Research Spotlight

Posted January 21st 2016

A genetic form of achlorhydria and gastritis: Reply to Schiffmann.

John Fordtran M.D.

John S. Fordtran, M.D.

Betesh, A. L., C. A. Santa Ana, J. A. Cole and J. S. Fordtran (2015). “A genetic form of achlorhydria and gastritis Reply.” American Journal of Clinical Nutrition 102(6): 1615-1616.

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We thank Schiffmann for calling attention to congenital achlorhydria in patients with mucolipidosis type IV (MLIV). As he and his coworkers at the NIH clearly showed, these patients secreted no gastric acid after maximal stimulation with pentagastrin. Although gastric biopsy samples revealed a normal density of parietal cells, they were distended with vacuoles. In addition, mucosal atrophy in the gastric fundus was mild in a 4-y-old patient, moderate in a 7-y-old patient, and severe in a 22-y-old patient. Antral biopsies revealed no gastritis. Half of the patients had iron deficiency anemia, and 24-h urinary iron excretion was low in all of the patients. None of the patients had occult blood in their stools. The anemia responded to oral iron therapy. Achlorhydria is the presumed primary event in this association between iron deficiency anemia and achlorhydria, and the above findings are consistent with the hypothesis that achlorhydria can cause malabsorption of dietary iron that results in iron deficiency anemia. It is possible that fundic mucosal atrophy in these patients with MLIV may predispose them to pernicious anemia in later life. The results of Schiffmann et al. also indicate that this lysosomal disease is a cause of chronic gastritis and achlorhydria. Therefore, we wish to modify point number 6 in the final paragraph of our article to include MLIV as a third known cause of chronic gastritis in patients with achlorhydria. A mechanistic distinction should be made between the chronic gastritis and achlorhydria that occurs in patients with autoimmunity and Helicobacter pylori compared with that in patients with MLIV. In the former 2 conditions, gastritis is the cause of achlorhydria. In contrast, in MLIV, achlorhydria is apparently primary and is the presumed cause of fundic gastritis. It seems likely that additional clinically important insights would be gained if the mechanism can be determined by which MLIVinduced achlorhydria causes fundic gastritis. Although we know of no convincing evidence that chronic suppression of gastric acid secretion by proton pump inhibitors or by H2 receptor antagonists leads to fundic gastritis and atrophy in humans, inhibition of acid secretion by such drugs is probably less severe and less consistent than it is in patients with MLIV. Studies in guinea pigs have shown ultrastructural changes in parietal cells following administration of omperazole. There was no evidence of such damage when similar experiments were conducted in rabbits.

Posted January 20th 2016

Cough Augmentation in a Patient with Neuromuscular Disease.

Haala Rokadia M.D.

Haala Rokadia, M.D.

Rokadia, H. K., J. R. Adams, K. McCarthy, L. S. Aboussouan and E. Mireles-Cabodevila (2015). “Cough Augmentation in a Patient with Neuromuscular Disease.” Ann Am Thorac Soc 12(12): 1888-1891.

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In patients with neuromuscular disease, an impaired cough can be augmented by techniques that increase inspired volume and expiratory pressure and air flow. We trained our patient to “breath-stack” using her sip ventilator. She was able to take two to three consecutive breaths without exhaling, and this increased her FVC to 2.5 L and her PCF to 2.0 L/s (120 L/min). When breath stacking was combined with synchronized compression of the chest and abdomen, her PCF increased to 4.72 L/s (283.2 L/min) (Figure 1). During subsequent clinic visits, there was a significant and sustained increase in unassisted FVC, which was attributed to improved thoracic mobility and reduced atelectasis.

Posted January 20th 2016

Microcystic Stromal Tumor of the Ovary: A Case Report of a Newly Described Ovarian Neoplasm With a beta-catenin (CTNNB1) G34E Mutation.

Varsha Podduturi M.D.

Varsha Podduturi, M.D.

Podduturi, V., T. Tuan, K. J. Champion, N. Onur and S. M. Shiller (2015). “Microcystic Stromal Tumor of the Ovary: A Case Report of a Newly Described Ovarian Neoplasm With a beta-catenin (CTNNB1) G34E Mutation.” International Journal of Gynecological Pathology 34(6): 541-545.

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Microcystic stromal tumor of the ovary (MSTO) is an exceedingly rare, unusual, and recently described entity with unique genetic alterations that assist in its diagnosis. We describe the case of a 50-year-old woman who presented with a complex right ovarian mass. A hysterectomy with bilateral salpingo-oophorectomy was performed and revealed an ovarian mass consistent with MSTO by histomorphology and immunohistochemical studies. Tumor cells were immunohistochemically reactive for vimentin, CD10, -catenin, and Wilms tumor 1. In addition, we detected a missense mutation c.101 G>A, p.G34E in exon 3 of the -catenin (CTNNB1) gene, which leads to an amino acid substitution of glycine at codon 34 by glutamic acid. The utility of genetic testing of this tumor and additional reporting of alterations detected is needed to verify pathogenicity of variants detected, as well as their potential roles with prognosis, behavior, and therapeutic targets. The overall clinical course of MSTO appears to be nonaggressive, although the number of reported cases are limited thus far.

Posted January 20th 2016

Tuberculous Pericarditis is Multibacillary and Bacterial Burden Drives High Mortality.

Jotam Pasipanodya M.D.

Jotam Pasipanodya, M.D.

Pasipanodya, J. G., M. Mubanga, M. Ntsekhe, S. Pandie, B. T. Magazi, F. Gumedze, L. Myer, T. Gumbo and B. M. Mayosi (2015). “Tuberculous Pericarditis is Multibacillary and Bacterial Burden Drives High Mortality.” Ebiomedicine 2(11): 1634-1639.

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Background: Tuberculous pericarditis is considered to be a paucibacillary process; the large pericardial fluid accumulation is attributed to an inflammatory response to tuberculoproteins. Mortality rates are high. We investigated the role of clinical and microbial factors predictive of tuberculous pericarditis mortality using the artificial intelligence algorithm termed classification and regression tree (CART) analysis. Methods: Patients were prospectively enrolled and followed in the Investigation of the Management of Pericarditis (IMPI) registry. Clinical and laboratory data of 70 patients with confirmed tuberculous pericarditis, including time-to-positive (TTP) cultures from pericardial fluid, were extracted and analyzed for mortality outcomes using CART. TTP was translated to log(10) colony forming units (CFUs) per mL, and compared to that obtained from sputum in some of our patients. Findings: Seventy patients with proven tuberculous pericarditis were enrolled. The median patient age was 35 (range: 20-71) years. The median, follow up was for 11.97 (range: 0 . 03-74.73) months. The median TTP for pericardial fluid cultures was 22 (range: 4-58) days or 3.91(range: 0 . 5-8 . 96) log(10)CFU/mL, which overlapped with the range of 3.24-7.42 log(10)CFU/mL encountered in sputum, a multi-bacillary disease. The overall mortality rate was 1.43 per 100 person-months. CART identified follow-up duration of 5 . 23 months on directly observed therapy, a CD4+ count of <= 199.5/mL, and TTP <= 14 days (bacillary load >= 5.53 log(10) CFU/mL) as predictive of mortality. TTP interacted with follow-up duration in a non-linear fashion. Interpretation: Patients with culture confirmed tuberculous pericarditis have a high bacillary burden, and this bacterial burden drivesmortality. Thus proven tuberculosis pericarditis is not a paucibacillary disease. Moreover, the severe immunosuppression suggests limited inflammation. There is a need for the design of a highly bactericidal regimen for this condition. (C) 2015 The Authors. Published by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (

Posted January 20th 2016

Epidemiology, Traditional and Novel Risk Factors in Coronary Artery Disease.

Ambarish Gopal M.D.

Ambarish Gopal, M.D.

Mack, M. and A. Gopal (2016). “Epidemiology, Traditional and Novel Risk Factors in Coronary Artery Disease.” Heart Failure Clinics 12(1): 1-10.

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Coronary artery disease (CAD) mortality has been declining in the United States and in regions where health care systems are relatively advanced. Still, CAD remains the number one cause of death in both men and women in the United States, and coronary events have increased in women. Many traditional risk factors for CAD are related to lifestyle, and preventative treatment can be tailored to modifying specific factors. Novel risk factors also may contribute to CAD. Finally, as the risk for CAD is largely understood to be inherited, further genetic testing should play a role in preventative treatment of the disease.