PubMed Health⌕ Search

Biomedical subjects

C Cole

Publications and source records attributed to C Cole.

At least 37 records · Page 2Linked to original sources

An "enigmatic" cause of back pain following regional anaesthesia for caesarean section: septic pelvic thrombophlebitis.

A case of septic pelvic thrombophlebitis is reported. This presented as back pain and leg weakness 18 days after regional anaesthesia for caesarean section. The patient was referred to the Department of Anaesthesia. Obstetric review of the patient at the request of the anaesthetist led to a CT scan that demonstrated the diagnosis. This condition may lead to fatal "on-table" pulmonary embolus if the thrombosed vein is handled during an exploratory laparotomy. Treatment should be conservative with antibiotics and anticoagulation. This case illustrates the need for awareness amongst anaesthetists of possible surgical causes for morbidity that may initially appear anaesthetic-related.

Adult↗

The rôle of thymidine phosphorylase/PD-ECGF in cancer chemotherapy: a chemical perspective.

The angiogenic growth factor thymidine phosphorylase/PD-ECGF has been identified as a potential target in the development of anti-cancer drugs. This review firstly discusses the biological rôle of TP/PD-ECGF and its importance in the activation of 5-fluorouracil and its prodrugs. The chemistry and chemotherapeutic potential of TP/PD-ECGF inhibitors are also discussed.

Animals↗

A similarity model for the human angiogenic factor, thymidine phosphorylase/platelet derived-endothelial cell growth factor.

Thymidine phosphorylase (EC 2.4.2.4), identical to the angiogenic factor, platelet-derived endothelial cell growth factor (PD-ECGF), is up-regulated in several tumour types. A similarity model of human thymidine phosphorylase was built, based on the crystal structure of the Escherichia coli enzyme. The high residue conservation between the two enzyme sources (39% sequence identity and 53% sequence similarity) aided model building. The human model was very similar to the E. coli enzyme's crystal structure, with the main tertiary structure difference being the destruction of helix 15 in E. coli by the presence of a loop in the human model. The model was used to rationalize the nature of the binding of the substrates thymine and thymidine, and of known inhibitors using a quantitative docking algorithm. Ab initio calculations on the nM inhibitor 5-chloro-6-(1-(2-iminopyrrolidinyl)methyl)uracil hydrochloride gave its conformation and distribution of charge. Subsequent quantitative docking studies have led to the suggestion, for the first time, that this inhibitor behaves as an oxycarbenium ion transition-state analogue, explaining its strong reported inhibition.

Amino Acid Sequence↗

Purification and activation of recombinant p38 isoforms alpha, beta, gamma, and delta.

p38 is a proline-directed serine/threonine kinase that is activated by inflammatory cytokines and cellular stress. At present, four isoforms of p38 have been identified and termed alpha, beta, gamma, and delta. We expressed each p38 homolog in Escherichia coli and purified the recombinant isoforms. p38alpha and C-terminal Flag-tagged p38beta were purified by Q-Sepharose fast flow, hydroxyapatite, and Q-Sepharose high-performance chromatography. His-tagged p38gamma was purified using Ni2+-NTA resin followed by Mono Q chromatography. Glutathione S-transferase-Flag p38delta was purified using M2 affinity agarose and gel-filtration chromatography. Upstream activators of p38, constitutively active (ca) MKK3 and MKK6, were also cloned, purified, and used to activate each p38 isoform. p38 alpha, gamma, and delta were phosphorylated by both MKK6 and caMKK3. p38beta was phosphorylated only by MKK6. Mass spectrometry analysis and kinase assays showed that MKK6 was the superior reagent for phosphorylating and activating all p38 isoforms.

Activating Transcription Factor 2↗

Blurred vision and high blood pressure in a young woman.

A 41-year-old woman presented with a short history of blurred vision. She had a 6-year history of refractory hypertension which had been treated with a variety of drug regimens. She was found to have bilateral branch retinal vein occlusion. Retinal vein occlusion is a recognised complication of hypertension but simultaneous involvement of both eyes is extremely rare. Following this episode, blood pressure control has improved without change in drug therapy, suggesting that treatment compliance may partly explain the previous difficulties.

Adult↗

Identification of a cellular protein that binds to Tat-responsive element of TGF beta-1 promoter in glial cells.

Tat is a transcriptional transactivator produced by the human immunodeficiency virus type 1 (HIV-1) and plays a pivotal role in enhancing expression of the viral genome in the infected cells. Although initial studies have suggested that interaction of Tat with the transactivation responsive element (TAR); located within the LTR, is essential for Tat function, subsequent studies indicated that Tat has the ability to augment transcription of viral and cellular genes by a TAR-independent mechanism. In early studies we demonstrated that HIV-1 Tat stimulates transcription of the transforming growth factor, TGF beta-1, gene in glial cells. In this study, we have identified a cellular protein that interacts with the Tat-responsive region located between nucleotides -323 to -453 of the regulatory sequence of the TGF beta-1 promoter. Results from footprinting analysis revealed association of cellular proteins with the 130 nucleotide sequence located in the Tat-responsive region. Analysis of the associated protein by UV-crosslinking suggested the involvement of a protein between 40-45 kDa in size which preferentially interacts with the GC/GA rich sequence of the TGF beta-1 Tat-responsive sequence in a single-stranded configuration. The ability of the previously identified 40 kDa protein, named Pur alpha to bind to the GC/GA sequence in the single-stranded configuration, similar to those from TGF beta-1 promoter prompted us to investigate its binding capacity to the TGF beta-1 sequence and its transcriptional activity on the TGF beta-1 promoter. Results from band shift studies indicated the association of the bacterially produced Pur alpha to the TGF beta-1 DNA sequences positioned within the Tat-responsive region. Overexpression of Pur alpha in glial cells constitutively producing Tat augmented transcription of the TGF beta-1 gene. These results are consistent with previous reports on the cooperative action of Pur alpha and Tat in modulating other eukaryotic promoters. The importance of these findings with regard to deregulation of other cellular genes by HIV-1 Tat is discussed.

Astrocytes↗

Social relationships among young adults with insulin-dependent diabetes mellitus: ten-year follow-up of an onset cohort.

Past cross-sectional studies have suggested that young adults with insulin-dependent (Type 1) diabetes mellitus (IDDM) may experience problems in their close peer relationships. For 10 years, we have followed an onset cohort of children and adolescents with IDDM (n = 57) and an age-matched group who were originally recruited after an acute illness, accident, or injury (n = 54). Now aged 19-26 years, these two groups were compared in terms of their friendship patterns, dating and love experiences, and sense of loneliness. All subjects in both groups had at least one friend. However, the IDDM group reported fewer friendships overall. The difference was accounted for by the number of less intimate friends. The two groups had similar frequencies of current romantic partners (IDDM = 63%; comparison group = 64%). While dating attitude and dating assertiveness did not differ between groups, some differences were found in terms of experiences of a primary love relationship. IDDM patients experienced less trust and sense of intimate friendship in these love relationships. No differences in loneliness were found. The preponderance of our findings indicate that the two groups had similar patterns and experiences of close peer relationships. Thus, the study does not suggest that IDDM leads to serious problems in forming social relationships for these patients during the transition to young adulthood. On the other hand, the IDDM patients' lower level of trust and intimacy within love relationships are consistent with other findings from this study suggesting specific areas of lowered self-worth that appear in social relationships.

Adolescent↗

Prophylactic oral dolasetron mesylate reduces nausea and vomiting after abdominal hysterectomy. The Canadian Dolasetron Study Group.

PURPOSE: The incidence of postoperative nausea and vomiting (PONV) varies from 50% to 75% after gynaecological surgery under general anaesthesia. This study evaluates the dose-response relationships, safety, and efficacy of the new 5-HT3 antagonist, dolasetron mesylate, in the prevention of PONV in women undergoing total abdominal hysterectomy (TAH). METHODS: Three hundred and seventy four women scheduled for TAH under general anaesthesia were studied at 13 Canadian centres. Patients received in a randomized, double-blind manner 25, 50, 100, or 200 mg dolasetron or placebo po one to two hours before induction of anaesthesia. The anesthetic protocol was standardized. Efficacy was evaluated for 24 hr after surgery by comparing the number of emetic episodes, administration of rescue medication, severity of nausea, and patient satisfaction. RESULTS: Analysis of complete response (no emetic episodes and no rescue for 24 hr) revealed a linear dose-response relationship across dolasetron groups (P < 0.002). Dolasetron 100 mg (P < 0.003) and 200 mg (P < 0.01) were superior to placebo. The percentage of patients with no emetic episodes increased from 29.3% (placebo) to 54.1 % (100 mg). Subgroup analysis revealed ASA status (I > II), previous history of PONV, previous history of motion sickness, and total morphine dose (> 55 mg associated with less PONV than < 55 mg) influenced the incidence of emetic symptoms, but did not alter the results of the primary analysis. CONCLUSION: Prophylactic dolasetron (100 mg and 200 mg) reduces the incidence of PONV in patients having total abdominal hysterectomy.

Adolescent↗

A structure/function analysis of Rat7p/Nup159p, an essential nucleoporin of Saccharomyces cerevisiae.

Rat7p/Nup159p is an essential nucleoporin of Sac-charomyces cerevisiae originally isolated in a genetic screen designed to identify yeast temperature-sensitive mutants defective in mRNA export. Here we describe a detailed structural-functional analysis of Rat7p/Nup159p. The mutation in the rat7-1 ts allele, isolated in the original genetic screen, was found to be a single base pair change that created a stop codon approximately 100 amino acids upstream of the actual stop codon of this 1,460 amino acid polypeptide, thus eliminating one of the two predicted coiled-coil regions located near the carboxyl terminus of the protein. These coiled-coil regions are essential since an allele lacking both coiled-coil regions was unable to support growth under any conditions. In contrast, no other region of the protein was absolutely required. The SAFG/PSFG repeat region in the central third of the protein was completely dispensable for growth at temperatures between 16 degrees C and 37 degrees C and cells expressing this mutant allele were indistinguishable from wild type. Deletion of the amino-terminal third of the protein, upstream from the repeat region, or the portion between the repeat region and the coiled-coils resulted in temperature-sensitivity, but the two alleles showed distinct phenotypes with respect to the behavior of nuclear pore complexes (NPCs). Taken together, our data suggest that Rat7p/Nup159p is anchored within the NPC through its coiled-coil region and adjacent sequences. In addition, we postulate that the N-terminal third of Rat7p/Nup159p plays an important role in mRNA export.

Alleles↗

Engineering department physical plant staffing requirements.

There is a considerable effort in the health care arena to establish credible engineering manpower yardsticks that are universally applicable as a benchmark. This document was created by using one facility's own benchmark criteria that can be used to help develop either internal or competitive benchmarking comparisons.

Contract Services↗

Somatosensory evoked potentials during hypoxia and hypocapnia in conscious humans.

PURPOSE: The objective of the study was to evaluate the effects of moderate hypoxia and hypocapnia on the latency and amplitude of cortical somatosensory evoked potentials (SSEPs) in conscious human subjects. METHODS: In ten volunteers the amplitude and latency of the cortical somatosensory evoked potentials were recorded during stimulation of the left posterior tibial nerve. Measurements of SSEPs and respiratory variables were made breathing ambient air, air containing a reduced oxygen percentage (17% O2, 14% O2 (n = 6) or 11% O2 (n = 10)), and again during voluntary hyperventilation breathing ambient air (PETCO2 = 20 mmHg, n = 10). RESULTS: Hypoxia (11% O2) caused mild stimulation of ventilation (P < 0.05) but had no effects on the latency or amplitude of the SSEP. Lesser degrees of hypoxia had no effects. Hyperventilation caused a small (2-4%) decrease) in the latency of the SSEP and an increase in the amplitude of the SSEP (P < 0.05). CONCLUSIONS: These findings in conscious subjects were consistent with previous observations in anaesthetized humans and anaesthetized dogs and show that the decrease in latency of the SSEP associated with hypocapnia is not due to changes in the depth of anaesthesia. These effects of hypocapnia may contribute to small variations in the latency of the SSEP when monitoring is performed during surgery, but are unlikely to be large enough to be of clinical concern.

Adult↗

Improving the outcome of emergency department patients with a chief complaint of chest pain.

Preliminary data developed by the Health Care Financing Administration under its pilot cooperative cardiovascular screening project indicate that 50 percent of Medicare heart attack patients arriving in emergency departments who are appropriate for thrombolytic therapy do not receive it within the time period specified by the American College of Cardiology. Indicators developed for quality assurance monitoring and evaluation of a hospital emergency department prompted closer review of some cases. It was determined that a critical outcomes team using the principles of total quality management and the FOCUS-PDCA models should be empowered to deal with these issues. Through this process, the need for the development of a chest pain center at the hospital was identified and supported.

Algorithms↗

Obesity in primary care patients in Kelantan, Malaysia: prevalence, and patients' knowledge and attitudes.

This study measured the body mass index (BMI), and assessed attitudes and knowledge about obesity, of 197 male and 217 female patients aged 20-59 years attending the primary care clinic of the university hospital in Kelantan, Malaysia. There was no significant difference between the mean BMI of males (23.7) and females (24.2). In the overweight group (BMI 25-29.9) were 60 men (30%) and 66 women (30%). In the obese group (BMI 30 and above) were 12 men (6%) and 22 women (10%). Both diabetes mellitus and hypertension were associated with significantly higher BMI's. Knowledge about obesity was lacking. Sixty-three (15%) failed to recognize that obesity is bad for health. When asked the causes of obesity, 88 (21%) failed to mention either diet or lack of exercise. "Being happy" was suggested as a cause by 32 (8%). When asked if certain foods would cause obesity if eaten in excess, 45 (11%) said "No" for fatty foods, and 164 (40%) said "No" for sweet foods. Concerning appearance, 30 (15%) men regarded an obese man as normal or even handsome, while 49 (23%) women regarded an obese woman as normal or beautiful. Obesity is common among our adult patients, and is associated with some of their common health problems. However, a substantial minority do not regard obesity as unhealthy, do not relate it to diet or lack of exercise, do not recognize important groups of fattening foods, and do not regard obesity as unattractive.

Adult↗

Physical findings in 21q22 deletion suggest critical region for 21q- phenotype in q22.

Multiple abnormalities were observed in a newborn infant with a deletion in the long arm of chromosome 21, from band 22q22.1-->qter. The phenotype of this infant was similar to that previously described in infants with deletions spanning the long arm of chromosome 21, from the centromere to 21q22 [Rethoré et al., 1972, Exp Cell Res 70:455-456, 1973, Ann Genet (Paris) 16:271-275]. However, as a phenotypically normal child with normal intelligence and with deletion of 21q11.1-21q21.3 has also been identified [Korenberg et al., 1991, Hum Genet 87:112-118], this case suggests that the critical region of deletion for the 21q- phenotype lies distal to 21q21, within 21q22.1-22.2.

Abnormalities, Multiple↗

Rapid detection of hereditary and acquired platelet storage pool deficiency by flow cytometry.

Platelet aggregation is commonly used to investigate patients with possible dense granule storage pool deficiency (delta SPD), but recent studies have shown that this investigation is not specific or sensitive for this disorder. We describe a simple one-step technique to detect mepacrine loaded platelets by flow cytometry and found a good correlation (r = 0.83) between this method and the enumeration of platelet dense granules by conventional fluorescent microscopy. Seven patients with congenital delta SPD had significantly (P < 0.001) reduced mepacrine labelling detected by flow cytometry (mean 15%; range 5-23%) compared to normal controls (mean 48%; normal range 32-64%). Six patients with other hereditary platelet disorders had normal mepacrine labelling (mean 49%; range 34-66%) and were clearly distinguished from patients with delta SPD despite similar platelet aggregation patterns. Acquired delta SPD is frequently associated with the platelet function defect described in the myeloproliferative and myelodysplastic disorders (MPD/MDS) and we compared platelet aggregation and mepacrine labelling in 15 of these patients. The results confirm that delta SPD occurs commonly in MPD/MDS with 7/15 patients having reduced mepacrine staining but, like the findings in hereditary delta SPD, 3/7 patients with normal platelet aggregation had delta SPD. Similarly abnormal platelet aggregation was not diagnostic of delta SPD as 4/8 of these patients had normal mepacrine levels. These results may contribute to the known lack of correlation between the limited assessment of platelet function and bleeding events in MPD/MDS. We found mepacrine labelling of platelets detected by flow cytometry to be a useful, simple and inexpensive method to detect hereditary and acquired delta SPD which will improve the definition of the platelet defect in these disorders in the clinical laboratory.

Adult↗