Enrichment of IL-17A+ IFN-γ+ and IL-22+ IFN-γ+ T cell subsets is associated with reduction of NKp44+ ILC3s in the terminal ileum of Crohn's disease patients.

Crohn's disease (CD) is a chronic inflammatory condition of the human gastrointestinal tract whose aetiology remains largely unknown. Dysregulated adaptive immune responses and defective innate immunity both contribute to this process. In this study, we demonstrated that the interleukin (IL)-17A+ interferon (IFN)-γ+ and IL-22+ IFN-γ+ T cell subsets accumulated specifically in the inflamed terminal ileum of CD patients. These cells had higher expression of Ki-67 and were active cytokine producers. In addition, their proportions within both the IL-17A-producer and IL-22-producer populations were increased significantly. These data suggest that IL-17A+ IFN-γ+ and IL-22+ IFN-γ+ T cell subsets might represent the pathogenic T helper type 17 (Th17) population in the context of intestinal inflammation for CD patients. In the innate immunity compartment we detected a dramatic alteration of both phenotype and function of the intestinal innate lymphoid cells (ILCs), that play an important role in the maintenance of mucosal homeostasis. In the inflamed gut the frequency of the NKp44- CD117- ILC1s subset was increased significantly, while the frequency of NKp44+ ILC3s was reduced. Furthermore, the frequency of human leucocyte antigen D-related (HLA-DR)-expressing-NKp44+ ILC3s was also reduced significantly. Interestingly, the decrease in the NKp44+ ILC3s population was associated with an increase of pathogenic IL-17A+ IFN-γ+ and IL-22+ IFN-γ+ T cell subsets in the adaptive compartment. This might suggest a potential link between NKp44+ ILC3s and the IL-17A+ IFN-γ+ and IL-22+ IFN-γ+ T cell subsets in the terminal ileum of CD patients.

Zinc absorption in celiac disease and dermatitis herpetiformis: a test of small intestinal function.

The increments in plasma zinc concentrations after an oral dose of elemental zinc (50 mg) as the sulphate were used to assess the intestinal absorption of the metal in 11 patients with dermatitis herpetiformis (DH) before starting a gluten-free diet, 12 patients with newly diagnosed celiac disease (CD), 10 patients known to have CD, and 15 healthy volunteers. The areas under the plasma zinc increment curve plotted against time were determined for 3 (AUC3) and 6 (AUC6) h. The AUC3 in healthy volunteers was 401 +/- 48 mumol 1(-1) 3 h (mean +/- SD); it was reduced in newly diagnosed CD 187 +/- 76 mumol 1(-1) 3 h (p less than 0.001), and in dermatitis herpetiformis 206 +/- 87 mumol 1(-1) 3 h (p less than 0.01); but it was normal in the known CD 396 +/- 204 mumol 1(-1) 3 h, the wide variation reflecting the variable compliance with a previously instituted gluten-free diet. The AUC6 was similarly affected, healthy volunteers 700 +/- 111 mumol 1(-1) 6 h, new CD 380 +/- 169 mumol 1(-1) 6 h (p less than 0.01); dermatitis herpetiformis 471 +/- 107 mumol 1(-1) 6 h (p less than 0.01); known CD 725 +/- 380 mumol 1(-1) 6 h. The AUC3 was more consistently abnormal than conventional tests of small intestinal function. In a prospective study the AUC3 and AUC6 improved and reflected compliance with a gluten-free diet.

Fatal Salmonella septicaemia with disseminated intravascular coagulation and renal failure.

Four elderly patients with salmonella septicaemia complicated by irreversible endotoxic shock and acute renal failure are described. The organism isolated from three of the patients with Salmonella typhimurium, which is not usually invasive; the fourth patient was infected with S. abony. The factors associated with the severe systemic infections are discussed. Clinical and haematological findings suggested disseminated intravascular coagulation, and this was subsequently confirmed histologically in each patient by the identification of haematoxylinophil bodies in the pulmonary and renal microcirculations.

Allergic mastocytic gastroenteritis and colitis: an unexplained etiology in chronic abdominal pain and gastrointestinal dysmotility.

Abdominal pain, bloating, early satiety, and changes in bowel habits are common presenting symptoms in individuals with functional GI disorders. Emerging data suggests that these symptoms may be associated with mast cell excess and/or mast cell instability in the GI tract. The aim of this retrospective study was to evaluate the contribution of mast cells to the aforementioned symptoms in individuals with a history of atopic disease. A retrospective chart review of individuals seen in a university GI practice was conducted and twenty-four subjects were identified. The majority had abdominal pain, early satiety, and nocturnal awakening. 66.7% and 37.5% had a history of environmental and/or food allergy. Solid gastric emptying was increased as were the mean number of mast cells reported on biopsies from the stomach, small bowel, and colon (>37/hpf) by CD117 staining. Mean whole blood histamine levels were uniformly elevated. This study suggests that in individuals with these characteristics, consideration should be given to staining their gastrointestinal biopsies for mast cells as this may provide them with relatively non-toxic but highly targeted treatment options. Allergic gastroenteritis and colitis may represent a third type of GI mast cell disorder along with mast cell activation syndrome and mastocytic enterocolitis.

Experimental results for H2 formation from H- and H and implications for first star formation.

During the epoch of first star formation, molecular hydrogen (H2) generated via associative detachment (AD) of H- and H is believed to have been the main coolant of primordial gas for temperatures below 10(4) kelvin. The uncertainty in the cross section for this reaction has limited our understanding of protogalaxy formation during this epoch and of the characteristic masses and cooling times for the first stars. We report precise energy-resolved measurements of the AD reaction, made with the use of a specially constructed merged-beams apparatus. Our results agreed well with the most recent theoretically calculated cross section, which we then used in cosmological simulations to demonstrate how the reduced AD uncertainty improves constraints of the predicted masses for Population III stars.

A comparison of the structure and function of the terminal ileum in Crohn's disease using radiology, the "Dicopac" Schilling test and [14C] G.C.A. breath test.

Twenty patients with Crohn's disease were studied. Thirteen had radiological evidence of involvement of the terminal ileum. None had significant bacterial overgrowth of the small bowel contents and none had had resection of the terminal ileum. In all patients a [14C] glycocholic acid ([14C] G.C.A.) breath test and a "Dicopac" Schilling test were performed to assess terminal ileal function. The data showed poor correlation between the radiological appearance of the terminal ileum and the results of the functional tests. There was also poor correlation between the results of the [14C] G.C.A. breath test and the "Dicopac" Schilling test. Without terminal ileal histology, any assessment of the extent of Crohn's disease of the terminal ileum and of its effect on terminal ileal function, must include the [14C] G.C.A. breath test as well as radiology and the "Dicopac" Schilling test. The limitations of the [14C] G.C.A. breath test as a test of terminal ileal function in Crohn's disease are discussed.

Cholestasis in acute alcoholic liver disease.

10 of a series of 108 patients with alcoholic liver disease presented with cholestasis associated with non-cirrhotic alcoholic liver disease and without evidence of extrahepatic biliary obstruction. In 7 patients liver histology and the associated conditions presenting as cholestasis were heterogeneous. However, in 3 patients who had been drinking excessively before cholestatic jaundice developed, cholestasis was a major feature of liver histology. The term acute alcoholic cholestasis is suggested for this apparently distinct syndrome of cholestatic jaundice in the absence of hepatitis.

Oral tripotassium-dicitratobismuthate in gastric and duodenal ulceration. A double-blind controlled trial.

One hundred ambulant outpatients with active, endoscopically proven peptic ulceration entered a double-blind trial of either tripotassium-dicitratobismuthate or placebo. Thirty-four patients had gastric ulceration, 56 had duodenal ulceration, three had both gastric and duodenal ulcers, and two had stomal ulceration. Five patients with gastric ulceration were withdrawn from the trial. Three patients with both gastric and duodenal ulceration and two patients with stomal ulceration were excluded from statistical analysis. After 28 days of tripotassium-dicitratobismuthate 94% of gastric ulcer patients had significant endoscopic healing (P less than 0.01). Although 75% of duodenal ulcers healed after 28 days of tripotassium-dicitratobismuthate, this was not statistically significant because of a 60% rate of healing with placebo. Tripotassium-dicitratobismuthate produced a significantly quicker symptomatic response in duodenal ulcer patients (P less than 0.01). No serious side effects were recorded, and patient acceptability was high. It is concluded that tripotassium-dicitratobismuthate is an effective agent for promoting gastric ulcer healing and for symptomatic relief in duodenal ulceration.

Microbiologically proven bacterial infections in AIDS.

We have reviewed the incidence, type and site of microbiologically proven bacterial infection occurring in 52 patients with the acquired immunodeficiency syndrome (AIDS) who presented to Southmead Hospital, Bristol between 1990 and 1994. A total of 30 (58%) patients had significant bacterial isolates. The majority of infections were community acquired. Overall, more infections were caused by Gram-negative organisms but Gram-positive organisms predominated in bacteraemia. Mycobacterium avium intracellulare (MAI) caused infection in the largest number of patients, followed by Staphylococcus aureus, Streptococcus pneumoniae, Pseudomonas sp, and Campylobacter sp. When individual episodes of infection were considered, after MAI, Haemophilus influenzae, Streptococcus pneumoniae and Pseudomonas sp were the organisms most frequently isolated; often these same organisms caused recurrent chest infection. Bacterial infections in AIDS patients are common and although they generally respond well to antimicrobial chemotherapy there is a high recurrence rate, particularly in the respiratory tract, which is the commonest site of infection.

Acute osteomyelitis in a district general hospital.

A survey of the 58 patients with acute osteomyelitis seen in one general hospital between 1969 and 1979 has shown that, although the condition is less common now than in the pre-antibiotic era, it remains a serious disease. Bone pain and tenderness are still the commonest symptoms, but the source of the infection is less apparent now than it used to be, and this may lead to delay in diagnosis. The antecedent trauma experienced by nearly half the patients probably predisposes to infection by causing local bone damage and thus a focus for secondary infection. The pattern of infecting organisms has not changed much over the past 11 years, but Haemophilus influenzae must be considered in children aged under 5 years. Treatment was the use of antibiotics, with surgical drainage if necessary. The commonest antibiotic used was clindamycin, and chronic osteomyelitis did not develop in patients treated with this antibiotic, whereas all 9 patients who had chronic sequelae necessitating sequestrectomy had received cloxacillin either alone or in combination with another antibiotic.

An open study of ceftazidime in the treatment of serious bacterial infection.

Ceftazidime, a new parenteral cephalosporin, was given by intravenous bolus injection to 50 patients admitted to hospital with a variety of serious infections. These included septicaemia, bronchopulmonary, urinary, gastro-intestinal and soft tissue infections. The drug proved to be effective against a wide range of organisms, notably opportunistic Pseudomonas aeruginosa infections. In the 32 patients with positive cultures there was a cure rate of 85%. All Ps. aeruginosa infections were eradicated, but two relapsed post treatment in patients with recurrent urinary infections related to indwelling catheters. The drug was well tolerated and no serious side effects occurred. Two patients with salmonella septicaemia relapsed after an initial clinical response, and one of these died.

Propranolol in hypertension: a dose-response study.

The effect of propranolol was studied in a double-blind crossover trial in 24 carefully selected hypertensive outpatients. Each patient received propranolol 60 mg/day, 120 mg/day, 240 mg/day, and placebo for four weeks each according to a randomised sequence. Propranolol 60 mg/day was no better than placebo in reducing blood pressure. The effects of propranolol 120 mg/day and 240 mg/day were not significantly different. Both doses reduced lying blood pressure by about 20/10 mm Hg from an initial level of 173/104 mm Hg. No difference was detected between the effects of the different doses of propranolol and placebo on weight or on the occurrence of adverse reactions.