Do We Need Surveillance Urethro-Cystoscopy in Patients with Neurogenic Lower Urinary Tract Dysfunction?

Purpose

To examine the value of surveillance urethro-cystoscopy in patients with neurogenic lower urinary tract dysfunction (NLUTD) in regard to the conflicting literature as it is generally agreed that patients with NLUTD are at increased risk for bladder cancer.

Materials and Methods

In a cross-sectional study, a consecutive series of 129 patients (50 females, 79 males, mean age 51, range 18–88) suffering from NLUTD for at least 5 years was prospectively investigated using urethro-cystoscopy and bladder washing cytology at a single university spinal cord injury (SCI) center.

Results

Due to suspicious urethro-cystoscopy and/or bladder washing cytology findings, 13 (10%) of 129 patients underwent transurethral resection of the bladder lesion and/or random bladder biopsies. Overall, 9 relevant histological findings were found in 5% (7/129) of our patients: bladder melanosis (n = 1), nephrogenic adenoma (n = 3), keratinizing squamous metaplasia (n = 1), intestinal metaplasia (n = 3), and muscle-invasive adenocarcinoma of the bladder (n = 1).

Conclusions

Using surveillance urethro-cystoscopy, we found relevant histological findings in 5% of our patients suffering from NLUTD for at least 5 years. Thus, surveillance urethro-cystoscopy might be warranted, although the ideal starting point and frequency remain to be determined in further prospective studies.     

Urothelial Dysfunction and Increased Suburothelial Inflammation of Urinary Bladder Are Involved in Patients with Upper Urinary Tract Urolithiasis – Clinical and Immunohistochemistry Study

Objectives

To investigate the urothelial dysfunction and inflammation of urinary bladder in patients with upper urinary tract (UUT) urolithiasis through the results of cystoscopic hydrodistension and immunohistochemistry study.

Methods

Ninety-one patients with UUT urolithiasis underwent cystoscopic hydrodistension before the stone surgery. Immunofluorescence staining of E-cadherin, zonula occludens-1 (ZO-1), tryptase (mast cell activation), and TUNEL (urothelial apoptosis) were performed in 42 patients with glomerulations after hydrodistension, 10 without glomerulations, and 10 controls.

Results

Of the 91 patients, 62 (68.2%) developed glomerulations after hydrodistension. Lower urinary tract symptoms (LUTS) were present in 53.8% patients, in whom significantly smaller maximal anesthetic bladder capacity (MBC) was noted. Patients with middle or lower 1/3 ureteral stones had a significantly higher glomerulation rate (88.6% vs. 55.4%, p<0.01) and lower MBC (618.4±167.6 vs. 701.2±158.4 ml, p = 0.027) than those with upper 1/3 ureteral or renal stones. Patients with UUT urolithiasis had significantly lower expression of E-cadherin (26.2±14.8 vs. 42.4±16.7) and ZO-1 (5.16±4.02 vs. 11.02±5.66); and higher suburothelial mast cell (13.3±6.8 vs. 1.3±1.2) and apoptotic cell (2.6±2.5 vs. 0.1±0.3) numbers than in controls (all p<0.01).

Conclusions

Urothelial dysfunction and increased suburothelial inflammation and apoptosis are highly prevalent in the bladders of UUT urolithiasis patients, indicating inflammation cross-talk between UUT and urinary bladder. Patients with UUT urolithiaisis concomitant with LUTS had a smaller MBC, which may explain the presence of irritative bladder symptoms.     

Prevalence of Symptomless Urinary Tract Disease in Birmingham Schoolchildren. I—Pyuria and Bacteriuria

In a pilot project 2,122 schoolchildren were screened for symptomless urinary tract disease by the examination of midstream urine specimens. These were tested for albumin, blood, and glucose with Labstix commercial strips, together with microscopy for abnormal cellular excretion.One case of renal glycosuria was found but none of previously undiagnosed diabetes mellitus. Out of 1,096 boys, 11 (1%) had pyuria—a leucocyte count greater than 10/cu.mm.—but only four showed abnormal counts on retesting. None had urinary tract infection.Out of 1,026 girls, 96 (9·3%) had pyuria initially but 35 were normal on retesting. Of the remaining 61 girls, 59 attended the outpatients department for further investigation, and in 30 vulvitis appeared to be the sole cause. Ten were proved to have significant bacteriuria and six of them showed radiological abnormalities.It is suggested that careful long-term studies are needed to study the economics and the implications of screening on a national scale.     

Incidence of Hospital-Acquired Pneumonia,Bacteraemia and Urinary Tract Infections in Patients with Haematological Malignancies, 2004–2010: A Surveillance-Based Study

Objective

This study charted incidence trends of hospital-acquired (HA) pneumonia, bacteraemia and urinary tract infections (UTI) in a haematology department.

Methods

Prospective surveillance of hospital-acquired infections (HAI) was undertaken in a 42-bed haematology department of a university hospital. All patients hospitalized ≥48 hours between 1^st January 2004 and 31^st December 2010 were included. Definitions of HAI were based on a standardized protocol. The incidence was the number of events per 1000 patient-days at risk; only the first HAI was counted. Multivariate Poisson regression was fitted to assess temporal trends.

Results

Among 3 355 patients (58 063 patient-days at risk) included, 1 055 (31%) had HAI. The incidence of HA pneumonia, HA bacteraemia and HA UTI was respectively 3.3, 12.0 and 2.9 per 1000 patient-days at risk. HA bacteraemia incidence increased by 11% (95% confidence interval: +6%, +15%, P<0.001) per year, independently of neutropenia, central venous catheterization (CVC) and haematological disease. The incidences of HA pneumonia and HA UTI were stable. The most frequently isolated pathogens were Aspergillus spp. (59.2%) for pneumonia, coagulase-negative Staphylococcus (44.2%) for bacteraemia and enterobacteria (60%) for UTI.

Conclusion

The incidence of bacteraemia increased, indicating that factors other than CVC exposure, including chemotherapy with its impact on the immune system, could explain this trend. Further analytic studies are needed to explore the factors that could explain this trend.     

Lower Extremity Amputations in Persons with and without Diabetes in Italy: 2001–2010

Objective

To analyze hospitalization for lower extremity amputations (LEAs) and amputee rates in persons with and without diabetes in Italy.

Research Design and Methods

All patients with LEAs in the period 2001–2010 were identified analyzing the National Hospital Discharge Record database. For each year, amputee and hospitalization rates for LEAs were calculated either for persons with diabetes or without. Time trend for major and minor amputations were analysed.

Results

From 2001 to 2010 a mean annual number of 11,639 individuals underwent a lower extremity amputation: 58.6% had diabetes accounting for 60.7% of total hospitalizations. In 2010, the crude amputee rate for LEAs was 20.4 per 100,000 inhabitants: 247.2 for 100.000 persons with diabetes, and 8.6 for those without diabetes. Having diabetes was associated to an increased risk of amputation (Poisson estimated RR 10.9, 95%CI 9.4–12.8). Over the whole period, a progressive reduction of amputee rates was observed for major amputations either among persons with diabetes (−30.7%) or without diabetes (−12.5%), while the rates of minor amputations increased progressively (+22.4%) among people without diabetes and were nearly stable in people with diabetes (−4.6%). A greater number of minor amputations were performed among persons with than without diabetes: in 2010, the minor-to-major ratio among persons with diabetes (2.5) was more than twice than in those without diabetes (1.0).

Conclusions

The nationwide analyses confirm a progressive reduction of hospitalization and amputee rates for major LEAs, suggesting an earlier and more diffuse approach aimed at limb salvage.     

Urinary markers of renal inflammation in adolescents with Type 1 diabetes mellitus and normoalbuminuria

Diabet. Med. 29, 1297-1302 (2012) ABSTRACT: Aims Patients with the highest albumin:creatinine ratio within the normal range are at an increased risk for developing microalbuminuria. The mechanistic basis for this is unknown, but may be related to renal inflammation. Our goal was to characterize the urinary excretion of cytokines/chemokines in normoalbuminuric adolescents with Type?1 diabetes to determine whether higher range normoalbuminuria is associated with evidence of renal inflammation. Methods Forty-two urinary cytokines/chemokines were measured in subjects who were screened for the Adolescent Type?1 Diabetes Cardio-Renal Intervention Trial. Urinary cytokines/chemokines were compared across low (n?=?50), middle (n?=?50) or high (n?=?50) albumin:creatinine ratio tertile groups. Results At baseline, participants in the upper tertile were younger and had shorter diabetes duration compared with the other groups. Other clinical characteristics were similar. Urinary levels of interleukin?6, interleukin?8, platelet-derived growth factor-AA and RANTES differed across albumin:creatinine ratio tertiles, with higher values in patients in the middle and high tertiles compared with the lower tertile (ANCOVA P?≤?0.01). Conclusions Within the normal albumin:creatinine ratio range, higher urinary albumin excretion is associated with elevated urinary levels of inflammatory markers. Ultimately, this may provide mechanistic insights into disease pathophysiology and stratify the risk of nephropathy in Type?1 diabetes.     

Distribution of CD4pos -, CD8pos – and Regulatory T Cells in the Upper and Lower Gastrointestinal Tract in Healthy Young Subjects

The gastrointestinal immune system is involved in the development of several autoimmune-mediated diseases, including inflammatory bowel disease, multiple sclerosis, and type 1 diabetes mellitus. Alterations in T-cell populations, especially regulatory T cells (Tregs), are often evident in patients suffering from these diseases. To be able to detect changes in T-cell populations in diseased tissue, it is crucial to investigate T-cell populations in healthy individuals, and to characterize their variation among different regions of the gastrointestinal (GI) tract. While limited data exist, quantitative data on biopsies systematically drawn from various regions of the GI tract are lacking, particularly in healthy young humans. In this report, we present the first systematic assessment of how T cells—including Tregs—are distributed in the gastrointestinal mucosa throughout the GI tract of healthy young humans by means of multi-parameter FACS analysis. Gastroduodenoscopy and colonoscopy were performed on 16 healthy volunteers aged between 18 and 32. Biopsies were drawn from seven GI regions, and were used to determine the frequencies of CD8⁺-, CD4⁺- and Tregs in the gastrointestinal mucosa by means of multi-parameter FACS analysis. Our data show that there is significant variation in the baseline T-cell landscape along the healthy human gastrointestinal tract, and that mucosal T-cell analyses from a single region should not be taken as representative of the entire gastrointestinal tract. We show that certain T-cell subsets in the gastrointestinal mucosa vary significantly among regions; most notably, that Tregs are enriched in the appendiceal orifice region and the ascending colon, and that CD8^pos T cells are enriched in the gastric mucosa.     

Urinary Tract Infections in Kidney Transplant Patients Due to Escherichia coli and Klebsiella pneumoniae-Producing Extended-Spectrum β-Lactamases: Risk Factors and Molecular Epidemiology

Urinary tract infection (UTI) is a common complication after kidney transplantation, often associated to graft loss and increased healthcare costs. Kidney transplant patients (KTPs) are particularly susceptible to infection by Enterobacteriaceae-producing extended-spectrum β-lactamases (ESBLs). A retrospective case-control study was conducted to identify independent risk factors for ESBL-producing Escherichia coli and Klebsiella pneumoniae in non-hospitalized KTPs with UTI. Forty-nine patients suffering from UTI by ESBL-producing bacteria (ESBL-P) as case group and the same number of patients with UTI by ESBL negative (ESBL-N) as control-group were compared. Clinical data, renal function parameters during UTI episodes, UTI recurrence and relapsing rate, as well as risk factors for recurrence, molecular characterization of isolates and the respective antimicrobial susceptibility profile were evaluated. Diabetes mellitus (p <0.007), previous antibiotic prophylaxis (p=0.017) or therapy (p<0.001), previous UTI (p=0.01), relapsing infection (p=0.019) and patients with delayed graft function after transplant (p=0.001) represented risk factors for infection by ESBL positive Enterobacteriaceae in KTPs. Interestingly, the period of time between data of transplantation and data of UTI was shorter in case of ESBL-P case-group (28.8 months) compared with ESBL-N control-group (50.9 months). ESBL-producing bacteria exhibited higher resistance to fluoroquinolones (p=0.002), trimethoprim-sulfamethoxazole (p<0.001) and gentamicin (p<0.001). Molecular analysis showed that bla _CTX-M was the most common ESBL encoding gene (65.3%), although in 55.1% of the cases more than one ESBL gene was found. In 29.4% of K. pneumoniae isolates, three bla-genes (bla _CTX-M-bla _TEM-bla _SHV) were simultaneously detected. Low estimated glomerular filtration rate (p=0.009) was found to be risk factor for UTI recurrence. Over 60% of recurrent UTI episodes were caused by genetically similar strains. UTI by ESBL-producing Enterobacteriaceae in KTPs represent an important clinical challenge regarding not only hospitalized patients but also concerning outpatients.     

Does Lower Limb Exercise Worsen Renal Artery Hemodynamics in Patients with Abdominal Aortic Aneurysm?

Renal artery stenosis (RAS) and renal complications emerge in some patients after endovascular aneurysm repair (EVAR) to treat abdominal aorta aneurysm (AAA). The mechanisms for the causes of these problems are not clear. We hypothesized that for EVAR patients, lower limb exercise could negatively influence the physiology of the renal artery and the renal function, by decreasing the blood flow velocity and changing the hemodynamics in the renal arteries. To evaluate this hypothesis, pre- and post-operative models of the abdominal aorta were reconstructed based on CT images. The hemodynamic environment was numerically simulated under rest and lower limb exercise conditions. The results revealed that in the renal arteries, lower limb exercise decreased the wall shear stress (WSS), increased the oscillatory shear index (OSI) and increased the relative residence time (RRT). EVAR further enhanced these effects. Because these parameters are related to artery stenosis and atherosclerosis, this preliminary study concluded that lower limb exercise may increase the potential risk of inducing renal artery stenosis and renal complications for AAA patients. This finding could help elucidate the mechanism of renal artery stenosis and renal complications after EVAR and warn us to reconsider the management and nursing care of AAA patients.     

A Lower Proportion of Regulatory B Cells in Patients with Henoch–Schoenlein Purpura Nephritis

Background

Henoch—Schoenlein purpura is the one of most common types of systemic vasculitis that involves impaired renal function and Henoch-Schoenlein purpura nephritis (HSPN). The diagnosis of this condition is largely based on immunohistologic detection of immunoglobulin A1-containing immune complex in the glomerular deposits of mesangium. Despite clinical advances, the etiopathogenesis of HSPN is still largely unknown.

Methods

In this study, we enrolled 25 newly diagnosed HSPN patients and 14 healthy controls. Then, fractions of B cell subtypes were determined in venous blood using flow cytometry. The serum interleukin (IL)-10 concentration was determined by enzyme-linked immunosorbent assay.

Results

Compared to those in healthy controls, the numbers of CD38⁺CD19⁺, CD86⁺CD19⁺, CD38⁺CD86⁺CD19⁺, and CD95⁺CD19⁺ B cells per microliter of blood were significantly higher in HSPN patients. In contrast, the numbers of CD5⁺CD19⁺, IL-10⁺CD19⁺, CD5⁺CD1d⁺CD19⁺, and IL-10⁺CD5⁺CD1d⁺CD19⁺ B cells per microliter of blood and the serum IL-10 concentration were significantly lower in HSPN patients. Following treatment, the numbers of CD38⁺CD19⁺ and CD86⁺CD19⁺ B cells per microliter of blood were significantly reduced in HSPN patients. However, the numbers of CD5⁺CD1d⁺CD19⁺, CD5⁺CD1d⁺IL-10⁺CD19⁺, and IL-10⁺CD19⁺ B cells per microliter of blood and the serum IL-10 concentration were significantly increased in HSPN patients following treatment. The estimated glomerular filtration rate (eGFR) was negatively correlated with the number of CD38⁺CD19⁺ B cells but positively correlated with the numbers of IL-10⁺CD19⁺, CD1d⁺CD5⁺CD19⁺, and IL-10⁺CD1d⁺CD5⁺CD19⁺B cells per microliter of blood and the serum IL-10 concentration. The 24-h urinary protein concentration was positively correlated with the number of CD38⁺CD19⁺B cells but negatively correlated with the numbers of IL-10⁺CD19⁺, CD1d⁺CD5⁺CD19⁺, and IL-10⁺CD1d⁺CD5⁺CD19⁺B cells per microliter of blood and the serum IL-10 concentration.

Conclusion

Our results suggest that CD38⁺CD19⁺ and CD1d⁺CD5⁺CD19⁺ B cells (Bregs) contribute to the pathogenesis of HSPN.     

Health-Related Quality of Life among Children with Recurrent Respiratory Tract Infections in Xi’an,China

Objective

The aim of this study was to investigate the health-related quality of life (HRQOL) in 2−7-year-old children diagnosed with recurrent respiratory tract infections (RRTIs) and the impact of RRTIs on affected families.

Methods

This was a cross-sectional case-control study evaluating 2−7-year-old children with RRTIs (n = 352), 2−7-year-old healthy children (n = 376), and associated caregivers (parents and/or grandparents). A Chinese version of the PedsQL™ 4.0 Generic Core Scale was used to assess childhood HRQOL, and a Chinese version of the Family Impact Module (FIM) was used to assess the impact of RRTIs on family members. HRQOL scores were compared between children with RRTIs and healthy children. In addition, a multiple step-wise regression with demographic variables of children and their caregivers, family economic status, and caregiver’s HRQOL as independent variables determined factors that influenced HRQOL in children with RRTIs.

Results

Children with RRTIs showed significantly lower physical, emotional, social, and school functioning scores than healthy children (p<0.05). Caregivers for children with RRTIs also scored significantly lower than caregivers for healthy children on physical, emotional, social, cognitive, and communication functioning (p<0.05). Caregivers for RRTIs affected children also reported significantly higher levels of worry. Multivariate analyses showed that children’s age, children’s relation with caregivers, the frequency of respiratory tract infections in the preceding year, caregiver’s educational level, and caregiver’s own HRQOL influenced HRQOL in children with RRTIs.

Conclusions

The current data demonstrated that RRTIs were associated with lower HRQOL in both children and their caregivers and negatively influenced family functioning. In addition, caregivers’ social characteristics also significantly affected HRQOL in children with RRTIs.     

Increased Skeletal Muscle 11βHSD1 mRNA Is Associated with Lower Muscle Strength in Ageing

Background

Sarcopenia, the loss of muscle mass and function with age, is associated with increased morbidity and mortality. Current understanding of the underlying mechanisms is limited. Glucocorticoids (GC) in excess cause muscle weakness and atrophy. We hypothesized that GC may contribute to sarcopenia through elevated circulating levels or increased glucocorticoid receptor (GR) signaling by increased expression of either GR or the GC-amplifying enzyme 11beta-hydroxysteroid dehydrogenase type 1 (11βHSD1) in muscle.

Methods

There were 82 participants; group 1 comprised 33 older men (mean age 70.2years, SD 4.4) and 19 younger men (22.2years, 1.7) and group 2 comprised 16 older men (79.1years, 3.4) and 14 older women (80.1years, 3.7). We measured muscle strength, mid-thigh cross-sectional area, fasting morning plasma cortisol, quadriceps muscle GR and 11βHSD1 mRNA, and urinary glucocorticoid metabolites. Data were analysed using multiple linear regression adjusting for age, gender and body size.

Results

Muscle strength and size were not associated with plasma cortisol, total urinary glucocorticoids or the ratio of urinary 5β-tetrahydrocortisol +5α-tetrahydrocortisol to tetrahydrocortisone (an index of systemic 11βHSD activity). Muscle strength was associated with 11βHSD1 mRNA levels (β -0.35, p = 0.04), but GR mRNA levels were not significantly associated with muscle strength or size.

Conclusion

Although circulating levels of GC are not associated with muscle strength or size in either gender, increased cortisol generation within muscle by 11βHSD1 may contribute to loss of muscle strength with age, a key component of sarcopenia. Inhibition of 11βHSD1 may have therapeutic potential in sarcopenia.     

Sexual dimorphism in a Lower Miocene moronid?

A series of questionable elements in certain specimens ofMorone cf.aequalis (Koken 1891) from Lower Miocene deposits near the village of Berkersheim, N of Frankfurt a. M. (Hessen, Germany) is described, which has not been known from any other percoid before. These elements are fully ossified and cover the cheek and the preopercular region. Even within well-preserved material, they are only present in some specimens. Therefore, they may be specialized structures that are indicative for sexual dimorphism. Nevertheless, they clearly differ from all other respective structures that have been described from teleosts: Multicellular epidermal horny tubercles (“breeding tubercles”) mainly consist of keratine and not of calciumphosphate. By contrast, contact organs consist of bone and are located mainly at the surface of the fin rays and scales, respectively. At present, “breeding tubercles” are the favorite interpretation and the original substance may have been replaced via post-mortem phosphatization.     

Is Remodelling of Corticospinal Tract Terminations Originating in the Intact Hemisphere Associated with Recovery following Transient Ischaemic Stroke in the Rat?

Following large strokes that encompass the cerebral cortex, it has been suggested that the corticospinal tract originating from the non-ischaemic hemisphere reorganises its pattern of terminal arborisation within the spinal cord to compensate for loss of function. However many strokes in humans predominantly affect subcortical structures with minimal involvement of the cerebral cortex. The aim of the present study was to determine whether remodelling of corticospinal terminals arising from the non-ischaemic hemisphere was associated with spontaneous recovery in rats with subcortical infarcts. Rats were subjected to transient middle cerebral artery occlusion or sham surgery and 28 days later, when animals exhibited functional recovery, cholera toxin b subunit was injected into the contralesional, intact forelimb motor cortex in order to anterogradely label terminals within cervical spinal cord segments. Infarcts were limited to subcortical structures and resulted in partial loss of corticospinal tract axons from the ischaemic hemisphere. Quantitative analysis revealed there was no significant difference in the numbers of terminals on the contralesional side of the spinal grey matter between ischaemic and sham rats. The results indicate that significant remodelling of the corticospinal tract from the non-ischaemic hemisphere is not associated with functional recovery in animals with subcortical infarcts.     

Urinary proteomic biomarkers in oncology: ready for implementation?

Introduction: Biomarkers are expected to improve the management of cancer patients by enabling early detection and prediction of therapeutic response. Proteins reflect a molecular phenotype, have high potential as biomarkers, and also are key targets for intervention. Given the ease of collection and proximity to certain tumors, the urinary proteome is a rich source of biomarkers and several proteins have been already implemented.

Areas covered: We examined the literature on urine proteins and proteome analysis in oncology from reports published during the last 5 years to generate an overview on the status of urine protein and peptide biomarkers, with emphasis on their actual clinical value.

Expert commentary: A few studies report on biomarkers that are ready to be implemented in patient management, among others in bladder cancer and cholangiocarcinoma. These reports are based on multi-marker approaches. A high number of biomarkers, though, has been described in studies with low statistical power. In fact, several of them have been consistently reported across different studies. The latter should be the focus of attention and be tested in properly designed confirmatory and ultimately, prospective investigations. It is expected that multi-marker classifiers for a specific context-of-use, will be the preferred path toward clinical implementation.     

Altitudinal Variation in Digestive Tract Length in Yunnan Pond Frog （Pelophylax pleuraden）

The digestive tract plays an important role in digestion and the acquisition of food energy. Understanding the impact of abiotic environments on digestive tract morphology is especially important for evolution of digestive tract across different environments. Here, we investigated altitudinal variation in digestive tract length in the Yunnan Pond Frog （Pelophylaxpleuraden） across five populations ranging from 1413 m to 1935 m a.s.1, in Ningnan County, Sichuan province in western China. Frogs were collected during the breeding season, from 1-5 June 2012. Our results revealed that females had longer digestive tract and relative digestive tract （i.e. digestive tract length / body size） lengths in com- parison to males, on average, but the differences between them decreased with increasing altitude. Digestive tract and relative digestive tract lengths increased with increasing altitude suggesting that a higher proportion of indigestible ma- terials may be consumed at high-altitude sites and result in a relative increase in digestive tract dimensions.     

Urinary zinc excretion and zinc status of patients with Β-thalassemia major

In this study, zinc status and urinary zinc excretion with and without desferrioxamine (DFO) infusion and the relationship between urinary zinc excretion and renal tubular dysfunction in thalassemia major (TM) patients were investigated. Forty TM patients were given four DFO infusions on alternate days over a 1-wk period prior to the transfusion. On each day that DFO was given, a 24-h urine collection initiated. DFO was omitted for 1-wk before the following transfusion and during the period four 24-h urine collections were performed. Twenty healthy children provided 24-h urine collection as controls. Blood samples were taken on each of two consecutive transfusion days of the patients and from the controls. Urinary zinc excretion was measured and plasma and red blood cell (RBC) zinc analysis were performed by inductively coupled plasma-atomic emission spectrophotometry. UrinaryN-acetyl-Β-D-glucosaminidase (NAG) activity and creatinine were determined in morning urine specimens. The mean plasma zinc concentration was significantly lower in the patients not given DFO compared to the values of the patients given DFO and the control group. The mean RBC zinc concentration (Μmol/g Hb) in the patients (with and without DFO) and the control group were similar. Urinary zinc excretion was significantly higher in the patients receiving DFO compared to the control group, whereas urinary zinc excretion in the patients not given DFO was not different from the controls. Urinary NAG indices (U/g Cr) were significantly higher in the patients compared to controls. Urinary zinc excretion was correlated with the urinary NAG indices.     

β-Hemolysin/Cytolysin of Group B Streptococcus Enhances Host Inflammation but Is Dispensable for Establishment of Urinary Tract Infection

Group B Streptococcus (GBS; Streptococcus agalactiae) is a major human pathogen that disproportionately affects neonates and women in the peripartum period and is an emerging cause of infection in older adults. The primary toxin of GBS, β-hemolysin/cytolysin (βH/C), has a well-defined role in the pathogenesis of invasive disease, but its role in urinary tract infection (UTI) is unknown. Using both in vitro and in vivo models, we analyzed the importance of βH/C in GBS uropathogenesis. There were no significant differences in bacterial density from the bladders or kidneys from mice infected with wild-type or isogenic βH/C-deficient GBS, and competitive indices from co-infection experiments were near 1. Thus, βH/C is dispensable for the establishment of GBS-UTI. However, βH/C-sufficient GBS induced a more robust proinflammatory cytokine response in cultured bladder epithelial cells and in the urinary tracts of infected mice. Given the near ubiquity of βH/C-expressing strains in epidemiologic studies and the importance of local inflammation in dictating outcomes and sequelae of UTI, we hypothesize that βH/C-driven inflammatory signaling may be important in the clinical course of GBS-UTI.