Biomedical subjects

Carlos Martinez

Publications and source records attributed to Carlos Martinez.

11 recordsLinked to original sources

PubMed2006

The impact of a diagnosis of fibromyalgia on health care resource use by primary care patients in the UK: an observational study based on clinical practice.

OBJECTIVE: To investigate the impact of a diagnosis of fibromyalgia (FM) in clinical practice on health care resource use in the UK. METHODS: Rates of visits, prescriptions, referral, and diagnostic testing were estimated in patients who had been diagnosed as having FM between 1998 and March 2003 in UK primary care and compared with those in matched controls. Rates were calculated in 6-month intervals from 10 years before until 4 years after the FM diagnosis. RESULTS: Patients (2260) were newly diagnosed as having FM; 81.3% were women. Their mean age was 49 years. FM patients had considerably higher rates of visits, prescriptions, and testing from at least 10 years prior to diagnosis compared with controls. By the time of diagnosis, FM patients had 25 visits and 11 prescriptions per year compared with 12 visits and 4.5 prescriptions per year in controls. Visit rates were highest for depression, followed by fatigue, chest pain, headache, and sleep disturbance. Following diagnosis, visits for most symptoms and health care use markers declined, but within 2-3 years, most visits rose to levels at or higher than those at diagnosis. CONCLUSION: Primary care patients who had been diagnosed as having FM reported higher rates of illness and health care resource use for at least 10 years prior to their diagnosis, which suggests that illness behavior may play a role. Being diagnosed as having FM may help patients cope with some symptoms, but the diagnosis has a limited impact on health care resource use in the longer term, possibly because there is little effective treatment.

Adolescent↗

PubMed2006

An algorithm to derive a numerical daily dose from unstructured text dosage instructions.

PURPOSE: The General Practice Research Database (GPRD) is a database of longitudinal patient records from general practices in the United Kingdom. It is an important data source for pharmacoepidemiology studies, but until now it has been tedious to calculate the daily dose and duration of exposure to drugs prescribed. This is because general practitioners routinely record dosage instructions as free text rather than in a structured way. The objective was to develop and assess the validity of an automated algorithm to derive the daily dose from text dosage instructions. METHODS: A computer program was developed to derive numerical information from unstructured text dosage instructions. It was tested on dosage texts from a random sample of one million prescription entries. A random sample of 1,000 of these converted texts were manually checked for their accuracy. RESULTS: Out of the sample of one million prescription entries, 74.5% had text containing the daily dose, 14.5% had text but did not include a quantitative daily dose statement and 11.0% had no text entered. Of the 1000 texts which were checked manually, 767 stated the daily dose. The program interpreted 758 (98.8%) of these correctly, produced errors in four cases and failed to extract the dose from five texts. CONCLUSIONS: An automated algorithm has been developed which can accurately extract the daily dose from almost 99% of general practitioners' text dosage instructions. It increases the utility of GPRD and other prescription data sources by enabling researchers to estimate the duration of drug exposure more efficiently.

Adverse Drug Reaction Reporting Systems↗

PubMed2005

Controlled electrophoretic patterning of polyaniline from a colloidal suspension.

We present a method for controlled deposition of polyaniline from colloidal suspensions. Stable suspensions of polyaniline colloids (approximately 115 nm in diameter) were formed by dispersing polyaniline/formic acid solution into acetonitrile. It was demonstrated that the positively charged polyaniline colloids can be electrophoretically deposited onto various substrate materials such as platinum and ITO, forming continuous ultrathin films. We examined the film morphology, as well as the effects of process parameters, such as deposition time, colloid concentration, and applied voltage, on the deposition efficiency. Furthermore, the efficacy of the technique was illustrated by electrophoretically patterning polyaniline thin films onto selected individual micrometer-scale sensing elements within a microfabricated sensor array, and by further demonstrating its sensitivity to gaseous analytes including water and methanol.

Journal Article↗

PubMed2005

Antidepressant treatment and the risk of fatal and non-fatal self harm in first episode depression: nested case-control study.

OBJECTIVE: To compare the risk of non-fatal self harm and suicide in patients taking selective serotonin reuptake inhibitors (SSRIs) with that of patients taking tricyclic antidepressants, as well as between different SSRIs and different tricyclic antidepressants. DESIGN: Nested case-control study. SETTING: Primary care in the United Kingdom. PARTICIPANTS: 146,095 individuals with a first prescription of an antidepressant for depression. MAIN OUTCOME MEASURES: Suicide and non-fatal self harm. RESULTS: 1968 cases of non-fatal self harm and 69 suicides occurred. The overall adjusted odds ratio of non-fatal self harm was 0.99 (95% confidence interval 0.86 to 1.14) and that of suicide 0.57 (0.26 to 1.25) in people prescribed SSRIs compared with those prescribed tricyclic antidepressants. We found little evidence that associations differed over time since starting or stopping treatment. We found some evidence that risks of non-fatal self harm in people prescribed SSRIs compared with those prescribed tricyclic antidepressants differed by age group (interaction P = 0.02). The adjusted odds ratio of non-fatal self harm for people prescribed SSRIs compared with users of tricylic antidepressants for those aged 18 or younger was 1.59 (1.01 to 2.50), but no association was apparent in other age groups. No suicides occurred in those aged 18 or younger currently or recently prescribed tricyclic antidepressants or SSRIs. CONCLUSION: We found no evidence that the risk of suicide or non-fatal self harm in adults prescribed SSRIs was greater than in those prescribed tricyclic antidepressants. We found some weak evidence of an increased risk of non-fatal self harm for current SSRI use among those aged 18 or younger. However, preferential prescribing of SSRIs to patients at higher risk of suicidal behaviour cannot be ruled out.

Adolescent↗

PubMed2004

The general practice research database: role in pharmacovigilance.

The General Practice Research Database (GPRD) is the world's largest computerised database of anonymised longitudinal clinical records from primary care. The database already has an international reputation in the field of drug safety signal evaluation where the results of GPRD-based pharmacoepidemiological studies have been used to inform regulatory pharmacovigilance decision making. The characteristics and richness of the data are such that the GPRD is likely to prove a key data resource for the proactive pharmacovigilance anticipated in risk management and pharmacovigilance plans. An update of recent developments to the database and new data available from it -- including spontaneously recorded suspected adverse drug reactions -- is presented in the article, with a description of how the data can be used to support a variety of pharmacovigilance applications. The possibility of using the GPRD in signal detection and assessment of the impact of pharmacovigilance activities in the future is also discussed.

Adverse Drug Reaction Reporting Systems↗

PubMed2004

Activated lactoferrin and fluconazole synergism against Candida albicans and Candida glabrata vaginal isolates.

OBJECTIVE: To evaluate the fungistatic activity of activated lactoferrin (ALF), fluconazole (FCN) individually and in combination against Candida vaginal isolates as well as to measure the time to recovery from the fungistatic effects after exposure in vitro to threshold minimal inhibitory concentrations (MIC). STUDY DESIGN: Fungistasis patterns for ALF (2.5 mg/mL) and FCN (0.25 mg/mL) were tested at threshold MIC against vaginal isolates of C albicans (n = 5) and C glabrata (n = 5) grown in Sabouraud's dextrose broth against 10(5) yeast inoculum at 37 degrees C for 48 hours by microscale optical density (OD) assay according to the following criteria: "Total stasis" indicates that an agent elicited no change or a change in turbidity <0.1 OD unit for >48 hours (complete growth inhibition), "stasis recovery" (SR) is the time point at which turbidity of a previous stasis system shows an upward growth trend for >0.1 OD unit (recovery from growth inhibition), and "partial stasis" (PS) is proliferation after stasis recovery, measured as a percentage relative to growth control at any time (incomplete growth inhibition). RESULTS: For ALF (2.5 mg/mL), the mean SR time was 15.6 +/- 2 hours for C albicans (n = 5) and 27.5 +/- 2 hours for C glabrata (n = 5). The SR patterns for FCN were strain dependent and showed a wide range of deviation for both Candida species; accordingly, the values were 15.8 +/- 9 hours for C albicans and 25.5 +/- 12 hours for C glabrata. After 48 hours exposure to C albicans, ALF and FCN elicited a mean PS of 27.5 +/- 2% and 24.8 +/- 7%, respectively. The PS values at 48 hours showed a marked variation between C glabrata isolates, 29.1 +/- 24% for ALF and 21.5 +/- 38% for FCN. However, a combination of ALF and FCN at their threshold MIC showed significant drug synergism, causing total stasis of both species of Candida isolates. Thus, no SR for any Candida isolate was detected at or beyond 48 hours. Conversely, native lactoferrin failed to demonstrate such potent synergism with FCN against either Candida species. CONCLUSION: The combination of ALF and FCN at the threshold MIC elicited potent synergism, leading to total fungistasis of C albicans and C glabrata vaginal pathogens. ALF is a new class of fungistatic agent with a mode of action distinct from that of azoles.

Analysis of Variance↗

PubMed2004

Activated lactoferrin's ability to inhibit Candida growth and block yeast adhesion to the vaginal epithelial monolayer.

OBJECTIVE: To study in vitro growth-inhibitory effects of activated lactoferrin (ALF) against vaginal isolates of Candida species and to measure the ability of ALF to block interactions of Candida albicans and Candida glabrata to the vaginal epithelial (VE) monolayer. STUDY DESIGN: In vitro effects of ALF on growth of C albicans and C glabrata in Sabouraud dextrose (SD) broth were measured as change in broth turbidity by microscale optical density assay. ALF was tested at 5 and 2.5 mg/mL concentrations against 105 yeast cell inoculum at 370 degrees C for 96 hours and compared with native lactoferrin and control (growth in broth without ALF). VE cells were isolated from human vaginal tissue biopsies to establish a functional monolayer for yeast interaction studies. ALF effects on Candida interactions with the VE monolayer were tested using 3H-thymidine-labeled yeast. Prophylactic (treatment prior to yeast inoculation onto VE) and therapeutic (treatment to detach VE-adherent yeast) potential of ALF (5 mg/mL) was evaluated against vaginal isolates of C albicans strain NTRL809A and C glabrata strain NTRL131G. RESULTS: Growth of Candida species indicated that a 105 yeast inoculum in SD broth proliferated to a stationary growth equilibrium (approximately 10(9) yeast cell density) in 18 hours (approximately 2 hours of generation time). ALF (5 mg/mL) elicited >96 hours of total stasis (100% growth inhibition) and was significantly effective against both Candida species (p < 0.0001). At 2.5 mg/mL dilution, ALF sustained total stasis activity to an average of 18 hours and 24 hours for C albicans (n = 5) and C glabrata (n = 5), respectively. Interaction studies indicated avid binding of C albicans (70 - 140 x 10(3) yeast) and C glabrata (50 - 75 x 10(3) yeast) per square centimeter of VE monolayer. ALF-treated VE showed significant blockade (p < 0.05) of yeast adhesion by 33% and 58% with C albicans and C glabrata, respectively. ALF treatment of yeast-VE complexes resulted in significant detachment (p < 0.05) of C albicans and C glabrata, by 58% and 51%, respectively. CONCLUSION: ALF is a natural fungistatic agent with potent yeast adhesion-blocking and detachment properties and is effective against the vaginal pathogens C albicans and C glabrata.

Candida albicans↗

PubMed2002

Differential expression of the mismatch repair gene hMSH2 in malignant prostate tissue is associated with cancer recurrence.

BACKGROUND: Mismatch repair (MMR) genes are responsible for coordinated correction of misincorporated nucleotides formed during DNA replication. Inactivating mutations in MMR genes have been described in sporadic cancers and a hereditary cancer predisposition syndrome. Mismatch repair deficiency causes instability at microsatellites and increased mutation rates. Although microsatellite instability (MSI) has been described in high-grade and lymph node positive prostate carcinoma specimens, an analysis comparing hMSH2 expression, MSI, and outcome in clinically organ confined prostate carcinoma has not been reported. METHODS: Immunohistochemical analysis of benign and malignant prostate tissue from 101 patients was performed using a monoclonal antibody specific for the hMSH2 protein. Expression was correlated with MSI using dinucleotide repeat markers and laser-captured microdissected DNA from normal and tumor cells. hMSH2 protein expression and MSI were assessed with respect to pathologic stage, Gleason score, and time to detectable serum prostate specific antigen (PSA) after prostatectomy in patients with clinically localized prostate carcinoma. RESULTS: In normal glands, hMSH2 staining was minimal to low and confined to the basal cell layer. In 32% of benign prostatic hyperplasia cases, hMSH2 staining was increased in the basal and luminal cell layers whereas 71% of cancer specimens had uniform moderate to high staining. Microsatellite instability was detected in 60% of absent to low staining and 26% of moderate to high staining prostate carcinoma specimens. Differential staining in benign versus malignant prostate tissues was statistically significant (P < 0.001) as was the correlation between absent to low hMSH2 staining and presence of MSI (P = 0.028). Decreased risk for PSA recurrence after radical prostatectomy correlated with absent to low hMSH2 staining in malignant prostate tissue but was only marginally significant (P = 0.05 for 24 month recurrence and P = 0.08 for overall time to PSA recurrence). CONCLUSIONS: The results of the current study demonstrate differential hMSH2 expression in benign and malignant prostate tissue. Moreover, hMSH2 expression is altered in a subset of clinically localized prostate carcinoma specimens independent of pathologic stage and Gleason pattern. A statistically significant correlation between hMSH2 immunohistochemical staining intensity and MSI also was identified in prostate carcinoma specimens. Furthermore, the time to cancer recurrence as determined by detectable serum PSA after prostatectomy was associated with hMSH2 staining intensity. Taken together, our results suggest that hMSH2 gene expression in prostate carcinoma may be a useful prognostic marker for outcome in men with clinically organ confined prostate carcinoma.

Aged↗

PubMed2002

Protein building blocks preserved by recombination.

Borrowing concepts from the schema theory of genetic algorithms, we have developed a computational algorithm to identify the fragments of proteins, or schemas, that can be recombined without disturbing the integrity of the three-dimensional structure. When recombination leaves these schemas undisturbed, the hybrid proteins are more likely to be folded and functional. Crossovers found by screening libraries of several randomly shuffled proteins for functional hybrids strongly correlate with those predicted by this approach. Experimental results from the construction of hybrids of two beta-lactamases that share 40% amino acid identity demonstrate a threshold in the amount of schema disruption that the hybrid protein can tolerate. To the extent that introns function to promote recombination within proteins, natural selection would serve to bias their locations to schema boundaries.

Algorithms↗

PubMedDate not supplied

Preferential prescribing of tibolone and combined estrogen plus progestogen therapy in postmenopausal women.

OBJECTIVE: To verify whether tibolone is preferentially prescribed to women at an increased risk for endometrial and breast cancer compared with women who were prescribed combined estrogen + progestogen therapies, including sequential conjugated equine estrogens/norgestrel, sequential conjugated equine estrogens/medroxyprogesterone acetate, continuous conjugated equine estrogens/medroxyprogesterone acetate, or continuous 17beta-estradiol/norethisterone acetate. DESIGN: This was a descriptive study using the General Practice Research Database, a UK primary care database. A total of 16,746 women who, between July 1, 1999, and June 30, 2001, were prescribed either tibolone or one of the estrogen + progestogen regimens listed above were included. The main outcome measures were risk factors associated with endometrial cancer and breast cancer. RESULTS: The clinical background of women who were prescribed tibolone differed from that of women who were prescribed combination products. More frequently than expected, women who were most recently prescribed tibolone had a history of chronic breast disease, a personal history of breast cancer, or a history of (long-term) estrogen-only therapy. Furthermore, medical records of this group of women showed more frequent reports of hypertension and previous uterine procedures. CONCLUSION: This study confirms previous findings that in the United Kingdom, general practitioners seem to prescribe tibolone preferentially to women with increased risks of breast and endometrial cancer as compared with women who are prescribed estrogen + progestogen products.

Breast Neoplasms↗

PubMedDate not supplied

Clinicopathologic implications of hMSH2 gene expression and microsatellite instability in prostate cancer.

Human mismatch repair (MMR) genes encode highly conserved interacting proteins that correct replication errors predisposing to hereditary gastrointestinal and genitourinary malignancies. We previously investigated expression of the prototype MMR gene hMSH2 in normal, benign prostatic hyperplasia and malignant prostate tissues (Velasco et al., Cancer 94:690-699, 2002). An association was detected between reduced hMSH2 staining and favorable outcome as determined by undetectable serum prostate specific antigen (PSA) after radical prostatectomy. We now investigate the association between clinicopathological variables and hMSH2 expression or microsatellite instability (MSI). A statistically significant association was found between tumors exhibiting MSI (MSI+ tumors) and lower preoperative serum PSA values, smaller tumor volumes and lower frequency of surgical specimens with extracapsular extension of tumor. No statistically significant association (P value less than or equal to 0.05) was found between hMSH2 staining and these clinicopathologic variables. Based on our analysis, we conclude that MMR deficiency has important clinicopathologic implications in prostate cancer. Furthermore, specific MMR genes may have different effects on prostate cancer biology.

Aged↗