Associations between Dietary Iron and Zinc Intakes,and between Biochemical Iron and Zinc Status in Women

Iron and zinc are found in similar foods and absorption of both may be affected by food compounds, thus biochemical iron and zinc status may be related. This cross-sectional study aimed to: (1) describe dietary intakes and biochemical status of iron and zinc; (2) investigate associations between dietary iron and zinc intakes; and (3) investigate associations between biochemical iron and zinc status in a sample of premenopausal women aged 18–50 years who were recruited in Melbourne and Sydney, Australia. Usual dietary intakes were assessed using a 154-item food frequency questionnaire (n = 379). Iron status was assessed using serum ferritin and hemoglobin, zinc status using serum zinc (standardized to 08:00 collection), and presence of infection/inflammation using C-reactive protein (n = 326). Associations were explored using multiple regression and logistic regression. Mean (SD) iron and zinc intakes were 10.5 (3.5) mg/day and 9.3 (3.8) mg/day, respectively. Median (interquartile range) serum ferritin was 22 (12–38) μg/L and mean serum zinc concentrations (SD) were 12.6 (1.7) μmol/L in fasting samples and 11.8 (2.0) μmol/L in nonfasting samples. For each 1 mg/day increase in dietary iron intake, zinc intake increased by 0.4 mg/day. Each 1 μmol/L increase in serum zinc corresponded to a 6% increase in serum ferritin, however women with low serum zinc concentration (AM fasting < 10.7 μmol/L; AM nonfasting < 10.1 μmol/L) were not at increased risk of depleted iron stores (serum ferritin <15 μg/L; p = 0.340). Positive associations were observed between dietary iron and zinc intakes, and between iron and zinc status, however interpreting serum ferritin concentrations was not a useful proxy for estimating the likelihood of low serum zinc concentrations and women with depleted iron stores were not at increased risk of impaired zinc status in this cohort.     

The Incidence of Major Hemorrhagic Complications After Renal Biopsies in Patients with Monoclonal Gammopathies

Background and objectives: Monoclonal gammopathies frequently cause renal disease, but they may be an incidental finding. Assessment of renal pathology in the context of renal dysfunction and a monoclonal gammopathy therefore serves as a useful diagnostic tool and, in addition, provides prognostic information. There is, however, a theoretical risk of increased hemorrhagic complications from renal biopsies in this setting. The purpose of this study was to determine the incidence of significant hemorrhagic complications after renal biopsies in patients with monoclonal gammopathies.Design, setting, participants, & measurements: The case notes of 1993 unselected patients from four teaching hospitals within the United Kingdom who underwent native or transplant renal biopsies between 1993 and 2008 were reviewed. Subjects were categorized as having a monoclonal gammopathy or not, and the incidence of major hemorrhagic complications between groups was compared.Results: In total, 74 (3.7%) patients (native and transplant biopsies) had a major hemorrhagic complication. One hundred forty-eight subjects with a monoclonal gammopathy were identified. The complication rate in this group was 4.1% compared with 3.9% in the control population (native biopsies only; P = 0.88).Conclusions: In the population studied, the rate of major hemorrhagic complications after percutaneous renal biopsy was not significantly greater in patients with a monoclonal gammopathy.Paraproteins are frequently detected in patients with renal disease, both as an incidental finding and as the underlying cause of the renal injury. The renal disorders associated with paraproteins are well described (1,2). In the context of severe acute kidney injury, cast nephropathy (myeloma kidney) is the most frequent finding (2,3). In contrast, patients presenting with heavy proteinuria and milder renal impairment are more likely to have amyloidosis (2,4) or light chain deposition disease (2,5). The conclusion that the presence of a paraprotein in the context of renal injury equates to a causal association cannot be drawn because of the high frequency of incidental paraproteins in this setting (6). For this reason, assessment of renal pathology is essential. In addition to confirming the underlying disorder and therefore allowing the initiation of disease specific treatment, pathologic features are also prognostic of clinical outcomes (2,5,7).Despite these advantages, many clinicians are reluctant to perform percutaneous renal biopsies in patients with paraproteins because of the theoretical risk of a higher rate of hemorrhagic complications (8,9). Indeed, there are a number of mechanisms by which paraproteins might confer this increased risk (10,11). Therefore, renal histology has not been used as an inclusion criterion for some studies that have investigated the optimal treatment strategies for paraprotein-related renal disease (9). In turn, this makes interpretation of the results of these studies difficult (12–14). However, clear evidence that performing percutaneous renal biopsies in these patients is associated with an actual higher incidence of clinically significant hemorrhagic complications is not well reported. In fact, recent work has implied that the procedure is relatively safe in patients with amyloidosis, traditionally the subgroup considered to be most at risk (15). The purpose of this study was to determine the incidence of major hemorrhagic complications after percutaneous renal biopsies in a large population of patients with monoclonal gammopathies.     

Connective Tissue Growth Factor Promotes Fibrosis Downstream of TGFβ and IL‐6 in Chronic Cardiac Allograft Rejection

Cardiac transplantation is an effective treatment for multiple types of heart failure refractive to therapy. Although immunosuppressive therapeutics have increased survival rates within the first year posttransplant, chronic rejection (CR) remains a significant barrier to long‐term graft survival. Indicators of CR include patchy interstitial fibrosis, vascular occlusion and progressive loss of graft function. Multiple factors have been implicated in the onset and progression of CR, including TGFβ, IL‐6 and connective tissue growth factor (CTGF). While associated with CR, the role of CTGF in CR and the factors necessary for CTGF induction in vivo are not understood. To this end, we utilized forced expression and neutralizing antibody approaches. Transduction of allografts with CTGF significantly increased fibrotic tissue development, though not to levels observed with TGFβ transduction. Further, intragraft CTGF expression was inhibited by IL‐6 neutralization whereas TGFβ expression remained unchanged, indicating that IL‐6 effects may potentiate TGFβ‐mediated induction of CTGF. Finally, neutralizing CTGF significantly reduced graft fibrosis without reducing TGFβ and IL‐6 expression levels. These findings indicate that CTGF functions as a downstream mediator of fibrosis in CR, and that CTGF neutralization may ameliorate fibrosis and hypertrophy associated with CR.     

Effect of IGFBP-derived peptides on incorporation of(35)SO(4)into proteoglycans.

18 amino acid peptides from the C-terminal region of IGFBP-3, -5 (P3, P5), increased the incorporation of(35)SO(4)into proteoglycans in endothelial cells with greater stimulation in large vessel than microvessel cells. The homologous region of IGFBP-6 (P6) also stimulated sulfate uptake, but less potently than P3 and P5. P6 variants were synthesized with one or two amino acids changed to the basic amino acid in the equivalent position of P3. The P6 variants with one additional basic amino acid behaved similarly to P6. The P6 mutant with two altered amino acids was equipotent to P3. P3F, a scrambled version of P3 was less effective than P3. P3, P5, P6, P3F and all P6 variants all stimulated glucose uptake, which occurred only in microvessel cells. P1, P2, P4, and equimolar intact IGFBP-3 stimulated neither glucose uptake nor sulfate incorporation. Thus, C-terminal basic portions of IGFBP-3, -5 and -6 alter two specific functions of endothelial cells with sufficient differences to suggest mediation by distinct mechanisms.     

Is the way to a man's heart through his stomach? Enteropericardial fistula: case series and literature review

Fistula formation between the pericardium and the gastrointestinal tract is rare. Enteropericardial fistulae may present dramatically, many have prodromal symptoms even though they are not symptoms usually associated with esophageal disease. Prompt diagnosis and expedient surgery can result in survival. We describe three cases of enteropericardial fistulae diagnosed during emergency surgery for sepsis or hemorrhage. All had previous surgery though the details were not available to the operating surgeons because of the time that had passed since their original operation. All three patients survived, albeit with prolonged hospital stay and repeated surgery. A review of the English language literature revealed 95 cases ( Table 1 ). Fifty‐eight had a history of previous surgery, particularly fundoplication or esophagectomy. Ten had advanced malignancy and were treated conservatively. All eight patients with fistulae, which were iatrogenic or due to foreign bodies, survived without aggressive surgery. For more extensive pathology, a successful outcome was achieved in 32 of the 36 cases when the upper gastrointestinal (GI) tract was defunctioned because of the presence of major sepsis or because the healthy vascularized tissue was transposed into the area at risk for further fistula formation. Where less aggressive surgery was performed only 12 of 27 patients survived (P < 0.0001). Esophageal surgeons need to be aware of the late complications and associated atypical symptoms of historical procedures which are no longer in common usage. Where an enteropericardial fistula is present, defunctioning of the upper GI tract or repair with transposition of vascularized tissue gives a better chance of a successful outcome.

Table 1. Summary of treatment strategies for enteropericardial fistulae

Recognition and Management of Depression in a Substance Use Disorder Treatment Population

This study examines the association between depressive symptomatology and return to substance use among a sample of 126 veterans consecutively admitted to treatment at a VA intensive outpatient program for substance use disorders. Controlling for numerous demographic and health-related covariates, depressive symptomatology measured at treatment exit with a Beck Depression Inventory (BDI) was significantly predictive of substance use at three-months post-treatment (p < .05). Analysis with a recoded BDI showed that the moderately-to-severely symptomatic (BDI = 20+) were 4.1 times more likely to have returned to substance use than those with a BDI score of under 20.