brain injury following prolonged hypoxemia and placental insufficiency: a review.

It is well-established that severe, acute episodes of hypoxemia can damage the brain before birth, but the effects of more sustained hypoxemia are less well understood. We have used fetal fetal sheep in a series of studies aimed at determining the effects of prolonged hypoxemia, induced by placental insufficiency of differing severity and duration, on fetal brain structure. Restriction of placental, and hence fetal, growth by carunclectomy caused impaired development of neural processes and connections in the hippocampus, cerebellum, and visual cortex; neuronal migration and neuronal numbers did not appear to be affected. Twenty days of placental insufficiency during late gestation induced by umbilicoplacental embolisation also caused abnormalities in brain structure; the cerebellum, which develops late in gestation, was particularly affected. In the cortex, there was evidence of white matter lesions, an increase in the size of capillaries and a proliferation of astroglia. We also examined the effects of shorter periods of hypoxemia (6-12 hr) near mid-gestation on brain structure; fetuses were allowed to recover for 7 or 35 days after the hypoxemic challenge. The major changes were mild focal damage in the cortical white matter, a reduction in the number of Purkinje cells, a delay in the growth of neural processes in the cerebellum and proliferation of blood vessels. The hippocampus was also affected, in particular the areal density of pyramidal cells was reduced. The use of several classes of pharmacological agents with the potential to protect neurons from hypoxemic injury is discussed in relation to the developing brain.

Animals↗

Effects of chronic placental insufficiency on brain development in fetal sheep.

Clinical evidence has linked intrauterine compromise such as fetal hypoxemia to poor neurologic outcome in the newborn. In this study we examined the effects of inducing chronic fetal hypoxemia by impairment of placental function on brain development in fetal sheep. Placental insufficiency was induced from 120 to 140 d of gestation (term = 145-148 d) by injection of microspheres into the umbilical circulation in five fetal sheep. Fetal partial pressure of oxygen, PaO2, was reduced from 24.1 +/- 0.5 mm Hg before embolization to 14.8 +/- 0.4 mm Hg after embolization (p < 0.05). In another three fetuses a similar level of hypoxemia (PaO2, 13.8 +/- 0.4 mm Hg) occurred spontaneously. At 140 d of gestation the fetal brains were perfused with fixatives and compared with five control fetuses for the assessment of structural and immunohistochemical alterations. Hypoxemic fetuses demonstrated severe gliosis in the cerebral cortex and reduced myelination of subcortical white matter as visualized by glial fibrillary acidic protein and myelin basic protein staining, respectively (p < 0.05). White matter lesions were observed in two fetuses. The diameter of cerebral capillaries was increased in hypoxemic fetuses (p < 0.05), but there was no change in the number of nitric oxide synthase immunoreactive cells. Growth of neuronal processes was affected in the cerebellum, where there was also a reduction in the number of Purkinje neurons (p < 0.05). These results show that a prolonged period of placental insufficiency, resulting in moderate fetal hypoxemia during the last third of gestation, can affect neurodevelopmental processes that occur late in gestation such as myelination and growth of the cerebellum. This prenatal damage could affect neural connectivity and have functional consequences after birth.

Animals↗

Personal costs associated with high-risk prenatal care attendance.

Personal costs associated with attending prenatal care may influence women's care-seeking behavior, particularly poor, pregnant women and those with complicated pregnancies who receive more visits. This study described personal costs incurred by poor, high-risk pregnant women while attending care. Personal costs included direct out-of-pocket and time costs. Also, the relationship between personal costs and attendance was examined. Mean direct costs throughout pregnancy were $101.96 per patient. Women waited a mean of 3.22 hours per visit for care and received direct physician care for a mean of 5 minutes. As child care costs increased, attendance decreased significantly (r = 0.60, p < or = 0.05). As transportation costs, meal costs, wages lost, and time spent awaiting care increased, attendance decreased. Prenatal care has associated dollar and time costs for patients. Problem solving these issues with patients is critical. System changes to decrease waiting times and to address child care issues are needed.

Adult↗

The vulnerability of the fetal sheep brain to hypoxemia at mid-gestation.

Our aim was to test the hypothesis that a brief episode of hypoxemia near mid-gestation in fetal sheep will result in damage to the fetal brain with the extent and type of damage in any particular region being related to the developmental processes occurring at the time of the insult. Hypoxemia was induced, sufficient to reduce arterial O2 content by approximately 50%, by restricting utero-placental blood flow in 14 chronically catheterised fetuses for 6 h or 12 h at 84 days of gestation (term 145-8 days). Age-matched fetuses (n = 14; 4 operated and 10 unoperated) were used as controls. Fetuses were killed 7 days after being exposed to hypoxemia, and brains removed for histological analysis at the light and ultrastructural levels. Body weights of hypoxemic fetuses did not differ significantly from controls but brain weights were significantly reduced both in absolute terms and when expressed in relation to body weight (P < 0.05). Most fetuses exposed to hypoxemia sustained no gross brain damage. However, in one hypoxemic fetus from a multiple pregnancy there was extensive leucomalacia in the cortical white matter; mild focal damage was seen in another 8 hypoxemic fetuses. In the cerebral cortex (frontal lobe) the surface folding index was significantly reduced (P < 0.05) in hypoxemic fetuses compared to controls suggesting that gyral formation had been delayed. In these fetuses there were also degenerating neurons in the deeper cortical layers. In the hippocampus of hypoxemic fetuses there was a delay (P < 0.05), compared to controls, in the migration of cells from the germinal layer to the pyramidal layer in the CA1 region, and decreases (P < 0.05) in the density (area1) of neurons in the pyramidal layer and in the width of stratum oriens. In the cerebellum of hypoxemic fetuses there was a decrease (P < 0.05), compared to controls, in the density (area1) of mitotic bodies in the external granule cell layer. However, there were no significant differences in the number of pyknotic cells in this layer, in the density of Purkinje cells, in their somal area, or in the width of the external granule cell or molecular layers. There was an increase (P < 0.05) in the proportion of the brain parenchyma occupied by blood vessels in both the hippocampus and cortex of hypoxemic fetuses compared to controls. This study has shown that an hypoxemic insult near mid-gestation can result, one week later, in white matter damage and in neuronal death in the hippocampus and to a lesser extent in the cerebral cortex and cerebellum. It can also retard neuronal migration and the growth of neural processes in the hippocampus where development is well established at this age. Such brain damage could result in less than optimal neuronal connectivity and could affect function postnatally.

Animals↗

Endoscopic laser therapy in malignant tracheobronchial obstruction using sequential Nd YAG laser and photodynamic therapy.

BACKGROUND: Because the survival after treatment of advanced inoperable endo-tracheobronchial carcinoma is so poor, a pilot study was undertaken to evaluate the combined cumulative effect on survival of neodymium yttrium aluminium garnet (Nd YAG) laser followed by photodynamic treatment used endoscopically. METHODS: Seventeen patients who presented between January 1992 and March 1996 with inoperable tracheobronchial lesions causing more than 50% endoluminal obstruction were selected to enter the pilot study. Initially they had bronchoscopic Nd YAG laser treatment to debulk the tumour, and this was followed six weeks later by photodynamic therapy to treat the residual tumour. RESULTS: All patients had symptomatic relief and at least a partial response, and seven had a complete response for 3-6 months. Eight of the 17 (47%) survived for at least two years and 11 (65%) survived for a year or more. The median survival of the 10 patients who had died by the time of writing was 18.5 months (range 5-39), 95% confidence interval (CI) 9.9 to 29.5. CONCLUSIONS: Combined Nd YAG laser and endoscopic photodynamic therapy may be an effective palliative treatment for patients with inoperable endotracheobronchial cancer.

Aged↗

Use of ultrasonography in the home care of high-risk childbearing women.

Antenatally, as more women are being treated in the home setting rather than the hospital setting, diagnostic modalities such as ultrasonographic imaging need to be available for use by the home care provider. In the home setting, the care provider and treatment modalities are brought to the patient, whereas patients managed in the hospital setting must attend the provider site to receive the same services. Without the availability of diagnostic ultrasonography in the home setting, pregnant women who are treated in the home rather than the hospital are required to incur an added financial and physical burden associated with attendance at care. Financially, nonreimbursed out-of-pocket costs incurred by the patient may include costs of transportation, costs of child care, and loss of wages. Physically, patients are prevented from maintaining recommended bed rest and dietary treatment regimens. Ultrasonographic evaluations can be performed safely in the home setting by nurses who have received added educational preparation and ultrasonographic imaging experience, thereby providing the essential care often necessary for women who experience pregnancies complicated by high-risk conditions.

Female↗

Nitric oxide synthase immunoreactivity and NADPH diaphorase staining are co-localised in neurons closely associated with the vasculature in rat and human retina.

Nitric oxide synthase (NOS) is widely distributed throughout the nervous system and is found in neurons which produce nitric oxide (NO). In attempting to elucidate the biological roles of NO in neurotransmission, vasodilation, and in neurodegeneration, nicotinamide adenine dinucleotide phosphate diaphorase (NADPHd) histochemistry has been widely used. NADPHd histochemistry and NOS immunoreactivity (NOS-IR) have been assumed to stain the same population of neurons. However, there have been numerous reports which suggest that this may not always be the case, and in all neuronal populations investigated, the coincidence of NOS and NADPHd must be unequivocally demonstrated. We have examined NADPHd histochemistry and NOS immunoreactivity in the human and rat retina and shown that these are 100% co-localised. Further, we have described the morphology of NADPHd and NOS-IR neurons in the human and rat retina and shown a close association of these neurons and their processes to the retinal vasculature. We have taken the NOS-IR to the ultrastructural level and have identified NOS-IR cells in close association with the basal lamina covering endothelial cells and pericytes of the retinal capillaries. We suggest that NO released from these neurons may be involved in the regulation of retinal microcirculation.

Aged↗

A sociodemographic comparison of families of very low-birthweight infants: 1982-1991.

Social and demographic characteristics were investigated in families who had very low birthweight infants between 1982 and 1984 (historical cohort). Since those data were collected, the number of women using drugs during pregnancy has increased significantly. Therefore, between 1989 and 1991 (current cohort) we continued to document sociodemographic characteristics of families of very low-birthweight infants (144 mothers, 156 infants). Data were collected from review of hospital charts and outpatient health records, and monthly interviews. The two cohorts were similar demographically. Changes in family composition occurred more frequently in the current cohort. There was a startling increase in illicit drug use between the two groups of women 3% in the historic cohort and 20% in the current cohort. In the historical cohort all infants went home to their mothers; however, in the current cohort 7.8% of infants were placed with other family caretakers. Infant health outcomes for the first six months after hospital discharge were similar in both groups. From 1982 to 1991 the increases in substance abuse, nonmaternal caretakers, family moves, and changes in family composition have implications for health care providers involved in infant follow-up care.

Adolescent↗