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Biomedical subjects

F Davies

Publications and source records attributed to F Davies.

At least 19 recordsLinked to original sources

Consigning "brutacaine" to history: a survey of pharmacological techniques to facilitate painful procedures in children in emergency departments in the UK.

OBJECTIVE: To determine the proportion of emergency departments in the UK that use modern pharmacological methods of pain and anxiety control in children, such as analgesia with intranasal diamorphine, procedural sedation using ketamine or midazolam, and adrenaline-cocaine gel, TAC or LAT for anaesthetising wounds in children. METHODS: A survey UK Emergency Departments conducted by email, post and telephone. RESULTS: Of the 183 (70%) of UK Emergency Departments responding, sedation is achieved using ketamine in 27% and using midazolam in 54%. In 55% of emergency departments intranasal diamorphine is used for analgesia and 41% use at least one of the topical local-anaesthetic mixtures to anaesthetise wounds before suturing. CONCLUSIONS: About half of UK emergency departments use modern pharmacological methods of procedural pain control in children. There is still considerable potential to improve the management of pain in children.

Administration, Intranasal↗

Immunomodulatory analogs of thalidomide inhibit growth of Hs Sultan cells and angiogenesis in vivo.

We have previously shown that thalidomide and its potent immunomodulatory derivatives (IMiDs) inhibit the in vitro growth of multiple myeloma (MM) cell lines and patient MM cells that are resistant to conventional therapy. In this study, we further characterize the effect of these drugs on growth of B cell malignancies and angiogenesis. We established a beige-nude-xid (BNX) mouse model to allow for simultaneous in vivo measurement of both anti-tumor and anti-angiogenic effects of thalidomide and its analogs. Daily treatment (50 mg/kg/d) with thalidomide or IMiDs was nontoxic. The IMiDs were significantly more potent than thalidomide in vivo in suppressing tumor growth, evidenced by decreased tumor volume and prolonged survival, as well as mediating anti-angiogenic effects, as determined by decreased microvessel density. Our results therefore show that the IMiDs have more potent direct anti-tumor and anti-angiogenic effects than thalidomide in vivo, providing the framework for clinical protocols evaluating these agents in MM and other B cell neoplasms.

Angiogenesis Inhibitors↗

Apparent life threatening events in infants presenting to an emergency department.

OBJECTIVE: To describe the aetiology and outcome of apparent life threatening events (ALTE) presenting to an emergency department (ED), and to assess the value of an initial investigation protocol. DESIGN: A 12 month prospective study of infants under 1 year of age who presented to a children's hospital ED after an ALTE. A standardised history sheet and initial investigation protocol were used. All infants were admitted to hospital and followed up at six months. RESULTS: There were 65 infants recruited, median age 7 weeks. None had died at the time of writing. Diagnoses included gastro-oesophageal reflux n=17 (26%), pertussis, n=6 (9%), seizures, n=6 (9%), urinary tract infection (5), factitious illness (2), brain tumour, atrial tachycardia, persistent ductus arteriosus and opioid related apnoea. No diagnosis was reached in 15 cases (23%). Fifty seven (88%) had only one admission to hospital for ALTE. More serious diagnoses were associated with a presentation age over 2 months, abnormal initial clinical examination, and recurrent ALTE. CONCLUSIONS: ALTEs presenting to the ED may remain as a single, unexplained event or be attributable to numerous causes, ranging from minor to serious. Knowledge of the commoner causes and factors associated with higher risk could result in a more targeted approach, improving the decision making process and benefiting both infants and parents.

Critical Illness↗

AIDS in an HIV-seronegative Ghanaian woman with intersubtype A/G recombinant HIV-1 infection.

A 29-year-old Ghanaian woman who developed AIDS while being HIV-antibody seronegative was investigated during a collaborative study aimed at the identification of viral causes of a HIV-seronegative AIDS syndrome in West Africa. Plasma was screened with a panel of EIA tests for antibodies to HIV and HIV-1 p24 antigen. Retroviral infection was investigated by detection of reverse transcriptase (RT) activity in plasma, viral RNA amplification and quantification, and virus isolation. Positive amplification products were sequenced and phylogenetic analyses were carried out. Most EIA tests were unable to demonstrate the presence of anti-HIV anti-bodies, whereas confirmatory assays yielded inconclusive results. Retroviral infection was documented by detection of RT activity, HIV-1-specific genomic amplification and virus isolation. This virus was HIV-1 subtype A with an unusual six amino acid insertion in the gp120 V4 loop and with the nef gene of subtype G. The patient's plasma did not react with either autologous or heterologous viral lysates or HIV-1 peptides, whereas antibodies to other viral antigens were present. In conclusion, the Ghanaian patient exhibited a rare subtype A/G recombinant HIV-1 infection with a near absence of a HIV-specific humoral response. The lack of detectable antibody response might be due to either a highly pathogenic, rapidly fatal, HIV-1 infection preventing the development of the typical humoral immune response or to a host-related dysfunction of the immune system. Direct antigenemia or genomic detection of the virus should be undertaken when clinical or biological data suggests an HIV infection in the absence of serological evidence.

Acquired Immunodeficiency Syndrome↗

Chronic pain and health care utilization in women with a history of childhood sexual abuse.

OBJECTIVE: This cross-sectional controlled study investigated the association between chronic pain, health care utilization and a history of childhood sexual abuse. SUBJECTS: Three groups, constituting 80 women in total, were studied (1) attendees at group therapy for individuals who had experienced childhood sexual abuse (n = 26); (2) Two control groups consisting of nonabused (a) psychiatric outpatients (n = 33); and (b) nurses (n = 21). SETTING: The setting was a university affiliated community and tertiary care hospital in London. Ontario. OUTCOME MEASURES: Each subject voluntarily completed questionnaires documenting history of childhood abuse, pain, psychological symptomatology and medical and surgical history. RESULTS: Sixty-nine percent of the women who had experienced childhood sexual abuse reported a chronic painful condition lasting more than three months, compared to 43% of the combined control groups (p = .026). Women who had experienced childhood sexual abuse reported a greater number of painful body areas (p = .003), more diffuse pain and more diagnoses of fibromyalgia (p = .013). They had more surgeries (p = .037), hospitalizations (p = .0004) and family physician visits (p = .046). CONCLUSIONS: Women with a history of childhood sexual abuse reported more chronic pain symptoms and utilized more health care resources compared to nonabused control subjects. Identification of such a history in the patient experiencing persisting pain may be the first step toward a successful combination of medical and psychosocial interventions.

Adult↗

Distribution of myeloma plasma cells in peripheral blood and bone marrow correlates with CD56 expression.

There is a wide variation in the degree of marrow and blood involvement between patients with multiple myeloma. Both of these parameters are known to be highly significant prognostic factors, and the differences between patients may be due to variable expression of adhesion molecules. To test this we used three-colour flow cytometry to study three adhesion molecules associated with myeloma, namely CD38, CD56 and CD138. The level of expression of these molecules was compared with the distribution of myeloma plasma cells in bone marrow (n=59) and peripheral blood (n=26) in patients at presentation or relapse. The extent of marrow infiltration on the trephine biopsy correlated inversely with CD56 expression (Mann-Whitney U Test, P=0.022); there was no difference in CD38 or in CD138 expression. CD56 expression also correlated inversely with the number of circulating plasma cells (linear regression, R2=0.4268, slope=-0.58, P=0.0003). Peripheral blood plasma cell numbers correlated weakly with bone marrow plasmacytosis, and inversely with CD38 expression. The level of CD56 expression by neoplastic plasma cells was assessed in 37 patients over a median of 11 months (range 6-25). There was no significant change in expression (Wilcoxon Signed Rank, P=0.6271). We conclude that plasma cell CD56 expression is constant over the course of the disease; unlike CD138 expression, it is significantly linked to the degree of both bone marrow and peripheral blood involvement.

Bone Marrow↗

Apparent life-threatening events presenting to a pediatric emergency department.

OBJECTIVE: To review the etiology, clinical decision-making process, and outcomes of apparent life-threatening events (ALTEs) presenting to a children's hospital emergency department (ED). DESIGN: Retrospective patient record review. SUBJECTS: One hundred thirty infants under the age of 1 year fulfilling the diagnostic definition of an apparent life-threatening event. RESULTS: In a calendar year, 130 infants presented to a large children's hospital ED. The total number of ALTEs studied was 196. The median age was 2 months, and 50% of infants had a normal clinical examination. Eighty-three percent of ALTEs resulted in admission to the hospital. The approach to investigation and management of an ALTE during admission appeared unstructured. Discharge diagnoses, both from the ED and the inpatient service, were numerous, the most common being convulsion, febrile convulsion, GOR, and lower respiratory tract infection. The diagnosis frequently changed in those attending more than once. Eighteen months after cessation of data collection, no infants had died. Follow-up information revealed a higher-than-expected prevalence of asthma and seizures. CONCLUSIONS: This is a diverse group of infants, many of whom appear normal following the ALTE. There are many possible diagnoses, but diagnosis correlates poorly with presenting symptoms. It also appears that many commonly performed investigations conducted in this group of infants may not be those that are most helpful for diagnosis, and doctors may be making diagnoses with little supportive evidence. Until research on this group of "first-presentation" infants provides management guidelines for family and emergency doctors, it may be prudent to advise that all such infants presenting with an ALTE should be admitted for a period of observation and further investigation. This would help ensure more accurate diagnosis, as well as provide reassurance for the family.

Apnea↗

Novel and recurrent mutations in the PKD1 (polycystic kidney disease) gene.

A search has been conducted for disease-causing mutations in the PKD1 gene in 147 unrelated ADPKD index cases. Using the polymerase chain reaction with primer pairs located in the 3' single copy region of the gene and single-strand conformation polymorphism analysis, we detected novel aberrant bands in five individuals that were absent in 100 control samples. Sequencing revealed three nonsense mutations (Q4010X, E4024X, Q4041X), a frameshift mutation (12262 del 2 bp), and a missense mutation (G4031D). In addition, three polymorphisms were detected [12346 + 19delG, heterozygosity (0.13), I4044V (0.23), 12212-34C > A (0.07)]. The mutational mechanism for the recurrent mutation (Q4041X) is likely to be slipped mispairing of an adjacent direct imperfect repeat sequence.

Amino Acid Substitution↗

Working models of attachment and representations of the object in a clinical sample of sexually abused women.

This study examined internal working models of attachment as assessed by the Adult Attachment Interview (AAI; George, Kaplan, & Main, 1984) and self-other differentiation as assessed by the Description of Significant Other (Marziali & Oleniuk, 1990) in a clinical sample of 40 women reporting a history of childhood sexual abuse. Although there was some relationship between the two measures, the association was not strong. The Cannot Classify category of the AAI, which is increasingly being assigned in clinical samples, needs refinement to increase the usefulness of the AAI for clinical purposes. Integration of concepts from objects relations theory may also enhance the value of the AAI in studies of clinical samples.

Adult↗

Detection and quantitation of the CBFbeta/MYH11 transcripts associated with the inv(16) in presentation and follow-up samples from patients with AML.

We have developed a competitor-based RT-PCR technique which will detect and quantitate the CBFbeta/MYH11 transcripts associated with inv(16)(q22;p13) and have used it to study presentation and follow-up samples of acute myeloid leukaemia (AML). The levels of the leukaemia-specific transcripts are expressed as a ratio to a ubiquitously expressed mRNA species (Abl) which controls for RNA degradation. This technique has been applied to 75 consecutive patients presenting with either de novo AML or tMDS; 6/75 patients analysed were positive for the inv(16), all were confirmed by conventional cytogenetics. The inv(16) has a strong association with M4Eo, but we found only 2/6-positive patients to have this diagnosis (two patients with M2, one patient M1 and one patient had MDS). At presentation the levels of CBFbeta/MYH11 transcripts were 0.1-10/Abl transcript (mean 3.3/Abl transcript). Seventeen follow-up samples were available on 5/6 of these patients, and on two further patients in whom stored material was available. Following the first cycle of chemotherapy the level of transcripts was at least 10(-2) lower (0.1-10 x 10(-2)/abl transcript) than their presentation sample. Subsequent samples on these patients when in remission gave transcript levels in the range (1.0 x 10(-4) - 2 x 10(-3)/abl transcript), and three long-term follow-up samples were negative. We have developed a quantitative test which opens the possibility of predicting relapse by detecting changes in the numbers of leukaemia-specific transcripts.

Acute Disease↗

How we did it: the development of a specialist registrar training programme by the Mersey Accident and Emergency Trainees' Association.

Over the last three years the accident and emergency trainees in Merseyside have developed a self directed training programme which now consists of twice monthly meetings. This has been achieved through a process of evolution, shaped by the core curriculum, and supervised by the region's consultants with the support of the postgraduate dean. The meetings have proved both popular and valuable. The development and format of the scheme is presented in the hope of stimulating others to work together to improve the training of specialist registrars.

Clinical Competence↗

p53 gene mutations in multiple myeloma.

AIM: To assess whether p53 gene mutation is important in the pathogenesis and progression of multiple myeloma. METHODS: Thirty eight DNA samples (derived predominantly from bone marrow) obtained from 31 patients with multiple myeloma were examined for mutations in p53 exons 5-9 by polymerase chain reaction single strand conformation polymorphism. Twenty three samples were analysed at the time of diagnosis (one patient had plasma cell leukaemia), three in plateau phase, and 12 at relapse (one plasma cell leukaemia and one extramedullary relapse). RESULTS: One p53 mutation was detected in this group of patients (3.2%). This was seen in the diagnostic bone marrow sample of a 35 year old man with stage IIA disease and occurred in exon 6 as a result of a silent A to G transition at codon 213 (CGA-->CGG), a polymorphism that has been reported in about 3% of breast and lung tumours. CONCLUSIONS: p53 gene mutations are rare events in multiple myeloma and would seem to be of limited value as a prognostic factor.

Adult↗

Relationship of obsessive-compulsive symptomatology to anxiety, depression and schizotypy in a clinical population.

The relationship of obsessive-compulsive symptomatology to anxiety disorders, mood disorders and schizophrenia continues to be controversial. In a sample of 117 psychiatric out-patients, we examined the relationship of obsessive-compulsive symptomatology to indices of anxiety, depression and schizotypy. The relationship between obsessive-compulsive symptomatology and schizotypy was found to be significantly higher than that between obsessive-compulsive symptoms and either anxiety or depression. These findings are consistent with recent studies suggesting that there are similar cognitive deficits associated with obsessive-compulsive symptoms and schizotypy and that obsessive-compulsive disorders may be more closely aligned to the schizophrenic constellation of disorders than to anxiety disorders.

Adult↗