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Biomedical subjects

M Holmes

Publications and source records attributed to M Holmes.

At least 37 records · Page 2Linked to original sources
PubMed2001

Evaluation of particle size distribution of salmeterol administered via metered-dose inhaler with and without valved holding chambers.

BACKGROUND: Administration of inhaled medications to very young children is sometimes difficult. Administration of inhaled medications via metered dose inhalers (MDIs) to pediatric patients younger than 4 years of age requires use of a holding chamber/spacer with an attached facemask. OBJECTIVE: This in vitro study was conducted to determine the particle size distribution and overall dose of salmeterol delivered in conjunction with the use of various US-marketed valved holding chambers (VHCs) in comparison to the dose-delivered via MDI without VHCs. METHODS: Cascade impaction methodology with high-performance liquid chromatography was used to evaluate the fine particle mass (FPM) of salmeterol administered without and with the use of the following VHCs: Optichamber, medium and large Aerochambers, adult Aerochamber, and medium Aerochamber Plus. RESULTS: Particle size distributions for the Optichamber, various sizes of Aerochamber, and the Aerochamber Plus were very similar and the particle size distributions for all VHCs were similar to the distribution of the control. The FPM for particles ranging from 0.7 to <3.3 microm in diameter (in the range shown to provide the greatest lung dose to negotiate the small airways of infants) was similar across the various VHCs tested. Statistical comparison of the fine particle fraction for these stages shows a very similar profile when differences from the salmeterol MDI control were evaluated. CONCLUSIONS: In vitro results obtained under these test conditions demonstrate that all FPM values for the VHCs tested were within 15% of the control range, a difference that is unlikely to be clinically meaningful. These results indicate that the difference in FPM does not warrant a change in the recommended dosage of salmeterol administered when using the VHCs tested. Our results demonstrate that the use of an MDI and VHC provides a reasonable therapeutic approach for administration of salmeterol MDI to young children and other patients who have difficulties administering the MDI alone.

Administration, Inhalation↗
PubMed2001

A mouse Mecp2-null mutation causes neurological symptoms that mimic Rett syndrome.

Rett syndrome (RTT) is an inherited neurodevelopmental disorder of females that occurs once in 10,000-15,000 births. Affected females develop normally for 6-18 months, but then lose voluntary movements, including speech and hand skills. Most RTT patients are heterozygous for mutations in the X-linked gene MECP2 (refs. 3-12), encoding a protein that binds to methylated sites in genomic DNA and facilitates gene silencing. Previous work with Mecp2-null embryonic stem cells indicated that MeCP2 is essential for mouse embryogenesis. Here we generate mice lacking Mecp2 using Cre-loxP technology. Both Mecp2-null mice and mice in which Mecp2 was deleted in brain showed severe neurological symptoms at approximately six weeks of age. Compensation for absence of MeCP2 in other tissues by MeCP1 (refs. 19,20) was not apparent in genetic or biochemical tests. After several months, heterozygous female mice also showed behavioral symptoms. The overlapping delay before symptom onset in humans and mice, despite their profoundly different rates of development, raises the possibility that stability of brain function, not brain development per se, is compromised by the absence of MeCP2.

Animals↗
PubMed2001

Interleukin-4 and tumour necrosis factor-alpha inhibit transforming growth factor-beta production in a human bronchial epithelial cell line: possible relevance to inflammatory mechanisms in chronic obstructive pulmonary disease.

OBJECTIVE: Human bronchial epithelial cells are known to secrete an array of inflammatory cytokines including tumour necrosis factor-alpha (TNF-alpha) and interleukin (IL)-4, which may play a role in immune responses in lung diseases such as chronic obstructive pulmonary disease (COPD). However, the regulatory mechanisms governing cytokine production in bronchial epithelia in COPD are largely unknown. Transforming growth factor-beta (TGF-beta) is an anti-inflammatory cytokine and is involved in airway repair. The purpose of this study was to study the effect of TNF-alpha and IL-4 (pro-inflammatory cytokines known to be up-regulated in COPD), on the production of TGF-beta (a negative regulator of inflammation) by epithelial cells. METHODOLOGY: A bronchial epithelial cell line was used as an in vitro culture model (16HBE). Cell cultures were stimulated with various combinations of TNF-alpha and IL-4 (20 ng/mL) for 24 h. Transforming growth factor-beta production was measured by flow cytometry, enzyme-linked immunosorbent assay and immunohistochemistry. RESULTS: Exposure to TNF-alpha significantly up-regulated production of IL-4 from cultured epithelial cells. Unstimulated cells spontaneously released TGF-beta. Exposure to TNF-alpha and IL-4 significantly inhibited production of TGF-beta. The inhibitory effects of TNF-alpha and IL-4 on TGF-beta synthesis were summative. CONCLUSIONS: The inhibitory effect of IL-4 and TNF-alpha on production of the regulatory cytokine TGF-beta in a bronchial epithelial cell line suggests that such mechanisms may contribute to the progression of the inflammatory response and compromise repair processes in inflammatory lung diseases such as COPD.

Bronchi↗
PubMed2001

Flexible cystoscopy: is the volume and content of the urethral gel critical?

PURPOSE: To determine whether volume (10 or 20mL) or the presence of 2% lidocaine (lignocaine) in the gel used for urethral lubrication alters the discomfort felt during flexible cystoscopy. PATIENTS AND METHODS: A randomized double-blind trial was performed in men attending for flexible cystoscopy. Patients were assigned to one of four groups: 10 mL of gel with or without lidocaine and 20 mL with or without lidocaine. Gel was retained for 10 minutes prior to cystoscopy. Pain felt during both the instillation of the gel and the cystoscopy itself was evaluated using a visual analog scale (0-10). RESULTS: Interim analysis after 147 patients had been recruited revealed a significant difference between the groups in terms of the pain felt on instillation of the gel, leading to an early termination of the trial. There was a significant reduction in pain on cystoscopy in patients receiving 20 mL of gel if this contained lidocaine. CONCLUSION: The least pain on cystoscopy occurred in patients receiving 20 mL of gel containing lidocaine.

Aged↗
PubMed2001

Predictors of medical examinations following child and adolescent rapes in a national sample of women.

Childhood rape occurs frequently in our society and is associated with adverse consequences. Despite the severity of these outcomes, there appear to be many obstacles for children to receive postrape medical care. To date, it is unclear what proportion of childhood rape victims receive postrape medical examination or what factors predict receipt of this medical care. This study instigated the factors predicting immediate medica care for women who were raped during childhood. Data for the study were obtained from the final wave of the 2-year, longitudinal National Women's Study. Results indicated that the majority of women did not receive medical care following their childhood rape. Although women raped as adolescents were more likely to receive a postrape exam, logistic regression analyses indicated that rape characteristics (e.g., reporting the assault, concerns about sexually transmitted diseases [STDs]) mediated the relationship between age of victimization and receipt of medical care. Implications of these findings are discussed.

Adolescent↗
PubMed2000

Eos and pegasus, two members of the Ikaros family of proteins with distinct DNA binding activities.

Members of the Ikaros family of transcription factors, Ikaros, Aiolos, and Helios, are expressed in lymphocytes and have been implicated in controlling lymphoid development. These proteins contain two characteristic clusters of zinc fingers, an N-terminal domain important for DNA recognition, and a C-terminal domain that mediates homo- and heterotypic associations between family members. The conservation of these domains is such that all three proteins recognize related DNA sequences, and all are capable of dimerizing with other family members. Here we describe two additional Ikaros family proteins, Eos and Pegasus. Eos is most highly related to Helios and shares its DNA binding and protein association properties. Pegasus is related to other Ikaros proteins in its C-terminal dimerization domain but contains a divergent N-terminal zinc finger domain. Pegasus self-associates and binds to other family members but recognizes distinct DNA-binding sites. Eos and Pegasus repress the expression of reporter genes containing their recognition elements. Our results suggest that these proteins may associate with previously described Ikaros family proteins in lymphoid cells and play additional roles in other tissues.

3T3 Cells↗
PubMed2000

Vagus nerve stimulation therapy for epilepsy in older adults.

The authors assessed the efficacy, safety, and tolerability of vagus nerve stimulation (VNS) for refractory epilepsy in 45 adults 50 years of age and older. They determined seizure frequency, adverse effects, and quality of life. At 3 months, 12 patients had a >50% decrease in seizure frequency; at 1 year, 21 of 31 studied individuals had a >50% seizure decrease. Side effects were mild and transient. Quality of life scores improved significantly with time.

Electric Stimulation↗
PubMed2000

Emergency evaluation and intervention with female victims of rape and other violence.

Given the high prevalence of crime within the general population and the increased rates of victimization among those seeking medical care, professionals who work in emergency departments, primary care medical facilities, or mental health settings need to be prepared to address physical and psychological problems related to sexual and physical assault. In this paper, interpersonal violence prevalence studies are reviewed in terms of study design and findings for sexual assault and physical assault. Common injuries following both forms of assault are documented, followed by a review of long-term medical outcomes. In addition to a review of physical health outcomes, primary psychological effects of violence are also reviewed. Strategies with which to screen for interpersonal violence in the medical setting are offered, and issues related to mandatory reporting are summarized. Interventions for assault victims that can be implemented in the medical setting are outlined, and a new hospital-based treatment for victims of rape is described.

Crisis Intervention↗
PubMed2000

The 1.9 A crystal structure of the "as isolated" rubrerythrin from Desulfovibrio vulgaris: some surprising results.

Rubrerythrin is a non-heme iron dimeric protein isolated from the sulfate-reducing bacterium Desulfovibrio vulgaris. Each monomer has one mononuclear iron center similar to rubredoxin and one dinuclear metal center similar to hemerythrin or ribonucleotide reductase. The 1.88 A X-ray structure of the "as isolated" molecule and a uranyl heavy atom derivative have been solved by molecular replacement techniques. The resulting model of the native "as isolated" molecule, including 164 water molecules, has been refined giving a final R factor of 0.197 (R(free) = 0.255). The structure has the same general protein fold, domain structure, and dimeric interactions as previously found for rubrerythrin [1, 2], but it also has some interesting undetected differences at the metal centers. The refined model of the protein structure has a cis peptide between residues 78 and 79. The Fe-Cys4 center has a previously undetected strong seventh N-H...S hydrogen bond in addition to the six N-H...S bonds usually found in rubredoxin. The dinuclear metal center has a hexacoordinate Fe atom and a tetracoordinate Zn atom. Each metal is coordinated by a GluXXHis polypeptide chain segment. The Zn atom binds at a site distinctly different from that found in the structure of a diiron rubrerythrin. Difference electron density for the uranyl derivative shows an extremely large peak adjacent to and replacing the Zn atom, indicating that this particular site is capable of binding other atoms. This feature/ability may give rise to some of the confusing activities ascribed to this molecule.

Bacterial Proteins↗
PubMed2000

Short-term effects of cervical manipulation on edge light pupil cycle time: a pilot study.

BACKGROUND: Edge light pupil cycle time (ELPCT) is one of the eye's light reflexes. Studies have shown ELPCT to be a measurable constant, unaffected by visual acuity, refractive error, eye color, pupil size, or sex. Control of this reflex occurs through the autonomic nervous system. Various authors suggest that spinal manipulative techniques can produce distant effects mediated in part by alterations in autonomic tone after intervention. OBJECTIVE: To investigate the effects of a C1-2 high-velocity, low-amplitude manipulation on ELPCT. DESIGN: A single-group, randomized pilot study without a control group. METHODS: Thirteen men (mean age 24.2 years) without a history of eye disease or central or autonomic nervous system pathologic conditions had their ELPCT measured before and after manipulation. The manipulation comprised a high-velocity, low-amplitude rotatory thrust, localized to the C1-2 joint on the left (n = 6) or right (n = 7) eye, determined randomly. RESULTS: ELPCT measures demonstrated a significant difference for both eyes before and after manipulation (P = .002; the right eye, P = .027; the left eye, P = .046). CONCLUSION: This suggests that ELPCT, which is mediated through the autonomic nervous system, can be directly influenced by high-velocity manipulation to the upper cervical spine.

Adolescent↗
PubMed2000

Hepatic resection for colorectal liver metastases: A cost-effectiveness analysis.

OBJECTIVE: To analyze the cost-effectiveness of resection for liver metastases compared with standard nonsurgical cytotoxic treatment. SUMMARY BACKGROUND DATA: The efficacy of hepatic resection for metastases from colorectal cancer has been debated, despite reported 5-year survival rates of 20% to 40%. Resection is confined to specialized centers and is not widely available, perhaps because of lack of appropriate expertise, resources, or awareness of its efficacy. The cost-effectiveness of resection is important from the perspective of managed care in the United States and for the commissioning of health services in the United Kingdom. METHODS: A simple decision-based model was developed to evaluate the marginal costs and health benefits of hepatic resection. Estimates of resectability for liver metastases were taken from UK-reported case series data. The results of 100 hepatic resections conducted in Sheffield from 1997 to 1999 were used for the cost calculation of liver resection. Survival data from published series of resections were compiled to estimate the incremental cost per life-year gained (LYG) because of the short period of follow-up in the Sheffield series. RESULTS: Hepatic resection for colorectal liver metastases provides an estimated marginal benefit of 1.6 life-years (undiscounted) at a marginal cost of 6,742 pound sterling++. If 17% of patients have only palliative resections, the overall cost per LYG is approximately 5,236 pound sterling (5,985 pound sterling with discounted benefits). If potential benefits are extended to include 20-year survival rates, these figures fall to approximately 1,821 pound sterling (2,793 pound sterling with discounted benefits). Further univariate sensitivity analysis of key model parameters showed the cost per LYG to be consistently less than 15,000 pound sterling. CONCLUSION: In this model, hepatic resection appears highly cost-effective compared with nonsurgical treatments for colorectal-related liver metastases.

Analysis of Variance↗
PubMed2000

Randomised controlled trial of two pressure-relieving systems.

The primary objective of this randomised controlled trial was to determine whether there were significant differences between two pressure-relieving systems. A secondary aim was to investigate whether the availability of extra pressure-relieving equipment would reduce the incidence of ulcers in an acute hospital setting. A total of 141 patients in a care-of-the-elderly unit, who were assessed to have a high risk of developing pressure ulcers using the Waterlow score, were recruited; 70 were nursed using Huntleigh Nimbus 3 in conjunction with the Aura cushion (Group A), and 71 using the Pegasus Cairwave Therapy System in conjunction with the Proactive 2 Seating cushion (Group B). The main outcome measure was visual assessment, supported by a photographic record. There were three main findings: for non-heel ulcers and overall improvement, there was no statistically significant difference between the two products tested; for heel ulcers there was a significant difference (P = 0.019) with more patients healing in Group A than in Group B. The average length of stay of patients who completed the trial was 21.6 days (Group A) and 21.7 days (Group B) for patients completing a live (range 1-121 days) and for patients who died 29.7 days (Group A) and 24.3 days (Group B). Routine monitoring showed that, before the trial, the incidence of hospital-acquired pressure ulcers (Torrance grade 2+) was 0.2%; during the trial, this dropped to 0.13%. The study showed differences in the efficacy of different mattress products; with a sufficiently large study, it is possible to demonstrate statistically significant results. Provision of extra pressure-relieving equipment can reduce the incidence of pressure ulcers but may not influence length of stay.

Aged↗
PubMed2000

A review of mind/body therapies in the treatment of musculoskeletal disorders with implications for the elderly.

BACKGROUND: A comprehensive, but not systematic, review of the research on complementary and alternative treatments, specifically mind/body techniques, on musculoskeletal disease was conducted at Stanford University. The goals of the review were to establish a comprehensive literature review and provide a rationale for future research carrying the theme of "successful aging." METHODS: Computerized searches were conducted using MEDLINE, PsychInfo, Stanford Library, Dissertation Abstracts, Lexus-Nexus, the Internet as well as interviews conducted with practitioners and the elderly. Mind/body practices evaluated were: social support, cognitive-behavioral therapy, meditation, the placebo effect, imagery, visualization, spiritual/energy healing, music therapy, hypnosis, yoga, tai chi, and qigong. Studies published after 1990 were the priority, but when more recent literature was scarce, other controlled studies were included. RESULTS: Mind/body techniques were found to be efficacious primarily as complementary treatments for musculoskeletal disease and related disorders. Studies provided evidence for treatment efficacy but most apparent was the need for further controlled research. CONCLUSIONS: Reviewers found a dearth of randomized controlled research conducted in the US. There is a lack of studies with which to determine appropriate dosage and understand the mechanisms by which many of the practices work. Anecdotal evidence, some controlled research, clinical observation, as well as the cost effectiveness and lack of side effects of the mind/body treatments make further investigation a high priority.

Aged↗
PubMed1999

hFOG-2, a novel zinc finger protein, binds the co-repressor mCtBP2 and modulates GATA-mediated activation.

We have identified a novel human zinc finger protein, hFOG-2, which is related to but distinct from the murine transcription factor Friend-of-GATA-1 (mFOG-1). The hFOG-2 gene was initially detected in K562 cells using a polymerase chain reaction approach with degenerate primers corresponding to zinc finger regions of mFOG-1. A murine homologue of hFOG-2 was also identified in the mouse expressed sequence tag data banks, indicating that a family of FOG genes exists in mammals. hFOG-2 appears to be widely expressed, while mFOG-1 is expressed primarily in erythroid and megakaryocytic cells and plays a fundamental role in the development of these lineages. Sequencing of the full-length hFOG-2 cDNA indicates that the interaction domains for transcription factors GATA-1 and mCtBP2 are both conserved and we have shown that this new FOG protein also physically interacts with these factors. We have demonstrated that hFOG-2, like mFOG-1, can act in concert with GATA-1 to activate gene expression from the p45 NF-E2 promoter region, but that it can also act to repress GATA-mediated activation of additional reporter constructs. Finally, we have identified a repression domain in hFOG-2 and show that repression is dependent upon the integrity of the mCtBP2 interaction motif Pro-Ile-Asp-Leu-Ser.

Alcohol Oxidoreductases↗
PubMed1999

Intraspinal and behavioral consequences of nerve growth factor-induced nociceptive sprouting and nerve growth factor-induced hyperalgesia compared in adult rats.

Intraspinal and behavioral events were studied in adult rats with nociceptive nerves that were undergoing collateral sprouting into adjacent denervated skin. This sprouting, which is driven by endogenous nerve growth factor (NGF), did not cause hyperalgesia. For comparison, we studied an exogenous NGF administration that induced hyperalgesia but was too brief to evoke sprouting. When nociceptive nerves sprouted in skin, back-labeling with wheat germ agglutinin-conjugated horseradish peroxidase revealed that their projections sprouted in the cord. The sprouted peripheral nerves now activated more c-Fos-containing interneurons, which stimulus-response studies showed was not due to an increased afferent discharge. We attribute the interneuron recruitment to synaptogenesis following the intraspinal sprouting. Nociceptive stimulation of dorsal skin reflexly activates underlying cutaneous trunci muscle (CTM). When a nociceptive field expanded by nerve sprouting, so did the area of the evoked CTM reflex: this implies a recruitment of CTM motoneurons. We interpret this "matching" of response to stimulus as an adaptive phenomenon ensured by an adaptive intraspinal sprouting of the nociceptive projections. Neither the intraspinal changes nor the reflex changes occurred if peripheral sprouting was blocked by systemic anti-NGF treatment, indicating that the role of endogenous NGF was only in that sprouting. No comparable adaptive events occurred during NGF-induced hyperalgesia. Neither nociceptive fields nor CTM reflexes were affected; however there was a recruitment of c-Fos-expressing interneurons. This recruitment was not explained by peripheral sensitization, and, because sprouting was not involved here, we attribute the recruitment to "synaptic unmasking," i.e., an increased effectiveness of the preexisting excitatory circuitry.

Adaptation, Physiological↗
PubMed1999

Transcriptional cofactors of the FOG family interact with GATA proteins by means of multiple zinc fingers.

Friend of GATA-1 (FOG-1) is a zinc finger protein that has been shown to interact physically with the erythroid DNA-binding protein GATA-1 and modulate its transcriptional activity. Recently, two new members of the FOG family have been identified: a mammalian protein, FOG-2, that also associates with GATA-1 and other mammalian GATA factors; and U-shaped, a Drosophila protein that interacts with the Drosophila GATA protein Pannier. FOG proteins contain multiple zinc fingers and it has been shown previously that the sixth finger of FOG-1 interacts specifically with the N-finger but not the C-finger of GATA-1. Here we show that fingers 1, 5 and 9 of FOG-1 also interact with the N-finger of GATA-1 and that FOG-2 and U-shaped also contain multiple GATA-interacting fingers. We define the key contact residues and show that these residues are highly conserved in GATA-interacting fingers. We examine the effect of selectively mutating the four interacting fingers of FOG-1 and show that each contributes to FOG-1's ability to modulate GATA-1 activity. Finally, we show that FOG-1 can repress GATA-1-mediated activation and present evidence that this ability involves the recently described CtBP co-repressor proteins that recognize all known FOG proteins.

Alcohol Oxidoreductases↗
PubMed1999

Gartner's duct cyst with unilateral renal dysplasia presenting as an introital mass in a new born.

A persistent Gartner's duct cyst associated with ipsilateral renal agenesis or dysplasia is rare. A vaginal cyst at the introitus as the presenting complaint is very rare, and has not been previously described in a neonate. Sepsis despite the presence of renal agenesis, or non- or poorly functioning renal tissue, is an indication for ureterectomy or nephroureterectomy on the affected side.

Cysts↗