A histopathologic study of gastric and small intestinal graft-versus-host disease following allogeneic bone marrow transplantation

Twenty-two stomach and 14 small intestinal biopsy specimens from 24 allogeneic bone marrow transplant recipients were reviewed to evaluate the histopathologic changes of graft-versus-host disease (GVHD) in these organs. Associations between these results and clinical symptoms and other biopsy results were sought. In both organs, single epithelial cell necrosis was found to correlate with GVHD. Gastric GVHD was diagnosed in eight patients and small intestinal GVHD in four. Gastric GVHD was characterized by nausea, vomiting, and upper abdominal pain without diarrhea (the latter being present in only two patients), while all four of the patients with small intestinal GVHD had upper gastrointestinal symptoms and diarrhea. These symptoms correlated with concurrent rectal biopsy findings; pathologic alterations were seen in only one of six specimens from patients with gastric GVHD but in three of four with small intestinal GVHD. These findings suggest that stomach biopsy may be necessary to diagnose GVHD in patients with upper gastrointestinal symptoms but no diarrhea and normal rectal biopsy specimens. Diagnostic problems may arise in the early posttransplantation period, when the effects of cytoreductive therapy may simulate GVHD, and in patients with gastrointestinal cytomegalovirus infection, which may also produce changes identical to those of GVHD.     

Inflamed fibronectin: an altered fibronectin enhances neutrophil adhesion

Recent investigations have emphasized the role of activated granulocytes in mediating vascular endothelial injury in the pathogenesis of shock lung. In vitro studies have indicated that tight adherence of the neutrophil to the endothelium is crucial for the development of cellular injury. Fibronectin is critical to cell-to- substratum and cell-to-cell interactions. Since fibronectin resides in plasma, on endothelial cell surfaces and is secreted into cell matrices, the adhesive properties of fibronectin must be modulated, lest universal cell agglomeration occur, yet be enhanced when cell attachment is appropriate. In these studies, treatment of fibronectin- coated surfaces with neutrophil release products increased the adhesion of activated neutrophils. Similarly, endothelial cells treated with neutrophil release products become a more adherent substrate for neutrophils. This enhanced adherence generated by treatment of fibronectin with neutrophil supernatants is inhibitable by heat and the lysosomal proteinase inhibitor, pepstatin-A. Neutrophil release products cause proteolytic fragmentation of fibronectin and enhanced fibronectin immunofluorescence on endothelial cells. In addition, neutrophils are more injurious to endothelial cells that have been pretreated with neutrophil release products. Neutrophils may enhance their own adherence to endothelial cells by altering fibronectin, and this altered, or "inflamed," fibronectin may serve as an amplifier of inflammation.     

Piezoelectric bone surgery for impacted lower third molar extraction compared with conventional rotary instruments: a systematic review,meta-analysis,and trial sequential analysis

The aim of this study was to evaluate whether piezoelectric bone surgery (PBS) for impacted lower third molar extraction reduces the surgical time and risk of intra- and postoperative complications in comparison with conventional rotary instruments. This meta-analysis followed the PRISMA guidelines and was registered in the PROSPERO database. The PubMed, Embase, Scopus, and OpenGrey databases were screened for articles published from January 1, 1990 to December 31, 2018. Selection criteria included randomized controlled trials (RCTs) comparing PBS with conventional rotary instruments for impacted lower third molar extraction and reporting any of the clinical outcomes (intra- and postoperative complications and duration of surgery) for both groups. A risk of bias assessment was performed using the Cochrane Collaboration tool. A meta-analysis was performed, and the power of the meta-analytic findings was assessed by trial sequential analysis (TSA). Strong evidence suggests that PBS prolongs the duration of surgery and low evidence suggests that PBS reduces postoperative morbidity (pain and trismus) in comparison with rotary instruments. Data were insufficient to determine whether PBS reduces neurological complications and postoperative swelling in comparison with burs.     

Respiratory syncytial virus infection in immunocompromised adults

Respiratory syncytial virus disease was documented in 11 immunocompromised adults, aged 21 to 50. Underlying conditions included bone marrow transplant (6 patients), renal transplant (3 patients), renal and pancreas transplants (1 patient), and T-cell lymphoma (1 patient). Diagnosis of infection was based on specimens from bronchoalveolar lavage, sputum, throat, sinus aspirate, and lung biopsy. The virus was detected simultaneously by antibody in either an immunofluorescence or enzyme-linked immunosorbent assay in 3 of 4 patients whose culture results were positive for respiratory syncytial virus. The virus was an unexpected finding, despite widespread infection in the community. Clinical symptoms included low-grade fever, nonproductive cough, rhinorrhea or nasal congestion, and radiographic evidence of interstitial infiltrates and sinusitis. Aerosolized ribavirin therapy was used in the 6 recipients of bone marrow transplants, 3 of whom required assisted ventilation but died. Death caused by virus infection was documented in 4 of 11 patients. Respiratory syncytial virus disease must be considered in the differential diagnosis of fever and pulmonary infiltrates in immunocompromised adults.     

Ferriporphyrins and endothelium: a 2-edged sword-promotion of oxidation and induction of cytoprotectants

Heme arginate infusions blunt the symptoms of patients with acute intermittent porphyria without evidence of the vascular or thrombotic side effects reported for hematin. To provide a rationale for heme arginate's safety, the present study examined the effects of various ferriporphyrins to sensitize human endothelial cells to free radical injury and to induce heme oxygenase and ferritin expression. Heme arginate, unlike hematin, did not amplify oxidant-induced cytotoxicity mediated by hydrogen peroxide (5.3 +/- 2.4 versus 62.3 +/- 5.3% (51)Cr release, P <.0001) or by activated neutrophils (14.4 +/- 2.9 versus 41.1 +/- 6.0%, P <.0001). Nevertheless, heme arginate efficiently entered endothelial cells similarly to hematin, since both markedly induced heme oxygenase mRNA (more than 20-fold increase) and enzyme activity. Even with efficient permeation, endothelial cell ferritin content was only minimally increased by heme arginate compared with a 10-fold induction by hematin; presumably less free iron was derived from heme arginate despite up-regulation of heme oxygenase. Hematin is potentially vasculopathic by its marked catalysis of oxidation of low-density lipoprotein (LDL) to endothelial-toxic moieties. Heme arginate was significantly less catalytic. Heme arginate-conditioned LDL was less than half as cytotoxic to endothelial cells as hematin-conditioned LDL (P <.004). It is concluded that heme arginate may be less vasculotoxic than hematin since it is an effective heme oxygenase gene regulator but a less efficient free-radical catalyst.     

Circulating ghrelin levels in the newborn are positively associated with gestational age

OBJECTIVE: Ghrelin exerts potent GH-releasing activity and stimulates food intake. Circulating ghrelin levels are increased in anorexia and cachexia, reduced in obesity and restored by weight recovery. Newborns are characterized by GH hypersecretion associated with low IGF-I levels reflecting peripheral GH resistance. STUDY DESIGN: The aim of our study was to measure cord ghrelin levels in 117 newborns appropriate for gestational age, born either at term or preterm. RESULTS: Ghrelin levels in cord blood (median; 25th-75th centile: 327.6; 206.0-413.0 pg/ml) were higher (P < 0.0001) than those in maternal blood at delivery (133.0; 89.0-173.7 pg/ml), without gender differences. A positive correlation between ghrelin levels in mothers and newborns (r = 0.26, P < 0.01) was observed. Ghrelin levels in newborns born at term (399.0; 229.0-438.0 pg/ml) were remarkably higher (P < 0.0001) than those in born preterm (208.0; 144.5-278.9 pg/ml). A clear positive association was present between ghrelin levels and gestational age. No association between ghrelin and GH, IGF-I, insulin, glucose and leptin levels were found. CONCLUSIONS: Cord ghrelin levels show clear gestational age-related dependency. The lack of any direct relationship between ghrelin and anthropometric or biochemical parameters in adequate for gestational age newborns does not support the hypothesis that ghrelin has major role in foetal GH secretion and growth.     

A 'touch' of the White platelet syndrome

Investigations into structural defects in platelets from a large family with the White platelet syndrome (WPS) separated the members into three groups. The first group of 22 members was the subject of our first report (White JG, Key NS, King RA, Vercellotti GM. The white platelet syndrome: A new autosomal dominant platelet disorder. Platelets 2004;15:173-184). A third group of 13 members had no abnormalities of platelet ultrastructure. The second group of 17 members, the focus of the present study, had a 'touch' of the WPS. Platelet counts, mean platelet volumes (MPVs) and platelet responses to aggregating agents were normal in 'touch' patients in contrast to platelets of those with the full WPS in whom these parameters were abnormal. Up to 13% of the full WPS platelets contained large, fully developed Golgi complexes, up to seven in number, extruding innumerable vesicles from the trans-Golgi face and filling the cytoplasm of many platelets. Many Golgi complexes had centrioles associated with them. 'Touch' platelets had one or two Golgi complexes of intermediate size in 3-5% of their platelets. Golgi vesicles were uncommon and centrioles absent. Gray platelets and hypogranular cells were infrequent in patients with a 'touch' of the WPS, whereas up to 44% of the platelets from those with the WPS were gray or hypogranular. Elements of the dense tubular system were prominent in full WPS platelets, together with their formation into areas of cytoplasmic sequestration and autodigestion. These features were absent in 'touch' platelets. As commonly observed in full WPS platelets, mitochondria were larger and more numerous than alpha granules in some 'touch' cells. Both 'touch' and full WPS platelets frequently contained giant and rod-shaped granules. Dense bodies, however, were normal in size and number in 'touch' platelets, and half normal size in full WPS platelets. The separation of ultrastructural abnormalities in the two varieties of the WPS suggests that genetic defects involve more than a single gene and the genes are variable in their penetrance. Genetic studies to determine if this is the case are currently in progress.