Biomedical subjects

S Howell

Publications and source records attributed to S Howell.

At least 19 recordsLinked to original sources

PubMed2001

The 22 kDa component of the protein complex on the surface of Plasmodium falciparum merozoites is derived from a larger precursor, merozoite surface protein 7.

The gene coding for merozoite surface protein 7 has been identified and sequenced in three lines of Plasmodium falciparum. The gene encodes a 351 amino acid polypeptide that is the precursor of a 22-kDa protein (MSP7(22)) on the merozoite surface and non-covalently associated with merozoite surface protein 1 (MSP1) complex shed from the surface at erythrocyte invasion. A second 19-kDa component of the complex (MSP7(19)) was shown to be derived from MSP7(22) and the complete primary structure of this polypeptide was confirmed by mass spectrometry. The protein sequence contains several predicted helical and two beta elements, but has no similarity with sequences outside the Plasmodium databases. Four sites of sequence variation were identified in MSP7, all within the MSP7(22) region. The MSP7 gene is expressed in mature schizonts, at the same time as other merozoite surface protein genes. It is proposed that MSP7(22) is the result of cleavage by a protease that may also cleave MSP1 and MSP6. A related gene was identified and cloned from the rodent malaria parasite, Plasmodium yoelii YM; at the amino acid level this sequence was 23% identical and 50% similar to that of P. falciparum MSP7.

Amino Acid Sequence↗

PubMed2001

A genomewide scan for loci predisposing to type 2 diabetes in a U.K. population (the Diabetes UK Warren 2 Repository): analysis of 573 pedigrees provides independent replication of a susceptibility locus on chromosome 1q.

Improved molecular understanding of the pathogenesis of type 2 diabetes is essential if current therapeutic and preventative options are to be extended. To identify diabetes-susceptibility genes, we have completed a primary (418-marker, 9-cM) autosomal-genome scan of 743 sib pairs (573 pedigrees) with type 2 diabetes who are from the Diabetes UK Warren 2 repository. Nonparametric linkage analysis of the entire data set identified seven regions showing evidence for linkage, with allele-sharing LOD scores > or =1.18 (P< or =.01). The strongest evidence was seen on chromosomes 8p21-22 (near D8S258 [LOD score 2.55]) and 10q23.3 (near D10S1765 [LOD score 1.99]), both coinciding with regions identified in previous scans in European subjects. This was also true of two lesser regions identified, on chromosomes 5q13 (D5S647 [LOD score 1.22] and 5q32 (D5S436 [LOD score 1.22]). Loci on 7p15.3 (LOD score 1.31) and 8q24.2 (LOD score 1.41) are novel. The final region showing evidence for linkage, on chromosome 1q24-25 (near D1S218 [LOD score 1.50]), colocalizes with evidence for linkage to diabetes found in Utah, French, and Pima families and in the GK rat. After dense-map genotyping (mean marker spacing 4.4 cM), evidence for linkage to this region increased to a LOD score of 1.98. Conditional analyses revealed nominally significant interactions between this locus and the regions on chromosomes 10q23.3 (P=.01) and 5q32 (P=.02). These data, derived from one of the largest genome scans undertaken in this condition, confirm that individual susceptibility-gene effects for type 2 diabetes are likely to be modest in size. Taken with genome scans in other populations, they provide both replication of previous evidence indicating the presence of a diabetes-susceptibility locus on chromosome 1q24-25 and support for the existence of additional loci on chromosomes 5, 8, and 10. These data should accelerate positional cloning efforts in these regions of interest.

Chromosome Mapping↗

PubMed2001

Casein kinase I associates with members of the centaurin-alpha family of phosphatidylinositol 3,4,5-trisphosphate-binding proteins.

Mammalian casein kinases I (CKI) belong to a family of serine/threonine protein kinases involved in diverse cellular processes including cell cycle progression, membrane trafficking, circadian rhythms, and Wnt signaling. Here we show that CKIalpha co-purifies with centaurin-alpha(1) in brain and that they interact in vitro and form a complex in cells. In addition, we show that the association is direct and occurs through the kinase domain of CKI within a loop comprising residues 217-233. These residues are well conserved in all members of the CKI family, and we show that centaurin-alpha(1) associates in vitro with all mammalian CKI isoforms. To date, CKIalpha represents the first protein partner identified for centaurin-alpha(1). However, our data suggest that centaurin-alpha(1) is not a substrate for CKIalpha and has no effect on CKIalpha activity. Centaurin-alpha(1) has been identified as a phosphatidylinositol 3,4,5-trisphosphate-binding protein. Centaurin-alpha(1) contains a cysteine-rich domain that is shared by members of a newly identified family of ADP-ribosylation factor guanosine trisphosphatase-activating proteins. These proteins are involved in membrane trafficking and actin cytoskeleton rearrangement, thus supporting a role for CKIalpha in these biological events.

Actins↗

PubMed2001

The merozoite surface protein 6 gene codes for a 36 kDa protein associated with the Plasmodium falciparum merozoite surface protein-1 complex.

A complex of non-covalently bound polypeptides is located on the surface of the merozoite form of the human malaria parasite Plasmodium falciparum. Four of these polypeptides are derived by proteolytic processing of the merozoite surface protein 1 (MSP-1) precursor. Two components, a 22 and a 36 kDa polypeptide are not derived from MSP-1. The N-terminal sequence of the 36 kDa polypeptide has been determined, the corresponding gene cloned, and the protein characterised. The 36 kDa protein consists of 211 amino acids and is derived from a larger precursor of 371 amino acids. The precursor merozoite surface protein 6 (MSP-6) has been designated, and the 36 kDa protein, MSP-6(36). Mass spectrometric analysis of peptides released from the polypeptide by tryptic digestion confirmed that the gene identified codes for MSP-6(36). Antibodies were produced to a recombinant protein containing the C-terminal 45 amino acid residues of MSP-6(36). In immunofluorescence studies these antibodies bound to antigen at the parasite surface or in the parasitophorous vacuole within schizonts, with a pattern indistinguishable from that of antibodies to MSP-1. MSP-6(36) was present in the MSP-1 complex immunoprecipitated from the supernatant of in vitro parasite cultures, but was also immunoprecipitated from this supernatant in a form not bound to MSP-1. Examination of the MSP-6 gene in three parasite lines detected no sequence variation. The sequence of MSP-6(36) is related to that of the previously described merozoite surface protein 3 (MSP-3). The MSP-6(36) amino acid sequence has 50% identity and 85% similarity with the C-terminal region of MSP-3. The proteins share a specific sequence pattern (ILGWEFGGG-[AV]-P) and a glutamic acid-rich region. The remainder of MSP-6 and MSP-3 are unrelated, except at the N-terminus. Both MSP-6(36) and MSP-3 are partially associated with the parasite surface and partially released as soluble proteins on merozoite release. MSP-6(36) is a hydrophilic negatively charged polypeptide, but there are two clusters of hydrophobic amino acids at the C-terminus, located in two amphipathic helical structures identified from secondary structure predictions. It was suggested that this 35 residue C-terminal region may be involved in MSP-6(36) binding to MSP-1 or other molecules; alternatively, based on the secondary structure and coil formation predictions, the region may form an intramolecular anti-parallel coiled-coil structure.

Amino Acid Sequence↗

PubMed2001

The high molecular mass rhoptry protein, RhopH1, is encoded by members of the clag multigene family in Plasmodium falciparum and Plasmodium yoelii.

Malarial merozoite rhoptries contain a high molecular mass protein complex called RhopH. RhopH is composed of three polypeptides, RhopH1, RhopH2, and RhopH3, encoded by distinct genes. Using monoclonal antibody-purified protein complex from both Plasmodium falciparum and Plasmodium yoelii, peptides were obtained by digestion of RhopH1 and their sequence determined either by mass spectrometry or Edman degradation. In both species the genes encoding RhopH1 were identified as members of the cytoadherence linked asexual gene (clag) family. In P. falciparum the family members on chromosome 3 were identified as encoding RhopH1. In P. yoelii two related genes were identified and sequenced. One of the genes, pyrhoph1a, was positively identified as encoding RhopH1 by the peptide analysis and the other gene, pyrhoph1a-p, was at least transcribed. Genes in the clag family present in both parasite species have a number of conserved features. The size and location of the P. yoelii protein complex in the rhoptries was confirmed. The first clag gene identified on chromosome 9 was implicated in cytoadherence, the binding of infected erythrocytes to host endothelial cells; this study shows that other members of the family encode merozoite rhoptry proteins, proteins that may be involved in merozoite-erythrocyte interactions. We propose that the family should be renamed as rhoph1/clag.

Amino Acid Sequence↗

PubMed2001

An electro-active system of immuno-assay (EASI assay) utilising self assembled monolayer modified electrodes.

Most immunoassays currently rely on optical methods for signal generation e.g. in ELISA and rapid assay formats. It has become apparent as in the Glucose sensor market that there is a need for simple direct electrical immuno-sensors. We have investigated the novel use of organic conducting monolayers used as a direct electrochemical detection support for an immuno-reaction. It was found that antibodies raised to a carbazole dimer monolayer could increase the charge movement across that monolayer surface. Antibody fragments were taken from a specific anti-carbazole antibody fragment library and combined with an antibody fragment directed to the hormone estrone 3 glucuronide (E3G), the target antigen to form a bispecific antibody fragment. The device utilised these specific antibody fragments and incorporated them on the top plate of a capillary fill format as the immuno-assay components. The immuno-reaction utilised a competition assay. Free E3G analyte in the sample displaced the bispecific antibody fragment from the immuno-surface leaving it free to bind the carbazole monolayer surface. There the binding was detected using amperometric or coulometric methods. By combining all there element it was possible to develop a sensitive immuno-assay that could detect E3G in a reproducible calibrated fashion down to 10 ng/ml.

Amino Acid Sequence↗

PubMed2001

Changes in gene expression in macrophages infected with Mycobacterium tuberculosis: a combined transcriptomic and proteomic approach.

We investigated the changes which occur in gene expression in the human macrophage cell line, THP1, at 1, 6 and 12 hr following infection with Mycobacterium tuberculosis. The analysis was carried out at the transcriptome level, using microarrays consisting of 375 human genes generally thought to be involved in immunoregulation, and at the proteomic level, using two-dimensional gel electrophoresis and mass spectrometry. The analysis of the transcriptome using microarrays revealed that many genes were up-regulated at 6 and 12 hr. Most of these genes encoded proteins involved in cell migration and homing, including the chemokines interleukin (IL)-8, osteopontin, monocyte chemotactic protein-1 (MCP-1), macrophage inflammatory protein-1alpha (MIP-1alpha), regulated on activation, normal, T-cell expressed and secreted (RANTES), MIP-1beta, MIP-3alpha, myeloid progenitor inhibitory factor-1 (MPIF-1), pulmonary and activation regulated chemokine (PARC), growth regulated gene-beta (GRO-beta), GRO-gamma, MCP-2, I-309, and the T helper 2 (Th2) and eosinophil-attracting chemokine, eotaxin. Other genes involved in cell migration which were up-regulated included the matrix metalloproteinase MMP-9, vascular endothelial growth factor (VEGF) and its receptor Flk-1, the chemokine receptor CCR3, and the cell adhesion molecules vesicular cell adhesion molecule-1 (VCAM-1) and integrin a3. In addition to the chemokine response, genes encoding the proinflammatory cytokines IL-1beta (showing a 433-fold induction), IL-2 and tumour necrosis factor-alpha (TNF-alpha), were also found to be induced at 6 and/or 12 hr. It was more difficult to detect changes using the proteomic approach. Nevertheless, IL-1beta was again shown to be strongly up-regulated. The enzyme manganese superoxide dismutase was also found to be strongly up-regulated; this enzyme was found to be macrophage-, rather than M. tuberculosis, derived. The heat-shock protein hsp27 was found to be down-regulated following infection. We also identified a mycobacterial protein, the product of the atpD gene (thought to be involved in the regulation of cytoplasmic pH) in the infected macrophage extracts.

Chemokines↗

PubMed2001

Survey of cancellation rate of hypertensive patients undergoing anaesthesia and elective surgery.

Hypertension is the commonest avoidable medical indication for postponing anaesthesia and surgery. There are no universally accepted guidelines stating the arterial pressure values at which anaesthesia should be postponed. The aim of this study was to determine the extent of variation across the South-West region of the UK in the anaesthetic management of patients presenting with stage 2 or stage 3 hypertension. Each anaesthetist in the region was sent a questionnaire with five imaginary case histories of patients with stage 2 or stage 3 hypertension. They were asked if they would be prepared to provide anaesthesia for each patient. The response rate was 58%. We found great variability between anaesthetists as to which patients would be cancelled. Departmental protocols may aid general practitioners and surgeons in the preparation of patients for surgery, but such protocols may be difficult to agree in the light of such a wide variation in practice.

Aged↗

PubMed2001

The irritable bowel syndrome and psychiatric disorders in the community: is there a link?

OBJECTIVE: Psychiatric morbidity is high among patients who present to referral centers with irritable bowel syndrome (IBS). However, few studies have investigated the relationship between psychiatric disturbance and IBS in community samples. We hypothesized that psychiatric disorders are linked to IBS in the general community, but this is influenced by the criteria used to establish a diagnosis of IBS. METHODS: The data were collected from a birth cohort born in Dunedin (New Zealand) between April 1972 and March 1973. This cohort consisted of 1037 members (52% male), who were assessed at ages 3, 5, 7, 9, 11, 13, 15, 18, 21, and 26 yr. GI symptoms were recorded at age 26 yr, using an abbreviated version of the Bowel Symptom Questionnaire; psychiatric history was obtained at ages 18 and 21 yr, using a modified version of the Diagnostic Interview Schedule. RESULTS: The prevalence of IBS was 12.7% according to the Manning criteria and 4.3% according to the Rome II criteria. The IBS was not significantly related to a diagnostic history for psychiatric illness overall, nor to a history of anxiety disorders, depressive disorders, and substance dependence. These results were independent of the IBS criteria used; there was no association between psychiatric history and IBS when IBS was defined according to the Manning criteria (p = 0.11 to 0.98) or the Rome criteria (p = 0.18 to 0.92): Rome and Manning criteria subjects did not significantly differ from each other in terms of psychiatric history (p = 0.16 to 0.89). CONCLUSION: In a cohort of young adults with IBS from New Zealand, IBS appears to not be related to psychiatric disorders.

Adolescent↗

PubMed2001

Low socioeconomic class is a risk factor for upper and lower gastrointestinal symptoms: a population based study in 15 000 Australian adults.

BACKGROUND: The association of social class with health has been extensively studied, yet relationships between social class and gastrointestinal symptoms remain almost unexplored. AIMS: To examine relationships between social class and gastrointestinal symptoms in a population sample. METHODS: The prevalence of 16 troublesome gastrointestinal symptoms was determined by a postal questionnaire sent to 15 000 subjects (response rate 60%) and compared with a validated composite measure of socioeconomic status (index of relative socioeconomic disadvantage). Comparisons across social class were explored for five symptom categories (oesophageal symptoms; upper dysmotility symptoms; bowel symptoms; diarrhoea; and constipation). Results are reported as age standardised rate ratios with the most advantaged social class as the reference category. RESULTS: There were clear trends for the prevalence rates of all gastrointestinal symptoms to increase with decreasing social class. These trends were particularly strong for the five symptom categories. Lower social class was associated with a significantly (p<0.0001) higher number of symptoms reported overall and with a higher proportion of individuals reporting 1-2 symptoms and more than five symptoms. In both sexes, the most pronounced effects for subjects in the lowest social class were found for constipation (males: rate ratio 1.83 (95% confidence intervals (CI) 1.16-2.51); females: rate ratio 1.68 (95% CI 1.31-2.04)) and upper dysmotility symptoms (males: rate ratio 1.45 (95% CI 1.02-1.88); females: rate ratio 1.35 (95% CI 1.07-1.63)). Oesophageal symptoms and diarrhoea were not associated with social class. CONCLUSIONS: Troublesome gastrointestinal symptoms are linked to socioeconomic status with more symptoms reported by subjects in low socioeconomic classes. Low socioeconomic class should be considered a risk factor for both upper and lower gastrointestinal symptoms.

Adult↗

PubMed2001

Testosterone deficiency and replacement.

In the human male, testosterone is the major circulating androgen. More than 95% of circulating testosterone is secreted by the testis with a production rate of 6-7 mg/day. The clinical effects of androgens are numerous, and testosterone deficiency is associated with a number of clinical abnormalities. Overt hypogonadism results in reductions in bone mineral density, alterations in body composition and effects on mood, aggressive behaviour, cognitive function, sexual function and several factors important for cardiovascular risk. Androgen replacement in this context is clearly beneficial, and numerous studies have demonstrated improvements in bone and muscle mass, reductions in body fat, and positive effects on quality of life following treatment. The benefits of therapy in men with milder degrees of hypogonadism, and elderly men with "physiological" testosterone deficiency, are less clear-cut, and the appropriate biochemical cut-off below which replacement should be offered has not been clearly defined. Several options are available for androgen replacement in adult men. Oral testosterone, intramuscular injections, subcutaneous implants and transdermal therapy have all been used. Each mode of delivery has advantages and drawbacks and the choice between them will often depend on patient reference. Recent advances include the development of longer-acting intramuscular preparations, which offer more stable androgen levels with fairly infrequent injections, and testosterone gel which appears to provide transdermal replacement without a high incidence of skin reactions. This article will examine the evidence concerning the impact of male hypogonadism and the response to androgen therapy. The question of who to treat will be addressed with particular reference to mild hypogonadism and hypogonadism in the elderly. Finally, an overview of the different modes of replacement therapy will be presented.

Behavior↗

PubMed2001

Human fructosamine-3-kinase: purification, sequencing, substrate specificity, and evidence of activity in vivo.

Nonenzymatic glycation appears to be an important factor in the pathogenesis of diabetic complications. Key early intermediates in this process are fructosamines, such as protein-bound fructoselysines. In this report, we describe the purification and characterization of a mammalian fructosamine-3-kinase (FN3K), which phosphorylates fructoselysine (FL) residues on glycated proteins, to FL-3-phosphate (FL3P). This phosphorylation destabilizes the FL adduct and leads to its spontaneous decomposition, thereby reversing the nonenzymatic glycation process at an early stage. FN3K was purified to homogeneity from human erythrocytes and sequenced by means of electrospray tandem mass spectrometry. The protein thus identified is a 35-kDa monomer that appears to be expressed in all mammalian tissues. It has no significant homology to other known proteins and appears to be encoded by genomic sequences located on human chromosomes 1 and 17. The lability of FL3P, the high affinity of FN3K for FL, and the wide distribution of FN3K suggest that the function of this enzyme is deglycation of nonenzymatically glycated proteins. Because the condensation of glucose and lysine residues is an ubiquitous and unavoidable process in homeothermic organisms, a deglycation system mediated by FN3K may be an important factor in protecting cells from the deleterious effects of nonenzymatic glycation. Our sequence data of FN3K are in excellent agreement with a recent report on this enzyme by Delpierre et al. (Diabetes 49:1627-1634, 2000).

Amino Acid Sequence↗

PubMed2000

Characterization of the DNA-binding domains from the yeast cell-cycle transcription factors Mbp1 and Swi4.

The minimal DNA-binding domains of the Saccharomyces cerevisiae transcription factors Mbp1 and Swi4 have been identified and their DNA binding properties have been investigated by a combination of methods. An approximately 100 residue region of sequence homology at the N-termini of Mbp1 and Swi4 is necessary but not sufficient for full DNA binding activity. Unexpectedly, nonconserved residues C-terminal to the core domain are essential for DNA binding. Proteolysis of Mbp1 and Swi4 DNA-protein complexes has revealed the extent of these sequences, and C-terminally extended molecules with substantially enhanced DNA binding activity compared to the core domains alone have been produced. The extended Mbp1 and Swi4 proteins bind to their cognate sites with similar affinity [K(A) approximately (1-4) x 10(6) M(-)(1)] and with a 1:1 stoichiometry. However, alanine substitution of two lysine residues (116 and 122) within the C-terminal extension (tail) of Mbp1 considerably reduces the apparent affinity for an MCB (MluI cell-cycle box) containing oligonucleotide. Both Mbp1 and Swi4 are specific for their cognate sites with respect to nonspecific DNA but exhibit similar affinities for the SCB (Swi4/Swi6 cell-cycle box) and MCB consensus elements. Circular dichroism and (1)H NMR spectroscopy reveal that complex formation results in substantial perturbations of base stacking interactions upon DNA binding. These are localized to a central 5'-d(C-A/G-CG)-3' region common to both MCB and SCB sequences consistent with the observed pattern of specificity. Changes in the backbone amide proton and nitrogen chemical shifts upon DNA binding have enabled us to experimentally define a DNA-binding surface on the core N-terminal domain of Mbp1 that is associated with a putative winged helix-turn-helix motif. Furthermore, significant chemical shift differences occur within the C-terminal tail of Mbp1, supporting the notion of two structurally distinct DNA-binding regions within these proteins.

Amino Acid Sequence↗

PubMed2000

The use of propofol for its antiemetic effect: a survey of clinical practice in the United States.

STUDY OBJECTIVES: To investigate the use of propofol by anesthesiologists for its antiemetic effect and to compare our findings with published evidence. DESIGN: Anonymous survey of U.S. anesthesiologists. SETTING: American Society of Anesthesiologists' annual meeting. MEASUREMENTS AND MAIN RESULTS: One hundred fifty anesthesiologists were surveyed on how they use propofol to achieve an antiemetic effect. A large majority (84%) of the anesthesiologists surveyed stated they used propofol for its antiemetic effect: 63% of those used propofol for induction only for cases lasting <1 h to achieve an antiemetic effect. In addition 37% used a "sandwich" technique, using propofol at the beginning and end of a case for a similar purpose. There is evidence that the antiemetic effect of propofol is associated with a defined plasma concentration range; mean, 343 ng/mL (10-90% confidence intervals [CI] 200-600 ng/mL). Simulation data demonstrated that after propofol 2 mg/kg, its concentration will drop below 350 ng/mL at 32 min. After 2 mg/kg and 20 mg within 10 min of the end of surgery, its concentration will drop below 350 ng/mL by 7 min after the 20 mg bolus dose. This finding suggests that the plasma concentrations of propofol, when used in these cases, will be below the effective range of antiemetic effect. CONCLUSIONS: Many anesthesiologists used propofol for its antiemetic effect. There is strong evidence for its antiemetic efficacy after anesthesia maintained by a propofol infusion and also for its use in the postanesthesia care unit (PACU). However, there is little evidence to support its use purely at induction of anesthesia or as part of a "sandwich" technique in an attempt to reduce postoperative nausea and vomiting. This is especially true in cases lasting longer than a few minutes.

Anesthesia, Intravenous↗

PubMed2000

Heat loss during induction of anaesthesia for elective aortic surgery.

We have studied core temperature changes occurring during induction of general anaesthesia and surgery in 18 patients undergoing elective aortic aneurysm repair. In the operating theatre, all patients were warmed with a forced-air warmer and a warming mattress, and received warmed (37 degrees C) intravenous fluids. Despite this, mean (SD) [range] core temperatures in the anaesthetic room decreased by 1.5 (0.3)[1.1-2.2] degrees C, while intravascular lines, epidural and urinary catheters were inserted before the introduction of warming methods in theatre. In one-third of patients, the core temperature was still below 36 degrees C at the end of surgery. The overall temperature decrease correlated significantly with the duration of time between induction of general anaesthesia and surgical incision (R2 = 0.6912), when the patients were not being warmed. Hypothermia may thus be prevented by minimising the period that the patient is anaesthetised without being warmed. Vascular lines, urinary and epidural catheters should be inserted before the induction of general anaesthesia or, alternatively, warming methods should be introduced in the anaesthetic room.

Aged↗

PubMed2000

Facial cutaneous tuberculosis: an unusual presentation.

Periocular cutaneous tuberculosis is a rare occurrence. We describe a 75-year-old Caucasian woman with tuberculosis of the left periocular region which responded completely to standard antituberculosis therapy. We hypothesize this unusual presentation may be due to minor trauma followed by inoculation.

Aged↗

PubMed2000

Endoscopic ultrasound guided biopsy of sub-carinal lymph nodes.

AIM/METHODS: Endoscopic ultrasound (EUS) guided biopsy is not widely available in the U.K., and sub-carinal nodes can be difficult to biopsy percutaneously. Tissue obtained from these nodes can influence patient management. We describe our initial experience with EUS guided transoesophageal biopsy of sub-carinal nodes using a Pentax FG-34 EUS probe and a 22 G Hancke-Villman or Echotip needle in 20 patients. RESULTS: Malignant cells were obtained from the nodes in 13 patients, and in another patient in whom the node biopsy was negative, small cell carcinoma cells were obtained from a lesion in the liver. There were no complications. CONCLUSIONS: Mediastinoscopy to obtain tissue, or the blind treatment of presumed malignancy was avoided in all the patients in whom a positive biopsy was obtained. In many of these patients, more conventional methods to obtain a tissue diagnosis had already failed. The problem solving capability of this safe, well-tolerated technique is discussed.Roberts, S. A. Clinical Radiology55, 832-836.

Adult↗

PubMed2000

Symptoms discriminate irritable bowel syndrome from organic gastrointestinal diseases and food allergy.

BACKGROUND: The value of specific gastrointestinal symptoms in discriminating irritable bowel syndrome (IBS) from organic disease has been documented. In contrast, there have been few attempts to identify symptoms that discriminate irritable bowel syndrome from food allergy, despite similarities in their respective symptom complexes. We aimed to investigate the value of symptoms in discriminating irritable bowel syndrome from organic disease and food allergy. METHODS: Subjects (n = 288) were recruited from consecutive patients presenting to the Internal Medicine, Gastroenterology and Allergy Units in Chieti. Patients completed the validated Bowel Disease Questionnaire (BDQ) prior to an independent diagnostic evaluation, which included endoscopy when appropriate. Food allergy was diagnosed using a 2-week elimination diet, followed by a placebo-controlled food challenge test, a skin prick test and serum RAST for specific IgE for suspected foods or additives. The results of the BDQ were not considered in formulating a diagnosis. In total, 99 patients were diagnosed with the IBS, 79 patients were diagnosed with organic disease and 22 patients were diagnosed with food allergy. A further 88 patients with extraintestinal allergies were included as a control group. RESULTS: Based on logistic regression analysis, six symptom items discriminated IBS from organic disease, while five symptoms discriminated patients with IBS from control subjects. A diagnosis of IBS compared to organic disease was positively associated with straining on defaecation (P=0.0001), diarrhoea (P=0.001) and abdominal bloating (P=0.01), but was negatively associated with pain in the upper abdomen (P=0.0004), reflux (P=0.0001) and appetite loss (P=0.004). A diagnosis of IBS compared to extraintestinal allergy was positively associated with pain relieved by bowel movement (P=0.0001), pain in the lower abdomen (P=0.0006), pain in both the upper and lower abdomen (P=0.003), frequent pain (P=0.001) and abdominal bloating (P=0.0009). In comparison between IBS and food allergy patients, a diagnosis of IBS was positively associated with pain in the lower abdomen (P=0.001), pain relieved by bowel movements (P=0.001), frequent pain (P=0.02) and abdominal bloating (P=0.03). CONCLUSION: Symptoms appear to be useful for discriminating IBS from organic gastrointestinal disease and food allergy.

Adolescent↗