A case of necrotizing enterocolitis associated with adenovirus infection in a term infant with 22q11 deletion syndrome

Infections with adenoviruses are a common problem in the pediatric population. Normally asymptomatic to mild, those infections tend to take a more severe course in immunocompromised patients. 22q11 deletion syndrome (22q11DS) represents a common genetic disorder causing immunodeficiency from thymic hypoplasia or aplasia, heart defects, a characteristic facial appearance, and velopharyngeal dysfunction. Necrotizing enterocolitis (NEC) is a frequent gastrointestinal emergency observed in neonatal intensive care units. The occurrence of NEC is more prevalent in preterm infants. However, there are cases in term infants, but usually, they are associated with predisposing disorders. In this case report, a child is presented with 22q11DS that postnatally developed NEC associated with an adenoviral infection. Although other viruses such as toroviruses or cytomegaloviruses have been implicated in the pathogenesis of NEC in preterm infants, we could not find any report in the recent medical literature describing an association between adenoviral infections, NEC, and 22q11DS in a term infant.     

Posterior urethral valves in adult with Down syndrome

Posterior urethral valves (PUVs) in patients with Down syndrome (DS) have been previously described. However, no case of PUVs has been reported in an adult patient with DS. We report on a 40-year-old man with DS, who presented with two severe urinary infections and obstructive symptoms. He was found to have type 3 PUVs associated with bladder neck sclerosis. PUV resection and bladder neck incision were done. Because PUVs seem to be more frequent in patients with DS, complete investigations should be performed, even in adults with DS, in the case of urinary infection or lower urinary tract symptoms.     

Expression of LOX-1, an oxidized low-density lipoprotein receptor, in experimental hypertensive glomerulosclerosis

Oxidized low-density lipoprotein (OxLDL) has been implicated in atherosclerosis and glomerulosclerosis. LOX-1 is a recently identified OxLDL receptor that is abundantly expressed in vascular endothelial cells. The aim of the present study was to investigate LOX-1 expression in the kidneys of hypertensive rats. Dahl salt-sensitive (DS) and salt-resistant (DR) rats were fed a 0.3% or 8% NaCl diet. Some DS 8% rats were treated with manidipine or hydralazine. LOX-1 gene expression was markedly elevated in the kidneys and glomeruli of hypertensive DS 8% rats compared with those of normotensive DR and DS 0.3% rats. Prolonged salt loading further increased the renal LOX-1 expression in DS rats. The LOX-1 upregulation in DS 8% rats was accompanied by renal overexpression of transforming growth factor-beta 1 and type I collagen, impaired renal function, and histologic glomerulosclerotic changes, all of which were ameliorated by antihypertensive treatment. LOX-1 was indeed expressed in the glomeruli in vivo and in cultured glomerular cells in vitro. However, LOX-1 expression was elevated in the aorta but not the kidneys of spontaneously hypertensive rats, which exhibited hypertension but minor glomerulosclerotic changes. In conclusion, the LOX-1 upregulation in the kidney of DS 8% rats was parallel to glomerulosclerotic changes and renal dysfunction, suggesting a possible pathogenetic role for renal LOX-1 in the progression to hypertensive glomerulosclerosis.     

The differently expressed proteins in MSCs of degenerative scoliosis

Purpose

Degenerative scoliosis (DS) is an important degenerative lumbar disease causing spinal dysfunction. The true reason or pathogenesis of DS is still unknown. Bone marrow-derived mesenchymal stem cells (BM-MSCs) are the stem/progenitor cells of the osteoblasts. The diseases associated with osteogenesis could be caused by abnormality of the MSCs. The purpose of this study was to find the differential proteins expressed in MSCs of patients with DS.

Methods

We collected and cultured the MSCs from 12 DS patients and 12 age- and gender-matched patients with lumbar spinal stenosis. Then the MSC samples were analyzed with 2D-DIGE and MALDI-TOF–MS to find the differential proteins which were further validated by Western blot.

Results

We found 115 spots that were differently expressed in the MSC of DS patients with 2D-DIGE, and 44 proteins were identified from samples of DS and control using MALDI-TOF–MS. Of these proteins, PIAS2, NDUFA2, and TRIM 68, which were up-regulated in DS more than 4 times were validated by Western blot.

Conclusions

The information obtained with this proteomics analysis will be useful in understanding the pathophysiology of DS. Further investigations on the functioning pathway, the specificity and the mechanism of these proteins will be carried out.     

天然型无机骨修复良性溶骨性骨缺损的临床观察

为寻找良性骨缺损理想的充填材料，特别是修复儿童良性溶骨性较大的骨缺损，采用天然型无机骨（ＮＮＢ）充填良性溶骨性骨缺损５例，其中骨囊肿３例，纤维异样增殖症１例，非骨化性纤维瘤１例。病变位于股骨中上段１例，股骨下段３例，肱骨上段１例。５例均行病灶开窗刮除，彻底清除内膜及瘤样病变。充填方块状ＮＮＢ，术后伤口均Ⅰ期愈合。术后３个月～６个月活动正常。术后Ｘ线片复查见方块状ＮＮＢ间及其内的间隙影消失，新生骨与周围骨壳融合，显示病灶愈合。经７个月～２年随访，病变区无复发。认为，ＮＮＢ是修复良性溶骨性骨缺损理想的充填材料。     

The Right Small-for-Size Graft Results in Better Outcomes than the Left Small-for-Size Graft in Adult-to-Adult Living Donor Liver Transplantation

BACKGROUND: The recent outcome of adult-to-adult living donor liver transplantation (ALDLT) using small-for-size grafts (SFSGs; GRWR <0.8%) has been excellent after right grafts were exclusively used in large-volume ALDLT centers. METHODS: We compared the outcome of ALDLTs using 11 right SFSGs (group R) with that using 18 left SFSGs (group L) of our center. The dysfunction of graft was defined dysfunction as hyperbilirubinemia (>5 mg/dl), prolonged prothrombin time (>2 INR), or uncontrolled ascites (>1,000 ml/day) on 3 consecutive days in posttransplant 7 days, and the dysfunction score (DS; the sum of points given per each sign) of the graft was used to describe the SFSG dysfunction severity. RESULTS: The pretransplant recipient status was similar between the groups, but the 1-year mortality rate was 0% in group R and 33.3% (n = 6) in group L (p = 0.038). The ICU stay was longer in group L (20 days) than in group R (11 days; p = 0.004). Hyperbilirubinemia in group R vs. L was noted in 54.5% vs. 50%, prolonged prothrombin time in 18.2% vs. 50%, and uncontrolled ascites in 54.5% vs. 100%. The DS was lower in group R than in group L (1.3 vs. 2; p = 0.007). The DS was zero in four right liver recipients. On multivariate analysis, the only factor affecting DS was the graft side. CONCLUSION: The clinical signs of SFSG dysfunction were less arduous and there was no 1-year mortality in cases in group R. Therefore, the right SFSG may be used for ALDLT in the future base on the transplant center's experience.     

Dhat syndrome, an emergent condition within urology in Spain

Background

Dhat syndrome (DS) consists of vague somatic symptoms and at times sexual dysfunction which the patient falsely attributes to involuntary emissions of semen outside of sexual relations.

Objective

Describe and analyse the occurrences of DS in patients attending the clinic and clarify the existence of this condition within the Spanish Urological service.

Materials and methods

Patients reporting semen loss in urine or involuntarily outside of sexual relations were studied during a period from May 2006 to December 2007. Variables of age, nationality, marital status, family situation, medical history, reasons for the consultation, physical condition and additional tests were studied. All treatments and its effectiveness were also recorded.

Results

DS affected predominantly southern Asian continent citizens (n = 32). The average age was 35.44. Seventeen patients reported semen loss during urination; 20 at the end of urination; 11 spontaneously; 5 while sleeping; 4 during defecation; 1 while showering; 1 while eating meat; and 3 produced by noticing stained clothing. In 28 cases, the supposed loss of semen was linked to sex-related symptoms. All examinations and tests ruled out the existence of actual loss of semen.

Conclusions

In urology consultations, we have been witnessing the unusual appearance of DS, a condition known by psychologists and psychiatrists and practically unheard of by urologists. A previously unknown condition in Spain, immigration from Asia, is causing the appearance of this syndrome. Its rapid identification will prevent patients from paying costly and unnecessary tests and provide alternative therapies, within a multidisciplinary approach involving psychologists and psychiatrists.     

Dysfunctional renal nitric oxide synthase as a determinant of salt-sensitive hypertension: mechanisms of renal artery endothelial dysfunction and role of endothelin for vascular hypertrophy and Glomerulosclerosis

This study investigated the role of renal nitric oxide synthase (NOS), endothelin, and possible mechanisms of renovascular dysfunction in salt-sensitive hypertension. Salt-sensitive (DS) and salt-resistant (DR) Dahl rats were treated for 8 wk with high salt diet (4% NaCl) alone or in combination with the ET(A) receptor antagonist LU135252 (60 mg/kg per d). Salt loading markedly increased NOS activity (pmol citrulline/mg protein per min) in renal cortex and medulla in DR but not in DS rats by 270 and 246%, respectively. Hypertension in DS rats was associated with renal artery hypertrophy, increased vascular and renal endothelin-1 (ET-1) protein content, and glomerulosclerosis. In the renal artery but not in the aorta of hypertensive DS rats, endothelium-dependent relaxation to acetylcholine was unchanged; however, endothelial dysfunction due to enhanced prostanoid-mediated, endothelium-dependent contractions and attenuation of basal nitric oxide release was present. Treatment with LU135252 reduced hypertension in part, but completely prevented activation of tissue ET-1 without affecting ET-3 levels. This was associated with a slight increase of renal NOS activity, normalization of endothelial dysfunction and renal artery hypertrophy, and marked attenuation of glomerulosclerosis. Thus, DS rats fail to increase NOS activity in response to salt loading. This abnormality may predispose to activation of the tissue ET-1 system, abnormal renal vasoconstriction, and renal injury. Chronic ET(A) receptor blockade normalized salt-induced changes in the renal artery and reduced glomerular injury, suggesting therapeutic potential for ET antagonists in salt-sensitive forms of hypertension.     

Chronic lung allograft dysfunction after lung transplantation: the moving target

Chronic lung allograft dysfunction is a major challenge in long-term management of lung transplant recipients. Both alloimmune-dependent factors (rejection) and alloimmune-independent factors contribute to the development of chronic lung allograft dysfunction. Thus, use of the term “chronic rejection” tends to be intentionally avoided among specialists in the field, although “chronic rejection” is still an acceptable lay word understood by many patients. Several different phenotypes have been identified in chronic lung allograft dysfunction, including restrictive allograft syndrome, neutrophilic reversible allograft dysfunction, and fibrous bronchiolitis obliterans syndrome. Restrictive allograft syndrome is characterized by restrictive physiology and peripheral foci of inflammation and fibrosis, which contrasts the obstructive physiology and pathological foci in small airways in conventional bronchiolitis obliterans syndrome. Among patients with bronchiolitis obliterans syndrome, there is a subpopulation that responds relatively well to azithromycin. Because these patients show airway neutrophilia, this subtype of chronic lung allograft dysfunction was named neutrophilic reversible allograft dysfunction. Conversely, patients with bronchiolitis obliterans syndrome unresponsive to azithromycin show airway fibrosis with less inflammation (fibrous bronchiolitis obliterans syndrome). In general, restrictive allograft syndrome shows poorer survival than does bronchiolitis obliterans syndrome, and early-onset bronchiolitis obliterans syndrome (within 2 years) shows a worse prognosis than does late-onset bronchiolitis obliterans syndrome. Until preventive and therapeutic options are refined, chronic lung allograft dysfunction will remain a major life-limiting factor. It has significant psychological, physical, social, and economic impacts. Early introduction of palliative care is another important strategy to improve patients’ quality of life.     

Erectile dysfunction as a predictor of the metabolic syndrome in aging men: results from the Massachusetts Male Aging Study

PURPOSE: The metabolic syndrome, characterized by central obesity, insulin dysregulation, abnormal lipids and borderline hypertension, is a precursor state for cardiovascular disease. We determined whether erectile dysfunction is predictive of the metabolic syndrome. MATERIALS AND METHODS: Data were obtained from the Massachusetts Male Aging Study, a population based prospective cohort observed at 3 points during approximately 15 years (T(1)-1987 to 1989, T(2)-1995 to 1997, T(3)-2002 to 2004). The metabolic syndrome was defined by using a modification of the Adult Treatment Panel III guidelines. The association between erectile dysfunction and the metabolic syndrome was assessed using relative risks and 95% confidence intervals estimated using Poisson regression models. RESULTS: Analysis was conducted of 928 men without the metabolic syndrome at T(1). There were 293 men with incident metabolic syndrome, of which 56 had erectile dysfunction at baseline. Body mass index and the presence of 1 or 2 conditions constituting the metabolic syndrome definition were the strongest predictors of the metabolic syndrome. The association of erectile dysfunction with the metabolic syndrome (unadjusted RR 1.35, 95% CI 1.01-1.81) was modified by body mass index, with a stronger effect of erectile dysfunction in men with body mass index less than 25 (adjusted RR 2.09, 95% CI 1.09-4.02), and no erectile dysfunction and metabolic syndrome association in men with body mass index 25 or greater (adjusted RR 1.06, 95% CI 0.76-1.50). CONCLUSIONS: Erectile dysfunction was predictive of the metabolic syndrome only in men with body mass index less than 25. This finding suggests that erectile dysfunction may provide a warning sign and an opportunity for early intervention in men otherwise considered at lower risk for the metabolic syndrome and subsequent cardiovascular disease.     

Nasal health in Down syndrome: a cross-sectional study.

OBJECTIVE: To investigate peripheral nasal pathology as a contributor to olfactory impairment in DS. STUDY DESIGN: Twenty DS and 16 non-DS subjects were recruited. Nasal history and symptoms were assessed by self-report or informant. Olfactory threshold, odor identification, and nasal endoscopy were assessed on each subject. RESULTS: DS subjects were impaired on olfactory threshold (P<0.0001) and odor identification (P<0.001). Although DS subjects tended toward upper-respiratory infections, sleep-disordered breathing, and nasal itching, differences were not significant (P=0.07, 0.06, and 0.058, respectively). There were no significant differences on self-reported nasal history or symptoms. Endoscopy showed equivalent health in DS and control subjects. CONCLUSION: This DS population shows olfactory impairment. However, nasal health is comparable in DS subjects and controls. Nasal dysfunction is unlikely to contribute to olfactory impairment in DS. SIGNIFICANCE: Olfactory deficits in DS appear to be secondary to central, rather than rhinologic, pathology. EBM rating: B-2b.     

Posterior urethral valves in patients with Down syndrome

Renal and urological anomalies in Down syndrome (DS) have received little attention compared with the nephrourological findings described in other chromosomal abnormalities. Renal hypoplasia, hydroureteronephrosis, ureterovesical and ureteropelvic junction obstruction, and vesicoureteral reflux, but not posterior urethral valves, have been associated with DS. We report the occurrence of posterior urethral valves in three male infants with DS at a single institution. All had multiple urological procedures for correction or palliation of obstruction. Children with DS may have an increased risk for developing posterior urethral valves and obstructive uropathy. Furthermore, they may also develop chronic renal failure secondary to posterior urethral valves. Therefore, we suggests that infants with DS be screened with ultrasonography for renal and urological abnormalities early in life and, if abnormal, a contrast voiding cystourethrogram be performed to rule out posterior urethral valves or other bladder or urethral abnormalities. A review of the renal and urological anomalies in DS reported in the literature since 1960 is presented.     

Hirschsprung disease in Down syndrome: An opportunity for improvement

BackgroundDown syndrome (DS) is the most common abnormality associated with Hirschsprung disease (HD). It has been suggested patients with HD and DS have worse outcomes, however the literature is controversial.MethodsThe Kids’ Inpatient Database (KID) from 2003 to 2012 was used to identify newborns with HD. Demographics, hospital characteristics, and outcomes were compared among patients with and without DS using standard statistical tests.ResultsThere were 481 patients identified with HD, of which 45 (9%) had DS. Patients with DS were older at the time of first rectal biopsy (6 [3–11] days vs. 4 [3–6] days, p = 0.012). There were no differences in operative versus non-operative management in patients with and without DS (p = 0.706). Hospital length of stay was longer in the DS cohort (22 [13–33] days vs. 15 [10–24] days, p = 0.019), and patients with DS were more likely to have a concomitant diagnosis of wound infection (<12% vs. 3%, p = 0.002) and necrotizing enterocolitis (<14% vs. 5%, p = 0.018). The mortality rate for patients with DS was four times higher than those without DS (< 5% vs. < 0.8%, p = 0.018).ConclusionIn this nationwide cohort of patients with Hirschsprung disease, those with Down syndrome experienced delays in diagnosis and worse outcomes.Level of evidenceLevel III.Type of studyTreatment study, retrospective comparative study.     

A systematic review of intra-arterial thrombolytic therapy for lower-limb ischaemia.

METHODS: a search of the major databases was carried out to identify randomised controlled trials of intra-arterial thrombolytic therapy in the treatment of limb ischaemia. The search was limited to English language articles, or those that provided a sufficiently detailed English summary, and to articles published after 1980. In addition, key journals were hand-searched and citations were also reviewed. Two reviewers independently performed data extraction and aggregate outcomes were obtained using a random effects meta-analysis. RESULTS: a total of 34 articles were found, but only 10 were reports of randomised controlled trials. Meta-analysis showed no significant differences between thrombolysis and surgery in terms of major amputation (relative risk (RR) 0.893 95% confidence interval (CI) 0.576, 1.383) and mortality (RR 1.24 95% CI 0.795, 1.9). However, there was an increased risk of haemorrhage with thrombolysis (RR 2.94 95% CI 1.1, 7.9). Sub-group analysis suggests that short-duration occlusions (relative risk reduction (RRR) 72%, numbers needed to benefit (NNB)=3) and occluded grafts (RRR 58%, NNB=4) may benefit from thrombolysis. However, thrombolysis should be avoided in occlusions of greater than 14 days - particularly native vessel occlusions. CONCLUSION: despite the theoretical advantages of thrombolysis, there is still insufficient evidence to justify its widespread use except in graft occlusions and short-duration ischaemia.     

Cervical spine abnormalities associated with Down syndrome

Atlantoaxial instability (AAI) affects 10-20% of individuals with Down syndrome (DS). The condition is mostly asymptomatic and diagnosed on radiography by an enlarged anterior atlanto-odontoid distance. Symptomatic AAI, which affects 1-2% of individuals with DS, manifests with spinal cord compression. Cervical spondylosis, which is common in DS, also has the potential for cord damage but it has received less attention because paediatric populations were mostly studied. Forty-four Kuwaiti subjects with DS, whose ages were > or = 15 years, were evaluated clinically and radiographically. Lateral neck radiographs were taken in the neutral and flexion positions. Asymptomatic AAI was diagnosed in eight subjects (18%) and congenital anomalies of C1-2 were found in five (12%). Five patients had AAI in flexion only while three patients had it in both views. Three patients with AAI had odontoid anomalies contributing to the condition. When assessing AAI, the posterior atlanto-odontoid distance has to be considered because it indicates the space available for the cord. Cervical spondylosis was noted in 16 (36%) subjects. Degenerative changes increased with age, occurred earlier than in the normal population, and affected mostly the lower cervical levels. Half the patients with AAI had cervical spondylosis, a comorbidity that puts the cord at increased risk.     

Is the metabolic syndrome an independent risk factor for erectile dysfunction?

PURPOSE: We determined the role of the metabolic syndrome as an independent risk factor for erectile dysfunction. MATERIALS AND METHODS: Men participating in a health screening project completed the International Index of Erectile Function-5. The metabolic syndrome was defined according to the 2005 International Diabetes Federation consensus definition. Multiple linear regression, ANOVA and chi-square tests were used to investigate the impact of the metabolic syndrome on erectile dysfunction. RESULTS: A total of 2,371 men with a mean age of 46.1 years (SD 9.9, range 30 to 69) were analyzed. Of the men 33.4% (652) had no erectile dysfunction (International Index of Erectile Function-5 score 22 to 25), 59.7% (1,166) had mild erectile dysfunction (International Index of Erectile Function-5 score 17 to 21) and 6.9% (134) had moderate to severe erectile dysfunction (International Index of Erectile Function-5 score 5 to 16). The metabolic syndrome was present in 33.8% (794). In a multiple linear regression analysis an increased waist-to-hip ratio (p = 0.01) and metabolic syndrome (p = 0.01) turned out to be independently associated with a decreased International Index of Erectile Function-5 score. When stratified according to age, the metabolic syndrome was correlated to erectile dysfunction only in men 50 years old or older with an increase of severe erectile dysfunction by 48% (p = 0.01). CONCLUSIONS: The metabolic syndrome and an increased waist-to-hip ratio are independently associated with a decreased International Index of Erectile Function-5 score. The metabolic syndrome in men older than 50 years is significantly associated with a higher proportion of moderate to severe erectile dysfunction.     

Bone mass and density in preadolescent boys with and without Down syndrome

Summary

Preadolescent boys with Down syndrome at 7–10 years of age have lower bone mass and density in the pelvis than age-matched children without Down syndrome. However, bone mass and density of total body less head and lumbar spine are not different between these two groups.

Introduction

This study aimed to assess bone mineral content (BMC) and density (BMD) in preadolescent boys with and without Down syndrome (DS) at 7–10 years of age.

Methods

Eleven preadolescent boys with DS and eleven age-matched children without DS participated in this study. Dual-energy X-ray absorptiometry was used to measure BMC and BMD in whole body and lumbar spine. Both BMC and BMD of total body less head (TBLH) and lumbar spine (vertebrae L2–L4) were compared between the two groups, with and without adjusting for physical characteristics such as bone area, body height, and total lean mass. Two bone mineral apparent density (BMAD) variables were calculated to estimate volumetric BMD in the lumbar spine.

Results

Both BMC and BMD in the pelvis were lower in the DS group, after adjusting for physical characteristics. However, with and without adjusting for physical characteristics, the two groups were not different in BMC and BMD of the arms, legs, and TBLH from the whole body scan and in BMC, BMD, and BMAD of the lumbar spine from the lumbar spine scan.

Conclusions

These findings indicate that the pelvis may be the first site to show the significant difference in BMC and BMD between preadolescent boys with and without DS. It also suggests that significantly lower BMC and BMD in whole body and lumbar spine, which is usually observed in young adults with DS, may not occur before adolescence.     

Eight case reports on sex‐hormone profiles in sexually mature male Down syndrome

Down syndrome (DS) is a congenital disorder usually caused by an extra copy of chromosome 21. Although the number of postpubertal patients with DS is increasing, only limited information is available on their gonadal and sexual development. The aim of this case report was to examine sex‐hormone profiles in sexually mature male patients with DS. Eight postpubertal male patients with trisomy 21 (mean age 28 years, range 15–54 years) participated in this study. The serum level of luteinizing hormone and follicle‐stimulating hormone was significantly elevated and testosterone was slightly decreased. The testicular volume was smaller in all eight cases than that observed in healthy male subjects. The elevated luteinizing hormone and follicle‐stimulating hormone levels, the lower testosterone levels and a smaller testicular volume observed in all eight cases suggest a significant degree of germinal cell hypoplasia in mature male patients with DS.     

Topical administration of a novel nitric oxide donor, linear polyethylenimine-nitric oxide/nucleophile adduct (DS1), selectively increases vaginal blood flow in anesthetized rats

The aim of the present study was to test the effects of a topical administration of a novel nitric oxide donor, linear polyethylenimine-nitric oxide/nucleophile adduct (DS1), on vaginal blood flow and hemodynamics in rats. Laser Doppler flowmetry was used to measure blood flow changes following topical application of DS1 (0.3 or 1.5 mg in 0.15 ml saline) into the vagina of anesthetized Wistar rats. In vivo hemodynamic parameters were measured with Millar-tip-catheter placed in the left ventricle. DS1 (1.5 mg) increased vaginal blood flow by 191+/-24, 226+/-22 and 166+/-23% of the baseline value (at 5, 15 and 30 min, respectively, after application) without affecting systemic blood pressure, heart rate and cardiac function. The increased vaginal blood flow following DS1 application returned to baseline between 45 and 60 min. Thus, topical application of nitric oxide donors such as DS1 may be useful for the treatment of female sexual dysfunction that develops due to an impairment of local blood flow supply to the vaginal tissue.     

Anesthetic management of a child with chromosome 22q11 deletion syndrome

Chromosome 22q11 deletion syndrome (22q11DS) is a congenital anomaly characterized by cardiovascular, oropharyngeal, immunologic, endocrine, and neurodevelopmental abnormalities. We successfully managed a 6-year-old girl with 22q11DS with general anesthesia. Potential problems in anesthetic management of patients with 22q11DS are reviewed.