Vesicular transport and secretion of penicillin G in Penicillium rubens P2-32-T.

The compartmentalization of penicillin G biosynthesis in Penicillium rubens has been extensively studied. However, how this compound is secreted has not been completely elucidated, although its transport could be of the vesicular type. This work was aimed at observing vesicles and penicillin secretion and proposing a hypothetical model for their compartmentalization and secretion. For this purpose, a high-penicillin-producing strain (P. rubens P2-32-T) was compared by transmission electron microscopy (TEM) and atomic force microscopy (AFM) with a null-producing strain (P. rubens npe10) in 24- and 48-h cultures. The results showed multivesicular bodies and secretory vesicles, suggesting that P. rubens transports and secretes penicillin G through vesicular excretion.

Pharmacokinetic variations of nimesulide in mongrel dogs according to age.

The purpose of this research was to investigate the possible variations to the pharmacokinetics of nimesulide by the effect of age using an animal model. An experimental, analytical, prospective and longitudinal study in five dogs, from birth to 730 days of age was carried out. Nimesulide blood levels were measured in different months; concentrations were determined by HPLC-UV. Pharmacokinetic parameters were calculated by using the WinNonlin software. There were statistically significant differences (p <0.05) in most of the pharmacokinetic parameters between study of 6 months against the other three studies in different ages. Changes in the pharmacokinetic parameters of nimesulide as a result of age, are determined by the growing and maturation of the animals. Resulting data suggest that nimesulide can be used safely as a long-term analgesic in dogs, but, the dosing regimens in humans should be different when administered at early age.

Discrepancy between bone density and bone material strength index in three siblings with Camurati-Engelmann disease.

Camurati-Engelmann (CE) is a very rare disease affecting one in every million persons worldwide. It is characterized by an enlargement of long bones. We aimed to assess bone characteristics in three siblings with different tools. Even if there was an excess of bone density, quality seemed to be deteriorated. INTRODUCTION: CE disease is a rare monogenic disorder affecting approximately one in every million persons worldwide. It is mainly characterized by a progressive hyperostosis of the periosteum and endosteum of the diaphysis of long bones. Limited data are available about bone characteristics in these patients. In three siblings with CE disease, we aimed to assess bone mineral density (BMD) and trabecular bone score (TBS) by dual-energy X-ray absorptiometry (DXA) and material characteristics at tissue level using bone impact reference point indentation. METHODS: Clinical data were collected and a general laboratory workup was performed. At the lumbar spine and hip, BMD and TBS were measured using DXA imaging. Bone material strength index (BMSi) was measured by bone impact microindentation using an Osteoprobe instrument. RESULTS: All three cases had densitometric values consistent with high bone mass (sum of Z-score at the lumbar spine and hip > 4). Hip BMD was extremely high in all three siblings at both total hip and femoral neck, while at the lumbar spine, two of them had normal values but the third again had very high BMD. TBS values were in the normal range. In contrast, BMSi measurements were at low or very low levels, compared with normal controls. CONCLUSION: Despite strikingly increased BMD and normal microarchitecture, BMSi is affected in patients with CE. Microindentation could be an appropriate tool for assessing bone fragility in these patients. Bone disease in this group of patients requires further study to better understand the underlying regulatory mechanisms and their alterations.

Non-arteritic anterior ischemic optic neuropathy as the only manifestation of a malignant hypertensive crisis: Report of a case.

Non-arteritic anterior ischemic optic neuropathy (NAION) is after glaucoma the most common optic neuropathy in patients over 50 years. It is known that high blood pressure (HBP) is an important risk factor for the development of NAION. It is also known that malignant arterial hypertension (MAH) could be accompanied by optic disc edema. However, MAH has not classically been considered a cause of NAION. We report the case of a 32-year-old patient who presented irreversible visual loss with a pattern compatible with NAION as the only manifestation of a hypertensive crisis.

Who are the men who have sex with men in Spain that have never been tested for HIV?

OBJECTIVES: The aims of the study were to describe the sociodemographic profile of men who have sex with men (MSM) who have never been tested for HIV and to analyse factors associated with never having been tested. METHODS: The European MSM Internet Survey (EMIS) was implemented in 2010 in 38 European countries on websites for MSM and collected data on sociodemographics, sexual behaviour, and other sexual health variables. A logistic regression analysis was conducted to assess variables associated with never having been tested for HIV. RESULTS: Of the 13,111 respondents living in Spain, 26% had never been tested for HIV. Those who had never been tested were significantly more likely to live in a settlement with fewer than 100,000 inhabitants, be younger than 25 years old, have a lower education level, be a student, and identify themselves as bisexual. In the multivariate analysis, to have never been tested for HIV was associated with being born in Spain [odds ratio (OR) 1.35; 95% confidence interval (CI) 1.192-1.539], living outside large settlements (OR 1.37; 95% CI 1.216-1.534), being younger than 25 years old (OR 2.94; 95% CI 2.510-3.441), being out to no one or only a few people (OR 2.16; 95% CI 1.938-2.399), having had no nonsteady partners in the last 12 months (OR 1.26; 95% CI 1.109-1.422), and being not at all confident to access HIV testing (OR 3.66; 95% CI 2.676-5.003), among others factors. CONCLUSIONS: The profile of the MSM who had never been tested for HIV indicates that most of them were men who were hard to reach (young, bisexual men, in the closet). Interventions should aim to improve access to and the convenience of testing.

One-year follow-up of dermoscopy education on the ability of medical students to detect skin cancer.

BACKGROUND: Learning skin cancer detection skills is important, yet many medical schools lack a standardized skin cancer examination (SCE) curriculum. OBJECTIVE: To determine medical students' skills in discriminating benign from malignant skin lesions on a 10-item image-based test one year after receiving a SCE intervention. METHODS: Cohort 1 received SCE teaching only. Cohort 2 received SCE teaching with dermoscopy tutorial, and a dermatoscope. The same test was given to assess students post-intervention and one year later. RESULTS: 43% (n = 145) and 38% (n = 143) of cohorts 1 and 2, respectively, participated one year later. Both cohorts improved or maintained their scores to correctly classify all lesions from post-intervention to one-year follow-up. After one year, cohort 2 maintained higher scores for successful identification of both benign and malignant lesions as compared to cohort 1. CONCLUSION: Medical students receiving a SCE intervention can improve their diagnostic skills after one year, especially with the aid of dermoscopy.

Hepatic resection and blood transfusion increase morbidity after cytoreductive surgery and HIPEC for colorectal carcinomatosis.

BACKGROUND AND OBJECTIVES: Cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (CRS-HIPEC) is an effective but complex treatment for peritoneal metastasis (PM). Our objective was to identify risk factors for postoperative morbidity and mortality following CRS-HIPEC. METHODS: Retrospective study of prospectively collected data of patients undergoing CRS-HIPEC for PM arises from colorectal cancer between January 2008 and December 2017. Perioperative variables were correlated with morbidity outcomes using a logistic regression model. RESULTS: Sixty-seven patients underwent CRS-HIPEC, and overall morbidity and mortality were 31.3% and 4.5% respectively. Major morbidity rate was 19.4%; 7.5% of patients were re-operated. Intraoperative blood transfusion (p = 0.01), liver resection (p < 0.01), and intestinal anastomosis (p < 0.01) were associated with a higher morbidity in univariate analysis. A multivariate analysis identified blood transfusion and liver resection as independent risk factors (OR 3.66, IC 1.13-16.54; OR 4.33, IC 1.17-11.46, respectively). Extension of visceral resection did not correlate with morbidity. Patients with lymph-node infiltration had a higher major complication rate (p = 0.01). CONCLUSIONS: CRS-HIPEC is a feasible treatment for colorectal PM with an acceptable morbi-mortality rate in experienced centers. In our study, digestive anastomosis, perioperative blood transfusion, hepatic resection, and lymph-node infiltration were associated with higher morbidity rates.

What is the best biomarker for diagnosis of rejection in heart transplantation?

INTRODUCTION: Acute cellular rejection is a major cause of graft loss in heart transplantation (HT). Endomyocardial biopsy remains the gold standard for its diagnosis, but it is an invasive procedure not without risk. A proinflammatory state exists in rejection that could be assessed by determining plasma levels of inflammatory biomarkers. OBJECTIVE: To analyze the utility of various inflammatory markers, which is most important and what values best classify patients to diagnose rejection. MATERIALS AND METHODS: A prospective study in 123 consecutive cardiac transplant recipients was conducted from January 2002 to December 2006. Fibrinogen protein (Fgp) and function (Fgf), C-reactive protein (CRP), tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6), and sialic acid (SA) determinations were performed at one, two, four, six, nine, and 12 months post-HT at the same time as biopsies. Coronary arteriography and intravascular ultrasound were performed on the first and last follow-up visits. Heart-lung transplants, retransplants, pediatric transplants, patients who died in the first month, and patients who refused consent were excluded. Also excluded were determinations that coincided with renal dysfunction, active infection, hemodynamic instability, or a non-evaluable biopsy. The final analysis included 79 patients and 294 determinations. The correlation between the levels of these biomarkers and the presence of rejection in the biopsy (> or = ISHLT grade 3) was studied. RESULTS: We did not find significant differences in the values of any of the markers analyzed on the six follow-up visits. Only CRP showed significant and sustained differences between the two groups (with and without rejection) from the second follow-up visit (month 2). The area under the curve showed significant differences in Fgp (0.614, p = 0.013), Fgf (0.585, p = 0.05), TNF-alpha (0.605, p = 0.02), SA (0.637, p = 0.002) and mainly CRP (0.765, p = 0.0001). CRP levels below 0.87 mg/dL ruled out rejection with a specificity of 90%. CONCLUSIONS: Among the inflammatory markers analyzed, CRP was the most useful parameter for non-invasive screening of acute cellular rejection in the first year post-HT.

Goal-directed therapy in cytoreductive surgery with hyperthermic intraperitoneal chemotherapy: a prospective observational study.

BACKGROUND: Cytoreductive surgery (CRS) with Hyperthermic Intraperitoneal Chemotherapy (HIPEC) in peritoneal carcinomatosis treatment causes significant hemodynamic, metabolic, and hematological alterations. Studies on the anesthetic intraoperative management are heterogeneous and scarce. There is a great heterogeneity in the anesthetic management of CRS and HIPEC. The aim of this study is to analyze perioperative hemodynamic goal-directed management and to evaluate the complications arisen until the seventh postoperative day. METHODS: Prospective, observational study of all CRS and HIPEC patients from March 2014 to May 2017. Hemodynamic and clinical parameters were registered during surgery and the first 3 postoperative days. We correlated intraoperative data with the postoperative course until the seventh day. RESULTS: A total of 92 patients were included in the study (age 58.5 ± 10.9 years, 47% colorectal carcinoma, and 38% ovarian carcinoma). Peritoneal Carcinomatosis Index (PCI) (median and ranges) was 10 [0-39]. Cardiac Index (CI) 3.15 l/min-1/m-2 [1.79-5.60]) and Systolic Volume Variation (SVV) (10% [3%-17%]) remained within the values of normality in all surgery phases. A large difference was observed between the minimum and maximum ranges of fluid therapy administered (median 9.8 ml/kg/h [5.3-24.3]), showing a great interindividual variation in the fluids requirement. A direct relationship was observed between PCI and surgery duration, fluid therapy, and intraoperative transfusion percentage (p < 0.02). CONCLUSIONS: There is a great variability in the intraoperative fluid therapy needs of the patients. SVV monitoring makes it possible to adjust the fluid therapy needs in each surgery phase. The use of a hemodynamic goal-directed anesthetic protocol in CRS and HIPEC enables to individually adjust the fluid therapy, avoiding over-hydration and ensuring hemodynamic stability in all surgery phases.

Analysis of heart rate turbulence in advanced heart failure and heart transplantation patients.

OBJECTIVE: The objective of this study was to describe heart rate turbulence (HRT) in advanced heart failure (HF) patients and in a group of patients who underwent heart transplantation (HT). MATERIALS AND METHODS: We performed 24-hour Holter recordings in 20 patients with advanced HF referred to our hospital for HT, including 16 males of overall mean age of 44 +/- 13 years and with a mean ejection fraction (EF) 21 +/- 7%. An additional set of recordings was obtained in a second group of 27 patients who had already undergone HT, including of 21 males of overall mean age of 47 +/- 14 years. We recorded the number of premature ventricular contractions (PVCs), mean heart rate (MHR), and 2 parameters of HRT-turbulence onset (TO) and turbulence slope (TS). RESULTS: Patients with HT showed a low density of premature ventricular complexes, in contrast to patients in the advanced HF group. For this reason, HRT could only be analyzed in 15 of the patients with advanced HF (66%) and in 10 of the patients who underwent HT (37%). MHR was 77 +/- 10 bpm in the advanced HF group and 90 +/- 10 bpm in the HT group. In both groups, TO and TS showed highly attenuated values. CONCLUSIONS: Patients with advanced HF showed a high number of PVCs with attenuated HRT parameters, reflecting increased circulating catecholamine levels and decreased response of the autonomic nervous system. Patients who underwent HT showed elevated MHRs, a small number of PVCs, and attenuated HRT values, as corresponds to a denervated heart.

Effect of circulatory assistance on premature death and long-term prognosis.

BACKGROUND: Patients undergoing urgent heart transplantation (HT) have a poorer prognosis and more long-term complications. The objective of this study was to compare the preoperative course in patients undergoing urgent HT according to the need for preoperative intra-aortic balloon counterpulsation (IABP). MATERIALS AND METHODS: We studied 102 consecutive patients including 23 patients with IABP who underwent urgent HT between January 2000 and September 2006. We excluded patients who received combination transplants, those who underwent repeat HT, and pediatric patients who underwent HT. The statistical methods used were the t test for quantitative variables and the chi(2) test for qualitative variables. A logistic regression model was constructed to assess the possible relationship between IABP and other variables on premature death within 30 days after HT. RESULTS: Mean (SD) patient-age was 50 (10) years. No significant differences were observed in baseline characteristics between the IABP and the non-IAPB groups. The IABP patient group had higher rates of acute graft failure (45.5% vs 35.4%; P = .46) and premature death (18.8% vs 14.8%; P = .67) and shorter long-term survival (40.6 [34.9] vs 54.5 [43.7] mo; P = .30). Multivariate analysis demonstrated no association between the need for IABP and increased frequency of premature death. CONCLUSIONS: Use of IABP is not associated with premature or late death. We recommend use of IABP in patients with acute decompensated heart failure to stabilize them before HT.

Effect of clinical trials on survival after heart transplantation.

UNLABELLED: The application of clinical trials (CTs) to daily practice is based on the assumption that the patients included in these trials are similar to those seen on a daily basis. We performed a retrospective study to evaluate patient survival depending on whether they were included in a CT. We studied 217 patients who underwent heart transplantation (HT) between January 2000 and September 2006. We excluded patients who received combination transplants, those who underwent repeat HT, and pediatric patients who underwent HT. In total, 54 patients were included in a CT and 163 were not (NCT). The statistical tests included the t test, the chi(2) test and the Kaplan-Meier method. RESULTS: Patients in the NCT group were in worse condition at HT, with a greater percentage of inotropic treatments pre-HT (36% vs 17%; P = .005), emergency transplants procedures (30% vs 13%; P = .01), and worse functional status pre-HT (P = .03). The NCT group exhibited lower survival (80.37% vs 87.04%; P = 0.13, log-rank test). There were no significant differences in the other analyzed variables. CONCLUSIONS: Patients included in CTs tend to have better long-term survival rates, for several reasons: patients in the CT group were more stable at HT (selection bias), and the close follow-up of patients in CTs makes it more likely that any complication will be detected and treated early (follow-up bias).

Evolution of right cardiac pressures during the first year after heart transplantation.

INTRODUCTION: Preoperative pulmonary hypertension is an adverse prognostic factor for early morbidity-mortality after heart transplantation (HT). The persistence of hypertension is likewise associated with a poorer patient prognosis. The present study investigated the evolution of right cardiac pressures in the first year after HT with respect to the background cardiac disease. METHODS: This study of 60 consecutive patients subjected to HT analyzed the baseline clinical characteristics and mean right atrial and right ventricle systolic and diastolic pressures in a pre-HT study and during biopsies performed in the first 2 weeks as well as at 1, 3, 6, 9, and 12 months after transplantation. The study excluded retransplantations, heart and lung transplantations, and pediatric patients, as well as patients not subjected to biopsy because of early mortality. RESULTS: The mean patient age was 50 years (83% males); 31.7% were diabetics, and 33% showed hypertension. The background heart disease was of ischemic origin in 35% of cases, and consisted of dilated myocardiopathy in 33%, with a mean left ventricle ejection fraction (LVEF) of 23% and a mean pulmonary artery systolic pressure of 50.1 mm Hg. During the postoperative course, an important decrease versus baseline was observed in right heart pressures as soon as 2 weeks post-HT, with a drop in right ventricle (RV) systolic pressure from 50.3 +/- 13.7 to 42.5 +/- 10.4 mm Hg (P = .013), and a drop in RV diastolic pressure from 17.4 +/- 5.8 to 14.2 +/- 4.1 mm Hg (P = .007). This decreased tendency continued to a more moderate extent to the third month, after which the pressures stabilized. The same behavior was observed in patients with diseases of ischemic origin and in those with dilated myocardiopathy. CONCLUSIONS: In our series, right cardiac pressures showed an important decrease in the first days after HT, with stabilization by the third month--though without returning to normal values and without modifications in the first year after transplantation. No differences in this evolutive trend were seen according to the type of background heart disease.

Early changes in optic coherence tomography in a child with laser pointer maculopathy. / Cambios precoces en la tomografía de coherencia óptica en un niño con maculopatía inducida por puntero láser.

CASE REPORT: A 9-year-old boy referred due to visual loss in his right eye after playing with a laser pointer. In the first visit (12hours later) visual acuity (VA) was 0.15. A hypopigmented lesion was present in the fovea, and optic coherence tomography (OCT) showed vertical hyper-reflective bands. In the last visit (6 months later), VA had improved to 0.5, and OCT showed a well-defined area of outer retinal layer disruption. DISCUSSION: An inadequate use of laser pointers can induce severe and permanent visual loss.

Diagnostic usefulness of inflammatory markers in acute cellular rejection after heart transplantation.

BACKGROUND: Acute cellular rejection (ACR) affects early morbidity and mortality after heart transplantation. The diagnostic technique of choice is endomyocardial biopsy. Our aim was to evaluate the diagnostic usefulness of inflammatory markers as a noninvasive method to monitor cellular rejection. MATERIAL AND METHODS: We prospectively analyzed 73 cardiac transplant patients by determining the serum levels of protein fibrinogen (fgpro), functional fibrinogen (fgfun), C-reactive protein (CRP), and sialic acid (SA) coinciding with an endomyocardial biopsy (5.1 revisions/patient). The statistical methods were chi(2), Student's t-test, and ROC curves. RESULTS: Of the 373 controls, significant rejection was detected in 19%. Analysis of the relationship between ACR and the markers showed significantly elevated levels of fgpro (345 +/- 90 versus 307 +/- 74 mg/dL; P = .03), fgfun (361 +/- 101 versus 318 +/- 89 mg/dL; P = .04), and SA (74 +/- 22 versus 66 +/- 15 mg/dL; P = .02), but not CRP (19 +/- 29 versus 10 +/- 21 mg/dL; P = .07). SA displayed a better diagnostic utility (area under the curve 0.7; P < .01), 35% sensitivity, 85% specificity, and 82% negative predictive value for a cutoff point of 80 mg/dL. CONCLUSIONS: Among the inflammatory markers increased in ACR, SA was the most useful noninvasive tool for screening.

Do cardiovascular risk factors influence cardiac allograft vasculopathy?

BACKGROUND: Cardiac allograft vasculopathy (CAV) is the leading cause of heart transplant failure after the first year. The etiological factors involved are currently a controversial matter. Intravascular ultrasound (IVUS) is considered the diagnostic procedure of choice. We assessed the relationship of cardiovascular risk factors with CAV. MATERIALS: We analyzed prospectively 22 patients. We conducted a first study with coronary angiography and IVUS at 36 +/- 3 days and a second at 598 +/- 49 days. We performed an average of 5.6 clinical revisions per patient, assessing the effect of the classic cardiovascular risk factors, the cause of heart failure, and the age of the patient and donor. The statistics used were chi(2), Fisher exact test, and Student t test. RESULTS: CAV was found in 10 subjects (45.5%). Univariate analysis showed statistically significant differences in the assessment of the presence of diabetes and dyslipidemia posttransplantation, but not pretransplantation. Among the patients with CAV there was a higher percentage of diabetics (32.8% vs 12%, P < .01). The patients with CAV also had higher levels of total cholesterol (211 +/- 40 mg/dL vs 195 +/- 35 mg/dL, P = .02), triglycerides (172 +/- 108 mg/dL vs 136 +/- 66 mg/dL, P = .03), low-density lipoprotein (133 +/- 35 mg/dL vs 117 +/- 30 mg/dL, P = .01), and lower high-density lipoprotein levels (46 +/- 15 mg/dL vs 52 +/- 12 mg/dL, P = .03). CONCLUSIONS: Only the diabetes and dyslipidemia present in the posttransplantation period were associated with CAV, which highlights the fact that it is a condition that both shares and has different features with atherosclerosis and probably requires a different diagnostic-therapeutic approach.

Photobiomodulation of pain and inflammation in microcrystalline arthropathies: experimental and clinical results.

OBJECTIVE: This article presents the results of laser therapy in crystal (hydroxyapatite, calcium pyrophosphate, and urates) deposition-induced arthritis in rats and the clinical applications in humans. BACKGROUND DATA: Microcrystalline arthropathies are prevalent among geriatric patients, who are more vulnerable to the side effects of drugs. The effectiveness of laser therapy for pain relief, free of side effects, has been reported in painful conditions. METHODS: Two milligrams of each of the above-mentioned crystals was injected in both joints of the back limbs in three groups of rats; these groups were then treated with laser irradiation. Three other groups received no treatment after the injections. We determined the plasmatic levels of inflammatory markers (fibrinogen, prostaglandin E2, and TNF(alpha)), tissues (prostaglandin E(2)) and conducted anatomopathological studies. Twenty-five patients with acute gout arthritis were randomized into two groups and treated over 5 days: group A, diclofenac 75 mg orally, twice a day; and group B, laser irradiation once a day. Forty-nine patients with knee chronic pyrophosphate arthropathy were randomized into two groups and treated over 21 days; group A, diclofenac 50 mg orally, twice a day; and group B, laser irradiation once a day. Thirty patients with shoulder chronic hydroxyapatite arthropathy were randomized into two groups and treated over 21 days; group A, diclofenac 50 mg orally, twice a day; and group B, laser irradiation once a day. RESULTS: Fibrinogen, prostaglandin E(2), and TNF(alpha) concentrations in the rats injected with crystals and treated with laser decreased significantly as compared with the groups injected with crystals without treatment. Both laser therapy and diclofenac achieved rapid pain relief in patients with acute gouty arthritis without significant differences in efficacy. Laser therapy was more effective than diclofenac in patients with chronic pyrophosphate arthropathy and in patients with chronic apatite deposition disease. CONCLUSION: Laser therapy represents an effective treatment in the therapeutic arsenal of microcrystalline arthropathies.