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Biomedical subjects

M Hudson

Publications and source records attributed to M Hudson.

At least 73 records · Page 4Linked to original sources
PubMed1996

The role of the C-terminal lysine in the hinge bending mechanism of yeast phosphoglycerate kinase.

Treatment of yeast phosphoglycerate kinase (PGK) with trypsin results in a fourfold increase in the Vmax of this enzyme, without affecting the Km. This activation is shown to be due to the removal of the C-terminal lysine residue. The C-terminal sequence folds back over the N-terminal domain and contacts the extreme N-terminal sequence which folds onto the C-terminal domain, thus making many of the inter-domain contacts in this two domain protein. Previous studies have shown that this C-terminal region is important in mediating the conformational changes required during catalysis by yeast PGK. Observation of the three-dimensional structure of this enzyme suggests that removal of the C-terminal lysine residue will strengthen the interaction between K5 and E413. This indicates that this salt bridge stabilises the enzyme in the higher activity form, while the presence of K415 reduces the strength of that interaction.

Enzyme Activation↗
PubMed1996

Assessing the impact of delayed discharge on acute care.

This study examined the incidence of delayed discharge in three acute treatment wards. Of 118 admissions during the eight-week study period, 13.5 per cent (n = 16) were categorised as 'inappropriately located' by the study tool. The staff cited lack of rehabilitative facilities or care of the elderly facilities as reasons for patients' inappropriate stay in the acute ward. The authors recommend that healthcare professionals and social services departments liaise more closely to reduce the incidence of delayed discharge and allow these patients to return to the community whenever feasible.

Acute Disease↗
PubMed1996

Morning versus evening dosing of lansoprazole 30 mg daily on twenty-four-hour intragastric acidity in healthy subjects.

BACKGROUND: Morning dosing is usually recommended with proton pump inhibitors, but there are few data from 24-h intragastric acidity studies comparing times of dosing. METHODS: A double-blind, placebo-controlled study was performed on the seventh day of dosing to compare the effects of lansoprazole 30 mg given either in the morning or evening on 24-h intragastric acidity in 32 healthy volunteers. RESULTS: The median integrated 24-h intragastric acidity on the seventh day of morning dosing with lansoprazole 30 mg was decreased to 36% of the placebo value, compared with 42% for evening dosing. For each daytime meal-related interval, morning dosing was significantly more effective for controlling acidity, but there was no significant difference between the regimens during the night interval (23.00-08.00 h). CONCLUSIONS: These data favour morning dosing of lansoprazole 30 mg for routine use, but patients with mainly nocturnal symptoms may be best treated by evening dosing.

2-Pyridinylmethylsulfinylbenzimidazoles↗
PubMed1996

Complications and effectiveness of gastrostomy feedings in pediatric cancer patients.

PURPOSE: The objective of this study was to assess the complications and efficacy of gastrostomy (GT) feedings in pediatric cancer patients. PATIENTS AND METHODS: We reviewed the medical records of 33 pediatric cancer patients who received enteral nutrition via a GT. RESULTS: Median age was 9.4 years (range, 1-19.8 years), and 28 of the 33 patients had solid tumors. Seventeen patients had a significant weight loss (median, 8.5%) and therapy-related weight loss was anticipated in 16 patients. The GT device was placed an average of 5.5 months after diagnosis. Twenty-five patients were fed via a tube and eight via a button device. The tube was placed surgically in 21 cases (including all eight button types) and endoscopically in 12. Nutritional support lasted a median of 9.5 months. One or more complications occurred in 30 patients and were categorized as (a) insertion site reactions (inflammation, 23; infection/colonization, 14; exuberant granulation tissue, 6); (b) mechanical problems (leaking, 3; obstruction, 2; breakage, 1; accidental dislodgement, 2); (c) insertion site bleeding, 8; and (d) feeding intolerance, 12. Only one insertion site cellulitis progressed to a systemic infection. All eight patients with a button GT experienced insertion site complications, with local infection occurring significantly more often in patients with the button than in those with the tube GT. There were no significant associations between insertion technique and type of complication. Twenty-seven patients (82%) achieved or maintained ideal body weight with this intervention. CONCLUSIONS: GT feeding was associated with minor complications, but permitted effective nutritional support for pediatric cancer patients.

Adolescent↗
PubMed1996

Thrombotic vascular risk factors in inflammatory bowel disease.

BACKGROUND: Thrombosis may be an important effector mechanism in the pathogenesis of Crohn's disease. METHODS: This study therefore investigated the prevalence of independent thrombotic risk factors (factor VII coagulant activity, lipoprotein (a), fibrinogen, plasma triglycerides, and smoking) in patients with Crohn's disease, ulcerative colitis, and normal controls. RESULTS: In Crohn's disease (n = 75), the mean plasma VII:C, lipoprotein (a) and fibrinogen concentrations were significantly greater than in the normal population (n = 85). In ulcerative colitis (n = 35), only the mean factor VII:C concentration was significantly higher than normal. Ninety three per cent of patients with Crohn's disease and 86% of those with ulcerative colitis had at least one risk factor for thrombotic vascular disease, compared with 61% of the normal population (p < 0.001). CONCLUSIONS: In many young patients with inflammatory bowel disease, plasma concentrations of these prothrombotic factors were in excess of the limits that are regarded as posing an increased risk for the development of occlusive vascular disease.

Adult↗
PubMed1995

Health-related behaviors of survivors of childhood cancer.

The health-related beliefs and behaviors of long-term survivors of childhood cancer are important because of vulnerability to adverse late effects from their primary malignancy and its therapy. A health behavior survey was completed by 110 parents of long-term survivors ranging in age from 11-17 years, and by 40 adult long-term survivors of childhood cancer ranging in age from 18-29 years. The survey included questions on the former patient's frequency of alcohol and tobacco use, as well as diet, exercise, sleep, dental, and seatbelt habits. The reported prevalence of tobacco and alcohol use was less than 10% among those less than 18 years old. Among the adults, tobacco (17.5%) and alcohol (72.5%) use was greater, but problem drinking was infrequently reported. In order to assess their perceived vulnerability, we asked the parents and the young adult patients to rate the strength of their belief that it is more important for the patient to keep healthy compared to most other children or young adults. Contrary to our expectation, demographic factors such as the patient's gender, socioeconomic level, or time elapsed since completion of therapy exerted minimal influence on their responses. Over 80% of parents and 60% of young adult survivors believed that it was more important for the former patient to remain healthy compared to most other people. However, this shared belief in increased vulnerability was inconsistently expressed in the patient's health behaviors. These results suggest that specific changes are needed in the health assessment and education of long-term survivors of childhood cancer.

Adolescent↗
PubMed1995

Protein extraction and western blotting from methacarn-fixed tissue.

Polyacrylamide gel electrophoresis (PAGE) of proteins with subsequent western blotting has become a routine technique for the analysis of proteins from both cultured cells and fresh whole tissue. We have developed a method to extract proteins from methacarn-fixed tissue which renders them suitable for SDS-PAGE and western blotting. With a panel of antibodies to specific intermediate filaments, transforming growth factor-alpha (TGF-alpha), and albumin, immunohistochemistry was performed in parallel with western blotting on sections cut from methacarn-fixed samples of normal rat liver and liver from rats treated under a regime which induces oval cell proliferation. Immunohistochemistry enabled the determination of changes in tissue distribution and abundance of the target proteins, which was mirrored by the corresponding western blot data. This technique can be especially effective when used in conjunction with immunohistochemistry. Tissue samples are easy to prepare, avoiding the precautions which need to be taken when handling fresh tissue (Abstract: J Pathol 1994; 173S: No. 41).

Acetates↗
PubMed1995

Serum concentrations of von Willebrand factor and soluble thrombomodulin indicate alteration of endothelial function in inflammatory bowel diseases.

Serum concentrations of immunoreactive von Willebrand factor (vWF) and soluble thrombomodulin (TM), and vWF multimer patterns were measured to assess endothelial function in patients with inflammatory intestinal diseases. In Crohn's disease and acute infective diarrhea, vWF concentrations were significantly higher than in normal controls. In all patient groups, multimeric analysis of vWF and the concentration of serum TM were not different from normal controls. The results indicate alteration of endothelial function in inflammatory intestinal disorders. They may be compatible with the presence of localized vasculitis, but indicate that systemic endothelial destruction does not occur in inflammatory bowel disease.

Colitis, Ulcerative↗
PubMed1995

Adjuvanticity and protective immunity elicited by Bordetella pertussis antigens encapsulated in poly(DL-lactide-co-glycolide) microspheres.

Purified Bordetella pertussis antigens, encapsulated in biodegradable poly(DL-lactide-co-glycolide) (DL-PLG) microspheres, were evaluated for their immunogenicity and ability to elicit a protective immune response against B. pertussis respiratory infection. Microencapsulated pertussis toxoid, filamentous hemagglutinin, and pertactin all retained their immunogenicity when administered parenterally. Intranasal immunization with a low dose (1 micrograms) of encapsulated filamentous hemagglutinin, pertussis toxoid, or pertactin elicited strong specific immunoglobulin G and immunoglobulin A antibody responses in respiratory secretions that were greater in magnitude than the responses elicited by the same doses of unencapsulated antigen. Intranasal immunization with as little as 1 micrograms of encapsulated pertussis antigen prior to infection reduced the bacterial recovery by 3 log10 CFU. However, intranasal immunization with the same low doses of unencapsulated antigens did not reduce infection. Intranasal administration of a combination of 1 micrograms of each of the microencapsulated pertussis antigens was more effective in reducing bacterial infection than administration of any single microencapsulated antigen. Intranasal administration of microencapsulated B. pertussis antigens elicits high levels of specific antibody coinciding with protection against infection when these microspheres are administered to the respiratory tract. These data provide evidence of the respiratory adjuvanticity of three different DL-PLC microsphere preparations, each of which contains a unique B. pertussis antigen.

Adjuvants, Immunologic↗
PubMed1995

Use of Tl-201 to detect untreated pediatric Hodgkin disease.

PURPOSE: To evaluate the usefulness of thallium-201 scintigrams in depiction of supradiaphragmatic lymphadenopathy associated with newly diagnosed Hodgkin disease in pediatric patients. MATERIALS AND METHODS: Thallium-201 and gallium-67 scans of the chest and neck were obtained in 33 consecutive patients. Mediastinal, cervical, supraclavicular, and axillary lymph node activity was evaluated by independent raters, and results were compared in a blinded fashion with those on chest computed tomographic (CT) scans. RESULTS: Gallium and thallium scans demonstrated similar accuracy in depiction of CT-defined mediastinal masses. The kappa statistic indicated moderate to strong agreement with CT results. Similarly, there was no statistically significant difference between the accuracy of thallium and gallium scans in depiction of extramediastinal lymphadenopathy. CONCLUSION: Thallium scintigraphy is effective for depiction of lymphadenopathy in pediatric patients with untreated Hodgkin disease. Serial thallium studies may provide an alternative to gallium scans in monitoring response to treatment.

Adolescent↗
PubMed1995

An intensive re-treatment protocol for children with an isolated CNS relapse of acute lymphoblastic leukemia.

PURPOSE: To assess the salvage rate and long-term complications among children treated with an intensive regimen for isolated CNS relapse during first remission of acute lymphoblastic leukemia (ALL). PATIENTS AND METHODS: Twelve boys and eight girls, diagnosed at a median age of 4 years, had CNS relapse at a median age of 7 years. Five had CNS leukemia at presentation, while five completed treatment before relapse. First complete remission lasted a median of 22.5 months. Ten patients had received cranial irradiation plus intrathecal (IT) therapy, and the remainder had received high-dose intravenous and/or IT methotrexate (MTX) as CNS-directed treatment. Retrieval therapy consisted of a five-agent intensive reinduction regimen followed by continuation therapy with four rotating drug pairs. Triple-IT therapy was administered weekly for 4 to 5 weeks, then every 6 weeks until craniospinal radiation (cranium, 24 Gy; spine, 15 Gy; both sites, 1.5 Gy per fraction) was administered. RESULTS: All 20 children achieved a second complete remission. The 5-year estimate of disease-free survival (mean +/- SE) was 70% +/- 11%. Thirteen patients remain in remission at 71+ to 126+ months (median, 104+), and 10 of 13 patients tested have normal IQ scores. Four patients have had a second relapse (one CNS and three non-CNS), and three have developed other malignancies. Prior cranial irradiation was associated with subsequent failure; only three of 10 patients who previously received radiotherapy, compared with all of the other 10 patients, remained in second remission. CONCLUSION: This intensive retrieval therapy is effective and well tolerated by children with an isolated CNS relapse of ALL, especially those who have not received prior cranial irradiation. Most patients have no significant neuropsychologic impairment.

Adolescent↗
PubMed1995

Procoagulant and prothrombotic responses of human endothelium to indomethacin and endotoxin in vitro. Relevance to non-steroidal anti-inflammatory drug enteropathy.

BACKGROUND: In view of the association between non-steroidal anti-inflammatory drugs (NSAIDs) and microvascular injury in the intestine, this study investigated the procoagulant changes in cultured human umbilical vein endothelial cells (HUVEC) when exposed to indomethacin either alone or in the presence of bacterial lipopolysaccharide (LPS). METHODS: Confluent HUVEC cultures were cultured for 1, 6, 12, and 24 h in the presence of LPS (10 micrograms/ml) with or without indomethacin (1-100 microM). After incubation, supernatants were analysed for 6-keto-prostaglandin (PG) F1 alpha and PGE2 content, whereas cells were freeze-fractured and assayed in a one-stage clotting assay for the expression of procoagulant activity (PCA). RESULTS: LPS induced a significant expression of PCA at 6, 12, and 24 h, with a significantly increased production of 6-keto-PGF1 alpha, whereas the increased PGE2 production was much less pronounced. Indomethacin alone induced a time-dependent PCA response; when coincubated with LPS the PCA response was greater than that produced by either indomethacin or LPS alone. Indomethacin totally abolished the synthesis of antithrombotic eicosanoids. CONCLUSION: Indomethacin induces PCA in HUVEC and augments LPS-induced PCA, while it abolishes the antithrombotic prostanoid response in these cells. These observations may be relevant to the microvascular injury and thrombosis observed in NSAID enteropathy.

6-Ketoprostaglandin F1 alpha↗