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Biomedical subjects

M Carter

Publications and source records attributed to M Carter.

At least 19 recordsLinked to original sources

Consuming the evidence: consumers and evidence-based medicine.

Consumers have varying expectations and knowledge about evidence-based medicine (EBM), but expect the healthcare system to offer best practice based on the latest evidence. With the increasing power of the consumer movement, EBM has the potential to promote informed participation in health decision making by individual consumers and carers. To more effectively incorporate consumer experiences, views and concerns into the evidence base, there needs to be greater value put on qualitative research and acknowledgement of its importance. Consumers would like the research agenda to reflect population health needs, and for there to be more consultation about evidence-based decisions on access to care and rationing, and greater understanding of consumers' attitudes in decisions about treatment. Consumers want patient-centred healthcare and therefore must be involved collaboratively in the way EBM is used by health services and health practitioners.

Australia↗

Indazolylamino quinazolines and pyridopyrimidines as inhibitors of the EGFr and C-erbB-2.

Described herein is the design and synthesis of indazolylaminopyridopyrimidines and quinazolines as inhibitors of the class 1 tyrosine kinase receptor family. Data is presented for N(4)-(1-benzyl-1H-indazol-5-yl)-N(6),N(6)-dimethylpyrido[3,4-d]pyrimidine-4,6-diamine 3B. This compound inhibited EGFr and c-erbB-2 enzymes selectively over other kinases. It inhibited the proliferation of a range of tumour cell lines in vitro and the growth of BT474 xenografts in SCID mice.

Animals↗

Psychiatric bed utilization: 1896 and 1996 compared.

BACKGROUND: The 1896 and 1996 populations of North West Wales are similar in number, ethnic and social mix and rurality, enabling a study of the comparative incidence and prevalence of service utilization over the course of a century. METHODS: We collected records on all psychiatric admissions from North-West Wales in 1894-1896 and 1996. These were assessed and diagnosed by the responsible sector area consultant. RESULTS: The data reveal substantially more patients admitted for all diagnoses in 1996. even when comparisons are restricted to detained patients. The incidence of hospitalization by detention for schizophrenia is slightly lower 1996 than in 1896 but the incidence of hospitalization is higher now than in 1996. The incidence of hospitalization by detention for non-affective disorder psychoses is the same in both 1896 and 1996 but there is a doubling of incidence of hospitalization. The incidence of hospitalization for bipolar disorders is similar in the two periods. Modern mental health services admit large numbers of personality disordered patients, where none were admitted 100 years ago. CONCLUSIONS: Factors general to changing health care and expectations and others specific to mental health would appear to have led to the increase in rates of admissions observed in the modern period.

Adult↗

Long-term outcome of patients surviving for more than ten years following treatment for acute leukaemia.

Between 1972 and 1988, 832 consecutive patients were treated for acute leukaemia at St. Bartholomew's Hospital; a retrospective analysis has been conducted to determine the clinical course and outcome for 101 who have survived > or = 10 years following treatment. At a median follow-up of 16 years (range 10-28 years), 86 patients (86 out of 834 total, 11%) were still alive. Long-term follow-up of patients who have survived > or = 10 years following treatment for acute leukaemia revealed that most patients were in normal health, although a significant number of complications had occurred.

Acute Disease↗

Surgical confirmation of ProstaScint abnormalities in two patients with high risk prostate cancer.

We describe our initial experience using ProstaScint scanning in addition to conventional imaging modalities for staging of high risk prostate cancer. Using our protocol, ProstaScint images detected abnormalities in pelvic lymph nodes not seen on CT scan or magnetic resonance imaging (MRI) in two patients. Subsequent surgical pelvic lymphadenectomy confirmed these abnormalities. Further patients will be accrued on this study to estimate the sensitivity and specificity of ProstaScint scanning.

Aged↗

High-dose treatment with autologous bone marrow support as consolidation of first remission in younger patients with acute myelogenous leukaemia.

BACKGROUND: Debate and controversy remain as to the optimal post-remission therapy for younger patients with acute myelogenous leukaemia (AML). The aim of this study was to evaluate high-dose treatment (HDT) with autologous bone marrow support (ABMS) as consolidation of first complete remission (CR). PATIENTS AND METHODS: One hundred forty-four patients (AML-M3 excluded, median age 38 years, range 15-49 years) received remission induction therapy comprising: adriamycin 25 mg/m2, days 1-3, cytosine arabinoside (ara-C) and 6-thioguanine, both at 100 mg/m2 bid, days 1-7. Patients in whom CR was achieved received two further cycles of the same treatment prior to bone marrow being harvested and cryopreserved. HDT comprised ara-C: 1 g/m2 b.i.d. x six days and total body irradiation (TBI): 200 cGy b.i.d. for three days. Thawed autologous marrow was then re-infused. RESULTS: Complete remission was achieved in 106 of 144 patients (73%) who were thus eligible to receive ara-C + TBI + ABMS; 61 actually received it. Following HDT, the median time to neutrophil recovery (> 0.5 x 10(9)/l) was 25 days (range 11-72 days) and to platelet recovery (> 20 x 10(9)/l), 42 days (range 15-159 days). There were eight treatment-related deaths. Analysis by 'intention to treat' shows both remission duration (log-rank, P = 0.001) and survival (log-rank, P = 0.004) to be significantly longer for the 106 patients eligible to receive HDT than for a historical control group (n = 133) who received identical remission induction and consolidation therapy but without ara-C + TBI + ABMS. With a median follow-up of 5.5 years, 39 of 106 patients remain in CR (37%) and 54 (51% of those in whom CR was achieved) remain alive, with a predicted actuarial survival of 52% at 5 years. CONCLUSIONS: The addition of ara-C + TBI + ABMS to conventional consolidation therapy significantly improved remission duration and survival over those of a historical control group of patients with AML (aged < 50, AML-M3 excluded). HDT was, however, associated with significant treatment-related mortality and slow blood count recovery. The use of ara-C + TBI supported by peripheral blood progenitor cells should make the treatment safer and more widely applicable in AML.

Adolescent↗

How residents spend their nights on call.

PURPOSE: Night call is a significant part of residents' education, but little information about their night-call activities is available. This study recorded residents' activities during night-call rotations on internal medicine and pediatrics wards. METHOD: In June and July 1997, on-call pediatrics and internal medicine residents at an urban academic medical center were accompanied by trained observers on the general wards between the hours of 7 PM and 7 AM. The types and duration of activities were recorded. RESULTS: Residents were observed for 106 nights. Internal medicine and pediatrics residents spent their time similarly. They spent 5.3 hours and 5.7 hours per night, respectively, on "basic" activities such as eating, resting, chatting, and sleeping, and an average of 2.6 hours and 2.2 hours, respectively, on chart review and documentation. In both programs, discussing the case with team members averaged 1.5 hours per night and use of the computer averaged slightly more than half an hour. Internal medicine residents spent approximately 1.5 hours on patients' history and physical examinations while pediatrics residents spent 1.3 hours. With each new patient, internal medicine residents spent an average of 19.7 minutes and pediatrics residents spent 16.5 minutes. The only significant difference between the two groups of residents was that the pediatrics residents spent more time per night on procedures than did the internal medicine residents (37 minutes versus 14 minutes, p < 0.01). CONCLUSIONS: Residents from both programs spent a surprising amount of time each night on chart review and documentation. In fact, they spent more time with charts than with patients. Whether this activity truly contributes to residents' education or improved patients' outcomes is not clear.

Humans↗

An autosomal recessive, lethal, neurologic disease of Gordon Setter puppies.

This report details clinical, necropsy, and pedigree data on an inherited, lethal, neurologic disease of young Gordon Setters. This disorder is characterized by an early age of onset, gait and postural abnormalities, progressive weakness, and recumbency by 5-6 weeks of age. Although clinically distinctive, postmortem changes in affected pups were minimal. Gross lesions were not observed. Microscopic changes were subtle and consisted of astrocyte swelling, primarily in the cerebrocortical and cerebellar white matter, and white matter tracts of the brainstem. Immunohistochemistry for glial fibrillary acidic protein revealed a marked increase in the number and staining intensity of astrocyte cytoplasmic processes in affected pups compared with age-matched controls. Neither cerebral inflammation nor neuronal necrosis was identified. Pedigree analysis of affected litters demonstrated an autosomal recessive mode of inheritance. A diagnosis of this heritable disease should be based on the early age of onset (3-4 weeks of age), characteristic clinical signs, rapid progression to recumbency by 5-6 weeks of age, identification of swollen astrocytes primarily in the cerebellar and cerebrocortical white matter and white matter tracts of the brainstem, and the exclusion of other disease processes.

Animals↗

Nucleotide sequence of UK and Australian isolates of feline calicivirus (FCV) and phylogenetic analysis of FCVs.

We have determined the first complete genome sequence and capsid gene sequences of feline calicivirus (FCV) isolates from the UK and Australia. These were compared with other previously published sequences. The viruses used in the comparisons were isolated between 1957 and 1995 from various geographical locations and obtained from cats showing a range of clinical signs. Despite these diverse origins, comparisons between all strains showed a similar degree of sequence variation within both ORF1 (non-structural polyprotein) and ORF2 (major capsid protein) (amino acid distances of 7.7-13.0% and 8.8-18.6%, respectively). In contrast, ORF3 (putative minor structural protein) sequences indicated a more heterogenous distribution of FCV relatedness (amino acid distances of 1.9-17.9%). Phylogenetic analysis suggested that, unlike some other caliciviruses, FCV isolates within the current data set fall into one diverse genogroup. Within this group, there was an overall lack of geographic or temporal clustering which may be related to the epidemiology of FCV infection in cats. Analysis of regions of variability in the genome has shown that, as well as the previously identified variable regions in ORF2, similar domains exist within ORFs 1 and 3 also, although to a lesser extent. In ORF1, these variable domains largely fall between the putative non-structural protein functional domains.

Amino Acid Sequence↗

Clinical sensitivity to anthracyclines in PH/BCR+ acute lymphoblastic leukemia.

Translocation t(9;22) or Philadelphia chromosome (Ph)/BCR-ABL rearrangement positive acute lymphoblastic leukemia (Ph/BCR+ ALL) is associated with a very short survival of about one year in most patients. We analyzed long-term outcome of 76 adults with Ph/BCR+ ALL, in order to detect which factors were associated with longer survival. Modifiable prognostic factors included type of treatment, allogeneic marrow transplant (allo-BMT), and early anthracycline dose intensity (high = H/A, low = L/A); unmodifiable factors were age, gender, FAB morphology, phenotype, blast count, P190/210 transcript, hepatospleno-lymphadenopathy, LDH level. Median patient age was 43 years (range 15-71). Four favorable prognostic factors (FPF) were found associated with greater likelihood of complete remission (blast count < 50 x 10(9)/l, p = 0.08), longer remission duration (age < 50 years, p < 0.001; H/A, p < 0.05), and lower relapse rate (allo-BMT, p = 0.017). Age and anthracycline dose intensity exerted a synergistic prognostic effect. According to the cumulative incidence of FPF in each patient (FPF 0-1 = 29, 2-3 = 42, 4 = 5), the probability of survival increased from nil to 0.22 to 0.60 at 5 years (p < 0.005). Adult Ph/BCR+ ALL is relatively sensitive to anthracyclines, which therefore should be prescribed at full dosage to patients not eligible to allo-BMT or in the waiting list for unrelated donor transplantation.

Adolescent↗

Acute promyelocytic leukaemia: a retrospective analysis of patients treated at St. Bartholomew's Hospital 1969-1995.

Seventy-two patients with acute promyelocytic leukemia (APML) were treated at St.Bartholomew's Hospital (SBH) over a 25-year period. Improvements in supportive care and the use of more intensive chemotherapy have led to an increase in the complete remission rate from 14 to 58%. Similarly, the median survival has increased from 3 weeks to 2 years; the median duration of remission, which was 7 months in 1974, has not yet been reached. There was also a significant difference in survival from first recurrence, compared with that of patients with other subtypes of acute myeloid leukemia. RT-PCR analysis on bone marrow samples from 14 patients confirmed the presence of the PML/RARA fusion; 13 of the 14 patients achieved 'molecular remission' after therapy. The one patient who remained persistently positive experienced recurrence within 4 months. In seven of the eight patients in whom the disease recurred, the translocation was identified by RT-PCR at the time of relapse, whilst in one patient it was noted 4 months prior to morphological recurrence. These results illustrate the improvement in prognosis that occurred over a 25-year period in patients with APML treated at a single centre.

Adult↗

Renilla luciferase as a vital reporter for chloroplast gene expression in Chlamydomonas.

The use of luciferases as reporters of gene expression in living cells has been extended to the chloroplast genome. We show that the luciferase from the soft coral Renilla reniformis (Rluc) can be successfully expressed in the chloroplast of Chlamydomonas reinhardtii. Expression of the rluc cDNA was driven by the promoter and 5' untranslated regions of the atpA gene. Western analysis with an anti-Rluc antibody detected a single polypeptide of 38 kDa in the luminescent cells. This is 3 kDa larger than native Rluc, and suggests that translation of the chimeric mRNA begins at the atpA start codon, 29 codons upstream from the rluc start site. We also show that the luminescence of the transformants was sufficient to enable imaging of colonies using a cooled CCD camera.

5' Untranslated Regions↗