Systemic inflammatory mediators and cystic fibrosis genotype.

Morbidity and mortality in cystic fibrosis patients is mainly attributed to pulmonary infection and inflammation. Chemokines play a pivotal role in the inflammatory process. Although genotype-phenotype correlation in cystic fibrosis patients has been defined, a clear relationship between the defect in the cystic fibrosis transmembrane regulator (CFTR) gene and pulmonary inflammation has not been established. The aim of this study was to assess whether serum chemokines levels in cystic fibrosis patients correlate with genotype and pulmonary function tests, as well as with other clinical characteristics. Serum levels of interleukin-8, RANTES, and monocyte chemoattractant protein-1 were measured in 36 cystic fibrosis patients grouped according to their genotype. Group A included 25 patients who carried two mutations associated with a pathological sweat test and pancreatic insufficiency (deltaF508, W1282X, G542X, N1303K, S549R). Group B included 11 compound heterozygote patients who carried one mutation known to cause mild disease with borderline or normal sweat test and pancreatic sufficiency (3849+10kb C to T, 5T). Associations between chemokine levels, genotype, pulmonary function, Pseudomonas aeruginosa colonization, age, sweat chloride level, and pancreatic and nutritional status were examined. Mean interleukin-8 and monocyte chemoattractant protein-1 levels were significantly higher in group A than group B (11.4 +/- 2.1 pg/ml vs. 5 +/- 0.9 pg/ml and 157 +/- 16 pg/ml vs. 88.8 +/- 16.4 pg/ml, respectively) (P < 0.01). No difference in RANTES levels were found between groups. interleukin-8 levels were inversely related to forced expiratory volume in 1 s (r = -0.37, P < 0.02), while there was no association between the latter and RANTES and monocyte chemoattractant protein-1 levels. The Pseudomonas colonization rate was higher among group A patients than group B (88% vs. 40%, P < 0.01). No relationship was found between measured chemokines and age, sweat chloride levels, and pancreatic and nutritional status. Our study demonstrates an association between interleukin-8, forced expiratory volume, and cystic fibrosis genotype. Hence, elevated interleukin-8 serum levels could serve as an indicator of an early inflammatory process and encourage the initiation of anti-inflammatory treatment.

Antibiotic prophylaxis of bacterial infections in cirrhotic inpatients: a meta-analysis of randomized controlled trials.

BACKGROUND: Antibiotic prophylaxis has been reported to decrease bacterial infections and fatality rates in inpatients with cirrhosis. We performed a systematic review to evaluate the efficacy of antibiotic prophylaxis in inpatients with cirrhosis, regardless of the underlying risk factors that led to hospital admission. METHODS: A comprehensive literature search strategy was performed including the Cochrane Library, Embase, Medline, a manual search of bibliographic references, and contacting the authors of each included trial. We included any randomized clinical trial comparing different types of antibiotic prophylaxis with placebo or no intervention in inpatients with cirrhosis. Two reviewers independently applied the selection criteria to all identified references, appraised the methodological quality of each trial and extracted the relevant data. Relative risks and 95% confidence intervals were estimated using the fixed effect model. A test of heterogeneity and a funnel plot were performed and an intention-to-treat approach was used for the outcome measures. RESULTS: Nineteen randomized trials were identified, 13 of which were included in the review. A significant beneficial effect on mortality (RR: 0.70; 95% CI: 0.56, 0.89) and prevention of bacterial infections (RR: 0.39; 95% CI: 0.32, 0.48) was observed, regardless of the underlying risk factors. Few adverse events were reported and there was no heterogeneity between studies. We identified a funnel plot asymmetry for the included trials. CONCLUSIONS: Antibiotic prophylaxis for inpatients with cirrhosis is efficacious in reducing the number of deaths and bacterial infections regardless of the underlying risk factors.

Hemodynamic effects of tracheal administration of vasopressin in dogs.

BACKGROUND: Intravenous administration of vasopressin during cardiopulmonary resuscitation (CPR) has been shown to be more effective than optimal doses of epinephrine. Earlier studies had been performed on a porcine model, but pigs produce lysine vasopressin hormone, while humans and dogs do not. This study was designed to compare the effects of tracheal vasopressin with those of NaCl 0.9% (placebo) on haemodynamic variables in a dog model. METHODS: Five dogs were allocated to receive either vasopressin 1.2 U/kg or placebo (10 ml of NaCl 0.9%) via the tracheal route after being anesthetized and ventilated. Haemodynamic variables were determined and arterial blood gases were measured. RESULTS: All animals of the vasopressin group demonstrated a significant increase of the systolic (from 135+/-7 to 165+/-6 mmHg, P<0.05), diastolic (from 85+/-10 to 110+/-10 mmHg, P<0.05) and mean blood pressure (from 98.5+/-3 to 142.2+/-5, P<0.05). Blood pressure rose rapidly and lasted for more than an hour (plateau effect). Heart rate decreased significantly following vasopressin (from 54+/-9 to 40+/-5 beats per min, P<0.05) but not in the placebo group. These changes were not demonstrated with placebo injection. CONCLUSION: Tracheal administration of vasopressin was followed by significantly higher diastolic, systolic and mean blood pressures in the vasopressin group compared with the placebo group. Blood gases remained unchanged in both groups. Vasopressin administered via the trachea may be an acceptable alternative for vasopressor administration during CPR, when intravenous access is delayed or not available, however, further investigation is necessary.

Departmental consumption of antibiotic drugs and subsequent resistance: a quantitative link.

OBJECTIVE: To look for a quantitative model linking departmental consumption of antibiotic drugs to the subsequent isolation of resistant hospital-acquired coliform pathogens. MATERIALS AND METHODS: Included in the study were all patients with hospital-acquired bloodstream infections caused by a coliform pathogen, detected in six departments of internal medicine of one university hospital during the period 1991-1996, who had not been hospitalized in the month before the infection (n = 394). Departmental consumption of antibiotics in the year before the infection [expressed as defined daily dosages (DDD)/100 patient days], antibiotic treatment given to the individual patient before the infection, the day of hospital stay on which the infection occurred, and the department and the calendar year were all included in a logistic model to predict the isolation of a resistant pathogen. We looked at five drugs: gentamicin, amikacin, cefuroxime, ceftazidime and ciprofloxacin. RESULTS: Five logistic models were fitted for the resistance to each of the antibiotic drugs. The multivariable-adjusted odds ratios for a pathogen resistant to the specific antibiotic were 1.03 [95% confidence interval (CI) 0.70-1.50] for gentamicin, 1.80 (95% CI 1.00-3.24) for amikacin, 1.12 (95% CI 1.02-1.23) for cefuroxime, 1.45 (95% CI 1.19-1.76) for ceftazidime and 1.06 (95% CI 0.57-1.97) for ciprofloxacin, per 1 DDD/100 patient days. CONCLUSIONS: The departmental consumption of cephalosporin drugs and amikacin in six autonomous departments of medicine in the same hospital was associated with a measurable and statistically significant increase in the probability of infection caused by a resistant pathogen.

Excess mortality in women with hospital-acquired bloodstream infection.

PURPOSE: We examined the outcomes of bloodstream infection in men and in women and whether any sex-related differences were explained by underlying disorders, severity of disease, or clinical management. SUBJECTS AND METHODS: Using a prospectively collected database, we compared in-hospital mortality in men and women. We used multivariable logistic regression analysis to test whether sex-related differences could be due to potential confounders. RESULTS: Of 4250 patients with bloodstream infections, 1750 (41%) had hospital-acquired infections. The overall case fatality was 31% (625 of 2032) in women and 29% (631 of 2218, P = 0.1) in men. However, 43% (325/758) of the women with hospital-acquired infections died, compared with 33% (327/992) of the men (P = 0.0001). In a multivariate analysis, female sex was associated with greater mortality in patients with hospital-acquired infections (odds ratio = 1.7; 95% confidence interval: 1.1 to 2.6). The excess mortality in women was mainly seen in patients with major underlying disorders (fatality rate of 45% [234 of 525] in women vs. 32% in men [234 of 743, P = 0.0001). CONCLUSIONS: Mortality in women with hospital-acquired bloodstream infections is substantially greater than in men. The excess mortality was concentrated in women with severe underlying disorders, suggesting that sepsis might have accentuated differences in the outcome of underlying disorders in women.

Hospitalization for early bonding of the genetic mother after a surrogate pregnancy: report of two cases.

BACKGROUND: In surrogate pregnancies the genetic parents have little opportunity for early bonding to their infant, either prenatally (in utero) or in the immediate postnatal period. The purpose of this article is to describe a new method for encouraging early parent-infant bonding after surrogate pregnancy by hospitalizing the genetic mother in the maternity ward immediately after the delivery. METHODS: Two genetic mothers were hospitalized in the maternity ward (rooming-in system) at the Rabin Medical Center in Israel immediately after delivery of their infants by surrogate arrangement. The first birth was a singleton pregnancy with vaginal delivery and the second, a twin pregnancy with delivery by cesarean section. The genetic parents were counseled by a social worker from the adoption agency, starting 3 months before the estimated date of delivery. The parents were referred to the hospital social worker before the delivery. To assess attachment, we observed the parents' behavior toward their children during two daily 15-minute periods of free, unstructured interaction. RESULTS: The parents showed good primary caregiving functions and established affective verbal and physical contact with the infants. They began to recognize the infants' needs and temperament, and exhibited an aura of self-confidence during their interactions. All expressed satisfaction with the method at discharge and reported on reduction of their fears about returning home with the infants. CONCLUSIONS: We believe that early hospitalization of the genetic mother in a surrogate delivery may be desirable to establish good and safe early mother-infant bonding, and that it should be considered for adoption as regular hospital policy. Further randomized studies with larger samples over the long term are warranted.

Relationship between Helicobacter pylori CagA status and colorectal cancer.

OBJECTIVES: Infection with Helicobacter pylori, particularly with strains positive for CagA protein, increases the risk of gastric adenocarcinoma. Few studies have explored the possible association between H. pylori infection and colorectal cancer. This study evaluated whether the seroprevalence of CagA in H. pylori-infected patients affected risk for colorectal cancer independently of H. pylori status. METHODS: In this study, we tested serum IgG antibodies against H. pylori (ELISA) and CagA protein (Western blot assay) in 67 patients with colorectal adenocarcinoma, 36 with gastric adenocarcinoma, 47 with other malignancies (cancer controls), and 45 hospitalized for transesophageal echocardiography (TEE controls). Colonic cancer and gastric cancer patients with H. pylori infection were compared to each control group and to the pooled controls using simple and adjusted analyses. RESULTS: H. pylori infection was noted in 50 colon cancer patients, 31 gastric cancer patients, 31 cancer controls, and 32 TEE controls. In all, 41 (82%), 29 (94%), 11 (35%), and 13 (41%), respectively, of these H. pylori-positive sera expressed CagA reactivity (p < 0.001 for all pairwise comparisons between cases and controls). In the adjusted analysis, infection with H. pylori CagA+ compared to H. pylori CagA- was associated with increased risk for colorectal adenocarcinoma (odds ratio = 10.6; 95% CI = 2.7-41.3; p = 0.001) and gastric adenocarcinoma (odds ratio = 88.1; 95% CI = 6.3-1229.2; p = 0.001). CONCLUSIONS: Among patients infected with H. pylori, CagA+ seropositivity is associated with increased risk for both gastric and colonic cancer. This finding should stimulate additional research into the role of cagA+ H. pylori infection in the development of colorectal cancer.

Relevance of CagA positivity to clinical course of Helicobacter pylori infection in children.

A potential virulence determinant of Helicobacter pylori is the cagA gene product. To determine the relevance of the expression of CagA to the clinical picture and outcome of H. pylori infection in children, we examined 104 consecutive children diagnosed with H. pylori infection. Serum samples were collected to test for the presence of immunoglobulin G (IgG) anti-CagA antibodies. Forty-five patients (43%) had antibodies to the CagA protein (group I), and 59 did not (group II). Seropositive patients had a longer prediagnostic history of abdominal pain (P = 0.02), more severe abdominal pain (defined as ulcer pain) (P = 0.05), a higher prevalence of duodenal ulcer (38 versus 7%; P<0.01), more active chronic gastritis (82 versus 32%; P<0.001), and a higher titer of serum IgG anti-H. pylori antibodies (P<0.001). Ninety percent of the patients were monitored for 27+/-18 months. On multivariate analysis, CagA-negative patients had a 3.8-fold-higher chance of achieving a disease-free state than CagA-positive patients (95% confidence interval, 1.5- to 9.5-fold). We conclude that infection with CagA-producing strains of H. pylori is a risk factor for severe clinical disease and ongoing infection.

The role of Helicobacter pylori and gastritis in children with recurrent abdominal pain.

BACKGROUND: Recurrent abdominal pain is a common pediatric diagnostic problem. Endoscopy is sometimes performed as part of the evaluation. Although gastritis and/or Helicobacter pylori infection is often present, it is not known if they contribute to the symptomatology. OBJECTIVES: To evaluate the role of either gastritis or H. pylori infection in the symptomatology of children with RAP. PATIENTS AND METHODS: We retrospectively studied two groups of patients, 70 children in each, who had undergone endoscopy. One group was evaluated endoscopically for RAP and the other was a heterogeneous group that underwent endoscopy for indications other than RAP. Biopsies were taken during endoscopy and Giemsa staining was performed for the presence of H. pylori. Triple therapy was given as indicated, and the children were followed for an average of 6 months. RESULTS: Microscopic gastritis was diagnosed in 39 patients (55.7%) of the RAP group and in 31 of the heterogeneous group (44.2%) (NS), and H. pylori was found in 32 patients of the RAP group and in 16 of the heterogeneous group (45.7% vs. 22.8%, P < 0.01). All children with H. pylori, except one in the heterogeneous group, had accompanying gastritis. On the other hand, gastritis without H. pylori infection was seen in 7 children in the RAP group and in 15 of the other. Endoscopy revealed macroscopic abnormalities in 52 of the 70 children with microscopic gastritis. There was a clinical improvement after triple therapy in 28 of 33 children with H. pylori-associated gastritis (84.85%), in 4 of 8 children with gastritis unassociated with H. pylori (50%), and in 8 of 15 without gastritis or H. pylori (53.3%) (P < 0.01 between the H. pylori-associated gastritis and each of the other groups). CONCLUSIONS: H. pylori infection and gastritis may be associated with RAP in a selected subgroup of children. We recommend a complete work-up, including endoscopy and invasive or non-invasive diagnostic modalities for H. pylori, and treatment of the infection.

Toxicity of adjuvant high-dose interferon-alpha-2b in patients with cutaneous melanoma at high risk of recurrence.

Interferon-alpha-2b (INF-alpha-2b) has been approved by the FDA as adjuvant treatment for patients with melanoma at high risk of recurrence. INF-alpha-2b is administered at 20 MU/m2/day IV, 5 days per week for 4 weeks, and then 10 MU/m2/day SC, three times weekly for 48 weeks. We investigated the toxicity of this protocol in 30 patients between June 1996 and February 1998. An intensive toxicity evaluation program was developed to monitor side effects. During both induction and maintenance phases, 60% of patients required a dose delay and/or reduction. Twenty percent were unable to complete the treatment plan, and 53% tolerated at least 80% of the scheduled dose. The frequently reported toxicity during induction included constitutional symptoms, myelosuppression, and hepatotoxicity. All were reversible on cessation of treatment or dose modification. During maintenance, toxicity included thyroid dysfunction, hypertriglyceridemia, retinopathy and a combination of mood disturbances, memory loss, cognitive slowing and impaired executive function. Administration of high-dose INF-alpha-2b is feasible, with close patient monitoring.

Pregnancy outcome in patients with insulin dependent diabetes mellitus and diabetic nephropathy treated with ACE inhibitors before pregnancy.

The preconception and intrapregnancy parameters that are relevant to outcome in women with insulin dependent diabetes mellitus (IDDM) and diabetic nephropathy remain controversial. We analyzed the types and frequencies of maternal and neonatal complications in 24 IDDM patients with diabetic nephropathy (24 pregnancies), all with preserved to mildly impaired renal function. All patients received treatment with captopril for at least six months prior to planned pregnancy and were maintained under strict glycemic control from at least three months before pregnancy to delivery. A successful pregnancy outcome (live, healthy infant without severe handicaps two years after delivery) was observed in 87.5% of the patients. Preexisting hypertension was the only parameter found to be significantly predictive of an unsuccessful outcome (p = 0.0004). We conclude that in patients with IDDM complicated by diabetic nephropathy, pre-pregnancy captopril treatment combined with strict glycemic control offers a prolonged protective effect against possible renal deterioration and probably improves pregnancy outcome.

Association between mitral annulus calcification and carotid atherosclerotic disease.

BACKGROUND AND PURPOSE: It has been established that mitral annulus calcification (MAC) is an independent predictor of stroke, though a causative relationship was not proved, and that carotid artery atherosclerotic disease is also associated with stroke. The aim of this study was to determine whether there is an association between the presence of MAC and carotid artery atherosclerotic disease. METHODS: Of the 805 patients in whom the diagnosis of MAC was made by transthoracic echocardiography between 1995 and 1997, 133 patients (60 men and 73 women; mean age, 74.3+/-8 years; range, 47 to 89 years) underwent carotid artery duplex ultrasound for various indications; the study group comprised these patients. They were compared with 129 age- and sex-matched patients without MAC (57 men and 72 women; mean age, 73.6+/-7 years; range, 61 to 96 years) who underwent carotid artery duplex ultrasound during the same period for the same indications. MAC was defined as a dense, localized, highly reflective area at the base of the posterior mitral leaflet. MAC was considered severe when the thickness of the localized, highly reflective area was > or =5 mm on 2-dimensional echocardiography in the 4-chamber view. Carotid artery stenosis was graded as follows: 0%, 20%, 40%, 60%, 80%, and 100%. RESULTS: Compared with the control group, the MAC group showed a significantly higher prevalence of carotid stenosis of > or =40% (45% versus 29%, P=0.006), which was associated with > or =2-vessel disease (23% versus 10%, P=0.006) and bilateral carotid artery atherosclerotic disease (21% versus 10%, P=0.011). Severe MAC was found in 48 patients. More significant differences were found for the severe MAC subgroup (for carotid stenosis of > or =40%) in rates of carotid artery atherosclerotic disease (58% versus 29%, P=0.001), and > or =2-vessel disease (31% versus 10%, P=0.001), in addition to bilateral carotid artery stenosis (27% versus 10%, P=0.004) and even bilateral proximal internal carotid artery stenosis (21% versus 8%, P=0.015). Furthermore, significant carotid artery atherosclerotic disease (stenosis of > or =60%) was significantly more common in the severe MAC subgroup than in the controls (42% versus 26%, P<0.05) and was associated with higher rates of > or =2-vessel disease (19% versus 7%, P=0.02) and bilateral carotid artery stenosis (17% versus 7%, P=0.05). On multivariate analysis, MAC and age but not traditional risk factors were the only independent predictors of carotid atherosclerotic disease (P=0.007 and P=0.04, respectively). CONCLUSIONS: There is a significant association between the presence of MAC and carotid artery atherosclerotic disease. MAC may be an important marker for atherosclerotic disease of the carotid arteries. This association may explain the high prevalence of stroke in patients with MAC.

Antenatal sonographic findings associated with scimitar syndrome.

Scimitar syndrome is a rare congenital anomaly that consists of secondary dextroposition in situs solitus, due to right pulmonary hypoplasia. The prenatal sonographic findings of this abnormality have not been previously described. We describe early sonographic findings in a fetus that included isolated cardiac dextroposition with normal abdominal situs, hydramnios and mild narrowing of the right pulmonary artery. Postnatally, the infant developed heart failure, and a right hypoplastic lung was found. Catheterization revealed collateral supply to the right lung arising from the descending aorta and anomalous drainage of right pulmonary veins to the inferior vena cava. The diagnosis of scimitar syndrome was therefore established. A coil embolization of arterial collaterals to the right lung was performed. Scimitar syndrome should be considered in a fetus with the sonographic findings of a right shift of the mediastinal structures, an intact diaphragm and narrow right pulmonary artery. This may allow early neonatal stabilization and treatment.

Helicobacter pylori and peptic disease in the pediatric patient.

The data accumulated on Helicobacter pylori infection in children suggests an important causative role of the organism in gastritis and peptic ulcer disease in this age group. The importance of eradication of H pylori in asymptomatic children in relation to its role in peptic disease and cancer in adults is debatable. This article describes the current data on bacteriologic features, pathologic spectrum, clinical significance, epidemiology, methods of diagnosis, and treatment of H pylori infection in children. Further studies will provide the information on the pathogenicity, mode of transfer, and optimal treatment of H pylori infection.

Serum pepsinogen I in childhood Helicobacter pylori gastritis: its relation to mucosal peptic activity.

Serum pepsinogen I (PG I) levels are raised in children with Helicobacter pylori gastritis. To ascertain if this is due to increased production or to increased secretion of pepsin by chief cells, we measured mucosal peptic activity in antrum and gastric body mucosal homogenates and correlated it to serum PG I levels in 122 children with and without H. pylori gastritis. In patients infected with H. pylori, mucosal peptic activity was decreased when compared to control and to children with non H. pylori gastritis. Serum PG I levels were increased (P < 0.001) and were inversely related to mucosal peptic activity (P < 0.01). These findings suggest that H. pylori can promote a leakage of pepsinogen into the circulation.

Colchicine enhances intestinal permeability in patients with familial Mediterranean fever.

OBJECTIVE: Colchicine therapy is complicated by frequent gastrointestinal adverse effects. METHODS: We compared intestinal permeability in 21 patients with familial Mediterranean fever on long-standing colchicine therapy (mean 5.8 years) and significant gastrointestinal complaints and 12 untreated patients and 14 healthy volunteers. The double probe (lactulose/mannitol) permeability test was performed using a hyperosmolar test solution (1580 mosmol) and the differential urinary recovery ratios were calculated. RESULTS: Familial Mediterranean fever patients on colchicine therapy had significantly higher lactulose/mannitol urinary excretion ratios (0.073) compared to untreated patients (0.035) and to healthy controls (0.021). Untreated familial Mediterranean fever patients had significantly greater urinary lactulose/mannitol recovery ratios than controls (P < 0.02). No correlation was found between the degree of enhanced permeability and the length of exposure to the drug or the severity of clinical symptoms. CONCLUSIONS: Intestinal permeability was significantly enhanced in patients with familial Mediterranean fever treated with colchicine.

Colchicine-induced lactose malabsorption in patients with familial Mediterranean fever.

Abdominal pain and diarrhea are frequent side effects of chronic colchicine therapy. Drug-induced lactose deficiency has been demonstrated in the experimental animal. Lactose malabsorption was assessed by the lactose breath test in 23 patients with familial Mediterranean fever (FMF) receiving colchicine for 0.25-15 years (mean 3.16). Twenty FMF patients not receiving colchicine and 38 non-FMF lactose malabsorbers served as controls. Patients receiving colchicine had a significantly higher percentage of lactose malabsorption (20/23, 87%) versus nontreated FMF patients (13/20, 65%; P < 0.05). Lactose intolerance was also more prevalent in colchicine-treated patients (17/23, 74%) versus nontreated FMF (5/20, 25%; P < 0.0005) and control lactose malabsorbers (16/38, 42%; P < 0.01). Of the 12 patients investigated before and 3 months after colchicine administration, 7 showed induction or aggravation of lactose malabsorption. The lactose-free diet resulted in partial improvement of symptoms. Colchicine induces significant lactose malabsorption in FMF patients and this is partially responsible for the gastrointestinal side effects of the drug.