Nursing and nursing education in Iraq: challenges and opportunities.

BACKGROUND: There has been extensive damage to nursing education and training in Iraq over the last two decades through three international wars, counterinsurgency struggles in the north and south, 13 years of economic sanctions, dictatorship and foreign occupation. Fortunately, there is wide agreement that nursing is a key area for further attention. Many nursing leaders have emigrated and the numbers of nurses working in professional roles in Iraq declined sharply after 1990. ISSUES: The number of nurses per population has always been low in Iraq, and fell off precipitously after foreign workers left. There is less than one nursing staff of any kind for physician today. Few of the nursing staff are qualified to what would be minimal standards of professional practice in many countries. There is a strong educational base for nursing education in three Iraqi universities, but it relates little to other schools or hospitals. Military nurses, now being integrated into the public system of hospital care, are considered to have far more technical skill levels than non-military nurses. ACTIONS: Iraq needs a new generation of well trained nurses to develop primary care and health education activities. Programmes in nursing administration and community health nursing need to be developed. The World Health Organization has supported the development of training centres and short courses for nursing leaders. The former six levels of entry to nursing practice have been streamlined to three. Nursing salaries since the 2003 invasion have been greatly increased. These are good beginnings, and much more remains to be done to restore nursing in Iraq.

Relationship of anti-Lewis x and anti-Lewis y antibodies in serum samples from gastric cancer and chronic gastritis patients to Helicobacter pylori-mediated autoimmunity.

Lewis (Le) antigens have been implicated in the pathogenesis of atrophic gastritis and gastric cancer in the setting of Helicobacter pylori infection, and H. pylori-induced anti-Le antibodies have been described that cross-react with the gastric mucosa of both mice and humans. The aim of this study was to examine the presence of anti-Le antibodies in patients with H. pylori infection and gastric cancer and to examine the relationships between anti-Le antibody production, bacterial Le expression, gastric histopathology, and host Le erythrocyte phenotype. Anti-Le antibody production and H. pylori Le expression were determined by enzyme-linked immunosorbent assay, erythrocyte Le phenotype was examined by agglutination assays, and histology was scored blindly. Significant levels of anti-Le(x) antibody (P < 0.0001, T = 76.4, DF = 5) and anti-Le(y) antibody (P < 0.0001, T = 73.05, DF = 5) were found in the sera of patients with gastric cancer and other H. pylori-associated pathology compared with H. pylori-negative controls. Following incubation of patient sera with synthetic Le glycoconjugates, anti-Le(x) and -Le(y) autoantibody binding was abolished. The degree of the anti-Le(x) and -Le(y) antibody response was unrelated to the host Le phenotype but was significantly associated with the bacterial expression of Le(x) (r = 0.863, r(2) = 0.745, P < 0.0001) and Le(y) (r = 0.796, r(2) = 0.634, P < 0.0001), respectively. Collectively, these data suggest that anti-Le antibodies are present in most patients with H. pylori infection, including those with gastric cancer, that variability exists in the strength of the anti-Le response, and that this response is independent of the host Le phenotype but related to the bacterial Le phenotype.

Relationship of blood group determinants on Helicobacter pylori lipopolysaccharide with host lewis phenotype and inflammatory response.

As Lewis a (Le(a)) and Lewis b (Le(b)) blood group antigens are isoforms of Lewis x (Le(x)) and Lewis y (Le(y)) and are expressed in the gastric mucosa, we evaluated whether the patterns of expression of Le(x) and Le(y) on Helicobacter pylori lipopolysaccharides reflected those of host expression of Le(a) and Le(b). When 79 patients (secretors and nonsecretors) were examined for concordance between bacterial and host Le expression, no association was found (chi(2) = 5.734, 3 df, P = 0.125), nor was there a significant difference between the amount of Le(x) or Le(y) expressed on isolates from ulcer and chronic gastritis patients (P > 0.05). Also, the effect of host and bacterial expression of Le antigens on bacterial colonization and the observed inflammatory response was assessed. In ulcer patients, Le(x) expression was significantly related to neutrophil infiltration (r(s) = 0.481, P = 0.024), whereas in chronic gastritis patients significant relationships were found between Le(x) expression and H. pylori colonization density (r(s) = 0.296, P = 0.03), neutrophil infiltrate (r(s) = 0.409, P = 0. 001), and lymphocyte infiltrate (r(s) = 0.389, P = 0.002). Furthermore, bacterial Le(y) expression was related to neutrophil (r(s) = 0.271, P = 0.033) and lymphocyte (r(s) = 0.277, P = 0.029) infiltrates. Thus, although no evidence of concordance was found between bacterial and host expression of Le determinants, these antigens may be crucial for bacterial colonization, and the ensuing inflammatory response appears, at least in part, to be influenced by Le antigens.

Salivary SIgA and SIgA 1 in coeliac disease, inflammatory bowel disease and controls.

Levels of secretory IgA1 (SIgA1) in the saliva have not been measured previously in either coeliac disease (CD) or inflammatory bowel disease (IBD). Saliva was collected from coeliacs, IBD patients and controls. The concentration of total SIgA in saliva was measured by enzyme linked immunosorbent assay (ELISA) with an anti-human SIgA antibody as the bound phase and human SIgA isolated from colostrum as the standard. The concentration of SIgA1 was determined using an ELISA with a lectin with a high affinity for human SIgA1. The IBD patients have a significantly higher concentration of SIgA1 than the controls. The rate of secretion of saliva and %SIgA1 was significantly lower in coeliacs than in the control and IBD groups. The rate of secretion of SIgA1 was significantly higher in the IBD than in the coeliacs. We describe hitherto unreported levels of SIgA1 in CD and IBD.

Lymphocytic gastritis and coeliac disease: evidence of a positive association.

AIMS: To investigate the prevalence of lymphocytic gastritis in patients with coeliac disease. METHODS: Gastric biopsies from 70 patients with coeliac disease were examined by light microscopy for the presence of lymphocytic gastritis, defined as 25 or more intraepithelial lymphocytes/100 gastric columnar epithelial cells. RESULTS: Lymphocytic gastritis was found in seven cases. Positive cases had a mean of 32.1 intraepithelial lymphocytes/100 columnar cells, compared with a mean of 13.9 in negative cases, and 5.15 in noncoeliac controls. No differences were found for age, sex, gastric corpus or antrum, or degree of inflammation in the gastric lamina propria. All intraepithelial lymphocytes were of T cell lineage. Cases not showing lymphocytic gastritis did however show significantly increased gastric intraepithelial lymphocytes compared with non-coeliac controls. Eighteen of 70 cases were positive for Helicobacter pylori, and four of seven cases of lymphocytic gastritis were H pylori positive; no significant difference was observed between H pylori positive and negative patients. Three cases had concomitant ulcerative enteritis, of which none showed lymphocytic gastritis, while five cases had concomitant enteropathy associated T cell lymphoma, of which one showed lymphocytic gastritis. CONCLUSIONS: Lymphocytic gastritis occurred in 10% of patients with coeliac disease. Cases without lymphocytic gastritis nevertheless showed increased gastric intraepithelial lymphocytes. Coeliac disease may on occasion be a diffuse lymphocytic enteropathy occurring in response to gluten. Lymphocytic gastritis outside coeliac disease may involve an immune response to luminal antigens, such as H pylori, not unlike the response to gluten in patients with coeliac disease.

Activated protein C resistance, thrombophilia, and inflammatory bowel disease.

Thromboembolic events frequently complicate the clinical course of patients with inflammatory bowel disease (IBD). Hereditary thrombophilia may contribute to this tendency. Resistance to activated protein C is the most recently described thrombophilic state and may account for up to 40% of patients with thrombophilia. Thirty-seven patients with IBD were studied (mean age 44 years, range 18-82 years). Three patients had a history of thrombotic episodes. The 37 controls included 23 men and 17 women (mean age 48 years, range 16-89 years). Disease activity was assessed using the Harvey Bradshaw index for patients with Crohn's disease and the Truelove and Witts grading system for patients with ulcerative colitis. Levels of fibrinogen, antithrombin III (ATIII), protein C, protein S, activated protein C resistance (APCR), and the presence of a lupus anticoagulant (LA) were determined. Median ATIII levels in patients with IBD were significantly lower than controls (98% vs 106%, P = 0.007), while fibrinogen was elevated (4.2 vs 3.3 g/liter, P = 0.026) despite quiescent disease activity. LA was detected in 7/37 patients in the IBD group compared to 0/37 controls. (chi2 = 5.68, P = 0.017). No significant difference was observed in levels of inherited thrombophilic factors and in particular APCR between IBD patients and controls. In conclusion, the presence of inherited thrombophilic defects, in particular APCR, is uncommon in patients with IBD and does not merit routine screening.

Effect of host Lewis and ABO blood group antigen expression on Helicobacter pylori colonisation density and the consequent inflammatory response.

The Lewis(b) blood group antigen has been implicated as a putative receptor for Helicobacter pylori in the gastric mucosa. Furthermore, an increased prevalence of duodenal ulcer was found in non-secretors and it has been suggested that secretor status may influence bacterial colonisation density. Other investigators have hypothesised that severity of antral gastritis may be related to colonisation density of the bacterium alone, and that a critical bacterial load is necessary for the development of duodenal ulcer. Our objectives were to investigate whether a relationship existed between host Lewis and ABO blood group phenotype and prevalence of H. pylori infection. In addition we investigated whether bacterial colonisation density and the ensuing inflammatory response was influenced by secretor status and ABO blood group phenotype. The Lewis and ABO blood group phenotype of 207 patients undergoing upper endoscopy was determined. Of these, 136 were secretors and 62 were nonsecretors. Forty-five percent of patients were infected with H. pylori. No significant association was found between H. pylori infection and expression of Lewis(a) or Lewis(b) blood group antigen. The mean histological density of H. pylori was 1.8 +/- 0.2 among non-secretors and 1.51 +/- 0.13 among secretors (P = 0.209), with a mean grade of lymphocytic infiltration significantly greater in H. pylori-infected non-secretors (2.23 +/- 0.123 vs 1.8 +/- 0.074; P = 0.003). In addition, blood group O non-secretors had a significantly higher grade of lymphocyte infiltration of their gastric mucosa compared to non-O non-secretors (2.53 +/- 0.133 vs 1.93 +/- 0.181, P = 0.027). These results suggest that although no in vivo relationship exists between H. pylori and preferential adhesion to the putative Lewis(b) receptor, bacterial colonisation and the ensuing inflammatory response may be influenced at least in part by host expression of ABO and Lewisa blood group antigens.

Evaluation of a 20 minute 14C urea breath test for the diagnosis of Helicobacter pylori infection.

The use of 14C-urea breath testing for diagnosis of Helicobacter pylori infection in gastric mucosa has gained widespread acceptance and utilisation. We evaluated a 14C urea breath test (UBT) in 116 patients undergoing endoscopy. Seventy four patients were administered 185 kBq (5 mCi-conventional dose), and 42 patients reduced dose (92.5 IBq, 2.5 mCi) of 14C-urea. All were tested for H. pylori using culture, direct microscopy of gastric biopsies and histological evaluation of paraffin stained sections. Using the mean + three standard deviations as the cut-off value, a sensitivity of 96% and specificity of 100% was found for the conventional dose test. At reduced dose, sensitivity was 100% and specificity 96%. Positive and negative predictive values were 100% and 93% for the conventional dose test, and 96% and 100% for testing at reduced dose. We conclude that the UBT is a simple, non-invasive and useful diagnostic alternative for detection of H. pylori in infected patients. We advocate its use in patients less than 45 years of age without alarm symptoms, and also in cases where the need for endoscopic evaluation is not vital, such as after eradication therapy.

Celiac sprue and immunodeficiency states: a 25-year review.

Immunoglobulin deficiency, especially deficiency of IgA, has been described in patients with celiac sprue (CS). Our study was performed in an area of high prevalence of CS to determine the prevalence of immunodeficiency states in patients with CS, to examine their clinical characteristics, response to treatment, and HLA phenotypes compared with a group of age- and sex-matched persons with CS but without immunoglobulin deficiency. Fourteen of 604 patients with CS were identified as being selectively deficient in IgA, whereas one had common variable immunodeficiency. At diagnosis, anemia was present in 8 of 14 IgA-deficient patients compared with 10 of 42 controls (p = 0.047), whereas abdominal pain was more common in controls with CS. Autoimmunity and recurrent infection were more prevalent in the IgA-deficient group. Response to gluten-free diet was similar in both groups in terms of histologic structure and recovery of intestinal brush-border enzyme activity. IgA-deficient participants with CS had no increased risk of associated malignancy or lymphoma. HLA phenotypes were similar in both groups. The prevalences of selective IgA deficiency and common variable immunodeficiency in this series of patients with CS are 2.31 in 100 and 0.16 in 100, respectively. Although this group is unique in character, close follow-up coupled with conscientious compliance with a gluten-free diet, remains the mainstay of treatment for these patients.

Enteropathy-associated T-cell lymphomas have a cytotoxic T-cell phenotype.

AIMS: Enteropathy-associated T-cell lymphoma (EATCL) is a rare complication of coeliac disease. We investigated whether EATCLs are the neoplastic counterparts of activated cytotoxic T-cells (CTLs). METHODS AND RESULTS: Eight cases, clinically and histologically defined, were stained with monoclonal antibodies against components of the cytotoxic granules of CTLs, granzyme B and T-cell restricted intracellular antigen (TIA-1). It was found that all cases had a cytotoxic phenotype, i.e. expression of TIA-1 in most of the tumour cells, whereas granzyme B was found in six of eight cases, mostly in a smaller number of tumour cells compared to TIA-1. Since TIA-1 and granzyme B are expressed at different stages of activation of CTLs it is hypothesized that differences in expression between granzyme B and TIA-1 in EATCL represent different stages of activation in which the tumour cells are arrested. Clinically, seven of the eight patients died within 10 months after diagnosis of EATCL. CONCLUSIONS: EATCL is a clinicopathological entity with a grim prognosis and with tumour cells representing a unique neoplastic equivalent of CTLs arrested in varying stages of activation.

Addison's disease and selective IgA deficiency in two coeliac patients.

Coeliac disease is associated with selective IgA deficiency and various autoimmune disorders. An association between Addison's disease and coeliac disease has been documented previously in the literature but never heretofore in coeliac patients with selective IgA deficiency. From a coeliac registry of over 700 biopsy-proven coeliac patients, studied closely over a 25-year period at University College Hospital, Galway, we now report the finding of Addison's disease and selective IgA deficiency in two patients with established coeliac disease. Previous reports of Addison's disease in coeliac patients were sporadic, and it was felt that the association between the two conditions was fortuitous. We now believe that coeliac patients, especially those who are selectively deficient in serum IgA, should be followed up with increased vigilance, as the association between IgA-deficient coeliac patients and Addison's disease is greater than can be explained by chance. Furthermore, we suggest that patients with established Addison's disease may have subclinical coeliac disease and should be screened with anti-reticulin or anti-endomyseal antibodies.

Abnormal pancreolauryl tests in coeliac disease: lack of correlation with the degree of intestinal mucosal damage.

AIMS: To determine the frequency of abnormal pancreolauryl tests in untreated and treated adults with coeliac disease and to see whether abnormalities in treated coeliac patients correlate with the degree of recovery of intestinal morphology or brush border enzyme activity. METHODS: Pancreolauryl tests were performed in a study population of 57 adult coeliac patients (25 on gluten containing diets and 32 on gluten free diets), 59 symptomatic controls, and eight patients with pancreatic disease. Brush border enzyme activity and morphological assessment were performed on small intestinal biopsies in 27 of the treated coeliac patients. RESULTS: Forty per cent of untreated coeliac patients and 18% of treated coeliac patients had abnormal tests. In treated coeliac patients, no significant correlation was detected between the pancreolauryl test result and either brush border enzyme activity or morphological parameters. CONCLUSION: Abnormal pancreolauryl test results are common in untreated and treated adult coeliac disease patients. Abnormalities in treated coeliac patients do not correlate with the degree of recovery of small intestinal morphology or brush border enzymes.

An autosomal screen for genes that predispose to celiac disease in the western counties of Ireland.

Celiac disease is a strongly heritable gastrointestinal illness that is an especially important model of the genetically complex multifactorial immune mediated diseases. The HLA component of celiac disease (a specific HLA-DQ heterodimer)is largely established and is relatively uncomplicated, and the environmental component (gluten and related grain storage proteins in the diet) is remarkably well understood. Previous family studies of celiac disease suggested that there is at least one important non-HLA locus. This locus may be a stronger genetic factor than HLA, and it apparently has a recessive mode of inheritance. We used a three step genome screening protocol to identify loci that contribute to celiac disease in the western counties of ireland, a region with the highest prevalence of celiac disease in the world. The most significant of several possible non-HLA loci that we found was on chromosome 6p about 30 cM telomeric from HLA. It has a multipoint maximum lod score of 4.66 (compared with 4.44 for HLA-DQ) and appears to have a recessive mode of inheritance. Our study localizes and provides strong evidence for linkage of at least one non-HLA locus to celiac disease and may serve as a prototype for an efficient approach to screening the human genome for loci that contribute to complex diseases.

Secretor status and human leucocyte antigens in coeliac disease.

BACKGROUND: The ability to secrete blood group antigens into body fluids and secretions is controlled by a single gene on chromosome 19. By means of erythrocyte Lewis (Le) antigen phenotype secretor status can be inferred. An increase prevalence of non-secretors of blood group antigens among coeliac patients has recently been described. METHODS: Blood was collected from 112 coeliac patients and 103 controls and tested for secretor status. Secretor status was correlated with human leucocyte antigens (HLA) in coeliac patients, thus evaluating a proposed interaction of susceptibility genes--that is, the secretor gene on chromosome 19 and HLA-linked genes on chromosome 6. Case notes for coeliacs were reviewed with regard to clinical outcome. RESULTS: Of 112 coeliacs who had either Le(a) or Le(b) antigens, 36 (32%) were non-secretors Le(a+, b-), compared with 27% (28) of 103 disease-free controls (P = 0.313). Recessive Lewis phenotype Le(a-, b-) was found in 9% of coeliacs versus 2% of controls. Prevalence of HLA-A1, B8, DR3, and DQ2 was unrelated to secretor status in coeliac versus patients. An increased prevalence of complications and coeliac-associated abnormalities was found in the non-secreting and recessive coeliac groups. CONCLUSIONS: This study shows no firm relationship between the non-secretor state and coeliac disease, nor any difference in the distribution of HLA markers among secretor and non-secretor coeliacs. It is unlikely, therefore, that the secretor gene is the much sought-after second coeliac gene.

HLA-DR, DQ genotypes of celiac disease patients and healthy subjects from the West of Ireland.

Celiac disease (CD) has one of the strongest class II HLA associations of any human illness. We used DNA-RFLP typing to study the class II HLA genotypes of celiac disease patients from the West of Ireland, the geographic area with the highest rate of celiac disease in the world. We confirmed the high frequency of HLA-DR3 in this population, and we were also able to demonstrate the additional risk of developing celiac disease imparted by HLA-DR7. This was done by clearly distinguishing DR7,DQ2 haplotypes from DR7,DQ9 haplotypes, and by "subtraction analysis" of haplotype frequencies. As reported in other populations, most of the patients without DR3 were heterozygous for DR7 and DR11 or 12 (DR5), or had DR4. We used PCR-RFLP and direct sequencing of amplified DNA to examine HLA-DR4 subtypes. The frequency of HLA-DR4 was markedly decreased in patients compared with controls (p = 0.000001) and there was a significant alteration of DR4 subtypes of the patients compared with controls (p = 0.0227). Moreover, all of the CD patients (5 of 5) with DR4 had a haplotype associated with the DQB1*0302 allele compared with only 11 of 23 control subjects with DR4. Our results in this population with exceptionally high risk of CD strongly support the DQ heterodimer hypothesis and suggest that the recently described sequence difference between the DQB1*02 alleles of DR3 and DR7 may contribute to a synergistic increased risk when these haplotypes are inherited together. In addition, our findings suggest a role for HLA-DQ in DR4-associated CD.