Factors predictive of relapse in adult bacterial osteomyelitis of long bones.

BACKGROUND: Osteomyelitis is a difficult-to-cure infection with a high relapse rate despite combined medical and surgical therapies. Some severity factors, duration of antimicrobial therapy and type of surgical procedure might influence osteomyelitis relapse. METHODS: 116 patients with osteomyelitis were followed for ≥1 year after hospital discharge. Demographic, microbiological and clinical data, eight severity factors and treatment (surgical and antibiotic) were analyzed. RESULTS: Mean age was 53 years and 74.1% were men. Tibia (62.1%) and S. aureus (58.5%) were the most commonly involved bone and bacteria, respectively. Mean follow-up was 67.1 months. Forty-six patients underwent bone debridement, 61 debridement plus flap coverage and 9 antimicrobial therapy only. Twenty-six patients (22.4%) relapsed, at a mean of 11.2 months since hospital discharge. Duration > 3 months (p = 0.025), number of severity factors (P = 0.02) and absence of surgery (P = 0.004) were associated with osteomyelitis relapse in the univariate analysis. In the Cox regression analysis, osteomyelitis duration > 3 months (P = 0.012), bone exposure (P = 0.0003) and type of surgery (P < 0.0001) were associated with relapse. Regarding the surgical modalities, bone debridement with muscle flap was associated with better osteomyelitis outcomes, as compared with no surgery (P < 0.0001) and debridement only (P = 0.004). CONCLUSIONS: Osteomyelitis extending for > 3 months, bone exposure and treatment other than surgical debridement with muscular flap are risk factors for osteomyelitis relapse.

Mercury Accumulation, Structural Damages, and Antioxidant and Immune Status Changes in the Gilthead Seabream (Sparus aurata L.) Exposed to Methylmercury.

In aquatic systems, mercury (Hg) is an environmental contaminant that causes acute and chronic damage to multiple organs. In fish, practically all of the organic Hg found is in the form of methylmercury (MeHg), which has been associated with animal and human health problems. This study evaluates the impact of waterborne-exposure to sublethal concentrations of MeHg (10 µg L(-1)) in gilthead seabream (Sparus aurata). Hg was seen to accumulate in liver and muscle, and histopathological damage to skin and liver was detected. Fish exposed to MeHg showed a decreased biological antioxidant potential and increased levels of the reactive oxygen molecules compared with the values found in control fish (nonexposed). Increased liver antioxidant enzyme activities (superoxide dismutase and catalase) were detected in 2 day-exposed fish with respect to the values of control fish. However, fish exposed to MeHg for 10 days showed liver antioxidant enzyme levels similar to those of the control fish but had increased hepato-somatic index and histopathological alterations in liver and skin. Serum complement levels were higher in fish exposed to MeHg for 30 days than in control fish. Moreover, head-kidney leukocyte activities increased, although only phagocytosis and peroxidase activities showed a significant increase after 10 and 30 days, respectively. The data show that 30 days of exposure to waterborne MeHg provokes more significant changes in fish than a short-term exposure of 2 or 10 days.

Oral bacteria in placental tissues: increased molecular detection in pregnant periodontitis patients.

OBJECTIVES: The objective of this study was to identify the DNA of oral bacteria in placental samples from women with and without periodontitis who had or had not had preterm births and/or low birthweight (PB/LBW) neonates. METHODS: Data were gathered from 57 puerperal women in relation to socio-demographic, gynaecological, and periodontal variables and to placental histomorphology. Fifty-seven biopsies, 28 from mothers with periodontitis, were taken aseptically from preterm placentas (n = 36) and from full-term placentas (n = 21). Total DNA was extracted, and the presence of 15 oral bacteria was assessed using Nested-PCR. RESULTS: The placentas from women with periodontitis showed a higher prevalence of periodontopathogens compared to those from women without periodontitis (P = 0.009). Samples showed low prevalences of Actinomyces israelii, Parvimonas micra and Tannerella forsythia. An association was found between Eikenella corrodens in placenta and periodontitis (P = 0.002). The most ubiquitous bacterium, Fusobacterium nucleatum, was more prevalent in mothers with periodontitis and PB/LBW (P = 0.033). Porphyromonas gingivalis, Treponema denticola, Prevotella intermedia and Aggregatibacter actinomycetemcomitans were not detected. CONCLUSIONS: These results, along with previous findings, show that oral bacteria may be normally present in the placenta, however, the levels of certain oral pathogens in the placenta would highly depend on the mother's periodontal state.

Trends in the dispensation of antidepressant drugs over the past decade (2000-2010) in Andalusia, Spain.

PURPOSE: To study antidepressant drug dispensation in the Spanish region of Andalusia and in the Almeria Health Area (AHA) over the past decade, analyzing the variability, trends, and influential factors. METHODS: We conducted an observational ecological study of antidepressant drug dispensation between 2000 and 2010 in Andalusia. Dispensation was measured as Defined Daily Dose (DDD) per 1,000 inhabitants per day. A multilevel analysis (STATA 11.1) was performed to determine the variability among the basic health zones (BHZs) (2004-2010) and influential factors. RESULTS: Between 2000 and 2010, the total dispensation of antidepressant drugs increased by more than 100 % in Andalusia and in the AHA. This increase was primarily caused by the greater dispensation of selective serotonin reuptake inhibitors (ATC-N06AB) and other antidepressants (ATC-N06AX). Multilevel analysis revealed a wide variability in the levels and trends of antidepressant dispensation among BHZs. Urbanicity and the percentage of immigrants in the BHZ were negatively associated with their dispensation, which was positively influenced by a higher proportion of women and over 65-year-olds in the population. CONCLUSIONS: The elevated dispensation of several groups of antidepressant drugs in this study population indicates the need for health policies to rationalize their use. Further research is required into the differences in antidepressant dispensations between immigrant and native populations and the implications for public health policies.

[Noninvasive imaging techniques to study coronary artery aneurysms]. / Técnicas de imagen no invasivas para el estudio de los aneurismas coronarios.

Given the growing evidence about the use of membrane-covered stents to treat coronary artery aneurysms, it is fundamental to know the exact anatomy of the aneurysm to enable patients to be selected correctly. Invasive heart catheterization has limitations for diagnostic purposes and can underestimate the size of the aneurysm. In this article, we review the noninvasive diagnostic imaging techniques for the study of coronary artery aneurysms, illustrating the usefulness of each technique.

Pressure waves in the aorta during isolated abdominal belt loading: the magnitude, phasing, and attenuation.

While rupture of the aorta is a leading cause of sudden death following motor vehicle crashes, the specific mechanism that causes this injury is not currently well understood. Aortic ruptures occurring in the field are likely due to a complex combination of contributing factors such as acceleration, compression of the chest, and increased pressure within the aorta. The objective of the current study was to investigate one of these factors in more detail than has been done previously; specifically, to investigate the in situ intra-aortic pressure generated during isolated belt loading to the abdomen. Ten juvenile swine were subjected to dynamic belt loads applied to the abdomen. Intraaortic pressure was measured at multiple locations to assess the magnitude and propagation of the resulting blood pressure wave. The greatest average peak pressure (113.6 +/- 43.5 kPa) was measured in the abdominal aorta. Pressures measured in the thoracic aorta and aortic arch were 70 per cent and 50 per cent, respectively, that measured in the abdominal aorta. No macroscopic aortic trauma was observed. To the authors' knowledge the present study is the first one to document the presence, propagation, and attenuation of a transient pressure wave in the aorta generated by abdominal belt loading. The superiorly moving wave is sufficient to generate hydrostatic and intimal shear stress in the aorta, possibly contributing to the hypothesized mechanisms of traumatic aortic rupture.

Use of polyvinylidene fluoride (PVDF) meshes for ventral hernia repair in emergency surgery.

PURPOSE: The implantation of non-absorbable meshes is the gold standard technique for ventral hernia (VH) repairs. However, emergency surgeries are often related to contaminated/infected fields, where the implantation of prosthetic materials may not be recommendable. Our aim was to evaluate the results of polyvinylidene fluoride (PVDF) meshes used for contaminated and/or complicated VH repairs in the acute setting. METHODS: We conducted a retrospective analysis of patients with VH who underwent emergency surgery involving PVDF meshes, in a tertiary hospital (from November 2013 to September 2019). We analyzed postoperative complications and 1-year recurrence rates. We evaluated the relationships between contamination grade, mesh placement, infectious complications, and recurrences. RESULTS: We gathered data on 123 patients; their mean age was 62.3 years, their mean BMI was 31.1 kg/m2, and their mean CeDAR index was 51.6. 96.4% of patients had a grade 2-3 ventral hernia according to the Rosen index. The mean defect width was 8 cm (IQR 2-18). 93 cases (75.6%) were described as contaminated or dirty surgeries. A PVDF mesh was placed using an IPOM technique in 56.3% of cases, and via interposition location in 39.9%. The one-month recurrence rate was 5.7% and recurrence after one year was 19.1%. The overall mortality rate was 27.6%. Risk of recurrence was related to patients with a Rosen score over 2 (p < 0.001), as well as with postoperative SSI (p = 0.045). Higher recurrence rates were not related to PVDF mesh placement. CONCLUSION: The use of PVDF meshes for emergency VH repairs in contaminated surgeries seems safe and useful, with reasonable recurrence rates, and acceptable infectious complication rates, similar to those published in the literature.

Transfection improvements of fish cell lines by using deacylated polyethylenimine of selected molecular weights.

A new tool for DNA transfer to fish cell lines such as epithelioma papulosum cyprini (EPC) and rainbow trout gonad (RTG2), has been optimized by testing commercially available polyethylenimine (PEI) polymers as transfectant reagents. Deacylated 25 kDa PEI polymers were selected amongst the most active and then low toxicity deacylated PEIs fractions around 15 kDa were obtained by gel filtration chromatography to increase 3-4-fold their initial in vitro transfection efficiency. The EPC and plasmids coding for reporter genes were first used to optimize variable values for best expression by transfection with deacylated low toxicity PEI while both EPC/RTG2 and a plasmid coding for the glycoprotein G gene of the fish pathogen, viral haemorrhagic septicemia virus (VHSV) were then used to demonstrate some of their practical applications. Due to its relatively low price, defined chemical composition and availability, low toxicity deacylated PEI might be used for numerous applications for all those studying fish cell immunology in vitro as well as in vivo.

Pattern of expression of immune-relevant genes in the gonad of a teleost, the gilthead seabream (Sparus aurata L.).

Immune responses in the testis are regulated in a way that provides protection for the developing male germ cells, while permitting qualitatively normal inflammatory responses and protection against infection. In addition, germ cells are potent targets for the growth factors and cytokines which regulate the reproductive process. Our study analyzes for the first time the pattern of expression of several immune-relevant genes in the gonad of a seasonal breeding teleost fish. The immune molecules analyzed include (i) inflammatory molecules, such as interleukin-1b (il1b), il6, tumor necrosis factor-a (tnfa), cyclooxygenase-2 (cox2) and the NADPH oxidase subunit p40(phox) (ncf4 gene); (ii) the anti-inflammatory cytokine transforming growth factor-b1 (tgfb1) and its type 2 receptor tgfbr2; (iii) innate immune receptors, including toll-like receptor 9 (tlr9), tlr5, tlr22 and macrophage-colony stimulating factor receptor (mcsfr); (iv) lymphocyte receptors, such as the beta subunit of T-cell receptor (Tcrb) and the heavy chain of immunoglobulin M (ighm); (v) the anti-bacterial molecules lysozyme (lyz), hepcidin (hamp) and complement component 3 (c3); (vi) the anti-viral molecule myxovirus (influenza) resistance protein (mx); and (vii) molecules related to leukocyte infiltration, including the CC chemokine ccl4, the CXC chemokine il8 and the leukocyte adhesion molecule E-selectin (Sele). Notably, all of them show a pattern of expression that depends on the reproductive stage of the first two reproductive cycles when the fish develop and function as males. Furthermore, we demonstrate that some of these immune-relevant molecules, such as Il1b and Mcsfr, are produced by germ cells (Il1b) and ovarian and testicular somatic cells (Mcsfr). These data suggest that, as occurs in mammals, there is a critical balance between immune molecules and that these may play an essential role in the orchestration of gametogenesis and the maintenance of gonad tissue homeostasis in fish.

A role for matrix metalloproteinases in granulocyte infiltration and testicular remodelation in a seasonal breeding teleost.

The testicular cystic structure and the abrupt morphological changes that the fish testis undergoes during the reproductive cycle (RC) make it an interesting model for studying the regulation of spermatogenesis, in particular the role of matrix metalloproteinases (Mmps). The gilthead seabream is a seasonal breeding teleost whose testis undergoes drastic remodeling events, especially during the post-spawning stage when a massive infiltration of a immune cell type, the acidophilic granulocytes, occurred. Bearing this in mind, we studied the gilthead seabream testis gelatinolytic activities involved in migration and tissue remodeling and its regulation by endocrine, immune and tissue stimuli. Thus, we demonstrated that the germinal epithelium of the testis showed gelatinolytic activity during spermatogenesis and post-spawning but not during resting, when only scarce interstitial cells were stained. Moreover, the precursor and mature forms of two gelatinases, Mmp2- and Mmp9-like, were active in the gonad, whose activities were up-regulated by 17beta-estradiol (E(2)) but not by lipopolysaccharide (LPS)/bacterial DNA (VaDNA) in testicular cell suspensions. E(2) and LPS/VaDNA also up-regulated a variety of cytokines and chemokines. We also cloned mmp9, mmp13, tissue inhibitors of Mmps (timp)-2a and timp2b genes and found that all of them were expressed in the gonad in a RC stage-dependent manner. Interestingly, mmps and timps were highly expressed by the testicular acidophilic granulocytes. Moreover, in these cells, the gelatinolytic activity seemed to correspond to the precursor and mature forms of putative Mmp2 and Mmp9 gelatinases, while the main gelatinolytic activity seemed to correspond to the mature form of Mmp2 in head-kidney acidophilic granulocytes. Finally, although none of the stimuli used were able to induce the gelatinolytic activity of Mmp9-like in head-kidney acidophilic granulocytes, the expression of mmp9, timp2a and timp2b were all up-regulated by LPS/VaDNA in these cells, while only mmp9 and timp2a expression increased upon stimulation with gelatin.

Malignant glaucoma after XEN45 implant. / Glaucoma maligno tras implante XEN45.

Minimally invasive glaucoma surgery for chronic open-angle glaucoma treatment tries to reduce the amount of chronic topical drug treatment, delaying invasive glaucoma surgery and diminishing the number of surgical complications. XEN45 uses subconjunctival drainage in order to reduce intraocular pressure. The report is presented of a patient following phacoemulsification, intraocular lens implantation and XEN45 implant. After four days acute malignant glaucoma was observed, with stage 3 athalamia requiring pars plana vitrectomy and secondary Ahmed valve implantation. The lower rate of complications due to minimally invasive glaucoma surgery has increased its use. Nevertheless, it is not free of severe adverse events, even requiring a multidisciplinary approach as in our malignant glaucoma report.

Pharmacology and therapeutic potential of sigma(1) receptor ligands.

Sigma (sigma) receptors, initially described as a subtype of opioid receptors, are now considered unique receptors. Pharmacological studies have distinguished two types of sigma receptors, termed sigma(1) and sigma(2). Of these two subtypes, the sigma(1) receptor has been cloned in humans and rodents, and its amino acid sequence shows no homology with other mammalian proteins. Several psychoactive drugs show high to moderate affinity for sigma(1) receptors, including the antipsychotic haloperidol, the antidepressant drugs fluvoxamine and sertraline, and the psychostimulants cocaine and methamphetamine; in addition, the anticonvulsant drug phenytoin allosterically modulates sigma(1) receptors. Certain neurosteroids are known to interact with sigma(1) receptors, and have been proposed to be their endogenous ligands. These receptors are located in the plasma membrane and in subcellular membranes, particularly in the endoplasmic reticulum, where they play a modulatory role in intracellular Ca(2+) signaling. Sigma(1) receptors also play a modulatory role in the activity of some ion channels and in several neurotransmitter systems, mainly in glutamatergic neurotransmission. In accordance with their widespread modulatory role, sigma(1) receptor ligands have been proposed to be useful in several therapeutic fields such as amnesic and cognitive deficits, depression and anxiety, schizophrenia, analgesia, and against some effects of drugs of abuse (such as cocaine and methamphetamine). In this review we provide an overview of the present knowledge of sigma(1) receptors, focussing on sigma(1) ligand neuropharmacology and the role of sigma(1) receptors in behavioral animal studies, which have contributed greatly to the potential therapeutic applications of sigma(1) ligands.

Bacterial osteomyelitis: microbiological, clinical, therapeutic, and evolutive characteristics of 344 episodes.

OBJECTIVE: Osteomyelitis is a difficult-to-cure infection, with high relapse rate despite adequate therapy. Large published osteomyelitis series in adults are rare. METHODS: A total of 344 adult osteomyelitis patients were studied and followed > 12 months after hospital discharge. Demographic, microbiological, clinical, therapeutic and outcome data were analyzed. RESULTS: Mean age was 52.5 ± 18.3 years and 233 (67.7%) were male. Main osteomyelitis types were post-surgical (31.1%), post-traumatic (26.2%) and hematogenous (23%). Tibia (24.1%) and femur (21.8%), and methicillin-susceptible S. aureus (29.6%) were the most commonly involved bone and bacteria, respectively. Median follow-up was 12.0 (IQR 0-48) months. Inflammatory markers were increased in 73.6%. Overall, patients were treated by IV and oral routes with one (IV: 44.5%, oral: 26.7%), two (IV: 30.1%, oral: 21.8%) or ≥ 2 (IV: 15.2%, oral: 6.1%) antibiotics. Median duration on IV/oral antimicrobials was 28.0 (IQR 24-28) and 19.5 (IQR 4-56) days, respectively. Anti-staphylococcal ß-lactams cloxacillin/cefazolin (19.2%) and ciprofloxacin (5.5%) were the most frequently used IV and orally, respectively. Overall 234 (68.0%) underwent surgery, 113 (32.8%) debridement, 97 (27.4%) debridement + muscle flap and 24 (7%) amputation. At the end of follow-up 208 patients (60.6%) did not have relapsed. Operated patients had significantly less relapses (p<0.0001). A total of 23 (6.7%) died, 11 (3.2%) by infectious complications and 48 (14%) were lost in the follow-up. CONCLUSIONS: Osteomyelitis is due to different causes complicating its therapy. Risk factors or causal microorganism could influence its treatment and outcome. Aggressive surgery along with adequate antimicrobial therapy are mandatory for cure.

[Drug-related mortality among inpatients admitted in Internal Medicine]. / Mortalidad hospitalaria asociada a medicamentos en un Servicio de Medicina Interna.

BACKGROUND: To analyze the mortality associated with prescriptions, the drugs most frequently involved and the associated risk factors in patients admitted to Internal Medicine. METHODS: A retrospective, observational study. The clinical records of adult patients who died consecutively in the department of Internal Medicine in a Spanish tertiary hospital over twenty-two months were reviewed. The main variable was the prevalence of hospital death suspected of being related to the medications administered during admission. RESULTS: Out of the 455 deaths analyzed, 22.2% were related to the medications received; in 55 cases (12.1%) the drugs were suspected of being the cause of death and in 46 cases (10.1%) of contributing to it. The most frequent diagnoses in cases of death associated with drugs were cardiac arrhythmia (23.7%), severe hemorrhage (19.8%) and aspiration pneumonia (12.8%). The drugs with the highest prevalence in deaths related to pharmacological treatment were an-tithrombotic drugs (23.7%), digoxin (21.7%), antipsychotics (17.8%) and benzodiazepines (14.8%). The only independent risk factor for mortality associated with treatment was the number of medications administered (OR=1.25, 95%CI: 1.14-1.37). No significant association was found with age, sex, number of pathologies or duration of hospital stay. CONCLUSION: A high percentage of deaths of patients admitted to Internal Medicine were considered related to the medications received. Antithrombotic drugs, digoxin and psychotropic drugs were the agents most frequently implicated. This mortality is independently and significantly associated with the number of medications administered.

Inhibitory action of a met-enkephalin on ACTH release in man.

In order to study the mechanism of action of a Met-enkephalin (FK 33824) on the pituitary-adrenal axis eight normal male volunteers were subjected to an ACTH stimulation test. Lysine-vasopressing (LVP), 5 IU, was injected intramuscularly after pretreatment with 0.5 mg FK 33824 i.m. or a placebo. In six of the subjects the opiate was again administered preceding a single injection of 0.25 mg ACTH beta 1-24 i.m. Blood was collected at regular intervals and ACTH and cortisol concentrations analyzed in all samples. LVP induced significant plasma ACTH (P < 0.05) and cortisol (P < 0.001) increases. Pretreatment with FK 33824 completely antagonized the effect of LVP. Furthermore, the cortisol elevation after exogenous ACTH was not modified by previous administration of FK 33824. It is concluded that the Met-enkephalin derivative FK 33824 directly suppresses ACTH release from the pituitary without influencing adrenal synthesis of cortisol.

Assessment of the Effectiveness of an Exposure Technique Intervention in a Case of Amaxophobia

Amaxophobia, or driving phobia, is an anxiety disorder; more specifically a situational phobia (SP). Main symptoms of SP may include an excessive and irrational fear to certain stimuli, to which exposure produces high anxiety levels, as well as the development of avoidance mechanisms or confrontation, at the expense of a high distress. Its prognosis is chronic in the absence of treatment, but empirical evidence reveals a high efficacy of psychological interventions based on exposure techniques. The case of a 47 years old female requesting treatment for an intense driving fear is presented. The assessment was made through an ad hoc self-report of anxiogenic episodes, the Short Form Health Survey (SF-12), the General Health Questionnaire (GHQ-28), the Perceived Stress Scale (PSS-14), the Beck Depression Inventory (BDI) and the State-Trait Anxiety Inventory (STAI). It was conducted a cognitive-behavioral intervention based on imagination and real life exposure techniques, along with breathing and relaxation techniques. After 10 sessions her anxiety levels and her negative affects decreased significantly, allowing her to resume driving and revealing the efficacy of the intervention (AU)

Role of 5α-dihydrotestosterone in testicular development of gilthead seabream following finasteride administration.

In teleosts, spermatogenesis is regulated by pituitary gonadotropins and sex steroids. 5α-dihydrotestosterone (DHT), derived from testosterone (T) through the action of 5α-reductase, has recently been suggested to play a physiologically important role in some fish species. In this study, gilthead seabream, Sparus aurata L., males received an implant of 1µgT/g body mass (bm) or vehicle alone and, 7days later, 1mg finasteride (FIN, an inhibitor of 5α-reductase)/kg bm or vehicle. Serum levels of T, 11-ketotestosterone (11KT), DHT and 17ß-estradiol (E2), and the mRNA levels of the main enzymes involved in their synthesis, were analysed. T promoted a transient increase in the serum levels of T, 11KT and E2 but a decrease in those of DHT at day 15 following T injection, in accordance with the up-regulation of mRNA levels of the enzymes involved in T transformation to 11KT (coding genes: cyp11b1 and hsd11b) and the down-regulation of mRNA levels of the enzyme responsible for T transformation to DHT (coding gene: srd5a). Interestingly, a similar effect was observed when FIN was injected. However, when fish were injected with T and FIN successively (T+FIN), control levels were not recovered at the end of the experimental period (28days). DHT seems to regulate E2 serum levels via the down-regulation of mRNA levels of aromatase (coding gene: cyp19a1a), which is needed for the transformation of T into E2. The testis histology, together with the proliferative rates recorded upon T, FIN or T+FIN treatment, suggests that DHT is involved in the onset of the meiotic phase of spermatogenesis.