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Biomedical subjects

M Hughes

Publications and source records attributed to M Hughes.

At least 91 records · Page 5Linked to original sources
PubMed1998

Meta-analysis of antisecretory and gastrokinetic compounds in functional dyspepsia.

In view of therapeutic advances, we carried out meta-analysis of results from 18 randomized, controlled clinical studies to update a previous meta-analysis and to provide an overview of clinical trials involving treatment of functional dyspepsia. The studies were included only if they satisfied inclusion and exclusion criteria and assessed treatment of functional dyspepsia with the antisecretory compounds cimetidine and ranitidine and the gastrokinetic compounds cisapride and domperidone. Outcomes of each of these trials were classified in terms of differences in therapeutic success between active treatment and placebo. For antisecretory treatments, the 95% confidence intervals for the difference in therapeutic success between active treatment and placebo were inconsistent for cimetidine, but analysis of both ranitidine trials gave favorable results. For the gastrokinetic compounds cisapride and domperidone, the differences in success rates were generally higher and more in favor of active treatment than placebo. By combining the results from both antisecretory treatments and comparing them with the combined results for gastrokinetic compounds, we observed that gastrokinetic compounds had a greater difference in success rates than did antisecretory agents. Overall, our meta-analysis shows that antisecretory treatment with cimetidine or ranitidine offers little advantage over placebo, whereas gastrokinetic treatment with cisapride or domperidone is significantly better than placebo for treatment of functional dyspepsia.

Anti-Ulcer Agents↗
PubMed1998

The role of the ran GTPase in nuclear assembly and DNA replication: characterisation of the effects of Ran mutants.

The Ran GTPase plays a critical role in nucleocytoplasmic transport and has been implicated in the maintenance of nuclear structure and cell cycle control. Here, we have investigated its role in nuclear assembly and DNA replication using recombinant wild-type and mutant Ran proteins added to a cell-free system of Xenopus egg extracts. RanQ69L and RanT24N prevent lamina assembly, PCNA accumulation and DNA replication. These effects may be due to the disruption of nucleocytoplasmic transport, since both mutants inhibit nuclear import of a protein carrying a nuclear localisation signal (NLS). RanQ69L, which is deficient in GTPase activity, sequesters importins in stable complexes that are unable to support the docking of NLS-proteins at the nuclear pore complex (NPC). RanT24N, in contrast to wild-type Ran-GDP, interacts only weakly with importin alpha and nucleoporins, and not at all with the import factor p10, consistent with its poor activity in nuclear import. However, RanT24N does interact stably with importin beta, Ran binding protein 1 and RCC1, an exchange factor for Ran. We show that Ran-GDP is essential for proper nuclear assembly and DNA replication, the requirement being primarily before the initiation of DNA replication. Ran-GDP therefore mediates the active transport of necessary factors or otherwise controls the onset of S-phase in this system.

Animals↗
PubMed1998

The effect of dietary intervention on changes in total cholesterol, blood pressure and weight in a Cambridge study.

The study examined the impact of dietary advice on cholesterol reduction, to see whether diet was more effective when preceded by a cholesterol estimation. A total of 635 healthy individuals aged between 40 and 60 years attended a general practice cardiovascular risk screening in 1990. All subjects had their blood pressure, body mass index and smoking history recorded, and 50% were randomised to cholesterol measurement. Two years later, all individuals were invited to participate in a follow-up screening and 356 individuals took part (158 men, 198 women). All the above estimations were undertaken in 100% of attendees. The mean total cholesterol levels and weight declined in the subjects who were given dietary advice and had their cholesterol measured, while the mean cholesterol level increased slightly in subjects who did not receive dietary advice but had their cholesterol measured. The was a significant increase in diastolic blood pressure in all patients. The figures for reported smokers decreased from 22.4% to 19.4% in men and 19.4% to 8.4% in women. The results suggest that dietary advice can achieve a sustained reduction in cholesterol levels, but may require the stimulus of a prior cholesterol estimation.

Adult↗
PubMed1998

Managing care in an integrated delivery system via an Intranet.

The CareGroup Provider Service Network is a managed care contracting organization which provides central administrative services for over 1800 physicians and 200,000 managed care lives. Services include utilization management, disease management and credentialing for the entire network. The management model of the Provider Service Network empowers local physician groups with information and education. To meet the managed care information needs of the network, we implemented an intranet-based executive information system, PSNWeb, which retrieves data from a managed care data warehouse. The project required the integration of diverse technologies and development of a complex security/confidentiality infrastructure to deliver information to 8 major clinician groups, each with different information needs.

Computer Security↗
PubMed1997

The cysteine residues of the M2 protein are not required for influenza A virus replication.

The M2 protein of influenza A virus functions as an ion channel. It contains three cysteine residues: cysteines 17 and 19, which form disulfide bonds in the ectodomain, and cysteine 50 which is acylated. To understand the role of these cysteine residues in virus replication, we used reverse genetics to create influenza viruses in which the individual cysteines were mutated and a virus in which all three cysteines were changed to serine. The M2 cysteine mutants that lacked either of the cysteine residues in the ectodomain and the mutant that lacked all three residues had appreciably lower amounts of M2 oligomers than did the wild-type virus when examined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. None of the mutants, however, were defective in replication, either in vitro or in ferrets and mice. These findings demonstrate that noncovalent interactions are sufficient for the M2 protein to form functional oligomers for virus replication and that its cysteine residues are dispensable for influenza virus replication in vitro and in vivo.

Amino Acid Substitution↗
PubMed1997

Does allopurinol reduce pain of chronic pancreatitis?

CONCLUSION: A dosage of 300 mg/d of allopurinol was not effective in reducing pain or improving activities of daily living in chronic pancreatitis. BACKGROUND: Allopurinol prevents the generation of oxygen-derived free radicals by inhibiting xanthine oxidase. The purpose of this study was to determine whether allopurinol is effective in reducing pain of chronic pancreatitis. METHODS: Thirteen patients with chronic pancreatitis who were experiencing abdominal pain requiring medication at least three times each week entered a randomized, double-blind, two-period crossover clinical trial. Patients evaluated their pain daily using a categorical pain intensity scale, numeric pain intensity scale, and a visual analog scale, and weekly completed a McGill Pain Questionnaire and activities of daily living (ADL) questionnaire. RESULTS: The mean baseline score of pain was approx 50% of most severe pain in all scoring systems. There was no significant decrease in pain associated with allopurinol compared to the placebo (p = 0.24-0.75). In addition, there was no benefit in terms of ADL score associated with allopurinol compared with placebo (p = 0.32). Mean uric acid level was decreased by 1.15 mg/dL while patients were taking allopurinol, compared to when they were taking placebo (p = 0.007).

Abdominal Pain↗
PubMed1997

Urinary trypsinogen activation peptide (TAP) predicts severity in patients with acute pancreatitis.

CONCLUSIONS: Urinary TAP obtained within the first 48 h of the onset of symptoms can distinguish patients with severe acute pancreatitis. BACKGROUND: Urinary trypsinogen activation peptide (TAP) has recently been described as an early marker of severity in acute pancreatitis. METHODS: In a multicenter study, urine samples were collected for TAP concentration at 6-12, 24, and 48 h after admission from 139 patients with acute pancreatitis (99 with mild disease, 40 with severe disease) and from 50 control patients. Severity of acute pancreatitis was defined by the presence of organ failure and/ or pancreatic necrosis on dynamic contrast-enhanced computed tomography. RESULTS: Median urinary TAP in the 139 patients with acute pancreatitis compared to the 50 control patients was significantly higher at admission, 4.6 vs 0.8 ng/mL (p < 0.001), and 6-12 h, 1.9 vs 0.55 ng/mL (p = 0.04). Among patients who presented within 48 h of the onset of symptoms, the median urinary TAP for severe pancreatitis (9 patients) compared to mild pancreatitis (40 patients) was significantly higher at admission, 29.6 vs. 3.6 ng/mL (p = 0.001). Also, when obtained within 48 h of the onset of symptoms, all patients with severe pancreatitis had an admission urinary TAP level > 10 ng/mL. The sensitivity and specificity of an admission urinary TAP > or = 10 for severe pancreatitis was 100 and 85%, respectively. Given a cutoff of 10 ng/mL for an admission urinary TAP obtained within 48 h of the onset of symptoms, the negative predictive value was 100% for mild pancreatitis.

Acute Disease↗
PubMed1997

Relationship of necrosis to organ failure in severe acute pancreatitis.

BACKGROUND & AIMS: Pancreatic necrosis and organ failure are principal determinants of severity in acute pancreatitis. The purpose of this study was to determine the relationship of necrosis to organ failure in severe acute pancreatitis. METHODS: Patients with necrotizing pancreatitis from May 1992 to January 1996 were retrospectively studied. Pancreatic necrosis was identified by characteristic findings on dynamic contrast-enhanced computerized tomography scan and infected necrosis by computerized tomography-guided percutaneous aspiration. Organ dysfunction was defined in accordance with the Atlanta symposium. RESULTS: Organ failure was present in only 26 of 51 patients (51%). There was no difference in the prevalence of organ failure in infected necrosis compared with sterile necrosis (approximately 50% in both groups). Patients with increased amounts of necrosis did not have an increased prevalence of organ failure or infected necrosis compared with those with lesser amounts of necrosis. Patients with organ failure had an increased morbidity and mortality compared with those without organ failure. CONCLUSIONS: Organ failure occurred in only one half of patients with necrotizing pancreatitis. Because organ failure increases the severity of illness, studies of patients with necrotizing pancreatitis must stratify for organ failure to facilitate interpretation of results.

Aged↗
PubMed1997

The optimum bowel preparation for flexible sigmoidoscopy.

With the proposed introduction of a flexible sigmoidoscopic screening programme for colorectal cancer, patient compliance is of paramount importance. Therefore, the bowel preparation providing optimum cleansing of the bowel with the least associated discomfort and inconvenience for the patient must be found. Patients were randomized to receive either Picolax the evening before the examination or self-administered Fleet enemas prior to the investigation. The endoscopist and nurse practitioner who collected data on a standard questionnaire were blinded to the preparation used. Bowel preparation was graded by the endoscopist as: excellent, good, adequate or poor. One hundred and two consecutive patients were randomized: 56 to the Fleet enema group and 46 to the Picolax group. Self-administered Fleet enemas provided a significantly superior bowel preparation with 52 (93%) being judged adequate or better, as opposed to 34 (74%) in the Picolax group. In addition, Fleet enemas were associated with significantly fewer adverse associated symptoms: 11 (20%) vs 24 (52%). Patients reported to be willing to receive Fleet enemas again in 53 (95%) vs 37 (80%) for the Picolax group. The self-administered Fleet enema is superior to Picolax in terms of bowel preparation for flexible sigmoidoscopy and the incidence of associated adverse symptoms.

Administration, Oral↗
PubMed1997

Microbial colonization of closed-system suction catheters used in liver transplant patients.

The microbial colonization and the associated risk of respiratory infection during the application of a multiple-use closed-system suction catheter (CSSC) and a single-use open-system suction catheter (OSSC) on liver transplant patients was evaluated in this preliminary study. The cost differential for the two systems was also compared. Twenty post-orthotopic liver transplant (OLTx) patients who were mechanically ventilated via an endotracheal (ET) tube were studied. Ten subjects were randomly allocated ET suction by the CSSC and 10 with OSSC. Both groups were similar according to age, sex, clinical severity, presence of a naso-gastric tube, use of H2 antagonists and antibiotics used. Standard protocols were followed to intubate and suction the patients and to change ventilatory equipment. Suctioning performed with the CSSC did not significantly increase the risk of microbial colonization of the respiratory tract. Similarly there was no apparent difference in the incidence of nosocomial pneumonia between the two suction systems, based on the microbiological and clinical data. The mean daily cost of using the CSSC compared to the OSSC was 11.6 times higher. This may be balanced by a reduction in nursing time and reduced risk of spread of infection associated with the CSSC.

Adult↗
PubMed1997

SHIP, a new player in cytokine-induced signalling.

We recently purified and cloned the cDNAs for the murine and human forms of a novel 145 kDa inositol polyphosphate 5-phosphatase (5-ptase) that becomes tyrosine phosphorylated and associated with Shc following stimulation of hemopoietic cells with multiple cytokines. Unlike most 5-ptases which hydrolyze phosphatidylinositol-4,5-P2-bisphosphate (PI-4,5-P2) and/or inositol-1,4,5-trisphosphate (I-1,4,5-P3), this enzyme selectively hydrolyzes the 5'-phosphate from inositol-1,3,4,5-tetraphosphate (I-1,3,4,5-P4) and phosphatidylinositol-3,4,5-trisphosphate (PI-3,4,5-P3), two inositol polyphosphates recently implicated in growth factor-mediated signalling. This 5-ptase is also unique among 5-ptases in that it is the only one to date to possess an SH2 domain. In this review we discuss the cloning, the Shc binding and the potential role of this protein, which we call SHIP, for SH2-containing inositol 5-phosphatase, in cell proliferation, differentiation and apoptosis.

Adaptor Proteins, Signal Transducing↗
PubMed1997

Pleural effusion as a predictor of severity in acute pancreatitis.

Our objective was to determine whether pleural effusion is a predictor of severity in acute pancreatitis and, if so, whether it is an independent predictor. One hundred ninety-six consecutive cases of acute pancreatitis from October 1, 1994, to September 30, 1995, were reviewed. Medical records were analyzed for evidence of pleural effusion by chest radiograph and severe acute pancreatitis by identification of pancreatic necrosis or organ system dysfunction. Data were analyzed to determine if identification of pleural effusion provided an early sign of severity. Among 135 patients who underwent chest radiography, pleural effusion was seen in 16 of 19 (84.2%) with severe pancreatitis and 10 of 116 (8.6%) of patients with mild pancreatitis (p < 0.001). Pleural effusion was noted in severe pancreatitis prior to clinical or computed tomography evidence of severity in only 20% of cases. Pleural effusion is strongly associated with severity in acute pancreatitis but provides independent information on severity in only a minority of cases.

Acute Disease↗
PubMed1997

Randomized trial comparing epirubicin, cisplatin, and fluorouracil versus fluorouracil, doxorubicin, and methotrexate in advanced esophagogastric cancer.

PURPOSE: We report the results of a prospectively randomized study that compared the combination of epirubicin, cisplatin, and protracted venous infusion fluorouracil (5-FU) (ECF regimen) with the standard combination of 5-FU, doxorubicin, and methotrexate (FAMTX) in previously untreated patients with advanced esophagogastric cancer. PATIENTS AND METHODS: Two hundred seventy-four patients with adenocarcinoma or undifferentiated carcinoma were randomized and analyzed for survival, tumor response, toxicity, and quality of life (QL). RESULTS: The overall response rate was 45% (95% confidence interval [CI], 36% to 54%) with ECF and 21% (95% CI, 13% to 29%) with FAMTX (P = .0002). Toxicity was tolerable and there were only three toxic deaths. The FAMTX regimen caused more hematologic toxicity and serious infections, but ECF caused more emesis and alopecia. The median survival duration was 8.9 months with ECF and 5.7 months with FAMTX (P = .0009); at 1 year, 36% (95% CI, 27% to 45%) of ECF and 21% (95% CI, 14% to 29%) of FAMTX patients were alive. The median failure-free survival duration was 7.4 months with ECF and 3.4 months with FAMTX (P = .00006). The global QL scores were better for ECF at 24 weeks, but the remaining QL data showed no differences between either arm of the study. Hospital-based cost analysis on a subset of patients was similar for each arm and translated into an increment cost of $975 per life-year gained. CONCLUSION: The ECF regimen results in a survival and response advantage, tolerable toxicity, better QL and cost-effectiveness compared with FAMTX chemotherapy. This regimen should now be considered the standard treatment for advanced esophagogastric cancer.

Adenocarcinoma↗