The relative contribution of environmental and genetic factors to phenotypic variation in familial Mediterranean fever (FMF)

Introduction

Familial Mediterranean fever (FMF) is an autosomal recessive disease, caused by mutations in the FMF gene MEFV (MEditerranean FeVer). It has a large phenotypic diversity even in patients with similar genotypes. Despite evidence that environmental factors (EFs) and genetic factors, including MEFV mutations (such as M694V, E148Q) and background modifier genes (MGs), affect the clinical manifestations of FMF, the relative contribution of each remains unknown.

Methods

To investigate the relative contribution of environmental and genetic factors to the phenotype of FMF, we compared the intra-pair clinical concordance of 10 mono and 7 dizygotic twins with FMF. The part played by EFs was determined by the phenotypic discordance of the monozygous twins, and the MGs effect was determined by deducing the environmental effect, computed for MZ twins, from the phenotypic discordance of the dizygous twins.

Results

The mean ± SD of intra-pair concordance was higher in the MZ than in DZ twin group (88.1 ± 13.2 vs. 70.7 ± 14.1 respectively, P value < 0.05). Based on the concordance in clinical manifestations in MZ and DZ twins, the environmental effect on the phenotype of FMF is estimated as 11.9% ± 6.6% and the MGs effect as 17.4% ± 15.5% in average.

Conclusions

In FMF the phenotype is affected by MEFV mutations, MGs and EFs in an estimated ratio of about 6:1.5:1 respectively.     

Association of TNF-α promoter gene G-308A polymorphism with metabolic syndrome, insulin resistance, serum TNF-α and leptin levels in Indian adult women

Background

Tumour necrosis factor alpha is a multifunctional proinflammatory cytokine involved in the pathogenesis of metabolic syndrome, insulin resistance, and obesity. Aim of this study is to investigate in a North Indian female population the impact of the G-308A TNF-α variant on various components of the metabolic syndrome, Insulin Resistance, serum TNF-α and Leptin levels.

Methods

The G-308A TNF-α polymorphism has been studied in 269 females with metabolic syndrome (NCEP ATP III criteria) (age 31.91 ± 6.05) and 272 healthy females without metabolic syndrome (age 30.96 ± 7.01). The G-308A variant was detected by PCR amplification and Nco-1 digestion.

Results

Homozygous mutant genotype (AA) (p = <0.001: OR = 3.24: 95% CI = 2.15-4.89) and mutant allele (A) (p = <0.001: OR = 3.04: 95% CI = 2.08-4.43) of TNF-α was significantly less frequently observed in the control population as compared to study group. Furthermore, on dividing the subjects into two groups according to the absence (TNF-1 allele) or presence of the mutant A (TNF-2) allele, significant results were obtained in most of the metabolic risk factors.

Conclusions

Our results suggest that the G-308A polymorphism of the TNF-α gene may be independently associated with hypertension, leptin level and hypercholesterolemia leading to metabolic syndrome independent of Insulin resistance and hyperglycemia.     

Neurohormonal and cytokine fluctuations following transcatheter closure for an atrial septal defect

Introduction

Inflammation and neurohormonal activation are considered to be involved in the development of earlier and/or later complications in congenital heart disease patients, even after a successful repair of the lesion. It is not yet clarified what is the role of the therapeutic interventions in the occurrence of such a response and how it could be associated with possible postoperative complications.

Aim

We sought to assess the inflammatory and neurohormonal response to transcatheter closure of secundum type atrial septal defects (ASD) over a six-month follow-up period. We also evaluated the association between the respective markers and catheterization data as well as echocardiographic measurements.

Methods

Plasma concentrations of interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), interleukin-10 (IL-10), N-terminal-proatrial natriuretic peptide (NT-proANP) and N-terminal-probrain natriuretic peptide (NT-proBNP) were assessed and echocardiographic measurements were performed in twenty-eight patients with atrial septal defect prior to, and at the first, second and sixth months post transcatheter closure. Thirty-three age-matched healthy volunteers were also enrolled.

Results

IL-6 plasma levels, although higher preoperatively, [physical logarithm (ln) IL-6: 3.37 ± 0.66 vs 2.92 ± 0.44 pg/ml, p = 0.015], reached control levels postoperatively, at the end of the third month, whereas TNF-α and IL-10 were not influenced by the procedure. NT-proANP levels were elevated preoperatively compared to the control group (ln NT-proANP 3.78 ± 0.572 vs 3.48 ± 0.30, p = 0.031), with a further significant increase during the 1st month (ln NT-proANP 3.78 ± 0.572 vs 4.2 ± 0.42, p = 0.006), following the pattern of the left atrial volume enlargement, and remained high even 6 months after the procedure .On the other hand, the initially normal concentrations of NT-proBNP, after a transient significant increase during the first month postoperatively (ln NT-proBNP 3.56 ± 0.94 vs 4.58 ± 0.91, p < 0.0001) returned to the controls’ levels at the end of the third month. Preoperative concentrations of NT-proANP positively correlated with NT-proBNP concentrations and pulmonary to systemic flow ratio (Qp/Qs).

Conclusions

Transcatheter closure could improve, on a mid- term basis, the inflammatory process but natriuretic peptides’ secretion continues in parallel with left atrial volume increase. Further follow up is required to determine the long-term progress of the inflammatory and neurohormonal response to the procedure.     

Características de la fractura de cadera y posterior recuperación en pacientes mayores de 65 años con historia de caídas recurrentes

Recurrent falls affect between 14.8% and 19% of the elderly population, and are associated with an increased risk of fracture. We know little about the influence the history of recurrent falls may have on recovery after hip fracture.

Methods

Cohort study. The patients included were, over 65 years admitted during a 1 year period to the General University Hospital of Albacete with a hip fracture due to a fall. Recurrent falls were defined as a history of two or more falls within the 6 months prior to the fracture. Variables: demographic data, circumstances of fall, number of falls in the previous 6 months, type of fracture and its repair, comorbidity and drug treatment, cognitive status at admission (Pfeiffer test) and independence for activities of daily living (Barthel Index - BI) were collected. A subsample of patients with pre-fracture BI≥60 and Pfeiffer at admission≤4 was followed up at 3, 6 and 12 months.

Results

A total of 335 patients were admitted. Data were collected on 279 of them, 19.4% of whom had previously suffered two or more falls. The recurrent fallers had a worse mental status on admission, a higher number of associated diseases, a lower percentage of independence in dressing and in bed-chair transferring than patients without history of recurrent falls, all statistically significant. In the 201 patients followed up, the impairment on the BI after 12 months compared to the BI previous to fracture was higher in recurrent fallers (-20.8 ± 31.54 vs -10.73 ± 20.21, P = .04), focusing more on independence in eating (76% vs 91.9%, P < .05), grooming (72% vs 91,9%, P < .01), faecal continence (60% vs 78.7%, p < .05) and walking indoors (80% vs 93.3%, P < .05).

Conclusions

The recovery of independence after hip fracture is significantly lower in the group of recurrent fallers in patients without moderate or severe functional impairment previous to fracture and cognitively stable.     

Evaluation impact of long-term usage of inhaled fluticasone propionate on ocular functions in children with asthma

Objective

Although systemic, topical, and periocular corticosteroid administration have long been associated with ocular side effects, there has been little evidence to suggest that long-term inhaled corticosteroids can cause ocular side effects. The aim of this study was to evaluate the effects of long term treatment inhaled fluticasone propionate spray usage the recommended dose on some ocular functions in pediatric patients with asthma.

Methods

The study group consisted of 266 prepubertal children with asthma who had used inhaled fluticasone propionate spray at 3-6 years intermittently. One hundred and sixty children who were newly diagnosed with asthma without any treatment made up the control group. Schirmer test results, central corneal thickness, visual acuity, intraocular pressure, cataract formation, keratometry and tear break-up time compared between study and control groups.

Results

The ages of the 266 study patients (150 male) were between 7 and 11 years. The average age (±SEM) was 8.2 ± 1.7 years, and the mean (±SEM) a daily dose of 323 μg (range 250-450 μg) inhaled fluticasone propionate spray, with 865.2 ± 215 g total steroid use during treatment. Eye functions including cataract formation, corneal ectasia, ocular hypertension or glaucoma, and dry eye were not observed in any of the patients in the study group and were not correlated with total steroid dosage (t = 0.150, p = 0.384).

Conclusion

Our findings suggest that long-term intermittent treatment for 3-6 years with inhaled fluticasone propionate spray, as much as average 320 μg daily, in children with asthma seems to be safe for some eye functions.     

Static pressure accelerates ox-LDL-induced cholesterol accumulation via SREBP-1-mediated caveolin-1 downregulation in cultured vascular smooth muscle cells

Objective

To investigate the effect of static pressure on cholesterol accumulation in vascular smooth muscle cells (VSMCs) and its mechanism.

Methods

Rat-derived VSMC cell line A10 treated with 50 mg/L ox-LDL and different static pressures (0, 60, 90, 120, 150, 180 mm Hg) in a custom-made pressure incubator for 48 h. Intracellular lipid droplets and lipid levels were assayed by oil red O staining and HPLC; The mRNA levels of caveolin-1 and ABCA1, the protein levels of caveolin-1 SREBP-1 and mature SREBP-1 were respectively detected by RT-PCR or western blot. ALLN, an inhibitor of SREBP metabolism, was used to elevate SREBP-1 protein level in VSMCs treated with static pressure.

Results

Static pressures significantly not only increase intracellular lipid droplets in VSMCs, but also elevate cellular lipid content in a pressure-dependent manner. Intracellular free cholesterol (FC), cholesterol ester (CE), total cholesterol (TC) were respectively increased from 60.5 ± 2.8 mg/g, 31.8 ± 0.7 mg/g, 92.3 ± 2.1 mg/g at atmosphere pressure (ATM, 0 mm Hg) to 150.8 ± 9.4 mg/g, 235.9 ± 3.0 mg/g, 386.7 ± 6.4 mg/g at 180 mm Hg. At the same time, static pressures decrease the mRNA and protein levels of caveolin-1, and induce the activation and nuclear translocation of SREBP-1. ALLN increases the protein level of mature SREBP-1 and decreases caveolin-1 expression, so that cellular lipid levels were upregulated.

Conclusion

Static pressures stimulate ox-LDL-induced cholesterol accumulation in cultured VSMCs through decreasing caveolin-1 expression via inducing the maturation and nuclear translocation of SREBP-1.     

Clinical significance of plasma CD146 and P-selectin in patients with type 2 diabetic nephropathy

Objective

To investigate the levels of plasma CD146 and P-selectin in patients with type 2 diabetic nephropathy at different stages.

Methods

A total of 80 patients with type 2 diabetes mellitus were enrolled in the present study. According to 24 h urinary albumin excretion ratio and renal function, they were further divided into group of diabetes without microalbuminuria (DN0, n = 20), microalbuminuria group (DN1, n = 20), macroalbuminuria group (DN2, n = 20) and renal insufficiency group (DN3, n = 20). Another 20 healthy subjects were enrolled as control group (non-DM). Plasma CD146 and P-selectin were measured by ELISA.

Results

Plasma CD146 and P-selectin were significantly increased in patients with type 2 diabetes with microalbuminuria (DN1) compared with health control (CD146: 415.3 ± 29.0 vs. 243.5 ± 14.7 ng/ml, P < 0.05; P-selectin: 66.8 ± 3.4 vs. 45.3 ± 2.7 ng/ml, P < 0.001). With the development of diabetic nephropathy, both plasma CD146 and P-selectin level progressively rise, with the highest levels in patients with significant renal insufficiency (DN3: 515.9 ± 36.9 and 81.5 ± 5.1 ng/ml respectively, P < 0.001). Moreover, the increase in CD146 is positively co-related to the rise of P-selectin in patients with type 2 diabetes.

Conclusion

Expression of CD146 and P-selectin in patients with type 2 diabetes is elevated, and they are positively correlated with severity of diabetic nephropathy.     

Chronic angiotensin-(1-7) administration improves vascular remodeling after angioplasty through the regulation of the TGF-β/Smad signaling pathway in rabbits

Objective

Angiotensin-(1-7) [ANG-(1-7)] has been reported to attenuate neointimal formation after vascular injury and stent implantation in rats, but the mechanism remains mostly unresolved. Interestingly, the levels of circulating transforming growth factor-beta1 (TGF-β1) after myocardial infarction were suppressed by ANG-(1-7), which suggests a possible downstream target for the anti-remodeling action of ANG-(1-7). Our study focused on the effects of ANG-(1-7) on vascular remodeling, including neointimal formation and collagen synthesis, and determining whether or not these effects were dependent upon the TGF-β signaling pathway.

Methods

Thirty-two New Zealand white rabbits underwent sham surgery or angioplasty in abdominal aorta. The animals were divided into four groups, which were sham, control, ANG-(1-7), and ANG-(1-7) + A-779. Subsequently, an osmotic minipump was implanted to deliver saline, ANG-(1-7) (576 μg kg⁻¹ d⁻¹) or ANG-(1-7) + A-779 (576 μg kg⁻¹ d⁻¹) for 4 weeks.

Results

The ANG-(1-7) group displayed a significant reduction in neointimal thickness (207.51 ± 16.70 μm vs. 448.08 ± 15.30 μm, P < 0.001), neointimal area (0.266 ± 0.009 mm² vs. 0.408 ± 0.002 mm², P < 0.001), and restenosis rate (28.13 ± 2.74% vs. 40.13 ± 2.74%, P < 0.001) when compared to the control group. ANG-(1-7) also inhibited collagen synthesis by significantly decreasing the mRNA expression of Collagen I and Collagen III (vs. Control group: 0.2190 ± 0.0036 vs. 0.3852 ± 0.0212, P < 0.001 and 1.1328 ± 0.0554 vs. 1.7378 ± 0.1164, P < 0.001, respectively). Furthermore, the expression of TGF-β1 and phosphor-Smad2 (p-Smad2) were significantly suppressed by ANG-(1-7) (vs. Control group: 1.21 ± 0.07 vs. 1.54 ± 0.08, P < 0.001 and 0.31 ± 0.01 vs. 0.43 ± 0.02, P < 0.001, respectively), but no effect on p38 phosphorylation was observed. [d-Ala⁷]-ANG-(1-7) (A-779), showed a tendency to attenuate the anti-remodeling effects of ANG-(1-7).

Conclusion

ANG-(1-7) decreases the amount of vascular remodeling, including a reduction in neointimal formation and collagen synthesis, after angioplasty in rabbits. The responsible mechanism may function through the possible down-regulation of TGF-β1 levels and inhibition of the Smad2 pathway.     

Calidad de vida percibida por las personas mayores. Consecuencias de un programa de estimulación cognitiva a través de la motricidad «Memoria en movimiento»

Introduction

This article presents the results of evaluation of health related quality of life in a group of elderly people who were engaged in the program of cognitive stimulation «Memory in movement».

Materials and methods

A content analysis was conducted to determine the type of experience that the subjects stated in the context of an interview. The statements were classified into categories created ad hoc. The sample consisted of 32 participants with a mean age of 69.92 ± 4.98 years. The software QSR NVivo-8 was used for data processing.

Results

The results show that the 48% of the elderly perceive some improvements in their memorisation abilities, 47% in attention and concentration, and 10% in the satisfaction with life after being in the program. They are especially worried about the loss of memory -stated by the 65.62%- and they came to the cognitive stimulation program with the aim of improving this capacity. The feelings that participants reported having experienced during the program have to do with fun, vitality and energy.

Conclusions

Programs on cognitive stimulation that incorporate some physical activities, together with a clear playful and social component, improve the psychic and social capacities and they open an important line of intervention due to their good acceptance by the elderly.     

Common polymorphisms in the P-selectin gene in women with recurrent spontaneous abortions

Background

To investigate possible associations of P-selectin polymorphisms with idiopathic recurrent pregnancy loss (RPL).

Methods

Study subjects comprised 270 consecutive RPL cases attending outpatient maternity services, and 322 multi-parous control women. P-selectin genotyping was done by PCR-RFLP and PCR-ASA methods.

Results

The P-selectin variants rs1800807, rs1800805, and rs6127, were in Hardy Weinberg equilibrium, and low linkage disequilibrium was noted between the three studied SNPs. The frequency of rs6127 A allele (P < 0.001I), but not rs1800807 C allele (P = 0.957) or rs1800805 A allele (P = 0.760), was higher in RPL cases than in control women. Significant differences in the distribution of rs6127 (P < 0.001), but not rs1800807 (P = 0.444) or rs1800805 (P = 0.391) genotypes were seen between cases and controls, and only rs6127 showed a significant association with RPL, with increments of 2.65 and 4.96 in disease risk seen for heterozygous and homozygous carriers, respectively. Among the 8 three-locus Pselectin haplotypes constructed (rs1800807/rs1800805/rs6127), increased frequency of GGG (Pc = 0.0249), CGG (Pc = 0.0256), and CAG (Pc = 0.0174) haplotypes, and lower frequency of CGA haplotype (Pc = 0.0091) were seen in RPL cases, thus conferring disease susceptibility and protective nature to these haplotypes, respectively.

Conclusions

P-selectin gene polymorphisms and haplotypes contribute to RPL development.     

Urinary free cortisone, but not cortisol, is associated with urine volume in severe obesity

Background

High urine volume enhances urinary free cortisol (UFF) and cortisone (UFE) excretion rates in normal-weight adults and children. Renal excretion rates of glucocorticoids (GC) and their metabolites are frequently altered in obesity. The aim of the present study was to investigate whether UFF and UFE excretion is also affected by urine volume in severely obese subjects.

Experimental

In 24-h urine samples of 59 extremely obese subjects (mean BMI 45.3 ± 8.9 kg/m²) and 20 healthy lean subjects (BMI 22.1 ± 1.8 kg/m²), UFF and UFE, tetrahydrocortisol (THF), 5α-tetrahydrocortisol (5α-THF), and tetrahydrocortisone (THE) were quantified by RIA. The sum of THF, 5α-THF, and THE (GC3), the three major GC metabolites, reflects daily cortisol secretion. 11β-Hydroxysteroid dehydrogenase type 2 (11β-HSD2) activity was assessed by the ratio UFE/UFF. Daily GC excretion rates were corrected for urine creatinine and adjusted for gender and body weight.

Results

In extremely obese subjects, urine volume was significantly associated with creatinine-corrected UFE and 11β-HSD2 activity after adjustment for gender and BMI (r = 0.47, p = 0.0002 and r = 0.31, p = 0.02, respectively). However, urine volume was not associated with creatinine-corrected UFF and GC3 (p = 0.4 and p = 0.6, respectively). In lean controls, urine volume was significantly associated with creatinine-corrected UFE and UFF (r = 0.58, p = 0.01 and r = 0.55, p = 0.02, respectively), whereas urine volume was not associated with 11β-HSD2 activity after appropriate adjustment (p = 0.3).

Conclusions

In severe obesity, in contrast to normal weight, renal excretion of UFE, but not of UFF is affected by fluid intake. This discrepancy may be due to the increased renal 11β-HSD2 activity in obesity.     

RANTES gene mRNA expression and its -403 G/A promoter polymorphism in coronary artery disease

Objective

Increased RANTES expression has been described to have a role in atherosclerosis plaque formation. Functional polymorphisms within RANTES promoter region have shown association with increased risk of coronary atherosclerosis (CAD). The aim of this study was to examine the RANTES mRNA expression in patients with CAD compared to patients without CAD and its association with RANTES − 403 G/A polymorphism in an Iranian population.

Methods

The study was performed on 319 patients who underwent coronary artery angiography and patients with > 50% stenosis in vessels considered as case groups (CAD+) N = 191 and normal vessels group as control (CAD−) N = 128. In each group 20 patients were examined for RANTES mRNA expression.RANTES mRNA expression was examined using quantitative real-time PCR. Genotyping of − 403 polymorphism was performed using PCR-RFLP technique.

Results

We found that RANTES mRNA expression was increased to 1.37 fold in CAD patients compared to the controls but the difference was not statistically significant. Also comparing the RANTES mRNA expression in patients with different RANTES − 403 G/A polymorphism showed that in patients carrying AA genotype RANTES mRNA expression was increased to 1.74 fold compared to patients carrying GG genotype and to 1.51 fold compared to patients carrying GA genotype. No significant difference for allele and genotype frequencies of RANTES − 403 polymorphism was found between cases and controls.

Conclusion

More studies on larger number of samples are required to further evaluate role of RANTES in pathogenesis of CAD.     

Cryopreservation of human ovarian tissue: Comparison of novel direct cover vitrification and conventional vitrification

Objective

To compare the effect of novel direct cover vitrification (DCV) and conventional vitrification (CV) for human ovarian tissue.

Study design

Ovarian biopsy specimens obtained from 12 patients were randomly allocated into five groups: Fresh, DCV1, DCV2, DCV3 and CV. Three concentrations of cryoprotectants were used in DCV group. The equilibration solution of DCV1, DCV2, DCV3 was 5% EG + 5% DMSO + DPBS, 7.5% EG + 7.5%DMSO + DPBS, 10% EG + 10% DMSO + DPBS, respectively. And the vitrification solution of DCV1, DCV2, DCV3 was 10% EG + 10% DMSO + DPBS, 15%EG+15% DMSO + DPBS, 20% EG + 20% DMSO + DPBS, respectively. The equilibration solution and the vitrification solution of CV group was same as DCV3 group. The effects of cryopreserved procedure on human ovarian tissue were studied by histology, TUNEL assay, transmission electron microscopy (TEM) and heterotopic allograft.

Results

The percentages of morphologically normal and viable follicles of DCV2 were significantly higher than DCV1, DCV3 and CV groups (P < 0.05). TUNEL assay demonstrated that the incidence of apoptotic cell in vitrification ovarian tissue was significantly higher than fresh tissue (P < 0.05), but there were no difference in various groups with cryopreservation. TEM showed that less damage was detected in DCV2 group. After grafting, the follicle density of DCV2 was greater than DCV1, DCV3 and CV groups (P < 0.05).

Conclusions

The novel cover vitrification with optimal concentration of cryoprotectants is superior to conventional vitrification. It is suitable for human ovarian tissue fragments with high efficiency and facility.     

Significant associations of the rs2943634 (2q36.3) genetic polymorphism with adiponectin, high density lipoprotein cholesterol and ischemic stroke

Background

rs2943634 C/A single nucleotide polymorphism (SNP), located in a non coding region of chromosome 2q36.3, has been associated with coronary artery disease in two genome wide association studies. Our goal was to investigate its relation with myocardial infarction (MI) and ischemic stroke (IS), as well as with 12 intermediate risk phenotypes, in a population-based prospective cohort study.

Methods

rs2943634 was genotyped in a case-cohort study including a random sample of 1891 individuals (subcohort) and all incident MI (n = 211) and IS (n = 144) cases during a mean follow-up of 8.2 ± 2.2 years, nested within the European Prospective Investigation into Cancer and Nutrition (EPIC)-Potsdam cohort comprising 27,548 middle-aged men and women.

Results

rs2943634 minor allele (A) was associated in an additive fashion with lower risk of IS but not with MI [hazard ratio (HR) = 0.66; 95% confidence interval (CI): 0.50-0.87; P = 0.003; HR = 1.02; 95% CI: 0.82-1.28; P = 0.83 respectively, for the age and sex adjusted model]. Furthermore, it was related to slightly higher levels of plasma adiponectin [CC 6.94, CA 7.27, AA 7.86 μg/ml, P = 0.0002] and high density lipoprotein (HDL)-cholesterol (CC 52.08, CA 53.05 and AA 55.27 mg/dl, P = 0.002), based on additive models. Adjustment for adiponectin and HDL-cholesterol did not attenuate the association between the SNP and IS risk. In contrast, adjustment for adiponectin abolished the association between the SNP and HDL-cholesterol and adjustment for HDL-cholesterol attenuated the association between the SNP and adiponectin.

Conclusions

Our findings suggest that rs2943634 is associated with IS risk and with plasma levels of HDL-cholesterol and adiponectin in this German population. Further investigations are needed to confirm these results and to clarify the mechanisms underlying the association.     

The influence of cryopreservation and seminal plasma on the chromatin structure of dog spermatozoa

It was the aim of the current study to investigate effects of seminal plasma on the chromatin structure of frozen-thawed canine (Canis lupus familiaris) spermatozoa. A total of 20 ejaculates were collected. Ejaculates were divided, and one half was centrifuged for removal of seminal plasma (c) while the other was left uncentrifuged (nc) before cryopreservation. This was performed according to the Uppsala system in a computerized freezing machine. Before freezing (bf) and after thawing (at), samples were investigated for motility (M), viability (CASA), and chromatin status (sperm chromatin structure assay; SCSA). Before freezing, the average DFI% and the SD-DFI from 20 nc ejaculates were 1.7 ± 4.0% and 18.6 ± 1.2, respectively. After thawing, all motility parameters decreased and were significantly lower in centrifuged than in noncentrifuged samples, whereas the percentage of morphologically abnormal spermatozoa (Morph) was significantly higher (nc: M bf, 84.1 ± 20.6%; M at, 51.9 ± 15%; c: M bf, 84.1 ± 20.6%; M at, 43.3 ± 22.2%; Morph nc: 28.3 ± 7.8% vs. c: 31.0 ± 9.8%). Furthermore, only in c samples did the DFI increase within 6 h after thawing (DFI c: bf, 41.8 ± 1.5%; 6 h at, 45.4 ± 6.6%; P < 0.01). The SD-DFI as well as the DFI% increased within 3 h of storage in both groups (SD-DFI nc: bf, 18.6 ± 1.2%; 3 h at, 25.8 ± 5.4%; DFI% nc: bf, 1.1 ± 4.0%; 3 h at, 6.1 ± 12.9%; P < 0.05). For both parameters, there was no significant difference between c and nc samples at any time investigated. In conclusion, centrifugation of semen samples before freezing decreased postthaw motility and increased the percentage of morphologically abnormal spermatozoa as well as the degree of sperm chromatin denaturation over time. Centrifugation of canine ejaculates before cryopreservation can therefore no longer be recommended.     

Association between the epidermal growth factor rs4444903 G/G genotype and advanced fibrosis at a young age in chronic hepatitis C

Background

The epidermal growth factor (EGF) rs4444903 A > G polymorphism has been associated with the development of liver cancer, which commonly complicates cirrhosis of viral origin; however, whether this polymorphism might be associated with fibrosis progression in chronic viral hepatitis is unknown. The present study was performed to assess the allelic and genotypic frequencies of the rs4444903 A > G polymorphism in patients with chronic hepatitis C virus HCV infection and to ascertain whether this polymorphism might be an independent predictor of the degree of fibrosis.

Methods

An RFLP-PCR technique was used to genotype 645 patients (211 with cirrhosis); 528 were referred for the diagnosis and treatment of chronic hepatitis C, and 117 were transplanted for HCV-related end stage liver disease. A group of 428 healthy subjects served as a control. All the subjects were of Caucasian ethnicity.

Results

The EGF rs4444903 A > G polymorphism genotype frequencies in HCV chronic infected patients were as follows: A/A = 227 (35.3%), A/G = 328 (50.9%), and G/G = 90 (14.8%). Genotype frequencies were found to differ between patients with an Ishak staging score ? 2 (A/A = 117, A/G = 157, G/G = 34) and patients with a score > 2 (A/A = 110, A/G = 171, G/G = 56, p = 0.038). A highly significant linear relationship between increasing stage scores and EGF genotype was detected in younger patients (A/A: 2.02 ± 0.18, A/G: 2.55 ± 0.17, G/G: 3.00 ± 0.32, p = 0.008). However, no significant association was detected between the stage score and EGF genotype in older patients (A/A: 3.79 ± 0.19, A/G: 3.64 ± 0.15, G/G: 3.98 ± 0.30 p = 0.579).

Conclusions

The EGF rs4444903 A > G polymorphism may facilitate liver fibrosis progression in Caucasian patients with chronic hepatitis C, especially in younger patients.     

Utilización del servicio de urgencia de un hospital universitario por los adultos mayores en Santiago de Chile

Introduction

An increase in visits to Emergency Departments by older adults has been reported, but there are no data available on this in countries in the early phases of demographic and epidemiological transition. This paper describes the characteristics of people over 60 years-old (AM) who visited the Emergency Department of the Hospital Clínico Universitario de la Pontificia Universidad Católica, Chile (SU-PUC), compared to those less than 60 years-old (AJ).

Material and methods

Demographic data and reasons for admission and re-admission were collected retrospectively from the SU-PUC monthly statistics report. Obstetrics, paediatrics and «scheduled admissions» were excluded. The frequencies were compared using Chi-squared (significance: P < .05).

Results

A total of 37,660 visits to the SU-PUC were recorded (81% AJ; 19% AM; with 8% being older than 75 years). No statistical differences were found in the visit time (70% daytime), or by season between the groups.A total of 7,414 (19.6%) of those who visited were hospitalised, with differences being detected between groups (AM: 48.9% vs 12.9% AJ; P < .001), particularly in those over 75 years (59%). The primary cause of admission was cardiopulmonary in AM (22%) and gastrointestinal in AJ (31%). Re-admissions were 10% in AM and 6% in AJ (P < .001).

Conclusion

The use of SU by AM and some characteristics of their care process (hospitalisation) are similar to those found in countries in more advanced phases of demographic transition.