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Donor selection may contribute to improve clinical outcomes of T cell-replete haploidentical stem cell transplantation (Haplo-SCT) with post-transplant cyclophosphamide (PT-Cy). Impact of second-degree related donor (SRD) was not fully elucidated in this platform. We retrospectively compared the outcome of patients receiving Haplo-SCT either from a SRD (n= 31) or a first-degree related donor (FRD, n= 957). Median time to neutrophil and platelet recovery did not differ between a SRD and a FRD transplant (p= 0.599 and 0.587). Cumulative incidence of grade II–IV acute graft-versus host disease (GVHD) and moderate-severe chronic GVHD was 13% and 19% after SRD vs 24% (p= 0.126) and 13% (p= 0.395) after FRD transplant. One-year cumulative incidence of non-relapse mortality (NRM) was 19% for SRD and 20% for FRD (p= 0.435) cohort. The 3-year probability of overall survival (OS) and progression-free survival (PFS) was 42% vs 55% (p= 0.273) and 49% vs 35% (p= 0.280) after SRD and FRD transplant, respectively. After propensity score adjustment or matched pair analysis, the outcome of patients receiving Haplo-SCT from a SRD or a FRD did not differ in terms of NRM, OS, PFS, acute and chronic GVHD. Our results suggest that a SRD is a viable option for Haplo-SCT with PT-Cy when a FRD is not available.

Reduced intensity conditionings (RIC) before after allogeneic hematopoietic stem cell transplantation (HSCT) allow older or unfit patients of being transplanted, but survival expectancy and burden of late complications are poorly described in this setting. All patients (N= 456) who were alive and relapse-free 2 years after HSCT following RIC were included. Cumulative incidences (CI), standardized incidence, or mortality, ratio (SIR or SMR), and competing risk models were used. The 10-year CIs of relapse and non-relapse mortality incidences were 13.9 and 13.4%, respectively. Seventy-eight patients died, late relapse being the most frequent cause of death leading to a SMR of 6.38 (95% CI, 5.1–8.0; p< 0.001). Among non-relapsing patients (n= 412), 30 died (SMR 4.38; 95% CI, 3.3–5.8: p< 0.001). A total of 37 patients developed 41 SM leading to a 10-year cumulative incidence of 12.9%, and a significant SIR relative to the general population (1.4). Finally, we found high CI of cardiovascular (CVC) and venous thromboembolic complications (VTE) (10-year CI; 15.1% and 11.7%, respectively). Older age was the only significant risk factor for CVC and VTE in multivariable analysis. In conclusion, with life expectancy rate of 70%, late survivors after RIC warrants long-term follow-up and active intervention on averting cardiovascular disease and screening cancers.

ABSTRACTIntroductionEculizumab, the first anti-C5 monoclonal antibody approved for patients with paroxysmal nocturnal hemoglobinuria (PNH), has revolutionized the natural history of this disease, blocking intravascular hemolysis, reducing the risk of thromboembolic events, resulting in a significant improvement in survival and quality of life. However, the hematological response to eculizumab is extremely heterogeneous, with only one-third of PNH patients reaching normal hemoglobin levels.Areas coveredThis article reviews the current new drugs being investigated in phase II and III trials for adult PNH patients. Literature search was performed using Medline and Clinicaltrials.org databases.Expert opinionThe new molecules have been classified according to the target of the complement system on which they act; we have novel terminal complement inhibitors, which target C5, and proximal complement inhibitors, which interfere with C3 or even further upstream (factor B and D). Ravulizumab is the first next-generation C5 inhibitor, approved by FDA and EMA, which reproduced the excellent results achieved with eculizumab, trying to improve the convenience of patients. However, unresolved issues remain, such as C3-mediated extravascular hemolysis, on which novel proximal complement inhibitors are showing their efficacy. Pegcetacoplan is the first C3-inihibitor approved by FDA. Long-term safety data for novel complement inhibitors are needed.

Scleroderma, or systemic sclerosis (SSc), is an autoimmune disease in which the immune system inappropriately produces antibodies against the body's own molecules. SSc is characterized by excess collagen production, antibodies to collagen, and other abnormalities in immune function. (Collagen is a fibrous protein in skin, ligaments, cartilage, bone and connective tissue.) In the early stage of the disease, the skin and subcutaneous tissue are infiltrated by blood cells and lymphocytes (immunological cells that fight foreign and abnormal cells). SSc then proceeds to a fibrotic stage in which the production of antibodies to type I and type IV collagen is associated with diminished lung function. The reactivity of blood cells to human collagen type I was evaluated in blood specimens from 17 patients with SSc as a means of identifying the stage of the disease. Blood specimens from 16 healthy subjects and 13 patients with rheumatoid arthritis (RA) were also evaluated. Reactivity was measured by blood cell production of the regulatory protein interleukin-2 (IL-2). Blood cells from SSc patients produced about 8-fold as much IL-2 as those from healthy subjects and 3-fold as much as RA patients. The four highest values of IL-2 were obtained from patients with early-stage disease while the three lowest values were from those with late-stage disease. Testing with a nonspecific stimulus produced similar amounts of IL-2 from each group. Analysis showed that T lymphocytes with the protein CD4 (CD4+ T cells) on their surfaces were responsible for the IL-2 produced in response to collage type I. Measuring CD4+ T cell production of IL-2 in response to collagen should be useful in determining the stage of SSc and may lead to further understanding of the development of this disease. (Consumer Summary produced by Reliance Medical Information, Inc.)

The haematological benefit of standard-of-care anti-C5 treatment for haemolytic paroxysmal nocturnal haemoglobinuria is limited by residual intravascular haemolysis or emerging C3-mediated extravascular haemolysis. Therefore, the aim of this phase 2 study was to assess the safety, tolerability, pharmacokinetics and pharmacodynamics, and activity of the new complement factor B inhibitor, iptacopan, in patients with paroxysmal nocturnal haemoglobinuria who have active haemolysis despite anti-C5 therapy.

Steroid-refractory graft versus host disease (GVHD) represents a fearsome complication after allogeneic hematopoietic stem cell transplantation (HSCT). We conducted a retrospective study on outcomes and risk factors associated with acute and chronic steroid-refractory GVHD in a large cohort of 1207 patients receiving HSCT in Saint Louis Hospital between 2007 and 2017. Among patients who developed an acute and/or a chronic GVHD, the cumulative incidences of acute and chronic steroid-refractory disease were 31% and 48%, respectively, at day +100 and 1-year post-HSCT. Through a multivariable analysis we selected several risk factors associated with the development of a steroid-refractory disease. For acute GVHD steroid refractoriness, we identified (1) a very high disease risk index, (2) an unrelated donor, (3) the absence of in vivo T-depletion as GVHD prophylaxis, and (4) a reduced intensity conditioning regimen. For chronic GVHD, (1) the use of peripheral blood stem cells, (2) unrelated donors, and (3) absence of in vivo T-depletion were more likely associated with a steroid-refractory disease. After the construction of a multistate dynamic model, we found that the probability of being alive without relapse after the resolution of all GVHD episodes was about 36% in the long term.

Donor selection contributes to improve clinical outcomes of T-cell–replete haploidentical stem cell transplantation (haplo-SCT) with posttransplant cyclophosphamide (PT-Cy). The impact of donor age and other non-HLA donor characteristics remains a matter of debate. We performed a multicenter retrospective analysis on 990 haplo-SCTs with PT-Cy. By multivariable analysis, after adjusting for donor/recipient kinship, increasing donor age and peripheral blood stem cell graft were associated with a higher risk of grade 2 to 4 acute graft-versus-host-disease (aGVHD), whereas 2-year cumulative incidence of moderate-to-severe chronic GVHD was higher for transplants from female donors into male recipients and after myeloablative conditioning. Increasing donor age was associated with a trend for higher nonrelapse mortality (NRM) (hazard ratio [HR], 1.05; P = .057) but with a significant reduced risk of disease relapse (HR, 0.92; P = .001) and improved progression-free survival (PFS) (HR, 0.97; P = .036). Increasing recipient age was a predictor of worse overall survival (OS). Risk of relapse was higher (HR, 1.39; P < .001) in patients aged ≤40 years receiving a transplant from a parent as compared with a sibling. Moreover, OS and PFS were lower when the donor was the mother rather than the father. Pretransplant active disease status was an invariably independent predictor of worse clinical outcomes, while recipient positive cytomegalovirus serostatus and hematopoietic cell transplant comorbidity index >3 were associated with worse OS and PFS. Our results suggest that younger donors may reduce the incidence of aGVHD and NRM, though at higher risk of relapse. A parent donor, particularly the mother, is not recommended in recipients ≤40 years.

Persistent cytopenia due to poor graft function (PoGF) is a relatively common complication which may affect up to 20% of patients undergoing allogeneic hematopoietic stem cell transplantation (HSCT). Treatment options for PoGF remain limited, and reinfusion of additional HSC is often the only way to rescue hematopoiesis. Here we describe a retrospective single-center experience with the thrombopoietin-mimetic agent eltrombopag for the treatment of PoGF. Thirteen patients have received eltrombopag for either PoGF (n= 12) or primary graft failure (n= 1). In the 12 PoGF patients eltrombopag was started at the median time of 79 days after HSCT, due to persistent thrombocytopenia, with concomitant anemia and neutropenia in 7 and 3 patients, respectively. The treatment was started at the dose of 50 mg per day, and eventually increased up to 150 mg in case of lack of response. Hematological response was seen in 7 patients, with 6 complete responses. Hematological responses were seen both in patients with evidence of immune-mediated pathophysiology, and with possible infectious/iatrogenic causes. In responding patients, eltrombopag was discontinued in 6/7 patients without further relapse. These results suggest that eltrombopag is safe and possibly effective in the setting of the treatment of PoGF, and pave the way for future prospective studies.

Drs Roeth and Kulasekararaj contributed equally as authors.

Background Celiac disease (CD) often manifests with dyspeptic symptoms and chronic gastritis is a common finding.Aim To evaluate the frequency of lymphocytic gastritis (LG), chronic active gastritis (CAG), and chronic inactive gastritis (CIG) in patients with CD, before and after gluten-free diet (GFD).Methods A five-year prospective study including all consecutive patients with a new diagnosis of CD was conducted. Gastric and duodenal biopsy specimens taken both at the time of the CD diagnosis and at the first endoscopic control after 18–24 months on GFD were evaluated.Results 213 patients with CD were enrolled. At the time of the diagnosis, 42 patients (19.7%) showed normal gastric mucosa, 34 (15.9%) LG, 67 (31.5%) CAG, and 70 (32.9%) CIG. Out of the 34 patients with LG, all were Helicobacter pylorinegative and the majority of them showed an improvement both of gastritis (94.1%) and duodenal lesions (82.3%) after GFD. GFD did not show significant effects on CAG and CIG.Conclusions LG is present in 16% of CD patients, it is not associated with H. pyloriinfection, and it improves after GFD. Both CAG and CIG are also frequently associated with CD, but fail to respond to a GFD.

Legionnaires disease (LD) is caused by a gram-negative aerobic bacterium, Legionella pneumophila, which is an important cause of both community-acquired and nosocomial pneumonia. Although an uncommon pathogen, L. pneumophilais associated with significant morbidity and mortality if left untreated. The clinical manifestations surrounding LD are often unreliable for diagnosis, underlining the importance of the urinary antigen test and cultures of the lower respiratory tract. As a primarily intracellular atypical organism, treatment modalities aimed at penetrating the bacterial cell wall are preferred and include the use of fluoroquinolones and macrolides. Several studies have attempted to determine the treatment of choice for L. pneumophila; however, no current algorithm exists. Prevention of LD is aimed at proper maintenance of building cooling towers, plumbing design, and construction, in addition to chemoprophylaxis in a subgroup of immunocompromised patients. In this review we outline the clinical manifestations with subsequent diagnosis, summarize the available diagnostic tools for LD, and evaluate the current literature regarding treatment and management.

Alcohol, in addition to well-known damages on the liver and pancreas, produces direct and indirect injuries in the mucosa of the oesophagus, stomach, small intestine and large bowel. Different damages can be produced both when a large amount of alcohol is acutely drunk and when this is taken chronically. Almost all these lesions can be detected and treated by endoscopy as shown in the present article. When, over time, cirrhosis ensues the role of endoscopy is not different from that played with cirrhosis of different etiology. Beside hemorrhagic episodes, esophagitis, gastritis and cancer are the main alcohol related diseases that can be managed by endoscopy.

The purpose of this review paper is to discuss many areas related to wounds, photobiomodulation, reactive oxygen species, biofilms, neutrophils in wounds, other cells and growth factors in wounds, T cells in wounds, additional role of stem cell in wounds, mast cells in wounds, trauma and injury, surgical management, burns, trauma and injury, cytokines and trauma.

To review the complex interactions and processes in systemic lupus erythematosus (SLE).

Pharmacological treatments of first episode schizophrenia are of particular relevance because most clinical and psychosocial deterioration with cognitive decline and changes in brain volume occurs in the first five years of disease onset. Although the efficacy of antipsychotic maintenance treatment has been demonstrated to reduce risk of relapse, nonadherence is common even in first episode schizophrenia patients. Antipsychotic long-acting injections (LAIs) could be an option in early treatment although international guidelines recommend their use in patients who have already experienced significant non-adherence and who have repeated relapse. At the present time there is some concern about the acceptability of LAIs in first episode schizophrenia: some studies suggest that LAI treatment is feasible in these patients because of distinct advantages in terms of better treatment adherence. In the present review, we analyze the few currently studies published on the use of risperidone long-acting injection (RLAI) to improve adherence in first episode schizophrenia. Further research is needed to support the routine use of LAIs and of the other second generation antipsychotic LAIs (olanzapine long-acting and paliperidone palmitato) in this population of patients to improve adherence.

Background There is a link with the upper and lower airway and disruption of alveolar epithelial cells, which is a potential trigger for the reactivation of the epithelial-mesenchymal trophic unit (EMTU) and induced characteristic airway changes associated with allergic asthma. Dermatophagoides pteronyssinus is a common inhalant indoor allergen and is known for causing allergic rhinitis and airway inflammation. Transforming growth factor beta 1 (TGF-beta1) is a major participant in the airway remodeling of asthma, a component of cellular stress response pathways, and enhanced epithelial immunoreactivity is known to occur in allergic rhinitis.Methods In this study, we show the ability of D. pteronyssinus allergens from dialyzed standardized immunotherapy extract to induce apoptosis and increase TGF-beta1 secretion in a confluent A549 cell line model. A549 cells were treated with either 600 AU/mL dialyzed D. pteronyssinus immunotherapy extract (eDp) or Ctl media (Ctl) for 24 hours. Cells and supernatants were collected, washed, and treated with Annexin V-FITC Apoptosis Detection Kit II (BD Pharmingen, La Jolla, CA) and then analyzed by flow cytometry. TGF-beta1 secretion was determined by ELISA using cell culture supernatants.Results The eDp group showed a fourfold increase in early apoptotic cells with a twofold increase in late apoptotic cells versus the Ctl group, along with a 1.65-fold increase of TGF-beta1.Conclusion eDp induced viable A549 cells to undergo apoptosis determined by flow cytometry analysis with a significant increase in TGF-beta1 secretion compared with Ctl.

Crying is a common complaint in infants. However, crying with bloody tears or hemolacria is an unusual finding in a pediatric emergency department. There are not many conditions that can present with bloody tears. Subconjunctival hemorrhage and hematomas are known to occur with acute Epstein Barr viral infections, accidental trauma, factor deficiencies, tumors such as malignant melanoma, Rendu-Osler-Weber disease, and idiopathic thrombocytopenic purpura. There are also unknown causes. We report an infant with immune thrombocytopenic purpura presented to the pediatric emergency department with bloody tears, who responded well to intravenous gamma globulin therapy. The presence of bloody tears should be carefully investigated as it may represent significant systemic illness, especially with a strong family history of this autoimmune condition.

Many patients with asthma have an IgE-mediated allergic component to the disease. Omalizumab, a monoclonal anti-IgE antibody, has demonstrated clinical efficacy in patients with allergic asthma. The effects of omalizumab on inflammation in asthma are not completely understood.

Chronic severe persistent asthma is associated with damaged epithelial cells with discontinuous tight junctions that contribute to dysregulated fibroblast and endothelial cell (mesenchymal) growth. Dermatophagoidesspecies-derived proteases have been shown to cause damage to epithelial cell tight junctions.

Background: Contributing factors in bronchopulmonary dysplasia (BPD) in neonatal infants includes inflammation and oxygen radicals. Nitric oxide (NO - 2), an important mediator of inflammation can lead to cell injury or induce proinflammatory cytokines. Glucocorticoids are known to decrease the transcription of inducible NO synthetase. Objective: To investigate if there are altered serum (NO 2) nitrite, a products of NO metabolism levels in very low birth weight infants with BPD and respiratory distress syndrome (RDS) as compared to healthy newborns before and after dexamethasone treatment. Methods: We clinically evaluated neonatal infants and obtained samples from 31 infants diagnosed with BPD (N15), RDS (N=6), prematurity without respiratory distress syndrome (N6), and full term (FT) neonates (N4). Levels of nitrite were measured using the Greiss Reagent, and absorbance was determined at 550nm. Results: The highest levels of NO- 2 were obtained in the BPD patients (9-253 M), mean 110 M, with low APGAR scores at 1 minute from 0 to 5. RDS patients with low APGAR scores at 1 minute from 5 to 7, also had high levels (8-93 M), mean54 M and patients with prematurity with normal APGAR scores at 1 minute from 6 to 9 had relatively low NO- 2 levels (29-76 M), mean 41mM. Dexamethasone treatment (0.5 mg/kg/d) of 12 hrs. for 3-8 days) in premature infants with low APGAR scores dramatically decreased from 85-253 M to 10-146M (p<0.05). In 2 of the severe BPD a rise in NO levels after dexamethasone correlated with severe systemic infection. NO - 2 levels in FT patients (21 - 37M), (mean30 M). Control serum samples from 16 infants randomly selected had NO levels of (8-53 M), mean 28 M). Supported by a fellow-in-training grant and Von Pirquet Awardsd from ACAAI.

Both IgE and non-IgE cell-mediated reactions can contribute to the immunopathogenesis of food hypersensitivity.

To review concepts of neuroendocrinoimmunology and provide an overview of the role of immune dysregulation, stress, and the understanding of the pathogenesis and treatment of allergic and autoimmune diseases.

Data about colonic mucosa transport of short-chain fatty acids in cirrhotic patients are still lacking. The aim of the present study was to compare the rectal mucosa transport of n-butyrate and its effect on transport of other electrolytes and endoluminal pH in normal subjects and in cirrhotic patients by using a rectal dialysis technique. Thirteen subjects with normal hepatic function tests and 17 cirrhotic patients were enrolled. Dialysis bags containing 80 mmol/liter of butyrate in a neutral pH (6.8) electrolyte solution were placed in the rectum of enrolled subjects for 60 min. Net transport rate was calculated for butyrate, sodium, chloride, potassium, and bicarbonate. The differences in pH between initial and final dialysis solutions was also evaluated in the two groups in the study. Net butyrate absorption was significantly lower in cirrhotic patients than in controls (65.2 ± 38.6 vs 101.2 ± 45.3 nmol/min/cm2, respectively; P = 0.02). Furthermore, cirrhotic patients showed a lower HCO3secretion than controls (−26.9 ± 19.9 vs −45.1 ± 20.0, respectively; P = 0.01). No differences were found in transport of the other electrolytes. The pH in the final dialysis solution in cirrhotic patients was not significantly lower than in the controls (7.15 vs 7.35; P = 0.1). In conclusion, the impairment of butyrate absorption and the concurrent reduction of bicarbonate secretion observed in cirrhotic patients may suggest a selective hypoactivity of apical HCO3−/SCFA−antiport located at the colonocyte apical membrane.

Butyrate represents the main source of energy for colonic epithelial cells; however, its availabilty/utilization is impaired in ulcerative colitis (UC). In the present randomized, double-blind, placebo-controlled pilot study, the safety and efficacy of colonic targeted oral sodium butyrate tablets, coated with a pH-dependent soluble polymer, have been evaluated in ulcerative colitis. Thirty patients with mild to moderate colitis underwent a six-week course of oral sodium butyrate (4 g/day) plus oral mesalazine (2.4 g/day), (Group A) or of oral mesalazine plus placebo (Group B). Clinical, endoscopic, and histologic data were collected at the beginning and the end of the study. Twenty-five patients completed the study (12 in group A, 13 in group B). No untoward side effects were reported. In group A, seven patients underwent remission and four improved; in Group B the numbers were 5 and 5, respectively. After treatment, all clinical parameters had significantly improved in both treatment arms compared to pretreatment findings. The UC disease activity index (UCDAI) score decreased from 7.27 ± 2.02 to 2.58 ± 2.19 (P< 0.05) in the combined treatment group and from 6.07 ± 1.60 to 3.46 ± 1.98 (P< 0.05) in group B. The endoscopic and histologic scores also significantly improved after treatment in both groups (P< 0.05). The difference between the two treatment arms was not significant, but a significantly better improvement vs baseline values (P< 0.05) was observed in the combined treatment group vs the mesalazine group, when considering both the clinical index (Δ9.58 ± 4.19 vs 5.92 ± 3.48) and the UCDAI score (Δ4.67 ± 2.19 vs 2.54 ± 2.18). A more favorable trend, although not significant, was observed for all individual parameters in group A. In conclusion, results of the present pilot study indicate that oral butyrate is safe and well tolerated. These data also suggest that oral butyrate may improve the efficacy of oral mesalazine in active ulcerative colitis and prompt the need of a large scale investigation to confirm the present findings.

Aim of this study was to assess the structural,ultrastructural, immunohistochemical, and clinicalaspects in Sprague-Dawley rats with dextrane sulfatesodium (DSS)-induced colitis. Colitis was induced in Sprague-Dawley rats by seven days of DSSoral administration followed by seven days of tap wateronly (for one, two and three cycles). Controls were fedwith water only. Segments of proximal, mid-, and distal colon of each animal were adequatelyprepared for light and scanning electron microscopeobservations. The severity of the lesions was scoredhistologically. For immunohistochemical study, acocktail of S-100, NSE, and antineurofilament antibodieswas used. Symptoms such as weight, feces consistency,diarrhea, hematochezia were recorded daily. From aclinical point of view symptoms appeared significantly later after the first cycle than after thesecond and third cycles and lasted significantly longerin the second and third cycles. Treated rats showed aslower weight gain rate by 20% compared to controls, and the whole colon length appeared to besignificantly shorter after colitis induction comparedto controls. Structural observations by light microscopyshowed prominent involvement of the distal colon. Immunohistochemical study of both submucosaland myoenteric nerve plexuses was similar to controls.Scanning electron microscope observations of the colonicmucosal surface in colitis rats showed a complete subversion of its architecture, characterizedby dilatations of gland crypt openings, dropout ofgoblet cells, and inhomogeneous distribution or lack ofmicrovilli. These were most evident after the third cycle. In conclusion, experimental DSS colitisin SD rats appeared to be highly reproducible and sharedmost features with human UC, not only from a structuraland clinical but also from an ultrastructural point of view.

In multiple myeloma (MM) an increase in circulating lymphocytes expressing plasma cell-associated antigens (PCAA) has been described. Its prognostic significance was evaluated in this study. The immunologic phenotype of peripheral blood lymphocytes was analyzed with a panel of monoclonal antibodies specific for B, T, natural killer lymphocytes, and PCAA (CD38, PCA1) in 52 MM patients at diagnosis, remission, and during relapse, 18 monoclonal gammopathy of undetermined significance (MGUS), and 25 normal controls. No significant phenotypic alteration was observed in MGUS. In MM, the number of B lymphocytes was in the normal range at diagnosis and during the subsequent phases. A CD4/CD8 ratio decrease, during relapse, was due to both a CD4+ reduction and to an expansion of a subset of CD8+ activated suppressor lymphocytes. CD38+ and PCA1+ lymphocytes at diagnosis were significantly higher than in MGUS, and a further increase was observed during relapse, suggesting a correlation between PCAA expression and disease activity. The prognostic significance of increased PCAA was confirmed by a survival analysis of 32 patients evaluated at diagnosis using a CD38 cutoff of 0.45 x 10(9)/L positive lymphocytes. Median survival for patients with high values was only 14 months, whereas it was not reached at 32 months by those with low values (P less than .0007).

Both antihistamines and cromolyn sodium have been suggested for the treatment of systemic mastocytosis. To determine If one drug regimen was superior to the other, eight patients with systemic mastocytosis were admitted to a double-blind, double-crossover study in which the therapeutic efficacy of cromolyn sodium was compared with that of a combination of chlorpheniramine and cimetidine. Response to therapy was assessed by the patients using symptom scores and by the attending physicians during clinic examinations in addition to sequential plasma and urinary histamine determinations. in the six patients who completed the trial, the patient symptom scores and the physician evaluations indicated that there was no advantage of one drug regimen over the other. Plasma and urinary histamine levels, markedly elevated in most of the patients, were not consistently altered by administration of either cromolyn sodium or the combined antihistamines. Thus, cromolyn sodium and the combined antihistamines were indistinguishable when used for the symptomatic treatment of systemic mastocytosis, and neither regimen altered systemic histamine levels.

Allergic rhinitis is an IgE-mediated inflammatory reaction characterized by an early “classic” immediate hypersensitivity response and/or a subsequent late phase response. Nasal provocation to antigen challenge is a useful method of evaluating this dual response. Several H1antagonists may exhibit antiinflammatory properties by diminishing histamine release or inhibiting eosinophil chemotaxis. To determine whether astemizole has any anti-inflammatory characteristics, we studied 20 patients with allergic rhinitis in a double-blind placebo-controlled fashion after a 4-week course of treatment with this H1antagonist. Nasal provocation over 30 minutes was performed out of season using increasing concentrations of grass or ragweed extract from 10–1000 PNU. Patients were evaluated for their clinical response, and nasal lavage secretions were analyzed over 6 hours by ELISA for alpha interleukin-1, interleukin-8, albumin, and histamine levels. Total sneezing and other symptom scores for rhinorrhea, nasal congestion, and pruritus were decreased in astemizole-treated compared to placebo-treated patients both at 30 minutes (early phase), and at 3 and 6 hours (late phase) after nasal provocation. However, these results did not reach statistical significance. Nasal α IL-1 levels diminished from diluent control lavage to a significantly greater degree in astemizole than in placebo-treated patients (P < 0.05). This diminution in late phase α IL-1 suggests that astemizole may possess anti-inflammatory properties.

Nitric oxide (NO), a reactive free radical synthesized from L-arginine by the enzyme NO synthase (NOS), may play a role in many pathophysiologic conditions, including asthma.

Mometasone furoate is a potent glucocorticoid that can markedly inhibit proinflammatory Th2cytokines in vitro. An aqueous nasal spray formulation has been shown to be clinically active in reducing the symptoms of perennial and seasonal allergic rhinitis.

Leukotriene B4(LTB4), a potent chemokinetic mediator for neutrophils, is enhanced by interleukin-8 (IL-8) and may play a key role in the inflammatory response of asthma.

Ulcerative colitis (UC) is associated with lowintracolonic pH and unbalanced transmucosal ionicexchanges. Along the gastrointestinal tract carbonicanhydrase isoenzyme I (CA-I) is specifically expressed in colon epithelium and is involved in mucosalcontrol of ion, fluid, and acid- base balance. Sincealtered CA-I expression may play some role in UC, CA-Iwas measured at the mRNA and protein level and carbonic anhydrase (CA) enzyme activity wasdetermined in colon biopsies of 14 UC patients (6remission, 4 mild, 4 moderate UC) and of 12 healthysubjects. Patients with mild or moderate UC showed asignificant reduction of CA-I mRNA and protein and of totalCA activity in the inflamed mucosa compared to controls.Patients with UC in remission showed a pattern of CA-Iexpression and CA activity similar to controls. This is the first report showing a reduction inthe expression of CA-I in active UC.

A 45-year-old man with an eight-year history of ulcerative colitis was evaluated for severe, nonbloody diarrhea. Symptoms, which began two years earlier, were characterized by 15 bowel movements per day, accompanied by urgency and incontinence. A reduced rectal compliance was measured at manometry. All conventional treatments were not able to modify the symptoms despite improvement of inflammatory colonic lesions. PURPOSE: The aim was to reduce bowel movements and incontinence by increasing rectal compliance. METHODS: Gradual pneumatic dilations of the rectum were performed three times per week for three weeks. RESULTS: The patient's diarrhea improved dramatically, decreasing in frequency from approximately 15 to only 3 bowel movements per day, while contemporaneously increasing rectal compliance. Such effect, still evident 15 months after discontinuation of dilation, was probably obtained by improvement of viscoelastic features of the intestinal wall. CONCLUSIONS: Rectal pneumatic dilation may be a successful attempt in some forms of intractable diarrhea in long-lasting ulcerative colitis.

Osteoporosis affects 40% of white women older than 45 years of age and 15% of white men older than 50 years of age, resulting in approximately 1.5 million annual fractures in the United States. Systemic corticosteroid therapy increases the probability of osteoporosis, even with alternate-day dosing and with dosages sufficiently low so as not to affect the hypothalamic-pituitary-adrenal axis. Inhaled corticosteroid therapy may affect bone density if high-dose therapy is given to select individuals. The potential of increasing osteoporosis with inhaled corticosteroid asthma therapy is a concern because of the availability of more potent inhaled corticosteroid agents and recommendations that inhaled corticosteroid therapy be initiated earlier in the course of asthma. This article provides suggestions, on the basis of the medical literature and consensus of the authors when specific information was not available, for assessing and treating osteoporosis in subjects with asthma. Suggested risk categories are “low risk” (inhaled corticosteroid dosage of ≤800 μg of beclomethasone dipropionate [BDP]/day in adults or ≤400 μg BDP or equivalent in children), “moderate risk” (inhaled BDP 800 μg/day in adults or 400 μg/day in children), and “high risk” (systemic corticosteroid therapy 4 times a year or daily or alternate-day systemic corticosteroid therapy). Dosage of nasal corticosteroid probably should be added to the orally inhaled corticosteroid for total burden of inhaled corticosteroid. Potential treatment strategies based on risk factors and bone density if indicated are offered to assist physicians treating patients with asthma. (J Allergy Clin Immunol 1998;102:353-62.)

T-lymphocyte subpopulations were evaluated longitudinally in 62 primigravidas. Beginning early in the second trimester, women who later developed preeclampsia showed a significantly lower proportion of T-helper cells compared with those who remained normotensive (27.0 ± 7.1 versus 34.7 ± 7.9; P<.001). The decrease in the T-helper cell count occurred several weeks before the development of preeclampsia and reverted to normal 6-10 weeks postpartum. (Obstet Gynecol 77859, 1991)

A retrospective analysis of data from a series of 22 patients with toxic megacolon complicating ulcerative colitis was performed in an attempt to detect factors associated with the fatal outcome of the attack. Of the 25 clinical findings studied, significant differences between survivors (17) and nonsurvivors (5) were observed in only seven. In nonsurvivors, duration of the disease was longer and blood pH and standard bicarbonate levels higher, whereas serum potassium, calcium, phosphorus, and ß-globulins were lower. Discriminant analysis showed that three pairs of features, namely potassium-ß-globulins, potassium-bicarbonate, and potassium-blood pH provided a good discrimination between survivors and nonsurvivors. Results of this study indicate that the severity of the electrolyte and metabolic disorder appears to be an important risk factor in toxic megacolon. Intensive fluid and electrolyte replacement should therefore be considered a crucial point for successful management of toxic megacolon.