Iron Deficiency Anemia Associated With Acid-Modifying Medications: Two Cases and Literature Review

Iron deficiency anemia is often listed among potential adverse effects of gastric acid-suppressive medications, given that gastric acidity promotes intestinal absorption of nonheme iron. Additionally, the antacid calcium carbonate can inhibit iron absorption. However, there is little direct clinical evidence that proton-pump inhibitors, histamine-2 receptor antagonists, or calcium carbonate cause iron deficiency anemia. Most case reports have had substantial limitations (e.g., minimal follow-up and presence of other causes of iron deficiency), and retrospective cohort studies have lacked sufficient patient-specific detail to make strong causal inferences. We present 2 cases—both with detailed, prospective 10-year follow-up—in which combinations of proton-pump inhibitors, histamine-2 receptor antagonists and calcium carbonate were clearly associated with development of iron deficiency anemia. Overt iron-deficiency anemia is probably uncommon in patients who use acid-modifying medications and who have no other conditions that predispose to iron deficiency. Nevertheless, clinicians should be aware of this potential complication, given widespread use of these agents.     

Anticoagulation Strategies in Patients With Cancer: JACC Review Topic of the Week

Patients with active cancer are at an increased risk of arterial and venous thromboembolism (VTE) and bleeding events. Historically, in patients with cancer, low molecular weight heparins have been preferred for treatment of VTE, whereas warfarin has been the standard anticoagulant for stroke prevention in patients with atrial fibrillation (AF). More recently, direct oral anticoagulants (DOACs) have been demonstrated to reduce the risk of venous and arterial thromboembolism in large randomized clinical trials of patients with VTE and AF, respectively, thus providing an attractive oral dosing option that does not require routine laboratory monitoring. In this review, we summarize available clinical trial data and guideline recommendations, and outline a practical approach to anticoagulation management of VTE and AF in cancer.     

Aneurysm detection using one-bit correlation

Intercranial aneurysm present an especially serious clinical problem, since their rupture generally results in death or permanent brain damage. Recent work, conducted by the authors, indicated that this anomaly can be detected using spectral signature analysis. A low-cost turnkey noninvasive aneurysm-detection system is being tested for this purpose. Using polarity-coincident noise-added one-bit correlators, aneurysms have been successfully detected.     

Segmental jejunal lipomatosis--a rare cause of intestinal obstruction

A rare case of a segmental small intestinal (jejunal) lipomatosis is described. A 33-year-old male was admitted with a clinical diagnosis of an acute intestinal obstruction. A plain erect abdominal x-ray showed multiple air-fluid levels. On an exploratory laparotomy, a jejunojejunal intussusception was found secondary to a segmental submucosal lipomatosis. This was treated by a segmental resection and anastomosis, which resulted in a complete cure. Here we present this case with a review of the relevant literature.     

Defective apoptosis in lymphocytes and the role of IL-2 in autoimmune hematologic cytopenias

Fas-mediated signaling is important for lymphocyte elimination. We investigated lymphocytes for Fas-signaling defects in 20 pediatric patients with chronic hematologic autoimmunity. In 5 of 20 (25%), there was profound resistance to exogenous FasL-mediated lysis, Fas mAb, and anti-CD3. FasL function, though variable, was not significantly different from that of simultaneously evaluated controls. Only 1 patient had a Fas mutation and manifestations of autoimmune lymphoproliferative syndrome. In contrast, lymphocytes from his clinically normal mother with the same mutation were normally sensitive to FasL. In 3 patients, normal Fas-mediated lysis was restored with rhIL-2. IL-2 had no effect in the other 2 patients. Activation and proliferation functions of IL-2 were normal in all 5. We conclude that altered Fas signaling, independent of Fas mutations, can precipitate hematologic autoimmunity. IL-2 can rescue some lymphocytes from this defect. In IL-2 refractory cases, a persistently defective response to IL-2 continues to confer a lymphocyte survival advantage. Hence, altered Fas pathway signaling with or without defective IL-2 responses should be considered in the etiology of hematologic autoimmunity.     

Mature teratoma arising from the middle cranial fossa

A 25-year-old man presented with a sudden spurt in size of a bony swelling around the external ear, which was present since birth. This was associated with a painful swelling of the right half of the face and pain, redness, and decreased vision in the right eye. Neurologic examination showed decreased visual acuity in the right eye and paresis of the fifth, seventh, and eighth cranial nerves. Neuroimaging showed an extra-axial, partly cystic tumor of mixed density, located entirely within the middle cranial fossa scalloping the temporal bone and extending into the right infratemporal fossa and the right middle ear and impinging on the ipsilateral cavernous sinus. The right temporal lobe was elevated and compressed. Histopathologic examination confirmed a mature teratoma.     

Learning by Selection in the Trion Model of Cortical Organization

The basic issue of whether mammalian learning in cortex proceedsvia a selection principle, as stressed by Edelman, versus aninstructional one is of major importance. We present here arealization of selection learning in the trion model, whichis based on the Mountcastle columnar organizational principleof cortex. We suggest that mammalian cortex starts out withan a priori connectivity between minicolumns that is highlystructured in time and in space, competing between excitationand inhibition. This provides a "naive" repertoire of spatial-temporalfiring patterns that stimuli and internal pro-cessing map onto.These patterns can be learned with small modifications to theconnectivity strengths determined by a Hobbian learning rule.As various patterns are learned, the repertoire changes somewhatin order to respond property to various stimuli, but the majorityof all possible stimuli still map onto spatial-temporal firingpatterns of the original repertoire. In order to show that theexample presented here is showing true selectivity and is notan artifact of more stimuli evolving into the learned pattern,we develop a selectivity measure. We suggest that some formof instructional learning (in which connectivities are finelytuned) is present for difficult tasks requiring many trials,whereas very rapid learning involves selectional learning. Bothtypes of learning must be considered to understand behavior.     

A pharmacoeconomic comparison of antithymocyte globulin and muromonab CD3 induction therapy in renal transplant recipients

Antithymocyte globulin (ATG) and muromonab CD3 (OKT3) are currently the only antilymphocyte preparations that are commercially available for induction immunosuppressive therapy for renal allograft transplantation in the US. ATG, in the usually prescribed doses, is more expensive than muromonab CD3, but muromonab CD3 is associated with more severe adverse effects that may affect clinical outcome and overall cost. We performed a retrospective study of all adult recipients of a first cadaveric renal allograft, who underwent transplantation between January 1991 and December 1994 who received either ATG (n = 92) or muromonab CD3 (n = 91) for induction therapy at our transplant centre. The average age of recipients was older (50 vs 44 yrs; p = 0.001) and extended donors were more commonly used in the ATG group (41 vs 13%; p = 0.0001) compared with the muromonab CD3 group. Nevertheless, at 1 year post-transplant, the incidence of rejection was lower (34 vs 47%) and graft survival was better (93 vs 85%; p = 0.03) in the ATG group. Patients who received ATG were discharged earlier (9.4 vs 13.3 days; p = 0.0001) and had similar serum creatinine levels on the day of discharge (2.4 +/- 1.5 vs 2.1 +/- 1.1 mg/dl; p = 0.25). Overall, the 1-year hospitalisation costs of transplantation and readmissions were similar [$US39,937 +/- 17,014 vs $US42,850 +/- 20,923 (currency year 1994); p = 0.22]. This is the first comparison of ATG and muromonab CD3 in renal transplant recipients to consider clinical as well as economic outcomes. For renal transplant patients in whom induction therapy is used at our centre, the initial expense of ATG can be justified by improved graft survival, fewer rejection episodes, and shorter hospital stays, which are associated with similar overall transplantation costs.     

Short colon variant

A one day old neonate with a short colon, associated exomphalos minor; bifid scrotum and ileovesical fistula is reported.