Phosphate homeostasis in Bartter syndrome: a case–control study

Background

Bartter patients may be hypercalciuric. Additional abnormalities in the metabolism of calcium, phosphate, and calciotropic hormones have occasionally been reported.

Methods

The metabolism of calcium, phosphate, and calciotropic hormones was investigated in 15 patients with Bartter syndrome and 15 healthy subjects.

Results

Compared to the controls, Bartter patients had significantly reduced plasma phosphate {mean [interquartile range]:1.29 [1.16–1.46] vs. 1.61 [1.54–1.67] mmol/L} and maximal tubular phosphate reabsorption (1.16 [1.00–1.35] vs. 1.41 [1.37–1.47] mmol/L) and significantly increased parathyroid hormone (PTH) level (6.1 [4.5–7.7] vs. 2.8 [2.2–4.4] pmol/L). However, patients and controls did not differ in blood calcium, 25-hydroxyvitamin D, alkaline phosphatase, and osteocalcin levels. In patients, an inverse correlation (P?P?P?Conclusions The results of this study demonstrate a tendency towards renal phosphate wasting and elevated circulating PTH levels in Bartter patients.     

Toll-like receptors,immunoproteasome and regulatory T cells in children with Henoch–Schönlein purpura and primary IgA nephropathy

Background

Henoch–Schönlein purpura (HSP) nephritis and primary IgA nephropathy (pIgAN) present with glomerular IgA deposits, but differ with regard to clinical features. The suspected involvement of different immune system pathways is largely unknown.

Methods

This study was aimed at investigating some of the immunological features including Toll-like receptors (TLR), proteasome (PS)/immunoproteasome (iPS) switch, and the regulatory T cell system (Treg/Th17 cells) in 63 children with HSP with/without renal involvement and in 25 with pIgAN. Real-time PRC (Taqman) was used to quantify mRNA levels in peripheral blood mononuclear cells (PBMC).

Results

The expression of mRNAs encoding for TLR4 in both HSP and pIgAN was higher than in controls (HC) and in both diseases FoxP3mRNA and TGF-β1mRNA expression was significantly lower than in HC. A switch from PS to iPS (LMP2/β1) was detected only in PBMC of HSP and it correlated with the level of TLR2mRNA, which was selectively increased only in children with HSP.

Conclusion

Children with HSP and pIgAN present with similar signs of engagement of the innate immunity and regulatory T cell depression. The increased immunoproteasome switch, which correlated with TLR2 activation, may suggest an innate immunity pathway peculiar to HSP vasculitic presentation. This research area also deserves further investigation for possible therapeutic applications.     

Adherence to transition guidelines in European paediatric nephrology units

Background

There is increasing focus on the problems involved in the transition and transfer of young adult patients from paediatric to adult renal units. This situation was addressed by the 2011 International Pediatric Nephrology Association/International Society of Nephrology (IPNA/ISN) Consensus Statement on transition.

Methods

We performed a survey of transition practices of 15 paediatric nephrology units across Europe 2 years after publication of the consensus statement.

Results

Two thirds of units were aware of the guidelines, and one third had integrated them into their transition practice. Forty-seven per cent of units transfer five or fewer patients with chronic kidney disease (CKD) stage 5 per year to a median of five adult centres, with higher numbers of CKD stages 2–4 patients. Seventy-three per cent of units were required by the hospital or government to transfer patients by a certain age. Eighty per cent of units commenced transition planning after the patient turned 15 years of age and usually within 1–2 years of the compulsory transfer age. Forty-seven per cent of units used a transition or transfer clinic. Prominent barriers to effective transition were patient and parent attachment to the paediatric unit and difficulty in allowing the young person to perform self-care.

Conclusions

Whereas awareness of the consensus statement is suboptimal, it has had some impact on practice. Adult nephrologists receive transferred patients infrequently, and the process of transition is introduced too late by paediatricians. Government- and hospital-driven age-based transfer policies distract focus from the achievement of competencies in self care. Variable use of transition clinics, written patient information and support groups is probably due to economic and human-resource limitations. The consensus statement provides a standard for evolving and evaluating transition policies jointly agreed upon by paediatric and adult units.     

Management of rectosigmoid obstruction due to severe bowel endometriosis

Bowel obstruction is a rare complication of intestinal endometriosis. The aim of this work was to evaluate outcomes after colorectal resection for bowel obstruction due to endometriosis. Of 720 patients who underwent colorectal resection for bowel endometriosis, 12 (1.7 %) presented with bowel obstruction. Preoperative work-up, management, perioperative and long-term outcomes were analyzed. All lesions were localized in the rectosigmoid tract. All patients underwent colorectal resection, which was carried out laparoscopically in 4 (33 %). Rate of low or ultra-low colorectal anastomoses was 83 %. Four patients (33 %) required blood transfusions. Two patients developed rectovaginal fistulas. After a median follow-up of 38 months, there were no cases of disease recurrence and dyschezia improved in 75 % of patients. Bowel endometriosis should be considered in the differential diagnosis of young women with bowel obstruction. Despite challenging operations, colorectal resections are associated with good outcomes.     

Point prevalence of pressure ulcers in three second‐level hospitals in Mexico

Pressure ulcers (PU) are the source of multiple complications and even death. To our knowledge, there is no available data about PU prevalence in Mexico. The objective of this study was to determine the point prevalence of PU in three second‐level hospitals in Mexico. Every adult hospitalised patient was included in each hospital. Age, gender, hospitalisation ward, Braden score, and the number, location and stage of the ulcers encountered were recorded, as well as any pressure relief measures. In total, 294 patients were examined (127 were male); of these, 63 were considered to be at risk. The average age was 48·6 years. The overall prevalence of the PU was 17%. The service with the highest prevalence was the ICU. The most frequent stage was II (32%) and they were most commonly found in the sacrum (74%). The average Braden score of the patients with ulcers was 10, and 21·4% of the patients obtained moderate‐ to high‐risk Braden scores. Of them, 60·3% had ulcers and only 46% had any preventive measures. The prevalence of PU in three hospitals in Mexico is 17%. The most common stage is II and the most commonly affected site is the sacrum. Only 46% of patients with PU had at least one pressure release measure.     

Energy-dependent accumulation of norfloxacin and porin expression in clinical isolates of Klebsiella pneumoniae and relationship to extended-spectrum beta-lactamase production

The relationships between porin deficiency, active efflux of fluoroquinolones, and extended-spectrum beta-lactamase (ESBL) production were determined for 53 clinical isolates of Klebsiella pneumoniae. Thirty-two ESBL-positive strains (including 22 strains expressing porins and 10 strains lacking porins) and 21 ESBL-negative strains were evaluated. Active efflux of norfloxacin was defined as a >/=50% increase in the accumulation of norfloxacin in the presence of carbonyl cyanide m-chlorophenylhydrazone (CCCP) in comparison with the corresponding basal value in the absence of CCCP. The quinolone resistance-determining regions of both gyrA and parC from 13 strains, representing all isolates with different porin profiles and with or without active efflux, were determined. Porin loss was significantly more common among ESBL-positive strains (10 of 32 [31.2%]) than among ESBL-negative strains (0 of 2 [0%]) (P < 0.01). Active efflux was observed in 7 of 10 (70%) strains lacking porins and in 4 of 43 (9.3%) strains producing porins (P < 0.001). The 11 strains showing active efflux corresponded to 3 of 21 (14.3%) ESBL-negative strains and 8 of 32 (25.5%) ESBL-positive strains (P > 0.05). Basal values of norfloxacin accumulation were higher in strains lacking active efflux than in those that had this mechanism (P < 0.05). In the absence of topoisomerase changes, the contribution of either porin loss or active efflux to fluoroquinolone resistance in K. pneumoniae was negligible. It is concluded that among K. pneumoniae strains of clinical origin, porin loss was observed only in those producing ESBL, and that a significant number of porin-deficient strains also expressed active efflux of norfloxacin. In terms of fluoroquinolone resistance, both mechanisms are significant only in the presence of topoisomerase modifications.     

Role of manidipine in the management of patients with hypertension

Manidipine is a third-generation dihydropyridine calcium antagonist, which causes systemic vasodilation by inhibiting the voltage-dependent calcium inward currents in smooth muscle cells. In clinical studies, manidipine has been shown to significantly lower office and 24-h blood pressure compared with placebo in patients with essential hypertension. The resulting reduction in blood pressure is maintained over 24 h, with preservation of the circadian blood pressure pattern; its blood pressure-lowering capacity appears to be similar to that of other calcium antagonists. In elderly patients with mild-to-moderate essential hypertension, manidipine is able to significantly decrease blood pressure compared with placebo for up to 3 years of treatment. The drug also significantly lowers blood pressure in patients with hypertension and concomitant Type 2 diabetes mellitus or renal impairment, and is devoid of adverse metabolic effects. It is well-tolerated with few untoward adverse effects related to vasodilation. In particular, manidipine appears to have less potential for pedal edema than other calcium channel blockers.     

IN VITRO ADHERENCE OF SOLUBLE IMMUNE COMPLEXES TO MACROPHAGES

The adherence of soluble immune complexes to stimulated alveolar macrophages was studied in vitro using HSA-anti-HSA complexes prepared in antigen excess. Those complexes containing more than two molecules of antibody preferentially adhered to macrophages in the absence of complement. Free γG in less than physiological concentrations inhibited the adherence of complexes, and the presence of complement did not significantly alter this inhibition. Complexes prepared with reduced and alkylated antibodies showed a decreased adherence. The strength of binding of soluble complexes to macrophages and their efficiency in fixing complement were greater than seen with small aggregates of homologous γG. These differences in biological properties were observed even though the immune complexes and aggregates contained comparable numbers of γG molecules. The γG receptor on rabbit macrophages exhibited species specificity. Pretreatment of macrophages with proteolytic enzymes led to adherence of larger amounts of soluble complexes. These observations suggest that the strength of binding of soluble immune complexes to macrophages and their efficiency in fixing complement are not determined solely by a random summation of individual binding sites. It is proposed that conformational changes in the γG antibodies or a specific molecular arrangement in the lattice work of complexes containing large protein antigens may influence the biological properties of the soluble complexes.