Local cytokine response in Helicobacter pylori-infected subjects

The host immune response to Helicobacter pylori infection might be of importance with regard to the outcome of infection by this organism, e.g., to explain why only a proportion of infected subjects develop peptic ulcers. In this study we have analyzed the local response of different cytokines-i.e., the proinflammatory interleukin-1beta, (IL-1beta), IL-6, tumor necrosis factor alpha, and IL-8; the immunoregulatory gamma interferon (IFN-gamma); and IL-4; and the anti-inflammatory transforming growth factor beta (TGF-beta)-in antral biopsy specimens from H. pylori-infected duodenal ulcer (DU) patients and asymptomatic (AS) carriers (i.e., with chronic gastritis only). For comparison, biopsy specimens from uninfected healthy individuals were also analyzed. An immunohistochemical technique was used to allow quantification of the cytokine responses as well as identification of the cell types associated with the cytokine expression. We found that the levels of all of the studied cytokines except IL-4 were increased in the H. pylori-infected subjects compared to the levels in the healthy individuals. Our results indicate that the antral cytokine response is of the Th1 type since IFN-gamma, but not IL-4, was up-regulated both in H. pylori-infected DU patients and in AS carriers. However, there were no significant differences in either proinflammatory or immunoregulatory cytokine levels when H. pylori-infected subjects with and without peptic ulcers were compared. Some of the cytokines, particularly IL-1beta and TGF-beta, were also found in the gastric mucosae of healthy, uninfected subjects. We also showed that the gastric epithelium contributes substantially to the antral cytokine response of the proinflammatory cytokines IL-1beta and IL-6 in addition to IL-8.     

Management of symptomatic and asymptomatic unruptured aneurysms

Intradural unruptured saccular aneurysms are being diagnosed with increasing frequency. Left untreated, these lesions usually progress, and the cumulative risk from bleeding usually outweighs the risk of treatment. Exceptions include patients with limited life expectancy and patients over the age of 70 with small asymptomatic or giant posterior circulation lesions associated with few symptoms. Therapeutic intervention offers little over the natural history for these patients, and therapy should be considered only if symptoms progress or growth is documented. Treatment options should be coordinated by an experienced cerebrovascular surgeon with access to interventional adjuncts; EC-IC bypass, and circulatory arrest. GDC coiling should be reserved for non-surgical cases, as the durability of this treatment is still being evaluated.     

Prevalence of Helicobacter pylori infection in asymptomatic children

OBJECTIVE: To determine the prevalence of Helicobacter pylori infection in a sample of asymptomatic Australian children. METHODOLOGY: A prospective observational study, during a 3 month period, of consecutive children aged 0 to 14 years undergoing minor elective surgical procedures in a Day Surgical Unit at a Melbourne paediatric hospital. Subjects without gastrointestinal symptoms or a family history of peptic ulcers had sociodemographic data recorded and serum collected. Serum anti-H. pylori immunoglobulin G antibodies were measured by an enzyme immunoabsorbent assay previously validated in children from the same population. RESULTS: H. pylori antibodies were present in 21/147 (14.3%) children aged 3 months to 14 years. Prevalence was not influenced by age or sex, but was greatest in children whose parents migrated from developing nations and lowest in children with Caucasian Australian or Western European parents (25.8 vs 5.9%; P < 0.001). An inverse relationship between social class and infection was also observed (P = 0.02). Multivariate analysis demonstrated the father's ethnic background as the only significant independent risk factor for H. pylori infection (P = 0.002). CONCLUSIONS: Although seroprevalence of H. pylori appears to be lower in Australian children than in developing countries there are some ethnic groups at substantially greater risk for the acquisition of H. pylori infection and its complications.     

Relationship of immune response to heat-shock protein A and characteristics of Helicobacter pylori-infected patients

This study assessed the minimum dose of clonidine required to prolong the duration of both anesthesia and analgesia after axillary brachial plexus blockade. Eighty patients scheduled for elective hand surgery were divided into eight groups in a randomized, double-blind fashion. An axillary brachial plexus block was performed with 40 mL 1% mepivacaine plus 1:200,000 epinephrine. The control group received no clonidine. In the other groups, increasing doses of clonidine (0.1, 0.2, 0.3, 0.4, 0.5, 1, and 1.5 micrograms/kg) were added to the local anesthetic solution. Onset time, duration of anesthesia and analgesia, postoperative pain score, intake of analgesics, and adverse effects were recorded. The eight groups were comparable in terms of onset time, postoperative pain score, and analgesic requirement. The minimum dose of clonidine required to significantly prolong the duration of analgesia and anesthesia was, respectively, 0.1 and 0.5 microgram/kg. No side effects (sedation, drowsiness, bradycardia, arterial hypotension) were reported. We conclude that the dose of clonidine required to prolong significantly the duration of both anesthesia and analgesia after axillary brachial plexus blockade is 0.5 microgram/kg and that, at this dose, clonidine may be used without important reported side effects even in outpatients.     

Isthmic spondylolisthesis in symptomatic and asymptomatic subjects, epidemiology, and natural history with special reference to disk abnormality and mode of treatment

Observations during the past 35 years on operative and conservative treatment of adult and young patients with isthmic spondylolisthesis, demonstrate the main indications of fusion are pain and risk of further progression of the slip. At one time, posterior fusion was recommended. Posterolateral fusion in situ was adopted in 1975, and during the past ten years anterior fusion combined with reduction and transpedicular fixation has been performed in severe slips. Surgery was mainly indicated to alleviate pain or to prevent further progression of the slip. It seems possible to alter the natural course of the disease by operation, but it is difficult to prove the connection between the radiographic findings and the pain. The epidemiologic study shows that the prevalence of spondylolisthesis in Finland is 6%, but there are no significant differences between these subjects and controls without spondylolisthesis. Symptomatic patients may have pain, however, even after a long observation time. Prevention of the slip is difficult because, statistically, 90% of the slip has already occurred when the patient is first seen. Posterolateral fusion in situ is the method of choice, especially for most young patients. Anterior fusion is indicated if the slip is greater than 40%-50%. Reduction of the slip is indicated in exceptional cases only.     

Prothrombin antigen levels in symptomatic and asymptomatic carriers of the 20210A prothrombin variant

A recently discovered variant in the prothrombin gene (20210A) has been found in approximately 5-10% of patients with venous thromboembolism. It has been shown that patients with this variant present with high levels of prothrombin in plasma and this is maintained to be the most likely mechanism by which the risk of thrombosis is increased. We have evaluated prothrombin antigen levels in 50 carriers of the 20210A allele and compared with non-carriers. 327 subjects were subdivided according to deficiency status and previous thrombosis. 30 symptomatic and 20 asymptomatic carriers had increased mean prothrombin levels as compared to symptomatic (n=178) or asymptomatic (n=99) non-carriers. The percentage of subjects with prothrombin levels above cut-off values of 1.15u/ml or 1.30u/ml was significantly higher in carriers of the prothrombin variant as compared to non-carriers, regardless of a previous thrombosis. However, among non-carriers the percentage of those with prothrombin levels above cut-off values was significantly higher in the group of symptomatic as compared to asymptomatic individuals. In conclusion, increased prothrombin antigen levels, as detected by a specific ELISA, were found among 50 symptomatic and asymptomatic carriers of the 20210A prothrombin variant as well as among a large group of symptomatic non-carriers. The data are in agreement with those found by using functional tests for the determination of prothrombin levels in these patients.     

The prevalence of Helicobacter pylori-positive serology in asymptomatic children

Surgeons frequently perform sural nerve biopsy as part of the work-up of patients with peripheral neuropathy. The indications for the procedure, therapeutic value, and complications associated with the procedure have received little attention in the surgical literature. A retrospective chart review of 60 patients with the suspected diagnosis of peripheral neuropathy undergoing sural nerve biopsy was performed. Vasculitis was suspected in 29 (48%) patients undergoing biopsy. This diagnosis was confirmed in 6 of the 29 patients and resulted in the alteration of therapy in 31% of patients with this suspected diagnosis. In 27 (45%) patients, the etiology of their peripheral neuropathy was unknown. Twelve (44%) patients in this group had sural nerve pathology; however, no change in therapy was required. Ten patients in our series had associated malignant tumors; some of these patients were diagnosed after referral for sural nerve biopsy. Twenty-five (42%) patients remained undiagnosed after biopsy. Nerve conduction studies were performed in 14 (22%) patients. Thirteen patients with abnormal lower extremity nerve conduction studies had 6 normal and 7 abnormal biopsy results. The one patient with a normal study had a normal nerve biopsy result. There were six (10%) patients with wound infections, seven (12%) patients with delayed wound healing, and three (5%) patients with new onset of chronic pain in the distribution of the sural nerve, for an overall complication rate of 27%. There was no correlation between the preoperative use of antibiotics, type of local anesthetic used, or length of nerve excised and complication rate. We conclude that the complication rate after sural nerve biopsy is significant. Strict criteria should be employed in selecting patients for sural nerve biopsy including a careful neurologic history and physical examination, nerve conduction studies, appropriate work-up for vasculitis if suspected, and implementation of a search for malignancy if this is not apparent. If the diagnosis is still in question, then sural nerve biopsy would seem appropriate, especially in patients with suspected vasculitis.     

Helicobacter pylori and gastroduodenal lesions in 547 symptomatic young adults

OBJECTIVES: Helicobacter pylori (H. pylori) is involved in the pathogenesis of gastric inflammatory disorders. Both antral chronic gastritis and H. pylori infection prevalence increase with age. The aim of the study was to assess the prevalence of H. pylori infection in young adults and to study the relationship between endoscopical and histological features and H. pylori infection. METHODS: The study concerned 547 young patients (age: 18-25 years), undergoing endoscopy for upper gastrointestinal symptoms. The severity and the activity of chronic gastritis was graded by histological examination of antral biopsies. The diagnosis of H. pylori infection was based on histology and culture or urease test. RESULTS: Fifty-three percent of the patients had a normal endoscopy; 44 ulcers were found: 34 duodenal ulcers and 10 gastric ulcers. H. pylori infection was detected in 34% of cases. The prevalence of H. pylori infection was 29.8% in non-ulcer patients, 50% in gastric ulcers and 91% in duodenal ulcers (P < 0.01). Duodenal ulcer, aspect of antral mosaic mucosa and nodular gastritis, were closely related to the presence of H. pylori. There was a significant relationship between H. pylori infection and both the severity (P < 0.01) and the activity (P < 0.01) of the antral chronic gastritis. The prevalence of follicular gastritis was 22% : it was present in 60% of H. pylori positive patients and 2.4% of H. pylori negative patients. H. pylori infection was more frequent in patients from Africa than in Europeans (P < 0.01). There was no significant association between H. pylori infection and different types of diets, settlements (rural vs urban) or symptoms. CONCLUSION: These results show that in the young population studied, duodenal ulcer, nodular gastritis, antral mosaic mucosa, active chronic gastric and follicular gastritis are closely related to H. pylori infection. They suggest that in the subgroup of non ulcer symptomatic patients, H. pylori prevalence is higher than in the general population.     

Analysis of cell damage and proliferation in Helicobacter pylori-infected human gastric mucosa from patients with gastric adenocarcinoma

Helicobacter pylori (HP) infection, a cause of multifocal atrophic gastritis, is considered an important factor related to the evolution of the human gastric mucosa from normal to intestinal-type adenocarcinoma. We examined cell proliferation and both double and single strand DNA damage in situ in 35 patients undergoing gastrectomy for adenocarcinoma with HP-infected gastric mucosa by immunolocalization of Ki-67, terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling, and in situ nick translation. We also studied the distribution of intraepithelial neutrophils by elastase immunolocalization. HP infection was confirmed in all cases by serum anti-HP antibodies, ureas testing, and histopathological examination. HP-infected gastric mucosa was classified according to the degree of inflammation and intestinal metaplasia. Ki-67, terminal deoxynucleotidyl transferase-mediated labeling, in situ nick translation, and intraepithelial neutrophil indices all increased with the progression of gastritis and were highest in glands with incomplete intestinal metaplasia. All indices were lowest in gastric glands with complete intestinal metaplasia. Significant positive correlations were observed among these markers. Increased proliferative activity in HP-associated chronic gastritis in response to cell damage or injury was clearly demonstrated, suggesting that both HP-associated toxins and intraepithelial neutrophils are important in HP-related gastric epithelial injury. Increased cell turnover associated with incomplete intestinal metaplasia may result in DNA instability and subsequent development of intestinal-type gastric adenocarcinoma in HP-infected mucosa.     

One-week low-dose triple therapy is effective in treating Helicobacter pylori-infected patients with bleeding peptic ulcers

Although lead has been extensively studied in children, its sources and effects remain unclear in adolescents. This study examined the relation of blood and tibia bone lead levels to lead determinants. One hundred adolescents living in Mexico City and surrounding suburbs were studied. Blood lead was measured by atomic absorption spectroscopy, and tibia lead was measured by a K X-ray Fluorescence (KXRF) instrument. Blood lead ranged from 1.8 to 29.2 microgram/dl, with a mean of 7.4 microgram/dl. Bone lead ranged from <1 to 44.82 microgram Pb/g bone mineral, with a mean of 4.8 microgram Pb/g. Predictors of bone lead included higher traffic density near the home, mother's smoking history, and time spent outdoors. Predictors of log-transformed blood lead included bone lead levels, male sex, use of lead-glazed ceramics, and living in Mexico City. Bone lead remained a significant predictor of blood lead after adjusting for covariates in a final multivariate regression model. In our final model, a rise in bone lead from the middle of the lowest quintile to the middle of the highest quintile (a difference of 21.6 microgram Pb/g) was associated with an increase in blood lead of 1.2 microgram/dl. Our data suggest that in addition to current sources of environmental lead exposure, bone lead accumulated over time constitutes a moderate source of circulating lead during adolescence and may account for some of the adverse health effects documented in recent studies.     

Antibody-secreting cells specific for simian immunodeficiency virus antigens in lymphoid and mucosal tissues of immunized macaques

OBJECTIVES: To examine whether the route of immunization affects the induction of antibody-secreting cells (ASC) in the circulation of macaques. The distribution of ASC in the rectal mucosa and lymphoid tissues following challenge with simian immunodeficiency virus (SIV) was investigated. DESIGN: Macaques were immunized with recombinant SIV gp120 and p27 antigens by the targeted iliac lymph node (TILN) route of immunization or the nasal and rectal route, augmented by intramuscular immunization [naso-rectal intramuscular (NRI)]. The macaques were challenged with live SIV by the rectal route and ASC were assayed in the circulation before and after SIV challenge, and in the tissues removed at post-mortem. METHODS: ASC were examined in the circulation by Elispot assay. Mononuclear cells were prepared from peripheral blood, iliac and axillary lymph nodes and spleen. Rectal tissue was treated by enzyme digestion to elute mononuclear cells. RESULTS: TILN and NRI immunization induced circulating IgA and IgG ASC to both gp120 and p27. Following rectal challenge with SIV, TILN macaques were protected from infection whereas NRI route-immunized and unimmunized controls became infected. IgA ASC to p27 were increased significantly in the iliac lymph nodes of the TILN immunized macaques compared with unimmunized controls (P < 0.05). Only IgA ASC were found in the rectal mucosa of the immunized protected macaques but both IgA and IgG ASC were detected in the unimmunized infected macaques. Overall the number of IgG ASC specific for p27 was significantly higher in the infected NRI and control macaques than in the protected macaques (P < 0.02). A progressive increase in IgG but not IgA ASC was detected in the peripheral blood mononuclear cells of the unimmunized infected macaques. CONCLUSIONS: The results suggest that cells secreting IgA antibodies to p27 in the iliac lymph nodes of the TILN immunized macaques correlate significantly with protection from infection. The unimmunized infected macaques showed a progressive increase in IgG ASC in the peripheral blood after SIV challenge; this was found in the iliac and axillary lymph nodes and also in the spleen, suggesting that it is an immune response to the SIV infection.     

Local immune response in Helicobacter pylori-infected cats and identification of H. pylori in saliva, gastric fluid and faeces

Helicobacter pylori-infected cats were screened by culture and polymerase chain reaction (PCR) for the presence of H. pylori in salivary secretions, gastric juice, gastric tissue and faeces. H. pylori was cultured from salivary secretions in six of 12 (50%) cats and from gastric fluid samples in 11 of 12 (91%) cats. A 298 base pair polymerase chain reactions (PCR) product specific for an H. pylori 26000 MW surface protein was amplified from dental plaque samples from five of 12 (42%) cats and from the faeces of four of five (80%) cats studied. Analyses of serum and mucosal secretions by enzyme-linked immunosorbent assay (ELISA) revealed an H. pylori-specific immunoglobulin G (IgG) response, and elevated IgA anti-H. pylori antibody levels in salivary and local gastric secretions. Immunohistochemical analyses of gastric tissue revealed the presence of IgM+ B cells assembled into multiple lymphoid follicles surrounded by clusters of CD4+ and CD8+ T cells. The lamina propria also contained single cells or aggregates of IgA+ and IgM+ B cells. These observations show that H. pylori can be identified in feline mucosal secretions, and that a localized IgA immune response develops in gastric tissue of H. pylori-infected cats. The findings suggest a zoonotic risk from exposure to personnel handling H. pylori-infected cats in vivaria.     

Neuropsychological deficits in tests of executive function in asymptomatic and symptomatic HIV-1 seropositive men

There has been much debate about the exact nature and time of onset of the cognitive impairments associated with infection by the human immunodeficiency virus type 1 (HIV-1). Studies to date have not reached consistent conclusions. The present study comprised 22 asymptomatic and 18 symptomatic HIV-1 seropositive men, whose only risk factor for contraction of the virus was sexual intercourse, and 18 seronegative controls matched for age and IQ. Subjects were given computerized neuropsychological tests from the CANTAB battery, which assessed visuospatial memory, attention and executive function. Both the asymptomatic and the symptomatic HIV-1 seropositive subjects showed a selective pattern of deficits relative to the controls. In addition, the seropositive subjects were subtly but significantly impaired on tests of executive function but unimpaired on certain tests of visual memory. This finding supports an hypothesis that frontostriatal dysfunction occurs in HIV-1 infected individuals prior even to the expression of clinical symptoms.     

Premenstrual Assessment Form typological categories: Classification of self-defined premenstrually symptomatic and asymptomatic women.

Newly developed assessment instruments for premenstrual syndrome include the Premenstrual Assessment Form (PAF) and associated PAF typological categories. This study investigates the use of the PAF as a retrospective assessment instrument and the use of PAF subtypes as accurate reflectors of subjective premenstrual symptomatology. Nineteen self-defined severely premenstrually symptomatic women and 26 self-defined premenstrually asymptomatic women completed the PAF to designate premenstrual changes experienced during the previous three menstrual cycles and, subsequently, changes experienced in the previous 24 hr during the premenstrual, menstrual, and intermenstrual phases of three menstrual cycles. All women were classified in PAF subtypes according to their responses on all PAF administrations. Results partially supported the use of the PAF with concurrently obtained data. The limitations of retrospective data in diagnosing premenstrual syndrome and the consideration of additional, nonpremenstrual data in diagnosis are discussed. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Histological findings of gallbladder mucosa in 95 control subjects and 80 patients with asymptomatic gallstones

BACKGROUND AND PURPOSE: Decisions on invasive arteriovenous malformation (AVM) treatment are currently based on natural-course risk estimates of AVM bleeding and assumptions on morbidity from cerebral hemorrhage in general. However, morbidity of AVM hemorrhage has rarely been reported. We sought to assess the morbidity of intracranial hemorrhage in patients with cerebral AVMs. METHODS: From a prospective AVM database, 119 patients were analyzed: 115 had a hemorrhage as the diagnostic event, and 27 of them suffered a second hemorrhage during follow-up; an additional 4 patients had other diagnostic symptoms but bled during follow-up. The type (parenchymal, subarachnoid, intraventricular) and location of AVM hemorrhage were determined by CT/MR brain imaging. Disability and neurological impairment were assessed with the Barthel Index, the Rankin Scale, and the National Institutes of Health Stroke Scale, with a mean follow-up time of 16.2 months. RESULTS: Of the 115 incident hemorrhages, 34 (30%) were subarachnoid, 27 (23%) parenchymal, 18 (16%) intraventricular, and 36 (31%) in combined locations. In 54 patients (47%; 95% confidence interval [CI], 38% to 56%) the incident hemorrhage resulted in no neurological deficit, and an additional 43 patients (37%; 95% CI, 28% to 46%) were independent in their daily activities (Rankin 1). Fifteen patients (13%; 95% CI, 7% to 19%) were moderately disabled (Rankin 2 or 3), and 3 (3%; 95% CI, 0% to 6%) were severely disabled (Rankin > or =4). Parenchymal hemorrhages were most likely to result in a neurological deficit (52%). Type and morbidity of hemorrhage during follow-up were similar to incident events. Twenty (74%) of 27 patients with both incident and follow-up hemorrhages were normal or independent (Rankin 0 or 1). None of the patients with a hemorrhage during follow-up died during the observation period. CONCLUSIONS: Hemorrhage from cerebral AVMs appears to have a lower morbidity than currently assumed. This finding encourages a reevaluation of the risks and benefits of invasive AVM treatment.     

Frequency of symptomatic and asymptomatic herpes simplex virus type 2 reactivations among human immunodeficiency virus-infected men

Herpes simplex virus (HSV) infection is common in persons coinfected with human immunodeficiency virus (HIV). In a prospective study, daily viral cultures of the mouth, genitals, and rectum were collected from 68 HIV-positive and 13 HIV-negative men who have sex with men. Subjects completed a median of 57 days of follow-up. Anogenital HSV-2 cultures were positive on 405 (9.7%) of 4167 days for HIV-positive men and on 24 (3.1%) of 766 days for HIV-negative men. Most reactivations were perirectal and subclinical. Risk factors for increased HSV-2 shedding among HIV-positive men were low CD4 cell count (odds ratio, 2.5; 95% confidence interval, 1.2-5.4) and antibodies to both HSV-1 and HSV-2 versus HSV-2 only (odds ratio, 1.9; 95% confidence interval, 1.0-3.7). Three isolates obtained from 3 separate subjects were resistant to acyclovir. Thus, subclinical HSV-2 reactivation is an important opportunistic infection in persons with HIV infection. Further studies are necessaryto determine the impact of subclinical HSV-2 reactivation on the natural history of HIV infection.     

Lateral cephalometric analysis of asymptomatic volunteers and symptomatic patients with and without bilateral temporomandibular joint disk displacement

Anecdotal evidence links silicone gel breast implants with the development of autoimmune connective tissue disease in women. To investigate whether silicone gel is capable of directly inducing and/or enhancing the development of autoimmune disease, female BALB/cAnPt (BALB/c) and New Zealand Black (NZB) mice were injected subcutaneously with silicone gel, pristane, a nonmetabolizable substance that can cause plasmacytomas in BALB/c and NZB mice, or saline and monitored for the development of glomerulonephritis and autoantibody production. NZB, but not BALB/c, mice spontaneously develop autoantibodies and an autoimmune hemolytic anemia by 12 months of age. Over a period of 10 months, biweekly screening for proteinuria revealed increases in urinary protein in NZB mice that received multiple injections of either silicone gel or pristane. In contrast, urinary protein was unaffected in identically treated BALB/c mice. Although, silicone gel had no effect on serum titers of antierythrocyte antibodies in NZB mice, the hematocrits were significantly decreased. Moreover, silicone gel both increased the concentration of IgM anti-type I collagen antibodies and skewed the immunofluorescent staining pattern of serum autoantibodies on HEp-2 cells. In contrast, silicone gel failed to induce the production of anti-erythrocyte or antinuclear antibodies in BALB/c mice and induced only slight increases in IgG anti-type I collagen antibodies. These results suggest that silicone gel can exacerbate the development of autoimmune disease in autoimmune NZB mice, but fails to induce disease in normal BALB/c mice. This is consistent with several epidemiological studies failing to demonstrate an increase in the incidence of autoimmune disease in women with breast implants. However, because silicone gel was able to exacerbate autoimmune disease in NZB mice, it may play a similar role in the development of autoimmune disease in a small percentage of women who are genetically susceptible to such diseases.     

Graft patency and saving the extremity as a function of asymptomatic/symptomatic aneurysm of the popliteal artery and the graft material used

A 27-year experience with 252 popliteal artery aneurysms in 167 patients is reviewed. Long-term results with respect to graft patency and limb salvage rates are analyzed. The results emphasize the importance of early surgical intervention and demonstrate the superiority of autologous saphenous vein over other graft materials.