Identification of a founder BRCA1 mutation in the Moroccan population.

Breast cancer (BC) is the most frequent cancer among women in Morocco. However, the role of the most prevalent BC-predisposing genes, BRCA1 and BRCA2, has been largely unexplored. To help define the role of BRCA1 in BC in Morocco, we characterized the first potential BRCA1 founder mutation in this population. Genetic testing of BRCA1 and BRCA2 in BC high-risk families identified mutation BRCA1 c.5309G>T, p.(Gly1770Val) or G1770V in five independent families from Morocco, suggesting a founder effect. To confirm this hypothesis, haplotype construction was performed using seven intragenic and flanking BRCA1 microsatellite markers. Clinical data were also compiled. Clinical data from carriers of mutation G1770V correspond to data from carriers of BRCA1 pathogenic mutations. Microsatellite analysis showed a common haplotype for the five families in a region comprising 1.54 Mb, confirming G1770V as the first specific founder BRCA1 mutation in the Moroccan population. Our findings contribute to a better understanding of BC genetics in the Moroccan population. Nevertheless, comprehensive studies of mutation G1770V in large series of BC patients from Morocco are needed to assess the real prevalence of this mutation and to improve genetic testing and risk assessment in this population.

Total hip arthroplasty in HIV-infected patients: a retrospective, controlled study.

BACKGROUND: Although HIV-infected patients are at greater risk of presenting with ischaemic necrosis of the femoral head, there have been concerns about whether total hip arthroplasty (THA) may have worse outcomes than expected. METHODS: From the Orthopedic and Trauma Surgery database we identified all patients who had undergone THA because of ischaemic necrosis of the femoral head from January 2001 until March 2010. Patient's diagnosis of HIV infection was confirmed at the time of arthroplasty by cross-matching with the HIV unit database. For every THA in HIV-infected patients, two THAs in patients not known to be HIV-infected, with the same diagnosis of ischaemic necrosis of the femoral head and having undergone surgery over the same period, were randomly selected. THAs were compared in HIV- and non-HIV-infected patients for surgical procedure, in-patient stay and long-term prognosis. RESULTS: There were 18 THAs in 13 HIV-infected patients and 36 THAs in 27 non-HIV-infected patients. No significant differences were observed in the mean time spent in surgery (106 vs. 109 minutes, respectively; P = 0.66), the need for red cell transfusion (1 vs. 4, respectively; P = 0.48) or the mean duration of hospitalization (7.8 vs. 9.4 days, respectively; P = 0.48). The two groups showed similar postoperative functional results, which were maintained until the end of the follow-up period (median 3.3 years in the HIV-positive group and 5.8 years in the HIV-negative group). CONCLUSION: Our study suggests that the outcome of THA in HIV-positive patients is not worse than that of HIV-negative patients, although future research on larger numbers of patients is required to confirm this.

Validación de un cuestionario de conocimientos adquiridos por los pacientes tras un taller educativo de artroplastia de rodilla.

INTRODUCTION: Total knee arthroplasty (TKA) is a surgery that aims to restore function and relieve pain in advanced osteoarthritis. The Educational Workshop (EW) for TKA is given to patients in the pre-surgery period to inform them and facilitating their participation in their health process (empowerment). The aim of this study was developing and validating a self-administered questionnaire to evaluate the acquired knowledge after the EW by the patients who will undergo the TKA procedure. MATERIAL AND METHODS: It was a longitudinal and prospective observational study with a sample of TKA candidate patients. The phases for the construction and validation of this ad hoc questionnaire were: Phase 1: A panel of experts who agreed on a final questionnaire of 20 items; Phase 2: Pilot test administered to 47 patients; Phase 3: Final test of 11 items administered to 50 patients, before and after the EW; Phase 4: Re-test, after the EW and 2 weeks after, administered to 58 patients. RESULTS: One hundred and fifty five patients were included. The Cronbach's alpha coefficient for the item's internal consistency of the final questionnaire, 11 items, was 0.78. To reach the criterion validity, in pre-EW the mean number of hits was: 4.92 (SD=1.78) and in post-EW 10.68 (SD=0.55), a difference that had a statistical significance p<.0001, with no overlap in the 95% CI of the mean: 4.46-5.38/10.54-10.82. The test for stability and reliability, re-test, obtained a mean of right answers 10.87 (SD=0.33) and for the re-test of 10.70 (SD=0.59). The correlation of the interclass coefficient for the re-test was 0.99, which corresponds almost to a maximum concordance. CONCLUSIONS: The questionnaire developed in this study is a reliable and easy tool to evaluate the acquired knowledge in the EW for patients who will be TKA operated.

[Comparison of hemostatic markers under different techniques for anesthesia-analgesia in total hip or knee replacement]. / Comparación de los marcadores de la hemostasia dependiendo de la técnica anestésica/analgésica empleada en cirugía de prótesis de rodilla y cadera.

BACKGROUND AND OBJECTIVE: Surgery promotes a state of hypercoagulability, predisposing to the possibility of postoperative thromboembolic complications. Our aim was to determine whether certain combinations of techniques (neuraxial, intravenous or both) for anesthesia and analgesia might be associated with attenuation of the prethrombotic state following total hip or knee replacement. METHODS: Prospective longitudinal study of 45 patients undergoing elective hip or knee prosthetic surgery. The patients were randomized to 3 groups to receive different anesthesia-analgesia combinations: spinal-intravenous, spinal-epidural, or general-intravenous. From induction until 36 hours after surgery, we recorded the postoperative time course of the following markers of coagulation and fibrinolysis: platelet count; fibrinogen level; activated partial thromboplastin time; international normalized ratio; and levels of prothrombin activation fragments 1 and 2, thrombin-antithrombin III complex, and D-dimer. RESULTS: No statistically significant between-group differences were found in patient demographic, clinical, surgical or postoperative data. No symptomatic thromboembolic complications or deaths were recorded in the 30 days after surgery. Statistically significant differences were found in laboratory results for samples taken 36 hours after surgery. Patients who received spinal-epidural anesthesia and analgesia had lower levels of prothrombin activation fragments 1 and 2 and longer activated partial thromboplastin times than the group receiving the spinal-intravenous combination. CONCLUSIONS: The anesthetic technique used during surgery did not affect hemostasis. However, continuous epidural analgesia in the postoperative recovery period attenuated some markers of hypercoagulability.

A novel analytical methodology for the determination of hydroxy polycyclic aromatic hydrocarbons in breast and cow milk samples.

Hydroxy polycyclic aromatic hydrocarbons (OHPAHs) in biological fluids, such as milk, are considered as biomarkers of exposure to polycyclic aromatic hydrocarbons (PAHs) in organism. The presence of OHPAHs in milk samples indicates a potential contamination on human organisms and milk producing animals. In this way, infants can be contaminated by lactation through the consumption of milk of both, human and animal origins. In this paper, eight OHPAHs have been analyzed in commercial cow milks and in human breast milk using HPLC and fast scanning fluorimetric detection (FSFD). Extraction and cleaning procedures of OHPAHs from milk samples have been investigated, and the experimental results using two bibliographic protocols and a new proposed protocol have been compared. The new protocol using enzymatic hydrolysis, proteins precipitation and, solvent extraction using acetonitrile, was proposed as the most adequate for the determination of 2-hydroxyfluorene, 1-/9-, 2-/3- and 4-hydroxyphenanthrenes, 1-hydroxypyrene and 3-hydroxybenzo[a]pyrene. The method recoveries ranged from 80-102% and 75-91% for fresh cow milk and for human breast milk, respectively, for all components except for 3-OHBz[a] Py. Low recovery values were calculated for 3-hydroxybenzo[a]pyrene in all cases. No statistical difference in the method performance was observed between fresh cow milk and human breast milk.

KLIC-score for predicting early failure in prosthetic joint infections treated with debridement, implant retention and antibiotics.

Debridement, irrigation and antibiotic treatment form the current approach in early prosthetic joint infection (PJI). Our aim was to design a score to predict patients with a higher risk of failure. From 1999 to 2014 early PJIs were prospectively collected and retrospectively reviewed. The primary end-point was early failure defined as: 1) the need for unscheduled surgery, 2) death-related infection within the first 60 days after debridement or 3) the need for suppressive antibiotic treatment. A score was built-up according to the logistic regression coefficients of variables available before debridement. A total of 222 patients met the inclusion criteria. The most frequently isolated microorganisms were coagulase-negative staphylococci (95 cases, 42.8%) and Staphylococcus aureus (81 cases, 36.5%). Treatment of 52 (23.4%) cases failed. Independent predictors of failure were: chronic renal failure (OR 5.92, 95% CI 1.47-23.85), liver cirrhosis (OR 4.46, 95% CI 1.15-17.24), revision surgery (OR 4.34, 95% CI 1.34-14.04) or femoral neck fracture (OR 4.39, 95% CI1.16-16.62) compared with primary arthroplasty, C reactive protein >11.5 mg/dL (OR 12.308, 95% CI 4.56-33.19), cemented prosthesis (OR 8.71, 95% CI 1.95-38.97) and when all intraoperative cultures were positive (OR 6.30, 95% CI 1.84-21.53). A score for predicting the risk of failure was designed using preoperative factors (KLIC-score: Kidney, Liver, Index surgery, Cemented prosthesis and C-reactive protein value) and it ranged between 0 and 9.5 points. Patients with scores of ≤2, >2-3.5, 4-5, >5-6.5 and ≥7 had failure rates of 4.5%, 19.4%, 55%, 71.4% and 100%, respectively. The KLIC-score was highly predictive of early failure after debridement. In the future, it would be necessary to validate our score using cohorts from other institutions.

[Socioeconomic determinants and utilization of emergency hospital services]. / Determinantes socioeconómicos y utilización de los servicios hospitalarios de urgencias.

BACKGROUND: Socioeconomic level is a key determinant for health status. It may also influence on the utilization of hospital emergency services, although the factor responsible for that is not known. The main objective of the present report is to assess whether patients using frequently hospital emergency services have one or more variables related to low socioeconomic level. PATIENTS AND METHODS: A standardized questionnaire was applied to 800 patients randomly selected from those attending the emergency services of a provincial reference hospital. It was gathered information on: income, education level, employment, loneliness, domestic violence, occupational accidents, and life style. Odds ratios (OR) and their 95% confidence intervals (CI) were estimated. Stepwise logistic regression analysis was used to ascertain the independent predictors for attending for than once to the emergency services. RESULTS: In crude analysis, low income and low educational level were significantly related to the use of emergency services (both chi 2 for a trend < 0.05). Alcoholism (OR = 2.3, 95% CI = 1.2-4.7) and domestic violence (OR = 2.6, 95% CI = 0.9-8.1) were also related. Stepwise logistic regression analysis selected income (OR for intermediate level = 1.6, 95% CI = 1.0-2.7, and OR for low level = 2.3, 95% CI = 1.4-3.7) and alcoholism (OR = 2.9, 95% CI = 1.3-6.4) as independent predictors. CONCLUSIONS: Patients with low income and/or alcoholism use emergency hospital services more frequently.

HPLC determination of serum pteridine pattern as biomarkers.

Pteridinic derivatives are important biomolecules considered as biomarkers for several diseases, especially in cancer and infectious pathologies. A new fluorimetric-HPLC method for the analysis of nine pteridines in human serum has been reported. Two analytical columns composed by C18 porous and fused core particles were assayed and the results compared. Fused core particle column allows us adequate separation, in only one run and in 15 min. Acid precipitation step of the proteins and clean-up process with an Isolute ENV+ (hydroxylated polystyrene-divinylbenzene copolymer) cartridge of the serum samples have been optimized. Analytes were determined by fluorimetric detection, exciting at 272 nm and measuring the fluorescence emission at 410 nm for isoxanthopterin, at 465 nm for xanthopterin, and at 445 nm for the analysis of the other pteridines. Detection limits between 0.07 and 0.61 ng mL(-1) were calculated according to Clayton criterium. Intraday precision varied from 1.2 to 5.3 and interday precision between 1.2 and 7.4, both expressed as RSD (%). External standard and standard addition calibrations were compared in the analysis of serum samples. The pteridine amounts in serum (expressed as ng mL(-1) ± confidence interval) were 3.69 ± 1.78; 1.35 ± 0.24; 0.46 ± 0.14; 0.54 ± 0.24; 0.84 ± 0.55; 2.10 ± 0.51 and 0.23 ± 0.11 for XAN, NEO, MON, ISO, BIO and 6HMPT, respectively, using the external standard method. Comparable results were obtained by the standard addition method. It is noticeable that 7BIO was not detected in the healthy serum samples analyzed.

Characteristics of prosthetic joint infections due to Enterococcus sp. and predictors of failure: a multi-national study.

The objective of this study was to review the characteristics and outcome of prosthetic joint infections (PJI) due to Enterococcus sp. collected in 18 hospitals from six European countries. Patients with a PJI due to Enterococcus sp. diagnosed between January 1999 and July 2012 were retrospectively reviewed. Relevant information about demographics, comorbidity, clinical characteristics, microbiological data, surgical treatment and outcome was registered. Univariable and multivariable analyses were performed. A total of 203 patients met the inclusion criteria. The mean (SD) was 70.4 (13.6) years. In 59 patients the infection was diagnosed within the first 30 days (29.1%) from arthroplasty, in 44 (21.7%) between 31 and 90 days, in 54 (26.6%) between 91 days and 2 years and in 43 (21%) after 2 years. Enterococcus faecalis was isolated in 176 cases (89%). In 107 (54%) patients the infection was polymicrobial. Any comorbidity (OR 2.53, 95% CI 1.18-5.40, p 0.01), and fever (OR 2.65, 95% CI 1.23-5.69, p 0.01) were independently associated with failure. The only factor associated with remission was infections diagnosed later than 2 years (OR 0.25, 95% CI 0.09-0.71, p 0.009). In conclusion, prosthetic joint infections due to Enterococcus sp. were diagnosed within the first 2 years from arthroplasty in >70% of the patients, almost 50% had at least one comorbidity and infections were frequently polymicrobial (54%). The global failure rate was 44% and patients with comorbidities, fever, and diagnosed within the first 2 years from arthroplasty had a poor prognosis.

A simple HPLC-ESI-MS method for the direct determination of ten pteridinic biomarkers in human urine.

Pteridines are important biomarkers metabolites related to several biochemical pathways such as activation of the cell-mediated immune system, biosynthesis of neurotransmitters, etc. The level of pteridinic compounds in urine is considered as an important clinic criterion. In this work, a new liquid chromatography-mass spectrometry (LC-MS) method is proposed to determine several pteridinic biomarkers in urine samples using 6-methylpterin as internal standard (I.S.). Matrix effect was evaluated and several dilutions of urine were tested in order to study the evolution of signal suppression. Sample preparation was limited to 10-fold dilution of the filtered urine followed by injection onto a reversed-phase column. The signal was recorded in selected ion monitoring mode. The lowest limit of detection was found for pterin (values ranged from 1.70 to 3.88 ng mL(-1)) whereas the highest limit was for xanthopterin (values ranged from 10.5 to 49.9 ng mL(-1)) for healthy volunteers between 17 and 51 years old.

[The construction and validation of a questionnaire on the satisfaction of primary health care users]. / Construcción y validación de una encuesta de satisfacción de usuarios de atención primaria.

The questionnaire was developed after establishing the domains that might be measured with it and selecting 16 items. During June and September 1987 it was administered to 163 patients, selected by quota sampling, who belonged to two health centers and two outpatient clinics from the city of Almería. With the obtained data several parts of the questionnaire were validated: stability, homogeneity, distorting variables and constructed validity. There were significant differences (analysis of variance) between the satisfaction of the users of health centers and outpatient clinics (p = 0.042) (higher satisfaction in health centers). There were not marked differences between the users of both health centers (p = 0.144) and between both outpatient clinics (p = 0.66). The measurement of satisfaction is a valuable instrument for the investigation and administration of health services and a good indicator of the quality of care.