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Biomedical subjects

G Richardson

Publications and source records attributed to G Richardson.

At least 37 records · Page 2Linked to original sources
PubMed2002

Isolex 300i CD34-selected cells to support multiple cycles of high-dose therapy.

BACKGROUND: We have previously reported that repeated cycles of high-dose therapy (HDT), can be supported by unmanipulated autologous PBPC. Here we investigate whether purified CD34+ cells, obtained by immunomagnetic separation using the Isolex 300i device, can support such therapy. METHODS: Twenty-nine consecutive patients with metastatic breast cancer had PBPC mobilized and harvested following chemotherapy and G-CSF (10 microg/kg per day). Patients with > 4.0 x 10(6)/kg CD34+ cells in the apheresis product underwent CD34-selection using the Isolex 300i (v2.0) device. All cells collected were equally divided into three aliquots and cryopreserved. Patients who did not achieve this threshold had unmanipulated cells collected and stored. Patients subsequently received three cycles of HDT with paclitaxel (175 mg/m2), thiotepa (300 mg/m2) and either ifosfamide (10 g/m2) or cyclophosphamide (4 g/m2). It was intended for patients to receive CD34-selected cells to support each of the three cycles of HDT (i.e 1/3 for each cycle) and to compare hemopoietic recovery between patients receiving CD34-selected cells or unmanipulated cells. RESULTS: Thirteen of the 29 patients (45%) did not mobilize sufficient CD34+ cells to undergo CD34-selection. The remaining 16 patients underwent CD34-selection with a median purity of 84.3% (range: 16.3-96.1%) and yield of 34% (range: 1-60%). Fifteen of these patients proceeded to HDT and 42 of the planned 45 cycles were administered. Nine patients had all three HDT cycles supported by CD34-selected cells. The median number of CD34-selected cells (x 10(6)/kg) infused per cycle was 1.5 (range: 0.04-3.01). Three of the 15 patients required infusion of 'back-up' unmanipulated cells because of delayed neutrophil recovery. Of the 13 patients whose PBPCs did not undergo CD34+ cell selection, 11 proceeded to HDT with a median of 3.2 x 10(6)/kg (range: 2.0-4.4) unselected cells infused per cycle and 31 of 33 planned cycles were delivered. When hemopoietic recovery was compared between cycles of HDT supported by CD34-selected (n = 34) and unmanipulated cells (n = 31), there was a modest slowing in the patients receiving CD34-selected cells; time to ANC > 1.0 x 10(9)/L = 11 days versus 10 days (P = 0.0122) and platelets > 20 x 10(9)/L = 14 days versus 13 days (P = 0.0009). No difference in recovery to 50 x 10(9)/L was observed (P = 0.54). CONCLUSION: We have demonstrated that Isolex 300i CD34-selected cells are capable of supporting multiple cycles of HDT. However, we were unable to acquire sufficient CD34+ cells to perform this processing in 45% (13/29) of patients and further improvements in yield are required to overcome the modest delay in neutrophil and platelet recovery.

Adult↗
PubMed2002

CliniMACS CD34-selected cells to support multiple cycles of high-dose therapy.

BACKGROUND: Traditionally, following high-dose therapy (HDT), unmanipulated autologous PBPC are infused. Alternatively, purified CD34+ cells can now be obtained by immunomagnetic separation using the CliniMACS device. Limited data currently exist examining hemopoietic recovery with such cells. METHODS: Ten patients with advanced breast cancer had PBPC mobilized with docetaxel (100 mg/m2) and G-CSF (10 microg/kg per day), harvested and processed using the CliniMACS CD34-selection device and equally divided into three aliquots for cryopreservation. Unmanipulated 'back-up' cells were also collected on a separate day of the same mobilization, divided into three and cryopreserved. Patients subsequently received three cycles of HDT with cyclophosphamide (4 g/m2), thiotepa (300 mg/m2) and paclitaxel (175 mg/m2). The intent was for patients to receive CD34-selected cells to support each of the three cycles of HDT (i.e., 1/3 for each cycle). If, however, hemopoietic recovery was delayed after Cycle 1, 1/3 of the unmanipulated cells were infused following Cycle 2 and the remaining CD34-selected cells (2/3) were used to support Cycle 3. RESULTS: PBPC from 10 patients underwent CD34-selection with a resulting median purity of 93% (range: 76-98%) and yield of 62% (range: 16-93%). Of the 10 patients, only two were able to be supported with CD34-selected cells for all three cycles of HDT. The remaining eight patients required unmanipulated 'back-up' cells to support Cycle 2. Three patients also required infusion of 'back-up' unmanipulated cells because of persistent neutropenia (n = 1) or thrombocytopenia (n = 2) following cycles initially supported by CD34-selected cells. The median number of CD34-selected cells (x 10(6)/kg) infused per cycle was 1.5 (0.7-2.6) (n = 20) and unselected cells was 1.7 (1.4-2.8) (n = 10). Comparing hemopoietic recovery between cycles of HDT supported by CD34-selected (n = 20) and unmanipulated cells (n = 10) there was a significant slowing with the CD34-selected cells; time to ANC > 1.0 = 13 days versus 10 days, platelets > 20 = 17 days versus 13 days, > 50 = 25 versus 17 days (all P values < 0.001). There was no correlation between the dose of CD34-selected cells infused and neutrophil/platelet recovery. DISCUSSION: We have demonstrated that, although unmanipulated PBPC achieve rapid hemopoietic recovery (at modest CD34 doses of < or = 2.8 x 10(6)/kg), CliniMACS-selected CD34+ cells (in the doses utilized in this study of < or = 2.6 x 10(6)/kg) result in significantly prolonged recovery.

Adult↗
PubMed2002

Potential therapeutic uses for S-nitrosothiols.

The S-nitrosothiols (RSNOs) are thought to represent a circulating endogenous reservoir of nitric oxide (NO), and may have potential as donors of NO, distinct from currently used agents. They have the general formula RSNO, and naturally occurring examples include S-nitrosocysteine, S-nitrosoglutathione and S-nitrosoalbumin, in which R is an amino acid, polypeptide and protein respectively. RSNOs have anti-platelet properties, a theoretical role in the treatment of asthma and the potential to be used as agents to treat infectious diseases ranging from the common cold to AIDS. RSNOs are relatively unstable, being degraded to release NO and the corresponding disulphide. Their stability is influenced by the properties of the R group, heat, light, the presence of transition metal ions (in particular copper) and the presence of other thiols. RSNOs participate in transnitrosation reactions in which the -NO group is transferred to another thiol to form a more stable RSNO. Thus the stability of RSNOs in vivo is difficult to predict, and this has led to the development of more stable analogues, in which the properties of R are modified. Potential interactions of RSNOs include that with ascorbic acid (vitamin C), which enhances the ability of copper to catalyse their degradation. Transnitrosation reactions with thiol-containing enzymes can influence protein function, and the intracellular thiol glutathione, levels of which are influenced by many disease states, can also influence stability. Thus, although RSNOs have many theoretically useful properties, there are also many aspects of their biochemistry that need to be addressed before their therapeutic potential can be fully realized.

Anti-Asthmatic Agents↗
PubMed2001

Retardation of cochlear maturation and impaired hair cell function caused by deletion of all known thyroid hormone receptors.

The deafness caused by early onset hypothyroidism indicates that thyroid hormone is essential for the development of hearing. We investigated the underlying roles of the TRalpha1 and TRbeta thyroid hormone receptors in the auditory system using receptor-deficient mice. TRalpha1 and TRbeta, which act as hormone-activated transcription factors, are encoded by the Thra and Thrb genes, respectively, and both are expressed in the developing cochlea. TRbeta is required for hearing because TRbeta-deficient (Thrb(tm1/tm1)) mice have a defective auditory-evoked brainstem response and retarded expression of a potassium current (I(K,f)) in the cochlear inner hair cells. Here, we show that although TRalpha1 is individually dispensable, TRalpha1 and TRbeta synergistically control an extended array of functions in postnatal cochlear development. Compared with Thrb(tm1/tm1) mice, the deletion of all TRs in Thra(tm1/tm1)Thrb(tm1/tm1) mice produces exacerbated and novel phenotypes, including delayed differentiation of the sensory epithelium, malformation of the tectorial membrane, impairment of electromechanical transduction in outer hair cells, and a low endocochlear potential. The induction of I(K,f) in inner hair cells was not markedly more retarded than in Thrb(tm1/tm1) mice, suggesting that this feature of hair cell maturation is primarily TRbeta-dependent. These results indicate that distinct pathways mediated by TRbeta alone or by TRbeta and TRalpha1 together facilitate control over an extended range of functions during the maturation of the cochlea.

Animals↗
PubMed2001

Thyroid hormone-deficient period prior to the onset of hearing is associated with reduced levels of beta-tectorin protein in the tectorial membrane: implication for hearing loss.

The genes for alpha- and beta-tectorin encode the major non-collagenous proteins of the tectorial membrane. Recently, a targeted deletion of the mouse alpha-tectorin gene was found to cause loss of cochlear sensitivity (). Here we describe that mRNA levels for beta-tectorin, but not alpha-tectorin, are significantly reduced in the cochlear epithelium under constant hypothyroid conditions and that levels of beta-tectorin protein in the tectorial membrane are lower. A delay in the onset of thyroid hormone supply prior to onset of hearing, recently described to result in permanent hearing defects and loss of active cochlear mechanics (), can also lead to permanently reduced beta-tectorin protein levels in the tectorial membrane. beta-Tectorin protein levels remain low in the tectorial membrane up to one year after the onset of thyroid hormone supply has been delayed until postnatal day 8 or later and are associated with an abnormally structured tectorial membrane and the loss of active cochlear function. These data indicate that a simple delay in thyroid hormone supply during a critical period of development can lead to low beta-tectorin levels in the tectorial membrane and suggest for the first time that beta-tectorin may be required for development of normal hearing.

Animals↗
PubMed2001

Reduction of fine airborne particulates (PM3) in a small city centre office, by altering electrostatic forces.

A two stage intervention study was carried out to establish the degree to which a newly developed, electrostatic air cleaning (EAC) system can improve indoor air quality (IAQ) by reducing the number of airborne fine particles. The IAQ and how employees in a city centre office (49 m2) perceived it, was monitored from May until November 1998. The number of fine particles, PM3 (0.3-3.0 microm); number of coarse particles, PM7 (3.0-7.0 microm); number of small positive and negative air ions; relative humidity and temperature were recorded in and out of doors. To assess the employees' perception of any changes in their work environment, a questionnaire was completed. Number of particles, relative humidity and temperature were also recorded in a nearby office, equipped with an identical air processor, where no interventions were made. The results from the first intervention (Stage 1), comparing number of airborne particles outdoors to indoors, gave a 19% reduction for PM3 and a 67% reduction for PM7 (P < 0.001). The reduction in PM3 was inconsistent and not statistically significant (P = 0.3). The reduction in PM7 from outdoors and the removal of PM7 created indoors was achieved by optimizing the existing air moving equipment. The results from the second intervention (Stage 2--with EAC units installed) comparing indoor to outdoor values, gave a further reduction in PM3 of 21% (P < 0.001) and a further 3% reduction for PM7 (P > 0.05). Therefore, at the end of Stage 2, the total reductions in particles from outdoors to indoors were 40% for PM3 and 70% for PM7 (P < 0.001). The Stage 2 results strongly suggest that electrostatic forces, created by the EAC unit(s) improved the removal of PM3, with no further significant improvement in the reduction of PM7. The questionnaire indicated an improvement in the IAQ, as perceived by the employees. The results suggest that the EAC system is effective in reducing PM3 and thereby improving IAQ in an urban office.

Air Movements↗
PubMed2001

Phase ii comparator study of oral versus intravenous topotecan in patients with chemosensitive small-cell lung cancer.

PURPOSE: Topotecan, administered intravenously, is active in small-cell lung cancer (SCLC). In this study, the comparability of oral topotecan to IV topotecan was investigated. PATIENTS AND METHODS: Patients with SCLC that had relapsed 90 days or more after cessation of initial chemotherapy were randomized to receive either oral topotecan (Hycamtin) 2.3 mg/m(2)/d x 5 (52 patients) or IV topotecan 1.5 mg/m(2)/d x 5 (54 patients), every 21 days. RESULTS: Response rates in this phase II randomized study were 23% (12/52) in the oral topotecan arm and 15% (8/54) in the IV topotecan arm. All radiological responses were confirmed by an independent radiologist. Median survival was 32 weeks (oral) and 25 weeks (IV). Good symptom control, defined as sustained improvement or no deterioration, was evident in both treatment groups. Topotecan was generally well tolerated, with myelosuppression being the major toxicity. Grade 4 neutropenia occurred in 35.3% of patients on oral topotecan and in 67.3% of patients on IV topotecan, which was statistically significant (P =.001). Fever/infection more than or equal to grade 2 associated with grade 4 neutropenia, together with sepsis, occurred in only 5.1% of courses (oral) and 3.3% of courses (IV). Non-hematological toxicity consisted mainly of vomiting (oral: 36.5% of patients; IV: 31.5% of patients) and nausea (oral: 26.9% of patients; IV: 40.7% of patients). CONCLUSION: This study found oral topotecan to be similar in efficacy to IV topotecan in the treatment of patients with relapsed SCLC, sensitive to first-line chemotherapy, with less grade 4 neutropenia and greater convenience of administration.

Administration, Oral↗
PubMed2001

Angiographic and clinical one-year follow-up of the Cordis tantalum coil stent in a multicenter international study demonstrating improved restenosis rates when compared to pooled PTCA and BENESTENT-I data: the European Antiplatelet Stent Investigation (EASI).

The Cordis tantalum coil stent was assessed in a nonrandomized multicenter trial: 275 patients with stable or unstable angina were entered. Clinical follow-up was for 1 year, with repeat angiography at 6 months. The major adverse cardiac event rates (MACE) were 3%, 14%, and 17% at 1, 7, and 13 months, respectively. The procedural success rate was 96% and the subacute occlusion rate 1.5%, in a group of patients over 60% of whom had ACC/AHA type B2 or C lesions. The binary restenosis rate at 6 months was 17.3%. Minimum lumen diameter increased from 1.07 +/- 0.28 mm preprocedure to 2.93 +/- 0.34 mm poststenting and at 6 months was 1.99 +/- 0.69 mm. These results demonstrate that the Cordis tantalum stent can be used to treat complex lesions with good procedural success and low rates of subacute thrombosis and restenosis at 6 months.

Aged↗
PubMed2001

Phase II study of paclitaxel and oral etoposide in patients with locally advanced or metastatic non-small cell lung cancer.

The combination of paclitaxel and etoposide was evaluated in a phase II study in patients with locally advanced or metastatic non small-cell lung cancer (NSCLC). Thirty-five patients, median age 61, received treatment with paclitaxel 200 mg/m (2) intravenous over 3 h on day 1, and oral etoposide, 100 mg daily on days 1-5. Cycles were repeated every 21 days for a maximum of nine cycles, or until progression occurred. Twenty-eight patients had stage IV disease, and seven patients had stage IIIA or B disease. There was one complete and seven partial responses (overall response rate, 23%). Two of these responses were in patients with stage III disease (29%) and six in patients with stage IV disease (21%). Median survival was 8.7 months, and 36% of patients were alive at 1 year. There were no treatment-related deaths and little grade 3 or 4 non-haematological toxicity although grade 3 or 4 neutropenia occurred in 60% of patients (33% of cycles). There were four episodes of febrile neutropenia. The combination of paclitaxel and oral etoposide is active in advanced NSCLC and can be delivered with acceptable toxicity.

Administration, Oral↗
PubMed2001

Economic evaluation of a nursing-led intermediate care unit.

OBJECTIVES: The aim of this paper is to examine the costs of introducing a nursing-led ward program together with examining the impact this may have on patients' outcomes. METHODS: The study had a sample size of 177 patients with a mean age of 77, and randomized to either a treatment group (care on a nursing-led ward, n = 97) or a control group (standard care usually on a consultant-led acute ward, n = 80). Resource use data including length of stay, tests and investigations performed, and multidisciplinary involvement in care were collected. RESULTS: There were no significant differences in outcome between the two groups. The inpatient costs for the treatment group were significantly higher, due to the longer length of stay in this group. However, the postdischarge costs were significantly lower for the treatment group. CONCLUSIONS: The provision of nursing-led intermediate care units has been proposed as a solution to inappropriate use of acute medical wards by patients who require additional nursing rather than medical care. Whether the treatment group is ultimately cost-additive is dependent on how long reductions in postdischarge resource use are maintained.

Aged↗
PubMed2001

Substitution of a nursing-led inpatient unit for acute services: randomized controlled trial of outcomes and cost of nursing-led intermediate care.

OBJECTIVES: To evaluate the outcome and cost of transfer to a nursing-led inpatient unit for 'intermediate care'. The unit was designed to replace a period of care in acute hospital wards and promote recovery before discharge to the community. DESIGN: Randomized controlled trial comparing outcomes of care on a nursing-led inpatient unit with the system of consultant-managed care on a range of acute hospital wards. SETTING: hospital wards in an acute inner-London National Health Service trust. SUBJECTS: 175 patients assessed to be medically stable but requiring further inpatient care, referred to the unit from acute wards. INTERVENTION: 89 patients were randomly allocated to care on the unit (nursing-led care with no routine medical intervention) and 86 to usual hospital care. MAIN OUTCOME MEASURES: Length of hospital stay, discharge destination, functional dependence (Barthel index) and direct healthcare costs. RESULTS: Care in the unit had no significant impact on discharge destination or dependence. Length of inpatient stay was significantly increased for the treatment group (P=0.036; 95% confidence interval 1.1-20.7 days). The daily cost of care was lower on the unit, but the mean total cost was pound sterlings 1044 higher-although the difference from the control was not significant (P=0.150; 95% confidence interval - pound sterlings 382 to pound sterlings 2471). CONCLUSIONS: The nursing-led inpatient unit led to longer hospital stays. Since length of stay is the main driver of costs, this model of care-at least as implemented here-may be more costly. However, since the unit may substitute for both secondary and primary care, longer-term follow-up is needed to determine whether patients are better prepared for discharge under this model of care, resulting in reduced primary-care costs.

Aged↗
PubMed2001

Quality of life in inflammatory bowel disease: a cross-cultural comparison of English and Canadian children.

BACKGROUND: Any disease and its treatment has an important impact on health-related quality of life for affected individuals. There have been few previous studies on the quality of life for children with inflammatory bowel disease (IBD). METHODS: A cross-cultural comparison was performed to determine whether the concerns of children with IBD in the United Kingdom are ranked similarly to those of children with IBD in Canada. An item reduction questionnaire, developed from interviews with Canadian children with IBD, was scored by 53 British children with IBD for importance and frequency, as a questionnaire had been scored previously by 117 Canadian children. RESULTS: There was a significant correlation between the mean scores (r = 0.831, P < 0.001) and ranks (r = 0.801, P < 0.001) for the 96 questions, and 43 of the 50 highest-ranking concerns corresponded for both populations. Confidence interval analysis showed a significant difference between the mean values for 21 of the 96 items; 20 of these 21 were ranked higher in the United Kingdom than they had been in Canada, suggesting that the frequency and/or degree of concern was greater for the British children with IBD. CONCLUSIONS: Health-related concerns of British children with Crohn disease and ulcerative colitis correlate closely with those of Canadian children with those diseases. Further studies are needed to determine the sensitivity of individual questions, the most appropriate wording of these questions, and the optimal length for a proposed instrument to assess quality of life in children with IBD.

Adolescent↗
PubMed2001

Congenitally missing maxillary lateral incisors and orthodontic treatment considerations for the single-tooth implant.

Implant restorations have become a primary treatment option for the replacement of congenitally missing lateral incisors. The central incisor and canine often erupt in less than optimal positions adjacent to the edentulous lateral incisor space, and therefore preprosthetic orthodontic treatment is frequently required. Derotation of the central incisor and canine, space closure and correction of root proximities may be required to create appropriate space in which to place the implant and achieve an esthetic restoration. This paper discusses aspects of preprosthetic orthodontic diagnosis and treatment that need to be considered with implant restorations.

Anodontia↗
PubMed2001

How do teenagers and primary healthcare providers view each other? An overview of key themes.

BACKGROUND: Teenagers have often been asked for their opinions about health services. However, relatively few studies have involved quantitative and qualitative methods of assessing them. Furthermore, there have been no United Kingdom studies of providers' views on the health of teenagers or of providers' opinions about their role in teenage health. AIM: To determine how teenagers view primary care, to discover how primary care providers view teenage patients, and to note any differences in opinions between the two groups. DESIGN OF STUDY: Questionnaire survey, focus group discussions, and semi-structured interviews. SETTING: Two thousand two hundred and sixty-five teenage patients, 16 general practitioners (GPs), 12 practice nurses, and 12 general practice receptionists in South Wales valley communities. METHOD: Selected practices provided age-sex registers of patients aged between 14 and 18 years and questionnaires were sent to these patients. Focus groups were assembled from those teenagers who had completed and returned the questionnaire. Semi-structured interviews between one member of the study team and GP surgery staff, chosen randomly from staff lists in the selected surgeries. RESULTS: The teenagers reported a lack of knowledge of services available from primary care, a feeling of a lack of respect for teenage health concerns, poor communication skills in GPs, and a poor understanding of confidentiality issues. The providers did not always share these concerns and they also had differing views on communication and confidentiality issues. CONCLUSION: The data demonstrated important findings about how teenagers would like primary care services to be improved. There was an apparent gulf between teenagers' own opinions about health care and the opinions held by primary care providers.

Adolescent↗
PubMed2000

Hormonal and pharmacological manipulation of the circadian clock: recent developments and future strategies.

The mammalian circadian oscillator, located in the suprachiasmatic nuclei of the anterior hypothalamus, serves as the principal source of rhythmic temporal information for virtually all physiologic processes in the organism, including the alternating expression of sleep and wakefulness. Recent studies, in both animal models and human subjects, have demonstrated the important modulation of sleep and wakefulness mediated by the circadian clock. Independent of other factors, notably prior sleep-wake history, the circadian clock potentiates wakefulness (and alertness) at one phase of the diurnal cycle, while facilitating sleep and its attendant processes at the opposite phase. The adaptive advantage of synchronizing sleep-wake behaviors with the daily changes in the external environment is clear. But in a modern world where the constraints of environmental time are less and less important, the circadian clock still imposes rigid boundaries on the timing of sleep and alert wakefulness that are increasingly perceived as limitations on human performance. This conflict underlies the sleep "disorders" of jet lag and shiftwork sleep disruption, problems that are not really diseases at all, but instead reflect normal function of circadian timing in the context of extraordinary demands on sleep-wake scheduling. Whatever their proper classification, both jet lag and shiftwork insomnia represent important societal problems deserving of public health and medical attention. Barring a worldwide rejection of air-travel, jet lag will continue to afflict tens of thousands of people annually. The effects of jet lag on human performance, while typically transient, can nonetheless be significant, affecting commerce, government, and even the outcome of professional sports contests. More important, only a global regression to an agrarian economy will eliminate the problem of tens of millions of workers in this country who regularly attempt to work at night and sleep during the day. In contrast to jet lag, shiftwork produces chronic sleep disruption lasting for the duration of shiftwork exposure. For while individual differences in the ability to adjust to a nocturnal work schedule clearly exist, recent studies suggest that few if any night workers regularly experience restful and restorative day sleep equivalent to that considered normal at night. This chronic sleep limitation is associated with significant increases in a number of consequent problems including sleepiness-related accidents, social disruption, and psychiatric disturbances. In addition, chronic exposure to shiftwork has now been shown to be an independent risk factor for the development of both cardiovascular and gastrointestinal diseases. While these epidemiological studies have not identified the specific aspect of shiftwork that is associated with increased risk of these disorders, the chronic limitation and disruption is foremost among plausible factors. The most important aspect of human circadian physiology that limits adaptation to the extreme schedules inherent in shiftwork and jet travel is the primacy of light among entraining signals, or zeitgebers. Exposure to sunlight for night shiftworkers, or for jet travelers at their destination, results in maintenance (or resetting) of the clock to environmental time. This response can be prevented or overridden with extraordinary avoidance of sunlight or with provision of artificial light of sufficient duration and intensity to negate the sunlight signal, an approach shown to be effective in the treatment of shiftwork sleep disruption. Practical issues sharply limit the application of artificial lighting to all shiftwork settings, however, and the role for a pharmacological chronobiotic agent capable of accomplishing the same end is potentially very large (Copinschi et al., 1995; Jamieson et al., 1998). For example, the effects of zolpidem vs. placebo on sleep, daytime alertness, and fatigue in travelers who complain of jet lag was co

Antidepressive Agents, Tricyclic↗