Adult celiac disease presented with celiac crisis: severe diarrhea, hypokalemia, and acidosis

An acute severe onset of celiac disease is very uncommon in adults. We describe a patient with adult celiac disease who presented with acute diarrhea that lead rapidly to a life threatening hypokalemia and acidosis, the so-called celiac crisis. Celiac crisis, described mainly in children younger than two years of age, has become very rare due to earlier diagnosis and effective therapy of the disease. The case described is an example of the heterogeneous clinical course of celiac disease and emphasizes the need to consider it in the differential diagnosis, even in adults suffering from acute diarrhea and acidosis.     

Matchmaking facilitates the diagnosis of an autosomal‐recessive mitochondrial disease caused by biallelic mutation of the tRNA isopentenyltransferase (TRIT1) gene

Deleterious variants in the same gene present in two or more families with overlapping clinical features provide convincing evidence of a disease–gene association; this can be a challenge in the study of ultrarare diseases. To facilitate the identification of additional families, several groups have created “matching” platforms. We describe four individuals from three unrelated families “matched” by GeneMatcher and MatchMakerExchange. Individuals had microcephaly, developmental delay, epilepsy, and recessive mutations in TRIT1. A single homozygous mutation in TRIT1 associated with similar features had previously been reported in one family. The identification of these individuals provides additional evidence to support TRIT1 as the disease‐causing gene and interprets the variants as “pathogenic.” TRIT1 functions to modify mitochondrial tRNAs and is necessary for protein translation. We show that dysfunctional TRIT1 results in decreased levels of select mitochondrial proteins. Our findings confirm the TRIT1 disease association and advance the phenotypic and molecular understanding of this disorder.     

Treatment of intestinal worms is associated with decreased HIV plasma viral load

BACKGROUND: We have previously suggested that helminthic infections make the host more susceptible to HIV infection and enhance its progression due to the chronic immune activation they cause. OBJECTIVE: To study the effect of antihelminthic treatment on HIV plasma viral load (VL) in HIV- and helminth-infected individuals living in Ethiopia. METHODS: Fifty-six clinically asymptomatic HIV-1-infected individuals, 31 (55%) of whom were also infected with helminths, were studied. All participants received antihelminthic treatment at baseline and at 3 and 6 months. Worm egg excretion, HIV plasma VL, and T-cell subsets were determined at baseline and 6 months after treatment. RESULTS: The mean age, number of CD4 T cells, and gender distribution were similar in the helminth-infected and -noninfected groups. At baseline, HIV plasma VL was strongly correlated to the number of eggs excreted (p <.001) and was higher in individuals infected with more than one helminth (5.28 +/- 0.35 versus 4.30 +/- 1.13 log RNA copies/mL, respectively; p =.16). After treatment of helminths, the 6-month change in HIV plasma VL was significantly different between the successfully treated group and the persistently helminth-positive group (p =.04) CONCLUSIONS: Helminth "load" is correlated to HIV plasma VL, and successful deworming is associated with a significant decrease in HIV plasma VL. The results of the current study, if confirmed in a larger study, may have important implications for slowing disease progression and reducing risks of transmission.     

Haiti earthquake 2010: a field hospital pediatric perspective

On January 12 2010, a 7.0-magnitude earthquake struck Haiti. The region had suffered an estimated 316,000 fatalities with approximately 300,000 injured and more than 1 million people who lost their houses. Following the quake, the Israeli Defense Force Medical Corps dispatched a field hospital unit to the capital city, Port au Prince. The hospital had a pediatric division which included pediatric emergency department, pediatric ward and neonatal unit. We elaborate on the various aspects of pediatric treatment that was provided by our hospital. A total of 363 pediatric patients (younger than 18 years) were admitted to our facility during its 10 days of operation. Out of this total, 272 pediatric patients were treated by the pediatric division, 79 (29%) were hospitalized and 57 (21%) required surgery. The pediatric team included seven pediatricians, one pediatric surgeon and six registered nurses. An electronic record and a hard copy file were created for each patient. Fifty-seven percent of the children presented with direct earthquake related injuries. Twelve patients required resuscitation and stabilization and three patients had died. The majority of injuries were orthopedic while infectious diseases accounted for most of the general pediatric diagnoses. In conclusion, operating a field hospital for a population affected by natural disaster is a complex mission. However, pediatric care has its own unique, challenging characteristics.     

Do deficiencies in growth hormone and insulin-like growth factor-1 (IGF-1) shorten or prolong longevity?

Present knowledge on the effects of growth hormone (GH) and insulin-like growth factor-I (IGF-I) deficiency on aging and lifespan are controversial. Studying untreated patients with either isolated GH deficiency due to GH gene deletion, patients with multiple pituitary hormone deficiency due to PROP-1 gene mutation and patients with isolated IGF-I deficiency due to deletions or mutations of the GH receptor gene (Laron syndrome); it was found, that these patients despite signs of early aging (wrinkled skin, obesity, insulin resistance and osteopenia) have a long life span reaching ages of 80-90 years. Animal models of genetic GH deficiencies such as Snell mice (Pit-1 gene mutations) the Ames mice (PROP-1 gene mutation) and the Laron mice (GH receptor gene knock-out) have a statistically significant higher longevity compared to normal controls. On the contrary, mice transgenic for GH and acromegalic patients secreting high amounts of GH have premature death. Those data raise the question whether pharmacological GH administration to adults is deleterious, in contrast to policies advocating such therapies.     

HIV infection rapidly induces and maintains a substantial suppression of thymocyte proliferation

The supply of naive T cells by the thymus normally requires precursor T cell proliferation within the thymus and would be particularly important in the setting of HIV infection when both naive and memory T cells are progressively depleted. As a robust, quantitative index of intrathymic proliferation, the ratio of different T cell receptor excision circles (TRECs), molecular markers of distinct T cell receptor rearrangements occurring at different stages of thymocyte development, was measured in peripheral blood-mononuclear cells (PBMCs). This ratio has the virtue that it is a "signature" of thymic emigrants throughout their entire life and, thus, can be measured in peripheral cell populations that are easy to obtain. Using the new assay, we evaluated the effect of HIV infection on intrathymic precursor T cell proliferation by longitudinal analysis of PBMCs from recently infected individuals. Our findings reveal a substantial reduction in intrathymic proliferation. The analysis also indicates the existence of a compensatory mechanism acting to sustain the numbers of recent thymic emigrants (RTEs) in the periphery.     

NKT lymphocyte polarization determined by microenvironment signaling: a role for CD8+ lymphocytes and beta-glycosphingolipids

Natural killer T-cell (NKT) regulatory lymphocytes have been shown to behave differently in various immune settings. The aim of the present study was to determine the effect of microenvironmental signaling on NKT polarization and the process of active CD8 and NKT intrahepatic lymphocyte sequestration. In an in vitro assay, double negative (DN) NKT hybridoma cells were incubated with Hep3B hepatoma cells. This caused a significant increase in the secretion of alpha-fetoprotein (AFP) from Hep3B cells. When NKT cells were exposed to beta-glucoslyceramide (beta-GC) prior to incubation, Hep3B cells exhibited increased proliferation, increased IFN secretion, and reduced AFP secretion. In vivo, the adoptive transfer of na?ve DN NKT cells into athymic nude-nu mice transplanted with human Hep3B hepatocellular carcinoma (HCC) caused accelerated tumor growth. This effect was inhibited by prior ex vivo exposure of DN NKT lymphocytes to beta-GC. To assess the effect of the immunological environment on NKT cells, immune mediated hepatitis and colitis were induced simultaneously in mice. Induction of TNBS colitis prior to administration of concanavalin A (Con A) hepatitis resulted in an aggravation of the liver damage caused by Con A hepatitis alone. This effect was associated with reduced intrahepatic CD8+ T cell trapping and an increase in intrahepatic NKT cells. The presence of different ligands altered host microenvironment signaling and influenced the fate and polarization of NKT cells and the sequestration of active intrahepatic lymphocytes. These data support the notion that NKT regulatory lymphocytes have an inherent plasticity that may be important for their regulatory function.     

Taking a toll on the bones: regulation of bone metabolism by innate immune regulators

The interplay between the immune system and bone metabolism has been recognized as important for both of these systems. Various factors produced and released during immune responses markedly affect bone cells and bone metabolism. Meanwhile, niches for lymphocytes in bone also play an important role in the biology of these cells. Osteoimmunology, a new area of research focusing on associations between the immune and bone systems, is based on the concept that deeper investigation of the relationships between these systems will enhance our understanding of their biology and contribute to the discovery of novel therapeutic approaches for diseases of the two systems. Toll-like receptors (TLRs), the focus of this review, sense pathogen-derived molecules and initiate the inflammatory reactions of innate immune cells. TLRs are also expressed in bone cells, and their activation affects osteoclast differentiation and activity in a complex manner: TLR activation in early osteoclast precursors blocks the differentiation of those cells, while in cells that have already started their osteoclastic differentiation, it stimulates this process and increases the survival rates of mature osteoclasts (OCs). Activation of TLRs in osteoblasts (OBs) induces the production of osteoclastogenic cytokines, such as RANKL and TNF-alpha, thereby contributing to TLR ligand-induced osteoclastogenesis. These processes are the reason for the bone loss observed in variety of infectious diseases. The inhibition of osteoclastogenesis by TLR activation in early precursor cells may play a role in reducing the excessive bone loss caused by pathogenic infection and shifting the balance between the bone and immune systems during infection to recruit immune cells.