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Biomedical subjects

M Gibson

Publications and source records attributed to M Gibson.

At least 55 records · Page 3Linked to original sources

A randomized trial of leukapheresis volumes, 7 L versus 10 L: an assessment of efficacy and patient tolerance.

High-dose chemotherapy followed by autologous PBSC transplantation (PBSCT) has become an accepted form of therapy for a number of malignant hematologic diseases. The optimal method for the collection of PBSC is yet to be defined. Large-volume leukapheresis may be able to collect adequate numbers of PBSC with the patient undergoing fewer procedures. We routinely process 7 L of blood per leukapheresis. Hence, we elected to assess whether a modest increase in the blood volume processed would, on average, decrease the number of leukaphereses each patient needed to undergo to collect > or =2 x 10(6) CD34+ cells/kg body weight. Sixty patients were randomized to undergo 7 L leukaphereses (n = 31 patients; 87 leukaphereses) or 10 L leukaphereses (n = 29 patients; 81 leukaphereses). The median number of leukaphereses required per patient to collect the target number of CD34+ cells was two (range one to five) for both groups (p = 0.83). The median number of nucleated cells collected per patient was greater for the 10 L group (8.2 x 10(8)/kg versus 5.3 x 10(8)/kg, p = 0.005), as was the median number of mononuclear cells (MNC) (4.7 x 10(8)/kg versus 3.6 x 10(8)/kg, p = 0.0001), whereas there was no statistical difference between the groups for the median number of CD34+ cells collected per patient (3.2 x 10(6)/kg versus 3.7 x 10(6)/kg, p = 0.98). Therefore, over the 18-month period of this trial, the use of a 10 L leukapheresis volume did not decrease the number of leukaphereses performed compared with a 7 L leukapheresis volume.

Adolescent↗

Increasing rates of cerebral palsy across the severity spectrum in north-east England 1964-1993. The North of England Collaborative Cerebral Palsy Survey.

OBJECTIVES: To report epidemiological trends in cerebral palsy including analyses by severity. DESIGN: Descriptive longitudinal study in north-east England. Every child with suspected cerebral palsy was examined by a developmental paediatrician to confirm the diagnosis. Severity of impact of disability was derived from a parent completed questionnaire already developed and validated for this purpose. SUBJECTS: All children with cerebral palsy, not associated with any known postneonatal insult, born 1964-1993 to mothers resident at the time of birth in the study area. MAIN OUTCOME MEASURES: Cerebral palsy rates by year, birth weight, and severity. Severity of 30% and above defines the more reliably ascertained cases; children who died before assessment at around 6 years of age are included in the most severe group (70% and above). RESULTS: 584 cases of cerebral palsy were ascertained, yielding a rate that rose from 1.68 per 1000 neonatal survivors during 1964-1968 to 2.45 during 1989-1993 (rise = 0.77; 95% confidence interval 0.2-1.3). For the more reliably ascertained cases there was a twofold increase in rate from 0.98 to 1.96 (rise = 0.98; 95% confidence interval 0.5-1.4). By birth weight, increases in rates were from 29.8 to 74.2 per 1000 neonatal survivors < 1500 g and from 3.9 to 11.5 for those 1500-2499 g. Newborns < 2500 g now contribute one half of all cases of cerebral palsy and just over half of the most severe cases, whereas in the first decade of this study they contributed one third of all cases and only one sixth of the most severe (chi(2) and chi(2) for trend p < 0.001). CONCLUSIONS: The rate of cerebral palsy has risen in spite of falling perinatal and neonatal mortality rates, a rise that is even more pronounced when the mildest and least reliably ascertained are excluded. The effect of modern care seems to be that many babies < 2500 g who would have died in the perinatal period now survive with severe cerebral palsy. A global measure of severity should be included in registers of cerebral palsy to determine a minimum threshold for international comparisons of rates, and to monitor changes in the distribution of severity.

Birth Weight↗

Wound infection in gynecologic surgery.

OBJECTIVE: We sought to determine the wound infection rate among patients undergoing elective gynecologic surgery at a single tertiary care center and to determine the predictive value of various factors that contribute to infection. We further investigated the adequacy of hospital records in documenting infection rates as well as the timing of presentation of wound infections. METHODS: The records of 115 patients undergoing elective gynecologic surgery at our institution were reviewed. Patients were further subdivided based on route of surgery. We analyzed the importance of antibiotic prophylaxis, route of surgery, smoking, diabetes, and body mass index (BMI). RESULTS: The overall wound infection rate was 12.17% with no significant difference in the subgroups by route of surgery. Overall, antibiotic prophylaxis significantly decreased infection rates (P = 0.0118), but the route of surgery, BMI, smoking, and diabetes were not significant predictors of infection. Only one case of infection was detected during the initial hospital stay (6.1%). Fifty percent of the patients with infection required readmission, and of these 35.7% required an additional surgical procedure. The average length of hospital stay was 2.4 days longer in patients with infection. CONCLUSIONS: Antibiotic prophylaxis has a role in the management of patients undergoing abdominal gynecologic surgery. In today's environment of cost containment, an increased hospital stay and the added likelihood of additional surgical intervention associated with wound infection are important targets for prevention. Most patients with wound infection were diagnosed after discharge from the hospital. In our population, among whom transportation problems and remote residence are prevalent, strategies for infection surveillance should be integral to discharge planning.

Antibiotic Prophylaxis↗

Laparoscopic colon resections: a five-year retrospective review.

In recent years, laparoscopic surgery has become a matter of growing interest. It has been shown that laparoscopic colectomy is well tolerated and safe for benign disease. However, there is some uncertainty about using this method for malignant disease when curative resection is the aim. These uncertainties mainly consist of spread of cancer to port site, long-term survival, and adequacy of resection. The majority of laparoscopic colectomies are technically assisted procedures in which anastomosis is performed outside the abdomen. However, some surgeons are now performing this surgery totally laparoscopically with the anastomosis performed inside the abdomen. Laparoscopic colectomy is currently practiced with great frequency by general surgeons. Its performance requires a steep learning curve and a large number of cases to obtain proficiency. The indications for laparoscopic colectomy are different from one institution to another. In some institutions all patients with colorectal disease are candidates for laparoscopic colectomy and in others it may be limited to benign disease only. The purpose of this review is to analyze all laparoscopic colectomies performed at our medical center since 1992. We conducted a retrospective chart review of both hospital and clinic charts of patients who underwent colectomies at our hospital. A total of 338 patient charts were reviewed. In a comparison of both laparoscopic (n = 285) and converted (n = 53) methods, the age and operative time were about the same. Age average and operating room time average were similar for both groups. With laparoscopy, there was a 3-day drop in length of hospital stay as well as a 1-day-earlier regaining of bowel function. Hospital cost dropped 5000 dollars average for the laparoscopic colectomy. The conversion rate at our center was 15 per cent. Complication rates were lower in the laparoscopic group. Recurrence of cancer at the port site (0.7%) was no higher than in the converted group (incisional recurrence, 1.8%). We conclude that laparoscopic colectomy does show an improvement in return of bowel function, hospital cost, and shorter hospital stay. Long-term follow-up will be necessary to determine the effectiveness of laparoscopic colon resection for colorectal cancer.

Age Factors↗

Splenectomy for idiopathic thrombocytopenic purpura: a five-year retrospective review.

Idiopathic thrombocytopenic purpura is a condition that is characterized by persistently low platelet counts. Idiopathic thrombocytopenic purpura results from splenic sequestration and accelerated platelet destruction mediated by antiplatelet antibody. Most cases arise in previously healthy patients, mostly women ages 20 to 40. Clinical symptoms consist of bruising, petechiae, mucosal bleeding, menorrhagia, and intracranial bleeding. Platelet-associated immunoglobulin G can be detected in 90 per cent of patients. Therapy for adults and children is somewhat different. Splenectomy in adults should be considered in patients who fail to respond to steroids, develop thrombocytopenia after taper, or develop steroid toxicity. Ninety per cent of children will maintain normal platelet counts in 9 to 12 months. Some will recover spontaneously without medical therapy. Splenectomy in children is recommended if idiopathic thrombocytopenic purpura persists for more than one year or fails to respond to steroids. Our purpose was to determine whether management of idiopathic thrombocytopenic purpura in patients who undergo splenectomy at our institutions is appropriate and effective. We undertook a 5-year retrospective review of 27 patients with idiopathic thrombocytopenic purpura which have undergone splenectomy. All of the 27 patients were referred to surgeons after initial medical management. The patients were divided into two groups on the basis of length of therapy: longer than 6 months and less than 6 months. The longer than 6 months group contained 15 patients. This group had a postoperative complication rate of 40 per cent. Those in the group with <6 months therapy had a complication rate of 7 per cent. Average follow-up for all patients was 20 months. Eighty-eight per cent of the patients had complete response. Three per cent had a partial response with platelet counts >50,000. The partial response group did not respond well to preoperative steroid boluses with a great rise in platelet counts. Eighteen per cent of patients received platelet transfusions. Sixty per cent of the transfusions were given for inappropriate reasons. A large percentage of our patients had prolonged medical therapy before splenectomy. The inappropriate use of platelets was a common error in management. Patients treated for more than 6 months had more postoperative complications. An initial increase in platelets after steroid bolus is a good indicator for favorable response to splenectomy. We conclude that splenectomy is a safe and effective method of treatment for idiopathic thrombocytopenic purpura with no deaths or postsplenectomy sepsis to date.

Adult↗

bioWidgets: data interaction components for genomics.

MOTIVATION: The presentation of genomics data in a perspicuous visual format is critical for its rapid interpretation and validation. Relatively few public database developers have the resources to implement sophisticated front-end user interfaces themselves. Accordingly, these developers would benefit from a reusable toolkit of user interface and data visualization components. RESULTS: We have designed the bioWidget toolkit as a set of JavaBean components. It includes a wide array of user interface components and defines an architecture for assembling applications. The toolkit is founded on established software engineering design patterns and principles, including componentry, Model-View-Controller, factored models and schema neutrality. As a proof of concept, we have used the bioWidget toolkit to create three extendible applications: AnnotView, BlastView and AlignView.

Amino Acid Sequence↗

Small bakeries--a cross-sectional study of respiratory symptoms, sensitization and dust exposure.

This cross-sectional study investigated the prevalence of respiratory symptoms and sensitization to dust components in 224 individuals in 18 small bakeries in Scotland. Each work practice in the bakeries was characterized by an assessment of dust exposure and assigned to a category with either a direct exposure to flour dust of an indirect exposure to flour dust. We found that work-related respiratory symptoms were significantly associated with specific IgE to wheat flour and amylase but not to exposure category (except for nasal/eye symptoms). However, specific IgE to wheat flour was significantly associated with exposure category. There was a higher prevalence of immunological sensitization, reporting of work-related respiratory symptoms and exposure to dust than in other studies and of the 144 personal dust sample results taken, 21 (14.6%) of the total exceeded 10 mg/m3, the substantial dust concentration as outlined by the COSHH Regulations. Follow-up of those with work-related asthma symptoms (questionnaire response) was inconclusive of the work-relatedness of their symptoms, although it did confirm respiratory morbidity.

Adult↗

Emergency cranial computed tomography in the management of acute febrile encephalopathy in children.

OBJECTIVE: Evaluation of the influence of emergency cranial computed tomography on the management of acute febrile encephalopathy in children. METHODS: A retrospective study in children with acute febrile encephalopathy who underwent emergency cranial computed tomography within 12 hours of admission to the paediatric intensive care unit. All scans were evaluated by two independent radiologists. RESULTS: Thirty nine children were included. Fourteen scans were abnormal and two had clinically insignificant incidental findings. Four children with focal neurological signs had scans demonstrating extra-axial collections. None required neurosurgical intervention. Clinically, raised intracranial pressure was present in 10 patients. Only five had cerebral oedema on computed tomography; these five children died. Emergency cranial computed tomography influenced subsequent management in no child without focal neurological signs and in only one child with focal neurology. CONCLUSION: Emergency cranial computed tomography in acute febrile encephalopathy in children without focal neurological signs has little influence on subsequent management. Where cranial computed tomography is thought to be necessary, it should be carried out when the child's clinical condition has been stabilised.

Adolescent↗

GAIA: framework annotation of genomic sequence.

As increasing amounts of genomic sequence from many organisms become available, and as DNA sequences become a primary reagent in biologic investigations, the role of annotation as a prospective guide for laboratory experiments will expand rapidly. Here we describe a process of high-throughput, reliable annotation, called framework annotation, which is designed to provide a foundation for initial biologic characterization of previously unexamined sequence. To examine this concept in practice, we have constructed Genome Annotation and Information Analysis (GAIA), a prototype software architecture that implements several elements important for framework annotation. The center of GAIA consists of an annotation database and the associated data management subsystem that forms the software bus along which other components communicate. The schema for this database defines three principal concepts: (1) Entries, consisting of sequence and associated historical data; (2) Features, comprising information of biologic interest; and (3) Experiments, describing the evidence that supports Features. The database permits tracking of annotation results over time, as well as assessment of the reliability of particular results. New framework annotation is produced by CARTA, a set of autonomous sensors that perform automatic analyses and assert results into the annotation database. These results are available via a Web-based query interface that uses graphical Java applets as well as text-based HTML pages to display data at different levels of resolution and permit interactive exploration of annotation. We present results for initial application of framework annotation to a set of test sequences, demonstrating its effectiveness in providing a starting point for biologic investigation, and discuss ways in which the current prototype can be improved. The prototype is available for public use and comment at http://www.cbil.upenn.edu/gaia.

Amino Acid Sequence↗

Absorption enhancers as tools to determine the route of nasal absorption of peptides.

The nasal absorption of a series of peptides was studied in order to examine the relationship between extent of absorption and lipophilicity and absorption enhancers were used to probe the mechanism of peptide absorption. An in situ rat nasal perfusion technique was employed to assess the nasal absorption of a series of peptides, D-FGGGGG (D-FG5), D-FD-FGGGG (D-F2G4) and D-FD-FD-FGGG (D-F3G3), [D-ala2, D-leu5]enkephalin (YD-AGFD-L) and thyrotrophin releasing hormone (TRH). The enhancers sodium tauro-24,25 dihydrofusidate (STDHF), ethylene diamine tetraacetic acid (EDTA and dimethyl-beta-cyclodextrin (DMbetaCD) were utilized to improve and elucidate the mechanisms of peptide absorption. There was no significant relationship between extent of peptide absorption and lipophilicity as determined by C log P values. STDHF was a potent absorption enhancer but demonstrated overt toxicity. Conversely, EDTA did not demonstrate extensive toxicity but was found to be a poor absorption enhancer. DMbetaCD displayed some toxicity and was also found to inhibit the absorption of D-FG5,D-F2G4 and D-F3G3. This reduction is likely to be a result of the peptide/DMbetaCD complex formation. The peptides studied appear to be predominantly absorbed by a passive paracellular mechanism.

Absorption↗

Reduction of the Human Placental Vascular Relaxation to Progesterone by Gestational Diabetes

>Background: We have recently described a dose-dependent, endothelium-independent relaxation to progesterone in human placental arteries and veins. This receptor-operated, cAMP-mediated relaxation may be of value in maintaining adequate blood flow in the placental circulation.Objective: To investigate if gestational diabetes alters this relaxation to progesterone.Study design: Isolated human placental vessels from pregnancies complicated by gestational diabetes and well matched controls (uncomplicated term pregnancies), incubated in Krebs-bicarbonate buffer and submaximally precontracted with KCl, were exposed to cumulative doses of progesterone (0.01-30 µmol/liter), nitroglycerin (0.001-1 µmol/liter), arachidonic acid (0.01-10 µmol/liter), forskolin (0.01-10 µmol/liter) and 5-hydroxytryptamine (serotonin, 0.01-10 µmol/liter).Results: The relaxation to progesterone in vessels from patients with gestational diabetes was reduced by 50-100% in both arteries and veins compared with control (for example, relaxation to 10 µmol/liter progesterone was reduced from 52 +/- 7 to 18.8 +/- 5.4% in arteries and from 58 +/- 8 to 19 +/- 5.2% in veins, n = 7-13, P < 0.05), whereas responses to the other vasoactive agents were unchanged.Conclusion: Based on these results, gestational diabetes significantly reduces the relaxation to progesterone in human placental vessels. This alteration of the relaxation to progesterone may lead to an increase in placental vascular resistance and possibly to a reduction of placental blood flow.

Journal Article↗

In Vitro Vascular Relaxation to Progesterone and Its Metabolites in Human Umbilical and Placental Blood Vessels

> Background: We have recently reported that progesterone caused a receptor-mediated, cAMP-dependent relaxation in isolated placental arteries and veins from normal term pregnancies that may be important in maintaining adequate blood flow in the placental circulation. Objective: To further investigate the activity of progesterone and some of its metabolites in both placental and umbilical vessels. Study design: Isolated human placental and umbilical arteries and veins from normal term pregnancies, incubated in Krebs-bicarbonate buffer and submaximally precontracted with potassium chloride, were exposed to cumulative concentrations (0.01-30 µm) of progesterone, 5beta-pregnane-3,20-dione, 5alpha-pregnane-3,20-dione, or 5alpha-pregnane-3beta-ol-20-one. Results: All experimental progestins produced concentration-dependent relaxations in precontracted human placental and umbilical arteries and veins. These relaxations were endothelium-independent. Progesterone and 5beta-pregnane-3,20-dione appeared to be the most potent and efficient of the tested progestins, whereas 5alpha-pregnane-3beta-ol-20-one produced the least relaxation in the same vessels. Conclusions: These results suggest that not only progesterone, but also its metabolites, may be of physiological importance in the regulation of umbilico-placental vascular tone. Additionally, it appears that the umbilical blood vessels possess the same relaxation to progesterone as placental arteries and veins. Taken together, these results indicate a potential role for progesterone and its metabolites in maintaining adequate blood flow in the umbilico-placental circulation.

Journal Article↗

The GAIA software framework for genome annotation.

We describe a software framework, GAIA, that supports semi-automated annotation of uncharacterized sequence data. The annotation framework incorporates annotation by data source integration, data analysis, and manual data entry. Components of the system include a configurable, open data analysis pipeline, a relational information storage manager, and Java-based graphical user interfaces. We discuss design decisions and tradeoffs in building such a system, and policies and strategies for producing consistent, uniform, high quality annotation.

Base Sequence↗

Retrieval of detached coating of a hydrophilic guidewire from the profunda femoris artery using an Amplatz gooseneck snare.

We present a case where during accidental puncture of the profunda femoris artery the plastic coating of a hydrophilic guidewire was stripped off against the bevel of a metal needle. This lay coiled in the profunda femoris artery. It was retrieved using an Amplatz gooseneck snare from an ipsilateral antegrade common femoral artery puncture.

Catheterization, Peripheral↗

The prognostic value of flash visual evoked potentials in the assessment of non-ocular visual impairment in infancy.

The results of flash visual evoked potentials (VEPs) in 44 infants blind or severely visually impaired from non-ocular causes are presented, and related to the subsequent visual outcome. Ocular causes of visual impairment were excluded by clinical examination and electroretinography. Using a 2 x 2 contingency table, a significant association between VEP and outcome was demonstrated (chi 2 = 3.51, 1 d.f., p = 0.05). Of 13 infants with normal VEPs, 11 demonstrated substantial visual improvement (negative predictive value = 84.6%). However, of the 31 with abnormal VEPs, only 14 remained severely impaired/blind; the other 17 demonstrating visual improvement (positive predictive value = 45.1%). The sensitivity of the method was high in that 14 of 16 (87.5%) infants who remained impaired/blind had abnormal VEPs, but specificity was low as only 11 of 28 (39.3%) who showed visual improvement had normal VEPs. The accuracy of the technique was therefore low, 25 of 44 (56.8%) being true positive/ negative. With regard to visual outcome when faced with an apparently blind infant, it is important not to be too pessimistic for, as is shown in this study, 28 of 44 demonstrated substantial improvement. There are no absolute indicators of prognosis, but the presence of structural cerebral lesions and a history of either neonatal meningitis or encephalopathy are relatively bad prognostic signs. The flash VEP, despite its limitations, is a useful prognostic tool, particularly in those apparently blind infants whose normal ocular examination/electroretinogram is accompanied by normal VEPs. Those with abnormal VEPs, however, do not necessarily have a poor prognosis, but should be followed-up as maturational changes and/or improvements in function of the sensory pathway will be reflected in the evoked potentials.

Blindness, Cortical↗