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Biomedical subjects

C D Johnson

Publications and source records attributed to C D Johnson.

At least 73 records · Page 4Linked to original sources
PubMed2000

CT arterial portography in the staging of pancreatic malignancy.

BACKGROUND: Detection of metastatic liver disease and malignant involvement of major peripancreatic vessels is important to determine resectability of pacreatic malignancy. Computed tomography with arterial portography (CTAP) is the most sensitive method for detection of colorectal liver metastases; it can also detect malignant vascular involvement. We have assessed CTAP in patients with pancreatic cancer considered suitable for resection after standard ultrasonography (US) and computed tomography (CT) examination. METHOD: CTAP was performed in 18 patients (8 with a biliary stent). All patients had previous US and CT with no clear evidence of irresectability. Findings of CTAP were compared with the prior CT and with findings at operation or clinical progress. RESULTS: CTAP suggested liver metastases in 7 patients. Three were confirmed at operation or at follow-up (sensitivity for detection of metastases in CT negative patients of 75%). There were 4 false-positive assessments (specificity, 71%). One further patient developed liver metastases within 6 mo after resection (1 false-negative). Nine patients had vascular involvement at operation. There was 1 false-positive and one false-negative assessment (sensitivity, 89% and specificity, 89%). CTAP detected vascular involvement in 4 patients in whom it was not detected by CT. CONCLUSION: This preliminary study suggests that CTAP is a sensitive test for detection of liver metastases and vascular involvement in patients with pancreatic malignancy. This invasive test should be reserved for patients who are considered operable on the basis of other preoperative tests.

Adult↗
PubMed2000

Therapeutic target discovery using Caenorhabditis elegans.

Use of the human genome sequence in disease therapy will require efficient identification of disease-causing and disease-associated genes with functions that are amenable to pharmacological manipulation. The validation and development of such genes as therapeutic targets requires information about both the genes' functions and the biochemical pathways in which they participate. One powerful means of obtaining such information is the study of homologous genes in model organisms amenable to laboratory manipulation. Among model organisms the nematode Caenorhabditis elegans offers several advantages, including well-established techniques for genetic and experimental manipulation and the first completed genome sequence for a multicellular organism. Molecular genetic experiments using C. elegans can contribute at several levels to drug discovery programs, from elucidation of genetic functions and pathways to the validation of candidate targets. Additionally, the ease of culture allows adaptation of the nematode for use in high-throughput chemical screens for the identification of lead compounds in drug development.

Animals↗
PubMed2000

Extra-pituitary growth hormone in peripheral tissues of early chick embryos.

Early embryonic growth is independent of pituitary growth hormone (GH), since it occurs prior to the differentiation of pituitary somatotrophs. Embryogenesis is therefore thought to be regulated by local growth factors. As GH is now known to be produced in many extrapituitary sites, in which it acts in an autocrine or paracrine manner, the possibility that extra-pituitary GH may participate in embryogenesis and organogenesis was assessed by determining the immunocytochemical presence and location of GH- and GH-receptor (GHR)-like proteins in the peripheral tissues of chick embryos during their 21-day incubation period. Immunoreactive (IR)-GH, detectable by a monoclonal and two polyclonal antibodies for chicken GH, was specifically and ubiquitously present in tissues of 3-day-old embryos. At embryonic day (ED) 5, IR-GH was widespread in ectodermal, mesodermal and endodermal tissues, but it was not present in every cell of each tissue. IR-GH was particularly abundant i! n the neural tube, notochord, limb bud, somites, heart, stomach, liver, kidney, Wolffian duct and the amnion. By ED8, IR-GH was still widespread and was now present in limb bud cartilage, although the heart and liver were no longer GH immunoreactive. GH receptor immunoreactivity was also present in most tissues and cells of ED3-ED8 embryos. These results demonstrate that extrapituitary GH is abundantly present during early embryogenesis, prior to the differentiation of pituitary somatotrophs (at ED12). Since GH- and GHR-like proteins are present in most tissues of the chick embryo, it is proposed that extrapituitary GH may act as a local growth factor during embryonic development.

Amnion↗
PubMed2000

A comparison of reports from referees chosen by authors or journal editors in the peer review process.

The aim was to analyse the peer review process by comparing reports produced by referees selected by journal editors, with those of referees selected by the authors of a scientific manuscript. Some 104 consecutive papers from the UK submitted to the British Journal of Surgery (BJS) were included. Of these, 102 were reviewed blind both by referees chosen by the journal editors, and referees chosen by the paper's principal author. Manuscripts were marked using a standard sheet for four basic aspects: originality, clinical/scientific importance, clarity and analysis; a final overall recommendation about possible publication was given. The time taken and the number of completed referee reports were similar in each group. Referees chosen by the BJS editors were more critical (scored higher) of the submitted articles. Mean scores for all domains were higher than for authors' referees, significantly for scientific importance (p = 0.009) and decision to publish (p = 0.029). In conclusion, reports produced by referees selected by BJS editors were more critical than those chosen by authors of the papers. Authors might argue that this reduced their chance of publication but constructive criticism might improve the final article and assist editors to make decisions about acceptance or rejection.

Authorship↗
PubMed1999

Regulation of the insulin-like developmental pathway of Caenorhabditis elegans by a homolog of the PTEN tumor suppressor gene.

The human PTEN tumor suppressor gene is mutated in a wide variety of sporadic tumors. To determine the function of PTEN in vivo we have studied a PTEN homolog in Caenorhabditis elegans. We have generated a strong loss-of-function allele of the PTEN homolog and shown that the deficient strain is unable to enter dauer diapause. An insulin-like phosphatidylinositol 3-OH kinase (PI3'K) signaling pathway regulates dauer-stage entry. Mutations in either the daf-2 insulin receptor-like (IRL) gene or the age-1 encoded PI3'K catalytic subunit homolog cause constitutive dauer formation and also affect the life span, brood size, and metabolism of nondauer animals. Strikingly, loss-of-function mutations in the age-1 PI3'K and daf-2 IRL genes are suppressed by loss-of-function mutations in the PTEN homolog. We establish that the PTEN homolog is encoded by daf-18, a previously uncloned gene that has been shown to interact genetically with the DAF-2 IRL AGE-1 PI3'K signaling pathway. This interaction provides clear genetic evidence that PTEN acts to antagonize PI3'K function in vivo. Given the conservation of the PI3'K signaling pathway between C. elegans and mammals, the analysis of daf-18 PTEN mutant nematodes should shed light on the role of human PTEN in the etiology of metabolic disease, aging, and cancer.

Alleles↗
PubMed1999

Reverse genetic analysis of Caenorhabditis elegans presenilins reveals redundant but unequal roles for sel-12 and hop-1 in Notch-pathway signaling.

Mutations in the human presenilin genes PS1 and PS2 cause early-onset Alzheimer's disease. Studies in Caenorhabditis elegans and in mice indicate that one function of presenilin genes is to facilitate Notch-pathway signaling. Notably, mutations in the C. elegans presenilin gene sel-12 reduce signaling through an activated version of the Notch receptor LIN-12. To investigate the function of a second C. elegans presenilin gene hop-1 and to examine possible genetic interactions between hop-1 and sel-12, we used a reverse genetic strategy to isolate deletion alleles of both loci. Animals bearing both hop-1 and sel-12 deletions displayed new phenotypes not observed in animals bearing either single deletion. These new phenotypes-germ-line proliferation defects, maternal-effect embryonic lethality, and somatic gonad defects-resemble those resulting from a reduction in signaling through the C. elegans Notch receptors GLP-1 and LIN-12. Thus SEL-12 and HOP-1 appear to function redundantly in promoting Notch-pathway signaling. Phenotypic analyses of hop-1 and sel-12 single and double mutant animals suggest that sel-12 provides more presenilin function than does hop-1.

Animals↗
PubMed1999

Violence prevention in the primary care setting: a program for pediatric residents.

OBJECTIVE: To measure the effect of a violence prevention program on pediatric residents' violence prevention guidance during well-child visits. DESIGN: Prospective study of an educational intervention. SETTING: Inner-city tertiary care hospital and satellite site. PARTICIPANTS: Pediatric residents. INTERVENTIONS: A 2(1/2)-hour violence prevention program, consisting of an introductory talk, role playing, a printed resident guide, and supplemental reading materials. MAIN OUTCOME MEASURES: Parent or guardian report of violence prevention guidance offered during the well-child visit, using a postvisit survey. RESULTS: Three hundred eight patient encounters were included in the survey: 93 prior to the program, 106 just afterward, and 109 after 6 months. Before the program, guns or violence was discussed at 9.7% of visits; this increased to 19.1% of visits after the program (odds ratio, 2.20; 95% confidence interval, 1.02-4.74). The improvement was sustained 6 months after the program. More than 80% of residents felt the program increased their fund of knowledge and taught them skills, and 93% stated that they would use these skills in the future. CONCLUSION: This one-time educational intervention significantly increased the amount of violence prevention guidance provided by pediatric residents to their patients and families. The effect was sustained after 6 months. Residents regarded the program as a successful method of providing the skills and knowledge needed to address the issue of interpersonal violence in their primary care encounters.

Adult↗
PubMed1999

Quality of life in stoma patients.

BACKGROUND: Patients with stomas face many difficulties both physical and psychological. Little is known about the long-term problems and the impact on patient lifestyle of a permanent stoma. This study was designed to address the problems faced by patients with stomas. METHODS: Patients were identified from the Stoma Care Department records for the years 1985 to 1992 and were contacted by mail. A questionnaire was designed to assess postoperative care, quality of life issues, and equipment problems. Responses were recorded on either a visual analog scale, a choice of yes-or-no alternatives, or by selection from a list of responses. RESULTS: A total of 542 eligible patients were contacted, and 391 replies were received. Major stomal problems included rashes (51 percent), leakage (36 percent), and ballooning (90 percent of patients with ileostomy). The majority of patients experienced some change in lifestyle (80 percent), and more than 40 percent of patients had problems with their sex lives. CONCLUSION: Many patients cope extremely well with a stoma; however, some patients experience considerable difficulty and distress. Improved preoperative assessment and counseling with longer follow-up by the stoma department would be helpful in the management of these patients and probably would contribute to improvement in the quality of their lives.

Adaptation, Psychological↗
PubMed1999

Diagnosis, objective assessment of severity, and management of acute pancreatitis. Santorini consensus conference.

BACKGROUND: The diagnosis, early assessment, and management of severe acute pancreatitis remain difficult clinical problems. This article presents the consensus obtained at a meeting convened to consider the evidence in these areas. The aim of the article is to provide outcome statements to guide clinical practice, with an assessment of the supporting evidence for each statement. METHOD: Working groups considered the published evidence in the areas of diagnosis, assessment of severity, nonoperative treatment, and surgical treatment of severe acute pancreatitis. Outcome statements were defined to summarize the conclusions on each point considered. The findings were discussed and agreed on by all participants. A careful assessment was made of the strength of the available evidence (proven, probable, possible, unproven, or inappropriate). FINDINGS AND CONCLUSIONS: There is reliable evidence to support much current practice. Clear guidance can be given in most areas examined, and several areas were identified where further investigation would be helpful. Diagnosis using plasma concentrations of pancreatic enzymes is reliable. Rapid advances are taking place in the assessment of severity. Several new therapeutic strategies show real promise for the reduction of morbidity and mortality rates. Surgical debridement is required for infected pancreatic necrosis, but is less often necessary for sterile necrosis.

Acute Disease↗
PubMed1999

Effects of altering cycling technique on gluteus medius syndrome.

OBJECTIVE: We discuss how altering the cycling technique of a cyclist receiving periodic chiropractic care helped in the management of gluteus medius syndrome. CLINICAL FEATURES: A 24-year-old male amateur cyclist had numbness and tingling localized to a small region on the superior portion of the right buttock. The area involved demonstrated paresthesia to light touch sensory evaluation. The cyclist had received chiropractic adjustments 2 days before the onset of the symptoms. One week earlier, the patient began riding a new bicycle with different gearing than his previous one. Manual-resisted muscle testing created soreness in the lumbosacral area and buttocks. Trigger points were identified in the right gluteus medius. Standing lumbar spine flexion was 70 degrees, limited by tight hamstrings. INTERVENTION AND OUTCOME: Because the patient was already receiving periodic chiropractic care, no passive therapy was used. Patient education regarding the difference in gear selection in bicycles of a higher quality was provided. He was instructed to train in lower gears than he had previously used and to maintain a cadence of 70 to 90 revolutions of the pedals per minute. After 2 days, the paresthesia on the right buttock resolved. The trigger points were only mildly tender with minimal residual soreness of the involved muscles. CONCLUSION: Management of gluteus medius syndrome by altering the cadence and gear development for a bicyclist is discussed. Either frank or cumulative injury to the gluteus medius muscle is the typical etiologic factor for this syndrome. Repetitive strain of the patient's gluteus medius muscle as a result of poor cycling technique appeared to be the cause here. Knowledge of bicycle fitting, training techniques, and bicycle mechanics appeared necessary to resolve the problem.

Adult↗
PubMed1999

Development of a disease specific quality of life (QoL) questionnaire module to supplement the EORTC core cancer QoL questionnaire, the QLQ-C30 in patients with pancreatic cancer. EORTC Study Group on Quality of Life.

There is overwhelming consensus that quality of life assessment is urgently required in pancreatic cancer, yet little research has been conducted. We report on the development of a disease specific questionnaire module to supplement the EORTC core cancer module, the QLQ-C30 in patients with pancreatic cancer, using EORTC quality of life study group guidelines for module development. Relevant QoL issues were generated from literature searches and interviews with health professionals and patients with pancreatic cancer. Issues were constructed into items and provisionally translated. The provisional module was pretested in patients in 8 European centres. The resulting module the QLQ-PAN26 includes 26 items related to disease symptoms, treatment side-effects and emotional issues specific to pancreatic cancer. This should ensure that the module will be sensitive to assess the small but important disease and treatment related QoL changes in pancreatic cancer. The use of the QLQ-C30 and QLQ-PAN26 will provide a comprehensive system of QoL assessment in international trials of pancreatic cancer.

Adult↗
PubMed1999

Dietary intake after pancreatectomy.

BACKGROUND: Nutritional intake after pancreatectomy may be impaired. The extent of the problem and the effect on intake of specific nutrients is unknown. METHODS: A 1-week weighed dietary food intake (using digital scales and a food diary) was studied in 15 patients, a median of 4 (range 1-30) months after pancreatectomy. Results were expressed as a percentage of estimated average requirement (EAR), reference nutrient intake (RNI) or lower RNI (LRNI) values. RESULTS: The median energy intake was 1914 (range 1154-2804) kcal/day, representing a median of 88 (56-154) per cent of EAR. Fat intake was low (72 (60-123) g/day); protein intake was adequate (139 (99-219) per cent of RNI). Deficiencies were observed in the intake of vitamin D (17 (6-56) per cent of LRNI) and, in some patients, selenium (107 (19-203) per cent of LRNI). CONCLUSION: Nutritional intake in the months after pancreatectomy could be improved by increasing fat intake (with enzyme supplements as appropriate). This 7-day study also suggests that these patients may require vitamin D and possibly selenium supplementation.

Adult↗
PubMed1999

Survey of antibiotic prophylaxis in acute pancreatitis in the UK and Ireland.

BACKGROUND: Current surgical practice with regards to antibiotic prophylaxis in acute pancreatitis in the UK and Ireland was overviewed. METHODS: The 1103 members of the Association of Surgeons of Great Britain and Ireland were surveyed by postal questionnaire. A total of 528 replies were received (48 per cent). Following exclusion of surgeons not treating patients with acute pancreatitis, analysis was carried out on 429 replies. RESULTS: Respondents treated a median of 12 (interquartile range (i.q.r.) 10-20) patients per year with acute pancreatitis. Prophylactic antibiotic therapy was used by 88 per cent of responding surgeons, of whom 24 per cent used it in all cases. For surgeons professing selective use of antibiotics, the most common indication for use was in patients with prognostically severe disease. A cephalosporin was prescribed in 72 per cent of patients; cefuroxime was the single most common antibiotic. Combination therapy with metronidazole was used in 48 per cent of attacks. The median duration of antibiotic therapy was 5 (i.q.r. 5-7) days. An adverse drug reaction attributable to the use of prophylactic antibiotics was reported by 11 per cent of respondents. CONCLUSION: This study has established that a significant body of clinicians charged with the responsibility of treating acute pancreatitis use antibiotic prophylaxis in the initial treatment of patients with predicted severe disease.

Acute Disease↗
PubMed1999

Pancreas regeneration after resection: does it occur in humans?

Although pancreatic regeneration after partial resection or pancreatic injury (restitutio ad integrum) has been demonstrated in animal models, whether regeneration occurs in the human pancreas is unknown. Our aim was to determine whether the human pancreas regenerates after subtotal resection. We reviewed pre- and postoperative computerized tomograms (CTs) of 21 patients after proximal pancreatectomy (50-60% resection) for malignancy with no recurrent disease during follow-up of pancreatic parenchymal abnormalities. Three fixed anatomic measurements (pancreatic body width, tail width, and length) were compared with the same region 10 and 21 months after surgery. Data are expressed as mean +/- SEM. Pancreatic measurements before and 10 months after resection did not differ for body width (2.0+/-0.1 cm vs. 1.8+/-0.1 cm), tail width (2.2+/-0.2 cm vs. 1.8+/-0.2 cm) or length (8.2+/-0.3 vs. 7.4+/-0.4 cm) (p> or =0.1 each). At 21 months after resection, measurements were less for body width and tail width (2.2+/-0.2 cm vs. 1.5+/-0.2 cm and 2.2+/-0.1 cm vs. 1.5+/-0.2 cm, respectively; p = 0.01) and unchanged for length (8.1+/-0.4 cm vs. 8.1+/-0.4 cm; p = 0.9). We conclude that the human pancreas does not regenerate after partial anatomic (50%) resection.

Adult↗
PubMed1999

High-throughput isolation of Caenorhabditis elegans deletion mutants.

The nematode Caenorhabditis elegans is the first animal whose genome is completely sequenced, providing a rich source of gene information relevant to metazoan biology and human disease. This abundant sequence information permits a broad-based gene inactivation approach in C. elegans, in which chemically mutagenized nematode populations are screened by PCR for deletion mutations in a specific targeted gene. By handling mutagenized worm growth, genomic DNA templates, PCR screens, and mutant recovery all in 96-well microtiter plates, we have scaled up this approach to isolate deletion mutations in >100 genes to date. Four chemical mutagens, including ethyl methane sulfonate, ethlynitrosourea, diepoxyoctane, and ultraviolet-activated trimethylpsoralen, induced detectable deletions at comparable frequencies. The deletions averaged approximately 1400 bp in size when using a approximately 3 kb screening window. The vast majority of detected deletions removed portions of one or more exons, likely resulting in loss of gene function. This approach requires only the knowledge of a target gene sequence and a suitable mutagen, and thus provides a scalable systematic approach to gene inactivation for any organism that can be handled in high density arrays.

Algorithms↗