How does long-term parenteral nutrition impact the bone mineral status of children with intestinal failure?

Patients on long-term parenteral nutrition (PN) are at significantly increased risk for the development of metabolic bone disease (MBD); this condition is characterized by incomplete mineralization of osteoid with consequent disturbances ranging from osteopenia to severe bone disease with fractures. The aim of the study was: (1) to evaluate the prevalence of MBD, (2) to identify the PN- or intestinal failure (IF)-related factors and (3) to assess annual changes of bone mineral status. Since September 2005 all patients affected by IF and treated with PN started a BMD evaluation program using dual-energy X-ray absorptiometry (DXA). Twenty-four IF patients were included [15 with short bowel syndrome (SBS), 5 with severe protracted diarrhea and 4 with chronic intestinal pseudostruction]. The bone mineral density (BMD) Z-score was significantly lower in patients than in the control group. In our series SBS patients showed a BMD Z-score significantly higher in comparison with the medical causes of IF. No significant correlations were found between bone mineral status and PN duration and nutrient intake. Nine IF patients were submitted to a second DXA evaluation after 1 year from the baseline. All bone mineral variables were significantly increased at the second DXA evaluation. The high prevalence of MBD in IF patients undergoing long-term treatment with PN requires that these patients undergo careful and periodic monitoring of their bone mineral status; patients with congenital gut dysfunctions, such as epithelium defects and motility anomalies, are at major risk of developing this complication, probably due to the association with extra-intestinal causes of bone loss.     

Independent FHC-related cardiac troponin T mutations exhibit specific alterations in myocellular contractility and calcium kinetics

Mutations in cardiac troponin T (cTnT) are linked to a severe form of Familial Hypertrophic Cardiomyopathy. Patients carrying mutations flanking the tropomyosin-binding domain of cTnT (R92L and Delta160E) develop distinct clinical syndromes. In order to better understand the cellular pathophysiology underlying these clinically relevant differences, we studied isolated adult left ventricular myocytes from independent transgenic cTnT mouse lines carrying either a 35% (Delta160E) or 50% (R92L) replacement of the endogenous cTnT with the mutant forms. Measurement of baseline myocellular contraction revealed that the Delta160E cells had significant decreases in the peak rate of contraction and percent shortening as compared to either R92L or Non-TG myocytes. In addition, while both Delta160E and R92L myocytes demonstrated a decrease in the peak rate of relaxation as compared to Non-TG, the magnitude of the difference was significantly greater in Delta160E cells. Concurrent myocyte [Ca2+](i) transient measurements revealed that while the alterations in the peak rates and times of the rise and decline of the [Ca2+](i) transient were similar to the changes in the respective measures of sarcomeric mechanics, R92L cells also exhibited reduced rates of the rise and decline of the [Ca2+](i) transient but did not exhibit these reductions in terms of sarcomeric mechanics. Of note, only Delta160E, and not R92L myocytes, demonstrated significant reductions in SR Ca2+ load and uptake, corresponding to the impairments seen in the [Ca2+](i) and mechanical transients. Finally, Western analysis revealed a significant Delta160E-specific reduction in the SERCA2a/PLB ratio, which may well underlie the observed alterations in Ca2+ homeostasis. Therefore, independent cTnT mutations result in significant mutation-specific effects in Ca2+ handling that may, in part, contribute to the observed clinical variability in cTnT-related FHC.     

Successful treatment with intravenous immunoglobulins in a patient affected by dermatomyositis/systemic lupus erythematosus overlap syndrome and tuberculosis

The case of a 56-year-old woman, with a previous history of systemic lupus erythematosus (SLE), later diagnosed as also affected by active dermatomyositis (DM) associated with tuberculosis (TB) is reported. Since TB is a contra-indication to receive immunosuppressive therapy for DM/SLE, intravenous immunoglobulins (IVIG) with low-dose steroids and anti-TB therapy were administered with excellent clinical results. This report underlines the crucial role of IVIG in the treatment of critical patients suffering from connective tissue disorders associated with severe infections.     

Early emergence of PNH-like T cells after allogeneic stem cell transplants utilising CAMPATH-1H for T cell depletion

CAMPATH-1H (C-1H) is widely used in vivo and / or in vitro for T cell depletion in hematopoietic SCT. This humanised monoclonal antibody is specific for CD52, a marker coexpressed on the majority of human lymphocytes with CD48 and other glycosylphosphatidyl-inositol (GPI) anchored proteins. We detected CD52 / CD48 dual expression on >99% of CD3(+) lymphocytes from normal individuals and all 15 post-SCT patients whose transplants did not utilise C-1H. By contrast, 23 / 26 patients with transplants involving C-1H (in vivo, in vitro or both) exhibited populations lacking CD52 expression that accounted for 49.7% (4.2-86.2%) of the CD3+ lymphocytes (median and range) in samples evaluated at a median of 2 months post-SCT. Most CD52- cells also lacked CD48 expression. These GPI- T cells were of either donor or mixed donor / recipient origin. They were predominant in the early months after SCT at times of profound lymphopenia and inversely correlated with the recovery of the absolute lymphocyte count (r= - 0.663, P<0.0001). The presence of CD52- cells has been correlated previously with clinical outcome after CAMPATH therapy for both malignant and nonmalignant diseases.     

Postoperative troponin T elevation as a predictor of early acute kidney injury after orthotopic liver transplantation: a preliminary retrospective study

Background

Slight alterations in cardiac enzymes are frequently observed perioperatively among liver transplant patients. The significance of these changes in the absence of ongoing acute cardiac pathology is unknown. We sought to evaluate the link between early postoperative anomalies of serum cardiac troponin T (cTnT) in the absence of an evident cardiac cause and kidney injury during the first week of hospital stay.

Methods

We retrospectively enrolled 30 patients in the study, recording several perioperative variables, particularly cTnT on intensive care unit ICU arrival as well as 6 and 12 hours later. We grouped patients with cTnT levels >0.03 ng/mL as the high-TnT group; the others were control subjects. We recorded the highest serum creatinine, aspartate aminotransferase, alanine aminotransferase, and bilirubin levels during the first week of the hospital stay. Glomerular filtration rate (GFR) was calculated according to the Cockroft-Gault formula.

Results

Ten patients composed the high-TnT group. Their perioperative variables showed higher Model for End-Stage Liver Disease (MELD) scores and significantly greater incidences of acute kidney injury, failure, and dialysis need than control patients. GFR dropped from 118 to 66 mL/min among this group versus 112 to 105 mL/min in control subjects (P = .021). Binary logistic regression analysis revealed a higher association between the high-TnT group and acute kidney injury (P = .036) than with the MELD score (P = .719).

Conclusions

Serum cTnT levels could be influenced by both preoperative and intraoperative conditions that predispose to kidney injury.     

Chronic pancreatitis as presentation of Crohn’s disease in a child

It is reported that a pancreatic disease may precede the diagnosis of inflammatory bowel disease(IBD) both in children and in adults.Idiopathic chronic pancreatitis,however,occasionally co-exists with the IBD,mainly at pediatric age.We report a case of a patient who progressively developed the features of a chronic pancreatitis,before the diagnosis of Crohn’s Disease(CD).Ten months after the onset of the first episode of pancreatitis the patient developed bloody diarrhea,mucus stools and biochemical findings of inflammation.The colonoscopy revealed a diffuse colitis without involvement of the last loop and the gastroscopy showed inflammation of the iuxta-papillary area.The histological findings confirmed the diagnosis of CD that involved the colon and the duodenum.In conclusion,in children the idiopathic chronic pancreatitis may be an unusual presentation of CD.Thus,if other known cause of chronic pancreatitis are not found,a not invasive work up to exclude the IBD should be warranted.An early coincidental diagnosis of the IBD may delay the progression of the pancreatic disease.     

Autoantibodies in Patients with Rheumatoid Arthritis

Aim:  The aim of this study is to examine the diagnostic value of autoanitbodies in patients suffering from rheumatoid arthritis. We evaluated the presence of the following autoantibodies: rheumatoid factor (RF), antinuclear antibodies (ANAs), antibodies against cadiolipin (a-CL) and antibodies against cyclic citrullinated peptide (anti-CCP).
Methods:  We studied the presence of RF, ANA, a-CL and anti-CCP in 40 patients with rheumatoid arthritis. Rheumatoid factor was measured using nephelometric method, while ANAs were examined by indirect immunofluorescence technique using Hep-2 cells as substrate. Sera that reacted at 1/80 dilution were classified as ANA positive. Positive sera were studied up to 1/1280 dilution. A-CL and anti-CCP were measured by enzyme-linked immunosorbent assay.
Results:  RF was positive in 30 patients (75%), ANA in 15 (37%), a-CL in 10 (25%) and anti-CCP in 36 (90%). Predominant pattern of nuclear staining of ANA-positive sera was homogenous and speckled type. ANA titres were particularly low; most patients (6) had ANA titre equal to 1/80, and five patients had a titre of 1/160, while only four out of 40 had an ANA titre of 1/320.
Conclusions:  Autoimmune disorders such as RA are characterized by various autoantibodies that usually are not specific, as they are present in many other diseases. However, RF and especially anti-CCP are very often and show higher specificity for RA, being useful diagnostic serological markers. On the other hand, ANA and a-CL are less common in RA paitents; they may be useful in terms of prognosis and treatment, but they always should be evaluated in correlation with the clinical features and the rest of the laboratory findings of each patient.     

Use of specific antibody for rapid clearance of circulating blood background from radiolabeled tumor imaging proteins

A major problem that arises when radiolabeled serum proteins are used for tumor imaging is the presence of a large amount of circulating background activity that persists for several days. This delays imaging for at least 2 days following injection and necessitates computer subtraction of simulated background (second radiopharmaceutical injection) which introduces artifacts that are difficult to control. We propose here the injection of specific antibody immediately before imaging as an alternate way of reducing blood background through clearance of the immune complex by the liver. ¹¹¹In-alkyl human transferrin and IgG were injected IV in BALB/c tumor mice, and followed in 18 h by anti-human transferrin and anti-human IgG antibody IV. Two hours later, the tumor and organ distribution of activity was compared with control mice not receiving antibody. ¹¹¹In-transferrin blood activity was reduced to 1/48 of control with no decrease in tumor concentration: as a result, the tumor to blood ratio increased from 1.4:1 to 78:1. ¹¹¹In-IgG blood activity was reduced to 1/17 of control, again with no decrease in tumor. The tumor to blood ratios increased from 0.7:1 to 17:1. The liver picked up most of the blood activity with none of the complex going to spleen, bone marrow, or kidney. Dog experiments showed clearance of blood was 90% complete in less than 15 min following antibody injection. Simultaneous scintillation images showed complete clearance of activity from the heart and great vessels in the chest and neck, and over the abdomen, with a concomitant increase in liver activity but no increase in spleen, kidney, or bone marrow activity. These studies show the feasibility of using specific antibody to lower the blood background just minutes prior to tumor imaging procedures using radiolabeled proteins.These studies were supported in part by a Veterans Administration Research Grant, and PHS Grant Number 5 ROI CA 28343 (D Goodwin), and CA 16861, RCDA CA 00462 (C Meares)     

Chelate conjugates of monoclonal antibodies for imaging lymphoid structures in the mouse

Radiolabeling of a mouse monoclonal antibody (MoAb) specific for the mouse histocompatibility alloantigen IAk expressed by the B lymphocytes of BALB/k and C3H mice but not BALB/c mice was performed by mixing the chelate-labeled anti (alpha) IAk MoAb with purified, no-carrier-added 111In citrate. Labeling efficiency was 85-95%, and the labeled alpha IAk MoAb retained its antigen binding properties in vitro and in vivo. The organ, spleen, and lymph node distribution of intravenously and subcutaneously administered 111In alpha IAk MoAb was compared in mice, two IAk positive and one IAk negative strains, and to 125I alpha IAk MoAb in one IAk positive strain. The 111In alpha IAk MoAb was more stable in vivo compared to 125I alpha IAk MoAb, as shown by a much slower excretion and a higher absolute uptake in lymph nodes and spleen. Lymph node to blood ratio was increased twofold by intravenous anti-EDTA MoAb. Subcutaneous injection permitted clear images of the tiny lymph nodes in the mouse. Potential clinical applications of 111In alpha lymphocyte MoAb include localization of normal lymph nodes and T & B cell leukemias and lymphomas, as well as detecting lymphatic metastases of other cancers. Therapy may also be possible using MoAbs labeled with beta-emitting metal ions such as yttrium-90.     

Distribution and characterization of cyclo (His-Pro)-like immunoreactivity in the human gastrointestinal tract

Cyclo (His-Pro) [C(HP)] has been measured by radioimmunoassay in perchloric acid extracts of human gastrointestinal (GI) tract structures derived from autopsy sources and fresh colonic biopsies. C(HP) was identified in all regions of the human GI tract, ranging in concentrations from 599 +/- 102 pg/mg protein in stomach, to 127 +/- 26 pg/mg protein in esophagus. The mean concentration of C(HP) from colonic biopsies was 335 +/- 30 pg/mg protein, statistically similar to values derived from postmortem sources. Since C(HP) concentrations are within the range of other gut peptide modulators, cyclo (His-Pro) is speculated to play a role as a new paracrine modulator of human GI tract function(s).