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Biomedical subjects

D Johnson

Publications and source records attributed to D Johnson.

At least 109 records · Page 6Linked to original sources
PubMed2000

Phase II trial of combination intraperitoneal cisplatin and 5-fluorouracil in previously treated patients with advanced ovarian cancer: long-term follow-up.

OBJECTIVES: This trial was performed to determine the response rate and progression-free and overall survivals of patients with advanced recurrent ovarian cancer who were treated with intraperitoneal cisplatin and 5-fluorouracil. METHODS: Twenty-four patients with ovarian cancer were entered on this trial and treated with intraperitoneal (ip) cisplatin (DDP) and ip 5-fluorouracil, every 3 weeks for eight cycles. Following iv hydration, the cisplatin and 5-fluorouracil were administered through an ip catheter in 2 liters of 0.9% normal saline with a 4-h dwell. RESULTS: All patients were evaluable for progression-free and overall survival and toxicity analysis, and 22 patients for response. The median age was 59 (range, 35-71); initial disease status included 9 patients with residual disease following chemotherapy prior to entry on this study; 5 patients had progressed, and 10 patients had recurrent disease more than 6 months following initial chemotherapy. Of the 9 patients with residual disease, 1 complete response and 3 partial responses were observed; of 10 patients with recurrent disease, 1 complete and 1 partial response were observed for an overall response rate of 27%. No objective responses were seen in the 7 patients who were platinum-refractory on protocol entry. The median progression-free and overall survivals are 7.0 (range, 0.5-137) and 15.5 (range, 3-147) months, respectively. Toxicity included hypomagnesemia, vomiting, abdominal pain, and mild anemia. Only one patient required a dosage adjustment of cisplatin for a serum creatinine elevation >2.0 mg/dl. CONCLUSIONS: We conclude that the combination of ip cisplatin and 5-FU is an effective regimen for patients with residual or relapsed epithelial ovarian cancer with survival durations, response rates, and toxicity profiles that compare favorably with those of other second-line ovarian cancer regimens. Patients who are primarily platinum-refractory are unlikely to benefit from these agents administered into the peritoneal cavity.

Adult↗
PubMed2000

The role of MRI in screening for neurogenic hypertension.

Neurovascular compression (NVC) of the left ventrolateral medulla (VLM) has been implicated as a cause of essential hypertension. We investigated whether high-resolution MRI of the posterior cranial fossa could identify patients with essential hypertension who may benefit from surgery. A retrospective analysis of imaging and clinical records from 162 patients was performed. There were 38 patients with essential hypertension and 124 who were normotensive. Contact or compression of the VLM was present in 42.1 % (16/38) of the hypertensive group on the left and 47.3 % (18/38) on the right. In the normotensive group it was seen in 32.2 % (40/124) on the left and 26.6 % (33/124) on the right. There was no significant difference between the hypertensive and control groups with regard to contact or compression of the left VLM. The results support the contention that neurovascular compression (NVC) of the left or right VLM is a common finding on MRI in normotensive individuals. We therefore believe that high-resolution MRI cannot be used as a screening tool to identify patients who may benefit from surgery.

Adolescent↗
PubMed2000

Ink used as first aid treatment of a scald.

We report here a case of a childhood scald injury where immediate first aid consisted of the application of fountain pen ink. Continuing education is required to inform parents of the use of cold water in the immediate first aid treatment of scalds.

Burns↗
PubMed2000

Potholes in the information highway: the use of health service utilization data by Alberta health care managers.

Reviews and consultations with regional health authority decision makers have indicated that both data quality and access can limit effective use of health services information when assessing outcomes, planning changes, testing solutions and making decisions. To further a more system-wide understanding of these data utilization issues, we asked senior managers, board members and information analysts in Alberta regional health authorities (n = 111) about the availability of, organizational supports for and barriers to the use of health service utilization data. Eighty percent of respondents stated that the lack of data impeded problem resolution, and 83 percent of managers stated that health service data alerted them to new problems. Examples of useful data related to good standardization and linkage of data sets, or to capacity for valid comparison and trending. Given the limitations highlighted in relation to meeting even the simplest needs of standardization, linkage, comparison and trending, Alberta health care managers indicate frustration in trying to use health service data as currently construed and distributed, particularly within their current frameworks and fast-paced timelines for decision making.

Administrative Personnel↗
PubMed2000

Prevalence of low albumin, suboptimal energy, and muscle stores in asian dialysis patients.

OBJECTIVE: Investigate the prevalence of low serum albumin levels (<3.2 g/L) and decreased arm muscle area percentiles and arm fat area percentiles in Asian patients compared with non-Asian patients treated with dialysis. DESIGN: Cross-sectional study in which serum albumin and anthropometric measurements were averaged over 6 months, and compared between patients of Asian ethnicity and patients of non-Asian ethnicity. SETTING: Eight outpatient dialysis facilities. SUBJECTS: Ninety-seven Asian and 513 non-Asian patients treated with hemodialysis or peritoneal dialysis. RESULTS: Height, weight, and body mass index were significantly lower in Asians compared with non-Asians (P <.001). Protein catabolic rate was significantly greater in Asian (1.17 +/- 0.29 g/kg) compared with non-Asian (0.97 +/- 0.28 g/kg) women (P <.001). Asian men (3.30 g/dL) and women (3. 26 g/dL) had lower serum albumin compared with non-Asian men (3.35 g/dL; P =.057) and women (3.34 g/dL; P =.040). The proportion of patients with serum albumin <3.2 g/dL was greater for both Asian women (35%) (P <.040) and men (30%) than non-Asian women (25%) and men (20%). After adjusting for important covariates, serum albumin remained significantly different between Asian and non-Asian patients (P <.05). The proportion below the fifth percentile for arm muscle area was significantly greater for both Asian men (54%) and women (19%) compared with non-Asian men (24%) and women (8%). Proportions of Asian and non-Asian women below the 10th and 5th percentile for arm fat area were similar. However, Asian men (54%) had a significantly greater fat depletion than non-Asian men (26%). CONCLUSION: Mean serum albumin was significantly lower in Asian patients on dialysis than in non-Asians. Muscle stores were depleted in Asian men and women compared with non-Asians, and fat stores were depleted in Asian men. Based on this study, Asian dialysis patients would seem to be at higher nutritional risk than non-Asians, particularly Asian men. Further research is needed to assess factors that affect serum albumin and mortality in Asian dialysis patients, and standards need to be developed to further assess anthropometric measurements in this population.

Adipose Tissue↗
PubMed2000

Does primary intraocular lens implantation prevent "aphakic" glaucoma in children?

PURPOSE: Open-angle glaucoma may develop after surgery for congenital or developmental cataract with an incidence ranging from 3% to 41%. The pathogenesis of "aphakic" (open-angle) glaucoma remains unknown. Despite numerous reported clinical series (>1000 eyes), we are unaware of any reported case of open-angle glaucoma after primary intraocular lens (IOL) implantation for congenital or developmental cataract. We decided to test the hypothesis that primary posterior chamber IOL implantation might decrease the incidence of open-angle glaucoma in children. METHODS: Pseudophakic eyes were collected from surgeons who contributed data to a refractive study and who monitored intraocular pressure on a regular basis. IOL implantation was commonly performed in eyes with a corneal diameter >10 mm. Comparable primary data on aphakic eyes were included from 2 published studies on aphakic glaucoma, which included corneal diameters and the patient's age at surgery. Glaucoma-free survival estimates for each cohort were estimated. RESULTS: Only 1 case of glaucoma was found among 377 eyes with primary pseudophakia (mean age of patient, 5.1 +/- 4.7 years; mean follow-up, 3.9 +/- 2.7 years). There were 14 eyes (11.3%) with glaucoma among 124 aphakic eyes (mean age of patient, 2.7 +/- 2.6 years; mean follow-up time, 7.2 +/- 3.9 years). CONCLUSIONS: We report a decreased incidence of open-angle glaucoma among eyes rendered primarily pseudophakic compared with those that remained aphakic after cataract surgery. We propose 2 theories on the possible mechanism of reduction in the incidence of glaucoma in pseudophakic eyes.

Adolescent↗
PubMed2000

9:45-10:00. Positron Emission Tomography (PET) is Superior to Computerized Tomography (CT) for Metastatic Staging in Melanoma Patients.

PET provides diagnostic information currently not available with traditional imaging. Retrospective analysis was performed of 104 patients with primary or recurrent melanoma who underwent PET for staging to determine sensitivity/specificity compared to body CT. 157 PET and 70 CT scans were analyzed with a mean follow up of 26 months. Metastatic events were confirmed with positive histology (73%) or documented disease progression.PET demonstrated 86% sensitivity and 97% specificity in 41 patients with metastasis. CT showed 57% sensitivity and 70% specificity in 30 patients with metastasis. Exclusion of areas not evaluated on CT (head, neck/supraclavicular, and extremities) increased CT sensitivity to 68%. Fifty-three patients underwent 67 consecutive CT and PET scans that detected 132 metastases in 30 individuals. PET detected a greater percentage of metastases (83%) compared to CT (56%), and specifically, in the soft tissue, neck, peripheral/mediastinal/intraabdominal lymph nodes, and small bowel. PET detected 100% of mediastinal metastasis while CT detected only 67%. Surprisingly, PET detected 84% of lung parenchymal metastasis compared to 72% with CT.PET is more sensitive and specific than CT for detection of melanoma metastasis and should be considered the primary staging study upon suspicion of recurrent disease. PET shows greater ability to detect soft tissue, small bowel, and lymph node metastasis that do not meet criteria designated as abnormal by CT. Likewise, CT does not routinely evaluate the supraclavicular area, neck, or upper/lower extremities. However, even when these sites are excluded from comparative analysis, PET is superior to CT in detecting melanoma metastasis.

Journal Article↗
PubMed2000

Stress and open-office noise.

Forty female clerical workers were randomly assigned to a control condition or to 3-hr exposure to low-intensity noise designed to simulate typical open-office noise levels. The simulated open-office noise elevated workers' urinary epinephrine levels, but not their norepinephrine or cortisol levels, and it produced behavioral aftereffects (fewer attempts at unsolvable puzzles) indicative of motivational deficits. Participants were also less likely to make ergonomic, postural adjustments in their computer work station while working under noisy, relative to quiet, conditions. Postural invariance is a risk factor for musculoskeletal disorder. Although participants in the noise condition perceived their work setting as significantly noisier than those working under quiet conditions did, the groups did not differ in perceived stress. Potential health consequences of long-term exposure to low-intensity office noise are discussed.

Adult↗
PubMed2000

Gene expression analysis by massively parallel signature sequencing (MPSS) on microbead arrays.

We describe a novel sequencing approach that combines non-gel-based signature sequencing with in vitro cloning of millions of templates on separate 5 microm diameter microbeads. After constructing a microbead library of DNA templates by in vitro cloning, we assembled a planar array of a million template-containing microbeads in a flow cell at a density greater than 3x10(6) microbeads/cm2. Sequences of the free ends of the cloned templates on each microbead were then simultaneously analyzed using a fluorescence-based signature sequencing method that does not require DNA fragment separation. Signature sequences of 16-20 bases were obtained by repeated cycles of enzymatic cleavage with a type IIs restriction endonuclease, adaptor ligation, and sequence interrogation by encoded hybridization probes. The approach was validated by sequencing over 269,000 signatures from two cDNA libraries constructed from a fully sequenced strain of Saccharomyces cerevisiae, and by measuring gene expression levels in the human cell line THP-1. The approach provides an unprecedented depth of analysis permitting application of powerful statistical techniques for discovery of functional relationships among genes, whether known or unknown beforehand, or whether expressed at high or very low levels.

Cell Line↗
PubMed2000

Prevalence and prognostic significance of neuroendocrine cells in esophageal adenocarcinoma.

Neuroendocrine differentiation is common in adenocarcinomas of the stomach and colon and may be associated with a slightly better prognosis in gastric adenocarcinoma. We studied neuroendocrine differentiation in esophageal adenocarcinomas and associated Barrett's esophagus (BE) to determine association with patient outcome. Fifty-eight cases of esophageal adenocarcinoma (15 biopsies, 43 resections) from 52 patients were stained with a monoclonal antibody to chromogranin (CG). Medical records were reviewed for tumor stage, response to therapy, and patient survival. Thirty-two patients received radiation and chemotherapy, and four received radiation. Twelve of 58 (20.7%) esophageal adenocarcinomas contained scattered CG-positive cells. Tumors with CG-positive cells were moderately to poorly differentiated, and many consisted of large cribriform glands, similar to intestinal-type adenocarcinomas. One case of small cell carcinoma of the esophagus was weakly CG positive; another was negative. Neuroendocrine differentiation was retained in lymph node metastases in two cases but lost in three other cases. In 10 CG-negative primary tumors, lymph node metastases were also negative. For five of six patients with paired biopsy/resection specimens, no CG-positive cells were seen in either specimen; one patient had CG-positive cells only in the resection. There was no difference in tumor stage at surgery or survival time between CG-positive and CG-negative tumors. BE was present in 34 cases and contained CG-positive cells in 21 of 34 (61.8%). Low-grade dysplasia contained CG-positive cells in 11 of 14 cases (78.6%) and high-grade dysplasia in 3 of 6 cases. Fourteen of 21 (66.7%) adenocarcinomas associated with CG-positive BE were negative for CG. In summary, neuroendocrine differentiation is common in BE and is retained in low- and high-grade dysplasia but is usually lost in esophageal adenocarcinoma. The presence of scattered neuroendocrine cells does not affect patient outcome.

Adenocarcinoma↗
PubMed2000

The extent of HLA class II allele level disparity in unrelated bone marrow transplantation: analysis of 1259 National Marrow Donor Program donor-recipient pairs.

A comprehensive analysis of the HLA-D region loci, DRB1, DRB3, DRB5, DQA1, DQB1, DPA1 and DPB1, was performed to determine allelic diversity and underlying HLA disparity in 1259 bone marrow recipients and their unrelated donors transplanted through the National Marrow Donor Program. Although 43.0% of DRB1 alleles known to exist at the beginning of the study were found in this predominantly Caucasian transplant population, a few alleles predominated at each locus. In recipients, 67.1% of DRB1 alleles identified were one or two of six common DRB1 alleles. Only 118 (9.4%) donor-recipient pairs were matched for all alleles of DRB1, DQA1, DQB1, DPA1 and DPB1. While 79.4% of the pairs were matched for DRB1, only 13.2% were matched for DPB1 alleles. Almost 66% of pairs differed by more than one allele mismatch and 59.0% differed at more than one HLA-D locus. DQB1 was matched in 85.9% of DRB1-matched pairs. In contrast, only 13.9% of the pairs matched for DRB1, DQA1 and DQB1 were also matched for DPA1 and DPB1. This database, highlighting the underlying HLA disparity within the pairs, forms the foundation of an ongoing study to establish the relationship between HLA matching and successful outcome in unrelated allogeneic stem cell transplant.

Alleles↗
PubMed2000

Regulation of both apoptosis and cell survival by the v-Src oncoprotein.

A number of oncogenes alter the regulation of the cell cycle and cell death, contributing to the altered growth of tumours. Expression of the v-Src oncoprotein in Rat-1 fibroblasts prevented cell cycle exit in response to growth factor withdrawal. Here we investigated whether survival of v-Src transformed cells in low serum is dependent on v-Src activity. We used a temperature sensitive v-Src to study the effect inactivating v-Src on transformed cells growing under low serum conditions. We found when we switched off v-Src the cells died by apoptosis characterised by activation of caspases and the stress-activated kinases, JNK (Jun N-terminal kinase) and p38 MAP (mitogen activated protein) kinase. We were able to prevent cell death by addition of serum or overexpression of Bcl-2. Thus v-Src transformed Rat-1 cells can be protected from apoptosis by serum, v-Src, or Bcl-2. We investigated how v-Src protects from apoptosis under these conditions. Amongst other effects, v-Src activates two kinases which have been shown to protect cells from apoptosis, phosphatidylinositol 3-kinase (PI3-K) and extracellular signal-regulated kinase (ERK1/2). We found that switching off v-Src led to a decrease in the activity of both PI3-K and ERK1/2, however, we found that adding a specific inhibitor of PI3-K (LY294002) to v-Src transformed Rat-1 cells grown in low serum induced apoptosis while a specific ERK kinase (MEK1) inhibitor (PD98059) had no effect. This suggests that v-Src protects from apoptosis under low serum conditions by activating PI3-K.

Animals↗
PubMed2000

A novel mutation, Ala315Ser, in FGFR2: a gene-environment interaction leading to craniosynostosis?

Mutations in the fibroblast growth factor receptor 1, 2 and 3 (FGFR1, -2 and -3) and TWIST genes have been identified in several syndromic forms of craniosynostosis. There remains, however, a significant number of patients with non-syndromic craniosynostosis in whom no genetic cause can be identified. We describe a novel heterozygous mutation of FGFR2 (943G --> T, encoding the amino acid substitution Ala315Ser) in a girl with non-syndromic unicoronal craniosynostosis. The mutation is also present in her mother and her maternal grandfather who have mild facial asymmetry but do not have craniosynostosis. None of these individuals has the Crouzonoid appearance typically associated with FGFR2 mutations. However, the obstetric history revealed that the proband was in persistent breech presentation in utero and was delivered by Caesarean section, at which time compression of the skull was apparent. We propose that this particular FGFR2 mutation only confers a predisposition to craniosynostosis and that an additional environmental insult (in this case foetal head constraint associated with breech position) is necessary for craniosynostosis to occur. To our knowledge, this is the first report of an interaction between a weakly pathogenic mutation and intrauterine constraint, leading to craniosynostosis.

Alanine↗
PubMed2000

The influence of gender and specialty on reporting of abusive and discriminatory behaviour by medical students, residents and physician teachers.

INTRODUCTION: The perception of whether a given behaviour is abusive differs between students and teachers. We speculated that attitudes towards reporting abusive and discriminatory behaviour may vary by specialty as well as by gender. METHODS: We report a cross-sectional survey of incoming medical students, medical students, residents, and teaching faculty at one Canadian medical school. The discrimination and abuse questions were in the following domains: (i) psychological abuse, (ii) sexual abuse, (iii) physical abuse, (iv) gender discrimination, (v) racial discrimination, (vi) disability discrimination, (vii) derogatory remarks regarding homosexuality. The frequency of self-reported witnessed or experienced abusive and discriminatory behaviour was compared by gender, specialty choice and stage of training. RESULTS: The response rates varied by respondent group: 44/56 (79%) of incoming medical students, 177/218 (81%) of medical students, 134/206 (65%) of residents and 215/554 (38%) of physician teachers. The frequency of these behaviours was perceived to be low by both male and female respondents. Abusive and discriminatory behaviour by physician teachers was noted more frequently by residents (P < 0.001) and physician teachers themselves (P < 0.001) compared with incoming medical students. As well, in general, women noted more abusive and discriminatory behaviour by all teachers, compared with men (P < 0. 003). Each response to the abuse/discrimination questions was also modelled as the independent variable using stepwise multiple regression. The area of specialization (surgical versus non-surgical) altered the reporting of abusive and discriminatory behaviour by women. CONCLUSION: We conclude that female surgical residents and medical students undergo a process of acclimatization to the patriarchal surgical culture. As female surgeons become physician teachers they revert to a culture more similar to that of their female non-surgical colleagues. Although a process of deidealization occurs in medical training, these attitudes are not necessarily retained throughout the practising lifetime of physicians as they regain autonomy and more personal control.

Adult↗
PubMed2000

Tension-free vaginal tape for primary genuine stress incontinence: a two-centre follow-up study.

OBJECTIVE: To assess the safety and efficacy of the tension-free vaginal tape procedure in the treatment of primary genuine stress incontinence. PATIENTS AND METHODS: A two-centre follow-up study was conducted on 40 women with urodynamically confirmed primary genuine stress incontinence who had a tension-free vaginal tape inserted under local anaesthesia with sedation. Operative details were recorded and all patients followed up both subjectively, and objectively with repeat urodynamic studies and pad testing. RESULTS: The mean (range) age of the women was 51.1 (33-86) years, the median parity 2 (0-4) and mean body mass index 25.1 (19-35). The mean anaesthesia and operative duration was 42 (25-65) min; 93% of the women resumed immediate spontaneous voiding with no need for catheterization. The mean inpatient stay was 2.2 (2-4) days (where 2 days is equivalent to one night in hospital). The follow-up was conducted at a mean interval of 12.3 (6-24) months. Subjectively, 80% of women were cured and 17.5% significantly improved; objectively, genuine stress incontinence was cured in 95%. Symptomatic postoperative detrusor instability was found in 15% of women and symptoms of voiding dysfunction identified in 5% of women. There were no defects in healing or tape rejection. CONCLUSION: The tension-free vaginal tape procedure is a promising new technique that, in this short-term analysis, appears to be safe and effective. Intra-operative complications are uncommon and both hospital stay and recovery are short. Voiding complications are rare but symptomatic postoperative detrusor instability had an incidence of 15%.

Adult↗
PubMed2000

Is all ventricular fibrillation the same? Influence of mode of induction on characteristics of ventricular fibrillation.

INTRODUCTION: Little information is available on the relationship between the mode of induction of ventricular fibrillation (VF) to VF characteristics. METHODS AND RESULTS: VF was induced from the anterior left ventricle by programmed electrical stimulation, burst pacing, alternating current (AC), high current S2 at a site remote from S1, T wave shock, and intersecting wavefronts in seven normal dogs and seven dogs with chronic myocardial infarction. Using two electrode arrays, 112 electrograms were recorded from the anterior and lateral wall. Cycle lengths were analyzed and activation vectors were created by summing orthogonally recorded bipolar electrograms. The magnitude of the vector loops was integrated over time to produce an "ensemble vector" index (EVI) whose magnitude is high when beat-to-beat activation direction is consistent and low when activation direction is variable. T wave shock-induced VF had a significantly longer cycle length 1 to 5 seconds after VF onset than other modes of induction (P < 0.05). The frequency-corrected EVI was significantly larger for AC current and T wave shock-induced VF as opposed to all other modes of VF induction in early VF (P < 0.0001). After 10 seconds of VF, these differences persisted only on the anterior wall. CONCLUSION: VF induced in animals by T wave shock and AC current had different characteristics than VF induced by other methods. These findings may have implications for our understanding of VF pathophysiology.

Animals↗
PubMed2000

Paternal origin of FGFR2 mutations in sporadic cases of Crouzon syndrome and Pfeiffer syndrome.

Crouzon syndrome and Pfeiffer syndrome are both autosomal dominant craniosynostotic disorders that can be caused by mutations in the fibroblast growth factor receptor 2 (FGFR2) gene. To determine the parental origin of these FGFR2 mutations, the amplification refractory mutation system (ARMS) was used. ARMS PCR primers were developed to recognize polymorphisms that could distinguish maternal and paternal alleles. A total of 4,374 bases between introns IIIa and 11 of the FGFR2 gene were sequenced and were assayed by heteroduplex analysis, to identify polymorphisms. Two polymorphisms (1333TA/TATA and 2710 C/T) were found and were used with two previously described polymorphisms, to screen a total of 41 families. Twenty-two of these families were shown to be informative (11 for Crouzon syndrome and 11 for Pfeiffer syndrome). Eleven different mutations in the 22 families were detected by either restriction digest or allele-specific oligonucleotide hybridization of ARMS PCR products. We molecularly proved the origin of these different mutations to be paternal for all informative cases analyzed (P=2. 4x10-7; 95% confidence limits 87%-100%). Advanced paternal age was noted for the fathers of patients with Crouzon syndrome or Pfeiffer syndrome, compared with the fathers of control individuals (34. 50+/-7.65 years vs. 30.45+/-1.28 years, P<.01). Our data on advanced paternal age corroborates and extends previous clinical evidence based on statistical analyses as well as additional reports of advanced paternal age associated with paternal origin of three sporadic mutations causing Apert syndrome (FGFR2) and achondroplasia (FGFR3). Our results suggest that older men either have accumulated or are more susceptible to a variety of germline mutations.

Acrocephalosyndactylia↗