Gastroduodenal lesions and Helicobacter pylori infection in dyspeptic patients with and without chronic renal failure

BACKGROUND: Patients with chronic renal failure (CRF) often have dyspeptic symptoms and may develop peptic disease or digestive disorders leading to severe gastrointestinal complications. The primary aim of this study was to evaluate the prevalence of peptic lesions and Helicobacter pylori infection, and the severity of dyspeptic symptoms, in dyspeptic patients with and without CRF. Our secondary aim was to investigate whether uremic status may affect the diagnostic efficiency of the [13]C-urea breath test ([13]C-UBT). PATIENTS AND METHODS: We consecutively enrolled in the study 50 dyspeptic patients with chronic kidney failure (mean age 52 +/- 5 years), of whom 11 were on hemodialysis treatment (HD), and 93 subjects (mean age 54 +/- 7 years) with chronic dyspepsia and normal renal function (NRF). All patients completed an oriented and validated questionnaire scoring the severity of nine dyspeptic symptoms (i.e. epigastric pain, epigastric burning, postprandial fullness, early satiety, bloating, belching, nausea and vomiting) and underwent upper endoscopy with multiple bioptic sampling for rapid urease test and histological examination, [13]C-UBT and HpSA test. RESULTS: The prevalences of peptic lesions and H. pylori infection and mean symptom score were 74%, 52% and 3.5 +/- 3, respectively, in dyspeptic patients with CRF and 18%, 36% and 8 +/- 5, respectively, in dyspeptic patients with NRF. The diagnostic accuracy of [13]C-UBT with respect to histological diagnosis was 94% and 97% for dyspeptic patients with and without renal failure, respectively. CONCLUSIONS: 1, A high frequency of peptic lesions and low symptom scores were observed in uremic patients in spite of H. pylori infection; 2, uremic status did not affect the diagnostic accuracy of [13]C-UBT.     

A potential double role of anti-Lewis X antibodies in Helicobacter pylori-associated gastroduodenal diseases

In this study, we found Lewis X (Le(x)) determinants on 68% of Helicobacter pylori isolates from patients with chronic gastroduodenal diseases. Anti-Le(x) IgG were detected more frequently in the sera from dyspeptic children and adults (45 and 46%), with or without proved (culture) H. pylori infection, than in the sera from healthy individuals (14% and 25%). In contrast, the prevalence of anti-Le(x) IgM was higher in the groups of healthy individuals than in the groups of dyspeptic patients. Moreover, anti-Le(x) monoclonal antibody of IgM class enhanced the uptake of Le(x)(+) but not Le(x)(-) H. pylori isolates by phagocytes. In the sera from some dyspeptic patients, we detected Le(x)-anti-Le(x) IgG immune complexes (Le(x) ICs). There was a great difference between children and adults as regards the presence of Le(x) ICs. The immune complexes were found in the sera from nine out of 29 (27%) H. pylori-infected and three out of eight (37%) uninfected adult dyspeptic patients. In comparison, Le(x)-anti-Le(x) IgG ICs were detected only for two out of 18 (11%) H. pylori-infected children. Le(x) ICs were not found in the sera from healthy individuals. Our results suggest that anti-Le(x) IgM may play a protective role in H. pylori infections. In contrast, anti-Le(x) IgG and particularly Le(x)-anti-Le(x) IgG ICs might contribute to the pathogenesis of chronic H. pylori infections.     

Immunohistochemical detection of carcinoembryonic antigen (CEA) in non-cancerous and cancerous gastric mucosa

Carcinoembryonic antigen (CEA) was stained by the PAP immunoperoxidase method in cancerous and non-cancerous gastric mucosa of 40 patients (25 non-cancerous dyspeptic patients and 15 patients with gastric carcinoma). The pattern of CEA localization was apical or membranous-cytoplasmic and immuno-reactivity was mild (+), moderate (++) or intensive ( ). No CEA immunoreactivity was detected in normal gastric mucosa whereas it was marked in gastric mucosa of non-cancerous dyspeptic patients with chronic atrophic gastritis and dysplasia (intense). In patients with superficial gastritis and epithelial hyperplasia it was mild or absent. The CEA localization pattern was also apical in non-cancerous dyspeptic patients with microscopic changes, e.g. superficial or chronic atrophic gastritis, epithelial hyperplasia and dysplasia, and in non-cancerous mucosa and cancerous tissue of patients with well (G1) and moderately (G2) differentiated adenocarcinoma.     

Carcinoembryonic Antigen in Faeces

Carcinoembryonic antigen (C.E.A.) was detected in the faeces of 5 out of 10 healthy volunteers, 12 out of 18 patients suffering from gastrointestinal cancer (including 10 out of 11 cases of colonic cancer), and 3 out of 13 patients suffering from non-neoplastic disease. It is suggested that C.E.A. may be present in small amounts in normal faeces but that in malignant conditions of the bowel the amount increases.     

Neuroendocrine response to cold in Raynaud's syndrome

Eleven patients with Raynaud's syndrome accompanied by monospecific IgG ANA, nine patients with Raynaud's syndrome in the absence of ANA, and nine normal volunteers were exposed to an ambient cold challenge during which time venous blood was continuously sampled. ANA negative patients were shown to have significantly higher levels of cortisol during a cold challenge than either ANA positive patients or normal controls, and exhibited significantly lower levels of plasma norepinephrine compared with normal controls. ANA positive patients did not differ significantly from normals in their neuroendocrine response to cold. It is suggested that the high plasma cortisol found in Raynaud's syndrome in the absence of ANA may be responsible for the vasospasticity in this group of patients.     

Higher frequency of dicentrics and micronuclei in peripheral blood lymphocytes of cancer patients

The presence of dicentric chromosome (DC) and micronuclei (MN) frequency in the peripheral blood lymphocytes of 25 cancer patients prior to chemo and radiotherapy and 21 healthy volunteers were studied. The overall DC and MN showed significantly higher frequency compared to those obtained in normal healthy volunteers (p<0.0001). However, among 25 patients only 15 showed a higher frequency of DC aberration, nine patients showed the presence of minutes (M) and seven patients showed chromatid breaks (ChB). The reasons for the higher frequency of aberration observed in these cancer patients are discussed in this paper.     

A reappraisal of the strength-duration test to assess neuromuscular impairment of critically ill patients

IntroductionNeuromuscular impairment (NMI) affects almost half of critically ill patients. The purpose was to investigate the role of neuromuscular electrical stimulation (NMES) to gain more insight into the nature of the NMI associated with ICU admission. To this aim, we analyzed the strength-duration (S-D) curves of the rectus femoris muscles of ICU patients compared to healthy volunteers.MethodsS-D curves were recorded from 44 healthy volunteers and 29 ICU patients. Three electrophysiological parameters were used to classify the neuromuscular function, from grade 0 (normal function), to grade 3 (no evocable muscle contraction). ICU patients underwent electroneurographic peroneal nerve testing (PENT) to analyze NMI by electroneurography (ENG).ResultsThree patients were classified as Grade 0; nine as mild NMI (Grade 1), 13 as Grade 2, and four showed unexcitable muscles (Grade 3). Mean CMAP amplitudes were 6.1, 3.4, 2.9 and 0.81 mV from Grade 0 to Grade 3, respectively. CMAP was inversely correlated to NMI grade (−1.7 mV, R² = 0.946, p < 0.05).ConclusionsThe normative parameters of the S-D curves obtained by NMES in healthy volunteers allowed identification of NMI in ICU patients. NMES was an affordable tool to evaluate NMI in ICU patients, providing additional information to that obtained by ENG.     

Monocyte receptors for the Fc portion of IgG increase in number in autoimmune hemolytic anemia and other hemolytic states and are decreased by glucocorticoid therapy

Peripheral blood monocyte receptors for the Fc portion of IgG were quantitatively studied in 43 normal subjects, in 14 patients with warm antibody autoimmune hemolysis (AIHA), and in nine individuals with nonantibody-mediated hemolysis. Monocytes of normal females expressed significantly greater numbers of Fc gamma receptors than did similar cells from male subjects, with no difference in affinity for the IgG1 probe. Monocyte Fc gamma receptor number was increased in patients of both sexes with AIHA; a similar, but smaller, increase in monocyte Fc gamma receptor number was noted in patients with nonantibody-mediated hemolysis. Glucocorticoid administration was associated with a dose-dependent decrease in monocyte Fc gamma receptor number in normal volunteers and patients. Possible etiologic mechanisms and pathogenetic consequences of enhanced monocyte Fc gamma binding in AIHA are discussed.     

Particular Candida albicans strains in the digestive tract of dyspeptic patients, identified by multilocus sequence typing

Background

Candida albicans is a human commensal that is also responsible for chronic gastritis and peptic ulcerous disease. Little is known about the genetic profiles of the C. albicans strains in the digestive tract of dyspeptic patients. The aim of this study was to evaluate the prevalence, diversity, and genetic profiles among C. albicans isolates recovered from natural colonization of the digestive tract in the dyspeptic patients.

Methods and Findings

Oral swab samples (n = 111) and gastric mucosa samples (n = 102) were obtained from a group of patients who presented dyspeptic symptoms or ulcer complaints. Oral swab samples (n = 162) were also obtained from healthy volunteers. C. albicans isolates were characterized and analyzed by multilocus sequence typing. The prevalence of Candida spp. in the oral samples was not significantly different between the dyspeptic group and the healthy group (36.0%, 40/111 vs. 29.6%, 48/162; P > 0.05). However, there were significant differences between the groups in the distribution of species isolated and the genotypes of the C. albicans isolates. C. albicans was isolated from 97.8% of the Candida-positive subjects in the dyspeptic group, but from only 56.3% in the healthy group (P < 0.001). DST1593 was the dominant C. albicans genotype from the digestive tract of the dyspeptic group (60%, 27/45), but not the healthy group (14.8%, 4/27) (P < 0.001).

Conclusions

Our data suggest a possible link between particular C. albicans strain genotypes and the host microenvironment. Positivity for particular C. albicans genotypes could signify susceptibility to dyspepsia.     

The TETRA study: a prospective evaluation of Helicobacter pylori 'test-and-treat' strategy on 736 patients in clinical practice

AIMS: To prospectively evaluate the effectiveness of the test-and-treat strategy in a large group of dyspeptic patients in clinical practice. METHODS: Patients with ulcer-like dyspepsia, < 45 years, without alarm symptoms, were prospectively studied. Helicobacter pylori infection was diagnosed with the 13C-urea-breath-test, and eradication or symptomatic treatment was prescribed accordingly. 'Symptomatic improvement' was defined as the percentage of patients with a decrease of > or = 2 levels in the dyspepsia-severity-score or with no symptoms after treatment. Health status and use of health resources were also assessed. Endoscopy was performed in therapeutic failures. RESULTS: Out of 736 patients initially included, 422 received eradication, and 314 symptomatic therapy; 87% returned at 6 weeks and 67% at 6 months. At 6 months, 'symptomatic improvement' was achieved in 73% and 54% of the patients, in eradication and symptomatic groups, respectively (p < .001), and overall in 66%. A reduction of 78% in mean self-assessment visual analogical score was observed at 6 months. More than 50% of patients were 'much better' at control visits. Endoscopy (18%) and physician's visits (13%) were the main health resources used. No gastric or oesophageal cancer was diagnosed. CONCLUSION: This large prospective study shows that the test-and-treat strategy is effective and safe for management of dyspeptic patients in clinical practice.     

Effect of Sustained Maternal Hyperglycaemia on the Fetus in Normal and Diabetic Pregnancies

The effect of prolonged maternal hyperglycaemia on fetal plasma glucose and insulin concentrations was investigated in eight normal and nine diabetic patients. It was found that under fasting conditions the fetal glucose concentration in gestational diabetic pregnancies tended to be lower than in normal pregnancies. Insulin measurements suggested that this may be due to fetal hyperinsulinism in the diabetic group. During glucose infusion, regardless of the degree of maternal hyperglycaemia, the fetal glucose concentration was limited in 12 out of 13 cases to less than 200 mg/100 ml, with only small differences between normal and diabetic pregnancies. It is proposed that the placenta prevents unlimited transport of glucose to the fetus; yet in diabetic pregnancies a sequence of increased maternal-fetal glucose transport, fetal hyperinsulinism, and fetal hypoglycaemia may contribute to the observed perinatal mortality.     

Impaired gastrocolonic response and peristaltic reflex in slow-transit constipation: role of 5-HT(3) pathways

Colonic motility is modulated by the 5-hydroxytryptamine (5-HT)(3)-dependent gastrocolonic response and 5-HT(3)-independent peristaltic reflex. We compared descending colon tone responses to antral distension, duodenal lipid perfusion, and colonic distension after double-blind placebo or granisetron in 13 healthy volunteers and nine slow-transit constipated patients. Antral distension (100-300 ml) and duodenal lipids (3 kcal/min) evoked increases in colon tone in volunteers, which were blunted in constipated patients (P < 0.05). Granisetron (10 microg/kg) reduced responses to antral distension and lipids in volunteers and to lipids in constipated patients (P < 0.05). The ascending contraction of the peristaltic reflex was blunted in constipated patients (P < 0.05), whereas descending responses were similar. Granisetron did not modify the peristaltic reflex. Colonic responses to bethanechol were similar in patients and volunteers. In conclusion, antral distension- and duodenal lipid-activated gastrocolonic responses and ascending contractions of the peristaltic reflex are impaired with slow-transit constipation with loss of both 5-HT(3)-dependent and -independent function. Thus abnormalities of neural reflex modulation of colonic motor function may play pathophysiological roles in slow-transit constipation.     

Artichoke leaf extract reduces mild dyspepsia in an open study

A recent post-marketing study indicated that high doses of standardised artichoke leaf extract (ALE) may reduce symptoms of dyspepsia. To substantial these findings, this study investigated the efficacy of a low-dose ALE on amelioration of dyspeptic symptoms and improvement of quality of life. The study was an open, dose-ranging postal study. Healthy patients with self-reported dyspepsia were recruited through the media. The Nepean Dyspepsia Index and the State-Trait Anxiety Inventory were completed at baseline and after 2 months of treatment with ALE, which was randomly allocated to volunteers as 320 or 640 mg daily. Of the 516 participants, 454 completed the study. In both dosage groups, compared with baseline, there was a significant reduction of all dyspeptic symptoms, with an average reduction of 40% in global dyspepsia score. However, there were no differences in the primary outcome measures between the two groups, although relief of state anxiety, a secondary outcome, was greater with the higher dosage (P = 0.03). Health-related quality of life was significantly improved in both groups compared with baseline. We conclude that ALE shows promise to ameliorate upper gastro-intestinal symptoms and improve quality of life in otherwise healthy subjects suffering from dyspepsia.     

Eradication of Helicobacter pylori has no effect on gastric acidity in duodenal ulcer patients--evaluation of 24-h pH monitoring.

It is accepted that eradication of Helicobacter pylori leads to healing of chronic active gastritis facilitates ulcer healing and prevents ulcer recurrence in duodenal ulcer (DU) patients. However, it is not entirely known whether the eradication of the bacteria normalizes gastric acid secretion and abolishes dyspeptic symptoms after ulcer healing. This study was aimed to evaluate the intragastric acidity and dyspeptic complaints before, and 3 months after, eradication in 18 endoscopically proven H. pylori positive DU patients. Gastric pH was measured by 24-h continuous intraluminal recording, serum gastrin measurements and Congo-red tests were also performed. Dyspeptic complaints and antacid consumptions were recorded in diary cards, antisecretory therapy was not allowed after the cessation of eradication therapy. Endoscopy, H. pylori status and Congo-red tests were controlled at the 6th and 12th week, while pH measurements and serum gastrin tests were performed at inclusion and 3 months later. Three patients dropped out and in 14 out of the remaining subjects healing of DUs and successful eradication was achieved by the 6th and 12th week controls. The 24-h median pH and the percentage of 24-h pH readings under pH 3 were not changing significantly by the 3-month controls (from 1.9+/-0.5 to 1.8+/-0.4 and from 52.6+/-5.5% to 58.6+/-5%, respectively). Similarly, no significant changes were observed in serum gastrin levels and dyspeptic symptom scores (from 72+/-7 pg/ml to 56.7+/-8 pg/ml and from 2.69+/-0.4 to 1.26+/-0.3, respectively). The antacid consumption was almost stable when compared with the pre- and post-eradication periods. It was concluded that despite successful H. pylori eradication and healing of DU, intragastric acidity does not change significantly at least 3 months after the therapy. The persisting dyspeptic symptoms and the need for antacid consumption suggest that some healed ulcer patients require antisecretory therapy in the post-eradication period.     

Why do patients with lupus nephritis die?

Over 20 years 42 of 138 patients with systemic lupus erythematosus "died"--that is, suffered actual death or went into terminal renal failure, or both; data from 41 were available for analysis. In most patients the causes of death were multiple. Twenty seven patients went into terminal renal failure, of whom 25 were offered dialysis treatment. Three regained renal function later, 12 survived on dialysis or with functioning kidney allografts--almost all with inactive lupus--but 13 died after starting dialysis, most within a few weeks or months. The principal causes were active lupus or infection. In those patients with renal failure after rapid deterioration in renal function (n = 14) there were nine deaths, while of 10 patients with a slow evolution into renal failure, only four died. Four patients with impaired and 10 with normal renal function died, again most often from complications of lupus or from infection. Vascular disease was a major cause of death in seven patients, all but two of whom were young; of 15 postmortem examinations, eight showed severe coronary artery atheroma, and three surviving patients required coronary bypass operations. Analysis of the timing of death or entry into renal failure showed that in 12 out of 13 patients who died within two years of onset the lupus was judged to be active, while this was true in only eight out of 19 patients who died later. Six of the seven vascular deaths occurred later than two years from onset, while only nine of 26 renal "deaths" occurred before two years; deaths from infections (n = 13) were distributed equally. Despite this and aggressive treatment of active disease, the principal cause of actual death was uncontrolled lupus.     

Twice-a-day quadruple therapy for eradication of Helicobacter pylori in the elderly

BACKGROUND: Midday and evening twice-a-day quadruple therapy appears to be the most effective therapy for Helicobacter pylori infection in Northern Sardinia, a site where antibiotics resistance is common. Aim: The objective of our study was to estimate the efficacy, side-effects, and compliance of a quadruple therapy containing esomeprazole in a group of dyspeptic elderly patients. PATIENTS AND METHODS: Consecutive elderly patients positive for H. pylori infection and not previously treated for eradication were enrolled. Therapy consisted of esomeprazole 20 mg, tetracycline 500 mg, metronidazole 500 mg, and bismuth subcitrate tablets 240 mg, all twice-a-day with the midday and evening meals, for 10 days. Efficacy was evaluated using 13C-urea breath testing. Compliance was assessed after completing treatment and at follow up. Side effects were graded based on daily activities. RESULTS: Ninety-five dyspeptic patients (range 65-81 years), 52 men and 43 women, were enrolled. The intention-to-treat cure rate was 91% (81 of 89; 95% CI = 88-99%) and, 95% (81 of 85; 95% CI = 83-96%) per-protocol analysis. Compliance was excellent. Mild-moderate side effects occurred in 27 patients. CONCLUSIONS: Esomeprazole containing quadruple therapy was highly successful for initial eradication of H. pylori in elderly patients.     

Ultrasound-guided fine needle aspiration of retroperitoneal, abdominal and pelvic lymph nodes. Diagnostic reliability.

A retrospective analysis was done of 37 ultrasonically guided fine needle aspirations (US-FNAs) from retroperitoneal, abdominal and pelvic lymph nodes. The cytologic examination diagnosed 15 cases of malignant and 13 of tuberculous lymphadenopathy. The aspirate was normal in the remaining nine patients. On further workup of the last group, five patients turned out to have false-negative cytology. Of them, two had neoplasms, another two had tuberculosis, and one had sarcoidosis. The neoplastic disorders consisted of 7 lymphomas, 5 secondary carcinomas, 2 seminomas and 1 carcinoid tumor. The diagnostic specificity was 100% and the sensitivity 85%. Neither major nor minor complications were encountered in these patients. US-FNA is safe, highly specific and sensitive in diagnosing malignant and tuberculous lymphadenopathy.     

Serological Indicators of Helicobacter pylori Infection in Adult Dyspeptic Patients and Healthy Blood Donors

The levels of IgM, IgG and IgA antibodies reacting with two Helicobacter pylori antigens (glycine acid extract (GE) and a recombinant CagA protein) were determined in the sera from adult dyspeptic patients, positive (H.p.⁽⁺⁾) or negative (H.p.^(-)) for H. pylori urease/culture, and from healthy blood donors. All sera were also examined against GE by Western blot (immunoblot) technique. Similar levels of anti-GE IgG were detected in the sera from all H.p.⁽⁺⁾ and almost all H.p.^(-) patients and from over 40% of the healthy volunteers. In contrast, higher levels of anti-GE IgA were found in the sera from patients than that from healthy subjects, although such antibodies were not detected in the sera from 30% of the H.p.⁽⁺⁾ patients. In general, our results suggest that a combination of ELISA and immunoblot may be more sensitive in the detection of H. pylori infection in dyspeptic patients than the examination of biopsy specimens by culturing or histology.     

Eradication of Helicobacter pylori infection in the management of patients with dyspepsia and non-ulcer dyspepsia.

Although H. pylori infection has been recognized as a major etiological agent for the development of chronic active gastritis, duodenal ulcer and benign non-NSAID related gastric ulcer, its role in the development of symptoms in patients with dyspepsia remains uncertain. Results from population-based epidemiological studies have been conflicting regarding a causal link between H. pylori infection and dyspepsia. Abnormalities in gastric acid secretion may exist in some dyspeptic patients. Whether disordered gastric motility seen in dyspeptic patients is related to the infection is not clear based on the results in the literature. Numerous clinical trials have been undertaken to eradicate H. pylori infection and improve the symptoms in dyspeptic patients; however, the results have been discrepant between studies. Many published studies suffer from methodological problems that have made interpretation difficult. Large, well-conducted, randomized, placebo-controlled, clinical trials with long-term follow-up are needed to justify the beneficial effect of H. pylori eradication treatment in dyspeptic patients seen in some small studies. H. pylori eradication therapy is cost-effective in H. pylori-infected dyspeptic patients although this benefit may take a long time to accrue, especially in younger patients.     

Liver Transplantation in Man—III,Studies of Liver Function,Histology, and Immunosuppressive Therapy

The experience gained from 13 hepatic transplant operations is described, with particular reference to the findings in nine patients who survived the immediate operative period. A major problem was found to be infection. Fulminant pneumonia caused death in two adults, at a time when liver function was virtually normal. Infection related to bile fistula and sepsis may be overcome by an improved method of biliary drainage by cholecyst-dochostomy, which was carried out in the last two patients. Jaundice in the second week due to rejection was observed in several patients. The striking histological change was centrilobular cholestasis. The jaundice, which was not prevented by administration of antilymphocyte globulin, was rapidly controlled by temporarily increasing die dose of prednisone. One patient who survived for four and a half months and who had a poor tissue match subsequently developed chronic rejection with progressive cholestatic jaundice. Five of the patients were able to go home and at time of publication two are alive and well 14 and 20 weeks after treatment.