Young dyspeptic patients: with a test-and-treat policy, are the benefits of decreased symptom severity and oesophago-gastric-duodenoscopy workload sustained?

OBJECTIVES: To examine the symptom severity and requirement for oesophago-gastro-duodenoscopy (OGD) in young dyspeptic patients 2 years after serological testing for Helicobacter pylori, and to compare the outcomes of seronegative patients with those of seropositive patients. DESIGN: Long-term follow-up study of 232 participants from our previous trial. METHODS: Telephone assessment of patients' symptom severity, scored using a previously validated questionnaire; return of patients for OGD determined using local patient administration system (PAS); and review of medical case notes. RESULTS: Dyspepsia symptom severity of both seronegative and seropositive patients remained reduced compared with initial scores at time of trial recruitment. Symptom severity of seropositive patients was significantly lower than that of seronegative patients (P< 0.001). Seventeen additional patients returned for OGD between six months and two years after the start of the serological study. As 61 of the original 232 study patients returned for OGD within the first six month follow-up period, a total of 78 individuals (34%) had OGD during the two years following the study. Thus, 66% of the original participants avoided OGD. CONCLUSIONS: This study of non-invasive testing for H. pylori in young dyspeptic patients has demonstrated an improvement in symptom severity and a substantial reduction in OGD workload over a 2-year period.     

Hyperammonemia with reduced ornithine, citrulline, arginine and proline: a new inborn error caused by a mutation in the gene encoding delta(1)-pyrroline-5-carboxylate synthase

delta(1)-pyrroline-5-carboxylate synthase (P5CS), a bifunctional ATP- and NADPH-dependent mitochondrial enzyme, catalyzes the reduction of glutamate to delta(1)-pyrroline-5-carboxylate, a critical step in the biosynthesis of proline, ornithine and arginine. Recently, we reported the cloning and expression of human and murine P5CS cDNAs. Previously, we showed that mammalian P5CS undergoes alternative splicing to generate two isoforms differing only by a 2 amino acid insert at the N-terminus of the gamma-glutamyl kinase active site. The short isoform has high activity in the gut, where it participates in arginine biosynthesis and is inhibited by ornithine. The long isoform, expressed in multiple tissues, is necessary for the synthesis of proline from glutamate and is insensitive to ornithine. Here, we describe a newly recognized inborn error due to the deficiency of P5CS in two siblings with progressive neurodegeneration, joint laxity, skin hyperelasticity and bilateral subcapsular cataracts. Their metabolic phenotype includes hyperammonemia, hypoornithinemia, hypocitrullinemia, hypoargininemia and hypoprolinemia. Both are homozygous for the missense mutation, R84Q, which alters a conserved residue in the P5CS gamma-glutamyl kinase domain. R84Q is not present in 194 control chromosomes and dramatically reduces the activity of both P5CS isoforms when expressed in mammalian cells. Additionally, R84Q appears to destabilize the long isoform. This is the first documented report of an inborn error of P5CS and suggests that this disorder should be considered in the differential diagnosis in patients with neurodegeneration and/or cataracts and connective tissue disease.     

Endocrine and metabolic response in the human newborn to first feed of breast milk

The hormonal and metabolic response to the first feed of breast milk was studied in 12 infants at 4-6 hours of age. After the feed there was an increase in blood glucose concentration but no changes in the concentrations of lactate, pyruvate, alanine, or ketone bodies. The feed was followed by an increase in the concentrations of plasma insulin, growth hormone, gastrin, and enteroglucagon, but no change in levels of plasma glucagon or gastric inhibitory peptide. Several hormone systems are functionally active at birth and are stimulated by the first feed of milk.     

Peroneal tendon tears: return to sports after operative treatment

BACKGROUND: Operative treatment has become the standard for peroneal tendon tears when nonoperative management fails. Successful return to sports has been reported in previous studies. We evaluated 30 patients who had operative treatment of peroneal tears. METHODS: Patients who were evaluated by a questionnaire and by review of medical records, MRI, radiographs, and operative reports. RESULTS: Nine of the 10 patients who were working outside the home were able to return to employment at the same level. A substantial number had residual symptoms, including scar tenderness (58%) and lateral ankle swelling (54%). Only 46% were able to successfully return to sports. CONCLUSIONS: Although operative treatment was very effective in allowing patients to return to work, only half of our patients were able to return to sports at an average followup of 31 months.     

Coralline hydroxyapatite bone graft substitutes: preliminary report of radiographic evaluation

A new bone graft substitute made by conversion of the calcium carbonate exoskeleton of reef-building sea coral into hydroxyapatite has recently become clinically available. The normal radiographic appearance of two forms of this material is described. In the immediate postoperative period, the exoskeletal architecture of these implants is readily appreciated. With graft incorporation over the ensuing months, their intrinsic structure is gradually lost in association with poor marginal definition. Evolving radiographic findings reflect the biocompatible nature of these implants, which provides the potential for ingrowth of native bone with preservation of the coralline scaffold, resulting in enhanced biomechanical properties.     

Increased tumor localization and reduced immune response to adenoviral vector formulated with the liposome DDAB/DOPE

We aimed to increase the efficiency of adenoviral vectors by limiting adenoviral spread from the target site and reducing unwanted host immune responses to the vector. We complexed adenoviral vectors with DDAB–DOPE liposomes to form adenovirus–liposomal (AL) complexes. AL complexes were delivered by intratumoral injection in an immunocompetent subcutaneous rat tumor model and the immunogenicity of the AL complexes and the expression efficiency in the tumor and other organs was examined. Animals treated with the AL complexes had significantly lower levels of β-galactosidase expression in systemic tissues compared to animals treated with the naked adenovirus (NA) (P < 0.05). The tumor to non-tumor ratio of β-galactosidase marker expression was significantly higher for the AL complex treated animals. NA induced significantly higher titers of adenoviral-specific antibodies compared to the AL complexes (P < 0.05). The AL complexes provided protection (immunoshielding) to the adenovirus from neutralizing antibody. Forty-seven percent more β-galactosidase expression was detected following intratumoral injection with AL complexes compared to the NA in animals pre-immunized with adenovirus.

Conclusions

Complexing of adenovirus with liposomes provides a simple method to enhance tumor localization of the vector, decrease the immunogenicity of adenovirus, and provide protection of the virus from pre-existing neutralizing antibodies.     

Perforated colorectal neoplasms: correlation of clinical, contrast enema, and CT examinations

Results of clinical, contrast enema (CE), and computed tomographic (CT) examinations in 39 patients with perforated colorectal neoplasms were retrospectively reviewed. Twenty patients were toxemic at initial presentation, but in only four patients was the diagnosis of perforated colorectal neoplasm initially suspected clinically. CE study was performed in 22 patients and enabled the diagnosis of perforated neoplasm in 11 cases, neoplasm alone in eight, and neither neoplasm nor perforation in three. CT was performed in 38 patients and enabled the diagnosis of perforated neoplasm in 36; pericolic phlegmon but no mass lesion was evident in two. In 16 patients, CT also demonstrated metastatic disease. Because of its reliability in establishing the diagnosis and staging the extent of the inflammatory and neoplastic disease, CT is indicated in cases of suspected or proved perforated colorectal neoplasm and in cases in which CE study findings are indeterminate or suggestive of perforated neoplasm.     

Bile duct obstruction: radiologic evaluation of level, cause, and tumor resectability

In a prospective study of 65 patients with bile duct obstruction, various radiologic modalities were compared for their capability to demonstrate the level and cause of obstruction and to indicate accurately tumor resectability. Ultrasound (US) was performed in 65 patients, computed tomography (CT) in 51, direct cholangiography (DC) in 57, and angiography in 35. The level of obstruction was correctly indicated by US in 95% of patients and by CT in 90%, and the cause was correctly indicated by US in 88%, by CT in 63%, and by DC in 89%. In predicting tumor resectability, US was correct in 71% of patients, compared with 42% for CT, 58% for DC, and 25% for angiography. US therefore appears to be the single most useful modality in the evaluation bile duct obstruction.     

Developing quality indicators for older adults: transfer from the USA to the UK is feasible

Background: Measurement of the quality of health care is essential for quality improvement, and patients are an underused source of data about quality of care. We describe the adaptation of a set of USA quality indicators for use in patient interview surveys in England, to measure the extent to which older patients receive a broad range of effective healthcare interventions in both primary and secondary care.

Method: One hundred and nineteen quality indicators covering 16 clinical areas, based on a set of indicators for the care of vulnerable elderly patients in the USA, were reviewed by a panel of 10 clinical experts in England. A modified version of the RAND/UCLA appropriateness method was used and panel members were supplied with literature reviews summarising the evidence base for each quality indicator. The indicators were sent for comment before the panel meeting to UK charitable organisations for older people.

Results: The panel rated 102 of the 119 indicators (86%) as valid for use in England; 17 (14%) were rejected as invalid. All 58 indicators about treatment or continuity and follow up were rated as valid compared with just over half (13 of 24) of the indicators about screening.

Conclusions: These 102 indicators are suitable for use in patient interview surveys, including the English Longitudinal Study of Ageing (ELSA). The systematic measurement of quality of care at the population level and identification of gaps in quality is essential for quality improvement. There is potential for transfer of quality indicators between countries, at least for the health care of older people.