Biomedical subjects

J Hammer

Publications and source records attributed to J Hammer.

At least 55 records · Page 3Linked to original sources

PubMed2001

Effect of jaw-thrust and continuous positive airway pressure on tidal breathing in deeply sedated infants.

OBJECTIVES: To examine the physiologic impact of the jaw-thrust maneuver or the administration of continuous positive airway pressure (CPAP) on tidal breathing in deeply sedated infants. STUDY DESIGN: Prospective, non-randomized study of infants undergoing elective fiberoptic bronchoscopy while sedated with intermittent doses of propofol. METHODS: Spontaneous tidal breathing was measured in the supine position by means of a spirometer attached to a bronchoscopy face mask. Tidal breaths were recorded under the following conditions: (1) neutral sniffing position, (2) jaw-thrust, (3) neutral sniffing position, and (4) CPAP of 5 cm H(2)O. Improvement was defined as a change of more than twice the coefficient of variation of repeated measurements of tidal volume and flows from baseline. RESULTS: Jaw-thrust increased tidal volume, minute ventilation, and peak tidal inspiratory and expiratory flows significantly in all 13 infants studied (mean +/- SEM age = 8 +/- 2 months). CPAP increased peak tidal inspiratory and expiratory flows by more than twice the coefficient of variation of baseline measurements in 6 patients and tidal volume and minute ventilation in 5 of 10 patients studied. CONCLUSION: Jaw-thrust and CPAP are effective techniques to improve ventilation of sedated infants undergoing interventions that compromise upper airway patency.

Bronchoscopy↗

PubMed2001

Identification of disease-specific genes in chronic pancreatitis using DNA array technology.

OBJECTIVE: To use DNA arrays to analyze the differential gene expression patterns in the normal pancreas and in pancreatic diseases. SUMMARY BACKGROUND DATA: Genome-wide gene expression analysis will provide new insights into gene function and cause of disease. METHODS: RNA was extracted from eight normal pancreatic specimens, eight specimens with chronic pancreatitis (CP), and eight pancreatic cancer (PCa) tissues. Poly A(+) RNA was purified, reverse-transcribed, and converted into cRNA using biotinylated nucleotides. The HuGeneFL DNA array containing 5,600 full-length human genes was used for analysis. RESULTS: First, normal pancreatic tissues were analyzed in comparison with a panel of other normal tissues (colon, liver, prostate, lung, lymph node). This analysis revealed 11 signature genes that were selectively expressed in the pancreas (e.g., pancreatic elastase-IIA). Comparison of the expression of 5,600 genes between the normal pancreas, CP, and PCa specimens showed that the expression of 34 genes was decreased in CP tissues compared with normal pancreatic tissues, and that the expression of all of these genes was simultaneously decreased in PCa. In addition, the expression of 157 genes was increased in CP tissues compared with the normal pancreas. Of those, 152 genes were simultaneously increased in PCa. Thus, only 5 of 5,600 genes were significantly overexpressed in CP compared with both normal pancreas and PCa. CONCLUSIONS: The majority of alterations observed in CP are present in PCa, and the number of genes whose expression is selectively deregulated in CP is surprisingly small. These results may provide new insight into the pathobiology of CP and help identify certain molecular alterations that might serve as targets for new diagnostic tools and disease-specific therapy.

Adult↗

PubMed2001

Nonulcer dyspepsia.

Therapy for nonulcer dyspepsia has largely been empiric because effective therapeutic agents are sparse and therapeutic trials show inconsistent results. The Cochrane collaboration has reviewed this matter and came to the conclusion that prokinetics and acid-suppression therapy might have a significant, although small, clinical benefit over placebo. Although the role of Helicobacter pylori in nonulcer dyspepsia is still a matter of controversy, one meta-analysis suggests that in H. pylori-positive dyspeptic patients, H. pylori eradication has a small but significant therapeutic benefit over a therapy that does not eradicate H. pylori. Other aspects of pathophysiology of nonulcer dyspepsia that have been studied in the past year include visceral hyperalgesia and abnormal sleep pattern. New studies have also investigated the clinical presentation of nonulcer dyspepsia and the possible reasons why some patients never consult a doctor whereas others do so frequently.

Journal Article↗

PubMed2001

Impact of chronic gastrointestinal symptoms in diabetes mellitus on health-related quality of life.

OBJECTIVES: Morbidity from GI symptoms in diabetes is considered to be high, but no studies have quantified the impact of GI symptoms in diabetes on health-related quality of life. We hypothesized that diabetics reporting increased GI symptoms would experience more impaired quality of life. METHODS: Subjects from the community with diabetes (n = 892) and outpatients with diabetes (n = 209) were recruited for this study. Subjects were divided into type 1 (diabetes diagnosed at age <30 yr and requiring insulin) and type 2. A validated questionnaire measuring GI symptoms and diabetes status and the Short Form-36 were completed. The results were compared with Australian normal data. GI symptom groups measured were frequent abdominal pain, bowel-related abdominal pain, reflux, dyspepsia, constipation, diarrhea, and fecal incontinence. RESULTS: There was a clinically significant decrease in quality-of-life scores in diabetics compared with population norms across all subscales. The impact on quality of life in diabetes was predominantly observed in type 2 diabetics. The quality-of-life scores in all subscales decreased markedly with increasing numbers of distinct GI symptom groups, and this was similar in community and outpatient diabetics. For all the Short Form-36 subscales, GI symptom groups were significantly (all p < 0.0001) associated with poorer quality of life in diabetes, independent of age, gender, smoking, alcohol use, and type of diabetes. CONCLUSIONS: GI symptoms impact negatively on health-related quality of life in diabetes mellitus.

Adult↗

PubMed2001

Helicobacter pylori infection is not associated with diabetes mellitus, nor with upper gastrointestinal symptoms in diabetes mellitus.

OBJECTIVE: The association between Helicobacter pylori (H. pylori) infection and diabetes mellitus is controversial. We aimed to determine the prevalence of H. pylori infection in patients with diabetes and nondiabetic controls, and assess whether H. pylori infection was associated with upper gastrointestinal (GI) symptoms in diabetes mellitus. METHODS: A total of 429 patients with type 1 (n = 49) or type 2 (n = 380) diabetes mellitus (48.6% women, mean age 60.7 yr) and 170 nondiabetic controls (34.7% women, mean age 60.4 yr) were evaluated. All subjects completed a validated questionnaire (the Diabetes Bowel Symptom Questionnaire) to determine upper GI symptoms, and a blood sample was tested for H. pylori infection using a validated ELISA kit (sensitivity 96%, specificity 94%). RESULTS: Seroprevalence of H. pylori was 33% and 32%, respectively, in patients with diabetes and controls (NS). In both groups, the seroprevalence was significantly higher in men than in women; 39% vs 25% (p = 0.002) in diabetic patients, and 40% vs 20% (p = 0.01) in controls. Patients with diabetes had a significantly higher prevalence of early satiety (OR = 2.30), fullness (OR = 3.15), and bloating (OR = 1.50) compared with controls. Upper GI symptoms were present in 49% of H. pylori-positive and 53% of H. pylori-negative patients with diabetes (OR = 0.87, 95% CI 0.58-1.31, p = 0.56). H. pylori infection was also not associated with any of the individual upper GI symptoms before or after adjustment for potential confounding factors. However, patient age and female gender were identified as independent risk factors for upper GI symptoms. Smoking was a risk factor for bloating and early satiety. CONCLUSIONS: H. pylori infection appears not to be associated with diabetes mellitus or upper GI symptoms in diabetes mellitus.

Diabetes Complications↗

PubMed2001

Psychological distress is linked to gastrointestinal symptoms in diabetes mellitus.

OBJECTIVE: Gastrointestinal (GI) symptoms are common in patients with long-standing diabetes mellitus, but the pathogenesis is controversial. We aimed to determine if GI symptoms are linked to psychological distress in diabetes. METHODS: A consecutive sample of outpatients with diabetes mellitus (n = 209) and a random sample of community diabetics (n = 892) completed a validated questionnaire measuring GI symptoms, the Hospital Anxiety and Depression (HAD) Scale for anxiety and depression, and the Eysenck short neuroticism scale. RESULTS: Overall, 42% reported one or more GI symptoms: bloating, abdominal pain, loose stools, and urgency were most common. The mean HAD and neuroticism scores were significantly higher for most GI symptoms (11 of 14, all p < 0.05), and a dose-response relationship was observed. GI symptoms were, in general, approximately twice as frequent in cases with anxiety or depression (HAD > or = 11). Anxiety, depression, and neuroticism were each independently associated with the number of GI symptoms, adjusting for age, gender, duration and type of diabetes, and self-reported glycemic control. CONCLUSIONS: Increased levels of state anxiety and depression and neuroticism are associated with upper and lower GI symptoms in diabetes mellitus. It is uncertain whether psychological distress is causally linked to symptoms, or whether GI symptoms per se increase levels of anxiety and depression.

Anxiety↗

PubMed2001

Effect of airway opening manoeuvres on thoraco-abdominal asynchrony in anaesthetized children.

Thoraco-abdominal asynchrony is frequently encountered during inhalation anaesthesia in children with adenotonsillar hypertrophy causing an upper airway obstruction. The study goal was to evaluate the impact of different airway opening manoeuvres on thoraco-abdominal asynchrony as a measure of airway obstruction. Thirty anaesthetized children (aged 2-8 yrs; sevoflurane 3% in 50% oxygen/nitrous oxide) were studied prior to elective adenotonsillectomy using respiratory inductance plethysmography to record ribeage and abdominal wave forms as a basis for calculation of the phase angle. Five airway situations were compared: 1) baseline (unsupported mandible); 2) chin lift; 3) chin lift combined with continuous positive airway pressure of 10 cmH2O; 4) jaw thrust; and 5) jaw thrust combined with continuous positive airway pressure of 10 cmH2O. Three children had complete upper airway obstruction at baseline and were excluded from the study. With chin lift, thoraco-abdominal asynchrony improved in three patients, worsened in three patients and was unchanged in 21 patients. Additional continuous positive airway pressure during chin lift did not markedly reduce thoraco-abdominal asynchrony (phase angle 89 +/- 43 , p = 0.33). Jaw thrust resulted in a significant decrease of the phase angle (from 106 +/- 53 at baseline to 65 +/- 49 , p < 0.01); when combined with continuous positive airway pressure, no further effect on thoraco-abdominal asynchrony was found (72 +/- 44). In anaesthetized children with adenotonsillar hypertrophy, airway opening manoeuvres have distinct effects on thoraco-abdominal asynchrony. Delivery of continuous positive airway pressure and jaw thrust can be the first airway opening manoeuvres to improve breathing patterns. Chin lift without additional continuous positive airway pressure should be used with caution in these patients because it may convert partial into almost complete airway obstruction.

Adenoidectomy↗

PubMed2000

Oligodendrocytes in aging mice lacking myelin-associated glycoprotein are dystrophic but not apoptotic.

Although MAG-null mice myelinate relatively normally except for subtle structural abnormalities in the periaxonal region of myelin sheaths, they develop more severe pathological changes as they age. The purpose of this study was to further define the biochemical aspects of CNS pathology caused by an absence of MAG. Proteins associated with myelin and oligodendrocytes were quantified by densitometry of western blots in whole brain homogenates, as well as in isolated myelinated axons and myelin. Neither myelin yields, nor levels of myelin basic protein and proteolipid protein, were decreased in comparison to control levels in 14-month-old MAG-null mice. On the other hand, 2',3'-cyclic nucleotide 3'-phosphodiesterase (CNPase) and the 120 kD neural cell adhesion molecule (N-CAM) were substantially reduced in whole brain, myelinated axons, and myelin. Tubulin, Na(+)K(+)ATPase and Fyn tyrosine kinase were also reduced significantly in myelin-related fractions, but not in whole brain homogenate. The decreased levels of these proteins suggest pathological abnormalities in oligodendrocytes. Furthermore, significant reductions of CNPase and 120 kD NCAM were also present at 2 months, indicating that the oligodendroglial abnormalities begin at a relatively early age. Neither TUNEL assays nor multiplex RT-PCR for mRNAs of apoptosis-related proteins in the aging MAG-null mice provided evidence for apoptotic oligodendrocytes. These biochemical findings suggest oligodendroglial damage in MAG-null mice and support the morphological observations pointing to a progressive "dying-back oligodendrogliopathy" as a consequence of MAG deficiency.

2',3'-Cyclic-Nucleotide Phosphodiesterases↗

PubMed2000

Home mechanical ventilation in children: indications and practical aspects.

An increase in the number of paediatric patients dependent on long-term or home mechanical ventilation has led to growing interest in this topic. Primary care physicians are becoming increasingly involved in teamwork with paediatric intensivists and pulmonologists in the care of such children. There are many causes of chronic respiratory failure and different options for provision of ventilatory support at home. Awareness of the possibilities of long-term ventilation is essential in organising discussion of these therapeutic modalities with chronically ill children and their parents prior to any respiratory compromise precluding an elective decision. Home ventilation offers the best option for these children's psychosocial development, social integration and quality of life. Many ventilator-dependent children can attend school. The main problems of paediatric home ventilation are its negative psychosocial impact on family life, limited home care resources, the financial burden, differences in ethical perception by the local community and the fact that the equipment is usually designed for adults. Unfortunately, only scant data are available on the number of home-ventilated children in Switzerland. The creation of a patient organisation dedicated to support of families with ventilator- or technology-dependent children may be helpful in mastering some of these problems.

Adult↗

PubMed2000

In vitro and in vivo induction of a Th cell response toward peptides of the melanoma-associated glycoprotein 100 protein selected by the TEPITOPE program.

The melanoma-associated Ag glycoprotein 100 was analyzed by the T cell epitope prediction software TEPITOPE. Seven HLA-DR promiscuous peptides predicted with a stringent threshold were used to load dendritic cells (DC), and induction of a proliferative response was monitored. PBMC of all nine donors including two patients with malignant melanoma responded to at least one of the peptides. The proliferative response was defined as a Th response by the selective expansion of CD4(+) cells, up-regulation of CD25 and CD40L, and IL-2 and IFN-gamma expression. Peptide-loaded DC also initiated a T helper response in vivo (i.e., tumor growth in the SCID mouse was significantly retarded by the transfer of PBMC together with peptide-loaded DC). Because the use of the TEPITOPE program allows for a prediction of T cell epitopes; because the predicted peptides can be rapidly confirmed by inducing a Th response in the individual patient; and because application of peptide-loaded DC suffices for the in vivo activation of helper cells, vaccination with MHC class II-binding peptides of tumor-associated Ags becomes a feasible and likely powerful tool in the immunotherapy of cancer.

Adoptive Transfer↗

PubMed2000

[Polyethylene glycol (Macrogol)--an overview of its use in diagnosis and therapy of gastrointestinal diseases].

The pharmacological rationale for the use of polyethylene glycol (PEG) in gastroenterology is its inverse relation between molecular mass and intestinal absorbability, with practically no intestinal absorption at molecular masses exceeding 3000, its lack of intestinal enzymatic degradation or bacterial metabolism, and its water binding capacity. PEG is used as a nonabsorbable marker in the evaluation of small intestinal and colonic absorption and secretion, as a marker for intestinal permeability studies, as an essential component of colonic lavage solutions used for the preparation of the colon for diagnostic and therapeutic interventions, and for the treatment of fecal impaction or chronic constipation. Since PEG has been used for decades, there is extensive data documenting its safety in short term use. Although animal experiments have also proved the safety of chronic PEG administration, the increasing use of PEG for the treatment of chronic constipation in the long term requires further surveillance to establish its safety.

Constipation↗

PubMed2000

Increased levels of platelet-derived growth factor in vitreous fluid of patients with proliferative diabetic retinopathy.

UNLABELLED: It is generally accepted that growth factors play an important role in the pathogenesis of proliferative diabetic retinopathy. Since platelet-derived growth factor AB (PDGF AB) is known to be involved in many angiogenetic and proliferative processes, it was the aim of our study to elucidate the role of PDGF AB in the angiogenetic process in proliferative diabetic retinopathy. We measured PDGF AB concentrations in the vitreous of 23 patients with proliferative diabetic retinopathy, 4 of them with additional rubeosis iridis as an indicator of very high vasoproliferative activity. Control measurements were done in 19 patients without diabetic or ischemic eye diseases and also in 4 non-diabetic patients with ischemic proliferative retinopathy with rubeosis iridis. To exclude PDGF remnants in the vitreous due to vitreous bleeding we additionally measured platelet factor 4 concentrations as a stable marker of activated thrombocytes in the vitreous. RESULTS: Significantly elevated concentrations of PDGF AB were found in the vitreous of patients with proliferative diabetic retinopathy, with higher levels in individuals with additional rubeosis iridis compared to controls. However, concentrations of PDGF AB were also elevated in ischemic non-diabetic retinopathy, supporting the concept that ischemia might be a strong stimulator of growth factor production in the retina. Platelet factor 4 was not detectable in any of the vitreous samples included in the study. In summary, our results indicate that the growth factor PDGF plays an important role in the pathogenesis of proliferative diabetic retinopathy, probably in synergistic action with other growth factors like IGF I, IGF II, VEGF and TNF alpha.

Body Fluids↗

PubMed2000

Epitope scanning using virtual matrix-based algorithms.

Protein sequence and expression databases (transcriptomes) contain the information required to identify epitopes capable of generating protective immune responses in humans. A key event in the initiation of an immune response against disease is the presentation of antigenic peptide epitopes to T cells by human leukocyte antigen (HLA) molecules. Computational filtering tools that allow the prediction of HLA/epitope interaction can be applied to sequence databases to select for candidate epitopes, thus minimising the subsequent amount of laboratory work. Here, the basic principles of epitope prediction and a summary of the available prediction approaches are presented, with a particular emphasis on the use of algorithms based on virtual HLA-II quantitative matrices, capable of predicting promiscuous HLA-II ligands.

Algorithms↗

PubMed2000

The motif for peptide binding to the insulin-dependent diabetes mellitus-associated class II MHC molecule I-Ag7 validated by phage display library.

The MHC class II molecule I-Ag7 is essential for the development of insulin-dependent diabetes mellitus (IDDM) in the non-obese diabetic (NOD) mouse but the requirements for peptide binding to I-Ag7 are still controversial. We have now isolated I-Ag7-binding phage from a large phage display library encoding random nonamer peptides. Ninety peptide-encoding regions of phage eluted from I-Ag7 were sequenced and >75% of the corresponding synthetic peptides bound to I-Ag7. Peptide alignment led to the identification of position-specific anchor residues. Hydrophobic (V and P) and positively charged (K) residues were highly enriched at P6 and positively charged (R and K), aromatic (Y) or hydrophobic (L) residues at P9. In addition, small amino acid residues (G and A) were enriched at P7 and G at P8. The primary anchors at P6 and P9 defining the phage-derived motif were present in most high-affinity I-Ag7-binding peptides from IDDM candidate antigens but only in < or =25% of peptides that were low-affinity binders or failed to bind to I-Ag7. A comparison of these results with the proposed motifs for peptide binding to I-Ag7 validates the one we have previously described.

Amino Acid Motifs↗

PubMed2000

Nonulcer dyspepsia.

New definitions of functional disorders in general and nonulcer dyspepsia in particular were published in the period of review. Although the definition of functional dyspepsia as persistent or recurrent unexplained upper abdominal pain or discomfort stayed essentially the same, new definitions of dyspepsia subgroups were introduced based on the predominant symptom; a reflux-like dyspepsia subgroup was not supported. It is hoped that these criteria, derived by a consensus among international experts in the field, will improve the reliability and the interpretability of future epidemiologic and interventional studies. A wide range of studies dealt with the role of putative etiological factors in functional bowel disorders including Helicobacter pylori, altered visceral sensation, or upper intestinal motility. Although eradication of H. pylori does not seem to relieve dyspepsia over placebo in recent studies of nonulcer dyspepsia, eradication of H. pylori has generally been advised because of suspected beneficial long-term effects (eg, treatment of misdiagnosed ulcer disease) that probably overweigh the potential risks.

Journal Article↗

PubMed2000

Advanced distal colonic lesions as predictors of advanced lesions in the proximal colon.

The characteristics of adenomas found during sigmoidoscopy have been suggested to predict synchronous adenomas in the proximal colon. Our aim was to examine whether the presence and characteristics of distal colonic lesions are associated with the presence and characteristics of lesions in the proximal colon. We performed a university hospital based case-control study with 3,268 consecutive subjects who received colonoscopy between January 1992 and December 1995. Subjects who had a history of colonic polyps, inflammatory bowel disease, intestinal resection, or had a contraindication against biopsies were excluded. Number size, and histologic characteristics of polyps in the distal and proximal colon were recorded. Advanced lesions were defined as neoplastic lesions with 1 or more of the following features: 1) > or = 1 cm diameter, and/or 2) villous histology, and/or 3) severe dysplasia or carcinoma, and/or 4) > or = 3 lesions. We found that 439 patients had neoplastic lesions in the distal colon only (61.3% with advanced lesions), 198 patients had lesions in the proximal colon only (55.1% advanced), and 197 had lesions in both the distal colon (74.6% advanced) and the proximal colon (55.8% advanced). Distal lesions were significantly more often advanced in patients with synchronous proximal lesions compared with patients with lesions in the distal colon only (odds ratio: 1.9; 95% confidence interval [CI]: 1.3-2.8; p < 0.001). The odds ratios for finding any neoplastic lesion in the proximal colon and an advanced proximal lesion, respectively, were 3.7 (2.6-5.3) (p < 0.001) and 2.2 (1.3-3.7) (p < 0.01) when a nonadvanced lesion was found in the distal colon, and 6.8 (5.3-8.7) (p < 0.001) and 6.7 (4.9-9.0) (p < 0.001) when an advanced lesion was found in the distal colon. Logistic regression analysis revealed number of distal polyps and villous histology as independent predictors of advanced lesions in the proximal colon; size and severe dysplasia were not independent predictors. In conclusion, characteristics of neoplastic lesions in the distal colon predict the presence and characteristics of lesions in the proximal colon.

Adenoma↗

PubMed1999

Diagnostic criteria for the irritable bowel syndrome.

The Rome criteria represent a consensus viewpoint based on currently available data, but their development certainly does not establish that the content is truly indicative of a specific disease process. There is a limit to the repertoire of gastrointestinal symptoms; because of the low specificity of symptoms, it is understandable that symptoms alone are unlikely to be accurate enough. However, in the absence of a reproducible and accepted biological marker, symptoms currently remain the primary means of identifying and recruiting patients for research. All diagnostic criteria will continue to be controversial until the pathophysiology of irritable bowel syndrome (IBS) is better understood and treatment more appropriately targeted to relevant disturbances. The aim of this review is to present the current Rome criteria and critically evaluate the arguments for and against the individual components being included as part of the criteria.

Colonic Diseases, Functional↗

PubMed1999

Cutting edge: identification of novel T cell epitopes in Lol p5a by computational prediction.

Although atopic allergy affects </=20% of the total population, the relationship between the protein structure and immunogenic activity of the allergens is still largely unknown. We observed that group 5 grass allergens are characterized by repeated structural motifs. Using a new algorithm, TEPITOPE, we predicted promiscuous HLA-DR ligands within the repeated motifs of the Lol p5a allergen from rye grass. In vitro binding studies confirmed the promiscuous binding characteristics of these peptides. Moreover, most of the predicted ligands were novel T cell epitopes that were able to stimulate T cells from atopic patients. We generated a panel of Lol p5a-specific T cell clones, the majority of which recognized the peptides in a cross-reactive fashion. The computational prediction of DR ligands might thus allow the design of T cell epitopes with potential useful application in novel immunotherapy strategies.

Allergens↗